METHOD OF INHIBITING PROTEIN TYROSINE PHOSPHATASE 1B AND/OR T-CELL PROTEIN TYROSINE PHOSPHATASE AND/OR OTHER PTPASES WITH AN ASP RESIDUE AT POSITION 48

Abstract: The present invention provides a method of inhibiting a member of a family of Protein Tyrosine Phosphatases (PTPases, PTPs) such as PTP1B, TC-PTP, CD45, SHP-1, SHP-2, PTP alpha , PTP epsilon , PTP mu , PTP delta , PTP sigma , PTP zeta , PTP beta , PTPD1, PTPD2, PTPH1, PTP-MEG1, PTP-LAR, and HePTP by exposing said Ptpase member by administration to a host or otherwise to at least one compound with certain structural, physical and spatial characteristics that allow for the interaction of said compound with specific residues of the active site of PTP1B and/or TC-PTP. These compounds are indicated in the management or treatment of a broad range of diseases such as autoimmune diseases, acute and chronic inflammation, osteoporosis, various forms of cancer and malignant diseases, and type I diabetes and type II diabetes, as well as in the isolation of PTPases and in elucidation or further elucidation of their biological function.

Description: Method of Inhibiting Protein Tyrosine Phosphatase 1 B and/or T-cell Protein Tyrosine Phosphatase and/or other PTPases with an Asp Residue at Position 48 Field of the Invention This invention relates to a method of inhibiting Protein Tyrosine Phosphatase 1 B (PTP1 B) and/or T-cell Protein Tyrosine Phosphatase (TC-PTP) and/or Protein Tyrosine Phosphatases (PTPases) having an aspartic acid (Asp) in position 48 (PTP1 B numbering, Chemoff et al., Proc. Natl. Acad. Sci. USA 87: 2735-2789 (1989)) by exposing such an enzyme to inhibitor compounds, i.e., to compounds possessing certain structural, physico-chemical and spatial characteristics that allow them to interact with specific amino acid residues of the active site (and the vicinity of the active site) of PTP1 B and/or TC-PTP and more generally Protein Tyrosine Phosphatases (PTPases) having an aspartic acid (Asp) in position 48. The resulting inhibition of the PTPase enzymatic activity makes these compounds useful for elucidating the function of PTP's e.g., by inhibiting a PTP and observing up-or down-regulation of other proteins. Additionally, such inihibitors serve as early development candidates, development candidates, or prototype drugs for treatment of or paliation of diseases and dysfunctions such as diabetes type I and II and obesity, cancer, immune disorders (including allergy and abnormal autoimmunity), and conditions involving disturbances in platelet aggregation as well as infectious diseases. This invention also relates to (I) the design and selection of inhibitors which bind to the active site of PTP1 B and/or TC- PTP and/or PTPases having an aspartic acid (Asp) in position 48 (II) the synthesis of said inhibitors, methods for their preparation and (III) to compositions comprising the inhibitor compounds. Background of the Invention Protein phosphorylation is now well recognized as an important mechanism utilized by cells to transduce and regulate signals during different stages of cellular function (Hunter, Phil. Trans. R. Soc. Lond. B 353: 583-605 (1998); Chan et al., Annu. Rev. Immunol. 12: 555-592 (1994); Zhang, Curr. Top. Cell. Reg. 35: 21-68 (1997); Matozaki and Kasuga, Cell. Signal. 8: 1 13-19 (1996); Fischer et al, Science 253:401-6 (1991 ); Flint et al., EMBO J. 12: 1937-46 (1993)). The level of tyrosine phosphorylation is balanced by the opposing action of protein tyrosine kinases and protein tyrosine phosphatases. There are at least two major classes of phosphatases: (1) those that dephosphorylate proteins (or peptides) that contain a phosphate group(s) on a serine or threonine moiety (termed Ser/Thr phosphatases) and (2) those that remove a phosphate group(s) from the amino acid tyrosine (termed protein tyrosine phosphatases or PTPases or PTPs). The PTPases are a family of enzymes that can be classified into two groups: a) intracellular or nontransmembrane PTPases and b) receptor-type or transmembrane PTPases. In addition, dual-specificity phosphatases and low molecular weight phosphatases are able to dephosphorylate phospho tyrosyl proteins. See, e.g., WO 97/ 39746; WO 97/ 40017; WO 99/ 15529; WO 97/08934; WO 98/ 27065; WO 99/46236; WO 99/46244; WO 99/46267; WO 99/46268 and WO 99/46237. Intracellular PTPases: Most known intracellular type PTPases contain a single conserved catalytic phosphatase domain consisting of 220-240 amino acid residues. The regions outside the PTPase domains are believed to play important roles in localizing the intracellular PTPases subcellularly (Mauro, L.J. and Dixon, J.E. TIBS ^ : 151-155 (1994)). The first intracellular PTPase to be purified and characterized was PTP1 B, which was isolated from human placenta (Tonks et al., J. Biol. Chem. 263: 6722-6730 (1988)). Shortly after, PTP1 B was expressed recombinantly (Charbonneau et al., Proc. Natl. Acad. Sci. USA 86: 5252-5256 (1989); Chernoff et al., Proc. Natl. Acad. Sci. USA 87: 2735-2789 (1989)). Other examples of intracellular PTPases include (1) T-cell PTPase/ TC-PTP (Cool et al. Proc. Natl. Acad. Sci. USA 86: 5257-5261 (1989)), (2) rat brain PTPase (Guan et al., Proc. Natl. Acad. Sci. USA 87:1501-1502 (1990)), (3) neuronal MISSING AT THE TIME OF PUBLICATION several different members of the receptor-type PTPase group. Thus, 5 different PTPases, (3) PTPα, (4) PTPβ, (5) PTPδ, (6) PTPε, and (7) PTPζ, were identified in one early study (Krueger et al., EMBO J. 9: 3241-3252 (1990)). Other examples of receptor-type PTPases include (8) PTPγ (Barnea et al., Mol. Cell. Biol. 13: 1497-1506 (1995)) which, like PTPζ (Krueger and Saito, Proc. Natl. Acad. Sci. USA 89: 7417- 7421 (1992)) contains a carbonic anhydrase-like domain in the extracellular region, (9) PTPμ (Gebbink et al., FEBS Letters 290: 123- 130 (1991)), (10) PTPK (Jiang et al., Mol. Cell. Biol. 13: 2942-2951 (1993)). Based on structural differences the receptor-type PTPases may be classified into subtypes (Fischer et al., Science 253: 401-406 (1991)): (I) CD45; (II) LAR, PTPd, (11) PTPσ ; (III) PTPβ, (12) SAP-1 (Matozaki et al., J. Biol. Chem. 269: 2075-2081 (1994)), (13) PTP- U2/GLEPP1 (Seimiya et al., Oncogene 10: 1731-1738 (1995); Thomas et al., J. Biol. Chem. 269: 19953-19962 (1994)), and (14) DEP-1 ; (IV) PTPα,_PTPε. All receptor-type PTPases except Type III contain two PTPase domains. Novel PTPases are frequently identified, and it is anticipated that between 100 and more than 500 different species will be found in the human genome. PTPases are the biological counterparts to protein tyrosine kinases (PTKs). Therefore, one important function of PTPases is to control, and especially down-regulate, the activity of PTKs. However, a more complex picture of the function of PTPases has emerged. Thus, several studies indicate that some PTPases act as positive mediators of cellular signaling. As an example, the SH2 domain-containing SHP-2 acts as a positive mediator in insulin-stimulated Ras activation (Noguchi et al., Mol. Cell. Biol. 14: 6674-6682 (1994)) and of growth factor- induced mitogenic signal transduction (Xiao et al., J. Biol. Chem. 269: 21244-21248 (1994)), whereas the homologous SHP-1 acts as a negative regulator of growth factor-stimulated proliferation (Bignon and Siminovitch, Clin.lmmunol. Immunopathol. 73: 168-179 (1994)). Another example of PTPases as positive regulators has been provided by studies designed to define the activation of the Src-family of tyrosine kinases. In particular, several lines of evidence indicate that CD45 is positively regulating the activation of hematopoietic cells, and that the mechanism of such positive regulation may involve dephosphorylation of the C-terminal tyrosine of Fyn and Lck (Chan et al., Annu. Rev. Immunol. 12: 555-592 (1994)). The association of many PTPases with cell proliferation, tranformation and differentiation has now been established. PTP1 B, a phosphatase whose structure was the first PTPase to be elucidated (Barford et al., Science 263:1397-1404 (1994)) has been shown to be involved in insulin-induced oocyte maturation (Flint et al., The EMBO J. 12:1937-46 (1993)) and the overexpression of this enzyme has been c-erb B2 implicated in p185 -associated breast and ovarian cancers (Weiner, et al., J. Natl. cancer Inst. 86:372-8 (1994); Weiner et al., Am. J. Obstet. Gynecol. 170:1177-883 (1994)). The association with cancer is on the basis of evidence that overexpression of PTP1 B is statistically correlated with increased levels of p185 c"er B2 in ovarian and breast cancer. The role of PTP1 B in the etiology and progression of the disease has not yet been elucidated. Inhibitors of PTP1 B therefore would help clarify the role of PTP1B in cancer and in some cases provide therapeutic treatment for certain forms of cancer. PTPases: the insulin receptor signaling pathway/diabetes Insulin is an important regulator of different metabolic processes and plays a key role in the control of blood glucose. Defects related to its synthesis or signaling lead to diabetes mellitus. Binding of insulin to the insulin receptor (IR) causes rapid (auto)phosphorylation of several tyrosine residues in the intracellular part of the β-subunit. Three closely positioned tyrosine residues (the tyrosine-1150 domain) must all be phosphorylated to obtain full activity of the insulin receptor tyrosine kinase (IRTK) which transmits the signal further downstream by tyrosine phosphorylation of other cellular substrates, including insulin receptor substrate- 1 (IRS-1) (Wilden et al., J. Biol. Chem. 267: 16660- 16668 (1992); Myers and White, Diabetes 42: 643-650 (1993); Lee and Pilch, Am. J. Physiol. 266: C319-C334 (1994); White et al., J. Biol. Chem. 263: 2969-2980 (1988)). The structural basis for the function of the tyrosine-triplet has been provided by X-ray crystallographic studies of IRTK that showed the tyrosine-1150 domain to be autoinhibitory in its unphosphorylated state (Hubbard er al., Nature 372: 746-754 (1994)) and of the activated IRTK (Hubbard, EMBO J. 16: 5572-5581 (1997)). Several studies clearly indicate that the activity of the auto- phosphorylated IRTK can be reversed by dephosphorylation in vitro (reviewed in Goldstein, Receptor 3: 1-15 (1993); Mooney and Anderson, J. Biol. Chem. 264: 6850-6857 (1989)), with the tri- phosphorylated tyrosine-1150 domain being the most sensitive target for protein-tyrosine phosphatases (PTPases) as compared to the di- and mono- phosphorylated forms (King et al., Biochem. J. 275: 413-418 (1991)). This tyrosine-triplet functions as a control switch of IRTK activity and IRTK appears to be tightly regulated by PTP-mediated dephosphorylation in vivo (Khan et al., J. Biol. Chem. 264: 12931- 12940 (1989); Faure et al., J. Biol. Chem. 267: 11215-11221 (1992); Rothenberg etal., J. Biol. Chem. 266: 8302-8311 (1991)). The intimate coupling of PTPases to the insulin signaling pathway is further evidenced by the finding that insulin differentially regulates PTPase activity in rat hepatoma cells (Meyerovitch etal., Biochemistry 31: 10338-10344 (1992)) and in livers from alloxan diabetic rats (Boylan et al., J. Clin. Invest. 90: 174-179 (1992)). Until recently, relatively little was known about the identity of the PTPases involved in IRTK regulation. However, the existence of PTPases with activity towards the insulin receptor can be demonstrated as indicated above. Further, when the strong PTPase-inhibitor pervanadate is added to whole cells an almost full insulin response can be obtained in adipocytes (Fantus etal., Biochemistry 28: 8864-8871 (1989); Eriksson et al., Diabetologia 39: 235-242 (1995)) and skeletal muscle (Leighton etal., Biochem. J. 276: 289-292 (1991)). In addition, other studies show that a new class of peroxovanadium compounds act as potent hypoglycemic compounds in vivo (Posner et al., supra). Two of these compounds were demonstrated to be more potent inhibitors of dephosphorylation of the insulin receptor than of the EGF-receptor, thus indicating that even such relatively unselective inhibitors may show some specificity in regulating different signal transduction pathways. It was recently found that mice lacking the protein tyrosine phosphatase-1B gene (PTP1 B) (Elchebly et al., Science 283: 1544- 1548 (1999)) yielded healthy mice thatshowed increased insulin sensitivity and were resistant to diet-induced obesity. These results were confirmed by Kaman at al Mol. Cell Biol. 20:5479-5489 (2000)The enhanced insulin sensitivity of the PTP " _ mice was also evident in glucose and insulin tolerance tests. The PTP-1 B knock-out mouse showed many characteristics which would be highly desirable results for an anti-diabetes treatment. Most importantly, the knock-out mice grew normally and were fertile and have exhibited no increased incidence of cancer. Blood glucose and insulin levels were lowered, and insulin sensitivity increased. Moreover, the insulin-stimulated tyrosine phosphorylation levels of IR and IRS-1 were found to be increased/prolonged in muscle and liver - but not in fat tissue. Thus, the main target tissues for this type of approach would appear to be insulin action in liver and muscle. Several other "diabetic" parameters were also improved, including plasma triglycerides which were decreased in the knock-out mice. The knock-animals also exhibited a resistance to weight gain when placed on a high-fat diet. This is in contrast to the action of the PPARγ agonist class of insulin sensitizers, which rather induce weight gain (Murphy & Nolan, Exp. Opin. Invest. Drugs 9:1347-1361 , 2000), and would suggest that inhibition of PTP-1 B could be a particularly attractive option for treatment of obese Type II diabetics. This is also supported by the fact that the heterozygous mice from this study showed many of these desirable features. The reduction in weight gain of the knock-out animals on the high fat diet was found to be due to a decreased fat cell mass, although differences were observed with respect to fat cell number. Leptin levels were also lower in the knock-out mice, presumably as a reflection of the decreased fat mass. Significantly, the Klaman et al group also found that the knock-out animals had an increased energy expenditure of around 20% and an increased respiratory quotient compared to the wild-type; again, heterozygote animals displayed an intermediate level of energy expenditure. Therefore, inhibition of this enzyme may be an effective anti-diabetic and perhaps also anti-obesity therapy . It should also be noted that in the PTP-1 B knock-out mice the basal tyrosine phosphorylation level of the insulin receptor tyrosine kinase does not appear to be increased, which is in contrast to the situation after insulin treatment where there is an increased or prolonged phosphorylation. This might indicate that other PTPs are controlling the basic phosphorylation state of the insulin receptor in the knock-out mice - and is expected to do so in man. Also other PTPases have been implicated as regulators of the insulin signaling pathway. Thus, it was found that the ubiquitously expressed SH2 domain containing PTPase, PTP1 D/SHP-2 (Vogel et al., 1993, supra), associates with and dephosphorylates IRS-1, but apparently not the IR itself (Kuhne et al., J. Biol. Chem. 268: 11479- 11481 (1993); (Kuhne etal., J. Biol. Chem. 269: 15833-15837 (1994)). Other studies suggest that receptor-type or membrane- associated PTPases are involved in IRTK regulation (Faure et al., J. Biol. Chem. 267: 11215-11221 (1992), (Haring et al., Biochemistry 23: 3298-3306 (1984); Sale, Adv. Prot. Phosphatases 6: 159-186 (1991)). While previous reports indicate a role of PTP in signal transduction through src activation (Zheng etal., Nature 359: 336-339 (1992); den Hertog et al., EMBO J. 12: 3789-3798 (1993)) and interaction with GRB-2 (den Hertog et al., EMBO J. 13: 3020-3032 (1994); Su etal., J. Biol. Chem. 269: 18731-18734 (1994)), Møller, Lammers and coworkers provided results that suggest a function for this phosphatase and its close relative PTPε as negative regulators of the insulin receptor signal (Møller et al., 1995 supra; Lammers, et al. , FEBS Lett. 404:37-40 (1997). These studies also indicated that receptor-like PTPases may play a significant role in regulating the IRTK, including through direct influence on the insulin receptor itself. Other studies have shown that PTP1 B and TC-PTP are likely to be involved in the regulation of several other cellular processes in addition to the described regulatory roles in insulin signaling. Therefore, PTP1 B and/or TC-PTP as well as other PTPases showing key structural features with PTP1 B and TC-PTP are likely to be important therapeutic targets in a variety of human and animal diseases. The compounds of the present invention are useful for modulating or inhibiting PTP1 B and/or TC-PTP and/or other PTPases showing key structural features with said PTPases and thus elucidating their function and for treating disease states in which said modulation or inhibition is indicated. Further, PTPases influence the following hormones or diseases or disease states: somatostatin, the immune system/autoimmunity, cell- cell interactions/cancer, platelet aggregation, osteoporosis, and microorganisms, as disclosed in PCT Publication WO 99/15529. PTPases: the immune system/autoimmunity Several studies suggest that the receptor-type PTPase CD45 plays a critical role not only for initiation of T cell activation, but also for maintaining the T cell receptor-mediated signaling cascade. These studies are reviewed in: (Weiss A., Ann. Rev. Genet. 25: 487-510 (1991); Chan et al., Annu. Rev. Immunol. 12: 555-592 (1994); Trowbridge and Thomas, Annu. Rev. Immunol. 12: 85-116 (1994)). CD45 is one of the most abundant of the cell surface glycoproteins and is expressed exclusively on hemopoetic cells. In T cells, it has been shown that CD45 is one of the critical components of the signal transduction machinery of lymphocytes. In particular, there is evidence that CD45 phosphatase plays a pivotal role in antigen-stimulated proliferation of T lymphocytes after an antigen has bound to the T cell receptor (Trowbridge, Ann. Rev. Immunol, 12: 85-116 (1994)). Several studies indicate that the PTPase activity of CD45 plays a role in the activation of Lck, a lymphocyte-specific member of the Src family protein- tyrosine kinase (Mustelin etal., Proc. Natl. Acad. Sci. USA 86: 6302-6306 (1989); Ostergaard et al., Proc. Natl. Acad. Sci. USA 86: 8959-8963 (1989)). Studies using transgenic mice with a mutation for the CD45- exon6 exhibited a lack of mature T cells. These mice did not respond to an antigenic challenge with the typical T cell mediated response (Kishihara et al., Cell 74:143-56 (1993)). Inhibitors of CD45 phosphatase would therefore be very effective therapeutic agents in conditions that are associated with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. Another important function of CD45 phosphatase inhibitors is in effecting immunosuppression, where such a result is indicated, e.g., in transplantation and other conditions in need of immunosuppressive treatment. CD45 has also been shown to be essential for the antibody mediated degranulation of mast cells (Berger er al., J. Exp. Med. 180:471- 6 (1994)). These studies were also done with mice that were CD45- deficient. In this case, an IgE-mediated degranulation was demonstrated in wild type but not CD45-deficient T cells from mice. These data suggest that CD45 inhibitors could also play a role in the symptomatic or therapeutic treatment of allergic disorders, such as asthma, allergic rhinitis, food allergies, eczema, urticaria and anaphylaxis. Another PTPase, an inducible lymphoid-specific protein tyrosine phosphatase (HePTP) has also been implicated in the immune response. This phosphatase is expressed in both resting T and B lymphocytes, but not non-hemopoetic cells. Upon stimulation of these cells, mRNA levels from the HePTP gene increase 10-15 fold (Zanke et al., Eur. J. Immunol. 22: 235-239 (1992)). Likewise, the hematopoietic cell specific SHP-1 acts as a negative regulator and thus appears to play an essential role in immune cell development.ln accordance with the above-mentioned important function of CD45, HePTP and SHP-1, selective PTPase inhibitors are early development candidates or prototype drugs both as immunosuppressors and as immunostimulants. Recent studies illustrate the potential of PTPase inhibitors as immunmodulators by demonstrating the capacity of the vanadium-based relatively nonselective PTPase inhibitor, BMLOV, to induce apparent B cell selective apoptosis compared to T cells (Schieven et al., J. Biol. Chem. 270: 20824-20831 (1995)). PTPases: cell-cell interactions/cancer Focal adhesion plaques, an in vitro phenomenon in which specific contact points are formed when fibroblasts grow on appropriate substrates, mimic, in certain respects, cells and their natural surroundings. Several focal adhesion proteins are phosphorylated on tyrosine residues when fibroblasts adhere to and spread on extracellular matrix (Gumbiner, Neuron 11: 551-564 (1993)). However, aberrant tyrosine phosphorylation of these proteins can lead to cellular transformation. The intimate association between PTPases and focal adhesions is supported by the finding of several intracellular PTPases with ezrin-like N-terminal domains, e.g. PTPMEG1 (Gu et al., Proc. Natl. Acad. Sci. USA 88: 5867-5871 (1991), PTPH1 (Yang and Tonks, Proc. Natl. Acad. Sci. USA 88: 5949-5953 (1991)) and PTPD1 (Møller et al., Proc. Natl. Acad. Sci. USA 91: 7477-7481 (1994)). The ezrin-like domains show similarity to several proteins that are believed to act as links between the cell membrane and the cytoskeleton. PTPD1 was found to be phosphorylated by and associated with c-src in vitro and is hypothesized to be involved in the regulation of phosphorylation of focal adhesions (Møller etal., supra). PTPases may oppose the action of tyrosine kinases, including those responsible for phosphorylation of focal adhesion proteins, and may therefore function as natural inhibitors of transformation. TC-PTP, and especially the truncated form of this enzyme (Cool et al., Proc. Natl. Acad. Sci. USA 87: 7280-7284 (1990)), can inhibit the transforming activity of w-erb and v-fms (Lammers et al., J. Biol. Chem. 268: 22456- 22462 (1993), Zander et al., Oncogene 8: 1175-1182 (1993)). Moreover, it was found that transformation by the oncogenic form of the HER2/neu gene was suppressed in NIH 3T3 fribroblasts overexpressing PTP1 B (Brown-Shimer et al., Cancer Res. 52: 478-482 (1992)). The expression level of PTP1 B was found to be increased in a mammary cell line transformed with neu (Zhay et al., Cancer Res. 53: 2272-2278 (1993)). The intimate relationship between tyrosine kinases and PTPases in the development of cancer is further evidenced by the recent finding that PTPe is highly expressed in murine mammary tumors in transgenic mice over-expressing c-neu and v-Ha-ras, but not c-myc or int-2 (Elson and Leder, J. Biol. Chem. 270: 26116-26122 (1995)). Further, the human gene encoding PTPγ was mapped to 3p21 , a chromosomal region which is frequently deleted in renal and lung carcinomas (LaForgia et al., Proc. Natl. Acad. Sci. USA 88: 5036-5040 (1991)). PTPases appear to be involved in controlling the growth of fibroblasts. In a recent study it was found that Swiss 3T3 cells harvested at high density contain a membrane-associated PTPase whose activity on an average is 8-fold higher than that of cells harvested at low or medium density (Pallen and Tong, Proc. Natl. Acad. Sci. USA 88: 6996-7000 (1991)). Two closely related receptor-type PTPases, PTPK and PTPμ, can mediate homophilic cell-cell interaction when expressed in non- adherent insect cells, suggesting that a normal physiological function for these PTPases in cell-to-cell signalling (Gebbink et al., J. Biol. Chem. 268: 16101-16104 (1993), Brady-Kalnay et al., J. Cell Biol. 122: 961-972 (1993); Sap et al., Mol. Cell. Biol. 14: 1-9 (1994)). Interestingly, PTPK and PTPμ do not bind to each other (PTPK does self-associate), despite their structural similarity (Zondag et al., J. Biol. Chem. 270: 14247-14250 (1995)). From the studies described above it is apparent that PTPases play an important role in regulating normal cell growth. Additionally, as pointed out above, PTPases may also function as positive mediators of intracellular signaling and thereby induce or enhance mitogenic responses. Increased activity of certain PTPases might therefore result in cellular transformation and tumor formation. See, Zheng, supra; Uchida et al., J. Biol. Chem. 269: 12220-12228 (1994 Hunter, Cell 80: 225-236 (1995). Inhibitors of specific PTPases are therefore likely to be of significant therapeutic value in the treatment of certain forms of cancer. PTPases: platelet aggregation PTPases are centrally involved in platelet aggregation. Thus, agonist-induced platelet activation results in calpain-catalyzed cleavage of PTP1 B with a concomitant 2-fold stimulation of PTPase activity (Frangioni et al., EMBO J. 12: 4843-4856 (1993)). The cleavage of PTP1B leads to subcellular relocation of the enzyme and correlates with the transition from reversible to irreversible platelet aggregation in platelet-rich plasma. In addition, the SH2 domain containing PTPase, SHP-1 , was found to translocate to the cytoskeleton in platelets after thrombin stimulation in an aggregation-dependent manner (Li et al., FEBS Lett. 343: 89-93 (1994)). Although some details in the above two studies have been questioned, there is overall agreement that PTP1B and SHP-1 play significant functional roles in platelet aggregation (Ezumi et al., J. Biol. Chem. 270: 11927-11934 (1995)). In accordance with these observations, treatment of platelets with the PTPase inhibitor pervanadate leads to significant increase in tyrosine phosphorylation, secretion and aggregation (Pumiglia et al., Biochem. J. 286: 441-449 (1992)). PTPases: osteoporosis The rate of bone formation is determined by the number and the activity of osteoblasts. In turn, these aredetermined by the rate of proliferation and differentiation of osteoblast progenitor cells, respectively. Histomorphometric studies indicate that the osteoblast number is the primary determinant of the rate of bone formation in humans (Gruber et al., Mineral Electrolyte Metab. 12: 246-254 (1987), reviewed in Lau et al., Biochem. J. 257: 23-36 (1989)). Acid phosphatases/PTPases are implicated in negative regulation of osteoblast proliferation. Thus, fluoride, which has phosphatase inhibitory activity, has been found to increase spinal bone density in osteoporotics by increasing osteoblast proliferation (Lau er al., supra). Consistent with this observation, an osteoblastic acid phosphatase with PTPase activity was found to be highly sensitive to mitogenic concentrations of fluoride (Lau et al., J. Biol. Chem. 260: 4653-4660 (1985), Lau et al., J. Biol. Chem. 262: 1389-1397 (1987), Lau et al., Adv. Protein Phosphatases 4: 165-198 (1987)). The mitogenic action of fluoride and other phosphatase inhibitors (molybdate and vanadate) may thus be explained by their inhibition of acid phosphatases/PTPases that negatively regulate the cell proliferation of osteoblasts. The complex nature of the involvement of PTPases in bone formation is further suggested by the recent identification of a novel parathyroid regulated, receptor-like PTPase, OST-PTP, expressed in bone and testis (Mauro et al., J. Biol. Chem. 269: 30659- 30667 (1994)). OST-PTP is up-regulated following differentiation and matrix formation of primary osteoblasts and subsequently down- regulated in the osteoblasts which are actively mineralizing bone in culture. In addition, it was recently observed that vanadate, vanadyl and pervanadate all increased the growth of the osteoblast-like cell line UMR106. Vanadyl and pervanadate were stronger stimulators of cell growth than vanadate. Only vanadate was able to regulate the cell differentiation as measured by cell alkaline phosphatase activity (Cortizo etal., Mol. Cell. Biochem. 145: 97-102 (1995)). More important, several studies have shown that biphosphonates, such as alendronate and tiludronate, inhibit PTPase activity in osteoclasts and that the inhibition of PTPase activity correlated with the inhibition of in vitro osteoclast formation and bone resorption.(Scmidt, et al., Proc. Natl Acad. Sci. U.S.A. 93: 3068-3073,1996; Murakami et al., Bone 20:399- 404, 1997; Opas et al., Biochem. Pharmacol. 54: 721-727, 1997; Skorey et al., J. Biol. Chem. 272: 22472-22480, 1997. Thus, other PTPase inhibitors are potentially effective in countering osteoclast activity, and thus treating osteoporosis. PTPases: microorganisms Dixon and coworkers have called attention to the fact that PTPases may be a key element in the pathogenic properties of Yersinia (reviewed in Clemens et al. Molecular Microbiology 5: 2617-2620 (1991)). This finding was rather surprising since tyrosine phosphate is thought to be absent in bacteria. The genus Yersinia comprises 3 species: Y. pestis (responsible for the bubonic plague), Y. pseudoturberculosis and Y. enterocolitica (causing enteritis and mesenteric lymphadenitis). A dual-specificity phosphatase, VH1 , has been identified in Vaccinia virus (Guan et al., Nature 350: 359-263 (1991)). These observations indicate that PTPases may play critical roles in microbial and parasitic infections, and they further point to PTPase inhibitors as a novel, putative treatment principle of infectious diseases. Availibility of PTPase inhibitors would help shed light in all the foregoing specualations about PTPase function because they would enable assaying techniques which would answer some of these questions as will be illustrated below. Summary of Background It has been found that PTPases play a major role in the above modulation and regulation of fundamental cellular signaling mechanisms involved in metabolism, growth, proliferation and differentiation (Fisher et al, Science 253:401-6 (1991); Tonks and Neel, Ce// 87: 365-368 (1966)" Neel and Tonks, Current Opinion in Cell Biology 9: 193-204 (1997); Hunter, Phil. Trans. R. Soc. Lond. B 353: 583-605 (1998); Hunter, Cell 100: 113-120 (2000); Zhang, Critical Reviews in Biochemistry and Molecular Biology 33 :1 -52 (1988)). Reports from many laboratories have shown that PTPases can act both as positive and negative regulators of signal transduction processes. PTPases have been implicated in a variety of human diseases, including diabetes, obesity, autoimmune diseases, acute and chronic inflammation, osteoporosis, proliferative disorders including various forms of cancer, growth disorders, and defective platelet aggregation (WO97/39748, WO97/40017, WO99/1529, WO97/08934, WO98/27065, WO99/46236, WO99/46244, WO99/46267, WO99/46268, WO99/46237). Accordingly there is increasing evidence which suggests that inhibition of these PTPases would help treat or manage these diseases (Hunter, vide supra; Neel and Tonks, vide supra: Frangione et al., EMBO J. 12:4843-4856 (1993); Zhang, Curr. Top. Cell. Reg. 35. 21-68 (1997): Zhang, vide supra; Evans and Jalian, Exp. Opinion. Invest. Drugs 8: 139-160 (1999); Burke and Zhang, Bioploymers (Peptide Science) 47: 225-241 (1998): Elchebly et al.; Science 283: 1544-1548 (1999); Wrobel et al., J. Med. Chem. 42: 3199-3202 (1999)). In addition, certain infectious diseases may also be treated or managed by administration PTPase inhibitors (Clemens et al., Molecular Microbiology 5: 2617-2620 (1991)). Both selective PTPase inhibitors and inhibitors that bind to several PTPases (non-selective inhibitors) can be used therapeutically to partially or completely restore PTPase-mediated perturbed signal transduction processes and thus for management, treatment, palliation or prevention of the above diseases. Description of Drawings Figure 1. Active site of Protein Tyrosine Phosphatase 1 B complexed with with 2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid. Figure 2. Active site of Protein Tyrosine Phosphatase 1 B complexed with 7-(5-methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid (Example 26). Figure 3. Active site of Protein Tyrosine Phosphatase 1 B complexed with 5-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid (Example 4). Figure 4. Active site of Protein Tyrosine Phosphatase 1 B complexed with 2-(oxalyl-amino)-7-(1 ,1,3-thoxo-1 H-benzo[d]isothiazol-3- yloxomethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid (Example 54). Selected water molecules are shown. Description of the Invention The present invention provides a method for inhibiting protein tyrosine phosphatase 1 B (PTP1 B) and/or T-cell protein tyrosine phosphatase (T- cell PTP/TC-PTP) and/or protein tyrosine phosphatases (PTPases) having an aspartic acid (Asp) in position 48 by exposing said PTPase to a compound having physico-chemical and spatial structural characteristics that interfere with the active site and/or vicinity of the active site of said PTPase thereby inhibiting its enzymatic activity. Specifically, the present inhibitors of PTP1 B and/or TC-PTP and/or PTPases having an aspartic acid (Asp) in position 48 interact with two or more residues of the following: arginine 221 , glycine 220, lysine 120, tyrosine 46, and phenylalanine/histidine 182 and one or more of the following (residue numbering correspondingto PTP1 B will be used through out (Chernoff etal., Proc. Natl. Acad. Sci. USA 87: 2735-2789 (1989)): 1. Isoleucine 219 backbone amide nitrogen; 2. Glycine 218 backbone amide nitrogen; 3. Alanine 217 backbone amide nitrogen ; 4. Serine 216 backbone amide nitrogen; 5. Cysteine 215 backbone amide nitrogen; 6. The side chain carboxylic acid group of aspartic acid 181 ; 7. The side chain carboxylic acid group of aspartic acid 48; 8. The side chain guanidinium group of arginine 47; 9. Arginine 47 backbone amide nitrogen; 10. Aspartic acid 48 backbone amide nitrogen; 11. The side chain hydroxy group of tyrosine 46; 12. The side chain amino group of lysine 41 ; 13. The methylene side chain atoms of lysine 41 ; 14. The backbone amide carbonyl of asparagine 44; 15. The methylene side chain atoms of arginine 45; 16. The backbone amide carbonyl of arginine 45; 17. The methylene side chain atoms of arginine 47; 18. The methylene side chain atom of aspartic acid 48; 19. The backbone amide carbonyl of aspartic acid 48; 20. The methylene side chain atoms of leucine 88; 21. The side chain hydroxy group of serine 118; 22. The backbone amide carbonyl of leucine 119; 23. The side chain amide nitrogen of glutamine 262; 24. The side chain atoms of methionine 258; 25. The aromatic group of phenylalanine 52; 26. The backbone amide nitrogen of glycine 259; 27. The alpha-methylene atom of glycine 259; 28. The guanidinium group of arginine 254; 29. The methylene side chain atoms of arginine 254; 30. The methylene side chain atoms of arginine 24; 31. The guanidinium group of arginine 24; or 32. Any conserved water molecule in the vicinity of the active site. Preferably, the present inhibitors of PTP1 B and/or TC-PTP and/or PTPases having an aspartic acid (Asp) in position 48 interact with any three or more of the above identified regions of the active site and its vicinity. In one preference, the inhibitors of PTP1B and/or TC-PTP and/or PTPases having an aspartic acid (Asp) in position 48 interact with arginine 221 , glycine 220, lysine 120, tyrosine 46, phenylalanine/histidine 182, aspartic acid 48 and one or more of the following 1. Isoleucine 219 backbone amide nitrogen; 2. Glycine 218 backbone amide nitrogen; 3. Alanine 217 backbone amide nitrogen; 4. Serine 216 backbone amide nitrogen; 5. The side chain carboxylic acid group of aspartic acid 181 ; 6. The side chain guanidinium group of arginine 47; 7. Arginine 47 backbone amide nitrogen; 8. Aspartic acid 48 backbone amide nitrogen; 9. The side chain hydroxy group of tyrosine 46; 10. The side chain amino group of lysine 41 ; 11. The methylene side chain atoms of lysine 41 ; 12. The backbone amide carbonyl of asparagine 44; 13. The methylene side chain atoms of arginine 45; 14. The backbone amide carbonyl of arginine 45; 15. The methylene side chain atoms of arginine 47; 16. The methylene side chain atom of aspartic acid 48; 17. The backbone amide carbonyl of aspartic acid 48; 18. The methylene side chain atoms of leucine 88; 19. The side chain hydroxy group of serine 118; 20. The backbone amide carbonyl of leucine 119; 21. The side chain amide nitrogen of glutamine 262; 22. The side chain atoms of methionine 258; 23. The aromatic group of phenylalanine 52; 24. The backbone amide nitrogen of glycine 259; 25. The alpha-methylene atom of glycine 259; 26. The guanidinium group of arginine 254; 27. The methylene side chain atoms of arginine 254; 28. The methylene side chain atoms of arginine 24; 29. The guanidinium group of arginine 24; or 30. Any conserved water molecule in the vicinity of the active site. Preferred key structural features of the inhibitors of the present invention include a phosphate isostere (P), a carboxylic acid perferably or a carboxylic acid or ortho-carboxylic acid or o-c acid isostere (B) and a hydrophobic group (A) as shown in Scheme 1. Scheme 1. ortho-carboxylic acid or Hydrophobic group In a preferred embodiment, the key structural features of the inhibitors of the present invention include a phosphate isostere (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B) and a hydrophobic group (A), preferably a phenyl, naphthyl or thiophenyl as shown in Scheme 1. In another preferred embodiment the key structural features of the inhibitors of the present invention include an oxalylamide (-NHCOCOOH) (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B) and a hydrophobic group (A). In another preferred embodiment the key structural features of the inhibitors of the present invention include an oxalylamide (-NHCOCOOH) (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B) and a hydrophobic group (A), preferably a phenyl, naphthyl or thiophenyl as shown in Scheme 1. In another preferred embodiment the key structural features of the inhibitors of the present invention include a phosphate isostere (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), a hydrophobic group (A) and a basic nitrogen (N) as shown in Scheme 2. Scheme 2. basic nitrogen Hydrophobic group In another preferred embodiment, the key structural features of the inhibitors of the present invention include an oxalylamide (-NHCOCOOH) (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), a hydrophobic group (A) and a basic nitrogen (N) as shown in Scheme 2. In another preferred embodiment, the key structural features of the inhibitors of the present invention include an oxalylamide (-NHCOCOOH) (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), a hydrophobic group (A), preferably a phenyl, naphthyl or thiophenyl and a basic nitrogen (N). In another preferred embodiment, the key structural features of the inhibitors of the present invention include a basic nitrogen which provides selectivity for PTPases containing an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - a phosphate isostere (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), a hydrophobic group (A) as shown in Scheme 3. Scheme 3. Aspartic acid 48 In another preferred embodiment, the key structural features of the inhibitors of the present invention include a basic nitrogen which provides selectivity for PTPases containing an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - an oxalylamide (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), a hydrophobic group (A) as shown in Scheme 3. In another preferred embodiment, the key structural features of the inhibitors of the present invention include a basic nitrogen which provides selectivity for PTPases containing an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - an oxalylamide (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), and a hydrophobic group (A), preferably a phenyl, naphthyl or thiophenyl as shown in Scheme 3. Scheme 4. Aspartic acid 48 In another preferred embodiment, the key structural features of the inhibitors of the present invention include a basic nitrogen which provides selectivity for PTPases containing an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - a phosphate isostere (P), an ortho-carboxylic acid or ortho-carboxylic acid isostere (B), an aromatic group (A), preferably a phenyl or thiophenyl and a hydrophobic group (H) as shown in Scheme 4. In another preferred embodiment, the key structural features of the inhibitors of the present invention include a basic nitrogen which provides selectivity for PTPases containing an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - an oxalylamide (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), an aromatic group (A), preferably a phenyl or thiophenyl and a hydrophobic group (H) as shown in Scheme 4. In another preferred embodiment, the key structural features of the inhibitors of the present invention include a phosphate isostere (P), an ortho-carboxylic acid or an ortho-carboxylic acid isostere (B), an aromatic group (A), preferably a phenyl or thiophenyl and a hydrophobic group (H) which include a basic nitrogen which provides selectivity for PTPases that contain an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - as shown in Scheme 5. Scheme 5. Aspartic acid 48 In another preferred embodiment, the key structural features of the inhibitors of the present invention include an oxalylamide (P), an ortho- carboxylic acid or an ortho-carboxylic acid isostere (B), an aromatic group (A), preferably a phenyl or thiophenyl and a hydrophobic group (H) which include a basic which provides selectivity for PTPases that contain an aspartic acid in position 48 - via formation of a salt bridge to said aspartic acid 48 and repulsion to PTPases that contain the corresponding asparagine in position 48 - as shown in Scheme 5. The key structural features of the inhibitors of the present invention described above are linked to each other via covalent bonds. The compounds of the present invention possess, but are not limited to, a phosphate isostere in which the centroid of the phosphate isostere is 5.0- 5.5 A from the centroid of a carboxylic acid or carboxylic acid isostere, and 4.5-5.1 A from the centroid of an aromatic group or a hydrophobic group. In a preferred embodiment, the compounds of the present invention possess, but are not limited to, an oxalylamide in which the centroid of the carboxylic acid moiety of said oxalylamide is 5.0-5.5 A from the centroid of a carboxylic acid or carboxylic acid isostere, and 4.5-5.1 A from the centroid of an aromatic group or a hydrophobic group. In an other preferred embodiment the compounds of the present invention possess, but are not limited to, a phosphate isostere in which the centroid of the phosphate isostere is 5.0-5.5 A from the centroid of a carboxylic acid or carboxylic acid isostere, 4.5-5.1 A from the centroid of an aromatic group or a hydrophobic group and 8.0-14.0 A from a basic nitrogen. These features must participate in the appropriate interactions (e.g. hydrogen bonds, salt bridges, hydrophobic interactions, cation-π interactions, or π, π interactions, or aromatic-aromatic interactions) with the PTP1 B and/or TC-PTP and/or other PTPases that are structurally similar to PTP1 B active site and vicinity e.g. having an aspartic acid (Asp) in position 48. The centroid of the phosphate isostere should be 3.50-4.20 A from the centroid of the side chain guanidinium group of arginine 221. The centroid of the carboxylic acid or carboxylic acid isostere should be 3.4-4.1 A from the side chain amino group of lysine 120. The basic nitrogen should be 3.4-4.1 A from the centroid of aspartic acid 48. The aromatic or, more generally, hydrophobic group should be near the following amino acid side chain atoms with appropriate distance ranges between the centroid of the side chain atoms and the centroid of the aromatic - or hydrophobic group given in parentheses: tyrosine 46 (4.4-5.1 A) and phenylalanine/histidine 182 (4.4-6.5 A). The centroid of the oxalylamide carboxylic acid moiety should be 3.50- 4.20 A from the centroid of the side chain guanidinium group of arginine 221. The centroid of the carboxylic acid or carboxylic acid isostere should be 3.4-4.1 A from the side chain amino group of lysine 120. The basic nitrogen should be 3.4-4.1 A from the centroid of aspartic acid 48. The aromatic - or hydrophobic group should be near the following amino acid side chain atoms with appropriate distance ranges between the centroid of the side chain atoms and the centroid of the aromatic - or hydrophobic group given in parentheses: tyrosine 46 (4.4-5.1 A) and phenylalanine/histidine 182 (4.4-6.5 A). In a specific embodiment, the invention is directed to a method of inhibiting at least one intracellular or membrane-associated PTPase that has aspartic acid (Asp) in position 48 using the numbering for PTP1B, the method comprising exposing the PTPase to an inhibitor compound which fits spatially into the active site and the vicinity thereof, said compound comprising the following features and moieties: I. (a) a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and a hydrogen bond with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; or (b) an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 wherein the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said Lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of features IV through V: IV. a hydrophobic group that interactswith the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and one or more of the following features VI-XXXVII: VI. an amino group which forms a salt bridge to the site chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said site chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; and VII. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond or forms a salt bridge with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 is 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 is 2 ranges from.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that interacts with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7- 4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that reaches a proximity interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7-4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7-4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX. a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7- 4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV. a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV. a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and (i) the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, (ii) the centroid of said glycine 259 ranges from 4.7-7.7 A, and (iii) the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9 1 A; In another embodiment, the invention provides a method of inhibiting at least one PTPase selected from the group consisting of PTP1B, TC-PTP andother PTPase that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity therof , said compound comprising the following features and moieties: I. (a) a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50- 4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5- 4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7- 3.5 A; or (b) an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5- 4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or acid isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and one or more of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and/or V. . a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and one or more of the following featuresVI through XXXVII: VI. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; and VII. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a salt bridge with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7- 4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7-4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 1 19 ranges from 2.7-4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX. a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7- 4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV. a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV. a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 ranges from 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; In yet another embodiment, the invention provides a method of inhibiting a PTPase selected from the group consisting of PTP1 B, TC-PTP and other PTPases that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising the following features and moieties: I. (a) a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50- 4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5- 4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7- 3.5 A; or (b) an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5- 4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said Lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at lest one of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 3.55.1 A; and/or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 is 4.4-6.5 A; and one or more of the following features VI-XXXVII VI. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; VII. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 is 3.4-4.1 A; VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7- 4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7-4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7-4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX. a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7- 4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV. a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV. a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 is 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; Further provided is a method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1 B (PTP1 B) and/or T-Cell Protein Tyrosine Phosphatase which (TC-PTP) and/or other PTPases that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof , said compound comprising: I. (a) a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; or (b) an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) acarboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A. In another specific embodiment, the invention provides a method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1B (PTP1B), T-Cell Protein Tyrosine Phosphatase (TC-PTP) and other PTPases that are structurally similar to PTP1 B which comprises exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising: I. a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50- 4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5- 4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7- 3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; wherein the distance between the centroid of the phosphate isostere and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said amino group ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said amino group ranges from 4.8-5.8 A or wherein the distance between the centroid of the phosphate isostere and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said oxygen atoms are ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said oxygen atoms are ranges from 5.0-7.9 A. The invention further provides a method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1B (PTP1B), T-Cell Protein Tyrosine Phosphatase (TC-PTP) and other PTPases that are structurally similar to PTP1 B which comprises exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising: I. an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and wherein the distance between the centroid of the carboxylic acid group of said oxalylamide group and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said amino group ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said amino group ranges from 4.8-5.8 A or wherein the distance between the centroid of the carboxylic acid group of said oxalylamide group and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said oxygen atoms are ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said oxygen atoms are ranges from 5.0-7.9 A. The hydrophobic groups that interact with tyrosine 46 and phenylalanine/histidine 182 include, but are not limited to, alkyl and aryl groups. These hydrophobic groups include cyclohexyl, phenyl, naphthyl, thiophenyl, pyrrolyl and furanyl. The hydrophobic groups that interact with one or more of the tyrosine 46 and the arginines 24, 45, 47, and 254 include, but are not limited to, alkyl and aryl groups. These hydrophobic groups include cyclohexyl, phenyl, naphthyl.thiophenyl, pyrrolyl and furanyl, optionally substitutedThe hydrophobic groups that interact with methionine 258, glycine 259 and phenylalanine 52 include, but are not limited to, alkyl and aryl groups groups. These aryl groups include phenyl, thiophenyl, pyrrolyl, furanyl, CrC 6 alkyl and arylCrC 6 alkyl which are defined hereinbelow. The hydrophilic groups that interact with the hydrogen atom donated by the side chain amide nitrogen of arginine 47, aspartic acid 48, leucine 119, glycine 259, lysine 41 , lysine 120, the side chain amide hydrogen atom donated by glutamine 262, the hydrogen atoms donated by the guanidinium group of arginine 254, arginine 45 or arginine 24 include, but are not limited to, hydroxy, C C 6 alkyloxy, aminocarbonyl, oxo, SO, SO 2 , SONH 2 , SO NH 2 , SO 2 NHCF 3 , COOH or a group selected from the following 5-membered heterocycles N' ° H HN' - OH or OH or ςr H The hydrophilic groups that interact with the side chain amide carbonyl group of asparagine 44, arginine 45 or aspartic acid 48 include, but are not limited to, amino, aminocarbonyl, hydroxy, SONH 2 , SO 2 NH 2 , or The hydrophilic groups that interact with the side chain carboxylic acid group of aspartic acid 181 include, but are not limited to, amino, aminocarbonyl, hydroxy, CrC 6 alkyloxy, SONH 2 , SO 2 NH 2 . The hydrophilic groups that interact with the side chain hydroxy group of serine 118 include, but are not limited to, aminocarbonyl, hydroxy, C C 6 alkyloxy, SONH 2 , SO 2 NH 2 . Unique structural elements in PTP1B To identify unique residues or combinations of residues of PTP1 B that could be utilised as points of interaction by selective inhibitors, alignment of the primary sequences of the catalytic domains of approximately 105 known vertebrate PTPases (Andersen, J.N. er a/., (1999) in preparation) was done (Table 1 , below). Using the crystal structure of PTP1 B (Andersen, H.S. et al. (1999) J. Biol. Chem. 275: 7107-7108 (2000);Barford, D., et al. Science 263:1397-1404 (1994)), unique combinations of residues in the active site pocket or in its vicinity were identified, i.e. in a distance (3-5.5 A) that would allow simultaneous binding to the active site and these residues, while still retaining a low molecular weight (for example, below 700 dalton). In particular, the combination of 4 residues seems unique for the PTP1 B family: arginine 47, aspartic acid 48, methionine 258, and glycine 259. arginine 47 and aspartic acid 48 contribute significantly to the binding of peptide substrates in PTP1 B (Jia, Z.C., et al., Science 268:1754-1758 (1995)). A comparison of these regions in representative members of 14 PTP families, indicates that in particular residue 48 is an attractive binding element for selective PTP1B ligands since this residues is an aspartic acid in PTP1 B and an asparagine in many other PTPases. Aspartic acid 48 is well-defined in the published PTP1B structures ((Puius, Y.A. et al. Proc. Natl. Acad. Sci. USA 94:13420-13420 (1997)), (Pannifer, A.D.B., et al., J. Biol. Chem. 273:10454-10462 (1998)) and it is believed to play an important role in positioning substrates correctly relative to the active site (Sarmiento, M., et al., J. Biol. Chem. 273: 26368-26374 (1998)). Table 1 Non-limiting examples of selected amino acid residues at positions in the vicinity of the active site (single letter code - PTP1B numbering) . ^ <? J$ f / < / < Optimization for potency The key structural features of 2-(oxalyl-amino)-benzoic acid (OBA) are the twocarboxy groups respectively bound - directly and through a carbonylamino group - to an aromatic ring. Replacement of the phenyl ring in OBA by thiophene, resulted in compounds with little difference in potency between the regioisomer 2-aminothiophene and 3- aminothiophene . Previous studies have shown that phenyl-based phosphonate inhibitors have little affinity for PTP1 B, while addition of a second phenyl ring (e.g. [(1,1-difluoro-1-naphthalenyl)-methyl]phosphonic acid) significantly increased the potency (Burke, T.R. et al., Biochemistry 35:15989-15996 (1996)). The enhanced potency of the naphthalene ring system is due to extensive hydrophobic interactions with the side chains of tyrosine 46, valine 49, phenylalanine 182, alanine 217 and isoleucine 219. Similarly, 3- (oxalyl-amino)-naphthalene-2-carboxylic acid interacts with the same residues. It was reasoned that a saturated ring fused to 2-(oxalyl-amino)- thiophene-3-carboxylic acid (2-OTA) and/or 3-(oxalyl-amino)-thiophene-2- carboxylic acid (3-OTA) would serve a similar function and increase the potency. Further, the proposed binding mode of such a compound should bring the saturated ring in close proximity to residues arginine 47 and aspartic acid 48. Introducing a basic nitrogen or polar changes in this saturated ring would allow further interactions with the side chains or backbone amides of arginine 47 and aspartic acid 48. In accordance with the above alignment studies, we anticipated that selectivity for PTP1 B and other PTPases with an aspartic acid in position 48 could be obtained by specifically addressing this area of the enzyme. Consequently, 2-(oxalyl-amino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3- carboxylic acid (2-OBTA) was synthesised and its potency analysed against a set of PTPases. Table II shows that 2-OBTA is about 10-fold more potent against PTP1 B than compounds 3-OTA and 2-OTA and 3- fold more potent than OBA when tested at pH 5.5 (the pH optimum for PTP1 B using pNPP as substrate). Further, the inhibitory profile against this set of PTPases is almost the same as that of 3-(oxalyl-amino)- naphthalene-2-carboxylic acid. Thus, although 2-OBTA retains the features of a general PTP inhibitor, it already shows some selectivity for PTP1 B. These results clearly indicate that 2-OBTA spatially fits in this region of PTP1 B. Various substitutions in the saturated ring of 2-OBTA were found to influence the binding affinities for different PTPases (not shown). Table 2 Kj values (μM) - pH 5.5 As indicated above, in comparison with OBA, 2-OBTA showed an approximately 3-fold increase in affinity for most PTPases. It was hypothesised that the saturated ring of 2-OBTA would occupy almost the same position as the distal ring of 3-(oxalyl-amino)-naphthalene-2- carboxylic acid, which was previously shown to bind in the proximity of arginine 47 and aspartic acid 48. Therefore, as expected, there was no apparent change in selectivity in accordance with the notion that the saturated ring makes hydrophobic contact with conserved residues such as tyrosine 46, alanine 217, valine/isoleucine219 and isoleucine/valine 49 (PTP1B numbering). Optimization for selectivity The combination of arginine 47 and aspartic acid 48 offers a rather unique, selective ligand-binding region in PTP1B. The side chains of both residues are charged at neutral pH and are therefore sutiable for salt bridge formation. Introducing a positive charge in 2-OBTA that could form a salt bridge with aspartic acid 48, would not only increase the potency of 20BTA against PTP1 B but also - due to repulsive forces between the positive ligand charge and the asparagine side chain found in many other PTPases - decrease the affinity of 20BTA for these PTPases. Three side chain rotamer conformations are normally defined for an aspartic acid residue (rota 1: 47.7%, rota 2: 33.6% and rota 3: 15.9%). In the published X-ray structures of PTP1 B, two rotamers have been described, rota 1 and 3. The rota 3 conformation is stabilised by an internal hydrogen bond between the side chain and main chain amide with the side chain bending towards the active site pocket. Further, rota 3 seems to be the preferred rotamer for aspartic acid 48. The rota 1 conformation has only been found in four of the eleven published X-ray structures, and in three of these cases the rota 1 position is necessitated due to ligand occupancy. The aspartic acid 48 rota 1 conformation is pointing away from the active site pocket. Thus, rota 3 was found both in the apo-enzyme and in PTP1 B complexed with peptide ligands that seem to stabilize this conformation. Further, we have recently co-crystallized PTP1 B with OBA and 3 derivatives and found aspartic acid 48 in the rota 3 position in all structures (Andersen, H.S. et al. J. Biol. Chem. 275, 7101- 7108 (2000)). Based on these observations, it was hypothesized that introduction of a basic nitrogen in the saturated ring in 2-OBTA would be sufficiently close to aspartic acid 48 to allow the formation of a salt bridge. A recent survey of 322 unrelated proteins has shown that aspartic acid and asparagine residues have a strong tendency to form hydrogen bonds with neighboring backbone amides and in both cases with a significant preference for internal hydrogen bonds. Assuming that asparagine 48 of other PTPases, e.g. PTPα, forms an internal hydrogen bond similar to that observed for aspartic acid 48 in PTP1 B, the side chain amide of the asparagine with its positive dipole would be in an unfavourable position to the proposed basic nitrogen and thus cause repulsion. 2-(Oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid (2-OTPyA) - containing a positively charged tetrahydropyridine ring (pK a > 10) - was synthesised in order to test the foregoing hypothesis. In agreement with the predictions, the affinity for PTP1 B was increased about 20-fold without any significant increase in molecular weight (Table 2). Further, this compound showed an almost astonishing selectivity for PTP1B versus all other PTPases tested. Again, this is in agreement with the hypothesis that repulsive forces between the basic nitrogen in 2- OTPyA and the positive dipole of the asparagine side chain decrease the potency against other PTPases. CD45, which also contains an aspartic acid in position 48, is a noticeable exception showing only a 2-fold decrease. It is speculated that the preferred rotamer of aspartic acid 48 in CD45 is the rota 1 conformation, which is too far away for salt bridge formation with 2-OTPyA. In addition, CD45 contains a valine in position 47, which may not have the same influence on aspartic acid 48 as an arginine. 2-(Oxalyl-amino)-4,7-dihydro-thieno[2,3-c]pyran-3-carboxylic acid (2- OTPA) - containing a negative dipole in the dihydropyran ring - was synthesised. In agreement with the predictions, the affinity for PTP1B was decreased about 2.5-fold compared to 2-OBTA without any significant increase in molecular weight (Table 2). Table A (at the end of the specification) discloses the protein coordinates of PTP1 B complexed with 2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid (2-OTPA) and in Figure 1 is the active site of PTP1 B complexed with 2-OTPA shown. Optimization for potency towards Arginine 47 and Aspartic acid 48 Using further the combination of the 4 unique residues for the PTP1 B family: arginine 47, aspartic acid 48, methionine 258, and glycine 259 it was hypothesised that an increase in potency could be obtained by introduction of a hydrogen-bond acceptor side chain that could form one or more hydrogen bonds with the main chain amides of arginine 47 and aspartic acid 48, would increase the potency against PTP1 B. 5-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyhdine-3-carboxylic acid (5-HTPyA) (Example 52) - still containing a positively charged tetrahydropyridine ring and three hydrogen-bond acceptors (oxygen atoms) - was synthesised. In agreement with the predictions, the affinity for PTP1 B was increased about 13- fold compared to 2-OTPyA. Changing the positively charged nitrogen atom with a non charged oxygen atom and still addressing the main chain amides of arginine 47 and aspartic acid 48, it was hypothesised that an increase in general potency could be obtained. Thus, 5-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid (5-HTPA) (Example 4) - containing a non charged dihydropyran ring and three hydrogen-bond acceptor oxygen atoms - was synthesised. In agreement with the predictions, only the general potency was increased compared to 2-OTPyA as shown in Table 3. Selectivity via steric hindrance Referring again to the combination of the 4 residues unique for the PTP1 B family: arginine 47, aspartic acid 48, methionine 258, and glycine 259, but this time more specifically to the combination of methionine 258 and glycine 259, which form part of a hydrophobic pocket in PTP1 B in contrast to most other PTPases where the pocket is filled out: PTPα: cysteine 258- glutamine 259; PTP β: valine 258-histidine 259; PTP-LAR: asparagine 258-tyrosine 259; and CD45: cysteine 258-leucine 259 (PTP1 B numbering), it was hypothesised that an increase in potency and selectivity could be obtained by introduction of a hydrophobic side chain that could form hydrophobic interactions to glycine 259 and to the side chain of methionine 258 and at the same time take part in repulsion-/stehc hindrance with the same residues in other PTPases. Thus, 7-(5-methoxy- 1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid (7-MOTPA) (Example 26) -- containing a hydrophobic 1 ,3-dihydro-isoindol side chain - was synthesised. In agreement with the predictions, both affinity and selectivity for PTP1 B was increased as shown in Table 3 compared to 2-OTPA. Table 3 K| values M - H 7 Table B (at the end of the specification) discloses the protein coordinates of PTP1 B complexed with 7-(5-methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid (7-MOTPA) (Example 26), and Figure 2 shows the crystal structure of the active site of PTP1 B complexed with 7-MOTPA. Table C (at the end of the specification) discloses the protein coordinates of PTP1 B complexed with 5-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid (5-HTPA) (Example 4), and Figure 3 shows the crystal structure of the active site of PTP1 B complexed with 5-HTPA. Table D (at the end of the specification) discloses the protein coordinates of PTP1 B complexed with 2-(oxaly1-amino)-7-(1 ,1 , 3-trioxo-1H -benzo [d] isothiazol-3-yloxomethyl)-4,7-dihydro-5 -, thieno [2,3-c] pyran-3- carboxylic acid (example 54), including key water molecules. Figure 2 is the active site with selected water molecules shown. Specific interactions of certain inhibitors of the present invention at the active site of PTP1 B are detailed below. The carboxy group of the oxamicN acid of 2-(oxalyl-amino)-4,5,6,7- tetrahydro-thieno[2,3-c]pyhdine-3-carboxylic acid is positioned 2.9-3.0 A from the guanidinium group of arginine 221 forming a salt bridge, as well as a hydrogen bond with the main chain amide of arginine 221 and serine 216, and the carbonyl forms a hydrogen bond with the main chain amide of glycine 220. The carboxy group in the 3 position is positioned 2.8 A from lysine 120 forming a salt bridge. The tetrahydro-thieno[2,3-c]pyridine ring forms hydrophobic interactions with phenylalanine 182, tyrosine 46, valine 49, alanine 217 and isoleucine 219. The basic nitrogen in the tetrahydro-thieno[2,3-c]pyridine ring is positioned 2.8 A from the carboxy group of aspartic acid 48 forming a salt bridge. The carboxy group of the oxamic acid of 7-(5-Methoxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-thieno[2,3- c]pyran-3-carboxylic acid (Example 26) is positioned 2.9-3.0 A from the guanidinium group of arginine 221 forming a salt bridge, as well as a hydrogen bond with the main chain amide of arginine 221 and serine 216, and the carbonyl forms a hydrogen bond with the main chain amide of glycine 220. The carboxy group in the 3 position is positioned 2.8 A from lysine 120 forming a salt bridge. The dihydro-thieno[2,3-c]pyran ring forms hydrophobic interactions with phenylalanine 182, tyrosine 46, valine 49, alanine 217 and isoleucine 219. The phenyl ring of the isoindol ring forms a hydrophobic interaction with the side chain methylene atom of aspartic acid 48 and the 5-methoxy substituent forms hydrophobic interactions with the side chain atoms of methionine 258. The carboxy group of the oxamic acid of 5-(4-hydroxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-thieno[2,3- c]pyran-3-carboxylic acid (Example 4) is positioned 2.9-3.0 A from the guanidinium group of arginine 221 forming a salt bridge, as well as a hydrogen bond with the main chain amide of arginine 221 and serine 216, and the carbonyl forms a hydrogen bond with the main chain amide of glycine 220. The the carboxy group in the 3 position is positioned 2.7 A from lysine 120 forming a salt bridge. The dihydro-thieno[2,3-c]pyran ring forms hydrophobic interactions with phenylalanine 182, tyrosine 46, valine 49, alanine 217 and isoleucine 219. The side chain methylene group at the 5 position of the thieno[2,3-c]pyran forms a hydrophobic interaction the side chain methylene group of aspartic acid 48. The phenyl ring of the isoindol ring forms a hydrophobic interaction with tyrosine 46 and both one of the oxo atoms and the hydroxy group at the isoindole forms hydrogen bonds respectively with the main chain amide of aspartic acid 48 and arginine 47. To further substantiate the generality in using steric hindrance/steric fit to obtain selectivity for PTP1 B, TC-PTP and structurally similar PTPases we also synthesized 7-(1 , 1 -dioxo-1 H-benzo[d]isothiazol-3-yloxymethyl)-2- (oxalyl-amino)-4,7-dihyd ro-5H-thieno[2,3-c]pyran-3-carboxylic acid ("Compound N"). The substitution was introduced in the 7-position to address the region defined by residues 258 and 259. As indicated above, this part of PTP1 B forms a hydrophobic pocket with direct access to the active site, whereas the same region is sterically hindered by more bulky side chains, in particular those corresponding to residue 259 in PTP1B. Compound N was synthesized with a substituent in the 7-position of 2-OTPA to sterically fit with this part of PTP1 B and TC-PTP, but cause steric hindrance in other PTPs. To test directly, whether the above compound was addressing the proposed region of PTP1 B, Compound N was subjected to detailed enzyme kinetic analyses using a set of wildtype (wt) and mutant PTPs. Two enzymes, PTPα and PTPH1 , were chosen as representatives for PTPs with bulky side chains in the 259 position. Using a combination of wt and PTP mutants it has previously been shown that Gln259 in PTPα, in addition to its direct effect, also indirectly influences the binding of inhibitors and substrates, most likely due to a negative influence on the rotational freedom of the side chain of Gln262 (Peters et al., J. Biol. Chem. 275: 18201-18209 (2000)). As described above, selectivity can be obtained by introducing a basic nitrogen into 2-(oxalylamino)-4, 5,6,7- tetrahydrobenzo[b]thiophene-3-carboxylic acid that causes attraction in PTP1B due to salt bridge formation to Asp48 and repulsion against PTPs with an asparagine in the 48 position, such as PTPα. To analyze if the current approach based on steric hindrance is generally applicable, it was decided to include a PTP with an aspartic acid in position 48. PTPH1, which like PTP1 B is an intracellular enzyme with one domain only, was selected for these studies. The results of these studies are shown below (Table 4 ). Table 4 It appears that introduction of bulky side chains in the 259 position in PTP1 B causes a very significant decrease in affinity for NNC 52-1153. Conversely, replacement of the bulky residues in PTPα and PTPH1 with a glycine increases the affinity. This clearly indicates that NNC 52-1153 addresses the 258-259 region of PTP1 B. Specificity against a broad set of PTPs -It was next analyzed if the side chain of NNC 52-1153 would cause the increased selectivity against other PTPs. NNC 52-1153 was tested against a set of 10 different wt PTP domains (Table 5). It appears from this table that a substantial increase in affinity for PTP1 B and TC-PTP has been obtained, while at the same time introducing a very high degree of selectivity against many other PTPs representing a broad spectrum of this class of enzymes (having Asp 48). Table 5 To unequivocally determine the binding mode, x-ray co-crystallization studies of PTP1 B and NNC 52-1153 were initiated. A well-suited electron density was identified in the active site pocket. The oxalylamino and o- carboxy groups show the exact same interaction with the PTP signature motif and salt bridge formation to Lys120 as described previously for 2- (oxalylamino)-benzoic acid and the thiophene-based derivatives. Significantly, the side chain of the ligand is positioned in close vicinity to residues 258 and 259. Several interaction points appear to be responsible for the observed significant increase in affinity for PTP1 B. Thus, a long hydrogen bond seems to interact with one carbonyl of the ligand side chain. In addition, important van der Waals contacts are made between the aromatic ring of the ligand side chain and the side chain of Met248 and Cβ atom of Asp48. As described above, we have utilized salt bridge formation to Asp48 to obtain potent and selective PTP1 B inhibitors. In these structures, Asp48 was in the so-called rotamer ("rota") 3 position - pointing towards the active site. In contrast, the side chain of Asp48 is pushed away from the active site by the oxygen molecules in NNC 52-1153 (i.e. the rotamer 1 position). This allows a novel water molecule to form a bridge between the two oxygen molecules in the ligand and Asp48. This surprising observation can be used to design additional inhibitors of PTP1B. The present invention encompasses, but is not limited to, compounds of the Formula 1 wherein n, m, X, Y, R 1 f R 2 , R 3 , R , R 5 and R 6 are defined below; Formula 1 In the above Formula 1 n is 0, 1 or 2 (if m = 0 then n is 1 or 2); m is 0, 1 or 2 (if n = 0 then m is 1 or 2); X is S, O, NR 8 ; Y is NR 7 , O, S, SO, SO 2 ; RT is hydrogen, COOR 3 , or selected from the following 5-membered heterocycles: R 2 is hydrogen, CrC 6 alkyl, hydroxy, NR 9 R 10 ; R 3 is hydrogen, CrC 6 alkyl, arylCrCβalkyl, Cι-C 6 alkylcarbonyloxyCr C 6 alkyl, C-i-CealkylcarbonyloxyarylCrCβalkyl; R , R 5 and R 6 are independently hydrogen, trihalomethyl, Cι-C 6 alkyl, aryl, arylCι-C 6 alkyl, hydroxy, oxo, carboxy, carboxyCrC 6 alkyl, Cι-C 6 alkyloxy- carbonyl, aryloxycarbonyl, arylCι-C 6 alkyloxycarbonyl, CrC 6 alkyloxy, d- C 6 alkyloxyCι-C 6 alkyl, aryloxy, aryloxy CrC 6 alkyl, arylCrC 6 alkyloxy, arylCrCealkyloxyd-Cealkyl, thio, CrC 6 alkylthio, d-Cβalkylthiod-C-βalkyl, arylthio, aryld-C 6 alkylthio, arylC Cealkylthiod-Cealkyl, NR 9 R 10 , d- CealkylaminoCi-Cβalkyl, arylCι-C 6 alkylaminoCι-Cealkyl, di(arylC Cealky aminoC Ceal yl, CrC 6 alkylcarbonyl, Cι-C 6 alkylcarbonylC C 6 alkyl, arylCrC 6 alkylcarbonyl, arylCrCealkylcarbonylCrCealkyl, C C 6 alkylcarboxy, d-Cealkylcarboxyd-Cβ-alkyl, arylcarboxy, arylcarboxyd- C 6 alkyl, aryld-C 6 alkylcarboxy, aryld-CealkylcarboxyCi-Cealkyl, C C 6 alkylcarbonylamino, d-Cealkylcarbonyl-aminod-Cealkyl, -carbonylNR 7 Cι-CealkylCORi 3 , arylCι-C 6 alkylcarbonyl-amino, arylCr C 6 alkylcarbonylaminoCι-Cealkyl, arylamino carbonylaminoCrC θ alkyl, arylaminoCrC 6 alkyl, arylcarbonylamino C C 6 alkyl, CONR 9 R 10 , RβRgNd-Ce alkyl, or d-Cealkyl-CONRgR wherein the alkyl and aryl groups are optionally substituted and R 13 is NR 9 R 10 , or C CealkylNRgRio; R 7 is hydrogen, d-C 6 alkyl, aryl, arylCι-C 6 alkyl, CrC 6 alkylcarbonyl, C C 6 alkyloxocarbonyl, arylcarbonyl, aryloxocarbonyl, arylCι-C 6 alkylcarbonyl, aryld-Cealkyloxocarbonyl, CrC 6 alkylcarboxy, arylCι-C 6 alkylcarboxy, R 9 RιoNcarbonylCι-C 6 alkyl wherein Rg and R 0 are independently selected from hydrogen, d-C 6 alkyl, aryl, arylC C 6 alkyl, C C 6 alkylcarbonyl, arylcarbonyl, arylCι-C 6 alkylcarbonyl, d-C 6 alkylcarboxy or aryld- C 6 alkylcarboxy; wherein the alkyl and aryl groups are optionally substituted; R 8 is hydrogen, d-C 6 alkyl, aryl, arylCι-C 6 alkyl, CrC 6 alkylcarbonyl, arylcarbonyl, arylCι-C 6 alkylcarbonyl, CrC 6 alkylcarboxy or aryld-C 6 alkyl- carboxy wherein the alkyl and aryl groups are optionally substituted; Rg and R 10 are independently selected from hydrogen, CrC 6 alkyl, aryl, arylC C 6 alkyl, d-Cβalkylcarbonyl, arylcarbonyl, arylCι-C 6 alkylcarbonyl, CrC 6 alkylcarboxy or arylCrC 6 alkylcarboxy wherein the alkyl and aryl groups are optionally substituted; or R 9 and R 10 are together with the nitrogen to which they are attached forming a saturated, partially saturated or aromatic cyclic, bicyclic or tricyclic ring system containing from 3 to 14 carbon atoms and from 0 to 3 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system can optionally be substituted with at least one d-Cβalkyl, aryl, arylC C 6 alkyl, hydroxy, oxo, d-C 6 alkyloxy, aryld-Cealkyloxy, C C 6 alkyloxyCrC 6 alkyl, NRnRι 2 or Cι-C 6 alkylamino-Cι-C 6 alkyl, wherein Rn and R- I2 are independently selected from hydrogen, d-C 6 alkyl, aryl, arylCι-C 6 alkyl, C C 6 alkylcarbonyl, arylcarbonyl, aryld-Cβalkylcarbonyl, CrC 6 alkylcarboxy or arylCι-C 6 alkylcarboxy; wherein the alkyl and aryl groups are optionally substituted; or Rg and Rio are independently a saturated or partial saturated cyclic 5, 6 or 7 membered amine, imide or lactam or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms. The compounds of Formula 1 are oxalylamide compounds having in common key structural features required of non hydrolysable protein tyrosine phosphatase inhibitors, most particularly PTP1 B and/or TC-PTP ' inhibitors. These structural features endow the present compounds with the appropriate molecular shape necessary to fit into the enzymatic active site, to bind to such site in a non covalently way, thereby blocking the site and inhibiting enzymatic biological activity. Referring to Formula 1 , such structural features include the oxalylamide and an ortho-carboxylic acid attached to a hydrophobic group, preferably an aryl as defined below The compounds of the invention can be further modified to act as pro- drugs. It is a well known problem in drug discovery that compounds, such as enzyme inhibitors, may be very potent and selective in biochemical assays, yet be inactive in vivo. This lack of so-called bioavailability may be ascribed to a number of different factors such as lack of or poor absorption in the gut, first pass metabolism in the liver, poor uptake in cells. Although the factors determining bioavailability are not completely understood, there are many examples in the scientific literature - well known to those skilled in the art - of how to modify compounds, which are potent and selective in biochemical assays but show low or no activity in vivo, into drugs that are biologically active. It is within the scope of the invention to modify the compounds of the invention, termed the Original compound' or "prototype", by attaching chemical groups that will improve the bioavailability of said compounds in such a way that the uptake in cells or mammals is facilitated. Examples of said modifications, which are not intended in any way to limit the scope of the invention, include changing of one or more carboxy groups to esters (for instance methyl esters, ethyl esters, acetoxymethyl esters or other acyloxymethyl esters). Compounds of the invention, original compounds, modified by attaching chemical groups are termed 'modified compounds' Said chemical groups may or may not be apparent in the claims of this invention. Other examples of modified compounds, which are not intended in any way to limit the scope of the invention, are compounds that have been cyclized at specific positions - so called 'cyclic compounds' - which upon uptake in cells or mammals become hydrolyzed at the same specific position(s) in the molecule to yield the compounds of the invention, the original compounds, which are then said to be 'non-cyclic'For the avoidance of doubt, it is understood that the latter original compounds in most cases will contain other cyclic or heterocyclic structures that will not be hydrolyzed after uptake in cells or mammals. Generally, said modified compounds will not show a behavior in biochemical assays similar to that of the original compound, i.e. the corresponding compounds of the invention without the attached chemical groups or said modifications. Said modified compounds may even be inactive in biochemical assays. However, after uptake in cells or mammals these attached chemical groups of the modified compounds may in turn be removed spontaneously or by endogenous enzymes or enzyme systems to yield compounds of the invention, original compounds. 'Uptake' is defined as any process that will lead to a substantial concentration of the compound inside cells or in mammals. After uptake in cells or mammals and after removal of said attached chemical group or hydrolysis of said cyclic compound, the compounds may have the same structure as the original compounds and thereby regain their activity and hence become active in cells and/or in vivo after uptake. A number of procedures, well known to those skilled in the art, may be used to verify that the attached chemical groups have been removed or that the cyclic compound has been hydrolyzed after uptake in cells or mammals. An example, which is not intended in any way to limit the scope of the invention, is given in the following. A mammalian cell line, which can be obtained from the American Tissue Type Collection or other similar governmental or commercial sources, is incubated with said modified compound. After incubation at conditions well known to those skilled in the art, the cells are washed appropriately, lysed and the lysate is isolated. Appropriate controls, well known to those skilled in the art, must be included. A number of different procedures, well known to those skilled in the art, may in turn be used to extract and purify said compound from said lysate. Said compound may or may not retain the attached chemical group or said cyclic compound may or may not have been hydrolyzed. Similarly, a number of different procedures - well known to those skilled in the art - may be used to characterize said purified compound structurally and chemically. Since said purified compound has been isolated from said cell lysate and hence has been taken up by said cell line, a comparison of said structurally and chemically characterized compound with that of the original unmodified compound (i.e. without said attached chemical group or said non-cyclic compound) will immediately provide to those skilled in the art information on whether the attached chemical group as been removed in the cell or whether the cyclic compound has been hydrolyzed. As a further analysis, said purified compound may be subjected to enzyme kinetic analysis as described in detail in the present invention. If the kinetic profile is similar to that of the original compound without said attached chemical group, but different from said modified compound, this confirms that said chemical group has been removed or said cyclic compounds has been hydrolyzed. Similar techniques may be used to analyze compounds of the invention in whole animals and mammals. Preferred prodrug classes for the present compounds include acyloxymethyl esters or acyloxymethyl carbamates of the compounds of the present invention which may be prepared by the following general procedure (C.Schultz et al, J. Biol. Chem., 1993, 268, 6316-6322.) and (Alexander, J. et al, J. Med. Chem. 1991, 34, 78-81). A carboxylic acid (1 equivalent) is suspended in dry acetonitrile (2 ml per 0.1 mmol). Diisopropyl amine (3.0 equivalents) is added followed by bromomethyl acetate (1.5 equivalents). The mixture is stirred under nitrogen overnight at room temperature. Acetonitrile is removed under reduced pressure to yield an oil which is diluted in ethyl acetate and washed with water (3 x). The organic layer is dried over anhydrous magnesium sulfate. Filtration followed by solvent removal under reduced pressure affords a crude oil. The product is purified by column chromatography on silica gel, using an appropriate solvent system. DEFINITIONS As used herein, the term "attached" or "-" (e.g. -C(O)-R 13ι which indicates the carbonyl attachment point to the scaffold) signifies a stable covalent bond, certain preferred points of attachment points being apparent to those skilled in the art. The terms "halogen" or "halo" include fluorine, chlorine, bromine, and iodine. The term "alkyl" includes Cι-C 6 straight chain saturated, methylene and C 2 -C 6 unsaturated aliphatic hydrocarbon groups, C C 6 branched saturated and C 2 -C 6 unsaturated aliphatic hydrocarbon groups, C 3 -C 6 cyclic saturated and C 5 -C 6 unsaturated aliphatic hydrocarbon groups, and d-C 6 straight chain or branched saturated and C 2 -C 6 straight chain or branched unsaturated aliphatic hydrocarbon groups substituted with C 3 -C 6 cyclic saturated and unsaturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, this definition shall include but is not limited to methyl (Me), ethyl (Et), propyl (Pr), butyl (Bu), pentyl, hexyl, heptyl, ethenyl, propenyl, butenyl, penentyl, hexenyl, isopropyl (i-Pr), isobutyl (i-Bu), terf-butyl (t- ), sec-butyl (s-Bu), isopentyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, methylcyclopropyl, ethylcyclohexenyl, butenylcyclopentyl, and the like. The alkyl group as defined above is optionally substituted wherein the substitutents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, hydroxy, oxo, COOR 3 , CONR 9 R 10 , C C 6 alkyl, d-C 6 alkyloxy, aryloxy, arylC C 6 alkyloxy, thio, d-C 6 alkylthio, arylthio, arylCrC 6 alkylthio, NRgRio, CrC 6 alkylamino, arylamino, aryld- C 6 alkylamino, di(arylC C 6 alkyl)amino, C C 6 alkylcarbonyl, arylCι-C 6 alkyl- carbonyl, d-C 6 alkylcarboxy, arylcarboxy, aryld-C 6 alkylcarboxy, Cι- C 6 alkylcarbonylamino, -Cι-C 6 alkylaminoCORι 4 , arylCι-C 6 alkylcarbonyl- amino, tetrahydrofuranyl, morpholinyl, piperazinyl, -CONR 9 R 10 , -d-C 6 - alkylCONR 9 R o, or a saturated or partial saturated cyclic 5, 6 or 7 membered amine, imide or lactam; wherein R 4 is hydroxy, d-C 6 alkyl, aryl, arylCrC 6 alkyl, d-C 6 alkyloxy, aryloxy, aryld-C 6 alkyloxy and R 3 is defined as above or NR9R 10 , wherein R 9 , R 10 are defined as above. The term "saturated, partially saturated or aromatic cyclic, bicyclic or tricyclic ring system" represents but are not limit to aziridinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, 2-imidazolinyl, imidazolidinyl, pyrazolyl, 2-pyrazolinyl, 1 ,2,3-triazolyl, 1,2,4-triazolyl, morpholinyl, piperidinyl, thiomorpholinyl, piperazinyl, indolyl, isoindolyl, 1 ,2,3,4-tetrahydro- quinolinyl, 1 ,2,3,4-tetrahydro-isoquinolinyl, 1 ,2,3,4-tetrahydro-quinoxalinyl, indolinyl, indazolyl, benzimidazolyl, benzotriazolyl, purinyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, iminodibenzyl, iminostilbenyl. The term "alkyloxy" (e.g. methoxy, ethoxy, propyloxy, allyloxy, cyclohexyloxy) represents an "alkyl" group as defined above having the indicated number of carbon atoms attached through an oxygen bridge. The term "alkyloxyalkyl" represents an "alkyloxy" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "alkyloxyalkyloxy" represents an "alkyloxyalkyl" group attached through an oxygen atom as defined above having the indicated number of carbon atoms. The term "aryloxy" (e.g. phenoxy, naphthyloxy and the like) represents an aryl group as defined below attached through an oxygen bridge. The term "arylalkyloxy" (e.g. phenethyloxy, naphthylmethyloxy and the like) represents an "arylalkyl" group as defined below attached through an oxygen bridge. The term "arylalkyloxyalkyl" represents an "arylalkyloxy" group as defined above attached through an "alkyl" group defined above having the indicated number of carbon atoms. The term "arylthio" (e.g. phenylthio, naphthylthio and the like) represents an "aryl" group as defined below attached through an sulfur bridge. The term "alkyloxycarbonyl" (e.g. methylformiat, ethylformiat and the like) represents an "alkyloxy" group as defined above attached through a carbonyl group. The term "aryloxycarbonyl" (e.g. phenylformiat, 2-thiazolylformiat and the like) represents an "aryloxy" group as defined above attached through a carbonyl group. The term "arylalkyloxycarbonyl" (e.g. benzylformiat, phenyletylformiat and the like) represents an "arylalkyloxy" group as defined above attached through a carbonyl group. The term "alkyloxycarbonylalkyl" represents an "alkyloxycarbonyl" group as defined above attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The term "arylalkyloxycarbonylalkyl" represents an "arylalkyloxycarbonyl" group as defined above attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The term "alkylthio" (e.g. methylthio, ethylthio, propylthio, cyclohexenylthio and the like) represents an "alkyl" group as defined above having the indicated number of carbon atoms attached through a sulfur bridge. The term "arylalkylthio" (e.g. phenylmethylthio, phenylethylthio, and the like) represents an "arylalkyl" group as defined above having the indicated number of carbon atoms attached through a sulfur bridge. The term "alkylthioalkyl" represents an "alkylthio" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "arylalkylthioalkyl" represents an "arylalkylthio" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "alkylamino" (e.g. methylamino, diethylamino, butylamino, N- propyl-N-hexylamino, (2-cyclopentyl)propylamino, hexenylamino, pyrrolidinyl, piperidinyl and the like) represents one or two "alkyl" groups as defined above having the indicated number of carbon atoms attached through an amine bridge. The two alkyl groups may be taken together with the nitrogen to which they are attached forming a saturated, partially saturated or aromatic cyclic, bicyclic or tricyclic ring system containing 3 to 14 carbon atoms and 0 to 3 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system can optionally be substituted with at least one d-C 6 alkyl, aryl, arylCι-C 6 alkyl, hydroxy, oxo, C C 6 alkyloxy, d-C 6 alkyloxyCι-C 6 alkyl, NR 9 Rι 0 , CrC 6 alkylaminoCι-C 6 alkyl substituent wherein the alkyl and aryl groups are optionally substituted as defined in the definition section and R 9 and Rio are defined as above. The term "arylalkylamino" (e.g. benzylamino, diphenylethylamino and the like) represents one or two "arylalkyl" groups as defined above having the indicated number of carbon atoms attached through an amine bridge. The two "arylalkyl" groups may be taken together with the nitrogen to which they are attached forming a saturated, partially saturated or aromatic cyclic, bicyclic or tricyclic ring system containing 3 to 14 carbon atoms and 0 to 3 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system can optionally be substituted with at least one d-C 6 alkyl, aryl, aryld-C 6 alkyl, hydroxy, oxo, C C 6 alkyloxy, Cι-C 6 alkyloxyCrC 6 alkyl, NR 9 R 10 , Cι-C 6 alkylaminoCrC 6 alkyl substituent wherein the alkyl and aryl groups are optionally substituted as defined in the definition section and R 9 and Rio are defined as above. The term "alkylaminoalkyl" represents an "alkylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "arylalkylaminoalkyl" represents an "arylalkylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "arylalkyl" (e.g. benzyl, phenylethyl) represents an "aryl" group as defined below attached through an alkyl having the indicated number of carbon atoms or substituted alkyl group as defined above. The term "alkylcarbonyl" (e.g. cyclooctylcarbonyl, pentylcarbonyl, 3- hexenylcarbonyl) represents an "alkyl" group as defined above having the indicated number of carbon atoms attached through a carbonyl group. The term "arylcarbonyl" (benzoyl) represents an "aryl" group as defined above attached through a carbonyl group. The term "arylalkylcarbonyl" (e.g. phenylcyclopropylcarbonyl, phenylethylcarbonyl and the like) represents an "arylalkyl" group as defined above having the indicated number of carbon atoms attached through a carbonyl group. The term "alkylcarbonylalkyl" represents an "alkylcarbonyl" group attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The term "arylalkylcarbonylalkyl" represents an "arylalkylcarbonyl" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "alkylcarboxy" (e.g. heptylcarboxy, cyclopropylcarboxy, 3- pentenylcarboxy) represents an "alkylcarbonyl" group as defined above wherein the carbonyl is in turn attached through an oxygen bridge. The term "arylcarboxyalkyl" (e.g. phenylcarboxymethyl) represents an "arylcarbonyl" group defined above wherein the carbonyl is in turn attached through an oxygen bridge to an alkyl chain having the indicated number of carbon atoms. The term "arylalkylcarboxy" (e.g. benzylcarboxy, phenylcyclopropylcarboxy and the like) represents an "arylalkylcarbonyl" group as defined above wherein the carbonyl is in turn attached through an oxygen bridge. The term "alkylcarboxyalkyl" represents an "alkylcarboxy" group attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The term "arylalkylcarboxyalkyl" represents an "arylalkylcarboxy" group attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The term "alkylcarbonylamino" (e.g. hexylcarbonylamino, cyclopentylcarbonyl-aminomethyl, methylcarbonylaminophenyl) represents an "alkylcarbonyl" group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of an amino group. The nitrogen atom may itself be substituted with an alkyl or aryl group. The term "arylalkylcarbonylamino" (e.g. benzylcarbonylamino and the like) represents an "arylalkylcarbonyl" group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of an amino group. The nitrogen atom may itself be substituted with an alkyl or aryl group. The term "alkylcarbonylaminoalkyl" represents an "alkylcarbonylamino" group attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The nitrogen atom may itself be substituted with an alkyl or aryl group. The term "arylalkylcarbonylaminoalkyl" represents an "arylalkylcarbonylamino" group attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The nitrogen atom may itself be substituted with an alkyl or aryl group. The term "alkylcarbonylaminoalkylcarbonyl" represents an alkylcarbonylaminoalkyl group attached through a carbonyl group. The nitrogen atom may be further substituted with an "alkyl" or "aryl" group. The term "aryl" represents a substituted or unsubstituted, mono-, di- or trisubstituted monocyclic, polycyclic, biaryl and heterocyclic aromatic groups covalently attached at any ring position capable of forming a stable covalent bond, certain preferred points of attachment being apparent to those skilled in the art (e.g., 3-indolyl, 4-imidazolyl). The aryl substituents are independently selected from the group consisting of halo, nitro, cyano, trihalo-methyl, d-C 6 alkyl, aryl, arylC C 6 alkyl, hydroxy, COOR 3 , CONR 9 R- 10 , C -C 6 alkyloxy, d-Cealkyloxyd-Cβalkyl, aryloxy, aryld- C 6 alkyloxy, aryld-Cealkyloxyd-Cealkyl, thio, C C 6 alkylthio, C C 6 alkylthioC C 6 alkyl, arylthio, arylC C 6 alkylthio, arylCi-Cealkylthiod- C 6 alkyl, NRgRio, d-C 6 -alkylamino, CrC 6 alkylaminoCι-C 6 alkyl, arylamino, aryld-Cβalkylamino, arylCι-C 6 alkyl-aminoCι-C 6 alkyl, di(arylC CealkylJaminoC Ceal yl, d-C 6 alkylcarbonyl, Cι-C 6 alkylcarbonyld- C 6 alkyl, arylCrC 6 alkylcarbonyl, arylCrC 6 alkyl-carbonylCrC 6 alkyl, C C 6 alkylcarboxy, d-C 6 alkylcarboxy-Cι-C 6 alkyl, arylCι-C 6 alkylcarboxy, arylCι-C 6 alkylcarboxyCι-C 6 alkyl, carboxyd-C 6 alkyl-oxy, d- C 6 alkylcarbonylamino, Cι-C 6 alkylcarbonylaminoCι-C 6 alkyl, -carbonylNR 7 C 1 -C 6 alkylCORι , aryld-C 6 alkylcarbonylamino, aryld- C 6 alkylcarbonylaminoC -C 6 alkyl, -CONR 9 R 10 , or -C CealkylCONRgRio; wherein R 3 , Rg, R 10 , and R 1 are defined as above and the alkyl and aryl groups contained therein are optionally substituted as defined above. The definition of aryl includes but is not limited to phenyl, biphenyl, indenyl, fluorenyl, naphthyl (1 -naphthyl, 2-naphthyl), pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), imidazolyl (1 -imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1 ,2,3-triazol-1-yl, 1 ,2,3-triazol-2-yl 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), thiophenyl (2-thiophenyl, 3-thiophenyl, 4-thiophenyl, 5- thiophenyl), furanyl (2-furanyl, 3-furanyl, 4-furanyl, 5-furanyl), pyridyl (2- pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl), 5-tetrazolyl, pyrimidinyl (2- pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6- isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl (2- benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, 5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3- dihydro-benzo[b]furanyl), 3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro- benzo[b]furanyl), 5-(2,3-dihydro-benzo-[b]furanyl), 6-(2,3-dihydro-benzo- [bjfuranyl), 7-(2,3-dihydro-benzo[b]furanyl)), benzo[b]thiophenyl (2- benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5- benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7-benzo[b]thiophenyl), 2,3- dihydro-benzo[b]-thiophenyl (2-(2,3-dihydro-benzo[b]thiophenyl), 3-(2,3- dihydro-benzo[b]-thiophenyl), 4-(2,3-dihydro-benzo[b]thiophenyl), 5-(2,3- dihydro-benzo[b]-thiophenyl), 6-(2,3-dihydro-benzo[b]thiophenyl), 7-(2,3- dihydro-benzo[b]-thiophenyl)), 4,5,6,7-tetrahydro-benzo[b]thiophenyl (2- (4,5,6,7-tetrahydro-benzo-[b]thiophenyl), 3-(4,5,6,7-tetrahydro-benzo- [bjthiophenyl), 4-(4,5,6,7-tetrahydro-benzo[b]thiophenyl), 5-(4, 5,6,7- tetrahydro-benzo-[b]thiophenyl), 6-(4,5,6,7-tetrahydro-benzo- [bjthiophenyl), 7-(4,5,6,7-tetrahydro-benzo[b]thiophenyl)), 4,5,6,7- tetrahydro-thieno[2,3-c]pyridyl (4-(4,5,6,7-tetrahydro-thieno[2,3-c]pyridyl), 5-4,5,6, 7-tetrahydro-thieno[2,3-c]pyridyl), 6-(4,5,6,7-tetrahydro-thieno[2,3- cjpyridyl), 7-(4,5,6,7-tetrahydro-thieno[2,3-c]pyridyl)), indolyl (1-indolyl, 2- indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), isoindolyl (1- isoindolyl, 2-isoindolyl, 3-isoindolyl, 4-isoindolyl, 5-isoindolyl, 6-isoindolyl, 7-isoindolyl), 1 ,3-dihydro-isoindolyl (1-(1 ,3-dihydro-isoindolyl), 2-(1 ,3- dihydro-isoindolyl), 3-(1 ,3-dihydro-isoindolyl), 4-(1 ,3-dihydro-isoindolyl), 5- (1 ,3-dihydro-isoindolyl), 6-(1 ,3-dihydro-isoindolyl), 7-(1 ,3-dihydro- isoindolyl)), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6- indazolyl, 7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8- benzimidazolyl), benzoxazolyl (1-benz-oxazolyl, 2-benzoxazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzo-thiazolyl, 4-benzothiazolyl, 5- benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1- carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl), 5H-dibenz[b,f]azepine (5H-dibenz[b,f]azepin-1-yl, 5H-dibenz-[b,f]azepine-2-yl, 5H- dibenz[b,f]azepine-3-yl, 5H-dibenz-[b,f]azepine-4-yl, 5H-dibenz[b,f]- azepine-5-yl), 10,11 -dihydro-5H-dibenz[b,f]azepine (10,11 -dihydro-5H- dibenz[b,f]azepine-1-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-2-yl, 10,11- dihydro-5H-dibenz[b,f]azepine-3-yl, 10,11-dihydro-5H-dibenz-[b,f]azepine- 4-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-5-yl), piperidinyl (2-piperidinyl, 3-piperidinyl, 4-piperidinyl), pyrrolidinyl (1 -pyrrolidinyl, 2-pyrrolidinyl, 3- pyrrolidinyl), phenylpyridyl (2-phenyl-pyridyl, 3-phenyl-pyridyl, 4- phenylpyridyl), phenylpyrimidinyl (2-phenylpyrimidinyl, 4-phenyl- pyrimidinyl, 5-phenylpyrimidinyl, 6-phenylpyrimidinyl), phenylpyrazinyl, phenylpyridazinyl (3-phenylpyridazinyl, 4-phenylpyridazinyl, 5-phenyl- pyridazinyl). The term "arylcarbonyl" (e.g. 2-thiophenylcarbonyl, 3-methoxy- anthrylcarbonyl, oxazolylcarbonyl) represents an "aryl" group as defined above attached through a carbonyl group. The term "arylalkylcarbonyl" (e.g. (2,3-dimethoxyphenyl)propylcarbonyl, (2-chloronaphthyl)pentenylcarbonyl, imidazolylcyclopentylcarbonyl) represents an "arylalkyl" group as defined above wherein the "alkyl" group is in turn attached through a carbonyl. The term "aryloxyalkyl" represents an "aryloxy" group as defined above attached through an "alkyl" group defined above having the indicated number of carbon atoms. The term "arylaminocarbonylaminoalkyl" represents an "arylaminocarbonylamino" group as defined above attached through an "alkyl" group as defined above having the indicated number of carbon atoms. The term "R8R9Nalkyl" is as defined under "substituted alkyl" or "optionally substituted alkyl". The term "arylaminoalkyl" represents an "arylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "arylcarbonylaminoalkyl" represents an "arylcarbonylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms. As used herein, the term "vicinity" applied with respect to the active site of a PTPase means the space occupied by a half sphere - with its apex pointing towards aspartic acid 48 - having its center in the side chain nitrogen atom of the guanidinium group of residue 221 (arginine), which points away from the phosphate binding loop (residue Arg221 to Cys215). The radius of the half sphere is 27 A. As used herein, the term "structurally similar" means any PTPase that contains an aspartic acid in residue position 48 (PTP1 B numbering - as defined in Chernoff et al, 1989, supra) and is more than 50 % identical and preferably more than 65 % identical and most preferably more than 80 % identical to PTP1 B (Chernoff et al., supra) and/or TC-PTP (Cool et al., Proc. Natl. Acad. Sci. U.S.A. 86: 5257-5261 (1989)) at the primary amino acid sequence level in the catalytic domain as defined below. Percent indentity can be determined using standard algorithms e.g. BLAST, BLASTP MEGALIGN, etc using default parameters. As used herein, the term "catalytic domain" means the primary amino acid sequence of a PTPase that corresponds to the primary amino acid sequence between Asn 40 and Gin 262 (both residues included) in PTP1 B (Chernoff et al., supra). As used herein, the term "centroid" means the position for the stated atoms calculated by averaging the x coordinates of the atoms to obtain the x coordinate of the centroid, averaging the y coordinates of the atoms to obtain the y coordinate of the centroid, and averaging the z coordinates of the atoms to obtain the z coordinate of the centroid. As used herein, the term "phosphate isostere" means a chemical group, which binds to one or more of the side chains or the main chain of the residues in the so-called P-loop or PTP signature motif of PTPases (i.e. Cys215-Xxx216-Xxx217-Xxx218-Xxx219-Xxx220-Arg221 , where Cys215 and Arg221 are absolutely conserved, whereas Xxx stands for less conserved residues). In PTP1B the P-loop residues are: Cys215- Ser216-Ala217-Gly218-lle219-Gly220-Arg221). As a non limiting example the following groups are phosphate isosteres: -CH 2 PO(OH) 2 , -CHFPO(OH) 2 ,-CF 2 PO(OH) 2 , -NHCOCOOH, -OCH(COOH) 2 , -OCF(COOH) 2 , -OCHzCOOH. -CONHCH 2 COOH, -CONHCHFCOOH and -CONHCF 2 COOH. As used herein, the term "carboxylic acid isostere" means a compound resembling a carboxy group in its electronic and steric configuration and in its biological action (effecting inhibition of the class of structurally similar PTPases) but having a different chemical structure. As a non limiting example, the following residues and heterocycles are carboxylic acid isosteres: -CONH 2 , -SONH 2 , -SO 2 NH 2 , u N -"γ OH HN ' OH Υ OH *Y O < X N Y As used herein the term "interact" or "interaction" when used in the context of a moiety or group of an inhibitor interacting with the active site or vicinity thereof of a PTPase, means the formation of noncovalent bonds, such as hydrogen bonds, salt bridges, hydrophobic interactions van der Waals forces, cation π interactions, or π, π interactions, aromatic- aromatic interactions, (Copeland, Enzymes-a practical introduction to structure, mechanism, and data analysis, VCH Publishers, Inc.. New York (1996)) or by forming covalent bonds. Preferably, interactions between inhibitors of the invention and PTPs occur through non-covalent bonds. As used herein, the term "hydrophobic" means a nonpolar chemical group (e.g. phenyl, naphthyl, cyclopropyl, cyclobutyl, cyclohexyl, tetf-butyl, isopropyl as nonlimiting examples) when present in the aqueous phase, in the vicinity of an enzyme, its hydrocarbon framework disturbs the degree of randomness of the water molecules, which forces the water molecules to associate by hydrogen bonding to form quasi-crystalline clusters or "ice-bergs". This localized increase in the ordered structure of water will result in a loss of entropy, accompanied by an increase in the free energy of the system. Thus, a driving force operates to reject the hydrocarbon region of the drug/inhibitor from the aqueous phase so that binding to one or more similar hydrocarbon chain(s) within the enzyme molecule is facilitated. As used herein, the term "hydrogen bond" means an association between an electronegative atom, e.g. fluorine, oxygen, nitrogen, or sulfur, and a hydrogen atom attached to another such electronegative atom. As used herein, the term "salt bridge" means any electrostatic bond between positively and negatively charged groups. The compounds of the present invention have asymmetric centers and may occur as racemates, racemic mixtures, and as individual enantiomers or diastereoisomers, with all isomeric forms being included in the present invention as well as mixtures thereof. Pharmaceutically acceptable salts of the compounds of formula 1 , where a basic or acidic group is present in the structure, are also included within the scope of this invention. When an acidic substituent is present, such as -COOH, 5-tetrazolyl or -P(O)(OH) 2ι there can be formed the ammonium, morpholinium, sodium, potassium, barium, calcium salt, and the like, for use as the dosage form. When a basic group is present, such as amino or a basic heteroaryl radical, such as pyridyl, an acidic salt, such as hydrochloride, hydrobromide, phosphate, sulfate, trifluoroacetate, trichloroacetate, acetate, oxalate, maleate, pyruvate, malonate, succinate, citrate, tartarate, fumarate, mandelate, benzoate, cinnamate, methanesulfonate, ethane sulfonate, picrate and the like, and include acids related to the pharmaceutically acceptable salts listed in Journal of Pharmaceutical Science, 66, 2 (1977) and incorporated herein by reference, can be used as the dosage form. Also, in the case of the -COOH or -P(O)(OH) 2 being present, pharmaceutically acceptable esters can be employed, e.g., methyl, .erf- butyl, acetoxymethyl, pivaloyloxymethyl, and the like, and those esters known in the art for modifying solubility or hydrolysis characteristics for use as sustained release or prodrug formulations. In addition, some of the compounds of the instant invention may form solvates with water or common organic solvents. Such solvates are encompassed within the scope of the invention. As used herein, "treatment" shall include therapeutic or preventative management, treatment, cure, or palliation of a disease state or a measurable delay in its onset or recurrence or measurable reduction in its severity. The term "therapeutically effective amount" shall mean that amount of drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal, or human that is being sought by a researcher, veterinarian, medical doctor or other other biological or clinical investigator.Also included in the present invention is a process for isolation of PTPases via affinity purification procedures based on the use of immobilized compounds of the invention. Isolation can be effected using procedures otherwise well-known to those skilled in the art. Such methods, may be used to identify novel PTPases or other molecules with phosphotyrosine recognition units and to elucidate the function of both novel and previously identified PTPases. As a non- limiting example, compounds of the invention may be immobilized by coupling to a solid-phase support, such as as exemplified in examples 119 and 120. See also Example 121. A tissue sample or a sample from a cell line prepared as a lysate by methods well-known to those skilled in the art may be passed over said solid-phase coupled with a compound of the invention. After appropriate washing procedures designed to remove material that binds nonspecifically to said solid- phase, using standard procedures well known to those skilled in the art, mostly PTPases or other molecules with phosphotyrosine recognition units will be bound to the compounds of the invention coupled to the solid phase. Said PTPases or other molecules with phosphotyrosine recognition units may in turn be released by procedures well-known in the art and further subjected to amino acid sequence analysis according to standard procedures well-known to those skilled in the art. By back-translation of said amino acid sequence into a nucleotide sequence of the corresponding cDNA can be deduced using the appropriate genetic code. Said nucleotide sequence can be used to design and produce an equivalent oligonucleotide, which in turn can be used to identify partial or full-length cDNA clones from appropriate cDNA libraries encoding a protein or glycoprotein corresponding to or similar to the isolated PTPase or molecule with pTyr recognition units. Said oligonucleotide or isolated cDNA clone(s) can similarly be used to isolate genomic clones corresponding to said cDNA clones. Said partial or full-length cDNA can be inserted into appropriate vectors and expressed and purified proteins with procedures well known to those skilled in the art. Said purified proteins, in particular PTPases, may be used to further analyze the inhibitory capacity and selectivity of compounds of the invention as described. The invention is further directed to compounds of the invention coupled to a suitable solid-phase matrix such as a Wang-resin or a Rink-resin, e.g., for further synthesis, combinational synthesis, or as a support for affinity purification. The invention is further directed to a method for isolating a protein or a glycoprotein with affinity for a compound according to the invention from a biological sample, comprising: • contacting a compound of the invention immobilized by coupling to a suitable solid-phase matrix with said biological sample in order for said immobilized compound to form a complex by binding said protein or glycoprotein, • removing unbound material from said biological sample and isolating said complex, and • extracting said protein or glycoprotein from said complex. The invention is further directed to a method for isolating a protein-tyrosine phosphatase with affinity for a compound according to the invention from a biological sample, comprising • contacting a compound of the invention immobilized by coupling to a suitable solid-phase matrix with said biological sample in order for said immobilized compound to form a complex by binding said protein-tyrosine phosphatase • removing unbound material from said biological sample and isolating said complex • extracting said protein-tyrosine phosphatase. The following compounds are encompassed by the invention: 5-(4-Chloro-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalylamino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(2,4-Dioxo-thiazolidin-3-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid; 5-(4,5,6,7-Tetrachloro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(1 ,3-Dioxo-1 ,3-dihydro-benzo[f]isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; Oxalic acid (3-carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran- 5-ylmethyl) ester methyl ester; Oxalic acid (3-carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran- 5-ylmethyl) ester; 7-Hydroxymethyl-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid; 7-(((Benzo[1 ,3]dioxole-5-carbonyl)-amino)-methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(3-lmidazol-1-yl-2,5-dioxo-pyrrolidin-1-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid; 2-(Oxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid; 2-(Oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7-dicarboxylic acid 7-ethyl ester; 7-Benzylcarbamoyl-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-b]pyrazin-6-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-(4-Chloro-phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihydro-pyrrolo[3,4- c]pyridin-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3 carboxylic acid; 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yloxymethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-b]pyridin-6-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(3-(2,4-Dimethoxy-phenyl)-ureidomethyl)-2-(oxalyl-amino)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-((3-Carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-5- ylmethyl)-carbamoyl)-nicotinic acid; 5-(4-Fluoro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Benzyloxy-1 ,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5,7-Dioxo-5,7-dihydro-[1,3]dioxolo[4,5-f]isoindol-6-ylmethyl2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(2,4-Dioxo-5-pyridin-2-ylmethylene-thiazolidin-3-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(2,4-Dioxo-5-pyridin-2-ylmethyl-thiazolidin-3-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(4-Methoxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(4-Acetylamino-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(3,5-Dimethoxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(1 H-lmidazol-4(5)-ylmethylene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-(4-Methanesulfonyl-phenyl)-acetylamino)-methyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(1 ,3-Dioxo-4,7-epoxido-1 , 3,4,5, 6,7-hexahydro-isoindol-2-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Amino-3-phenyl-propionylamino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(((2R)-2-Amino-3-phenyl-propionylamino)-methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino)-methyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Acetylamino-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Acetylamino-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-b]pyridin-6-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-c]pyridin-6-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Nitro-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-7-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 H-benzo[d]isothiazol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-7-(3-oxo-3H-benzo[djisoxazol-2-ylmethyl)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-ethyl ester; 5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; (L)-5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Hydroxy-1,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(1 -oxo-1, 3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(5-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(((Benzo[1 ,3]dioxole-5-carbonyl)amino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-(4-Chloro-phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihydro-pyrrolo[3,4- c]pyridin-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid; 7-(3-(2,4-Dimethoxy-phenyl)-ureidomethyl)-2-(oxalyl-amino)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-(4-Methanesulfonyl-phenyl)acetylamino)methyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Acetylamino-3-(4-hydroxy-phenyl)propionylamino)methyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(S)-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(S)-(1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-methyl-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-((1 , 1 -Dioxo-1 H-benzo[d]isothiazol-3-ylamino)methyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-((1 , 1 -Dioxo-1 H-benzo[d]isothiazol-3-ylamino)methyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Methoxy-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Hydroxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Benzyloxy-1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Hydroxy-1-oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 2-(oxalyl-amino)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(7-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(7-Hydroxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 2-(oxalyl-amino)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; MISSING AT THE TIME OF PUBLICATION 6-(4-Methoxy-benzyl)-5-((2-(5-methoxy-2-methyl-1 H-indol-3-yl)- acetylamino)methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 5-(R)-(7-Methoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-(7-Methoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-(4-Hydroxy-1 -oxo-1, 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(S)-(Oxalyl-amino)-5-((4-phenoxy-benzylamino)methyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-((4-Acetylamino-benzylamino)methyl)-2-(oxalyl-amino)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(S)-((Ace tyl-(4-phenoxy-benzyl)amino)methyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(S)-((Acetyl-benzyl-amino)methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-((1 , 1 -Dioxo-1 H-benzo[d]isothiazol-3-ylamino)methyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(6-Methoxy-4-methoxycarbonyl-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 H-benzo[d]isothiazol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-7-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 H-benzo[d]isothiazol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(R)-Carbamoyl-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3-carboxylic acid; 2-(Oxalyl-amino)-5-(S)-(2-oxo-tetrahydro-thiophen-3-ylcarbamoyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(S)-phenylcarbamoyl-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-7-(R)-phenylcarbamoyl-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 5-(R),7-(R)-Bis-benzyloxymethyl-2-(oxalyl-amino)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid; 6-Benzyl-2-(oxalyl-amino)-5-(1 ,1,3-trioxo-1 ,3-dihydro-1 ,6- benzo[d]isothiazol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid; or a pharmaceutically acceptable salt thereof PHARMACOLOGICAL METHODS The compounds are evaluated for biological activity with a truncated form of PTP1B (corresponding to the first 321 amino acids), which was expressed in E. coli and purified to apparent homogeneity using published procedures well-known to those skilled in the art. The enzyme reactions are carried out using standard conditions essentially as described by Burke et al. (Biochemistry 35; 15989-15996 (1996)) incorporated by reference. The assay conditions are as follows. Appropriate concentrations of the compounds of the invention (e.g., 0.1 to 100μM) are added to the reaction mixtures containing different concentrations of the substrate, p-nitrophenyl phosphate (range: 0.16 to 10 mM - final assay concentration). The buffer used was 50 mM HEPES pH 7.0, 100 mM sodium chloride, 0.1 % (w/v) bovine serum albumin, 5 mM glutathione, and 1 mM EDTA. The reaction was started by addition of the enzyme and carried out in microtiter plates at 25° C for 60 minutes. The reactions are stopped by addition of NaOH. The enzyme activity was determined by measurement of the absorbance at 405 nm with appropriate corrections for absorbance at 405 nm of the compounds and p-nitrophenyl phosphate. The data are analyzed using nonlinear regression fit to classical Michaelis Menten enzyme kinetic models. Inhibition is expressed as Kj values in μM. The results of representative experiments are shown in Table 6. Table 6 Inhibition of classical PTPases by compounds of the invention PTP1 B TC-PTP PT α PTP β PTP ε residue residue residue residue residue 48 48 48 48 48 Example No. Asp Asp Asn Asn Asn 48 0.25 900 47 380 49 0.085 8.6 50 0.07 1000 8 52 1.2 > 400 107 > 500 THE SYNTHESIS OF THE COMPOUNDS In accordance with one aspect of the invention, compounds of the invention are prepared as illustrated in the following reaction schemes wherein n, m, X, Y, Ri, R 2 , R 3 , R , R5 and R 6 are defined as above: Method A a) NCCH 2 COOR 3 , sulphur, morpholine or triethylamine, ethanol; b) R 3 OCOCOimidazole, tetrahydrofuran; c) 25 % trifluoroacetic acid/dichloromethane. Method B MISSING AT THE TIME OF PUBLICATION MISSING AT THE TIME OF PUBLICATION The pharmaceutical carrier employed may be a conventional solid or liquid carrier. Examples of solid carriers are lactose, terra alba, sucrose, talc, gelatine, agar, pectin, acacia, magnesium stearate and stearic acid. Examples of liquid carriers are syrup, peanut oil, olive oil, water, and physiologic saline. Similarly, the carrier or diluent may include any material that impacts controlled release of taste-masking properties, known to the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. If a solid carrier for oral administration is used, the preparation can be tabletted, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge. The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatin capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution. Generally, the compounds of this invention are dispensed in unit dosage form comprising 10-200 mg of active ingredient in or together with a pharmaceutically acceptable carrier per unit dosage. The dosage of the compounds according to this invention is 1- 500 mg/day, e.g. about 100 mg per dose, when administered to patients, e.g. humans, as a drug. A typical tablet that may be prepared by conventional tabletting techniques contains Core: Active compound (as free compound 100 mg or salt thereof) Colloidal silicon dioxide (Areosil ® ) 1.5 mg Cellulose, microcryst. (Avicel ® ) 70 mg Modified cellulose gum (Ac-Di-Sol ® ) 7.5 mg Magnesium stearate Coating: HPMC approx. 9 mg * Mywacett ® 9-40 T approx. 0.9 mg Acylated monoglyceride used as plasticiser for film coating. The route of administration may be any route which effectively transports the active compound to the appropriate or desired site of action, such as oral or parenteral e.g. rectal, transdermal, subcutaneous, intranasal, intramuscular, topical, intravenous, intra urethra I, ophthalmic solution or an ointment, the oral route being preferred. EXAMPLES The process for preparing compounds of Formula 1 and preparations containing them is further illustrated in the following examples, which, however, are not to be construed as limiting. Hereinafter, TLC is thin layer chromatography, CDCI 3 is deuterio chloroform, CD 3 OD is tetradeuterio methanol and DMSO-d 6 is hexadeuterio dimethylsulfoxide. The structures of the compounds are confirmed by either elemental analysis or NMR, where peaks assigned to characteristic protons in the title compounds are presented where appropriate. 1 H NMR shifts (δ H ) are given in parts per million (ppm) down field from tetramethylsilane as internal reference standard. M.p.: is melting point and is given in °C and is not corrected. Column chromatography was carried out using the technique described by W.C. Still et al., J. Org. Chem. 43: 2923 (1978) on Merck silica gel 60 (Art. 9385). HPLC analyses are performed using 5μm C184 x 250 mm column eluted with various mixtures of water and acetonitrile, flow = 1 ml/min, as described in the experimental section. Wang-resin is polystyrene with a 4-hydroxymethylphenol ether linker. Compounds used as starting material are either known compounds or compounds which can readily be prepared by methods known per se. EXAMPLE 1 5-(4-Chloro-1.3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4.7-dihydro-5H-thienor2,3-clpyran-3-carboxylic acid To a mixture of benzyloxyacetaldehyde (8.3 g, 0.06 mol) in benzene (80 mL) was added 1-methoxy-3-trimethylsilyloxy-1 ,3-butadiene (10.6 g, 0.06 mol). The reaction mixture was stirred under nitrogen for 15 min., cooled to 0 °C and a solution of 0.5 M zinc chloride (55 ml, 0.03 mol) was added dropwise. The reaction mixture was allowed to warm to room temperature over 16 h and evaporated in vacuo. The resultant oil was diluted with ethyl acetate (100 ml), washed with 1N hydrochloric acid (3 x 50ml), saturated sodium bicarbonate (3 x 50 ml), brine (3 x 50 ml), dried (MgSO ) and evaporated in vacuo. The resulting oil was subjected to flash chromatography using a mixture of ethyl acetate/hexanes (1 :2) as eluant. Pure fractions were collected affording after evaporation in vacuo 7.1 g (60 %) of benzyloxy-methyl-2,3-dihydro-pyran-4-one as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 7.39 - 7.31 (m, 6H), 5.42 (dd, J = 6,1 Hz, 1 H), 4.61 (d, J = 3 Hz, 1 H), 4,57 (m, 1 H), 3.70 (m, 2H), 2.74 (dd, J = 17 Hz, 14 Hz, 1 H), 2.41 (ddd, J = 17 Hz, 2 Hz, 1 Hz, 1 H). The above 2,3-dihydro-pyran-4-one (7.1 g, 0.032 mol) and 10 % palladium on carbon (0.4 g) in ethyl acetate (50 ml) were placed in a Parr bomb shaker and hydrogenated at 30 psi. The reaction mixture was shaken for 2 h, at which time TLC analysis (methanol/dichloromethane 1:9) indicated the reaction was complete. The reaction mixture was filtered through a pad of Celite and the volatiles evaporated in vacuo. The residue was subjected to flash column chromatography using ethyl acetate as eluant. Pure fractions were collected affording after evaporation in vacuo 3.0 g (75 %) of 2-hydroxymethyl-tetrahydro-pyran-4-one as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 4.36 - 4.29 (m, 1 H), 3.77 - 3.66 (m, 3H), 3.61 - 3.54 (m, 1 H), 2.65 - 2.43 (m, 2H), 2.34 - 2.27 (m, 2H), 2.04 (bs, 1 H, CH 2 OH). The above tetrahydro-pyran-4-one (1.90 g, 0.015 mol), terf-butyl cyanoacetate (2.7 g, 0.019 mol), sulfur (0.51 g, 0.016 mol) and morpholine (2.55 ml, 0.03 mol) were dissolved in absolute ethanol (20 ml), and heated to 50 °C for 16 h. The reaction mixture was cooled, filtered and the filtrate evaporated in vacuo. The resultant oil was dissolved in ethyl acetate (50 ml), washed with water (2 x 50 ml), brine (2 x 50 m) and dried (MgSO ). The solvent was evaporated in vacuo and the residue was subjected to flash column chromatography using ethyl acetate/hexanes (1 :1) as eluant. Pure fractions were collected affording after evaporation in vacuo 3.7 g (90 %) of 2-amino-5-hydroxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid terf-butyl ester as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 4.64 (s, 2H), 3.80 - 3.67 (m, 3H), 2.77 - 2.72 (m, 1 H), 2.57 - 2.53 (m, 1 H), 1.54 (s, 9H). The above carboxylic acid tert-butyl ester (1.0 g, 3.5 mmol), 4- chloro-1 ,3-dioxo-1 ,3-dihydro-isoindol (0.67 g, 3.7 mmol) and triphenylphosphine (1.01 g, 3.9 mmol) were dissolved in dry tetrahydrofuran (30 ml) and cooled to 0 °C under a nitrogen atmosphere. Diisopropyl azodicarboxylate (DIAD) (0.62 ml, 3.9 mmol) was added dropwise at 0 °C and the solution allowed to stir overnight, slowly warming to room temperature. The volatiles were evaporated in vacuo and the resultant solid dissolved in ethyl acetate (50 ml). The organic phase was washed with brine (3 x 50 ml), dried (Na 2 SO 4 ), filtered and evaporated in vacuo. The residue was subjected to flash column chromatography (300 ml silicagel) using a mixture of ethyl acetate/hexanes (1 :3) as eluant. Semi pure fractions were collected affording after evaporation in vacuo 0.7 g which was trituated with diethyl ether. The solid was filtered off and washed with diethyl ether and dried in vacuo affording 0.13 g (27 %) of 2- amino-5-(4-chloro-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as a solid. The filtrate was evaporated in vacuo. The residue (0.48 g) was subjected to flash column chromatography (300 ml silicagel) using a mixture of ethyl acetate/hexanes (1:3) as eluant. Pure fractions were collected affording after evaporation in vacuo an additional 0.36 g (23 %) of 2-amino-5-(4- chloro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid terf-butyl ester as a solid. To the above 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert butyl ester (0.36 g, 0.8 mmol) dissolved in tetra hydrofu ran (20 ml) was added a mixture of imidazol-1-yl-oxo-acetic acid tert butyl ester (0.31 g, 1.6 mmol) in tetra hydrofu ran (3.4 ml) under nitrogen. The reaction mixture was allowed to stir at room temperature for 18 hours. An additional portion of imidazol-1 -yl-oxo-acetic acid tert butyl ester (0.3 g, 1.6 mmol) in tetrahydrofuran (2 ml) was added. The reaction mixture was allowed to stir at room temperature for an additional 60 h. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (3 x 50 ml). The combined organic phases were washed with brine (3 x 50 ml) dried (Na 2 SO 4 ), filtered and the organic phase evaporated in vacuo. The residue (0.5 g) was purified by column chromatography (300 ml silicagel) using a mixture of ethyl acetate/heptane (1 :2) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 0.36 g (80 %) of 2-(terf-butoxyoxalyl-amino)-5-(4-chloro-1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester as a solid. The above di-terf-butyl ester (0.3 g, 0.52 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.5 ml) was added. The reaction was stirred at room temperature for 18 h. The volatiles were evaporated jn vacuo and the residue trituated with a mixture of diethyl ether and heptane (1:1) (5 ml). The precipitate was filtered off, washed with heptane and diethyl ether, dried in vacuo at 50 °C for 18 h which afforded 200 mg (69 %) of the title compound as a solid. M.p.: > 250 °C Calculated for C 19 H 13 N 2 CIO 8 S; C, 49.09 %; H, 2.82 %; N, 6.03 %. Found: C, 48.79 %; H, 2.79 %; N, 5.89 %. EXAMPLE 2 5-(4,5.6.7-Tetrachloro-1 ,3-dioxo-1.3-dihvdro-isoindol-2-ylmethvn-2-(oxalyl- amino)-4,7-dihvdro-5H-thienof2,3-clpyran-3-carboxylic acid In a 4 ml scintillating vial, a solution of tetrachloro phthalimide (148 mg, 0.52 mmol) in N,N-dimethylformamide (2.0 ml) was heated to 100°C for 10 minutes and treated with potassium hydride (55 mg, 0.48 mmol, 35 % w/w dispersion in mineral oil). The resulting mixture was stirred until gas generation ended, 2-(ter_-butoxyoxalyl-amino)-5-(4-nitro-benzenesulfonyl- oxymethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (151 mg, 0.25 mmol) and 18-crown-6 ether (31 mg, 0.12 mmol) were added. The solution was flushed with nitrogen gas before being stirred at 80°C for 25 h. The volatiles were evaporated in vacuo and the residue purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (5:1) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 39 mg (23 %) of 2-(te/t-butoxyoxalyl- amino)-5-(4,5,6,7-tetrachloro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid .erf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 12.50 (s, 1 H), 4.80 (d, J = 16, 1 H), 4.67 (d, J = 14, 1 H), 4.14-3.99 (m, 2H), 3.84( d, J = 9, 1 H), 2.99 (d, J = 17, 1 H), 2.70 (dd, J = 17, 5, 1 H), 1.60 (s, 9H), 1.56 (s, 9H). HPLC (254.4 nm) R t =5.80 min, 95%. In a 25 ml round bottom flask, 2-(te/t-butoxyoxalyl-amino)-5-(4,5,6,7- tetrachloro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (39 mg, 0.06 mmol) was dissolved in 20 % trifluoroaceetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring for 24 h. A precipitate was filtered off and washed with diethyl ether, affording after drying 29 mg (90 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.32 (s, 1 H), 4.76 (d, J = 16, 1 H), 4.59 (d, J = 14, 1H), 4.0-3.6 (m partially obscured by water, 3H), 3.1 (d partially obscured by water, J = 17, 1 H), 2.61 (dd partially obscured by DMSO, J = 20, 11, 1H). HPLC (254.4 nm) R,=4.15 min, 75 %. EXAMPLE 3 5-(5-Methoxy-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihvdro-5H-thieno.2,3-c1pyran-3-carboxylic acid To a solution of 4-hydroxyphthalic acid (0.25 g, 1.37 mmol) in anhydrous N,N-dimethylformamide (3 ml) under nitrogen was added sodium hydride (0.22 g, 5.48 mmol). The solution was stirred for 5 minutes and then methyl iodide (0.68 ml) was added and continued stirring for 3 hours. Several drops of water were added to quench the reaction and the mixture was concentrated in vacuo. The crude material was partitioned between ethyl acetate (40 ml) and water (10 ml). The layers were separated and the organic layer washed with brine (2 x 10 ml), dried(Na 2 SO ), filtered and the solvent evaporated in vacuo. The resulting oil was dissolved in methanol (8 ml) and 1 N sodium hydroxide (4 ml) was added. The reaction was stirred at ambient temperature for 24 h., after which LC-MS indicated only partial hydrolysis. The material was reconstituted in methanol (5 ml) and treated with of sodium hydroxide (0.12 g, 3.0 mmol) dissolved in water (1 ml). The reaction mixture was stirred for 48 h., at which time a precipitate had formed. The mixture was acidified with 6N hydrochloric acid until pH = 1 , causing the solution to become homogeneous. The reaction was concentrated in vacuo and the residue partitioned between ethyl acetate (30 ml) and 0.5N hydrochloric acid (10 ml). The layers were separated and the organic layer concentrated in vacuo to give 100 mg (51 %) of 4-methoxy-phthalic acid as a solid. 1 H NMR (300 MHz, CD 3 OD) δ 7.83 (d, J = 8, 1H), 7.10-7.06 (m, 2H), 3.87 (s, 3H). LC-MS: R,=1.45 min, [M+H] + = 197.1 A solution of 4-methoxy-phthalic acid (0.10 g, 0.51 mmol), 1-hydroxy- benzotriazole (0.15 g, 1.1 mmol), 1-(3-dimethylaminopropyl)-3-ethyl- carbodiimide hydrochloride (0.22 g, 1.1 mmol), and triethylamine (0.35 ml, 2.5 mmol) was prepared in distilled acetonitrile (4 ml) under nitrogen. 2- Amino-5-aminomethyl-4,7-dihydro-5H-thieno-[2,3-c]pyran-3-carboxylic acid tert-butyl ester (0.11 g, 0.39 mmol) was added in small portions and the reaction was stirred at ambient temperature for 18 h., and then concentrated in vacuo. The crude mixture was diluted in ethyl acetate (30 ml) and washed with 1% hydrochloric acid (5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The organic layer was dried (Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a 10 % mixture of ethyl acetate/dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 54 mg (31 %) of 2-amino-5- (5-methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno-[2,3-c]pyran-3-carboxylic acid terf-butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 7.76 (d, J = 8, 1 H), 7.32 (s, 1 H), 7.14 (d, J = 8, 1 H), 4.62-4.48 (m, 2H), 4.00-3.72 (m, 3H), 3.91 (s, 3H), 2.86 (d, J = 17, 1 H), 2.55 (dd, = 17 , 10, 1 H), 1.49 (s, 9H). To a solution of the above 2-amino-5-(5-methoxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno-[2,3-c]pyran-3- carboxylic acid tet -butyl ester (54 mg, 0.12 mmol) in distilled dichloromethane (3 ml) under nitrogen was added midazol-1-yl-oxo-acetic acid terf-butyl ester (0.25 g, 0.36 mmol) and triethylamine (50 μl, 0.36 mmol). The reaction was stirred for 4 h., concentrated in vacuo and the residue reconstituted in ethyl acetate (20 ml). The organic layer was washed with 1 % hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The organic phase was dried (Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a 5% mixture of ethyl acetate/dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 56 mg (81 %) of 2-(tert- butoxyoxalyl-amino)-5-(5-methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,7-dihydro-5H-thieno-[2,3-c]pyran-3-carboxylic acid te/ -butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 12.48 (s, 1 H), 7.75 (d, J = 8, 1 H), 7.32 (d, J = 2 , 1 H), 7.15 (dd, J = 8, 2, 1 H), 4.78 (d, J = 15, 1 H), 4.65 (d, J = 15, 1 H), 4.03-3.75 (m, 3H), 3.91 (s, 3H), 2.95 (d, J = 17, 1 H), 2.66 (dd, J = 17, 9 , 1 H), 1.58 (s, 9H), 1.54 (s, 9H). APCI-MS: [M+H] + = 574 The above 2-(.er.-butoxyoxalyl-amino)-5-(5-methoxy-1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno-[2,3-c]pyran-3- carboxylic acid .erf-butyl ester (55 mg, 0.096 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (4 ml). The reaction was stirred at ambient temperature for 7 h., concentrated in vacuo and evaporated vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 17 mg (40%) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.32 (s, 1 H), 7.81 (d, J = 8 , 1 H), 7.40 (d, J = 2, 1 H), 7.31 (dd, J = 8 , 2, 1 H), 4.75 (d, J = 15, 1 H), 4.56 (d, J = 15, 1 H), 3.92 (s, 3H), 3.91-3.69 (m, 3H), 2.98 (d, J = 17, 1 H), 2.57 (dd, J = 17, 9, 1 H). APCI-MS: [M-H] " = 459 HPLC (254.4nm): R,=3.36 min, 98% EXAMPLE 4 5-(4-Hvdroxy-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thienof2,3-clpyran-3-carboxylic acid 5-(4-Benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(te/t- butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid te/t-butyl ester was prepared in a similar way as described in Example 1. To a solution of the above benzylether (0.7 g, 1.08 mmol) in ethyl acetate (50 ml) was added 10 % palladium on carbon (0.2 g). The mixture was hydrogenated at 1 atm. for 5 h, filtered and the volatiles evaporated in vacuo. The residue (0.6 g) was purified by column chromatography (500 ml silicagel) using a mixture of ethyl acetate/heptane (1 :1) as eluant. Pure fractions were collected and the solvent evaporated m vacuo affording 0.4 g (67 %) of 2-(.er -butoxyoxalyl-amino)-5-(4-hydroxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid terf-butyl ester as an oil. TLC: R f = 0.2 (ethyl acetate/heptane 1 :1 ) The above di-.e -butyl ester (0.4 g, 0.72 mmol) was dissolved in 25 % trifluoroacetic acid in dichloromethane (25 ml). The reaction was stirred at room temperature for 18 h. The volatiles were evaporated in vacuo and the residue trituated with diethyl ether (5 ml). The precipitate was filtered off, washed with heptane and diethyl ether, dried in vacuo at 50 °C for 18 h which afforded 230 mg (72 %) of the title compound as a solid. M.p.: > 250 °C; Calculated for Cι 9 Hι 4 N 2 O 9 S, 0.5 x H 2 O; C, 50.1 1 %; H, 3.32 %; N, 6.15 %. Found: C, 50.06 %; H, 3.17 %; N, 5.98 %. EXAMPLE 5 5-(4-Benzyloxy-1 ,3-dioxo-1.3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4.7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid 5-(4-Benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(tetιf- butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylιc acid .ett-butyl ester (0.7 g, 1.08 mmol) (prepared in a similar way as described in Example 1 ) was dissolved in 25 % trifluoroacetic acid in dichloromethane (25 ml). The reaction was stirred at room temperature for 18 h. The volatiles were evaporated in vacuo and the residue trituated with diethyl ether (25 ml). The precipitate was filtered off, washed with diethyl ether and dried m vacuo at 50 °C for 3 hours which afforded 400 mg (69 %) of the title compound as a solid.. M.p.: 194 - 196 °C; Calculated for C 26 H 2 oN 2 O 9 S, 1 x H 2 O, 0.6 x CF 3 COOH; C, 52.44 %; H, 3.66 %; N, 4.50 %. Found: C, 52.33 %; H, 3.65 %; N, 4.62 %. EXAMPLE 6 5-(4-Fluoro-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-arnino)- 4,7-dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid Prepared in a similar way as described in Example 1. M.p.: > 250 °C; Calculated for C 19 Hι 3 FN 2 O 8 S, 1 x H 2 O; C, 48.93 %; H, 3.24 %; N, 6.01 %. Found: C, 48.90 %; H, 3.15 %; N, 5.86 %. EXAMPLE 7 5-(1 ,3-Dioxo-1.3-dihvdro-benzorflisoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid In a 4 ml scintillating vial, a solution of benzo[/]isoindole-1 ,3-dione (145 mg, 0.74 mmol) in N,N-dimethylformamide (2.0 ml) was treated with potassium hydride (55 mg, 0.48 mmol, 35 % w/w dispersion in mineral oil). The resulting mixture was stirred until gas generation ended and the resulting precipitate was filtered off and washed with dichloromethane which afforded 121 mg (69 %) of benzo[ ]isoindole-1 ,3-dione potassium salt as a solid. 1 H NMR (300 MHz, D 2 O) δ 8.00-7.87 (m, 4H), 7.62 (s, 2H). In a 4 ml scintillating vial, the above potassium salt (121 mg, 0.5 mmol) in N,N-dimethylformamide (1.5 ml) was treated with 18-crown-6 ether (34 mg, 0.13 mmol) and 2-(.etf-butoxyoxalyl-amino)-5-(4-nitro- benzene-sulfonyloxymethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid erf-butyl ester (148 mg, 0.25 mmol). The solution was flushed with nitrogen gas before being stirred at 80 °C for 7 h. The volatiles were evaporated in vacuo and the residue purified by silica gel chromatography using a mixture of ethyl acetate/dichloromethane (1.49) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 85 mg (57 %) of 2-(terf-butoxyoxalyl-amino)-5-(1 ,3-dioxo- 1 ,3-dihydro-benzo[/]isoindole-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid te/t-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 12.52 (s, 1 H), 8.37 (s, 2H), 8.08 (m, 2H), 7.72 (m, 2H), 4.84-4.65 (m, 2H), 4.16-3.90 (m, 3H), 3.02 (d, J = 17, 1 H), 2.73 (dd, J = 17, 10, 1 H), 1.61 (s, 9H), 1.58 (s, 9H). In a 25 ml round bottom flask the above 2-(ter.-butoxyoxalyl- amino)-5-(1 ,3-dioxo-1 ,3-dihydro-benzo[ ]isoindole-2-ylmethyl)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid tetf-butyl ester (85 mg, 0.14 mmol) was dissolved in 20 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring for 24 h. The precipitate was filtered off and washed with diethyl ether, affording after drying 62 mg (90 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.32 (s, 1 H), 9.02 (s, 2), 4.81-4.59 (m, 2H), 3.97-3.81 (m partially obscured by water, 3H), 3.08 (d, J = 18, 1 H), 2.74-2.53 (m partially obscured by DMSO, 1 H). EXAMPLE 8 5-(5-Acetylamino-1 ,3-dioxo-1.3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihvdro-5H-thienof2,3-c1pyran-3-carboxylic acid To a solution of N-(1 ,3-dioxo-2,3-dihydro-1 H-isoindol-5-yl)- acetamide (51 mg, 0.25 mmol) in N,N-dimethylformamide (1.5 ml) under nitrogen at room temperature was added potassium hydride (35 wt.% dispension in mineral oil, 29 mg, 0.25 mmol). The solution was stirred at room temperature for 3 hours. A solid precipitated during this period. 2- (.ert-Butoxyoxalyl-amino)-5-(4-nitro-benzene-sulfonyloxymethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid .erf-butyl ester (100 mg, 0.17 mmol) was added to the suspension and the solution was stirred at 80 °C for 12 h. The solvent was evaporated in vacuo, the resulting residue purified by silica gel chromatography using a gradient of ethyl acetate/hexane (10-25%) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 50 mg (50 %) of 5-(5-acetylamino- 1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(ter.-butoxyoxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tetf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 12.53 (s, 1 H), 8.03 (d, 1 H, J = 1.5 Hz), 7.91 (dd, 1 H, J = 7.8, 1.8 Hz) 7.83 (d, 1 H, J = 8.1 Hz), 7.45 (s, 1 H), 4.80 (d, 1 H, J = 16 Hz), 4.66 (d, 1 H, J = 16 Hz), 4.03 (m, 2H), 3.83 (q, 1 H, J = 15 Hz), 2.98 (d, 1 H, J = 9 Hz), 2.64-2.78 (m, 1 H), 2.27 (s, 3H), 1.62 (s, 9H), 1.57 (s, 9H). To a mixture of trifluoroacetic acid/dichloromethane (2 ml, 1 :1 ) at room temperature was added the above 5-(5-acetylamino-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-2-(fer.-butoxyoxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid tetf-butyl ester (40 mg, 0.067 mmol). The solution was stirred for 5 h. at which time the solvent was removed in vacuo. The residue was washed with dichloromethane, filtered off, and dried in vacuo which afforded 23 mg (70 %) of the title compound as a solid. 1 H NMR (DMSO-d 6 ): δ 12.32 (s, 1H), 10.58 (s, 1H), 8.21 (s, 1H) 7.84 (s, 2H), 4.76 (d, 1 H, J = 15 Hz), 4.58 (d, 1 H, J = 15 Hz), 3.80-4.00 (m, 3H), 3.00 (d, 1H, J= 17 Hz), 2.58-2.73 (m, 1H), 2.13 (s, 3H). MS:488(M+1). EXAMPLE 9 5-(4-Acetylamino-1,3-dioxo-1.3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid The title compound was prepared in a similar way as described for Example 8. '1 H NMR (DMSO-d 6 ):δ 12.32 (s, 1H), 9.76 (s, 1H), 8.45 (d, 1H, J = 8.4 Hz) 7.79 (t, 1H, J = 8.4Hz), 7.58 (d, 1H, J = 8.4 Hz), 4.77 (d, 1H, J=15Hz), 4.58 (d, 1H, J = 15 Hz), 3.68-3.94 (m, 3H), 3.02 (d, 1H, J = 16 Hz), 2.55- 2.78 (m, 1H), 2.20 (s, 3H). MS:488(M+1). EXAMPLE 10 5-(5,7-Dioxo-5,7-dihvdro-pyrrolo[3,4-blpyrazin-6-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid In a 4-ml scintillating vial, a solution of 2-amino-5-aminomethyl- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid erf-butyl ester (148 mg, 0.5 mmol) in tetrahydrofuran (1.0 ml) was treated with a solution of pyrazine phthtalic acid anhydride (85 mg, 0.56 mmol) in tetrahydrofuran (1.0 ml) and N,N-dimethylformamide (0.5 ml). The reaction mixture was allowed to stir at room temperature for 1 h. Diisopropylethylamine (220 μl, 0.13 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (121 mg, 0.6 mmol) were then added. The reaction mixture was shaken vigorously for 10 seconds before being stirred at room temperature for 14 h. The volatiles were evaporated in vacuo and the residue purified by silica gel chromatography using a mixture of dichloromethane/ethyl acetate (3:1 ) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 25 mg (12 %) of the 2-amino-5-(5,7-dioxo-5,7-dihydro-pyrrolo[3,4-b]pyrazin-6-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid .erf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) d 8.97 (s, 2H), 4.62-4.49 (m, 2H), 4.21-4.04 (m, 2H), 3.94 (dd, = 14, 4, 1 H), 2.91 (d, J = 17, 1 H), 2.63 (dd, J = 17, 10, 1 H), 1.68 (s, 9H). In a 4 ml scintillating vial a solution of the above 2-amino-5-(5,7- dioxo-5,7-dihydro-pyrrolo[3,4-b]pyrazin-6-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (25 mg, 0.06 mmol) in tetrahydrofuran (3 ml) was treated with midazol-1-yl-oxo-acetic acid ferf- butyl ester (0.36 mmol). After stirring for 3 hours at room temperature the reaction solution was concentrated to dryness in vacuo. The residue was purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (3:1 ) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 31 mg (95 %) of 2-(.erf-butoxyoxalyl- amino)-5-(5,7-dioxo-5,7-dihydro-pyrrolo[3,4-b]pyrazin-6-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 12.49 (s, 1 H), 8.96 (s, 2H), 4.80-4.61 (m, 2H), 4.21-4.04 (m, 2H), 3.96 (dd, = 14, 4, 1 H), 3.03 (d, J = 16, 1 H), 2.70 (dd, J = 17, 10, 1 H), 1.60 (s, 9H), 1.59 (s, 9H). In a 25 ml round bottom flask the above 2-(fetf-butoxyoxalyl- amino)-5-(5,7-dioxo-5,7-dihydro-pyrrolo[3,4-b]pyrazin-6-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester, (31 mg, 0.06 mmol) was dissolved in 20 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring for 24 h. A precipitate was filtered off and washed with diethyl ether, affording after drying 22 mg (90 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 9.02 (s, 2), 4.81-4.59 (m, 2H), 3.97-3.81 (m partially obscured by water, 3H), 3.08 (d, J = 18, 1 H), 2.74-2.53 (m partially obscured by DMSO, 1 H). HPLC (254.4 nm) R t =2.97 min, 89%. MS (APC-0 [M-H] 432.4 EXAMPLE 11 -(5,7-Dioxo-5,7-dihvdro-pyrrolof3,4-b.pyridin-6-ylmethyl)-2-(oxalyl-amino)- ,7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid A solution of furo[3,4-b]pyridine-5,7-dione (86.1 mg, 0.58 mmol) and of 2-(fer-butoxyoxalyl-amino)-7-aminomethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (194 mg, 0.47 mmol) in acetonitrile (2.0 ml) was stirred for 10 min. at room temperature. 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (89.2 mg, 0.564 mmol) and triethylamine (198 μl, 1.41 mmol) were added and the mixture was stirred at room temperature for 20 h. The volatiles were removed vacuo and the crude product dissolved in dichloromethane (60 ml) and washed with water (3 x 30ml). The organic layer was dried (MgSO ), filtered and the solvent removal in vacuo. The residue (338 mg) was purified by column chromatography on silica gel utilizing a mixture of hexane/ethyl acetate (90/10 to 50/50) as gradient which afforded after evaporation of the solvent in vacuo 85 mg (33 %) of 2-(ferf-butoxyoxalyl- amino)-7-(5,7-dioxo-5,7-dihydro-pyrrolo[3,4-b]pyridin-6-ylmethyl)-4,7- dihyd-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ), δ 9.00 (d, J = 4.8, 1 H), 8.21 (d, J = 7.5, 1 H), 7.64 (dd, J = 4.8, J = 6.8, 1 H), 5.12 (d, J = 7.2, 1 H),4.24-4.1 (m, 2H), 3.97- 3.91 (m, 1 H), 3.75 (m, 1 H), 2.90 (m, 1 H), 1.29 (s, 9H), 1.27 (s, 9H). MS: 544 (M+1). The above 2-(ferf-butoxyoxalyl-amino)-7-(5,7-dioxo-5,7-dihydro- pyrrolo[3,4-b]pyridin-6-ylmethyl)-4,7-dihyd-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester (47.4 mg, 0.087 mmol) was stirred in 50% trifluoroacetic acid in dichloromethane (2 ml) at room temperature for 5 h. The solvent was removed in vacuo and the residue was washed with diethyl ether (4 x 3.0 ml) and dried which afforded 26.5 mg (70 %) of the title compound as a solid. 1 H NMR (400MHz, CD 3 OD): δ 8.96 (d, J = 5, 1 H), 8.30 (d, J = 7.6, 1 H), 7.79 (dd, J = 5.2, J = 5.2, 1 H), 5.10 (d, J = 6.4, 1 H), 4.16 (m, 2H), 3.96 (dd, J = 3.2, J = 3.6, 1 H), 3.78 (m, 1 H), 2.95 (m, 2H). MS: 432 (M+1 ). EXAMPLE 12 5-(5,7-Dioxo-5,7-dihvdro-pyrrolo[3,4-blpyridin-6-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid Pyrrolo[3,4-b]pyridine-5,7-dione (74.2 mg, 0.5 mmol) was stirred with sodium hydride (60% dispersion in mineral oil, 20.04 mg, 0.5 mmol) in N,N-dimethylformamide (4.0 ml) at room temperature under inert atmosphere. 2-(fetf-Butoxyoxalyl-amino)-5-(4-nitro-benzene- sulfonyloxymethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (198 mg, 0.33 mmol) was added to the sodium salt formed and the reaction was stirred at 80 °C for 20 h. The solvent was removed vacuo and the crude product was purified by preparative TLC (hexane:ethyl acetate 50:50) which afforded 58 mg (21 %) of 2-(ferf- butoxyoxalyl-amino)-5-(5,7-dioxo-5,7-dihydro-pyrrolo[3,4-b]pyridin-6- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ): δ 9.00 (d, J = 5, 1 H), 8.20 (d, J = 7.5, 1H), 7.65 (dd, J = 5, J = 5, 1 H), 4.80 (d, = 14.7, 1 H), 4.66 (d, J = 14.7, 1 H), 4.10 (m, 2H), 3.91 (d, J = 13.2, 1H), 3.02 (d, J = 16.5, 1 H), 2.70 (m, 1 H), 1.61 (s, 9H), 1.58 (s, 9H). MS: 544 (M+1 ). The above 2-(.erf-butoxyoxalyl-amino)-5-(5,7-dioxo-5,7-dihydro- pyrrolo[3,4-b]pyridin-6-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester (46.4 mg, 0.09 mmol) was stirred in 20 % trifluoroacetic acid in dichloromethane (3.0 ml) at room temperature for 2 h. The volatiles were removed in vacuo and the residue was washed with diethyl ether (5 x 3 ml) affording 37 mg (99 %) of the title compound as a solid. 1 H NMR (300 MHz, CDCI 3 ): δ 8.96 (d, J = 5.4, 1 H), 8.20 (d, J = 1.1, 1 H), 7.64 (m, 1 H), 4.77 (d, J = 14.7, 1 H), 4.61 (d, = 14.7, 1 H), 4.07 (m, 2H), 3.86 (d, J = 10.5, 1 H), 3.12 (d, J = 17.4, 1 H), 2.77-2.68 (m, 2H). MS: 432 (M+1 ). EXAMPLE 13 5-(5,7-Dioxo-5,7-dihvdro-pyrrolof3,4-clpyridin-6-ylmethyl)-2-(oxalyl-amino,- 4,7-dihydro-5H-thieno[2,3-c1pyran-3-carboxylic acid To a solution of pyrrolo[3,4-c]pyridine-1 ,3-dione (74 mg, 0.50 mmol) in N,N-dimethylformamide (1 ml) under nitrogen at room temperature was added potassium hydride (35 wt.% dispersion in mineral oil, 57 mg, 0.50 mmol). The solution was stirred at room temperature for 3 hours. A solid precipitated during this period. 18-Crown-6 (33 mg, 0.13 mmol) and 2- (fetf-butoxyoxalyl-amino)-5-(4-nitro-benzene-sulfonyloxymethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (150 mg, 0.25 mmol) were then added. The solution was stirred at 80°C for 12 h and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a gradient of ethyl acetate/hexane (10-25%) as eluant. Pure fractions were collected and the solvent evaporated m vacuo affording 93 mg (68 %) of 2-(ferf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-1 ,3- dihydro-pyrrolo[3,4-c]pyridin-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 12.49 (s, 1 H), 9.20 (s, 1 H), 9.11 (d, 2H, J = 4.8 Hz) 7.80 (d, 2H, J = 4.8 Hz), 4.80 (d, 1 H, J = 16 Hz), 4.66 (d, 1 H, J = 16 Hz), 4.00-4.18 (m, 2H), 3.70-3.95 (m, 1 H), 3.01 (d, 1 H, J = 17 Hz), 2.64-2.78 (m, 1 H), 1.60 (s, 9H), 1.59 (s, 9H). To a mixture of trifluoroacetic acid/dichloromethane (1 ml, 1 :1) at room temperature was added the above 2-(ferf-butoxyoxalyl-amino)-5- (1 ,3-dioxo-1 ,3-dihydro-pyrrolo[3,4-c]pyridin-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (29 mg, 0.053 mmol). The solution was stirred for 5 h. and the solvent evaporated in vacuo. The residue was washed with dichloromethane afford after drying in vacuo 22 mg (96 %) of the title compound as a solid. 1 H NMR (DMSO-d 6 ): δ 12.32 (s, 1 H), 9.15 (s, 1 H), 9.11 (d, 2H, J = 4.8 Hz) 7.92 (d, 2H, J = 4.8 Hz), 4.76 (d, 1 H, J = 15 Hz), 4.58 (d, 1 H, J = 16 Hz), 3.75-4.00 (m, 4H), 3.04 (d, 1 H, J = 17 Hz). MS: 432 (M+1 ). EXAMPLE 14 5-(5-Nitro-1.3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid In a 4-ml scintillating vial, a solution of 2-amino-5-aminomethyl- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (58 mg, 0.2 mmol) in tetrahydrofuran (2.0 ml) was treated with 4-nitrophthalic acid (63 mg, 0.3 mmol), diisopropylethylamine (190 μl, 1.1 mmol), and 1 ,3-diisopropylcarbodiimide (120 μl, 0.77 mmol). The reaction mixture was shaken vigorously for 10 seconds before being stirred at 50 °C for 43 hours and at room temperature for 20 h. The solution was diluted with ethyl acetate (25 ml), washed with 0.5N aqueous hydrochloric acid (25 ml), saturated aqueous sodium bicarbonate (25 ml), and brine (25 ml). The organic layer was dried(MgSO ), filtered and the solvent evaporated in vacuo. Crude 2-amino-5-(5-nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester was obtained as a solid and used immediately in the next step. In a 4 ml scintillating vial a solution of the above crude 2-amino-5-(5-nitro- 1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester in dichloromethane (3 ml) was treated with midazol-1-yl-oxo-acetic acid ferf-butyl ester (147 mg, 0.75 mmol). After stirring for 2 h. at room temperature the reaction mixture was concentrated to dryness in vacuo. The residue was purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (3:1) as eluant. Pure fractions were collected and the solvent evaporated in vacuo which afforded 30 mg (26 %) of 2-(ferf-butoxyoxalyl-amino)-5-(5-nitro-1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 12.47 (s, 1 H), 8.71 (s, 1 H), 8.64 (d, J = 8, 1 H), 8.08 (d, J = 9, 1 H), 4.79 (d, J = 14, 1 H), 4.65 (d, J = 14, 1 H), 4.21- 3.97 (m, 2H), 3.89 (d, = 12. 1 H), 3.01 (d, = 16, 1 H), 2.83-2.61 (m, 1 H), 1.63 (ds, 18H). In a 25 ml round bottom flask, the above 2-(fetf-butoxyoxalyl-amino)-5-(5- nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester (30 mg, 0.05 mmol) was dissolved in a mixture of 20 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring of 24 h. A precipitate was filtered off and washed with diethyl ether, affording after drying 22 mg (90 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 8.63 (d, J = 8, 1 H), 8.15 (d, J = 8, 1 H), 4.76 (d, J = 16, 1 H), 4.57(d, J = 16, 1 H), 4.42-3.74 (m partially obscured by water, 3H), 3.04 (d partially obscured by water, J = 16, 1 H), 2.61 (m partially obscured by DMSO, 1 H). HPLC (254.4 nm) R t =3.40 min, 86%. MS (APCI + ) [M+H] 407.6 EXAMPLE 15 5-(5-Hvdroxy-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino,- 47-dihydro-5H-thienor2,3-clpyran-3-carboxylic acid To a solution of 4-hydroxyphthalic acid (0.45 g, 2.47 mmol) in anhydrous N,N-dimethylformamide (5 ml) under nitrogen was added chloromethyl methyl ether (1.13 ml, 14.8 mmol) and diisopropylethylamine (2.6 ml, 14.8 mmol). The reaction was stirred at ambient temperature for 18 h. and then concentrated vacuo. The crude material was partitioned between ethyl acetate (50 ml) and water (15 ml). The layers were separated, the organic layer washed with water (3 x 10 ml), brine (2 x 10 ml), dried (Na 2 SO ), filtered and the solvent evaporated in vacuo. The resulting oil was dissolved in ethanol (5 ml) and sodium hydroxide (0.12 g, 7.4 mmol) dissolved in water (1 ml) was added to the reaction. The solution was stirred at ambient temperature for 48 h. and then concentrated in vacuo affording 4-methoxymethoxy-phthalic acid di-sodium salt which was used without purification. 1 H NMR (300 MHz, CD 3 OD) δ 7.59 (d, J = 8, 1 H), 7.06 (d, J = 3, 1 H), 6.89 (dd, J = 8, 3, 1 H), 5.18 (s, 2H), 3.42 (s, 3H). A solution of 4-methoxymethoxy-phthalic acid di-sodium salt (0.19 g, 0.70 mmol), 1 -hydroxybenzotriazole (0.2 g, 3.6 equiv.), 1-(3-dimethylamino- propyl)-3-ethylcarbodiimide hydrochloride (0.28 g, 3.6 equiv.), and triethylamine (0.33 ml, 6 equiv.) was prepared in distilled acetonitrile (5 ml) under nitrogen. The mixture was stirred for 5 minutes before 2-amino-5- aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (115 mg, 0.40 mmol) was added in small portions. The reaction was stirred at ambient temperature for 18 h., then concentrated in vacuo. The crude mixture was diluted with ethyl acetate (30 ml) and washed with 1% hydrochloric acid (5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The organic layer was dried(Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (5 to 10% gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 44 mg (23 %) of 2-amino-5-(5-methoxy- methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 7.75 (d, J = 8, 1 H), 7.48 (d, J = 2, 1 H), 7.27 (dd, J = 8, 2, 1 H), 5.26 (s, 2H), 4.60-4.46 (m, 2H), 3.99-3.71 (m, 3H), 3.47 (s, 3H), 2.85 (d, = 17, 1H), 2.55 (dd, J = 17, 9, 1 H), 1.48 (s, 9H). To a solution of the above 2-amino-5-(5-methoxy-methoxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (44 mg, 0.095 mmol) in distilled dichloromethane (3 ml) under nitrogen was added midazol-1-yl-oxo-acetic acid fetf-butyl ester (56 mg, 0.29 mmol) and triethylamine (26 μl, 0.19 mmol). The reaction was stirred for 4 h., concentrated in vacuo and reconstituted in ethyl acetate (20 ml). The organic layer was washed with 1 % hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The resulting solution was dried(Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a 5 % mixture of ethyl acetate/dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 35 mg (63 %) of 2-(ferf-butoxyoxalyl-amino)-5-(5-methoxymethoxy- 1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 12.50 (s, 1 H), 7.75 (d, J = 8, 1 H), 7.49 (d, J = 2, 1 H), 7.28 (dd, = 8, 2, 1 H), 5.26 (s, 2H), 4.77 (d, J = 15, 1 H), 4.64 (d, J = 15, 1 H), 4.03-3.74 (m, 3H), 3.47 (s, 3H), 2.95 (d, J = 17, 1 H), 2.65 (dd, J = 17, 9, 1 H), 1.58 (s, 9H), 1.54 (s, 9H). APCI-MS: [M+H] + = 603.7 The above 2-(ferf-butoxyoxalyl-amino)-5-(5-methoxymethoxy-1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester (35 mg, 0.058 mmol) was dissolved in a mixture of 50 % trifluoroacetic acid/dichloromethane (2.5 ml). The reaction was stirred at ambient temperature for 7 h., concentrated in vacuo and the residue evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 20 mg (77 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 10.97 (s, 1 H), 7.72 (d, J = 8, 1 H), 7.18 (s, 1 H), 7.10 (d, J = 8, 1 H), 4.74 (d, J = 15, 1 H), 4.58 (d, J = 15, 1 H), 3.96-3.62 (m, 3H), 2.99 (d, J = 17, 1 H), 2.60-2.50 (m, 1 H, partially obscured by DMSO). APCI-MS: [M-H] " = 445.4 HPLC (254.4nm): R,=2.92 min, 95% EXAMPLE 16 5-,4-Methoxy-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino,- 47-dihvdro-5H-thieno[2 1 3-c1pyran-3-carboxylic acid To a solution of 4-hydroxy-isobenzofuran-1 ,3-dione (195 mg, 1.2 mmol) in anhydrous N,N-dimethylformamide (4 ml) under nitrogen was added sodium hydride (61 mg, 1.56 mmol). The solution was stirred for 15 minutes and then methyl iodide (0.37 ml, 6.0 mmol) was added. The reaction was stirred for 48 h. and then quenched with saturated ammonium chloride. The mixture was concentrated in vacuo, diluted in ethyl acetate (20 ml) and the organic phase washed with 1 N hydrochloric acid (5 ml) and brine (3 x 5 ml). The organic layer was dried(MgSO 4 ) and concentrated in vacuo. To the crude solid was added methanol causing a precipitate to form. The flask was cooled in an ice bath for 2 h. and the solid filtered off, washed with methanol and dried in vacuo which afforded 0.1 g (47 %) of 4-methoxy-isobenzofuran-1 ,3-dione as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.95 (t, J = 8, 1 H), 7.61 (d, J = 8, 1 H), 7.58 (d, J = 8, 1 H), 3.99 (s, 3H). APCI-MS: [M+H] + = 179.1 A solution of 2-amino-5-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester (122 mg, 0.43 mmol, prepared as described in Example 17) and 4-methoxy-isobenzofuran-1 ,3-dione (92 mg, 0.52 mmol) was prepared in distilled tetrahydrofuran (4 ml) under nitrogen. 1- hydroxybenzotriazole (87 mg, 0.65 mmol), 1-(3-dimethyl-aminopropyl)-3- ethylcarbodiimide hydrochloride (123 mg, 0.65 mmol), and triethylamine (0.29 ml, 2.15 mmol) were added. The reaction was stirred at ambient temperature for 18 h., then concentrated in vacuo. The crude mixture was diluted with ethyl acetate (25 ml) and washed with 1 N hydrochloric acid (5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The organic layer was dried (Na 2 SO ), filtered, and the solvent evaporated in vacuo to give 0.18 g (94 %) of 2-amino-5-(4-methoxy-1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 7.66 (t, J = 7, 1 H), 7.43 (d, J = 7 , 1 H), 7.19 (d, J - 7, 1 H), 4.59-4.46 (m, 2H), 4.06-3.72 (m, 3H), 4.00 (s, 3H), 2.87- 2.81 (m, 1 H), 2.60-2.51 (m, 1 H), 1.48 (s, 9H). To a solution of the above 2-amino-5-(4-methoxy-1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.18 g, 0.42 mmol) in distilled dichloromethane (5 ml) under nitrogen was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (0.25 g, 1.26 mmol) and triethylamine (0.23 ml, 1.68 mmol). The reaction was stirred for 12 h., concentrated in vacuo and reconstituted in ethyl acetate (25 ml). The organic layer was washed with 1 N hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The resulting solution was dried(Na 2 SO 4 ), filtered, and the solvent evaporated jn vacuo. The crude material was purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (0 to 10 % gradient). Pure fractions were collected and the solvent evaporated vacuo to give 195 mg (81 %) of 2-(ferf-butoxyoxalyl-amino)-5-(4-methoxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 12.48 (s, 1 H), 7.65 (t, J = 7, 1 H), 7.43 (d, J = 7, 1 H), 7.19 (d, J = 7, 1 H), 4.77 (d, J = 15, 1 H), 4.63 (d, J = 15, 1 H), 4.04- 3.75 (m, 3H), 4.00 (s, 3H), 2.94 (d, J = 17, 1 H), 2.65 (dd, J = 17, 10, 1 H), 1.58 (s, 9H), 1.53 (s, 9H). LC-MS: R t =4.17 min, [M+H] + = 573.2 The above 2-(ferf-butoxyoxalyl-amino)-5-(4-methoxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (0.15 g, 0.26 mmol) was dissolved in a mixture of 50 % trifluoroacetic acid/dichloromethane (5 ml). The reaction was stirred at ambient temperature for 7 h., concentrated in vacuo and the residue evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 100 mg (83 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 7.79 (t, J = 8, 1 H), 7.48 (d, J = 8, 1 H), 7.42 (d, J = 8, 1 H), 4.74 (d, J = 15, 1 H), 4.56 (d, J = 15, 1 H), 3.95 (s, 3H), 3.91-3.79 (m, 2H), 3.69-3.63 (m, 1 H), 2.98 (d, J = 17, 1 H), 2.57 (dd, J = 17, 10, 1 H). LC-MS: R t =1.26 min, [M+H] + = 461.0 HPLC (254.4nm): R,=3.10 min, 100 % EXAMPLE 17 5-(4-Nitro-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,7- dihvdro-5H-thienof2,3-c1pyran-3-carboxylic acid In a 50-ml round-bottom flask, a suspension of 2-amino-5-(1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (2.00 g, 4.8 mmol) in absolute ethanol (20 ml) was flushed with nitrogen and sealed with a rubber septum. Hydrazine (0.5 ml, 15.9 mmol) was added, followed by an additional portion of absolute ethanol (20 ml) at room temperature. The reaction mixture was heated to 80 °C for 3.5 h., then allowed to stir at room temperature for 14 h. The precipitate was filtered off and washed with absolute ethanol. The filtrate was concentrated in vacuo leaving an oil, which was dissolved in dichloromethane (30 ml) and refiltered. The solvent was evaporated in vacuo affording 1.2 g (86 %) of 2-amino-5-aminomethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) d 5.92 (s, 2H), 4.64 (s, 2H), 3.68-3.60 (m, 1 H), 2.98-2.74 (m, 3H), 2.56-2.44 (m, 1 H), 1.54 (s, 9H). MS (APCf) [M+H] 285.3 In a 4-ml scintillating vial, a solution of the above 2-amino-5-aminomethyl- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (63 mg, 0.2 mmol) in tetrahydrofuran (2.0 ml) was treated with 3-nitro-phthalic acid (66 mg, 0.3 mmol), diisopropylethylamine (190 μl, 1.1 mmol), and 1,3-diisopropyl-carbodiimide (120 μl, 0.77 mmol). The reaction mixture was shaken vigorously for 10 seconds before being stirred at 50°C for 43 hours and at room temperature for 20 h. The reaction mixture was diluted with ethyl acetate (25 ml) and washed with 0.5N aqueous hydrochloric acid (25 ml), saturated sodium bicarbonate (25 ml), and brine (25 ml). The organic layer was dried(MgSO 4 ), filtered and the solvent evaporated in vacuo affording crude 2-amino-5-(4-nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. In a 4 ml scintillating vial a solution of the above crude 2-amino-5- (4-nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester in dichloromethane (3 ml) was treated with midazol-1-yl-oxo-acetic acid ferf-butyl ester (147 mg, 0.75 mmol). After stirring for 2 h. at room temperature the reaction solution was concentrated to dryness in vacuo. The residue was purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (3:1) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 30 mg (26%) of 2-(ferf-butoxyoxalyl-amino)-5-(4-nitro-1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 8.17 (d, J = 5, 1 H), 8.1 1 (d, J = 6, 1 H), 7.94 (t, J = 8, 1 H), 4.80 (d, J = 14, 1 H), 4.67 (d, J = 15, 1 H), 4.16-3.97 (m, 3H), 3.88 (d, J = 10, 1 H), 3.01 (d, J = 16, 1 H), 2.70 (dd, J = 16, 10, 1 H), 1.62 (s, 9H), 1.59 (s, 9H). In a 25 ml round bottom flask, the above 2-(ferf-butoxyoxalyl-amino)-5-(4- nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester (30 mg, 0.05 mmol) was dissolved in a mixture of 20 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring. After standing for 24 h. a precipitate was filtered off and washed with diethyl ether, affording after drying 22 mg (90 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.33 (s, 1 H), 8.32 (d, J = 9, 1 H), 8.20 (d, J = 9, 1 H), 8.07 (t, = 9, 1 H), 4.77 (d, J = 14, 1 H), 4.59 (d, J = 16, 1 H), 4.00-3.65 (m partially obscured by water, 3H), 3.04 (d partially obscured by water, J = 16, 1 H), 2.63 (dd partially obscured by DMSO, J = 17, 13, 1 H). HPLC (254.4 nm) R t = 3.33 min, 100%. MS (APCI + ) [M+H] 391.6 EXAMPLE 18 5-(4-(4-Chloro-phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihvdro-pyrrolo[3,4- clpyridin-2-ylmethyl)-2-(oxalyl-amino)-47-dihydro-5H-thienor2,3-clpyran-3- carboxylic acid Under a nitrogen atmosphere, 4-(4-chloro-phenylsulfanyl)-6-methyl- pyrrolo[3,4-c]-1 ,3-dione (914 mg, 3.0 mmol), tributylphosphine (1.66 ml, 4.5 mmol) and 2-amino-5-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester (855 mg, 3.0 mmol) were successively dissolved in dry benzene (90 ml). Solid azodicarboxylic dipiperidine (1.13 g, 4.5 mmol) was added under stirring at 0 °C to the solution. After stirring for 10 min, the reaction mixture was brought to room temperature and the stirring continued for 4 h. The mixture was cooled on ice, and additional portions of tributylphosphine (1.66 ml, 4.5 mmol) and azodicarboxylic dipiperidine (1.13 g, 4.5 mmol) were added. After stirring for 10 min, the reaction mixture was brought to room temperature and the stirring continued for 18 h. Heptane (30 ml) was added to the reaction and the precipitate filtered off (discard). After evaporation of the solvent the product was purified by flash chromatography to give 1.3 g (76 %) of 2- amino-5-(4-(4-chloro-phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihydro- pyrrolo[3,4-c]pyridin-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as an oil. Mp: 1 18 - 1 19° C; 1 H NMR (CDCI 3 ) δ 1.55 (s, 9H), 2.50 (s, 3H), 2.50-2.65 (m, 1 H), 2.85- 2.95 (m, 1 H), 3.75-3.85 (m, 1 H), 3.95- 4.05, (m, 2H), 4.50- 4.15 (m, 2H), 5.95 (bs, 2H), 7.30 (s, 1 H), 7.40 (d, 2H), 7.55 (d, 2H). To an ice cooled solution of 2-amino-5-(4-(4-chloro-phenylsulfanyl)-6- methyl-1 ,3-dioxo-1 ,3-dihydro-pyrrolo[3,4-c]pyridin-2-ylmethyl)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (572 mg, 1 mmol) and dry triethylamine (2 ml) in dry tetrahydrofuran (10 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (588 mg, 3 mmol). After 10 min, the reaction mixture was brought to room temperature and the stirring continued for 18 h. The mixture was concentrated in vacuo and submitted to flash chromatography using a mixture of toluene/ethyl acetate (30:1 ) as eluant. Pure fraction were collected and the solvent evaporated m vacuo to give 360 mg (51 %) of 2-(ferf-butoxyoxalyl-amino)-5-(4-(4-chloro- phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihydro-pyrrolo[3,4-c]pyridin-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. M.p.: 134 - 136° C; 1 H NMR (CDCI 3 ) δ 1.60 (s, 9H), 1.63 (s, 9H), 2.50 (s, 3H), 2.65-2.75 (m, 1 H), 2.95- 3.05 (m, 1 H), 3.75-3.90 (m, 1 H), 4.00- 4.10, (m, 2H), 4.60- 4.85 (m, 2H), 7.30 (s, 1 H), 7.40 (d, 2H), 7.55 (d, 2H), 12.50 (s, 1 H). To 2-(ferf-butoxyoxalyl-amino)-5-(4-(4-chloro-phenylsulfanyl)-6-methyl-1 ,3- dioxo-1 ,3-dihydro-pyrrolo[3,4-c]pyridin-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (324 g, 0.46 mmol) was added a mixture of trifluoroacetic acid (2.5 ml) and dichloromethane (7.5 ml). The mixture was stirred for 5 h, and added petroleum ether/ethyl acetate. The precipitate was isolated off and re-suspended in ethyl acetate. The title compound 136 mg (50 %) was isolated by filtration. Mp: 239 - 240° C; Calculated for C 25 H 18 CIN 3 O 8 S 2 , 0.75 x H 2 O; C, 49.92 %; H, 3.27 %; N, 6.99 %. Found: C, 49.83 %; H, 3.16 %; N, 6.85 %. 1 H NMR (CDCI 3 ) δ 2.48 (s, 3H), 2.65-2.75 (m, 1 H), 2.95- 3.05 (m, 1 H), 3.50-4.00 (m, 3H), 4.50- 4.90 (m, 2H), 7.50-7.68 (m, 5H), 12.30 (s, 1 H). EXAMPLE 19 5-(3-lmidazol-1-yl-2,5-dioxo-pyrrolidin-1-ylmethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid To a solution of 2-amino-5-aminomethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester (0.53 g, 1.86 mmol, prepared as described in Example 17) in tetrahydrofuran (10 ml) was added, maleic acid (0.24 g, 2.05 mmol) and diisopropylcarbodiimide (0.58 ml, 3.72 mmol). The reaction mixture was heated to reflux for 3 hours and then allowed to cool to room temperature over an 18 hour period. The solvent was stripped off jn vacuo and the residue diluted into ethyl acetate (50 ml). The organic phase was washed with saturated sodium bicarbonate (2 x 50 ml), 1 % hydrochloric acid (2 x 20 ml), brine (3 x 50 ml), dried(MgSO 4 ), filtered, and the solvent evaporated in vacuo affording an oil which was subjected to flash chromatography using a mixture of ethyl acetate/hexanes (6:4) as eluant. Pure fractions (R f =0.25) were collected and the solvent evaporated jn vacuo to give 0.60 g (90 %) of 2-amino-5-(2,5-dioxo-2,5-dihydro- pyrrol-1-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 7.31 (d, J = 5.7, 1 H), 6.63 (d, J = 5.4, 1 H), 5.94 (bs, 2H), 4.67 (s, 2H), 3.93 (m, 1 H), 3.82 (m, 2H), 2.89-2.83 (m, 1 H), 2.69-2.60 (m, 1 H), 1.54 (s, 9H). MS: APCI (+): 365.2 (M+H); To a solution of the above 2-amino-5-(2,5-dioxo-2,5-dihydro-pyrrol-1- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf- butyl ester (60 mg, 1.64 mmol) in tetrahydrofuran (2 ml) was added midazol-1-yl-oxo-acetic acid fetf-butyl ester (50 mg, 2.46 mmol). The solution was stirred at room temperature for 48 h. The solvent was stripped off in vacuo and the resultant oil diluted in ethyl acetate (20 ml), washed with brine (3 x 25 ml), dried(MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was subjected preparative thin layer chromatography using a mixture of methanol/dichloromethane (1 :9) as eluant which afforded 25 mg (28 %) of 2-(fetf-butoxyoxalyl-amino)-5-(3-imidazol-1-yl-2,5-dioxo- pyrrolidin-1-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as a mixture of diastereoisomers. 1 H NMR (300 MHz, CDCI 3 ) δ 7.65 (s, 1 H), 6.94 (s, 1 H), 5.92 (m, 1 H), 5.22 (m, 1 H), 4.68-4.53 (m, 2H), 4.00 (m, 3H), 3.71 (m, 1 H), 3.47-3.38 (m, 1 H), 3.03-2.87 (m, 1 H), 2.61 (m, 1 H), 1.60 (s, 9H), 1.54 (s, 9H). MS: APCI (+): 561.2 (M+H). To the above 2-(ferf-butoxyoxalyl-amino)-5-(3-imidazol-1-yl-2,5-dioxo- pyrrolidin-1-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (25 mg, 0.05 mmol) was added a mixture of 20% trifluoroacetic acid in dichloromethane (2 ml). The reaction mixture was allowed to stir at room temperature for 2 h., at which time the mixture was concentrated jn vacuo. The resultant solid was triturated with diethyl ether (2x) which afforded 13 mg (65 %) of the title compound as a solid. 1 H NMR (300 MHz, CD 3 OD) δ 9.15 (s, 1 H), 7.78 (s, 1 H), 7.63 (m, 1 H), 5.75 (m, 1 H), 4.69 (m, 2H), 4.46 (m, 1 H), 3.85 (m, 2H), 3.66 (m, 1 H), 3.02 (m, 1 H), 2.83 (m, 1 H), 2.64 (m, 1 H), 2.46 (m, 1 H). MS: ESI (-): 447.4 (M-H). EXAMPLE 20 Oxalic acid 3-carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thienof2,3-c1pyran- 5-ylmethyl ester methyl To a solution of 2-amino-5-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester (8.0 g, 28 mmol) in dry tetrahydrofuran (50 ml) was added midazol-1-yl-oxo-acetic acid fetf-butyl ester (27.51 g, 0.14 mol) and triethylamine (3.93 ml, 0.14 mol). The reaction mixture was stirred at room temperature for 20 h. The volatiles were removed in vacuo and the crude product was dissolved in ethyl acetate (300 ml) and washed with a saturated solution of sodium bicarbonate (3 x 100 ml), dilute hydrochloric acid (3 x 100 ml), water (3 x 100 ml) and brine (100 ml). The organic layer was dried(MgSO 4 ), filtered and the solvent removed in vacuo affording a foam (16 g) which was purified on column chromatography on silica gel using a gradient of hexane/ethyl acetate (90:10 to 50:50 gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo which afforded 11 g (91 %) of oxalic acid 2-amino-3-ferf-butoxycarbonyl-4,7-dihydro-5H- thieno[2,3-c]pyran-5-ylmethyl ester fetf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ): δ 5.94 (s, 2H), 4.86 (d, J = 14.7, 1 H), 4.77 (d, J = 14.4, 1 H), 4.64 (m, 1H), 3.82-3.71 (m, 2H), 2.85 (d, J = 16.8, 1 H), 2.68 (d, J = 10.5, 1 H), 1.62 (s, 9H), 1.61 (s, 9H). MS: 414 (M+1). A solution of the above oxalic acid 2-amino-3-ferf-butoxycarbonyl-4,7- dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl ester fetf-butyl ester (8.3 g, 20.1 mmol) and potassium carbonate (1.7 g, 12.3 mmol) was stirred in methanol (80 ml) in presence of water (3 ml) at room temperature for 10 min., at which time TLC indicated reaction complete. Methanol was removed in vacuo and the crude product was dissolved in dichloromethane (300 ml) and washed with water (3 x 150 ml). The organic phase was dried(MgSO ), filtered and the solvent evaporated in vacuo. The residue was purified on flash chromatography on silica gel using a gradient of hexane/ethyl acetate (90:10 to 50:50 gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 0.65 g (9 %) of oxalic acid 2-amino-3-ferf-butoxycarbonyl-4,7- dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl ester methyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ): δ 4.86 (d, J = 15, 1 H), 4.78 (d, J = 15, 1 H), 4.00 (s, 3H), 3.82-3.70 (m, 3H), 2.86 (d, J= 17, 1 H), 2.66 (dd, J = 10.2, J = 10.5, 1 H), 1.62 (s, 9H). MS: 316 (M-55). To a solution of the above oxalic acid 2-amino-3-fetf-butoxycarbonyl-4,7- dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl ester methyl ester (160 mg, 0.43 mmol) in dry tetrahydrofuran (3.0 ml) was added midazol-1 -yl-oxo-acetic acid fetf-butyl ester (420.4 mg, 2.15 mmol) and triethylamine (120 μl, 0.86 mmol). The resulting mixture was stirred at room temperature for 20 h. The solvent was evaporated in vacuo and the crude product was purified by flash chromatography on silica gel using a gradient of hexane/ethyl acetate (95:5 to 80:20 gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 173 mg (81 %) of oxalic acid 2-amino-3-ferf-butoxycarbonyl-2-(fetf-butoxyoxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl ester methyl ester as a solid. 1 H NMR (300MHz, CDCI 3 ): δ 4.81 (dd, J = 14.7, J = 14.2, 2H), 4.40 (m, 2H), 4.00 (s, 3H), 2.96 (d, J = 15.3, 1 H), 2.69 (dd, J = 10.8, J = 10.8, 1 H), 1.61 (s, 9H), 1.57 (s, 9H). MS: 388.3 (M-1 1 ). The above oxalic acid 2-amino-3-ferf-butoxycarbonyl-2-(ferf-butoxyoxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl ester methyl ester (93.8 mg, 0.19 mmol) was stirred in 20 % trifluoroacetic acid in dichloromethane (2 ml) for 20 h. at room temperature. The solvent was removal in vacuo which afforded 73 mg (95 %) of the title compound as a solid. 1 H NMR (300 MHz, CD 3 OD): δ 4.76 (d, J = 5.7, 2H), 4.18 (d, J = 4.8, 2H), 3.97 (s, 3H), 2.99 (d, J = 16.2, 1 H), 2.65 (d, J = 10.8, 1 H). MS: 386 (M-1). EXAMPLE 21 Oxalic acid (3-carboxy-2-(oxalyl-amino)-47-dihvdro-5H-thienof2,3-c.pyran- 5-ylmethyl) ester To a solution of a mixture of 2-amino-5-hydroxymethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester and 2-amino-7- hydroxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf- butyl ester (1 :4 estimated based on 1 H NMR) (200 mg, 0.70 mmol) and diisopropylethylamine (0.25 ml, 1.4 mmol) in dichloromethane (6.0 ml) cooled to 0 °C under nitrogen was added triethylchlorosilane (0.18 ml, 1.1 mmol). The solution was stirred at 0 °C for 5 min. and then stirred at room temperature for 15 min. The solution was washed with saturated sodium bicarbonate and brine, dried(MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a 5 % mixture of ethyl acetate/hexane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 42 mg (16 %) of 2-amino-5- triethylsilanyloxymethy-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (1) and 193 mg (69 %) of 2-amino-7-triethylsilanyloxy- methy-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (2). (1) 1 H NMR (CDCI 3 ): δ 4.58 (m, 1 H), 4.18-4.07 (m, 1 H), 3.84 (dd, 1 H, J = 9.6, 6.0 Hz), 3.80-3.70 (m, 1 H), 3.60 (dd, 1 H, J = 9.6, 7.8 Hz), 2.92- 2.70 (m, 2H), 1.58 (s, 9H), 0.98 (t, 9 H, J = 7.8 Hz), 0.64 (q, 6H, J = 7.8 Hz); (2) 1 H NMR (CDCI 3 ): δ 4.62 (s, 2H), 3.85-3.64 (m, 3H), 2.82 (dm, 1 H, J = 15 Hz), 2.49 (dd, 1 H, J = 15, 1 1 Hz), 1.58 (s, 9H), 0.98 (t, 9 H, J = 7.8 Hz), 0.64 (q, 6H, J = 7.8 Hz). To a solution of 2-amino-7-triethylsilanyloxymethy-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (6.0 g, 15 mmol) in dichloromethane (10 ml) cooled to 0 °C under the nitrogen was added a solution of imidazol-1-yl-oxo-acetic acid ferf-butyl ester (4.5 g, 18 mmol) in dichloromethane. The solution was stirred at 0 °C for 10 min. The reaction was quenched with water (1.0 ml). The solution was washed with brine and dried(MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a 10% mixture of ethyl acetate/hexane as eluant. Pure fractions of two compounds were collected and the solvent evaporated i vacuo affording 4.5 g (56 %) of 2-(fetf- butoxyoxalyl-amino)-7-triethylsilanyloxymethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (A) as a solid and 50 mg of oxalic acid 3-(fer-butoxycarbonyl-2-(fetf-butoxyoxalyl- amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (B) as a solid. (A) 1 H NMR (CDCI 3 ): δ 12.53 (s, 1 H), 4.85 (d, 1 H, J = 12 Hz), 4.65 (d, 1 H, J = 12 Hz), 3.90-3.60 (m, 3H), 2.94 (d, 1 H, J = 15 Hz), 2.63 (dd, 1 H, J = 15, 11 Hz), 1.63 (s, 9H), 1.61 (s, 9H), 0.98 (t, 9 H, J = 7.8 Hz), 0.64 (q, 6H, J = 7.8 Hz). (B) 1 H NMR (CDCI 3 ): δ 12.47 (s, 1 H), 4.82 (q, 2H, J = 14 Hz), 4.43 (m, 2H), 4.01 (m, 1 H), 2.97 (d, 1 H, J = 14 Hz), 2.69 (dd, 1 H, J = 19, 9 Hz), 1.63 (s, 9H), 1.61 (s, 9 H), 1.58 (s, 9H). To a solution of the above 2-(_etf-butoxyoxalyl-amino)-7-triethylsilanyl- oxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf- butyl ester (4.5 g, 8.5 mmol) in tetrahydrofuran (10 ml) at room temperature was added 0.5 N hydrochloric acid (2.0 ml). The solution was stirred at room temperature for 0.5 h. Ethyl acetate (100 ml) was added and the resulting solution was washed with saturated sodium bicarbonate, brine, dried(MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a 10 % mixture of ethyl acetate/hexane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 3.0 g (84 %) of 2-(.etf-butoxyoxalyl-amino)-7-hydroxymethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 12.53 (s, 1 H), 4.86 (d, 1 H, J = 12 Hz), 4.60 (d, 1 H, J = 12 Hz), 3.85-3.65 (m, 3H), 2.85 (d, 1 H, J = 15 Hz), 2.65 (dd, 1 H, J = 15, 1 1 Hz), 1.63 (s, 9H), 1.61 (s, 9H). To a solution of the above 2-(ferf-butoxyoxalyl-amino)-7-hydroxy- methyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (3.0 g, 7.1 mmol) in dichloromethane (10 ml) at room temperature was added pyridine (2.5 ml, 28.5 mmol) and 4-nitro- benzenesulfonyl chloride (4.7 g, 21.4 mmol). The solution was heated to 50 °C and stirred for 4.5 h. The solution was cooled to room temperature and washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate, brine, dried(MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a gradient of ethyl acetate/hexane (0-100 %) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 3.6 g (84 %) of 2-(ferf-butoxyoxalyl-amino)-7-(4-nitro- benzenesulfonyloxymethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 12.40 (s, 1 H), 8.43 (d, 2H, = 9.0 Hz), 8.17 (d, 2H, J = 9.0 Hz), 4.72 (d, 1 H, J = 14 Hz), 4.64 (d, 1 H, J = 14 Hz), 4.38- 4.24 (m, 2H), 3.98-3.86 (m, 1 H), 2.92 (d, 1 H, J = 17 Hz), 2.65 (dd, 1 H, J = 17, 12 Hz), 1.63 (s, 9H), 1.61 (s, 9H). MS: 598 (M-1 ). To a solution of 50 % trifluoroacetic acid/dichloromethane (1 ml) at room temperature was added oxalic acid 3-(ferf-butoxycarbonyl-2-(ferf- butoxyoxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (50 mg, 0.092 mmol). The solution was stirred for 3 hours. The solvent was removed in vacuo. The residue was washed with dichloromethane affording after filtration 25 mg (73 %) of the title compound as a solid. 1 H NMR (DMSO-d 6 ): δ 12.32 (s, 1 H), 4.82 (d, 1 H, J = 15 Hz), 4.68 (d, 1 H, J = 15 Hz), 4.37 (s, 1 H), 3.92 (m, 1 H), 2.93 (d, 1 H, J = 16 Hz), 2.60 (dd, 1 H, J = 30, 10 Hz)-. MS: 372 (M-1). EXAMPLE 22 7-Hvdroxymethyl-2-(oxalyl-amino)-4,7-dihvdro-5H-thienof2 1 3-clpyran-3- carboxylic acid To a mixture of 2-hydroxymethyl-tetrahydro-pyran-4-one (35 g, 0.27 mol), ferf-butyl cyanoacetate (58.68 ml g, 0.4 mol), and sulphur (9.47 g, 0.3 mol) in absolute ethanol (400 ml) was added morpholin (47 ml, 0.54 mol), and the resulting mixture was heated to 45 °C for 16 h. The reaction mixture was cooled, filtered and the filtrate evaporated in vacuo. The resultant oil was dissolved in ethyl acetate (600 ml), washed with water (3 x 200 ml), brine (200 m), dried (Na 2 SO ), filtered and the solvent evaporated vacuo. The residue was crystallised from diethyl ether (100 ml) followed by addition of a mixture of diethyl ether and heptane (100 ml, 1 :1 ). The precipitate was filtered off, washed with a mixture of diethyl ether and heptane (90 ml, 1 :1) and dried in vacuo at 50 °C for 52 h affording 44.51 g of a mixture of 5 and 7 regioisomers according to NMR. The mixture of regioisomers (44.51 g) was suspended in diethyl ether (500 ml) and stirred at room temperature for 96 h. and at reflux temperature for 2 h. After cooling to room temperature the precipitate was filtered off and washed with a mixture of diethyl ether and heptane (100 ml, 1 :1) which afforded after drying in vacuo at 50 °C, 22.12 g (29 %) of 2-amino-5-hydroxymethyl- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as a solid. All filtrates were pooled and evaporated in vacuo affording 55 g of a mixture of regioisomers. To 40.16 g (0.141 mol) of this regioisomer mixture dissolved in dichloromethane (450 ml) was added diisopropyl- ethylamine (49.5 ml, 0.28 mol) and the mixture was cooled to 0 °C. Chlorothiethylsilane (38.2 ml, 0.23 mol) was added dropwise and the mixture was stirred for 10 minutes and for 15 minutes at room temperature. The reaction mixture was washed with saturated aqueous sodium carbonate (3 x 150 ml), brine (3 x 150 ml), dried (Na 2 SO 4 ), filtered and the solvent evaporated vacuo. The residue (70.4 g) was partitioned into two portions which were subjected to flash chromatography (2 I silicagel) using a mixture of ethyl acetate/hexane (1 :20) as eluant. Pure fractions of 2-amino-5-triethylsilanyloxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester and 2-amino-7-triethylsilanyl- hydroxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf- butyl ester were collected. A fraction containing both isomers (18.84 g) was re-subjected to flash chromatography (2 I silicagel) using a mixture of ethyl acetate/hexane (1 :20) as eluant. A total of 28.1 g (50 %) of 2-amino- 5-triethylsilanylhydroxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester was obtained. A total of 18.2 g (32 %) of 2- amino-7-triethylsilanylhydroxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester was obtained. To the above 2-amino-7-triethylsilanylhydroxymethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (18.2 g, 0.046 mol) dissolved in dichloromethane (200 ml) was added a mixture of imidazol-1- yl-oxo-acetic acid ferf butyl ester (17.9 g, 0.091 mol) in dichloromethane (30 ml) under nitrogen. The reaction mixture was allowed to stir at room temperature for 18 h. The reaction mixture was evaporated i vacuo and the residue was dissolved in ethyl acetate (100 ml) and washed with 1 N hydrochloric acid (3 x 50 ml), brine (3 x 75 ml), dried (Na 2 SO ), filtered and the organic phase evaporated in vacuo affording in quantitative yield 2- (ferf-butoxyoxalyl-amino)-7-triethylsilanyloxymethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester ester as a. oil. To a mixture of the above 7-triethylsilanyl ether (24.0 g, 0.046 mol) in tetrahydrofuran (100 ml) was added 1 N hydrochloric acid (18 ml) and the reaction mixture was stirred at room temperature for 1.5 h. Ethyl acetate (150 ml) was added and the reaction mixture was washed with saturated aqueous sodium carbonate (3 x 100 ml), brine (3 x 100 ml), dried (Na 2 SO ), filtered and the solvent evaporated in vacuo. The residue was tritituated with a mixture of diethyl ether and heptane (1 :5) and the precipitate was filtered off, washed with heptane and dried in vacuo at 50 °C for 16 h affording 13.55 g (57 %) of 2-(fetf-butoxyoxalyl-amino)-7- hydroxymethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf- butyl ester as a solid. The above 2-(ferf-butoxyoxalyl-amino)-7-hydroxymethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (16 mg, 0.033 mmol) was dissolved in 50 % trifluoroacetic acid in dichloromethane (1 ml). The reaction was stirred at room temperature for 3 hours. The volatiles were evaporated in vacuo and the residue washed with dichloromethane which afforded 7 mg (73 %) of the title compound as a solid. 1 H NMR (DMSO-d 6 ): δ 12.32 (s, 1 H), 4.62 (s, 1 H), 4.12 (m, 1 H), 3.62-3.78 (m, 2H), 3.40-3.52 (m, 1 H), 2.83 (m, 2H). MS: 300 (M-1 ). EXAMPLE 23 7-(2 1 4-Dioxo-thiazolidin-3-ylmethyl)-2-(oxalyl-amino)-4 1 7-dihydro-5H- thienof2,3-c]pyran-3-carboxylic acid To a solution of 2-amino-7-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester (0.13 g, 0.46 mmol) in tetrahydrofuran (3 ml) was added triphenylphosphine (0.13 g, 0.51 mmol), and 2,4-thiazolidinedione (60 mg, 0.51 mmol). The reaction mixture was cooled to 0 °C and diisopropylazodicarboxylate (99 μl, 0.51 mmol) was added via syringe. The resultant mixture was stirred for 18 hours, gradually warming to room temperature. The volatiles were evaporated in vacuo and the resulting oil was diluted in ethyl acetate (50 ml). The organic phase was washed with saturated sodium bicarbonate (3 x 50 ml), brine (3 x 50 ml), dried(MgSO 4 ), filtered and the solvent evaporated vacuo. The residue was subjected to flash chromatography using a mixture of dichloromethane/methanol (9:1) as eluant. Pure fractions were collected (R f =0.70) and the solvent evaporated i vacuo which afforded 89 mg (51 %) of 2-amino-7-(2,4-dioxo-thiazolidin-3-ylmethyl)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 6.02 (s, 2H), 4.82 (dm, 1 H), 4.13-4.02 (bm, 2H), 3.99 (s, 2H), 3.75-3.67 (m, 1 H), 3.60 (dd, 1H, J = 14, 3.3,), 2.81-2.74 (m, 2H), 1.54 (s, 9H). MS: APCI (+): 385.6 (M+H). To a solution of the above of 2-amino-7-(2,4-dioxo-thiazolidin-3- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf- butyl ester (89 mg) in tetrahydrofuran (5 ml) was added imidazol-1-yl- oxo-acetic acid fetf-butyl ester (79 mg, 0.312 mmol) and the mixture allowed to stir overnight at room temperature. The volatiles were evaporated in vacuo, the residue diluted with ethyl acetate and subjected to preparative chromatography using a mixture of dichloromethane/methanol (9:1) as eluant. Material eluting with R f = 0.72 was collected and the solvent evaporated in vacuo affording 40 mg (25 %) of 2-(.erf-butoxyoxalyl-amino)-7-(2,4-dioxo-thiazolidin-3- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf- butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 12.53 (s, 1 H), 5.03 (dm, 1 H), 4.12-4.04 (m, 2H), 4.01 (s, 2H), 3.79-3.71 (m, 2H), 2.88 (m, 2H), 1.62 (s, 9H), 1.59 (s, 9H). MS: APCI (+): 513.3 (M+H). The above 2-(ferf-butoxyoxalyl-amino)-7-(2,4-dioxo-thiazolidin-3- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf- butyl ester (40 mg) was dissolved in 50 % trifluoroacetic acid in dichloromethane (1 ml) and stirred at room temperature for 3 hours. The mixture was concentrated vacuo, the residue titurated with dichloromethane and methanol which afforded after drying in vacuo 18 mg (87 %) of the trtle compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 + CD 3 OD) δ 4.98 (dm, 1 H), 4.16 (s, 2H), 4.14-4.02 (m, 2H), 3.78-3.72 (m, 2H), 2.91 (m, 2H). APCI (-): 399 (M-H); LC-MS: s, 99%. EXAMPLE 24 7-(1 ,3-Dioxo-1 ,3-dihvdro-isoindol-2-yloxymethyl)-2-(oxalyl-amino)-4,7- dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid To a mixture of 2-(ferf-butoxyoxalyl-amino)-7-hydroxymethyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.5 g, 1.2 mmol), 2-hydroxy-isoindole-1 ,3-dione (0.21 g, 1.3 mmol) and triphenylphosphine (0.35 g, 1.33 mmol) in dry tetrahydrofuran (20 ml) cooled to 0 °C under a nitrogen atmosphere was added diethyl azodicarboxylate (DEAD) (205 μl, 1.33 mmol). The reaction mixture was allowed to stir overnight, slowly warming to room temperature. The volatiles were evaporated vacuo and the resultant solid dissolved in ethyl acetate (50 ml). The organic phase was washed with saturated aqueous sodium hydrogencarbonate (3 x 30 ml), water (3 x 50 ml), dried(Na SO ), filtered and evaporated in vacuo. The residue (1.02 g) was subjected to flash column chromatography (300 ml silicagel) using a mixture of ethyl acetate/hexane (1 :2) as eluant. Pure fractions were collected affording after evaporation in vacuo 0.37 g (54 %) of 2-(fetf-butoxyoxalyl-amino)-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- yloxymethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. The above di-ferf-butyl ester ( 0.33 g, 0.59 mmol) was dissolved in 25 % trifluoroacetic acid in dichloromethane (2 ml). The reaction was stirred at room temperature for 6.5 h. The volatiles were evaporated in vacuo and the residue trituated with a mixture of diethyl ether and heptane (5 ml, 1 :1). The precipitate was filtered off, washed with heptane and diethyl ether, dried in vacuo at 50 °C for 18 h which afforded 200 mg (77 %) of the title compound as a solid. M.p.: 251.5 - 254 °C; Calculated for Cι 9 H 4 N 2 O 9 S; C, 51.12 %; H, 3.16 %; N, 6.28 %. Found: C, 51.46 %; H, 3.71 %; N, 5.87 %. EXAMPLE 25 7-(4-Hvdroxy-1 1 3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihvdro-5H-thienor2.3-c1pyran-3-carboxylic acid To a solution of 4-hydroxy-isobenzofuran-1 ,3-dione (0.5 g, 3.03 mmol) in anhydrous N,N-dimethylformamide (6 ml) under nitrogen was added diisopropylethylamine (1.05 ml, 6.06 mmol). The solution was stirred with cooling in an ice bath and chloromethyl methyl ether (0.46 ml, 6.06 mmol) was added. The reaction was allowed to slowly warm to ambient temperature and then stirred for an additional 7 h. The mixture was concentrated vacuo to a small volume and diluted with ethyl acetate (75 ml). The organic layer was washed with water (2 x 40 ml), brine (20 ml), dried(Na 2 SO 4 ), filtered, and the solvent evaporated vacuo to give 0.6 g (95 %) of 4-methoxymethoxy-isobenzofuran-1,3-dione as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 7.81 (t, J = 8, 1 H), 7.62 (d, J = 8, 1 H), 7.59 (d, J = 8, 1 H), 5.43 (s, 2H), 3.55 (s, 3H). A mixture of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (0.15 g, 0.53 mmol) and 4- methoxymethoxy-isobenzofuran-1 ,3-dione (135 mg, 0.64 mmol) was dissolved in distilled acetonitrile (7 ml) under nitrogen. The flask was cooled in an ice bath with stirring and 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (0.12 g, 0.64 mmol), and triethylamine (0.22 ml, 1.59 mmol) were added. The reaction was warmed to ambient temperature and stirred for 18 h. The solution was concentrated in vacuo and the residue dissolved in ethyl acetate (40 ml). The organic layer was washed with 1% hydrochloric acid (2 x 10 ml), saturated sodium bicarbonate (10 ml), and brine (10 ml). The resulting solution was dried (Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo which afforded 0.18 g of a crude 2-amino-7-(4-methoxymethoxy-1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester which was used without further purification. 1 H NMR (400 MHz, CDCI 3 ) δ 7.65-7.58 (m, 2H), 7.51 (d, J = 8 , 1 H), 6.00- 5.86 (2s, 2H), 5.39 (s, 2H), 4.94-4.89 (m, 1 H), 4.18-4.02 (m, 2H), 3.86- 3.65 (m, 2H), 3.54 (s, 3H), 2.85-2.73 (m, 2H), 1.55 (s, 9H). APCI-MS: [M+H] + = 475.4 To a solution of crude 2-amino-7-(4-methoxymethoxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (0.18 g) in distilled dichloromethane (4 ml) under nitrogen was added midazol-1-yl-oxo-acetic acid fetf-butyl ester (0.23 g, 1.2 mmol). The reaction was stirred for 3 hours., concentrated vacuo and reconstituted in ethyl acetate (30 ml). The organic layer was washed with 1% hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The resulting solution was dried (Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (0 to 5 % gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 90 mg (28 % in two steps) of 2-(ferf-butoxyoxalyl-amino)-7-(4-methoxymethoxy-1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 12.54 (s, 1 H), 7.64 (t, J = 8, 1 H), 7.51 (d, J = 8, 1 H), 7.46 (d, J = 8, 1 H), 5.40 (s, 2H), 5.1 1-5.07 (m, 1 H), 4.16-4.08 (m, 2H), 3.84-3.72 (m, 2H), 3.55 (s, 3H), 2.95-2.81 (m, 2H), 1.62 (s, 9H), 1.59 (s, 9H). APCI-MS: [M+H] + = 603.8 The above 2-(fetf-butoxyoxalyl-amino)-7-(4-methoxymethoxy-1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (86 mg, 0.143 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (4 ml). The reaction was stirred at ambient temperature for 7 h., concentrated vacuo and evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 55 mg (86 %) of the title compound as a solid. 1 H NMR (400 MHz, d 6 -DMSO) δ 12.34 (s, 1 H), 11.10 (s, 1 H), 7.63 (t, J = 8, 1 H), 7.31 (d, J = 8, 1 H), 7.22 (d, J = 8, 1 H), 4.99-4.95 (m, 1 H), 4.05-4.00 (m, 1 H), 3.91-3.86 (m, 1 H), 3.76-3.66 (m, 2H), 2.88-2.80 (m, 2H). APCI-MS: [M+H] + = 447.4 HPLC (254.4nm): R t =2.921 min, 100% EXAMPLE 26 7-(5-Methoxy-1.3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid The title compound was prepared in a similar way as described in Example 25. M.p.: 234 - 236 °C; Calculated for C 20 H 16 N 2 O 9 S, 0.25 x H 2 O; C, 51.67 %; H, 3.58 %; N, 6.03 %. Found: C, 51.95 %; H, 3.92 %; N, 6.06 %. EXAMPLE 27 7-(57-Dioxo-5,7-dihvdro-[1 ,31dioxolor4,5-f1isoindol-6-ylmethyl2-(oxalyl- amino)-47-dihvdro-5H-thieno[2,3-c1pyran-3-carboxylic acid The title compound was prepared in a similar way as described in Example 25. M.p.: 239.5 - 242.5 °C; Calculated for C 2 oH 14 N 2 OιoS, 0.1 x H 2 O; C, 50.45 %; H, 3.01 %; N, 5.88 %. Found: C, 51.06 %; H, 3.43 %; N, 5.93 %. EXAMPLE 28 7-(((Benzo[1 ,31dioxole-5-carbonyl)-amino)-methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thienof2,3-clpyran-3-carboxylic acid Phthalimidoacetaldehyde diethyl acetal (100 g, 0.38 mol) and 1 N hydrochloric acid (600 ml) was mixture was stirred at reflux temperature for 5 min. or until a homogeneous solution is obtained. The reaction mixture was cooled and the precipitate was filtered off and dried i vacuo at 50 °C for 16 h which afforded 63.3 g (88 %) of phthalimidoacetaldehyde as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 4.58 (s, 2H), 7.76 - 7.78(m, 2H), 7.90 - 7.92 (m, 2H), 9.67 (s, 1 H). To a mixture of phthalimidoacetaldehyde (64 g, 0.34 mol) and trans-1- methoxy-3-(trimethylsilyloxy)-1 ,3-butadiene (81.5 g, 0.38 mol) in benzene (600 ml) stirred for 15 min. under nitrogen was added dropwise a 45 % solution of zinc chloride diethyl ether complex in dichloromethane (55.5 ml, 0.17 mol) at 0 °C. The reaction was allowed warm up to room temperature overnight. To the reaction mixture was added water (500 ml) and the resulting mixture was extracted with ethyl acetate (200 ml). The organic extract was washed successively with 1.0 N hydrochloric acid (2 x 200 ml) and brine (200 ml). The organic phase was dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo which afforded a slowly crystallising oil (98 g). To the solid was added a mixture of ethyl acetate and diethyl ether (400 ml, 1 :1) and the resulting precipitate was filtered off, washed with a small portion of diethyl ether and dried at 50 °C for 1h affording 59.8 g (69 %) of 2-(4-oxo-3,4-dihydro-2H-pyran-2-ylmethyl)- isoindole-1 ,3-dione as a solid. The filtrate was evaporated in vacuo and the residue purified by column chromatography on silica gel (1 L) using a mixture of ethyl acetate and heptane (1 :2) as eluant. Pure fractions were collected and the solvent evaporated in vacuo to almost dryness, the solid was filtered off and dried in vacuo at 50 °C for 16 h affording an additional 15 g (17 %) of 2-(4-oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindole-1 ,3- dione as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 2.61 (d, 2H), 3.85 (dd, 1 H), 4.18 (dd, 1 H), 4.76 (m, 1 H), 5.43 (d, 1 H), 7.28 (d, 1 H), 7.69 - 7.77 (m, 2H), 7.84 - 7.88 (m, 2H). 2-(4-Oxo-3,4-dihydro-2H-pyran-2-ylmethyl)-isoindole-1 ,3-dione (13 g, 0.051 mol) was dissolved in ethyl acetate (250 ml) and placed in a Parr bottle. 10 % Pd/C (1.5 g) was carefully added and the mixture was shaken under a pressure of 30 psi of hydrogen for 6.5 h (Parr apparatus). Filtration followed by evaporation of the ethyl acetate vacuo afforded a crude 11.5 g of 2-(4-oxo-tetrahydro-pyran-2-ylmethyl)-isoindole-1 ,3-dione pure enough for the next step. Analytical pure compound could be obtained by purification of a small sample (250 mg) by column chromatography on silica gel, utilising a mixture of hexane/ethyl acetate as a gradient (from 100/0 to 50/50). Pure fractions were collected and the solvent evaporated in vacuo affording 142 mg (55 %) of 2-(4-oxo- tetrahydro-pyran-2-ylmethyl)-isoindole-1 ,3-dione as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 2.30 - 2.68 (m, 4H), 3.62 (m, 1 H), 3.74 (m, 1 H), 4.00 (m, 2H), 7.75 (m, 2H), 7.88 (m, 2H). To a mixture of 2-(4-oxo-tetrahydro-pyran-2-ylmethyl)-isoindole-1 ,3-dione (11.5 g, 44 mmol), ferf-butyl cyanoacetate (6.9 g, 49 mmol) and elemental sulfur (1.6 g, 49 mmol) in ethanol (250 ml) was added morpholin (15 ml) and the resulting mixture was stirred at 50 °C for 16 h. The cooled reaction mixture was filtered and the precipitate filtered off and washed with diethyl ether and dried in vacuo affording 6.5 g (35 %) of 2-amino-5-(1 ,3-dioxo- 1,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as a solid. The filtrate was evaporated vacuo and the residue was dissolved in ethyl acetate (200 ml) washed with water (2 x 100 ml), brine (100 ml), dried (Na 2 SO ), filtered and the solvent evaporated in vacuo affording 6.0 g (33 %) of almost regioisomer pure 2-amino-7-(1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as a solid. 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester 1 H NMR (300 MHz, CDCI 3 ) δ 1.50 (s, 9H), 2.54 - 2.63 (m, 1 H), 2.84 - 2.90 (m, 1 H), 3.79 (q, 1 H), 3.96 - 4.04 (m, 2H), 4.48 - 4.62 (m, 2H), 5.91 (bs, 2H, H 2 ), 7.70 (m, 2H), 7.84 (m, 2H). 2-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester 1 H NMR (300 MHz, CDCI 3 ) δ 1.50 (s, 9H), 2.71 - 2.90 (m, 2H), 3.67 - 3.77 (m, 2H), 4.02 - 4.15 (m, 2H), 4.90 (m, 1 H), 6.04 (bs, 2H, NH ), 7.70 (m, 2H), 7.84 (m, 2H). To a solution of 2-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (6.0 g, 0.014 mol) in ethanol (100 ml) was added hydrazine-hydrate (1.4 ml, 0.029 mol). The mixture was stirred at reflux temperature for 1 h. The cooled reaction mixture was filtered and the solvent evaporated vacuo. The residue was dissolved in diethyl ether (200 ml) and washed with water (100 ml), brine (100 ml), dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo affording 2.9 g (71 %) of 2-amino-7-aminomethyl-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. To a ice cooled mixture of 2-amino-7-aminomethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (1.4 g, 4.92 mmol), triethylamine (2 ml) in dichloromethane (100 ml) was added dropwise a solution of benzo[1 ,3]dioxole-5-carbonyl chloride (1.0 g, 5.41 mmol) in dichloromethane (25 ml) during 1.5 h. The ice cooled reaction mixture was stirred for an additional 0.5 h. The volatiles were evaporated in vacuo and the residue was dissolved in ethyl acetate (200 ml) and washed with water (2 x 100 ml), brine (100 ml), dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue (2 g) was subjected to flash column chromatography (1 I silicagel) using a mixture of ethyl acetate/hexane (1 :2) as eluant. Pure fractions were collected affording after evaporation m vacuo 0.3 g (14 %) of 2-amino-7-(((benzo[1 ,3]dioxole-5-carbonyl)amino)- methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. TLC: R f = 0.44 (ethyl acetate/heptane 1 :1) A mixture of the above 2-amino-7-(((benzo[1 ,3]dioxole-5- carbonyl)amino)methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.3 g, 0.69 mmol), imidazol-1-yl-oxo-acetic acid ferf- butyl ester (0.16 g, 0.83 mmol) in dry tetrahydrofuran (50 ml) was stirred at room temperature for 16 h. The volatiles were evaporated in vacuo and the residue was dissolved in ethyl acetate (100 ml) and washed with water (2 x 50 ml), brine (50 ml), dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue (0.35 g) was subjected to flash column chromatography (500 ml silicagel) using a mixture of ethyl acetate/hexane (1 :1 ) as eluant. Pure fractions were collected and the solvent evaporated In vacuo. The residue was trituated with diethyl ether (5 ml), filtered off and dried in vacuo at 50 °C for 5 h which afforded 0.17 g (44 %) of 7- (((benzo[1 ,3]dioxole-5-carbonyl)amino)methyl)-2-(ferf-butoxyoxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. TLC: R f = 0.37 (ethyl acetate/heptane 1.1). The above di-fetf-butyl ester ( 0.17 g, 0.30 mmol) was dissolved in 25 % trifluoroacetic acid in dichloromethane (20 ml). The reaction was stirred at room temperature for 5.5 h. The volatiles were evaporated in vacuo and the residue trituated with diethyl ether (10 ml). The precipitate was filtered off, washed with diethyl ether, dried in vacuo at 50 °C for 72 h which afforded 100 mg (74 %) of the title compound as a solid. M.p.: 227 - 230° C; Calculated for Cι 9 Hι 6 N 2 O 9 S, 0.5 x H 2 O; C, 49.89 %; H, 3.75 %; N, 6.12 %. Found: C, 50.02 %; H, 3.68 %; N, 5.98 %. EXAMPLE 29 7-r3-(2,4-Dimethoxy-phenyl)-ureidomethyl1-2-(oxalyl-amino)-4,7-dihvdro- 5H-thieno[2,3-clpyran-3-carboxylic acid To a solution of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester (64 mg, 0.22 mmol) in dichloromethane (1 ml) was added 2,4-dimethoxyphenylisocyanate (40 mg, 0.22 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate (30 ml), washed with saturated sodium carbonate (3 x 25 ml), brine (3 x 25 ml), dried (MgSO 4 ), filtered and the solvent evaporated vacuo. The residue was subjected to preparative thin layer chromatography (100% dichloromethane). R f =0.8 was isolated and the solvent evaporated in vacuo which afforded 55 mg (53 %) of 2-amino-7-(3-(2,4-dimethoxy- phenyl)ureidomethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 7.75 (d, J = 9.6, 1 H), 7.62 (d, J = 8.1 , 1 H), 6.45 (m, 3H), 5.00 (bs, 2H), 4.68 (m, 1 H), 4.12 (m, 2H), 3.80 (s, 3H), 3.76 (s, 3H), 3.76-3.67 (m, 1 H), 3.30 (dd, J = 14, 6.9, 1 H), 2.76 (m, 2H), 1.55 (s, 9H). MS: APCI (+): 464.3 (M+H). To a solution of the above 2-amino-7-(3-(2,4-dimethoxy- phenyl)ureidomethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (47 mg, 0.11 mmol) in dichloromethane (1 ml) was added triethylamine (28 μl, 0.22 mmol) and midazol-1-yl-oxo-acetic acid fetf-butyl ester (40 mg, 0.22 mmol). The mixture allowed to stir at room temperature for 18 h. The volatiles were evaporated vacuo and the residue diluted with ethyl acetate (35 ml). The organic phase was washed with saturated sodium carbonate (3 x 25 ml), brine (3 x 25 ml), dried (MgSO ), filtered, and the solvent evaporated vacuo. The resultant oil was subjected to preparative thin layer chromatography (60 % ethyl acetate/40 % hexanes). Pure 2-(ferf- butoxyoxalyl-amino)-7-(3-(2,4-dimethoxy-phenyl)ureidomethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester 34 mg (58 %) was isolated as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 12.49 (s, 1 H), 7.70 (d, J = 9.6, 1 H), 6.62 (bs, 1 H), 6.47 (m, 3H), 5.02 (bs, 1 H), 4.84 (m, 1 H), 4.19 (dm, 1 H), 3.82 (s, 3H), 3.79 (s, 3H), 3.75-3.70 (m, 1 H), 3.36 (dd, J = 13.5, 7.5, 1 H), 2.87 (m, 2H), 1.61 (s, 9H), 1.60 (s, 9H). MS: APCI (+): 592.4 (M+H). The above 2-(ferf-butoxyoxalyl-amino)-7-(3-(2,4-dimethoxy- phenyl)ureidomethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (34 mg) was dissolved in 20 % trifluoroacetic acid in dichloromethane (2 ml) and stirred at room temperature for 3 hours. The volatiles were evaporated in vacuo and the residue was titurated with diethyl ether (2x), filtered off and washed with a small amount of dichloromethane which afforded after drying in vacuo 16 mg (89 %) of the title compound as a solid. 1 H NMR (300 MHz, CD 3 OD) δ 7.66 (d, J = 9, 1 H), 6.53 (d, J = 2.7, 1 H), 6.44 (dd, J = 9, 2.7, 2H), 4.82 (m, 1 H), 4.2 (m, 2H), 3.82 (s, 3H), 3.76 (s, 3H), 3.67 (dd, J = 13, 4.5, 2H), 2.94 (m, 2H). MS: APCI (+): 480.3 (M+H); EXAMPLE 30 2-(Oxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro-5H-thienor2,3-clpyran-3- carboxylic acid A solution of glyoxylic acid ethyl ester, polymer form (2.02 g, 8.9 mmol) and (3-methoxy-1-methylene-allyloxy)-trimethyl-silane (1.9 ml, 8.9 mmol, Danishefsky's diene) in benzene (12 ml) was placed under nitrogen. Zinc chloride (0.5N in tetrahydrofuran, 8.9 ml, 4.45 mmol) was added and the reaction stirred at ambient temperature for 72 h. The mixture was concentrated in vacuo, diluted with ethyl acetate (100 ml) and washed with 1N hydrochloric acid (20 ml), saturated sodium bicarbonate (20 ml), and brine (20 ml). The organic layer was dried (Na 2 SO ), filtered, and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a mixture of ethyl acetate/hexane (1 :2) as eluant. Pure fractions were collected and the solvent evaporated in vacuo which afforded 1.2 g (75 %) of 4-oxo-3,4-dihydro-2H-pyran-2-carboxylic acid ethyl ester as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 7.40 (d, J = 6, 1 H), 5.48 (d, J = 6, 1 H), 5.01 (t, J = 8, 1 H), 4.28 (q, J = 7, 2H), 2.85 (d, J = 8, 2H), 1.29 (t, J = 7, 3H). To a solution of the above of 4-oxo-3,4-dihydro-2H-pyran-2-carboxylic acid ethyl ester (1.0 g, 5.9 mmol) in ethyl acetate (12 ml) was added 10 % palladium on activated carbon (0.15 g). The reaction was shaken on a Parr hydrogenator under a hydrogen atmosphere (30 psi) for 1.5 h. The mixture was filtered through celite and concentrated in vacuo. The residue was purified by silica gel chromatography using diethyl ether as eluant. Pure fractions were collected and the solvent evaporated vacuo which affording 0.6 g (60 %) of 4-oxo-tetrahydro-2H-pyran-2-carboxylic acid ethyl as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 4.41-4.35 (m, 1 H), 4.26 (q, J = 7, 2H), 3.81- 3.70 (m, 1 H), 2.73-2.58 (m, 3H), 2.44-2.36 (m, 1 H), 1.29 (t, J = 7, 3H). To a solution of 4-oxo-tetrahydro-2H-pyran-2-carboxylic acid ethyl (0.6 g, 3.5 mmol) in absolute ethanol (6 ml) was added sulfur (0.12 g, 3.85 mmol) and ferf-butyl cyanoacetate (0.64 g, 4.55 mmol). The solution was stirred under nitrogen in a 50 °C oil bath and morpholin (0.61 ml, 7.0 mmol) was added. The reaction was stirred for 18 h. and then cooled to ambient temperature and excess sulfur removed by filtration. The filtrate was concentrated in vacuo and reconstituted in ethyl acetate (50 ml). The organic phase was washed with brine (2 x 10 ml), dried (Na 2 SO ), filtered, and the solvent evaporated vacuo. The residue was purified by silica gel chromatography using a gradient of ethyl acetate/hexane (20 to 25 % gradient) as eluant. Pure fraction of the two isomers were collected and the solvent evaporated in vacuo which afforded 0.47 g of 2-amino-4,7- dihydro-5H-thieno[2,3-c]pyran-3,5-dicarboxylic acid 3-fetf-butyl ester 5- ethyl ester (A) and 0.3 g of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran- 3,7-dicarboxylic acid 3-fetf-butyl ester 7-ethyl ester (B) in 62 % combined yield. (A) 1 H NMR (300 MHz, CDCI 3 ) δ 5.96 (bs, 2H), 4.77-4.61 (m, 2H), 4.32-4.18 (m, 3H), 3.19-3.12 (m, 1 H), 2.90-2.80 (m, 1 H), 1.52 (s, 9H), 1.29 (t, J = 7, 3H). APCI-MS: [M+H] + = 272.4 (loss of t-butyl) (B) 1 H NMR (300 MHz, CDCI 3 ) δ 5.10 (s, 1 H), 4.28-4.13 (m, 3H), 3.98-3.91 (m, 1 H), 2.82-2.76 (m, 2H), 1.51 (s, 9H), 1.31 (t, J = 7, 3H). APCI-MS: [M+H] + = 272.4 (loss of t-butyl) The above 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,5-dicarboxylic acid 3-fetf-butyl ester 5-ethyl ester (275 mg, 0.84 mmol) was dissolved in a mixture of ethanol (4 ml) and tetrahydrofuran (1 ml). Sodium hydroxide (1 N, 1.6 ml, 1.68 mmol) was added and the reaction stirred at ambient temperature for 5 h. after which TLC analysis indicated that the reaction was complete. The reaction was monitored with a pH meter and neutralized with 1 N hydrochloric acid until pH = 6.9. The solution was concentrated in vacuo to give 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran- 3,5-dicarboxylic acid 3-ferf-butyl ester as a solid. Sodium chloride remained as an impurity. 1 H NMR (300 MHz, CD 3 OD) δ 4.67-4.54 (m, 2H), 4.00-3.95 (m, 1 H), 3.20- 3.12 (m, 1 H), 2.74-2.63 (m, 1 H), 1.54 (s, 9H). APCI-MS: [M+H] + = 300.0 To a solution of the above 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,5- dicarboxylic acid 3-fetf-butyl ester (94 mg, 0.31 mmol) and 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg, 0.37 mmol) in distilled dichloromethane (4 ml) under nitrogen was added aniline (32 μl, 0.34 mmol) followed by 2,6-lutidine (0.11 ml, 0.93 mmol). The reaction was stirred for 72 h., concentrated in vacuo and reconstituted in ethyl acetate (30 ml). The organic layer was washed with 1% hydrochloric acid (10 ml), saturated sodium bicarbonate (10 ml), brine (10 ml), dried (Na 2 SO ), filtered, and the solvent evaporated vacuo to give 51 mg (45 %) of 2-amino-5-phenylcarbamoyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 8.40 (s, 1 H), 7.60 (d, 1 H, J = 7), 7.49 (d, 1 H, J = 8), 7.34 (t, 1 H, J = 8), 7.32 (t, 1 H, J = 8), 7.13 (t, 1 H, J = 7), 6.03 (s, 2H), 4.82-4.73 (m, 2H), 4.25-4.22 (m, 1H), 3.43-3.38 (m, 1H), 2.79-2.72 (m, 1 H), 1.54 (s, 9H). APCI-MS: [M+H] + = 375.5 To a solution of the above 2-amino-5-phenylcarbamoyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (51 mg, 0.14 mmol) in distilled dichloromethane (3 ml) under nitrogen was added midazol-1-yl- oxo-acetic acid fetf-butyl ester (80 mg, 0.42 mmol) and triethylamine (38 μl, 0.28 mmol). The reaction was stirred for 4 h., concentrated in vacuo and reconstituted in ethyl acetate (25 ml). The organic layer was washed with 1% hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), brine (5 ml), dried (Na 2 SO ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a 4 % mixture of ethyl acetate/dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 41 mg (26 % over two steps) of 2-(fetf-butoxyoxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 12.56 (s, 1 H), 8.40 (s, 1 H), 7.59 (d, J = 8, 2H), 7.33 (t, J = 8, 2H), 7.12 (t, J = 7, 1 H), 5.01-4.85 (m, 2H), 4.27-4.22 (m, 1 H), 3.54-3.47 (m, 1 H), 3.89-2.79 (m, 1 H), 1.60 (s, 9H), 1.58 (s, 9H). APCI-MS: [M+H] + = 503.2 The above 2-(fer-butoxyoxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (37 mg, 0.074 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (3 ml). The reaction was stirred at ambient temperature for 7 h., concentrated in vacuo and evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with ethyl ether and dried in vacuo to give 18 mg (62 %) of the titie compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.32 (s, 1 H), 9.85 (s, 1H), 7.69 (d, J = 8, 2H), 7.31 (t, J = 8, 2H), 7.07 (t, J = 7, 1 H), 4.98 (d, J = 15, 1 H), 4.83 (d, J = 15, 1 H), 4.35-4.31 (m, 1 H), 3.23 (d, J = 17, 1 H), 2.84 (dd, J = 17, 10, 1 H). APCI-MS: [M+H] + = 391.3 HPLC (254.4nm): R t =3.22 min, 100% EXAMPLE 31 5-Benzylcarbamoyl-2-(oxalyl-amino)-4,7-dihvdro-5H-thieno[2,3-clpyran-3- carboxylic acid To a solution of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,5- dicarboxylic acid 3-ferf-butyl ester (101 mg, 0.34 mmol, prepared in Example 31 ) and 1 -(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (78 mg, 0.41 mmol) in distilled dichloromethane (4 ml) under nitrogen was added benzylamine (40 μl, 0.37 mmol) followed by 2,6-lutidine (0.12 ml, 1.02 mmol). The reaction was stirred for 72 h., concentrated in vacuo and reconstituted in ethyl acetate (30 ml). The organic layer was washed with 1 % hydrochloric acid (10 ml), saturated sodium bicarbonate (10 ml), brine (10 ml), dried (Na 2 SO 4 ) over sodium sulfate, filtered, and the solvent evaporated vacuo to give 72 mg (56 %) of 2-amino-5-benzylcarbamoyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester. 1 H NMR (400 MHz, CDCI 3 ) δ 7.36-7.28 (m, 5H), 4.66 (s, 2H), 4.44 (d, J = 5, 2H), 4.17-4.13 (m, 1 H), 3.40-3.33 (m, 1 H), 2.75-2.66 (m, 1 H), 1.54 (s, 9H). APCI-MS: [M+H] + = 389.5 To a solution of the above 2-amino-5-benzylcarbamoyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3, carboxylic acid fetf-butyl ester (72 mg, 0.19 mmol) in distilled dichloromethane (4 ml) under nitrogen was added midazol-1-yl- oxo-acetic acid ferf-butyl ester (0.11 g, 0.57 mmol) and triethylamine (51 μl, 0.38 mmol). The reaction was stirred for 4 h., concentrated in vacuo and reconstituted in ethyl acetate (25 ml). The organic layer was washed with 1 % hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), brine (5 ml), dried (Na 2 SO ), filtered, and the solvent evaporated vacuo. The crude material was purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (5 to 10 % gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo to give 42 mg (24 % over two steps) of 5-benzylcarbamoyl-2-(ferf-butoxyoxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3, carboxylic acid fetf-butyl ester as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 12.56 (s, 1 H), 7.37-7.29 (m, 5H), 6.97 (t, 1 H, J = 6), 4.89-4.77 (m, 2H), 4.58-4.46 (m, 2H), 4.20-4.16 (m, 1 H), 3.50-3.44 (m, 1 H), 2.84-2.76 (m, 1 H), 1.61 (s, 9H), 1.60 (s, 9H). APCI-MS: [M+H] + = 517.3 The above 5-benzylcarbamoyl-2-(ferf-butoxyoxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3, carboxylic acid ferf-butyl ester (36 mg, 0.07 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (3 ml). The reaction was stirred at ambient temperature for 7 h., concentrated vacuo and evaporated vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 14 mg (50 %) of the title compound as a solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 8.48 (t, J = 6, 1 H), 7.31- 7.20 (m, 5H), 4.91 (d, J = 15, 1 H), 4.76 (d, J = 15, 1 H), 4.32-4.29 (m, 2H), 4.20-4.16 (m, 1 H), 3.22 (m, 1 H, partially obscured by water), 2.70-2.63 (m, 1 H). APCI-MS: [M+H] + = 405.2 HPLC (254.4nm): R,=3.06 min, 100 % EXAMPLE 32 2-(Oxalyl-amino)-4,7-dihydro-5H-thienof2,3-clpyran-3,7-dicarboxylic acid 7-ethyl ester To a solution of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7- dicarboxylic acid 3-fetf-butyl ester 7-ethyl ester (60 mg, 0.18 mmol) in distilled dichloromethane (3 ml) under nitrogen was added midazol-1-yl- oxo-acetic acid fetf-butyl ester (0.11 g, 0.54 mmol) and triethylamine (50 μl, 0.36 mmol). The reaction was stirred for 4 h., concentrated in vacuo and reconstituted in ethyl acetate (20 ml). The organic layer was washed with 1 % hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), brine (5 ml), dried (Na 2 SO 4 ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a 6 % mixture of ethyl acetate/dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 78 mg (95 %) of 2-(fetf-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7- dicarboxylic acid 3-fetf-butyl ester 7-ethyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 12.54 (s, 1 H), 5.28 (s, 1 H), 4.27 (q, 2H, J = 7), 4.25-4.18 (m, 1 H), 4.04-3.96 (m, 1 H), 2.96-2.80 (m, 2H), 1.60 (s, 9H), 1.57 (s, 9H). LC-MS: R t =3.97 min, [M+H] + = 456.3 The above 2-(ferf-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran- 3,7-dicarboxylic acid 3-fetf-butyl ester 7-ethyl ester (72 mg, 0.16 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (4 ml). The reaction was stirred at ambient temperature for 7 h., concentrated in vacuo and the residue evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 48 mg (88 %) of the title compound as a solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.34 (s, 1 H), 5.47 (s, 1 H), 4.19 (q, J = 7, 2H), 3.98-3.94 (m, 2H), 2.90-2.78 (m, 2H), 1.23 (t, J = 7, 3H). APCI-MS: [M+H] + = 344.2 HPLC (254.4nm): R,=2.82 min, 100 % EXAMPLE 33 7-Benzylcarbamoyl-2-(oxalyl-amino,-4,7-dihvdro-5H-thienor2,3-clpyran-3- carboxylic acid To a solution of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7- dicarboxylic acid 3-fetf-butyl ester 7-ethyl ester (0.12 g, 0.37 mmol) in ethanol (3 ml) was added potassium hydroxide (56 mg, 1.0 mmol) dissolved in a minimum amount of water. The mixture was stirred for 24 h., then 1N hydrochloric acid was added until pH = 7. The solution was concentrated in vacuo and the residue partitioned between ethyl acetate (35 ml) and water (10 ml). The layers were separated and 1 % hydrochloric acid (1 ml) was added to the aqueous layer. The aqueous layer was then extracted further with ethyl acetate (3 x 15 ml) and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ) and filtered. Triethylamine (3 drops) was added to the solution to stabilize the acid-sensitive compound. The solution was concentrated in vacuo affording 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7-dicarboxylic acid 3-fetf-butyl ester triethylamine salt (approximately 0.13 g) as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 5.01 (s, 1 H), 4.28-4.23 (m, 1 H), 3.90-3.85 (m, 1 H), 2.88-2.71 (m, 3H), 1.56 (s, 9H). A solution of the above 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7- dicarboxylic acid 3-fetf-butyl ester triethylamine salt (0.12 g, 0.30 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (71 mg, 0.36 mmol) was prepared in distilled acetonitrile under nitrogen. Benzylamine (36 μl, 0.33 mmol) was added followed by 2,6-lutidine (70 μl, 0.60 mmol). The reaction was stirred at ambient temperature for 18 h., then concentrated in vacuo and reconstituted in ethyl acetate (30 ml). The organic layer was washed with 1 % hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (2 x 5 ml), and brine (10 ml), dried (Na 2 SO ), filtered, and the solvent evaporated vacuo which afforded crude 2-amino-7- benzylcarbamoyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf- butyl ester which was used without purification. To a solution of the above crude 2-amino-7-benzylcarbamoyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (77 mg, 0.2 mmol) in distilled dichloromethane (3 ml) under nitrogen was added midazol-1-yl- oxo-acetic acid fetf-butyl ester (0.11 g, 0.6 mmol) and triethylamine (55 μl, 0.4 mmol). The reaction was stirred for 5 h., concentrated in vacuo and reconstituted in ethyl acetate (20 ml). The organic layer was washed with 1 % hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (5 ml), brine (5 ml), dried (Na 2 SO ), filtered, and the solvent evaporated in vacuo. The crude material was purified by silica gel chromatography using a 5 % mixture of ethyl acetate/dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 29 mg (19 % over two steps) of 7-benzylcarbamoyl-2-(ferf-butoxyoxalyl-amino)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 12.49 (s, 1 H), 7.35-7.26 (m, 5H), 6.96 (t, J = 6, 1 H), 5.20 (s, 1 H), 4.55-4.41 (m, 2H), 4.22-4.17 (m, 1 H), 3.87-3.81 (m, 1 H), 2.97-2.84 (m, 2H), 1.61 (s, 9H), 1.59 (s, 9H). APCI-MS: [M-H] " = 516 The above 7-benzylcarbamoyl-2-(ferf-butoxyoxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (29 mg, 0.06 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (2 ml). The reaction was stirred at ambient temperature for 7 h., concentrated vacuo and the residue evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried vacuo to give 18 mg (80 %) of the title compound as an solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.33 (s, 1 H), 8.67 (t, J = 6, 1 H), 7.30- 7.21 (m, 5H), 5.23 (s, 1 H), 4.31-4.28 (m, 2H), 4.13-4.10 (m, 1 H), 3.88-3.85 (m, 1 H), 2.86 (bs, 2H). APCI-MS: [M+H] + = 405 HPLC (254.4nm): R t =3.12 min, 94 % EXAMPLE 34 7-((2-(4-Methanesulfonyl-phenyl)-acetylamino)-methyl)-2-(oxalyl-amino)- 4,7-dihvdro-5H-thieno[2,3-c1pyran-3-carboxylic acid To a solution of (4-methanesulfonyl-phenyl)-acetic acid (90.4 mg, 0.42 mmol) in a mixture of dichloromethane (3 ml) and N,N- dimethylformamide (1 ml) cooled at 0 °C was added diisopropylethylamine (306 μl, 1.76 mmol), diisopropylazodicarboxylate (72 μl, 0.45 mmol) and 1-hydroxy-benzotriazole (56.6 mg, 0.42 mmol). After being stirred for 20 minutes, 2-amino-7-aminomethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (100 mg, 0.35 mmol) dissolved in dichloromethane (1 ml) was added via syringe. The reaction mixture was stirred for 18 h. while slowly warming to room temperature. The volatiles were evaporated vacuo and the residue diluted with ethyl acetate (50 ml). The organic phase was washed with saturated sodium bicarbonate (3 x 50 ml), 1 % hydrochloric acid (3 x 50 ml), brine (3 x 50 ml), dried (MgSO ), filtered, and the solvent evaporated in vacuo. The resultant oil was subjected to preparative thin layer chromatography using a mixture of methanol/dichloromethane (1 :9) as eluant. Fraction with R f =0.5 was isolated which afforded after evaporating the solvent vacuo 115 mg (69 %) of 2-amino-7-((2-(4-methanesulfonyl-phenyl)acetylamino)- methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 7.87 (d, J = 8.7, 2H), 7.39 (d, J = 7.5, 2H), 5.91 (bs, 2H), 4.65 (m, 1 H), 4.09 (dt, J = 7.8, 3.3, 1 H), 3.85-3.65 (m, 2H), 3.61 (s, 2H), 3.45-3.38 (m, 2H), 3.05 (s, 3H), 2.75 (m, 2H), 1.56 (s, 9H). MS: APCI (+): 481 (M+H). To a solution of the above 2-amino-7-((2-(4-methanesulfonyl- phenyl)acetylamino)-methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (1 10 mg, 0.23 mmol) in dichloromethane (3 ml) was added triethylamine (96 μl, 0.69 mmol) and midazol-1-yl-oxo-acetic acid ferf-butyl ester (134 mg, 0.69 mmol). The reaction was stirred at room temperature for 18 h. The reaction mixture was concentrated i vacuo, diluted in ethyl acetate (50 ml), washed with saturated sodium carbonate (3 x 50 ml), brine (3 x 50 ml), dried (MgSO ), filtered and the solvent evaporated in vacuo. The resultant oil was subjected to preparative thin layer chromatography using a mixture of methanol/dichloromethane (1 :9). Fraction with R f =0.5 was collected and the solvent evaporated vacuo affording 70 mg (50 %) of 2-(fetf-butoxyoxalyl-amino)-7-((2-(4-methanesulfonyl- phenyl)acetylamino)-methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 12.49 (s, 1 H), 7.88 (d, J = 8.1 , 2H), 7.46 (d, J = 8.1 , 2H), 5.88 (bs, 1 H), 4.78 (m, 1 H), 4.15 (dt, J = 12, 4, 1 H), 3.86-3.71 (m, 2H), 3.64 (s, 2H), 3.42-3.34 (m, 2H), 3.04 (s, 3H), 2.85 (m, 2H), 1.62 (s, 9H), 1.61 (s, 9H). MS: APCI (+): 609 (M+H)[minor], 497 (-2 tert butyls)[major]; LC-MS: s, 99 % The above 2-(ferf-butoxyoxalyl-amino)-7-((2-(4-methanesulfonyl- phenyl)acetylamino)-methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid fetf-butyl ester (60 mg, 0.098 mmol) was dissolved in 50 % trifluoroacetic acid in dichloromethane (2 ml) and allowed to stir at room temperature for 3 hours. The reaction mixture was concentrated i vacuo, the residue titurated with diethyl ether (3x), and dried in vacuo which afforded 45 mg (92 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.34 (s, 1 H), 8.47 (m, 1 H), 7.82 (d, J = 7.8, 2H), 7.50 (d, J = 7.8, 2H), 4.75 (bs, 1 H), 4.10 (m, 1 H), 3.69 (m, 1 H), 3.60 (d, J = 3.6, 2H), 3.52 (m, 1 H), 3.35 (m, 2H), 3.18 (s, 3H), 2.83 (m, 2H). MS: APCI (-): 495 (M-H); LC-MS: s, 95 %. EXAMPLE 35 2-((3-Carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thienof2,3-c1pyran-5- ylmethvQcarbamovQnicotinic acid 2-(ferf-Butoxyoxalyl-amino)-5-aminomethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester (164 mg, 0.58 mmol) was stirred for 20 h at 80 °C with furo[3,4-b]pyridine-5,7-dione (86.1 mg, 0.58 mmol) in a mixture of tetrahydrofuran (1.0 ml) and N,N-dimethylformamide (0.25 ml). The volatiles were removed in vacuo and the residue was dissolved in ethyl acetate (50 ml) and washed with water (3 x 30ml). The organic layer was dried(MgSO ), filtered, and the solvent evaporated in vacuo. The residue (78 mg) was purified by preparative TLC (hexane/ethyl acetate, 50:50) which afforded 2 products: 2-((2-amino-3-ferf-butoxycarbonyl-4,7- dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl)carbamoyl)nicotinic acid (A) (27.9 mg, 11 %) and 2-amino-5-(5,7-dioxo-5,7-dihydro-pyrrolo[3,4- b]pyridin-6-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (B) (21.3 mg, 9 %). (A) 1 H NMR (300 MHz, CDCI 3 ): δ 9.02 (s, 1 H), 8.74 (d, J = 3.3, 1 H), 8.14 (d, J =7.5, 1 H), 7.40 (dd, J = 4.8, J = 5.1 , 1 H), 6.71 (m, 1 H), 5.98 (s, 2H), 4.63 (s, 2H), 4.00 (m, 1 H), 3.42 (m, 1 H), 2.90 (dd, J = 3.3, J = 3.6, 1 H), 2.59 (dd, = 1 1 , J = 11 , 1 H), 1.48 (s, 9H). MS m/z 434 (M+); (B) 1 H NMR (300 MHz, CDCI 3 ) δ 8.99 (d, J = 5.1 , 1 H), 8.20 (d, J = 9, 1 H), 7.64 (dd, J = 5.7, 4.8, 1 H), 5.94 (s, 2H), 4.60 (d, J = 14, 1 H), 4.51 (d, J = 14, 1 H), 4.05 (m, 2H), 3.87 (d, J = 12.5, 1 H), 2.92 (d, J = 17, 1 H), 2.61 (m, 1 H), 1.53 (s, 9H). MS: APCI (+): 416 (M+1)[minor], 360 (M- ferf-butyl) [major]. To a solution of the above 2-((2-amino-3-ferf-butoxycarbonyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-5-ylmethyl)carbamoyl)nicotinic acid (27.9 mg, 0.064 mmol) in tetrahydrofuran (2 ml) was added midazol-1-yl-oxo-acetic acid fetf-butyl ester (38 mg, 0.193 mmol) and triethylamine (9 μl, 0.064 mmol). The resulting mixture was stirred at room temperature for 20 h. The solvent was removed in vacuo and the residue was dissolved in dichloromethane (20 ml) and washed with water (3 x 10 ml). The extracts were dried(MgSO ), filtered and the solvent evaporated in vacuo. The residue was purified by preparative TLC (0.5mm, hexane/ethyl acetate, 1/1 to 2/3 gradient). After evaporation of the solvent vacuo 917 mg (46 %) of 2-(3-ferf-butoxycarbonyl-2-(ferf-butoxyoxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-5-ylmethyl)carbamoyl)nicotinic acid was isolated as a solid. 1 H NMR (300 MHz, CDCI 3 ): δ 9.04 (s, 1 H), 8.75 (s, 1 H), 8.15 (d, J = 7.5, 1 H), 7.42 (dd, J = 6.9, J = 5.1 , 1 H), 6.73 (m, 1 H), 4.81 (dd, J = 15.3, J = 14.4, 2H), 4.03 (m, 1 H), 3.83 (m, 1 H), 3.47 (m, 1 H), 2.99 (d, J = 17.1 , 1 H), 2.59 (dd, J = 1 1.1 , J - 10.8, 1 H), 1.61 (s, 9H), 1.48 (s, 9H). MS: 506 (M-55). The above 2-(3-ferf-butoxycarbonyl-2-(fetf-butoxyoxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl)carbamoyl)nicotinic acid (13.1 mg, 0.023 mmol) was stirred in 50 % trifluoroacetic acid in dichloromethane (2 ml) at room temperature for 7 h. The solvent was evaporated vacuo which afforded 10 mg (96%) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ): δ 9.04 (s, 1 H), 8.77 (d, J = 7.7, 1 H), 8.16 (d, J = 7.5, 1 H), 7.60 (d, J = 7.8, 1 H), 4.88 (d, J = 9, 1 H), 4.76 (d, J = 9, 1 H), 3.96 (m, 1 H), 3.02 (m, 1 H), 2.78 (m, 1 H). MS: 481 (M+33). EXAMPLE 36 7-(2,4-Dioxo-5-pyridin-2-ylmethylene-thiazolidin-3-ylmethyl)-2-(oxalyl- amino)-4,7-dihvdro-5H-thienor2,3-clpyran-3-carboxylic acid To a mixture of 2-(ferf-butoxyoxalyl-amino)-7-hydroxymethyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (1.0 g, 2.42 mmol), 5-pyridin-2-ylmethylene-thiazolidine-2,4-dione (0.55 g, 2.66 mmol, prepared in a similar way as described in J. Med. Chem. 41 (10), 1619- 1630 (1998)) and triphenylphosphine (0.7 g, 2.66 mmol) in dry tetrahydrofuran (75 ml) cooled to 0 °C under a nitrogen atmosphere was added diethyl azodicarboxylate (DEAD) (420 μl ml, 2.66 mmol). The reaction mixture was allowed to stir overnight, slowly warming to room temperature. The volatiles were evaporated in vacuo, the resultant solid was washed with diethyl ether, filtered off and dried i vacuo at 50 °C for h affording 1.4 g (96 %) of 2-(ferf-butoxyoxalyl-amino)-7-(2,4-dioxo-5- pyridin-2-ylmethylene-thiazolidin-3-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester as a solid. TLC: R f = 0.46 (ethyl acetate/heptane 1:1). The above di-ferf-butyl ester ( 1.0 g, 1.66 mmol) was dissolved in 25 % trifluoroacetic acid in dichloromethane (30 ml). The reaction was stirred at room temperature for 16 h. The volatiles were evaporated in vacuo and the residue trituated with diethyl ether (50 ml). The precipitate was filtered off, washed with diethyl ether, dried vacuo at 50 °C for 16 h which afforded 0.8 g of semi pure title compound. The title compound (0.8 g) was suspended in ethyl acetate (25 ml) and heated at reflux temperature for 0.5 h. Isopropanol (5 ml) was added and the mixture was cooled to room temperature the precipitate filtered off and dried in vacuo at 50 °C for 16 h which afforded 0.37 g (37 %) of the title compound as a solid. Calculated for C 2 oHi 5 N 3 O 8 S 2 , 0.5 x H 2 O, 0.75 x isopropanol; C, 49.17 %; H, 4.08 %; N, 7.73 %. Found: C, 48.97 %; H, 4.03 %; N, 7.45 %. EXAMPLE 37 7-(2,4-Dioxo-5-pyridin-2-ylmethyl-thiazolidin-3-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-clpyran-3-carboxylic acid To a solution of 5-pyridin-2-ylmethylene-thiazolidine-2,4-dione (5.0 g, 0.024 mol, prepared in a similar way as described in J. Med. Chem. 41 (10), 1619-1630 (1998)) in tetrahydrofuran (300 ml) was added 10 % palladium on carbon (1 g) and the resulting mixture was hydrogenated. After 50 ml of hydrogen was consumed and additional portion of 10 % - palladium on carbon (5 g) was added and the hydrogenation was continued at 50 psi for 16 h. The mixture was filtered and the filtrate evaporated in vacuo. The residue was subjected to flash column chromatography (1 I silicagel) using a mixture of ethyl acetate/hexane (1 :1) as eluant. Semi pure fractions were collected and the solvent evaporated vacuo affording 0.8 g (16 %) of 5-pyridin-2-ylmethyl- thiazolidine-2,4-dione as a solid. To a mixture of 2-(.etf-butoxyoxalyl-amino)-7-hydroxymethyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.7 g, 1.69 mmol), 5-pyridin-2-ylmethyl-thiazolidine-2,4-dione (0.36 g, 1.86 mmol) and triphenylphosphine (0.49 g, 1.86 mmol) in dry tetrahydrofuran (40 ml) cooled to 0 °C under a nitrogen atmosphere was added diethyl azodicarboxylate (DEAD) (290 μl ml, 1.86 mmol). The reaction mixture was allowed to stir overnight, slowly warming to room temperature. The volatiles were evaporated in vacuo, the resultant residue was subjected to flash column chromatography (0.5 I silicagel) using a mixture of ethyl acetate/hexane (1 :2) as eluant. Pure fractions were collected and the - solvent evaporated in vacuo affording 0.6 g (59 %) of 2-(ferf-butoxyoxalyl- amino)-7-(2,4-dioxo-5-pyridin-2-ylmethyl-thiazolidin-3-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. TLC: R f = 0.43 (ethyl acetate/heptane 1 :1). The above di-ferf-butyl ester ( 0.5 g, 0.83 mmol) was dissolved in 25 % trifluoroacetic acid in dichloromethane (25 ml). The reaction was stirred at room temperature for 16 h. The volatiles were evaporated i vacuo and the residue trituated with diethyl ether (20 ml). The precipitate was filtered off, washed with diethyl ether, dried vacuo at 50 °C for 1 h which afforded 0.3 g of semi pure titie compound. The titie compound (0.3 g) was suspended in isopropanol (15 ml) and heated at reflux temperature for 5 min., cooled to room temperature and the precipitate filtered off and dried vacuo at 50 °C for 16 h which afforded 0.2 g (49 %) of the titie compound as a solid. M.p.: > 250 °C; Calculated for 0.25 x H 2 O; C, 48.43 %; H, 3.56 %; N, 8.47 %. Found: C, 48.41 %; H, 3.57 %; N, 8.10 %. EXAMPLE 38 7-(5-(4-Methoxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl.-2-(oxalyl- amino)-47-dihvdro-5H-thienof2,3-c1pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 37. M.p.: 236 - 238 °C; Calculated for C 22 Hι 8 N 3 O 9 S 2 , 0.5 x H 2 O; C, 50.09 %; H, 3.63 %; N, 5.31 %. Found: C, 49.92 %; H, 3.59 %; N, 5.18 %. EXAMPLE 39 7-f5-(4-Acetylamino-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl1-2- (oxalyl-amino)-4,7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 37. M.p.: > 250 °C; Calculated for C 23 H 19 N 3 O 9 S 2 , 2 x H 2 O; C, 47.50 %; H, 3.99 %; N, 7.23 %. Found: C, 47.60 %; H, 3.45 %; N, 6.80 %. EXAMPLE 40 7-f5-(3,5-Dimethoxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethvπ-2- (oxalyl-amino)-4,7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid The title compound was prepared in a similar way as described in Example 37. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.37 (s, 1 H), 7.92 (s, 1 H), 6.80 (d, J = 1.8, 2H), 6.66 (t, J = 2.1 , 1 H), 5.00 (m, 1 H), 4.06 (bm, 2H), 3.81 (s, 6H), 3.71 (dd, J = 6.6, 6, 2H), 2.83 (m, 2H). MS: APCI (+): 549 (M+H); LC-MS; s, 90 %. EXAMPLE 41 7-[5-(1 H-lmidazol-4(5)-ylmethylene)-2,4-dioxo-thiazolidin-3-ylmethvn-2- (oxalyl-amino)-4,7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 37. M.p.: > 250 °C; Calculated for C 18 H 14 N 4 O 8 S 2 ; C, 40.65 %; H, 2.56 %; N, 9.17 %. Found: C, 40.54 %; H, 2.55 %; N, 9.46 %. EXAMPLE 42 5-(1 ,3-Dioxo-4,7-epoxido-1 ,3,4,5,6,7-hexahydro-isoindol-2-ylmethyl)-2- (oxalyl-amino)-4,7-dihvdro-5H-thienof2,3-clpyran-3-carboxylic acid To a solution of 2-(ferf-butoxyoxalyl-amino)-5-hydroxymethyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.20 g, 0.48 mmol) in tetrahydrofuran (5 ml) was added 10-oxa-4-aza- tricyclo(5,2,1 ,0,2,6)decane-3,5-dione (81 mg, 0.48 mmol) and triphenylphosphine (126 mg, 0.48 mmol). The mixture was cooled to 0 °C and diisopropylazodicarboxylate (94.5 μl, 0.48 mmol) was added via syringe. The reaction was stirred for 18h. while slowly warming to room temperature. The volatiles were evaporated in vacuo, and the residue diluted into ethyl acetate (50 ml), washed with saturated sodium bicarbonate (3 x 50 ml), brine (3 x 50 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The semi-solid residue was subjected to preparative thin layer chromatography using a mixture of ethyl acetate/hexanes (4:1) as eluant. Fraction with R f =0.68 was isolated which afforded 64 mg (24 %) of 2-(ferf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-4,7- epoxido-1 ,3,4,5,6,7-hexahydro-isoindol-2-ylmethyl)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 12.47 (s, 1 H), 4.89 (m, 2H), 4.80-4.61 (m, 2H); 3.93-3.86 (m, 1 H), 3.83-3.79 (m, 1 H), 3.62-3.57 (dd, J = 12.6, 3.6, 1 H), 2.92 (q, 6.9, 2H), 2.60 (dd, J =17.1 , 10.5, 2H), 1.85 (m, 2H), 1.60 (s, 18H). MS: APCI (-): 561 (M-H). The above 2-(fetf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-4,7-epoxido- 1 ,3,4,5,6,7-hexahydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester (51 mg) was dissolved in 50% trifluoroacetic acid in dichloromethane (5ml) and stirred at room temperature for 2 h. The reaction mixture was evaporated in vacuo and the residue titurated with diethyl ether (3 x 10 ml). The solid was filtered of and dried affording 30 mg (71 %) of the title compound as a solid. 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 7.68 (bs, 1 H), 4.69 (s, 2H), 4.67 (d, J = 15, 1 H), 4.56 (d, J = 15, 1 H), 3.63 (bm, 1 H), 3.50 (d, J = 5, 1 H), 3.46 (d, J = 5, 1 H), 3.08 (d, J = 15, 2H), 2.94 (d, J = 2.4, 1 H), 2.89 (m, 1 H), 1.64 (s, 4H). MS: APCI (-): 449 (M-H); LC-MS: s, 95 % EXAMPLE 43 7-(((2R)-2-Amino-3-phenyl-propionylamino)-methyl)-2-(oxalyl-amino)-4,7- dihvdro-5H-thienor2,3-c1pyran-3-carboxylic acid, trifluoroacetic acid salt. To a stirred solution of a mixture of 2-amino-7-aminomethyl-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester and 2-amino-5- aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (4.7 g, 16 mmol) was added diisopropylethylamine (2.8 ml, 16 mmol) and succinimidyl-2,2,2-trichloroethylcarbonate (4.8 g , 16 mmol) portion wise. The reaction mixture was stirred at room temperature for 18 h, washed with saturated sodium hydrogen carbonate, dried (MgSO ), filtered and the solvent evaporated vacuo. The residue was chromatographyed on silica (90 g) using a mixture of ethyl acetate/heptane (1 :1 ) as eluant. Pure fraction were collected and the solvent evaporated in vacuo affording 6.78 g of crude product which was dissolved in dichloromethane (5 ml) followed by heptane (30 ml) which was added as a top layer. After crystallisation and filtration 5.44 g (74 %) of 2-amino-7-((2,2,2-trichloro-ethoxycarbonyl-amino)methyl)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester was obtained as an oil. 1 H NMR (CDCI 3 ) δ 1.55 (s, 9H), 2.78 (m, 2H), 3.32 (m, 1 H), 3.62 (m,1 H), 3.72 (m,1 H), 4.15 (m, 1 H), 4,68 (m, 1 H), 4.71 (s, 2H), 6.00 (s, 2H). The above 2-amino-7-((2,2,2-trichloro-ethoxycarbonylamino)methyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (4.0 g, 8.0 mmol) was dissolved in a mixture of tetrahydrofuran (15 ml) and a aqueous phosphate buffer (pH 3; 5 ml) followed by addition of zinc (16 g, 0.244 mol). The reaction mixture was stirred for 6 h at room temperature at which time the solvent was removed vacuo. To the residue was added diethyl ether (20 ml) and water (40 ml). Sodium carbonate was added to the aqueous phase until pH = 8 and the aqueous phase was extracted with dichloromethane (3x). The combined organic phases were dried (MgSO 4 ), filtered and the solvent removed in vacuo. The residue was purified by flash chromatography on silica gel (90 g) using a mixture of dichloromethane/ethanol/25 % ammonia in water 100:10:0.7 as eluant. Pure fractions were collected and the solvent evaporated i vacuo affording 1.52 g (61 %) of 2-amino-7-aminomethyl-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester. 1 H NMR (CDCI 3 ) δ 1.45 (s, 9H), 2.69 (dt, 2H). Calculated for C 13 H 20 N 3 O 3 S; C, 54.91 %; H, 7.09 %; N, 9.85 %. Found: C, 54.53 %; H, 7.19 %; N, 9.61 %. LC-MS : Mw = 285,2 R,= 4.14 min To a solution of boc-D-phe-OH (0.28 g, 1.05 mmol) in dichloromethane (10 ml) was added 1 -hydroxy benzotriazole (0.14 g, 1.05 mmol) and 1- ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.18 g, 1.054 mmol). The reaction mixture was stirred for 15 min at room temperature. 2-Amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.30 g, 1.054 mmol) dissolved in dichloromethane (15 ml) was added. Ethyl diisopropylamine (0.18 ml, 1.05 mmol) was added and the reaction mixture was stirred over night at room temperature. The reaction was washed with 10 % aqueous citric acid (15 ml), saturated aqueous sodium hydrogencarbonate, dried (MgSO 4 ), filtered and the solvent removed in vacuo affording 594 mg (100 %) of 2-amino-7-(((1 R)-2- fetf-butoxycarbonylamino-3-phenyl-propionylamino)-methyl)-4,7-dihydro- 5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester. 1 H NMR(CDCI 3 ) δ 1.42 (s, 9H), 1.55 (s, 9H), 2.73 (m, 2H), 3.05 (m, 2H), 3.16 (m, 1 H), 4.06 (m, 1 H), 4.32 (m,1 H), 5.05 (s, 1 H), 6.01 (s, 2H), 6.10 (s, 1 H), 7.20 (m, 5H). LC-MS : Mw = 532.2, R, = 7.11. 2-Amino-7-(((1 R)-2-ferf-butoxycarbonylamino-3-phenyl-propionylamino)- methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.58 g, 1.09 mmol) was dissolved in dichloromethane (15 ml). Triethylamine (0.3 ml, 2.18 mmol) was added and the reaction mixture was cooled with in a ice bath, lmidazol-1-yl-oxo-acetic acid ferf-butyl ester (0.43 g, 2.18 mmol) dissolved in dichloromethane (5 ml) was added to the reaction mixture. The reaction mixture was stirred overnight at room temperature diluted with dichloromethane (20 ml), washed with 1 N hydrochloric acid (15 ml), saturated sodium hydrogencarbonate (15 ml), dried (MgSO 4 ), filtered and the solvent removed in vacuo. The residue was purified by flash chromatography silica gel (40 g) using a mixture of ethyl acetate/heptane 1 :1 as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 512 mg (69 %) of 7-((1 R)-(2-ferf- butoxycarbonylamino-3-phenyl-propionylamino)methyl)-2-(ferf- butoxyoxalylamino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid . fetf-butyl ester as an oil. 1 H NMR (CDCI 3 ) δ 1.42 (s, 9H), 1.59 (s, 9H), 1.61 (s, 9H), 2.86 (m, 2H), 3.02 (m, 2H), 3.15 (m, 1H), 3.64 (m, 1H), 3.87 (m, 1 H), 4.09 (m, 1 H), 4.28 (m, 1 H), 4.51 (m, 1 H), 4.67 (m,1 H), 5.10 (s, 1 H), 6.00 (s, 1 H), 7.20 (m, 5H), 12.5 (s, 1 H). 7-((1 R)-(2-ferf-Butoxycarbonylamino-3-phenyl-propionylamino)methyl)-2- (ferf-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyrran-3-carboxylic acid ferf-butyl ester (0.51 g, 0.76 mmol) was dissolved in dichloromethane (5 ml). Trifluoroacetic acid (5 ml) was added and the reaction mixture was stirred for 2 h at room temperature. The solvent was removed vacuo ( stripped 3 times with dichloromethane) which afforded 314 mg (92 %) of the titie compound. Calculated for C 2 oH 2 iN 3 O 7 S; 1 x CF 3 COOH, 1 x H 2 O; C, 45.60 %; H, 4.17 %; N, 7.25 %. Found: C, 45.78 %; H, 4.20 %; N, 7.05 %. LC-MS : RT=3.61 / RT=3.77 Mw = 448.2 EXAMPLE 44 7-((2-Acetylamino-3-(4-hvdroxy-phenyl)-propionylamino)-methyl)-2-(oxalyl- amino.-4,7-dihvdro-5H-thienor2,3-c1pyran-3-carboxylic acid To a mixture of Ac-D-Tyr-OH (235 mg, 1.05 mmol) dissolved in dichloromethane (10 ml) was added 1-hydroxybenzotriazole (0.14 g, 1.05 mmol), 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride (0.20g , 1.05 mmol) and the reaction mixture was stirred for 15 min at room temperature. 2-Amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester (0.3 g, 1.05 mmol) dissolved in dichloromethane (10 ml) was added followed by N,N-diisopropyl- ethylamine (0.18 ml, 1.05 mmol). The resulting reaction mixture was stirred for 18 h at room temperature, diluted with dichloromethane (15 ml) was washed with 10 % aqueous citric acid (25 ml), saturated sodium hydrogencarbonate, dried (MgSO 4 ), filtered and the solvent removed in vacuo. The residue was purified by flash chromatography on silica gel (4C g) using ethyl acetate as eluant. Pure fractions were collected and the solvent evaporated vacuo affording 304 mg (59 %) of 7-((2-acetylamino- 3-(4-hydroxy-phenyl)propionylamino)methyl)-2-amino-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H NMR (CDCI 3 ) double set of peaks from diastereomers; selected peaks: δ 1.55 (s, 9H), 1.95 (s, 3H), 2.74 (m, 2H), 2.92 (m, 2H), 3.23 (m, 1 H), 3.63 (m, 2H), 6.05 (s, 2H). LC-MS: R, = 5.17, Mw = 490.4 7-((2-Acetylamino-3-(4-hydroxy-phenyl)propionylamino)methyl)-2-amino- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.3 g, 0.61 mmol) was dissolved in dichloromethane (15 ml). Triethylamine ( 0.17 ml, 1.22 mmol) was added and the reaction mixture was cooled to 0° C. lmidazol-1-yl-oxo-acetic acid ferf-butyl ester (0.24, 1.22 mmol) dissolved in dichloromethane (10 ml) was added dropwise. The resulting reaction mixture was stirred at room temperature for 18 h. Dichloromethane (20 ml) was added and the mixture was washed with 1 N hydrochloric acid (15 ml), saturated sodium hydrogencarbonate (20 ml), dried (MgSO ), filtered and the solvent removed in vacuo. The residue was purified by flash chromatography on silica gel (40 g) using ethyl acetate as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 208 mg (55 %) of 7-((2-acetylamino-3-(4- hydroxy-phenyl)-propionylamino)methyl)-2-(fetf-butoxyoxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. LC-MS : Mw = 618.4, R, = 6.97 7-((2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino)methyl)-2-(ferf- butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.2 g, 0.32 mmol) was dissolved in dichloromethane (8 ml) and trifluoroacetic acid (4 ml) was added. The reaction mixture was stirred 7 h at room temperature. The solvent was evaporated in vacuo (stripped 3 times with dichloromethane) which afforded 200 mg (100 %) of the title compound. Calculated for C 22 H 23 N 3 O 9 S, 3 x H 2 O; C, 47.22 %; H, 5.22 %; N, 7.51 %. Found: C, 47.05 %; H, 4.88 %; N, 7.39 %. LC-MS : R, = 3.64, Mw = 506.4. EXAMPLE 45 7-((2-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7- dihvdro-5H-thieno[2,3-c1pyran-3-carboxylic acid. To a solution of Ac-D-Val-OH (0.17 g, 1.09 mmol) dissolved in dichloromethane (15 ml) was added N,N-dimethylformamide (1 ml), 1- hydroxybenzotriazole (0.15 g, 1.09 mmol) and 1-ethyl-3-(3-dimethylamino- propyl)carbodiimide hydrochloride (0.21 g, 1.09 mmol). The reaction mixture was stirred for 15 min. at room temperature at which time a solution of 2-amino-7-amϊnomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester (0.31 g, 1.09 mmol) in dichloromethane (10 ml) was added followed by N-N-diisopropylethylamine (0.186 ml, 1.09 mmol). The resulting mixture was stirred over night at room temperature diluted with dichloromethane (10 ml) washed with 10 % aqueous citric acid (20 ml), sodium hydrogencarbonate, dried (MgSO 4 ), filtered and the solvent was evaporated in vacuo affording 415 mg (90 %) of 7-((2- acetylamino-3-methyl-butyrylamino)methyl)-2-amino-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. 1 H NMR (CDCI 3 ) δ 0.88 (t, 3H), 0.98 (t, 2H), 1.55 (s, 9H), 2.02 (d, 1 H), 2.77 m, (2H), 3.40 (m, 1 H), 4.14 (m, 1 H). LC-MS : R t = 5.17 Mw= 426.4 To a mixture of 7-((2-acetylamino-3-methyl-butyrylamino)methyl)-2-amino- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.4 g, 0.94 mmol) dissolved in dichloromethane (10 ml) and triethylamine (0.26 g, 1.87 mmol) cooled to 0° C was added a solution of imidazol-1-yl-oxo- acetic acid fetf-butyl ester (0.37 g, 1.87 mmol) in dichloromethane (10 ml). The resulting mixture was stirred for 18 h at room temperature diluted with dichloromethane (20 ml) washed with 1 N hydrochloric acid (15 ml), saturated sodium hydrogencarbonate, dried (MgSO ), filtered and the solvent evaporated vacuo which afforded 515 mg (97 %) of 7-((2- acetylamino-3-methyl-butyrylamino)methyl)-2-(fetf-butoxyoxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. LC-MS: R t = 7.11 , Mw = 554.4. HPLC: R t = 34.16, Area (%) = 100 %. To a solution of the above 7-((2-acetylamino-3-methyl-butyrylamino)- methyl)-2-(fetf-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3- carboxylic acid ferf-butyl ester (0.5 g, 0.90 mmol) dissolved in dichloromethane (3 ml) was added trifluoroacetic acid (1 ml) and the reaction mixture was stirred for 18 h at room temperature. Trifluoroacetic acid (4 ml) was added and the mixture was stirred for an additional 3 hours at room temperature. The volatiles were evaporated in vacuo (and stripped 3 times with dichloromethane) affording 282 mg (71 %) of the title compound. Calculated for C 18 H 23 N 3 O 8 S, 2 x H 2 O; C, 45.28 %; H, 5.70 %; N, 8.80 %. Found: C, 45.20 %; H, 5.50 %; N, 8.80 %. LC-MS: R t = 3.60, Mw = 442.2 EXAMPLE 46 2-(Oxalyl-amino)-7-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 H-benzordlisothiazol-2- ylmethyl ,7-dihvdro-5H-thieno.2,3-c.pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 25. M.p.: 210 - 212 °C; Calculated for C 18 Hι 4 N 2 O 9 S 2 , 0.5 x H 2 O, 0.75 x Ethyl acetate; C, 44.49 %; H, 3.83 %; N, 5.32 %. Found: C, 44.70 %; H, 3.61 %; N, 4.90 %. EXAMPLE 47 2-(Qxalyl-amino)-7-(3-oxo-3H-benzord1isoxazol-2-ylmethyl)-4,7-dihydro- 5H-thienor2,3-c1pyran-3-carboxylic acid The title compound was prepared in a similar way. as described in Example 25. M.p.: 236 - 237 °C; Calculated for C 18 Hι 4 N 2 O 8 S, 0.3 x H 2 O; C, 51.02 %; H, 3.47 %; N, 6.61 %. Found: C, 51.16 %; H, 3.47 %; N, 6.31 %. EXAMPLE 48 5-(1 ,3-Dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahvdro-thienor2,3-clpyridine-3,6-dicarboxylic acid 6-ethyl ester To a solution of 1 ,4-dioxa-8-aza-spiro[4,5]decane (51.5 g, 0.36 moles) in a mixture of dichloromethane (500 ml) and saturated sodium bicarbonate (500 ml) was added di-fetf-butyldicarbonate (69.8 g, 0.32 moles) and the reaction was vigorously stirred for 3 hours, and the layers separated. The organic layer was washed with 1 N hydrochloric acid (2 x 150 ml), brine (100 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo affording 75.5 g (97 %) of 1 ,4-dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid fetf-butyl ester as a crystallizing oil. 1 H NMR (400 MHz, CDCI 3 ): δ 3.96 (s, 4H), 3.49 (bm, 4H), 1.65 (bm, 4H), 1.45 (s, 9H). To the above 1 ,4-dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid fetf-butyl ester (4.0 g, 16.4 mmol) dissolved in dry diethyl ether (32 ml) was added 2,2' bipyridyl (1 mg) and the solution was cooled to -75 °C. Tetramethyl- ethylenediamine (3.2 ml, 21.4 mmol) was added followed by dropwise addition of sec-butyl lithium (16.4 ml, 21.4 mmol, 1.3M in cyclohexane). The mixture was stirred at -75 °C for 10 min, then slowly warmed to -20 °C and stirred at that temperature for 0.5 h, then cooled to -30 °C. At this temperature, formaldehyde was generated by heating paraformaldehyde at 150 °C and passed through the mixture with dry nitrogen until the color faded to off-white, at which time water (40 ml) was added. The layers were separated, and the aqueous layer was washed diethyl ether (2 x 50 ml). The combined organic extracts were washed 1 N hydrochloric acid (2 x 75 ml), saturated sodium bicarbonate solution (50 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue (2.9 g) was purified by silica gel chromatography (hexane/ethyl acetate, 10 % ethyl acetate to 30 % ethyl acetate, gradient). Pure fractions were collected and the solvent evaporated in vacuo affording 1.3 g (29 %) of 7-hydroxy-methyl-1 ,4-dioxa- 8-aza-spiro[4.5]decane-8-carboxylic acid ferf-butyl ester as a thick oil. H NMR (400 MHz, CDCI 3 ) δ 4.42 (bm, 1H), 4.08-3.96 (m, 5H), 3.96-3.88 ( m, 1 H), 3.78-3.70 (m, 1 H), 3.30-3.16 (bm, 1 H), 2.30-1.98 (bs, 1 H), 1.96- 1.78 (m, 2H), 1.74-1.64 (m, 2H), 1.49 (s, 9H). To 7-hydroxy-methyl-1 ,4-dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid fetf-butyl ester (0.4 g, 1.5 mmol) dissolved in dry tetrahydrofuran (20 ml) was added phthalimide (0.28 g, 1.9 mmol), triphenylphosphine (0.5 g, 1.9' mmol) and the mixture was cooled to 0 °C in an ice bath. Diethylazodicarboxylate (0.29 ml, 1.82 mmol) was added dropwise and the mixture was stirred at 0 °C for 0.5 h, then at ambient temperature for 18 h. The solvent was removed vacuo and the residue was purified by silica gel chromatography (hexane/ethyl acetate, 18 % ethyl acetate to 25 % ethyl acetate, gradient). Pure fractions were collected and the solvent evaporated in vacuo affording 0.29 g (48 %) of 7-(1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-1 ,4-dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid ferf-butyl ester. 1 H NMR (400 MHz, CDCI 3 ) δ 7.94-7.80 (bs, 2H), 7.80-7.64 (bd, 2H), 4.96- 4.70 (2bs, 1 H), 4.66-4.52 (m, 1 H), 4.30-4.14 (bm, 1H), 4.12-4.04 (m, 2H), 4.04-3.94 (m, 2H), 3.56-3.32 (m, 2H), 2.04-1.92 (m, 1 H), 1.90-1.60 (m, 4H), 1.22-1.0 (2bs, 9H). MS: (M + 1 ) = 403, (M - Boc) = 303. To the above 7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-1 ,4-dioxa-8- aza-spiro[4.5]decane-8-carboxylic acid fetf-butyl ester (1.1 g, 2.7 mmol) dissolved in dichloromethane (6 ml) was added 1.0 N hydrogen chloride in diethyl ether (50 ml) and the solution kept at ambient temperature for 62 h. The precipitate was filtered off and washed with diethyl ether and dried with nitrogen which afforded 0.83 g (90 %) of 2-(1 ,4-dioxa-8-aza- spiro[4.5]dec-7-ylmethyl)-isoindole-1 ,3-dione hydrochloride as a solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.2-8.8 (2bs, 2H), 7.8-8.1 (m, 2H), 4,1-3.6 (m, 5H), 2.9 (bs, 1H), 2.2-1.6 (m, 5H). MS: (M + 1) = 303.5. To a suspension of the above 2-(1,4-dioxa-8-aza-spiro[4.5]dec-7- ylmethyl)-isoindole-1 ,3-dione hydrochloride (0.7 g, 2.1 mmol) and ethyl chloroformate (0.24 ml, 2.5 mmol) in dry tetrahydrofuran (14 ml) cooled in an ice bath under nitrogen was added diisopropylethylamine (0.95 ml, 5.4 mmol) and the reaction mixture was stirred at ambient temperature for 3 hours. The volatiles were removed in vacuo and the residue was partitioned between dichloromethane (25 ml) and 1 N hydrochloric acid (25 ml). The layers were separated, and the aqueous layer extracted with dichloromethane (20 ml). The combined organic extracts were washed with a saturated sodium bicarbonate solution (50 ml), dried (MgSO 4 ), filtered and the solvent evaporated vacuo. The residue was triturated with n-butylchloride, filtered and dried with nitrogen which afforded 0.47 g (61 %) of 7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-1 ,4-dioxa-8-aza- spiro[4.5]decane-8-carboxylic acid ethyl ester. 1 H NMR (400 MHz, CDCI 3 ) δ 7.9 (s, 2H), 7.7(s, 2H), 4.9-4.7 (2bs, 1 H), 4.7-4.5 (m, 1 H), 4.3-3.9 (m, 5H), 3.9-3.6 (bs, 1 H), 3.6-3.3 (m, 2H), 2.0-1.9 (m, 1 H), 1.9-1.5 (m, 4H), 1.1-0.7 (2bs, 3H). MS: (M-1) = 373. A solution of the above 7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-1 ,4- dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid ethyl ester (0.44 g, 1.2 mmol) in a mixture of 1 N hydrochloric acid (18 ml) and tetrahydrofuran (18 ml) was heated a 75 °C under nitrogen with stirring for 18 h. The tetrahydrofuran was removed in vacuo and the residue was extracted with dichloromethane (2 x 75 ml). The combined organic extracts were washed with a saturated sodium bicarbonate solution (50 ml), dried (MgSO 4 ), filtered and the solvent removed in vacuo affording 0.42 g (> 100 %) of 2- (1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4-oxo-piperidine-1 -carboxylic acid ethyl ester as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 7.9 (s, 2H), 7.8 (s, 2H), 5.3-5.0 (bm, 1 H), 4.6-4.2 (bm, 1 H), 4.0 (m, 2H), 3.8-3.6 (bm, 3H), 2.8 (m, 1 H), 2.7-2.4 (bm, 3H), 1.0 (bs, 3H). MS: (M+1)= 330.56. A mixture of the above 2-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4- oxo-piperidine-1 -carboxylic acid ethyl ester (0.39 g, 1.2 mmol), ferf-butyl cyanoacetate (0.22 g, 1.55 mmol), sulfur (42 mg, 1.3 mmol) in ethanol (1.5 ml) was degassed. To this mixture, under nitrogen, morpholine (205 μl) was added and the mixture was heated a 50 °C for 13 hours. The solvent was removed in vacuo. The residue (0.74 g) was purified by silica gel chromatography using a mixture of hexane/ethyl acetate (7:3) as eluant. Pure fraction were collected and the solvent evaporated in vacuo. The residue (0.29 g) was titurated with acetonitrile, filtered, and dried with nitrogen affording 84 mg (15 %) of 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid 3-fetf-butyl ester 6-ethyl ester. 1 H MNR (400 MHz, CDCI 3 ) δ 7.9-7.7 (2m, 4H), 6.0 (bs, 2H), 5.1-4.8 (bm, 1H), 4.8-4.5 (m, 1H), 4.5-4.2 (m, 1H), 4.1-3.4 (3m, 4H), 3.0 (m, 2H), 1.8- 1.4 (m, 10H), 1.1-0.9 (m, 3H). MS: (M + 1) = 486. To the above 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 3-ferf-butyl ester 6-ethyl ester (48 mg, 0.1 mmol) dissolved in dry tetrahydrofuran (1 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (0.4 ml) and the solution stirred for 18 h. at ambient temperature. The solvent was removed vacuo and the residue was dissolved in dichloromethane (25 ml) and a saturated sodium bicarbonate solution (25 ml) was added. The layers were separated and the aqueous layer was extracted with dichloromethane (25 ml). The combined organic extracts were dried (Na 2 SO 4 ), filtered and the solvent evaporated in vacuo. The residue (63 mg) was dissolved in ethyl acetate and passed through 1 g of silica gel and the solvent evaporated m vacuo affording 55 mg (90 %) of 2-(ferf- butoxyoxalyl-amino)-5-(1,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 3-fetf-butyl ester 6- ethyl ester as a solid. The above 2-(ferf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 3- ferf-butyl ester 6-ethyl ester (55 mg, 0.09 mmol) was dissolved in 50 % trifluoroacetic acid in dichloromethane (2 ml) and stirred at ambient temperature for 18 h. The volatiles were removed in vacuo and the residue was purified by preparative hplc (column: Kromasil C18, 250 x 4.6 mm. , flow: 2 ml/min., gradient: acetonitrile/water, 20 % acetonitrile to 60 % acetonitrile over 20 min.) affording after evaporation in vacuo 13.8 mg (31 %) of the title compound as a solid. (Kromasil™ available from e.g. Richard Scientific Inc, Novato CA. 1 H NMR (400 MHz, DMSO-d 6 ) δ 14-13 (bs, 1 H), 12.4 (s, 1 H), 7.9 (s, 4H), 4.9 (m, 2H), 4.4 (m, 1 H), 4.0-2.8 (m, 13H), 0.8 (m, 3H). MS: (M + 1 ) = 502. EXAMPLE 49 5-(1 , 3-Dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-1 ,4-dioxa-8-aza- spiro[4.5]decane-8-carboxylic acid ferf-butyl ester (353 mg, 0.88 mmol) was cooled in an ice bath and then dissolved in a solution of 20 % trifluoroacetic acid/dichloromethane (7 ml). The reaction was stirred for 5 minutes in the ice bath then another 3 hours, at ambient temperature, after which it was concentrated in vacuo affording a solid residue. To the solid was added 2N hydrochloric acid (9 ml) and the mixture was heated at 50 °C (oil bath) with stirring for 24 h. The cooled reaction mixture was quenched with saturated sodium bicarbonate solution until the pH was basic. The aqueous layer was extracted with chloroform (3 x 20 ml) and the combined organic extracts dried (K 2 CO 3 ), filtered, and the solvent evaporated in vacuo to give 205 mg (91 %) of 2-(4-oxo-piperidin-2- ylmethyl)-isoindole-1 ,3-dione as a solid. 1 H NMR (400 MHz, CDCI 3 ) δ 7.90-7.83 (m, 2H), 7.78-7.71 (m, 2H), 3.81- 3.73 (m, 2H), 3.43-3.35 (m, 1 H), 3.30-3.22 (m, 1 H), 2.83 (dt, J = 13, 3, 1 H), 2.46 (d, J = 15, 1 H), 2.42-2.32 (m, 2H), 2.21 (dd, J = 14, 13, 1 H). APCI-MS: [M+H] + = 259 The above 2-(4-oxo-piperidin-2-ylmethyl)-isoindole-1 ,3-dione (0.20 g, 0.76 mmol) was dissolved in dichloromethane (5 ml). Saturated sodium bicarbonate solution (5 ml) was added followed by di-ferf-butyl dicarbonate (0.20 g, 0.91 mmol). The reaction was stirred vigorously for 16 h. after which the organic phase was separated. The aqueous layer was extracted with dichloromethane (2 x 10 ml) and the combined organic extracts were dried(Na 2 SO ), filtered, and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (0 to 10% gradient) as eluant. Pure fractions were collected and the solvent evaporated vacuo affording 0.23 g (85 %) of 2-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4-oxo-piperidine-1- carboxylic acid fetf-butyl ester. 1 H NMR (400 MHz, CDCI 3 ) δ 7.86 (bs, 2H), 7.72 (bs, 2H), 5.15-4.98 (m, 1 H), 4.23-4.14 (m, 1 H), 3.90 (t, J = 12, 1 H), 3.61-3.52 (m, 2H), 2.78- 2.70 (m, 1 H), 2.57-2.39 (m, 3H), 1.15 (s, 9H) APCI-MS: [M+H] + = 359 The above 2-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4-oxo-piperidine- 1 -carboxylic acid fetf-butyl ester (0.43 g, 1.2 mmol) was dissolved in absolute ethanol (9 ml). To the solution was added sulfur (42 mg, 1.32 mmol) and ferf-butyl cyanoacetate (0.22 g, 1.56 mmol). The mixture was placed under nitrogen and stirred in a 50 °C oil bath. Morpholine (0.21 ml, 2.4 mmol) was added and the reaction was stirred for 16 h. The precipitate formed was filtered off and washed with acetonitrile (2 x 3 ml) and dried which afforded 0.18 g of 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-ferf-butyl ester (A) (30 %). The filtrate was concentrated in vacuo and the residue purified by silica gel chromatography using a gradient of ethyl acetate/hexane (1 :4 to 1 :3 gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 0.3 g of a mixture of 2-amino-5-(1 ,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3,6-dicarboxylic acid di-ferf-butyl ester and 2-amino-7-(1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-ferf-butyl ester. HPLC purification of a small portion of the mixture gave 28 mg of pure 2-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol- 2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester (B). (A): 1 H NMR (400 MHz, CDCI 3 ) δ 7.87-7.82 (m, 2H) 7.73-7.66 (m, 2H), 6.00 (bs, 2H), 5.02-4.87 (m, 1 H), 4.72-4.21 (m, 2H), 4.03-3.93 (m, 1 H), 3.51 (t, J = 14, 1 H), 2.97-2.91 (m, 2H), 1.56 (s, 9H), 1.12-1.09 (s, 9H). LC-MS: R t =3.96 min, [M+H] + = 514.4 (B): 1 H NMR (400 MHz, CDCI 3 ) δ 7.88-7.82 (m, 2H), 7.74-7.66 (m, 2H), 5.39- 5.19 (m, 1 H), 4.30-4.02 (m, 2H), 3.78-3.70 (m, 1 H), 3.33-3.18 (m, 1 H), 2.86 (dd, J = 18, 4, 1 H), 2.75-2.61 (m, 1 H), 1.54 (s, 9H), 1.13-1.05 (s, 9H). LC-MS: R t =4.01 min, [M+H] + = 514.4 To a solution of the above 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- ferf-butyl ester (50 mg, 0.097 mmol) in dichloromethane (3 ml) was added midazol-1-yl-oxo-acetic acid fetf-butyl ester (60 mg, 0.29 mmol). The reaction was placed under nitrogen and stirred for 3 hours, at ambient temperature. The solution was concentrated in vacuo and the residue purified by silica gel chromatography using a 5 % mixture of ethyl acetate/ dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 54 mg (87 %) of 2-(fetf-butoxyoxalyl- amino)-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester. 1 H NMR (400 MHz, CDCI 3 ) δ 12.52 (s, 1 H), 7.85 (bs, 2H), 7.74-7.67 (m, 2H), 5.08-4.92 (m, 1 H), 4.93-4.40 (m, 2H), 3.97-3.87 (m, 1 H), 3.53 (t, J = 14, 1 H), 3.1 1-2.99 (m, 2H), 1.62 (s, 18H), 1.14-1.12 (2s, 9H). APCI-MS: [M-H] " = 641 The above 2-(fetf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- ferf-butyl ester (54 mg, 0.084 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (2 ml). The reaction was stirred at ambient temperature for 7 h., concentrated in vacuo and the residue evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane, filtered off and dried in vacuo which afforded 41 mg (90 %) of the titie compound as a solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.31 (s, 1 H), 9.36 (bs, 2H), 7.93-7.90 (m, 2H), 7.88-7.85 (m, 2H), 4.43 (d, J = 16, 1 H), 4.26 (d, J = 16, 1 H), 4.03-3.91 (m, 2H), 3.83-3.76 (m, 1 H), 3.31 (dd, J = 18, 4, 1 H), 2.82 (dd, J = 18, 10, 1 H). APCI-MS: [M+H] + = 430 HPLC (254.4nm): R t =6.72 min, 98 % EXAMPLE 50 (L.-5-(1 ,3-Dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl,-2-(oxalyl-amino.-4, 5.6.7- tetrahvdro-thienof2,3-c1pyridine-3-carboxylic acid To a solution of L-aspartic acid (120 g, 0.90 mol) in methanol (600 ml) cooled to -20 °C was added thionylchoride (93 ml, 1.29 mol) dropwise over 0.5 h. The cooling bath was removed and the mixture was stirred for 1 h, before diethyl ether (1.8 L, containing 50 ml 1 N hydrochloric acid in diethyl ether) was added upon cooling. The resulting precipitate was filtered off and washed with diethyl ether. The product was recrystallized twice: First recrystallization: The product was dissolved in warm methanol (600 ml) and reprecipitated with 1.8 ml diethyl ether (containing 50 ml 1 N hydrochloric acid in diethyl ether). Second recrystallization: The product was dissolved in warm methanol (250 ml) and reprecipitated with 1.0 m diethyl ether (containing 50 ml 1 N hydrochloric acid in diethyl ether). This afforded 75 g ( 45 %) of L-aspartic acid β-methyl ester hydrochloride as a solid. To a solution of the above β-methyl ester (50 g, 0.27 mol) in water (120 ml) cooled to 0 °C was added triethylamine (95 ml, 0.68 mol) and methyl acrylate (74 ml, 0.82 mol). The reaction mixture was stirred for 3 hours before the cooling bath was removed. After stirring for an additional 1 h the mixture was washed with petrol ether (2 x 400 ml), before ferf-butanol (40 ml) and di-ferf-butyl dicarbonate (74 g, 0.34 mol) was added and the reaction mixture was stirred for 16 h. The mixture was washed with petrol ether (2 x 400 ml), cooled to 0 °C and the pH was adjusted to 3 with concentrated hydrochloric acid. After extraction with ethyl acetate (3 x 200 ml) the organic phase was washed with brine (200 ml), dried (MgSO 4 ), filtered and the volatiles evaporated in vacuo. The residue was subjected to column chromatography on silicagel using a mixture of ethyl acetate/hexane/methanol/acetic acid (25:25:2.5:1) as eluant. Pure fractions were collected and the solvent evaporated in vacuo which afforded 60 g (66 %) of 2-(fetf-butoxycarbonyl-(2-methoxycarbonyl-ethyl)- amino)-succinic acid 4-methyl ester as a solid. To a solution of the above di-ethyl ester (96.9 g, 0.29 mol) in dry degassed tetrahydrofuran (1.0 I) was added sodium methoxide (161 ml, 30% solution in methanol) and the reaction mixture was refluxed under nitrogen for 16 h with mechanical stirring. The reaction mixture was cooled to room temperature, the volatiles remove vacuo until a wet cage was observed. Water (500 ml) was added and the reaction mixture was refluxed for 16 h. The remaining organic solvents were evaporated n / vacuo before the pH was adjusted to 2.5 with concentrated hydrochloric acid. The aqueous phase was extracted with ethyl acetate (3 x 300 ml) and the combined organic phases were washed with brine (100 ml), dried (MgSO 4 ) and filtered. fetf-Butyl amine (25.36 g, 0.350 mol) was added dropwise under stirring whereupon a off white precipitate was formed. Th« precipitate was filtered off and washed with ethyl acetate, dried in vacuo affording 74.4 g (81 %) of 4-oxo-piperidine-1 ,2-dicarboxylic acid 1 -ferf- butyl ester, fetf-butyl amine salt as a solid. Analytically pure compound can be obtained from recrystallisation of the crude product from ethanol-diisopropyl ether by heating the compound in ethanol (ca 100 ml per 10 g compound) and while still hot diisopropyl ether is added (ca 250 ml per 10 g compound). Yield in recrystallisation is approximately 50 %. A solution of the above 4-oxo-piperidine-1,2-dicarboxylic acid 1 -fetf-butyl ester, ferf-butyl amine salt (3.0 g, 9.48 mmol), fetf-butyl cyanoacetate (2.01g, 14.22 mmol), sulfur (0.456 g, 14.22 mmol) and diisopropylethylamine (1.64 ml, 9.48 mmol) was heated to 50 °C under nitrogen for 12 h. The orange-yellow solution was allowed to cool to room temperature before a small precipitate was filtered off. The filtrate was evaporated in vacuo and the residue was divided between ethyl acetate (50 ml) and saturated ammonium chloride (100 ml). The aqueous phase was extracted with ethyl acetate (3 x 50 m) and the combined organic phases were washed with brine (50 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was subjected to column chromatography using a mixture of petrol ether/ethyl acetate/methanol (8:4:1) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 2.22 g (58 %) of 2-amino-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,5,6-tricarboxylic acid 3,6-di-ferf-butyl ester as a solid. To a solution of the above 3,5,6-tricarboxylic acid 3,6-di-ferf-butyl ester (0.63 g, 1.58 mmol) in dimethoxyethane (10 ml) cooled to -20 °C was added N-methylmorpholine (174 ml, 1.58 mmol) followed by isobutylchoroformate (205 ml, 1.58 mmol) and the reaction mixture was stirred for two min. before a precipitate was filtered off. The precipitate was rapidly washed with dimethoxyethane (2 x 2.5 ml), recooled to -20 °C and a solution of sodium borohydride (90 mg, 2.37 mmol) in water (1 ml) was added in one lot. (Caution - gas evolution). The reaction mixture was stirred until gas evolution ceases (app. 3 min.) and the mixture was poured into water (25 ml) and extracted with ethyl acetate (10 ml), washed with brine (5 ml), dried (MgSO 4 ), filtered and the solvent evaporated vacuo affording 0.40 g (66 %) of 2-amino-5- hydroxymethyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester as a solid. To a mixture of the above 2-amino-5-hydroxymethyl-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester (2.00 g, 5.20 mmol), phthalimide (0.92 g, 6.24 mmol) and triphenylphosphine (1.64 g, 6.24 mmol) in dry tetrahydrofuran (30 ml) cooled to 0 °C under a nitrogen atmosphere was added diethyl azodicarboxylate (DEAD) (0.98 ml, 6.24 mmol). The reaction mixture was allowed to stir overnight, slowly warming to room temperature. Next day the reaction mixture was again cooled to 0 °C and phthalimide (0.46 g, 3.12 mmol), triphenylphosphine (0.82 g, 3.12 mmol) and diethyl azodicarboxylate (DEAD) (0.49 ml, 3.12 mmol) was added in sequence and the reaction mixture was allowed to stir overnight, slowly warming to room temperature. The volatiles were evaporated in vacuo and the resultant solid dissolved in dichlorormethane (20 ml). The residue was subjected to flash column chromatography using a mixture of ethyl acetate/hexane (1 :2) as eluant. Fractions were collected affording after evaporation in vacuo 1.0 g of the desired compound contaminated with phthalimide. Recrystallization from ethanol gave 0.23 g (9 %) of pure 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester as a solid. To the above di-ferf-butyl ester (0.20 g, 0.39 mmol) dissolved in dichloromethane (4 ml) was added a mixture of imidazol-1-yl-oxo-acetic acid ferf butyl ester (0.23 g, 1.17 mmol) in dichloromethane (1 ml) under nitrogen. The reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was added dichlorormethane (5 ml) and washed with 1 % hydrochloric acid (10 ml), dried (Na 2 SO 4 ), filtered and the organic phase evaporated in vacuo affording 0.25 g (100 %) of 2-(ferf- butoxyoxalyl-amino)-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester. The above tri-fetf-butyl ester (0.25 g, 0.39 mmol) was dissolved in 20 % trifluoroacetic acid in dichloromethane (5 ml). The reaction was stirred at room temperature for 24 h. before diethyl ether (5 ml) was added. The precipitate was filtered off, washed with diethyl ether, dried in vacuo to give 0.150 g of a solid. NMR revealed the presence of a trace amount of material arising from incomplete deprotection. 0.100 g of the crude product was redissolved in 20 % trifluoroacetic acid in dichloromethane (5 ml), and stirred at room temperature for 24 h. before diethyl ether (5 ml) was added. The product was filtered off and washed with diethyl ether and dried in vacuo to give 0.05 g (40 %) of the title compound as a solid. M.p.: dec> 240° C Calculated for Ci 9 H 15 N 3 O 7 S 1/3 C 2 HF 3 O 2 1/2 H 2 O ; C, 49.58 %; H, 3.46 %; N, 8.82 %. Found: C, 49.84 %; H, 3.83 %; N, 8.99 %. EXAMPLE 51 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,5,6,7- tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid To a solution of pure 2-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- ferf-butyl ester (28 mg, 0.057 mmol) in dichloromethane (2 ml) was added midazol-1-yl-oxo-acetic acid ferf-butyl ester (35 mg, 0.17 mmol). The reaction was placed under nitrogen and stirred for 12 h. at ambient temperature. The volatiles were evaporated in vacuo and the residue was purified by silica gel chromatography using a mixture of ethyl acetate/ hexane (1 :3) as eluant. Pure fractions were collected and the solvent evaporated vacuo affording 25 mg (67 %) of 2-(ferf-butoxyoxalyl- amino)-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester as an oil. 1 H NMR (400 MHz, CDCI 3 ) δ 12.59-12.53 (bs, 1 H), 7.89-7.84 (m, 2H), 7.75-7.67 (m, 2H), 5.61-5.41 (m, 1 H), 4.36-4.15 (m, 1 H), 4.12-4.06 (m, 1 H), 3.90-3.82 (m, 1 H), 3.34-3.21 (m, 1 H), 2.99-2.93 (m, 1 H), 2.84-2.68 (m, 1 H), 1.62-1.59 (s, 18H), 1.12-1.06 (s, 9H). The above 2-(ferf-butoxyoxalyl-amino)-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- ferf-butyl ester (25 mg, 0.039 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (1.5 ml). The reaction was stirred at ambient temperature for 7 h., concentrated m vacuo and the residue evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane, filtered off and dried in vacuo to give 41 mg (85 %) of the titie compound as a solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.32 (s, 1 H), 9.48 (bs, 2H), 7.95-7.91 (m, 2H), 7.89-7.84 (m, 2H), 4.89 (s, 1 H), 4.15-4.07 (m, 2H), 3.43-3.28 (2m, 2H, partially obscured by water), 3.04 (bs, 2H). LC-MS: R t =1.51 min, [M-H] " = 428.4 EXAMPLE 52 5-(4-Hvdroxy-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-1 ,4-dioxa-8-aza- spiro[4.5]decane-8-carboxylic acid fetf-butyl ester (1.55 g, 3.85 mmol) was cooled in an ice bath and then dissolved in a solution of 20 % trifluoroacetic acid/dichloromethane (15 ml). The reaction was stirred and allowed to slowly warm to ambient temperature during 3 hours. The solution was concentrated i vacuo to give crude 2-(1 ,4-dioxa-8-aza- spiro[4.5]dec-7-ylmethyl)-isoindole-1 ,3-dione which was used directly in the following step (assumed 100 % yield). 1 H NMR (400 MHz, CDCI 3 ) δ 9.26 (bs, 1H), 8.19 (bs, 1H), 7.78-7.75 (m, 2H), 7.74-7.71 (m, 2H), 4.11-3.98 (m, 5H), 3.90-3.79 (m, 3H), 3.26-3.17 (m, 1 H), 2.10-2.00 (m, 3H), 1.92-1.88 (m, 1 H). To a suspension of the above 2-(1 ,4-dioxa-8-aza-spiro[4.5]dec-7- ylmethyl)-isoindole-1 ,3-dione (3.85 mmol) in absolute ethanol (25 ml) was added hydrazine (0.36 ml, 11.55 mmol). The reaction was stirred at 80 °C (oil bath) for 6 h., then cooled to ambient temperature and stirred for an additional 12 h. The thick precipitate was filtered off and washed with ethanol. The filtrate was concentrated vacuo and reconstituted in dichloromethane (20 ml), forming a small amount of a second precipitate which was filtered off. The filtrate was evaporated in vacuo and the resulting oil was dissolved in water (10 ml) and basified with 1 N sodium hydroxide until pH = 10. The aqueous layer was extracted with 20 % isopropyl alcohol/chloroform (12 x 40 ml). The combined organic extracts were dried (K 2 CO 3 ), filtered and the solvent evaporated in vacuo affording 0.42 g (63 %) of (1 ,4-dioxa-8-aza-spiro[4.5]dec-7-yl)methylamine as an oil. 1 H NMR (300 MHz, CDCI 3 ) δ 3.94 (bs, 4H), 3.11-3.05 (m, 1 H), 2.81 (dt, J = 12, 3, 1 H), 2.76-2.65 (m, 2H), 2.58-2.50 (m, 1 H), 1.70-1.57 (m, 3H), 1.31 (t, J = 12, 1 H). APCI-MS: [M+H] + = 173.2 To a solution of 4-hydroxy-isobenzofuran-1 ,3-dione (0.51 g, 3.09 mmol) in anhydrous N,N-dimethylformamide (7 ml) under nitrogen was added sodium hydride (130 mg, 3.25 mmol). Immediate evolution of gas and bright yellow color was observed. The mixture was stirred for 5 minutes after which benzyl bromide (1.8 ml, 15.45 mmol) was added. The reaction was stirred for 72 h. Saturated sodium bicarbonate (2 ml) was added and the mixture stirred for 2 minutes, diluted in ethyl acetate (35 ml) and washed with saturated sodium bicarbonate (5 ml), 1 N hydrochloric acid (5 ml), and brine (2 x 5 ml). The organic layer was dried (MgSO 4 ), filtered and the solvent evaporated vacuo. To the crude material was added hexane and the formed precipitate was filtered off, washed further with hexane and dried in vacuo to give 0.54 g (69 %) of 4-(benzyloxy)- isobenzofuran-1 ,3-dione as a solid. 1 H NMR (300 MHz, CDCI 3 ) δ 7.74 (t, 1 H, J = 8 Hz), 7.54 (d, 1 H, J = 8 Hz), 7.47-7.29 (m, 6H), 5.36 (s, 2H). A solution of (1 ,4-dioxa-8-aza-spiro[4.5]dec-7-yl)methylamine (0.19 g, 1.1 mmol) and 4-(benzyloxy)-isobenzofuran-1 ,3-dione (0.27 g, 1.05 mmol) was prepared in a mixture of distilled dichloromethane (3 ml) and anhydrous N,N-dimethylformamide (2.5 ml) under nitrogen. 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.23 g, 1.21 mmol) was added followed by triethylamine (0.46 ml, 3.3 mmol) and the reaction stirred at ambient temperature for 18 h. The solution was concentrated m vacuo and the residue diluted with ethyl acetate (25 ml) and washed with water (5 ml), saturated sodium bicarbonate (5 ml), and brine (5 ml). The organic layer was evaporated vacuo and the residue purified by silica gel chromatography using a mixture of 5 % methanol/dichloromethane/1 % triethylamine as eluant .Pure fractions were collected and the solvent evaporated in vacuo affording 0.22 g (50 %) of 4-benzyloxy-2-(1 ,4-dioxa-8-aza-spiro[4.5]dec-7-ylmethyl)-isoindole- 1 ,3-dione as a semi-solid. 1 H NMR (400 MHz, CDCI 3 ) δ 7.57 (t, J = 8, 1 H), 7.48 (d, J = 7, 2H), 7.42- 7.29 (m, 4H), 7.18 (d, J = 8, 1 H), 5.31 (s, 2H), 3.94-3.90 (m, 4H), 3.65 (d, J = 6, 2H), 3.16-3.09 (m, 1 H), 3.07-3.02 (m, 1 H), 2.76 (dt, J = 13, 3, 1 H), 1.78 (d, J = 12, 1 H), 1.64-1.54 (m, 3H), 1.37 (t, J = 12, 1 H), 1.08 (t, J = 7, 1 H). LC-MS: R t =2.59 min, [M+H] + = 409.2 To a solution of the above 4-benzyloxy-2-(1 ,4-dioxa-8-aza-spiro[4.5]dec-7- ylmethyl)-isoindole-1 ,3-dione (0.22 g, 0.54 mmol) in 1 ,4-dioxane (4 ml) was added 4N hydrochloric acid (4 ml) and the reaction stirred in a 65 °C (oil bath) for 6 h. The mixture was basified with saturated sodium bicarbonate until pH = 8 and extracted with dichloromethane (3 x 20 ml). The combined organic extracts were dried (MgSO 4 ), filtered, and the solvent evaporated vacuo affording crude 4-benzyloxy-2-(4-oxo- piperidin-2-ylmethyl)-isoindole-1,3-dione as an oil. Which was used without further purification or characterization. The above crude 4-benzyloxy-2-(4-oxo-piperidin-2-ylmethyl)-isoindole-1,3- dione (0.17 g, 0.47 mmol) was dissolved in dichloromethane (4 ml). Saturated sodium bicarbonate (4 ml) was added followed by di-fetf-butyl dicarbonate (0.11 g, 0.52 mmol). The reaction was stirred vigorously for 16 h., then the layers were separated. The aqueous layer was extracted with dichloromethane (2 x 10 ml) and the combined organic phases were dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a mixture of ethyl acetate/hexane (1:2) as eluant. Pure fractions were collected and the solvent was evaporated in vacuo affording 0.14 g (64 %) of 2-(4- benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4-oxo-piperidine-1 - carboxylic acid fetf-butyl ester. 1 H NMR (400 MHz, CDCI 3 ) δ 7.57 (bs, 1H), 7.47-7.31 (m, 6H), 7.18 (bs, 1 H), 5.34 (s, 2H), 5.03 (bs, 1 H), 4.45-4.14 (m, 1 H), 3.89 (t, J = 12, 1 H), 3.55 (bs, 2H), 2.76-2.71 (m, 1H), 2.57-2.38 (m, 3H), 1.17 (s, 9H). A solution of 2-(4-benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4- oxo-piperidine-1 -carboxylic acid fetf-butyl ester (0.14 g, 0.30 mmol), sulfur (10.6 mg, 0.33 mmol), and ferf-butyl cyanoacetate (55 mg, 0.39 mmol) in absolute ethanol (4 ml) was stirred at 50 °C (oil bath). Morpholine (53 μl, 0.6 mmol) was added and the reaction placed under nitrogen and stirred for 16 h. The solution was cooled to ambient temperature, concentrated in vacuo and the residue purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (0 to 5 % gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording a mixture of regioisomers 0.15 g (80 %) of 2-amino-5-(4- benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester and 2-amino- 7-(4-benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester which were not separable by chromatography. To a solution of the above mixture of 2-amino-5-(4-benzyloxy-1 ,3-dioxo- 1,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3,6-dicarboxylic acid di-fetf-butyl ester and 2-amino-7-(4-benzyloxy-1 ,3- dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester (0.15 g, 0.24 mmol) in distilled dichloromethane (4 ml) under nitrogen was added imidazol-1-yl- oxo-acetic acid fetf-butyl ester (0.14 g, 0.72 mmol) and the reaction mixture was stirred at ambient temperature for 1.5 h. The volatiles were evaporated vacuo and the crude residue was purified by silica gel chromatography using dichloromethane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 50 mg of 2-(tert- butoxyoxalyl-amino)-5-(4-benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- ferf-butyl ester (A) and 50 mg of 2-(fetf-butoxyoxalyl-amino)-7-(4- benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester (B). Another 50 mg remained as a mixture of the two isomers (A) and (B). (A): 1 H NMR (300 MHz, CDCI 3 ) δ 12.52 (s, 1 H), 7.60-7.31 (m, 7H), 7.20-7.10 (m, 1 H), 5.33 (s, 2H), 5.05-4.38 (m, 3H), 3.96-3.83 (m, 1 H), 3.52-3.41 (m, 1 H), 3.01 (bs, 2H), 1.60 (s, 9H), 1.59 (s, 9H), 1.17-1.14 (s, 9H). LC-MS: R,=4.93 min, [M+H] + = 748.1 (B): 1 H NMR (300 MHz, CDCI 3 ) δ 12.58-12.52 (s, 1 H), 7.60-7.30 (m, 7H), 7.20-7.10 (m, 1 H), 5.60-5.39 (m, 1 H), 5.34 (s, 2H), 4.36-4.02 (m, 2H), 3.86-3.75 (m, 1 H), 3.33-3.18 (m, 1 H), 2.97-2.90 (m, 1 H), 2.83-2.68 (m, 1 H), 1.60 (s, 9H), 1.58-1.57 (s, 9H), 1.15-1.09 (s, 9H) LC-MS: R,=4.93 min, [M+H] + = 748.1 The above 2-(ferf-butoxyoxalyl-amino)-5-(4-benzyloxy-1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester (50 mg, 0.067 mmol) was dissolved in a mixture of ethyl acetate/ethanol (3 ml, 1 :1). Palladium on activated carbon (10 %, 10 mg) was added and the solution degassed and stirred under hydrogen (1 atm.) for 72 h. TLC analysis indicated that the reaction was incomplete. The mixture was filtered through celite and the filter cake washed with hot ethyl acetate. The filtrate was concentrated m vacuo and purified by silica gel chromatography using a gradient of ethyl acetate/dichloromethane (0 to 5 % gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 15 mg (30 %) of 2-(fetf-butoxyoxalyl-amino)-5-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-ferf-butyl ester. 1 H NMR (300 MHz, CDCI 3 ) δ 12.50 (s, 1 H), 7.61-7.51 (m, 1 H), 7.39-7.34 (m, 1 H), 7.17-7.09 (m, 1 H), 5.04-4.64 (m, 2H), 4.49-4.34 (m, 1 H), 3.90- 3.78 (m, 1 H), 3.51-3.42 (m, 1 H), 3.02 (bs, 2H), 1.60 (s, 18H), 1.17-1.14 (2s, 9H). The above 2-(ferf-butoxyoxalyl-amino)-5-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester (15 mg, 0.023 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (2 ml). The reaction was stirred at ambient temperature for 12 h., concentrated in vacuo and evaporated in vacuo from dichloromethane (3 x 10 ml). The resulting precipitate was washed with dichloromethane and dried vacuo affording 6 mg (47 %) of the titie compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.32 (s, 1 H), 11.17 (s, 1 H), 9.25 (bs, 2H), 7.64 (t, J = 8, 1 H), 7.32 (d, J = 8, 1 H), 7.24 (d, J = 8, 1 H), 4.41-4.23 (m, 2H), 3.96-3.71 (m, 3H), 3.5-3.2 (obscured by water, 1 H), 2.83-2.75 (m, 1 H). LC-MS: R t =1.53 min, [M+Hf = 446.2 EXAMPLE 53 2-(Oxalyl-amino)-5-(1-oxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid 2-Methyl-benzoic acid methyl ester (1.50 g 10 mmol), N-bromosuccinimide (1.96 g, 11 mmol) and 2,2'-azobis(2-methylpropionitrile) (AIBN) (25 mg, 0.15 mmol) were dissolved in chloroform (3 ml). The solution was heated at reflux for 16 h. cooled and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a gradient of ethyl acetate/hexane (1-2 %) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 2.05 g (89 %) of 2-bromomethyl- benzoic acid methyl ester as a solid. 1 H NMR (CDCI 3 ): δ 7.97 (d, 1 H, J = 7.6 Hz), 7.45-7.52 (m, 2H), 7.38 (dt, 1 H, J = 1.2, 7.6 Hz), 4.96 (s, 2H), 3.95 (s, 1 H). To a solution of 2-amino-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester (100 mg, 0.20 mmol) and pyridine (0.1.8 ml, 2.0 mmol) in acetonitrile (1 ml) at room temperature was added benzyl chloroformate (0.28 ml, 2.0 mmol) in 10 aliquots over 48 h. The solution was then taken into ethyl acetate (30 ml), washed with 0.5 N hydrochloric acid (3 x 10 ml), saturated sodium bicarbonate (3 x 10 ml), brine (10 ml), dried (MgSO ) and filtered. The solvent was evaporated vacuo. The resulting oil crystallized upon standing for 2 days. The precipitate was filtered off and washed with diethyl ether (3 x 1 ml) affording after drying in vacuo 59 mg (47 %) of 2- benzyloxy-carbonylamino-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 10.60 (s, 1H), 7.60-7.92 (m, 4H), 7.38 (m, 5H), 5.26 (s, 2H), 4.30-5.10 (m, 3H), 3.40-4.00 (m, 2H), 1.57 (m, 9H), 1.15 (m, 9H). To a solution of 1 N hydrochloric acid in ethyl acetate (1.0 ml) was added 2-benzyloxy-carbonylamino-5-(1,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester (52 mg, 0.08 mmol). The solution was stirred at room temperature for 48 h. A precipitate was filtered off which afforded 42 mg (90 %) of 2- benzyloxy-carbonylamino-5-(1 ,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester hydrochloride as a solid. 1 H NMR (DMSO-d 6 ): δ 10.45 (s, 1 H), 9.40 (s, 1 H), 9.25 (s, 1 H), 7.89 (m, 4H), 7.39 (m, 5H), 5.22 (s, 2H), 4.39 (d, 1 H, J = 15 Hz), 4.28 (m, 1 H), 3.95 (m, 2H), 3.79 (m, 1 H), 3.20 (m, 1 H), 2.70 (m, 1 H), 1.48 (s, 9H). To a solution of the above 2-benzyloxy-carbonylamino-5-(1 ,3-dioxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester hydrochloride (42 mg, 0.072 mmol) in ethanol (0.5 ml) was added hydrazine (68 μl, 0.22 mmol). The solution was stirred at 80 °C for 5 h. and at room temperature for 16 h. The mixture was filtered and the filtrate evaporated in vacuo. The residue was extracted with dichloromethane (5 x 1 ml). The combined dichloromethane washes were evaporated in vacuo affording 20 mg (67 %) of 5- aminomethyl-2-benzyloxy-carbonylamino-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H NMR (CDCI 3 ): δ 10.55 (bs, 1 H), 7.37 (m, 5H), 5.23 (s, 2H), 3.92 (s, 2H), 2.60-3.10 (m, 3H), 1.53 (s, 9H). To a solution of the above 5-aminomethyl-2-benzyloxy-carbonylamino- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (20 mg, 0.048 mmol) in acetonitrile (1 ml) at 0 °C was added diisopropylethylamine (18 μl, 0.15 mmol) and 2-bromomethyl-benzoic acid methyl (12 mg, 0.048 mmol). The solution was stirred at 0 °C for 3 hours, and at room temperature for 16 h. Di-fetf-butyl dicarbonate (21 mg, 0.096 mmol ) was then added to the solution. The solution was then stirred at room temperature for 16 h. The solution was taken into ethyl acetate (30 ml), washed with 0.5 N hydrochloric acid (3 x 10 ml), saturated sodium bicarbonate (3 x 10 ml) and brine (10 ml), dried (MgSO 4 ) and filtered. The solvent was evaporated vacuo. The solid residue was purified by silica gel chromatography using a 5 % mixture of ethyl acetate/hexane as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 10 mg (33 %) of 2-benzylόxycarbonylamino-5-(1-oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester as a solid. H NMR (CDCI3): δ 10.59 (s, 1 H), 7.81 (m, 1 H), 7.52 (m, 1 H), 7.39 (m, 7H), 5.25 (s, 1 H), 4.22-5.00 (m, 4H), 4.40-4.80 (m, 2H), 2.80-3.10 (m, 2H), 1.55 (s, 9H), 1.25 (s, 9H). To a solution of the above 2-benzyloxycarbonylamino-5-(1 -oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester (9 mg, 0.014 mmol) in methanol (2 ml) was added 10 % Pd/C (4 mg). The mixture was stirred under hydrogen (1 atm.) for 3 hours, and then filtered. The filtrate was evaporated vacuo affording 6 mg (93 %) of 2-amino-5-(1 -oxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- fetf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 7.80 (m, 1 H), 7.50 (m, 1 H), 7.44 (m, 2H), 4.22-5.00 (m, 4H), 4.40-4.80 (m, 2H), 2.80-3.10 (m, 2H), 1.63 (s, 9H), 1.25 (s, 9H). To a solution of the above 2-amino-5-(1 -oxo-1 , 3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- ferf-butyl ester (6 mg, 0.013 mmol) in acetonitrile (0.5 ml) at room temperature was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (27 mg, 0.13 mmol). The solution was stirred for 3 hours, at room temperature and then diluted with ethyl acetate (20 ml), washed with 0.5 N hydrochloric acid (2 x 5 ml), saturated sodium bicarbonate (2 x 5 ml), brine (5 ml), dried (MgSO ) and filtered. The solvent was evaporated in vacuo. The residue was purified by silica gel chromatography using a gradient of ethyl acetate/hexane (10-25 % gradient) as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 4 mg (50 %) of 2- (fetf-butoxyoxalyl-amino-5-(1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester as a solid. 1 H NMR (CDCI 3 ): δ 12.49 (s, 1 H), 7.80 (m, 1 H), 7.50 (m, 1 H), 7.44 (m, 2H), 4.22-5.00 (m, 4H), 4.20-4.90 (m, 2H), 2.90-3.20 (m, 2H), 1.63 (s, 9H), 1.60 (s, 9H), 1.25 (s, 9H). MISSING AT THE TIME OF PUBLICATION EXAMPLE 55 2-(Oxalyl-amino)-7-(1 ,1 ,3-trioxo-5-phenyl-1 ,3-dihydro-isothiazol-2- ylmethyl)-4,7-dihvdro-5H-thieno[2,3-clpyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-7-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 1 ,1-dioxo-5-phenyl-1 ,2- dihydro-1 H-isothiazol-3-one as starting material. O- and Λ/-alkylated products were separated by column chromatography. 1 H-NMR (DMSO-d 6 ) δ 2.85 (bs, 2H), 3.75 (m, 1 H), 3.92 (dd, 1 H), 4.10 (m, 2H), 5.08 (m, 1 H), 7.64 (m, 3H), 7.69 (s, 1 H), 7.92 (m, 2H), 12.35 (s, 1 H, NHCO). LC-MS: R, = 4.90 min, m/z: 493 [M+H] + EXAMPLE 56 7-(1 , 1 -Dioxo-5-phenyl-1 H-isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7- dihvdro-5/-/-thieno.2,3-clpyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-7-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 1 ,1-dioxo-5-phenyl-1 ,2- dihydro-1H-isothiazol-3-one as starting material. O- and Λ/-alkylated products were separated by column chromatography. 1 H-NMR (DMSO-d 6 ) δ 2.86 (bs, 2H), 3.79 (m, 1 H), 4.13 (m, 1 H), 4.75 (m, 2H), 5.17 (bs, 1 H), 7.60 (m, 3H), 7.70 (s, 1 H), 7.88 (m, 2H), 12.35 (s, 1 H, NHCO). LC-MS: R t = 4.78 min, m/z: 493 [M+H] + EXAMPLE 57 2-(Oxalyl-amino.-5-(1 , 1 ,3-trioxo-5-phenyl-1 ,3-dihvdro-isothiazol-2- ylmethyl)-4,7-dihvdro-5H-thieno[2,3-c1pyran-3- carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5 - -thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 1,1-dioxo-5-phenyl-1 ,2- dihydro-1H-isothiazol-3-one as starting material. O- and Λ/-alkylated products were separated by column chromatography. 1 H-NMR (DMSO-de) δ 2.62 (dd, 1 H), 3.05 (d, 1 H), 3.88 (m, 2H), 3.98 (m, 1 H), 4.60-4.86 (dd, 2H), 766 (m, 4H), 7.93 (m, 2H), 12.3 (s, 1 H, N/-/CO). EXAMPLE 58 5-(1 , 1 -Dioxo-5-phenyl-1 H-isothiazol-3-yloxymethyl,-2-(oxalyl-amino)-4,7- dihvdro-5/- -thienor2,3-c]pyran-3-carboxylic acid The title compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5/-/-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester and 1 , 1 -dioxo-5-phenyl-1 ,2- dihydro-1 H-isothiazol-3-one as starting material. O- and V-alkylated products were separated by column chromatography. Mp.: 230 - 232 °C; Calculated for C 2 oHι 6 N 2 O 9 S 2 , 1 xH 2 O; C, 47.06 %; H, 3.55 %; N, 5.49 %. Found: C, 46.88 %; H, 3.44 %; N, 5.45 %. 5-(6-Chloro-1 ,1.3-trioxo-2.3-dihvdro-4/-/-thienor3.2-e1-1.2.4-thiadiazin-2- ylmethyl)-2-(oxalyl-amino)-4,7-dihvdro-5/- -thienof2,3-c1pyran-3-carboxylic acid The title compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester and 1 , 1-dioxide-6-chloro-2,3- dihydro-4H-thieno[3,2-e]-1 ,2,4-thiadiazine-3-one as starting material. O- and Λ/-alkylated products were separated by column chromatography. 1 H-NMR (DMSO-de) δ 2.60 (dd, 1 H), 2.98 (d, 1 H), 3.87-3.96 (m, 2H), 4.04 (m, 1 H), 4.56-4.82 (dd, 2H), 7.0 (s, 1 H), 1 1.95 (s, 1 H, NHCO), 12.3 (s, 1 H, NHCO). EXAMPLE 60 5-(6-Chloro-1 ,1-dioxo-4/-/-thieno[3,2-el-1 ,2,4-thiadiazine-3-yloxymethyl)-2- (oxalyl-amino)-4.7-dihvdro-5/-/-thieno[2,3-c1pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 1 ,1-dioxide-6-chloro-2,3- dihydro-4H-thieno[3,2-e]-1 ,2,4-thiadiazine-3-one as starting material. O- and /V-alkylated products were separated by column chromatography. Mp.: > 250 °C; Calculated for C 16 Hι 2 CIN3θ 9 S 3 , 0.75xH 2 O; C, 35.89 %; H, 2.54 %; N, 7.85 %. Found: C, 35.84 %; H, 2.36 %; N, 7.74 %. EXAMPLE 61 7-(1 ,3-Dioxo-1 ,3-dihvdro-benzofd1isothiazol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5/-/-thienor2,3-c1pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-7-hydroxymethyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 1 -oxo-1 , 2-dihydro-1 H- benzo[d]isothiazol-3-one as starting material. O- and Λ/-alkylated products were separated by column chromatography. LC-MS: R, = 3.82 min, m/z: 451 [M+H] + EXAMPLE 62 5-(1 ,3-Dioxo-1 ,3-dihydro-benzordlisothiazol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5/-/-thieno[2,3-c1pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5 -/-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 1 -oxo-1 ,2-dihydro-1 H- benzo[d]isothiazol-3-one as starting material. O- and Λ/-alkylated products were separated by column chromatography. Mp.: 230 - 231 °C; Calculated for Cι 8 Hι 4 N 2 O 8 S 2 , 0.5xH 2 O; C, 47.06 %; H, 3.29 %; N, 6.10 %. Found: C, 46.94 %; H, 3.42 %; N, 6.26 %. EXAMPLE 63 5-(5-Benzyl-1 ,1-dioxo-π ,2,5ithiadiazolidin-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihvdro-5/-/-thienor2,3-c1pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5/- -thieno[2,3- c]pyran-3-carboxylic acid ferf-butyl ester and 2-benzyl- [1 ,2,5]thiadiazolidine 1 ,1 -dioxide as starting material. Mp.: 188 - 192 °C; LC-MS: R t = 5.00 min, m/z: 496 [M+H] + EXAMPLE 64 5-(5-Ethyl-1 , 1 -dioxo-, 1 ,2,5Uhiadiazolidin-2-ylmethyl .-2-(oxalyl-amino.-4.7- dihydro-5/-/-thienor2,3-clpyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 23 using 2-amino-5-hydroxymethyl-4,7-dihydro-5/- -thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester and 2-ethyl-[1 ,2,5]thiadiazolidine 1 ,1 -dioxide as starting material. LC-MS: R t = 4.18 min, m/z: 434 [M+H] + EXAMPLE 65 2-(Oxalyl-amino)-7-(1-oxo-1 ,3-dihvdro-isoindol-2-ylmethvπ-4,7-dihydro-5/-- thieno[2,3-clpyran-3-carboxylic acid o a solution of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran- -carboxylic acid ferf-butyl ester (100 mg, 0.38 mmol) and N,N- diisopropylethylamine (72 μL, 0.41 mmol) in acetonitrile (6 ml) at 0 °C was added 2-bromomethyl-benzoic acid methyl ester (43 mg, 0.19 mmol). The reaction mixture was stirred for 16 hours and the solvent evaporated vacuo. The residue was diluted in ethyl acetate (50 ml), washed with 1 N hydrochloric acid, saturated sodium bicarbonate, brine, dried (MgSO 4 ), filtered and the solvent evaporated vacuo, which afforded 50 mg (68 %) of 2-amino-7-(1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5/-/- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 7.86 (d, 1 H, J = 8 Hz), 7.55 (t, 1 H, J = 8 Hz), 7.45 (t, 2H, J = 8 Hz), 4.88 (dt, 1 H. J = 6, 2 Hz), 4.68 (d, 1 H, J = 17 Hz), 4.48 (d, 1 H, J = 17 Hz), 4.25-4.10 (m, 1 H), 4.03 (dd, 1 H, J = 17 and J = 3 Hz), 3.80-3.75 (m, 2H), 2.92-2.70 (m, 2H), 1.54 (s, 9H). To a solution of 2-amino-7-(1-oxo-1,3-dihydro-isoindol-2-ylmethyl)-4,7- dihydro-5/-/-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (50 mg, 0.13 mmol) in tetrahydrofuran (1 ml) was added imidazol-1-yl-oxo-acetic acid ferf-butyl ester (100 mg, 0.51 mmol). The mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo. The residue was taken into ethyl acetate (50 ml), washed with saturated sodium bicarbonate and brine, dried (Na 2 SO 4 ) and filtered. The solvent was removed in vacuo and the residue was chromatographed using a mixture of 10% ethyl acetate/dichloromethane as eluent, which afforded 55 mg (83 %) of 2-(ferf-butoxyoxalyl-amino)-7-(1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.59 (s, 1 H), 7.88 (d, 1 H, J = 7 Hz), 7.54 (t, 1 H, J = 7 Hz), 7.46 (t, 2H, J = 7 Hz), 5.04 (dd, 1 H, J = 6 Hz and J = 2 Hz), 4.69 (d, 1H, J = 17 Hz), 4.46 (d, 1H, J = 17 Hz), 4.26-4.10 (m, 2H), 3.77 (dd, 1 H, J = 9 Hz and J = 3 Hz), 3.70 (dd, 1 H, J = 15 Hz and J = 9 Hz), 3.02-2.80 (m, 2H), 1.55 (s, 18H). A solution of 2-(fetf-butoxyoxalyl-amino)-7-(1 -oxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (55 mg, 0.11 mmol) in 50 % trifluoroacetic acid/dichloromethane (2 ml) was stirred for 16 hours. The volatiles were removed in vacuo and the residue was washed with dichloromethane and dried, which afforded 29 mg (50 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de) δ 12.35 (s, 1 H), 7.70 (d, 1 H, J = 8 Hz), 7.61 (d, 1 H, J = 3 Hz), 7.52-7.47 (m, 2H), 5.04 (s, 1 H), 4.59 (d, 1 H, J = 18 Hz), 4.58 (d, 1 H, J - 18 Hz), 4.19-4.08 (m, 1 H), 3.88 (d, 1 H, J = 6 Hz), 3.78-3.66 (m, 1 H), 3.38 (q, 1 H, J = 7 Hz), 2.85 (s, 2H); LC-MS: R t = 2.12 min, m/z: 417 [M+H] + . EXAMPLE 66 2-(Oxalyl-amino)-5-(2,2,2-trifluoro-acetoxymethvπ-4,7-dihvdro-5/- - thienof2,3-clpyran-3-carboxylic acid 2-(ferf-Butoxyoxalyl-amino)-5-hydroxymethyl-4,7-dihydro-5/-/-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester (0.5 g, 1.21 mmol) was dissolved in dichloromethane (9 ml) and trifluoroacetic acid (3 ml) was added. The reaction mixture was stirred 64 hours at room temperature. The precipitate was filtered off and washed with diethyl ether and dried in vacuo at 50 °C for 4 hours, which afforded 180 mg (50 %) of the title compound as a solid. Mp.: 231 - 233 °C; Calculated for C 13 H 10 F 3 NOsS; C, 39.30 %; H, 2.56 %; N, 3.57 %. Found: C, 39.30 %; H, 2.54 %; N, 3.53 %. EXAMPLE 67 5-(((Benzof1 ,3.dioxol-5-ylmethyl)-amino)-methyl,-2-,oxalyl-amino)-4,7- dihvdro-5H-thienor2,3-c1pyran-3-carboxylic acid To a solution of oxalyl chloride (1 ml, 11.13 mmol) in dichloromethane (40 ml) cooled to -78 °C under an atmosphere of nitrogen was added dropwise a solution of dimethylsulfoxide (1.6 ml, 21.78 mmol) in dichloromethane (16 ml) during 5 min. After stirring for 15 min at -78 °C a solution of 2-(ferf-butoxyoxalyl-amino)-5-hydroxymethyl-4,7-dihydro-5 -/- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (2.0 g, 4.84 mmol) in dichloromethane (30 ml) was added dropwise and the resulting mixture was stirred for 0.5 hour at -78 °C. Λ/, /-Diisopropylethylamine (4.2 ml, 24.18 mmol) was added and the reaction mixture allowed reaching room temperature at which time heptane (700 ml) was added. The mixture was filtered through anhydrous sodium sulfate and the solvent evaporated in vacuo. The residue (2.71 g) was purified on column chromatography using a mixture of ethyl acetate/heptane (1 :4) as eluent which afforded 0.93 g (47 %) of 2-(ferf-butoxyoxalyl-amino)-5-formyl-4,7-dihydro-5/-/-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester as an oil. To a mixture of 2-(fetf-butoxyoxalyl-amino)-5-formyl-4,7-dihydro-5/-/- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (0.46 g, 1.12 mmol) and piperonylamine (145 μl, 1.12 mmol) in 1 ,2-dichloroethane (25 ml) was added sodium triacetoxyborohydride (0.35 g, 1.57 mmol) and the resulting mixture was stirred at room temperature for 1 hour. The mixture was washed with saturated aqueous sodium hydrogencarbonate (2 x 30 ml) and dried (Na 2 SO 4 ), filtered and the solvent evaporated m vacuo. The residue (0.56 g) was purified on column chromatography using a mixture of ethyl acetate/heptane (1 :1) as eluent followed by a mixture of 10% triethylamine in ethyl acetate/heptane (1:1) as eluent. Semi pure fractions were collected and the solvent evaporated in vacuo. The residue (180-mg) was subjected to preparative TLC using a mixture of 10% triethylamine in ethyl acetate/ethanol (4:1) as eluent. The desired band was taken off and extracted with methanol (400 ml) for 0.5 hour, filtered and the solvent evaporated in vacuo, which afforded 250 mg (> 100%, contains dichloromethane and silicagel) of 5-(((benzo[1 ,3]dioxol-5-ylmethyl)- amino)methyl)-2-(ferf-butoxyoxalyl-amino)-4,7-dihydro-5/-/-thieno[2,3- c]pyran-3-carboxylic acid fetf-butyl ester as an oil. LC-MS: R t = 5.75 min, m/z: 547 [M+H] + . 5-(((Benzo[1 ,3]dioxol-5-ylmethyl)-amino)methyl)-2-(ferf-butoxyoxalyl- amino)-4,7-dihydro-5/-/-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (250 mg) was dissolved in dichloromethane (9 ml) and trifluoroacetic acid (3 ml) was added. The reaction mixture was stirred 16 hours at room temperature. The volatiles were evaporated in vacuo and the residue trituated with a small portion of diethyl ether. The solid precipitate was filtered off and washed with diethyl ether and dried in vacuo at 50 °C for 16 hours, which afforded 160 mg of the title compound as a solid. Calculated for C 19 Hι 8 N 2 O 8 S, 2xTFA, 3xH 2 O; C, 38.56 %; H, 3.66 %; N, 3.91 %. Found: C, 38.61 %; H, 3.90 %; N, 4.22 %. EXAMPLE 68 5-((2-Methoxy-benzylamino)methyl)-2-(oxalyl-amino)-4,7-dihvdro-5/-f- thieno[2,3-c1pyran-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 66 using 2-(ferf-butoxyoxalyl-amino)-5-formyl-4,7-dihydro-5/-- thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester and 2-methoxy- benzylamine as starting material. Calculated for C 19 H 2 oN 2 O 7 S, 0.75xTFA; C, 48.67 %; H, 4.13 %; N, 5.54 %. Found: C, 48.61 %; H, 4.42 %; N, 5.35 %. EXAMPLE 69) 5-((2-Benzo[1 ,3ldioxol-5-yl-acetylamino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5/-/-thieno[2,3-c1pyran-3-carboxylic acid To a solution of 3,4-methylenedioxy phenylacetic acid (0.22 g, 1.09 mmol), 1 -(3-dimethylaminopropyl)-3-ethylcarbodiimide, hydrochloride (0.27 g, 1.42 mmol) in acetonitrile (6 ml) was added triethylamine (0.46 ml, 3.27 mmol). The resultant mixture was allowed to stir at ambient temperature for 10 min. before 2-amino-5-aminomethyl-4,7-dihydro-5/- - thieno-[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.311 g, 1.09 mmol) was added. The reaction mixture was allowed to stir at ambient temperature for 18 hours and then concentrated i vacuo. To the residue ethyl acetate and water were added and the layers separated. The organic layer was washed with hydrochloric acid (0.5M, (v/v)), saturated sodium bicarbonate (2 x 25 ml) and brine (2 x 25 ml). The organic layer was dried (MgSO ), filtered and the solvent evaporated in vacuo. The crude 2-amino-5-((2-benzo[1,3]dioxol-5-yl-acetylamino)-methyl]-4,7- dihydro-5/-/-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester was used immediately in the next step. 1 H-NMR (CDCIr.) δ 678-6.69 (m. 3H), 5.97 (bs. 2H). 5.95 (s. 2H), 4.60- 4.58 (m. 1 H). 4.53 (s, 2H). 3.73 (ddd, 1 H, J = 14 Hz. J = 7.6 Hz and J = 3.2 Hz.. 3.65-3.59 (m, 1 H). 3.49 (s. 2H). 3.11 (ddd. 1 H. J = 12.4 Hz. J = 4 Hz and J = 4.4 Hz). 2.76 (dm. 1 H , . 2.44 (ddt. 1 H. J = 19.6 Hz. J = 13.2 Hz and = 2.4 Hz), 1.51 (s, 9H). To a solution of the above crude 2-amino-5-((2-benzo[1 ,3]dioxol-5-yl- acetylamino)-methyl]-4,7-dihydro-5/- -thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.17 g, 0.38 mmol) in dichloromethane (5 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (0.22 g, 1.14 mmol). The reaction mixture was stirred at room temperature for 18 hours, the volatiles evaporated in vacuo and the residue diluted with ethyl acetate. The organic layer was washed with hydrochloric acid (1 % (v/v), 2 x 25 ml), saturated sodium bicarbonate (2 x 25 ml) and brine (2 x 25 ml). The organic layer was dried (MgSO 4 ), filtered, concentrated in vacuo and the residue subjected to flash chromatography using a mixture of ethyl acetate/hexanes (1 :2) as eluent, which afforded 0.12 g (55 %) of 2-(ferf- butoxyoxalyl-amino)-5-((2-benzo[1 ,3]dioxol-5-yl-acetylamino)-methyl]-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.51 (bs, 1 H), 6.78 (d, 1 H, J = 8 Hz), 6.77 (d, 1 H, J = 1.6 Hz), 6.71 (dd, 1 H, J = 8.4 Hz and J = 1.6 Hz), 5.96 (s, 2H), 4.70 (m, 2H, J = 35 Hz, J = 15.2 Hz, J = 14.4 Hz and J = 2 Hz), 3.77 (ddd, 1 H, J = 10.8 Hz, J = 7.6 Hz and J = 3.2 Hz), 3.67-3.62 (m, 1 H), 3.50 (s, 2H), 3.15 (ddd, 1 H, J = 12.8 Hz, J = 8.4 Hz and J = 4.4 Hz), 2.87 (dt, 1 H, J = 16 Hz and J = 3 Hz), 2.57-2.50 (m, 1 H), 1.61 (s, 9H), 1.57 (s, 9H); LC-MS: m/z: 575.0 [M+H] + 2-(fetf-Butoxyoxalyl-amino)-5-((2-benzo[1 ,3]dioxol-5-yl-acetylamino)- methyl]-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.12 g, 0.20 mmol) was dissolved in a 50% solution of trifluoroacetic acid/dichloromethane (2 ml). The reaction mixture was stirred at ambient temperature for 18 hours, concentrated in vacuo to 1/5 of the volume and the precipitate filtered off and washed with dichloromethane (2x) affording 50 mg (50 %) of the titie compound as a solid. 1 H-NMR (DMSO-d 6 ) δ 12.32 (bs, 1H), 8.20 (t, 1 H, J = 6.8 Hz), 6.81 (m, 2H), 6.70 (m, 1 H), 5.95 (s, 2H), 4.80 (d, 1 H, J = 19.6 Hz), 4.63 (d, 1H, J = 20 Hz), 3.65 (m, 1H), 3.34 (s, 2H), 3.30-3.20 (m, 3H), 2.87 (dm, 1H); LC-MS: m/z: 463.0 [M+H] + . 5-(((5-Methoxy-2-methyl-1/-/-indol-3-carbonyl)amino)methyl)-2-(oxalyl- amino)-47-dihydro-5H-thienof2,3-c1pyran-3-carboxylic acid To a solution of 5-methoxy-2-methyl indole-3-acetic acid (0.26 q. 1.18 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, hydrochloride (0.27 q, 1.4 mmol) in acetonitrile (10 ml) was added triethylamine (0.46 ml, 3.2 mmol). The reaction mixture was allowed to stir for 10 min at room temperature before compound 2-amino-5- aminomethyl-47-dihvdro-5/--thieno[2.3-c1pyran-3-carboxylic acid ferf- butyl ester (0.307 q, 1.08 mmol) was added. The reaction mixture was allowed to stir for 18 hours and then concentrated in vacuo. Ethyl acetate and water were added and the layers separated. The organic layer was washed with hydrochloric acid (0.5M, (v/v)), saturated sodium bicarbonate (2 x 25 ml) and brine (2 x 25 ml). The organic layer was dried (MgSOA filtered and concentrated in vacuo. The crude 2-amino- 5-(((5-methoxy-2-methyl-1H-indol-3-carbonyl)amino)-methyl)-4,7- dihvdro-5/- -thienof2,3-clpyran-3-carboxylic acid ferf-butyl ester was used immediately in the next step. 1 H-NMR fCDCIa) δ 7.90 (bs. 1 H), 719 (d. 1 H. J = 8.8 Hz). 6.87 (d. 1 H. J = 2.4 Hz). 679 (dd. 1 H. J = 8.8 Hz and J = 2.4 Hz). 6.18 (m. 1 H). 5.94 (s. 2H). 4.33 (m. 2H. J = 25 Hz. J = 14 Hz. J = 2.8 Hz and J = 1.6 Hz). 3.80 (s, 3H). 376 (ddd. 1 H, J = 14 Hz. J = 8 Hz and J = 2.8 Hz). 3.65 (s, 3H), 3.53 (m, 1 H). 2.99 (ddd, 1 H. J = 13 Hz. J = 5.6 Hz and J = 4 Hz), 276 (dt. 1 H. J = 16.8 Hz, J = 2.8 Hz). 2.42-2.40 (m, 1 H). 2.38 (s. 3H), 1.51 (s. 9H). To a solution of the crude 2-amino-5-(((5-methoxy-2-methyl-1 H-indol-3- carbonyl)amino)methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.35 g, 0.72 mmol) in dichloromethane (5 ml) was added imidazol-1-yl-oxo-acetic acid ferf-butyl ester (0.42 g, 2.1 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated vacuo and the residue diluted with ethyl acetate. The organic layer was washed with hydrochloric acid (1 % (v/v), 2 x 25 ml), saturated sodium bicarbonate (2 x 25 ml) and brine (2 x 25 ml). The organic layer was dried (MgSO 4 ), filtered, concentrated i vacuo and the residue subjected to flash chromatography using a mixture of ethyl acetate/hexanes (1 :1) as eluent, which afforded 0.24 (55 %) of 2- (ferf-butoxyoxalyl-amino)-5-(((5-methoxy-2-methyl-1H-indol-3- carbonyl)amino)methyl)-4,7-dihydro-5/- -thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.50 (bs, 1 H), 7.92 (s, 1 H), 7.20 (dd, 1 H, J =8.4 Hz and J = 0.4 Hz), 6.88 (d, 1 H, J = 2.4 Hz), 6.80 (dd, 1 H, J = 8.8 Hz and J = 2.4 Hz), 6.21 (m, 1 H), 4.56 (dd, 1 H, J = 14.8 Hz and J = 2.8 Hz), 4.44 (dt, 1 H, J = 14.4 Hz and J = 2.8 Hz), 4.11 (q, 1 H, J = 7.2 Hz), 3.81-375 (m, 1 H), 3.79 (s! 3H), 3.66 (s, 2H), 3.58-3.54 (m, 1 H), 3.01 (ddd, 1 H, J = 14 Hz, J = 8.8 Hz and J = 4.4 Hz), 2.85 (dt, 1 H, J = 16.8 Hz and J = 6 Hz), 2.52-2.45 (m, 1 H), 2.38 (s, 3H), 1.60 (s, 9H), 1.57 (s, 9H); LC-MS: m/z: 614.1 [M+Hf. 2-(fetf-Butoxyoxalyl-amino)-5-(((5-methoxy-2-methyl-1/-/-indol-3- carbonyl)amino)-methyl)-4,7-dihydro-5/-/-thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (0.24 g, 0.39 mmol) was dissolved in a 50 % solution of trifluoroacetic acid/dichloromethane (2 ml). The reaction mixture was stirred at ambient temperature for 18 hours, concentrated vacuo to 1/5 of the volume and the precipitate filtered off. The filtrate was washed with dichloromethane (2x) and dried, which afforded 100 mg (50 %) of the title compound as a solid. 1 H-NMR (DMSO-de) δ 12.31 (bs, 1 H), 10.58 (s, 1 H), 7.98 (t, 1 H, = 6.8 Hz), 7.08 (d, 1H, J = 11.2 Hz), 6.98 (d, 1H, J = 2.4 Hz), 6.58 (dd, 1H, J = 11.6 Hz and J = 2.8 Hz), 5.75 (d, 1 H, J = 0.8 Hz), 4.77 (d, 1 H, = 19.6 Hz), 4.58 (d, 1H, J = 20 Hz), 3.69 (s, 3H), 3.64-3.62(m, 1 H), 3.43 (s, 2H), 3.31-3.20 (m, 1 H), 2.92-2.84 (m, 1 H), 2.52 (m, 1 H-partially obscured by DMSO), 2.30 (s, 3H); LC-MS: m/z: 500.1 [M-H] " . 5-(1 ,3-Dioxo-5-propylcarbamoyl-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihvdro-5H-thienof2,3-clpyran-3-carboxylic acid In a 10-mL scintillating vial, a solution of 2-amino-5-aminomethyl-4,7- dihydro-5/-/-thieno[2,3-c]pyran-3-carboxylic acid fetf-butyl ester (149 mg, 0.5 mmol) in Λ/,Λ/-dimethylformamide (4 mL) was treated with trimellitic anhydride (120 mg, 0.62 mmol) and stirred at 100 °C for 24 hours. The solution was then diluted with ethyl acetate (25 mL) and washed with 0.5N aqueous hydrogen chloride (25 mL) and brine (25 mL). The organic layer was dried (MgSO ), filtered, and concentrated in vacuo affording 229 mg (100 %) of 2-(2-amino-3-ferf-butoxycarbonyl-4,7-dihydro-5/- -thieno[2,3- c]pyran-5-ylmethyl)-1 ,3-dioxo-2,3-dihydro-1 H-isoindole-5-carboxylic acid as a solid. 1 H-NMR (300 MHz, CDCI 3 ) δ 8.58 (s, 1H), 8.49 (d, 1 H, J = 9 Hz), 8.00 (d, 1 H, J = 10 Hz), 4.64-4.54 (m, 2H), 4.08-4.02 (m, 2H), 3.88-3.80 (m, 1 H), 2.98-2.83 (m, 1 H), 2.68-2.54 (m, 1 H), 1.57 (s, 9H). HPLC (254.4 nm) R t = 3.98 min. In a 250 mL round bottom flask, a solution of 2-(2-amino-3-fetf- butoxycarbonyl-4,7-dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl)-1 ,3-dioxo- 2,3-dihydro-1H-isoindole-5-carboxylic acid (500 mg, 1.1 mmol) in dichloromethane (7 mL) was treated with a solution of imidazol-1-yl-oxo- acetic acid fetf-butyl ester (633 mg, 3.2 mmol) in dichloromethane (1.0 mL). After stirring for 4 hours at room temperature the reaction solution was dissolved in ethyl acetate (100 mL) and washed with distilled water (2 x 50 mL), 0.5 N aqueous hydrogen chloride (3 x 50 mL), and brine (50 mL). The organic layer was dried (MgSO 4 ), filtered, and concentrated in vacuo to yield 370 mg (58 %) of 2-(2-(fetf-butoxyoxalyl-amino)-3-ferf- butoxycarbonyl-4,7-dihydro-5/-/-thieno[2,3-c]pyran-5-ylmethyl)-1 ,3-dioxo- 2,3-dihydro-1/-/-isoindole-5-carboxylic acid as a solid. H-NMR (300 MHz, CDCI 3 ) δ 12.49 (s, 1 H), 8.58 (s, 1 H), 8.50 (d, 1 H, J = 8 Hz), 8.00 (d, 1H, J = 8 Hz), 4.84-4.65 (m, 2H), 4.17-4.00 (m, 2H), 3.92- 3.84 (m, 1H), 3.08-2.94 (m, 1H), 278-2.64 (m, 1H), 1.61 (s, 9H), 1.57 (s, 9H). In a 50 mL round bottom flask, a solution of 2-(2-(ferf-butoxyoxalyl-amino)- 3-fetf-butoxycarbonyl-4,7-dihydro-5H-thieno[2,3-c]pyran-5-ylmethyl)-1 ,3- dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid (208 mg, 0.36 mmol) in dichloromethane (5.0 mL) was treated with Λ/,Λ/-diisopropyl ethylamine (200 μL, 1.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (84 mg, 0.44 mmol). The solution was allowed to stir for 50 minutes at room temperature before propylamine (30 μL, 0.36 mmol) was added dropwise. The solution was stirred for an additional 18 hours at room temperature. The volatiles were evaporated vacuo and the residue was purified by silica gel chromatography using a mixture of hexane/ethyl acetate (9:1) as eluent, which afforded 51 mg (23 %) of 2- (fetf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-5-propylcarbamoyl-1 ,3-dihydro- isoindol-2-ylmethyl)-4,7-dihydro-5/- -thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester as a solid. 1 H-NMR (300 MHz, CDCI 3 ) δ 12.48 (s, 1 H), 8.24-8.16 (m, 2H), 7.93 (d, 1 H, J = 8 Hz), 6.39 (t, 1 H, J = 6 Hz), 4.18-4.63 (m, 2H), 4.10-3.96 (m, 2H), 3.92-3.78 (m, 1 H), 3.47 (q, 2H, J = 1 Hz), 2.99 (d, 1 H, J = 17), 276-2.60 (m, 1 H), 1.68 (q, 2H, J = 7 Hz), 1.61 (s, 9H), 1.57 (s, 9H), 1.01 (t, 3H, J = 7 Hz). In a 25 mL round bottom flask 2-(fetf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-5- propylcarbamoyl-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5/-- thieno[2,3-c]pyran-3-carboxylic acid ferf-butyl ester (40 mg, 0.07 mmol) was dissolved in 20 % trifluoroacetic acid in dichloromethane (4 mL). The solution was left open to the atmosphere without stirring. After 24 hours the precipitate was filtered off and washed with diethyl ether, affording 32 mg (90 %) of the titie compound as a solid. 1 H-NMR (300 MHz, DMSO-d 6 ) δ12.32 (s, 1 H), 8.81 (s, 1 H), 8.58 (s, 1 H), 8.00 (s, 1 H), 4.90-4.48 (m partially obscured by water, 2H), 4.00-3.64 (m partially obscured by water, 3H), 3.36-3.16 (m partially obscured by water, 2H), 3.13-2.90 (d partially obscured by water, 1 H), 2.69-2.53 (m partially obscured by DMSO, 1H), 1.69-1.38 (m, 2H), 1.00-074 (m, 3H). HPLC (254.4 nm) R t = 3.09 min. MS (APCI " ) m/z: 515.4 [M-H] " . EXAMPLE 72 7-(4-Hvdroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thienof2,3-c1pyridine-3-carboxylic acid 2-(ferf-Butoxyoxalyl-amino)-7-(4-benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol- 2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester (50 mg, 0.067 mmol) was dissolved in a mixture of ethyl acetate/ethanol (3 mL, 1:1). Palladium on activated carbon (10%, 10 mg) was added and the solution degassed and stirred under hydrogen (1 atm) for 72 hours. The mixture was filtered through celite and the filter cake washed with hot ethyl acetate. The filtrate was concentrated vacuo and the residue purified by silica gel chromatography (10% ethyl acetate/dichloromethane) to obtain 42 mg (95%) of 2-(ferf-butoxyoxalyl- amino)-7-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester as an oil. 1 H-NMR (400 MHz, CDCI 3 ) δ 12.59-12.53 (2s, 1 H), 7.64-7.53 (m, 1 H), 7.42-736 (m, 1H), 7.19-7.11 (m, 1H), 5.58-5.37 (m, 1H), 4.37-4.00 (m, 2H), 3.86-3.78 (m, 1H), 3.32-3.18 (m, 1 H), 2.99-2.94 (m, 1 H), 2.84-2.69 (m, 1 H), 1.62-1.59 (3s, 18H), 1.17-1.11 (2s, 9H); LC-MS: R t = 4.55 min, m/z: 658 [M+H] + , 2-(ferf-Butoxyoxalyl-amino)-7-(4-hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindoI-2- ylmethyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di- fetf-butyl ester (42 mg, 0.064 mmol) was dissolved in a solution of 50% trifluoroacetic acid/methylene chloride (3 mL). The reaction was stirred at ambient temperature for 7 hours, concentrated in vacuo and evaporated from dichloromethane (10 ml) three times. The resulting precipitate was washed with dichloromethane and dried in vacuo to give 29 mg (81 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (400 MHz, DMSO-d 6 ) δ 12.32 (bs, 1 H), 11.26 (s, 1 H), 9.30 (bs, 2H), 7.64 (t, 1 H, J = 7 Hz), 7.33 (d, 1 H, J = 7 Hz), 7.25 (d, 1 H, J = 7 Hz), 4.84 (s, 1 H), 4.06-3.96 (m, 2H), 3.56 (m, 2H), 3.05 (bs, 2H), LC-MS: R t = 1.26 min, m/z: [M+H] + , EXAMPLE 73 5-(4-Hvdroxy-1-oxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid Acetyl chloride (5.4 ml, 5.96 g, 76 mmol) was added dropwise to methanol (15 ml) at 0 °C in a sealed 50 ml round-bottom flask. This solution was allowed to warm to room temperature for 1 hour while stirring. To this solution 3-hydroxy-2-methyl-benzoic acid (519 mg, 3.4 mmol) was added and the solution was stirred at room temperature for 42 hours. The reaction was quenched with saturated aqueous sodium bicarbonate and solid sodium bicarbonate. The volatiles were removed vacuo and the basic aqueous solution was then extracted with dichloromethane (4 x 40 ml). The combined organic extracts were dried (MgSO ), filtered, and the solvent evaporated in vacuo affording 493 mg (87 %) of 3-hydroxy-2- methyl-benzoic acid methyl ester as a solid. 1 H-NMR (300 MHz, CDCI 3 ): δ 7.43 (d, 1 H, J = 9 Hz), 7.12 (t, 1 H, J = 8 Hz), 6.95 (d, 1 H, J = 8 Hz), 5.05 (bs, 1 H), 3.90 (s, 3H), 2.47 (s, 3H). To a solution of the above methyl ester (256 mg, 1.54 mmol) and N,N- diisopropylethylamine (530 μl, 3.0 mmol) in dichloromethane (8 ml) at 0 °C methyloxymethyl chloride (175 μl, 2.3 mmol) was added dropwise. The solution was allowed slowly to warm to room temperature and stired for 24 hours. The solution was diluted with dichloromethane (12 ml), washed with water (20 ml), brine (20 ml), dried (MgSO 4 ), filtered, and concentrated in vacuo. The resulting oil was purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (4:1) as eluent, which afforded 269 mg (85 %) of 3-methoxymethoxy-2-methyl-benzoic acid methyl ester as an oil. 1 H-NMR (300 MHz, CDCI 3 ): δ 7.48 (d, 1H, J = 8 Hz), 7.24-7.15 (m, 2H), 5.22 (s, 2H), 3.90 (s, 3H), 3.50 (s, 3H), 2.47 (s, 3H). In a 25 ml round-bottom flask, Λ/-bromosuccinimide (236 mg, 1.3 mmol) and azobis(cyclohexanecarbonitrile) (33 mg, 0.14 mmol) were added to a solution of 3-methoxymethoxy-2-methyl-benzoic acid methyl ester (265 mg, 1.26 mmol) in carbon tetrachloride (6.5 ml). The reaction was heated to reflux with stirring for 3.5 hours. The volatiles were removed in vacuo and the residue purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (9:1) as eluent, which afforded 364 mg (100 %) of 2-bromomethyl-3-methoxymethoxy-benzoic acid methyl ester as a solid. 1 H-NMR (300 MHz, CDCI 3 ): δ 7.55 (dd, 1 H, J = 6,3 Hz), 7.29 (d, 2H, J = 3 Hz), 5.27 (s, 2H), 5.05 (s, 2H), 3.91 (s, 3H), 3.50 (s, 3H). In a 100 ml round-bottom flask, 2-amino-5-aminomethyl-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (298 mg, 074 mmol) and N,N-diisopropylethylamine (195 μl, 1.12 mmol) were dissolved in acetonitrile (40 ml). 2-Bromomethyl-3- methoxymethoxy-benzoic acid methyl ester (193 mg, 0.67 mmol) in acetonitrile (5 ml) was slowly added to the amine solution via gastight syringe over 24 hours, followed by stirring at room temperature for an additional 36 hours. The solution was concentrated in vacuo, the residue redissolved in ethyl acetate (25 ml), and washed with saturated aqueous sodium bicarbonate (25 ml) and brine (25 ml). The organic phase was dried (MgSO 4 ), filtered, and the solvent evaporated vacuo. The residue was purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (1 :1) as eluent, which afforded 345 mg (81 %) of 2-amino-6-(4- methoxy-benzyl)-5-(4-methoxymethoxy-1 -oxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (300 MHz, CDCI 3 ): δ 7.67 (d, 1 H, J = 8 Hz), 7.57-7.38 (m, 5H), 7.14 (d, 2H, J = 8 Hz), 6.96 (m, 2H), 6.77 (d, 2H, J = 9 Hz), 6.20 (d, 2H, J = 6 Hz), 5.96 (s, 2H), 4.69-2.58 (m, 17H), 1.55 (s, 9H). In a 50 ml round-bottom flask a solution of 2-amino-6-(4-methoxy-benzyl)- 5-(4-methoxymethoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5, 6,7- tetrahydro[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (338 mg, 0.58 mmol) in dichloromethane (20 ml) was treated with imidazol-1-yl-oxo- acetic acid fetf-butyl ester (575 mg, 2.9 mmol). After stirring for 18 hours at room temperature, the mixture was concentrated to dryness in vacuo. The residue was purified by silica gel chromatography using a mixture of hexanes/ethyl acetate (1 :1) as eluent, which afforded 310 mg (75 %) of 2- (fetf-Butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-(4-methoxymethoxy-1 - oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (300 MHz, CDCI 3 ): δ 12.57 (s, 1 H), 7.53 (d, 1 H, J = 8 Hz), 7.43 (t, 1 H, J = 8 Hz), 7.26 (d, 1 H, J = 8 Hz), 7.13 (d, 2H, J = 9 Hz), 6.78 (d, 2H, J = 9 Hz), 5.28 (s, 2H), 4.47 (q, 2H, J = 18 Hz), 4.02-3.44 (m, 11 H), 2.97 (dd, 1 H, J = 18 Hz and J = 5 Hz), 2.76 (dd, 1 H, J = 17 Hz and J = 5 Hz), 1.63 (s, 9H), 1.59 (s, 9H). 10 % Pd/C (145 mg, 50 % by weight) was added to a mixture of 2-(ferf- butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-(4-methoxymethoxy-1-oxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (283 mg, 0.40 mmol) in 10 % formic acid and methanol (10 ml). After stirring at room temperature for 18 hours, more Pd/C (141 mg, 50 % by weight) was added to the reaction mixture. After stirring at room temperature for an additional 20 hours, the catalyst was removed via fitration through celite. Fresh Pd/C (255 mg) and ammonium formate (1.0 g) were added to the residue (253 mg, 0.36 mmol) dissolved in 10 % formic acid in methanol (10 ml). The solution was heated to 40 °C for 48 hours. Catalyst was removed via filtration through celite and liberal washing with methanol. Purification by chromatotron (ethyl acetate/triethylamine (99:1)) afforded 63 mg (27 %) of 2-(ferf- butoxyoxalyl-amino)-5-(4-methoxymethoxy-1 -oxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf- butyl ester A and 46 mg (19 %) of 2-(ferf-butoxyoxalyl-amino)-5-(4- methoxymethoxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-methyl-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester B. A: 1 H-NMR (300 MHz, CDCI 3 ): δ 12.54 (s, 1 H), 7.50 (d, 1 H, J = 8 Hz), 7.41 (t, 1 H, J = 8 Hz), 7.25 (d, 1 H, J = 8 Hz), 5.27 (s, 2H), 4.52 (dd, 2H, J = 30 Hz and J = 19 Hz), 4.08-3.90 (m, 2H), 3.86-3.67 (m, 2H), 3.51 (s, 3H), 3.27 (m, 1H), 2.99 (dd, 1 H, J = 18 Hz and J = 4 Hz), 2.53 (dd, 1 H, J =18 Hz and J = 11 Hz), 1.61 (s, 9H), 1.53 (s, 9H). LC-MS (APCI + ) m/z: 588 [M+H] + ; R t = 1.32 min. B: 1 H-NMR (300 MHz, CDCI 3 ): δ 12.56 (s, 1 H), 7.50 (d, 1 H, J = 7 Hz), 7.41 (t, 1 H, J = 8 Hz), 7.25 (d, 1 H, J = 8 Hz), 5.27 (s, 2H), 4.50 (dd, J = 28 Hz and J = 18 Hz), 3.93-3.68 (m, 4H), 3.51 (s, 1 H), 3.51 (s, 3H), 3.31 (m, 1H), 2.88 (dd, 1 H, J = 18 Hz and J = 4 Hz), 2.68 (dd, 1 H, J =19 Hz and J = 9 Hz), 2.46 (s, 3H), 1.61 (s, 9H), 1.54 (s, 9H). LC-MS (APCI + ) m/z: 602 [M+H] + ; R t = 1.35 min. 2-(ferf-Butoxyoxalyl-amino)-5-(4-methoxymethoxy-1 -oxo-1, 3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester A (63 mg, 0.11 mmol) was dissolved in 30 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring. After 24 hours the precipitate was filtered off and washed with diethyl ether, affording 57 mg (90 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (300 MHz, DMSO-d 6 ): δ 12.30 (s, 1H), 10.17 (s, 1 H), 9.23 (s, 2H, J = 5 Hz and J = 7 Hz), 7.34 (t, 1 H, J = 6 Hz), 7.19 (d, 1 H, J = 5 Hz), 7.03 (d, 1 H, J = 6 Hz), 5.76 (s, 2H), 4.53 (d, 1H, J = 13 Hz), 4.43-4.22 (m, 3H), 4.07 (m, 1H), 3.91 (m, 1H), 3.70 (m, 1H), 3.10 (m, 1H), 2.82 (dd, 1H, J = 14 Hz and J = 8 Hz). EXAMPLE 74 5-(4-Hvdroxy-1-oxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-6-methyl-2-(oxalyl- amino)-4,5,6,7-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid The above 2-(ferf-butoxyoxalyl-amino)-5-(4-methoxymethoxy-1 -oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-6-methyl-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester B (46 mg, 0.08 mmol) was dissolved in 30 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring. After 24 hours the precipitate was filtered off and washed with diethyl ether, affording 41 mg (90 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (400 MHz, CDCI 3 ): δ 12.39 (s, 1H), 10.19 (s, 1H), 10.10 (s, 1H), 7.32 (t, 1 H, J = 7.6 Hz), 7.17 (d, 1 H, J = 7.2 Hz), 7.02 (t, 1 H, J = 7.2 Hz), 4.55 (d, 2H, J = 15 Hz), 4.0-4.5 (m, 4H), 2.95-370 (m, 5H), 2.85 (s, 3H). LC-MS (APCI + ) m/z: 446 [M+H] + ; R t = 1.02 min. EXAMPLE 75 5-((1 , 1 -Dioxo-1 H-benzofd1isothiazol-3-ylamino)methyl)-2-(oxalyl-amino)- 4,5,67-tetrahvdro-thienof2.3-c1pyridine-3-carboxylic acid Saccharin (8.8 g, 48 mmol) and phosphorous pentachloride (15 g, 72 mmol) were added neat to a round bottom flask equipped with a short path distillation column. The mixture was heated to 175 °C. After approximately 0.5 hour, phosphorous oxychloride slowly distilled off. Upon completion of the reaction, the mixture was cooled and the resultant solid recrystallized from benzene affording 3.6 g (37 %) of 3-chloro- benzo[d]isothiazole 1 ,1-dioxide as a solid. 1 H-NMR (CDCI 3 ): δ 7.92 (d, 1 H, J = 6.9 Hz), 7.8 (m, 3H). To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylicacid ferf-butyl ester (155 mg, 0.384 mmol) and triethylamine (59 μl, 0.423 mmol) in dichloromethane (2 ml) at 0 °C, was added a solution of 3-chloro-benzo[d]isothiazole 1 ,1- dioxide (85.2 mg, 0.423 mmol) in dichloromethane (2 ml). The reaction mixture was stirred at 0 °C for 1 hour. The reaction was judged complete by tic (dichloromethane/ethyl acetate (1:1)). The reaction mixture was washed with water (3 x 20 ml), dried (MgSO 4 ), filtered and the solvent evaporated m vacuo. The crude residue was subjected to flash chromatography using a gradient from 100 % dichloromethane to dichloromethane/ethyl acetate (80/20) as eluent, which afforded 200 mg (92 %) of 2-amino-5-((1 ,1 -dioxo-1 H-benzo[d]isothiazol-3-ylamino)methyl)- 6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as a foam. 1 H-NMR (CD 3 OD): δ 7.99 (m, 1 H), 7.87 (m, 1 H), 7.79 (m, 2H), 7.19 (d, 2H, J = 8.4 Hz), 6.75 (d, 2H, J = 8.7 Hz), 3.88-3.79 (m, 2H), 375-3.59 (m, 3H), 3.69 (s, 3H), 3.52-3.46 (m, 2H), 2.84 (dd, 1H, J = 15.3 Hz and J = 5.4 Hz), 2.68 (dd, J = 18 Hz and J = 4.5 Hz), 1.46 (s, 9H). LC-MS: R t = 2.83, m/z: 569 [M+H] + To a solution of 2-amino-5-((1 ,1 -dioxo-1 H-benzo[d]isothiazol-3-ylamino)- methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester (129 mg, 0.227 mmol) in tetrahydrofuran (3 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (1.1 ml, 1.1 mmol, 1 M in tetrahydrofuran). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue subjected to flash chromtography using a mixture of ethyl acetate/dichloromethane (10:90) as eluent, which afforded 142 mg (90%) of 2-(fetf-butoxyoxalyl-amino)-5-((1 , 1 -dioxo-1 H-benzo[d]isothiazol-3- ylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.92 (d, 1H, J = 6.3 Hz), 7.73 (m, 2H), 7.56 (d, 1H, J = 5.7 Hz), 7.20 (d, 2H, J = 6.3 Hz), 7.05 (bs, 1 H), 6.87 (d, 2H, J = 6.6 Hz), 3.91 (m, 2H), 3.82-3.72 (m, 2H), 3.79 (s, 3H), 3.61-3.49 (m, 2H), 3.44 (m, 1 H), 3.11 (dd, 1 H, J = 15 Hz and J = 3.6 Hz), 2.72 (dd, 1 H, J = 12 Hz and J = 4.2 Hz), 1.63 (s, 18H); LC-MS: R,=3.48, m/z: 697 [M+H] + 2-(ferf-Butoxyoxalyl-amino)-5-((1 , 1 -dioxo-1 -/-benzo[d]isothiazol-3- ylamino)-methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester (120 mg, 0.172 mmol) was dissolved in a mixture of ethanol (4 ml) and formic acid (0.5 ml). 10 % Pd- C (20 mg) was added and the reaction mixture stirred at ambient temperature for 4 days (after the second day, 150 mg of additional 10 % Pd-C was added). The reaction mixture was filtered through celite and the celite washed with dichloromethane. The organic fractions were combined and concentrated in vacuo. The resultant oil was subjected to preparative thin layer chromatography (dichloromethane/methanol (95:5)), which afforded 17 mg (17 %) of 2-(ferf-butoxyoxalyl-amino)-5-((1,1 -dioxo-1 H- benzo[d]isothiazol-3-ylamino)-methyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 7.91 (m, 1 H), 7.72 (m, 3H), 7.34 (bs, 1 H), 4.16-4.08 (m, 1 H), 4.07 (dd, 2H, J = 36.3 Hz and J = 8.7 Hz), 3.38-3.30 (m, 1 H), 3.22-3.06 (m, 2H), 2.51 (dd, 1 H, J = 16.8 Hz and J = 9.9 Hz), 1.61 (s, 18H). 2-(_erf-Butoxyoxalyl-amino)-5-((1 , 1 -dioxo-1 H-benzo[d]isothiazol-3- ylamino)-methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (15 mg, 0.026 mmol) was dissolved in a solution of 50 % trifluoroacetic acid/dichloromethane (3 ml). The reaction mixture was stirred at ambient temperature for 18 hours, concentrated in vacuo and re- evaporated from acetonitrile (2x). The residue was washed with dichloromethane and dried in vacuo to give 16 mg (90 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (CD 3 OD): δ 7.98 (d, 1 H, J = 7.2 Hz), 7.92 (d, 1 H, J = 6.6 Hz), 7.83 (m, 2H), 4.51-4.39 (m, 2H), 4.11-4.08 (m, 1 H), 3.97-3.91 (m, 2H), 3.53-3.47 (m, 1 H), 3.16-3.10 (m, 1 H). EXAMPLE 76 7-((1 , 1 -Dioxo-1 H-benzo[d1isothiazol-3-ylamino)methyl)-2-(oxalyl-amino)- 4,5,67-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid 3-Chloro-benzo[d]isothiazole-1 ,1 -dioxide (160 mg, 0.79 mmol) and diisopropylethylamine (150 μl, 0.86 mmol) were dissolved in dichloromethane (7 ml) at 0 °C. 2-Amino-7-aminomethyl-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (284 mg, 0.70 mmol) was added and the mixture was stirred for 15 minutes at 0 °C, diluted with dichloromethane (10 ml) and washed with water (20 ml) and brine (20 ml). The organic phase was dried (MgSO 4 ), filtered, and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using a gradient of hexanes/ethyl acetate (1:1) to pure ethyl acetate as eluent, which afforded 309 mg (77 %) of 2-amino- 7-((1 , 1 -dioxo-1 H-benzo[d]isothiazol-3-ylamino)methyl)-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an foam. 1 H-NMR (300 MHz, CDCI 3 ): δ 7.89 (d, 1 H, J = 8 Hz), 777-7.63 (m, 2H), 7.37 (d, 1 H, J = 7 Hz), 7.25 (d, 2H, J = 10 Hz), 6.82 (d, 2H, J = 8 Hz), 6.62 (bs, 1 H), 6.08 (s, 2H), 3.91 (m, 1 H), 3.71 (s, 3H), 3.49-2.65 (m, 8H), 1.59 (s, 9H). LC-MS (APCI + ) m/z: 569 [M+H] + , [M+Na] 591 ; R, = 2.85 min. 2-Amino-7-((1 , 1 -dioxo-1 /- -benzo[d]isothiazol-3-ylamino)methyl)-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (102 mg, 0.18 mmol) in dichloromethane (10 ml) was treated with imidazol-1-yl-oxo-acetic acid fetf-butyl ester (85 mg, 0.43 mmol). After stirring for 18 hours at room temperature, the reaction solution was concentrated to dryness in vacuo. The residue was purified by silica gel chromatography using a gradient of hexanes/ethyl acetate (1 :1) to pure ethyl acetate as gradient, which afforded 98 mg (78 %) of 2- (ferf-butoxyoxalyl-amino)-7-((1 , 1 -dioxo-1 /-/-benzo[d]isothiazol-3-ylamino)- methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (300 MHz, CDCI 3 ): δ 12.57 (s, 1 H), 789 (d, 1 H, J = 8 Hz), 7.77- 7.63 (m, 2H), 7.39 (d, 1 H, J = 7 Hz), 7.25 (d, 2H, J = 9 Hz), 6.84 (d, 2H, J = 9 Hz), 6.64 (bs, 1 H), 3.99-2.76 (m, 12H), 1.64 (s, 9H), 1.63 (s, 9H). 10 % Pd/C (100 mg) was added to a mixture of 2-(fetf-butoxyoxalyl- amino)-7-((1 , 1 -dioxo-1 H-benzo[d]isothiazol-3-ylamino)-methyl)-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (98 mg, 0.14 mmol) in 10 % formic acid in methanol (10 ml). After stirring at room temperature for 48 hours, the catalyst was removed via filtration through celite and liberal washing with methanol. The volatiles were removed in vacuo and the residue purified by chromatotron (ethyl acetate/triethylamine, 99:1), which afforded 32 mg (40 %) of 2-(ferf-butoxyoxalyl-amino)-7-((1 , 1 -dioxo-1 H-benzo[d]isothiazol-3- ylamino)-methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (300 MHz, CDCI 3 ): δ 12.48 (s, 1H), 10.21-9.15 (m, 2H), 8.49-7.42 (m, 3H), 5.62-5.00 (bs, 1 H), 4.53-2.87 (m, 8H), 1.61 (s, 18H). HPLC (254.4 nm) R t = 3.67 minutes. 2-(fetf-Butoxyoxalyl-amino)-7-((1 , 1 -dioxo-1 H-benzo[d]isothiazol-3- ylamino)-methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (32 mg) was dissolved in a mixture of 30 % trifluoroacetic acid in dichloromethane (4 ml). The solution was left open to the atmosphere without stirring. After 24 hours the precipitate was filtered off and washed with diethyl ether, affording 29 mg (90 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (300 MHz, DMSO-d 6 ): δ 12.36 (s, 1 H), 9.92 (bs, 1 H), 9.73 (bs, 1 H), 9.38 (bs, 1 H), 8.20 (m, 1 H), 8.05 (m, 1 H), 7.89 (m, 2H), 4.95 (s, 1 H), 4.12-3.00 (m partially obscured by water, 8H). LC-MS (APCI + ) m/z: 466 [M+H] + ; R t = 0.66 min. EXAMPLE 77 5-(7-Methoxy-1-oxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thieno[2,3-clpyridine-3-carboxylic acid 2-Methoxy-6-methylbenzoic acid ethyl ester (500 mg, 2.67 mmol), N- bromosuccinimide (483.8 mg, 2.72 mmol) and 2,2'-azobis(2-methyl- propionitrile) (30.2 mg, 0.123 mmol) in carbon tetrachloride (10 ml) were heated to reflux. After 18 hours, the reaction mixture was evaporated to dryness in vacuo. The residue was dissolved in dichloromethane (100 ml) and washed with water (2 x 50 ml). The organic layer was dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue (702 mg) was purified by column chromatography using a mixture of hexanes/dichloromethane (1 :1) as eluent, which afforded 573 mg (85 %) of 6-bromomethyl-2-methoxy-benzoic acid ethyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.37 (t, 1 H, J = 8.4 Hz), 7.01 (d, 1 H, J = 8.1 Hz), 6.90 (d, 1 H, J = 8.4 Hz), 4.54 (s, 2H), 4.45 (q, 2H, J = 7.2 Hz), 3.82 (s, 3H), 1.42 (t, 3H, J = 9 Hz). 6-Bromomethyl-2-methoxy-benzoic acid ethyl ester (71.1 mg, 0.260 mmol) dissolved in acetonitrile (5 ml) and diisopropylethylamine (453 μl, 2.60 mmol) was stirred at room temperature. To this mixture 2-amino-5-amino- methyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (200 mg, 0.52 mmol) dissolved in acetonitrile (5 ml) was added syringe pump (0.2 ml/min.). Once addition was complete, the reaction mixture was allowed to stir for 2 hours. The reaction mixture was concentrated in vacuo. and the residue diluted with ethylacetate (50 ml). The organic layer was washed with saturated sodium bicarbonate (2 x 25 ml) and brine (2 x 25 ml). The organic layer was dried (MgSO ), filtered and concentrated in vacuo. The residue (308 mg) was subjected to column chromatography using a gradient of hexane/ethyl acetate (95:5) to (50:50) and then dichloromethane/ethyl acetate (95:5) as eluents, which afforded 106 mg (75 %) of 2-amino-6-(4-methoxy-benzyl)- 5-(7-methoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.48 (t, 1 H, J = 7.5 Hz), 7.12 (d, 2H, J = 8.4 Hz), 7.01 (d, 1 H, J = 7.5 Hz), 6.91 (d, 1 H, J = 8.4 Hz), 6.76 (d, 2H, J = 7.8 Hz), 5.95 (bs, 2H), 4.37 (s, 2H), 4.05 (m, 1 H), 3.97 (s, 3H), 3.88-378 (m, 2H), 3.81 (s, 3H), 371-3.39 (m, 4H), 2.90 (dd, 1 H, J = 18 Hz and J = 5.4 Hz), 2.62 (dd, 1 H, J = 18 Hz and J = 5.4 Hz), 1.53 (s, 9H). To a solution of 2-amino-6-(4-methoxy-benzyl)-5-(7-methoxy-1-oxo-1,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (105 mg, 0.192 mmol) in tetrahydrofuran (3 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (0.534 ml, 0.534 mmol, 1 M in tetrahydrofuran). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture concentrated vacuo and the residue subjected to flash chromtography using a mixture of ethyl acetate/dichloromethane (10:90) as eluent, which afforded 85 mg (66 %) of 2-(ferf-butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-(7-methoxy- 1-oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester. 1 H-NMR (CDCI 3 ): δ 7.47 (t, 1 H, J = 5.7 Hz), 7.10 (d, 2H, J = 6 Hz), 6.99 (d, 1 H, J = 57 Hz), 6.90 (d, 1 H, J = 6.3 Hz), 6.76 (d, 2H, J = 6.3 Hz), 4.37 (q, 2H, J = 11.4 Hz), 3.99-3.92 (m, 1 H), 3.97 (s, 3H), 379-376 (m, 2H), 3.77 (s, 3H), 3.66 (d, 1 H, J = 12.6 Hz), 3.58-3.50 (m, 3H), 2.95 (dd, 1 H, J = 13.5 Hz and J = 3.6 Hz), 2.70 (dd, 1 H, J = 13.5 Hz and J = 3.6 Hz), 1.61 (d, 9H), 1.57 (s, 9H). 2-(ferf-Butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-(7-methoxy-1-oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester (66 mg, 0.12 mmol) was dissolved in ethanol (2 ml) and formic acid (0.3 ml). 10 % Pd-C (15 mg) was added and the reaction mixture stirred at room temperature for 3 days. TLC (hexane/ethyl acetate (1/1)) indicated reaction complete. The reaction mixture was filtered through celite and the celite washed with dichloromethane. The organic fractions were combined and subjected to preparative thin layer chromatography (hexane/ethyl acetate (1/1) to yield 14.7 mg (22 %) of 2-(ferf-butoxyoxalyl-amino)-5-(7-methoxy-1 -oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.48 (t, 1H, J = 7.5 Hz), 7.01 (d, 1 H, J = 7.2 Hz), 6.90 (d, 1 H, J = 8.4 Hz), 5.50 (d, 2H, J = 6.6 Hz), 4.04-3.90 (m, 1 H), 3.97 (s, 3H), 3.24 (m, 1 H), 3.01-2.95 (m, 1 H), 2.57-2.43 (m, 2H), 1.62 (s, 9H), 1.57 (s, 9H). 2-(fetf-Butoxyoxalyl-amino)-5-(7-methoxy-1-oxo-1 ,3-dihydro-isoindol-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert- butyl ester (14.7 mg, 0.026 mmol) was dissolved in a solution of 50% trifluoroacetic acid/dichloromethane (2 ml). The reaction mixture was stirred at ambient temperature for 18 hours, concentrated in vacuo and re- evaporated from acetonitrile (2x). The resulting precipitate was washed with dichloromethane and dried in vacuo to give 13 mg (89 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (CD 3 OD): δ 7.56 (t, 1 H, J = 8.1 Hz), 7.13 (d, 1 H, J = 7.2 Hz), 7.01 (d, 1 H, J = 8.1 Hz), 4.87-4.44 (m, 4H), 4.15 (m, 1H), 3.90 (s, 3H), 3.88- 379 (m, 1 H), 3.43 (m, 1 H), 2.98 (m, 2H); LC-MS: R t = 0.71 , m/z: 446 [M+H] + . EXAMPLE 78 5-(7-Hydroxy-1 -oxo-1 , 3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thienof2,3-clpyridine-3-carboxylic acid To a solution of 2-hydroxy-6-methyl-benzoic acid ethyl ester (5.00 g, 27.8 mmol) and t-butyl-di-methylsilyl chloride (6.27 g, 41.6 mmol) in dichloromethane (100 ml) was added diisopropyl ethylamine. The solution was stirred at 50 °C for 24 hours, washed with water, brine, dried (MgSO ), filtered and the solvent evaporated in vacuo, which afforded 7.6 g (93 %) of 2-(ferf-butyl-dimethyl-silanyloxy)-6-methyl-benzoic acid ethyl ester as an oil. 1 H-NMR (CDCIg): δ 7.13 (t, 1 H, J = 7.5 Hz), 678 (d, 1 H, J = 7.5 Hz), 6.67 (d, 1H, J = 7.5 Hz), 4.35 (q, 2H, J = 7.2 Hz), 2.29 (s, 3H), 1.38 (t, 3H, J = 7.2 Hz), 0.97 (s, 9H), 0.23 (s, 6H). 2-(ferf-Butyl-dimethyl-silanyloxy)-6-methyl-benzoic acid ethyl ester (7.6 g, 25.8 mmol), N-bromosuccinimide (4.82 g, 27.1 mmol) and azobis(cyclohexanecarbonitrile) (0.32 g, 1.3 mmol) were dissolved in tetrachlormethane (130 ml). The solution was stirred at room temperature for 60 hours. The solvent was evaporated in vacuo and the residue was chromatographed on silica gel column using a gradient of 1-2% ethyl acetate/hexane as eluent, which afforded 8.0 g (83 %) of 6-bromomethyl- 2-(ferf-butyl-dimethyl-silanyloxy)-benzoic acid ethyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.21 (t, 1 H, J = 8.4 Hz), 7.00 (d, 1 H, J = 8.4 Hz), 6.81 (d, 1 H, J = 8.4 Hz), 4.51 (s, 2H), 4.40 (q, 2H, J = 7.2 Hz), 1.42 (t, 3H, J = 7.2 Hz), 0.98 (s, 9H), 0.23 (s, 6H). To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (3.00 g, 7.45 mmol) and diisopropyl ethylamine (1.93 ml, 11.2 mmol) in acetonitrile at room temperature was added a solution of 6-bromomethyl-2-(ferf-butyl- dimethyl-silanyloxy)-benzoic acid ethyl ester (2.78 g, 7.45 mmol) in acetonitril over 48 hours. The solution was stirred for 12 hours after the addition was complete. The volatiles were evaporated in vacuo and the residue was taken into ethyl acetate (50 ml) and washed with water, 1 N hydrochloric acid, brine, dried (MgSO 4 ), filtered and the solvent evaporated vacuo. The residue was chromatographed on silica gel column eluted with a mixture of 20 % ethyl acetate/Hexane, which afforded 3.2 g (66 %) of 2-amino-5-(7-(ferf-butyl-dimethyl-silanyloxy)-1- oxo-1 , 3-dihydro-isoindol-2-ylmethyl]-6-(4-methoxy-benzyl)-4,5, 6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.36 (t, 1 H, J = 8.0 Hz), 7.11 (d, 2H, J = 8.8 Hz), 6.99 (d, 1 H, J = 8.0 Hz), 6.82 (d, 1 H, J = 8.0 Hz), 6.76 (d, 2H, J = 8.8 Hz), 5.94 (s, 2H), 4.48 (d, 1 H, J = 16.8 Hz), 4.33 (d, 1 H, J = 16.8 Hz), 3.90-3.45 (m, 7H), 3.78 (s, 3H), 2.95 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 2.72 (dd, 1 H, J = 17 Hz and J = 5.6 Hz), 1.52 (s, 9H), 1.05 (s, 9H), 0.26 (s, 6H). To a stirred solution of 2-amino-5-(7-(fetf-butyl-dimethyl-silanyloxy)-1-oxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (2.37 g, 3.64 mmol) in tetrahydrofuran (50 ml) was added imidazol-1-yl-oxo-acetic acid tert- butyl ester (2.14 mg, 10.9 mmol) in tetrahydrofuran (10 ml). The mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo. The residue was taken into ethyl acetate (100 ml). The solution was washed with 0.5 N hydrochloric acid solution (2 x 20 ml), saturated sodium bicarbonate (2 x 20 ml) and brine (20 ml), dried (MgSO 4 ), filtered and the solvent removed in vacuo. The residue was chromatographed using a gradient of 10-20 % ethyl acetate/Hexane as eluent, which afforded 2.40 g (92 %) of 2-(fetf-butoxyoxalyl-amino)-5-(7-(fetf-butyl- dimethyl-silanyloxy)-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 12.59 (s, 1 H), 7.37 (t, 1 H, J = 8.0 Hz), 7.10 (d, 2H, J = 8.8 Hz), 7.00 (d, 1 H, J = 8.0 Hz), 6.83 (d, 1 H, J = 8.0 Hz), 6.77 (d, 2H, J = 8.8 Hz), 4.50 (d, 1 H, J = 16.8 Hz), 4.34 (d, 1 H, J = 16.8 Hz), 3.90-3.45 (m, 7H), 3.77 (s, 3H), 2.95 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 2.72 (dd, 1 H, J = 18 and J = 5.6 Hz), 1.61 (s, 9H), 1.58 (s, 9H), 1.06 (s, 9H), 0.26 (s, 6H). To a solution of 2-(ferf-butoxyoxalyl-amino)-5-(7-(ferf-butyl-dimethyl- silanyloxy)-1 -oxo-1, 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (2.40 g, 3.34 mmol) in 10 % formic acid/methanol (50 ml) at room temperature under nitrogen was added 10 % Pd/C (1.2 g). The mixture was stirred for 48 hours. The Pd/C was filtered off and the filtrate was evaporated in vacuo. The residue was dissolved in dichloromethane (10 ml). The resulting solution was poured into hexane. The precipitate was filtered off and dried vacuo affording 1.3 g (61 %) of 2-(tert- butoxyoxalyl-amino)-5-(7-(fetf-butyl-dimethyl-silanyloxy)-1 -oxo-1 , 3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester. 1 H-NMR (CDCI 3 ): δ 12.45 (s, 1 H), 8.05 (s, 1 H), 7.39 (t, 1 H, J = 8.0 Hz), 7.00 (d, 1H, J = 8.0 Hz), 6.83 (d, 1H, J = 8.0 Hz), 4.50 (d, 1H, J = 16.8 Hz), 4.45 (q, 2H, J = 17 Hz), 4.05 (q, 2H, J = 17 Hz), 3.82 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 3.72 (dd, 1H, J = 17 Hz and J = 5.6 Hz), 3.40 (s, 1H), 3.08 (d, 1H, J = 17 Hz), 2.61 (dd, 1H, J = 18 Hz and J = 7.2 Hz), 1.61 (s, 9H), 1.54 (s, 9H), 1.05 (s, 9H), 0.26 (s, 6H). To a solution of trifluoroacetic acid (33.3 ml) and H 2 O (2.7 ml) was added 2-(fetf-butoxyoxalyl-amino)-5-(7-(fetf-butyl-dimethyl-silanyloxy)-1-oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester (0.70 g, 1.04 mmol). The solution was stirred at room temperature for 40 hours. The solvent was poured into ethyl ether (400 ml). The precipitate was filtered off and dried in vacuo, which afforded 450 mg (80 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (DMSO-d 6 ): δ 12.30 (s, 1 H), 9.71 (s, 1 H), 9.20 (s, 2H), 7.39 (t, 1 H, J = 8.0 Hz), 6.99 (d, 1 H, J = 8.0 Hz), 6.82 (d, 1 H, J = 8.0 Hz), 4.52 (d, 1 H, J = 16.8 Hz), 4.36 (d, 2H, J = 17 Hz), 4.22 (d, 2H, J = 17 Hz), 4.00 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 3.86 (s, 1 H), 3.62 (d, 1 H, J = 17 Hz), 2.81 (dd, 1 H, J = 18 Hz and J = 7.2 Hz); LC-MS: R t = 1.20 min; m/z = 432 [M+H] + EXAMPLE 79 5-(7-Benzyloxy-1 -oxo-1 , 3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5, 67-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid To a solution of 2-(fetf-butoxyoxalyl-amino)-5-(7-(ferf-butyl-dimethyl- silanyloxy)-1-oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (2.40 g, 3.34 mmol) in 10 % formic acid/methanol (50 ml) at room temperature under nitrogen was added 10 % Pd/C (1.2 g). The mixture was stirred for 48 hours. The Pd/C was filtered off and the filtrate was evaporated in vacuo. The residue was dissolved in dichloromethane (10 ml) and the resulting solution was poured into hexane. The precipitate was filtered off (1.3 g) and the filtrate was evaporated in vacuo. The residual foam (1.1 g) was taken into dichloromethane (50 ml) and treated with di- ferf-butyl-dicarbonate (1.1 g, 5.0 mmol) and saturated sodium bicarbonate (20 ml). The mixture was stirred for 2 hours and the organic layer was separated and dried (MgSO 4 ). The solvent was evaporated in vacuo and the residue was chromatographed using a gradient of 10-30% ethyl acetate/Hexane as eluent, which afforded 175 mg of 2-(ferf-butoxyoxalyl- amino)-5-(7-hydroxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,7-dihydro- 5H-thieno[2,3-c]pyridine-3,6-carboxylic acid di-fetf-butyl ester. 1 H-NMR (CDCI 3 ): δ 12.55 (s, 1 H), 8.53 (s, 1 H), 7.37 (t, 1 H, J = 7.6 Hz), 6.92 (d, 1 H, J = 7.6 Hz), 6.83 (d, 1 H, J = 7.6 Hz), 4.95 (s, 1 H), 4.84 (d, 1 H, J = 16.4 Hz), 4.72 (d, 1 H, J = 16.0 Hz), 4.56 (d, 1 H, J = 16.0 Hz), 4.28 (d, 1 H, J = 17.6 Hz), 4.13 (m, 1 H), 3.68 (s, 0.5H), 3.42 (s, 0.5H), 3.16-2.94 (m, 2H), 1.62 (s, 9H), 1.61 (s, 9H), 1.26 (s, 9H). To a solution of 2-(fetf-butoxyoxalyl-amino)-5-(7-hydroxy-1-oxo-1 ,3- dihydro-isoindol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6- carboxylic acid di-fetf-butyl ester (16 mg, 0.025 mmol) in N,N- dimethylformamide (0.5 ml) under nitrogen was added sodium hydride (1.0 mg, 0.026 mmol) at room temperature. The solution was stirred for 2 hours and followed by addition of benzyl bromide (5.9 ml, 0.050 mmol). The solution was stirred for 16 hours, diluted with ethyl acetate (20 ml) and washed with 0.5 N hydrochloric acid solution (2 x 10 ml), saturated sodium bicarbonate (2 x 10 ml), brine (10 ml), dried (MgSO 4 ), and filtered. The solvent was removed in vacuo. The residue was chromatographed using a gradient of 10-20 % ethyl acetate/Hexane as eluent, which afforded 14 mg (76 %) of 5-(7-benzyloxy-1 -oxo-1 , 3-dihydro-isoindol-2- ylmethyl)-2-(ferf-butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyridine- 3,6-carboxylic acid di-fetf-butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 12.49 (s, 1 H), 7.48 (d, 2H, J = 7.2 Hz), 7.35 (m, 3H), 7.28 (d, 1 H, J = 7.2 Hz), 6.97 (d, 1H, J = 7.6 Hz), 6.80 (d, 1 H, J = 7.6 Hz), 5.32 (s, 2H), 4.97 (m, 2H), 4.82-4.62 (m, 2H), 4.45-4.15 (m, 2H), 3.68 (s, 0.5H), 3.48 (s, 0.5H), 3.16-2.94 (m, 2H), 1.62 (s, 9H), 1.60 (s, 9H), 1.26 (s, 9H). To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (2.7 ml) was added 5-(7-benzyloxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(ferf- butoxyoxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-carboxylic acid di-fetf-butyl ester (14 mg, 0.019 mmol). The solution was stirred at room temperature for 40 hours. The reaction mixture was poured into ethyl ether (20 ml). The precipitate was filtered off and dried in vacuo affording 8.0 mg (68 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de): δ 12.25 (s, 1H), 9.28 (s, 1H), 9.02 (s, 1 H), 7.53 (m, 3H), 7.39 (t, 2H, J = 7.6 Hz), 7.13 (d, 1 H, J = 7.6 Hz), 7.11 (d, 1H, J = 8.4 Hz), 5.27 (m, 2H), 4.54 (d, 1H, J = 17.2 Hz), 4.38 (d, 2H, J = 17.6 Hz), 4.22 (m, 2H), 4.00 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 3.86 (s, 1 H), 3.64 (d, 1H, J = 17.2 Hz), 2.81 (dd, 1H, J = 18 Hz and J = 7.2 Hz); LC-MS: R t = 2.96 min; m/z: 522 [M+H] + EXAMPLE 80 5-(7-Hydroxy-1 -oxo-1.3-dihvdro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 2-(oxalyl-amino)-4,5,67-tetrahvdro-thieno[2,3-clpyridine-3-carboxylic acid To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (0.5 ml) was added 2-(fetf-butoxyoxalyl-amino)-5-(7-(ferf-butyl-dimethyl-silanyloxy)- 1-OXO-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (11 mg, 0.014 mmol). The solution was stirred at room temperature for 16 hours. The reaction mixture was poured into ethyl ether (20 ml). The precipitate was filtered off and dried in vacuo, which afforded 7.0 mg (79 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de): δ 12.39 (s, 1H), 9.95 (s, 1 H), 975 (s, 2H), 7.42 (t, 1 H, J = 8.0 Hz), 7.30 (s, 2H), 7.02 (d, 1 H, J = 7.2 Hz), 6.96 (s, 2H), 6.85 (d, 1 H, J = 7.2 Hz), 4.95-3.65 (m, 11 H), 3.76 (s, 3H). LC-MS: R, = 1.93 min, m/z: 553 [M+H] + EXAMPLE 81 5-(1 ,3-Dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5 1 6,7-tetrahvdro-thieno[2,3-clpyridine-3-carboxylic acid To a stirred solution of 2-amino-5-(1 ,3-dioxo-1,3-dihydro-isoindol-2- ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (15 mg, 0.028 mmol) in tetrahydrofuran (1.0 ml) was added imidazol-1-yl-oxo-acetic acid ferf-butyl ester (27 mg, 0.11 mmol) in tetrahydrofuran (1.0 ml). The mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo. The residue was taken into ethyl acetate (20 ml). The solution was washed with 0.5 N hydrochloric acid solution (2 x 10 ml), saturated sodium bicarbonate (2 x 10 ml) and brine (10 ml), dried (MgSO ) and filtered. The solvent was removed vacuo. The residue was chromatographed using a gradient of 10-25 % ethyl acetate/hexane as eluent, which afforded 17 mg (93 %) of 2-(ferf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6- (4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (CDCI3): δ 12.54 (s, 1 H), 7.86 (m, 2H), 7.40 (m, 2H), 7.08 (d, 2H, J = 8.4 Hz), 6.72 (d, 2H, J = 8.4 Hz), 4.08 (dd, 1 H, J = 13.6 Hz and J = 8.8 Hz), 3.94 (d, 1 H, J = 16.8 Hz), 3.82 (d, 1 H, J = 12.8 Hz), 3.78 (s, 3H), 3.92 (s, 3H), 370-3.56 (m, 3H), 3.53 (d, 1 H, J = 12.8), 2.93 (dd, 1 H, J = 16.8 Hz and J = 4.8 Hz), 2.75 (dd, 1 H, J = 18.0 Hz and J = 5.6 Hz), 1.61 (s, 9H), 1.58 (s, 9H). To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (0.5 ml) was added 2-(fetf-butoxyoxalyl-amino)-5-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (15 mg, 0.023 mmol). The solution was stirred at room temperature for 40 hours. The reaction mixture was poured into ethyl ether (20 ml). The precipitate was filtered off and dried in vacuo, which afforded 13 mg (87 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de): δ 12.38 (s, 1 H), 7.89 (d, 4H, J = 11.2 Hz), 7.18 (s, 2H), 6.85 (s, 2H), 4.20-3.60 (m, 9H), 371 (s, 3H); LC-MS: R, = 2.05 min, m/z: 550 [M+H] + EXAMPLE 82 7-(7-Hydroxy-1 -oxo-1 , 3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5.6,7-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid To a solution of 2-amino-7-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (80 mg, 0.20 mmol) and diisopropyl ethylamine (35 μl, 0.40 mmol) in acetonitrile (10 ml) at room temperature was added a solution of 6-bromomethyl-2- (ferf-butyl-dimethyl-silanyloxy)-benzoic acid ethyl ester (69 mg, 0.20 mmol). The solution was stirred for 12 hours at room temperature and the solvent was evaporated vacuo. The residue was dissolved in ethyl acetate (50 ml) and washed with water, 1 N hydrochloric acid, brine, dried (MgSO ), filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel column eluted with 20 % ethyl acetate/hexane to yield 42 mg (33 %) of 2-amino-7-(7-(fetf-butyl-dimethyl- silanyloxy)-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 7.64 (d, 1 H, J = 8.8 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.10- 6.80 (m, 5H), 6.09 (s, 2H), 5.0-4.2 (m, 4H), 3.80 (s, 3H), 3.66-2.92 (m, 3H), 1.55 (s, 9H), 1.04 (s, 9H), 0.22 (s, 6H). To a stirred solution of 2-amino-7-(7-(ferf-butyl-dimethyl-silanyloxy)-1-oxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (40 mg, 0.060 mmol) in tetrahydrofuran (1 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (59 mg, 0.30 mmol) in tetrahydrofuran (1 ml). The mixture was stirred at room temperature for 24 hours. The solvent was removed i vacuo. The residue was dissolved in ethyl acetate (20 ml) and the solution was washed with 0.5 N hydrochloric acid (2 x 20 ml), saturated sodium bicarbonate (2 x 20 ml), brine (20 ml), dried (MgSO ) and filtered. The solvent was removed in vacuo and the residue was chromatographed using a gradient of 10-20 % ethyl acetate/Hexane as eluent, which afforded 40 mg (83 %) of 2-(fetf-butoxyoxalyl-amino)-7-(7-(fetf-butyl- dimethyl-silanyloxy)-1-oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 12.52 (s, 1H), 7.37 (t, 1 H, J = 8.0 Hz), 6.97 (d, 2H, J = 8.4 Hz), 6.94 (d, 1 H, J = 8.0 Hz), 6.83 (d, 1 H, J = 8.0 Hz), 6.54 (d, 1 H, J = 8.4 Hz), 4.26 (d, 1H, J = 16.8 Hz), 3.93-3.84 (m, 2H), 3.77 (d, 1H, J = 16.8 Hz), 3.69 (s, 3H), 3.66-3.48 (m, 3H), 3.42-3.32 (m, 1 H), 2.95 (dd, 1 H, J = 14.4 Hz and J = 4.8 Hz), 2.92-2.82 (m, 1 H), 2.73 (dd, 1 H, J = 14.4 Hz and J = 4.8 Hz), 1.60 (s, 9H), 1.59 (s, 9H), 1.02 (s, 9H), 0.22 (d, 6H, J = 1.6 Hz). To a solution of 2-(fetf-butoxyoxalyl-amino)-7-(7-(ferf-butyl-dimethyl- silanyloxy)-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (4.0 mg, 5.1 μmol) in 10 % formic acid/methanol (1 ml) at room temperature under nitrogen was added 10 % Pd/C (4 mg). The mixture was stirred for 1 hour. The Pd/C was filtered off and the filtrate was evaporated in vacuo to afford 2.8 mg (82 %) of 2-(ferf-butoxyoxalyl- amino)-7-(7-(fetf-butyl-dimethyl-silanyloxy)-1 -oxo-1 , 3-dihydro-isoindol-2- ylmethyl)-5H-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf- butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 12.45 (s, 1 H), 8.05 (s, 1 H), 7.39 (t, 1 H, J = 8.0 Hz), 6.99 (d, 1 H, J = 8.0 Hz), 6.79 (d, 1 H, J = 8.0 Hz), 4.50 (d, 1 H, J = 17.2 Hz), 4.45 (d, 1 H, J = 17.2 Hz), 4.24 (d, 1 H, 8.4 Hz), 4.03 (dd, 1 H, J = 16.0 Hz and J = 7.2 Hz), 378-3.68 (m, 2H), 3.38-3.28 (m, 1 H), 3.21 (d, 1 H, J = 18.8 Hz), 3.08-2.98 (m, 1 H), 1.57 (s, 9H), 1.56 (s, 9H), 0.98 (s, 9H), 0.15 (d, 6H, J = 1 Hz). To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (0.5 ml) was added 2-(ferf-butoxyoxalyl-amino)-7-(7-(ferf-butyl-dimethyl-silanyloxy)- 1-OXO-1 ,3-dihydro-isoindol-2-ylmethyl)-5H-4,5,6,7-tetrahydro-thieno[2, 3- c]pyridine-3-carboxylic acid ferf-butyl ester (2.8 mg, 0.0042 mmol). The solution was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was washed with dichloromethane affording 1.8 mg (79 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de): δ 12.30 (s, 1 H), 9.76 (s, 1H), 9.40 (s, 1 H), 8.95 (s, 1 H), 7.40 (t, 1 H, J = 7.6 Hz), 7.00 (d, 1 H, J = 7.6 Hz), 6.83 (d, 1 H, J = 7.6 Hz), 4.92 (s, 1 H), 4.54 (d, 1 H, J = 18.4 Hz), 4.40 (d, 2H, J = 18.4 Hz), 4.08-4.00 (m, 1H), 3.91 (d, 1 H, J = 15.2 Hz), 3.60 (s, 2H), 3.06 (s, 2H); LC-MS: R t : 1.41 min, m/z: 432 [M+H] + EXAMPLE 83 7-(7-Hydroxy-1 -oxo-1 , 3-dihvdro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)- 2-(oxalyl-amino)-4,5.67-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (0.5 ml) was added 2-(fetf-butoxyoxalyl-amino)-7-(7-(fetf-butyl-dimethyl-silanyloxy)- 1-0X0-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (10 mg, 0.013 mmol). The solution was stirred at room temperature for 16 hours. The solvent was removed vacuo and the residue was washed with dichloromethane, which afforded 6.8 mg (92 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de): δ 12.35 (s, 1 H), 9.90 (s, 1 H), 9.70 (s, 2H), 7.41 (t, 1 H, J = 8.0 Hz), 7.28 (s, 2H), 7.04 (d, 1 H, J = 7.2 Hz), 6.92 (s, 2H), 6.83 (d, 1 H, J = 7.2 Hz), 4.90-3.60 (m, 11 H), 3.80 (s, 3H). LC-MS: R t = 1.92 min, m/z: 552 [M+H] + 7-(1 ,3-Dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4.5,67-tetrahvdro-thienor2,3-clpyridine-3-carboxylic acid To a stirred solution of 2-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (10 mg, 0.019 mmol) in tetrahydrofuran (1.0 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (18 mg, 0.092 mmol) in tetrahydrofuran (1.0 ml). The mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate (20 ml) and washed with 0.5 N hydrochloric acid solution (2 x 10 ml), saturated sodium bicarbonate (2 x 10 ml), brine (10 ml), dried (MgSO 4 ), and filtered. The solvent was removed in vacuo and the residue was chromatographed using a gradient of 10-25 % ethyl acetate/hexane as eluent, which afforded 11 mg (89 %) of 2-(ferf- butoxyoxalyl-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 12.54 (s, 1 H), 7.76 (m, 4H), 6.82 (d, 2H, J = 1 1.6 Hz), 6.33 (d, 2H, J = 11.6 Hz), 4.02 (d, 1 H, J = 14.4 Hz), 3.98 (d, 1 H, J = 14.4 Hz), 3.62 (s, 3H), 3.62-3.54 (m, 2H), 3.48-3.34 (m, 2H), 3.02-270 (m, 3H), 1.60 (s, 9H), 1.59 (s, 9H). To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (0.5 ml) was added 2-(ferf-butoxyoxalyl-amino-7-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2- ylmethyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester (10 mg, 0.015 mmol). The solution was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was washed with dichloromethane, which afforded 6.8 mg (80 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (DMSO-d 6 ): δ 12.38 (s, 1 H), 7.86 (m, 4H), 6.82 (s, 2H), 6.30 (s, 2H), 4.00-2.86 (m, 9H), 3.58 (s, 3H); LC-MS: R t = 2.02 min; m/z: 550 [M+H] + EXAMPLE 85 7-(((5-Benzyloxy-1H-indole-2-carbonyl)amino)methyl)-6-(4-methoxy- benzyl)-2-(oxalyl-amino)-4,5,67-tetrahydro-thienof2,3-clpyridine-3- carboxylic acid 2-Amino-7-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (0.50 g; 1.2 mmol) was dissolved in Λ/,Λ/-dimethylformamide (20 ml). 1-Hydroxy-7- azabenzotriazole (0.19 g; 1.3 mmol) and Λ/-(3-dimethylaminopropyl)-/V - ethylcarbodiimide hydrochloride (0.26 g; 1.3 mmol) and diisopropylethylamine (0.23 ml; 1.3 mmol) were added and the mixture was stirred for 15 min. 5-Benzyloxyindole (0.36 g; 1.3 mmol) was dissolved in N,N- dimethylformamide (20 ml) and added. Diisopropylethylamine (0.23 ml; 1.3 mmol) was added and the mixture was stirred overnight. The solvent was removed vacuo, the residue dissolved in dichloromethane (30 ml) and the organic phase washed with an aqueous solution of sodium hydrogencarbonate (15 ml). The organic phase was dried (MgSO ), filtered and the solvent removed vacuo. The residue was chromatographed on silica using ethyl acetate/heptane (1:1) as eluent affording 569 mg of 2-amino-7-(((5-benzyloxy-1H-indole-2- carbonyl)amino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. The titie compound was prepared in a similar way as described in Example 48 using the last two steps. MS: m/z: 669.4 [M+H] + Calculated for C 35 H 32 N 4 O 8 S, 2/3xC 2 HF 3 O 2 , 4/3xH 2 O ; C, 56.77%; H, 4.63%; N, 7.29%. Found: C, 56.43%; H, 4.57%; N, 7.13%. 7-(((6-Bromo-2-p-tolyl-quinoline-4-carbonyl)amino)methyl)-6-(4-methoxy- benzyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acidThe titie compound was prepared in a similar way as in Example 84 using 6-bromo-2-p-tolyl-quinoline-4-carboxylic acid and 2- amino-7-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 745.2 [M+H] + Calculated for C 36 H 3 ιBrN 4 O 7 S, 2xC 2 HF 3 O 2 ; C, 49.44%; H, 3.42%; N, 577%. Found: C, 49.19%; H, 3.59%; N, 6.00%. EXAMPLE 87 6-(4-Methoxy-benzyl)-7-(((5-methyl-2-phenyl-2/-/-π .2.3ltriazole-4- carbonyl)amino)-methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- clpyridine-3-carboxylic acid The titie compound was prepared in a similar way as in Example 84 using 5-methyl-2-phenyl-2/-/-[1 ,2,3]triazole-4-carboxylic acid and 2-amino-7- aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester as the starting material. LC-MS: m/z: 605.2 [M+H] + Calculated for C29H 28 N 6 O 7 S, 1.3xC 2 HF 3 O 2 , 17xH 2 O; C, 48.14%; H, 3.94%; N, 10.94%. Found: C, 48.35%; H, 4.19%; N, 10.68%. EXAMPLE 88 7-(((1H-lndole-3-carbonyl)amino)methyl)-6-(4-methoxy-benzyl)-2-(oxalyl- amino)-4,5,67-tetrahvdro-thienof2,3-c1pyridine-3-carboxylic acid The title compound was prepared in a similar way as in Example 84 using 3-indole-carboxylic acid and 2-amino-7-aminomethyl-6-(4-methoxy- benzyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 563.2 [M+H] + Calculated for C 28 H 26 N 4 O 7 S, 5/3xC 2 HF 3 O 2 ; C, 49.63%; H, 3.82%; N, 7.35%. Found: C, 50.00%; H, 3.71%; N, 7.44%. EXAMPLE 89 7-((4-Ethoxy-2-hvdroxy-benzoylamino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6.7-tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid The titie compound was prepared in a similar way as in Example 84 using 4-ethoxy-2-hydroxy-benzoic acid and 2-amino-7-aminomethyl-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 584 [M+H] + HPLC: (B6): 23.8 min. EXAMPLE 90 7-((4-Benzoylamino-benzoylamino)methyl)-6-(4-methoxy-benzyl)-2-(oxalyl- amino)-4,5,67-tetrahvdro-thieno.2,3-c1pyridine-3-carboxylic acid The title compound was prepared in a similar way as in Example 84 using 4-benzoylaminobenzoic acid and 2-amino-7-aminomethyl-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 643.1 [M+H] + Calculated for C 33 H 3 oN 4 O 8 S, 3xC 2 HF 3 O 2 ; C, 47.57%; H, 3.38%; N, 5.69%. Found: C, 47.34%; H, 3.55%; N, 5.62%. EXAMPLE 91 7-(((Biphenyl-4-carbonyl)amino)methyl)-6-(4-methoxy-benzyl)-2-(oxalyl- amino)-4,5,67-tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid The title compound was prepared in a similar way as in Example 84 using 4-phenylbenzoic acid and 2-amino-7-aminomethyl-6-(4-methoxy-benzyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as the starting material. LC-MS: m/z: 599.0 [M+H] + Calculated for C 32 H 29 N 3 O 7 S, 2xC 2 HF 3 O 2 , 1xH 2 O ; C, 51.13%; H, 3.93%; N, 4.97%. Found: C, 52.02%; H, 4.02%; N, 5.16%. EXAMPLE 92 7-(((1H-lndole-2-carbonyl)amino)methyl)-6-,4-methoxy-benzyl)-2-(oxalyl- amino)-4,5,67-tetrahvdro-thienor2,3-c1pyridine-3-carboxylic acid The title compound was prepared in a similar way as in Example 84 using indole-2-carboxylic acid and 2-amino-7-aminomethyl-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 563.2 [M+H] + HPLC (B6) R t = 23.07 min. EXAMPLE 93 7-((3-Biphenyl-4-yl-acryloylamino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c)pyridine-3-carboxylic acid The titie compound was prepared in a similar way as in Example 84 using 3-biphenyl-4-yl-acrylic acid and 2-amino-7-aminomethyl-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 626.2 [M+H] + HPLC (B6) R t = 28.74 min. Calculated for C 34 H 3 ιN 3 O 7 S, 2xC 2 HF 3 O 2 ; C, 53.46%; H, 3.90%; N, 4.92%. Found: C, 53.89%; H, 4.23%; N, 5.08%. EXAMPLE 94 6-(4-Methoxy-benzyl)-7-(((5-methoxy-1/-/-indole-2-carbonyl)amino)- methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahvdro-thienof2,3-c1pyridine-3- carboxylic acid The titie compound was prepared in a similar way as in Example 84 using 5-methoxyindole-2-carboxylic acid and 2-amino-7-aminomethyl-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 593.2 [M+H] + HPLC (B6) R, = 21.81 min. EXAMPLE 95 7-((4-Benzyl-benzoylamino)methyl)-6-(4-methoxy-benzyl)-2-(oxalyl- amino)-4,5,6,7-tetrahvdro-thieno[2,3-cipyridine-3-carboxylic acid The titie compound was prepared in a similar way as in Example 84 using 4-benzylbenzoic acid and 2-amino-7-aminomethyl-6-(4-methoxy-benzyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 614.2 [M+H] + HPLC (B6) R t = 27.23 min. Calculated for C 33 H 31 N 3 θ 7 S, 1.5xC 2 HF 3 O 2 , 1xH 2 O; C, 53.87%; H, 4.33%; N, 5.23%. Found: C, 53.92%; H, 4.24%; N, 5.18%. EXAMPLE 95 6-(4-Methoxy-benzyl)-7-(((naphthalene-1-carbonyl)amino)methyl)-2- (oxalyl-amino)-4,5,6,7-tetrahvdro-thienor2,3-clpyridine-3-carboxylic acid The title compound was prepared in a similar way as in Example 84 using 1-napthylcarboxylic acid and 2-amino-7-aminomethyl-6-(4-methoxy- benzyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as the starting material. LC-MS: m/z: 574.0 [M+H] + HPLC (B6) R, = 22.51 min. Calculated for C 3 oH 27 N 3 O 7 S, 2xC 2 HF 3 O 2 ; C, 50.94%; H, 3.65%; N, 5.24%. Found: C, 51.39%; H, 3.79%; N, 5.16%. EXAMPLE 96 6-(4-Methoxy-benzyl)-5-((2-naphthalen-2-yl-ethylamino)methyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid A solution of 2-naphthalen-2-yl-ethanol (1.02 g, 5.8 mmol), 2,2,6,6- tetramethyl-1-piperidinyloxy (TEMPO) (9 mg, 0.058 mmol) and sodium bromide (0.65 g, 6.4 mmol) in a mixture of toluene (18 mL), ethyl acetate (18 mL), and water (3mL) was cooled to 0 °C and added dropwise over 1 hour a solution containing the following: sodium hypochlorite (17.2 mL, 0.37 M, 6.4 mmol) and sodium hydrogencarbonate (1.46 g, 17.4 mmol). The reaction mixture was stirred at 0 °C for 10 min., and the phases separated. The aqueous layer was extracted with ethyl acetate (150 mL). The combined organic phases were washed with a solution of potassium iodone (0.2 g) in 10 % aqueous potassium hydrogensulfate (150 mL), water (150 mL), brine (150 mL), dried (MgSO 4 ), filtered, and concentrated in vacuo to provide 980 mg of a 3:1 mixture of naphthalen-2-yl- acetaldehyde and 2-naphthalen-2-yl-ethanol. 1 H-NMR (CDCI 3 ): δ 9.81 (t, 1H, J = 1.5 Hz), 7.92-7.80 (m, 3H), 7.68 (bs, 1 H), 7.55-7.42 (m, 3H), 3.87 (d, 2H, J = 1.5 Hz). To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (290 mg, 0.71 mmol) in 1 ,2-dichloroethane (3 ml) was added the above mixture of 2-naphthyl-acetaldehyde (100 mg, 0.59 mmol), sodium triacetoxyborohydride (190 mg, 0.88 mmol) and the mixture was stirred at room temperature under nitrogen for 2.5 hours. The crude reaction mixture was quenched with saturated sodium bicarbonate (50 ml) and the solution extracted with ethyl acetate (100 ml). The organic phase was dried (MgSO 4 ), filtered, and concentrated in vacuo providing a foam, which was taken directly to the next step. LC-MS showed that 2-amino-6- (4-methoxy-benzyl)-5-((2-naphthalen-2-yl-ethylamino)-methyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester was the major component. LC-MS: m/z: 558.1 [M+H] + , R f = 2.23 min. To a solution of 2-amino-6-(4-methoxy-benzyl)-5-((2-naphthalen-2-yl- ethylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester in tetrahydrofuran (3 ml) was added di-ferf-butyl- dicarbonate (188 mg, 0.85 mmol) and Λ/,Λ/-dimethylformamide (18 mg, 0.14 mmol). The reaction was stirred at room temperature for 7 hours under nitrogen. The crude reaction mixture was diluted with dichloromethane (50 ml) and washed with water (50 ml) and brine (50 ml). The organic phase was dried (MgSO 4 ), filtered, and concentrated in vacuo affording a foam, which was used without further purification in the next step. LC-MS showed that 2-amino-5-((ferf-butoxycarbonyl-(2-naphthalen-2-yl- ethyl)-amino)-methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester was the major component. R f = 2.74, m/z: 658.1 [M+H] + , Calculated: 657.4. To crude 2-amino-5-((fetf-butoxycarbonyl-(2-naphthalen-2-yl-ethyl)- amino)-methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester was added dichloromethane (5 ml) and imidazol-1-yl-oxo-acetic acid ferf-butyl ester (400 mg, 1.78 mmol) and the reaction mixture stirred at room temperature for 12 hours. The crude reaction mixture was added to dichloromethane (50 ml) and washed with water (50 ml) and brine (50 ml). The organic phase was dried (MgSO 4 ), filtered, and concentrated in vacuo. The residue was purified by flash chromatography using a mixture of dichloromethane/ethyl acetate (10:1) as eluent, which afforded 20.3 mg (39 % over tree steps) of 2-(ferf- butoxyoxalyl-amino)-5-((fetf-butoxycarbonyl-(2-naphthalen-2-yl-ethyl)- amino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester as a foam. 1 H NMR (CDCI 3 ) δ 7.99-7.92 (m, 3H), 7.88 (s, 1 H), 7.68-7.57 (m, 3H), 7.45 (d, 2H, J = 7.8 Hz), 6.99 (d, 2H, J = 8.1 Hz), 3.90-3.75 (m, 7H), 3.56-3.42 (m, 5H), 3.19-3.13 (m, 2H), 2.88-2.82 (m, 2H), 1.79 (s, 9H), 1.71 (s, 18H); LC-MS: m/z: 786.2 [M+H] + , R f = 3.03 min. To a solution of 2-(fetf-butoxyoxalyl-amino)-5-((fetf-butoxycarbonyl-(2- naphthalen-2-yl-ethyl)-amino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (20 mg, 0.03 mmol) in dry dichloromethane (200 μl) at 0 °C was added 50 % trifluoroacetic acid in dichloromethane (2.5 ml). The reaction was stirred for 14 hours at room temperature and then concentrated in vacuo. The resultant solid was re-suspended in dichloromethane, filtered, and dried in vacuo to provide 13 mg (90 %) of the title compound as a solid. 1 H NMR (DMSO-d 6 ) δ 9.15 (s, 1 H), 8.09-8.01 (m, 3H), 7.93 (s, 1 H), 7.68- 7.57 (m, 3H), 7.45 (d, 2H, J =7.8 Hz), 6.99 (d, 2H, J = 8.1 Hz), 4.18-4.12 (m, 2H), 3.90-375 (m, 7H), 3.56-3.42 (m, 3H), 3.19-3.13 (m, 2H), 2.88- 2.82 (m, 2H); LC-MS: m/z: 574.7 [M+H] + , R f = 1.36 min. EXAMPLE 97 5-((2-Benzo[1 , 3]dioxol-5-yl-acetylamino)methyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahvdro-thienor2,3-clpyridine-3-carboxylic acid To a mixture of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (300 mg, 0.74 mmol), benzo[1 ,3]dioxol-5-yl-acetic acid (134 mg, 0.74 mmol), 1- hydroxybenzotriazole hydrate (111 mg, 0.82 mmol), and Λ/,Λ/-diisopropyl- ethylamine (258 μL, 1.48 mmol) in acetonitrile (5 ml) at room temperature was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (157 mg, 0.82 mmol). The reaction mixture was stirred for 16 hours and the solvent evaporated in vacuo. The residue was taken into ethylacetate (50 ml), washed with water, 1 N hydrochloric acid, saturated sodium bicarbonate, brine, dried (MgSO 4 ), filtered and the solvent evaporated vacuo. The residue was subjected to flash chromatography using a gradient of 10-20% ethylacetate/hexanes as eluent, which afforded 268 mg (64 %) of 2-amino-5-((2-benzo[1 ,3]dioxol-5-yl-acetylamino)methyl)-6- (4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 6.95 (bs, 2H), 675-6.85 (m, 5H), 5.96 (bs, 2H), 5.95 (s, 2H), 3.81 (s, 3H), 375-3.30 (m, 5H), 3.53 (s, 2H), 3.18 (bs, 2H), 2.82 (d, 1 H, J = 17 Hz), 2.52 (d, 1H, J = 17 Hz). To a solution of 2-amino-5-((2-benzo[1 ,3]dioxol-5-yl-acetylamino)methyl)- 6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (133 mg, 0.235 mmol) in tetrahydrofuran (1 ml) was added imidazol-1-yl-oxo-acetic acid ferf-butyl ester (100 mg, 0.51 mmol). The mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo. The residue was taken into ethyl acetate (50 ml) washed with saturated sodium bicarbonate, brine, dried (Na 2 SO ) and filtered. The solvent was removed in vacuo and the residue was chromatographed using a gradient of 10-20% ethyl acetate/dichloromethane, which afforded 130 mg (80 %) of 2-(ferf- butoxyoxalyl-amino)-5-((2-benzo[1 ,3]dioxol-5-yl-acetylamino)methyl)-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.50 (s, 1 H), 7.95-775 (m, 7H), 5.96 (s, 2H), 3.81 (s, 3H), 3.80-3.40 (m, 5H), 3.15 (bs, 2H), 2.90 (d, 1H, J = 17 Hz), 2.58 (d, 1 H, J = 17 Hz), 1.61 (s, 9H), 1.60 (s, 9H). A solution of 2-(fetf-butoxyoxalyl-amino)-5-((2-benzo[1 ,3]dioxol-5-yl- acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester (130 mg, 0.188 mmol) in tetrahydrofuran (2 ml) was passed through a Raney Ni bed (120 mg, 50% Raney Ni-water washed with methanol (6 ml) and tetrahydrofuran (6 ml) and dried before use). The Raney Ni bed was washed with tetrahydrofuran (10 ml). The filtrate and washes were combined and the solvent evaporated in vacuo. The residue was dissolved in 10% formic acid/methanol (6 ml) and stirred with 10% Pd/C (120 mg) for 13 hours. Saturated sodium bicarbonate solution (60 ml) was added to the solution. The mixture was extracted with dichloromethane. The extracts were combined, dried (Na 2 SO 4 ) and filtered. The solvent was removed in vacuo and the residue was washed with 50% hexane/diethyl ether to afford 62 mg (57 %) of 2-(.etf-butoxyoxalyl-amino)-5-((2-benzo[1 ,3]dioxol-5-yl- acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.59 (s, 1 H), 6.80-670 (m, 3H), 5.96 (s, 2H), 4.05 (q, 2H, J = 15 Hz), 3.85-3.60 (m, 2H), 3.25-3.00 (m, 4H), 2.58 (m, 1 H), 1.61 (s, 9H), 1.59 (s, 9H); LC-MS: R t = 1.75 min, m/z: 574 [M+H] + . A solution of 2-(fetf-butoxyoxalyl-amino)-5-((2-benzo[1 ,3]dioxol-5-yl- acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (62 mg, 0.11 mmol) in 50% trifluoroacetic acid- dichloromethane (2 ml) was left in an open flask over the weekend and then the solvent was removed in vacuo. The residue was washed with dichloromethane and the solid filtered off affording 39 mg (62 %) of the title compounds as a solid trifluoroacetate. 1 H-NMR (DMSO-de) δ 12.39 (s, 1 H), 9.18 (bs, 1 H), 9.10 (bs, 1 H), 8.35 (s, 1 H), 6.83 (d, 1 H, J = 1.2 Hz), 6.82 (d, 1 H, J = 8.4 Hz), 6.70 (dd, 1 H, J = 8.4 Hz and J = 1.2 Hz), 5.96 (s, 2H), 4.38 (d, 1 H, J = 14 Hz), 4.28 (m, 1 H), 3.60-3.40 (m, 4H), 3.16 (d, 2H, J = 14 Hz), 2.80 (dd, 1 H, J = 14 Hz and J = 11 Hz); LC-MS: R t = 1.11 min, m/z: 462 [M+H] + . EXAMPLE 98 5-((2-Dibenzofuran-2-yl-ethyl)amino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,67-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid To a solution of 2-dibenzofuran-2-yl-ethanol (200 mg, 0.94 mmol) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) (2 mg, 0.009 mmol) in dichloromethane (2 mL) was added an aqueous solution of sodium bromide (97 mg in 1.3 mL of water for a 0.7M solution, 0.94mmol) and cooled to 0 °C. To this mixture was added dropwise over 30 min., a solution containing the following: sodium hypochlorite (1.4 mL, 0.74 M, 1.03 mmol) and sodium hydrogencarbonate (120 mg, 1.4 mmol) and water (1.4 mL). The reaction mixture was stirred at 0 °C for 0.5 hour and allowed to warm to room temperature. The organic phase and aqueous layer were separated and the aqueous layer extracted with dichloromethane (20 mL). The combined organic phases were washed with a solution of potassium iodone (0.2 g) in 10% aq. Potassium hydrogensulfate (20 mL), water (20 mL), brine (20 mL), dried (MgSO 4 ) filtered, and concentrated in vacuo to provide 198 mg of a 5:1 mixture of dibenzofuran-2-yl-acetaldehyde and 2-dibenzofuran-2-yl-ethanol as an oil. 1 H-NMR (CDCI 3 ): δ 9.80 (t, 1 H, J = 1.5 Hz), 8.02 (d, 2H, J = 8.2 Hz), 7.71 (bs, 1 H), 7.75-7.42 (m, 4H), 3.82 (d, 2H, J - 1.5 Hz). To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (340 mg, 0.85 mmol) in 1 ,2-dichloroethane (3 ml) was added the above mixture of dibenzofuran-2-yl-acetaldehyde (150 mg, 0.70 mmol), and sodium triacetoxyborohydride (225 mg, 1.07 mmol) and the mixture was stirred at room temperature under nitrogen for 2.5 hours. The crude reaction mixture was quenched with saturated sodium bicarbonate (50 ml) and the solution extracted with ethylacetate (100 ml). The organic phase dried (MgSO 4 ), filtered, and the solvent evaporated i vacuo. The crude residue was taken directly to the next step. LC-MS showed that 2-amino-5-((2- dibenzofuran-2-yl-ethylamino)methyl]-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester was the major component in the crude mixture: m/z: 598.1 [M+H] + , R f = 2.40 min). Crude 2-amino-5-((2-dibenzofuran-2-yl-ethylamino)methyl]-6-(4-methoxy- benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester was diluted in tetrahydrofuran (3 ml) and di-fetf-butyl dicarbonate (262 mg, 1.20 mmol) and 4-(Λ/,Λ/-dimethylamino)pyridine (25 mg, 0.20 mmol) were added. The reaction was stirred at room temperature for 7 hours under nitrogen. The crude reaction mixture was added to dichloromethane (50 ml) and washed with water (50 ml) and brine (50 ml). The organic phase was dried (MgSO 4 ), filtered, and concentrated jn vacuo. The residue was used directly in the next step. LC-MS showed that 2-amino-5-((ferf-butoxycarbonyl-(2-dibenzofuran-2-yl-ethyl)amino)- methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester was the major component in the crude: R f = 276, m/z: 698.2 [M+H] + . To compound 2-amino-5-((ferf-butoxycarbonyl-(2-dibenzofuran-2-yl- ethyl)amino)-methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester was added dichloromethane (5ml) and imidazol-1-yl-oxo-acetic acid ferf-butyl ester (420 mg, 2.12 mmol). The reaction mixture was stirred at room temperature for 12 hours. The crude reaction mixture was added to dichloromethane (50 ml) and washed with water (50 ml) and brine (50 ml). The organic phase was dried (MgSO ), filtered, and concentrated in vacuo. The residue was subjected to flash chromatography using a mixture of dichloromethane/ethyl acetate (10:1) as eluent, which afforded 35.2 mg (51 % over 3 steps) of 2-(ferf- butoxyoxalyl-amino)-5-((fetf-butoxycarbonyl-(2-dibenzofuran-2-yl- ethyl)amino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester as a foam. 1 H-NMR (CDCI 3 ) δ 7.95-7.90 (m, 3H), 7.84 (s, 1 H), 7.68-7.57 (m, 3H), 7.45 (d, 2H, J = 7.8 Hz), 6.95 (m, 3H), 3.90-375 (m, 7H), 3.56-3.42 (m, 5H), 3.19-3.13 (m, 2H), 2.88-2.82 (m, 2H), 179 (s, 9H), 1.71 (s, 18H); LC-MS: R f = 3.03 min, m/z: 826.2 [M+H] + . To a solution of 2-(ferf-butoxyoxalyl-amino)-5-((ferf-butoxycarbonyl-(2- dibenzofuran-2-yl-ethyl)amino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (28 mg, 0.034 mmol) in dry dichloromethane (200 μL) at 0 °C was added 50% trifluoroacetic acid in dichloromethane (2.5 ml). The reaction was stirred for 14 hours at room temperature and then concentrated in vacuo. The resultant solid was re-suspended in dichloromethane, filtered, and dried vacuo, which afforded 22 mg (90 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (DMSO-d 6 ) δ 9.15 (s, 1H), 8.11-8.21 (m, 3H), 7.93 (s, 1H), 7.68- 7.57 (m, 3H), 7.45 (d, 2H, J = 7.8 Hz), 6.99 (d, 2H, J = 8.1 Hz), 4.18-4.12 (m, 2H), 3.90-3.75 (m, 7H), 3.56-3.42 (m, 3H), 3.19-3.13 (m, 2H), 2.88- 2.82 (m, 2H); LC-MS: R f = 3.03, m/z: 614.7 [M+H] + . EXAMPLE 99 6-(4-Methoxy-benzyl)-5-((2-(5-methoxy-2-methyl-1H-indol-3-yl)- acetylamino)methyl)-2-(oxalyl-amino)-4,5,67-tetrahydro-thienof2,3- clpyridine-3-carboxylic acid To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (202 mg, 0.50 mmol), in Λ/,Λ/-dimethylformamide (4 ml) was added 5-methoxy-2- methyl-3-indole acetic acid (170 mg, 0.74 mmol), 1-(3-dimethylamino- propyl)-3-ethylcarbodiimide, hydrochloride (150 mg, 0.75 mmol), and 1- hydroxybenzotriazole (105 mg, 0.74 mmol). The mixture was stirred at room temperature for 12 hours. The crude reaction mixture was diluted with dichloromethane (100 ml) and washed with water (100 ml), brine (100 ml), dried (MgSO 4 ), filtered, and concentrated in vacuo, which afforded 2- amino-6-(4-methoxy-benzyl)-5-((2-(5-methoxy-2-methyl-1H-indol-3- yl)acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 7.16 (d, 2H, J = 10.8 Hz), 6.99 (d, 1H, J = 2.5 Hz), 6.94 (m, 1 H), 6.85 (dd, 1 H, J = 8.4 Hz and J = 1.2 Hz), 678 (dd, 1 H, J = 8.3 Hz and J = 1.2 Hz), 6.65 (m, 3H), 6.57 (m, 4H), 3.57 (t, 4H, J = 3.0 Hz), 3.53 (m, 6H), 3.59-3.29 (m, 5H), 3.12-2.92 (m, 4H), 2.39 (s, 3H), 1.6 (s, 9H); LC-MS R,= 2.19, m/z: 605 [M+H] + . To a solution of 2-amino-6-(4-methoxy-benzyl)-5-((2-(5-methoxy-2-methyl- 1/- -indol-3-yl)acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3-carboxylic acid fetf-butyl ester (96 mg, 0.5 mmol) in dichloromethane (5 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (583 mg, 3.0 mmol) and the reaction stirred at room temperature for 24 hours. The mixture was then concentrated vacuo. The residue was purified by flash column chromatography (25% ethylacetate/dichloromethane) to give 53 mg (15 %) of 2-(fetf-butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-((2-(5- methoxy-2-methyl-1/-/-indol-3-yl)acetylamino)methyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 7.16 (d, 2H, J = 10.8 Hz), 6.99 (d, 1 H, J = 2.5 Hz), 6.94 (m, 1 H), 6.85 (dd, 1 H, J = 8.4 Hz and J = 1.2 Hz), 6.78 (dd, 1 H, J = 8.3 Hz and J = 1.2 Hz), 6.65 (m, 3H), 6.56 (m, 3H), 3.57 (m, 3H), 3.53 (m, 6H), 3.59-3.29 (m, 5H), 3.12-2.92 (m, 4H), 2.39 (s, 3H), 1.6 (s, 18H); LC-MS R t = 2.36 min, m/z: 733 [M+H] + . 2-(ferf-Butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-((2-(5-methoxy-2- methyl-1/- -indol-3-yl)acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester was dissolved in 50% trifluoroacetic acid/dichloromethane (3 ml) and stirred at room temperature for 48 hours. The solvent was removed in vacuo and the residual trifluoroacetic acid was removed under reduced pressure to give 17 mg (49 %) of the title compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de) δ 10.62 (s, 1H), 7.31 (s, 1 H), 7.08 (d, 1H, J = 10.2 Hz), 6.93 (s, 2H), 6.58 (dd, 1 H, J 1 = 5.25 Hz and J 2 = 2.8 Hz), 3.84-3.44 (m, 19H, partially obscured by solvent), 2.95 (s, 1H), 2.28 (s, 3H), 1.31 (s, 1 H), 1.19 (s, 2H); LC-MS R t = 1.89 min, m/z: 621 [M+H] + . EXAMPLE 100 5-((2-(1H-lndol-3-yl)-2-oxo-acetylamino)methyl)-2-(Oxalyl-amino)-4,5.67- tetrahvdro-thienor2,3-clpyridine-3-carboxylic acid To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (209 mg, 0.51 mmol) in dry Λ/,Λ/-dimethylformamide (4 ml) was added 3-indole- glyoxylic acid (141 mg, 0.74 mmol), 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide, hydrochloride (152 mg, 0.76 mmol), and 1-hydroxybenzotriazole (100 mg, 0.74 mmol). The mixture was stirred at room temperature for 16 hours, diluted with dichloromethane (100 ml) and washed with water (100 ml), brine (100 ml), dried (MgSO 4 ), filtered, and concentrated vacuo. The residue was subjected to flash chromatography using a mixture of ethyl acetate/hexanes (2:5) as eluent, which afforded 143 mg (40 %) of 2-amino-5-((2-(1H-indol-3-yl)-2-oxo- acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. LC-MS R t = 2.31 min, m/z: 574.9 [M+H] + . To a solution of 2-amino-5-((2-(1 -/-indol-3-yl)-2-oxo-acetylamino)methyl)- 6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (143 mg, 0.25 mmol) in dichloromethane (5 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (144 mg, 0.75 mmol) and the flask was purged with nitrogen. After 24 hours an additional portion of imidazol-1-yl-oxo-acetic acid fetf-butyl ester (169 mg, 0.86 mmol) was added and the reaction mixture allowed stirred for an additional 24 hours. The mixture was then concentrated m vacuo. The residue was purified by flash chromatography using a mixture of ethyl acetate/hexanes (2:5) as eluent, which afforded 101 mg (58 %) of 2-(tert- butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo-acetylamino)methyl)-6-(4- methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as a oil. 1 H-NMR (CDCI3) δ 9.23 (s, 1 H), 9.07 (d, 1 H, J = 3.6 Hz), 8.50 (d, 1 H, J = 7.6 Hz), 8.15 (d, 1 H, J = 4.0 Hz), 7.47 (d, 2H, J = 7.2 Hz), 7.38-7.27 (m, 6H), 6.89 (d, 2H, J = 8.8 Hz), 3.87-3.59 (m, 6H), 3.04 (dd, 2H, J = 23.6 Hz), 2.74 (dd, 2H, J = 22.4 Hz), 1.62 (s, 18H); LC-MS R, = 2.49 min, m/z: 703 [M+H] + . 2-(ferf-Butyoxyoxalyl-amino)-5-((2-(1 rV-indol-3-yl)-2-oxo- acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester (101 mg, 0.143 mmol) was dissolved in dry tetrahydrofuran (6 ml) and passed through a pipette, plugged with cotton containing Raney 2800 Nickel (0.38 g). The pipette was flushed with dry tetrahydrofuran (6 ml) and the filtrate was concentrated in vacuo. Pd on carbon (10%, 102 mg, source: Avocado) and formic acid (10% in methanol, 5 ml) were added to the flask containing 2-(ferf-Butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2-oxo- acetylamino)methyl)-6-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester. After stirring for 18 hours, the solution was filtered through a pad of celite and concentrated in vacuo. The residue was diluted in ethyl acetate, washed with saturated sodium bicarbonate (2 x 25 ml), brine (2 x 25 ml), dried (MgSO ), filtered and concentrated in vacuo. The residue was subjected to flash chromatography using a mixtureof 10% methanol/dichloromethane as eluent, which afforded 2-(fetf-butyoxyoxalyl-amino)-5-((2-(1H-indol-3-yl)-2- oxo-acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester. 1 H-NMR (CDCI 3 ) δ 9.23 (s, 1 H), 9.07 (d, 1 H, J = 3.6 Hz), 8.50 (d, 1 H, J = 7.6 Hz), 8.15 (d, 1 H, J = 4.0 Hz), 7.27 (s, 2H), 7.09 (d, 1 H, J = 8.8 Hz), 6.81 (d, 1 H, J = 8.8 Hz), 3.79 (s, 1 H), 2.29 (s, 1 H), 1.62-1.57 (m, 18H), 0.08 (s, 5H); LC-MS: R, = 2.17 min, m/z: 583 [M+H] + . The above 2-(fetf-butyoxyoxalyl-amino)-5-((2-(1 /-/-indol-3-yl)-2-oxo- acetylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester was dissolved in 50% trifluoroacetic acid/dichloromethane (3 ml) and stirred at room temperature for 18 hours. The solvent was removed vacuo and residual trifluoroacetic acid was removed under reduced pressure affording 17.1 mg of the title compound as a solid trifluoroacetate. 1 H-NMR (DMSO-d 6 ) δ 12.28 (s, 2H), 9.26 (s, 1 H), 9.13 (s, 1 H), 8.83 (d, 1 H, J = 2.8 Hz), 8.26 (d, 1 H, J = 8.8 Hz), 7.55 (d, 1 H, J = 4.8 Hz), 7.27 (d, 2H, J = 7.6 Hz), 4.42 (d, 1 H, J = 15.2 Hz), 4.29 (d, 1 H, J = 16.4 Hz), 3.76- 3.22 (m, 4H, partially obscured by solvent), 2.91-2.834 (m, 1 H), 1.23 (s, 1 H); LC-MS: R t = 0.99 min, m/z 471.4 [M+H] + . GENERAL CHIRAL SYNTHESIS 4-Oxo-l -((S)-1 -phenyl-ethyl)-piperidine-(R)-2-carboxylic acid ethyl ester Dichloromethane (1 L) and mol sieves 3 A (113 g) and amine (S)-(-)α- methyl-benzylamin (71 ,7 ml) were mixed in a 2 I three-necked bottle cooled to -5 °C (using a ethanol/water/ice bath). A 50 % solution of ethylglyoxylate in toluene (117,6 ml) was added drop wise over 20 min., keeping the temperature between -5 °C and 0 °C The mixture was stirred for 0.5 hour before it was cooled to -30 °C. Trifluoroacetic acid (45,2 ml) was added over 3-4 minutes. Boron trifluoride diethyl ether (69,8 ml) was added drop wise over 5 min at -55 °C. The ice bath was removed and the mixture was allowed to warm up to -45 °C whereupon 2-(trimethylsilyloxy)-1 ,3-butadiene (100 ml) was added drop wise over 10 minutes. During the addition the mixture was cooled and the temperature kept below -20 °C. The above additions are all exothermic hence the cooling bath should have sufficient capacity to remove the heat generated during the rapid addition. The reaction mixture was stirred for 2 hours at - 15 °C and 1 hour at 0 °C and then poured on ice/water and stirred for 15 minutes. Solid sodium hydrogen carbonate was added until pH 7-8. The mixture was stirred overnight at room temperature. The layers wee separated and the aqueous phase extracted with dichloromethane. The combined organic phases were filtered through a plug of silica eluting with dichloromethane. The relevant fractions were concentrated vacuo. The residue was dissolved in hot heptane and cooled. This leaves a yellowish gummy material on the side of the flask and crystals starts forming. The heptane solution was heated again to dissolve crystals, leaving the gummy material on the side of the flask and the mixture was filtered hot. The heptane solution was cooled to room temperature and the precipitate was filtered off and dried in vacuo, which afforded 38 g of 4-oxo-1 -((S)-1 - phenyl-ethyl)-piperidine-(R)-2-carboxylic acid ethyl ester as a solid. The filtrate was put in a refrigerator and a second crop was formed which was less pure and needed recrystallization from heptane to yield another 7,5 g of 4-oxo-1 -((S)-1-phenyl-ethyl)-piperidine-(R)-2-carboxylic acid ethyl ester. 4,4-Diethoxy-1 -((S)-1 -phenyl-ethyl)-piperidine-(S)-2-carboxylic acid ethyl ester The mother liquor from the above crystallization was concentrated i vacuo. 5.0 g of the resulting material (18.16 mmol) was dissolved in ethanol (100 ml) and triethylorthoformate (26.9 g, 181.6 mmol) and para- toluensulphonic acid (6.9 g, 36.32 mmol) was added. The reaction was stirred at room temperature for 16 hours before the mixture was poured on aqueous sodium hydrogen carbonate (200 ml) and extracted with ethyl acetate (4 x 75 ml). The combined extracts were concentrated vacuo and purified by column chromatography (SiO 2 , Flash 40, petrol ether-ethyl acetate 10:1). Collection of the first band (R f = 0.68) gave 1.14 g (18 %) of 4,4-diethoxy-1 -((S)-1 -phenyl-ethyl)-piperidine-(R)-2-carboxylic acid ethyl ester and collection of the second band (R f = 0.4) gave 3.60 g (57 %) of the title compound. 4,4-Diethoxy-1 -((S)-1 -phenyl-ethyl)-piperidine-(R)-2-carboxylic acid ethyl ester 4-Oxo-l -((S)-1-phenyl-ethyl)-piperidine-(f?)-2-carboxylic acid ethyl ester (11.0 g, 0.040 mmol) was dissolved in a 1 :1 mixture of triethyl orthoformate and ethanol (140 ml) and para-toluene-4-sulphonic acid (15.2 g, 80 mmol) was added and the reaction mixture was stirred for 16 hours. The reaction mixture was neutralized with sodium bicarbonate (to pH 7-8), and extracted with dichloromethane (3 x 100 ml), dried (MgSO 4 ), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO 2 , petrol ether/ethyl acetate 10:1 ), which afforded 12.0 g (86 %) of the title compound as an oil. 4,4-Diethoxy-1-((S)1-phenyl-ethyl)-(R)-2-hydroxymethyl-piperidine To a solution of 4,4-diethoxy-1-((S)-1-phenyl-ethyl)-piperidine-(/ : ?)-2- carboxylic acid ethyl ester (36.0 g, 0.103 mol) in dry diethyl ether (150 ml) was added a suspension of lithium aluminum hydride (5.88 g, 0.155 mol) in dry diethyl ether (300 ml) under an atmosphere of nitrogen at such a rate that the solution gently reflux. The reaction mixture was stirred over night before it was cooled to 0 °C and ethyl acetate (30 ml) was added drop wise to destroy excess lithium aluminum hydride. After stirring for another 0.5 hour, water (12 ml) was added drop wise. After stirring for 10- 15 min the precipitate was filtered off through celite and the filter cage was washed with plenty of diethyl ether. The filtrate was washed with brine (100 ml), dried (MgSO ), filtered and the solvent evaporated in vacuo, which afforded 30 g (95 %) of the titie compound as an oil. 4,4-Diethoxy-1-((S)-1-phenyl-ethyl)-(R)-2-phthalimidomethyl- piperidine A solution of 4,4-Diethoxy-1-(( piperidine (65.35 g, 0.213 mmol), triphenylphosphine (61.3 g, 0.234 mol) and phthalimide (34.4 g, 0.234 mol) in tetrahydrofuran (700 ml) cooled to 0 °C was added diethyl azodicarboxylate over the course of 1.5 hour. The reaction mixture was stirred at 0 °C for another 2 hours before the solvent was removed in vacuo. The residue was dissolved in hot heptane-toluene (3:2) (650 ml) before it was cooled on an ice bath. The precipitate consisting of triphenyl phosphine oxide was filtered off and washed with heptane. The filtrate was concentrated in vacuo and the residue subjected to column chromatography using a mixture of toluene-ethyl acetate- heptane (3:1 :3) as eluent. The solvent was evaporated jn vacuo whereupon a viscous oil was obtained. Upon addition of light petrol ether the product crystallized to give 67.4 g (73 %) of the title compound as a solid. EXAMPLE 101 5-(R)-(7-Methoxy-1 -oxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thienof2,3-clpyridine-3-carboxylic acid A mixture of 4,4-diethoxy-1 -((S)-1 -phenyl-ethyl)-(R)-2-phthalimidomethyl- piperidine (5.25 g, 12.0 mmol) and hydrazine hydrate (2.92 ml, 60 mmol) was stirred overnight in ethanol (100 ml) at room temperature. The solvent was removed in vacuo and the solid residue was extracted with refluxing diethyl ether. The diethyl ether fractions were combined and evaporated vacuo, which afforded 3.94 g (94 %) of 4,4-diethoxy-1-((S)-1-phenyl- ethyl)-(R)-2-aminomethyl-piperidine as an oil. 4,4-Diethoxy-1-((S)-1-phenyl-ethyl)-(R)-2-aminomethyl-piperidine (2.25 g, 7.37 mmol), and triethyl amine (1.49 g, 14.7 mmol) in acetonitrile (50 ml) was heated to 60 °C before 2-chlormethyl-6-methoxy-benzoic acid methyl ester (1.58 g, 7.37 mmol) in acetonitrile (25 ml) was added over the course of 1.5 hour. After addition the reaction mixture was stirred overnight at 60 °C. The solvent was removed in vacuo and the residue was dissolved in dichloromethane (50 ml) and washed with saturated sodium bicarbonate. After drying (MgSO ), filtration and evaporation of the solvent in vacuo the residue was subjected to flash column chromatography (SiO 2 , ethyl acetate-light petrol ether (1:1)) to give 2.3 g (69 %) of 2-(R)-(7-methoxy-2,3-dihydro-isoindol-1-one-2-ylmethyl)-4,4- diethoxy-1-(1-(S)-phenyl-ethyl)-piperidine. 2-(R)-(7-Methoxy-2,3-dihydro-isoindol-1 -one-2-ylmethyl)-4,4-diethoxy-1 (1 - (S)-phenyl-ethyl)-piperidine (2.0 g, 4.4 mmol) was dissolved in a ice cold mixture of trifluoroacetic acid and water (10 ml, 9:1) and stirred or 0.5 hour on an ice bath. The reaction mixture was poured on aqueous sodium carbonate (100 ml) and extracted with dichloromethane (2 x 50 ml). The organic phase was dried (MgSO 4 ), filtered and evaporated in vacuo, affording 1.67 g (100 %) of 2-(R)-(7-methoxy-2,3-dihydro-isoindol-1-one-2- ylmethyl)-4-oxo-1 (1 -(S)-phenyl-ethyl)-piperidine. 2-(R)-(7-Methoxy-2,3-dihydro-isoindol-1 -one-2-ylmethyl)-4-oxo-1 (1 -(S)- phenyl-ethyl)-piperidine (1.67 g, 4.41 mmol), sulphur (0.155 g, 4.85 mmol), ferf-butylcyanoacetate (0.684 g, 4.85 mmol), Λ/-methylmorpholine (0.892 g, 8.82 mmol) and molecular sieves (4A, 2 g) was heated to 50 °C in ethanol under an atmosphere of nitrogen for 16 hours. The reaction mixture was filtered through a plug (1 cm) of SiO 2 , the silica was washed with dichloromethane-ethyl acetate and the solvent was removed in vacuo. The resulting residue was subjected to column chromatography (Flash 40, SiO 2 , toluene-ethyl acetate (3:1)), which yielded 1.17 g (50 %) of 2-amino-5-(f?)-(7-methoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(1 - (S)-phenyl-ethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester and 2-amino-7-(S)-(7-methoxy-1 -oxo-1 ,3-dihydro-isoindol- 2-ylmethyl)-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-. 3-carboxylic acid fetf-butyl ester as a 3:1 mixture. The above mixture of 5- and 7-regioisomers (1.17 g, 2.19 mmol) and imidazol-2-yl-oxo-acetic acid fetf-butyl ester (1.29 g, 7.57 mmol) and triethylamine (0.66 g, 6.57 mmol) was stirred under an atmosphere of nitrogen in dichloromethane (25 ml) for 16 hours. The solvent was removed jn vacuo and the residue was subjected to column chromatography (SiO 2 , Flash 40, ethyl acetate-petrol ether (1 :1)). Collection of relevant fractions gave 0.61 g (42 %) of 2-(ferf-butoxyoxalyl- amin)-5-(R)-(7-methoxy-1 -oxo-1 ,3-dihydro-isoindo-2-ylmethyl)-6-(1 -(S)- phenyl-ethyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester. 2-(fetf-Butoxyoxalyl-amin)-5-(R)-(7-methoxy-1 -oxo-1 , 3-dihydro-isoindo-2- ylmethyl)-6-(1-(S)-phenyl-ethyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester (0.60 g, 0.91 mmol) was stirred for 16 hours in a mixture of methanol and formic acid (10:1) (20 ml) in the presence of 10 % palladium on carbon (50 % water). The reaction mixture was filtered through a plug of Celite and washed with methanol. The volatiles were removed vacuo and the residue was dissolved in dichloromethane (50 ml), washed with semi saturated aqueous sodium carbonate (50 ml), dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was purified by column chromatography (SiO 2 , Flash 40, ethyl acetate-methanol (100:15)), which afforded 0.36 g (71 %) of 2- (fetf-butoxyoxalyl-amin)-5-(R)-(7-methoxy-1 -oxo-1 ,3-dihydro-isoindo-2- ylmethyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf- butyl ester. 2-(ferf-Butoxyoxalyl-amin)-5-(R)-(7-methoxy-1 -oxo-1 , 3-dihydro-isoindo-2- ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf- butyl ester (349 mg, 0.63 mmol) was stirred for 16 hours in a mixture of trifluoroacetic acid and dichloromethane (1 :1) (10 ml) whereupon diethyl ether (20 ml) was added. The precipitate was filtered off and washed with diethyl ether, which afforded 215 mg (61 %) of the title compound as a solid trifluoroacetate. LC-MS: R, = 1.17 min, m/z: 446 [M+H] + Calculated for C 20 H 19 N 3 O 7 S, C 2 HF 3 O 2 , 0.5xH 2 O C, 46.48%; H, 3.72%; N, 7.39%; Found: C, 46.45%; H, 3.97%; N, 7.43%; EXAMPLE 102 5-(S)-(7-Methoxy-1 -oxo-1 1 3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thieno[2,3-clpyridine-3-carboxylic acid A solution of 4,4-diethoxy-1-((S)-1-phenyl-ethyl)-piperidine-(S)-2- carboxylic acid ethyl ester (35.98 g, 0.103 mol) in diethyl ether (150 ml) was added drop wise to a suspension of lithium aluminum hydride (5.88 g, 0.155 mol) in diethyl ether (300 ml) over the course of 1 hour. The reaction mixture was stirred at room temperature overnight before it was cooled on an ice bath and the reaction was quenched by dropwise addition of ethyl acetate (30 ml), followed by drop wise addition of water (12 ml) whereupon a gray precipitate was formed. The mixture was filtered through a plug of Celite and the filter cage was washed with plenty of diethyl ether. The filtrate was dried (MgSO ) before it was filtered and the solvent removed in vacuo, which afforded 24.5 g (79 %) of 4,4-diethoxy-1- (1-(S)-phenyl-ethyl)-(S)-2-hydroxymethyl-piperidine as an oil. A suspension of 4,4-diethoxy-1-(1-(S)-phenyl-ethyl)-(S)-2-hydroxymethyl- piperidine (20 g, 65 mmol), triphenylphosphine (18.76 g, 72 mmol) and phthalimide (10.52 g, 72 mmol) in tetrahydrofurane (200 ml) cooled to 0 °C was added diethyl azodicarboxylate (11.34 ml, 72 mmol) over the course of 1 hour. The reaction mixture was stirred at 0 °C for another 2 hours before the volatiles were removed in vacuo. The residue was dissolve in hot heptane-toluene (3:2) (100 ml) before it was cooled on an ice bath. The precipitate was filtered off and washed with heptane. The filtrate was concentrated in vacuo and the residue subjected to column chromatography using a mixture of toluene/ethyl acetate/heptane (3:1 :3) as eluent. The solvent was evaporated in vacuo and the residue was crystallized by addition of light petrol ether (250 ml). The precipitate was filtered off, which afforded 24 g (85 %) of 4,4-diethoxy-1-(1-(S)-phenyl- ethyl)-2-(S)-phthalimidomethyl-piperidine as a solid. 4,4-Diethoxy-1-(1-(S)-phenyl-ethyl)-2-(S)-phthalimidomethyl-piperidine (4.0 g, 9.2 mmol) was dissolved in a mixture of trifluoroacetic acid and water (9:1) (100 ml) at 0 °C and stirred for 2 hours at this temperature. The mixture was basified with half saturated aqueous sodium carbonate, extracted with ethyl acetate and dried (MgSO 4 ) for 2 hours. The solvent was removed in vacuo and the residue was dried in a vacuum own at 40 °C for to days. This afforded 3.23 g (98 %) of 4-oxo-1 -(1 -(S)-phenyl-ethyl)- 2-(S)-phthalimidomethyl-piperidine pure without further purification (98 %). A mixture of 4-oxo-1-(1-(S)-phenyl-ethyl)-2-(S)-phthalimidomethyl- piperidine (17.28 g, 47.73 mmol), ferf-butylcyanoacetat (7.41 g, 52.17 mmol), sulphur (1.71 g, 52.17 mmol) and morpholine (8.31 g, 95.46 mmol) in ethanol (150 ml) was heated under an atmosphere of nitrogen at 50 °C. The volatiles were removed in vacuo and the residue was subjected to column chromatography on silica gel (heptane-ethyl acetate 5:1). The fractions consisting of a mixture of 5- and 7-isomer were collected and the solvent evaporated jn vacuo. The residue was purified on a reverse phase (C 18 ) column using a Flash 40 system. The residue was applied in a minimum volume of acetonitrile and eluted with 40 % acetonitrile in water containing 0.1 % trifluoroacetic acid. When the 5-isomer was collected the eluent was changed to 50 % acetonitrile in water with 0.1 % trifluoroacetic acid and the 7-isomer was collected. Yield of 2-amino-5-(S)-(1,3-dioxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-6-(1 -(S)-phenyl-ethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester was 7.96 g and yield of 2-amino-7-(R)-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(1-(S)- phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester was 3.72 g (47 % total). 2-Amino-5-(S)-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(1 -(S)-phenyl- ethyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (7.96 g, 15.4 mmol) and hydrazine hydrate (3.85 g, 77.0 mmol) in ethanol (250 ml) was stirred for 16 hours at room temperature. The solvent was removed in vacuo and the solid residue was extracted with diethyl ether (3 x 200 ml). The fractions were combined and the solvent removed vacuo to give 5.9 g (100 %) of 2-amino-5-(S)-aminomethyl-6- (1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester. 2-Amino-5-(S)-aminomethyl-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (0.55 g, 1.42 mmol) and triethylamine (396 μl, 2.84 mmol) was heated in acetonitrile (15 ml) under an atmosphere of nitrogen to 60 °C whereupon a solution of 2- chloromethyl-6-methoxy-benzoic acid methyl ester (0.32 g, 1.49 mmol) in acetonitrile (5 ml) was added dropwise over the course of 3 hours, keeping the reaction mixture at 60 °C. The reaction was allowed to cool to room temperature and was left for 16 hours before the solvent was evaporated vacuo. The product was purified by column chromatography (SiO 2 , Flash 40, ethyl acetate-petrol ether) to give 400 mg (53 %) of 2- amino-5-(S)-(7-methoxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-((S)-1 - phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. The titie compound was obtained as a trifluoroacetate in a similar way as described in example 101 using the last three steps. EXAMPLE 103 5-(S)-(4-Hvdroxy-1 -oxo-1 , 3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thienof2,3-c1pyridine-3-carboxylic acid 3-Hydroxy-2-methylbenzoic acid (0.5 g, 3.2 mmol) was dissolved in HPLC grade methanol (5 ml) and cooled to 0 °C under nitrogen. Acetyl chloride (5 ml) was added dropwise. Once the addition was complete, the ice bath was removed and the reaction mixture allowed warming to room temperature over a period of 18 hours. The reaction was complete by tic (R f =0.5, 1 :1 ethyl acetate/hexanes) and quenched with saturated sodium bicarbonate. The reaction mixture was concentrated, diluted with dichloromethane and water and the layers separated. The aqueous layer was extracted with dichloromethane (3x). The organic layers were combined, dried (MgSO ), filtered and concentrated in vacuo, which afforded 0.5 g (91 %) of 3-hydroxy-2-methylbenzoic acid methyl ester as a solid. 1 H-NMR (CDCI 3 ) δ 7.39 (dd, 1H, J = 8.1 Hz and J = 1.5 Hz), 7.09 (t, 1H, J = 8.1 Hz), 6.92 (dd, 1 H, J = 8.1 Hz and J = 1.2 Hz), 5.11 (bs, 1 H), 3.87 (s, 3H), 2.43 (s, 3H). 3-Hydroxy-2-methylbenzoic acid methyl ester (0.5 g, 3.01 mmol) in dichloromethane (15 ml) and Λ/,Λ/-diisopropylethylamine (1.57 ml, 9.03 mmol) was cooled to 0 °C under nitrogen. Chloromethyl methyl ether (0.46 ml, 6.02 mmol) was added dropwise and the reaction allowed warming to room temperature over a period of 18 hours. The reaction was judged to be 50 % complete by tic (1:2 ethyl acetate/hexanes, l 2 ) and therefore, Λ/,Λ/-diisopropylethylamine (1.57 ml, 9.03 mmol) was added, the reaction mixture cooled to 0 °C and chloromethyl methyl ether (0.46 ml, 6.02 mmol) added once more. The reaction mixture was warmed to room temperature and stirred for 5 hours. The reaction was quenched with water and the layers separated. The aqueous layer was extracted once with dichloromethane and the organic layers combined, dried (MgSO 4 ), filtered, and concentrated vacuo. The crude residue was purified by column chromatography (20 % ethyl acetate/hexanes) affording 0.44 g (69 %) of 3-methoxymethoxy-2-methyl-benzoic acid methyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 7.46 (dd, 1 H, J = 7.6 Hz and J = 1.2 Hz), 7.21 (dd, 1 H, J = 8 Hz and J = 1.2 Hz), 7.18 (d, 1 H, J = 8 Hz), 5.21 (s, 2H), 3.88 (s, 3H), 3.48 (s, 3H), 2.46 (s, 3H). To a mixture of 3-methoxymethoxy-2-methyl-benzoic acid methyl ester (0.44 g, 2.09 mmol) in carbon tetrachloride (10 ml) was added N- bromosuccinimide (0.39 g, 2.19 mmol) and 1 ,1 '-azo bis(cyclohexane- carbonitrile) (0.051 g, 0.21 mmol). The mixture was heated at reflux for 3 hours, at which time the reaction was judged complete by tic (1 :4 ethyl acetate/hexanes). The reaction mixture was cooled to room temperature and concentrated in vacuo to a solid. The solid was recrystallized from hexane leaving 0.44 g (82 %) of 2-bromomethyl-3-methoxymethoxy- benzoic acid methyl ester as a solid. 1 H-NMR (CDCI 3 ) δ 7.58 (dd, 1 H, J = 6.8 Hz and J = 2.4 Hz), 7.33-7.29 (m, 2H), 5.30 (s, 2H), 5.07 (s, 2H), 3.94 (s, 3H), 3.52 (s, 3H). To a stirred mixture of 2-amino-5-(S)-aminomethyl-6-(1-(S)-phenyl-ethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (0.24 g, 0.67 mmol) in acetonitrile (30 ml) was added N,N- diisopropylethylamine (0.16 ml, 0.93 mmol) under nitrogen. 2-Bromo- methyl-3-methoxymethoxy-benzoic acid methyl ester (0.16 g, 0.55 mmol) dissolved in acetonitrile, was added via syringe pump at a rate of 0.3 ml/hour. Once the addition was complete, the reaction mixture was stirred at room temperature for 24 hours. Tic analysis (1 :1 ethyl acetate/hexanes) indicated the reaction to be complete. The volatiles were removed in vacuo and the resultant oil dissolved in ethyl acetate/water. The layers were separated and the aqueous layer extracted with ethyl acetate (3x). The organic layers were combined, dried (MgSO ), filtered and the solvebt evaporated in vacuo, which afforded 0.34 g (100 %) of 2-amino-5-(S)-(4- methoxymethoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(1 -(S)-phenyl- ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester, which was used without further purification in the next step. 1 H-NMR (CDCI 3 ) δ 7.51 (d, 1H, J = 6.8 Hz), 7.42 (t, 2H, J = 7.6 Hz), 7.23- 7.17 (m, 5H), 5.93 (s, 2H), 5.25 (s, 2H), 4.23 (s, 2H), 4.12 (q, 1 H, J = 7.2 Hz), 3.94 (m, 1 H), 3.85 (q, 1 H, J = 6.4 Hz), 3.66 (d, 1 H, J = 16.4 Hz), 3.50 (s, 3H), 3.48-3.46 (m, 1 H), 3.20 (dd, 1 H, J = 14 Hz and J = 6 Hz), 2.94- 2.87 (m, 1 H), 2.60 (m, 1 H), 1.49 (s, 9H), 1.36 (d, 3H, J = 6.4 Hz); LC-MS: m/z: 564.1 [M+H] + . To a solution of 2-amino-5-(S)-(4-methoxymethoxy-1 -oxo-1 , 3-dihydro- isoindol-2-ylmethyl)-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester (0.34 g, 0.60 mmol) in dichloromethane (10 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (0.35 g, 1.8 mmol). The reaction mixture was stirred at room temperature for 18 hours and the solvent concentrated jn vacuo. The residue was dissolved in ethyl acetate and washed with water (2 x 20 ml) and brine (2 x 25 ml). The organic layer was dried (MgSO ), filtered and the solvent evaporated in vacuo. The residue was subjected to flash chromatography using a mixture of ethyl acetate/hexanes (1 :1) as eluent. The obtained residue was then subjected to chromatotron purification (1 % methanol/ dichloromethane) and later to another flash chromatography (20 % ethyl acetate/hexanes to 25 % ethyl acetate/hexanes) to obtain 210 mg (50 %) of 2-(fetf-butoxyoxalyl-amino)-5-(S)-(4-methoxymethoxy-1-oxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-6-(1 -(S)-phenyl-ethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.50 (s, 1 H), 7.51 (dd, 1 H, J = 6.8 Hz and J = 1.2 Hz), 7.42 (t, 2H, J = 8 Hz), 7.25-7.17 (m, 5H), 5.23 (s, 2H), 4.24 (q, 2H, J = 16.8 Hz), 4.08 (d, 1H, J = 16.8 Hz), 4.01 (dd, 1H, J = 14 Hz and J = 8.8 Hz), 3.89 (d, 1 H, J = 17.6 Hz), 3.82 (q, 1 H, J = 6.8 Hz), 3.56 (q, 1 H, J = 6.4 Hz), 3.51 (s, 3H), 2.28 (dd, 1 H, J = 14 Hz and J = 6.4), 2.98-2.92 (m, 1 H), 2.69 (d, 1 H, J = 17.2), 1.56 (s, 9H), 1.54 (s, 9H), 1.38 (d, 3H, J = 6.8 Hz); LC-MS: m/z: 692.5 [M+H] + . To a solution of 2-(fetf-butoxyoxalyl-amino)-5-(S)-(4-methoxymethoxy-1- oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(1-(S)-phenyl-ethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (0.16 g, 0.23 mmol) in formic acid (10 % in methanol, 5 ml total) was added 10% palladium on carbon (85 mg, source: Avacado) and the reaction mixture allowed to stir at room temperature. After 6 hours, tic (1 :1 ethyl acetate/hexanes) analysis indicated reaction complete. The reaction mixture was filtered through a pad of celite and concentrated in vacuo. The crude product was purified via flash chromatography (gradient: 3% isopropyl alcohol/dichloromethane to 5 % isopropyl alcohol/dichloromethane (in 1% increments of isopropyl alcohol)) to provide 0.1 1 g (82 %) of 2-(fetf-butoxyoxalyl-amino)-5-(S)-(4- methoxymethoxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.50 (bs, 1 H), 7.48 (dd, 1 H, J = 7.6 Hz and J = 0.8 Hz), 7.38 (t, 1 H, J = 8 Hz), 7.22 (dd, 1 H, J = 8 Hz and J = 0.8 Hz), 5.24 (s, 2H), 4.50 (q, 2H, J = 17.3 Hz), 4.02-3.90 (m, 2H), 3.74 (ddd, 2H, J = 34 Hz, J = 13.6 Hz and J = 5.6 Hz), 3.49 (s, 3H), 3.24 (m, 1 H), 2.97 (ddd, 1 H, J = 20 Hz, J = 4.4 Hz and J = 2.8 Hz), 2.50 (m, 1 H), 1.59 (s, 9H), 1.51 (s, 9H); LC-MS: m/z: 587.8 [M+H] + . 2-(ferf-Butoxyoxalyl-amino)-5-(S)-(4-methoxymethoxy-1 -oxo-1 ,3-dihydro- isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (0.11 g, 0.18 mmol) was dissolved in neat trifluoroacetic acid (4 ml) and stirred at room temperature for 48 hours. The reaction mixture was concentrated vacuo and the resultant solid washed with dichloromethane several times affording 100 mg (83 %) of the titie compound as a solid trifluoroaceatet. 1 H-NMR (DMSO-d 6 ) δ 12.29 (bs, 1 H), 10.13 (s, 1 H), 9.29 (bs, 1 H), 9.10 (bs, 1 H), 7.32 (t, 1 H, J = 7.6 Hz), 7.17 (d, 1 H, J = 7.2 Hz), 7.01 (d, 1 H, J = 8 Hz), 4.52 (d, 1H, J = 17.2 Hz), 4.40-4.22 (m, 3H), 4.05 (dd, 1 H, J = 14.4 Hz and J = 9.6 Hz), 3.90 (bs, 1 H), 3.69 (dm, 1 H), 3.22 (dm, 1 H), 2.80 (dm, 1 H); LC-MS: m/z: 432.2 [M+H] + . EXAMPLE 104 2-(S)-(Oxalyl-amino)-5-((4-phenoxy-benzylamino)methyl)-4,5,67- tetrahvdro-thienor2,3-c1pyridine-3-carboxylic acid A solution of 2-amino-5-(S)-aminomethyl-6-(1 -(S)-phenyl-ethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (500 mg, 1.29 mmol) and 4-phenoxybenzaldehyde (256 mg, 1.29 mmol) was heated to 50 °C in ethanol (50 ml) for 1 hour in the presence of molecular sieves (4 A, 5 ml). The reaction mixture was cooled on an ice bath before sodium borohydride (98 mg, 2.59 mmol) was added in three portions over 45 min. The cooling bath was removed and the reaction mixture was allowed to reach room temperature. The mixture was filtered through a plug of Celite and the filter cage was washed with dichloromethane (3 x 25 ml). The solvent was removed in vacuo and the residue was redissolved in ethyl acetate (50 ml), washed with sodium bicarbonate (50 ml) and dried (MgSO ). The solvent was removed in vacuo before the residue was redissolved in acetonitrile (20 ml). Triethylamine (130 mg, 1.29 mmol), di- fetf-butyl dicarbonate (282 mg, 1.29 mmol) and 4-(Λ/,Λ/-dimethyl- amino)pyridine (5 mg, cat.) was added and the reaction mixture was stirred for 16 hours at room temperature. The volatiles were removed vacuo and ethyl acetate (50 ml) was added and the solution was washed with saturated sodium bicarbonate (50 ml) and dried (MgSO 4 ). The crude product was purified by column chromatography (SiO 2 , petroleum ether- ethyl acetate (9:1)) to give 325 mg (38% overall) of 2-amino-5-(S)-((4- phenoxy-benzylamino)methyl)-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester. The titie compound was obtained as a trifluoroacetate in a similar way as described in example 96 using the last three steps. Oxalation: Standard procedure (16 hours, 82 %) Hydrogenolysis: standard procedure (Pd/C, 10% Pd, methanol-formic acid, 16 hours, ((10:1 )) (82% yield) TFA cleavage: Standard procedure. Yield 150 mg (87%). LC-MS m/z: 482 [M+H] + , R, = 1.87 min Calculated for C 24 H 23 N 3 O 6 S, 2x(C 2 HF 3 O 2 ) C, 47.40%; H, 3.55%; N, 5.92%; Found: C, 47.47%; H, 3.87%; N, 5.88%; EXAMPLE 105 5-(S)-((4-Acetylamino-benzylamino)-methyl)-2-(oxalyl-amino)-4,5,6,7- tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid The title compound was prepared as a trifluoroacetate in a similar way as described in Example 96 using 2-amino-5-(S)-aminomethyl-6-(1-(S)- phenyl-ethyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester and Λ/-(4-formyl-phenyl)acetamide as the starting material. Calculated for C 20 H 22 N 4 O 6 S, 1.5xC 2 HF 3 O 2 , 1.5xH 2 O C, 43.78%; H, 3.99%; N, 8.88%; Found: C, 44.20%; H, 4.43%; N, 8.75%; EXAMPLE 106 7-(S)-((Acetyl-(4-phenoxy-benzyl)amino)methyl)-2-(oxalyl-amino)-4,5,6,7- tetrahvdro-thienor2,3-c1pyridine-3-carboxylic acid A solution of 2-amino-7-(S)-aminomethyl-6-(1-(S)-phenyl-ethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic aicd fetf-butyl ester (500 mg, 1.29 mmol) and 4-phenoxybenzaldehyde (256 mg, 1.29 mmol) was heated to 50 °C in ethanol (50 ml) for 1 hour in the presence of molecular sieves (4 A, 5 ml). The reaction mixture was cooled on an ice bath before sodium borohydride (98 mg, 2.59 mmol) was added in three portions over 45 min. The cooling bath was removed and the reaction mixture was allowed to reach room temperature. The mixture was filtered through a plug of Celite and the filter cage was washed with dichloromethane (3 x 25 ml). The solvent was removed in vacuo and the residue was redissolved in ethyl acetate (50 ml), washed with sodium bicarbonate (50 ml) and dried (MgSO ). The solvent was removed in vacuo before the product was dissolved in dichloromethane (10 ml). The solution was cooled on an ice bath before di-isopropyl-ethyl amine (101 mg, 1.29 mmol) was added followed by drop wise addition of acetyl chloride (101 mg, 1.29 mmol) in dichloromethane (1 ml). The reaction mixture was stirred 1 hour at 0 °C and the solution was washed with sodium bicarbonate (10 ml) and dried (MgSO 4 ). The crude product was purified by flash column chromatography (SiO 2 , ethyl acetate-petrol ether 1 :3) to give 320 mg (41%) of 7-(S)- ((acetyl-(4-phenoxy-benzyl)amino)methyl)-2-amino-6-(1-(S)-phenyl-ethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid The titie compound was obtained as a trifluoroacetate in a similar way as described in example 96 using the last three steps. Oxalation: Standard procedure (Yield 69%) Hydrogenolysis and trifluoroacetic acid cleavage in one step, Standard procedure (Overall yield 6%) LC-MS m/z = 524 [M+H] + , R t = 2.58 min Calculated for C 2 eH 25 N 3 O 7 S, C 2 HF 3 O 2 , 0.5xH 2 O C, 52.01 %; H, 4.21 %; N, 6.50%; Found: C, 51.82%; H, 4.34%; N, 6.36%. EXAMPLE 107 7-(S)-((Acetyl-benzyl-amino)methyl)-2-(oxalyl-amino)-4,5 1 6,7-tetrahydro- thienor2,3-clpyridine-3-carboxylic acid A solution of 2-amino-7-(S)-aminomethyl-6-(1-(S)-phenyl-ethyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic aicd fetf-butyl ester (400 mg, 1.03 mmol) and benzaldehyde (105 mg, 1.03 mmol) was heated to 50 °C in ethanol (20 ml) for 1 hour in the presence of molecular sieves (4 A, 7 ml). The reaction mixture was cooled on an ice bath before sodium borohydride (78 mg, 2.06 mmol) was added in three portions over 45 min. The cooling bath was removed and the reaction mixture was allowed to reach room temperature. The mixture was filtered through a plug of Celite and the filter cage was washed with dichloromethane (3 x 25 ml). The solvent was removed in vacuo and the residue was redissolved in ethyl acetate (50 ml), washed with sodium bicarbonate (50 ml) and dried (MgSO 4 ). The solvent was removed in vacuo before the product was dissolved in dichloromethane (20 ml). The solution was cooled on an ice bath before di-isopropyl-ethyl amine (267 mg, 2.06 mmol) was added followed by drop wise addition of acetyl chloride (81 mg, 1.03 mmol) in dichloromethane (1 ml). The reaction mixture was stirred 1 hour at 0 °C before sodium bicarbonate (20 ml) was added. The mixture was extracted with dichloromethane (2 x 10 ml) and the combined organic fractions were dried (MgSO 4 ). The crude product was purified by flash column chromatography (petrol ether/ethyl acetate (3:1 )), which afforded 250 mg (46 %) of 7-(S)-((acetyl-benzyl-amino)methyl)-2-amino-6-(1-(S)-phenyl- ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester. The titie compound was obtained as a trifluoroacetate in a similar way as described in example 96 using the last three steps. Oxalation: Standard procedure (54%) Hydrogenolysis: Standard procedure (methanol-formic acid (10:1 )) Yield 38 mg (26%) Trifluoroacetic acid cleavage: Standard procedure 33 mg (80%) LC-MS m/z: 432 [M+H] + , R t = 1.52 min Calculated for C 2 oH 2 ιN 3 O 6 S x 1.5xC 2 HF 3 O 2 , 2xH 2 O C, 43.26%; H, 4.18%; N, 6.58%; Found: C, 43.19%; H, 3.86%; N, 6.46%. EXAMPLE 108 5-(S)-((1 , 1 -Dioxo-1 H-benzo. dlisothiazol-3-ylamino)methyl)-2-(oxalyl- amino)-4,5,67-tetrahvdro-thienof2,3-c1pyridine-3-carboxylic acid To a solution of (S)-2-amino-5-aminomethyl-6-(1-(S)-phenyl-ethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (1.0 g, 2.58 mmol) in dichloromethane (10 ml) at 0 °C was added N,N- diisopropylethylamine (0.54 ml, 5.16 mmol). A solution of 3-chloro- benzo[d]isothiazole 1 ,1-dioxide (0.52 g, 2.58 mmol) in dichloromethane (10 ml) was then added dropwise and stirred for 30 min. The solution was warmed to room temperature and washed with water and dried (MgSO ). The solvent was then removed in vacuo. The residue was taken into dichloromethane (15 ml) and imidazol-1-yl-oxo-acetic acid fetf-butyl ester (1.0 g, 5.16 mmol) was added. The solution was stirred for 2 hours. The solvent was removed vacuo. The residue was taken into ethyl acetate (100 ml). The solution was washed with 0.5 N hydrochloric acid solution, saturated sodium bicarbonate and brine, dried (MgSO 4 ) and filtered. The solvent was removed in vacuo. The residue was chromatographed using a mixture of 0-5% ethyl acetate/dichloromethane as eluent, which afforded 0.6 g (34 %) of 2-(ferf-butoxyoxalyl-amino)-5-(S)-((1,1 -dioxo-1 --benzo[d] isothiazol-3-ylamino)methyl)-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil 1 H-NMR (CDCI 3 ) δ 12.50 (s, 1 H), 794-7.92 (m, 1 H), 779-7.71 (m, 2H), 7.59-7.50 (m, 1 H), 7.38-7.27 (m, 4H), 6.86 (d, 1 H, J=4 Hz), 4.14 (d, 1 H, J=12 Hz), 3.95 (d, 1 H, J=17 Hz), 3.88 (q, 1 H, J=6 Hz), 370-3.62 (m, 1 H), 3.47 (t, 1 H, J=13 Hz), 3.34-3.24 (m, 1 H), 3.06 (dd, 1 H, J=17, 6 Hz), 2.53 (d, 1H, J=17 Hz), 1.62 (s, 9H), 1.61 (s, 9H), 1.44 (d, 3H, J=7 Hz). A solution of 2-(ferf-butoxyoxalyl-amino)-5-(S)-((1 , 1 -dioxo-1 H-benzo[d] isothiazol-3-ylamino)methyl)-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester (252 mg, 0.37 mmol) in tetrahydrofuran (12 ml) was passed through Raney Ni (0.95 g, 50% Raney Ni-Water washed with methanol (6 ml) and tetrahydrofuran (10 ml) and dried before use). The solvent was removed in vacuo. The residue was dissolved in acetic acid (7 ml) and hydrogenated with 10% Pd/C (250 mg) at 50 psi for 15 hours. The mixture was filtered and the filtrate was added to saturated sodium bicarbonate solution. The solution was then extracted with ethylacetate (3 x 100 ml). The extracts were combined and dried (MgSO 4 ). The solvent was removed in vacuo. The residue was washed with diethyl ether affording 156 mg (73 %) of 2-(ferf-butoxyoxalyl- amino)-5-(S)-((1 , 1 -dioxo-1 H-benzo[d] isothiazol-3-ylamino)-methyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ) δ 12.59 (s, 1 H), 794-7.90 (m, 1 H), 770-7.66 (m, 3H), 7.51 (s, 1 H), 4.11 (d, 1 H, J=12 Hz), 4.08 (q, 2H, J=17 Hz), 3.40 (dd, 1 H, J=12, 6 Hz), 3.26-3.18 (m, 1 H), 3.18 (d, 1 H, J=17 Hz), 2.55 (dd, 1 H, J=12, 6 Hz), 1.62 (s, 18H). LC-MS: R, = 3.58 min, m/z: 577 [M+H] + . A solution of 2-(ferf-butoxyoxalyl-amino)-5-(S)-((1 ,1 -dioxo-1 H-benzo[d] isothiazol-3-ylamino)methyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester (149 mg, 0.26 mmol) in 50 % trifluoroacetic acid/dichloromethane (1 ml) was left in an open flask for 60 hours. The volatiles were removed vacuo and the residue was washed with dichloromethane to yield 80 mg (54 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR (DMSO-de) δ 12.29 (s, 1 H), 9.80 (s, 1 H), 9.51 (bs, 2H), 8.19 (d, 1 H, J=5 Hz), 8.02-8.00 (m, 1 H), 7.89-7.84 (m, 2H), 4.46 (d, 1 H, J=16 Hz), 4.30 (d, 1 H, J=16 Hz), 3.96-3.80 (m, 3H), 3.30 (d, 1H, J=17 Hz), 2.93 (dd, 1 H, J=18, 10 Hz); LC-MS: R, = 0.68 min, m/z: 465 [M+H] + . EXAMPLE 109 5-(4-Benzyloxy-1 ,3-dioxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahvdro-thienor2,3-clpyridine-3-carboxylic acid The titie compound was prepared in a similar way as described in Example 52 as a trifluoroacetate. 1 H-NMR (400 MHz, DMSO-d 6 ) 8 12.31 (s, 1 H), 9.25 (bs, 2H), 7.80 (t, 1 H, J = 8 Hz), 7.59-7.32 (m, 7H), 5.37 (s, 2H), 4.42-4.21 (m, 2H), 3.95-370 (m, 3H), 3.4-3.2 (obscured by water, 1 H), 2.83-2.75 (m, 1 H) LC-MS: R t = 2.16 min, m/z: 536.1 [M+H] + EXAMPLE 110 5-(6-Methoxy-4-methoxycarbonyl-1 -oxo-1 ,3-dihvdro-isoindol-2-ylmethyl)-2- (oxalyl-amino)-4,5,6,7-tetrahvdro-thienor2,3-clpyridine-3-carboxylic acid To a solution of 2-amino-5-aminomethyl-6-(4-methoxy-benzyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (57.4 mg, 0.142 mmol) and diisopropyl ethylamine (49 μl, 0.28 mmol) in acetonitrile (20 ml) at room temperature was added 2-bromomethyl-5-methoxy- isophthalic acid dimethyl ester (3.00 g, 7.45 mmol). The solution was stirred for 16 hours and the solvent evaporated in vacuo. The residue was taken into ethyl acetate (50 ml) and washed with water (2 x 20 ml), 1 N hydrochloric acid (20 ml), brine, dried (MgSO ), filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1 :1) as eluent, which afforded 62 mg (71 %) of 2-amino-6-(4-methoxy-benzyl)-5-(6-methoxy-4- methoxycarbonyl-1-oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as a solid. 1 H-NMR δ (CDCI 3 ): δ 7.75 (d, 1 H, J = 2.4 Hz), 7.55 (d, 1 H, J = 2.4 Hz), 7.11 (bs, 2H), 6.74 (d, 2H, J = 8.0 Hz), 5.97 (s, 2H), 4.71 (d, 1 H, J = 18.4 Hz), 4.62 (d, 1 H, J = 18.4 Hz), 4.09 (m, 1 H), 3.93 (s, 3H), 3.92 (s, 3H), 3.80 (m, 1 H), 3.76 (s, 3H), 3.66-3.40 (m, 5H), 2.80 (d, 1 H, J = 17.2 Hz), 2.64 (d, 1 H, J = 17.2 Hz), 1.52 (s, 9H). To a stirred solution of 2-amino-6-(4-methoxy-benzyl)-5-(6-methoxy-4- methoxy-carbonyl-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (60 mg, 0.10 mmol) in tetrahydrofuran (1.0 ml) was added imidazol-1-yl-oxo-acetic acid fetf-butyl ester (60 mg, 0.30 mmol) in tetrahydrofuran (1.0 ml). The mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo. The residue was taken into ethyl acetate (20 ml) and washed with 0.5 N hydrochloric acid (2 x 10 ml), saturated sodium bicarbonate (2 x 10 ml) and brine (10 ml), dried (MgSO ) and filtered. The solvent was removed in vacuo and residue was chromatographed using a gradient ethyl acetate/hexane (10-25 %) as eluent, which afforded 40 mg (58 %) of 2-(ferf-butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-(6-methoxy- 4-methoxycarbonyl-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester as a solid. 1 H-NMR δ (CDCI 3 ): δ 12.54 (s, 1 H), 7.75 (d, 1 H, J = 2.4 Hz), 7.55 (d, 1 H, J = 2.4 Hz), 7.10 (d, 2H, J = 8.0 Hz), 6.74 (d, 2H, J = 8.0 Hz), 4.74 (d, 1 H, J = 18.4 Hz), 4.62 (d, 1 H, J = 18.4 Hz), 4.05-3.90 (m, 2H), 3.94 (s, 3H), 3.92 (s, 3H), 3.82-3.48 (m, 5H), 3.77 (s, 3H), 2.95 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 2.67 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 1.61 (s, 9H), 1.58 (s, 9H). To a solution of 2-(ferf-butoxyoxalyl-amino)-6-(4-methoxy-benzyl)-5-(6- methoxy-4-methoxycarbonyl-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester (38 mg, 0.055 mmol) in 10 % formic acid/methanol (1.0 ml) at room temperature under nitrogen was added 10 % Pd/C (38 mg). The mixture was stirred for 16 hours and the Pd/C was filtered off and the filtrate evaporated in vacuo. The residue was taken into dichloromethane (1.0 ml) poured into hexane. The precipitate was filtered off, affording 28 mg (82 %) of 2-(ferf-butoxyoxalyl-amino)-5-(6-methoxy-4-methoxycarbonyl-1 -oxo- 1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid ferf-butyl ester as a solid. 1 H-NMR δ (CDCI 3 ): δ 12.45 (s, 1H), 10.90 (s, 1 H), 10.69 (s, H), 7.73 (s, 1 H), 7.42 (s, 1H), 4.85 (bs, 2H), 4.65 (bs, 1 H), 4.42 (bs, 2H), 3.99 (bs, 2H), 3.96 (s, 3H), 3.89 (s, 3H), 3.35 (bs, 1 Hz), 3.21 (bs, 1 H), 1.62 (s, 9H), 1.56 (s, 9H). To a solution of trifluoroacetic acid (0.5 ml) and dichloromethane (0.5 ml) was added 2-(ferf-butoxyoxalyl-amino)-5-(6-methoxy-4-methoxycarbonyl- 1-oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid ferf-butyl ester (14 mg, 0.023 mmol). The solution was stirred at room temperature for 40 hours. The reaction mixture was poured into diethyl ether (20 ml). The precipitate was filtered off, which afforded 10 mg (75 %) of the titie compound as a solid trifluoroacetate. 1 H-NMR δ (DMSO-de): δ 12.28 (s, 1 H), 9.32 (s, 1 H), 9.10 (s, 1 H), 7.65 (d, 1H, J = 2.4 Hz), 7.50 (d, 1H, J = 2.4 Hz), 4.82 (d, 1H, J = 17.2 Hz), 4.65 (d, 1H, J = 17.6 Hz), 4.40 (d, 1H, J = 17.6 Hz), 4.30 (m, 1 H), 4.10 (dd, 1 H, J = 17.2 Hz and J = 5.2 Hz), 3.95 (s, 1 H), 3.89 (s, 6H), 3.85 (d, 1 H, J = 17.2 Hz), 2.81 (dd, 1 H, J = 18 Hz and J = 7.2 Hz). LC-MS: R t = 1.30 min; m/z: 504 [M+H] + EXAMPLE 111 2-(Oxalyl-amino)-5-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 /-/-benzordlisothiazol-2- ylmethyl)-47-dihvdro-5/-/-thienof2.3-c1pyridine-3-carboxylic acid and 2-(Oxalyl-amino)-7-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 /-/-benzordlisothiazol-2- ylmethyl)-47-dihvdro-5/-/-thieno[2,3-clpyridine-3-carboxylic acid To a solution of 2-aminomethyl-4-(2-spiro[1,3]dioxolane)-piperidine (193 mg, 1.12 mmol) and diisopropyl ethylamine (0.46 ml, 2.55 mmol) in acetonitrile (10 ml) cooled to 0 °C was added 2-chlorosulfonyl-benzoic acid methyl ester (278 mg. 1.18 mmol). The solution was stirred at 25 °C for 24 hours. Solvent was removed in vacuo and the residue was chromatographed using a mixture of ethyl acetate/hexane (1 :3) as eluent, which afforded 199 mg (51 %) of 2-(4-(2-spiro[1 ,3]dioxolane)piperidin-2- ylmethyl)-1 ,1 -dioxo-1 , 2-dihydro-1H-benzo[d]isothiazol-3-one as a solid. 1 H-NMR (CDCI 3 ): δ 7.99-7.96 (m, 1H), 7.66-7.53 (m, 3H), 5.01 (s, 1 H), 4.73 (dm, 1 H, J = 14.4 Hz), 4.06-3.93 (m, 6H), 3.25 (dd, 1 H, J = 12.6 Hz), 3.06 (td, 1H, J = 13.5 Hz and J = 3.6 Hz), 1.93 (dd, 1H, J = 14.1 Hz and J = 5.7 Hz), 1.87 (dd, 1 H, J = 14.1 Hz and J = 3.0 Hz), 1.76 (dd, 1 H, J = 13.5 Hz and J = 5.1 Hz). LC-MS: R t = 1.78; m/z: 339 [M+H] + . 2-(4-(2-Spiro[1 ,3]dioxolane)piperidin-2-ylmethyl)-1 ,1 -dioxo-1 , 2-dihydro-1 H- benzo[d]isothiazol-3-one (199 mg, 0.588 mmol) was dissolved in 2 M hydrochloric acid (12 ml) and the solution was heated to 50 °C for 24 hours. The volatiles were removed in vacuo and the residue (341 mg) was treated without further purification with saturated sodium carbonate (12 ml), dichloromethane (8 ml) and di-t-butyl dicarbonate (1.64 g, 7.5 mmol). The mixture was stirred at 35 °C for 3 days and extracted with dichloromethane (30 ml). The organic solution was washed with saturated sodium bicarbonate, brine, dried (MgSO 4 ), filtered and the solvent evaporated in vacuo. The residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1 :3) as eluent, which afforded 115 mg (50 %) of 4-oxo-2-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 H- benzo[d]isothiazol-2-ylmethyl)-piperidine-1 -carboxylic acid ferf-butyl ester as an oil. 1 H-NMR (CDCI 3 ): δ 8.06 (dd, 1 H, J = 6.0, 1.8 Hz), 7.95-7.80 (m, 3H), 5.02 (bs, 1 H), 4.35 (bs, 1 H), 3.91 (dd, 1 H, J = 15.0 Hz and J = 8.4 Hz), 378 (dd, 1 H, J = 14.7 Hz and J = 57 Hz), 3.53 (t, 1 H, J = 10.8 Hz), 2.74 (dd, 1 H, J = 15.0 Hz and J = 7.5 Hz), 2.60-2.38 (m, 3H), 1.32 (s, 9H). To a solution of 4-oxo-2-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 H-benzo[d]isothiazol-2- ylmethyl)-piperidine-1-carboxylic acid ferf-butyl ester (115 mg, 0.292 mmol) in absolute ethanol (5 ml) was added t-butyl cyanoacetate (57 μl, 0.41 mmol), sulfur (13 mg, 0.41 mmol) and morpholine (55 μl, 0.63 mmol). The solution was stirred at 50 °C for 14 hours. The solvent was evaporated in vacuo and the residue was chromatographed on silica gel column using a mixture of ethyl acetate/hexane (1 :4) as eluent, which afforded 100 mg (62 %) of 2-amino-5-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 H- benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester and 2-amino-7-(1 ,1 ,3-trioxo-1 ,3- dihydro-1 H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5/-/-thieno[2,3- c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester as a mixture. 1 H-NMR (CDCI 3 ): δ 8.10-8.00 (m, 1 H), 7.98-777 (m, 2.8H), 7.66-7.58 (m, 0.2H), 6.11 (s, 0.4H), 6.06 (s, 0.6H), 5.59 (m, 0.2H), 5.39 (t, 0.3H, J = 5.7 Hz) 5.23 (bs, 0.3H), 5.04 (bs, 0.4H), 4.77 (d, 0.4H, J = 14.4 Hz), 4.60 (d, 0.4H, J = 14.4 Hz), 4.45-4.18 (m, 1 H), 4.02-3.82 (m, 1.5H), 3.64 (dd, 0.5H, J = 14.7 Hz and J = 5.2 Hz), 3.30-2.60 (m, 2H), 1.54 (s, 7H), 1.53 (s, 2H), 1.26 (s, 7H), 1.21 (s, 2H). To a stirred solution of the above 2-amino-5-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 H- benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5/- -thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester and 2-amino-7-(1 , 1 ,3-trioxo-1 ,3- dihydro-1 H-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3- c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester mixture (100 mg, 0.18 mmol) in acetonitrile (7 ml) was added imidazol-1-yl-oxo-acetic acid tert- butyl ester (290 mg, 1.46 mmol) in acetonitrile (1 ml). The mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was taken into ethyl acetate. The solution was washed with 0.5 N hydrochloric acid solution, saturated sodium bicarbonate, brine, dried MgSO 4 ) and filtered. The solvent was removed in vacuo and the residue was chromatographed on silicagel using a mixture of ethyl acetate/hexane (1 :4) as eluent, which provided 98 mg (80 %) of a mixture of 2-(ferf-butoxyoxalyl-amino)-5-(1,1,3-trioxo-1,3-dihydro-1H- benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-fetf-butyl ester and 2-(ferf-butoxyoxalyl-amino)-7- (1 ,1 ,3-trioxo-1 ,3-dihydro-1/-/-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro- 5/-/-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester as a solid. 1 H-NMR (CDCI 3 ): δ 12.60 (s, 0.3H), 12.54 (s, 0.7H), 8.12-8.06 (m, 1H), 7.98-7.80 (m, 2.8H), 7.66-7.58 (m, 0.2H), 5.83 (bs, 0.1 H), 5.61 (t, 0.2H), 5.40-4.54 (m, 0.9H), 4.53-4.40 (m, 0.8H), 4.02-370 (m, 1.42H), 3.66 (dd, 0.58H, J = 14.7 Hz and J = 5.2 Hz), 3.30-2.99 (m, 3H), 1.68 (s, 6H), 1.62 (s, 6H), 1.60 (s, 6H), 1.31 (s, 4.5H), 1.25 (s, 4.5H); LC-MS: R t = 4.45; m/z: 678 [M+H] + . To a solution of trifluoroacetic acid (4 ml) and dichloromethane (2 ml) was added the mixture of 2-(ferf-butoxyoxalyl-amino)-5-(1 , 1 ,3-trioxo-1 ,3- dihydro-1/-f-benzo[d]isothiazol-2-ylmethyl)-4,7-dihydro-5/-/-thieno[2,3- c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester and 2-(ferf-butoxyoxalyl- amino)-7-(1 ,1 ,3-trioxo-1,3-dihydro-1/-/-benzo[d]isothiazol-2-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester (78 mg, 0.12 mmol). The solution was stirred at room temperature for 24 hours. The solvent was then evaporated in vacuo, which afforded 50 mg (72 %) of the titie compounds as a mixture of trifluoroacetates. 1 H-NMR (DMSO-de): δ 12.32 (s, 1 H), 975-9.20 (m, 2H), 8.40 (t, 1 H, J = 6.0 Hz), 8.22-8.02 (m, 3H), 5.03 (bs, 0.5H), 4.52 (d, 1 H), 4.38-4.10 (m, 2H), 3.88 (bs, 0.5H), 370-3.64 (m, 0.5H), 3.44-3.34 (m, 0.5H), 3.20-2.90 (m, 2H). LC-MS: R t = 1.28 min, m/z: 466 [M+H] + EXAMPLE 112 7-(R)-Carbamoyl-2-(oxalyl-amino)-4,5.67-tetrahvdro-thienof2,3-c1pyridine- 3-carboxylic acid To a solution of 2-(S)-4-oxo-piperidine-1 ,2-dicarboxylic acid 1-fetf butyl ester (18.4 g, 75.6 mmol) and triethylamine (12.65 mL, 90.79 mmol) in tetrahydrofuran (50 mL) cooled to -20°C was added isobutylchloro- formate (11.81 mL, 90.79 mmol) and the mixture was stirred for 10 min at -20°C before a 25 % solution of ammonia in water (100 mL) was added. The temperature was kept at -20°C for 30 min before the cooling bath was removed and the reaction mixture was allowed to reach room temperature and stirring was continued for another hour. The reaction mixture was extracted with ethyl acetate (6 x 50 mL) and the combined organic phases were dried (MgSO 4 ). The solvent was removed in vacuo and the residue was purified by column chromatography (SiO 2 , Flash 40, ethyl acetate) to give 8.51 g (46 %) of 2-(S)-carbamoyl-4-oxo-piperidine-1 -carboxylic acid 1 -ferf-butyl ester. A solution of 2-(S)-carbamoyl-4-oxo-piperidine-1 -carboxylic acid 1-ferf butyl ester (3.51 g, 14.48 mmol), fetf-butyl cyanoacetate (2.04 g, 14.48 mmol), sulphur (0.464 g, 14.48 mmol) and diisopropyl ethylamine (2.5 mL, 14.48 mmol) in methanol (20 mL) was heated 16 hours at 40°C under N . The volatiles were removed vacuo and the residue was purified using column chromatography (SiO 2 , Flash 40, petroleum ether/ethyl acetate 3:1) to give 1.33 g (23%) of a mixture 2-amino-5-(S)-carbamoyl-4,7- dihydro-5/-/-thieno[2,3-c]pyridine-3,6-di-carboxylic acid di-ferf-butyl ester and 2-amino-7-(R)-carbamoyl-4,7-dihydro-5/-/-thieno[2,3-c]pyridine-3,6-di- carboxyϊic acid di-ferf-butyl ester isomers. 0.5 g (1.25 mmol) of the above mixture was dissolved dichloromethane (10 mL) and imidazole-1-yl-oxo-acetic acid ferf-butyl ester (0.74 g, 3.77 mmol) and triethylamine (0.525 mL, 3.77 mmol) was added. The reaction mixture was stirred for 16 hours at room temperature before the volatiles were removed in vacuo. The residue was purified by column chromatography (SiO 2 , Flash 40, petroleum ether/ethyl acetate (4:1)) too give 75 mg (11 %) of 2-(fetf-butoxyoxalyl-amino)-7-(/ ; ?)-carbamoyl-4,7- dithydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester. This was dissolved in a mixture of trifluoacetic acid/dichloromethane (1 :1) (10 mL) and stirred for 16 hours at room temperature before the solvent was removed in vacuo. The residue was recrystallized from methanol to give 24 mg (39%) of the title compound. LC-MS; R t = 1.56 min, m/z: 314 [M+H] + Calculated for CnHnNsOβS, 0.25xC 2 HF 3 O 2 , 075xH 2 O C, 38.88 %; H, 3.62 %; N, 11.83 %; Found: C, 38.92 %; H, 3.92 %; N, 11.81 %. EXAMPLE 113 2-(Oxalyl-amino)-5-(S)-(2-oxo-tetrahvdro-thiophen-3-ylcarbamoyl)-4,5,6,7- tetrahvdro-thienor2,3-c1pyridine-3-carboxylic acid A solution of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,5-(S),6-tri- carboxylic acid 3,6-di-ferf-butyl ester (0.30 g, 0.75 mmol) and triethylamine (0.21 mL, 1.51 mmol) in tetrahydrofuran (10 mL) was cooled to -20°C before isobutyl chloroformate (0.103 mL, 0.75 mmol) was added. The reaction mixture was stirred 15 min at -20°C before homocystein hydrochloride (116 mg, 0.75 mmol) was added. The cooling bath was removed and the reaction mixture was left for 16 hours at room temperature. The solvent was removed vacuo and the residue was subjected to column chromatography (SiO 2 , Flash 40, heptane/ethyl acetate 2: 1 ) to give 212 mg (56%) of 2-amino-5-(S)-(2-oxo-tetrahydro- thiophen-3-ylcarbamoyl)-4,7-dihydro-5/- -thieno[2,3-c]pyridine-3,6- dicarboxylic acid di-ferf-butyl ester A solution of 2-amino-5-(S)-(2-oxo-tetrahydro-thiophen-3-ylcarbamoyl)- 4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-ferf-butyl ester (200 mg, 0.40 mmol), imidazole-1-yl-oxo-acetic acid fetf-butyl ester (235 mg, 1.20 mmol) and triethylamine (168 μL, 1.20 mmol) in dichloromethane (10 mL) was stirred for 16 hours at room temperature before the solvent was removed vacuo. The residue was purified by column chromatography (SiO 2 , Flash 40, heptane/ethyl acetate 2:1) to give 250 mg (100%) of 2-(fetf-butoxyoxalyl-amino)-5-(S)-(2-oxo- tetrahydro-thiophen-3-ylcarbamoyl)-4,7-dihydro-5/-/-thieno[2,3-c]pyridine- 3,6-dicarboxylic acid di-fetf-butyl ester. This was dissolved in a mixture of trifluoroacetic acid/dichloromethane (1 :1) (3 mL) and stirred for 16 hours at room temperature before diethyl ether (6 mL) was added. The precipitate was filtered off and washed with diethyl ether to give 172 mg (81 %) of the titie compound as a solid trifluoroacetate. LC-MS; R, = 0.41 min, m/z: 414 [M+H] + Calculated for Ci 5 H 15 N 3 O 7 S 2 , 1.5xC 2 HF 3 O 2 , H 2 O; C, 35.88 %; H, 3.10 %; N, 6.97 %; Found: C, 35.91 %; H, 3.54 %; N, 6.97 %. EXAMPLE 114 2-(Oxalyl-amino)-5-(S)-phenylcarbamoyl-4,5,6,7-tetrahvdro-thieno[2,3- clpyridine-3-carboxylic acid A solution of 2-amino-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3,5-(S),6- tricarboxylic acid 3,5-di-ferf-butyl ester (300 mg, 0.75 mmol) and triethylamine (210 μL, 1.51 mmol) in tetrahydrofuran (10 mL) was cooled to -20°C before isobutylchloroformate (103 mg, 0.75 mmol) was introduced. The reaction mixture was stirred for 20 min before aniline (70 mg, 0.75 mmol) was added. The cooling bath was removed and the reaction was left for 16 hours at room temperature before the solvent was removed in vacuo. The residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was dried (MgSO 4 ) and the solvent was removed in vacuo. The residue was dissolved in dichloromethane (10 mL) and imidazole-1-yl-oxo-acetic acid ferf-butyl ester (443 mg, 2.26 mmol) and triethylamine (315 μL, 2.26 mmol) was added. The reaction mixture was stirred 16 hours at room temperature before the solvent was removed in vacuo. The residue was purified by column chromatography (SiO 2 , Flash 40, heptane/ethyl acetate (3:1) to give 250 mg 2-(ferf-butoxyoxalyl-amino)-5-(S)-phenylcarbamoyl-4,7- dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester. 2-(ferf-Butoxyoxalyl-amino)-5-(S)-phenylcarbamoyl-4,7-dihydro-5/-/- thieno[2,3-c]pyridine-3,6-dicarboxylic acid di-fetf-butyl ester was dissolved in a mixture of trifluoroacetic acid/dichloromethane (1 :1) (3 mL) and stirred for 16 hours at room temperature before diethyl ether (6 mL) was added. The precipitate was filtered off and washed with diethyl ether to give 155 mg (41 %) of the titie compound as a solid trifluoroacetate. LC-MS; R t = 0.86 min, m/z: 390 [M+H] + Calculated for C 17 H 15 N 3 O6S, 1.5xC 2 HF 3 O 2 , H 2 O; C, 41.53 %; H, 3.22 %; N, 7.26 %; Found: C, 41.77 %; H, 3.29 %; N, 7.28 %. EXAMPLE 115 2-(Oxalyl-amino)-7-(R)-phenylcarbamoyl-4,5,6,7-tetrahydro-thienor2,3- clpyridine-3-carboxylic acid To a solution of 2-(S)-4-oxo-piperidine-1 ,2-dicarboxylic acid 1 -ferf butyl ester (2.06 g, 8.47 mmol) and triethylamine (1.42 mL, 10.16 mmol) in tetrahydrofuran (20 mL) cooled to -20°C was added isobutylchloroformate (1.39 g, 10.16 mmol) and the mixture was stirred for 10 min at -20°C before aniline (946 mg, 10.16 mmol) was added. The cooling bath was removed and the reaction mixture was stirred for 16 hours at room temperature before the solvent was removed vacuo. The residue was divided between water (50 mL) and ethyl acetate (50 mL). The organic phase was washed with saturated sodium chloride (25 mL) and dried (MgSO 4 ). After filtration and concentration vacuo the residue was purified using column chromatography (SiO 2 , Flash 40, petroleum ether/ethyl acetate 5:1) to give 1.3 g (48%) of 4-oxo-2-(S)-phenyl- carbamoyl-piperidine-1 -carboxylic acid ferf-butyl ester. A solution of 4-oxo-2-(S)-phenylcarbamoyl-piperidine-1 -carboxylic acid ferf-butyl ester (1.3 g, 4.08 mmol), ferf-butylcyanoacetate (0.58 g, 4.08 mmol), sulphur (0.133 g, 4.08 mmol) and diisopropyl ethylamine (0.7 mL, 4.08 mmol) in methanol (10 mL) was heated under nitrogen to 40 °C for 16 hours before the solvent was removed in vacuo. The residue was subjected to column chromatography (SiO 2 , Flash 40, petroleum ether/ethyl acetate 6:1 ) to give 0.70 g (36%) of a mixture of 2-amino-5-(S)- phenylcarbamoyl-4,7-dihydro-5/-/-thieno[2,3-c]pyridine-3,6-di-carboxylic acid di-fetf-butyl ester and 2-amino-7-(R)-phenylcarbamoyl-4,7-dihydro- 5/- -thieno[2,3-c]pyridine-3,6-di-carboxylic acid di-fetf-butyl ester isomers. The above mixture was dissolved in dichloromethane (20 mL) and imidazole-1-yl-oxo-acetic acid fetf-butyl ester (872 mg, 4.44 mmol) and triethylamine (618 μL, 4.44 mmol) was added. The reaction mixture was stirred 16 hours before the solvent was removed in vacuo and the residue was subjected to column chromatography (SiO 2 , Flash 40, petroleum ether/ethyl acetate 5:1) to give 0.50 g (56%) as a mixture of 2-(ferf- butoxyoxalyl-amino)-5-(S)-phenylcarbamoyl-4,7-dihydro-5/- -thieno[2,3- c]pyridine-3,6-di-carboxylic acid di-fetf-butyl ester and 2-(ferf-butoxyoxalyl- amino)-7-(R)-phenylcarbamoyl-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-di- carboxylic acid di-fetf-butyl ester 300 mg of the mixture was dissolved in a mixture of trifluoacetic acid/dichloro-methane (1 :1) (6.0 mL) and the solution was stirred for 16 hours at room temperature before the solvent was removed in vacuo. The residue was purified on preparative HPLC to give 70 mg (34%) of the title compound as a solid trifluoroacetate. LC-MS; R t = 0.95 min, m/z: 390 [M+H] + Calculated for Cι 7 H 15 N 3 O 6 S, C 2 HF 3 O 2 , H 2 O; C, 43.77 %; H, 3.48 %; N, 8.06 %; Found: C, 43.92 %; H, 3.44 %; N, 7.97 %. EXAMPLE 116 5-( ),7-(R)-Bis-benzyloxymethyl-2-(oxalyl-amino)-4,5,67-tetrahydro- thienof2 1 3-clpyridine-3-carboxylic acid Benzyloxyacetaldehyde (0.90 g; 6.0 mmol) and dimethyl (2- oxomethyl)phosphonate (1.0 g; 6.0 mmol) were dissolved in a mixture of tetrahydrofuran (25 ml) and water (20 ml). 1N Aqueous potassium hydroxide (6 ml) was added and the mixture was stirred for 30 min. Dichloromethane (50 ml) was added and the organic phase was separated, dried (MgSO 4 ) and evaporated in vacuo leaving 5- benzyloxypent-3-en-2-one. 1 H-NMR: 2.25 (s, 3H); 4.19 (dd, 2H); 4.55 (s, 2H); 6.34 (dt; 1 H); 6.70 (dt, 1 H); 7.26 (m, 5H). 5-benzyloxypent-3-en-2-one was dissolved in methanol (5 ml) and ammonium acetate (13 mmol, 1.03 g) was mixted together with benzyloxyacetaldehyde (1.8 g; 12 mmol) and acetic acid (0.69 ml) and the mixture was stirred for 2 days. The solvent was removed in vacuo and the residue was chromatographed on silica using gradient elution from 100 % dichloromethane to 100 % ethyl acetate. A fraction (411 mg) contained (according to LC-MS; m/z 340.4) 2,5-di(benzyloxymethyl)-4-piperidone in an impure state was isolated. The crude mixture was dissolved in ethanol (3 ml) and ferf-butylcyanoacetate (400 mg), sulfur (100 mg) and triethylamine was added and the mixture was stirred at room temperature overnight. The mixture was filtered and the solvent removed in vacuo. The residue was chromatographed on silica in a mixture of dichloromethane/(7% of 25% aqueous ammonia in ethanol) (40:1), which afforded 0.14 g of 2-amino-5-(R),7-(/ : ?)-bis-benzyloxymethyl-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. LC-MS: R t : 6.03 min; m/z: 495.2 [M+H] + 2-amino-5-(R),7-(/ : ?)-Bis-benzyloxymethyl-4,5,67-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid fetf-butyl ester (0.14 g; 0.28 mmol) was dissolved in dichloromethane (5 ml) and treated with imidazol-1-yl-oxo- acetic acid ferf-butyl ester (0.1 g; 0.5 mmol) and triethylamine (70 μl; 0.5 mmol), and stirred overnight, washed with water, dried (MgSO ) and the solvent removed in vacuo. The residue was chromatographed on silica using ethyl acetate/dichloromethane (1 :3) as eluent. The residue was treated with trifluoroacetic acid (0.5 ml) in dichloromethane (0.5 ml) and stirred for 4 hours. Evaporation of the solvent in vacuo afforded 37 mg of the title compound. LC-MS: R t : 4.74 min; m/z: 511.4 [M+H] + . EXAMPLE 117 6-Benzyl-2-(oxalyl-amino)-5-(1.1 ,3-trioxo-1.3-dihvdro-1 ,6- benzord1isothiazol-2-ylmethyl)-4,5,6,7-tetrahvdro-thienor2,3-c1pyridine-3- carboxylic acid 1-Benzyl-4-oxo-piperidine-2-carboxylic acid ethyl ester (2.9 g; 11.1 mmol) (prepared in a similar way as described in "GENERAL CHIRAL SYNTHESIS" for 4-OXO-1 -((S)-1-phenyl-ethyl)-piperidine-(R)-2-carboxylic acid ethyl ester using benzylamine instead of l-(S)-phenethylamine) was dissolved in abs. ethanol (50 ml) and sulfur (0.35 g, 11.1 mmol), triethylamine (1.6 ml, 11.1 mmol), and ferf-butylcyanoacetate (1.7 g, 11.1 mmol) were added and the mixture was stirred 2 days at room temperature. The solvent was removed in vacuo and the residue was chromatographed on silica using a mixture of ethyl actetate/heptane (1 :4) as eleuent leaving a mixture (700 mg; 1 :1 based on NMR) of 2-amino-6- benzyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3,7-dicarboxylic acid 3-fetf- butyl ester-7-ethyl ester and 2-amino-6-benzyl-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3,7-dicarboxylic acid 3-fetf-butyl ester 5-ethyl ester which was used in the next step without separation. To this mixture was added tetrahydrofuran (5 ml) and lithium borohydride (1.1 ml of a 2M solution in tetrahydrofuran) and the mixture was stirred 18 hours. More lithium borohydride (5.0 ml of a 2M solution in tetrahydrofuran) was added and the mixture stirred for an additiona 4 days. Ethyl acetate (10 ml) was added dropwise and after 1 hour the mixture was poured onto water (100 ml) and extracted with dichloromethane (2 x 100 ml) and chromatographed on silica (using ethylacetate/heptane 1 :1 as eluent), which afforded a mixture of 2-amino-6-benzyl-7-hydroxymethyl-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid ferf-butyl ester and 2- amino-6-benzyl-5-hydroxymethyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3-carboxylic acid ferf-butyl ester (in total 187 mg). To this mixture was added dry tetrahydrofuran (10 ml), 2,3-dihydro-1 ,2-benzisothiazol-3-one- 1,1-dioxide (100 mg; 0.55 mmol), triphenylphosphine (144 mg 0.55 mmol) and the mixture was cooled with ice. Diethyl azodicarboxylate (86 μl) was added and the mixture was stirred overnight at room temperature. The solvent was evaporated in vacuo and the residue was chromatographed on silica using a mixture of ethyl acetate/heptane (1 :1) as eluent leaving 94 mg of 2-amino-6-benzyl-5-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 ,6- benzo[d]isothiazol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester. 1 H-NMR: (CDCI3): 1.52 (s, 9H); 2.75 (dd, 1H); 2.90 (dd, 1H); 3.55 (d, 1H); 3.72 (m, 4H); 3.94 (d, 1 H); 4.12 (d, 1 H); 5.97 (s, 2H); 714-737 (m, 5H); 7.80-8.03 (m, 4H). LC-MS: R, 5.47 min, m/z: 540.4 [M+H] + 2-Amino-6-benzyl-5-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 ,6-benzo[d]isothiazol-2- ylmethyl)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert- butyl ester (94 mg; 0.17 mmol) was dissolved in dichloromethane (5 ml) and treated with imidazol-1-yl-oxo-acetic acid ferf-butyl ester (0.07 g; 0.3 mmol) and triethylamine (49 μl; 0.3 mmol), and stirred overnight, washed with water, 1N aqueous citric acid, dried (MgSO ) and the solvent removed in vacuo leaving 104 mg of 2-(fetf-butoxyoxalyl-amino)-6-benzyl- 5-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 ,6-benzo[d]isothiazol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid fetf-butyl ester as an oil. LC-MS : R t : 5.50 min, m/z: 668.6 [M+H] + 2-(ferf-Butoxyoxalyl-amino)-6-benzyl-5-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 ,6- benzo[d]isothiazol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid fetf-butyl ester (100 mg; 0.15 mmol) was treated with trifluoroacetic acid (1 m) in dichloromethane (4 ml) and stirred for 2 days. Evaporation of the solvent in vacuo afforded 90 mg of the title compound as a solid trifluoroacetate. Calc. for C 25 H 2 ιN 3 O 8 S 2 , 1.5xC 2 HF 3 O 2 , 0.5xH 2 O C, 4572%; H, 3.22%; N, 571 %. Found: C, 45.48%; H, 3.46%; N, 5.72% LC-MS: R t : 4.16 min; m/z: 556.2 [M+H] + EXAMPLE 118 Crystallisation of protein and protein-inhibitor complexes Co-crystallization of PTP1B with inhibitors; A 6-10 mg/ml preparation of PTP1 B in 10 mM Tris pH 7.5, 25 mM NaCI, 0.2 mM EDTA and 3 mM DTT, was used for crystallization. Crystals were grown by the sitting as well as the hanging drop vapor diffusion methods. A 1 :10 (PTP1 B:inhibitor) molar ratio mixture was prepared at least one hour prior to crystallization. Two μl of PTP1 B-inhibitor solution was mixed with 2 μl reservoir solution consisting of: 0.1 M Hepes buffer pH 7.5, 0.3- 0.4 M Na-acetate or Mg-acetate, 12-16% Peg 8000 and/or 4% glycerol. The reservoir volume was 1 ml. Crystals grew to the size of 0.3-0.6X0.1- 0.3X0.1-0.3 mm over 2-3 days. Data collection. All crystal data collections were performed at 100 K. The following cryo conditions were used: to the hanging or sitting drop 3 μl of 50% glycerol (containing 0.5 mmol inhibitor) were added. The crystal was removed from the drop after 5-30 min. and transferred to 50% glycerol (containing 0.5 mmol inhibitor) and rapidly flash frozen. Data were collected using a mar345 image plate either at the MAX-lab synchrotron facilities in Lund (Sweden) or in-house equipped with a rotating anode (RU300) and Osmic multilayer mirror system. Typically a 1° oscillation was used for 60 images data sets in the resolution range 2.7- 1.8 A were obtained. The space group was determined to be P3121 for all crystals used. Refinements. As P3121 contains a polar axis and, thus, possesses more than one indexing possibility, a molecular replacement solution using Amore [ref] solution was found prior to the refinements. A high resolution PTP1 B structure was used as a starting model, with ligand and water molecules omitted from the structure. All refinements were performed with * Xplor. v. 3.851 [MSI]. Interchanging cycles of model building using X-build [MSI] and refinement were performed. The 2Fo-Fc maps were inspected by the use of X-ligand [MSI] at a 1.3 sigma level for densities that could correspond to the structures of the inhibitors. In all cases a well-suited inhibitor electron density was identified in the active site pocket, see figures 1-4. No other densities were identified to fit the inhibitors. Water molecules were inserted using the X-solvate program [MSI]. EXAMPLE 119 Coupling of 2-(oxalyl-amino)-4,5,6,7-tetrahvdro-thieno[2,3-c1pyridine-3- carboxylic acid to Epoxy-activated Sepharose 6B. This example describes the preparation of an immobilized compound suited for affinity chromatographic purification of PTPases (eg PTP1 B or T-cell PTP). 3.5 g Epoxy-activated Sepharose 6B (Pharmacia Biotech) was prepared for coupling according to the manufacturers directions, and divided into 3 portions (3 x 8 ml gel-suspension, corresponding to 4 ml drained gel each). 8 ml portions of 2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3-carboxylic acid dissolved to 10, 1 and 0.1 mM in a 0.2 M sodium carbonate coupling buffer pH 9 were mixed with the gel suspensions and agitated gently overnight at room temperature. Exces ligand was washed away, the remaining active groups were blocked and the product was washed extensively at alternating pH, all according to the the manufacturers directions. The products were stored refrigerated in 0.1 M acetate pH 4.0 containing 0.5 M sodium chloride. Significant inhibition of PTP1 B was demonstrated in the 20 μmole ligand/ml gel preparation, when diluted to 1 μl drained gel/ml. EXAMPLE 120 Affinity purification of PTP1 B using the compound 2-(oxalyl-amino)- 4,5,6,7-tetrahvdro-thieno[2,3-c1pyridine-3-carboxylic acid coupled to Epoxy-activated Sepharose 6B. This example describes the affinity chromatographic purification of a PTPase. 2 ml of the product with 20 μmole ligand/ml described in example 55 was loaded into a 1.6 cm diameter column and eguilibrated with a buffer (buffer A) containing 20 mM L-histidine 1 mM EDTA 7 mM Mercaptoethanol 100 mM Sodium chloride and adjusted to pH 6.2 with 1 M HCI. 1.5 mg conventionally purified PTP1 B in 5 ml buffer A, was applied to the column at 0.5 ml/min followed by a wash with 10 ml buffer A. UV absorbing material without PTPase activity, corresponding to approx. 10 % of the totally applied material, passed through the column. The flow direction was reversed, the flow increased to 2 ml/min and linear gradient elution started with a combined salt and pH gradient for 20 minutes using buffer B containing 20 mM L-histidine 1 mM EDTA 7 mM Mercaptoethanol 1 M Sodium chloride and adjusted to pH 9.0 with 1 M NaOH. Maximum elution took place at approx. 32 % buffer B (0.39 M NaCI and pH 6.8) in a broad peak. The total activity yield in the elution peak was 70 %, and the specific activity of the enzyme was improved by a factor 1.4. EXAMPLE 121 Use of compounds of the invention to identify substrates that are specifically dephosphorylated by PTPases that are inhibited by the compounds of the invention or by other PTPases. The compounds of the invention are unique tools for identification of cellular substrates of the PTPases that are inhibited by the compounds of the invention. Substrates are herein defined as cellular proteins that (i) are phosphorylated on tyrosine residues, (ii) are dephosphorylated by PTPases that are inhibited by compounds of the invention or by other PTPases. If said substrates are dephosphorylated by PTPases that are inhibited by compounds of the invention, administration of the compounds of the invention will result in partial or total prevention of dephosphorylation of said substrates. As a result, a concomitant prolonged or increased activation may be observed of the signal transduction pathway (for definition, vide infra) in which said substrate is involved. Non-limiting examples of substrates are: the insulin receptor β subunit, IRS-1 , IRS-2, IRS-3, IRS-4, JAK1, JAK2, shc-2, grb-2 (Hunter, Cell 100: 113-127 (2000)). Importantly, the compounds of the invention can also be used to identify novel substrates. When the compounds of the invention have been used to identify the substrates of the PTPases that are inhibited by the compounds of the invention, a person skilled in the arts will be able to use this knowledge to establish animal models that will reflect a human condition or disease in which a compound of the invention will be indicated. Non-limiting example of the usefulness of said compounds of the invention will be in the following disease areas: diabetes, obesiittyy y cancer and conditions with unwarranted platelet aggregation. x- To identify the substrates of the PTPases that are inhibited by the substrates of the invention the following methods may be employed. Whole animals and/or primary cells and/or cell lines that represent the target organ or tissue may be used for these experiments. Non-limiting examples of animals are: ob/ob mice (worldwide web @ jax.org); db/ύb mice; Zucker obese rats. Non-limiting examples of target tissues or organs are: skeletal muscle, liver, adipose tissue, pancreas, the spleen, the bone marrow. Non-limiting examples of cell lines are: Chinese hamster ovary (CHO) cells (CHO-K1 - American Type Culture Collection (ATCC) Number CCL-61), Baby Hamster Kidney (BHK) cells (ATCC Number CRL- 1632), HepG2 cells (ATCC Number HB-8065), C2C12 cells (ATCC Number CRL-1772), L6 cells (ATCC Number CRL-1458), RD cells (ATCC Number CCL-136). Said cells can either be unmanipulated or fransfected transiently or permanently with plasmid vectors that encode proteins or substrates. Non-limiting example of a plasmid that allows expression in mammalian cells are: pcDNAI and pcDNA3 (worldwode web @ invitrogen.com). Non-limiting examples of proteins or substrates that are fransfected into said cell lines are: the insulin receptor, the IGF-I receptor, the EGF-R receptor, the PDGF receptor, IRS-1 , IRS-2, IRS-3, IRS-4, p56Lck; Jak1 , Jak2 (Hunter, supra). The analysis consists of the following steps: (A) stimulation of signal transduction pathways with and without the presence of the compounds of the invention. Signal transduction pathways are herein defined as a series of cellular processes that are initiated by a triggering event (such as stimulation of a tissue or cell by a hormone and/or a cytokine and/or cell-cell interaction and/or cell-cell substratum interaction) leading to various cellular effects including metabolic effects, cell differentiation and cell proliferation (Hunter, supra). Non-limiting examples of signal transduction pathways include: the insulin signaling pathway; the leptin signalling pathway; thrombin signalling pathway; the erythropoietin signaling pathway; the epidermal growth factor signaling pathway. Non-limiting examples of the effects of stimulating signal transduction pathways: glucose uptake; glycogen synthesis; cell proliferation; cell differentiation; platelet aggregation. (B) Analysis and identification of substrates that show increased (or decreased) phosphorylation on tyrosine residues after administration of the compound of the invention in comparison with controls that did not receive the compound. Step A. Stimulation of signal transduction pathways. As a non-limiting example, insulin (concentration range: 0.1 to 100 nM, final concentration) is administered to primary hepatocytes in tissue culture plates. The compounds of the invention (concentration range: 10 nM to 100 μM) are administered to half of the plates, with the other plates acting as controls. The plates are incubated at 37 °C for various time periods: Typically for 0, 1 , 2, 5, 15, 30 and 60 mins. Following this stimulation, the plates are treated as follows: The medium is rapidly aspirated and the cells washed twice with ice-cold PBS. Two milliliters of ice-cold lysis buffer (see below) is added and the plates are placed on ice for 2 minutes after which the cells are scraped off using a cell scraper ('rubber policeman'). The lysates are placed at 4 °C at a rotary shakerr. Dithiotreitol is added to a final concentration of 10 mM, and the lysates are centrifuged at 20,000 r.p.m.. Aliquots of the supernatants, i.e. lysates, are stored at -80 °C until further use. Lysis buffer - for a total of 20 ml add the following 0.8 ml of 500 mM Tris-CI, pH 7.4 0.2 ml of 100 mM EDTA 2.0 ml of 1 M NaCI 2.0 ml of 10 % (vol/vol) Triton X-100 80 μl of 250 mM PMSF 2 μl of 10 mg/ml aprotinin 20 μl of 1 mg/ml leupeptin 5 mM 100 mM iodoacetate 11.88 ml demineralized water Step B. Analysis and identification of substrates that show increased (or decreased) phosphorylation on tyrosine residues after administration of the compound of the invention in comparison with controls that did not receive the compound. As a non-limiting example, said lysates are subjected to two- dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by detection of proteins that are phosphorylated on tyrosine residues (pTyr) by western blotting, techniques well-known to those skilled in the art (Marcus et al. Electrophoresis 21: 2622-2636 (2000)). Proteins that show increased (or decreased) pTyr are identified by comparing the western blots made from said lysates derived from said hepatocytes treated with both insulin and the compounds of the invention with said control lysates derived from said hepatocytes that were treated with insulin only. Increased pTyr of a protein shows that the said protein is regulated by the PTPase or PTPases that are inhibited by the compounds of the invention. Said protein may either be a direct substrate of the PTPase or PTPases that are inhibited by the compounds of the invention or the substrate of other PTPase(s) which activity is regulated by the PTPase or PTPases that are inhibited by the compounds of the invention. Decreased pTyr of a protein shows that said protein is the substrate of other PTPase(s) that is/are activated, directly or indirectly, by the PTPase or PTPases that are inhibited by the compounds of the invention. Having identified and visualized proteins, i.e. substrates, that show changed pTyr levels, the spots are cut out, digested with trypsin and analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF- MS) (Marcus et al., supra). To identify the nature of said substrate with changed pTyr levels the obtained mass fingerprints are analyzed as described by Marcus et al. (supra) or other methods well-known to those skilled in the art. Said substrate can either be an already described protein or a novel protein. In both cases, the identification may be followed by cDNA cloning procedures with the aim of obtaining a full-length clone corresponding to said substrate using standard techniques well-known to those skilled in the art (Ausubel, F. M., et al. (ED.). Short Protocols in Molecular Biology, 2 nd ed, John Wiley and Sons, inc., New York, ISBN 0- 471-57735-9 (1992)). Said full-length clone may be expressed as recombinant proteins in prokaryotic or eukaryotic expression systems well- known to those skilled in the art (worldwide web @ invitrogen.com; worldwide web @ stratagene.com; worldwide web @ promega.com), and the function of said substrate may in turn be studied both at the biochemical and cellular levels. Further, said recombinant proteins may further be used as an antigen to produce either polyclonal or monoclonal antibodies using techniques well-known to those skilled in the art. As a non-limiting example, with said full-length clone, said antibodies, and the compounds of the invention at hand, those skilled in the art will be able to study the tissue distribution and expression levels of said substrates in normal animals and animal models of diseases, such as diabetes, obesity, cancer and disturbances of platelet aggregation. A person skilled in the art will be able to use this knowledge to establish animal models or use already established animal models that will reflect a human condition or disease in which a compound of the invention will be indicated. Non- limiting example of the usefulness of said compounds of the invention will be in the following disease areas: diabetes, obesity, cancer and conditions with unwarranted platelet aggregation. EXAMPLE 122 Identification of substrates that are dephosphorylated by PTPases that are inhibited by the compounds of the invention The analysis consists of the following steps: (A) preparation of hyperphosphorylated substrates; (B) identification of said substrates that are dephosphorylated by PTPases that are dephosphorylated by compounds of the invention. To identify the substrates of the PTPases that are inhibited by the compounds of the invention the following method may be employed. Primary cells and/or cell lines that represent the target organ or tissue may be used for these experiments. Non-limiting examples of target tissues or organs are: skeletal muscle, liver, adipose tissue, pancreas, the spleen, the bone marrow. Non-limiting examples of cell lines are: Chinese hamster ovary (CHO) cells (CHO-K1 - American Type Culture Collection (ATCC) Number CCL-61), Baby Hamster Kidney (BHK) cells (ATCC Number CRL- 1632), HepG2 cells (ATCC Number HB-8065), C2C12 cells (ATCC Number CRL-1772), L6 cells (ATCC Number CRL-1458), RD cells (ATCC Number CCL-136). Said cells can either be unmanipulated or transfected transiently or permanently with plasmid vectors that encode proteins or substrates. Non-limiting example of a plasmids that allow expression in mammalian cells are: pcDNAI and pcDNA3 (worldwide web @ invitrogen.com). Non-limiting examples of proteins or substrates that are transfected into said cell lines are: the insulin receptor, the IGF-I receptor, the EGF-R receptor, the PDGF receptor, IRS-1 , IRS-2, IRS-3, IRS-4, p56Lck; Jak1, Jak2 (Hunter, supra). Step A Said primary cells, tissues or cell lines are exposed to a general inhibitor of PTPases. This treatment results in induction of hyperphosphorylation of a multitude of cellular substrates. A non-limiting example of a general PTPase inhibitor is bisperoxovanadium 1 ,10 phenanthroline (bpV(phen)) (Posner et al. J. Biol. Chem. 269: 4596-4604 (1994)). A non-limiting example of a hyperphosphorylation protocol: CHO cells that stably overexpress the insulin receptor are grown in 15 cm Petri dishes to 80-90 percent confluence (using F-12 medium with 10 percent fetal calf serum). The culture medium is replaced with medium that does not contain calf serum and are grown for additional 2 hrs at 37 °C. The plates are washed twice with phosphate buffered saline (PBS) and incubated for further 2 hours with 100 μM bpV(phen) and 100 nM insulin (Novo Nordisk) (final assay concentrations). Following this stimulation the plates are treated as follows: The medium is rapidly aspirated and the cells washed twice with ice-cold PBS. Two milliliters of ice-cold lysis buffer (see below) is added and the plates are placed on ice for 2 minutes after which the cells are scraped off using a cell scraper ('rubber policeman'). The lysates are placed at 4 °C at a rotary shaker for 1 hour. Dithiotreitol is added to a final concentration of 10 mM, and the lysates are centrifuged for 10 minutes at 20,000 r.p.m.. Aliquots of the supernatants, i.e. lysates, are stored at -80 °C until further use. Lysis buffer - for a total of 20 ml add the following: 0.8 ml of 500 mM Tris-CI, pH 7.4 0.2 ml of lOO mM EDTA 2.0 ml of 1 M NaCI 2.0 ml of 10 % (vol/vol) Triton X-100 80 μl of 250 mM PMSF 2 μl of 10 mg/ml aprotinin 20 μl of 1 mg/ml leupeptin 5 mM 100 mM iodoacetate 11.88 ml demineralized water Step B For these studies both novel and known PTPases may be used. The PTPases may be either isolated using the compounds of the invention as described in Example 120 or recombinant proteins. Non-limiting examples of known PTPases that are inhibited by compounds of the invention are PTP1 B and TC-PTP. The cDNA for these PTPases are inserted in prokaryotic expression vectors and are expressed in E. coli. An overnight culture is diluted 1 :25 into a total volume of 2 liters of SOB medium and grown at 37 °C for 3 hours. Isopropyl β-D-thiogalactoside (IPTG) is added to a final concentration of 0.1 mM, and the incubation is continued at room temperature for 3 hrs. The fusion proteins are purified according to the manufacturer's instructions (Amersham Pharmacia Biotech). Aliquots of said lysates (60 μl) are mixed with said PTPase that is inhibited by said compound of the invention and incubated on ice for 1, 10, and 30 minutes. At each time point, 20 μl aliquots are removed and mixed with SDS loading buffer (20% (v/v) glycerol, 3% (w/v) SDS, 3% (v/v) 2- mercaptoethanol, 10 mM EDTA, 0.05% (w/v) bromphenol blue) , heated at 100 °C for 2 minutes and stored at - 20 °C until use. Control lysates without addition of PTPase are treated identically. As a non-limiting example, said lysates are subjected to two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by detection of proteins that are phosphorylated on tyrosine residues (pTyr) by western blotting, techniques well-known to those skilled in the art (Marcus et al. Electrophoresis 21: 2622-2636 (2000)). Proteins that show decreased pTyr are identified by comparing the western blots made from said lysates treated with said PTPase with said control lysates. Decreased pTyr of a protein shows that the said protein is a substrate of the PTPase or PTPases that are inhibited by the compounds of the invention. Having identified and visualized proteins, i.e. substrates, that show decreased pTyr levels, the spots are cut out, digested with trypsin and analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) (Marcus et al., supra). To identify the nature of said substrate with decreased pTyr levels the obtained mass fingerprints are analyzed as described by Marcus et al. (supra) or other methods well-known to those skilled in the art. Said substrate can either be an already described protein or a novel protein. In both cases, the identification may be followed by cDNA cloning procedures with the aim of obtaining a full-length clone corresponding to said substrate using standard techniques well-know to those skilled in the art (Ausubel, F. M., et al. (ED.). Short protocols in molecular biology, 2 nd ed, John Wiley and sons, inc., New York, ISBN 0- 471-57735-9 (1992)). Further use of the knowledge include analysis in animal models as described in Example 59 EXAMPLE 123 Analysis for blood glucose lowering effects The compounds of the invention are tested for blood glucose lowering effects in diabetic, obese female ob/ob mice. The mice are of similar age and body weights and they are randomized into groups of ten mice. They have free access to food and water during the experiment. The compounds are administered by either by gavage, subcutaneous, intravenous or intraperitoneal injections. The control group receives the same volume of. vehicle as the mice that receive the compounds. Non- limiting examples of dose-range: 0.1 , 0.3, 1.0, 3.0,10, 30, 100 mg per kg body weight. The blood glucose levels are measured two times before administration of the compounds of the invention and vehicle (to the control group). After administration of the compound, the blood glucose levels are measured at the following time points: 1 , 2, 4, 6, and 8 hours. A positive response is defined either as (i) a more than 25 percent reduction in blood glucose levels in the group receiving the compound of the invention compared to the group receiving the vehicle at any time point or (ii) statistically significant (i.e. p<0.05) reduction in the area under the blood glucose curve during the whole period (i.e. 8 hrs) in the group treated with the compounds of the invention compared to the group receiving the vehicle. All documents cited herein are incorporated by reference in their entirety. In case of conflict in definitions, the present definitions control. TABLE A Table of the orthogonal three dimensional coordinates in Angstroms and B factors (A 2 ) for Protein Tyrosine Phosphatase 1 B complexed with 2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid. No Amino acid X Y Z B 1 GLU N 69.819 14.736 20.949 51.88 2 GLU CA 69.381 16.070 20.592 50.12 3 GLU C 68.816 16.123 19.177 50.96 4 GLU O 69.477 15.855 18.147 47.57 5 GLU CB 70.340 17.247 20.871 48.87 6 GLU CG 69.694 18.607 20.512 43.78 7 GLU CD 68.658 19.051 21.547 100.00 8 GLU OE1 68.838 19.978 22.327 100.00 9 GLU OE2 67.553 18.331 21.549 100.00 10 MET N 67.550 16.476 19.190 38.96 11 MET CA 66.810 16.619 18.000 33.41 12 MET C 67.438 17.710 17.211 32.40 13 MET O 67.335 17.745 16.010 34.44 14 MET CB 65.376 17.042 18.345 34.94 15 MET CG 65.321 18.129 19.414 36.89 16 MET SD 63.595 18.598 19.738 37.03 17 MET CE 63.053 17.127 20.689 35.19 18 GLU N 68.060 18.625 17.893 31.60 19 GLU CA 68.666 19.756 17.226 34.56 0 GLU C 69.903 19.379 16.393 37.49 1 GLU O 70.082 19.836 15.267 37.90 2 GLU CB 68.955 20.859 18.236 36.57 3 GLU CG 68.694 22.256 17.685 54.02 4 GLU CD 68.602 23.271 18.792 84.59 5 GLU OE1 68.338 22.965 19.970 60.30 6 GLU OE2 68.826 24.499 18.340 56.97 7 LYS N 70.740 18.506 16.928 34.63 8 LYS CA 71.925 18.073 16.173 36.36 9 LYS C 71.504 17.225 14.995 35.30 0 LYS O 72.071 17.271 13.926 33.46 1 LYS CB 72.858 17.280 17.069 44.20 2 LYS CG 73.694 18.196 17.980 95.46 3 LYS CD 74.837 17.496 18.729 100.00 4 LYS CE 74.640 17.419 20.241 98.28 5 LYS NZ 73.758 16.304 20.653 100.00 6 GLU N 70.463 16.441 15.234 32.09 7 GLU CA 69.894 15.573 14.227 31.58 8 GLU C 69.285 16.367 13.096 33.03 GLU O 69.380 16.076 11.917 33.46 GLU CB 68.841 14.653 14.863 33.60 GLU CG 67.823 14.152 13.814 51.32 GLU CD 66.936 13.044 14.309 61.90 GLU OE1 66.302 13.085 15.370 49.63 GLU OE2 66.918 12.042 13.457 46.46 PHE N 68.648 17.422 13.475 31.95 PHE CA 68.008 18.269 12.488 32.19 PHE C 69.072 18.712 11.539 37.60 PHE O 68.928 18.630 10.309 32.52 PHE CB 67.340 19.508 13.152 32.26 PHE CG 66.508 20.348 12.196 30.98 PHE CD1 65.161 20.064 11.967 29.63 PHE CD2 67.094 21.402 11.499 29.81 PHE CE1 64.398 20.834 11.096 31.86 PHE CE2 66.354 22.185 10.621 32.68 PHE CZ 65.004 21.896 10.423 34.10 GLU N 70.164 19.160 12.179 36.63 GLU CA 71.310 19.627 11.440 36.44 GLU C 71.889 18.598 10.519 37.22 GLU O 72.034 18.827 9.312 41.43 GLU CB 72.309 20.346 12.308 40.39 GLU CG 71.810 21.794 12.529 71.18 GLU CD 71.946 22.266 13.953 100.00 GLU OE1 72.735 21.752 14.751 100.00 GLU OE2 71.139 23.288 14.223 100.00 GLN N 72.140 17.413 11.024 31.25 GLN CA 72.622 16.443 10.091 30.97 GLN C 71.717 16.227 8.911 37.58 GLN O 72.187 16.205 7.798 35.23 GLN CB 72.828 15.118 10.746 32.09 GLN CG 73.907 15.196 11.804 59.96 GLN CD 74.286 13.786 12.123 100.00 GLN OE1 73.653 12.854 11.579 100.00 GLN NE2 75.309 13.631 12.975 100.00 ILE N 70.403 16.026 9.164 37.32 ILE CA 69.439 15.745 8.091 33.95 ILE C 69.451 16.857 7.112 35.04 ILE O 69.497 16.713 5.871 32.60 ILE CB 68.007 15.516 8.591 33.88 ILE CG1 67.983 14.281 9.450 33.37 ILE CG2 67.062 15.263 7.427 27.69 ILE CD1 66.734 14.241 10.340 41.16 ASP N 69.392 17.990 7.705 31.68 ASP CA 69.374 19.138 6.893 34.74 SP C 70.643 19.193 6.028 45.86 85 ASP O 70.614 19.383 4.778 46.01 86 ASP CB 69.131 20.360 7.773 36.60 87 ASP CG 67.950 21.114 7.297 41.28 88 ASP OD1 67.080 20.557 6.700 43.16 89 ASP OD2 67.978 22.408 7.544 44.81 90 LYS N 71.777 19.003 6.699 41.67 91 LYS CA 73.008 19.033 5.954 43.82 92 LYS C 73.035 17.928 4.864 46.27 93 LYS O 73.357 18.177 3.709 45.13 94 LYS CB 74.246 19.032 6.859 48.59 95 LYS CG 74.736 17.622 7.242 93.12 96 LYS CD 75.455 17.518 8.604 100.00 97 LYS CE 76.327 16.267 8.797 100.00 98 LYS NZ 75.740 15.262 9.683 100.00 99 SER N 72.692 16.706 5.240 40.90 100 SER CA 72.713 15.593 4.309 41.87 101 SER C 71.575 15.604 3.324 48.03 102 SER O 71.464 14.678 2.502 46.24 103 SER CB 72.726 14.225 4.998 47.13 104 SER OG 72.148 14.254 6.292 62.32 105 GLY N 70.729 16.629 3.441 45.84 106 GLY CA 69.560 16.743 2.595 46.85 107 GLY C 68.809 15.410 2.577 51.28 108 GLY O 68.437 14.883 1.532 56.29 109 SER N 68.578 14.814 3.724 41.13 110 SER CA 67.894 13.545 3.650 37.67 111 SER C 66.529 13.420 4.344 33.83 112 SER O 66.192 12.328 4.793 32.66 113 SER CB 68.822 12.442 4.043 39.40 114 SER OG 69.368 12.791 5.268 49.16 115 TRP N 65719 14.495 4.371 28.03 116 TRP CA 64.390 14.413 4.947 24.69 117 TRP C 63.521 13.375 4.242 30.79 118 TRP O 62.773 12.639 4.915 30.44 119 TRP CB 63.700 15.754 4.922 24.38 120 TRP CG 64.317 16.654 5.925 24.63 121 TRP CD1 65.208 17.670 5.685 27.42 122 TRP CD2 64.101 16.581 7.359 22.65 123 TRP NE1 65.553 18.274 6.893 27.47 124 TRP CE2 64.916 17.588 7.946 28.99 125 TRP CE3 63.346 15.749 8.195 21.13 126 TRP CZ2 ' 64.926 17.778 9.345 24.85 127 TRP CZ3 63.385 15.932 9.554 20.43 128 TRP CH2 64.168 16.938 10.115 2 21.06 129 ALA N 63.620 13.268 2.876 26.09 130 ALA CA 62.799 12.286 2.153 24.22 CJ) CD σ. o CN O CD CN CO r-- LO CD CN CN CN CN T- - CN * h- co LO σ. LO h- CD t*- <N CN o CN IO C σϊ O O ■ <fr oo IO CD N O CD CN I- C0 00 CN OO O M- IO CO CO O O CM O CNi cn cτ ) o6 D 0 0 o. - τ- O lf. CM CO ifi o CD - CM t- - CN - CN " r ~ CN T- CN DQ < C0 < Gα O O O < mO Q Q UJUJNl < CD O Q LU UJ < CQOQQ υoozoooozooooooo ooooooooooo OOOOOOOZ o o o o o o Q. III < in C0 NS y o ©o m H U α. CN o LO LO r-- co Tt Tt LO CM CM CM LO 00 LO "t 00 CN CO CM cb co oo CO CN h- CN LO CO CN O CO LO CD LO t O CO CM CJ) o LO O CD CN t- CD LO 00 CN Tt Tt LO r-- h- o Tt O CD CO C CD CN t- CO CD CO Tt CJ) Tt' CM CN CD CO CN CJ) Tt T- Tt LO h- CD O LO CM CO Tt O CO CD CM CN CO 1- in co CD o) oo N 1^- τt CM OO - O CM τt O O τt CN Tt Tt v- CJ) O CO CO T CO CO CM LO O CD CN CO CΩ CN CD CD LO r^. co oo CN - CO CD CO CD CN CD Tt N - CD O Oθ m c r- OO in CM CO ^ ■ NCOCD N CO CJ ) CJ ) O CM CM CD 0. N N 000) 0. N CD CD «. (Dm ir) f C <. ( N 00 SN 0. OOOO O C000(D C00) O LO Tt CO CO CO CO CM T^ d ιn ιn ιn ιn Λ in ιn ιn ifi in ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ifi ifi in (D (D (D tD (D in ιn ιo ιn ιn cD co co cD in ιn ιo ιn ιn iβ in ιn ιn T- CM - - CN - CM - CN T- CN < CQOOQ < X X < m O Q Q UJ UU < CO O Q LU LU < m o o o o o o o oυo Cυ Q Oo Q oUzJNo Z Z O O O O O Z O O Z oooooooo o o o o o o o r-- d d d d d d d < < < < < < < < < < < X X X X X X X X X X O O D O U U O O < < < < < CO CO o N co ιn (θ N o σ) - O S N T- T- T- T- r CM T- T- CN CN o C oq CO -r- CO CM CN CD CD O — CM CD LO r- CO CD 00 T LO CM O r~- ιq ιq Tt CD CD Tt h- oo CO d --: --: d CN . co 00 0000 r^ co ¬ CD O Tt — CO co 00 T- CD - CO o CD 00 CO h>- CJ) CM T- CN /rι - CM τ- CM r- CM co O < co O Q Q oozoυooooo < CO O Q Q LU UJ N < CQ CD Q < CQ O < CQ UQ lil N I I Z O O O O O O O O O O O O O O O O O O O O (Λ O O O O O O Z O Z Z ϋϋ j [ϊ:iϊ:tt:< < < < > ιn D S oo LO o r- CD LO CD r^ r^ σi CO T- CJ) CM CN I"-. h- σ> 00 CO Tt CJ) CO CO OO LO 00 CO CM CM τt N O O) c CD CD 00 O cM h- t ι D C3J θ CO - CN x- CM < CQ CD CD < CQ < CQ CD Q UJ N < CQ CD Q Q < CQ CD Q < CQ CD Q UJ N < O O O O O Z O O O O Z O O O O O O O Z Z O O O O O O O O O O O O O O O O O O O O Z Z O Tt CO CD - IO CN CN CN N- CO — CO CO O LO CO- Tt CO CM O Tt O CD O) CM- CO¬ - CN - CN T- CN T - CN CQ CD Q Q < C Q CD Q LU N < co CD Q Q ooυoozzυo < O Q CD Q LU N XX < CQCD Q Q < O O O O O Z O O O O O O Z O O O O O Z O zzzoυoooozzoo Z Z Z Z Z Z c^ c c C Λ CΛ ϋD CΛ C Λ C Z Z Z Z Z Z Z Z CD CD CD CD CD CD CD CD CD CD CD Z Z Z Z Z Z Z Z CD CD CDCD CΛ C ω W CΛ CO CΛ CΛ CΛ W CΛ W CΛ CΛ < < < < < < -l -J -J _J -l -l -l -J _J < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < o O LO CD I - 00 CD O - CS C ^ Λ (D N OO CS O r- CNl C τf lf) (D S CO O) O τ- C\| C lO (D N OO O) O - C\| C in CO N Cθ σ) 0 CN CN CN CN CN CN CN CM CN CN CO CO CO CO C CO CO CO 00 00 τt τt τt τt τt τt τt τt τt τt lΛ lΛ LΩ lΩ LO LO LO LΩ LO lΛ co co o co oo CO CO OO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO OO CO CO OO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO C^ CO τt O τt CD LO τt τt CO C CN CJ) CO CO - CD OO τ- C h-.τt CJ) CD N- Cθ -r- τ- CN O CM CN CD τt O CN h- τt r-- - ffl r- - O CO CN CN CN O CD CO CD CO τt CD CO τt τt CD t- O CJ) Oθ r-- τt CD O CN Cθ τ- r s - τt - u CDj uC 1 0j C CO CD Cθ τ- CJ) τt CM co in CM cj) co CD O τt CN CO 00 CN -«- CN Tt LO LO LO LO Tt LO LO Tt Tt lO CO CO CO Tt CM CD r^- CO CJJ OO ~ O " OO Tt CM CN CM CO CO LO CM Tt r~- Tt ». CO r— h- CD LO LO Tt CO OT CD O O O O O O O O O CD CD O O CD O - CN OO CO T - C CO Tt Tt Tt CO Ln CN CN - O CM CM CO r- CO Cθ C CO CO CO C 00 CO CO 00 τt τt t τt τt τt τt τt 00 00 τt τt 00 t Tt Tt t T Tt Tt T Tt Tt Tt Tt Tt Tt Tt t Tt T Tt t - CN „ - CN T- CM v- CM - CM T- CN C Q CD Q LU N X X < CQ CD Q Q UJ UJ N X < C Q CD Q LU N X X < CQ CD Q Q < CQ CD CD O O O Z O Z Z O OOOO OO ϋ ϋOO Z OO O o o o z o z z o o OϋϋOO OOOOOO <<<<>>>>>>>W in (D N oo o. o T- M CO t in CD C» C3. 0. CJj σ5 O O OO OO O CO Cθ CO CO 00 τt Tt t Tt Tt Tt Tt LO CM CO h- CO O CO T- - CM C_D. CD LO Tt CD CD CO OO O N- CD CD LO Tt OO CM CO CD CO N- CD O I s - CN v- T- CJ) h- CD CO CJ) O CN LO CN CD C "D- > > - O CM I s - CD CO O CJ) O CD CO CJ) O Lθ CO Lθ r- CD τ- LΩ O O O LO CJ) ' Tt CO CJ) CD O CO CD CD CD I s - I s - in c) cj) CN O τ- CD Ln CJ) CD CD LO τt CN CM ■ r- - CN - - - mr-cj)CDr s -ι s -oor s - T σ) I s - CN CN CN CN CM CN T- - CN CM CN T- - I s - co N τ- CD θNN C τ- N O O CM τt τt τt „ Λ - CN T- CM - CM /n 1- CM r- CM < CQ CD < CQ CD Q < O Q CD Q Q LU LU N < CQ CD Q Q < CQ CD O Q LU LU < CQ O O O ϋ o OOOOOO oooooooooo o o o o o o o OOOOOZOOZZOOOO Q_: Q; Q_: Q_: Q_: O O O O O O O LU LU LU UJ LU UJ UJ LU LU LIJ LU Q_ 0.0.0. Q_ 0. Q_ QL fΛ cn (r , , n , Λ , n Cd CC d 0. Cd LU LU UJ UJ LU Q C__ Q: Q-: Q Q_: Q^ X X X X X X X X X X X i V) U) U) V) U) V, V, ^ — ^ ^ ^ ^ — — ^ Ul \Al U l} \^ V3tnt0WWllCLQ.llQ.liα.D.Q.D. W © O N 000) O - N C ^ Λ m N 00 CB O v- CM C0 f W (D N C0 C8 O ^ CM C0 ^ li. (0 N 00 σ) O - CM C0 ^ lf) CD S C0 σ) O - CM O O O τ- τ- τ- - - τ- τ- τ- - - CN CN CM CN CM CM CN CN CM CN CO CO CO CO CO CO CO OO CO OO τt τt τt τt τt τt τt τt τt τt Ln L^ y o © © m H U α. τ- O CM N O T- c O) N ro uO O O) tD ^ CD i \ ^ C!) D O. O ^ <]O O C OO (D - Tl- O N CO T- f c OO ^r i N Tt CD CM O Tt T- (D CM r- CD CM S O C O T- O OO CNl in tO Tf T- CO CO - CO CD rM OO O O O O CO C in CD CO lO in iO C C - CD T- h- r- cj) co ro CM N N S in O CO C '< - OO in ^ O CO '^ CO C CM O (D O (NI CM N C Tf O) T- lO t CM rM CM (J) 00 '<f C N o h- oo LO c) o CO LO CD LO CD r s - τt LO CO τt τt τt τt CD I- r s - LO (- r s - co c) oo r s - co cD co t- co co co ι s - r s - co co cD Lθ co Lθ CD θ CD d - * - CN cb v- 1 cb T- - - T- - T- T- T- T- T- T- - - - - T- T- - T- T- - - CN T- CM CN CM CM CM CM CO coc)coτtc)omιn Tt LO LO o O LO LO OO O CD LO CO CN CD co I s - r- Ω I S - CN CO CO CD CΩ C τt CN I s - - CD τt -«- CM CM CN <^ c) CJ) co in cM Tj- t Tt oo co co r s - - cD r- m CN O O I D LΩ I- CO CN co cM C o O CD - CO CN o in co t cN t^ OT c i r-- . oo oo r^ co cD CD co Tt T- cD in o co cN o o ^ CM Ln c in T- . CO CO h- LO CD CD CO CJΪ Tt co in T- CN CO T- CJ) o CM CN cb oO CN CM -r- : d 9 d 9 τt Lb τr τ cb ι^ r^ r^ τt cb τt Lb cM -r ^ T t in Tt cb in b c r^ ib Tt t m m m co Tt co o cj) c co c) CM v- co co r s - cD in τt r s - τ- - o cj) co o τt cj) CJ) r s - oo -»- τt o co oo co CD LO CO O CD O (3) r IO O S CO f C ^ O ( N O M CD < <0 ( τ - N n tM B O) N M O 't N p p M in S CN CO CO CD CO CD CD CO CD in O Tt Tt CD CD CJ) O CD OO Cθ r s - τt O CD CJ) τt C r s - τt CO CO C CM CJ) O CO OO τ- cθ OO OO CM LO CD CD r-- τ t cD θ t- cN in co cj) oo ι s - r- i s - cD in τt oo oo cN CD Ln τt τt Lθ CD τt r- co cN CN OO CN Tt CO O OT OO CO CO CD OO O - CO LO Tt CD CO OO CD CJ) Tt CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CN CN CN CN CN CN CN CM CN T- CN T- T- CN - CM v- CD < C Q CD Q UJ N X X < ω CD CD Q < C Q CD Q LU N < CQ O Q Q < DQ O Q QLIJ O Z O O O O O O Z O Z Z o υ o o o o o O O O O O O O Z o o o υ o o o zooooozoo I I I I lΛCONOO ca βfflσ) C0 CD CO CO τt CN CJ) C0 LO CN '<- C0 C0 τt CJ) τt cM co τt τt cN CO O CJ) τt O CJ) - OO OO O Lθ m θ t s - CN CD 00 CM C0 CD O CJ) CN 001- CD CM CO O OO CN CN O CO CO CO CD τt τ J cb cb Ln σ. cb CO CO t Tt Tt Tt in r- l- CD lO lΩ lΩ τt in r s - CN CN CN CO T- T- C CO CM T- CN T- CN v- CM - CM - CM LU < CQ CD Q LU UJ < CQ CD Q J UJ < co CD Q Q < CQ CD Q Q < OQ CD Q Q < Z Z O OOO O O O Z O O O O O O O O O O O O O O O O OO O O O Z Z O O O O O O O O O C0 Z Z Z Z Z Z Z Z Z D D D D D D D D D. Q. Q. Q. D. Q. D. D. Z Z Z Z Z Z Z Z D. H. D. I D. Q. D. Q. D. Q: ^ ^ __J ^ _J _J __J ^ ^ _-J ._J ._J __J __J __J __J __J __J ^ C/5 CO CO C/) C > C5 C/) rø XCDCDCDCDCDCDCDCDCDCDCDCDCDCDCDCDCDCD<<<<<<<< << <<<<<<<<<<<<<<HI-I- © O O T- CN CO Tt lO CD N- OO Cn O CM OO τf Ln CD r- ∞ CJ) O - CN CO τt in CD r s - C CJ) O τ- CN CO τt LO CD I s - CO CJ) O τ- CN C τt o CD O O O O O O O O O O T- τ- τ- τ- - ^ - ^ - CM CM CN CM CN CN CN CM CM CN CO CO CO CO OO CO CO OO CO CO τt τt τt τt τt Tt m Ln Ln LO LΩ LO LO LO LO LO LO in io m LO Lo io io iO LO O Lo m m m m in Ln LO LO Lo m in m in m Ln m Ln Ln m Ln Ln L m Tt CD CJ) CO O τ- CN CO cb CM - τ- I s - T- CD O CD O - CD in O T- d CJ) CM CO - oO CO O C CD CD I^ T-; Ln cN c m O- CM in cO N CD CO ^ O- CM N CM O CO CM N τt τ- CO CM CD CO τt CD CM co oo o cθ Lo o c ) CN CD oo ιn τt CO CO I s - CD CN τ - τt o m σ) τ- o lΩ lΩ CN C0 CN 00 m CN C0 C uD_/ CN CJ) O O O CM LO CD CD N- LO τt τt O τ- LO O C LO τ- σ T- CO t CO t 0O IO 00 O CO N- CM O Tt CD T- CO N- CO o co co co cj) CM co ιn O N co m ro cM oo cD m o Tt co oo o cD I s - CN O T- CM CO CN Tt CO Tt CD CN CN Tt LO CN CN CO CN Tt CD CD r^ CD N- OO h- N- N- CO C ) OO CO CO O CO CO CO CO CO CO CO CO CO CO C "O C CO CO CO CO CO OO CO CO CO CO CO CO CO CO C O C 'D O-C C ~J co co d ^ ^ d cb in O " o T —t " d ^ Tt Tt T Tt t T Tt Tt Tt t Tt Tt Tt ■ <- CM - CM T- CN - f - CN CQ CD O Q UJ UJ N X < OQ CD CD Q < mO Q Q < CQ < CQ CD < CO CD Q Q < O O O O O O O O O Z o o o o o o o O O O O O O Z oooozooooozooooooozo ct c ai aKZ cc ai cr ce..... Mll lll lll lll z z z z z z z <r <; <r < <; κ cr o^ _£ _£ :D D :33 D D 33 llMll >- >->- - >- ^ >- >- >- LULU W UJ LU LU W W WW(O O W W J J J J J h h h h h h h - hd __._ d dd d d < < << < < < << << < <WWϋ3W WW JJ J J J J J j d d © lΛ (D N OO Cn θ - CM C τf ιn (D N ∞ σ. O - CM C \. U1 CD N CO CJ) O τ- CM C ^ lfi CD N CO Ca θ ^ CM C ^ ιn (D N CO O. O o 't ^ ^ ^ 'ψ in in in in in in in in m m cD co cD CD CD CD co co cD CD N N N N N N N N N N oo oo co oo oo oo co oo oo oo σ) LO in in in in in Ln in Ln in in in in in Ln in Ln Ln in i Ln i i in in in in in in in in in in Ln i in Ln in Ln Ln Ln L^ CM CO CD CN CN CN CN CN CN CN CN CN CM CJ) CO CN OO Tt 00 CM CM CO Λ N in τ- ιn (M O (O CO O CO CO (D τ- lfi ro oθ (0 (M O (D CO O OO ^- - v- τ- t t (D CD C CO lO CM CM CO N O CO CM (D ^ CN O Tt CN D OT in CO CO CO OT CD CM r^ l^ O CN i O CD CO - T- CO CO Tt CO CN Ci Tt C lΩ O Tt T^ lO O CO O) C I s - (-D - CO CM O CJ) τ- CM O CN CD CO I s - CN O LO O r- CM CN OO CD τt in τt τt Ln in CN C CO - C^ in in m m I s - Tt LO CD r- CO Lθ τt τt τt τt CO CD CJ) CJj O O O CN O O τ- O O O O τ- CΛ CN CO CO CO τt CD I s - r- OO CN CN τ- τ-- CN Tt Tt Tt Tt Tt Tt ^ ^ ^ ^ ^ ^ ^ ^. ^ ^ ^ ^ ^ in in in in in in in in in io io io ^ io in in uo in in in io in in in in in in - CM τ- T- CM T- CN 00 CD CD Q < CQ CD Q LU N < CQ CD Q LU < CQ CD Q LU LU < OQ CD Q LU LU < CQ O O O O O O oooooooz U ϋ O ϋ ϋ W ϋ OOOOOOOOZOOOOOOOOZOOOO CO O O O CΛ W Λ W K K H H H H l-3D-D33-DZ)-DDZ 3=)3Z)DD=)D<<<<< LU LU LU UJ LU LU LLI _I _I _I _I _I _I _I _I _I _I _1 _I _I _I _I _I _I J J J _1 J _J - CD CD CD CD CD CD CD CD CD CD CD CD CD CDCDCD CD CD < < < < < © - CM CO τt lO Cθ r s - CO CT) O τ- CM CO τt lO CD r- CO CJ) O - CN OO τt lO Cθ r- CO CJ) O τ- CN CO τt LO CD O CΛ CΛ CJ5 CJ) CJ) σ) CJ) CJ) CJ) O O O O O O O O O O - - x- τ- - - - τ- - - CN CN CN CN CM CM CN CN CM CM O CO CO OO CO CO C ιn ι ιn u) in ιn ι ι ιn ω D D D (D CD ω ω ω ω D D D ω D D D Φ ω D o cD o ω ω D (D CD D D D CD (θ (θ θ D θ OO CD CM O CO CO LO q τt ιn N- cN cq cj. C) τ- : τ- : C ) - X- - CN CN - - CJ) τ- O CD in CD C7) N- CO m O N- O CO CM CJ) 00 m N- CM CM OO CO CD CO CJ) N- 0 T- T- - - T- T- CM CO I s - 0θ m τt CM τt CN O CN CO CJ) CD O N- τj cD N : ∞ CM <<-; ^ ( C τ- d 'r : r T t CD CD O τt τt N- O C0 CJ) CD τt CN CD O τ- Tt T- 00 CJ) O CO Tt T- CO Tf CD CO N- 00 LO m v- CJ) O CO N- in θ 00 l s - 0 w0_" C VN 0 y0j N i--- CΛOJ C vDi_ι C*Oj C yO CO_/ v v-— v- C UJ)J I s - in o CM m co N- CN in LO o CO N- Tt T- I s - I s - CD O in CM N- N- C0 00 l s - CN CD CD N- N; oo o co m co N- q CD CM CM d cj) oo N- " σi d CJ) 0000 I s - N- CD N- N- CD N- cN CN T t cb ib Ni cb r-i σi T d d d CD 00 CO Ni in Tt Tt Tt m Tt Tt Tt Tf Tt Tf T Tt Tt τt τt τt j- t τt Tt Tt Tt Tt Tt Tt CO CO CO CO "* " CM T- CM T- CM T- CN < CQ CD Q LU LU < CQ CD Q LU N X X < ω O < OQ CD Q Q UJ LU N X < OQ CD CD Q υooooooz oooooozo z z z ooooozooooooooυoo o o o o o o o 000000000000.0.0.0 0 ^^^^0:0:0:0:^^0:0:0: _I _I _I _I _I _J _I _I _I O: Q: Q CC: Q: Q: O: (_C: Q_: D Q: UJ UJ UJ UJ L1J LU ^ >- ^ ^ ^ ^ .>- ^ . S - U W UJ UJ W UJ UJ UJ 000000000<<<<<<<<<<<cocococo © N OO O) O r- CM C ^ in (D N OO C. O - CM CO ^ lO (D N OO CJ) O - CM C \f lO CD N Cθ σ) O - CM C f ir. (O N CO O. O τ- CM o C ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ i in iD in in in ifl tn i i CD D D O D CD O D O CD N N N N N N N N O CO OO CD CD CD CD CΩ CD CΩ CO CD CD CO CO CO CΩ CΩ CO CD CO CO CO CD CO CO CO CD CD CO CD CO CO CO CΩ CD CD CO CO CO CO CO CO CO CD Φ CD CO CO CM CM T- CO Tt ∞ r ( qqq CO CJ) ιb τt oo cb ιb ιn ιb CM CO τt CN CD CN N- OO τ- CN CO CN OO O CO CM r- CD N- τt lO CO CO LO N. CM in θ τ- σ) τ-- φ q ^ r oo - o σϊ tO f in M O CD N Λ D to ^ io ^ q r- N q ^ T- q ^ t lO ^ o n cd ^ iri cd ^ d ui d ui N ^ ^ cM ' d ^ cd d d CN CN CN CM CN CM CN CD Ln cO CO CO CM LO CM OO CD LO CD m O LO O T- Tt CO CΛ Tt CJJ OO CD N- Ln OO T- CD CO CM N- O CO CO N. τt OO CO I- τt CO τt CD Lθ r- CN τt O τ- C0 τ- τt C0 00 C0 C0 CJ) CM N- O O N- N- N- - CD CJ) τ- CD O N- CD CO O O CD 00 CJ) in CN τt τt τ- - C0 C0 τt O 00 τt τ- τt C0 O OO CD CO CO CO CO CN CJ) CN τt CO CN CΩ τt CO CO τt τt CO CO CN CN O O CN CN CO ^ ^ c ι iβ io o τ- M q N c κ OO CM CO CD CO CD O N- N- CO N- CO LO ra ra N d in N ' i oό iri ^ ^ iri ^ b b N Tt CO CM CO in Tt co 0000 CO I s - LO LO O CD OO CD CD N- CM CO τt τt τt N- O CN CN O τt lO LO CJ) CJ) lO τ- CJ ) CM Ln CD CJ ) m N- t- h- CO -5- CN CM Tt co in N- T o o CJ) Tt Tt CM T- CD LO τt CN O τt CJ) τt CM τt CM CD O CO CM CN N- τt N- O τ- O CO CJ) OO in CD σ) τ- in CD CN I s - in co oo Tt c c CJ) CJ) C 00 00 τt τ- CO M- ( co co(Dτ- ( Nθ. o ιo ιo o N Mn ^ cβ σ) σ) '* cM ∞ ∞ CN CN CN CN CM CN CN cb cN " c cN cb Tt T cN -^ d d d ib in Tt ib Ln T Tt Tt cM c^ CD in CD CJ) CD LO Tt 1- O Tf CD CO τt O CD CM O τt τ- N- CN L0 in CD CD 00 CN N- τt O Ln N- O CM CD O CN CN CJ) CN CN 00 CJ) CN CD CD co I s - m oo co N- CO CO LO CN 1- 00 τt LO CD CO CD N- τt τ- CD - lO lO Ln CJ) LO CD N- Ln θ N- -r- O τ- CM CD CN CN Ln Ln oθ CD LO CM τ- 00 CD CD CO O T- i CN q q -^ I s - CD in cθ τt τt τt LO O lθ σ) CD N- LO LO CN O CM CJ) τt CD O CD CO CO CD LO θ σ) CO CO N- CO LO CD T^ -^ O O CO Tt ib t d σi σi σi N- CD - CO CO ^- CD CO CD Ln Tt CD N- CD m in Tt CN CN CM CN CN Tt O CD CD O CN CN CM CO I- CD t T Tt Tt Tt τt τt τt 00 C CO CO CO Cθ CO CO CO CO CO CO CO C CO CO CO C CO C CO CO CO CO CO CO Cθ Cθ CN CN 00 CO CO CO CN CM CM T- CM *- CN ~ CM T- CN < OQ Q Q < CQ < OQ Q LU UJ < < OQ Q < OQ O Q Q < o o O o o o o oooooozυυ O O O O O z OOOZOOOOOOZOOOOOOOZOO 33333333 J_: : O: Q_: : Q: Q Z Z Z Z Z Z Z Z >- >- >- O O O O O O O ) Z) Z) Z) 33 D D O O O LU LJ liJ UJ UJ UJ llJ l I I I I I I ^ ^ T J -J ^ ^^ ^^^ J ^ ^ ^^ lϊi L -i -J _J -_J _J _J _J _l _l H l- H l- H H I- α. Q. Q_ l_L Q_ Q. Q_ _J _l _l _l _l _l _l _l l_L Q. QL © o co T in cD co o o - N c Tt in cD N- oo D O - co Tt in cD N- oo cn o CM CO τt LO CD N- OO CJ) O τ- CM CO τt Lθ CD N- CO 00 00 00 C0 C0 C0 C0 CD CD CD CD CD CJ ) CD CD CD CD O O O O O O O O O O '^ - - - - T- - v- - CN CN CN CN CN CN CM CN CN CD CD CO CO CD CD CD CD CD CD CD CD CD CD CD CD CD N- N- N- N- N- N- N. N. N- N- N. N. N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- y o © © m H U α. o CN CD CJ) O O CN LO CD N- τ- CD m m co CN Tt I s - N- O T- m τt N- m - τ- o τt - • r- CM LO T- N- CJ) σ> σ> d Ni cb cd oo Ni Ni d d cd Ni lb CM T^ ιb Tt in v- CN - T- x— - T— - CN CN - - - CN CN r^ Tt t oo cN T m o o o in O CD I s - Tt 00 CO CN o CN CO co ■r^ q q cq cq cq cD N- cq Tt co Tt T- T- N- oq CD oq CM CN - Tt o O LO CJ) OO Ni CM CO 00 Tt Tt cb lb v- 1 co σi cb cb co σi cb σi CO CN CN CN CN CM CM CM CN - T- C T- CN d CM CD CO CO ιo o σ) τt cD oo co σ) o CD CD - CD N- O Tt Tt O CN N- N- N- CO CM CO Tt CO CJ) O CO - CN CD CO O CO CM O O T- CM N- OO CD O) in cO OO CM CD CO N- CO O CN co in co O co in oo co oo co O CO CN CN CN T- O O I s - t CN CO in q - CO Tt -r- CO CO T-; N- - N- CO O CJ) Tt Tt CO CD CN LO CN CO CJ) CO D CM M v- I s - T- CJ) CJ) CM CJ) CM " cb τt cN cb c τt " cM- CO CO LO CD CN CO Tt τt CM - CM τt lO CD N- τt OO CO CN CD CO CD N N oό σii- C0 O 00 C0 CD CM 00 -«- CD τ- in Tt N- τt τt CD N- CD - CO N- N- m co LO CM CO CD CD N- I s - CN co σ> T- 00 CM O I s - lΩ CO CM N- CO OO O CO OO CD CD CO 0O CD 0O CN τt N- σ) N- Tt cj) CM m CO CN CJ) O - T- T Tt in oo o CD - O CM 00 O CM Tt CO CN O LO CN O CD CO cq CD CO CO N- CN CO CM m τt co t m cN CD C) τ m ^ M M q q c CO CO CM O OO CO O I s - 00 O CO I s - 00 in co m in oo CM CM - b ^ ^ M CM c O N d τt ιb ιb ιb cb Ni τt τ ' cb 00 CN CM - O CD CN CO CO CD CO CO Tt Tt Tt LO CD - T- T- OO T- T- T- T- CD CD CD CO CO Tt N- N- O CO OO CO CO T- T t O τt τ- ι co ιo τt o co co co τt co ιn cN τt cN θ CJ n τ ιn t co τt t cD CD θ - cM τt τt ιn cD CD N- -!- LO CJ) N- CD O N. CD N- CD - σ) CM co c) CJ) c) co co co N- - cN in ιn ιn τ-- N- cD in cN θ CJ) co o c) σ) CM CJ) CJ) - c) CN CJ) τt LO O O CN CJ) O CD O) OO T- - CN N- CO Tt O CD CD CD N- CO - CD OO CN O CO CN CN CO N- OO Tt CO CO N- O LO CD Tt in CN CO O O N- ιn N OO CΛ CD ω cθ in ιn N ∞ N N OO Cθ ro CD O Cn N N N N N OO CD in CD CD CD N CO O. CO N N CO CO in θ. O O O τ- CM τ- CM CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CO CN CN CN CN CN CN CN CN CN CN CN CN CM CM CN CN CN CN CN CN CN C^ - CN - CN - CM T- CM C Q Q < CQ CJ Q Q o CD < CQ Q Q LU LU Q Q O O O O o o o o o o z < c < OQ υ o O O O O o o O O O O O O o υ o o o z o o z < C o o O O O O θ o:θo:θQ:θα:zwz t owzwz«zwz{zj . zcooι^ιQ^ιo:Dιoι:oι:ιQ^c^c>o-c>o-c>o-c>o-w>->J-J^J>--i^ fΛ i f 2 Λ i5 f !i n ] f w n f w Λ ww fΛ f w Λ Mιιιιιιι Q. CL CL Q. < < < < < < < < |- H H H H H H O O O O O O X X X X X X X X X X CL Q_ CL CL Q_ Q_ D. © 0) O - CM ( U. (D N OO Cn θ - CM C O c co co CD co cD o D N N N N r s - r s - t s - N- r s - CO CM - τt CO CO CJ) OO OO N- O - T- CN CO T- cD o m σ) τ- τt o oo τt cj) in σ o cD Tt - co N- Tt cM OT - in CO Tt O Tt CO CD Tt CN OO OO CO O CO in CM Tt CJ) CN od αJ ω N D D N d dcd Ncό CO lΩ - N- LΩ LΩ C-D CΩ N- lΩ O τ- CO N- CD OO lΩ LΩ m - τ- - - t - τ- - - - CN '»- τ- τ- T- T- CM T- - - - - T- - CN CN - - - CM CM CN CM CO00 - CNLOLOCDCJ)CJ)τ- CJ)τ- C0 - CN T- CO T- CJ) τ- o ιn ιn r- - co r- Lo cD co cD θ - CD CN CD CD oo τt τt ιn cN co τt N- o c3) CN oq cq cq O CN O CM N- 00 CJ) O I s - i cb lb CJ) CJ) -^ CM CJ) o CO ^ CN CO T CN - - T- - T- CM CM CM CM CN CN CM m CO CD O T- Tt O T- T- OO O I s - CJ) I s - LO LO CO CJ) in CN CD 00 CM Tt CO Tt CD Tt Tt T- 00 O CD Tt Tt t 00 Tt Tt CJ) CO CO I s - N- CO I s - T- CM CM Tt CO T-; CM — — CM CM O O CM CO Tt Tt Tt CD Ni CD Tt Tt CO CO CD Tt in iO CD CM N- CD CD CN CO 00 I s - I s - CD C0 Ln C000 CJ) O O CD Ln L000 CN 00 τt CD in CD N- CD L0 CJ) N- CN in θ O O τ- 0000 CD CO N- CJ) CJ) CO τt CO N- CD O CO Tt CD O_ C.N- CD CN CD σ) CO CO N- CO O CN CN N- - τ- θ σ) CM OO τt O CN t- lO CM CO CO CJ) CN O Tt - Tt q q c -r- cN in c oo CcMM NN-- iιnn o∞o iLnn oco - -- c -N ■ τt t " iιnn rocΛ Doco D ωc iτtt o. roq cM iinn cD cq ocqooq iιnn mMn N o c r cb cM τt τt cj) cb cb cb Ni ώ N ' d oo d b d d ^ N cd ra i — ■ -iri- ■ i-n- ■ i-ri- ■ —' d— ■ ^ - ^ ' ^ ' b — ' ^ ■' ^ ■ ^ c^ j C oo cj) i OO CO CO CO CN CN CN CN CN CN CN CN CN CN CN CO CO CO CN CM CN CN CN CN CN CM CN CN CO CO CO CO CO CO CO CO CO CO OO CO CO CO CN CN CN CM CN τ- CN t- CM τ- CN 00 CN Cθ CN - CM - CM Q LU LU N < OQ O Q QoUzJ UoJ CQ Q LU LU < OQ Q LU oooozoooooo UoJ NoNoXoz <oo < OQ OO oυoooozoo O O O O o o o O o o o o o o LU UJ LU IJJ Q_ CL Q_ Q_ Q. Q. Ω_ Ω_ Q_ Q_ Q_ Ω_ CL Q_ D _D Z D D D _D D 3 h h l-l- h J J J J J J J 1 Q. Q. Q. X X X X C_ Q: Q: Q: Q O: Q: Q: O O: Q_: Q: Q: Q_: LU LU LU LU LLJ UJ LU LIJ Q L θ. CL H - H H I- 1- l- H H H I- l- h- h- O O > > > > > > > 1- H 1- 1- © ιn CD N C0 σ) O τ- CM C0 ^ in (D N 00 σ) O τ- CM C0 \f lΛ CD N 00 O - CM C f lO CD N C0 σ) O τ- CM ( ^ in CD N C0 CJ) O o |^ r^ N- N- N- CO C» CO CO OO CO CO CO CO OO OT CJ) C3) CJ) CD C_θ σ) CD CD CJ) O O O O O O O O O O - - - τ- τ- τ- τ- τ- τ- τ- CM N N N N N N N N N N N N N N N N N N OO OO OO CO OO CO OO CO CO OO CO OO CO OO CO CO OO OO CO CO OO -<- CN τ- CO LΩ CN τt CO oq -r- N- Tt q Ni 'r- : τ- : cj) Ni Ni c t- CN CM τ- τ- τ- - - Tt CN in CO O CN Tt N- N. τt CJ) O CD -«- 00 O O CN CN 00 CN τ-; τt q LΩ 0q q τ c τt τ cN c i τ ' ,,: CN CN CN CN CN CN CM CN CM C Cθ σ) τt CO CN τt CD r- ιn - cN m co cN in τt o CO CO N- O v- OO m CJ) CO Ln CD N- 00 C0 τt 00 C_ O - T- T- T- T- - T- T- CN CN CO τ- CJ ) O OO t- CM O C0 I- τt τt CO 00 τ- cM τ- N- N- oo co τt σ) CN CD CM O C0 σ) Tt in - CJl OO CN O CO CO τt τt l s - CD CO N- S (θ o iΛ io uo D t ιn c ιn ιn ιn ιn ιo CN CN CN CN CN CN CN CN CN „ τ- CM τ- (N CO CM Cθ CM - CM " r ~ CM C D Q U N N < 00 O Q LU LU < CQ O Q LU LU < DQO Q LU oQ OooozJ LoUoLUoooX N < CQ O < OOOOOOOO OOOOOOOZ OO O o o o o o o OOO o o Q_ Q_ Q_ Q_ CL Q_ α_ CL Q. CL D-D-D-DD-DDID-DZZZZZZZZZ o cocow w cj c/j co ^ ^ ^ ^ ^ Q^ ^ tD 0: 0: 0: 0: 0: 0: 0: 0: 0 0: I I I I 1 I I I I I t I I I I I I I >: > > >: > > Lu _u - _ LU Lu c o α: H H H H H h- H h- H- - 000000000000000000 _J _l _l _l _J _J _J J _l C0C0 C0 C0 C0 C0 < < < © o τ- M ( f lO !D ^ CO σ) O r- M ^ Λ O ^ CO O - M CO ^ ιn (D N OO σ) O - CM C 't lβ D ^ CO O. O 'r r ^f ) (D CN CN CN CN CN CM CM CM CN CO C CO C CO CO CO Cθ Cθ Cθ τt τt τt τt τt τt τt τt τt τt lΩ lΩ in in co oo ∞ oo ∞ oo ∞ ∞ ∞ oo co oo co co co ∞ co co rø ω ∞ ∞ ∞ ∞ co φ oo ∞ co ω co oo co ∞ ω ∞ co co co ∞ co ω oo co oo co O OO CN N- CJ) N- OO CD OO - CO O CD Ω CN CD oo co CD CD CO CO CN O - CD N- N- CN CD LΩ t O Tt O in Tt co co co CO CM CO CD LO t in co co co cN Tt co h- m oo o Tt m c) T- d d cb cb co N- CO CN CO ιn θ - CN C ιn N- τt τ- CN CJ) LO CN CM CM O N- OO CN LO CO CO CO O N- 't- CO τt CO Tt CJ) CJi OO Tt CO CO τt - O τt τt CJ) - τt CO τt CD Cθ CJ) CO N- CD τt LO N- Ln τt CO N- CO CO CO CD N- CN CM Ln - CO in I s - I s - I s - I s - N- ID - CD τt C_D in θ CO CO τt τt ∞ N- τt τt Cθ σ) OO CN -r- N- N- CO τ- CD CN CD CO - CO CO CD CO C_D τt O CN CD 00 I s - I s - CO CM CJ) O O O CO LO CO CD CO CD CD N- CM v- O O CD N- N- N- N- in N- CD CD Tt Tt CD LO OO C CN O O CN O O 00 CN . O CN CN CN co CD co in CM CM CM CM CM CN CN CM CN CN CN CN 00 OO 00 cb cb cb r-i N- CN CO OCD CO Tt O N- C.O. O.O. O CD CD CD O LΩ O-O_ l.Ω. T,t C_D O τt - O τt t- N- LΩ CO τt CD CO τt LO OO τt τt m m o Ln CN CN in N- 00 CN LO t- τt - cθ τt τ- τ- LΩ N- τt CM CJ) τt CO 00 m CN m c -o_ cM co ιn cj) - cM τt co τ- co τt cj) τt co ιn τt σ) N- ιn τt - cM CJ) Ln CJ ) 0O N- C0 τ- lO C0 N- CO τ- 00 - - lO τt CD N- 00 00 00 CO CM oo m co cN oo o OT oo co o o m oo cM in cM i- m N- cϊ co cN - θ - N τt τt oo ι o - o cj T- O T- CM O O CJ) O - τ- O - τ- - CM CN CM τt CM CN OO CO CN CN CN CO τ- - O CN CM CN 00 vι N CM CN CN CN CN CN CN CM CN CN - CN CN CM CM CN CN CN CM CM CN CN CM CM CN CM CM CM CM CN CN CM CN CM CN CN CN CN CN CM CM CM CN CN O CO T- N- I s - I s - O m CO CO CO CD CJ) Tt CO CO q CM N- oq T- q CJ) i ub ωcb i Un c ωb c ωb UinJ τt σi CO OO OO OO CO CO CO CO CN - CN T- CN - CN O Q Q LU N X < < C Q O < CQ LU O o o o z o < CQ Q Q zzooozoooooozoo O o o o o < CQ Q o O O O CO O O O O O O O O O O O 00000000>->- >-_ι_ι_ι_ι_ι_ι_ι_ι_ι_j_j_ι_ι_ι I- H H h- I— I- I- I- _3 _D D _ Z) _D 3 _ Z Z Z Z O: Q: Q_: O: O O: O: Q -I -I -I -I < < < < < < < < < < < < < < LU LU LU LU LU LU LU ^J LU LU LU LU LU LU LU LU CO CO CO CO <<<<<<<<oooo>>>>>>> >>>>>>> _> _I _J _J _I _I _I _J _I < < < < © o N ∞ cn o ^ M ^ ιn (D oo σ θ τ- N ^ ιn (D N ∞ o) θ - cM ^ ιn (D N oo σ) θ τ- M co \f io co N oo σ) θ τ- tD CD (D N N N N N N N N N N OO OO OO CO CO OO ∞ CO CO Cθ σ> C» O. CB C). σ) CI> Cn θ. σ) O O O O O O O O O O r- τ- τ- ∞ OO CO OO CO CO CO C» CO CO CO CO CO OO OO OO C» CO ∞ OO OO OO CO CO CO C» ∞ OO OO CO CO CO OO C_D CJ) CJ) CJ) CJ) CΛ CO Tt Tt ιn cD Lθ cb cb T- - T- O CO in T- LO OO CO N- CD ιb O CO CN CJ) τt CM Ni T- q cb lb cb Tt Tt Tt - CM - CN T- CN t- CN CO O Q Q < C Q O Q LU N X X < O Q O O < CQ OQ LU < CO O Q UJ LU < CQ O Q O O O z ooooυozo zzzoooooozoooυocoo O O O O O O OO O O O O O O Z Z Z Z O O O O O O O _j _i _i _i _i _i _i l- H I- l- H !- H I- D o co o co o co c co c o^ o^ o Qi Qi Q: Q: Qi Qi o: Q < < < < < < < ω ω ω !^ !^ uJ !i. ω I I I I I IDIDI I o <<<<<<<<<<<<<<<>>>>>>>^ΈΈΈΈΈΈΈ OOOOOOOOO © < U1 CO S CO Cfi O T- C C f lO CO N CO Cn O - CM CO ^ in (D N OO <B O ^ CM CO W (D N CO Cj. O '- CM CO ^ lO CO N OO o τ- τ- - - - - τ- CN CN CN CN CN CN CN C CN CN CO CO CO CO CO CO CO CO CO CO τt τt τt τt τt τt τt τt τ^ CJ) CJ) C_D C_D C_D CJ) CJ) CJ) CJ) C_D O) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ s . C_D (3) CJ) C_D CJ) CJ) CJ) τt cD CJ) τt σ) c o cN τt LΩ t- σ) in τ- CO T- OO N- 00 T- LO Tt CO CD OO O N- CN CO N- CD - CN CD - lΩ τt CO LΩ CJ) τt O τt CJ ) CN '»- - CD N- N- - CN CJ) LO CO - CN CO CD CO N- OO CM CJ) CJ) CN Tt Tt CD CO CO Tt CO in CD Tt O CN OO OO N- T- CO CN OO - Tt O CO CO N- OO c. cb c ' τt cj. cb c) CN- d Lb I s - in Tt CD LO - 'r- CD N- τt N- CO τt O τ- O τt CD CO CJ) 0O CD C0 CD τt CD r-. OO - Tt Tt Tt D CO N- CN CN CN CN - T- CN CN CM t — — CN CM CN CM CN CN CN CO CM v- T- CN CN CN CN CN CN CN - CD O CO N- O O - O N- 00 CO Tt CN I s - T- CO I s - CO n o CD CN OO N- - OO Ln CN in O N- N. CO CD I s - O I s - CO CO CD CD CO OO CO CO lΩ CJ) i CJ) CD - in o CD T- I s - O τ- τt σ) N- O CD O LΩ τ- LO CO CO τt CO τt τt ιn q q q τt cD CM CJ) θ - in CD 00 in CD Tt CM Tt Tt CO 00 CN CO N- CD Tt LO OO O CO OO OO OO N- OO CD OO CD Tt Tt CM in CO I s - CD o c) CM t- co N- N- o iΩ CN τt q τt oq o CN cb Lb ιb b τt τt cM CM τt in CN — o o T- CM CN T- o T— CM CO T- o O O T- 1 τ cb c ιb τt τt ιb cb LΩ ib cb Ni Ni ιb cb CD CM CJ - N- CO CJ) CD OD CO CD N- CO O - CJ) τ- CO O CO N- CO CN - OO O O CJ) - in Ln τt CO N- CN N- CO oo Tt t I s - in T- CD LO CD CD CD O o co cn i- co cN θ co o co o cN CD - co ιn - ιn cN τt c σ) r- CM co r s - co co ιn co ι s - ι s - τt cj) O_ LΩ - IO Tt in CD 't co oo CD t O O r- O O OO CO CO in CN O N- N- CO N- LΩ CD N- LO O - - N- CD CO T- O CN CO OO O CD CD CO N- N- CD - CDCOOuO COT-^f W ^ ^ CM τ-τ- M θ nooc»co o ^r- o n coN Q θ cnωN cnrocj. oc» B » c» θ τ-ωτ- cM ^ ιn CN CM CM CN CN CN CM CN CN CN CN T- CN CN T- T- CN CN CN CN CN ^ T- T- T- CN T- T- T- T- T- T- CN - T- T- T- C Tt Tt in CD O O CJ) CD o O lΩ CJ) CD OO - τt O O N- N- τ- cD oo co o cj) τt c_D CJ) Lθ - co co τ- o ιn co oo N- t- ιn τ- Ln o - CN CM CD O CO CJ) CO CO O N- CN Tt CO CD OO N- O N- OO N- CO Tt O CO Tt CJ) O N- CJ) OO lO Tt CD Tt OO CD f- CD OO CD CD CD CJ) l s - CO CD τt oq cD CD cq q oo c j > co cq cD co cN m -<- co σ)qq - O Tt o cΛ - oo cD oo - N- in o oo i^ Tt co cN Tt Tt q i cq Ln N^ c d cj c Ni oo Ni Ni Ni o o cb Lb cb ι τt CO - CO N N N cii d ^ iri iri co b iri iri cMV ^ cM o d d d cd cji o. τt τt τt C CO CO CO CO CO CO CO CO CO C CO CO CO Cθ CO CO CO CO CO CO CO CO τt τt τt CO CO OO CO CO CO CO CO OO CO CO OO CO CN - CN LU N < CQ O C Q O Q Q < O O Q UJ N < mo < CO < OQ O o z o o o o o O O O O O O O O O O O O O O O O O Z O O CO o o o o o o o o υ W >->->->-p^ ^p ^p Q 3=)_D33333COC COC COW >->-- J J J - J J ii JL i J ii JULUu j u j iiJi_JiiJ>->- >->->->->->->->- ->->->->- J ^^- J ^ dd jθθθθc wmto(θ(ojjjjjjjjjjjjjjjjjυuϋϋϋϋ<<< < O τ- CM C \f © 0) O r- CM C f in CD N CO O. O r- CM C '< in CD N CO CI) 0 ^- CM C ^ lO (D N CO O) O r- CM C '5 lfi CD N CO O) 0 0 000 o cD CD CD co cD CD CD CD CD co N N N N N N N oo oo ω rø ∞ co ω oo co rø ro cτ) ro cn σ) c» (j) CJ) σ) cn o o o o o O CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CD CJ) 0) 0) C_0 CJ) CJ) CJ) CJ) OT CO O O CM T- OO N- CN LΩ CO m O o in q N- Tt cN Tt h- q - O cj) d c τt ' d τt σ. d τt d cd Tt T- - CN CM CN CN T- CN CN OO CN CM I s - OO CD CJ) T co CN lΩ - N- CO O Tt CD CO CO 00 CN CJ) Tt co in WN CD CD Tt CO - CO in o N- in cb cb ' CN in co CD m T- CN CO CM CM CN CN CN co in Tt in 00 O CN O O ■ «- CN OCD inθOCDN-τ-τ- σ) -r-C OO Tt CM O N- 00 CO I s - CO in O Tt m O O N- Tt T t CO CM CJi T - T t T- CN -CO COO. C» COτ-O)00CO^- CO00CO N τt CJ) O CN -5- O N- CO OO OO OO OO CM τt CD m τt θt- τtocoN.N-oom τt cj cθLnN. CO N- CO OO CN N- - OO O CD OO C CO - CO CN CO CO CO O CN CO N- in - CN CO v- O m N- Tt T-; CO CM Tt Tt oo O CN CN O O CN CM CM Ni oo cb c σi oo CD o o CO Tt CN CM CO Tt CO o o - I s - CO O 0) 0) 0) CD cb r-i cb o CO CO CO CD CO CO N- CO CD CO CO OO N- O τ- OO CM CM τt CO LΩ LΩ N- CD lΩ CO Tt CM in CD - oO LΩ LΩ O O Tt T- OO Tt Tt O CN O CD CD O CM co o cD co m m m co cD CN CN m cN CN co co co Tt CO O CN CO in τt in CD CD C_D CO Cθ in N- CO CJ) - CD OO C_ O OO N- CJ ) CD OO CO CN CJ) T- CM 00 T- 00 C0 C0 V- 00 00 CD CD 00 O CM O C0 N- τt τt N- CN τt lO τ- | s - oO CD CJ) - cθ CD CO LΩ LO t- c CD CD in cθ m CM O τt lO (D (D τ- - - τ- σ) O O O O O O - ^ lO lO lO CO lO N (O ^ CO ^ in iO M» OO N (O θ σ) O - (M O O. O. O. O - CM CN CN CN CN CN CN - CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CO C^ cD c o CJ ) ) - ( C.D ) Ttr N CI) CD C0 Cβ 0. N d d CO CO - CM „ - CM T- CM v- CM ^- CM CO CM CO CM " " CN Q UJ UJ m X oozz <ooooo Q oQoUoJ loil No < CQ O Q Q LU LU LU N N X < CQ O Q < CO Q LU LU ozoooooυo ZOOOOOZOOOOOOZOO O O O O O Z Z o:o α:o:o α:o:o o: o:o: o: Q - Q - Q - Q - Q .CL Q _ Q _. Q . Q .o. Q _ Q .o_θθθθθθθzzzzz zzzz o >->->->->->-^ ->- >->- >-o_irQ:i]_D Q_( Q_D_Q_Q_Ktt:Q:D:aQ_ [i_[i.D-ir j j j o o o HHI—l-l- Hl-l-HHHHHHHHI-HI-l-HI—H -h-HQ-Q_α.Q_Q_Q.Q. OOO OO O_l © lO (OS Oθ σjO - lfi CDN CO O) 0 O O O O O - - τt τt τt τt τt LΩ O O O O O O O O O O O O O O CO CO CD 00 CO - c) in co oo o co t N- O 00 I s - Ln N- Ln co Ln cM t- co ci o co cN O co N- m m cN N- co O O τt O CJ) CO CN OO CJ) in CM N- - O CO OO CD CO CD N. CO CM I s - I s - N- oo co oo cD O N- N- o oo cD in co co - oo Ln N- co o Tt m oo cM T- oo N- N- co N- m LΩ O τt N- 00 CJ) 00 CJ) l- C000 O CO CM CO CN CD I s - Tt CD τt CM in τ- O N- τt CM CO CO τt CD - Λ - oO Tt cM co in L cO Tt CN CN OO CM CO CO CO CN CN CN Tt Tt in in in co CN τ- τt τt ιn ιn cD τ-- o co c» o - o o σ) co ιb LΩ cb Ni Ni cb cb τt c CO CO CO CO OO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CN CN CO OO CO CO CN CN CN CN CN CN CN C^ Tt CN CD O N CJ) CO lΩ CO τt CD CD 10 CO - T- CM - CN CM T- CM T- CM CN < D0O Q UJ N < CQ O Q LU LU < 00 O O LU LU < CQ Q LU N < CO Q LU UJ < OOOOOOOZZOO OOOOOZOOOOOOOOZOO OOOOOZZOO OOOOOOZO WWWCOωWWtO ^Dp pD DDDDDtOW oooooooooooooooooo >- >- >- >- >- >- >- >- >- LU LU ooooooooo © - CM C ^ O(D N Oθ σ) O τ- CM C ^ Λ tD NCθ ro θr- CM C ^ U1 tD N CO O) Oτ- CM C 't inCD N Cθ σ) O - CMC ^ in (D o ιnιnιnιnιnιnuou)incD(DCDCDCDCDcoco cocDNN NNNNNN SNωcoωcococococococoacnσ.σ. σ)c>. cj. OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO CN Tt o co CN N- -— Tt O CD — CO I s - N- Tt N- o o — in o CO in C CD O) — O CN o m CO CO CJ) m N- O Tt CN O CO Tt CN CM CO CO CO CO - o CM CM CN CM CM CO 00 CO CN CN CN CN - OO N- CM CN — LΩ Tt I s - — LO o CN CN in m τ- in Tt T— oo o Tt 00 T— o CN — CO O O CN Tt m CM CO in O — o LΩ CO — Tt in CD -. CM CN CO Tt T- o Tt in co N- CN CO CO N- O LΩ O CJ) τt CN CO CO CN LO N. τt OO CD CD CO τ- CO CO LO CJ) CJ) CN τt OO O CJ) co in I s - - CD N- ^ O CO LΩ CO CO CM Tt CO in O CO - CO OO CD CD OO N- CO - O OO CD N- O m m CO CJ) O CD -ϊ- C0 τt σ) CJ) O N- O oo m oo N- T- in CD CO O OO OO OO Tt Tt O in in cq CN ∞ τt τ- Lq τt - - CO τt τ- CO CN CJ) CO τt CΩ ∞ τt C∞O τt CD N- CJ) τt ∞ OT CO CJ) CN CN O N- co M CM b b o d d^ ro oό in i N N o cό d d iri CM CM CM CM CM " CM CN CM CM CN CM CN CM ^ - CN CN - CM - - τ- - - - - - - - - - - τ- τ- τ- τ- - - - τ- τ- v- τ- - CD τ- CD CO CD CD Tt T- cn CD CO N- CD N- N. τ- <X) N- l s - l s - τ- τt CM CJ) O - CJ s . O N- N- O CJ) CO lΩ CJ) CO LO CD CN LΩ τt CD LO CO O CJ) CM Tt CD LO CD U Tt T- N- N- CD N- CD r- in τt σ) CN r- LΩ O -t- O - τt τt τt OO CN I s - CO OO CO CD CJ) LO CO LO CO O CO CO CO CJ) in - CO CD CO CJ) CD CM τt CO -r- O CN CJ. N. | s - CD O CJ) O τt τt CJ) σ) C0 00 CN O CJ) C0 N- 00 LΩ 00 τt CN CN CD τ- CJ) CD CD O N- CD τt 00 00 - - co co in m o CJ) o o CO I s - I s - CD 0 >r- CD O CN CO CO CO τt τt in C_D N- co N- co co m in Tt cD o cD O - CM CN O T- O - CM CM CN CN CN CN CN CN CN CN CN T- CN CN CM CN CN CN CN CN T- - - T- T- T- T- - - T- CN T- CN CN CN CN CN CN CN CN t- CM T- T- CN - CM t- CN - CM OQ O Q LU < CD O O Q < CQ O Q Q LU UJ N < CO O Q LU LU < OQ o a Q < O O O O CO o O O O O O O O Z O O oooooooo O O O O O O OO ooooooozooo I— h- h- I— t— h- J UJ UJ L_l liJ lU l_J lU UJ LU liJ D D D D D D D Q. l Q. l (L 0.11 Q: Q: D: o: UJ UJ UJ UJ _J UJ UJ UJ _J _J UJ UJ _J _J I I ii i I I I I I I j j j j j j j j j W ( t0(j. (0 W WWI I II 22225Σ dd dd__ddD._.iD.D. D. Q .ll_.D.C9 ( Dϋϋ 5 { . ϋO ( l ) <<<.<<<<<l-l-l-l- © cM τt o - y o © © ! _ H U α. CD CJ ) CN - CJ) in cO CN O CM O N- co cN co τt co co co σ) θ co cj) cr) CM τt c) co co o c) θ θ c) in co cD CJ) θ CD in ιn co cN co LΩ CO N- Tt in Tt Tt in cM CN Tt co o cD c i c o Tt - in o co Tt co co oO Tt cN Ln c q cq - q cM - q ^ in - Tt CM O Ω N-i d N ' N ' b d ^ b b ^ iri i iri o M ' b^ ^ d N od ^ ^ o bN CN CM CN CN CN CN CN CO CD in CD CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ CN CO m T- CD CN Ln τt CD CO O N- l s - CO LO CD CO I- - αθ O lΩ O CN CO N- O CN CJ) CM CJ) O N- CN CO CN in τt τ- O CD CJ) CD in Ln θ CJ) 00 T- CM CO T- ra o cM M co D N co c in o in co D io ^ co c in in co co - ^ ^ Tt ^ cD N cM N co N ω D - N B Tt o in CM oo o co cθ N- o co co σ) oθ - oo cD θ θ τ- σ) CJ) co cD θ τt cj) θ CN Cj) cθ - τ- τt q oq cD i s - oq q q ^ ι ιb τt r s ^ c cd c c i s ^ r s ^ i^ .^ cd c d c t^ ι s ^ c - - - T- T- - - - - - - - - - T- - T- T- CN - - - - T- - T- - T- T- - - - - - - T- - - - T- - - - - - - CO CO o co - cN in Tt Tt T- Tt N- U CN C N- Tt Tt in CN O T- CD CD CO in CN I^ CN Ln N- T- CD N- OO - O CO CD O CD CN CO o co o o τ- ιn o CD CD CN CO OO Tt CD O CN CN - co cD CN co ιn τt N- Ln ιn N- cN θ CD c o co cN τt cD in ιn cN in < r- N- σ) oo cD CD τt co τt σ) - ■ «- τt τ- τt τ- CM CN CN CO τt τ- O τ- ιn cθ CO CD O O lO CO LO CO CD O N- CN CD CO CJ) τt C» CO CO LΩ CM CN CD LO CM CN Ln N- Ln oθ τt CM CO C , UOin c C \f C ω N CO Cθ ω U. in CD CBOr- τ- ^ c CO ^ ^ CM CM ^ '*CM CM CM CM in cθN N N (D CO COO. O t- T- r- - r- T- - T- ^ T- r- r- T- ^ T- - T- CM N CM CM CM CM CM CM CM CM CM CM CM rM CM CM CM CM r CM CM CM CM CM rM CO - C0 CJ) σ) τ- O τt 00 O CD CJ) C0 O CD τ- N- N- O in CM in CD N- O O OT OO CM CO OO r^ CO Tt N- OO O CD CO Tt LO N- N- Tt Tt 1- CN CM CO N- in τ- O O τt OO CO τt O O CO CO τt O OO O CO CD N- τt N- CO CD OO CD CD O τt CN OO CJ) Cθ σ) in CD in oθ l s - τ- CJ) O CO CD N- O CO N- Tt O OO LΩ CD Tt CN o oo co CD m co in θ O OO LΩ LO CN CD CM τ- | s - CN CD OO τt τt CO LΩ CO CO τ- N- in CO CO CO CD CD CJ) CJ) OO N- CD CD O CM cb Tt cb CM C O CΛ CO CO - CN Tt Tt CO in CD N- N- Tt Tt Ln CD CO CM CO Lb cb cb CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CM CN CN CN CN CN CN CN CN CN CN CM CM CN CN CN CM CM J" CM - CM v- CM - CN T- CM 00 O O < OQ O Q Q < OQ O Q Q < O O Q LUN < OQ O Q Q < CQ O O < O O O Z O O O O O O Z Z O O O O O O O Z O O O O O O O Z Z OO O O O o o O o o o o o DDDDL θ: ( -:o Q :^DDD lil lJJ l_J UJ l I I I I II ω I I — I — I i — I — I — I — 1 — 1 — I — — I — I — I ιn CD N Cθ σ. θ - cM cθ f io cθ S co N N N N N CO CO CO CO CO CO CO CO CO - CD LO O Tt OO CD - CO N. CO - CO CO I s - CD 00 co ιn cN CN q cM τt cN q oo N- 00 CD CN CO CD "in * * "LO * * rt CO"- *T —- OT r> / C v O *1 ■ T β "t 1 " ^CO^ / O~~ 'O " ^ x- - Tt CD m m CM CO CN CN CO CO CN τj- ^ t cθ CO CO CO CO Cθ CO CD CM CN Tt m t- m cD t- m cD m o N- Tt O) C0 00 CM CN CM CN t- Tt CM CN in CN 00 Tt Ln m co τt oo o cj) in o ι s - ι s - cN O LΩ CN N- CJ) CD Tt Tt oo o co in cD co o Tt oo C CN CM OO CO - τt r s - CJ) CD CO CD r- l- CN O τt CD CO O0 CM CD τt N- CJ) τt τt CJ) I s - LΩ CN T- Tt CD - N- N - cq cN cq -r- τt r- : q N- N : ιn N ; CD co m T- co Tt in c) c) CD cN iq τt cq q cq q τ- τt cM cq q O OO I s - CO o o ∞ b iri d ^ b d d d ^ ^ c T- σi σi oci cό b T- oi. ' r-i Ni -i in Tt cb cb cb i r^ cb cj- C- od d in Tt Tt Tt c cM " 00 Tt Tt - T- - - - - CM CN CN CN CN CM CM -Ϊ- - T- T- CN CM T- T- - - - T- T- - CN - - - T- - T- o τt cM co τt oo m oo τt Ln o τt τ- σ) CD t- OO τ- CO OO t OO CD O LΩ τt LΩ N- O O N- - τt C0 CD LΩ CD τj- r-- -<- CM t- N- τt N- CN Tt oo r- co N- oo cN in co oo cN Tt lΩ CJ) N. O τt CD N- CO O LO CD N- CJ) CD O CN O CD N- CD CO O O Tt CO τ- N- CO τ- O O CO CO N- - - CM CD CO Tj- OO in CO LΩ τt ιq cq cq iΩ CM O - - τ- CD CD 'r- in CD τt τt CD LΩ c τ- τ- o N- oo cj) θ θ CD co cD q q q τt ■ d -r- 1 d ^ d cM c o ^ cN cb c c c < t t c t c ιn τt ιb Lb τt ι ιb τt b cb cb Ni cb LΩ cb cb ιb cb CO CO CO CO CO CO CO CO CO CO CN CO CN OO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ oo oo oo in co o UO CB ^ CO N CO C» CD C CM C ^ CO ^ UO (M CM CD CD Cn θ C ^ O CO C). CO ιn CM in θ CM CM CM ^- CD N N OO LO CO CN T- CO OO OO O 0θ0 rCMM Tt. T.t CCOO τ-- OO. CCO CCOO ( CθD πO I s - CCDO * τt 00_O ( CDO ττ-- ( OT0) τtt rCN. I s - τ'«-- ( CD0 ( CJJ)) <τ*t CCNM ττt. NN- σCJ) ) tCOD τ-- *τt SN- CCTD ) τι-- Nι~ r>.M (VΛD_. LO - C IM C uD_> τ -str τ "tr C IN - C UDJ LΩJ ULΩJ Vt OJ 0 V'0J - C.O'J C (JDJ CDU C V.O'J C UJ)J CM CD N- O CN - C VJOU τ '^tr C <AOJ L UOJ C LNN C IMN L UΩJ O UOU C IMN τ "NtT C LNN C UDJ N H- τt O U C INN C UJ)J C UD σ U)I iD N OO C» OO N N CO S N CD N in CI) O - τ- θ τ- τ- c ^ CO CM CO (M (M '- ιn CD S OO N CO Cθ σ) N CO O. σ5 N (O Cθ - O τ- CN CN CN CN CN CN CN CN CN CN CN C C CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ - CM - CN T- T- CM - CM - CM v 00 O Q Q < CQ O O Q < CQ O < CQ O Q LU LU < OQ O Q Q < 00 O Q < O o o o o o υ o υ o υ o O O O O O O O O O O O O O O O O O O O O O O O O O O O Z O co I s - T- Tt co in CN CO τ- O CN CO lΩ CD CO CO N- τ- m O CD CO I s - CD CO N- co Tt I s - CD T- CN τt τt - CJ) CO τt τ- LΩ LΩ τt m CD Tt Tt Tt CD CD N- o - o o - σ) o v- cM τt oo oo cN θ τt - - - cN θ θ Ln - ιn co N- CD CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CM CN CN CN CN CN v- - O N- o o o CJ) T— in CD CM CN CO CN CO CO CM OO Tt N- CO N- T- O Tt CD T- O in Tt CN oo co I s - I s - Tt CO CM 00 I s - co oo co o cj) oo O m co Tt o CN CD Tt CJ) o Tt CD CD O LΩ CO CD O CJ) CD CO CD CO CJ) LΩ O in N- CO CJ) CN N- N- in N- - co I s - LO O CM CO CO CD N- o in in CO CO o CO ■ *- CJ) N- CJ) Tt o CD 0O LΩ τt CJ)CD -»- CJ) t- - I s - co m N- o o - CM CO CO LΩ CD CO 0O - Cθ 00 CJ) τt CN "- LO CD N- oo CD CM "- o IM CN co co co m cN CN co co co in m co cD N- N- co co Tt m in oo cN co co CJ) d d T^ d d - co cN Ln co - co σ - CD CD C Tt O CD O co S N iq o oq cM ro ιτ-- : τ- dO θC3.. -- : CCMM C CM - CO CO OO CN 00 CO CO CO CO in τ- OO ^ ιn θ 0. ιn θ CO CD CM ω cθ CM CO \T ^ CD C» N CO CM N 0 N ^ O CD CM CM O O) N N CO in C3) CD ^- ιn c O O OO τt O CN CJ) CJ) N- τt CD - τt CJ) CJ) O N- τt CO τt CN CO CO CN CN O CJ) CN O CO in in CN τt τ CO in CO O (X» - CD rt τt N τt ∞ cN q cN CN ∞ cD co ∞ r s - co - co co σ) co co o cj) oo o cθ u co co co i s - σ) CJ) CN CN τ^ CM -^ CN CN CM CN c c Tt Tt c ib d ib Tt Tt Tt Tt i^ N^ o ^ ^ ^ ^ r ^ f \f ^ ^ ^ ^ . ^ l ■ ^ ■ ^ ^ ^ ^ ^ ^ ^ ^ r ^ ^ ^ ^ ^ ^ ^ , it ' N ■ , • ^ ^ r co c c o J- CN T- CN v- CM T- CM T- CN _ T - CN O Q O Q LU N < CO O < D Q O Q Q UJ lU N l < CQ O < co O O O O O O O O Z Z O O O O O O Z O O O O O O O O O O O ooooooQoQ LoU LoU NoXo υ υ o o o o z CO CO ^^^^^ C C CL CL LCL L L L^ C^ α: cc a: ca ct cc _ι 5^ ^ ^ χ χ >->-^>-^^^^^ >-^?-^^^^^ ^^^ -^ χ χ X χ X χ XX χ X χ x < JJJJJ|-H h hl-l-Hhhl-l-hl-l-hl-f-hhhhl-hhl- hf-hhh hhh 1h-Hh l- > © uO (D N MO)O τ- CM ( M- u1 CDN OO O) O - CM C ^ UO (O N CO CB O ^CM C ^ in (O N Cθσ) O - CM O ^ lfi CON CO O) 0 o c Tf ^ ^ ^ ^ ^ ^ ^ N - in in in in in in in io in in o co D CD CD o cD CD D CD N N N N N N S N N N co o CN CN CN CN CN CM CM CN CN CN CN CN CN CN CN C CM CM CN CM CM CM C CN CM C CN CN CN CN CN CN CN CN CN CN CM CN CN CN C^ y o © © !_ H U α. co co m o m m c) τt CM co oo o CJ) CD - LΩ OO CM CN OO LO N- O CO CO CD - CO CD N- N- CO Tt LO O CJ) CJ) τ- oO CD OO τ- CO CD - N- CO τt N- OO OO CO O τt T- - CJ) v- I s - N- O CD CO CJi - O N- CD CM O OO LO CD CO CO CO Tt h- T- CO CO - CN CD t- N- CD CD CM O CO CD N- CO CO CM CO CO O CJ) CO O CD τt CD in - CM τt CD O CO CO CO τ- N- CM CD I- OO CD CJ) CJ) τt CO CJ ) θ σ) Cθ LO CN τt LΩ v- CM T- CM I s - ■ <- CN CN CN CN CN CN τ- CN CM '<- CN CN 0O 0 O τt - CM CN CN CN τt CD in m τ- τ- CM CM -«- CN CN τ- CM τ- CM CN CM CN τt m O M M M CO <_D OO τt CN N- LΩ OO τt N- LΩ CO LΩ τt - o r- CJ) 00 0 "r- CD τt CD CM t- CD CD O τt CO CJ) CM CN OO CO CO OO -ϊ- CN CJ) O N- TT CO I s - CN CJ) O CN τ- cθ O ιn N- uO τt N. - CD CM CO CO CJ) LΩ CD τ- O CO N- co Tt m o cN - m T- co co m m cN N- r- O O CD CO T- I s - CN CD N- CJ) CJ) O I- CO OO - Ln i s - τt CN CJ) τt CJ) OO N. CO CN N- τ- τ- - CO OOCOOθ σ) CJ)CO N- τ- CD N- l- '«- O τt LΩ OO N- - 0000 CO I s - I s - I s - CO O 00 N- N- CD CD CO in τt CN CM CN oo o o σ) CN oo τt τt τt o σ) O T- 00 I s - I s - CD O τ- τ- O CM OO CO τt CO - - CM ■ 5- CN CN - CN CN CN CN CN CN τ- CM CM - - T- CN CN CM CM CM CN CN CN CN CM CM CM CO 00 O O N- CO CD CO CO τ- CN -t- CN OO CO LΩ τt CO LΩ LO CO CO N- CD in 00 O in 00 CN τt O CN CJ) 00 τt O C0 CD τt - O N- τt in t- N- CD CO co cj) co cN τt θ - co o o co co oo co co ιn cj) CN τt m o c_D - ιn o co τt m N- cN t- m cj) co N- N- co oo oo co - co cN Ln cj) - Ln N- CJ) CJ) σ) C0 N- N- O CD τ-- CD τt O Ln Ln - CD CD τt CN N- θ σ) - τt τ- LΩ OO τt τt CO LO CO N- O CO C_D C_ '«- O CO CD N- τt O o o - o cB θ cn c» σ) N σ) c» cs o σ) ∞ o j. α3 o σ) CB » σ) τ- ro s cD in ιn ιn Λ ^ D io ιo uo uι ιo o uθ ^ ^ CO CO CO CO CN CO CN CN CN CN CN CN CN CO CM CN CO CN CN CN CN CN CN CN CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ iCOncτDt c VD m UJ CN CN T- CM T- CN - CM T- CN T- CN < co O O < DOOQ JN X X < OQ Q LU LU < CDUDQ < OQ O Q UJ UJ < o o O o o o oυoooozo o o o o o υ oz oo o o o o o oo O o o ooo o o UJ © T- CM C ^ U1 CD N OO O) O T- CM CO ^f in tD N CO IJ) O ^ CM CO ^ U1 (D N CO Oj O - CM C ^ lO (O N OO O) O - CM CO ' - lO (D CO CO CO CO CO OO CO CO ∞ CJ) CJ) CJ) CJ) CJ) C_D O CJ) CJ) CJ) O O O O O O O O O O - - τ- - - - - τ- τ- τ- CM CN CN CN CM CN CN o CN CN CN CN CN CN CN CN CN CN C CN CN CN CN CM CN CN CN OO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ y o © © ! _ H U α. - co cN N- ιo cN co N- τt cj) in co cN CJ) τt co ιn Ln cN co σ) co cj) N- oo o τt τt ιn co ιn ιn c _j) C_J) - CO - N- 0O CN LO τt τ- LΩ CO O O CJ) CJ) CD O - N- CN O O C C_D τ- O τt ιn cθ O CJ) τt CN CJ) CO CO CO CD θ r s - in CM in ττJt- ιmn CσD) CoOo r- τt oo τt o o cN Ln τt co cD τt co o cθ Ln cD co τt oo τ- N- Ln cM τt m ιn cD Tt CN τt cM _D θ τt cD co τt τt σ) co m o o - Tt CD Tt CN CO CN m cO O - CO CN CN CN CN CN CN CM OO CO CN CO CO CO CO CO CO OO CO Tt m Tt Tt cN oo Tt Tt cN co oo co Tt Tt Ln m r-- oo N- τt τt τt m m cD in τt CO cM oo ιn c» iΛ in co co ^ M N ^ co N - ∞ ^ c uo w ιn ιn ω co ^ o. o o ιn o N in - θ - CD i N N co u τ- cM CN CD Tt Tt - cO CD Tt CO CO T- CD CJi in CM CN CN CO T- in cO CJi CO N- CΩ O CN in CM OO O in Tt ∞ CO O N- in i^ O ^ in rM CD ^ CO N ^ σ. ω cθ CM C N (3. C» N N N CO » C Cθ in in CM C - ^ 0> - N '< CO CO CM C» 0 '" OO O - ^ N CM O r- co - o σ) O τ- CN τ- O CN CO CO CN OO CM CM CN CO OO OO CO τt - - CM CN O CJ) N- O CN CO τt m cθ - τt Ln CD N- OO I- CD r s - CD CD CM CM CN T- CN CN CN CM CN CM CM CN CN CM CN CN CN CN CN CM CN CM CM CN CN CN CN i- - CM CN CN CN CM CM CN CN CN CM CN CN CN CM CN CN CM CD - q c τ- CN CJ) CM τt CO CN - cθ O CO CO CD I s - CO 00 CD CD CO i ooocNom'ϊ-O -T- o in in m N- τt τt CN - τ- CN τt CD O τt CD (D in m oo o ocfl ^ N - M T- CM CO LΩ CD N- τ- CD 0O τt CO LO τt τ- CN CJ) CD N- CO - lΩ CO CO CN CO CN lΩ OO Tt m oO CN N. OO in - N- τt CO N. τt O OO N- co I s - CD ιn CJ) CO CD in cθ CJ) lΩ CD τt O CD CN O CN Tt CO CM r o c ιo ^ q q τ- N s Tt cb cb cb N cb cN -r^ -r^ T-÷ rococo N CD CO O CJ) CO N- CD U N- N- N- N- r-i cb cb in Ni Ni cb Ni Ni Ni cb c d c i i CN CN CN CN CN CN CM CN CM CN CN CN T- CN CN CM V- T- T- - T- - CN T- - - T- CN T- CM ■ «- CN CM - CN ■ «- CN OQ O Q Q < CQ Q J LU < co O Q Q Q O Q Q CQ < CQ O O < O O O O O o o O O O O OO O O O O O z z < O o o OOO O o < O o O O O O o o OO O o o © N oo ro o - c co - u cD N oo ro o - rM ^ in o N oo ro o r- o ^ in o N co ro o ir C c - in to N co ro o ^- cM C co c c c co c c - ^ ^ - - ^ - - ^ - o o i in in i in uo i in ω cD CD co o co D D D D N N N o C CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO y o © © !_ H U O o α. O CD CO I s - CD O O in θ CO CJ) CD CD uO O τt CO CM O N- N- CO CD Tt LΩ CD O Tt CO CM in N- CM CJ) CD CD CN τt N- N- 0 in co co CN CN C0 CD -; τt CD τt C0 CM 00 O τ- CD 00 C0 t- CN in N- v- CO CM v- co - in CJ) o CO CO O Tt CD Tt OO CD CD CD r-; cq q CM T- CJ) O - - CJ) CJ) o in iridcdcocDNVddcDcodcocoo CD in τt m N- Ln ιn o cN CJ) CM - τt oo I s - o o r-i d σi CM " 00 Tt Tt CO CO CD - CO CO Cθ CO CO ιn cθ τt CD CO CO C 00 CO u0 CN CO CN CN CN CO τt Cθ τt N- τt in CM CN CN CN CN CO N- CO CM T- CN 00 in 00 CD τ- N- LΩ CN τ- CN Cθ CJ) 00 CD τt CJ) CN CO CD τ- t- co o τ- co cD -«- τt ιn m oo cM - cj) i s - CD - ω r- m N N ^- - C τt τt CM I s - CJ) τ- m - C0 N- CN CD τt O 00 CJ ) 00 Ln -r- CM τ- co oo ιn cN σ) oo m co τt m o τt co τ- o CO CD OO CJ) CO O τt O τt τt CJ) CO CD uO O CO - CN OO CO CO CO O OO CN τt CO τt CO O τt O - N- CJ) O CJ) in CD CO CN N- m cθ N- -»- τt t- - CO CO CM - CN LΩ CJ) D N co in co N in N N CD o o ro ro ro ro N CD ω o o in N i in i co in ω D S CD i N in i - i cD in cD N D o cM - CN CN CN CN CN CN CN CM CN CN CN CM CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN 00 CO OO O t- OO OO CD N- CM in CN T- O CO N O CO T- O CD CO MO r- N O) N O. IO f CM N CO C N (M N O C O O Oj UT<f N Cn in CO CN C0 CJ) CN CD CO C0 m τt τt T- 00 CJ) CO CD T- CO T- N- τt CD CJ) 00 CD - O C0 00 τ- O τ- τt CD CM CM in τt C0 CN in CM C0 m θ N- τt τ-; CN τ-; CN q τ- τt CN τt CO CO in CN τ~ CO 00 T- τ- - τt N- ιn cN co τt cD σ) CJ) σ. r- ιn cθ LΩ θ θ τt N- o o cD in oo N : -r-; cq roddrodddoόoororosN in d ^ ^ ^ c C b ^ ^ c CM ro ∞ N iri iri ^ b ^ b cM in N d τ- CM v- τ- τ- CM CN τ- τ- τ- τ- τ- τ- - - - CN CN CN CN CN CN CN CN CN CN CM - - T- - - - T- CM CN CN CN CN CN CN CN CN CM CN CN - oo σ. 1- ro N τ- N co ro o OO OO CM 00 CO CO "^ CN T- CN T- CN T- CM - CM CO O Q LU LU < OQ O Q LU LU < OQ O O < CO O Q J N X X < CO O Q LU LU < OOOOOOZZOO oυoooozoooooozoo o o o o z o zzzoυoooooo o o Z Z Z Z Z Z Z Z) Z) Z) =) 3 Z) Z. Z) Z) O: O: Q_: Q: Q_: O: O: O O O O O O O O O O O =) Z) =) =) -D _ =) Z _D , j j _i j _ j j j j j j j j T T i T T TT Q: Q: Q: tt: a: o:Q: D_ : c_ Q: -i -i -i -i -i -i -i -i -i iJJ llJ lJJ 0000000000000000(r-HHI-l-HH<<<<<<<<<<< OO OOOOOddd CO ^, lO CD N CO (» O - (M t ^ UO u N CO C)j O - C CO ^ ιn (D N ω θ) O τ- CM C ^ lO (D N OO ffl O τ- CM CO 'J- lO (D N OO © S S S S N CO OO OO OO OO OO CO CO CO (n O) 0) 01 (3) C. (3) 0) 0) 0) C!) 0 0 0 00 0 0 0 0 0 'r T- r T- r T- T- T- T- O O CO C C C rO C C O O C C C CO C C CO ^ ^ - - ^ ^ ^ ^ ^ ^ ^ ^ ^ - ^ ^ - - " - CD CD O OO N- Tt LΩ T- LO Tt CO CO CD O Tt T- CN O CN Tt CD - CO CO CO CJ) τt CO CN τt CD O CN Tt co oo co oo m cM co LO CO oo co σ ) co co τt σ ) i o cN i s - θ τ - cN co m τt co cN N- - N- CJ) ococoscMT-iomococo OO CD LO O Tt O CO O CJ) T- CN 'ϊ- O Tt CD CO T- O CO CD N- Tt CD Tt o o in N- 00 CO N- N- τt τt COCJ)τt Ln σ) CJ) CJ) CO CD CM O CO CM CO Ni CN CN CN CN CN - - CN CM T- CN CN CN -!- - M ΓM - CM CN CN CN CM CM CM N- LΩ τt CO Tt CO CN CD OO OO CO OO CD CJ) in CJ) τt CO CJ) 'i- ; ro c c ffl - M N CM CN CM CJ) CO CN CD CD CJ) 00 in CD CD CO τt ∞ O CD r- CO CO CO CO Tt O CO CO in CD OO Tt Tt in CO CO CN in cO OO OO CN O CO CN CN LO - CO CO - CO O OO CO τ- N- CD CM CJ) τt O - ιn co cN co N- σ) co co ιn ιn ιn r s - N- cN CD τt co co N- τ- cD in ιn co τt τt N- co c) in - N. cj) Lθ θ CO CN CN N- T- CN OO N- CD N- τ- τt CO CD τ- O CN CO CO CD lΩ CO LΩ τt CN CJ) Cθ r s - CO O OO τ- OO O CJ) CO in N- τt O in cθ O CN r- CO ιn cM - - θ - ιn ^ ιn ω o N io ιn D N in ^ ιn ^ ι co ι j- ιn ιθ N ' - S - o o o N co N N N (θ s o D N CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CM CM CM CM CN CN CN CN CN CM CM CN CN CN CN CM CN CN CN C^ Tt OO OO CN t- CD N- T- CO - cN CN - ιn co ιn co cD θ τt ιn co co cD CN in τt τt co cN CD co τ- cD σ) o co cD N- τt r- cN in co oo N- lO cOO CO CN Tt N- cO CD CN τt θ τ- τt co - N- τ- ιn ιn σ) τt τ- - ιn τt o cN in τt τ- cD σ) σ) in cM in co ιn cj) θ co cN CD oo cM N- τt CO 00 τ- CO 00 - CD t- CO CJ) - O CD - CN ^ CJ) - CO O LO CO τt CO CJ) CN CO lΩ CO CJ) τt CD CJ) N- CO O O LO LO τt CO CD N- O CN CN -»- O CO τ- τt in uO CD CD LΩ N- lΩ LO CD N. N. Tt lΩ lΩ lΩ LΩ LΩ OO CJi CJ) O o o o CJ) O CJ) CJ) CJ) CJ) - - CO CO N- OO CO CN CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO OO CO CO CO CO CO Tt Tt Tt Tt CO Tt CO CO CO O Tt Tt CO CO CO CO CO CO Tt Tt v- M τ- - CM ^ T- CN T- CN ,. - CN - CM ^ - CM T- CM CQ O O Q < CQ O Q Q < CO O Q Q LU LU CQ OQ O Q Q LU LU < O o o o o o o O o o o o ooooozooz o <oooOoQoQυLoUoLU Noz <oo O OOZ OO Z ZO D D D D LU ocococo n c u Δ mwww ococococ J J J Jύ wcoc J J _.:I I I I I I I I I I © ro θ - CM C ^ O Θ N Cθ ro θ v- CM < r Lθ ω N OO O. O - (M C ^ Ifl CD N CO O. O τ- CM C ' in CD N CO C5) O τ- CM C ' - τ- CM CN CN CN CN CN CM CN CN CN OO OO Cθ C CO CO CO CO CO CO τt τt τt τt τt τt τt τt τt τt in LO in in in in in in u in CD C^ o CM CO CM CD LΩ CD LO CO OO N- CD Tt Tt CO OO O O m N- Tt Tt O CN CD O m 00 T- CO CN IΩ OO CM CO CO CO CO OO Tt O 00 CD OO CO CM N- CM CD Tt Tt OO Tt CD CM CD CO CO CJ) CJ) N- LΩ CN CN CD CN cb σi oo CM oo oo in co o o co oo N- m CM 00 CO CJ) u0 u0 N. m CO O0 O CJ) c) co co CM T- _ ___ CM CM CN CM CM CM CN CN CN CM CN CM CN CN it-- CCNM rt- r- rτ- r- r- r- r- _ ^ CN _ CN CN CM CM CM CN CN T- I s - CJ) CO O v- CO Tt CJ) in CO CO O O CN CO I s - O CN ∞ ιn CJ ) τt CD C0 00 u0 O CJ) CD u0 00 CN τt 00 O CN θ r- in σ) CD CN r- O N. CD O N. O -r- CN - N- in 00 CD CO LO CO Tt CO lO τt CJ) CJ) CO τt O N- CN CO τ- Ln CD CN N- CO N- '»- N- CD I s - CO LΩ CO CJ) C CO O Ln cN I- Ln CJ) 0 CN - CN CO C CN T- t ■ O ~ ~ q ~ Tt σ LΩ CD in co o co co N- N- τt τt σ) o o cN m cj) C ^ d σi cq oq q N- CM Tt CJ) D ^ T- T- - T- d v- σi cd in c oo 00 N- CO CD CD N- 00 CO CD CD u0 in r- CO N- CJ) N- 00 σi T- Tt cb 00 CO CM- CN CM in cN O x- Tt m cO N- CO N- CD N- Tt CN I s - O C CO CO Tt CD CO O Tt O0 CO CD Tt lΩ N- O CO CO lΩ CO -«- O CD CO CO CD OO τt CO - in O τt in θ CO CN LΩ CO LΩ CO CD N- m CD V CO CO - CO o co oo Tt CN CJ) in Tt CO LΩ CN CO CN CJ) in CN CN Cθ in θ σ) O CO CD O τ- Tt in cN co m in o cD N- cN CD oo C- _". o D O o CM CD T- Tt CM LO CD Tt CJ) O CO O Tt o σ) τt cM τt cN co τt ιn m -«- ιn σ) τt c) i- c) τt Ni cb cb cb N CD co cD N co co co ro ro o - ro σ) σ) co co o o - s ιn ιn - ιn c M M τ- c '- Lθ - CM " in Lθ CM CN CN CN CN CN CN CN CN CN CN CN C C CN OO CO C CN CN CM CM OO CO OO CM CN CN CN CN CM CN CN CN CN CN CN CN CN CM CN CM CN CN C^ CN N- Tt OO CN CM CO CO O T- in CM CN N- CD O O CD τt o iΩ co i s - co co o τt ιn o cM τ- cj) θ o cD θ co co co ιn σ) τt τ- o τt i s - CN CO τ- τt CN CO Cθ m θ N- N- CN CO Tt m CD CN N- O OO O LΩ OO Tt N- T- in CN CN CO CO OO T- CJ Tt CD Tt CO O OO O N- CO CD O N- Tt CO CO N- CD O in N- O N- OO CD CO CM Tt T- τ- τ- c0 CJ) CN O N- CD CN τ- LΩ LΩ CM 00 O 00 C0 CN 00 N- CJ) m C0 in in in CN CD CO CN Tt lΩ CD CD N- CO CO OO CO CN CO CO C .N . o _ in C _D N- CO CD I s - CD CD N N CD N CO O. CO O O. CO O 00 OO I s - I s - I s - CO CO O) D CD Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt T T Tt Tt Tt τ τt τt τt τt τt τt in t τt m T Tt Tt Tt Tt Tt t t Tt CM 1- CM -<- CM -«- CM v- CN CN CO CM CO CM oo CoO OoQoQoLoU LoU NoXo < CQ O O < OQ O O < 00 O Q Q LU LU LU N N X < CO O Q oooooozoooooozooooooo Z O O O O O Z O O O OO O c_:α:Q:o:o:o:o:o:o:o:Q Q Q-:o:o:o:α:o:o:Q o:o:o: Q_: 0_. CL Q. 0L Q_ Q_ Q. Q_ Q. Q. Q. Q- Q. Q_ O O O O O O O Q. ^^^-^^^^^^^xxxxxxxxxxxxx X O: O: O: O: O: O: O: O: O: O: O: Q: O: O: O-: O-: Q-: O-: Q-: Q-: Q CO I- H H H H I— I— I- H H H H H I- I- Q- Q.0- Q- Q- Q- CL < © uo cD N ra ro o ^ c - uo cD N oo ro o - c co ^ ιn o N oo o. o ^- CM c r ιn o N co σj θ - c - ιn o s co σ) θ CO CO CO CD CO N- N- r- r- N- N- N- N- l- CO CO C» CO CO CO CO C0 a0 C0 CJ) O) CJ) C3) a> CJ) CJ) CJ) CJ) CJ) o ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ' ^ - ' ^ ^ ' ^^ ^ ^ ^ ^ ' -^ ^ ^ ^ '^ ^ ^ ^ ^ ioinio io inio ioin io inio CN CN o Tt CO O OO CO CO CO N- CO CN in cO O CO CM CJ) I s - CO CO CO CO IΩ CN CO N 00 00 CM O) O) N 0O CD CJ) CD CO N- CJ) ιn cq o cD ' r- cj) co cj) τ- v- ιn o co co τt CD Tt Tt CD cj) m in cq C O 00 CN N- O 00 00 CD τt O CO CN CD o o in q d Tt I s - I s - Ni cb -r^ Lb cj d cb cb d ib cM cb ib cb d co in CD O OO T- 1 CO OO CD Tt Tt O O CN -t- O CD LO σi Tt cb 00 cb in Tt o σi ^ CM τ- CM CN τ- τ- CN v- τ- CN CN CN CN CO τt τt Tt Tt Tt CM τ-CM - - t- CN CN CN -t- CN CN CN CN CN CN CM CN CM CM CD I s - CJ) CM O o LΩ LΩ CJ) τ- N- O CO τt CD CO OO CD CO CN in LΩ I s - 00 - oooT- inmTtcDcoco t I s - CO Oi CN N- o in co O - CM LO OO CD CD Tt O CN CN CO Tt CN Tt CO oo o " CO CN O CO CO CJ) CJ LΩ τt τt lΩ CJ) -«- lΩ Ln in Tt CO CJ) CD CJ) N- CM q N- τt c τt q cN co v- co co cM CN CD Tt CN N- in q θ N ιr) C q q q τ- s O ( o T ir rxi tM M T- d ^ 9d 9CM- cb t in uO cb cb in cb cb ib cb od od Ni d d CM CM I s - in CD CD 00 T- O C cb cb r-i CO r-i r-i cb Ni oo b σi Tt τ- oo ιn o oo τt - m m cM - t- τt -«- CN CD in τt - τt t- N- N- N- CN N- CO CN r- t- 00 00 O CJ) lΩ l- - 00 CJ) - O -r- N- N- 00 CO co CD CD O CN Tt CN Tt - CD Tt Tt OO O N- T- CD CD N- O N- O CN -«- CO Ln CD Cθ CM CO -»- τt N- CO CN O CJ) CD OO CM O C CJ ) lΩ CO CD t- τt CD τt CJ ) CJ) N- CO τt τt CM CM CJ) O O CJ) - CN CN τt CO CD τt O τt - τt lΩ CM CO OO N- OO CD CO - O T- CM O CO O O - O CJ) 00 CO O0 00 CD CD C0 N- CD N- LO LΩ LΩ CN OO CO Tt lΩ CO CN Tt lΩ CO N- N- CD τt τt CO O CJ) O - - CN CM OO CD CM CN CM CN CN CM CN CM CN CN CN CN CN CN CM CN CN CN CN CM CN CN CM CN CN CO CO CO CO CO CO CN 00 N- τ- CJ) CO CD CD τt O N- CO Tt Tt N- Tt CD CO CO CN CO Tt CD T- CD Tt CN CO O OO T- O CO CO lΩ Tf CO CO CD N- 00 CD CD T- O0 CO O O Tt OO OO Tt Tt N- LΩ O CN O O OO CD CD T- CO CO O CD CD T- oo r- - r- N- N- oo oo o - scncBcoo- oo. T-t, N-- ■ «.- co in CO O CD Tt - CO CN m OO CD O ) i- CM O LO CO CD CD CO O CD CO o m t- ιn cj) θ τt o o cM - CN CO CO in CO CD CO LΩ Tt N- OO CO CD CD C in in in τt CO CJ) O CM CJ) CJ) CJ) OO CO N- N- O - CN ^ CN C CN CN τt τt in CM CN O τt CN CN CN CN OO τ^ τt τt τt τt τt τt τt τt τt ιn ιn τt τt τt τt τt τt τt ι ιn ιn ιn ιn ι ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ι^ T- CM v- CN T- CM T- CM T- CM < CQ Q Q < C Q Q Q LU LU CO O Q LU LU O O O O O O O Z O O oooooo Nozo <ooz <oooo CQ Oυ Oυzo <ooo CQυo Qz <oo O O O O OO Q. l Q.0. Q. l CL LU UJ _J lU UJ liHlJ lU LlJ UJ LlJ >- >. >- >- j j j j j j j O O O O O O θ D D D D D D D D Q: W (O W(OW (0(. I I I I I I I I I I I-I -I -I -I < < < << < < D: D O: O: Q: Q: Q -I -I -I J -J -J -J-I - | -J < < < < < < < Q- 0_ Q_ Q. Q_ . Q. Q. CL CL Q. O O O > > > > > > > L Q. Q. Q. Q_ Q- Q. O O O O O O O CO © - CM CO ^ UO CD S CO C» O r- CM CO lfi (D N Oθ σ) O - C CO ^ lO (O N Oθ ro θ - CN CO ^ uO CO N Cθ σ) O - CM C 't -. CD τ- τ- τ- - τ- τ- τ- τ- τ- C CN CN CN CN CN CN CN CN CN CO CO CO CO CO CO OO CO OO CO τt τt τt τt τt τt τt τt τt τt l^ O ιn ιn Ln u in n ιn ιn ιn ιn ιn ι ιn ιn LΩ LΩ iΩ uθ i ιn ι ι ιn LΩ i ιn L ι uθ in ιn ιn ιn ιn ιn ιn ιn Ln ι ι u^ CO N- T- OO lΩ T- OO OO LΩ LΩ CN CD Tt O CN CD O CO N- O LΩ I s - O CJ) LO N- O LO OO O CD CJ) N- CD CO O CO I s - CN - co oo co in co oo CO LΩ CM CJ) CO CD O CD τt CD O OO LΩ CD CJ) CD O τ- lΩ τ- 00 O O OO ro CB CM O CO CM O CN CO CO CJ) CJ) T- - CN O - T- CO CJ) CO o co ^ co r- cM co (θ co c co r- o ro - o - ^ co ιn o ro ιn τ- o co co co ro oo co - o ci co co o cM CM co cM ι- - τ- CN CN CN CN CN CN CN C CN CN CN CN CN ( CM τ- CN CN CN CN CN CN τt τ- τ- CN CN τ- τ- τ- - τ- CN CN CN ^ m CN τt CJ) O CM O N- rø cN q O T -÷ CM T - CJ ) CJ ) CO O CD Lθ m N- τt Ln θ CM CO τ- τ- - t - CJ) N- N- N- O CO τ- CO C O τt CD Tt CO O OO CO Tt OO CO OO CΛ N- LΩ T- O O N- OO CN 00 00 LO 00 σ) N- LΩ CJ) O LΩ τt N- C0 00 LΩ O - L0 N- N- τt O N. C0 O - C0 - CD CN CD τt CN τt - - τt CO CO CD CO CN CJ) τt CM N- C0 u0 τ- CD τt N- CD τ- LΩ LΩ τt CJ) C0 CO CO 00 CJ) CJ) CD C0 C0 O u0 CN CM C0 τ- OO O CO CO - τt LO τt CO CJ) CD m CD CO in τt OO CD ro cO CO r- T- CO N CO CO N CO Q O O O CM O O ro ro T- T- CO S N CD CO ' - 't - CM CO CM N N CO N N CD CD in σ. O CB CS CM CN CN OO CO CN CN CN CN CN CN CN CN CO CO CO CO OO CO CN CN CO OO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ o co co cN - o ιo o co o oo r- o σ) co co co iΩ τ- cj) i- cj) o cj) Ln o cj) - oo τt cM N- Ln o τt CD CO OO O CM CJ) CO CO - CO CO OO CJ ) C» in CN N- O u OO CO τt CJ) O CN -5- τt τt N- O CO uO CD CO CN CO in u - CJ) CO CO O CO O N. CD CO CO OO -^ I- τt N- O O CJ) q ∞ N- cq cN cq q cN CN v- oq q - q cN q cN Lq τt N- N- cN CD CD CD co cN CM q q c^ N- CO CO CN CM CM CD CO N- CO Tt CD UiΩJ ^Tt ω UibJ lϋ lϋ ω Uib) Wc UJ «cJ lϋ UibJ PodJ «. ϊcb'J «cM τ^- Ud T^- lcN (CNN ^- τ^- Od (c^ l>| - W U lN '- l CM l CNN '- '- ^t U LO) l CϋD ^f '- OU U CDJ C0OU ιn ιn ιn ιn ιn ιn ιn Ln ιn ιn ιn ιn uθ uθ u LΩ in ιn ιn ιn Ln Ln ιn ιn ιn ιn Ln ιn ιn ιn ιn ιn ιn Ln ιn ιn ιn ιn ιn ιn ι^ - CN - CN T- CM < OQ O < C Q O Q < CQ < 0Q θ < CQ O Q Q L LU N < DQ O Q Q < OOOOOZOO oooozoooozoooυozooooooooUoo ooooooozooo D:D:D:D:Q:OOOOOOO < < < Q: __ O: O: O: O: LU LU LU LU LU LU LU LU LU LU LU =) Z) Z) Z _D 3 Z) D Z Z Z Z m uLumD:o o o:[_:o:c_:jjjj_iLuι_jLu jι_jLu X X X X X X X X X X X LU LU LU LU LU LU LU LU CΛ CO CO CO CΛ CO CO CO CO Q_ CL Q. CL Α. CL 0L < < < < < (Λ CO (5 CO CO CO QL Q_. Q. Q. CL Q_ O. Q ^ © N co ro o - cM t ^ ι cD N co ro o - cM ^ ιn co N co ro o τ- M c , ιn o N o β θ - \i χrιn (D N co σ) θ - c o . Ln ιn co cD CD ω σ) θ o o lΩ in LΩ uo iΩ in Ln y o © © ! _ H U α. CN OO O CM - CO - N- CO m co in Tt oo N- CO CO CO CO IO OO CO CO CN CN O CO LΩ OO CO C-D N- t I s - CD N- OO CO T- O CN O CO m OO CN CJ) uO CN CD Cθ O CN CM CN I s - CN O - CJ ) τt CM CO -5- LO τt O CO τt CD CJ) r s - CN O 'r- CM LΩ OO LΩ CO CN OO CO OO CD m T- O Tt T- CJ) CO Tt CD CJ) in CD CN Tt O CN CO CO N- T- OO CO τ- CO LΩ O τ- τt τt O LΩ τt CO LO CD O CD CD CO O O τt CO CJ ) O CO N- t- CM CN CM - 1- CN x- CM T- T- v- T- CN τ- τ- CN CN -5- CM CN CN CN CN CM CN CO CN CO CO - - CN CN CN in ιn r- CJ ) -r- - CM N- CD CO Tt CO CO t- OO N- CD CN OO CO CO CO CN CD O CD 00 O - CJ) CD CJ) CD v- τt 00 CD C0 N- O co T- oo in o o o) T- O CO CO I s - 00 CN τ- CO τt τt CN N- CO CD τt O CO CO CN OO CD τt O LΩ O LΩ τ- CD τ- OO O CD τt CD CD CO CD O CJ) CO CD CD T- O T- I s - Tt O CO 1- O q N- ∞ N- q ιn cM τ- cD CD θ τt co ιn cD m o N- Tt Tt CO OO Tt N- O O CN Ln cO N- O T- v- oo T- in in cj) o co co Tt co - in ∞ ∞ c Lb -b cb b in in cb CD O O O - CM CO τt CO CO CN τt CN LO τt - CN CM OO O -^ - τ- O τ- CM OO CN CN CN CN CN CN C CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN ιn N OO O N Oθ O CD uo ■ «- CM r- CM - CM - CN „ - CM T- CM CoQ Ooo Q Qzz <ooo CoO OυoQ QooLU LoU No < CD U Q Q < OQOQQLULUN < COOQU N < o o o o o oo OOOOOOOOOOZOO OOOOOZZOO LU LU LU LU LU LU LU LU UJ LU UJ cocococoxxxxxxxxxxx DD D^ m m mu j Lu Jc wwwwwww -j-l LijmLu mLUiiJLUiιιιιιιιιιι> >- >->-^ < < < < Q- Q_ Ω_ Q_ Q. α. Q_ Q_ Q_ Q_ Q_ _l _l _l _l _l _l _l _J O_ l_L Q_ Q_ Q_ 0_ Q_ Q_ Q_ Q_ 0 l _J _l _J _J _J _l _l _l > > > © cθ - ιn D N ∞ ro o τ- M o ^ ιn (D N co ro o τ- c ^ ιn D N co σ) θ ^- ( co χ. ιn cD N co σ> θ - M - ιo cD N oo O O O O O O O - τ- - ^ τ- ^ τ- τ- τ- - CN CN CM CM < CN CM CN CN CN CO CO CO C CO C CO CO CO CO τt τt τt τt τt τt τt τt Tt o CD CD CD CO CD CO CD CD CD CD CD CO CD CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CD CD CD CD CD CD CD CM Tt CO CD in N- CJ) CD I s - CD CN O C N- τ- T- LΩ CO OO CO CN CO Tt CJΪ OO CD CM N- in oO CO N- CD CO - - OO Tt CM CO OO O LO OO CO N- in O CD in Tt oq I s - CN Tt oO N- O CO CN CO T- CO CD T- O CJ) N- τt in uO I- - in CJ) CO CJ) CO - CN CD OO CJ) OO τt OO O CN q σi Ni cb ib d σi Ni Tt CM- CD 00 CD O CO N- i b ro d d d N N ' s ' ^ iri cό b co co - N- d d oo co ro CN CM CM CN CM CN d Tt CN CN CN CM CN OO CN OO CD CD IΩ CN CN CO CO CN CN CM CO CO CN CN OO CO CM CN CO CO CO CO CN CO Tt N- OO OO CN T- σϊ OO OO CN O CD CO LO CD N- OO τt τt CO CO CO CO CO C CO I s - τt O CJ) lΩ CD τt τt CD I s - ιn τt CO in τt CJ) CM CN N- τ- 00 τt τt CN 0O CD lΩ Cθ m N- CN - Λ- CD CJ) τt CN - - ιn N- CO CO N- - O CO τt OO CJ) in oθ CJ) O LO OO CN -t- O CD CJ) uO τt CJ) in CD CN θ 00 CD 00 - CM CN 00 CD CD τt τ- O N- O O CM O N- τ- C O in CN τt OO N- -«- N- r s - CD OO LΩ LO I s - OO CD CO O CN CO I- CD r- τt ^ - τ- ca θ uO D N in ^ ^ ^ O ( D ^ D N N 00 CD N ( O u N ( D CD N N iO ^ N CO N C0 (D UO ιn ιO ^ ' (O (O N N ifi ' k CN CN CN T- CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CM CN CN CM CM CN CN CN CN CN C^ O αi - - IO tO C0 N O C0 - - co cθ N CD io O C» CO N CJ) o CM - τ- τ- v- CM CO CN CM CN CM N- iO Tt O CN τt CJ) τt CO CJ) τt x- OO CO CD N- CD CN Cθ r s - CO CJ) τt τt OO O τt N- τ- CO τ- CN CN t- OO CO O CO CO CO O LΩ CO CJϊ LΩ - Tt LΩ LΩ CD CM CO CD CO O O τt CO CN τt OO CO CO LΩ CJ) CO O CD '»- OO in CN - N- 00 Tt O O in CD -t- O O N- - CO in τt CD O I s - O τt σ) LΩ CO OO τt τt O OO CD C0 CM CD O I s - CM C000 τt O C0 r- CJ) 00 C0 00 lΩ l- cN θ τt τ- cN co τ- v- cD in m CO τt CO τt LΩ CD lΩ τt N- CO OO O -5- CN -ϊ- LO Ln cθ CO in N- N- N- CO CN -ϊ- τ- CD O O ^- t- O O O O - O O CD CM CO CO CO Tt Tt τt τt τt τt τt τt τt τt τ τt τt LΩ in i L τt t τt τt τt τt τ τt τt τt t τt 0O τt τt τt τt τt τt τt t t τt τt C τt τt τt τt τt τt - CN τ- CN - CN co O O < OQ O Q LU N X X < CQ O Q LU LU < CO < < CQ O < CO O o υ o o O O O O O O Z O ZZZOOOOOOOOZOOOOOZOOOZOOOOOZOOOOO ^ <^<^<^<oiOct:Occ:OzOa:Oo£Oc:O£Oa:O:Oc:D-iI--DiZ^ ) Z^ ) Z^ ) =^ ) Z^ ) D^Z^ ) Q uI Q uj: Oj: Ou: Om: Ouj: >^- >- >- >- D: Q : : : Q : Q : ) Z) Z) Z) Z) =) >>>><<<<<<<<<<<OOOOOO Ococococococo OOOcocococococo_ι_ι_ι_ι_ι_ι © ro o τ- ( c ^ o D N co ro o - r c ^ ι D N co ro o τ- c c - ιn D N co ro o - cM ^ ιn D N co cn o r- c , - ^ in in in in in in in in in Λ co to cO u CD CD co co u CO N N N S N S N S N N co co co co co co co co co co cn cn cn cn cJ) o CΩ CΩ CO CO CΩ CO CO CO CO CD CO CO CO CO CO CO CO CD CO CΩ CD CO CO CO CO CO CD CD CO CO CO CO CD CD CQ CO CO CO CD CD CO CO Φ y o © © ! _ H U o α. co cN -«- cj) oo τt oo cD co ιn co τt co m oo co c) CN in cj) o uO N- T - CD O T t CO CN CD u CN -r- CO CO CΛ CO CO CO O m τ- O N- CO r s - CM q τ- τt N- τt CO oq 'r-; ∞ O CO N- τt CD OO OO τt N- d Tt Tt Tt N- OO CO in Ln Tt CD CN CD CD CD CO CM O CD - CO in Tt CN Ni f ^ ^ ro iri roro oO N M od co ' M co ^ ^ N i o CJ) CO τ- τt τt CO CJ) CN τt CO Ln θ co Tt CD O CD CO T- OO CO - I s - CM CO CO CO CO CO CO Ln oO CO Cθ CO τt τt τt CO CO CO CO CO CD CJ) N- CM CM CN CM CN CN CO CO CO CO CN CN CN CN v- - CM T- CM CN T- τt τt τt C0 CN CJ) O - 00 C0 LΩ N- C0 C0 CD τt - C0 τ- O O CJ) - ιn σ) N ^ N (DC o - m ro CN CO CO lO OO CJ) N- O CJ) - lΩ τt CD CN CD 00 CO τt τt 0 τt σ) CN σ) τ- CJ) CD CO τt τt 00 LΩ Tt UO O Tt CN N- o oo m C CO CM I s - O CO N- CJ) CO CJ) CM O CO CD OO O CO N- - OO O N- CO OO N. CD CM N- CD CD OO CN LΩ T- 1- Tt Tt in I s - t CD CN oO I s - CO LO CD N- OO CO OO O UO OCOCON Tt OO CO OO O CD O CN O CM CN CN CO OO CO τt CO O CJ) OO CO Oθ σ) CD CJ) O CD N- CD lΩ in τt cb cb CN co co ' Tt CN CN CN CN CN CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CM CM CM CN CN CO CM CN CM C^ co N - σ) o u. D σ) co co co cN cj) τt ιn co - - τ- ιn cN τt co i s - co ∞ ιn τt q N : ^ io o n - - -- τ- -r- -r- - - - - OO O OO CO N- LO T- CO CD OO O OO CN CD CO CN C0 CD N- 00 CO CD N- I- C000 τt - CD '«- '^ 00 - 00 CD L0 σ) O τt C0 Ln LΩ τt LΩ N- τt CM CD CD τt CN O LΩ LΩ CJ) CO CN CO in Ln -»- θ CN m τt _ . C __D CN - τt N- CD CO in CN CJ) O τt CO CO CN Ln CN CN O - CD τ- τt N- q cq τt q c» q m co τt o t- τ- v- i s - CN CN CJ) co co cD co co co q cN CN in Ln cq - τ-- cN τt N- q c q c τt oq q cN CN CN uO cb cN CN ^ d -^ T^ cN CN d d cb cb cb d cb N c c d cb ∞ cb cb Ni cb cb od cj) cj) cb d cD cb d τt τt τt τt τt τt τt τt τt τt τt τt τt τt τt τt 0O CO CO CO C C τt CO CO CO CO CO CO CO CO CO CO CO 00 CO C CO " CO " CO CO " CO Tt 00 CO Tt T- CN - CM - CN T- CM Q Q < 00 O < CO O O < OO O Q LU LU < ω O Q Q LU LU <C < CQ O Q O O O O O O O OOOOOOZOO oooooozooooozoυzzooozoooooo 330:0:0:0:0:0:0000000 333333333 cocococococococococo >->->->-0000000_J LU LU LU LU LU LU LU LU Q O: _ O: O: Q: O _ι_ j _ι_ι co:o_:o:c_:cco:< _I _J C CO C CO CO CO Q- CL Q_ Q_ Ω_ Q_ CL O OOOOOXXXXXXXXXXOOOOQ-CLCLO.Q.Q.Q.> © ιn cD Nco ro o τ- cM ^ Λ D S co ro o - c c ^ ιn DN co ro o r-c ^ιo θ Nωrooτ- ^ uι o sωo. o CJ) CJ) CJ) CJ) CJ) O O O O O O O O O O τ- - - - - τ- - τ- - - CN CN CN CN CN CN CM CM CN CM CO CO CO CO CO CO CO CO CO CO τt o CD CD CD CD CD N N N N N N N S N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N - CM Ln Ln CN CN C0 CD LΩ LΩ N- CN CM CO C 00 0O C0 CD - N- O T- CO N- CJ) LO Tt CD CO Tt CO Tt Tt T- Tt OO CO N- CO T- T- N- CO m CN in cO O CO CJ) CJ) I s - CD CO co CD O O O CM O CD CO O CM CD CD CD CD Tt CD OO CD N- N- lΩ CN OO OO C in CO CO 00 CM CM CM CM CM '- - CM rM - T- - T- r- T- T- T- v- T- r- T- T- T- T- - CO CN CD CD τt CO LΩ CO τt N. N- in iΩ CO CD σ) N- CO ■t- q τt q q q ιn q -r- q cN τt τt in cb Ni τt < i cd ι ιb c τ Ni τt cb c Ni oo ro oo N N co ro co co cD co N σ) m cM (D co N τ- ro ro τ- cθ Lθ in N τ ~ co ιn - 1" ~~ ∞ in o c T- ro r- o cM ^ co - t co t rt D ro o v- oo - ro co ^ co ro ω ^ ro ^ N ^ - co o co oo σj ro D - Ti- oo N v- - N - N CD CM CO C N CO in ιn CD CM ro cθ ro c CM ro cθ - ιn (M N O O CM Oθ N- CD ^ CM CD - O C CD CD CM Cvi ro ' '- ^ d d ^ ^ d ro co N ' N d ∞ ui ^ b iri ^ N ' o ^ d ^ ^ ^ ^. d ^ ® 10 . ^ ^ ^ 9 ^ ^ ^. ^ I ^ 9 |S ^ C .9 CM CM CM rM rM CM ^ τ- - - - - - τ- τ- r- - - τ- τ- τ- τ- t- r- ^- τ- 0) - τ- τ- σ) CO N N CO CO CO ifi ιn ιO C (M UO in N N CD Tt CD O N- O LΩ CN N- O - N- CN O τt O CJ) CO CO N- - CO l s - CN O LO Tt CN CJ) CJ) CN CO O CO - O CN O CD OO O N- CJ) N. CN T- N- OO N- OO O LΩ CN CO O CO CΩ O co in cD CD m cN o o oo -5- OO CO Tt CN O CO - CO LΩ T- O CD CN CN Tt Tt Tt O O OO CO T- O CM N ι- O CO - θ (D O O) τ- '- N- τ- cM q τt r s - ιn o iΩ θ θ CM CD σ) τt cD LΩ CD τt cM cq q cq ιn c_ τt r s - cM q N- cq r- : d LΩ N- σi cb cb cb cb cb in Lb cb N-i cb in cb Ni Ni ' N ω ro ω c ώ ro ro N d N ∞ ω N iri - N ' b CN t- co m in coo cN N- o m CD I s - CD CD CD Tt t CO Tt CD CO CO CO N- CO N- - O N- O CJ) OO Tt CD uO O) CD CO CJ) CM CN in CO O CM m CN N- CN -ϊ- OO N- Tt O CO CD CO CD Tt co in Tt O 00 CJ) CJ) OO I s - C0 I- CD 00 CD 00 l- CJ) CJ) N- m 0) N- O CN CO Tt CN CJ) N- O O q oo Tt - co co cD co N- oq cq in in oo .9 ^ "^ P ^ M Tt CO Tt CO CD uO - Tt CO CD OO CO O Tt CD LO Tt O O CD CD OO N- αi d ^ M ' d od co cb Or : r : r : CMCOCθddr : ' r σ) OO OO I- I- l- - τ- O CJ) CO τt '<- O O CD CO CO τt τt τt τt CO CO CO CO CO 0O 0O Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt Tt 00 CO 00 CO CO 00 τt τt τt 00 τt τt τt τt τt CO Tt Tt Tt t t - CN - CM T- CM T- CN - CN < co O O < OQ O O < C Q O < OQ O Q Q LU LU < OQ O < CQ CD < oooooozυooooozυooooozoo O o o Z O O Z O O O O CO o o OOO OO m <<<<<<<<<<<<<<<<<<<< wc m twn mwwn ewn twrs twnwwL_.^L.. WL.. CLO„ C > O_ m CL i C J L J C Li t j C liJ C L1 t J C Li t j << ] < s * j <^ <^ >>>>>>>>>>>> >>>>>>>>xχχχχχxx χχ υooooococococococo<<<< © - M c ^ ιn o N o ro o - N ^ ιn u N co ro o r- cM N - ιn o N co cs o τ- (M c ^ ιo cD co o. θ - cM - ιn D ^ ^ - - ^ - ^ ^ ^ O i in uO in in in i in in D D D D CD D D D D CD N N N N N N N N N CO CO CO CO OO OO OO o N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- N- y o © © !_ H U α. co co co CO CD CM CO LΩ CO LΩ CO OO CN O Tt O LΩ CD CO O LΩ I s - Tt CO OO -ϊ- lΩ CO LO Tt h- CD N- CO CD N- OO CD 00 CD CD r-i σi in I s - CD I s - N- m I s - I s - CD in CD I s - 00 σi ib T- T- T- T- T- 1- CM - o in c) Tt CD OO N- N- m O OO o O I s - N- co OO I s - t I s - OO Tt Tt oo Tt t q N- τt - co cN in τ n N- Tt CO CM CD co in co c) co co oo in cb in c CO co σ) CD N- m τt co co σ) θ τt τt CN OO CD T- co in o CM - T- _ o CN O N- LΩ τ- OO CJ) τt CO CD LΩ τt O N- τt OO - CO S CO LΩ T- O O OO CD O LΩ - m CD T- oo oo O OO CD O I s - σ) N- - O CJ) - O τt τ- N- CD OO CN τ- CO CO CD O t- CD τt r s - N- CO O OO N- N- CD CO CO - CN N. Tt O CD 00 CO Tt I s - o o oo in Tt cj) oo r s - oo cM i s - cj) co o co co σ) τt c) τt cD CD τ- co cD in -»- co τt co 00 O Tt CO I s - CJ) N- Tt CO LO N- CO Tt cO CN CN O LO CN CD OO CJ) Tt O CM CN CO CN CN CO CN CN cb Tt -^ CO Tt CO O CD - OO CO CO OO CO CD OO m N- N- OO O CO CD 00 N- CD LΩ LΩ Tt Tt T- - - T- T- T- - - CD I s - Tt CO N- CO OO CO CN CΩ N- OO T- CD Cθ r- C CJ ) CJ ) N- CD CM LΩ 00 τt CO CD τt τt lO CJ) CD I s - 'r- N- O CD CJ) CO CO -— - LΩ N- τt 00 C0 N- O CO O CD OO O OO CO Tt Tt Tt Tt co ιn Ln τt co co cD Ln o c τ- τt co <-θ τt ιn co o oo -«- co co T- CO I s - CD - Tt CO CM CD OO CO CM -ϊ- CN N- OO in CO CD O Tt OO OO t- CO -ϊ- O t- CJ) Λ- τ- - CO CO CN τt O CJ) CM CO τ- - CJ) Ln CO O in T- CJ) CN CM o CN CM CJ) - - τt CN τt CM OO CO CN - CO CM OO CO O O Tt Tt CO CD C CO O O O O CN O CO CD lΩ CO LΩ CD Tt Tt in in CD N- N- OO OO N- CD CO - '-T- - -y i- T- r- rNr N N MN M'- - rr - T- - T-T- T-r -T- CO CO o x- OO CD CN CD in N- OO OO CD CD CD CD C 'c- Tt m CN Ln Tt CD CO Ti-- Tt O O CO O Tt O o CO N CM CM O CO O C .D O _ O _O N- O CD CD CD OO CO CJ) I s - Tt CJ) I s - N- σi T- N- in I s - CO CD CJ) O CJ) CN τt OO τt CO OO τt OO CD N- CD OO OO CO CN CO CD LO CD CD v- N- T- C COO CM CN CM 00 Tt TtcbNiodcbcbibcb Ni OO CO CD I s - I s - I s - 00 I s - I s - CD LΩ Tt C INN — C IM C IMN O L_ Tt t Tt Tt t Tt Tt Tt Tt Tt Tt Tt t Tt Tt t Tt t t T Tt Tt Tt Tt Tt Tt Tt m ιn m Ln Ln - CN - T- CM T - CM OQ < < CQ O Q < < CQ O Ω LU N X X < OQ O < < CQ O O O Z O O O Z O O O O O O O Z O O O Z O O O O O O Z O Z Z Z O OO O O Z O O O Z O O O O O O < r >->->- >- >->->->-ooooooooooocco:o:o:o:o:>->->->-α:o:o:o:o:o:o:Lu j j j j j Lu ιiJ iiJiiJ i_ι ιiJiiJiu j j j ^ rj:Q Q:Q: rι: D: rι: D:(][:Q: ujiijujujιijι_i J j j -ιιι ιι ιιι ι < OOC. d dd d d d d d O O O 5< < < < < < < << < < t. Wtj. WW (j. OOO O i- l- l- l-H I- hθL © N ω ro o^ c c ^ ιn oN co ro o - cM c - uθ θ N o ro o - cM θ - i (D Nω ro o - cM c '- ι D N co σ) θ - (M CO OO ∞ CD CJ) CJ) CJ> CJ> CJ> CJ) CJ) CJ) CD O O O O O O O O O O - - - - - - - - - - CN CN CN CN CM CN CM CN CN CN CO OO OO o ^ ^ ^ ^ ^ ^ ^ o oo co oo co co co co oo oo co oo co co co oo co oo oo oo oo oo co co oo oo oo co o o oo (O oo co co m cN m oo o o cM O co i s - cθ - cN N- τt ιn cD oo o co ιn i- σ) θ co c) θ CN τt o σ) CN τt N- CD CO N- - N- CN - N- CO I s - CD CO τt CM uO CO τt v- τt τt - N- OO CO CM CO Tt T- Tt in Tt CD OO T CD Tt - CO in - N- Tt in ∞ CN N- CD cj) in in o T- OO CO LO d O N N N N N CO N' τt ^ d c b c c d Lb τt Ni d ι τt cM 00 CD OO CN m CO D rNNrrrrrrr ■«- -«- CM CN -!- CN t- τ- τ- - - - τ- - - -r- v- - - -«- - CN - - CM - CN t- T- - - CM - T- T- CO OO m CM N- Ln cO CO Tt N- CO CD Tt CN - - cθ ιn r- CD in uO - N- C CN -t- CD CO I- CO N- OO CJ) CD O τt CO O τt CJ) τ- CD CD in i- 00 τt O N- CJ) Ln C0 N. - m 00 CD CD τt σ) CO O) - CJ) CO O CD O - - - OO O N- in CJ) OO CO CN uO CN CN CJ) τ-- τ- O CJ) CD τt O τt σ) CM CO I s - CJ) t- CD CM τ- CN τ- C0 CD 00 - o cD o r- r- ι s - σ) N- cD co o τt τt cN Ln oo oo o oo - co cD oo cM co co ιn ιn τt cD σ) Tt CD Tt in CO CD N- ∞ ∞ CO N- ∞ N- N- CD N- N- CO in Ln CD Tt N- CO CD O CJ) O τ- CO O CN CN CM v- CM CM OO -»- - CN -«- -r- T- - - T- - T- - - T- T- - - - - T- T- T- - T- - - - - - - - - CN T- CN CM CN CN CN CN CN CN CN CN CN CN CM CM CN CN 00 T t co o cn o o - ιo ιθ (M τ- M - (D ^ t N θ ^ o ^ o κ (j) θ θ) ^ o ιn σ) N co o ci) C θ 't (D N σ) o σ) Cδ (M θ θ co Tt lΩ N- CD O OO CO N- O CΛ CO O O CΛ CO O CN O O in CN OO Tt Tt Tt CO OO N- in CN in in Tt LO in T- CN O - Ln CN in ∞ -^ cM ιn cN n τ τ- q o cN co co cj) o ι - cN c) c ιn c CN τt ιn cD N- » ιn q q LΩ q τ^ ^ ro cb ώ d d ^ b cM ^ N d ι ιo ' \. ιo ιo ι ι ^ N- c ' ^ N ω » - - - τ- CN CN τ- CN CN CN - -- - - τ- -r- τ- ^ - - τ- τ-- τ- - τ- ^ - τ- τ- - τ- - - τ- -- - - - - - τ- τ- -r- τ- - τ- o cj) m o co m N- co τ- m o cM co m co τt co co τ Ln cN co cM CN t- cj) i- cj) m o T- OO N- N- Tt CM CO in CN N- CO CO m N- Tt CO OO O CM CO OO N- CD CO CD CD OO CO Tt CN N- O Tt CJ) - CN CD OO OO Tt t CD - OO 00 CO CJ) CO N- I s - oo 00 CO CO O CO CM I s - CJ) - τt cM in LΩ q oo τt co cN Ln co co cD N- τt N- CN τt CD LΩ CN CO τt CO N- CO CD CN CD O CO CO I s - CM lΩ Tt O O O Tt d o) d cd Ni Ni cb cb cb cb c. c. d -r- : cb cb CN 00 τt 00 in m Ln 00 τt C0 τt τt CN τ- CN CN O CJ) O CO CN CN Tt Tt CM co in CD τt τt iΩ τ τt τt τ τt τt τt τ τt LΩ LΩ τt τt iΩ iΩ iΩ in ι LΩ in ιn u i ι ιn ιn ιn ιn ι Ln ιn t in Tt LΩ in LΩ lΩ LΩ LΩ in in LΩ „ T- CN - CM T- CM CM - CN < OO O Ω Ω LU LU N < O Q < OQ O Ω Ω < OQ < OQ Ω Ω < ω o < O O O O O O O O O O O O O O CO O O O O O O O O O O o O O O O O O OZOOOOOOZO LU LU LU LU LU LU LU LU LU LU CO CO CO CO C C033333333 < <I: < < Q- Q- D- CL Q_. CL Q. Q- O: Q Q O: O: Q_: D: CO CO X X X X X X X X X X >- >- >- >- >- >- LU LU LU LU UJ LU LU LU jjjjJwwwωwwwωιιιιιιι>->- Q_Q_Q_ Q_CLQ_0_Q_Q_ Q_OOOOOO_J_l _J_l_l_l_J_J <<<<<<<<<<<<<H-l-l-HHHI-00 © C ^ ιn CD N CO C» O - CM C ^ lO CD N ω cn θ r- (M C ^ ιn CD S ∞ C!) O ^ N C ^ Λ CO N CO O. O - CM C f lO CD N CO co o co co c < ^ ^ ^ ^ t ^ \f \f \f i ιn ι ι ιo ιn ιn ιn ιn u D D D D ø D o D o cD N N N N N N N N N o CO CO CO OO CO CO CO CO OO OO CO CO OO OO OO CO CO CO OO CO OO CO OO CO OO CO CO CO ∞ CO CO CO CO CO ∞ ∞ CO CO t CO T- OO Tt CD OO in CD O N- CN CO OO N- CD CJ) C CO CO ιn c» τt l s - N- τt N- σ) CD OO CO I- in CJ) CN O N. CO O CD CN O τt CD uO OO I s - CM CM τt CM 0 τ- CO τt CD CO τt lΩ 0O lΩ - cM O T- o cq Tt o q Tt ∞ - co q - - cq i q Tt q q - Tt N- d cb cb τ- : Ni cb cM -r uό cb cb c . cb d d N d b ' d c ώ b d ιri b N b τ d ^ ; N' τ ro d ιn d b ω τ d N (M r r- CM t- - CN CN T- x- T- - T- T- CN T- CM CM CM CN CN CM CM - CN OO CO CN T- CN CN CN CN OO OO CM CN T- CN CN t- CN CM CM CN CN co cN co co co m m τ- m m o - τt CO T- CD τ- O N- CD N- τt CJ) OO τ- CO CM CM CN CD O CO CD t- CD N- τt I s - CN I s - CD O Tt N- CD T- CO -ϊ- O N- CO O CO O OO in CD CO T ,t CD T- O - CM in cθ -»- τ- cO τt N- CO N- CO O τt τt τt τt O CO CD τ- I s - Tt 00 CD CD CD O T- CJ) CO N- LΩ 00 CO CN CO m m CM m CM Tt Tt N- m cO Tt O LΩ m CΛ CD CN CO CN Ln Tt O CM O CO CD I s - O Tt CO O 00 CJ) CN OO O CJ) CM CO LΩ CO OO CM - CN LO CD N- C» CD N- CO N- CO N- N- CO LΩ LΩ τt CD CD N. CO CJ) CD CD in cO ∞ CO τ- CM CJ) O O O O - CN CN CN ^ CN CN CM CN CN CN CN CM CM CN CM CM CN CN CN CN CM CN CM CM CM CN CM CN CN CN CM CN CN CN CN CN CN CN CO CO CM OO OO OO CO CO CJ) Tt MD CO i- ro O N CM T O CM O. τt τt τt CO ∞ τt N- τt C I s - ιn CN OO O CN C» ιn CD - CT) N- '^ O - O CM -'- O CO OO N- CO O τ- oo CN CM CN CN CD T- O CO - CN LO CO ^ ιn cN CJ) co c) in cN CN CD σ) CN co co ιn - - cN cj) co co cM θ τt Ln cj) τ- cD CJ) N- co o -r- N- O CO t- O - - O Tt O T- Tt σ) τt τt co co τt N- ∞ ιn ιn cN cj) in τt cj) τt co o i s - c_ c» co - cj) CN CJ) τ- τt τt r-- co cN cj) CD CD CD CO τt N- CJ) CO CJ) O τ- CM τ- N- N- CO CD CD CD N- m m τt in τt CO CN CD N- N- N- N- CJ) O 00 C0 C0 C0 00 C_D O CD LΩ - - - - - T- - - CN CM CN CN i- T- - T- v- - - - T- - - T- - - CM CM CM CN - N- LΩ CD CO CO CO CO - CO Tt CN CJ) I s - I s - cr> co co cj) co τ- N- co co τt oo iΩ c» i s - τ- co ιn cD co σ) co r- .- LΩ σ) CD CN co co - iΩ LΩ Tt CO N- CO O LΩ Tt O LΩ I s - Tt o CO CN o ιn oo oo ιn cD o σ) co o cN cθ uθ τt - cj) CN -«- cN -5- -«- oo ιn ιn cD oo cD '«- cN τt oo N- CD CO CO CD CN N- CO IΩ CN Tt CD I s - T- Tt I s - O N- I s - CD CD N- OO CN CN in oθ CN τt O CJ) 0 '^ CO CM CO CO CO CD CD CD LO τt OO CO co N N N in D in o in cD i N ^ - i in c' C '- o i tD N co N D D D co ro ro cn o o - - N N N N in i D 'N- co io in in in in Lo iΩ iΩ iΩ i iΩ Lo iΩ in in Ln in in in L in in in in in Ln in in in in Ln in i co cD co cD i i in Ln in in L^ - CN T- CM - CN T- CN co O < CQ O Ω Ω CQ O Ω Ω < CQ O Ω LU CQ O Ω Ω O O O CO o o O O O O o < o < CQ O Ω Ω < O O O O O o o O O O O O o o O O O CO O o υ O O O O O o < < < < < < < < < _ι _J © ro o - M co ^ ι o N co ro o τ- cθ - ιn cD N co ro o - M θ - ιn D N o ro o - (M o ^ ιo o N co ci) θ - cM θ - I- CO CO CO CO CO CO C CO CO C» 0) C_D CJ) 0) CJ) CJ) CJ) C_D C_ O O O O O O O O O O ^ - T- T- - - - - - - CM CN C CN CN o C0 CO CO 00 C C0 CO CO C» C C» CO C» CO CO C» 00 C CO CO C0 CJ0 CJ) CJ) CJ) CJ) O) C3) CJ) CJ) CJ) CJ) C_D C_D N- τt CJ) CO CJ) C0 C N- 00 CO uO O N- OO N- N- CD CD lΩ CO O lO σ) τ- 00 CN CN τt m Tt C LUO C IN L UΩJ CN 00 CO τt τt τt CD N- 0O τt τt C τt - C)0 τ-- C0 CN O CN CD CJ) τt ( X) I- lΩ O O CM 00 CM τ- C0 C0 N- u0 CJ) CN τt C0 C0 u0 C0 CD C0 00 - m r- x- - x- co co o co o 00 CM - N N O CD σ3 in C00 N CM CD - CD C0 CM in C0 ' L C0 in in N - - CM θ σ5 O CD τ- O N r- ιn cM σ) i- Ln - i s - oo cj) co Lθ ιn CO in CD N- O CO N- CO CN CD in - CN τt in CN O N- CO O τt CJ) τt in CN O O τt CO τt O τt f<-> Nι s - - N o. σ)C u. (D i ωσ) - CM C - CM CN τt CO ^ CN CN CN ^ O CJ) CJ) C N- σ) - - τ- - CN C CN CO CM O C_D I s - N- O CJ) Cθ σ) N- in τt OO in CO N- LΩ τt τ^ CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CN C C CO CO CO CO CO CO CO CO CO CN CN CN CO CN CN CN CN CN CN C^ CM 0 CO N- CJ) 00 N I s - IN s - CσD) q N - CM T- CN CO O Ω UJ N < CQ O Ω LU N X X < CQ O Ω LU N < CQ O Ω Ω < CQ O Ω < oooooozzoooooozozzzooooυoozzooooooozυooooozooo o OO O O CO CO Tt OO Tt CO CM lΩ N- LΩ CO τt CN ^ CJ) Cθ CJ) CN CJ) O τt CJ) τ- uO CN O in τt CN τt - | s - LΩ CO CN CJ) ∞ CN CO CO τt O CO CO 00 I s - CO OO o CD Tt lO O Tt CD uO uO O OO CN CD LΩ CD OO LO T- CJϊ O N- CΛ CD CD Tt O Tt O - N- OO N- CO CN O T- CD O T-- LΩ 1- LΩ CJ) 00 CM CO O lO Tt CD CD CD LO O τt i s - ιn ιn o Ln co v- ιn τt oo N- N- cj) co co co τt N- co ιn cN τt N- -»- co co τt ιn oo ιn 00 σ) in τt CO C0 τt C0 00 CN CM C0 - O - CM CN - O C0 C0 C0 τt τ- O CJ) C0 O θ σ) - O O C» - CN C0 τt in θ CJ) C0 I s - O O CD CO CD CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CD CD CD CD in in CO CD Ln CD CD CD in Ln CD CD CD CD CD C^ 1- CN - CM T- CN - CD < CQ CD < co O < m O Ω Ω < CQ Ω < O Q Ω LU N < co O OO o o o oo o o O o o o o o O O O O o o o O o o o o O O O O O O O Z O O O O O α m:α:om:cm_:om:omoLU:ouj:_<ι_<ι_<ι_<ι_<ι _<j _<jQco_ccoLC(_oLQco_Qc_Qco_Qco.Qco_ l LU ll l L l U l l L l ULULULULULU cococococococococococococococo C WWWWWWC >>>>>>>< < <<<<<< jjjjjjjjj JJ_J_J_J r- rM C ^ lO (D N CO © O - CM CO O (O N CO O) O τ- CN CO ^ UO (D N Oθ ro θ - C CO ^ UO CO S CO C» 0 '- CM CO 't in CD © S ss N N NoooooooocococococooororororororororororooooooooooOT-^ - -r- - - o 0) CJ) CJ) C_D CJ) CJ) CJ CJ) CJ) CJ) CJ) C_ C_ CJ) CJ) CJ) CJ) CJ) C_D a) OT CJ) CJ) CJ) CJ) C3> CJ) CJ) O O O O O O O - - - τ- τ- - - - - - ^ - - τ- - - - - - τ- - - - - - τ- r- - - CN CN CN CN CN CN CN CN CN CN CN CM CN CN CM CN CN CO CO CO OO O OO CO OO N- Tt OO O CD O x- CD Ln τt τt CM CO LΩ LΩ OO O N- OO LΩ CO CO CO O CD 'r- LO CD CD O τt O CN N- τ- CO CO 00 C0 CM O C0 N- C0 CD CN C0 τt CD 00 τt - 00 - O C _O CD C CO T- v- cO CN OO O OO CN O N- CN OO CO Tt OO CD OO in in - CO Tt CN CD CM L0 CN C0 C0 N- 00 Tt N- C0 Tt O CJ) t- CM CJ) O O N- N- CJ) 0 ∞ CN ^ CO CJ) LΩ Ln CN τt CD CO τt - Ln cθ CN I s - τt N- τt σ) τt - - - C» CD in τt CD in N- CD in ιn cθ CD in c CD CD in τt C N- N- CJ) N- τt CO CM τ- τt OO CO CM CN -«- O CD T- - - O ^ O O C 9) co cD CD in Ln ιn ιn ιn ιn ιn Lθ in ιn Ln ιn Ln ιn ιn ιn ιn ιn ιn ιn ιn ιn u in ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn τt m m m m m m m Tt - CN - CM T- CM - CN Ω LU N < CQ O < CQ Ω Ω < 00 O Ω Ω < CQ O Ω Ω < OQ O Ω LU < o o z υ o o o o o o o o o o o o o O o o o o o o O o o O O Z O O O O O CO O Z O O r_ c_ -_ _ J --J _J — J _ J _ l - J 3333333333333333 Q- Q-. Q- 0_ 0_ CL Q_ Q_ l— I— H I— - I— - l— O OO O < < < < < < .u E_j [u [u .u _u _u m ^ _J _J _l > > > > > > > _J _J _l _l _l _J _J _J _l _J _J _l _l _l _l _J < < < < < < < < -> -> 2 S ^ S S S < < < < N co ro o ^- c - uo D Nco ro o r- cM co ^ o D Nω ro o - ( ^u)uN co σ. θ - c θ '-ιn (D Ncoσ) θ - M © - - - CN CN CN CN CN CN CN CN CM CM 0O CO CO CO CO CO CO C C CO τf f t τt τt τt τt τt τf xt in in in in in u0 U^ o O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O CN CN CN CN CM CN CM CN CM CN CN CN CN CN CN CN CM CN CN C CN CN CN CN CN CN CN CN CN CN CN CM CN CM CN CN C Tt CO CO CN m CO CD Tt CM CN I s - CJ) O CO Tt CN CM CJ) CO I s - CN o Tt o σi cb 00 cb ib cb CD 00 cb N-i in c T— OO LO Tt CM T— Tt Tt CN τ~: CO CM CN in _ ~ - CO N -— CD T- -— o OO N N CO Tt N x— CN Tt CD CO CD m CM CM CD I s - D CJ) CO N- CM m CJ) o CM CN I s - N- CN O N LΩ o Tt N CD 00 Tt CM CD CJ) in CD o CJ) t I s - τ— o CD m o O co Tt Tt N- D CM 00 in CJ) I s - CD CJ) 00 00 N- o m I s - CO σ> o CO CD Tt CJ) - T- CJ) LO O0 CO CD 00 o o CO I s - 00 CD 00 CD 00 9 — 9 LΩ T- q o CN N- CD CN I s - 00 T- CO CO I s - CO I s - CO CM — CO CO Tt CJ) OO in CO Tt 00 CD LΩ T- CO N in r-i CO r-i Ni oo cb cb CM CM -r^ CM- T^ τ-^ T-^ -^ Tt Tt Tt Tt in CO ib cb T cb ib in in cb Ni r-i CO σi cb σi in in CD N Tt l Tt CM N N CN O CD x- x- O CO CD CO CJ) N CO CO CO CO CD in σ) CD CN CO CO O τt OO N x- CO τ- τt N χ- C N CD in τt CO ιn CJ) CM O in τ- τt τt CN N CN CO O τ- τ- lΩ OO CN CD CD N CD τ CJ) CO CD σ) N CD τt - τ- σ) CO ιn CD CN τt CJ) CD in τt ιn τ- CO CD τt N x- cq N c» q oq q q q ιn N τt cΛ oo c» cN θ CD co cD τt o oo oo c) q cM in c) θ τ- cq ιn cD ∞ q q T^ cN CN CN od c cb d d c - d T^ CN o Tt c ib Tt c c c ιn ιn ιn u^ ιn ^n ^n ιn ιn ^ ιnιn u^ ιn ^n ^r χ f ^ ^f χf τr ^ ^ ^ r ^ ^ M ■ f f ■ ^ ^ ■ N • f ^ f ^ ' ^ ^ ^ ■ , !f T- CM , n - CN - CM ' - CM OQ O Ω LU N X X < CQ Ω LU N < CQ O Ω Ω LU LU N < OQ O Ω LU N X X < 00 O Ω LU O O O Z O O O O O O O O Z O O O O O O O O O O OO O O O O Z O Z Z o o O O O CO O O O O O O O O o co co co co co co co co Lu m m m LU Lu O O OO O O O OO O O i- H H H H H H μ- o o^ Q^ Q: Q^ Q^ o: ^ ^ ^ ^ ^ ^ ^ x x x x x x Q: Q: Q: : o: o o o: o^ o^ o^ ω m m < < < < < < < ^ ^ ^ L L L Li Li C L CL C θ C . a. C < < < < < < < < < < < Ε Ε Ε Ε Ε Ε Ε Ε © CO τt in CD N CO CJ) O - CN CO τt ιn cθ N C C_D O τ- CN CO τt ιn CD N C CJ) O - CN O τt Ln CD N CO C3 O τ- CN CO τ^ CD CO CD CD CD CD CD N N N N N N N N N N CO CO CO CO CO CO CO CO CO CO CJ) CJ) CJ) CJ) CJ) 0) CJ) CJ) CJ) CJ) 0 0 00 000 0 0 o O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O τ- - τ- τ- τ- τ- τ- τ- t- CN CN CN C CN CN CN CN CN CN CM CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CM CM CM CN CN CN CN CM C^ CO CJ) CM CJ) m m τt CM τt CO CN CM CO Cθ CO CM N τ- CD OO CD Tt OO - CO C0 - N O CD CO 00 LΩ 00 N N 00 τt c0 τt CD N O CN O LΩ CD CN CN CM t 00 OO CN O CJ) CM CO N CJ) O CO CO CD CN CO CM Tt Tt O O CO CO CO T- CN CN x- CN CM - CM CM CN CN CN CN CN CN CN CM CM CN CN CN CN CN - CO <t- CD CO CO O - N CM LΩ T- CN N τt τt N LO τt CO O OO CJ) τt CD CO Tt CO N CM LΩ - O O CJ) - di M LO N N Tt CO O in CD N m CN CN O coro ∞co cor OO 00 CO CD Tt N 00 Nt-ooin -T-Noooox-oco CD CO CM T Tt T CN τt ' τt cb τt ιb cN cb cN cb Tt m cD CO Tt Tt CO N CO 0 00 O CD CM τt CJ) τt CO τt - O CO O χ- CN O CO CO CD v- Tt Tt Tt O CO T- CN τt CM CO N τt Cθ 00 - τt τ- C τt τ- CM - - O OO C in CM CO τt N N CN LD " " in CO CO CO CN Tt CO O CN 'r- CN CN CJ) O Tt CD in cO N CD N N CO CO OO CO CO CN τ- τ- O τt τt ιn in CD N CD τt LO CD CD τt N CO CO CJ) CJ) LO O CO LO CN τt t -- cD CJ) N C UDJ CUJ)J O*—' ιUn./ oLUO τXtI CD CO N N m θ CM τ- N τt O - m CN O CD O O C0 - τ- N CD CJ) CM in CJ) O) CN Tt t O C _M. .N T- _N CD CO CD O .in_ - m co co _ . . N in ~ τ- 0O CM τt CN N CD CO O - τt CD t- N in CN N O O Tt N m CM CD O) Tt T- in N oo o co oo o N oo m CM q N in CM Tt Tt σ) oo o o ιn co co τ- CD OO O CN CM CO O m oO CD CO Tt N CM Tt ιn do q ro ro d 'r Md oo cb N T- CCNN CCNN CCNN cObO cCbO TTtt TTtt ^- TT^- cCbO cCO dO O) CJ) C_D O) cCbO iibn CO CO TTtt iibn ccO NN cCO cCO CJ) CJ) cCO oOO NN NN cCO τt τt τt τt τt LΩ lΩ lΩ m τt τt τt i in in in in in in i Ln in in in in Tt Tt Tt Tt Ln in in in in in in in Ln Ln O Ln in u uO u uO - CN - "^ CM - CM < < oo O Ω Ω < CO O O Ω < CQ Ω LU LU < OQ CD O < co < CQ O O O Z O O O O O O O O O O O O O O O O O OOO O Z O O O O O O O OO o o o o o >- >- >- >- 333333 3 , ,,, II 1 Z Z Z Z Z Z Z Z Z Q: Ω_: -_ Q O: O: Ω_: < < <; < < CL Q_ Q_ Q_ Q_ ^ ^ ^ ^ Qj m ώ [I j [L j j j LU LU LU LU L_J LU LU m ϋϋϋU J j jjj j j j d d d dd d d dϋ(. ϋ ϋ (. (. C)ϋ C ) h h h l- h h < <<< < < << << © CJ ) O τ- CM 00 τt in CD N C 00 O τ- CN CO τt in CD N 00 CJ) O x- CN C0 τt in CD N CO CJ) O - CN CO τt in CD N 00 σ) O - C^ O τ- τ- τ- τ- τ- τ- τ- τ- τ- τ- CN CN CN CN CN CN CN CN CM CN CO O CO Cθ CO CO CO CO CO CO τt τt τt τt τ^ o CN CN CN CN CN CN CN CN CN CN CN CN CM CN CM CM CN CN CM CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CM CM CM C^ T- CO UO Tt Tt CO t CO CM CO CO CN in τ- N CO CO CO CO T- CO τ- 00 00 q oq co CM q CM d d ^ d CM " - 1 T-^ cb T in m m co N CN θ τt co ro cN ro ro ro ro cN N CD Lθ CD co τ- τt ro LΩ N ro τ- co co uo co τt N CN - uo uo co ro o N τt ro co uo τt oo co τt CD co ro ro ro ιn - co o o c» co cM CN τ- co -- τt cN in o cM Ln cD ro co ∞ cM - - - ro τt τt τt co cN co uθ o ro cM - oo co ro ^ CN - - CN N C LΩ τt CD CO CN N τ- - CO CO - Cθ ro N N CO O CN - N lΩ CO in τt C O ro N N ro CN CO CO CD O N ^ τt CO T- T- CN 00 00 N 00 N OO N CD OO CO CD N N Tt Tt cO CN N co ro o ro O O - CM C CO O τ- θ t- - CN τt in co m ro ro ro ro CN CM CM T- T- T- T- CN CN CN CN CM CN CM CN CN CN CN CM CN CM CM CM T- T- T- -r- - oθ Ln n cN oo ro Ln Ln τ- co τ- ro co - co o ro cD CD - cN ro N CO N r- UO CM CO N CO O u uθ ro - τ- OO CD τt CN CO τt N ro ro OO CN t- v- CD CN ro N CO N Tt Tt CD CD N N CD O OO ro cO CO CN CD CN LΩ LΩ Tt O O N co N co ro co co co co cD uo ro o -ϊ- uo cD N m N m co oo cN θ o o oo - τ- co N oq Tt N N - CD CO LΩ - CO CO CM LΩ O oo τ- co o co cD τt q cq '»- N τt N cq OO CD N CD lO CO CO Tt OO CN CN N odrorocbrocbd ro o o o cM c N- - co m ro oo co oo N co cD in cD t in r-i N c c inininininininininininininininuoiouoincD ocDcocDiDiococDCDtDCDinininininuoininininuiinw - CM ■ «- CM - CN - CM ,, - CM T- CM O Ω Ω < CQ Ω LU UJ < OQ O Ω Ω < ω O Ω LU N XX < ω O Ω Ω LU LU N < OOO o o O o o o O Z o o O O O O OOOOOOZO ZZZOOOOOOOOOOZOO Q_ Q_ 0_ 33333333 O O O O O O O O O O LU LU LU LU LU LU LU LU LU LU LU O: O: Q: O: CO CO CO zzzzzzzzz U LU LU LU O: O: Q: O_: Q^ Q_: O: O_: O: Q: O X X X X X X X X X X X LU UJ LU LU <<<ooooooooo LU LU LU LU L < < < < < < < < < < < Q- Q. Q_ CL Q. CL Q. Q_ Q_ Q_ CL C0 C0 C0 C0 ιn CD N Cθ ro θ - CN 00 τt ιn CD N Cθ ro θ - CN CO τt L0 CD N C0 ro θ ^ CN 00 τt in CD N C» ro θ τ- CM 00 τt LΩ C0 N C0 CJ) O © o uO uo uo uo io cD CD CD CD CD CD CD CD co cD N N N N N N N N N N co co co co co co oo oo co oo ro ro ro ro ro ro ro ro ro ro o - - - - T- T- T- - - T- T- - T- T- V - T- - - - - - T- - - - T- T- T- - - - T- T- - - - - v- r- T- - - T- T- CM CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN C^ Lθ ro ro τ- CN -r- CM CO N O CO CN N N - CN CD LΩ CO N in θ OO CD N O τ- co m m T in N CN Tt 00 N LΩ N ro ro N CN LΩ Tt ooocDinrocoLΩ -τ-cDCDrorocθLnLnocDroτt τtooroLncD τt CD O ι- CN CM CN O 00 Tt O CO CD Tt CN ro N 00 CD - o ro τ- θ ro τt τt CO τt LΩ τt CM CD N CO UO CD CD τt CO CD CO θ ro CD N N OO τ- O CO CJ) O in t LΩ CM N CD N CM O - C CM ι- CM (M - CM CM CM CM (M CM C τ- - CM CM - CM rM CM τ- τ- CM - - - - CM CM CM τ- τ- m T CN CN CN CM CN CM CN CN CM CM ■- co τt LΩ ro co co cN τt τ- ro τ- ro ro o co τ- cM CN CM ro CO - OO Tt CO CO lΩ uO CO CD UO N T t N lO CO CD 0000 T- CO O 00 CO CO Tt CD OO t- OO OO N OO 1- τ- τt τ- N τ- co ro cN ro CM -5- τt O CN O CO Cθ CJ) - CN CD LΩ O OO N ro CD -«- - - 00 T- oo oo CN N lO CO CD CO LΩ CΩ O CN T- co N oo co ro o oo N LO τt o o o τt τt t co co cq τ^ cq L ro τt τt N LΩ - T- N CN Tt CO CO CN CO Tt Tt UO CO CO CO Tt OO Tt CO CO CO CO UO UO CN ocNib NcoibNcbroocbocbcbcbroo NNcbcbcb OOr T- ^- ^- - T- T- T- T- - - M - r- - - - CM - r- T- - - T- CN CM CD v- CD T— CO O CO Tt CN LO CD O - ro co o CD Tt U0 CO CD O Tt N τ- τ- τ- CO O CO LΩ τt CO CO O CN O CN τt CO CO O N N τt O CD CO CO CJ) CD CO — CD N CJ) CN UO N CD CM CM 00 O CD - O CO O CO O LO CN ro co ro in ro ro o o o ro co ro o in in N co cN CN CD LO O CM N v- ro Tt Tt O - N N Tt CD O Tt CO CO N CD O O Tt ro iΩ T- CO CN CO t- CD O O T- N O Tt N Tt N CN OO CN CN O N N CJ) CD O r— oo N CD N O LΩ Tt CO ^ CO CO τt CO CO τt τt CO CO CN Cθ CO - - - CN ro ro CD CM CN τt τt CN τ- CO τ- τt CO CD N T— — T— — CM CM v- W CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM v- T- T- CM CM CM CM CM CM CM CM CM CM CM CM CM - O N N CO Tt N CM LΩ O N m o m co o co ιn cN θ "»- τt N N U0 CD 00 CM CO UO Tt uo - o ro ro cN CD ro N o in cD U000 t 00 O LΩ N UO N N Tt Tt CN oo io cN O co ro co o ro in cN oo oo O O T OO N CD oo o co cN CD co co co co N co co m CM CJ) CO O CM LO CN CD CO 00 CN oq ro CN CO CO OO UO CO ro O Tt CM UO ro CN Tt UO CO CO O Tt cD Tt ro co cM N co m cN cq in N iriro ^ CN CN co CM T cb cd d odd co co co co D co ro o o ro ro b ^ cM C ' - ' - N' ^ - d b i oi D DωωcD D oωcDωωcDωωco D DCDωinωini ini u cDCDi ini co o o D DCDCDCD DCDCD o CoQ Ooz <ooo CoQ Oo Ωo Ωo LoU LυU No Xozo <oo CυO Ooo Ω Ωozo <oo CoQzo <υo OoQ Oo Oozo <ooo O Q Oo Ooo Ωzo <o DtCtCtO CtCtCtCt CtCLCt CtCtCt∑)ID∑) )Z, )Z) ) LU LU CO 33 <;<; 3333 ^^>- >-^>->->->->-_j ιιiJ_j_j_jω_j <<<<<<<^^^^^^ wf-hi-hhl-hhhhHhJJJJJJJJ<<<<<>>>>>>>dddddddd(. (. (Du © v- C\| C ^ lfi CD N Oθ ro θ τ- CM C uO (D N Cθ ro θ r- CM C τ. lO (D N Cθ ro θ r- CM CO O u N Cθ σ) O τ- C\I CO M- lO CD O O O O O O O O O - - - - - - τ- - - - CM CN CN CN CN CN CN CN CN CN CO CO Cθ CO CO CO CO CO CO CO τt τt τt τt τt τt τt o CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CM C^ ro co ro cD ro τ- co iΩ N co cD N Tt o uo ro cM CN CD ro co ro o o cD CD Tt uo o co ro co oo N CD - CO UO Tt UO T- O O CM - O o oo τt ro cN oo co ro ro uo - cD t- CO CO τt CO O in CM CD N LΩ O CN CD CN O ro O Tt O Tt m - N 00 O O 00 N 00 CO T- ro CM ro o ro co CD o co co co oo co co uo co ro ro Lo cN - Tt co co co o N θO CO CJ) CO O LO - O CO t- - CD CO τt τt CD CM ''- cθ CO -»- CN CM CN CN CM -!- CN - CN CN CN CN CN τ- -r- CN CN CN CN CM CO CO CN T- CM CN -t- CM OO CN CO CO CN CN CN CN CM CN CN CN CN CN CM CN CO τt ro τt 00 C0 U0 00 N CN N τt CN O O CM CD L0 O C0 N N O CJ) 00 - C0 - CN C0 U0 N CN U0 CM CJ) O τt U0 U0 CD CD O τt θ ro CO UO OO Tt CD CN - Tt O N N O CO O OO τt O lΩ ro 00 U0 O CM C0 O N CD ro N '«- τ- C0 CD - - 00 N '«- CO C0 τt O CD CN τt ro τt O CO N Tt Tt m CD ro O CO OO CD CD CO O 00 ro θ C0 00 ro 00 00 CD L0 L0 N N N C0 O CM O C0 τ- O O τ- 00 τt C0 N U0 τt CN N CO CO OO Oθ ro θ f- CN τt CN C τt UO C τt xt UO N CO CN - θ ro in CD N CO LO CD N N OO CO CO N OO ro O N CD CO CD CO ro O O T- T- T- T- - CM CM CN CN CN CN CN CN CN CM CN CM CN CM CN CN CN - CN CN CN CN CM CM CM CM CN CN CN CM CM CM CO CN CN CN CN CM CM OO CO N LO OO co ro N co Tf co ro oo N o N CM CO - oO CM Tt N CO ro N N O CN CN N O oo ro cN O O Tt ro uo o ro o LΩ oo T- LΩ LΩ co o OO lΩ CM CO Tt ro oO OO CN N CD O CD CO CO CD CO CM Tt CO Tt N CO CM τt τt ιn uo τt - o ro cD oo oo uo ro cD Lθ CN co cN ro -r- CD CO OO - OO CM - CO T- co N ro q cN Lq ro τt cN τt τt τt τt cD ∞ N ro q cN q τt cM q cM cq ro cq τt N τ-; N cq q τt cΩ od ro " ro " d ιb ιb τt ιb Tt cό ^ M- CM CD N N N cd cd σi σi d N N N N ro N ro ∞ ιb τt ^ cb cN CN 'r- : cb t t b cb CN CN CN CN CO CN CN CN CN CN CM CN CN CN CN CN C CN CN CN CN CN CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ o co uo cD co co co ro o cD co uo cN ^ N uo co uo uo ro N ro c» cN co τt ro co N θ τt co cN θ - uo - cj) τt oo ro oo N uo uo oo - ro cN τ- ro cN ro LΩ N in co c£» co N τt Ln ro N CN τt cN in N CN in co co τt o o - oo oo oo τt - o τt τ- τt co cθ 't- o cN ro uo ro - cq τt τ rvj ∞ cq ^ L N τt N -; - uo cN cq cq cq ro ro ∞ cq d ro ^ CN o ro c ro c d ^ ^ T-^ cN ^ cN T^ -^ cM cb cb Tt cb ro c cb cd N CD uO CD CD CD UO UO UO O CD CD CD CD CD CD CD CD CD CD CD CD CO CD UO UO UO UO UO in uO uO Ln in Ln in UO CO LΩ LΩ LΩ LΩ L^ - CN T- CM - CM - CM - CQ Ω LU LU < < O Q < C Q O Ω LU N o <oo CυO Oo Ωo Ωo LoU O O O O O ooozoooozoooooooz o LU Noz <ooo CoQo Oυ Ωυz <oo ^ ^ ^ =l =1 ^ ^ ^ ^ 3 ^ ^ ^ ^ ^ ^^^ ^ X X X X X X X X X X U LU LJ L_j LU LU U UJ m 000000000<<<<< J J J J J J JlJ iQ_Q._ CLQ.CL L .CLQ_Q.dddddddd2SSS N co ro o - cM oo τt ιn cD N co ro o - cM co τt Ln cD N co ro o τ- cN oo τt ιn cD N co ro o ^ cN co τt Lθ CD N co ro o -!- cN © Tt t x uo LΩ in iΩ iΩ in in Ln in in cD CD CD CD CD Co co cD co cD N N N N N N N N N N co co co co co co co oo ∞ co ro ro ro o CN CN CN CN CN CN CN CN CN CM C C CN CM CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CM C^ CN CN CN CN CN CN CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN C^ y o t- J © © ! _ H U ro N ro 1- co t- in co o co Tt O Tt Tt Tt CO Tt CM T- CO CM Tt O Tt CN O Cθ ro CO lΩ CD O ro τt N τt τ- D ro CN Tt - α. CN N ∞ ro N Tt CN N m o ro o o CM co in N O O LO o o CD CD CO LΩ O N ^ cN ro τt ro ιn c» oq cM CN ∞ N o co o N Tt 00 CO i Un0 roro roro cCbD Tτtt τt LUΩ0 Tτtt - CCNM NN roro iun0 CCDD O CC0O Tτtt CC0D C0O0 c0b0 cC0 NN CC0O cCbD CCNM dO CCNN Tτtt C0 cCO cCNN cC0 oroo NNi -^^ dθ roro dθ NN CCNN cCbD ^- Tτtt CCNM CroD θ CN CN CN CM CN CN CN CN CN CN CN CN CN CO Tt CO CN CN OO CO CN CN CN CN CO OO CN CO CN CN CO CN CN CN CO CO CN CO CN C^ CD CN ro OO O CO CO OO CD CM N CD OO CO CN in CO O CΩ τt τt CN CD τt CO τt OO co co ro ro oo LO N N CD N CO UO Tt CO O T- CO N UO Tt CN UO CO o LO t Tt CD CO O CD O O UO CO Tt - CD N UO ro CD CD ro CD CD T Tt CN ■ «- N O O UO 00 o o Tt ro CO T- CO, uo Tt ro N CD CM N LO CD O UO O t- - cθ CM τ- CN τt ro θ N Cθ m UO ro co uo Tt q t uq CN ro co O Tt - CO CO cb ro d d -r- d . C _D.- ro c N C N CO CD ro ro c N O - cCOb NN iUn0 iLnΩ rN-i cCb0 uUo0 τt cθ CN C0 τt CM Tτtt τt C0O0 CCMM UUO0 Tτtt ιUb0 N U0 τt ' CCOO CN CN CM CO CO CO CO CO CN CM CM CM CM CM CM CM CM CN CM CM CO CO CM CM CM CM CM CM CM CM CM CM CM N CM CM CM CM CM CM CM CM CM CM CM CM CO m oo CO N CO O CO τt τf θ m ro cO N CN in CO CO CN N τt o o oo co co o ro cN ro N co ro ro m o CD CM τt N CO CD τ- τ- N O CM CN N oo co m co co m ro co . t- N τt CD CN τt lΩ CJ) O τt 00 τt U0 C0 CN τt CD τt τt 00 τt CD τt 00 τt N 00 C0 O C0 CD 00 - CD O co o cD ro co ro co cN m ro O CN CD Tt CO LO N ro oo co ro -«- oo cD CJ) uo cD CN CM uo ro co ro co - cM Tt Tt o o q cN Tt CO - τ- CD N ro θ ro θ - τ- τ- CN CO CN ^ ^ CN CO τ- dO cCbO ιibn ττtt LLnb ιLbn uUoO cCbO cCbO cCbO cCbO ττ-- d0 ^- CN CN τt τt CCNM CCMM Tτ^- T-r^- Tτ-- 1 LUOO CCDD CN CM CM CN CN CN CN CO CN CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ o co co τt oo ro τt τ- CO CD CO Tt Tt 00 CO CO O Tt O CO UO CM CD CO CD CM CM N . C_D C.O. C_O_ N O Tt CO N CO v- UO CJ) 00 UO UO CN O CD τt N 00 - τt CO CO CO CD CO CM CN O N N uo CN ro N O. - IO - CD UO ro CN Tt - N N O N N CD O CM o ro o if ) CO T- N M - " ^ CO CN N Tt CN q CN N ro uO Tt UO UO U0 Tt 00 CN CO CD N CO N CO O CD OO O oO ro uO o uo co CM N co m cbb ccbd ccbb TTtt T^ ^ ^ T- v^ ^ CroD CroJ) ' CcNM CCNN ^ c c N N c cb c c N Tt CO CN O Tt Tt CO CO CD CD CD CD CD CD CD CD IΩ LΩ CD CD CD CD LO LΩ UO UO UO UO UO IΩ UO UO UO CD UO UO UO UO UO UO CD UO UO m m m m m uo m m m - CN T- CN T- CN CO O Ω LU < < CO O Ω Ω < oo O < oα O < CO O O < OO O Ω LU LU < O O CO O Z O O O Z O O O O O O O Z O O O O O Z O O OO O Z OO O O O O Z O O O O O O O Z Z O H H H H >-. >- >- >-. Q_ CL OL DL Q_ Q_ Q_ Q_ O: O: O: O Q_: O: O: Q: C_: C^ O: Q: Z Z Z Z Z Z Z Z Z CL Q. LU LU LU LU ^ J ^ -J CΛ CO CO CO CO CO CO CO LU LU LU LU LU LU LU UJ LU LU LU LU _ -> _> _ _> 0000 < < < < < < < < C C C CO CO CO CO CO CO CO CO CO $$$$$$$ oi _oi _o j o_ j o_i _o j o_io_io_J C<0 C<0 CO τt LΩ CO N ∞ ro θ - CM C τt in CD N ∞ ro θ τ- CM OO τt lΩ CO N Cθ ro θ - CN CO τt in CD N C» ro θ - CN CO τt UO CD N CO © ro ro ro ro ro ro ro o o o o o o o o o o - - - - - 'r- - - - T- cM CN CN CN CN CN CN CM CN CN oo oo oo co co co oo co co o CN CN CN CN CN CN CN CO CO CO CO OO CO CO CO CO CO CO CO OO CO C CO OO CO CO CO CO CO CO CO CO CO CO CO CO OO OO OO CO OO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ CO CO CD CN N Tt Tt CO CO in O CO N CO CO O CO CD N N N N co Tt ro N co ro iΩ CM ro cM ro cN co co co ro ro o co Tt co N CO CO in cθ CN - ro τj θ - CM ro τt U CN N τt τ- UO CO τt - CD CJ) τt τ- CD ro CD CO τt CO oo CO N Tt CD O CD UO Tt Tt N ro O q Tt N q CM O -r- CJ) 00 N τ- τ- τ- O 00 O O N U0 τt 00 τt N CD CO U0 CD CN 00 N τt in in N Tt CD N ro co ro uo Lo m ro ro ro CN i ^- τt cb cb N CM d ro co -5- cM CM - co o ro co N θo ro ro o ro o τ- τ- CM CM ro ro cb r-i CN co N cb ib cb ro ro ro CM N CM CM CM CM CM CM T- T- CM CM CM CM CM CM CM v CM CM CM CM CM d CNo CM CN " CN " CM ro UO 00 - ro ro ro co τt o τt - N χt o cM τt τ- cD N uo cD CN N uo cD θ CN τ- ro ( - ro ( D N in uθ rM o ro ιn σ) ω ro ro o σ) in - '!i- '«- ro τt q cM ro q τt uq q cq ro τt cN ro N ro co c» o co o oo τt Lθ N cD N N N ' N b in D uo CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ C0 O CD 00 O 00 τt C0 τt CD U0 N '«- 00 N CD U0 CD O CM N N CN N C0 O τt ro C0 C0 T- ro co o ro CN LΩ Tt ro o co N co ro cN co co co o uo N N N θ co τt uo τ- uo co Ln o ro iΩ ro m co cD τt cM τt cM CD N uo N co ro Tt T- O CD τ- 00 CM U0 - U0 τt CM uo ro co CN CO - CO CM τt 00 N CM CO CD -<r- CD LΩ N CO - C0 CD — ~ 00 » — T CN O CN LΩ CO O CO - CD CO CD O U CO UO UO OO u τt τt τt co uo cD N CD CD ∞ ro o ^ - LD Ln co co τt ιn N Ln N τt N Ln cD co cN CN ^ ^ o ro c» N oo co τt co τt τt co co Ln uo uo uo uo uo uo uo uo Ln in in co co cD in Ln uo uo uo uo uo uo uo uo uo uo uo uo uo uo uO uO uo uO Tt Tt Tt in in in uo uo uo uo uo ■ «- CN τ_ CM , ΓN - S-. ,Γ ~ C | C CM CO CN 00 Ω Ω < OQ O Ω LU LU < CO O Ω Ω LU LU LU N N X < CO Ω UJ N < CO O Ω LU o O O O O O OOOOOOOZ OOOOOOOZOOOOO OOOOOOOZZOOOOOOO Q.D.D.Q.Q.Q.ZZZZZZ Z ZZQ.Q.Q.CLQ.α.Q.CLQ.Q.CLQ.Q.IlwcΛWWWWωWW^3DDD DD CO CO CO CO CO CΌ -J -I -J ^ ^ -I - J -J ^ O: O: O: O: Q: O: O: O: O: O: Q: O: O: O: >- >- >- >- V V <<<<< <OOOOOOOO HHI-l-l-HI-HHHHHHH-J-J-J-J-J-J-J-J-JθOOOOOOO © ro o - cN co τt Ln cD N ∞ ro o τ- cN co τt Ln co N co ro o ^ cN c τt Ln cD N co ro o - cN co τt LΩ co N co ro o τ- cN oo τt CO τt τt τt τt τt τt τt τt τt τt lΩ LΩ UO LΩ LΩ UO U UO UO UO CO CD CO CD CD CO CO CD CD CD N N N N N N N N N N CO CO CO CO CO o co co co co co oo co co oo co co co co co oo co co co co co co co co co co co co co oo co co oo co co co co co co co co co CN CM CN CN CM CN CN CN CN CN CN CN CN CN CM C CN CN CN CN CN CN CN CN CN CN CN CM CM CN CN CN CN CN CN C^ O - N CO CM CO cM co cD N ro - τt ιn ιn uo -«- τt co oo ro co - co cM θ τt cD co cD co cD co uo τt N o uo t- ro T- o ro o c .o. . N ro _. O ooO oN N τ- C CO CM τ- ιn CN τt r-- LΩ τt CM N O CO CO N CO CN N - CO OO τt CO O UO CO N τ- CN Tt Tt CO N o oo o OO co ro co cM τt τt co cD co cM CM CM oθ Lθ τt cM oo ro cM Ln o cD co ro -»- ιn - - ro co cθ N CO Tt 00 o T o oo ro t co ro CN CN τt lO τt τt CD N CO CO CO CN ^ O τ- O τ- O C» C» O CN CN CN CO τt CO N CD τt CO N CD CO CO CD lO U CD in ιn cθ in oO CN N χt ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn ιn tn ιn τt τt ιn ιn ιn ιn ιn ιn τt τt τt τt τt τt τt τt τt τ^ CM -<- CM rn - CN T- CN - CN - CN LU < CQ O Ω Ω < CQ O < CO Ω Ω LU UJ < 00 O Ω LU LU < CO O Ω Ω Ozooooυυozooooozooooozooz OOOOOOOOZOO OOOOOOOOO © LO CD N co ro o - N cO Tt in cD N co ro o - cN oo Tt in co N co ro o - cN co Tt in cD N co ro o - cN oo Tt in co N co ro o o oo oo co co oo ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o χ- τ- - τ- - - - -r- τ- τ- cM CM CN CN CM CN CN CN CN CN co C CO CO C C C CO CO CO CO 00 C CO C Cθ τt τt xt τt τt τt τ τt τt τt τt τt τt τt τt τt τt τt τt τt τt τt τt τt τ^ CN CN CN CN CN CN CN CN CN CN CN C C CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ CM Tf N o O oo CO Tf o LΩ "«— CD Tf N 00 CM N CO o o CM O Tt ro CO Tt O 00 ro O ro ro CO Tf 00 T— N CN co cb N CO cb cb ib Tt CO N N cb CD ro CM " CO Tf d uό ro cb CN CN CN CN CM CN CN CN CM CM CN CN CM CO CN CM CO CO CO Tt τ- cN θ cD τ- ιn co - co co Ln ro ro ro τt ro co τt - τt c» τt o cD θ o co θ Lθ oo cN CD ro τt co co ro cD in τt cD co o co co co co co cN θ τf N co co cN N in co ro ro ιn ∞ cD ro cN co uo co co co - - oo cD co ro uo c» CD CN ro N ro cN θ co cM co cM uo oo cD O N U0 N U0 C0 C0 U0 O CD ro u0 - N CO τt c0 N τt 0000 N ro c00000 N CD CM - N CN CD CD C0 CD O U0 τ- c0 CD N CN CN N 00 T- O 00 CO 00 CM O CD Tf CO O CO O CM CO LΩ CD T- - τt cθ O CM θ ro N CD CN CD N - CD CD -r- CO Tf N CO CD CN N UO ro CN CO UO CO CO Tf CM U0 UO Tf CN CO CO CD Tf in CM - Tf Tt CO UO CD Tf OO UO UO CO CO CO O Tt CO CO UO UO UO CM CO UO Tt UO CD Tt UO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx © - CN C0 τt LΩ CD N C0 ro θ - CN C0 τf U0 CD N C0 ro θ - J 00 τt LΩ C0 N Cθ ro θ - CN C0 τt i0 CD N C0 ro θ v- CN C0 τt L0 CD o 00 00 00 CO CO CO CO CO CO τt τt τf τt xt xt τt τt τf τt U0 U0 U0 U0 in U0 U0 U0 U0 U0 CO CO CD CD CD CD CD CD CD CD N N N N N N N ^ - ^ ^ ^ ^ ' ^ - - ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ . \f ^ \f r - ^ ^ ^ ^ ^ - ^ ' k - ^ ^ ^ ^ ' l f ' b ^ CN CM CN CN CN CN CM CN CN CN CN CN CM CN CM C CN CN CN CN CN CN CN CN CN C CN CN CN CN CN CN CM CN C^ CM O o CD O CO CO CM CD CJ) in co Tf N N O) Tf CJ) Tf UO CN Tf O CD - UO co oo oq q - Tf CO I-i CD T- CM oo oo d N od cb r-i ro LΩ N CM LΩ Tf CN CN Tt Tf CM Tf Tf CM oo oo uo CM CO Tf CD UO oo - in t CO N CM O CO O ro ro θ O τt c0 τt CD CN CN CJ) τt τ- N 00 O U0 CN - CN CN U0 O - CM C0 U0 CN ro ro ro c0 C0 - N U0 ro co co co v- CO CO O CD Tf ro t- o cD N oo ιn cD θ τf o uo τt cj) co o cD uo co m o uo co o uo cj) θ oo co uo N uo - uo co ro N CO N Tf CD CO LO CO N O ^ CD U0 C000 CD O τt U0 ro τ- CM C0 N 00 N CD C0 C0 ro 00 CM O CN C000 CJ) C0 τt U0 N U0 U0 CD '^ C0 Ln o cD co τt N CN Lθ co ro cN -r- oo cD co ro oo o co oo cN ro τt co co N τf xt cN cθ LΩ N ro Tt LO CO CO N CO Tt U U CN CO - - CD CO LO C CN 00 CN CO τt CO CN τt CN U0 ^ τt CN CM U0 CN CD CN τt CM CO U0 Cθ CN U0 CO CD CD U0 - CD UO CO CO CN CO CN CD CD CO CO Tt CD OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx N Cθ ro θ - CN C0 τt L0 CD N 00 ro θ - CN C0 τt ιn CD N C0 ro θ - CN 00 τt Ln C0 N C0 ro θ ^ CN C τt U0 CD N C0 00 O - CN © N N N oo co co oo co co c» co co co ro ro ro ro c) ro ro ro ro ro o o o o o o o o o o v- τ- ' l r- - - - -r- 'r- - - cN CN CM o τt τt τt τf τf τt t τf τt xt τt t τt τf τt τt τf τt τt τt τ τt t ιn ιn ιn ιn u in Ln ιn u uo uo uo uθ Ln L^ CM CN CN CM CN CM CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CM CN CN C^ M N M Iv) W M M I N. M W M W M W M M I M M M N. N) M M IV) M M K) W M M M rorororororororororororororororororororororo rorororo rororo ro ro roro rororororo ro rororororororo ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro 4 s - 4 s - 4 s » 4 s - 4 s .4 s - 4 s » 4 s - 4 s - 4 s - C oo oo oo oo oo ω (B J(SW^WM-'O O O jro n^«M-iOC003 O) )l^UM-iO(OOO J(I)W^«M-»0(D03 !(J)01^W XXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXX OOOOOOOOOOOOOOOOOOOOOO OOOOOO OOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO ro to ro ro ro ro to ro -». ro to oo ro ro co ro io ro ro 4 s - ro ro ro 4 s - ω ω j - ro J J θi ω J> r -A r ω σ) oι ω ω N. -V] CJ) O0 C0 CJ0 -VJ 4 S - -»- -vi ro ro o ->■ 4 s - 4 s - CJi 4>- CD ro oo -»■ ro o ro -»■ oo J α. M -g ro c_o --4 to 4 s - .o -v. ro cD -». ro oo oo ro co co ro ω -i M ω c boo ' N oo ro ω w o ω co ^ r o ci. ro N- r ω oo cD -' xi o o ro -vj ro 4 s - 4 s - 4>- 4 s - -χi oo -vi -». oo co -». -j -». to .o N ^ ι -^ -ι J ro ro ro w ^ α M -ι ^ -ι r *. N. j. oo ^ -ι. χi oo w s - ro -χi -i -^ ro -χi ro co -». --j -C-. ro -vi ro ->. αi cn oo cD θD CD Ui ω cD D Ui ro σ) χi co -j » cD ω o - j . ω ^ -i -i ro r ui cD ω 4. -*. co ro ^ ro -»- ro ro ro ro cj) co co ro co co -». _i. _i -N ro ro O ro ro ro _». ro to to to _ ro to -j O to oo . CD ro 4- to to __ 00 to _», CD O -j 00 -vl to --J ro O O O o ■ -J CD bo -j ro bo CD bo oo -* ro CO CO o 00 CD ^ 4 s - CO ro ro ro -j 4 s - -* 00 ro 4 s - CD ■0- bo 00 O CJ) CD O to ro ro ro ro ro CO i- 4 - CD CO ro ro ^ CJ) ^vl ro ro CD d s - • vj 4 s - ^ CO - CO O O d 4 o 4 s - o 00 bo 4 s - to D ro — _ —-. 4 s bo d CO — -. CO bo _ _. 00 __. — _ CD to -» ■ C ro ro ___ -si CO _ __ CD ^1 O ro ro CD ro O ^J — -. o CO 00 CD 00 CO co 4>- to - l ro — _. ro o ro o o CO — -. 00 -j CO ro ro o ro 00 n ro 4 s - ro — _. oo CO O -ti00 -vl CO O 00 CD O O -vl o O —_. O ro ro ro CO — -. 00 CO o CO 4 s - 4 s - ro 00 00 ro ro —_. bo oo CΩ to ro to d 4 s - CD ^ 4 s - ro o CO o 00 bo 00 " 4 s - i __. — -. 4 s - ro O bo CD ro d ro CO — _. ro 00 CO co — -. to ro -si -J 00 ro — _. 00 ro ro _^ o O CO ro o to CO -J 4 s - -fc» ro O IO — -. ^J ro to O ro O — -. CO CO to —_. to CO -vj 00 — _. 4 s - to _ _. _ _. to _ _. 4 s - to ro CD ro — -. * r 4 s - io ro r 00 ro fo ^ O 4 s - ro o ro co to CO ro ro o ro d -J ro q CO 4 s - o T 4 - ro ro —_. o CD J CO O ro o ro ro ^-j o to CD CAO ^ bo it>- _- 4 s - 9 CO 4 s - CD co t . ro CD ro bo __. O -j bo CD or ro d 4 s - O CO to d d CD CJ) o C O D ro CJ) 00 4 s - — -. O CTI ro O — __ 00 CO ro o ro O CD ro 4 s - 4 s - 00 ro CO —_. C O to to r o ro C to 00 00 CD ^j 00 to OO CD o D co CD 4 s - CO _!. o o o CO 00 CO to CD ro _!. to ro 4 s - 4 s - 4 s - o ω CO to — _. 4 s - D ro ro —. 4 s - ro q 9 ro O CD q to CO ro D 4 s - q ro O 4 s - bo ro !__ d ro bo ' 4 s - ' __. i__ bo d 4 s - d ro d q co ro ro ■ -J __. o oo o -j ro ro CO 4 s - 4 s - to d 4 s - o O O o 4 s . 4 s - r CO CO CO O O to to ro 4 s - 4 s - 4 s - ro ro ro 4 s - 4 s - ro 4 s - 4 s - CO ro — >- 4 s - o o ro ro o ro -v| -v| CO ro 00 co ro 00 ^ l 00 4 s - O 00 ro 4 s - CO 00 CO i. ro to O 4 s - 4 s - 4 s - 4 s - -vl o CO — »• o CO 4 s - CO CO ro CO ro 4 s - 00 ro ro ro LO © © ! _ H U α. CD ro x— Tf CO ro CO N CD CN Tf N CN uo co ro ro N O o CO CM O 00 O N CO CN uo CD T-; in σi CO CN d Tf CD σi CO uό in ro cb Tf in cb CM Tt Tf 00 o in Tf CO in CD ▼ ~ CO in Tf Tt Tt Tf CO CO Tf CM CO CD CM CN CN O ro Tt CO oo CM CO CO CM CN N Tf cb X— x— 00 τt - CO UO τ- CO CN CJ) CO τt O CO - N O CO N UO O CO N Tt O T- CD UO - CD O CD Tf CD N N N N UO OO O ro CD O N CD N O CN Tf O N Tt CN CM CD x- 1- oo uo m in cN CJ) Tt N 'xf N O T- CJ) - T- Tf orouo τtuocj)N uo uoouoτtcouoro N θ τ- ιn ro UO N τ- cN N CN ∞ t N CM q in N <Ω cq Tt Tt Tf CO m oO Tt CO O co oO Tt cb cM cb o cb cN O O CO CO LΩ LΩ Tt CN Tt CO CO CO Tt CM x- Ln in CO U0 CN τt CD U0 τt - - iric N cb ro cb CN in in Tt ' τt - co τf co m m oo co Tt Tt in in co cM OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx ro θ x- CN CO τf ιn CD N ∞ ro θ - CN CO τt UO CD N Cθ ro θ τ- CN C τt UO CO N Cθ ro θ - CN OO τf UO CD N Cθ ro θ 'r- CN OO τt © cDNN N NNNN NN Ncocococooooocococ»c»rorororororororororoooooooooooτ- --r- -'r- o ininLninininLn inin ininininuo uououououououououououououououououocococDCDCDcocDCDCDCDCDCDCDCDCD CN CN CN CN CN CM CN CN CN CN CM CN C CN CM CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CM CM CN C^ LO © © ! _ H U α. Tf 00 ro o X— ro N O CN CO Tf Tf CM Tf Tt CD O x- 9 CD x— CO CM ro co o CO Tt CD LO O CN d in x~: CD O in CO Tt Tf d CO N N d oi CD N uo N Tf O CO N CO CD CD Tf CD N CO CD Tt ro o CO CN CD O CO CD CN τt N CN CO x- 0 0 ro uo τt uo ro τt τt uo o uo co o ro o cN ro N co O xt x- CD x- CD Tt ro cO CO co in N U CO CO ro O CM x- CO x- N O O O UO CO 00 uo x- xt N CO 0 N τt N CO U0 χ- CD CD N U0 τf O CM Tt OO ro O CD CO CO CN N cq cq in in cq q cq cq in cq in t ro CM N -xt- UO N CD N UO OO CO CN Tt OO O OO CO C co Tf cO CO ro cO N CD Tt CN CN N ro d ιb χ -^ oo N cb cb τt τt cb cM d od ∞ Tt cd d d uo x^ uό cb N uό cb cb cj. cN d cb T^ c O iri iri - - - - iri iri - CO m t UO UO CN CN CM Tf UO CD Tt CN N CD τt CO τt CD LO CM CO 0O χ - x- CO CD CO CO CO CN CO CM τt CO CO CD τt τt τf τt xt τt Tf τt τf ■<- CN C0 xt m CO N CO CJ) OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO CO O O O Z OOO xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx OxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOxOx LO UO UO UO UO UO UO UO UO rororororororororo © LΩ CO N C0 ro θ x- CN C0 τt U0 CD N 00 ro θ x- CN C0 τt U0 CD N 00 ro θ - CN C0 τt U0 C0 N C0 ro θ x- ^ - x- x- x- CN CN CN CN CN CN CN CN CN CN CO CO CO CO (r) CO CO CO CO CO τt τt τt τt t τf τt τt τt τt Ln in o CD CD CO CD CO CD CD CD CD CD CD CD CD CD CD CD CD CD CO CD CO CD CD CO CO CD CD CD CD CD CD CD CD CD CD CD CD CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN cN co Tt m cD N co ro 95 O10 45.978 17.336 6.42020.00 95 011 46.159 14.860 5.251 20.00 95 C12 43.503 15.119 0.77620.00 95 013 43.428 15.102 -0.45220.00 95 014 42.803 15.898 1.35820.00 95 C18 44.232 12.358 -0.36820.00 95 C19 44.430 10.836 -0.52120.00 95 N20 45.675 10.345 0.08720.00 95 C21 45.756 10.616 1.531 20.00 LO t- © © ! _ H Q- Tt 00 CN Tf CD Tt O CO O O x- CD OO CN UO τt x- τf CJ) τt cθ CN N x- CO CJ) ro θ N CM ro τ- CO T- UO CN 00 CO N O N UO CO CD Tf x- co τt o co τf cθ LΩ o ro cD oo co τ- cθ Ln χ - ro m m χ - oo N x- CO 00 Tf o x- ro ro co N CN τt τt CD CN O CO χ - O Uθ ro θ χ - χ - CN CO N ro oθ χ - o x- ro ro uo x- co ro cN oo Ln U t τt LΩ in CO CO CD τt τt τt C τt ^f cθ CO τt τt t τt τt τf τt τt Ln Tt Tt co Tt in Ln LO CD co τf x- O O CN CD N ro CD CD τf cθ ro θ Cθ ro CO x- N ro CN N CN N CN τt CO CO CM τt τt CO CD CO CD CD 00 lΩ CD CN L0 x- θ ro x- ro CD CD U0 τt x- ro U0 U0 U0 c0 N CN ro θ N C0 τ- θ ro U0 O τf C0 CJ) N CN Cθ O U CO CN τt N N CD τt CN O x- CD N CN ro θ τt CD χt CO CM CD CD in CM CO x- 0 -r- CN cq N ∞ uq Tf Tt ' cN ^ Tt Tt ib Lb cN x^ d ro x^ cM cb cb x^ d ro c x^ x^ cb cM d ro cb ιn uo uo uo LΩ uo uo uo uθ Ln ιn uo τt uo uθ Ln Ln LΩ uo τf τt uo uo uo uo uo uo τt τt τt uo uo uo uo uo τt N ro N CN UO LO OO CD UO 00 x- CD O N x- N CJ) 00 O CD CD CO CO CO CD CD N xr- CM uo co N ro Tt N CO o uo ro ro x- co N ro N co o N CD oo ro x- CO N CD CN CD ro oo m oo Tf CO N CD O O ro CN co t co CN uo ro χ - o ro N τ- τt co χ - χ - m Tf CO o ro N CD co ro CM x- x- x- 00 Tf N C x- o ro o oo ro ro ro oo N N uo uo ro ro o o oo oo N N CD CN CM CO Tt Tf iO Tt m CN Ln UO UO Ln Ln UO τt Ln τt τt τt τt τt τt τt τt τt τt τt LΩ U0 τt τt τt xt xt LΩ LΩ LΩ U0 LΩ UO UO UO UO UO U000 ro τt O N CN O 00 U000 N O C0 O U0 U0 ro C0 N ro CD CM τt CN x- O CO Tt Tf oO CO CO O CO N CD CJ) O τt N Ln N N x- CJ) UO τt τt CN CJ) τ XtI ro UJ x "*- — C UOJ C LDU O »-_J U UOJ C VUD τ Xf| c Lθ'J O O lΩ LΩ CO Tt N O LΩ CN xt τt N x- ro CN UO CD N UO τt N UO CD τ- CO CN Tf O N Tt x- oO CN N OO O N CO LΩ CD UO O xt OO ro co ro co N (D CD CD N ro ro co co o o. ro N CD UO UO UO OO OO CO CN CD UO CD CD LO Tf UO Tt UO CO CO CO OO CO CO CO CO CO CO OO CO CO OO Tt CO CO CO OO OO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO x- CN x- CN < OQ Ω LU LU < CO Ω LU < OQ O Ω LU LU < CQ Ω LU N OOOOOOOO O O O O O CO O O O O O O O O O O O O O O O O Z LO 3_33333333tl]t t_]ti_ _ t_]t33≡3333_3_3_3ξ2^^?^?^^^≡3 00000000022S2S2^^000000000_J_J_J_-J_J_J_J_J--J0 © o CM 00 τf m CD N 00 ro θ χ - CN C0 τt U0 CD N 00 CD O x- CM C0 τt LΩ CD cN co xt m co N oo ro x- x- x- x- x- x- x- x- CM CN CN CN CN CN CN CN CN CM CO OO OO CO CO C CO χ- cN θ co uo uo ro χ- cN τ- uo N -«- co q N ω LU LU N XT' c LoU N I— ■ q L_J ro UJ c UsJ c LoU c LoU LU XI >— ' < » C τt LO Ln in cθ CN CN CN N UO CO x- ro τt χ - ∞ Ln ro N co χ- o ro t ro ro co cN ro cN ro ro ro χ- χ- N CN co χ- oo oo χ- oo oo uo uo N uo τt o uo uo χ - co x- co co o x- x- τf C0 L0 ro U0 τf C0 CD CD CO θ ro θ U0 x- O CN O CN CN CD C0 U0 ro 00 CJ) CJ) τt ro θ C0 ro CN τt CD 00 CN C0 CM CN UO CO CM x- O x- ro CN N N CO CD LΩ LΩ O O x- O CD τt CD N LΩ CO - x- CD CO CN τt CM τ- CO O x- x- CO τt τt CO χ - N CD τt CO CO N ud cb N N N CD CO U0 τt cθ CD U0 Lb Ln τt τf CO UO τt cθ CN UO CD N N N τt OO CN - τf xt uo uθ CO CN - 0 CD x- CM O OO O Tt Tt Tf Tf Tt Tf Tt Tt xt Tf Tt Tt Tt Tt Tf Tf Tt Tf Tt Tt Tt Tt Tt Tt Tt Tf Tt Tt Tt t t xt xt xt t t Tf f Tt xt CO Tf Tf Tf Tf Tf CO CD CO CN O Tf O CO Tt CN CO OO CO N τt O CO x- CN t CO CO CO CJ) N OO CN Oθ ro τf 00 CO UO CO x- CO CD - x- ro CN O CO xt O CO ro CM r- N CM CO τt O Oθ ro τt cθ OO CN τt 00 N τt CD ro N CM CN ■ «- N - O CO CN 00 CN O x- x- τt CN N U0 0O xt uq ro x- uq t θ LΩ 00 CD CN O CD CD τt N x- t f t- ro cθ CN 00 CN CO CN Cθ C0 CO LΩ CD LΩ x- x- CM x- in in co f x- CO CD CM x- N χ- m co o ιo ιn τf co CN ^ x^ CN x-^ x^ d cM d ro O ro oO N CD N UO CD UO O CM CN O O x- CJ) CO τt CO τt lΩ CO CO CD N CN CN o d d in uo o L LΩ Ln iΩ Ln m Tt Ln τf t r xt τf t τt τf LΩ U0 U0 U0 U0 O uO U τt U0 U0 U0 U0 U0 U0 U U0 O U0 U0 U0 U0 U0 U0 U0 Ln U0 CD 00 Tf x- CD N CN CO UO O N CO CO CN CO CO N τt LΩ CO U CN χ- CN x- τt U N UO τt O CO τt O CO UO τt UO τt τt CN O Tτfr N | v. N r ^ χ- C LO'J C LUO u UoJ o V—J C LMN N I— N I—- C LN C yDJ C LO'J N I— • C LNN τ XfT C LU O L_J C L0U N l^> C L0U C L0U x x ^ - CN CD N ro ro τt 00 C0 N τ-- N CD 00 C0 00 O θ ro C0 τt CM CN τt τt x- τt CN CO O CD LΩ O CD N cO CO N OO x- C " D C " D OO " CM O " ro cO " N O N UO χ- O N τt CO CD CN O CO τt lΩ N τ- ro N ro CN Cθ ro uθ N ro ro co ro θ χ - CO CO CO CO N CO CD N CD N LΩ N UO UO UO τt UO τt CO C CN -t- '»- LO CD N N N CO CJ) O CJ) N CO N Cθ ro θ O '- CD CO CO CO τt τt τt xt τf CO CO CO CO CO C C C .C C C CO CO CO CO CO Cθ CO CO C0 00 CO CO Cθ CO 00 CO τt C CO CO C^ ■ «- CN „ x- CN x- CN ■ «- CN τ ~ M < CO Ω LU LU < 00 O Ω Ω LU LU N < 00 Ω LU LU < CQ Ω LU LU < CQ Ω O O O O O O O O oυoooooooo O O O O O O O O OOOO O O O Z o o o o o o o D 3333333 LU UJ LU LU LU UJ UJ UJ LU LU LU 33333333 =) Z Z Z Z Z Z Z Z Z 111 1 , ,,, ,,, .,..,.0. .-J --J -J -J -J --J -J --J X X X X X X X X X X X _J __J .J _J _J .-J _J -_J _J ._J -_J -J -_J -J O θ Q. L L CL CL α. Q. Q. CL CL CL O O O O O O O O O =i =_! =! =_ -=! =! =_! < © o N co ro O x- CN CO τf in CD N Cθ ro θ χ- CN CO τt LO CD N Cθ ro θ x- CN CO τt iΛ CD N ∞ ro θ χ- CM CO τ iΛ CO N CO CJ) O χ - CN CO CO CO τt τt τt τt τt t τt χt τt t Ln ιn LΩ U0 U0 LΩ U0 U0 U0 U0 CD CO CD CD CD CD CD CD CD CD N N N N N N N N N N CO CO 0O LO © © ! _ H U α. θ χ- cM co ro ιn τt N co ro ro co co -5- cD CM co χ-- o co co cθ Lθ co ro uo co N CD τf uo co uo uo co cD θ x- O CN N N CO CO N UO OO CD N CN O τt CN UO N CO x- N τt CD Cθ ro CJ) x- CD t- - O CD CO CO x- CO CD CM O O OO CD CJ) τf OO N ro cN o ro uo cD co co co t cD N xt Tt Tt m oo o o x- Tf ro cN x- ro ro x- x- Tt x- cO ro CO UO N CN t- ro OO CN CO CO -r- x- x- CN O x- x- x- O OO O CO CJ) oo co oo co oo co oo co τt τf τt t τt ιn m τt oo Tt Tt Tf Tt Tt C CO CO OO CO CO CM CN OO CO CN CN CN CM CN CN CN CN CN CN - CM r r x- CD N O O CD CN CO x- CO UO N O CD N ro CN C N ro x- CD N N CO O - 00 oo N CM co N ro ro ro oo x- N oo oo x- o oo ro Tt CD Tf CN - Ln ro O O O CD CO CO CO N CD CD O x- Tt CD UO CD CN C .M-, C-N-, O_. O ^ . x- ro cθ N O CN - τt χ - CO UO O CO UO N UO UO ro O CO CO CD t- CO N ro oO CO CO N ro CN CN x- O CN x- UO CO N C -M ■ C —O O — O —O OO CM O O N CN τt O χ - OO χ - N τt o UO N ro Ln ro ro N O O O o ro oo N CD ro ro o x- x- co N CD in N oo cD CD co in N N N co co oo N co N co oo ro ro o o x- T- cM CM co CO CO 00 τt τf τt τt CO 0O 00 CO CO CO τt τt τt CO CO CO CO 00 00 Cθ CO Cθ CO CO CO CO 00 CO CO Cθ 00 CO CO CO CO CO τt χ^ CJ) CO T ,f C-M_ C_3 ) . C_M_ C_D N. C _O C.N. - O CD UO . Tt uo ro co oo ro _. c .N CD Tt O CO x- CO LO CO CD lΩ LO N CO O x- co co ro ro o ro _. Tf Tf x- CO 0O N CO 00 ro CD -»- N CJ) 00 N Cθ x- CN U0 CD τf Cθ ro τt CO - LΩ - OO N ro oO xt OO CD N CD Tt OO UO ro UO O Tf CN CO UO x- oo ro in co x- x- q χ - CD CM ro CM CM ro θ τt N CO CD O CO N UO N uo co co cN CN N oq ro N χ-; cq τt cq χ- q χ-; x- Tf O UO CO N CM N ro O x- x- roro NN NN CD cCNN cCbO cCbO ττff ττtt ' ιUb CD NN NN ττtt ττtt cCdO cCbO LUΩO τt CM χ- τ- dO xx--^ xx--^ ooO ooO ccCbOO TTτttt rororo cccboθ coCbOo coCbOo NNN " r-i r-i N N N CD ' N " cb cb iΩ uo uo τt τt τt τt uo uo uo uo ιn uo uθ Ln ιn ιn uo uo uo uθ Ln ιn uθ uθ uo u uo uo uo uo τt τt t τf τt Tf Tf Tf Tf Tf Tt Tf Tf Tf CD LΩ O OO CM CD CO O CO CN CD x- O O O x- N O Ln cO CD N CD ro x- CO CD O CO x- N τt ro N 00 ro CN CM CM τt x- O CO N UO CD UO N CM OO N O CD UO x- ro ro CN CO ro CD UO CO CM CN CD OO N ro CN N - N CO CD Tt oo uo x- co cN ro co co ro co co N CO Tf 00 uo O CN CN x- CO τt τt N O CO τt OO x- N CO CN O OO τt ro ro cθ OO x- CD CO CN N LO N CO τt O N χ - f- CO CD UO q ro CM ∞ -r- ro CD UO UO UO UO CD τt χ t τt τt τt cθ τt CO τt CD CD CO N N N CO N Cθ ro θ O CM CO CN CM CN Tf UO ro x^ ro ro cNi ro cM o CO CO CO CO CO CO C C 00 CO C CO CO CO CO CO CO CO CO CO CO 0O Cθ CO CO τt τt τt τt τf xt τt τt t τt τt τf τt CO τt OO OO τt Cθ τt τt x- CN x- CN x- CN CO CN CO CN < CQ Ω Ω CQ O < CQ O < < CQ < CO O Ω Ω LU LU LU N N X O O O O O O o o <oooo Ωo LυU Nz OOOOOZOOOZOOOOOZOOOOOOOZOOOOO Q_ Q. CL Q. QL Q. Q. CΛ CO ( ) CO CO C CO CO Cθ Lr L^ Q^ Qi Q 0_: >- >- >- >- CL CO CO CO CO CO CO CO O- V V V V V V V LU LU tlJ LU LU I.U ^ J ^ ^ W W t < < < < < < < _-J _J -_J _J _J __J _. _J W C0 C0 C0 C0 C0 O O C0 W © o O x- CM OO τt UO CD N Oθ ro θ x- CM CO τt Ln CD N OO CD O x- CM CO τt UO CO N CO CO τt in CO N ∞ ro θ x- CN CO τt lO CD N Cθ ro θ O O O O O O O O O x- v- x- x- x- x- x- x- x- x- CN CN CN CN CN CN CM CN CN ∞ ∞ ∞ co ∞ ∞ ∞ ro ro ro ro ro ro ro ro ro ro χ- χ- χ- χ- χ- χ- χ- χ- χ- χ- χ -- χ - χ - χ - χ - χ - χ - χ -- x- x- χ - χ -- χ - χ - χ - χ - χ - χ - χ - LO © © ! _ H U α. Uθ ro ∞ OO N τf CD CO N ro CO τ- x- O C OO O CO θ ro σ) UO CO CO x- N CO τt CO CO x- τt cθ CM τf N CO N x- ro uo co CD co CN o N CN t N UO CO CO x- τt CD CO CN CM CM UO OO UO CM ro uθ CD O τt UO N O CO CM CO τt N UO CO lO N N N OO τf CD N N CM N O O CD N τ- x- o o co χ - o o ro O x- LO CO CD CO CO ro x- lΩ O LΩ N Ln OO N CO O CO x- CN ro cO O CO x- CN CO x- x- CO v- x- CN CN - CN CN CN CN CM CM CN CN x- CN CN CN CN CN - x- x- CN - x- x- x- x- x- x- x- CM CN CN CN CN Tt UO UO UO CM CM CN CN CN OO OO CD U0 CD CD LΩ LΩ ro CD O CD 00 L0 LΩ CD O O O N τ- U0 CO N CN N U0 C0 CO C» τt U0 O N C0 CO CJ) CO N LΩ C0 N CD ro cθ C0 in U0 ro θ ro c x- CM ^ χ - CO CO lO x- O N N CN CN CD CN Lθ ro ro ro cθ CO τ- ro x- χt O OO CN - CD ro cO CD ro CD CO τt O x- UO UO CM O τt CD N ro ro cθ CO x- x- N -^ τ- CD ro CN OO CN τt CN τt ro _. L _Ω. lΩ .. C _D C .O . U _ CN OO x- C oOo CcDD CCDD UuOo χxtt CcNN CCNN χxtt Oo UuOq CD CD NN CcqO CD Oq CO UO UO UO CO UO CD N CO CD CO O O o o CM cN ro ro cb cb od c ro N ro N cb od N N N uo T cb cb cN od ro d d d ro ro co co co oo oo oo co co co co oo Tf Tf Tf T Tf T -^f Tt CO CO OO CO CO OO OO CO CO OO OO OO CO CO OO OO OO OO CO OO CO CO CO Tt Tt t CO CO o N CN N CO OO CD OO O CD CJ) Oθ ro x- OO θ ro oθ CO χt τt UO x- CD CN CD O N x- CO Tt x- O UO UO CD N O CM CO - Tf UO N N ro UO CO CO N N x- N UO CM CM O O τt N τt x- CO CN CO N CO CN CD CN CN N OO O N LO τt CM - Tχtr uuoj OoOo θo roro x- uo uo N N uo ro o oo co cN N CN O x- N ro cθ τf oθ τt U ro CD UO UO CN C LO τt xt CN CO τt x- ro CN τt O OO CD LΩ CN ro N τt CO O CD Tt O Tt x- CO OO O Tf CJ) ∞ oo ro ∞ N θ χ- χ- χ- cM θ o ro ro o χ- ro cN co N N N co χt τf τt co co cN -5- oo co ro ro ro ro ro o ro o χ- o o cN co co ^ ^ ^ ^ ^ Λ uo o uO in i in ^ - i in ^ in xr ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ' ^ ^ ^ ^ ^ in ^ o in io in in in in CO CO uo Tf CN CO CN O CM N Tf O CD N CO co Tt 00 N CO N N O UO UO CO CN CD CM ro N OO x- CD CO Tf OO LΩ CM O CD Tt o CD CJ) o LO N CO CO CO o N UO N CD N LΩ CO N N CO Tf oO O CD ro N N CO Ln cO CO Tt CD N CO N O Tf O oo ro Tt N Tf uo CO x— CD Tf CD CD UO o O x— N CD x— O CD UO OO CJ) N in ro ro CD N - ro N CO CO O CN CD UO CO UO CN CD N CD OO CD UO Tf in cb N in cb CD N CO LΩ cb N 00 ro uό Tf CD UO N CO oό d N co oo oo ro ro o o ro o co o ro co N oo CN CO o o Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf Tf Tf uo τt τf xt xt τt τt LΩ LΩ τt LO Ln U0 U0 τf τf τt τt U0 Ln U0 U0 U0 U0 U0 x- CM x- - CM x- CM ■ «- CM < C0 < C0 < CQ θ θ Ω < CQ O Ω Ω LU LU N X < CQ O Ω LU LU < CQ O Ω OOOOZOOOOZOOOOOOOZOOO O O O O O O OO Z O O o o o υ o z O O OOO O < _J J<_<]<<-J<J<__l<_3<_j<j LU LU LU LU LJj m o:cco^cϊ:QiQ:o:Q:Q:o: :oizzzzzzzzzQ.CLa. L LCLC <<<<<<<<<< HHi-i-HHf-HKf-h-f-000000000<<<<<<< © ro θ x- CN C O τf ιn CD N ∞ ro θ x- CN C O τt uθ CD N C θ ro θ x- CN C O τt lO CD N Cθ ro θ x- CM CO τt LO CD N C ro θ χ- CM OO τt o c co co c co c t o - ^ - ^ ^ - ^ - ^ ^ o uo ι ιn ιn ιn uo ιn uo ιo D D ω ^ ω D CD o D CD N N N O x- Ln τt UO CO CO CD Tt CD ro - N N r- CM - - τ- ^ rM CM CD ω ro ro - N ^f ^ N ro N θ in cD o ro cM - CM ω ∞ f M u M CD ^ oo D ro τ- ιn D o ιn ro c co ro co c N τt O CD -^ N N O O OO ∞ CO Cθ ro cθ ro N CO CO < CO CO CO O Cθ ro o ro CN CO uO O CO OO UO τt x- x- UO N χ - N χ - CO CN CN CN CO CN ro x- UO UO UO CO τf CO O O O CD CM N CD N CD - O CO x- O x- C» U CO CM CO CN UO CN O τt O CJ) x- Cθ ro UO τf Uθ ro cθ CD ro χ- χ- χ- χ- cN co co co ro ro ro ro N N in ιn τ oo ιn ro co o o co co co ιn o τf x- cN co τt co co co ιn co cN co co cN CN τt τt CO ^ ^ ^ ^ ^ ^ ^ ^ C C C C CO C C ^ ^T CO O C - - - ^ ^ ^ ^ ^ ^ ^ ^ - ^ - ^ ^ N 00 ιn co o co o ro cD χ - N ro τt N ro N oo ro o co τt x- t o co τt co τt x- uo ro uo χ - χ - o uo N co ro o uo ro uo co co ro χ - co N C0 ro N N N χ - CN CO C0 CO C0 N C0 χ - χ - C0 CD CD C0 CO τt N L0 CO χ - C0 CN N CD τt N CN U0 ro χ - N C0 θ ro τf O N N U0 CD ro co cN Ln co cN θ θ τt x- τt τt ro cN ro Ln χ- χ- τt ∞ N N CN co ro v- ro τt χ- χt oo cD uo N θ χt cD CD ro cN - x- N co co τt C0 ro C0 N N N 00 CD N N C0 N CD CD τt τt C0 CM CN O C0 ro θ O O χ- O χ- χ- χ- O θ ro ro x- CM CN CN CN CO N N N LO CD CD U0 τt τt τt τt τt τt τt τt τt xt τt τt τf τt τf t τt τt τt τt τt U0 LO Ln Ln U0 U0 U0 U0 U0 U0 τt τt Ln m m o uo t τt τt τt τt xt τt Tf O x- xt ro co cM co co in N CD CM co o Tt ro co Tt uo uo o o OoO cCoO ro x- ro UO OO CO CO CN N O CO CN Tt N OO OO x- OO N Tt CO O Tf CN Tf N. OO. C.O. CO OO CD CD CD T- CO CN CN O CO CD O CO - OO CCDD NN N - τf τf O x- x- CM O N N Cθ ro uθ x- U N x- C x- CD O LΩ O N CO CJ) CD N CN co w uo. - u*o. u cou u ro/ O CO CN CD O N ro CD N τt CD -«- CO x- x- CO x- N CM ro N O τt CN τt CN τt O CD v- UJ CM N CJ) CM CM CO Tf x-^ O CN ro cθ τt U0 C0 τt C 00 CM C0 C0 CN U0 CD N 00 CD CD CO CD C0 N CD N N 00 C0 U0 τf τf Cθ N C0 ro θ N O x- Tf uo uo uo uo o LO LΩ Tt LΩ UO LΩ LΩ UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO in UO UO UO LO LΩ LΩ LΩ LΩ UO UO UO UO CD UO CD CD CN x- CN x- CM - CM x- CM x- CN Ω < CQ Ω < C Q O Ω LU N X < CQ O Ω Ω LU LU < CQ O Ω LU LU < CQ <r O Z O O O O O O O O O O O O O Z O Z Z O O O O O Z O O Z OOOOOOOOZOOOOZO < < X X X X X X X X X X O O O O O < < < < < C0 C0 © U0 CD N C0 ro θ x- CN Cθ τt LΩ CD N Cθ ro θ χ- C C τt LΩ CD N C0 ro θ x- CN 00 τt U0 CD N C0 CJ) O x-- CM C0 τf U0 CD N 00 CJ) O o N N N N N oo oo oo co co co oo oo oo co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- - x- cN x- x- x- χ- x- x- x- x- x- χ- x- χ- x- x- x- x- x- x- x- x- x- x- x- x- x- CM C CM CN CN CN C CN CN CM CM CN C CN CN CN CN CM CN LO © © ! _ H U α. Tf CN N O UO CN O N O τt CN O CD xt OO CO t CD CJ) N t CD co t ro ro N N - cO O CO CN CD UO CN ro CN OO UO O CO CD Tt OO CO O CD CO O xt O ro oO LΩ CN N CO CO N ro CN O O 00 O N uo cM CD ro ro co χ- ro τt N χ- oo τt oo χ- N co χ- CO O O CD N CO UO Tt O O in N O O N ro oO UO Tt Tt x- cO CN Tt ro N N CO N N N CD CD N UO N τ- N ro ro ro τt τf cN τ- x- oo CN CN τ- x- CM CN CN CN CO CO CO τt CM CN - x- x- x- CM CO τf LΩ U0 τt CO 00 CO 00 N . UO 00 UO CD CM CD CO UO O CO Tt U0 C0 CN N CO CN N CJ) x- x- O O τt x- x- O CM τ- 00 x- C0 Tf CN CM CO CO ro CO ro CM oo co uo co Tf CO O N Tf LO CM CM 00 CM N uo m co Ln cN uo χ- τt τf co N CN co uo ro o ro τt cD oo CM 1- CD O Tf CO O O O N CO LO CO CO UO LΩ IΩ O CO N ro o Tt Tt M CM q N q q Tt Ln N Tt c CM N Ln N N co co ro CD x- O CD CO CO CD N CO CN CO CO o o ro Tf Tt cb CM " cb N c o c b cb cb Tt cb Tt t c CN ^ d x^ x^ cM ^ x-^ O CM ^ CM t in Tt Tt Tf Tf Tt Tt xt t xt Tf Tf oo Tt Tf Tf Tf x τt τt t t t τf τt τ4- τ τt τf x τ4- τt t }- t τt τt τ Tf Tf Tf Tf Tf Tf Tf CM N CO O N CN N ro c CO Ln N CD CO CM CN UO CD N CN CO CM x- x- OO CD CO ro CD CO UO x- x- ro oo ro ro O C CDΩ CCDD CCNN roro NN O CO CN N N ro co ro co cD ro uo ro ro uo co cN ro co cM τt co τt o co ro τf x- o LΩ τt cN CD N ro co co χ- χ- oo cN co τt ro τf uo co uo ro oo uo UO N CO O N ro CO τt CO CO x- x- CO O O CO τt τt CD x-- τt O CN ro N CO CJ) N CD CD UO O OO UO UO CD CO CN CD O co cr — Λ o ~ co~ ιn ^ ιn o uθ ^ M- Ω in ιo χf (θ o ^ co τf o uθ ^ ifi τ- o ro ω o ^ cM co N Φ uθ o N o (θ ^ ^ o N ffi ro c» τ- Tt Tf xt. xf xf x ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ r ^ ^ C CO C C CO C C f L0 U0 N 00 CD C0 C0 t N ro cN CN Cθ ro CJ) x- C0 θ ro x- χt CJ) CO lΩ τf CD U0 x- N CN U0 τf in N N O N o ro co ro o χ- χ- co τ- N N 00 O O O U0 C0 N O C0 U0 CN CN ro N τt O O 00 CJ) N C_D τt U0 N N O τt CD C0 O ro x- o co CD N -^ CD N CO x- N CN O τt 00 ro ro ∞ Cθ ro C0 U0 τt N CD τ- τt x- U0 x- τt O O CN C0 ro LΩ x- U0 τt C0 U0 τt CN CN Tf Tf O UO CO ro χ- τf o ro co τt co N CN ^ - O C0 τf U0 CD τt U0 U0 L0 CD N ∞ N N CD N L0 CD τt τf ro θ ro ro τ- x- θ ro ro θ O CO CD - CN C0 C0 τt τt U0 U0 τt τt CO CO CD CO CO CD CD CO CD CD CD CD CD CD CO CD CD CΩ CO CD CO CO CO CO N CO CO N N N CO CO N N CΩ CD N N N N N N N N N N x- CM x- CN x- CM cα O < OQ O Ω Ω < C0 Ω Ω LU LU N < 00 Ω < C Q O < CQ O Ω LU N X O O O O Z O O O O O O O Z O O O O O O O O O O O O O O O O O O O O CO O O O O O O Z O Z α: Q^ O^ Q: Q_ α_ -L α. Q- Q- CL CL W W W W IJJ W W LU LU LU LU θ O O O O O O CO CO W ι_ιιijujuJwwwwc ww(j. ιιιιιιιιιιiD:D (ϊ(ϊ:(ϊ:D:D:>->->->->>-( (ϊD:(ϊD:D:D:Q:Q:α: C0 C0 C0 C0 < < < < < < < < Q_ QL CL CL CL CL C Q_ Q_ Q_ CL Q_ 0. 0. CL CL Q_ CL O O O O O O < < < < < < < < < < © x- CN CO f LΩ CD N Cθ ro θ x- CN CO τf UO CD N ∞ ro θ x- CN CO τt UO CD N Oθ ro θ x- CN CO τf UJ CD N C ro θ χ- CM CO τt LΩ CD o CM CN CN CN CN CN CM CM CM CO CO C C C CO 0O C C C τt τJ χ τf τt τt τt τt Tt τf in in Ln U0 U0 U0 U0 U0 Ln Ln CD CD C^ CN CN CN CN CN CN CN CN CM CN C C CN CN CN CM CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ LO © © ! _ H U α. N N O UJ UO XT- N CO CO CO o x- CM O O O χt N CD τt CD ro cθ CD CN CJ) N τt ro x- τf CO CN CD LΩ CM O CO χ - UO Cθ ro LO LΩ O CM OO CO O xt o O LΩ Tf Tf x- CD LΩ N CD CD CN ro CO N τt o x- ro θO OO CO x- OO CD τt CN CO x-- N N CO CN CD ro x- x- τt CD - oo N CD Ln m oo Ln N xt Tt m cD CN N N ro cN ro ro — Tf CO O CJ) x- O CO N ro N CO Tt CM CO CD N CD CN CN CN in cO Tt N CN x- CN CN CN CN - CM CN CN CM CN CM CN CN CN CN CM CN CM CN CN CM OO CO CD τt C0 00 N CN O ∞ x- ∞ ro L0 C0 C0 CN N CD CN CN ro N N C0 U0 O O C0 CM O CD CN N - θ N CN τt C0 C0 CJ) CJ) C0 O τt CN U0 CO CN τf ro N - CN ∞ OO CO lΩ ro CM CN CO χt N CO CN Cθ ro UO CO CD O CO CN N O CD τt CD ro ro c CN CN CO CO CO CD UO CD CD Ln θ χ - ro ro ro co co ιn co co o co ro χ- co ro c» N Ln cD co τt N ro cD N co ro ro τt cN N N co N CD oo oo cD CN τf uo co co co co ro CO CN CN τ- x- τt τf U0 x- x- CJ) C0 x- ro N N CD N N CD CD uO CO CO N N CD O O CM CD LO CO UO xt Tf CO N CO OO CO ro O T- CM CO χt τt τt τt τt τf τt τt τt τt cθ CO τt O CO CO CO OO CO CO OO CO CO CO CO CO CO xt τf τt CO CO CO 0O CO CO CO Cθ CO CO CO CO Tf Tf Tf Tf CO N CO cD co ro τt co cN o ro N o o m cN ro τt χ- o ιn o o χ- co N in cN oo co cM ro χ- N -5- . C >_O_• CD O -_- C ~D. N , CO . C * N -, C ~O C -O . . τt τt N _. O -^ N_. C , » O-. l.Ω.-. τ_t_. CO x- ro ^ θ — C C—0O i U _nO. _D0 x-- O o CΩ O C0 C0 CD C0 τt N N τt t- - CD o o - CD- _ N-_ - x ._ x _-__ N .. C ._N. C —D O __. C .M Λ x __-. C —D C —M 0 ^ 0 ^ 0. —0. C _N ^ N __ ^ τt O lΩ OO N O N CJ) τt OO CO CO CD CD N CN CN N CO CO Tt OO CD CO CN CN CO CD xt Tt O Tt ro oo in co x- co o oo oo ro τt CN χ - O CN O CM CN χ - x- O CM CM CN CN CM τt LΩ τt LΩ τf x- θ ro C0 O x- CM O CJ) C0 N C0 C0 ro θ C0 U0 U0 τt U0 U0 U0 U0 τt co co co co co co co co co co co CO CO OO CO CO CO CO CO CO CO CO CO OO CN CN CO CO CO CO CN CN CM CN CM CM CO CN CN CM CN CN CN CN CN CN O O CO CN CD CO CO CD ro UO CO N U CD LΩ CO O CO CO C CO CO χ- C» CN OO UO τt cθ CD -^ ro τt τ4- ιo cD ro CN CD τf N N τ- lΩ CO CO LO Cθ ro ro θ N N N - ro x- τt cθ N CD ro ∞ ιn N ro N CO CO CN CJ) O OO CM τt O CN CJ) x- N N ro CO -r- CD LΩ CO CD CD CJ) O-CO cq q ro ro cq cN LΩ cq ∞ N CM N uo o cD ro uo co LΩ xt cN CN LΩ ro N ro Lo ro co in N CN q cq q co q uq Tt c CN -^ cN cb cN CN d ro d ro c x-^ x-^ cN c x^ d ro cb N cb Tf Tt- cb o uό N N N N N N N N N CO N CD CD N N N N N N CD CO CD N N N N N N N N N N N N N N N N N N N N N N N N CN - CN T- CN X C < OQ Ω < CQ Ω LU N z z < CO < O Ω oo o υ υ oυooOzoooo Q OoΩoLoU Nzzo <o < CO Ω O o o o o o o o o o o oooooooz 0 _ι ^ ^ ^ ^ ^ ^ < < <: C0 C0 C0 C0 C0 C0 C C 3 -D 3 D ID 333θ O O O O O O c0 W CL < < > > > > > > > < < < < < _J _l _J _J _J _J _J _J _J _l _J _J _J _J _l _J _l Q_ Q_ Q- Q_ Q. CL O l _J _J _J _J _J _J _J _l © N C0 ro θ x- CN C0 τt L0 CD N C0 ro θ χ- CN CO χt U0 CD N C0 ro θ x- CN C0 τt U0 C0 N C0 ro θ x- CN 00 τt i0 CD N C0 ro θ x- CN o CD CD CD N N N N N N N N N N co co oo oo co co oo co co oo ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- CM CM CM CN CN CN CM CN CN CN CM CM CM CM CN CN CM CM CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN OO OO CO CO CO CO CO OO O^ LO t- © © ! _ H α. ro uo OO x- C co ro Tf o uo ro ro N co N CD CD N N CN N CD CD CO N UO CO CN O CN OO CN CD N CD -«- O τf Cθ ro τt τt O x- χ- - Tf ro 00 CD 999 o uo CO ro N N CM T- N C0 C0 C0 m 00 U0 x- CN C0 χt O N CD N O CM ro C0 N C0 N τt U0 N C0 x- τt O C0 CN d cb σi cb o CO cb N " CD d N N Tf UO O CO x- CD N Tf Tf N x- 00 CM CO Tf x- xt UO CO t UO Tt CO CN CN CN LΩ UO CO LΩ CM - x- CN x- x- CN CO Tf Tf x- CN CN CM x- x- T- τf τf CD O C O CO CM CO N ro CN O Cθ CO N in cθ τt ro cθ CN CD C» O O UO CD U ro N CO N CD ro ro uθ UO N CD OO CD x- CM - N O C CO x- CO x- ro CD in χ- ro UO ∞ x- ro N ∞ CN τt O UO CN N CD τt CD CO CN CO τt CO LO CN C CN O O CN CD ro uθ N CN CD θ ro c ^ c uq N D L M M -_ ro c» L c c cM in ιn τ^ cb ro N cd d χ- χ- χ- ιb uό uo τt cb χ- d ro uo uo N N uό N uo N ro ro ro C CO CO CO τ τt τt τf CO CO CO CO CO CO CO CO CN CO CO Cθ CO CO CO CO CO CO CO CO CO τf τf Tt τt τ^ CM OO Tt CN T- CN OO CO CO CN N UO Tt CD ro oO CD CD CM N CO CO CD O CN OO UO UO UO ro CD CN N UO x- CD CD OO N Tt CD OO UO CD CN CN CO CO O O CO CD CN CO CO CO CD CN ro o co in CD Tt O CM - T- N CD in m cO ro CD CO CM CO CM N CO O x- OO CO O N UO CN Tt CN CO Tf cO O ro CN CN UO UO CO f co CN oo ro co co o o CO N CN CN CO Tt Tt CD OO LO CO O CD O co cN N O uo q q cq ro xt CO CO CO CO N N lO CO CO CD m iΩ CO N N CO N Tf CO cO CN CN x- - d τt t ιb Lb t cb cb cN CN CN cb N cb cb cb ro ro ro cb cb CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CM CN CN CN C^ co N co Tt CD ro Tt O LO CO O N CN UO O CO UO ro ro cO CM CO OO CD CN UO x- Tf CO N OO x- CD CD N ro O CO CO CD CO Tt cO CO CM O O τt N CD CN τ- N CO ro N CM O O OO θ ro τt CO CN τt LO CN CJ) OO OO LΩ CO O CN O CO CM OO CO CN CD CM CD -»- cθ UO UO N O UO ro uo uo co co oo N CD x- ro oo x- N N uo o cM t- xt o N N O x- t co oo ro ro oo in oo N co cD ro oo oo co co cN oo Tf co CM ^ CM C CM o CO N x- O x- cM ro co N N oo ro o o N CD uo t N oo ro o o o m Tt co Tf LO CD in N CM N N N CO N N N N N N CO CO N N N N N CD CO CO CD CO CD N N CD CD CD CD CD CO CD N N N N CO CO CO CO CD CD CD CO CD CO - CN - CM x- CM - CN < CO Ω Ω < CQ Ω LU N < CO Ω Ω < CQ O Ω LU N X X < CO Ω Ω < O O O O O Z O O O O O O O Z Z O O O O O O Z o o O O O O Z O o o O O O O Z O ZZZZZZZZOOOOOOOOOOOZZZZZZZZOO Wy wΛw wctct&aiaiaiQt t tctctyviw ww < < < < < < < < — J —J — I — I — I — I — I — I — I < < < < < < < < < < < < < < < < < < < < < < < < < < < < < © C τf LO CD N C ro θ x- CM CO τt UO CD N Cθ ro θ x- CN OO τt Ln CD N C ro θ τ- CM CO τt LΩ CD N Cθ ro θ - CN CO τt LΩ CD N CO o x- x- x- x- x- x- x- CN CN CM CN CM C CN CN CM CM CO 00 00 CO CO CO CO CO CO Cθ τt τf τt τt τt τt τt τt τt t U0 U0 Ln Ln CO C C C CO C CO C C CO CO C ( C CO C C C C C C CO C CO CO CO CO C C ( C C C C CO C ( C C CO CO C CO LO © © ! _ H U α. N CO CO x- N 00 CO O CD CO ro CO τf LO O OO CN τ- 0 0 C0 O τt C0 C0 CD τt O C0 L0 τt CN C0 U0 τt 00 x- 00 CN ro OO x- Tf N τt m τt o τt N in O O ro m LO Tt L N N O Tt CD CN Tt θ f - ιo ro M in - ro ιn co N ' N ' ^ ro o - (M co ^ τ- τr -- 1 d ό ^. O O O x-^ o CM o co uo CD __ O CM CM cb od Tf N cb cb cN Tt cb cb c CN C ^ cb Lb Tt - cN T^ ^ x^ ro x- x- x- x- x- x- x- CN CN Cθ CO CO CO x- x- x- x- x- x- x- x- x- x- CJ) x- x- 'r- CN ro CD CN U0 CN τf ro CN ro x- CN ro ro χ - N C0 O U0 C0 CD U0 U0 O O O τf x- C0 N C CN τt c0 N 00 τt O τf CD τf x- C0 CN CD 00 CO O CN CO τf N CO CO CO x- N x- x- N OO CN O O CO OO C» x- x- CD CN - cO O CD '^ O OO CO CD CN OO τt N O UO CN CM N CO CM O q ro ro ro ιn N in ιn τt j U ^ U 3 ∞ r . cD ro co ∞ N co co co - ∞ τt x- x- x- ro ι cb ιb N ιb N ib χt τt L τt ' τf d uo cd uo t cb cb CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CN CN CN CO CO C CO CO CO CO CO CO O^ uo N O Tf CM N N N Ln x- UO ro cO O UO Tt N CN N CJ) CO CO N N 00 CD CO CJ) U0 U0 τt U0 Cθ ro τt CJ) 0O CN CJ) CD CO N O x- O 00 CO r- CO UO Tt oo o cD co in oo o oo uo co oo co Tf CM CN τ- χt CO CO τt CO CD x- N CO O N OO CO CN τt CO CO x- N O o CM N in ro oo N uq cM c» ιn ιn τt M ro q ∞ cj) oo o N CD CM ro τt χ- co τt oo Tf O co Tt x- ro ro oo O CO x- x- CN N CN UO uo o co x- ro N o N N ib ib ib Tf cb cN CN cb oo d x-^ o ro ro ro cb ro cb N CM 00 Tf CN 00 Tf Tf Tf Tf ιn cb ιb uo uo cb cb cb τt cb cb CO CO CN CN CN CN CN CN CN CN CN CN CN CO CO CO CN CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO C^ τt CN ro U0 CO U0 τt U0 N τ- CD τt CO CO CN CO τt cθ CO N CN x- OO N τt O CO CO O τt CN UO x- UO τf xt C CO UO CO OO CO OO O CN τf τt τt CO CO CO O O τt xt cθ O τf x- CO O CM O N CD N CO CN CD τf O O τ- CD CD O CO x- N O x- ro cθ CD CO LΩ CO CO CD O CD CD co ro uo xt o co cD oo co uo Tt cD co x- ro uo OO CD lΩ Tt O CM CD OO CD LΩ x- CO O Tt N CD OO N x- CM N ro ro CO OO OO CO CO in x- O θ ro cθ N N N N x- x- CN CO O CO (X5 CO N CD CD LΩ CO τt cθ τt τt UO LΩ CO OO OO x- CN CM χ - χ -- χ - χ - CN O χ - - CM CN CJ ) CJ) D D D i in in in in in cD CD CD CD D uo i in i in in i ω cD co cD D D DCD ω ω cD CDco D D Dωco ω ω ω D CD i Lo x- CN x- CM x- CM x- CN O Q O Ω LU N X X < C Q O Ω Ω LU LU N X < ω Ω LU N X X < OQ Ω Ω < OQ O O O O O Z O Z Z Z O O O O O O O O O O O Z O O O o o o z o zzzooooooozooooo o o oθQiQ:Q o:Q Q Q:( Q:ι:Q:o_: oo o Q_o.Q_Q.Q.α.Q.Q__ι_ι_ι_j_ι_ι Ct Ct CL CL CL CL CL CL ^ >- >- >- CL CL L L L C C^ << <<<<<<<Hi- l-HHI- r-HI-l-HH<<<<<<<<<<< <<<<<< <<>>>>>> © ro θ x- CN CO τf LO CD N Cθ ro θ x- CN CO τ4- ιo CD N ∞ ro θ x- CN CO τt lO CD N Cθ ro θ x- CN OO τt LO CD N CO CD O x- CN OO τt O uo cD co cD CD CD Co co co cD CO N N N N N N N N N N co oo oo oo co co co co co oo ro ro ro ro ro ro ro ro ro ro o o o o o CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO Tf T^ CD CO O OO O CO OO O O N N N O CO OO CM ro cO Tt LO O x- OO UO N t- ro O Tt oO CM T- Tf O N OO CO ro CN CN CM LO x- N ro CN CN O CO CO OO Cθ ro ro θ O CD CN N x- Oθ ro CO - CN O CD CO CN CO x- O CN τf x- x- x- O LO x- CO N CO OO OO O Tf lΩ O CN x- τt O UO τt CO CJ ) CO CO CO CO CD - O O N CM UO τt CO Cθ N CO τt Cθ ro CD OO CN N CD CJ) UO O CJ) x- lO CO Tt CD UO UO Tf O OO N CN N N ro θ χ - x- ro C0 CN τt τf τf UJ τt CN U0 L0 C0 N C0 L0 τt C0 C0 L0 τt CD N 00 CJ) CD LΩ U0 τf ro θ χ - CN O O χ -- CD x- ro o x- o < o ^ ^ ^ ^ ^ f xf χt xf χf χr ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ M- ^ ιn u. ιn ιn ιn ιo ^ ιn Tf uo uo uo CD N N CO OO lΩ x- N CΩ CO CD xt T t CN T t oo CO CM CD N 0O 0O τt 00 CJ) 00 χ - τt ro cN ro ro o oo iΩ CD N CN LΩ co N ro co o o uo cN oo co CO τt lΩ CO O O O O CΩ N lΩ τJ- CJ) τt x- o co ro co oo τf co N CO UO CO Tt N CO CD - UO N CO CO x- CN O CN UO x- N CD CO CO CO C q CD CM CM CN CM CD O xT- q N ro oO CO CO CO N UO CN CD CO Tt LO ro O Tt N CD ro oO N N CD CO Tt O OO CN x- OO CO O O CM N c Ld'J τ Xt| Lb'J τ XtI ι UbJ τXtI τ Xt| c Lb'J Xt| L UnJ uUoJ cLMN χ X —- c LN C LΩU N I — - C LDU i UΩJ c LUo ro LJJ ro UJ ro UJ O b ό b uό cd ' ro o ^ OO CO CO CO CO OO OO OO CO CO CO CO CO CO CO CO CO CO CO CO CO OO Tt τf τt 00 00 0O CO CO CO CO CO CO CO CO CO CO τt τt τf xt t cθ CO 0O CO CN - Tf CN xt U0 CN CJ) CD 00 O χ t O 00 CD C0 ro N τ- CD N ro CM ro CD - O uo o Tt x- CD N N ro ro oO UO OO CN x- CN CD o ro uo t CO N ro iO N OO CD N LO UO OO ro CD CD CM CM ro CD CO oo ro co N O) CO r- χ- ro co co uo χ- co χ- cj) N cj) χ- cθ χ- O CM CO o cN q N q q N cq q ro q q cq τf q ∞ N N oq N oq N cq τt o uo uo r 03 (3) q o r Cλl If) O M Q N (D ro cb τ ^ cb uό uό τt τt- u uo uό θ ud N N uό τf x^ cb o^ cM " cb cb rø cb cb N " cb cb ιb ιb cb ιb ιb UO CO CO CD CD CD CD CO CD CO CD CD CD CD CD CD CD CD CD CD CD CD CD CO CO CO CO CD CO N N N N CD CD CD CD CD CD CD CD CD CO CD CD CD x- CM x- CM < 00 O < CQ O Ω < CO Ω Ω LU LU N < CQ O Ω Ω < CQ O Ω Ω LU LU < O Z O O O O O Z O O O O O O Z O O O O O O O O O O Z O O O O O O O Z O O O O O Z O O Z Z O O Q_i CC 0 Q_: Q: Q O O O O O O O UJ LU LU LU LU LU LU LU LU UJ UJ Q. Q. Q- α. Q. QL Q. Q. : 0: < LU LU LU LU LU LU O_: Q_: D O: Q_: O: Q: X X X X X X X X X W CO C CO W CO CO CO c^oc^oc^oc^oc^oc^oc^oc^oc^oc^o 0: 0 LU LU LU > CO CO CO CO CO CO Q- Q_ CL Q- Q- Q- Q_ CL 0_ Q_ Q_ Q_ Q_ Q_ Q_ Q_ Q_ Q_ < < < < < < < < X X X X X X X X X X CO CO CO © in CD N CO ro O x- CN CO Tt LO CD N OO ro O x- CM CO Tt LO CD N CO ro O x- CN CO Tt LΩ CD N OO ro O x- CN CO Tt LΩ CD N CO ro O o O O O O O x- χ - x- x- x- x- x- x- x- x- CN CN CN CN CN CN CN CN CN CN CO CO OO CO CO CO CO CO CO OO Tf τt τt τt τt τt τt τ4- τ- j uj LO © © ! _ H U α. N u ^ CO N in CD CD i- O CO O CM ^ ^ ∞ T- tO CO ro - O CM CO O in oO - ^ in CD O ro ^ O CO CD CO CO CD CD CD CM CM CM CD C - cθ N ro ∞ Cθ ro cθ CM N O CO CD rM UO (DCM in CM CD COCθ ro Cθ ro CM CM CO OCOCM CM CO N CM CDτ- ro cθCO OCO -χ- N co o o CO CO CN co co Tf in N Tt CN Tt LΩ CO CO CO CO LΩ LΩ N ro N N CM CO ■ «- N OO O ro OO CO N Tf CN UO O x- CD UO UO x- x- CN CN CO x- X- CM T- X- X- X- X- CN CN OO CO CN CN CM O in N CM τf O CO CN τt CN χt τf C τt O N O N C ro CO CO CN CO τt LO CO CN CO ιn τt ro oθ N CN τt ιn UO OO N CD CO CO CJ) CN N OO UO CO CD CO CO CN N CO O CO CN N OO O χ - CN CO x- N O OO x- x- lΩ CO N -«- CN N O N O O τt UO N CN O O CO -«- N CO UO UO CN CD CN CD τ- cθ CN O U CD ^ uq τ j ( q cq CN N LΩ CO CO O OO CO Cθ ro x- θ ro τt τt ro x- C N LO CD ∞ χ ^ d ro ro ro d χ - cb cb N cb cb ∞ c» d χ -- d ro χ - χ ^ cN cb χ - χ - χ - cb cN -- : cN c^ ιn uo τf τf τt uo τt τf τt τt t f τt LΩ LΩ uo τt LΩ in ι ιn u uo u o Ln ιn ιn ιn L uo o LΩ in ιn τt τt Ln ιn ιn ιn ιn ι^ N N CO Cθ ro CN CD x- O CO CO CD O CD CO N ro c ιn cθ x- τt O N τt χ- τt O ιn oO x- N N ro τt CD CO χ- ro CO τf τt CO CO τt CD x- χ- CD cθ u ^ ro - ∞ ιn oo cM τ- co ιo o cM M , ^ - N θ ^ r o (D u N in c ^ ∞ co - ιn o o ιn oo ιθ (D ^ c o ro ro ro N o o co N co ro co q ιn q ∞ q N cN N in τt ro q N cN cq co χ-; N CN cb Tt cb cN CM CN CN x^ x- d ro d d ro c c cd ro N ro c N- cb cb ro d ^ CO CO CO CO CO CO CO OO CO CO CO CO CN OO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO CN CN CN CN CN CN CN CN CN C^ CN ro cθ ro θ CO CN CN C N τ- CN CD τt τt CO UO CD CN O N χ- θ ω CD τt C ro c» τt N CO - O Cθ CD N CO UO N CO CD CO χ- ro ro ιn LΩ N ∞ χ- O iΩ ∞ CD C» Ln ιn oθ CO UO τt UO χ - CN χ- N N UO N ro c» τt C CN N CO C ro CN CD CN N O O CN N N CN τ- CD CD ∞ τt q c τ- cq q χ- uq ro uq ro N ro χ- c N q ro uq χ- CN q ro τt q cq N χ- χ^ τf τt q q ^ f t ω d d N N ro ro b ^ M iri ir. N N xf co ' ^ b ω ro ro ω d cM N CD CO CO CD CD CD CO CD CD CD N N N N CD CD CD CD CD CD CO CO CO CD CD CD N N N N N CD CD N N CO CO CD CD N N N N N N CO CM x- CM x- COO < CQOΩLUN X X < CO O Ω < CO Ω LU N < CQOΩΩ < CO O Ω OOOZOOOOOOZO ZZZOOOOOOO OOOOOOOZ OOOOOOOZOOOOOZ 0:0:0: 0000000 0 m m m o Q: Q Q: o: D: o: o: o: Q: o LU Ljj LU LU U LU LU LU Cθ CO CO CO C CO C0 CO 33333333 Λ CΛ (Λ CΛ C y J CΛ CΛ >- - ^ >- >- >- >- >- >. LU LU LU LU LU LU LU LU ^ ^ ^ ^ ^ ^ ^ C CO CO < < < < < < < < < < < d d d d d d d d _I _J _J _I _I _I _I _! _J _J _J _I _I _I _I _J _J X X X X X X X © o x- CN CO τt in cD N Cθ ro θ x- CM C0 τt U0 CD N C0 ro θ x- CM 00 τf U0 CD N Cθ ro θ x- CN CO τt U0 CD N C» ro θ x- CM 00 τt U0 CD LO LΩ UO UO UO UO UO UO UO CD CD CD CD CD CO CD CD CO CD N N N N N N N N N N ∞ ∞ OO CO CO CO CO CO CO CO ro ro ro ro ro ro σ) LO © © ! _ H U α. χ - CM oo τt θ N co ιn co co ro ro ιn o χ- co N CN oo cD ∞ co co o cD χ- cD uo ro N ro τt N τt τt uo cD θ co uo χ- oo o uo co uo ro uq q ro ιn ro χ - ro q q τf τt χ -; N cq q ιn cN CN cq τ4- uq r v - _q τf cN ro Tt ' ib cN d N N N d Tt ^ x-^ x-^ ro c L Tt d cb cN ∞ N cb ib cb ro c^ CN CN CN C CO CO CO CO τt τt τ ^ ^ xj τt OO CO τf ιn CD CD CO OO CO CO CO τf τf LO LΩ CM CN CN CN χ - x- x- x- x- x- χ - x- χ ^ O CO ro CO LΩ O O CO CO N CO x- x- CN O Tf T- CO CO CD T- τ- CN CM O τ- C0 CN τf C0 C0 CJ) C0 θ ro θ τt CN CD O C0 x- C0 CD τ- uo N ro cO CN Tt ro UO UO CO CO O N N CO CN Tf X- CO x- O Tt o ro ro uo ro o o co uo uo ro uo co co co co cN co co cN CD co uo cM N CO CN τt in CO τf CO CD U0 x- x- CO CO CD τt ro uo O UO N N m CD -T-- mCD M CN x Tf ( . nO i N L -- (θ ( ( ) CM σ) O lO N O CO O CO O. CM O CO cDcό NC ^ ^ d ro cd N cd " o J ro co x- 00 CO CM Tf CO N. CD CD CD UO Tf Tt N N Tt Tt Tt cN cb cd c c ro ro c d cb LΩ LΩ LΩ UO UO UO UO UO t τt τt τf LΩ LΩ τf Tf o uo o o uo Tt Tf Tf Tf Tf Tf Tt τt τt τt τt τt τf τt τt τf τt τt τt τt τf τf τt lΩ Tf τt Tt LΩ CO τt CO N x- LΩ CD τt UO CO CD OO x- CD CO CO x- N O ro τt 00 C0 C0 C0 CM τt O 00 O CD CO xt OO CO O CD UO UO O Tt U0 x- x- U0 N CO O τf 00 U0 N N UO UO O CD CN O Tf OO CN N cN ro ro CM CN CM CN CN CN CM CM CN CM CN CM CM CN CN CN CM CN CJ ) τt τf CD LO N UO O CD CD ro oθ UO CO cN m ro τf co co m ro ro CO CO CN OO Tt CM ro N CD OO CD CN UO CD CO N CO CM N CD lΩ UO N Tf ro oo cN oo ro co co N uo co co co x- x- o m N o co OO Tf CD uo uo ro x- uo cN CD co in cN co co co co N ro O CD Tf OO CD N CN N OO CD CO CO O τ- x- N O CO N θ m c CO N CO CO CN in cO CO O N τt N τt CO CM co CN cq ro CM ro co ro CN oo Tt Tt CM CN x- CN O UO N N co oo oo co ro co co N N " N " ιb ιb τt cb cM " τt cb cb cb cb cN T- 1 d CM cb C cb x^ CD CO CD N N N N N N N N N N NNNNNNNNNN NNNNNNNNNNNNNNNN N N N N N N N CN x- CM ■ «- CN T- CM v- CM - CN T- CN Ω LU LU < OQ Ω LU LU < CQ Ω LU LU zzooooooozzoooooooozo < 00 Ω Ω CO Ω Ω oooooozo <ooooozz < OQ Ω Ω oo ooooooo CO CO CO Ξ:ZZZZZZZ333333333Q.Q.Q.CLQ_Q.CLQ.ZZZZZZZZQ.Q.Q-Q.CLQ.Q_Q.o: J -J -_J --J -J -_ -_J -_J -_J -_J -_J __J __J __J __J -_J J(OCOCOC)COC)COCOCOW XXXO O OO OO O O<<<<<<<<<<<<<<<<<<<<<<<<.- © o N C0 ro θ x- CN C0 τt L0 CD N ∞ ro θ x- CN C0 τf U0 CD N C0 ro θ x- CN C0 τt U0 CD N 00 ro θ x- CN C0 τt ιf5 CD N C0 ro θ χ - CM ro ro ro θ O O O O O O O O O χ- x- x- x- x- x- x- x- x- x- CN CN CN CN CN CN CN CN CM CN CO CO OO OO OO CO OO OO Cθ OO τt τt τt Tt Tf Tf in Ln in in uo Ln in uo Ln LΩ iΩ uo LΩ in uo uo uo uo uo uo LΩ LΩ uo uo uo uo uo uo uo uo uo LΩ in in uo uo uo uo uo uo uo uo uo LO © © ! _ H U α. 00 N CD CM UO o ro x- ro CD x- CM ro 00 τ- N N CO uo co CM x- co uo co m co co m uo oo co in o ro CN CO CO Tf UO 00 N N N CJ ) O Tf 00 x- roro co ro co co m oo o 00 Tf ro co o uo ro o U0 CM CO Tf UO CM CN CN O CN O 0 x- CO o T t xt lΩ x- CO t - lO xt ro *- x- d ^. o CO CN - CM CN N r 0 uo 00 ro ro ro o d 9ro 9r o CM Λ r Oi-x- o x— ro ro ". o O CN in d x- cM cb cb cb ib uo LΩ CO CM IΩ x- LO CD t- Tf cO N CO CM Tf CD CO x- CO x- CO CO τt CM CD τf N O CN UO x- x- CO CO CO UO UO O CD ro CD ro UO UO N CM CD ro co ro CM uo CD oo χ- ro uo oo co uo τt co τt o co τt N N x- C0O0 OO O0O0 CroD xx-- CCNM CCO0 O0O0 O0O0 CD CD C0 xt CN x- N O U0 CN C0 τf CN - 00 t 00 N CM UO N O N xt O Tt ro CN CO CO OO CD T f CN ro cO T- ro cO O N CO CN CN ■ O — CN CD Tt N N LO CN N O CO N x- CD O Tt ιn ιn ) , ^ M c cM M τ- D in ιn ιn co cD co D - ^ ιo ^ rM CM M θ u N co co co co ro o o co N ^ M r 't iD D D ^ ^ ^ . xf xf xf xf ^ ^ ^ ^ ^ - ^ ^ ^ ^ ^ ^ ^ - ^ ^ ^ ^ ' ^ ^ ^ ^ ^ io o ^ ^ in in in in in in in in ro N oo CN N CO CN N O CO CO T- CN - CN N 0O U0 χ - 0θ ro 0O τt CN N χ- 0θ ro CD UO CO ro CN ro cO CN CO OO OO CO N Tt CO O N CD UO CN UO OO N CD Tf O O OO x- N CO CD CO Tt Tt CN CM O CO N CO N O CO CD CO τt x- CN τ- Cθ ro CN CO O O τt CN CO CO τ- x- CN CD τt Tf CO UO CD UO ro O CD N O CJ ) CO O CO τt CO O x- N CN τt τt O CO CD CO CM U N O CO CO CD N τt Cθ ro CN τf CO CO CO O τf CN cD LΩ τf CD N c» N ro N ro ro o cD N co uo uo cD cθ N ∞ co co co ro o ro ro ro o χ- c» χ- cN CN CN co co co co τt uo oo oo cM τt C CN C CN CN CN CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CN CN CN CO CO CN CO CO OO CO CO CO O^ ro iΩ lΩ CN τf O CD CO CM τ- CO C O CO CO CO CD ^ τt CN ^ N ro ro τt χ LΩ CO t O τf CO x- N CD O O CM LΩ Oθ ro CN O τt CD O ro N CO N CO N CN CO O CN Cθ τt N CM CM τf x- cO CO O CD N CD O O CO - LΩ N ro CO τt O CD C» x- τt CO CD CN LΩ CD O x- τt CJ) χ- cq ∞ N rø q q co o c» cq ∞ τt N q q cN uq cq ro N co τt co o cN θ θ τt cD CN Uθ N ro oo cN co co o τt x- x- N co ro d c c d ro ro ro c co N L in Tt uo cb Tf cb cN ^ cb cN CN cb N CO CD N CD CD CD CO CD CD CD CO CD CO CO CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD LΩ CD CD CD CD CD CD CO CD CO CD < CQ Ω Ω LU LU N < CQ O O Ω < OQ Ω Ω < OQ < OQ < 00 Ω Ω OOOOOOOOOOOZOOOOOOOZOOOOOOZZOOOOZOOOOOZOOOOOOO £ [ 0: 0: 0 0: 0 0: 0: 0 0 ,. Z Z Z Z Z Z Z Z <; <; <; <; <; O Q: Q: O O O: 333 33 333 >- >- >- >- >- >- >- >- > >- ^ ^ ^ ^ WW W ( Λ ( OWW W _lJ J J J UJ UJ _J _J UJ _J ιiJiij ω l- l- |- H f- f- H H h- H I- d d d d d d d d < < < < < < < < < < < < < CO C0 C0 C0C0 C0 -_l _l _l _l _l _l __J _l © Cθ τf LΩ CO N Cθ ro θ x- CM O τ^ u^ cD N Oθ ro θ χ- CN CO τt ιn CD N Cθ ro θ χ- CN CO τt LO CD N Cθ ro θ x- CN C τt LO CD N CO o τt τt τt τt τt τt τt Ln U0 U0 Ln ιn U0 Ln ιn U0 U0 CD CD CD CO CD CO CD CD CD CD N N N N N N N N N N CO 00 CO CO 000000 C0 CO in in uo uo uo uo uo uo uo uo uo uo uo Ln in in uo uo uo Ln uo uo uo uo uo uo LΩ iΩ in uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo LO © © ! _ H U α. ■ «- N N OO LO CM N LΩ CO CO CD CJ ) CD O UO CD CD τt N τt N CO N x- ro N τf cθ CO CD UO O U0 τt x- x- τf N ro ro CD CN CO N Tf CD ro oθ τf N LΩ OO CD N CO O N CO OO N OO CO CN τt θ O OO τf τt N OO CM UO CO O CO CN O x- UO xt CO N N CD N O CO CO t- CO f ocD oco Mco Droo3co\rωιnro NN©ιn ocoNθ C v- D oo ^'" -ωιn ocoro τ-c x- x- x- x- x- x- x- x- x- x- x- χ - CN Cθ τ 4- τ 4- ιn χ - χ - χ - χ - χ - χ - χ - χ - cN CN CN CN CM CO τf τt τt CN CN CN CN CN CO τf τt τt CM C^ O τt cθ ro CD O O N τf cθ CM x- CO lΩ CN LΩ x- ro cθ τt ro CO x- x- O CM τt CN O CM CO CO O O CO UO CO UO N CO τt x- CM CO N O x- lΩ CO CM CN CO τt CO LΩ CD ro N lO x- x- x- CD CD O CO N τ- x- Cθ ro iΩ Ln in ro CD N CO CO CO O x- OO x- CO O OO x- CN CD τt CD N OO OO O x- LO CD ro ro O N CO N CM Tt CO OO O UO O CO x- CD U0 τt C0 N U0 τt N τ- x- 00 τf χ- N CJ) O 00 CD CD Ln θ C0 ro CD CN CN τt uθ CN O CN ro τt CD CO CO CO C» ∞ ro ro N N ro ro N lΩ τt τt ro θ x- CM O CN CM x- CN x- τ-- x- CO O x- O CD χ - O O x- UO UO UO UO UO UO UO Tf UO UO UO UO UO UO UO UO in UO UO UO UO UO UO UO UO UO CD CD CD CO CD CD CD CD CD CD CD CD CD CD CD LO CO CD CO CD o 00 CO Tt O CΩ CO O CO m iO Tt CO N CO O CM N CD CO 0O CO CO CO τt x- τt ro τt CO uoχ-CMN θououoooro uo τtrocououoocDco CD τf x- CN θ ro N CO CN OO τt CD CD OO χ - O LΩ CJ) χ - CD CO CD Oθ ro θ C .N . O _ x- CN CN U0 ro θ τt CD CN ro CD O N - CD N U0 O CN rocM τf coτ-oχ- cNτf uocorocDco O lΩ x- UO N CD CN Oθ σ) x- CO O τf " ~ O τf OO τt in N CO x- CD τf CM N CD N N τt N N LO Tf CO CD UO CD CD N UO N N OO CD N N N CO CD CO CD ro ro ro cO O x- x- x- CN τ- CN CN 0O τt cθ CO 00 CM CN τt UO CO CO N x- O ro CO CO CO CO CO CO CO CO CO CO CO O CO CO CO OO CO CO CO CO CO CO CO Tf Tf Tf Tt Tt Tt Tt Tt Tt Tt Tt Tf Tt f Tf Tt Tf Tf Tf t Tf Tf CO CN co ro o CO CO Tf Tf Tf CO CD t- CO CN N N CN CN CJ) CO x- f CJ) m θ CN CJ) N τt CN τ- CD N CO CO Oθ ro N CM CD τt O x- U CO OO ■ xf co ro CN N UO CO CO UO CO x- CO CD OO CO O τt cθ OO x- CJ) τf cθ N N ro iΩ CM O Cθ ro x- N CD CO CM UO CO CO N N OO CD CD N '«- x- Tf x- LΩ O O O x- N N CJ) CO x- M on x- uθ CD N O τt OO CN O CD N O OO CO CM Cθ ro τt O CN θ ro τt τf uo ro τf O CD CD CN ro rø CO N N N CO CO CO CO N CO O O χ- CN CO CD UO CD UO τt τt UO CO CD N LΩ in CO Cθ ro ro x- Ln τt CM CN CO CN x- CM τ- CN - CN inininuoinininininin ininωωωωcDininin inininin inininininintnininωinininininininininininin x- CN x- x- CN x- CN < OQ O O Ω < CO O Ω LU N < CQ Ω LU < CO Ω LU LU < OQ Ω LU LU < O O O o o o o O O O O O O O Z o o o υ o co o O O O O O O O O O O O O O O O Z O O LU LU LU LU LU LU LU LU cococococococococo LULULU hLUrUτJ:hLUhLUrL-U:333333333333333333 oooooooooooooooooo 5<<< © ro θ x- CN C0 τf Ln CD N C0 ro θ x- CN CO τf LΩ CD N C0 ro θ x- CN C0 τt U0 CD N Cθ ro θ x- CN 00 τt U0 C0 N 00 CD O x- CN C0 τf O co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cN CN CN CN CN CN CN CN CN CN co oo co co co in UO UO UO UO UO UO UO UO UO UO CD CD CD CD CD CD CD CD CD CO CD CO CO CD CD CD CO CD CO CD CD CD CD CD CD CD CD CD CO CD CD C^ LO © © ! _ H U α. UO CO Tf O CM co co ro τt ro co χ- τf cD co cD o ro τt co o CN CO N CD CD T- ro CM CN CN ro oO UO OO O O CO CM UO in o O LO N CO ro N CO O oo uO Tt ro oo ro uo co N CN ro cD Tf CO τt cθ x- OO θ ro x- CD CO OO O lΩ LΩ ro x- x- CM CO N CO CM LO CN Tt O CO N CD N CN O N CN CD CO CO CD N CO CD N N lO CO CO CO CN 00 CM ro O O O O O O CN CN OO CO O CJ5 N r O O ^ O CN CN CN CN CN CM 0O χt χt m τf CN x- χ - χ - χ - χ - x- x- x- x- x- x- x- N ro x— ro x- ιn ιn N ro τt co cN θ uo N τt x- co ro χ - N τt Lθ CD oo co cD CN CD χ- τ- co co ιn oo χ-- CD τt ro Tt CM CN xt CD UO N x- CO CO O o co ro τt cD c» τt ro uo o τt oo co ro oo χ- N uθ co ro N uo co cD N CM θ N χ-- uo o uo co τt U0 CM τt CO τf cθ τt U0 CO U0 τt χ - iΩ N co τ- ro χ- ro N co χ- N ro N θ τt oo un oo ro ro χ- uo co τt c_D CD co cN τt N τt co oo x- U0 CD 0O CO CN - 0O CO τt N CN ro x- CN CN CN τt τJ 5 CD U0 θ ro C 00 ro C0 C0 ro ro 00 x- C0 N C0 CD N CO U0 τt C0 C0 C0 CO τt τt τt τt τt U000 CN O O CM 00 CD UO CD CD CD CD CD CD CD CO CD CD UO UO UO UO UO UO UO UO LO CD lΩ in iΩ in UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO 00 θ χ- cD in cN oo iΩ CD ro τt o τt oo co Ln O xt ro N in cO N O N T- N N N OO UO CO N Tt CO O O CO O CO UO CD CO x- OO CO CO CO ro ro τt N τt N ro cM oo ro ro χ- τt o co N ro cN τ- co χ- τt N uo oo co N o ro ro ro co co o co co cM CN co co ιn uo χt co oo CD τ- τt cθ ro θ CD CD N χ- CD ∞ Ln ιn τt τt ro q cq cN τt ro τ cN -r-; CN ro χ- co iΩ τt χ-^ q t ιn c τt N τt c χ- CO d ro cb od ro cb cb cd uό uo uo cb cb cb cb cb cN τt τt cb cN CO Tf CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO OO OO CO CO CO CO CO CO CO C^ o o co χ- τt cN τt N N oo ro co cN CN θ ∞ co χ- N ro ro τt x- τf c» ro χ-- N τt τf co o cD ro cD co ro ro o τt χ iv. oo co oo o N x- O U0 CD x- O U0 C0 x- O N χ- C0 C0 O 00 C0 x-- CN CD C0 00 C0 CO CJ) O x- O O U000 x- CD CJ) O CD C0 C0 CN O N N CD U0 τt τt co ιn ro τf <>j cD uo cD τt c» uo uo uo cD χ - ro uo ro cD c» χ- co χ- Ln co co co o N ro N CD τt cD CN N CN in ιn χ- θ χ- cN ro N χ- χ- co co co co co τf in ιn cD oo co τt τf cN χ - o ro co N oo ιn cD in τf N co cD in cD N τt co co cM CM ^ ^ θ N co N Cθ co ro uj in in in Ln uo uo uo uo uo uo uo uo uo uo uo uo uo Tf Tj j- T^ uj O uO uO uo uo uo uo O uO in uo uo uo uo uo uo uo Ln in in Ln in u^ - CM x- CM x- CM τ_ CO < CO O Ω LU LU < OQ O Ω LU N X X < CQ O < O Q O Ω Ω UJ LU N X < O Q O O Z O O O O O O O Z Z O O O O O O Z O Z Z Z O O O O O zooooυυooooozooooo 5 θθ θ o:o:D:Q:Q:Q:Q:o:Q Q o:α:c_:c_:α: _:α:ct ^-j-j^- ^-j--j-Jo:o Q Q cι D:o:o:o:Q:Q: m>->->->->->->->->->->->- LU LU LU LU LU LU <5 zzzzzzzzz θθ θ < 000000000 < < < < < < < < < < < CO CO CO CO CO CO |- l- f- l- l- r- l- l- H r- l- l- © o Ln CD N ∞ ro θ x- CN C0 τf LD CD N C0 ro θ x-- CM C0 τt in CD N C0 ro θ x- CN C0 τt U0 C0 N C ro θ x-- CN C0 τf U0 CD N C0 ro θ CO CO CO CO CO τt τt τt τt τt τt τt τt τt τt U0 Ln Ln U0 U0 U0 U0 U0 U0 U0 CD CD CD CD CD CD CD CD CD CO N N N N N N N N N N CO CO CD CD CΩ CD CΩ CΩ CD CO CO CO CO CO CD CO CO CD CO CO CO CO CO CO CΩ CΩ CΩ CO CO CO CO CO CD CΩ CD CO CD CD CD O LO t- J © © ! _ H α. o ro co ro N co N uo rocDOuoroox-ro ro cN co uo ro ro oo x- x- N CO CO CO - Tf UO UO x- Tf CO CD OO N CM CO UO x- UO CD CM 00 τt CD CD O in C0 U0 CJ) τt U0 C0 U0 C0 N x- q ro ro cq cD CN CN cq q oq N ^ ^ o oo • CD UO UO x- CN N Tf cb τ ~i r ~: 9 d cM - : d cM CM- d χ 9 cb t od cN cb τf od cM cb CO CO CO CO x- x- 9ro x_-. CN CO CJ) CO CO CO N N OO ro N N N x- CDCO CO x-x- x-x- x- x- x- x- ro N CO CO LO CD CN O CD UO CO x- U C τt N CN τt ro CD ro cθ N N τt CD ∞ x- CN CO CO UO CO τt CD τt cθ N τt x- xt N CN UO θ ro CD ro τ - c0 CD CN U0 CD CN CD C0 CD ro 00 CD τf N τt x- N ^ τt C0 χ - 00 C0 C0 CN N O U0 θ ro τt N C0 N τt U0 x- CD U0 N C0 ro cθ O CO CN CO τf lΩ UO CO CO UO C» N C» τt CN CD ro oθ UO x- CN x- O CO Cθ x- CO CN CN '^ - O C» τt N ro cθ χ- ro N ro x- τt x- oθ LO O x- xt ro cO N N N CO N CD CD UO Tt -t cΩ LΩ N CO CN CN CO x- x- O O ro x- x- x- O CM T- o ro CN CO CO ro cO OO O CO N N CD CO in Ln τt τt t t τf τt τt τt x τt t Tf τt τt τt τt τ τ3- l- τ4- f τ4- -J- CO τt τt τt τt τt τt τf C τf τt τf cθ CO C τf CO CO CO OO Cθ CM CO CD CD τf CN CD CD τt CO N O C CO N O O CO CO x- O CM O N Tt oO CD CO UJ N CM O CO ro UO x- CM O ro UO CO CM CN N CO CO CN OO O ro χ- co cM oo N τt cN τt xt o co ro oo o CD x- x- N UO CJ) τt OO CO CJ) O N CO CO OO N τt o ro θ Oθ ro cθ CN N x- O CM CO O CD Tt OO O ro CM UO CN OO x- CD CN CO O CO x- CO CN CD x- N ro CM x- CO CO UO Cθ ro x- CO x- τt CD LΩ τr oθ CO CD τt ro CD CO x- τt τt O OO N x- O O O CN CN χt CN CD CO OO OO N CD CD N N UO τt N CO CD UO N UO CO CO CO CN τ- O O O O x- O O CO OO x- CN CO CM CO CN CN CO CO CO CO O oO CO CO CN CN CN CN CN CN CM CM CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM x- x- CN CM CM CN τ- N τt C0 in U0 O x- N C0 O CN ro C0 ro ro C0 C0 CD O N C0 O O N N τ- 00 C0 O τt CN CD ro CN ro N N C0 00 00 χ-- C0 x- CM C0 CN lΩ N O ιn θ x- CO LO x- N ro CO ∞ UO N O O CD CO CN CD CO LΩ N - O CO CN LΩ CD CJ) N ro CO UO x- CN CN CO O N OO CD O CD ro - ^ co ro - ιn M ro M ; cM io ^ (a ro oo ιo ro ^ N θ - ro uo ιo M in M N ro τ- τ- co N ro ^ ro M 'φ - τ- co cθ 't ro ' c σ. uό t ib o N b ro N od ro ^ T^ ^ ώ UO CD UO UO UO UO LO Ln in UO UO UO UO UO UO UO UO UO UO UO UO UO CO CD CD CD UO UO UO UO UO UO UO UO UO UO UO CD CO CD CD CD CD CO CO CD CN x- t- CN T- CN "" CM x- CM O Ω < CQ O Ω Ω < CQ O O < CO O Ω LU LU < < CQ Ω < CQ O Ω Ω O O Z O O OO O O O Z O O O O O O Z O O O o o o o z z υ o O O O O O O O o o o o 333 Q: Q: D: O D: Q: Z Z Z Z Z Z Z Z Z >- >- >- 0000000 3 333 30 i j ii i j ii j i^ijm^ ι^ijiH ιH ιI- ιH ιH ιi- ιH O J O O J O O J D Q :- aϊ.Q_: Q Q :-D Q :- Q_: D0_: i j ii ι_i j jι_i j jι_i j j ι L i U j Q Q :- © χ- CM 00 τf U0 C0 N C0 ro θ x- CN C0 τt U0 CD N C0 ro θ x- CN C0 τt U0 CD N C0 ro θ x- CN C0 τt U0 CD N C0 ro θ x- CN 00 τ3- L CD o co rø ∞ ∞ ∞ oo oo co ro ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cN CN CN CN CN CN CN CO CD CD CD CO CD CD CO CD CO CO CD CD CD CD CD D CD CD N N N N N N N N N N N N N N N N N N N N N N N N N N N LO © © ! _ H U α. τt LO τt CM N UO O CD CD τt OO CO CO N CN CD CD CJ) N CN CD τt N N O CO τt uo x- N - τt ro cθ ro ro cθ CO UO OO N CN CO CN CN CN CO ∞ CN x-; τt τt cq ∞ cq ∞ τt O CO CD O CN ro CD CO CD τt O x- ro CJ) x- CN CN τ- N N q co ^ co ( ) co c N (D (\i τ- co N ooNrodiri^iriiri^ roini ^ddd^ -cMbbi b τt- χt ' uo ' uo b τt ιb cN τt cb τt ιb cN CN c cN CN oo 00 CO χ- χ- N τt rø χ- co ro co co cN ro co τf xt ιn cN θ co χ- c» ιn co co ιn χ- co τt τt oo ro cθ N Ln χ- CN χ- χ- co ro τt χ- co co N N τt 00 τt CD τt CD ro τt N O U0 O χ- N N C0 CD U0 O CN χ- θ ro CD U0 00 00 ro N U0 U0 O L0 CD CN C0 C0 CM 00 CN C0 O x- CJ) ro t CO CN CN CO ∞ CN x- ro CD N Tt ro CM N OO x- CO CO CD N CN UO x- N CO O Tt CO ro x- O OO CD CN N CD - Tt CO N O CN CD OO Tt cO CD CD UO UO CD OO N CO N N N CO CD CD OO ro cO CD O O x- N N CD CD CD CD CD LΩ N N CO ro O O O O O ro ro CD O O ro O O X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- CN CN CN X- - X- X- X- X- X- X- X- X- X- X- CM CM CN CM CN T- X- X- CN CN - CN CN C£) CN CN N CM O O χt N CO N LΩ CO ∞ τt CN χ - C ro τt x- τt oO ∞ τt τt lΩ lΩ x- CO CD lΩ LΩ x- 00 CO CO UO N O Tf N CM CO CO CD C0 CD CN - CM O O O C0 O CD N LΩ N C0 τf x- x- τt CN CJ) 00 C0 C0 CD τt CD θ ro C0 τt C0 x- O oo ro co N - CJJ Tf CD CO Tf CO CO CD ro x- u ro o ro CN τt CD - ro θ ∞ τt τt CN N O N CO CD τf O τt CD LΩ τt x- N OO τ- τt x- O 00 O O x- O N CJ) N UO Tf UO τ- CM CO x- O x- C0 U0 U0 CD C0 U0 u0 CD τf τt C0 CN τt CN τt CN τ- CN - θ ro cθ τt τt τt UO UO τf τt UO N N CO CO CO CM -ϊ- t- x- 0 CD CD CD CD CD CD CD CD CD CD CO CD CO CD CO CD CO CD CD CO CD CO CD CO CD CO UO CD CO CD CO CD CD CD CD CD CD CD CO CO CO CD CO CD CD CD t - CN - CN x- CN x- CN < CO Ω < CO Ω Ω < co O O < CO < < CQ O Ω Ω LU LU < CQ O O O O O O o o o υ o o z OOOOOO υooocozooozooooozoozzoooo O O O O O O Z Z Z Z Z Z Z Z CL CL CL CL CL CL Ct O) W ( O W W <Λ > ■ m tn tn tn m m Q: D: Q: Q:Q: Q: W (O W(0(O COC (O I I I I I I I>- >->- >- ^ J J J J^^^ ^ ^ !2^^ ^^II II I Q_ Q_ CL CL Q_ CL < < < < < < < < H H I- H I- H H O O OO O O O X X X X X X X X X X Q. Q. Q- Q- 0- © N Cθ ro θ x- CN CO χf LΩ CD N Cθ ro θ χ- CM CO τt LΩ CD N Cθ ro θ x- CN CO τt LΩ CD N Cθ ro θ x- CN CO τt U CD N C» CD O x- CM o C c c o oc ^ ^ ^^ ^^ -^^^ininini inini inuouoω o D D D D DCD D DN NN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN O χ- χ- ro CM τt N N UO τt N CO UO χ- τt χ- ιn uo ro ro co cN χ- co χ- uo ro Tt x- Tt co x- lΩ 00 τf CN τt CO τt 00 CO CM CO N CN CD CO UO CO CN CD UO N CO N CN UO CD x- N χ - x- OO τf x- CD CO CD CO CM O co ro co o ro oo x- U0 CN CN ro CO CD CO 0O CN CN CJ) 00 CO τt τt χ - cM q co co cq cD cq τ t ro N Uq uθ CD CO CO x- O CM - CO x- τt CN CM - ro t m Ln co N co uo χ- χ- τf uo uo cq τt co uo N cb N co N cb oo d x-^ cM d ro cb doo ^ cM ^ M t CM - O CMV CM ΓO " d ro cb xt ' ib cb cb cN Tt ' ib cb τt τt τf τt τt xt τt lΩ lΩ lΩ lΩ τt τf ιn τt τt m τt Ln Ln uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo τf uo uo uo uo uo uo uo uo m CD LΩ τt CO N N CD O O N ro x- OO N τt τ4- τt τt N UO CO CO τt LΩ ro CO CO O CM ro ro CM Cθ ro θ CM τf x- N τt x- CO CO O CD 'i- O χt O Oθ ro τt CD CD τ- ro ro CN O UO N N UO CN O τt oO CD CO CD N U x- ro N τt N τ- τf CO CM O OO CD CN CM -5- CO CN CD ro N CO ro x- OO xt CD UO ro x- N Tf Tt O CO x- CO CO O N UO UO N O O N CO UO CN CO O OO CO ro CN Tt CD CD Tf CM CD O CO CM ro CD O o ro CN O CN - 00 N CO N CO CD CD CD CD CO N N N N CO CO O O Cθ ro ro CJ) CJ) x- CN CN CN CO τt ιn τt x- x- O x- O x- CD ro ro CM T- CM CM CM CM v- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CN CN x- x- x- x- x- CN CN CN CN CN CN CN CN CN CN CM CM CN CN x- T- x- U0 N ro U0 x- cj) U0 CM τt x- ro θ CD CM N 00 CO CD x- 00 in ro U0 CN in τ4- 00 CM N 00 U0 CD cM cq rø χ-; uq roc N N ω ιn ιn ιn ιn cD CD CD ω ω cD in ιn ιn ω ω _ - CM T- CM x- CN x- CN CO CN OO CM - CN x- CN Ω Ω LU LU N m O Ω < OQ Ω LU LU < CQ < O O OO O O o <υoυoooΩ LzU LoUoLU NoNoXo < OQ Ω LU OO O O O O OO O-O O O O CO O Z O O O OOO Z O _ι _j Q_ Q_ Q Q: uθCD N CO χ--5-τ-x- CO CO CO OO LO © © ! _ H U α. Tf CN N CD T- ro iΩ O ro CD UO CO CD UO O N CO N CO N x- CD O ro oθ τt N CM in xτ- τt x- CD τ- x- LO N CM CD CN CN CN CO OO τt N O CN CJ ) Tf CD N OO N O N x- CN O O UO CO xt N Tf OO CD ro x- N q ∞ T- co x- cM q ro o cN co Tf co oo N CM x- Tt r^ LΩ c lb CD CN i s -^ CD CO CN x- x- x- co uo co co oo co Tf uo m Tt Tt Tt Tt cb Tt d -^ cb xt Lb cM cb ro ^ ro x^ N Tt t LΩ Tt cN cb cb x- x- x- x- CM x- CN CN CN CN CN CN x- x- x- x- x- x- CN CM τ- x- x- χ - χ - χ - CN CN CO 0 x- x- x- x- x- x- x- Ln cN χ- cN θ CN CN θ τt o cD - ιn ιn ∞ ro ro ιn co cD ino Ln co o N Lθ c» ιn χ- cN θCD τt cN -«- co o N CDroo rororo co x- N x- U N CN CN ro UO C - C CO x- O x- ro cN τt oθ N CO CO N CO τt N CJ) CD N -t- Cθ ro θ O x- CJ) τt CN O x- O OO CO C CO Uθ x-; CO O χ - CN CN ro CN ro q ro q θ LΩ x- x- LΩ ro CN CO CD - C CO O CO O θ ro cθ CD χt N τ- CD N τf O Cθ x- τt O CD s ' ω d s co rø ro ro s ' d co d s ' oό ro d iO ' ^ s ' s ' od cii uo u LO LΩ in uO UO UO UO LΩ LΩ CD UO CD UO LΩ UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO CO CD CD CD CD CD LO Ln UO UO UO UO Ln LΩ CO CO OO CO CO O CD LΩ N Tt cO Tt ro CD CM CD O x- OO O UO N CO CO N CD CD O U0 τt C0 τ- τt C0 O CN CN ro ro CD U0 ro CN CN N ro x- CD O ro O x- O CO N N ro N N O xt O CO CO Tt CO CO O CO CO N CN Tt N ro τt o co m co ro ro χ- θ N χ- θ N co τt ro τt o - x- CN CJ) CN LO CN N ro uθ O CD τt N CD CO τf ro co ro o o cN τt cM '«- - ιn uo uo co cj) τt oo ro ro co co cN χ- o cN θ oo cD N oq O O N N N CD CO UO UO UO Tt Tf d x^ CN cb x^ d d cN d cO Tt uό uό uo ' N cN CN C CN C CN CM CN CN x- x- x- x- x- x- x- x- C CN CN C CN CN CN CM CN CN CN C CN CN CN C CN CN CN CN CN CN CN CN CN CN CM CM CM CN CN C CN CM CO LO OO CO x- CN x- x- ro θ Cθ τf CD τt CD OO CD CO O CD CM O CM θ ro 00 CN τf τt x- x- N N τf τf U0 U0 x- UO CM CO UO Tf C CO CD CO CO CD x- τt OO CM τt CM ro N CM CJ ) LΩ CD CO CN CJ) Cθ ro N Tt x- ro CD N lΩ CN CD CD CO lΩ CO CO τt ro ro τt uo cM θ τt O CD CN CD CO ro oO N N OO OO O O O CO N O N CO CO CD CO CD UO CO O CN CD Tt CN CN N ro uO O CM CD CO Tt O CN CD OO CN CO OO Tt CM Tt oO CO CM τt LΩ τt τt CO CD N N CO CO CM - O CM CO τt OO LΩ x- O CO N O CN CN OO τt cθ N CD CD N OO U CO CD CO CD CD CD CD CD CD CD CD CD CD CO CO CD CO CD CD CD CD CD CD CD CO CO CO CD CD CO CD CD LΩ in CD CD CD CD CD in u^ T- CN - CN CO CN CO CN T- CN ^~ CM OQ Ω Ω LU LU LU N N X < CQ Ω LU LU < CO Ω LU LU < CQ O Ω LU N < cαO O O O O O O O OO O O Z O O O O O O O O O O O OOO O Z ooooooozzooooo Q_ CL O. Q. _ Q_ _ Q. O_ Q_ Q_ 3 3 3 3 3 3 333 Z Z Z Z Z Z Z Z Z CO CO CO CO CO CO CO CO CO ^ D: O: Q: O O O Q: Q: Q: D: Q Q: Q; O: Q: Q: O ^ - I ^ - --I -J -I -I -I -I -J ^ ^ ^ ^ ^ ^ ^ - >- _>- - _>- _>- I- I- H H H I- I- I- I- I- H H ^ ^ ^ ^ ^ ^ ^ ^ ^ COCO CO COCO CO < © ro o χ- cN co χt Ln cD N oo ro o χ- cN c τt ιn cD N co ro o χ- cN co τt ιn cD N co ro o χ- cN oo τt Lθ co N oo ro o χ- cN oo τt o ^ CN CN CN CN CN CN C CN CN CN CO CO CO Cθ CO C CO CO CO CO τf τt τt τt τt τf τt τt τt τt U0 Ln Ln U0 Ln Ln U0 U0 U0 U0 CD C^ OO CO ∞ CO CO ∞ CO CO ∞ OO CO ∞ CO CO OJ CO Ol CO OO OO CO OO CO CO CO ∞ CO CO CO CO CO CO Φ OO CO ∞ ∞ CO ffl rø CO ∞ LO © © ! _ H U α. cN N CN ro cN ro o o co ro N O CO CO CO N Tf CO CM CN CJ) LO CD N N CO O Tt CM ro cO Tf x— x— ro x- CO CO CD O N N N X — x— CD XT- T O CM CN Cθ ro CO CO CN lΩ O iΩ CD ro N CN CO Cθ ro iΩ CO Tf Tf CO Tf co N o ro x- o m co CM CM 00 CN CD CD O CO CO O N CN 00 O CD CO CO CM CN CO CN CO CO d 9d O x^ d UO CD CO N N CO CO in CO N CO ro CD N CD CO CO ro ro cO CD x- N CO CO OO OO OO CD CD CO OO N co m ro o co cN CN O co N ro in ro co cN τ- T- co co N io N co cD io co o x- cD co x- UO CM OO x- Tf O UO CN ro CN CO x- O LO ∞ uo ro ∞ ro xt cD CN uo co cN ro co ro cN oo cD Tt cN N oo cN co o oo x- ro o Tt co oo x- T- CM - CN UO Tt oO OO Tf Tt x- N O CO N U0 CM ro N χ t τt U0 ro x- C0 N τt C0 τt O τf U0 CN N N C0 O CD τ- CD O 00 C0 00 CD N x- CO CO lΩ ro c N τ- τt 0000 N CM N CO N N ro θ O x- x- O CN CD UO τt τt C CN x- x- χ- x- ro θ O CO OO O CN ro N CD uO u CD τt τ CN τt τt CM CN τt UO CD UO CN O U0 LO in U0 CO CO CO CD CO CD U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 τt U0 U0 τt Tt U0 U0 τt τt τt τt τt τt τf τt τt τt τt τf τ^ CD 00 CD O CJ) τt x- CO CN CD Tf O CO O CO CM 00 Tt N OO O N N CN ro CO CN CD CO LO ro uO OO CN Tt CO CD CO Tf CO CM ro Tt x- _ _ ro uo oo uo o N o x- O CM N CM O LΩ CN UO CO N - cM oo cM τt ro ro co ro τt x- τt τt o ro o oo χ- τt C LNT. C-O-. CD-- N ■ - C»N,. N. o xt oo oo o o ro cN ro cN cco T XtKO oo in tM x— C IΠ __ (_) ΓJ N N I_) T- O N O oa in σi xh i- C COO τt_- UmO CCMM COO CCOO CCOO CO O CO O N τ- r- O CM r- O θ ω ω ω CM CM CM C CM CM ( CM ^ O - ^ ^ xt in CO u Cθ " C r c CM CM O O lO CO (D CD N CO Cθ ro in 't CN CN C C CN CN CN - X- X- CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN C CN CN x- CN x- CN x- CN < O Q Ω LU N X < < CQ O < CO O O < CQ Ω LU < CQ Ω Ω < oooooozo zzoυozoooooozoooυoozooooocoυzooooooozo 0 o:o:0o:0Q:o:0Q:0Q:0o:Q:o:^-_j^-_j-_j.j^<^<^<^<^<^<^<^<^<j<j<j<j<j<KujI-ujH H HωH H; h-; - D 3 = , 3 - D 3 - D 3 Z Z © L0 CD N ∞ ro θ x- CN C0 τt ιn CD N C0 ro θ x- CN 00 τt LΩ C0 N C0 ro θ x- CN C0 τt U0 CD N Cθ ro θ x- CN C0 τt u^ cD N C0 CJ) O o co co cD CD CD N N N N N N N N N N co co oo oo co co oo oo co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o T- co co co ω oo co co co co co co co co co co co ∞ ω ω co co co co co co co co ∞ co co ω co co co co ro ro ro ro ro ro ro ro ro ro ro LO © © ! _ H U α. CD CN CD CO O x- τt CD CN CD O O CD CM ro ro cθ CM CO Cθ ro 00 CM x- CM OO τt CO Cθ ro τt OO CN τt CM τt CN CO N τt τt CO O ro uo uo x- co τt oo co o N θ N τf LΩ τt ro ro τf - ιn N o 00 uo CO Tf CN LΩ t τt CM τf CO CO CO U0 CO CJ) U0 CJ) x- x- N CO U0 ci τ ci i co 9 cN CN oo co m co τt τt x- τt CO CO CD CO τt τt Tf CD N ro N CD CN O CD CM N CO N CO CD CD UO m uO ro O CO CO CD - x- x- x- x- CN CO τf ιn ιn ιn χ- χ- χ- χ- χ- x- CN CO CO CO - x- x- x- x- x- x- x- x- x- CN t- x- CN χ t x- N N CJ) τt τf O C0 ro U0 C0 U0 U0 CD N 00 CM τt N τt O 00 O C0 C0 N C0 O x- OO CO CN CO N CD CN CD CM O x- Tt oo CM ro oo x- UO x- CO τf U N N ro CD CO LΩ x- ro x- CO O LΩ O τt CO N LΩ CO UO N CO CO CO x- ro CO CD CD CO UO x- CN N OO x- Tf Tf O Tf CD U0 χ t -«- τt N CD CN ro 00 00 O τt O U0 CD N τf τt N x- U0 O U0 x- τt x- CM N - N t x- N U0 CN CD U0 CJ) N CD CO Tt - CN Tf CO O x- O O ro x- ro cθ CO N ∞ C CO CD LΩ U τt cθ N CO UO C ro N U τt τt τt cθ x- O O Cθ CO CN - τf uo CD CD N x- θ ro θO O t Tf Tf Tf oo Tt CO OO CO C CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO OO CO CO CO OO CO CO OO OO CO CO CO CO CO CO CN CN CO N 00 ιn χ- o τt co co o co τt ιn co o cD ^ ro cN CD Ln cD in co co χ- cN oo cD CD u τt co cD co c» o χ- CN τ- ro χ- co cM o ro τt τt CO N CN co co N in Ln o Ln co τf τt ro ro χ - ro uo ro uo cD CN co cD co N -t- θ χ- N ro cN τt co cN uo χ- ro co N CN ro ro χ- co τt oo ■ ^ τt O O CN O N Cθ ro ∞ ro N O CD CD CO CN CO CN UO CN N CD - O CO CD Cθ τt CO CD Cθ N CJ) UO CD O N ro θO O CJ) CO N CN ro OO CN UO τt cθ τt CN x- O x- O x- x- O x- CM 'r- ro ro ro o N N N CJ) ro θ O CO CO N CO - CN CO CO τt cθ xt lΩ lΩ CO τf CO Tf uo CN CN CN CN CM CN CN CN CN CN CM CN CN CN CM CN CN - x- x- CN X- X- X- CM CM T- X- X- X- CN CN CN CN CN CN CN CM CN CM CN CN CM CN ro CN CO OO N CJ) τt CO CD CN τ- O τt 0O τf N τt U0 CD 0O τt ro θ ro ro CJ) N t- cθ O CO χ- UO CN CN CO CJ) CM CD N N UO CO CO χ- τf CD τ- ro cθ CN CN CM CM N U0 0O CD χ - oo co co ro ro τt N χ - U0 00 C0 CN ro N N τf CN 00 ro CM CO U0 U0 O U0 x- x- CN θ ro x- U0 O N O CO UO χ - χ - τt xt N τt CM ro CD τf 00 τf CD x- CO CN - LnroqcNNLnτtιnroτtqroqιnN τt quq uqqcq N CO CJ) O N N co ro co Tf co co oo co cN ro o o dd^σic s(θo6odo6( s ' s ' soόss ' scd (is ' cbs ' τt τt τt LΩ LΩ LΩ τt t τf τt τt τf τt xt xf 4- 4- x^ J LΩ LΩ UO UO UO f τt f τt τ t τt τt ^ t τt τt τf τf τ^ T- M CO Ω Ω < CO Ω UJ N X X < CQ < CQ Ω UJ < CQ Ω LU LU < CQ O O O O O Z Z O O O O O O Z O Z Z Z O O O O O O Z O O O O O CO O Z O O O O O O O O Z O O O O Z Z Z Z Z Z O O O O O O O O O O _ι _ _j _ι _ι _ _j CO CO CO CO CO CO Q: O: O: Q Q: D: Q: Q: O Q: Q: < < < < < < < SΣΣS^ΣSSϋϋϋϋϋϋϋϋϋJJJJ © τ- CM CO τf LΩ CD N C ro θ x- CN C τt LΩ CD N C» ro θ x- CN CO τt in CD N Cθ ro θ x- CN OO τ^ J CD N C» ro θ x- CN CO τt lO CO O x- x- x- x- x- x- x- x- x- CN CM CN CN CN C CN CN CN C CO CO CO CO CO CO CO 00 CO CO τt τt τt τt τt τt τt τ^ rorororororororororororororororororororororororororororororororororororororororororororororo 957 LYS CG 46.267 26.889 31.035 24.11 958 LYS CD 46.770 28.322 31.089 28.82 959 LYS CE 45.657 29.354 31.107 30.30 960 LYS NZ 44.532 28.741 31.820 32.58 961 GLY N 47.273 22.392 29.319 18.79 962 GLY CA 47.911 21.493 28.344 17.83 963 GLY C 49.363 21.124 28.602 19.02 964 GLY O 49.889 20.163 28.022 18.80 965 SER N 49.994 21.951 29.434 16.08 966 SER CA 51.417 21.727 29.690 17.76 967 SER C 51.563 21.319 31.153 16.07 968 SER O 50.624 21.508 31.921 15.80 969 SER CB 52.195 22.984 29.281 21.32 970 SER OG 51.454 23.745 28.215 29.95 971 LEU N 52.706 20.665 31.433 16.19 972 LEU CA 53.044 20.095 32.721 14.22 973 LEU C 53.814 21.162 33.523 14.90 974 LEU O 54.937 21.513 33.212 16.30 975 LEU CB 53.928 18.847 32.505 13.16 976 LEU CG 53.098 17.636 32.063 12.66 977 LEU CD1 52.255 17.105 33.249 15.43 978 LEU CD2 53.993 16.510 31.569 13.88 979 LYS N 53.070 21.738 34.484 14.30 980 LYS CA 53.355 22.962 35.234 11.19 981 LYS C 54.103 22.727 36.555 10.51 982 LYS O 54.480 23.691 37.202 11.24 983 LYS CB 51.969 23.563 35.492 11.90 984 LYS CG 51.377 24.141 34.173 15.22 985 LYS CD 52.251 25.323 33.894 16.86 986 LYS CE 51.945 26.341 32.815 20.26 987 LYS NZ 52.785 27.477 33.270 18.45 988 CYS N 54.265 21.458 36.919 10.35 989 CYS CA 54.800 21.085 38.199 10.12 990 CYS C 55.093 19.570 38.124 13.34 991 CYS O 54.346 18.872 37.449 13.61 992 CYS CB 53.752 21.438 39.298 13.04 993 CYS SG 54.171 21.096 41.056 11.06 994 ALA N 56.092 19.102 38.912 11.84 995 ALA CA 56.384 17.664 39.115 11.47 996 ALA C 55.350 16.986 39.954 13.20 997 ALA O 54.725 17.565 40.853 10.87 998 ALA CB 57.698 17.551 39.874 9.90 999 GLN N 55.227 15.685 39.755 12.25 1000 GLN CA 54.380 14.965 40.731 13.18 1001 GLN C 55.285 14.601 41.907 13.71 1002 GLN O 55.974 13.592 41.922 14.92 LO © © ! _ H U α. Tt ro CO CN ro CJ) Tf CN o ro o N CO ro ro N LΩ LΩ CO CO CN co CN ro CD o CD o lΩ N OO CD N UO uo N CD N x— CM x— CO CO q o Tf Tf N 9 oo uo uo CO CO LO Tt o O CO CO Tt ro o N Tf o N N m CN CO Tf Tf d CO CM d CN d CN d CM- d CM Tt Tf CM- CO t CM Tt CM- cb CM- Tf cb uo " cb CO o CM cb uo " O CO CO ro cθ N LO x- CO CO θ ro θO CM O x- x- CO C O CM CO CO CO O CD O CN CO CO CD τt CO CO x- CO CD ro CN CN Tf CN CD CO N N CN N x- x- UO CM O O O N τt N CN ro x- τt O χ- CO UO CO O UO N CJ) CJ) CD CD CD CM CO τt CM ro ro cθ ro τt x- U0 x- CD U0 CO N N C0 τt x- N N τt ro ro oθ CO CJ) N CJ) CO N χ- CO CM O O CD -»- τf O O N CD τt CD x- -r- in CD CN CM CD O CM ' t- CO CO N CO UO CO Tf UO x- CO CO CM τ- O O UO CD UO CO CD UO UO UO τf τt 4- cθ τt τt CO CO CO x- O x- ro o cN ro x- o co cN x- o co co co o ro co N ro ro ro ro mLnminmuouo uouo uouououo uouo uo uouo uo uououououo uo τt LΩ LΩ χt U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 τt τf τt τt τt τt τt " r ~ CM x- CN x- CN ^ t- CN x- CN CO CM CO CN CO Ω LU UJ < OQ O Ω Ω LU UJ N Π: < CQ Ω LU o o o o z z ooooυoooυoo < C Q Ω Ω LU LU LU N N X < CO O Ω O O O O O O O Z O OO OO O O O O O O O O O O O O O zzzzzo:o:c_:Q:α:_£.r(£Q:Q:_ϊ:ccQ-Q-Q-Q-α-Q-CLCLΩ_Q_Q_Q.Q_α-OOOOOθθzzzzzzzz ^-i^-i-i ctctctctctctctctctctc£ctctctctctctctfc O O O θ f- f- H H H H H H H H H H H H I- H H H H H H H H H H H Q- -l. α.0.0. Q_ Q- C0 τf U0 CD N Cθ ro θ χ- CN C0 τt U0 CD N ∞ ro θ χ- CM CO τt U0 CD N Cθ ro θ x- CN C0 τt U0 C0 N C0 ro θ x- CN 00 τt U0 CD N CO © O O O O O O O x- x- x- x- x- χ- χ- χ- χ- x- CM CM CN CN CN CN CN CN CN CN OO CO CO CO CO CO CO CO CO Cθ τt τt τf τt τ4- τ4- x^- τt τf O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O CD o cD co ro τt cθ N τt co N ro ∞ cN ro o cN N CN Uo cD ro oo co ro co co co o N N CM oo ro ro oo cD τt N co co cN CN N Tt CO x- τ^ ιθ LΩ ro UO O x- CO CO CD CD N CM C» CO CN τt ro N τt N ro ro CO U CO Uθ ro uθ ro CN UO OO τt CN CD N CO CO OO x-- CO Tf d ro CO CD CN τt O CN O UO UO LΩ CO CD τt CO χ- x- CO O O O O LΩ UO OO UO x- x- x- CN CM N UO CO CO -5- CN x- OO CM Oθ ro cθ OO CM τ- x- x- CM CN CO CO τt ^ ^ - χ - χ - x- x- CN CN x- CN CN CM CN CN CN CN CN CN CN CN CN CN CM 00 τt τ4- CM CN CN CN CN C^ ro ro co ro ro ro χ - Ln o Lθ cD co cD ro τf co χ- θ LΩ co χ- τt τt LΩ N ro LΩ θ o o ιn χ- N CN oo ιn cD N oo co co o co cD CM x- ro N CO - ro cθ CO UO O N ro CD CD CD OO N CN τt CD CN ro cθ CO τt ro CD N O UO N x- O Uθ ro x- τt OO x- O CO τf τt CN CO q N N Lθ cq ro q uq N cq q ro q ro cN CN θ N χ- oo χ- o ro ro co χ--; τt N CN N CN Uo o co cD CN CD co N θ N ro N U^ O c tD S S uo ^ ^ co cM co dro d d ^ d ro d ro ' co oό αi s s ' cD iri ro M Tf Tf Tf Tf Tf τt τt τt τt τt U0 τt U0 0 Ln in τt U0 τt t t τ^ x τJ x^ τJ ^ 4- τ xJ τa- τt τf τt τt τt τt τt τt τt UJ UO τf τt τf oo 00 CM ro ro o t x- N CO N U0 CD CD 00 U0 CJ) τf CO τ- τt co ro cθ CO CJ) CM N CO CO CN x- CD N 0O U0 x- O O UO Cθ ro CO CN x- O CN - CM CN CO CO N N N -«- OO CD CO x- CD N CN O CN ro cθ CO CD CN CO O CO CJ) τt x- CM U UO τf CO N oo o co oo o x- x- N uo uo oo ro ^ CM CM f CO CM τt x-; χ - ro cD τf in co uo N uo o τt co N ro oo cN θ cJ) CJ) ro τf N co uo χ- ro N uo uo N O CN Tf x- ro co q x- N CD UO UO UO T cb T b T t T t c cb Tt LΩ ib L cM x- x-^ d d d ^ d ^ cN cb Tt ib cb c^ x^ CN CM Tt lb lb lb Tf CN CN CN N CN co N ro Tf CN N CO x- O CN Tf O CD τt CD τt CD χ- CN in τt N O OO CM CO N CD O N τ- O CD τ- Tτtt ULOO CCOO CCNM Tτtr xx-- CcoO UO N O CN x- N t Tf O CN Tf N UO N OO N T- CM CN OO LO ro O CO OO OO O ro LO N N N CD CN xt CN CN CD O CD ro uO CN CN OO O UO Tf X- CD CO LΩ Tf CD O O CN CO - N CM CM CO χ- cN θ CN ro o ro cM CN χt co cN CD oo cN τt χ- oo χ- χ- uo ro o ro co ro cN co oo N ro ro N ro cθ ro θ Cθ ro cθ CD CO Cθ ro θ χ- CO N CO CD τt O O CN CO O CO CO CO N CN CO τt c CO CO CO τt CD τt UO CD N CD CD CD N UO t Tt. f τt ιn t f τt t τt τf τf in ιn τt t τt τt ιn Ω uθ uθ u τt τt τt τt LΩ in uo uo uo Ln ιn uo uo uo uo uo u uo Ln ιn ^ CN v- CN ■ «- CN T- CN LU < CD Ω UJ N < CQ O Ω LU LU < OQ O Ω LU LU < CQ O Ω LU N < CQ O Ω LU LU zzooooυoozzoooooooo ZOOOOOOOO OOOOOOOZZ O OO OO O O O Z m V) (j <Λ ~D ) ) ^ D /Ω ^ _J _ V V V V > _>- '_- '_-- '_>- — J — J — I — I — I — I — I I — I — I — I — I — I — I l _J _l -J >_ '_>- V V V 'i- V V — i — I — I — 1 — I — I — I — I — I lJ_J_j_ilJ_JOOOOOOOOOOOOOOOOOO_J_JlJlJlJlJ J J JOOOOOOOOO ro θ x- CN CO τf UO CO N Cθ ro θ x- CN CO τt UO CD N Cθ ro θ χ- CN CO τt UO CD N ∞ ro θ x- CN CO τt UO CD N Cθ ro θ x- < CO τt © TtinininLnuououo LnuouocDCDCDCDCD CDCDCDCDCDNNNNNNN NNNcocococococococo∞oorororororo o oooooooo oooooooo oooooooooooooooooooooooooooooo LO © © ! _ H U α. CO o CD O Tf UO N UO Tf CN co CM N N N N CM CD N m ro ro o CO N Tf N ro CO co uo N CO ro CD N CN N 00 CO 00 ro o co - ro CO CO CD oo cb Tf cb cb Tf Tt f CD N LO Tt Tt CD m cO N O CN O τ- CN CN CN CN CN CM CN CN CM CO CM CM CD CO O N CD CN lΩ LΩ CO Tt CO x- OO LO Tf x- cO CD CD UO CΩ CO x- CΩ CO CD CO CO N O cbcbcboduouououdcbd χt τt τt τf τf τf τf τt τt ιn CD τt CN O N CD N - O CD X— in uo CO ro CO Tf CN CO O ro CN CO CD N CO UO CO CO m CN N Tt CO CD d χ- cM cb cb cb τf cb uό cb cb x— UO CN O OO OO CO N CN CD OO UO UO CN O xt LΩ Tf CO O CO o uo co o ro x- ro cM ro cN CD uo Tt CO O N LO CN CO m O ro o cN oo co co ro oo ro o cM CD CD oo oo cD oo cN oo uo ro m Tt x- o CD CN CO O x- CN CO CN CO ro CD CD N UO OO CD Tt ro CD N CO LΩ N LΩ O O Tt OO OO O 00 CD CO ro oo CM CD N CN 00 CO U0 O in ^ N co co M coo o T- N q io uo Tf x- x- CM CO CM N OO ro ro oO N CD N O CN OO CO CN CO Tf U0 CD CO CM o o ro c _b N cb oo cb N cb cb cb cb ro ro o ro co N cb cb cb in in in in O in in in CD CD CD CO CD O ω CD CD CD CD CO CD CD ω CO CD ω in CD CD CD CD CD CQ CD CD CD CD CD CD S ω CD CD ω CO CD x- CM x- ,_ r- CM τ- CM x- CN x- CN < 00 Ω LU < CQ O Ω < cαOΩΩLU UfxJ < OQ Ω LU LU < OQ O Ω Ω < oooυocoυzoo o o o o o OOOOOOOOOO OOOOOOOOZOOOOOOOZO I — 1 — I — I — I — I — I — I — LU LU UJ LU LU LU LU LU LU LU I_U 333333333 Q- Q- Q- Q. Q- Q_ Q- Q- Q Q: ^ωωu^j j ωiiiωiLiiijωωiJiiiiiiiiiiijjjjjjjjjMcotowwwtowii ^^22^^^2d ddd ddd dQ.C Q.0.CLQ.α.Q.Q.0.Q. OO <<<<<<<<|-|- © U0 CD N C0 ro θ x- CN 00 τt U0 C0 N 00 ro θ x- CN C0 τt U0 CD N 00 ro θ x- CN C0 τt U0 CD N 00 ro θ x- CN C0 τt U0 CD N 00 ro θ ro ro ro ro ro θ O O O O O O O O O χ- χ- χ- χ- χ- χ- χ- x- x- x- CN CN CN CN CN CN CN CN CN CN 00 C0 C0 C0 00 C0 C0 C0 C0 C0 τt o O O O O O x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- LO © © ! _ H U α. o in N CD o CO 00 LO CO N Tt N Tf Tf N CO CN CM OO oo CM uo x- x- uo 9 CN co CN CJ) N 9 ro 9 CM x— 9 CM Tf o ro Tf N d d cd ib cb -^ CO cb Tf r-i M- x~: d x~: CO N d CD LΩ cb uo cb CM CN CN CN CM CM CM CM CM CM CM CM CN CM ro CN Tf ro O co Tf Tf N N CO Tf ro UO uo o Tf co x— Tf CO in CO ro 00 CN CO Tf 00 N CD J ro ro N CM- Tf ro cb CN ro CM CD cb cb cb N N CD CD uo LO C CO CO CM CN x — x— dN CN CN oo co 00 N o o CM CO CD 00 x — CN N ro CN O CD CD o N N ro co o N Tt x— CO uo CD CD CD N CO O 00 o Tf in CD CM CN N CM uo ro CO o ro o 00 CJ) CO O CO x— CD o CM CM CD in in N N N Tf 9 CN o ro ro o CN Tf CM CM CN CM CN COCN Tf CO x — m m Tf Tf uo m in UO O m LΩ m O LO UO m m UO d o x~: uo d r in o Tf uo Tf ro m uo CO CO O m O CD CO o 00 ro N N CM ro CD N ro ro Tf x — ro CD CO 00 CN in 00 UO CO co CD CM CD N CD o o ro f o o Tf 00 Tf 00 N CO m CM O CO CO 9 T f CO CO CO Tf CN Tf N O LΩ CN CO CM Tt d CN CM CM cb CO CO cb Tf x~: d CM CM CM cb cb cb cb x- ro uo m uo uo J in in in UO uo uo UO uo uo LO UO UO UO o uo LΩ uo uo o CO CO uo ro CD CO ro N uo Tf CO CO UO N CO CM CM O CO CD ro CM N CO CO o O oo 00 00 x— o Tf Tf CO o CO CO N CN Tf o in N CN ro o CO Tf CM CO CN CD N 00 CM CD CO m Tf N CN o CO CM ro CO N N 00 9 9 Tf ro N ro CN CN Tf CD N Tf O CO CO Tf Tf UO CO CN O Tf CO CD CO in co CM CM CD UO CO Tf CN o ro 00 cb UO Tf cb d d d d Tf CO Tf d ,_' d ro o CD d CD CD CM Tt x- uo O CO CN cb uo CO CO r f " d Tf 9 T^ CM cb CO C o ro CO CM oq co x— x— x— x— x— x- x— x- x— σi CO ro x— x— x— CD x— x— x— x— ro cb ro x— N < uό T cb CD x— σi CO x— x— x— x- ro CO ro ro N N LΩ CO CO OO CD ι- τt UO CO CD OO CO LO OO OO CD CO N CO CD O UO τt τt O CD CD LΩ Cθ τt x- θ ro CO - CM CM τ- CM O OO χt CD CD τt x- LΩ LΩ CO Tf N Tt x- OO CM Tt in x- OO CD Tt xt CN T- N OO O UO CN N CN O CO CO N v- CO CO in O CO T- Tt N CO ro oO CM CO CD CN N ro x- ro ro τt o cN N CD co co ro cM ro o cN CD ro ro uo co o c N ro ro cD τt χ- ro τt x- C0 CD τt x- x- m CN C0 O x- x- N U0 τt CO CN CO N N N CD C0 N N CD CD C0 ro cθ O U0 C CN CN 00 C0 τt τt x- o ro ro x- ro θ ro ro C0 N CD CD N CD CD CD L0 τt CM CN τt U0 τf x- CDωcDωcDCDCDωcDωcoωNCDCDωωωωcDCDωωinincDincoinininininininininininin ininininin CO < CO Ω Ω < CO Ω Ω < CO Ω LU N < CQ O Ω Ω < CQ O O O O O O Z O O O O O O Z Z O O O O O O O Z O O O O O O O Z Z O O O O O O O Z O O O O O O Z O:O:Q:Q:O:ZZZZZZZZ xxxxxcocococococococo 3 3 3 33 33 3 CO CO CO CO CO CO CO CO CO =) =) 3 3 3 3 3 3 D: O: Q: O: Q: O: O: 3 m m LU LU LU LU >- >- >- >- >- >- >- >- >- LU LU LU LU LU LU LU LU X X X X X X X LU HHHHI-<<<<< <<< _I _I _J _I _J _I _J _J _J _J _J _J _J _I _J _J _J _J _I _1 _J _J _I — 1 — l - h- I— I— I— \— \— — 1 © x- CM CO τt Ln CD N CO CD O x- CM CO Tt o CD N CO ro O x- CN co t uo co N co.ro o T- CN CO Tf UO CD N CO ro O x- CN CO T t UO CO o τf τt xt τt τt τt τt xt τt LO LΩ in U0 UO LΩ LΩ uo uo uo CD CO CD CD CO CO CO CD CD CD N N N N N N N N N N CO CO CO CO OO OO CO 1677 . 1855 . LO © © ! _ H U α. o CO Tf x- x- N CN Tt ro O CM N t- m O UO CM CO x- N N OO x- m x- CM CO x- N CO CD uo ro uo v- ro CN OO O CO C N CO CO CD x- O N Tt ro UO x- UO CO N CD ib T--CN Tf CN UO UO OO N CM CO CO x- O OO CjO N -5- cθ CO Cθ ro θ CN m CN CM OO CM CN CN CN CN CN CN CN CM CO CO Tf Tf CM - x- T- CN CN CN CO x- CN CN CN CN CN CN CN x- 00 ro oo co CN CD O x- x- Tf cD N CD CN O 00 uo oo o uo O x- Tt CO CO Tt xt x- cO CN O xt CN cb ro oo ino UO CO co co oo ro N CD N uo co ro CN - N x- N ^ OO N CD N CO N N χ t χ t ro CM τ- CN u0 lΩ LΩ τf τt CO N CM lΩ C0 CO Cθ ro N Tf CD CO LΩ CD N C0 τt ro CJ) τt U0 ro x- 00 00 x- U0 CJ ) O O CJ ) C0 x- τt CD O CN Tf ^ ^ T f r- CD S ro CM CM ro S CM ω cθ in ^ r- x ro CM CD CM τ- CO CM CO CO CM O CN CN lb CN x^ x- ^ d ro N N N x- ^ d d cb cb c Tt ro ∞ o c N N Lb cb in LΩ UO UO in u0 U0 U0 U0 τt τt τt τt U0 in U0 U0 U0 U0 U0 U0 τf τf τt τt τt τt τt τt τ- Tf o N CO CN Tt ro co CO O CD CO CM CO UO O CO CN CN CD CO CD ro co CO N CO CO LO C CO CD N N CO 00 O 99 CD T- CN CD 00 f q Tt CO co ^ CM CN o O CD cb Tt f UO cb cb N cb t c ¬ Tf ro ιn uo uo uo UO Tf uo o uo uo uo uo uo rn LΩ o „ uO CO Tf ro in CD -^ N CO CO CO OO CN LO - CO O CO CM CO CO Tt OO CO N CO CO CO CO o CN Tf Tf UO CO UO CO CO N CN ro N co Tt x- ro CO x- O CD CD LΩ OO N CO O CD O CN CO UO ro CD CO xt CM O CN CN OO CN x- CD CN Tf ro CO o Tf CM CN OO CM co ro O N CD o co N CO 00 CO 00 χ- τf LΩ C0 CM CD N N N χ- O χ- CJ) C0 U0 00 χt O N θ ro χ- τt χ- CM Tf CN o N Tf ,- CN CD Tf Tf CO x- N oo in in dx-« O CN CN CM x- CN O 00 τt U0 CD τt lΩ U0 CD τt U0 U0 U0 C0 C0 τt CN ro co N ro CD CD x— ro oo CO N ro ro cb r-i ro ro x- x- ro Tt ro N Tt x- UO CO x- LO ro CD CO N O cD τf Lθ χ- χ- τt cD CD ro ro co o ro co f CO N CO CN OO OO UO N CN N O Tf O d ro ro ro oo N od ro cd N cb oJ d cb UO τt τt τt τf xt χt τf τt τf τt τt LO Tf T- CM x- x- CN x- CN x- CN x- < OQ Ω Ω < oα O O Ω < CΩ O < CQ O Ω LU LU < OQ Ω Ω ooooooozoo < CO Ω O O O O O Z O O O O O Z O O OO O O O O O O O O O O O o o o o o υ o 3333333 Q Q: O: Q: O: O: 333333333 Q_ CL O_ Q_ Q. O. Q. Q. j^^l_j^Zj_ιdddddddd ocococococoO OO OOO <<<<<<<<dddddddd © N co ro o χ- CM co τt ιn cD N ∞ ro o χ- cN co τt uo co N co ro o τ- cM oo τt Lθ CD N co ro o χ- CM co τt uo co N oo ro o χ- cM co co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cN CN CM CM CM CM CM CM CN CN oo oo oo o - x- x- χ - χ - χ - x- x- x- χ - χ - x- x- CN CN CM CN CM CN CN CN CN CN C CN CN CN CN CN C CN CM CN CN CN CN CN CN CN CN CN CN C^ LO © © ! _ H U α. ^ uo o co N ιn CM ro c ffi c ( ^ N (θ D in (D θ D oo ro cD ^^ M r f o s ωτ- τf ro cM - cM ^ ' t u. ιn χ - τt oq cN oq q ∞ q q c» uq ∞ uo χ- N τt N ro τt c» ιn uo N cq τt coro N N θ - co N τf N uo co co cD ro x^ d d cN CN Lb ro cb uo ro x^ d cN Tt T^ o N- uo uo o cN CN Tt xt ib CN CN CM CN CN CN CN CO CO x- CN CN CN CM CN CO x- x- χ- χ- x- x- x- χ- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- χ- x- x- x- x- x- CD CD -«- N xf O -»- N CD CN CO CM CD UO ro CD Tt OO CM OO O CO CO CO co UO OO o O CD ro cO CN CN T- N UO N UO cM co ro co uo co co uo co x- x- ro ro i un C LDU T XtI O) Tf ro oo co Lo ro oo ro cM co ro co ro CO CO x- CO CN CO LΩ x- LO Tf N UO cq τt cM τt Tf N N cb ib cb d d cN CM Lb t C xt ' L LΩ τf- χt- τf t τt N τt τt τf τt τf in L o uo τt τ4- ib cb uo r-i ro ro N CD Tt Tt xt Tf Tf Tt Tt Tt f Tt Tf Tf Tt Tt τt τf f Tf Tf CD x- C CO OO χ - CO f- O U CO UO x- UO U CD τt CO N N O CN OO CO CD CD CO N N N CN O ro ro uO x- CD Tf Tf CD Ln CD f f N O) Tf CM CD - cθ CM N O x- OO LΩ χ - LΩ UO UO CD τf oθ CO CO CO CD UO UO CM O Tt ro CD UO x- CO Tf ro CD CO CO C -N_, T-t « C-D * _- . CN N CO CO x- lΩ o co co o ro cN CN uo N ro co x- ro o cM - o ro o co co o N o m N τt CM χ - O CD ro τ- τ- U0 N Tt cD ro co cN ro cM ∞ ro uo N N oo co oo co co N N oo ro o ro CD CN CN CO Tf O LO Tf UO UO CD ro co CN CN CM CN x- x^ ro N cb cb cb cb x- x- x- x- x- x- x- x- x- x- x- CM CN CN CN CN CN CN CN CM CN CN CN CN CN CN CM CM CM CN CN CN CN CN CN CM oo ro co Tf co LO f M N Tf CO x- O CD ro N O CN CO O CN N OO LO CO _ C _O CO . T _t ro _ co co ro _. m ro _ τf CJ) O UO CO τt N CD τ- UO χ- LΩ UO CO CD CD UO UO x- ro ro CD N t Tf o CO UO CN CN ro CD OO Tt Tt co N ro " N oo co Lθ co N CD co N CD τ- co τt ro ιn ιn ιn cD UO OO x- O CD N CO CN N o ro ro cN CD co in iΩ uo σo N oo N N N 9 9 τt o co τt τt Lq N cq τt LΩ N CM Lθ CD ro ro ro N N cb c b cb ιb ιb cb ιb τt ιb cb cb cb cN cb N co ro cb cb LΩ 9N cb cD ro o o ro o ro d cb ro N " cd N χ - '<-- : cM cb τ- CO CO CO C CO CO CO CO CO OO CO Cθ CO CO C CO CO CO C CO CO OO CO Cθ CO CO C CO CO τt t cθ Tf co τt O CO CO CO CO τt τt τt τt τf ■ «- CM x- CN x- CN T- CN x- CM < O Q Ω LU N < CQ < CQ O Ω Ω LU LU X < CO Ω Ω LU LU N I O O O O O O O Z O O O O O O Z O O O O O O O O O O O ooooυooooooz <ooo CoO Oo C > CO CO CO CO CO CO CO CO Q Q O: Q Q O Q : Q; O: Q O: O: Q Q: O D: O Q O >->- ^^^>- ^ XXX XX>->- ^i- - ^^^?-ϊ->->- ->-^^^^>- ^XXXXXX -- -J-J-J-J--J--J--J-JHI-l-HHHI-l-HH HI-HHHHI-HHI-l-HHh-HHHHH h- l-HI-l-l-HI- © C τf lΩ CD N Cθ ro θ x- CN OO τf LΩ CD N Cθ ro θ x- CN CO τt ιn CD N C ro θ x- CN CO τt UO CD N Cθ ro θ χ- CN CO τt U CO N CO CO CO CO CO CO CO CO Tt Tt T^ x^ T^ x^ T^ Tt Tt Tf UO UO LO Ln uO UO UO UO UO UO CD CO CD CO CD CD CD CD CD CD N N N N N N N N N O CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM N CM CM CM CM CM CM W LO © © ! _ H U α. x- Ln x- CD N CD C0 τt C0 O N x- CM CN C0 O CN U0 O U0 O C0 CD CJ) CJ) ro 00 O O O U0 CJ) N CD CN U0 CD C0 τt ιn cN CN N ∞ LΩ ro c» cN ro Lq ιn cN CN τt N q N cq ro cN ro χ- ro q cN --; CN co ib Tt ib Lb Ln N Lb ib cN Tt T M t N ro c d cN uo uo j uJ ro Tt cb N x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM CN - x- x- x- x- CN CO CO CO x- x- x- x- x- x- x- x- x- x- x- x- ∞ OO τf CM τf x- O CO Uθ ro τt ro cθ x- CO CN CO CD CN N N CD τt UO CN CD O x- CM O CJ) CN LO N O O CO OO χt CD τt N O N UO CD CM O O x- CO N x- x- τt ιn ro CO χ- OO CN CN τf CO CD CD N Cθ ro CN UO τt ro CD N ro CN O CN UO CN ∞ N CM LO CD O N CO τt CD CM χ- CO CD CN lΩ ro CM O lΩ CN O CΩ CN t CO UO Cθ ro uθ x- x- CN O τt c τt CN O τt CD CO N τt O CN N CO τt N c iM o ^ cM CM ^ uo d N N tD N ' d co c uo N od roroN ^ ^ ^ ^ ^ ^^ ^ - ^ ^ ^ - ^ ^ ^ ^ ^ ^ - ^ ^^ ^ ^ ^ ^ ^ o ininin in uoin io in ifi in inu in winin u - CN < CO < CO Ω LU N X X < CO Ω LU LU < 00 Ω Ω < CO Ω LU LU O Z O O O O O O Z O O O O O O Z O Z Z Z O O O O O O O Z Z O O O O O O O O O O O O O O O Z Q : _l _J _J _ J _ J _ J _ l O O O O O O O O O O O Z Z Z Z Z Z Z Z Z 33333333 => 333333333 x < < < < < < < o: ι: o Q Q : Q : Q : Q : Q : o: o -- j j -J j j ^ ^ - j ^ LU LU LU LU LU - l - , - l - l - l - l - l d - | LU h>>>>>>><<<<<<<<<<<ϋϋ ϋϋϋϋϋ(3jJJ JJjJU(5(3e) ϋϋϋC)j © ro o χ- CN co τf in cD N co ro o χ- cN oo τt uj cD N co ro o χ- cN co τt Ln cD N co ro o CN OO Tt u CD N CO CD O x- CN CO Tf N co oo co co co co oo oo oo co ro ro cj) ro cD CD CD ro cj) CD θ θ θ o o o o o o o χ- χ- χx-- χx-- χx-- x-- xx-- xx-- x- x- CN CM CM CN CN o CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN OO CO OO CO CO CO CO OO CO CO CO OO OO CO CO OO OO CO CO OO OO O CO O CO LO © © ! _ H U α. O Tf X— UO in 00 uo o o Tf ro CO CD o CO x— • CM CD CO uo Tt LΩ ro CM o 9 00 UO CD CO CO Tf oo co Tf CO O CO ro CM CD N x— Tf N CN o ro ro x~: ro N ro d N Tf Tf in Tf " cb 00 ro r-i d CO ~: Tf in Tf ro CN N CN CM x— CM CN CM CM CM CN CM CM CO CM CO Tf Tf Tf CO Tf CO uo CJ) CO CD CO o o CN CN CM 00 X— CO oo Tf uo x— CO Tt CD CM o N N CO CD CD 9 CM CN O CD uo uo CD r-i uό Tt CO uό CO N cb uό in in in O uo uo o UO UO uo o CD CD CM o D X— ro CM 00 CO Tf CO o CO CO ro CO CN CO 00 x— X— Tf ro ro in 9 Tf X— CO 9 X— o Tf N uo oi x— CN Tf Tf CO cb d d d N CN O τf χ - ro τ- N N CO CD CD N CO CO CO CD CO O O O 00 x- CJ) x- N U0 C0 C0 CD CM Tf ro oo o co ro ro q q q ro q q N x- co uo CO Tf x- CO CM lΩ N cd ro cd ro ro ro ro d cN CM d N cb cb N cb cb in in u in in in in in CO CD CD CD CO CO CD CD CD CD x- CM x- CN *- CN - CM x- C x- CM <oooo OQ Oo Ωo Ω Ω LU LU oz < CQ O ooooooooz <oooυCQ Oυ Ωo Ω O Ω Ω zz < CQ oooooooz <ooo CoQ Oo Ooz <ooo CoQ Ooυ 33333333=>3333333ZZZZZZZZ33333333O: Q :Ω: Q : Q : Q : Q :O: Q : Q : Q : Q : Q : Q : mm m m -^^^- J ^^^^^yV)V)yV)yV) )(/)V)yV)mm m mmmi:τ.τ.ι: .ι:ι:ι:ι: ^ι:ι:ι: © ιn CD N C0 ro θ x- CN C0 τt LD CD N C0 ro θ x- CN 00 τ Ln CD N C0 ro θ x- CN C0 τt U^ CD N 00 CD O χ- CN 00 τf in C0 N C0 ro θ o CN CN CN CN CN C0 C0 C0 C00000 C0 C0 C0 CO τt τt τ^ τt τf τt τt τt τt τt in U0 U0 U0 U0 U0 U0 U0 U0 U0 CD CD CO CD CD co co co oo co co co co co co co co co co oo co co oo co co co co co co co co co co co co co co oo oo co co co oo co co co co c^ LO © © !_ H U α. Tf CO Tf co x- x- O CO τt N τt CN O CO O CO CM CO τt CO N τ- N x- CD in θ CO CO N x- in x- N N CD O χ - N CN τt CO CO CO Tf ro co o q o cq o cN q N q.χt co uo N uq oo ro ro co N O Tf cb x- N ro ro cb x- d x- N CN ro cb τt N d χ- cb c τt ro d cb ro cd d N " cN ro N " CO CO CO Tf uo uo uo uo co co co co CM CN t- t- CN CM CO C OO CM CO x- CM t- T- CN CO OO Tf cO x- 00 ro c» CN τt C0 N 00 x- U0 N N CD N ro U0 N CD CM C0 τt c0 C0 O τt ro θ CD O N CN 00 ro ro c0 N N 't- N -r- N τt ro U0 CN N L0 ∞ 00 CM C0 ro N x- U0 C CN CN O N CD U0 L0 O L0 U0 CD - ro U0 U0 O O U0 N τ- N θ ro U0 C0 ro θ ro θ U0 τt O θ σ) τf C0 cqcM co co cM co roqq ss q oD rM CM oo q - xt cM cocM ^ co o co roωcD uos τ- cM N θ co O T o cN Tt t Lb o cb cM ^ x^ cb cN CN Tt cM d ro c c c c CD CD CD CD CD CO CD CO CD CO CD CO CD CO CD CD CD CD CD LO UO U O UO U O U O U O U O U O U O U O U O L Ω C O CD C O CD in UO UO LΩ LΩ UO Tf Tt T^ x- CN x- CM ■ <- CN T- CM x- CM < oα O Ω LU LU < CQ O Ω LU LU < OQ O ω o Ω LU x x .< OQ Ω LU LU O OOOO OZZOOOOOOOOZOOOOOOZOOOOOOZOZZZOOOOOOOO Z Z Z Z Z Z Z Z Z 333333333 O Q: O: O: O: O: Q: O O O O O O O O O O O 333333333 , , _I _I _I _I _J _J _I _I _I _J _J _I _I _I _I _ _J _I X X X X X X X Q: O: O: O: O: O: O: O: Q: Q: Q: — I — J — I -J — I — J — I — I — I LU OOOOOOOOOOOOOOOOOOl-l-HHI-l-l-<<<<<<<<<<<OOOOOOOOOd © x- CN C0 τf in CD N C0 ro θ x- CN 00 τf UJ CD N C ro θ x- CN C0 τt U0 CD N C0 ro θ x- CN 00 τt U0 CD N Cθ ro θ x- CN CO τt U0 CD N N N N N N N N N oo oo co oo co oo co co oo co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- o CO CO CO CO C CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO τf τt τt τf τt τt LO © © ! _ H U α. τt c Cθ N CJ) x- CD lΩ UO CM CM CD CO O CO UO CD O xt m τt cM τ- co ro τt m o τf o co χ- CD θ co ro co ro oo τt iΩ N Tf O N N ro cO OO CN CO Tt N LΩ N CO CO CD UO N N O C CM CO CO CN CN CO OO UO OO CD CO Tt ro cj) τt cD q cM N N CM τf cj) ro ro O O CO f CO CO CO ro O CN 00 χ- N τt U0 O χ- CN τt CO . O O CM CM O CO CO o cN uό cb χ- : d χ - : d χ - d cb 9 ' ^ cM ro ro ro co χ - CN τt ro τt cθ N N CD 0O O x- CO CM CO UO O in cO N O 00 00 N ro m C0 N 00 CN - x- CN CN τ- τt CN C UJ N C0 CJ) x- O C0 N CN N O CD x- CO CD CD OO O τf |v. m cM CN CD C0 N τ- O C —O τt N CM CD -r- τf τf O CO N LO CO τt ro UO O CD N τf CO τ- CN N CN cD t- LO uo ro co ro cN uo cN τ- τf τt CD 0O CN 0O τf xt ro U0 τt O CO N x- CO CO CD CO O N N x- x- N UO - τt cθ UO O CM Oθ ro θ CD CD in UO UO τt CD CD UO τt τ f cD N CO N CO x- x- x- θ ro c» ro N N - o ro ∞ x- CO CO C lΩ UO UO C» N CD CD CO UO τ4- τj cM CO U0 U0 UO U0 U0 U0 UO UO U0 UO U0 U0 U0 U0 UO UO U0 U0 U0 U0 τf τt τf 'xt τt UO U0 τt τt U0 U0 in in uθ UO U0 τt τt τt τt τt x τt τt ^ 00 ro C0 00 LΩ τt x- CD x- O N O N τt O C0 χt C0 N CN C0 lΩ τf Ln CM CN CD CO x- CM N Tf Tt lO x- CN CN CD CN - cO CO 00 x- O CM OO CO O CN UO CD Cθ ro CM CM OO CO N x- CO CD τt o CD - - x- τt m CM τt CN OO CM O x- C CO τt lΩ CO CO C _O N. O_ N. COr- in N co χ- χ- CN CN O τf θ CM τf x- x- cθ CD CD CM UO χ- CO OO O τt x- O LΩ C — J) O CO ' N 00 UO CD co co ro CM oo co oo co ro N Tt x- N N CD N N co co co oo ro o ro oo oo N oo ro ro co oo co co oo co ro O x- x- CM CN CN CN CN CN ro ro o co o ro x- x- x- x- x- x- x- CN CM CN CN CN CN CM CN CN CN CM CN CN CN CM CM x- x- CN - CM x- Tf CO "xt Tf x- UO x- ro C0 N O τt x- N CD N CN C0 x- ro CD ro iΩ CD CD ro τt N CO in θ ro L0 O x- 00 x- N ro ro U0 CD N CD τt N CN CM CO CD LΩ O x- O CD - OO O N ro cO CD CO in ro θ τf τt N CD τt CD N τt cθ CO x- CO CN CM O τt UO CO x- CO OO x- θ ro CN τf co Tt ro co co CD o N τt cD CN co co co o ro o ω uo co o ro co co uo cN co χ- ro o cN co co cj) χ- uo cD τf co ro co τt uo N co CN τ- o co uo co co o ro cj) θ oo . N .N C0 00 CJ) N CD ro CJ) ro θ CJ) O N CD CD N u0 CD N τt N τf CD U0 U0 τt c0 U0 CD CD C0 CD CD U0 U0 U0 U0 U0 LO U0 U0 τt τf U0 τf xt τt τt τt τt τ4- Tf Tf Tf Tt ιn t Ln τt τt τt τt τt τt t τt τf τt τf τt τt χ τf τt xt τt τt τt τt x- CM x- T- CN „ T- CM x- CN x- CN x- CN x- CM x- CN < 00 O ( D Ω < CO Ω Ω < CO Ω Ω UJ LU < CO O Ω Ω LU LU N < CO O Ω Ω LU LU o o o o o o o o o O o o o o ooooozooz O O O O OO O O O O Z O O O O O Z OO Z LU LU LU LU LU LU LU W LU LU LU LU LU LU LU LU LU LU LU d d d d d d d X X X X X X X X X X QL . Q. Q. Q_ α. CL Q_ CL Q_ Q_ X X X X X X X X X X © N CO ro O x- CN CO Tf Ln CD N CO ro O x- CN CO Tf LO CO N CO ro O x- CM OO Tt uO CD N CO ro O x- CM CO Tt uo CO N CO ro O x- CN x- x- x- CN CN CN CN CN CN CN C CN CN C CO CO CO CO CO CO Cθ CO CO τf τt τt τt τt τf τt τt τt τt U0 LO in U0 U0 U0 Ln ιn o LO © © ! _ H U α. CO OO UO Tf x- x- CM N CN N N OO CD N N Tf CN co ro χ- cM ro o N co τf cN oo oo ro cD τt co co ro oo co oo co x- Tt UO CN x- in N ro ro Tt 9 CD CM N UO O CD CO CO N roro CN t- N N CM τt O UO CO CM τt CN CO in oθ τt CN CO UO N CD CO CO CO O ro N t ro d^ CMV CM N- CM Tf Tf uό CD CO CO Tf " CD ro CO Tf Tf N N Nor N - o CM CN CN T- c 0 o o o X^ X^ CN " 9 X- 9 CN d ^ uό cb xo 0 - x- x- x- x- ro x- ro N O 00 N CJ) Tf C C X - N CO UO UO OO τt CD N τt ro CD τt θ ro ro τf CO τ- τt τt CN Tf CD CD LO CD CN CO CO CO x- CM - c ND roO OoO cNo roN Nτt χ T -- CuΩo T co- CuNo No Cχ-D co oo o x- UO x- CO O OO N - xt x- OO OO CM CO CD τf ro CN O N CM CN CM T- CM O CO CO CN UO Tf CM τf CN τt CN CN τt o CJ) N τ- CD CD CO τt CO ro cO x- CO CO Tt CN T- N CO CO O CO CO CO CD CO O x- ro ro LO ro CD cD in co co ιn uo τt C_D τt CD UO UO Cθ CN O CD CN CN CN τ- 0 0 ro θ CN O O θ ro ro x- x- O CO x- CN τt cθ UJ UO CO CD CD N UO CD Tf Tt xt Tt Tf Tt Tf Tf Tt Tf Tf Tf x τ4- Tj- CO f Tf Tf T Tf Tf C τt τ- t x^- τ- cθ CO Tf τt τt τt τt τr τt τf τt τt OO OO CO CO OO CO ro CD CO ro N UO O O CD τ- ro ro CO N CD N O ro θ CN O τt CD ro cθ ro CD τf x- OO τf Cθ ro CD N τt CD O O O x- CN CO N N τt Uθ ro CN oo ro χ- cN - c» cD uo o ro uo N ro cN oo uo uo χ- cD co τf τt co uo N co τt x- o ro τt cN oo co oo cD τ- uo χ- τ4- cθ χ- τf o uo ro x- N τf CO CO x- x- O O C» CO CO N CN ro CD N Cθ ro θ C CO x- N CM CO CD O x- UO CO OO CO τt O CO O N ro CN N N UO CD CN CO OO CO OO CO UO CD CD N N N N OO CN CN CN CN O O CD Tt Tt cD N Tt iΩ co co oo co N co ro o o cN x- o cN o cN co co ro o ro ro CN CN CM CN CN CM CM CN CN CN CN CM CN CN CN CN CM CN -5- CN CN CN CN CN CN CN CN C CN CM CN CN CO OO CO CO CO CO CO CO CN CN CM CO CN CN co cD co co ro co N θ N CN τf χ - θ N τt co cN θ χ - co oo ιn N N in ιn τt ιn cN Ln Ln cM CN τt uo co χ- τt ro cD co τf cM τ- o cD ro ro τf τt ro in x- ro ro CD CN CN N U0 ro c» CN C0 ro θ CN τt x- C0 τt CD CN CN ro θ N CN N τt C0 CN CN N CD τt N U0 U0 τt τt CJ) LΩ τt LΩ U0 CD τt CD τ- τf O CN τ- τj uj N N τ- N O x- CN U0 N N CD ^ C0 C0 x- C0 x- U0 U0 ro ro CN τ- LΩ C» CD τt N C0 τt O τt CO CO τf CO CM τ- CM O χ- θ ro CN CN τ- x- CN O CO O θ σ) 00 00 00 x- CN C0 τt C0 C0 C0 0000 τf τt xt τt τt CN 00 τt τt CN τ- τf τt xt τt τt τt τt τt τf τf τt oθ τt τf τr t τt xt τt τt τt τt CO CO CO CO τt τt τf τt τt τt τf τt τt τf τf τt t τt τf τf τt τf τt τt x- CM x- CN *- CN ■ «- CM x- CN x- CM CO cN CO CN < OO O Ω Ω LU LU fxj X < CQ O < CQ < OQ Ω Ω LU LU LU N N X < C Q O O O O O O O O O O O OOOOOOZOOOOOO O O O O O O O Z O O O O O Z O O O O O O: O: Q: D: O D: Q O Q: Q: Q: D: O Q Q: CI O Q: Q Q: Q Q O O O O: Q_ Q_ Q. Q_ Q_ Q. CL Q ^ >- >- >- >- >- >- >- >- >- >- >- ^ X X X X X X X X X X X X X X O O CI Q O: O D Q O: __ Q O Q: CI: O Q: Q: O: O: Q^ h h h h f- h h h h H h H I- h l- 1- r- H h l- hl- l- l- h h h l- h h l- h h h l- H Ll D. O. Q . -.-. © CO t LΩ CD N Cθ ro θ x- CN Cθ τf U0 CD N C ro θ x- CN 00 τt U0 CD N C0 ro θ x- CN C τt U0 CD N C0 ro θ x- CN 00 τt U0 CD N 00 CD CD CD CD CD CD CD N N N N N N N N N N oo co co oo oo oo co co co oo ro ro ro ro ro ro ro ro ro ro o o o o o o o o o O t τt τt τt τt τt τf τj ^ x t τ4- τ^ τ xt t j τ4- ^ x^ t τt τt τf τt τt τt j τj - τj τ4- x^ LO © © H U α. O O CN UO CD O CO Tt cD CN UO OO CO N LΩ Tt χ t CN CO N χt CO O CD CD in τf xt CD CD ro ro θ N τt OO CD N ro x- CD τt O CO CO Tf CO UO Tf x- x- x- CO CO CD CM CO v- O CO CO O UO OO CD t- N UO OO CN CO CO OO CD ro UO O CN N Tt cN CO ro cO CD O CM UO UO CO CN CN 9 cb Lb d τt N ' ό cb c τt uό cb cM u O CM CN CN CN CO CN xt CO in CO CN CO CN CD Tf CD UO CN OO O CN τt CN τ- CD τ- x- OO x- x- T- x- x- x- x- x- x- T- x- x- x- x- x- x- CM CN CN CN CO OO CO τt x- OO x- Tt CM m uo OO O x- N N T— O O O CN O CO m Tf x— Tf CO CO C iDu C ιDu UU0J τ- x- x- cN co co CO CO CO Tt Tt Tt Tf Tt ro Ln N Tf uo N CD N ro ro cM co Ln ro χ - co o cN ro ro N χ- o co ro χt co τt cD x- CD CN x- x- Tt cO N ro cO CN N CO N τt lΩ UO τt O CO CO x- N UO CJ) x- τf CO Cθ qc qc NNiin_qiunqr χ ---τ'iftccoororoqoωoq ccooiinnuiooorooroNCNCNcoroococDTtNco cb τt cN τt cN cb cb cb cb cb cb cb cN CO O CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CM CM CM CM 00 CD CD CD U0 τf x- C0 x- C x- CD CD CN CD L0 O Ln CD CO O CM O C0 τt CM N O C0 CD N O C0 τt C0 L0 N x- χ- χ- Ln τt (χ) x- CM t ro τt oo co N uo co cN N θ uo ro co cN τf N ro N ∞ ro ro o co cN uo uo N N oo τt Ln χ- cN θ co cN ro χ- ro cM CD χ- N τt cN τf cθ N ro cD co ro co cD C co ro τt o uo o co uo cN ro N N τt x- o co co τt ro uo cN co oo co ro uo τt N θ θ N co o ro ro uo cN x- LΩ CD CD LΩ N ro ro O N CD U UO N CD CD CD x- O x- Tt CO CO Tf x- x- O ro o ro x- o ro N N ro o x- N UO Tf Tf Tf UO CO N xt Tf τt τt τt x τf τf lΩ τt τt τt τt t τt τt τf lΩ LΩ UO Tf Tf Tf Tf Tf Tf Tf OO Tf CO Tf Tf CO CO 00 CO Tf Tf CO CO 00 CO CO CO CO CO x- CN r . T- CM T- CM x- CN x- Ω < CQ Ω Ω < CO O Ω Ω LU LU N < < C0 < OQ Ω < CQ O Ω LU O Z O O O O O O O O O O O O O O O O O ooozoooooozoooooozooooυoo O θ_ CL O. O_ Q. Q_ Q_ Q_ LU LU LU LU LU LU LU LU LU LU >- >- >- >- _j _| _| _| _j _| _ι O O O O O O θ 333 =) =) D =) D Q CO CO CO CO COCO CO CO X X X X X X X X X X X -I -I -I -I < < < < < < < O: O: Q: Q: O: Q: Q: -I -I -I -I -I -I -I -I 0- < < < < < < < < Q_ 0_ Q_ Q_ Q_ CL QL Q.0_ Q_ Q. > > > > > > > Q.0. Q. Q. Α. Q. Α. © ro o τ- N o \f in tD S co ro o - (M c ^ ifi (θ N oo ro o τ- M M , uθ o N co ro o - c co ^ ιn o N co c» o ^- M ' - O -τ- - τ- τ-τ- τ- τ- τ- τ- CMCM N rN CMCM CM (M (M CM C C C C C C C C C C xf f xf xf xr r ^^ ^ τf UOin iO iniO o in Ln in in uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo ro UO Tf CM O t CO CO UO N CN CN CO Tf ro x- CN τt ro iΩ CO CJ) CO O O CD Tf N x- CD x- x- CN C _D 00. OL_J T X Tf NI— N 1— χ - ro cO N CN ro CO N τt τt CO N N τ- CO τt CM lΩ CO CO O O CO N τf CO CJ) x- O N χ - CD Tf CD CO C ) Tf xf OO O CM N O xt O OO x- O Tt N CM CO N CM CD CO CD LO UO O OO CN x- CN Tf CD CD τt cN τf C0 N τt O C0 τf x- N CO Tt cO CO CN CN CN 00 x- 00 τf τt CO CM N CN CD CN N CN CO 00 CO CO CO CO CD CN CJ) 00 ro x- CD cM oo τf in uo τt uo co N co ro N CD uo co ro ro o ro co N co co co uo N co ro o N c» N ro co ro ro o χ- CM co cN - cN - cN CN τt τt τt χ f τt χ τf τf τt t χ τf τt τ^ τ4- ιr) x^ x4- -f χ^ ^ χ τt χ τt U0 τt t τt τf τt τ^ O f CM in C0 U0 x- ro τt x- CD CD U0 C0 00 00 CD N N CN O U0 χ- N ro ro o cM -t- uo ro co N - co co uo ro o o co τt co χt cN θ cD CD CN t- 00 O C0 U0 C0 CD C0 ro τf O N U0 U0 U0 CD CN x- CO N CO CM OO CO CD O τt N τ- Cθ σ) OO τt CM CD CO O CM CM N CD CO uO CN CN UO N N τt N ro ro τt OO O CO τt cθ O τt ro CD UO CO N CD N O O τf τt CO CM OO CD τ- LO OO O N τf x- Ln θ τt σ. Ln CD CN CO CO CN CN τ- τ^ τ^ c Cθ CD N lΩ C CN χ - O x- θ ro ro cθ ∞ ro θ x- x- O CN CN CN O CN τt CO x- CN O O CO τt lΩ UO CD C CM CO C CO CO CO C CO C CO C C C C C CO CO CO C ( O CM CM CM CM CM C C CO CO CO CO C CO CO C CO C CO CO CO C CO CO CO x- OO θ ro CD N CN CO lΩ CO τt UO CM CO CN CD CO τ- CD x- 00 τt CO CN CD τt τt x- N N O CO x- CN LO CM O CO O CO Tf CN CD CM CO O x- CN CD τf O N ro ro τt N 00 x- x- x- CN ro θ CN O N Tf Tt CN OO CD CD CN x- ro CD uo o ro co r- S CM CM CD O Tf CM N CM CN CN LO OO x- x- x- x- CD CO x- O ro uO x- N xt CD CM N Tt ro UO CN Tt x OO O ro CM co co N o ro x- O 00 uo o UO CO CO 00 N cD LΩ τt ι co c Ln Ln uo D uo τt τt τf co t τr cN t ιn cD N uo uo N oo ro ro ro O x- O cO x- cO OO CO N CO N N CO CD CO CO co co co co co co co oo co co co co co co co co co co co co co co co co co co co co co co Tf Tf Tf -xJ- l- Tt CO CO CO CO CO CO CO CO CO CO CM rr ,_, x- CN x- CN x- CN LU < OQ < CO O Ω < CO < OQ < CQ Ω Ω LU LU N < CQ Ω Ω < O Z O O O O O Z O O O O O O Z O O O O Z O O O O O Z O O O O O OO O O O Z O O O O O O O Z O DQ:Q:Q:O O:Q:OOOOOOO<< < << Q Q: O: O: D: O UJ LU LU LU LU LU LU LU LU LU LU 33333333 Z Z ^wmwwwwo:o:o:o:c_:__:Q:_j_j___]_. LU LU LU LU LU LU X X X X X X X X X X X LU LU LU LU LU LU LU LU CO CO OC0C0C0C0C0C0Q.Q_CLD_ Q_0_Q_ <<< < < CO CO CO CO C CO Q- CL Q_ 0. 0.0L Q. Q. . Q. CL _J _I _I _I _I _J _I _J < < © L0 CD N ∞ ro θ χ - CM C0 τf U0 CD N C» ro θ χ - CN C0 τt U0 CD N ∞ ro θ χ- CM 00 τt LΩ C0 N CO CJ) O χ- CN C0 τf U0 CD N C0 CJ) O o LnLnuououocDCDCDCDCDCDCDCDcocoN N N NNN NNN Nco∞cocooooococococororororororororororoo UO UO UO UO UO UO UO UO UO UO UO UO UO UO LO IΩ UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO CO LO © © ! _ H U α. CO 00 x- xt N N N O x- UJ Tt OO O Tt x- N Tt CN CO Tf N CO ocorocococo uoNocococoNTtrocNmcoro CO Tf CO O CD N CM CO CO - ro N O CD CD O CN N CO CN O CN N 00 CO T- χ- τt ιn oq cD τt q ro o o cD N τ- N cq τt x- co co co iri c s iri CM CO τ- Tf O CN O O O N CO ■ CJ) O co xt Tt CD Tt N N O N ro c c co c cM Tt ro c co ro ro co CN CM CO CO CO θ ro CM C0 CN o LΩ CO x- CN O O UO CN C0 CN CD τt O N U0 U0 x- ro C0 CD τf τf ro U0 c0 CN ro CM 00 τt O O CN CD τ- ιn θ τf O τt c0 U0 CD O O Tf Tt — ro ro N CD CO CO CD O Tf LΩ CD N CN x- τ CM CO CN CO x- O θ ro τt CO O CM τt Oθ ro CN CN CD Uθ ro θ CD Tt CO OO CO CN CN ro N x- ; CO Tf CM Tf N O co ro o Tt CM O N UO CO O CD CO O CM O UO UO OO ro uO CN Tt OO OO CN CN UO UO UO CN O CO CN CN OO CD LO N N N N cb cD O N N N CD N CD N UO CD Tt UO ro ro ro ro CM CO ro co N N ro o OO CM OO CD LO UO Tt Tt CO o ro uo CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CN CM CM CM CO CO CO CO CM CM CM CM CM CO CO O CO CO CM CM CM CM CM CM CM CM CN ro c0 U0 τt O CN τ- N CM N O ∞ ro 00 CD ro θ C0 x- CN C0 ro ∞ x- CD ro c» x- U0 CD CN N CN C0 x- x- N τt ro τt U0 CD ro CN τt x- χ- LΩ uo uo co ∞ o ro Lo ro ro co o co ro cN CD θ co ro N co o c» N c» N ro uo cD N Lθ co co cM CD CN CJ) cθ χ- cN χ-- uo co ro o o τt LΩ CM N in N ro q τt co o o cN co τt cN χ- c» N o ro N cθ L n χ- co co N N co χ- co χ- N CN q - ιn uq τt N τt c c Lb uO Tt ib c ro x-^ x^ d x-^ cb cM Tt od T^ x^ cM x- CM CN CN CN Tt CO CO CO CO CO CO CO 0O τt τf τj τ^ t τf τt τt χ τt τt x τf τt τt τt τt τt τt τt τt cθ CO CO CO 00 CO CO τt τt τt - CM x- CN x- CM x- CN „ x- CN x- CN ω O Ω Ω < CQ O Ω Ω LU LU N < C0 O Ω Ω < Ω LU N O O O O Z O O O OO O O O O O Z O O O O O O O Z OO o Co0υΩooΩ LoU UJ N < O Q O oozoo o o o o o z Z Z Z Z Z Z UJ UJ LU LU LU LU I1J LU IJJ LU LU 33333333 LU LU I1J LU LU W W LU LU LU LU CΛ CO CO CO CO CO CO X X X X X X X X X X X LU LU UJ LU UJ UJ LU LU X X X X X X X X X X X >- >- >- >- >- >- >- >- >- < < < < < < Q- Q.0_ 0- Q_ Q_ CL Q_ Q_ Q_ 0 I J J J J J J J Q. Q. D. Q. Q. Q. Q. Q. D. D. D 1 I I I I I I — I — ■ x- CN CO τf Ln CD N ∞ ro θ x- CN Cθ τt UO CD N Cθ ro θ x- CN CO τt UO CD N Cθ ro θ τ- CN CO τt UO CD N Cθ ro θ x- CN CO τt LO CO © O O O O O O O O O x- x- χ- x- x- x- x- x- x- x- CN CN CN CN CN CN CN CM CN CN CO CO CO CO CO OO CO CO OO CO τt τt τt τt τt τf χsr o CD CO CD CO CD CO CD CO CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CO CD CD CD CD CO CO CD CD CD CD CD CD CD CD CO CD CD CO CD CD CD CO LO © © ! _ H U α. CD CD OO O OO N O CO UO CN CD CN N OO x- x- CO CO CN CO UO N CN UO UO O CO x- O τt CN CN UO CN UO N N O τt x- N τf CO OO τt OO OO ro O CO CO ro Tt Tf CN N CN CD CD CN ro O CM CD CD O N CO N CN U0 CO τt ro 00 ro N N CD N N 0 0 CJ) CN τ- τt U0 x- U0 CN - CN CN Tf CD N CO CN Cθ m τt CN CN CO CO CO N - O N CN ro cθ N O τ- Tf CO O O CN UO O O CM CN N CO CN θ ro τt x- x- x- x- x- x- x- x- x- x- x- x- CM CO CO Tf CO x- x- CM CN CM CM CM CM CM CM CM CM - T- CM CM CM C CN uo cN x- ro uo ro oo ro co O τt τf CD CD O O CD CO OO CO CD N CN CD in x- O UO CO UO CJ) x- CO x- x- CM CO UO N t- OO CN OO CO N iΩ CO N O OO O N CO co ro co ro o oo cD N CJ) co N - oo oo oo ro oo uo cj) θ oo χ- N co oθ τf N N co co uo cD τt ro uo ro oo ro m CM co ro x- O Tf T f N N U0 ro ro CN CO τt CO U0 N τt CM τt τt CD x- N ro cθ 0O τf Lθ N N Ln CM x-; ro ro CN U0 lΩ N OO Tf CO UO N CO O rocooocooorocoroo CN o o CN o d x^ x-^ ro cb x^ cN x^ cM ' d ro ro ro cb cb ro cj. in UO UO UO UO UO UO UO CD CD UO UO UO UO UO UO UO UO CO CD CD CO CD CO CO CO CO CD CO UO UO CO CO CD CO CD UO UO UO UO UO UO UO CD O o ro N co o Tt Tt m co CM Tt N co co O Tf o x- Tf o N x- CM Tf O CM CD - CO CN CO Tf ∞ N 00 CD C» τt CD CO N 00 CN τt CD ro CM N LO N CD CD U0 C0 C0 x- CM 00 O CM τt x- N Tf cD co ro o ro m co oo Tt cN cj) CM N O C.O. C_D τf. CN - N C0 CO CO CN - ιn CN N CM CD N CO τt CD C0 CO N Cθ ro 00 in N U0 x- 00 CJ) x- x- in CD LO C0 CM τt CN N τt Tf CD CO CM ro N CM N τt OO O O N UO CD CO CD O CJ) O CO CO OO χ- ro N UO N UO x- CN O CM τf in τf cD co m τt o m o U " J CO " Tt Tf UO UO Tf CD Tf Tt oo Tt co Tt co co co cN Tt cN CM CN co o ro oo co co co Tt in cD uo cD CD N co ro co ro o x- ro ro ro o o o xt f T t Tt Tf T t x Tf xt τt f t τt τt t t τ τf τt τt χ 0 0 CO CO τf τt τf t τf τ τt τt τ t f LΩ LΩ τt τt τt 0 U0 U0 x- CM '«- CM T- CM < co < C Q O Ω LU N X X < CQ θ Ω LU LU < CQ < < Cθ O < O O O O O O Z O O o υ o o z o ZZZOOOOOOOOZOOOOOZOOOZOOOOOZOO _I _I _I _J _I _J 00000000000333333333 Q Q : Q : O: O: O: ^ >- ^ - Q Q O: Q Q : Q : 3333 <<<<<<D:o:(rD:iro:D:D: D:Q:D: j JJJJJ JJ-JiiJ_JUJiiJiJLUJJJ JiJiiJUJiiJiiJ_Jiijiijiijiij >>>>>><<<< << <<< <<O OO cocowcococo OOcocococococo_ι_ι_ι_ι © N C0 ro θ x- CN C0 τf lΩ CD N ∞ ro θ x- CN C τt U0 CD N Cθ ro θ x- CN C0 τt U0 N C ro θ x- CN 00 τt U0 CD N C0 ro θ χ -- CN Tt Tf Tf UO UO UO UO UO UO UO LO in uO CD CD CD CD CD CD CD CD CD CO N N N N N N N N N N CO CO OO CO OO OO CO CO CO CO ro ro ro o CO CD CD CD CD CD CO CO CO CD CD CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CO CD CD CD CO CD CD CD CO CO CD CD CD CD CD CD CD CD CD C^ LO © © ! _ H U α. cN CD oo ro oo oo N co co cN ro LΩ Tt co Tf x- r- ro ro o ro uo cN Tt LΩ Tf CN CD OO N Tt O CN ro N CO x- N UO CD CD CD O CO CM CN CO CD CD lΩ CO ro x- CM m co ro x- CO Tf x- CD N CO x- O CO lΩ O N cM o ro ro co o ro N τt co ro ro oo o oo τf LΩ θ N CD oo τt oo cN co in N co ro ro ro co co co N oo ro co oo m N CD Ln oo x- N ro CO N N O O CM CD CO ro CO Tt CN CO 00 CM CO CN CM CM CM CM CM CM CM CM CM CO CM CM CM CM CM CM CM CM CM CM CM CO Tf Tf Tf UO CM X- X- CN CN CN - X- X- X- X- X- X- ro N C0 N CO τf ro θ N CM CD U0 CN CD τt CD CN CO N 00 CD CN τf x- N ro N CD τt τt O N OO CN CO τt OO CN N UO CO CO τf x- O τt CO CN ro oθ O τt CN CO CD τt CD UO x- UO CN OO CJ) τf ιf) CO τt ro θ O x- UJ CO CO CO CD N τt CO UO CO τt CM CO θ ro ro oθ OO CN τ- CN Tf O O Tt CN LO OO CM CO Tt N ro N N CO LΩ CO CN N CD ro N UO O - τt τt CM τt UO CN O CN CD O CM CD UO CO CD CD CO OO CO CN CO ro ∞ N N CN OO CO OO τt τt τt τt ιn Ln Ln CD UO CD CO LO UO N N N N CD τt cθ CN CN CN CO CO OO τt τt χ - o ro ro cθ N CD CD N N lΩ UO UO UO CO CO CΩ CO CO CO CO CO CO CO CO CO CO CD CO CD CD CO CO CD CO CO CO CO CO CO CO CΩ CO CΩ CO CO CO CD LΩ CD UJ CN N UJ CO N Tt CO x- ro cO CN CO OO O O UO CO CO x- N CD LΩ CN O N UO CM OO CO UO CM CM O CO CJ) CJ) ro τr cθ CN χ - N τt N t- CO CN O 00 CD x- O UO CD CO x- OO CO UO UO CO CO x- UO χ- N τf OO N N χ- χ- CM CM CO τf N N CO CD τt co θ CO χ - CN OO CM N CO CN Tf O CN J N x- LΩ OO CΩ CD CD CD CO x- CO CO N CO OO O CN x- CO lΩ O τt cθ U O O CN OO x- C CD τt O OO CD CD CD CO N CN ro ro ro θ CO C0 00 C» N N ro ro c C0 x- x- O N C0 U0 τ - cD U0 C0 N U0 C0 U0 CD N L0 τt τt CM C0 CN U0 C0 N CD N C0 N CD CJ) CJ) CM N CM CO CM CM CM CM N CM CM CM CM CM CO CO CO CM CM CM N CM CM CM CM CM CM CM CM CM CM CM N CM CM CM CM CM CM CM CM CM CM CM CM N x- CO CD Tf ro Tf uo CM co o ro co co co o Tt ro cN O x- UO x- x- CN - O CO OO CD ID CO CO N N CO O CM O CM T- ro co m CM UO Tf CO Tf Tf CO CD x- CM N xt CO ro O Tf CO CO CN CO CΩ o oo ro x- CM uo CD CO CO Tt CD CD N CO ro cO O o Tf co co uo ro ro uo CD Tt D CD CO CM Tf o co o oo x- ro N N CN ro uo Tf O CO uo uo uo CD LΩ τf LΩ CO Cθ θ ro CJ) τt x- ro co co ro CD xt co C000 ro N O O CN 00 θ ro CN τt τt CD C0 CN x- τf xt U0 CD τt CN τ- x- O U0 U0 CD CD τf c0 CN τf x- CN N C0 N U0 N CD U0 CD N C0 τt τt τt τ4- ιr) lΩ lΩ UO U0 τt U0 U0 uO U U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 u0 UO U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U^ T- CN T- CM x- CM x- CN CQ Ω Ω < CQ O < CO O Ω < 00 Ω LU LU < CQ Ω Ω LU LU CQ o o o o o o OOO o o O o o o o o O o o o oo o o O O O z o o z < o o oz < o o O O O 3333 θ: o: o: o: o: o: O O O O O O θ 333333333 fn fn fΛ fΛ fΛ fn fΛ fΛ fΛ fΛ >- >- >- >- 000000 m m m iij iii iii ij ij ιij (ϊ: (£ Q: α: _: Q: [ϊ Ϊ - ^ i2 ^ ^ ^ ^ ^ ^ j j j Q: (ϊ: (ϊ Q: Q: iϊ ^ ^ J _J CO CO CO CO CO CO Q_ Q_ α. Q_. α. Q. Q. O O θ X X X X X X X X X X O O θ Q. Q. Q- . Q_ Q_ © CO τf Ln CD N Cθ ro θ x- CN CO τt UO CD N Cθ ro θ x-- CN CO τ- ιn cD N C» ro θ x- CN CO τt LO CO N C ro θ x- CN OO τf UO CO N OO o ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cM CN CN CN CM CN CN CN CN CN co oo co co co co co co co CD CD CD CO CD CD CD N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N LO © © ! _ H U α. CM o χ- ro τf CD uo ro ro oo oo τt CD x- UO N CN co CD ro N ro x- cD o cN oo m ro co cN x- ro O UO x- O x- Tf N CO CO CO CD - Tt Tf CD Tf CO CM x- Tt ro io co in m co co x- cD CM CN CO CO Tf CO CM CN UO in xt O O O CM uq CM cd Tf or ro CD Tf UO x- ro o χ^ N U0 χ- ro cM q ro ro ro cb ro x- cb CD CO CO N c ro d 9c ro ro ro ro cd cb cb N cd cb N CD O N CO CD N UO N O CD N N CD ro cθ τf uθ CD UO CO Cθ ro cθ N CN N C» CN ro θO x- θ ro τt CO x- CD τt CD N τt O τf O U x- ro χ - uθ χt cN θ τt co cM θ uo ro o ro χ- co τf τt c» ro τt co co τt co τt uo cD - τt co ro N co χ- cD uo uo uo N ro co co co N τf uq C ro uq N ro uq x--; x- O N UO CM τt τt O N CD x- CD τ- N N O τt x- ro θ ro CN UO CO CO CD ro θ O x- CN CO N CO CO UO ∞ ib Tt cb Lb Tt T c cN x^ x^ x^ cN o d ro ∞ ro -^ ∞ N uό Tt L i^ in U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 τt τf τt τt U0 τt x^ τt τt τt τt τt τt x τt x τt τt τt τt τt τf τf CO CO Cθ CO C^ uo o Tf O x- CO x- τ- oθ x- CM - O τt x- N CO τt ro oθ CO O x- CN N UO CD CN CM CO CJ) UO CO θ ro CD CO CO O CO UO CO Cθ ro O N N N Tf τ χ- co ro co N CM ro c» (x> co N θ τt τt oo cD oo co uo ro uo co co cN co uo cD ro cN co co cD τt ro τt co ro N τt co o Tt co ro CM C ro x- CO τt ιn CD ro CM CO LO N x- ro χ - CO CJ) CD LΩ C U0 CD CM CM CN N x- N CO N - N N U0 ro CM N CN Cθ 00 CD x- oo Tt ro oo C» N N N CO N CO CO CO CD CD UO UO χt UO N N N Cθ ro ro ro N N N CD CD τt τ4- (- cO CN N N CO CO OO O N CD N N CD CD Cθ ro CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CM CN CN CN CM CM CN CN CN CN CN CN CN CN CN CN C CO Tt Tt Tt o ro CM x- Tt m x- CO x- CD Tt co iv. CN x- U000 U0 CN τt cθ τt 00 x- CM C O CO 0O U0 CD x- N 00 τt CN O CO N CO OO CD CO CD N CO Tt CN ro ro CN N CD O OO CD x- UO CN N χ- co co ιn cN co o N m Ln ro N o ro τf ro oo cN CD uo o UO ro CN CN O O N CO CJ) CD CJ) N CN τt U0 C0 C0 CM x- x- O C0 τf x- O N N τt ro cθ O U0 C0 CM U0 ro U000 O CN CD C0 C0 CD τ- x- CD CD O x- - x- cO O C0 τt CO τt Ln CN τ- CN τt U0 τt CO CD N CD τt cθ Cθ τf CM x- x- CO 00 CM τ- τt CO CO 00 CO CO CN x- CN CO x- CN CN CO U0 CD CO τt τ^ in uO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO uO UO uO UO UO UO O in uO O UO UO UO UO UO O uO UO - CM x- CN - CN _. - CN x- CN Ω < co < 00 < OQ < 00 Ω Ω LU LU < oo < CD O < O Z O O O O O O Z O O O O O O Z O O O O O O O OOOO Z O O Z O O O O CO o o OOO o O i i i i i i i i i i i i i i i i i i i i I o:<<<<<<<<<<<<<<<<<<<<< <-j <_. 0->>>>>>>>>>>>>>>>>>>>> < < © o ro θ x- CN CO xf lΩ CD N C ro θ x- CN C τ^ uj CD N Cθ ro θ x- CN CO τ Ln CD N Cθ ro θ x- CN CO τf Ln CD N CO CD O x- CN CO τt 0O τt τt τt ^ τj t τt τt τf τt in Ln U0 U0 U0 U0 U0 U0 U0 U0 CD CO CD CO CD CO CD CD CD CD N N N N N N N N N N 0O 0O CO CO 00 N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N LO © © ! _ H U α. UO CM Tt N CD UO OO O O T- CO OO N CO N σ) t lO xt OO N CN O CM N O CO CM CD - χ - θ N co oo N oo cD co o ro cN θ CD - ro cN co oo ro m χ - 00 O CO τ- cθ ro θ τt O CN OO CO O χ - CN CO oo_: q (Dco O CN O CN i o ro Tt o o O O O N.999 o 9 o c N o o 9 χ _- o 99 χ __ χ __ d oo uo 00 N co co ro co ro oo N ro ro ro N co ro -5- ro χ- oo'χ- χ- oo χ- χ- oo ro χ - χ- χ- ro σi CN OO UO CM UO Tf cO CO ro CN Tf Tt Tf CO CD CD O Tt 00 ro iΩ τf U0 N Cθ Cθ ro U0 U0 CO τt CM CN N O f CO CO LO CO O N T- CD O cM oo cD N in ιn χ - ro χ - ro τf co ro χ- co N τf CD Ln x- OO N CD CD CO x- O CN UO CM CD CN x- Tf CO O CO UO N Tf oo CN ro co O CO CO OO CN Tt Tt Tt LO OO O CD O CM CN CD CD N OO N CN CN CJ) CN Cθ ro cθ CM 0O N CO U0 N CN U0 x- τt Tf CD ro CM x- N U0 00 CO CO Tt CN CN CN CO x- O CN CD x- O x- x- CM Tf UO CN O O " ro ∞ ∞ cb τt " ιb cb Ni uό ιb uό cb cb N UO UO N 00 Tf CO Tt Tf CO τf τt τt τt τf τt τt τt χ τt cθ Tt T f Tf Tf Tf T Tf Tf Tf Tf OO CO OO OO t T f τt τf τt τ- t f τ4- Tf Tf Tf Tf Tf Tf Tf OO Tt CN O CO CO x- CD CO CO ro O x- x- N N CD N r- i NL. τ- ro cN - co ro co co cD θ o N N xt co ro co CN τt CJ) O τ- UJ CD CD OO Uθ ro τt x- ro CM co co N co cθ N N CN CN C0 C0 x- O τt U0 CD N U0 CD U0 CD U0 CD CM CM CM CO CO CO CO CO CO CO CO CO CO CO CO CO CO CM CO χt CN t CO O CO τf OO OO τf τt CM CO CD CN CO CD CO CO χt χt m N N oo χ- co cD co τf τf ro τr ιn cM N oo oo uo Tf x- 00 CN CN CD τt ro co o o χ - ro ro τt cN co N CD CM CD CO CO Tf CD U0 U0 CM τt O C0 CN N 00 U0 U0 CD CM ro τf CJ) C0 Tt CM LO CN Tt CM ro cO CO τt ro co m co co m co σ) τt τf cN co oo cN ro N co co τt ro CM O CN O x- CM - CN CN 00 C0 U0 CN τt x- x- N UO N OO OO OO CO CO C0 N U0 U0 U0 U0 U0 τt τt CN CM U0 U0 C0 CD CM θ ro ro CD 00 00 C0 00 N N C0 C0 N ro θ O O O CM CN - xτ- ro ro cos cD CD CDCD LO U0 U0 LΩ LΩ U0 U0 U0 U0 U0 U0 U0 U0 U0 UJ U0 U0 τt τj τt τt τt τt τt τf τf τt τt τt τt U0 U0 U0 U0 U0 U0 U0 LΩ Tt Tf Tf Tt Tt xt Tt Tf x- CN x- - CM m < < coOOΩ < < o C Q O Ω LU N X X < CQ O CQ O ooozooozooooooυzooozo o υ υ o z o o o o o o z o o o < o o O OO >- >- >- >- O O O O O OO O O O O O: Q: D: O: D: O: >- >- >- >- Q: O: Q: Q: Q: O: l j l j l j l j l-JLiJliJLUmiiJLULiJ j ■ r-i'^-'C-t'K--K-'D-i'D-i'Q-i'a-l'D-i'Q-i'ij LUW x x x x x x <<< d ddddd dd <<<<<<<<<<<C0C0C0C0C0C0 I- I- I- I- I- I- © o U CO N Cθ ro θ x- CN C τf ιn CO N C ro θ x- CN C τt UO CD N C ro θ - CN CO τt UO CO N Cθ ro θ x- CN CO τt Uθ ω N Cθ ro θ oo co co oo co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cN CM CM CN CN CN CM CN CM CN oo N N N N N N N N N N N N N N N ∞ CO CO OO CO CO ∞ CO CO CO CO CO CO CO CO CO OO OO OO OO CO CO OO OO CO OO CO OO OO CO CO LO © © ! _ H U α. O 00 Tf Tf CO o CN ro CM N IT- x- N CM CO CN CD T- O CO CD LΩ χ- UO LΩ CΩ CO χ- CO N CN ro cJ) N O CD co O CD UO CN CO OO UO CM Tt N N O CO CO x- Tf O CO x- o cN CN co ro ro co co N co N C_D Ln ro x- τt cθ CD CD O N CJ) O OO CO N . r O . r O . _ CO in Tt ro Tt O O O CN CM UO ' d ό cό co o o v- o co x^ x^ x^ x^ d cb cM M d -^ ^ -^ -^ x^ d co ro x- co ro CD ro co ro ro N - uo. N CD x- x- CO x- LO CO O ro cO CM CM CM CO CD OO UO x- N CD UO UO Tt o ro CN UO CO CM N C roJ) N CO CO x- N τt CO x- C-D. .N CM CO CD N CN χ - χ - χ - U0 U0 τt CM CN CO CM Cθ ro U0 CN 00 o co co ro ro τt N ro N θ oo O CO ro CM Tt CO N CM Tt CM CN - CM CO O N Tt ro ro N in N ∞ ro θ ∞ ro ro θ x- x- CN ro θ x- CN O O O O x- CN ro ro N O O τ- CM CO O CO τt τt τf τt iΩ τt τt τ LΩ Uo uo uo τt uo uo uo uo uo uo uo uo uo τt τf τt uo u LΩ in uo uo u θioco τt rø o ro cN N CO 00 Tf CM x- C0 N x- x- U0 N 00 00 N U0 ro τt CD N τt o ro 00 N C0 lΩ τt CD τf τt 00 CD O CD O CD Tt oO UO N Tf CM CN UO CD CM ro co co o x- x- O u0 τt C0 00 O x- CM τt CM N CD C0 ro ro τf L0 CM N 'r- CN O U0 CD N ro θ U0 Tt UO UO N CN Tf O O CD CN OO ro o co oo N 00 χ - ro x- N ro N N τt O CD CD U0 N CN ro C0 x- N τt N O N CJ) τt N CD CJ) C0 τ- co ro ro o co co iΩ uo co cD co Tt N CD N CD N N UO CO UO N CD CO ro ro oO O x- OO OO CO CD CO N N OO CD Tt Tt T CO UO UO CD CD CD CD UO OO N OO N N ro O O τt τt τt τt τt τt τt τf t τt t t τt τf τt U UO τt τ χ τt τt τt τt τ τt τf τt τ τt τ τt τ^ CN T- CM x- CM x- CN x- CM ■ «- CN O < ω O Ω Ω LU UJ N < OQ < OQ O Ω Ω < CQ < OQ O Ω Ω < OQ O ozoooooooooυzooooco O O O O O O O o ooozooooooozoooooυ Q: LU LU LU LU LU LU LU LU UJ UJ UJ C0 C0 C0 C0 C0 C0 3 3 33333 3 < < • < < < Q-. Q-. Q- Q- Q_ Q_. Q_ Q_ 0:0:0:0:0:0:0: X X X X X X X X X X X X >- >- >- - >- LU UJ LU LU LU LU LU LU _J _J _J _J -J C0 CO (O CΛ C0 C0 C0 C0 X X X X X X X H Q_ Q_ Q_ Q_ Q_ α. Q. CL CL CL CL θ O O O O O _l _J _l _J _l _l _l _l <<<<<<<<<<<<< h h h h h h h © x- CN C0 τt lO C0 N Cθ ro θ χ - CN 00 τt ιn CD N Cθ ro θ x- CM C0 τt U0 CD N C0 ro θ x- C C τt U0 CD N Cθ ro θ x- CM C0 τf U0 CD o co oc c c co c c - ^ ^ ^ ^ ^ ^ ^ ^ 'f i in i in i in in in in in co D D o cD CD D DCD o s s ss s s s ∞ OO∞ ∞ OOCO OO CO ∞ OOCO CO OO OO∞OOCO CO ∞ CO OOCO OO ∞ CO OO OO CO OOCO røCOCO ∞ CO OO COCOΦCOCO CO OOCO ∞ © © ! _ H U α. in cO CD CD OO CN Tf CO UO Tf co co τt O CD O O τ- O x- CD CO CD CO co co ro m τt τt co cN CD Tf ro N CD Tf x- ro co co co O N CM O OO 00 CD CN CN CD N CO O CO cN oo co o ro cq ro ro q oo co Tt ro CM oo CN o x- co oo ro co ro CD N N xt N N CO O d d cM cb d cb o ^ cM Tf ^ 9o cb cN cb uό cM N N N Tt ib uό uό uό cb O CD f CO CO N N CN N N cb o cb ib ib ib cN x- ro co CN - x- x- x- x- x- CN CM CN X- X- CM T- X- X- X- X- CO O N in cD ro τt m oo ro cN N co co cD CM co χ- co --- CO CO CN x- Tf CO N CN τt τf OO UO CO N O x- N O τt OO CO CD τ- ro θ τf cθ O Tt Tt CO O x- CN UO N Tf CN UO CO CM CO O UO UO x- O x- CO N CN CN 00 O OO CO N N O N CN UO OO CO UO x- CO Tt CD O Tt x- CD CN ro cN cq χ- ro ro N cq τt cq N χ- co χ- q N N χ- τf x- O O O O Tf x- CD CN N U0 00 ro τt C0 in χ - U0 CN N U0 N C0 τt C0 CN N O d ^ T^ ^ ^ cM ro ro ro ro c oό ro s ' c co d d CO N N N x- CN CO CO CO CO CO CO CN CO CM CO OO CO C CO x- O x- x- CD CO CO N τt τt τt τt τt τt cθ CO CO CO CO CO C 00 CO CO τt τt CO CO CO OO xf τt τt τt τt τt τt τf τt τt τt τt τr τt τf Tt τt τt τt τt CO 0O C CO OO UO x- O x- Tt CN x- UO CO Tf CD CO CO CO CM CO OO x- O UO CO x- CN CO CD O CN UO τt N O N CN - x- 0 N ro -.. U_O. C_D C.O. UO OO CO CD (θ N Tf f CN CD O CD 00 '-- CD --- x- N CO CD CD N τt ro CN CO UO u -. u -O N . o -o_ ro_- ro_- Tt . CO CM CM CM O OJ O CM CM CO CM CO CM T- CM Tf Tt τt τt τf τf τf τt τt 'xf τt τt τt τf C τt τt τf τt τt τt τf τt τt x- CN T- CN T- CN T- CN < OQ Q Ω Ω o o < C < CQ O Ω Ω < CQ Ω Ω < 00 O Ω LU < ω Ω Ω O O CO o o O O O O O o o O O O O O O O O O O O O o o O O O CO O o o O O O O O CO CO CO CO CO C 333333333333333333333333 H I— I— I— I— I— I— I— Q. Q. Q. D. Q. Q. Q. D. >- >- >- >- >- >- m m m m m m m m m m m m m m m m m m m m )^ \^ ^ ^ ^ ^ ^ }^ V) W W yy) y7)W 7)tD 000000_J_ι_ι_ι_ι_ι_ι_ _ι_ι_ι_ι _j_j _ι_j_ι_ι_j_ι_ι_ι_ι_ι≥- ^S2^SI_E<<<<<<<< © o N CO O) O τ- N Cθ ' uO (O N (O O. O τ- (M CO ^ uO lD N Oθ σ) O - CN CO τf lO CO N I» ro θ τ- CM C ' uO CO N CO Cn θ τ- (M N N N oo co oo co co co oo co co ∞ ro ro ro ro ro ro ro ro ro ro o o o o o o o o o θ χ- χ- χ- χ- ^ '»- --- x-- x- x- cM CN CN co co co co co co co co co co co co co ω co co co co oo co ω co ∞ ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro LO © © ! _ H U α. N ro x- UO CO x- UO CO CM OO UO x- CO CD O CN CN CD UO N CO CD ro τt lΩ O τ- τt CM CO lO x- CO CO τt N x- CO τt CN N CM CD N ro x- N ro cN q cN χ -- cq uq χ -; CN uq rø ro q N N τt ιn cM q cθ τ- ιn τ^ x- ιv. cj> N τf co N N^ b ^ iri bro coroiri i ro - rob^ ^cM c CN CN CN CN OO C τt τf τf CM C CN C C O CO τt τt τt ιn CM CN CN CN CN CN CN - CN CN CN C CN CN CN CO C^ ro UO OO CN OO N τt N CJ) τt τt CD CO CN ro τt O oo Tf ro co co ro N τt o τt cD co cN co uo τt uo τt co o χ- CD ro oo τf ro ro cD co θχ- χ- rocDco χt ooo τt χ- χ- ro cN θ ro co Tf x- CO CD CO C0 O N C0 CD N CN τt τ- τt C0 U0 x- 00 τ- C0 CM '-- U0 O τ- N C0 cq in x- cN co co co roro NN CCMM oooq ocoq ccNN Oq LιOn NN ocoq roc j) NN CCMN - co χ - OcOo x χ -- UuOo CcDD '-- C CNN CCNN LLnn θO τTff CCNM CCDD CCOO CroJ) CcOO COOO x- --- τ Ttf NN C COO CCOO OOOO Tf UO CD N UO Tf Tf co Tt uό uό uό d uό cb c CN T^ d cN uό Tt t t uό uό cb cM x- d od CD CO CD CD CD CD CO CO CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CD CD CD CD CD CD CO CD CD CO CD CD LO UO UO UO UO CD UO UO ro o ro co m o N - x- o m oo oθ χ- τt o τt χ- N N LΩ N x- OO O CD LO N CO CD CO x- O N ro cθ O τf τt CO CN lΩ CO CN CD CO N x- Tf N oo co τt χ- χ- cD co ro oo uo o ro ro o cD CN o uo xt co ro cN - in uo x- x- CD LΩ N N x- ro cO CO CN N CM x- CO CO CD x- uO CD CD O C CD x- O Ln θ x- x- τt N CD τt cθ CN CO x- CO C0 N CO CM ro τt c . 00 CO x- lO CO OO x- OO CM LO O UO CO UO τt O CD τt CO CO x- CN CO 00 CN 00 CN x- O τr ιn U0 CD CD CD N CD N N CD τf . τf _ C _D C_D χt CM τ- o ro cθ N N OO OO O O χ - N N CO OO N CD N ro θ xt Tt Tf Tf Tt Tt Tt Tt Tt t f Tt Tf f t Tt Tt t Tt Tt τt Tf τt τt τt τt τf τt CO -χr τt τ- t τt U0 U0 U0 τf τf τf τt τf τt τt τt U0 LΩ CM O CO ro cO CO CN O CO N O x- CD O O OO CM CO CD CO CO ro N O CN CO LO CO T- CO ro N T- ro CM Tt LO CO CN Tt cO N CO CN OO CN LO ro θ τ- O O CO N τf CM x- Tf Tf o in CO Tt CO x- N CO CD x- x- Tt N CM - Tt Tt ro T- N N Tt O -; ro CD CJ) τt x- CD t- CJ) N CD θ ro CD CD N CM - N χ - o co co ro ro χ - ro cN oo co LΩ ro χ - co Tf N Tf U UO UO CD N ro ro ro τt t N CM- τt τt ιb N N N ro ro ro ro CO - T- X- CN -- -- --- CN O O O - CO OO 00 t Tf Tf Tf Tf Tf Tt Tf t t t Tf Tf t Tt Tt t d co co CO CO CO t t f t Tt Tt Tt Tt t Tt t CO CO CO Tf dTf CM V- CM < 00 Ω LU N < CQ Ω LU N X < OQ Ω LU N < OQ Ω Ω < CO Ω < OOOOOOOZZ OOOOOOZO Z Z O O O O O OO Z OO O O O O O O O O O O O (D S θθ ro ro ro LO © © ! _ H U α. CO CO CO N τf N N - CO C UO O CD ro cθ CO N CN C χ- χ- ro τ- CO CO O N O x- ro N C ιn x- CM CN CN τt xτ- cθ O CD ro N - 00 χ- ro co ιn ro ro o τt ιn χ- τt cN CN τt Lθ N τ- ro ro co uo co oo uo o o χ- CM N co o τ- co co - co τ- oo co N τt o -- χ- co co CO O CM N UO CO CO CO Tt CD CN x- x- CN CN O N ro CD N CO x- UO CO CN CO CD CD CD CO O CD CN UO CO UO UO CO x- N OO N CD N UO C CM C CO CO CN CN CM CN CM CM CM CN CN CN CN CN --- X- X- X- CM CM CM CO x- τ- x- x- x- CM τ- CN τ- x- x- x- x- CO CO χt τt τ- x- x- x- UO N ro CD O O x- CD O CN UO OO τt cθ CO UO x- τ cθ O UO τ- ro c N N - ro CD τ- UO τt τt CD OO O N --- CN cor- τ- xf N θco (D ro»o tDθNoor τ- racNθ uo - c o ιo o - c c c cθuro c io D o O C in CN CN OO CN τt x- CD τf O τ- CN τ- CO Cθ ro τt CD N N ro θ τ- τt ro θ N C CN CO CD N OO CO CO CM CN CO O O N CD τt τt CD Ln N τt CO CN CN OO τ- O x- - θ ro ro ro x- ro o oo co coco N CD in cD CD ro o x- - U0 CD CO U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 LΩ LΩ LΩ LΩ U0 U0 U0 τt τt τt ιn t m τt τt τt τt t τt τt τt τt m m m o x— x- CO O CN T- in N O OO CO Tt x- N CN OO CO O CO lΩ CO CN Tt O CN N CD in ro N OO OO CO N Tt N T- Tt Ln O in CO O OO CN CO O Tf CM f O N CD O N Tt CO CD CD CO ιnorouococococMθocoτf oouoco--uouocNro N τt O Oθ ro in - CO CD OO τf CD CN CN CN ro x- x- in CO CD CD CN OO CO O UJ CO Tt CD O CO CN T- N Tt x- lO CN UO CO UO CD N Tt Tf OO CD OO ro cO O O CO Tf Tt CD CD CO O x- x- CN CM O O ro ro o co co co oo oo cD uo cD co ro oo N O x- o cN N CO CD m in LΩ Tf Tf N N N N ro ro O x- CN OO OO N N in in in uo uo uo τt τt ιn t τt τt τt τt τt τt τt τf t τt t m uθ Ln m xt τt τt τt t τt t τf τt LO LΩ U0 t Tt τt t Tf CJ) CO CO CN Tf CM x- N CM - N OO CN CN τt τt LΩ lΩ x- CN ro cθ θ ro τt cθ CD UO τt uo ro ro cD CD uo oo cD N -- t co ro cN uo ro Tf CO T- 00 CN CO Tf CO CO O CN CO CM ro O OO N LΩ O OO CO OO LΩ CN O CO OO CN CO Tt oo ιn oo τt ro co uo co τt ro co τt ro co τt cN CM N ro CD ro co x- Cθ ro CJ) τf x- x- O O CO x- CO CD O CN CD ro cθ τt x- τt cθ τt CM x- in cθ CO N τ- x- CO τf O CN CN O CN N ro CN CN ro cO CN Tt in CD Tt Tf Tt LO UO Tt uO Tt -t CO CD N CO N N N CO CO CO N CO UO Tt UO CN N OO O xT- CO N N N CD O x- x- CN τt τt CO C t t τt τt τt τf t τt τ τt τf t Tf τt τt τt τt τt τt τt t τt τt τt t Tf τt τt t τf L L τt τt T- C T- CN x- CN x- m < CO < CQ Ω o < O Q < CO Ω Ω < CQ Ω LU N < OOO O OOO O oooυoozooooooo OOOO O OO OOOOOOOZZOO Q O O: Q: O O: O: Q: O: Q: _I _J _J _J _I _J _I Q_ Q_ Q_ Q_ O_ O_ Q_ CL wwcocowrøcococococococo COC0C0C)C0C0COCOCOC0> >>> >> ><<<<<<<<dddddddd ^ ^ ^J_J_J_J © o ro θ χ- CN C O τt L n cθ N ∞ ro θ χ- CN CO τt LΩ N ∞ ro θ χ- CN C O τt lΩ CO N Cθ ro θ χ- CN C τf LΩ CD N C » ro θ χ- CN C θ τt cD N N N N N N N N N N co oo co co co oo co co oo co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- --- --- ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x-.x- x- x- x- x- x- x- x- x- x- x- x- x- CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN M IO M fO IO IO IO IO ro rO tO IO IO IO M IO IO M IO ro rO NJ W oooooooooooooooooooooooooooooooooooooooooooooo ro ro ro ro ro ro ro ro ro ro ro 4 s - 4- 4- 4 s » 4 s - 4 s » 4 s .4 s - 4 s » 4 s - Cjθ CΛ) co co co cj ω ω co cj M o cD ∞ -vi ro ro 4 ω ro --- θ LD ∞ -»j ro ro 4 s . Cj ^ o D ∞ -Li ro ro s - c r ^ o D ∞ -Li ro ro 4 s - c M ^ 3> ^ 5 >> 5> 3> >> 3> i — i — i — i — i — i — i — i — i — i — i — i — i — i — i — i — < < < < < < < ι- r- r- r- r- ^ j ^ m m m m m m m m c5 co C- co o> co co co m m m m m m m m m m m m m m m m ΩO-H-H-I-H Ji3i)-Dτnnι-oτ]CCcccccccccccccc r- r- r- r- i- i- i- CO C7. C7. CO CO ozocoooooo o o o o o o o o o o o o o o ooooooozoooooozzoooo > m o o DD > o α o CD > DDOD > oσoro > CDODO > NΓΠOOCD ro -v ro ->. ro - M -L ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro roro roro roro roro roro roro roro roro 4 s - ro ro ro ro ro ro ro ro ro ro ro -vi ro ^ ro cJ 4 s . -vi ro ro ro -vi -vi - ro -vi ro ro ro 4 s - Cj 4 s - 4v ro ro 4 s - c_o r ^ o o 4 s - CO co o o ro o to to ro b ro. ro ro ∞ oo r ro ^ -vi i 4ι_-> roj. ^ --J ^ -vj 4 ss -- ^ -vl 4 ss -- O -j ro CD " 44 s --- -* r c» -j ^ ro ∞ 4 s - O to 00 o -vj CO 4 s - ro -v| ro -vl o -v| o to o 4-. -»■ -- o -J co 4=- to ro co ro ro 4- o ro oo ro co ro ro o o to ro roro ro o 4 s - ro CO CO ro to ro 00 to 4 s - -vj ro 00 ro o 4 s - ro co -vi ro 4 s - 4>- ro ro o 4 s - co ro ro ro o o o CD ro oo ro o 0o0 o -vl ro ro 4 s - CO CD ro 4 s - ro co O 00 -vl o ro 4 s - ^ 4i ωω ω i 4- J> ^ ^ ^J> 4.4- Ji ^ *. J ^ ^ J> J J J- 4- 4- 4k ^ ^ ^ 4- ^ 4 s - 4 s - 4 s - 4 s - 4 s - 4 s - 4 s - 4- 4 s - ro ro ro ro 4 s - ∞ co cD θ o -^ ^ ιo 4 s - ro ro 4 s - SJ CJ 4 s - ro -vi co oo -vi ro ro ro ro co co co O 4>- Cj0 4 s - ro tO 4- C0 4>- ro CD 4 s . tO -». O C0 o o ro o _ o_o. ro_.. ro- i. ro w ji ω oco ω ∞ cfl ω N. ro ^ ro o cji ro ω -i iD ω -i M A W co ω ro r -' o ∞ ro r σ) ro o o o o ro ro ro to 4 s - o 4 s .4 s - ro ro ro ^ r o w ro ro ro io o 4 s . -vi ro M co -vi 4 s - -^ ro co w ro ro ■ vl ro -j ω -sj ∞ ^ ^ ω M -vi ^ ro o ro ∞ -^ ω ω co -vi co ro ro -vi co ro -^ -j ro ro 4 s - 4 s - ro ro ro 4 s - 4 s - 4- ro ro ro ro ro ro ro ro ro ro 4 s - 4- 4 s - 4 s - 4- 4 s .4 s - 4 s - 4 s » 4 s - 4 s - 4 s - 4 s - 4- 4 s - 4 s - ro ro ro ro ro ro ro ro ro ■ vJ oo t o -- co co p q q 4 s - 4 s » ω c_o -_v -^ --. q ro ro ro ∞ c» q cx> ∞ ro ro ro -vi ro OT oo q co ω o -». o co o co -^ --A». ωco moo mcj) bo bco ---^ to itLo) «ro ro_ιι A4 s . ro ^Ji bo fflco to ro_ ωco rocD bo kro_ 4- bo ωco fflrooocooro-».o-».-viooocDfo-vi co co cD 4 s - ro ro ro 4 s - -^ co cD c_o ω co oo oo oo o o co ro <_o -- ro o oo -vicoro->.cD-vi 4 s .roro-vjιo4 s .4 s .ro-vi4 s -roto ro ro cj cD Cjo ro ro ^ 4 s - ∞ 4 s - o -vi ro cD θ 4 s - -vj to o to ro o co 4 s - CD co co o-viroro-».oco-vico4 s -co^jrooro4 s -θ4 s - ro ro to θ-----iN)N. N. -i-ι---ι--r -iJ-i-i-ι-k-ι-i-i-i-ι-i---i-i--------------. _ co co ro to 4 s - ro o 4 s - ;oo U^N3UWJJMUOC000CJlO-»C- iiW^J>.r O-'( -i^UNlWMU().- ' --j to ro -->• o oo -- to CD -- ro M fl b α - ^ M ^ M co o i j co ro ' -i ro o όi b ro b ^ i M M CO 4s. d ^vl 4 s - if- co -^ ro ro ro oo ro co co w oo oo ϋi ro j > o ro n ro σ ) M θi oo χ i o ^ σ) - ι j > ϋi -i f ω σ) θ (o r o oo 4 s - -»• ro -»■ -vj LO t- -t J © © CΛ H α. O) N N T- N O CO O N CM OO CN N O x- ro uO Tf CO CO OO CO N xt N CD T- Tt CO CO CN O O M - ro o CN X-- oq CM Tt uo q O CO Tf OO OO UO CO CJ) CD OO CN CD τt CD CD O CO N CO --- CD OO N N '-- N O UO Tf UO UO Tf Tf Tf U0 CM Tt x- sT LO LO O M T- ro N in CN CM O O CD CO CO o o O O Tf CO Tf CN q uq f xt N uo d CM " ^ CM cb x- x- x- CM CM CN ro cb cb cb cb cd oό CO CO CD OO CD CD CO ro CD N N CD CD τf O O OO LΩ Cθ x- x- CM τt CD ro x- O x- τt ro oθ ro CD χ- O CO UO UO x- N CD CO CN --- τf x- ro iΩ CO UO N CO O N CN CD CN CD --- τt CM OO τf N O UO OO N CM Cθ ro CN CO OO CO CO CN CJ) x- CJ) x- x- CO OO x- CO OO CO τt O CD CD CM U0 N τf CN O 00 00 ro U0 O τ- x- 00 CM C0 N x- τt CD τf c0 C0 O C0 00 O τt C0 U0 C0 x- τt τt C0 CD τf x- N χ- ro C000 τf CD -r- N CD U0 U0 τf c0 x- x- O 00 ro ro ro θ O x- χ- Cθ ro ro C0 00 O CN CN CN τt cθ τt N CD U0 U0 CD U0 U0 τt τt τt C0 C0 CN CN CN ' -- x- τt τt τt f t τt t τt τt τt τt τt τt U UO U0 UO UO τt τ τ τ UO UO UO O UO UO UO t τf t τt τt t τ τt τt τt τt τt τ^ CN f U0 τt U0 O CN x- x- O CD CN CM O τt x- ro CD CD U0 00 O τt τt CN 00 τt CD Tt ro oo co cM uo N o ro N co uo ro uo cN co uo co N oo CO x- CD τt CO CO CJ) τt N x- CD CO CD CD CD CO OO CD N τt CD O CO LO N CO N CO CO O lΩ x- N CD CO N ro O x- CD Tt uo UO ro UO CJ) xt CN N N O N LO O O ro CD CD Tt N x- N CM CD UO CN CN CO UO Tt cO OO x- x- O UO N CD CM CO OO O O CO Tt CO UO CM N UO x- CD CN CN CN CN CN CM CN CN CO CN CM χ - χ - CO UO UO N N θ ro ∞ N ∞ ro ro θ O x- x- C» N C» ro CD UO τt OO CM CN τ- CO CD CO N CD N -r^^^ -f ^^^^ ^^^^^ ^ ^^ -f ^c c c c c ^^^^c c c c c co c c co c c CO CO CD CO O N CO ro cD oo o ro oo co oo Tf o o cN 00 CM N O N U0 CN ro χ- C0 C0 N τ- N σ) N CN N O τf τf c0 CD U0 C0 x- UO O O O CD O OO CM x- CO Tf N ι^ O_j Tτfr CrO», C tDu CtDu x— x— τj- Nr^ N|v» O t j xχ-— C D θ ro θ ) -τfr ccθo cC N M C CO D -τtr CN oO x-- C_D) N|L. C(Dϋ - x--- C CMM τ T-- xx-- C tϋO o ro o uo co o co Tf Tt CN CD CO UO N x- O N OO UO O CD N CO OO Tf CN UO OO Tt ro O Tt Tf CO UO CO CO CO ro CD O LΩ x- N LΩ CD ro ro N LΩ τt LΩ τt co uo ro θ τ- CN θ θ o ro ro o χ- θ χ- o o χ- ro χ- ro o ro o ro co ro ro co co ro o ro o ro oo N θ θ in in Ln UO UO UO UO UO UO UO CD CD CD CD CD CD LO UO CD CD CD CD CO CD CD UO CD UO CO UO CO UO UO UO UO UO UO UO CD LO CO LΩ UO U^ T- CN /n τ- CM τ- CM CN C Q O Ω LU N X X < 00 O Ω LU NJ < CO O Ω Ω LU LU N < C Q O Ω LU N X < CQ O O O O O Z O Z Z Z O O O o o o o z oooooooooo O O O O O O Z O O O O O O O co co co co co co co co co LU LU LU Lu m m m m m m O O O O O O O O O O O i- i- i- i- i- H; O: Q: Q O: Q: Q: O: O: Q: >: >- >- >- >- >- >- S ^ :^ X X X X X X X X X X X O: O: O: _Ϊ: Q O: Q: Q: Q^ © τ- CM CO (00)0 'r(M CO <D cD CD CD ro ro o o o o o o O O O O O X- X- X- X- T- CN CN CN CN m CΩ τt O N lO CD χ- χ- o cq t q χ-; N " N cb ιb cb cb τt OO O CN N CO CO τf x- ro x- N CO O χt N OO CO CD CO CO CO CO x- CN O CD ∞ CD O CN ro cθ N CD CN O N - LO CN CO '-- O LΩ ro θ N CO CN xt N CD CN CO N CD ro cO CN iΩ ro LΩ N ro CD CO O x- CM Tf CD N CN CO CD ro CN CN lΩ CD ro iΩ CO CO CN CD Tt UO CO ∞ CD O Cθ ro uθ ∞ ro CD CN CM x- N CO CN C» x- CD ' CO CO CN θ ro N C CO CN OO CO τt CN O CO O C» O CO CN UO x- N CO OO N CD CN τt ro O x- O x- O CN CO CO CO in UO UO N CN CN O O CN Tt CM Tf CD OO N CD N CO N CO CO N N N CD CD N UO N N CO ro CD N CO CJ) CO Tf Tt T Tt Tt Tt Tf Tt t Tt xt Tt x xt Tt Tt T^- Tt Tt Tt cO CO CO CO CO OO CO CO OO CO CO OO CO CO CO CO OO CO CO CO CO CO CO CO CO x— Tf N CD N N 00 O in N τf O τt U0 U000 CD N CN CD O CN 00 N τ- U0 CM O U0 C0 CN τf C0 CD O CO ro uo cN CN ro co oo ro uo N co oo cD ro oo N τt ιn ro N ro N uo cD τt ro χ- oo χ- CD τ- co cD ro co ro _ CO _ lO OO Uό UO UO CO UO CO CN CD Tf UO UO N ro oo N N uq cN q cq N oq cq τt x- cq cD ro τt x- cN N θ θ N CN χ- ro cM cθ χ- τt " ro ~ u " o " c ' o " q ~ co r- O CN N O x- x- LΩ q CM Tf N ro N cb ro ro cb cb cb cb ro d cb N ∞ cb cd ro d ro ro d ro cb od ro ro cb cb N CD 06 O x- x- ro c cb cM cb cM cb Tt x-^ d ro OO CO CO CO CO CO CO CO CO τt CO CO CO CO CO CO OO τt O CO τt CO CO CO CO CO OO CO CO CO CO OO Tf Tf Tf Cθ CO CO τt τ3- τ3- τt τt τt τt cθ OO CO τt τt τf CO in cN C τt O χ- CO CD CO Cθ ro CD N N CN CO N CM CD CO N - N N CX) ro N N CD τf CO CN τ-- CO UO UO N N OO x- O U0 C0 τt x- x- ro θ x- C0 U0 C0 CN C0 ∞ ro ro cθ U0 N x- N U0 CD C0 C0 C0 O CN N τt x- CD 00 U0 U000 in c0 τt C0 ro C0 CD C0 U0 N CN CO CN O x- ro ∞ ιn c O CN CO CO UO CO CO τf UO x- CO O x- CD N τ- O τt τt τf CN UO UO N CD UO UO x- CM CO O τt CJ) UO OO CD x- CO N CD UO Tt Tt CO CN CN t m UO UO x- O O x- ro CD CO CO O O ro o T- CN co co xt OO N CD CD CD UO N CD UO xt CO Tt oO CN CN CD CD UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO UO xt Tf Tt T^- io j Tf o uo uo uo uo uo xt Tt xt xt Tt Tt Tt T Tt T f Tt T f t - CM x- CN x- - CM Ω LU < m Ω Ω < CO O Ω < 00 Ω LU LU < OQ < 00 < CO O O O O O O O o o o o O O O o o o o O O O O O O O Z O O O O O O O O O o o o 7,\τ, > Z Z Z Z Z Z Z ,,, ,, Z Z Z Z Z Z Z Z Z O: Q : O: O: Q : Q : O: < < < < < -I..I. CL Σ ϋϋϋUJ-JJJJJJj _ J ϋ ( . ( . ϋ ( D ( 3ϋ ( . ϋr-hr-hhhh <<<<<<<< © N Cθ ro θ x- CN C τt LO CD N Cθ ro θ x- CN CO τt ιn CD N ∞ ro θ - CN C τt lΩ CD N Cθ ro θ x- CN CO τt UJ CO N Cθ ro θ x- CN O O O x- -- -- - x- x- x- χ- χ- x- CN CN CN CN CN CM CN CM CN CN C CO CO CO CO CO CO CO CO CO τt τf τt τt τt τt τ- τt τt τ^ o CN CN CN CN CM CN CN CN CN CN CN CM C CN CN CN CN CN CM CM CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ LO © © ! _ H U α. UO CD x- N N τt N CN CO τt oθ CD N N x- τt x- lΩ CO CN N CN CO CO CD Tt CD ro CN N ro oO CN - O CN Tt N OO CN OO OO x- CO CD CN cN ro cN χt N τt τt co ro ro ∞ cN χ -; CN t cq cq o co oo τt c χ - CD τt CN UO τ- τt CO CO τt q τt rø CO O CO τt CO N τt CO θq c c ro ro cN CN c c d d -^ cb d LΩ cb Tt uό c cb cN CN cb cb t T cb c^ - d ro d x-^ b od cN Tt M cd ib cb Tt Tf cb cM c CN τ- CN CM - x- x- x- x- x- x- x- x- x- x- x- x- O O UO ro oO CN CO Tf x- Tt CD Tf UO CD Tt x- in τf UJ CJ) UO UO CO UO CD CN CO CD N τf CN τt cθ CM τt N CD τt O CM τt O N CJ) N CO OO CO CD UO Tf UO OO O UO N CO x- CM UO x- CN O N τt CO C ro θ CO CD CN ∞ N τf UO CO CO N x- UO CO CD CN --- CD CN --- τt rv- CM CO x- . TTtf NN T Ttf uo cO CD x- N CO CD CO x- CD CO O CN O O ~ co cN ro oo χ- o o cN ro cN q q τf N o ro ro N τt N CN oq cN q O N N N N ro d x^ c o ro ro ro ro ^ c c Tt cM c cM t " ^ cN cb Tt x-÷ ^ ro d d d d cN cd ib ib cN cb o T Tt Lb uό ib c xt CO OO CO OO OO τt τt τf τt CO CO OO CO τt τt τt τt τt τf τt τf t t τt τf τt t t f τt t τt f t t t τf τf τt τt τt τt Tf Tf O OO OO OO CN N UO N CD O N x- o ro co ro N co τ- 0O CJ) U0 x- CD τt CM CO LΩ τf OO iΩ CD CO CN '-- τt ro θ ro co uo x- N co ro co co co m co cN ro τ- ιn τt τt N O CD UO CO O CO N τt ro co o ro co co ro τ- CM - CN OO CO O CJ) UO CD U O CM CO CO CN ro CM CO t ro CΛ cOoJ cCoD cLDD iUn1 c0oO coO oCOo cLDD O^ N| V - X— C cDu CcOo Ot_J ClN UUO) CLDL; Tτχt iuor) oOoO cCNN coD roO) roLθ cN CNN Uu^O N CM Tf x- x- CD UO UO CN CM o uo xt CD t x- ro ro ro ' ro d cd σi cd ro ro cd cb cb cb Tt x^ cM CN c^ CO CO τt C CO CO CO CO CO CO CO CO CO τf τ τt τt τf 4- τ τ τt τf τt τt t τ t τ^ C N CD O CD N N - CD ro N UO Cθ ro CN CO OO ∞ O x- τt O CO xτ- C CD N in x- Cθ CN N O Cθ ro x- CO CN τf CD CM ro τt N CD x- χ - ro o τf N UO UO UO O N CD ro CD C ro x- O N CD C» N τt t CD CO x- O CN N CM N O UO CO N OO O UO CN χ - CO CO N CO CO CO CO N CO CD ∞ CO CN 00 ro LΩ τt N C» N 00 C0 τt O U0 C0 τ- U0 U0 x- τt N τt CJ) x- C0 N 00 CD CD CN N O CD O N N O O N O CD x- x- θ ro ro cθ τt τt oθ UO UO CO N CD τt τt CO CO UO UO CD CD CN τ- 0 ro O OO CO CO UJ UO Tt O O O O O O 00 CO o 00 CM CM τt τt τt CO CO τt τ τt τt τt t τf τt τf t τt τt τf τt τt τt τf τt τt τt CO τt CO CO Cθ Cθ Cθ Cθ Tf τt τt τt τt τt CO CO Tt OO Tf Tf x- CN "<- CM x- CN x- CM x- CN x- CN CQ O Ω Ω < OQ Ω LU LU < CO O Ω Ω Ω L O O O O o o o o o o o OQ OZ o o < O O O O O ooooυoΩzLU No XzXzz <ooo CυQ OooΩooU LoUoNz <o CL CL CL Q. α. Z Z Z Z Z Z Z Z Z 33333333 O O O θ LU LU LU LU LU LU LU LU LU LU LU Q: o: w(owww-i J J J -J -i-i-i J iij uj yj uj iij iij iij iij Q: Q: Q: Q: D:D: [_ D: tt: D:Q: i ii i i i i iii i _j _j < < < < < O O _J _J -J _l _J _l _l _l < < < < < < < < < < < 0_ Q- Q- CL Q. Q. CL Q- Q- Q- Q- C0 C0 © 00 τf U0 CD N C0 ro θ x- CN C0 τf U0 CD N Cθ ro θ x- CN C0 τt U0 CD N C0 ro θ τ- CN C0 τt U0 CD N Cθ ro θ x-- CN 00 τt U0 CD N C0 Lo uo uo uo uo uo uo cD CD CD CD CD CD CD CD CD co N N N N N N N N N N co co co co co co co co co cO ro ro ro ro ro ro ro ro ro O CN CN CN CN CN C CN CN CN CN CN CN CN CN C C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ LO © © ! _ H U α. CD CD O N N CO CN CM CD O x- ro CO CD x- CO O O Tf CN CN C _D C —O . OO LO CO O CN CO CO CN CD CD Tt CD xt UO CD O x- Tt CD N CD O OO UO O OO ro N CD UO x- O CD CN N CD O CD OO CO CN CN CD CO CO CD τ- O O N UO CO OO CO CN CM CN ro χ- O UO CJ) N ro CM N UO UO ro τt CO τt CD U0 U0 U0 CD N N CO CM xt OO CO UO UO N N N CO CN Tt Tt CO CN CO CN τ- Cθ 9 cN CO xt Tt CO Tt CN OO CO CN T- CN χ- Cθ CD Uθ ro CN CO χ- ro oθ χ- N CN Cθ CN - CD Cθ ro x- CD CN CO O CO CO CD N ro τt cθ '-- OO O N CD N χ- CO OO CO U τt θ CM x- Cθ ro θ UO τt UO CD O CO N N CO N N τt ro CD - LO CD CO O O τt CO CN θ ro cθ C LO CN N τt N CN Ln cθ CO CD O τt N CO UO CO UO θ ro CD ro θ CO ∞ x- τt CN τt C» ro ro CN τt Oθ ro θ CD CN CO τt CO C» O CO τ- CO OO O N OO N x- CD N CJ) N CO Cθ ro LO N CO CO CD CO N N ro CD CD O N CD N CO CD CD N CO ro UO UO CO UO CO ro O x- ro O CN CN CO CN x- CO x- CN CN CO O O x- ro x- CN τt τf t τt τt τt τt τt τf τf τt τt τt τt t τt τ^ t t x τt τt t t τt τt U0 UO τt U0 UO O UO UO UO O UO U O U U ^ Tf in in LΩ uo uo o CO UO CO LΩ CO O CJ) τt O UO OO CO x- CM O CO ro CD CO CD CD Tt O CD CO O UO ro O N CO UO x- Tf CO x- N UO CO CO T- CM O f ro uo ro O N CO CD N CD CD Tf x- θ ro x- Uθ ro CD UO CN UO τf CO CO τt CD UO CD N OO CD --- CN CN '-- C .J) O CO CM - CN N Tf CO CO Tf O N N 00 CN - LO CD C τt CO N Tf N CD CO OO O τtrouocococoroτf co O N UO f N ro Tf CN CO CO O N CO CN UO CD CD x- 1 d o ro cN cb cN CN Tf ib ib cb cb N ' N ' CO ^ ^ ddd dcMro ' cocoods O O X- - X- O CN CN CM X- CN oo t Tf in o ro Tf Tf Tf CO τt τt τt τt τt τt τt τt τt Tf Tf Tf Tf Tt Tt Tt xt t Tt Tt OO CO CO CO CO Tf Tt t Tt f xiJ- j- Tj- Tt Tt Tf Tf Tf Tf Tf Tf CO CM CD N N x- OO τ- O N N τf CO CO CD CN O --- N O UO Cθ roτ- CJ)CJ) CJ>N ---COx- CO x- τ- x- O CD CM CN CO τ- O CM CO N τt OO ro cD co cD τt co ro cM co uo o ro oo oo uo N CD CD uo co ro co co cD --- cN ro N CD CM U0 ro x- C0 x- CD CJ) τf U0 U0 CO 0O Cθ CN CN q uq o co uo uo x- N CN CN uo oo Tt N q ro uq cN cq uo ro co co co N N ro cD CN v-; co q ro cD CD θ χ- χ-- N ∞ uq " -r^ o ro ' cd o -^ c θ c -- c c ∞ d c uθ b Lb ∞ CM x^ N ' cb uό uό cb N ' xt cb uό xt τt τt xt τt τt xt cθ CO τt τt τt τt τt τf τt τt CO CO CO CO CO CO OO CO CO CO CO C C C CO CO CO Tt τf τf cθ C C CO -- CN x- CN x- CM x- CM x- CM x- cαO < CQ O Ω Ω UJ LU N I < CO Ω Ω < OQ < oo < oα Ω < OOOOZOOOOOOOOOOO OOOOOOOZOOOOZOOOOOOZOOOOOOOZO m 33 _ι _ι d d d O O LO © © ! _ H U α. CM OO OO ro x- OO N O UO CN CD x- τt O τt UO CO N N CN CD CD LΩ UO CO CD CD UO UO Tt N N CD CD CD CO CD UO CN CO UO O OO cM ro co co co co o x- co Tt o χ -- cM in N co τf ro χ - N oo OO CO Tt UO O CM CO CO O x- N Tt UJ CM N x- ro CN UO CO CN OO Tf Tf CN co ro o Tt CN Tf CN cb τf ib cN Lb N cb cb N o ro x^ ∞ N N N N cb cb od N- co N cb N ' cb cb ro cb ib N " x- x- x- CN T- CN T- CN CN - X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- o cM oo co N o ro N xt ro oo uo ro co co ro oo N uo cN Tf O CD CO N N CO CM N CO N CD τ- N CN τf τf τt CJ) N N CO CO x- x- CM LΩ ro U0 x- O CM N O C0 CN CD CD τf x- C0 O τ- 00 OO O N τf CO χ - τf CN '-- CN O Cθ ro τt cθ CN N --- τt oθ CD O q co Tt ^- q N N q o cN Tt o x- ro x- cD co o oo xt x- O CN O τ- ro θ O CN CO Cθ CD CD ∞ CD CM UO τt τt UO CO CD CD cb Tt -^ x-^ cN -^ cN cb ib N c N N ro cb N cb ro d N ib xt c ∞ d ^ cM ro d d d x- τ- cN d x-^ CN c d ro x^ m uo uo uo uo uo uo uo Ln m uo uo uo uo uo uo Ln m uo cD uo in UO UO UO UO CO CD CD UO CO CD CO CD CD CD CD CO CD CD CD UO CD CD Tt O OO ro CD CN x- CO ro CN LO CD Tt Tt CO Tt OO LO N CD ro CJ) N N OO CO CD CD CO O T- CO CN CD ro N CD OO CN O Tt x- m O CO CO - cθ O N t- N v- O CO τf ro cθ O CM τ- N CN O N LΩ N τ- x- ro cθ CO UO N CO O UO CO O τf LO Cθ ro cθ CN τ- ro oo τt ∞ ∞ q iΩ o ro τt cN χ- ro χ- cD τt o χ- co τt Tt N CO CD O x- N N OO CO ro cO O OO O Tf O O CN OO O uO cb o cb N N cb N cb cb cb cd d x-^ d x^ cN d d ro cjJ ro o ro o ro co N N N uo Tf Tt co Tt cM co co ro o o ro ro o CO CO CO CO CO CO CO CO CO CO CO Tt j- j- Tf t Tt Tt CO CO CO Tf O Tt CO CO CO CO CO CO OO CO CO CO CO CO CO CO Tf Tf CO CO Tf Tt CO CD N xt CN N x- CD CO CM CD CD UO N N CM CD x- N CN co co ro o oo o χ- oo co o ro cN co o χ- χ- N θ N CM ro uo UO χt CO N χt CO OO UO CD θ ro cθ OO UO CD x- CM --- x- O CO τf ro τf iΩ ro χ- co χ- τf x- ro τt cM co uo τt co cD θ u ro τt q cq t LΩ χ - q τf cq ro ro N ro N LΩ uo N uo co uo o cN ∞ N CM N CM N τt cN N ro co τt cN uq N ro q N τt N uO t Tt cb c x^ ^ o uo Tf c c cb cN x^ d d ro Tf t i i Lb uό d Tt N uό cb cb N cb Ni c ro ro oo co co co co co co oo oo co oo co co co co co co co co co co CO OO CO CM CO CO CO CO CO CO CO CO OO CO OO CO CO OO OO CO CO OO T- CN T- CN x- CN - CN 0Q Ω LU LU < < 0Q < CO O Ω UJ N < CO O Ω Ω LU LU N < oo O O O O O OO Z O O O Z O O O O Z O O O O O OO Z Z O O O O O O O O O O O O O O O O D=)=)3333^ >->- 5 5 O CO CΛ CΛ CΛ CΛ LU LU LU LU LU LU LU LU UJ LU LU ooooooooooo 5<<<5 CO CO CO C << >> _l _l _J _l Q. Q- Q. Q- O. Q. Q. Q. Q- Q- Q_ d d d d d d d © UO CD N CO ro O x- CN CO xt UO CD N CO ro O x- CM CO Tt UO CD N CO ro O x- CM CO Tt lO CD N OO ro O x- CN OO Tt UO CD N Tt Tt Tt Tt Tf lΩ lΩ LΩ lΩ lΩ LO lΩ m m in cO CO CΩ CD CD CO CD CD CD CO N N N N N N N N N N CO OO OO OO CO CO CO CO o CN CM CN CM CM CM CN CN CN CN CN CN CN CM CM CN CN CN CN CN CM CN CN CN CN CN CN CN CM CN CN CM CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CM CM CN CM CM CN CN CN CM CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CM CN CM CM CN CM CN CN CN CM LO © © ! _ H U α. o co uo ro CM CO CO -- Tf CM x- CO O CO CD CM CN v- CD CO CO ro cO CO LΩ O Tt LΩ CO N OO N CM CO CO ro CD O OO CO LO CN CD Tf o N T- uo ro CO ro CO C T- CO UO o o ∞ cN in uo N ro co co χ- cN uo N N q cq cN cN N co co N N CN N CN -- Lq q c s s co cdco cocM rM s ro ro co co s oro d ro b bbb bs ^ s∞ s ' co ro ^ s ωra ro d s ' b∞ ro co CN CN CN CN CM CM CN CM CN CN CM O ro CO Tt CO CD N CD CO N Tt cO C.M..N CN ∞ N Uθ ro CN C» CM CO CO τf τt CD τt lO CO CD Ln oO N N CJ) Cθ LO CD N τf x- CD τt N O OO CD O UO CO UO CO N CN OO CD O UO N CO O N τt OO CO CO CO τf θO CO CD O UO CN N CO UO O θ ro CD UO O O τt Uθ ro ro CN U T- co N Lo ro oq cN Tt ro N N co o ro Tf CN N CO CD τ- Cθ ro CN --- CO CD O LO N OO N --- N CN x- - ro CD CN CO CM --- O CO d x- CN cb cb x^ x- CM CM CO τf τt ιn CN CM CN O χ- O χ- CD CO CM -- χ- τt τt x- x- CD CO x- O CD N N CD N N CD OO N N CD CD CO CD CD CO CD CD CD CD CD CO CD CO CD CD CD CO CD CD CD CD CO in CD CD CD CD CD CD CO CD in UO CD CD UO UO UO UO UO UO UO UO UO UO UO UO UO N 5 OO CD CD CO CD CN ro N UO CO N CN CO x- CM x- N CD - LO O CD CO O CO ro Tf Tf CJ) N ro cM oo oo oo Tf x- ro uo o co ro uo ro co CO N OO x- O O N CO . N .- >, CO Uθ ro N N CJ) N O UO UO CD CN OO O UO CO CO O τt CNτ COu C>O. - m -.. i-n.. u-.o. co o N O CM Tf ro N CD co cN q ro iq x- CD ∞ CO τt CO τt CD CM CO CO CO CD CJ) τf x- CN OO OO CO UO OO Oθ ro x- τt CD CO CD CM O τf ro co co uo co N d ^ x-^ CM CM OO Tf Uθ ro ro rø N CO N CD UO C» N CD N UO τt CO CM OO CO OO CN CM - oO τt C CO CN CN UO UO CD CM θ ro CD O CD Cθ χt τt τt τt τf τt τf Tt CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO O CO CO CO CO CO CO OO CN CN CO CM OO co r- d Tf x- CN x- CM Ω < CO O Ω LU < CO Ω Ω < CO < CQ O O < C Q o z o O O CO o O O υ o o o o o o < CQ O O O O O O O O O O OO O O O o o o o υ h- I- h- h- H h- H H >- - >- >- Q_ CL Q_ Q_ Q_ CL O_ Q_ Q: Q: Q: D: Q: D: O: O: Q: Q: O: O: _J _l _l _l _l _l _l Z Z Z Z Z Z LU LU LU LU LU LU LU LU y j j j (/)(/3 (θ(θto ww (θ uJ iiJ iiJUJ UJ iιι_Jiii _J i_ιuj _j < < < < < << -ι - j -ι -ι -;- j ^ θ < < < < < < < < co ω co ω coco coco co co co co > > > > > > > 000000 © C» ro θ χ- CN C0 τt LO C0 N C0 ro θ x- CN C0 τt U0 CD N Cθ ro θ τ- CN C0 τt U0 CD N Cθ ro θ x- CN C0 τt LΩ CD N CO CJ) O --- CM C0 c» co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o χ- χ- χ- χ- χ- χ- χ- χ- χ- χ- cM CN CN CM CN CM CM CN CM CM co co co co o CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO O^ CN C CN CN C CN CN C CN CN CN CN CN CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN C^ LO © © ! _ H U α. CD Tt CN x- CN CD CN CO CN Tf ro θO CM CO N O CN CO N CN CJ) x- N O CD LΩ χt in τt CD CD OO N Cθ ro N CO UO CO O N N Tf CN N CO CN O Tf cO O N CO N CD O LO CO OO x- CN O N x- UO CO CN CO O CM CM CO CD CO UO CO OO N CO in x- - CM - Tf o CO Tf N CN CO UO N τ- ro uo N uo uo uo τt o o co τt co χ- oo uo co oo co o ro ro ro ro uo τf uo uo uo Tf CO Tf lΩ x- τf ιo cθ CD CN OO LO x- CD N CD C CO CN CN CN C CN CO τf ιn ιn CN CN CN CN CN CO τf t τt CN x- x- x- x- x- x- x- x- x- x- CN CN CN CN CN 0O CO τt UJ CM CN CM CO UO CN UO Tt CN UO O OO ro uO o co co uo oo N ro ro o Tf O CO Tf cN N co ro x- ro cD Tt cN O T- ro cD in co o T- uo CO τf O N UO O τt τt χ- cN τt OO OO N CO τt N χt τt o χ- m co N τ- co ιn ro N N CO N UO CO CO UO O UO CD UO N O CN OO ro UO N N CD O xt CN CO LO CN UO τf q N Uq τf ∞ ∞ s- ro ∞ N τt cM x- τt σ> cq Tt CO - x- ro ro Tt x- CO CO Tt CN CD OO CN CD OO Tt ro d ro co N- uό cb oό cb d cb xt cb cN Tt ib ib xt cb cM CN -r^ c cb cN f c f Lb ιb ό uό o c cN τ- : t t ό ι N- CM in cD in Ln LO uo uo uo uo uo cD uo uo uo uo LO LΩ LΩ uo uo uo uo uo uo uo LΩ in O uO uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo uo oo t χ- uo co uo N ro co N uo N CD τt ro ro co o N τt -- uo c» cM ro N ro oo ro N θ uo N CN co cM ro o τt o uo ro ro cN τt co co N CO CN CO CD τt CD τf ^ σ) O x- N OO Cθ ro N CO CN C ro N O CN N τt CO CN C» τt ro θ OO N N CD UO CO O O x-- τt OO CD UO N O N ∞ Tt Tf N ro co cD oo oq q uq q oiq CN N C co cD co ro iΩ N CM CN oo τt cN CN - x- uo o cD - co ro τt ro τt o cD co cq ro ro N ro od c N- N uό d d d ro ^ cN c T^ Tt d d c od d cN cb cN Tf Tt N CN CN CN CN CN CM CN CN CN CM CN OO CO CO CM CO CO CO CO OO CO CO CM CM OO CO CO CO CO CO CO CO CO CO CM CN CN CM CN CM C^ co cD co ro o N θ ∞ o τf co τt co uo co ro τt uo ro oo cN CD co o τf ro χ- uo cM oo cN o ro o LΩ o ro ro uo o cD N θ N oo uo cM in ro ^ τ- co co ιn co ^ (D co ro o co cD co o ^ o oθ ' CD in co o co cD S CM τ- cM ro cD co ro ro τ- co s cM τ- cD 'r cM S CN τt N ∞ ro cD θ θ co cN τ- x- ∞ N o uq τt q co τt τt N ro χ- co o cD ro τt o τt o τt cN ^ uό uό uό d ro cb cb ro d d d cb c ro cb Ni cb cb d x^ x^ x-^ cN CN CN cb cN cb Tt CO CO CO CO CM CM CM CM CO CO CO CM CM CM CM N CM CM CM CM CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO n x- CN "<- CM /κ τ- CM τ- CM CO CM C CM Ω LU LU < CO O Ω Ω < CQ Ω UJ UJ < CQ O Ω Ω LU LU LU N N X < 00 Ω LU N < O O Z Z O O O O O O O O O O O O O O Z Z O O OOOOOZOOOOO OOOOOOOZZOO ZZZQ.Q.D.11Q.Q.D.ZZZZZZZZZQ.Q.Q.111[LD.Q.1D.Q.1Q.WW(O(OWC W( C033D -_JJJCOCOCOCOCOCOCOCO^-I-I-I-I-I-I^-JQ:Q:Q Q:O:Q:O:O:Q:O O:O:Q O >->- >->- r-- 000<<<<<<<<OOOOOOOOOHHHHHI-l-HH HI-l-H--J--J^--J--J--J--J--J--JOOO © τt LΩ CD N C» ro θ x- CN CO τt UJ CD N Cθ ro θ x- CN CO τt UO CD N C» ro θ x- CN CO τt UO CD N Oθ ro θ x- CN CO τf LO CD N Cθ ro o C CO CO CO Cθ 00 τt τ4- τj xj τt τt τt τt t τ u0 U0 U0 Ln LΩ U0 U0 U0 U0 U0 CO CD CO CD CD CD CD CD CO CD N N N N N N N N N N CO OO OO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C CO CO CO CO CO CO CO OO OO CO CO OO CO CO CO CO OO CO OO CO CO C^ CN CN CN CN CN CN CN CN CN CN CN CN C CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ LO © © ! _ H U α. cN O x- oo co co ro co co uo cN ro co o CN CO N N CM CO O CO xt O x- x- N CO O N O O O OO CM O CO O Tf cO o ro co co in o Tt CO CO CO N O x- Tf O CO O CO O Tf CN uo co Tf ro co oo x- CD CO LO N CJ) CD CO CD - N CD U0 00 CM CJ) CD - CO t x- co ro co in O τf N in ro x- τt cθ τf CM UO UO N C C τt CO CD Cθ N ro cθ CO x- CO O CO CN CO CM UO CD CO N UO CD CO CO - CN CD N CD O N O Cθ CO τ4- u U0 CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO 00 τf τt τt τt τf CO CO CO CO CO CO CO CO τt τ^ CD ∞ ro τt C τt CN CN x- CO CO Uθ ro ∞ CN O CO CN - N UO C CN ro ro oθ τt O C» N O x- O CO UO N τt cθ Cθ ro τt CO N τt ro N ro τf τf CO CO CD O N N τt CD ∞ ro N CD τt CO τt τt N CD UO τf C» O CO LO O N UO CN CO CN τt ro x-- CM CN N CO UO x- N ro UO x- τt uq ro ro c q cq ro o ∞ χ - q co τ4- | v . o τt co ro o co cq τt τ ro i . cq q ^ cD N τt N χ - c^ ro cM cb cb oo " τt d ∞ cb ro ro ro ro cb cb N cb ro N N N ιb ιb τt " τf UO O UO UO UO UO t τt τt τt t τt τt τt τ τt t t τt τt t τt t t t t t τt τt τt τt τt τt τt U UO Ln in τf τt τ^ ro co α. co co -o s co co co o cM co o uo χt s ^ co ^ τ- ω co co τt ro co co co cM uθ θ s co ^ cM ^ ^ uo ro co (D \f ^ co ιn - Tf Tt CO Tt CO CN CO CD CO O CO x- CD UO N CD CO N UO CD ro uO x- ro CD CD O ro ro O O CO CD CD O ro N CN CN CO UO CM UO Tt CO N O x- cq oq ro ro ro x- N x- -i x- - q i ro uo q c uq ro T^ N t^ oq uq q Tt L q cq ro q ro Tt Tf ' o ' c cb cb cb d x^ cN d N Lb uo uO t o cN -^ c T^ CM CM CM N CM CM CM CM ( CM CO CO CO CO CM CM CM CM CM CM N CM CM CM CM CM N CM CM CM CM CM CM r- CM CM CM CM CM τ- τ- τ- x- x- r- τ^ uo ro co ro oo Tf oo ro co co Tf o X— Tf 00 CM χ- τt ∞ ro cN N CO O CN τt CO CO CO Cθ ro CJ) χ- LΩ N CO CO CO O CN CD CN CO O χ- CO oo uo x- ro xt ro uo ro cD uo X— oo Tf X— O uo O N UO N N O CD - O O x- CO - O x- CD x- CN CD UO CO x- CJ) O UO N CD CD CD CD CO CD CO Ln oO CN CN Tf UO UO O ro Tf CD in CO τt x- 00 00 CN ro ro CN 00 CN CN O - τt CD N CD U0 CD ro ro ro 00 τf x- N O CN τ- O N CD C0 in χt CD C C ro ro ro N CO C0 O x- χ- CN CM CM θ ro θ x- ro 00 00 N N CD - CM CM C0 00 CN 00 τt CO x- x-- O O O x- CN CN CN CN CN CM CN CN CM CN CM CN CN CN CN CO CO CO CO CO CO CO CM CO CO CN CN CN CN CM CM CO CO CO CO CO CO - CN x- CN ^ T- CM x- CN - CN CQ Ω LU LU < CQ Ω Ω < OQ < CQ O Ω Ω LU LU < OQ O Ω LU LU < CQ O Ω O O O O O O O O O o o o o O O O O O OO OO O Z O O Z O O O O O O O O O O O OOO 33333333333333 θ: o: Q: o: o: : w w w w w c/ - c/ . CΛ CΛ fΛ 333333333 CL 0. CL Q_ 0_ Q_ Q_ CO CO CO CO CO CO CO _ι _ι _ι _J _J _J _J _i C0 C0 C0 C0 C0 C0 X X X X X X X X X X O < < < < < < < © O x- CN C0 τt in C0 N C0 ro θ x- CN 00 τ4- ιn CD N C0 ro θ x- CN C0 τ^ UJ CO N 00 ro θ x- CN C0 τt U0 CD N ∞ ro θ x- CN C0 <» co co oo oo co αo ∞ co oo ro ro ro ro ro ro ro ro ro cD θ θ θ θ θ θ θ θ θ θ - x- x- x- x- x- x- x- x- x- cM CM CN CN CN CN o CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO τ τt τt τt τ τt τt τt τ τt τf τf τt τt τt τt τ^ CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM N CM CM CM CM CM N CM CM CM CM CM CM CM CM CM CM CM CM CM CM W LO © © !_ H U α. CN N o in oooooooooooooooooooooooooooooooooooooooooooooooooooo OOO ooo ooooOOoOoOoOO ooooo ooOqOq x- CO O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O ddddddddddd D N- CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CN CN CN CN CN CN CN CN ro co CO CN CO OO x- x- x- Tt CD x- 00 Tf cM oo ro ro uo o co N CN ro N UO CD UO CO CO CO N UO Tf- f cos ' scDs ' cds ' coσi Tf Tf Tf CO CO OO CD CD CD CO CO - Tf O CN Tf O N x- CD T- N O LΩ CO x- Tf o O Tf CN O CD CO CM x- O CM CM x- O O O CD CO CO Tt O CD O N N CO CN x- CO CO CO τf c τr cθ CO O τt τf ro Ln ro Ln ∞ χ- cN co cN o ro ro cN θ uo co ro ro co N τt N N τt cN N CN CD co ro cN τ- cD τ- N CN CN ro oo LΩ ro ro co cM θ co ro Ln χ- ∞ ιn χ- τf τt τt ro N N ro co cD - co Ln ro cD uo cD uo co - ro ∞ co N co ro τt τt oo ro χ- τt x- co o cN N CN τt oo cD ro cN N ro co τf τt uo co co τf co o co co co o uo o c» τt cM co ro τt cN CD τ-- co τt χ- ro c co ∞ N CN - o ro χ- χ- cq uq ro d ^ d d d d d ro uό cb Tt cb uό cb c t r c LΩ ib i ib Lb ^ CO CO CD CD CD τt τt CO τt τt τt Ln u0 U0 CD CD CD LO U0 U0 CD CD CD CO CD CD τt τt τt τt τt τt τf τt τt CD CD CD U0 U0 U0 C^ CN CNSθ n n CO CO CO CO CO CO OO CO CO OO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO C^ <<HI-l-HHHHHI-HI-H H H HHHh-h-l-l-HHHHHHHHHI-HHI-HHHHI-Hh-l-HH © CD N o CM CM Tf Tf CN C τt ιn CD N ∞ ro θ χ- CN CO τt UO CD N OO CD O x- CM OO τt U5 CO N OO CD O χ- CM CO τt CN CN CN CO Tt LΩ CΩ N CO CD x- x- x- x- x- x- x- x- CN CN CN CN CN CN CN CN CN CN CO O O O CO CO CO CO CO CO τt f τt τt τt co ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ro ro -j -vi -vi -vi -vj -vi ^ -vi -vj -j ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro o ∞ -vi ro ro 4 s - ω M - i o co ∞ -v] ro ro 4» ω -* o co ∞ -vi ro ro 4 s - ω ιo --* o cΩ ∞ -j ro dddddddddddddddddddddddddddddddddddddddddddddd HD J T. I ^ T: ^ ^ TD I TJ TD I ^ I I I I I I T. I ^ I I T3 I TD I TD TD TD TD I I I J TD ^ CJO CJ OO W CA- CO CO CO CO W OO CO CJO W OO CO CO CO CO W OO CO CJO CA- OO OO CA- CO CO ro ro ro ■ vl -v] -v. ro ro -vi -v j ro ro ro ro ro ro 4 s * 4 s - 4 s - ro ro ro ro ro ro ro o - » - co co 4 s - 4 s - 4 s - CO CO CO o O 4 s - ro 4 s - CO co -». rror. oo co co ro -vi co ro o -vi o CD ro oo ro -vi 4 s - co o ro o 4. s .4. s - c _j). c_o_ o_ 4. s - c _o c _D 4. s - to oo o oo to -»■ ro ro co oo fo cD ro o 4- r co ro 4 s - co 4 s - 4 s » 4 s - C0 C0 C0 W fO rO 4 s - 4 s - 4 s - fO IO NJ IO IO 4 s » 4 s » 4 s » CJ C0 CO C0 C0 CO CO C0 Cj0 l^ O O O 4 s - M -i -A ^ ω ω o co o ∞ M M ro Λ ro ro ro w M -A ^ N ro M M ro ro w ω Nj ω ro o α vi vi -i o o ϋi 4 s - 4 s - • vl -v| CD IO 4 s - co ro ro ro oo -- > ro -J 4 s .4 s» 4 s« ro 4 s - -^ o ro ro - vj -g cD co -^ - j ro co cD ro ro ro ro -vi ∞ ro ∞ ω co ω ro co ro ro ro ro o M o co ^ M o ω co iv. ω o -i ω oo ϋi σ. iL. -i vi vi o -i co o xi oo oi -i -i Ui o ω -si oi co -' ro M oo ω ^rooo roo A ro ro ∞ ro --^ ^ ω M --i C) 4 s » co ^ -Li ^ co co ro 4 s » --^ ro ro 4 s - o ro M co ω -vi ro ro -vi ro co M Cj c^ ω co co co co co co co co ro ro ro co co co ro ro ro co co co 4_- 4 s - 4 s - ro ro ro co co co ro ro ro co co co ro ro ro 4 s - 4 s - 4 s - CO O CO CO ---. M ^ 4 s - ro ro oo cD θo ro oo -vi ro ro ro c» LD Lθ 4 s - ro 4 " >- ro ro ro 4 s - 4>- ro ro ro ro ro ro c» co oo to to o ro 4 s . ro ro CD co -vi oo -vj oo ro co 4 s - ro co -»■ to ro -vi ro co co - j .4 s - ro ^j co -vi co -j -J co 4 s - --J ro • -J O o ro ro oo ro co 4 s - co -vi co cD 4 s - ro ro oo -vi -vj o 4i. ro oo ro -»■ -»■ -». ro oo ro oo cD -vi co ro cD ->• 4 s - co -_. n --j co 4 s - ro o ro co o ■ vi 4 s - ro 4 s - 4 s - 00 CD o co ro co -si oo co -». -». co ro -vi o co 4 s _ co -vi co o co ro co ro --. oo ro ro to ro co ro 4 s - 4 s - ro ro o 4 s - -v| oo to -J 4 s - -J o MqMoIqNq) Nq) WqNqWqqN) IqIqMqWqqM MqIoMoIoMpMoWoMoMoWoMoMqqM MqNo) IoNoJ MoMoMooM MoMoooooooooo dododododododododododoooododododododododododododododododododododododododododododododododo ooooooooooooooooooooooooooooooooooooo o CMoCNoCMoCMoCNoCNoCNoCMoCNo oooooooooo CNoCNo ooo CN O O O O O O O O O O O O O O τf N ro τt N 00 CN C0 U0 U000 CD τt CN CN O N CD O C0 CD θ ro CD ro τ- ιn iΩ LΩ N N CM C0 CD LΩ CN τt CN 00 N O ro θ ro N τt CO N CD τ- τt ro cθ x- O CO CM O UO CO CM CM Tt t N ' a roc cb Tf Tf t ' cbc uOTtcbuON- τt τt τf τf τt 0O CO C CO 0O CO CO CO CO CO CO CO CO 0O CO CO C0 CM C0 x- x- CJ) C0 CM ro 00 N N C0 x- τt ro θ τt C0 C0 CM x- Tt oo ro ro N O CM ro cM co co xt cD CD oo co ro ro co cN lΩ LΩ CO CD xt N N N CJ) τt cθ CM N CD CD ro τf x- CO OO CN CD N CD CJ) O N N OO OO Tt cO CM x- CN CO x- x- O ro ro x- x- x- CO CO Tt OO CO CO CO CO CO CO CO CO CO CO CO CO CN CM CO N UO OO CO x- OO CO CN CO UO x- CJ) CM CM o o cocoχ-cooτf coooooouooχ-oococDCJ)cθLθCNLΩCMθoooouocoτtLnro 0O CD - N U0 x- U0 CJ) U0 N N CM UO CM CO CO CN τ- N CD CJ) ro ro 00 τr cM CM CM ro N C0 CD U0 θ ro N O O τt O C0 x- N τt U0 U0 Tt ro ro uo co co ro ro N CN O Tf CO CO x- Tf N τt cN τf '^ cN co uo N - ro uo ro ro ro τ- ro uo χ- cN θ oo o co N θ co uo co ro τt τt co o χ- o ro ro ro N c» N τ- x- x- ro ro ro o o o N CD N co τt co co N N oo ro ∞ cD CD in ιn Ln N τt co τt co co cN CN τf τt t in in Ln τ- τ^ τt τt τt τt N N N CN CN CN CD CD CD CO CO CO τt τt τt CO CD CO 0 LΩ LΩ U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U0 U^ CN CM CM CM CM CN CN CM CN CM CN x- CN O Tf UO CD N =■= X X ^ X χ χ χ χ χ 1 X X =■= X X ^ X χ X χ χ X χ χ τ- CN CO τf U0 CD x- - x- x- x- x- χ- O÷CMO^CMO CN O X- CN O xX- xCN 5O x x CN O X- CN O X- CN O - CM O X- CN O - CN O O O O O O C0 O O O O O Z oo co co co co co o co co oo oo co co co co co co co co co co co oo co oo oo co oo oo oo co co co x Ix Ix Ix Ix Ix Ix Ix Ix Ix Ix Ix Ix I IΛ -_= 9= ._= -_= .__: ._= __= __ι __= __= ._= ._= ._= ._= -_= _-= __= --= _-= 9^ H h- l- H I- h- l- H H H H H H H I- l- l- l- h- H - l- H H H H H H H H H H H Z Z Z Z Z Z Z Z Z Z Z Z Z © O x- CN CO τf lO CO N Oθ ro θ x- CN CO τt UO CO N CO ro O x- CN CO o x- CN CO Tf lO CΩ N CO CD O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CM CN CN CN CM 00 ro ro ro ro ro ro ro ro ro x— x— x— x— x— x— x— x— x— x— x— x— x— — x— CN CO Tf lΩ CO N OO ro cococororororororo to->.ocooo-viroro4 s - OOOOOOOOOOOOOOOOOOO I IxIxIxIxIxIxIxIxIxIxIxIxIxIxIxIxIxIx o 4 s -o4 s -o4 s -ocoocoocoooocoocoocoocoocozroorooroorootoo--.o->. ro4 s -ocDθo-vi ooro 4 s -coro-irocoro-iθcooo ro ιo 4 f ir iro o cococo co roro ro co roώ j>. r coroo ro corococo roro-vi 4 s - tococo4 s .ro-J 4 s - coro-».ro qqqqqqqoooooooooqq ddddddddddddd ddd OOOOOOOOOOOOOOOOOOO GLU 1 HB 54.780 70.799 36.314 20.00 GLU 2HB 53.860 69.333 36.440 20.00 GLU 1 HG 52.473 70.1 18 34.379 20.00 GLU 2HG 53.234 71.688 34.607 20.00 LYS N 57.077 70.71 1 34.138 40.99 LYS CA 58.1 15 71.521 33.434 41.50 LYS C 58.730 70.802 32.190 39.57 LYS O 58.673 71.310 31.076 39.12 LYS CB 59.261 71.933 34.428 45.89 LYS CG 58.918 73.024 35.497 51.71 LYS CD 59.986 73.136 36.630 56.13 LYS CE 59.423 73.478 38.036 59.81 LYS NZ 60.210 72.951 39.186 62.35 LYS H 57.200 70.440 35.092 20.00 LYS HA 57.601 72.409 33.064 20.00 LYS 1 HB 60.122 72.290 33.861 . 20.00 LYS 2HB 59.590 71.028 34.944 20.00 LYS 1 HG 57.935 72.822 35.923 20.00 LYS 2HG 58.812 73.990 35.000 20.00 LYS 1 HD 60.756 73.854 36.348 20.00 LYS 2HD 60.497 72.177 36.711 20.00 LYS 1 HE 58.404 73.085 38.137 20.00 LYS 2HE 59.313 74.564 38.135 20.00 LYS 1 HZ 61.199 73.268 39.140 20.00 LYS 2HZ 60.194 71.902 39.141 20.00 LYS 3HZ 59.783 73.242 40.090 20.00 GLU N 59.247 69.571 32.450 38.42 GLU CA 59.583 68.656 31.386 37.30 GLU C 58.523 68.608 30.274 34.58 GLU O 58.814 68.798 29.094 33.74 GLU CB 59.912 67.281 31.966 40.63 GLU CG 60.000 66.235 30.835 46.16 GLU CD 60.673 64.854 31.065 49.22 GLU OE1 60.508 64.217 32.105 50.86 GLU OE2 61.374 64.376 30.167 51.79 GLU H 59.306 69.279 33.408 20.00 GLU HA 60.487 69.052 30.916 20.00 GLU 1 HB 59.208 66.970 32.737 20.00 GLU 2HB 60.879 67.339 32.462 20.00 GLU 1 HG 60.482 66.668 29.959 20.00 GLU 2HG 58.967 66.050 30.534 20.00 PHE N 57.266 68.373 30.681 31.46 PHE CA 56.238 68.253 29.653 30.49 PHE C 56.102 69.457 28.733 33.05 PHE O 56.072 69.315 27.517 31.17 PHE CB 54.928 67.999 30.280 26.00 PHE CG 53.774 67.886 29.306 23.39 PHE CD1 53.283 66.628 28.992 24.75 PHE CD2 53.136 69.002 28.777 23.83 PHE CE1 52.145 66.498 28.272 21.69 PHE CE2 52.023 68.860 27.977 23.15 PHE CZ 51.514 67.599 27.755 22.50 LO © © UI H U α. O O O O O O O O O CO CN CO CD CD X- CM O OO O O O O O O N CD CD CO X- C.M. O CO U) O O O O O O O O LΩ CJ) x- CM χ- LO N . O _ O _ O _ O O O O O O O O O N CD CO CO LO CO CM N CO O O O O O O X- N UO CO O N CD Tf CO O O O O O O O O N N CΩ CD O CD CD CO O q Oo Oo d d d d d d ^ d ^ ^ CN ^ cd d r O c i _ Tt od N d d d o d d d d d cD CD co co cD Tt o d d d CM CM CM CM CM CM CM CM CM CO CO CO CO xr iO in CO CO CM CM CN CM CM CM CO CO CO CO CO Tt LO in Ln CM CM CM CM CM CM CM CM CO CN CN CM CM CM CM CO CM CM CM τt x- C0 O C0 CM x- CD U0 CD N C C0 τf |v- cD U0 U0 U0 U0 -n θ xr CD O C CD O LO CO CD N xt Tl- T UO N N CO CO OO N N O CD Ta- CD CO CO x- CM O τt CM CO CD C χ- CJ) C CD C CM LO O CO χ- CD τf Ln c χ- CO χ- m x- CD CN CM CJ) N CJ) τt cD O C CO CD CD C CM N O χ- CD CD CO CM O CM C C C CO CD O CD CO CO O O LO x- CO LO LO Tl- j- O x- O CO CO CD CO CO CJ) CO O CO x- O CO ro CM CO CM O ro CO x- CO x- CO CO CO CM O CO CO N CD CM x- cq X- CD O O CJ) CJ) CO N N CJ) CO N LO CJ) O O O O O N d d s d iri o N ro d co N N d d iri ^ io d ^ N iri CO CN CO CO CN CM CN CM CM CM CM CM CM CM CO CO CO CO CO CM CO CO CM CN CM CM CM CM CN CN CN CO CN CN CN CN CM CN CO CO CN CN CN CN CN CM CN CM CN CM CN xr CJ) CJ) UJ O N x- CD U0 x- U0 N CJ) Tf x- CN in CO lO CJ) Tj- C ro θ CD x- CD 00 χ- O LΩ O O τf x- x- x- C0 CJ) CM t CD CM O U0 C0 xt C0 t τf U0 N CM O CD CO Tt O O CM CD CD CJ) χ - τt σ) χ- χ- χ- xf CM CM N CM CO ∞ C0 C0 θ σ) CN C0 N C0 C0 U0 σ) τf U0 N C0 L0 x- τt cθ UJ CD C0 C0 x-- CD CM CM χ - τf N O N O O N τt co oθ q τt o cD CM co co N cq ro cj) χ- C0 LΩ CD CD O CN O CN O O C0 CD C0 O CJ) C0 U0 O τt c0 N C0 CD τf CJ) t CM χ- O ra cd sNc(Do Niuriidoirii o) NN dθ r- ( CM CrM fCO. nCO LιnO LιoO ιLrio do ιx--^ ncb w CN cco n ' χ r-' : rx- : θd χτ- τχ- χτ-- : od rocJ) χ -- : xτ-- : CtM θd CcMNi ^ Oo oO rCMN fflCD CroO CiDO ωCO CιoD (LDD Uu). LuOι oCJ ) . C ^DO N^ CD CD CD CD CD N CD CD CD N N N N N N N N N N N N N N N N N N N N N N CD N N N N N N N N N CD CD LO LO CD CD CD CO CD CD CD LO x- N D UJ C ro τr cM C CN C C CO τr C » τf LD θ CO τf CM LD J C N ro τr ro CN C D ro χ- O Ln CO τt c co roo røιn τtcθ χ- ro cN LΩ Lθ co cD roLnro oo c»co Lθχ- Nro LθcococMτtrouj t oco uj tτf χ- UO CD ro c» τf N Uj LD O CO x- O CO τr J CD τf ro ro CM UJ CM CN UO CD x- LO O CD Lq x-; CN q CM Lq CD ^ ^ c co ^ d O N N io xt N- uo ro uo ^ cD ^ ∞ o. UO lΩ LO -Ω J in LO lΩ lΛ LO in uO in iΩ lΩ lΩ LO Ln in iΛ lO O Ln iΩ lΩ lΛ LO CQ DQ J" CM x- CM x- CM DQ 00 O O oo oo O O LU LU x- CM x- < χ χ Q Q LU LU N < CQ Q U LU < X X X X < m O Q j LU < X X X I < mO OQ < DQ X I X- CM X X X X X o υoox x-cMx-cM oooυυoozxx X X x- CM x- CN x- CN oυooυυυxxx LU LU UJ UJ UJ LU LU UJ UU 3 33333333333333 xxxxxxxx LU LU LU LU LU LU LU LU LU LU LU CL CLCL CLQ. CLCL Q.Q.00000000000000000000000000000000 © o O x- CM CO Tt LO CD N CO CD O CM C τf Ln cD N Cθ ro θ χ- CM C τf in CD N CO CJ) O χ- CM C τt U CD N Cθ σ) O χ - CM C xt ιn cD LO CD N CO CD O O O O O O O O O O x- χ- χ-- x- χ- χ- χ- χ- x- CM CM CM CM CM CM CN CM CM CM CO CO CO CO CO CO CO CO CO CO τ τt τj τa- t }- τi- CJ) CJ) CJ) CJ) CJ) χ- x- x- x- x- x- x- x- x- χ— x— LO © © UI H U α. O O O O O O O O CD O x- CN CO CD UO xt O O O O N CO ro CD CO CD x- CD CN O O O O O O O O O O O O O CO x- O CO CO CD O O O O O O O O O O θ q UO Cθ N CM O χt cM O O O O UO N OO χ- N χt CD CO CD O O O O O O O O O O O O O CJ) χ- CD χ- χ-; q θ θ q xt T ^ f u o o cb x-^ t c M ^ ro d CN CN CM CM CN CN CN CN CO CO CO CO CO CO CO CO CM CM CN CN CO Tt T^ x^ T Tfr J lO Tt CN CN CM CM CN C Tf CO C CD O CO UO Tt CO LO CO Tf CD O x- Tf N UO CO CD CD 0 ∞ ιn τf cD CO CD O CO χ- τf CJ) C CD N Lr) CM CM N N CO τf CM C CD N CD N CJ ) CO CM x- CO CO f r-. o N CD O xt x- CD CM CO N CO CD CO LO CD CD N ro N O x- τf ιr) σ. UO x- CN C CD O CM CJ) CO O CO CJ) O τf τt CM O CM τf UO τf CM N C O O CD CD co o co co o N co co co m ιn τ- o N cD co m ^ N N σ ~) co cD uo N co N cq cq cq x- uo co co x- co N cq q uo q N x- ro cq N CD Tf CO Tf N ∞ ∞ Tt co c x-^ Tf f c Tf ib b ib ib c cM T- o c c Tt lO Tt Tf cM Tf c cM c ib b t c ib L ^ o σ- ro x^ cM CM O x^ o CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CN CM CM CM CM CM CN CM CM CM CM CM CM N CM CN CN CM CM CM CM CM CM CM CM CM CN r- CO o L CθD C CNN x- x- CM CM τf θO CO CJ ) Ln oθ CM τf cθ θ m cD C CD CO CM CN Tf x— UO CM CD CO CO LΩ UO CJ) O CO Tf Tf |v_ CO τf CD LO CD CD U0 CJ) χ- χ- o O N τ Ttt N N l LΩΩ θO L θ CN N xt LO C x- σ) CJ) x- CJ- CJ) τf CJ"> τf τf LΩ if) CO τf χ- CO τf CN lO CJ) CΩ N τf co Tt σ. σ cj) o N CD 0O CJ) CM χ- τf x- N P COJ x^—- CUDJ CI -NN- U C-J)J U- LO-J - NI s - ^" I CNN N^ UCJ)J C«OU OU UU) CC 1 ) iχ-- CIMN UCJ)J UO LUOJ CUD) Tχ-- |NS OU x-- U CItΩ) ICNN OGOU CUJ)) (CUO xr-- xT-- PC) UCJ)J CTJ Nis TXTf W CO UUJ) x^-- TXfT ou CD Tf CD x- CO CD UO x- CO N ιri τ f τ f ' ιri oro σ_ o o ro ∞ oro ∞ χ- roχ c c cbτ f τ f τ^ x- O CJ) x- O x- CM CM o O CO CO LD LO CO CD CD CΩ CD N N N CO CD N O LD N CO N N N N N N N N N N N N N N N N N N N N N N N N N CD N N N N N N C N CN CO CO x- CO CD τf |v_ ι ; c CD χ - CN x- CD O CM x- Tf N x- UO N CD CO CO CO CM O CM UO CO CO uO CN T- N CN O CO CNCN CN Tt Tf O x- Tf CO O CO Tf co m CN lΩ N x- O CM CO CD CO x- O CO CO CJ) CJ) CO CM CD C CO CD CD τf CJ) x- CD N N N O χ- CM CD CO CD χ- Q τf N CJ) Tf O o T t CO i n CN ∞ l Ω CM CD N q q CD CN x- CN N i n i O N co c χ- cθ χ- N co co o N τf cq ro χ-; ro cq c χ - LΩ σ) τt o cN χ- N uq co ro cq τf CO CM d ro N cb cb cb d d ιb χ t cb cb cM uό τf τf dcD NN ∞co N ccbo croj. o χχ-- : CCNN CD c^ N N ' ro σ. cN CM cb c) d cj- d χ- d cj) d co couo inioinin cDuo inininuoinuoin inin u in in inin uoin iotocDCDinioinincoininω x- x- CM CM CM x- x- x- OOOOOQQQ x- CM CQ ω ω ωOO Q Q N ,_. ^ co ω XXXXXXX < ω o Q Q < x x < CO Q LU N < OQ O < χ X x- CN x- CN C x- CM C υυoυoooxx x- CM υυ oo υ υ o -∑. x <xx UJ LU N N X x- CMxx-xCMxx-xCMxx-xCMxx-xCM CO O OX X χ- cN c C CΛC0Cθ <ΛCOWC CΛCΛW J JJJJjj J_lJJJJJ_iJ JJ JJ J(/)(/)C/)()COC CO(. C)(β o N CO CJ) θ χ- CN τf iΛ CD ∞ θ - CN C f UO CD ∞ θ χ- CN C τf lΩ O ∞ ro θ x- N C xf iΛ Φ Tt Tf Tf LO in LO UJ LO LΩ in iΩ Ln Ln cD CD O LO CD CD CD LD CD CD N N N N N N N N N N CO CO CO CD CO CO CO CO CO CD ro ro C^ LO © © UI H U α. o O CO J) o O O O CD N CD Tf LΩ CO O O O O O UO UO CO CD O x- O CN N N CO CD N UO O O O O O O O O O O UJ CD CO CO N O O O O o CD CO CO x- O O O CD CD CM oocoooooocDroτf coNrocMθCDuocDcocDcooooooooqqqNCMτf Nuιqqqq o ro d iri N o cM x^ ro cb c cb o x^ x^ ^ cN x^ x^ x-^ cb d c ro CM CO C C C CM CM CM CO CO CM CM CO C CN CN CM CN CN CM CM CN CM CM CM CM CM CM CM x- CM x- x- CM CM CM CM CM CM CM CN CM CM C^ OO O CN CO CD CD x- CD CD CM Tf f CM CM CO CO Tf rv. LO CD CD CD CD O x- CO N lΩ CM CD CO CD N N CD CM x- N CD CD CD CD N N CN O CD N N x- CO CD CM x- CD CM CO Tf Ln uO Tf CD CD CD N CM Ln cO CD O C LO CJ) CM U N UO CO CJ) O N CO CM CJ) τf τf c CN χ- O χ- CD O C CJ) CD C .O_ N UJ CD N 00 CD O C τf U ) τf CM CD CD CO LO CO CM O τf cO C N N CM Tf CDi CNI CNI O CD CM CM Tf CD N Tf ιq CN Tf CM x- Tf CJ x- CO LO x- CO O CO CD CD Tf CO ( d o- ric dc cnd o ' ^^ ^ N ^ cfl - ' x^ CM x- x— CN (b cb f lb lri ( τ— CO CM x- CM ^ f |v. CN CM x- x- x- CM x- x- CM CM CM CM CM CM CM x- CM CM CN CM CN CN CM CM CM CN CM CM CN CM CM CM CM CM CM CM CN CM CM CM CM CM CM x- x- CM x- x- x- x- x- xt CD O x- CO N CD CO CN N x- CD CD LΩ LO N CM CD CO Tf x- f CD CO CD CD CM N CO CJ) N CO CO O C C CM CN CJ) CD CM τf O τf c C CM O C C N CJ ) OO O lΩ x- τf cD CJ ) UO CJ ) O CO χ- C CD x- CM f CD C CJ) O CM O LΩ CJ) CM O CO CO Tt LΩ N x- CD CD CN CD N UO CO Tf Tf CD LO CD CO N N C roD NN τ Tff C ∞O U inO Oo U inO O q O coO Lιθq cθo CCMM Cco CCDD LιOo x- C CO xx-- CCO O O C COO NN C CO CCO C CDD x- x- C COO xx--; CCOO x-; CcO χ- ro ccoo qq qq qq ccNM CCNM cco NN LLqq xτtf cCDD CCDD ccqq NN xχ---; ro " ro cb N cb __ d _ cJ) cb N iri τf co cΩ _ N . N . Lri c _o uo co_ τf cb τ- ; d cb τf ib τf cD uό cb Lb cb τ Mf- i inri CM N CM CC N CCM db cN Od Od cJnj dp ccMM ' Cσi LO LD LO CD LD N CΩ CΩ CΩ LD CD O CD CΩ CD CD CO CΩ CΩ CΩ CΩ CΩ CΩ CΩ CD CD CΩ CD CD CD CD CD CD CJ) Tf CD CM CD CM CO x- x- CO CJ) CM CO CJ) CM CD LO N CN x- Tf d d cd N cd oo CQ OQ ^- x- CO CM C CN o < < 00 00 .. ,„ τ- CM x- CM CO CM C CM ^ oo co X X < oo O < χ χ O < COO Q Ω UJ UJ UJ N N X < χ χ Q LU LU N N X < Λ oo < x x X o o x- CM O O O OO X X X- CM X Z O OO OO OO ZO OO O O X X- CN X X X X X X υooυxxx-cN 0_ >->- >->- >->- >--_ a_ Q: _E _E Qi .__-rQ_:Q ct Q- a. CLCL CL_ iΩ-i- -i-i- - -imm [Ω[iι [Ωu m{Ω x Y.QLo:cLCLCLfc C ϋϋ ϋ ϋ(30(0(βC. (0(Λ(ΛW(Λ WCO(Λ I- h hl- H h h h h h h r- l- © o ro θ χ- CM CO τf U) CD N Cθ ro θ χ- CN C τf u CD N Cθ ro θ x- CN C xt UJ CD N Cθ ro θ χ- CM O xt Lθ LD N Cθ ro θ χ - CM C^ ro θ O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CM CM CN CN CN C C C C C C C C C C τf τf τf -^ τf τf τf τf τf τf UJ χ - CN CM CM CM CM CM CM CN CN CN CN CM CN CM CN CM CM CM CN CM CN CN CM CM CM CN CN CM CM CM CM CM CM CN CM CM CM CN CN CN C^ LO t- t JN © © UI H U α. O Tf CO CO N C O O O O o CD x- x- O OO C O OO O O O O O O O O O O O O CD CD LO CO CO x- N CO Tf cO CO O O O O O O O O O x- O CO CO x- Tf D o o o o o CO CN CN CN in cO LO CN o o o o o o o o o o o σ) Lθ CD θ τf U) N θ co cM CD τf o o o o o o q q q N d^ dcoV T- o o o o o o o ro o ^ i co iD d d d d d d d d d d d o ffl oi ^ io io iri N io ffl N io d d d d d d d d d d CM CM CM CM CN CM CM CM CN CN CN CM CM x- CN CN CN CN CN CM CM CN CN CM CM CM CM CM CM CM CN CN CN CM CN CN CM CM CM CM CM O τf NN roCN roN U C D0 OO Uin0 C x O- χO- C C OO NN CND ro C χ C D- τ L Ωf CroM N C M CroD τCDf U L O0 LOΩ N C D CroM CcθM C C OO N x - 0τ0f CCNJ) CroO NU CO0 C x M- CC0M ττft c x 0-- iNn C C 0 xτtf L x n- ccθθ ττff clv0. Ccs0g τ--f- U^0 χ^-- C^ N " roo ^ ^ oro roo co o M c f t t t c ιricM t tιb tω χ - x- CM CM CM CM x- x- CM x- CM CM CM CM CM CM CM CM CN CM CM CN CM CN CM CM CN CM CM CN CN CN CM CM CM CM CM CM CM CN CN CN C^ si t LO CO χ- CN CO CO O CN ro x- CO LO N τf CD χ- τf |v. |v. τf cθ CD f cτ. CM O CM N CM C τf cO χ- χ- O O CO Ln cD CO UJ U^ CO N N N N CO τf CJ) τf uθ ro CN τf θ ro u CO χ- O LO LO C x- τf τf CD χ- χ- CM N CD CM CD τf x- CM χ- N ro LΩ LO UJ τf r-. τf UJ x- ∞ O UJ C N N N C O C D τf x- N τf CD τf UJ CO C O C O CD C N O N C θ ro c C M ro C M x- C D O N N C D CO τf r-- rv. cq τf ^ x- x^ " cN CN θ co cb cN χ ^ d cj ) co χ ^ cb χ - : cb cN χ - : χ - : cb c χ d χ co CO CD CO CD LO CD CD CD CD CD CD CD CD LO lΩ CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD in LO lΛ LO UO LΩ Ln in Ln i^ ro O N O N O CD CO C .O. C.O. O C -M . O C —O N . N C —O C —O O CO CJ) I _O. C .O . -' S . CO X— C CO O L-J C IMN C LDU C IMN C UOJ C LOU X- N I-- T XTf c COJ T Xf C LDU C LDU x X-- N 1^ C INN! C LDU C UDJ T XfT c LDU CO O CJ ) τf O CM τf U inO CcOo CcDo CroD CcoCD CroD NN CcOo CcDo χ x-- χ x-- CcDo CcOo rocN Tf co inro Nro cNcocD CNCNTf cN coN ro Tf cN cocN inco roco ro cNCD N I—- O L_J O L'OJ C LDU C IO'J C UDJ C LDU C LUO τ XTt N I-- C U —DJ C U -J)J N - I—- C L -O'-J O L —-J N - I—- C U —DJ U - U-OJ τ XfT τ XfT | Iv—.- | Iv—.- C -J N I -— - τ XfT X- r Iv—.- o L-J C LDU C L Ω U C I N NC L θ U L LDU N I — C LO'JN I—-C I N NL UOJ N I— - O L-JC LDU C I N NC LUO τ XfTι UnJ C LDUC CJ C LOUC LO'J C UJ)JC LLOJ C L'J cb x- CM CM cb cM O CM CM CM cb x^ x- ' x^ CN d d o CN x^ CM CD d d LO CD CD CD CD CD CD CD LD CD CD LD CD CD CD CD CD CD CD LD LD LO LD CD CD CD LO CD CD CD CD IΩ CD CD UO - . — i x —- . CsMi r CsMr r CsMl - - - ω CO CO CO x- CM x- ^ OOOOOQQQ x- CM x- CM CO 0O τ- CM χ - CM x < CQ < X X X < oo Q <coχxxxxxxx < OOOQQUJUJN X <χ χQ QLU LU X CO ZO O o X x- CM CO υooooυ υ X X x- CM x- CM CO x- CM CO O O O O O O O O O O O X X X- CM X X X X X <<<<<<<<<<< C£Q . αιctα_: tQ_:Ω;ct:Q . c£Q_ι_ t :ctQ__ECtQ;ctctcκ.z: <<<<<<<<<<<dddddddddddddddddddf-PPPh-HI-l-l-l-HI-i-l-i-l-h-l-l-l-l-0 © o χ - CM C τf uθ CD N CO CJJ O χ - CM C τf LO CD N CO CJ) O χ - CM C τf ) CD N CO CJ) O x- CM C τf ) CO N CO CJ ) O χ - CM C τ^ in iΩ Ln iΩ lΩ lΩ LO O LO CD CO CΩ CO CD CD CΩ CD CΩ CD N N N N N N N N N N OD CO CO CO CO CO CO CO CO CO CJJ C^ CN CM CM CM CM CM CM CM CN CN CM CN CN CM CN CN CN CN CN CN CN CM CM CM CN CN CN CN CM CM CM CM CM CM CM CM CN CM CM CM CM CM C^ LO © © UI H U α. Tf CO CM f |v_ D N O O O O O O O O CD LO CO C _D CO CM O CO _ O_ O_ O_ O_ C.O. C.O. C_D .N UO x- uJj τ TfΓ θC_> OLJ OL_> OLJ OL_J OL_) O1-J OL_J OL-J OL_J OL-J τf O τf O O J CO J N N N CO Tf O O O O O O O O CD N N CM NN OO OO TTff Oo OO OO OO CCDD CCOO CCDD OO NN CCDD CCDD TTff OO OO OO OO OO OO OO OO OO OO OO CD CN N CM CO co χ - cM CJ) co o co χ - 0d 0d 0d 0d 0d 0d 0d 0d cM cd χ- χ- cD χ- : χ - : cM d d d d d cD cb OT CN CN CM CN τf U0 U0 U0 CN CN CM CM CM CM CN CM CM CM CM CM CM CO CO CO CM CN CN CM CM x- x- x- x- x- x- CM CM CM CN CN CM CN CN C^ CM CD N CO CD CD CD O N in LΩ N CM O O CD D CO LO Tf O N CD CM CO CM CD CD CD CO Tf Tf CM N CM N CD CO Tf LO CO O O CO CD N O UO UO CD CD CM o coco ^co c co ^ ifi N CM CD in cM N CDin co co ro cθ τ- co o rτ- cM ro co ιo cM c o ro co ro ιn co oo co(ø cocD N θcn O O CM N 00 cj) cp co ro c N co cM CM τ-; co co ro ^ ιn ιnuo (o ιn co c^ x- CM CM CJ) CO N d ^ d cb cN cb Tf u. ' cb cM c cM co i L uό CM CM CM x- x- χ- χ- CN CN x- χ- x- χ- χ- χ- CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CN CM CM CM CN CN CN CN C^ o ro t o M ^ Nx- f c ^^ iocNin ^ -O xf o ro in c o coio ^ ro io ro ^uo N C O O co T-io oo in N oo o o CD f Tf O LO x- CM CD O ιn σ c c ιo o co ιo c Ncoω co ^ N ^ ^ N ro oj - θ o co ^ cD θ) o σ) τ- cn θ - o o c o cs co ^ ' '- Tf CO CD CO N LO Tf CO N CO θσ) ω ifl Cθ ω CM ^ CO CM CO C CD ^ ^ ^ (S O. τ- C - τ- (DO lO - (O O OOIO f CM CM O O CO N lθ ro N CD rN CM Tt c co Tf cM N Lq cq d^ d N ro N∞ ό N io d N iri io ∞ d ∞ d co d ^ f b N N c cM x^ CM O LO in uj j o j Ln in LO u iΛ LO LO LO in LΩ Ln in LO Ln LΩ LO D O in iΩ LO iΛ in in LO iΛ LO iΛ o L^ CD x- CD N O Tf |v. |v. CM C0 CD Tf rv. C0 CD CD O U0 C0 N x- C0 CJ) CO Tf Tf CD CD CD CD Tf x- CM N O N Tf r-. CO N O CD CN CN Tf T f x- CN CO CN T f cO N CJ ) CD C CO CM x- τt CO χ - N CO CD τf c χ - CJ ) χ - LΩ CM O χ - CD O N C CD CO CM CD CO CD CD N x- CO CM CD CO CJ) N CM CO x- CD lΩ CD CO xt CD CO CO τf cD N τf x- CO CD CN CJ) UO O Ln CD N CO OO CJ ) τf CM CO N CO Tf CD N x- τf x- CD CD O χ- x- U CD CD C UO CJ) τf χ- τf n χ- LO O χ - CN N CJ ) CM cb co cN χ- ' χ- : χ-- : d χ- χ-- cb cd o ' χ- ; d d cb τf τf lΩ lO LO CD Lb cb lb cΩ Tf CO CM CM CO O C CM CO O d c5) CJ- CJ. d cM CN cb co CΩ O CD CΩ CO CO LD CΩ CO LΩ LO LO CΩ CD CΩ CD CΩ CΩ LO LO LO LO CΩ CΩ CΩ CD CD CO CΩ CD CD CO CD CO CΩ L^ .„ ,_ CM CM 0000 LU LU 7~ CM OO 00 < ω O Q LU UJ < X X X X X X < oo O Q Q <χ χ < 00 δ O Q υoooooozx X x- CM x- CM x- CM υoooυooxxx-cM oooυυoυ z z z z: -∑. -z. z -Z Z ZZZ ZD.D.Q.Q.Q. D.D. D-Q. Q.Q. D. OOOOO OOOOOOOOOO jOjOjOjjOOjjOt <nω<(<β(<oc<nw<w<(<nc<o(<ΛC<flt< ω d ω dd ωω d ω d ω d ω d ω d ω dd tul d lJl d lJ1 d 1JL d 1Jl d lJ l d lJl d lJl d lJl d lJ Q<:Q<:Q<:D<_tt<: © o CO τf ) CD N CD CJ) O x- CM CO f uO CD N CO C_ O χ - CM CO xf lΛ CD N CO CD O x- CN CO τf UJ Lθ N CO CD O x- CN CO xt l^ O O O O O O O χ- χ- x- x- x- χ- χ- χ- χ- χ- CM CM CM CM CM CM CM CM CM CM C C C C C C C C C C τf τf τf τf τf τf τf τf τf τf ιr) L^ c coc coco co co coco co co cococo co co co co co co co coco coco coco coco co co co cococo co oococo coco c^ LO © © UI H U α. OO N χ - CN O CN O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O τf |v. cθ x- N CO CO O O O O O O CM CN x^ N CM x-^ cq q O q O O O O O O O O O O O O O O O O O O O O O O O O O O O CD CO αO N N N CD O O O O O O O O CN ώ ώ i^ ώ ^ ή ό ό ό o o ό ό ci o o CM CO τf .χf iΛ CO CN CN CM CM CM CM CM CM CM CM CN CM CM CN CM CM CM CN CM CM CM CM CN CM CM CM CM CN CN CN CM CN CN CM CM CO CD CD CD CO Tf x- CD CO CD UJ CO f CD x- CN CO in CO Tf CM x- CD CO O CM CJ) C0 N x- CN x- U0 N τf 00 τf σ) CJ) C0 CM O χ- τf C0 χ- CD N CJ) CD UJ C0 C0 x- CD OO CM χ - CD LΩ CD τt c x- LO OO CD O N LΩ o CO O M- N N x- CO CO CD CD CJ) CM UO O CO C CD CD CJ) C CM CD CO N CD CO CO CD CO χ - CD x- CD N Tf CD N N q N CM cq cD N CJ) Tf CO CO N CM CM CD CD t Ln c D N iΩ C) co χ-- N N q θ n τf cj) τ cD c LΩ q c c c O) CD σj r-i a. cb cb CM CD CD N N CD O CO CO Tf Tf N T- ^ oi cN N c cd iri N N c N N c ro N uo d d N d CN CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM x- CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM O LΩ CD Tf CD Tf CO N N N CΩ CD C N CO CO N CN CO N χ - CD x- CM U0 N CD N τt CD N N LΩ x- x- x- Tf Tf uO χ - N CO N lΩ τf O CO O CD CN Tf CD CO N . - U -O CM Tf CO O _O. C-N- O_O x.- C -O__ CN CN O C „O . CJ) CD CD χ - UO N x- CJ) CO N O χ - CO CN CD CD CO Tf in CO Tf CLOj U«OJ Nι^ CLLOJ CO CM Tf Tf CJO x- CO CO N CO cO in in CM CM CD N Tf x- CM OJ in CM CD CD N CO CD N UO x- N N UO CD O CO N UO CD O CM CO CN Tf J CO CO CO Tf . x- x- CO N x- CO CN x- x- ^ ^ d ^^ o o - d ^ ^ d d ^ cN ^ T^ d cM co c iri ^ uo c d o ' cN τt CM CM d d cb τf U U CD cb CM cb cθ Tf Tf O LΩ LΩ LΩ in iΩ LΩ lΩ lΩ IΩ lΩ lΩ lΩ UJ lO UO lΩ lΩ lD lΩ lD lΩ LO O in iΩ UO UJ in in in in in iΩ lΩ UO lΩ lΩ lΩ CO CD CD Tf CO CD N CD N CO x- CD N O OO N LO CM LO CD Tf cO CO CO x- C Tf cO CO CO ) O O CN N x- CM N CD CO CO CD O CO CO CD CD CD CM CD x- CO CD τf UO CJ ) x- x- x- UJ U) Ln θ CJ ) CO CO O CM O CD τf τf tv- UO CN CO O CD LΩ CD CO CM CM LΩ χ- σ) LΩ Cθ CO x- CO τf CD N LΩ N CN CN CJ) U0 U0 U0 CD C CN CO C x- x- O CD CD C .M. C.M. C_O. C_O. C.. O_ O_ C.N. C_D. C.N. C_O_ N. O _ C_D Tf . x- tv. O CD CD Tf tv- CJJ OO N N UJ N CO CO CM N UJ UO U Tf r^ CO CO CD UO Ln Ln x-- cj cd D ^ ^ cN CM C i σi cb N- iri ib Tt b cb CD LO LO LO LO ιn CD CD CD CD Ln u CO CD in Ln ιn ιn iΩ CD CD CD CD CD CD CD Lθ Lθ CD Lθ CD CD CD CD CD CD ω x- CM oo oo Q Q C. "- 000Q ■ «- CM x- x- CM ω oo Q LU N X X < X X X X X X LU Q LU LU < X X Q Q LU < CO o Q J LU < X X X X O O Z ~Z- ~Z- X X X- CN X- CN -<Γ- CN X O O -Z X X x- CM X x x OOOOOOO X x- CM x- CM O O O O O O O ϋ O O O O O m fn m m m . - rn fn , n m Z> 33333333333333 < OL CL L CL L C T CL OL CL CL fZ CL ttl Ω CZ C^ <<<<<<<<<<<<<<<<<<<xxxxxxχxxxxxxxxxxoooooooo ooooo< © o lD CD N ∞ CJ) O x- CN CO τt lΩ CΩ N ∞ σ) O χ- CN CO τf lO CD N ω C- O x- CN C τf Ln CD N ∞ C_ O χ- CN ιθ uθ io uo uj co co coco cD co co co co co N N N N N N NN NN co ω co co ω ∞ co ω ∞ (D cn cn c. cn (j) σ) CDσ) θ) σ) θ θ θ θ θ o o CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO LO © © UI H U α. UO O x- O O O O O O O CO CD C q q q q q θ O ∞ & -r o o o o o o o χ - χ - CM CD UJ CO CO O ) O CO O UO CO CO CJ) UO CD O χ- χ- Ln CJ) CM CM LD CJ) τf N N CN x- τf cO τf τf CM τf cθ x- CJ) CO N in χ^ CJ) N x- CD CM C CM CO LΩ C CO CD CJ) CO χ- CM CM CO CD CM CO C CO CD CM CO τf CM CD N CD 0O N N CO χ - CJ) CD χ t CJ) τf x- CD O OO CO x- OO OO CO LO CO U -J C —D C —D x- x- C —Ω x- CO - "N N x- O — CN τf ) CN CN OO CM CO O x- CD CJ) CO CO N CM τf CD CD CO CO Tf UJ CO CO CO Ln O Tf O CD Tf Tf cq c q in c M Tf N N CD N cb c cD N N cd cD cd N θ χ c CbD σ C. oO d O χ- : cb N N N iri τf τf - ∞ j uO o N ro ^ T^ N N N cd ffi ^ d cN r CN CN CN CN CN CN CN CN CN CN CN CN CN CO CO CN CN CO CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO CO CO CO CN CN CO CN CO CO CO CO CO n in CM CM N LO UJ CD O CD N CO CD Ln CN τf x- τf θ UO χ- τf c τt lv, CM CO CD x- CD C O UO C CD O O CJ) o O x- C0 00 O O Ln CM Ln τf c0 τf C0 LΩ O UJ x- O O C0 00 O CD x- in CM N LΩ C0 C0 N τf |v. cM C0 CD 00 U0 τf O 00 C0 τf UJ 00 00 CD O O LΩ LΩ o χ - C CD N CD CD N N τr χ - UO O CM x- co ro c co ro q co in cM ro ro ro io co in o N ro co ffl ro co io c cM N S cn co c cMS U in oo co Tf CM LO x- τf CM CD C cq τf c cD cq c q d N N ' d co N Lri Tf f ' j D ' d Tf Tf i ^ cd cM x^ x^ N CO CN C τf O CJ) CO CO CJ) 0 d x-^ x-^ CM CM O CJ- Cb CD CJ- x^ x^ cb cb τt τf τf τf ιθ τf τf ιO τf τf τf τf τf τf τf τf τf τf τf τf τf ^ τf ^ τf τf τ f τf τf τf τf τf τf c CO M LΩ x- O CJ) CD x- CD CD CD LO CO O CD CN in U0 CD CO CM CJ) C0 U0 χ- CO χ- C0 lO χ- τf 00 CD C0 C0 CM CD CD O U0 C0 C0 x- O τf C0 C0 UO N T CM O O IO CN N OO N CO x- OO CD O O O CO x- L0 CM τf C0 O x- CM U0 C0 U0 C0 CM x- C0 N CD O O χ- χ- O C0 C0 C0 UJ C0 O N χ - χ - UJ C0 Tf CJ) CM CD O CJ) UO Tf x- O CD N f CO UJ Tf N CO O - lD uθ σ) C C N uθ ro uOO C CO O CO C!)CO in ^ O τ- xt N OON CM ^ UJ Cθ τ- CN ^ OO CD O UO CO CN Tf Tf LO CD CN Tf CM CN CM Tf LO LΩ τt τ τ c Lri τf j ' uo cb d τ ^ D Lri u τf c τ^ Tf CO N CO N Tf CD LD CD CΩ CD LD LO LD CΩ LD LD LD LO LD CD CD LO CD CD CΩ CD CΩ CO LD CΩ CD CO CO CD CΩ 00 CO 00 00 OQ x- CM 00 CQ x- CM x- CM OQ 00 _- CM x- <N < Λ C < x x x < CQ < X X θ < CQ Q Q <χχ < CQ O Q Q LU LU N < χ χ Q Q LU LU N oooυx xx- cNco OO OO o X X x- CM X OOOOOO x xx-cM-zυoooooυoυo X X X- CN X X X X X < < < < < < < < < Qi Ct Ω_ Ωi _£ Ct Ct α_ Ω_ Ω_ Ω: CL CL CL α- CL CL CL CL Ω- Ω- J JJ J J J J J J UJ UJ UJ LU J LJ UJ UJ UJ UJ UJ (/. (β(/3COC/)(/)(t) (/. CΛ (0(/3tΛ l I I I I I I I I I I I I I I II I I I < < < < < < < < < C C C C C σ) CΛ CO C C C < < < < < < < < < < < < C CL CL Cu C CL CL CL Q- ( CL Q_ CL C CL Q- CL C C Q- © o N 00 CD θτ-cNc ιn DNco O O O x- x- x- x- f Tf Tf τf τf τf τf CO Tf CD x- CD N N O O O O O O O x- CO O CO CM CD O O O O O UO CM CD CM CO Ln O CO N CD N O O O O O O O O O O O O O N O UO O N UO x- CM CD CJ) O O O O O O O CD CO x- CD Tf r~- O O O O o χ- co τf co χ- N co χ- τf co cM θ θ θ θ o o o o o o q q CD N N CO N N N O O O O O O O CO CD N lΩ x- ' d d d d d N d d Tf Tf M x^ x^ cb cb d d d d d d d N- u CM CM CM CN CN CM CM x- x- x- x- CM CM CM CM CN CM x- x- χ- x- CM C τt LO LO τf τf C CM CM CM CM CM CM CM CM CM CM CM CN x- x- x- CJJ CN x- in CM χ - CM CM CJ) C CJ) CJ ) τf LD CJ) CD CJ) CO CO in c U0 CJ) CJ) UJ x- σ) C CO τt τf CJ) ro ιn CO x- C x- N CD x- CM CO C LΩ x- UO LO N CD CO CO CM CO CN O O O x- CM CO O N N CO C CM LO CO x- N LΩ CD CD O CM x- CO N O τf cn N O τf ) τf J LO O LO CD lΩ τf O lΩ CO xt N CO N O τf UJ O N CN CO N N CO CM τf O UO UO CM N CM q x- CO τf cq q cθ ro N ' N ' N ' ωsωωdd ' co∞ io^ ό uo ' xfiridu. CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CN CM CM CM CM CM CM CM CM CN CM C^ ro ro CD O O CD C CO CO N CM CO CO CD CM CO CM x- x- CJ ) τf χ - χ - CD LΩ O O 00 CD N C τf θO CD CO CO CO τf x- CM CO N x- CO x- Tf O CD x- x- x- LΩ CO CO CJJ Tf Tt CD CO OJ x- CN CN CN Tf CO CD lΩ CO CN Tf CO C CM CD O CO O CM χ- τf C„D. T ,f .N Tf CD O LΩ N CD CO CM O CO x- CO CM O O O x- CO UO UJ CO CJ) x- O N N C0 CM C0 CM CD CD CD CJ) x- CM τf C0 τf χ- N lO CO N τf CD O CD CN CN CO τt CD CO CO Tf UO Tf oO Tf Tf uO O CD Tf q cO N UJ Tf UJ x- CM N CD UJ UO τf J (b CD τf c τf τf r-- r s - Ln τf c CO Ln N UO τf LO lΩ CO CM x- O CJ) O O x- x- x- x- x- CCMMVx- cOTri d T^ rocvi O x— χ- χ — X-- X— O CJJ CJ) CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CM CO CO CO CO CO CO CO CO CO CN CO CO CN CO CO CO CO CO CO CO CO CM CO CΩ x- Tt CN Tt N- Tt O T f O CN CO x- CD CΩ lΩ CΩ x- x- LΩ CO CM N τf lΩ O O N CO CO N CM CM CD CO CO N CO CO O UO CO CD x- CM Tt CO CO OJ Tt CO L LΩΩ CCOO UUJJ CCJD) CαOD CCDD CCDD NN OCJJ) CCOO OO CCJD) CCNN OO CCMM xx-- UUJ Tτff Tτff xχ-- ττff ccθθ xx-- ττff ccθθ UlΩO ττff ccθθ τf CCDD OO CCNN CCNN CCJJ)) CCOO ττff xx-- OO lLΩΩ OO CCMN NN tLΩO NN CCOO N N O C x- N CCNN CCDD xx-- CCDD lLOO LLOO Tτff cCOD xx-- OO CCNM LLOΩ CC LUOJ xxtt xx-- xx-- Tτff ---- CcO OCOO CCOO xx-- CCNN CCNN OO CCMM OO N τf CcOO OO CCDO CCDD CCJD) xx-- Tτft Txff CCMM UUOJ CD x- O OJ CO CD CN N uo cb N iri b b T L b M ^ ^ N CO CD CD CD CD CD CD CD CD CD CD CD CD CD CD LD LD LD CD CD LD CD UJ CD LD CD CD CD CD CD CD CD CD CD CD C^ x- x- C CMM CCMM CQ 00 O Q Q DQ CQ x- CN ωO , ω O Ω < x x x x x x < Λ co <xχO _u xχxxxx < < ωxxxOxΩxΩ X x xx_< υ o xx-cNx-cMx- N-zυ o co N X o < ooo C0 LU X X x- C υυΩzoNXz z X X X- CM X- CN X- CN X X- CM X- CM Z O O OOOOOOOOOOOOOOcocococococ co coco coco OOOOOOOOOOOOOOOOOO 000000 _J _J _J 01CtCtCLCtCLCtCtCtCtCtCtCtCt >> >> 1C^ CLCLCLCLQ-C CLCLCLCLCLCLCLCL Oθυ υθθυθO<<<<<<<<<<<<<<<<<<<<<<<<>>> © o u CJoJωOωx- CcoM CcO D τcfouc D o ccDoωN CcOoOco)sO χs- CsM CsOsτf sLΩsLDsN LsθsCDcOoχ∞-cCMoCcOoτcof LcOoCcDoNco∞CO CcJoJ Oroχro- CcMncCOncτof ro)cCDnNroroCOroCJ)ooooooooooT- τf τf -^ τf τf τf τf τf τf τf τf τf τf τf τf xf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf f τf τf τf τf τf τf x^ © © UI H U α. UO x- CD N O O O O O O O O O CO CO CD O x- O O O O O CM O O O τf r-- CD τf CD O O O O O O O O O O O O θ σ) Cθ L θ CM CD N τf Tf O CD O O O O O O O O O O lΩ Tf Tf x- CD O O O O O UO N CD CD CM CD CD N Tf O O O O O O O O O O O O O CO x- CD CO CO CO x- Lθ cb u N d d d d d d d d d τf ' τf UO CD CM O O O O O N N CD CM OO CD x- Tf CD O O O O O O O O O O O O O O CD x- O CO N CD x- x- x- x- CM CM CM CM CM CM CM CM CM x- x- x- x- x- CM CM CN CM CM x- x- x- CM x- x- CM CM CM CM. CM CN CN CN CN CN CN CN CN CN CN CN CN x- CN CN x- CO CM x- χ- CO CO CM τf τf θ N CD x- CD LO CJ) Ln c N N O N O CN CD C CM O N τf CO CN CN N O UJ CD CD O τf CM C CJ) O C CJ) in x^ CM CD x- O x- CJ) x- CO LO CJ) O O N N CD N CJ) CJ) N x- O χ- CM CM O CM O CO CO N N CO CD x- CJ) CD CM CO ιn CN CO CO CO N CM CO x- ω 0 f c) D N τf τ f _ x-- r ^ OT W -^ α: , r Λ ι O r Λ [v. -^ C Lb cb cb cjJ N ' d cb <» c3J d uό τf co cM τt u. τf u ^ CM CM CM CM CM CM CN CM CM CM CN CN CO CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM x- CM CM CM CN CM CM CM x- χ - CM x- χ - χ - xt ro Tf CD O x- CM Tf O O OO x- N CO Tf O CJ) χ - τt LO Ln cθ CM CD O UJ CO CM CM UO CD τf rv. C τf N CD χ - CM N CJ) CD O CO CD O N C _D CM N C . O . C_D C . M . C_O O_ C . M . x- τf χ-- C c τf q x- x- τf ro cdco o. d ∞ N cd σJ co d ro CN CN CN CN CO CN CN CN CN CN CO CN N CO CN x- Tf CO UO Tf CO CD O CO 00 C CO Tf CD O CJ ) CO OO Tf O ) i N^- uLO CCJ LCDU LOUO LC'J XτfT CcJ LOVOJ VCMN LO N CO τf o σ) CM CO CJ) N CD CM θ σ) CJ) χ- CM CD CO CD CM N x- m cθ - cθ - co cD co cM ro co cM in co c N ro co ro rΛ con rorn croΛ c.o. c no-> c.oo rorι or-> cror> + ( c CD τf τf τf CD O O C CDD CCD CCMM OO τ Tff C O _J)). Oo _ CO CN , C _J ) . Tf 0 u0j C COJ N r « C LDU L UOJ O L-J N I— ■ C UDJ C IMN τ XfT r I—--- L UOJ O UOJ C LOU O L_J O LJ C UJ)J τ XfT c UJ)J C UDJ C LDU x XtT C IMN C LθU σ U)J τ XfT χX-- o L_J O LJ xx-~ xX-- C UJ)J x ^ C LDU C LUO O L-J N I— - O L_J I CNN xχ ^ - y0-> I-NN LCDU LCDU χ Ttf τTtf cq in CD N coN _ d_ _ d_ d_ c_bN ' d _ d_ _ N ' d _ N ' _ _ cb_ LbN d _ d_ cb_ cb_ cb_ _ d_ d_ _ _ _ _ _ __ _ _ _ _ _ CD N CcOd CcOd ccbb ccbb NN CCDD ccbd CcDD dd LO in in LΩ CD LΩ LO in iΩ LO UO CD UO UO UO UJ LΩ in in LΩ LO LO UO UO UO UO UO CD CD UO UO UJ UO UJ CD CD CD UO UJ UO CD UO UO UO UO LO CN CN CM x- CM ^ OOOOO 00 OQ 00 Cα OQ O O Ω Ω LU -U N N N O Q O < C Q χ χ χ χ χ χ < OQ ooo ox < X X X < 00 Ω LU N X X x- CM CO x- CM CO oooυ x- CM CO oooυoooz < Xxx-x X CMxx-xCMx X x-xCNxx-xCNxxx < ω Ω x- CM CO OOOOO -J J-J ^ J -JJ J J J J J J < < < < < < < < << (ΛCjOCnCO (βCβWWWWC CO CO(OW C (Λtθ m > > > > > > > > > > > > > < < < < < < < < < < _J _J _I _J _J _I _I _J _I _I _I _ l _J _J _J _J _J _J _J _J _J _J - _ I — I — I — I — l -J © o χ- CM CO τf UO CD N CO CJ) O χ- CM CO τf ιn cθ N CD CJ) O χ- CM CO τf Ln CD N CO CJ) O x- CM CO τt ιn CD N Cθ σ) O x- CM CO x- x- x- x- x- x- x- x- x- CN CN CN CN CN CN CM CN CN CN C C C C C C C C C C τf xf τf τf τf τf τf τf τ^ u uo uj uj uo uo uo iΩ io uj uo u in in uo uo in in LO LΩ in in uo iΩ uo in uo in uj uo uo u iΩ uj uj u uo iO LΩ in in u^ LO © © UI H U α. CJ ) O O O O O O O O O O O x- Tf c CM CD U) CM O O O O O O O O CD x- UO CO OJ UJ UJ O O O O O O O O O O O O O O OO in cO x- co o o o o o o o o o o o cD τf cM co χ- N N θ θ θ θ θ θ θ co cN CD CJ) χ- χ- τf cD »- o o o o o o o o o o q q q τt o q N d d d d d d d d d d d co ^ cM c N d d d d d d d f. CN CN iri t M : N τ- N d d d d d d χ - CM CM CM CM CN CN CM CM CM CM CM CM CM CM CN CM CN CN CM CN CM CM CM CM CM CM CM CM CN CN CM CM CO CO CM CN CN CM CM CM CM C^ O UO OO CO O UO CN CO N OO CD x- O C OO CO OO O OO CO CD N CD O CD CJ) CD CN CD CD LΩ CJ) τf c x- CJ) CO ) CD τf τf CD N CD O O N O CJ ) CO N O OJ OO UO OO Tf J N CO O N O x- O O N CD O x- Tf O UO CD uO Tf cO CO OO N CD O O Tf OO N Tf CJ) N CD CN CO C m x- O C LO CJ ) CO N LO CO O O ; ιn q co q ιn ra N ( CD co o ό N x- CO CM CM O Tf CO CO CO UO D 00 x- N CO CO CD CD CM C O x- in O xt cq cq CM O CO c x^ c Tf Tf co co Tf J d c d d N C CJD) cCOd cCO O x- x- CCNM CCNM CCMN CCO TTff liOn CCOO CCOO x- x- CCMM cCOb Tτff Tτfr uuό. cθ NN CLDD CLOO cCbO cCbO cCMN cCbO cCMM CCMM CM CN CN CN CN CM CM CM CM CM CM CM CM x- CM CM x- x- x- CM CN CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM Tt x- C0 J CD CM LΩ CD C0 O CM τt C0 N L0 C0 τf c0 C0 U0 τf C0 C0 x- N σ ) τf O U0 τf τt (O τf x— u N N CM CO Tf r— CO CO OO τf σ. CM O CJ ) N τt o CM τt CO lO UJ CN CO CO CO τf cθ C CO CO τf CD CM x- x- CN in CO CM CD CO xt σ) CO CD N N O CD CN CO N N CD O lO CD CO O x- x- CO CO CN CN C in O- in cD CD O LΩ CM CD τf τf τf O CD τf CM CO CM x- CM CO χ - x- x- CN CO LΩ O CN CJ ) 0 O CO Tf CD CD CM Tf CN x- CO O O O in CM Tf cO CO ιn CO CD in CD N in τf UJ τf CD U0 U0 U0 τf U0 τf τf τf CD f cθ CO τf UJ τf τf c ιn τf CM CO CM CM CM CO CO x- CM τf cO x- C^ CM CM CD N CO CJ ) CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ CM CD LO LΩ UJ CD UJ τf O τf CM CO CO τf τf x- r s - CM O τf CM O O UUOO N CO CD UJ O Tf cO Tt UJ OO UO UJ N Tf CM O CD CO CD CO CO O CO O _ T -f CD CO N τt x- N CO O O UJ x- CM CJ ) OO N CM CJ) O CM C .O . U _O. CM O Tf CO UUOJ NN CCJDJ NN lUΩO CCOO CCNM CCOO OCOO x- CM CD CM CO UO τt σ) O N x- CM CM CO CJ) x- τt x- χ - CM CD x- τf C0 χ - τf ιO CD CM CJ ) CD CD CM CO CD CD m OO CO N CM CM CD x- CD O CD CD N CO CO in O lΩ CD CN OO CO CO CO CO CO CM N CJ) CO CD 00 N CJ) θ - co co ro N o ιn ^ s o oo (D (θ (D ro ro ro ro ιn c co ^ " " " i ιn cD c " c ιn ιn c ιn (θ CD N" Cθ c c cM CM LΩ LΩ UO UO UO LΩ CD C "D" C'D" U"O in in LO in Ln in iΩ LO LΩ in in LΩ LΩ LΩ LΩ LΩ u u uo uj uo uo uo uo u uo LO UJ uo uo uo uo uo uj u u uo uo uo uo uo uo x- x- x- CM CM CM CM DO OQ ,_ Ω Ω Ω Ω Ω Ω DO ω Ω Ω LU LU N N N Q < X X < _. CO Ω < x x x x x x < CQ Ω LU N < X X X X X X X X X X X _ < _. O XX x- CM X x- CM CO x- CM CO OOOθυθX χ- CNχ- CMχ- CM oooυooozx X x- CN x- CN x- CN x- CN x- CN CO Z O O O 33333333333 3 OOgOOOOOOOQOOO ( 3 W W C 0 C 0W C 0WWWWW _I _I _I _I _J _J _J _I _J _J _J _J Q- Q- Q- CL CL Q. CL Q- Q- Q- CL Q_ Q. Q l _J _J _J _J _l _J _l _l _l _l _J _J _J _l _l _l -J _l _J _l _l < < < < © o CO τf UO CD N CO CD O x- CM C τf lΩ CD N C CD O χ- CM C τf J CD N Cθ σ) O x- CM C τf iΛ CD N CO CD O χ - CM O τf UO CD CO CD CD CD CD CD CD N N N N N N N N N N CO CO CO CO CO CO CO CO CO CD CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CD CD O O O O O O O O O O x- x- x- x- x- lΩ LO UJ UJ UJ UJ LΩ LO in LΩ LΩ LΩ lΩ LΩ lΩ LΩ Ln iΩ lΩ UO UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UO UO UJ UJ UO UO UJ CD CD CD CD CD CD CD C^ LO © © UI H U α. CM CO CD Tf O O O O O O O LΩ CD CD CM CO CO O CO o q q q q q q uo cD N N O iri cd cD N d d d d d d d N N Tf iri x- x- x- x- CM CM CM CM CM CN χ - CM x- χ - UO CO N CO OO CD CO U Tf CO CD CD Uj Tf uO O x- χ - CO CM N CO N τf x- CJ ) O LΩ N CD in CM CD CD τf cD CM χ - τf CD x- N C N UO x- CJ ) τf O UO CM CD LΩ Tf CO CD τf O CD O χ - χ - C O CO τf cθ ) CO χ - O CD UO CD CO O τf τf CD χ - CO C O CD CM CM CO O O U CN ) CN C x- CD N N x- CD CM O LΩ Tf N M cq S- τt N χ - cj ) CO N N CΩ CO CN C0 N Tf N CD CJ) Tf UJ x- LO CJ) N CO CM CO CD N N O x- C xt Tf O CD CJ) Tt O CD x- CD CM x- x- xt N Tf in uό cb CN cd τt o N iri d cD CD CJ) cb N iri τf CO O CD N CO N N UJ Tf Tf cO CO CM CD CJ) O ) O o oj co co x^ c cd Tf Tf Tf CN CM CM CM CM CM CM CM CM CM CM x- CN x- CM CM x- CM CN CN CN CN CM CM CM CM CM CD ro xt CO CD CO CD CN CJJ CN lΩ CN CO CO CO LΩ O x- lΩ CN LΩ x- N x- Tf h- x- LO N O CD x- O CO N CO N N CO CO t CM O CO CO C O O CO x- N CD CD O χ - χ - U0 CM CO CD CO in N CM C0 CJ ) x- CD CM U0 x- C CD CD CO CN CD τ- x- σ) CD x- CO O CM xt O CM CO CO τ- N CN CD CJ) CO x- x- Tf CM CD O Tf Tf χ - cq q χ t CM x- χ - χ - CD CJ ) CJ ) CJ ) UO CD CO CN CD CD O 00 N UO N O OO CO UO O O CD UO OO LΩ N LO xt UO Tt CD UJ O N N UO N T f 00 CD N T o. s ' ώs-cds ' bcbbs ' s ' fflrodcbo.cdroro CD N N CD O ffiN ' d αJ cdco N io N O ' NN'jinσ) CM CD CO CN CN CN CN CM CM CM CM CM CM CM CM CM CO CN CM CM CM CM CM CN CM CM CM CO CM CM CM CO CM CM CM CM CM CM CM CM CN CN CM CM CM C^ χ - CD LO χ - CD τf cD N Cθ LD CN O CM CD τf CM C C C O N x- O Ln cθ CO CJ) CD O N CO C CD N τf cO C CM N lΩ U χ- CM O O CO CO O CM C^ CJ ) τf U0 C0 CD C0 N O χ - C0 in C0 CD N CM C0 x- C0 C0 CO lΩ in CD Ln θ CJ) U0 CJ) N CD lΩ O CD O CD τf r- | s -. N CM CM L^ x- x^ x- CN O CM OO CM x--; q θ CO τf x-- CM N O xt x- lΩ UO CO CJ) CD O O N τf CO O τf U. UJ x- τ^ t ' O lri Tf CM O lri lri d cd cM x^ ^ cd cO T Tf Tf cx. iΩ in Lθ in ιn uo uo u θ Lθ o o uj j Lθ LΩ Lθ in Lθ Ln L n o j u o ιn iΩ iΩ uo uo uo τf τ τ τf t x f u f τf τ^ CM CM CM CM __: CM 00 OQ Ω Ω ω Ω LUUJ NNN ■ <- CM 00 CQ Ω Ω ω Ω Ω < X X X X OQ < DO Ω Ω < X X X X < OQ O OO ZX CM x- CM o <υoυυo Ωυ UJ N X x- z _ X_ X< ^ . ωxT-xOOΩ CNxX-xCNxX-xCNxX-xCNxX-xCMxCO oooυ oo z X x- CM x- CM υυoυo 2 Z Z Z Z Z Z Z Z Z θ CO C Cθ cθ CO CO CO CΛ CΛ C CO WC COCO COCO C C C 2 Z Z Z Z Z Z Z Z Z Z Z Z Z w co oo co co co co www>->:>->->->->->->. J ^ ^ >>- ^>-c9 < < < < < < < < < < --J --J J --J -J ^ ^ ^ ^ ^ -J ^ ^ ^ _J _ -- - - -_J -_J -_J < < < < < < < < < < < < < < < < < < < < © o UO CD N CO CJJ O χ - CM CO xt UO CD N CO CD O x- CN C τf U CD N CD σ) O x- CN CO τ^ u CD N CO CJ) O x- CM CO τf uO CD N C^ x- χ - χ - χ - x- CN CN CM CM CM CM CN CN CM CM C C C C C C C CO CO C τf xt xf τf τf τf τf τf τf τf u^ u^ U0 UJ U0 l^ CD CΩ CO CΩ CO CO LO LO D CΩ LO LO CΩ LD LD LO CΩ CO CΩ CO CΩ CΩ CD CO CO CO CO CO CO CD CΩ CD CO CD CO CO CO CD CΩ Φ CM CD N CD x- O O O O O O O O O O O O O O τf CO CD τf τf O x- O O O O O O x- x- N Cθ CO x- N OO C OOOOOOOOOO cM qα3 Nc oo qo q o o o ooo o o N τtLθ Nc χ-τt oo oo o ooco cMNτtLn τf qτttv. uo oooooooooo cb τf uό τtd dd dd d d dd ddo ' o o ' cMCMCM χ- : uό uόco uόd dd dddχ dχ-- : d d ~: ά o ό ^ό e ό ό ό i c cό cό x- χ - χ - x- x- CN CM CM CM CM CM CM CM CM CM CN CN CN x- x- x- x- χ - x- x- x- CM CM CM CM CM CM χ - x- x-- x- x-- CJJ x- χ - χ - x- x- CM CN CM C^ OO N CM N CD CD CD CD C C O O CM O LΩ CJ ) C CD Uθ O C x- CD CM CO O UO xt τf O τf c O OO UO CD CD O CD LO CM O O N CD CO O CD O CJ ) q __ C_Ω O_ O_ C.O. ,N- C_Ω. ,N- x.- C _.n. -CM- -.O. . CO CD CO O CD CO N OO _ CO . C _D C .N . x- C .N . C _D O _J N . CM CD CO N CO CO OO N CD CD CM CM CO O Tf CD N OJ CD LO N O CJ) CJ) CN τf UJ τf |v. c CM CM CO CD CO OO τf cO τf c LΩ O OO N N τf c CDD NN Tf CN N CM CD LΩ O O CD N N oo ιn τf r- cqcq oiΩ cq τt cM χ- cq cM cq ιri N co N τ : b ιri ; N ; b ιri ιri ro od ώ τ J d ro - c τ : CN τ d c ' ^ . T .^d _cd N d d χ d cJ. χ CN CJ. x- x CJ ) CJ- CJ. x CN CM CM CM CN CM CM CM CM CM CM CM CM CN CN CM CM CM CN CM CM CM x- CN CN CM CM CM CM CM CN CM CM CM CM x- CM x- CM CM CM x- CM CM x- CM CM x- x- x- CM CM ro t CD x- CJ) Tf x- CN CN X — x— CM CO CD CO O CM N x- CD CO CD N CM O O x- CD x- N CD CM N τt N O LΩ x- τf CD CΩ N CN CO χ - CO τf CJ) CD τf O N N CO Tf CN O N Tf N N O CO N CM CJ) U C C N U x- x- O L D CO N UO OO O OO UJ OO CD L O O O LO C CO Tf CD N CO Tf x- cO CN CD CO CN CO CO CO CD CO N LΩ CD f N Tf CO Tf CD N LD C τf x- θ C CM C C N CM LD N CM CD τt CD CM N x- x- O τf O N CD O CO CO CO O CO CM CD CM CD UO CN CO CO Tf x- N τt cb d N ' cb cb b f τf ' cM cd τ ' d c cb CN CN CN CN CN CN CO CO CN CM CN CN CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ CO CD OO CD N τf NN NN NN CC00 lUΩ) 0000 NN 0000 UL00 CC0 OO CCDD CCDD CC00 OO CCO0 CCDD OO ττff χx-- |Nv , χ -- cσ3)) rN-- ττff cCMM NN O O N O O τt cD LΩ CM N CD O CD CD τt C0 CD C0 CD O O CO CD CO CM N CD N OO OO x- CΩ O N CΩ CD O O CD C—D O _ τf . C _D O CN x- σ) CM χf CM lΩ CO CD CO CD x- xt C CO τf UJ χ- CJ) CO x- O O CD τt N CJ) CO CM CM CO N 00 O CD N UO x- N χ - CJ ) CJ ) τf lO CO C0 N lΩ CO CM CM O CM CO OO x- O CD CO LO CO CD in CO CD OO in OJ CD q CM U Tf N cj) co oo oό co 0000)0 (5) 00 (3) O _ CO CJ) CD αD N CJ) O CD CD χ- CM CM C O O CM CM ττtf cc cC»» cCbO CJJ cCbO NN CD in ττf ccd cCo cCMM ' cCbO NN NN ' CD iLΩn NN- ιLbn cCbD tT Tf Tf Tf Tf Tf UO f Tt UO Tf Tf Tf UJ Tf Tf Tf Tf Tf f L Ω τf τf ιr) ιΛUJ U0 U 0 L O L Ω L Ω I Ω L O τt τt τf τt τf τf x t x t τf τf τf τf τf τf τf τf τf τf τf τf x- x- CM CM CM CM x- CM 00 CO Ω Ω x x x x _r CM 00 DQ Ω Ω x- CM OO CO O O Ω Ω Ω LU N X X _ < XX X XXX LU XXXX < 00 ΩΩ < X X X X < 00 Ω LU N X X < X X X X X X LU O ZO Z Z X X X- CN X- CN X- CN X X- CN X- CM Z O O OO ZX X x- CM x- CM ZOOOOOOZO Z Z X X X- CM X- CM X- CM X OOOOOOOOOOOOOOOOOOZZZZZZZZZZZZZZOOOOOOOOOOOOOOOOOOOO _£Q^Q_Ω_Q_Q_Ω_c_:Q_Ω_ctα_Q_Ω__:o___:c_: c)co c7jw <<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<< © O N 0000 O χ- CM C0 τf u. cD N 00 CJ) O χ- CM C0 xf ιn CD N Cθ σ) O χ- CM C0 τf J CD N C0 CJ) O χ- CM C0 τf J CD N CO CD O x- ω (D (0 N N N N N N N N N N α. (0 (0 (00. C0 C00. C0 C0 σ) (J) σ) (!) σ) σ) 0) (I) 0) 0) O O O O O O O O O O τ- τ- τ- τ- τ- - r r- τ- CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CO CD L O CD CD CD CD CD CD CO CD CD CD N N N N N N N N N N N N N N N N N N N LO © © UI H U α. O O O O CD CO CJJ CO Tt iO O CO CN x- O O O O O O O O O O O CO O Tf OO CO CD Tt O UJ CO O O O O O O O O O O O O O Tf CM CO O O O O O CD lΩ lΩ Tf UO N N UO f CD CM O O O O O O O O O Tt CM O Tf Tf co u cD CM x- uo o o o o o o o o o o q q q uo O O O O CM O CO UO . CD O CM CM CO O O O O O O O O O c cb cb N c cd cM Tt cb cb d d d d o ' d d d d d d cM CM CM CM CM CM CM x- CD x- x- CN CN CM CM CM CM CM CN CM x- x- CM CM CO C CO CO CM CM CM CM CM CM CM CM CM CM CM CN CN x- x- x- CO UO CO O CD O CD O UO CO CO CM CO CM CO CO CJJ CO N CO Tf UJ x- CO LΩ CD O N UO OO CD CD CM UO CO N CO N x- Tf UO O OO CM CO CM CD CD CM Tt CD CD N CM Tf N CO LΩ x- CO N N CM O N UJ N CM CN x- x- O CM CO x- CD CO CJ) OO τt CJ) CD x- CM UO CD CM C O xf CM CO χ- xt CO x- CD U UJ O O CD x- CJ) CO CD N CM CO UJ CO CD CO CD LO N Tf N lΩ Tf cO LΩ CO CD N CΩ CΩ N CD CD LΩ CM C0 O τt CD O τt CM CM CJ) x- CD N O LΩ C0 m CD N in N l- q q q CO CO O CM OO CO CO CD CO CO N C N CD CO CO O N CO CD CD O CD O CO N N oo cb ib cb cb cM CM CM cd uj ib ib cb cb cN x^ cM x^ cM rø x- x- CM CN x- x- x- x- x- x- x- x- x- CM x- x- x- x- CM x- CM x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CN 00 ro t O UO CN τf |v- LO x- OO CD O UJ CD xt O Tf CD CM N xf CD Lθ τf cO LO CO CO CD UO CO UJ CJJ N O CO CJ) UO CO CO x-- CM CJ) CD O CO CO O O CO Tf CD UO CD UO Tf CM CD CD CO CN N LΩ Tf CO OO CD CD OO x- O CD O O O O CO O CM CD OO CM N CJ) CM CO UO N UJ χ- C τf c CJ) CD N CD CO UJ O) CO CO Tf CD OO CD O CO O Tf Tf O CM CJ ) N LΩ τf CJ ) CO CD O U χ - N O N χ - CD CD CM xt CD χ - LO CD CM O χ - N UO τf τf |v. CM CD lΩ CN N N CD O Tf N OO CD N N OO N N CD O O O O χ - x- x- N N O CJ) CJ) x- O CM CM N CD N N CD CD N CD CD CO CD N UO UJ N N UO OO CD O CD LΩ CO CO CO O O C C C C C C Cθ C CO τf τf τf τf τf f τf cO CO τf cO C t Tf Tf Tf CO CO C C C C C C C C C C C C C C C C C C CO CO CO C C τf τf CD in τf τf θ τf CM CD O CJ ) τf O 0D CM σ ) x- CD CN τf O CD C0 CM x- N C0 C0 τt τf U0 U0 CD CD UJ x- CN CJ ) CJ ) CD χ - lΩ N O UJ O x- x- ∞ CD CO N CM N τf CM CD CM in τf c O τf cθ lΩ CD CD CO ιn cθ CD N x- UJ UJ τt |v. ιθ χ - O χ - CM CO N CO UO N O χ - CO CO χ - χ - CD CO O O^ uo q cq N χ - χ - uo cM αj co cD χ - < o cN co cj) in co cjJ χ- o co χ- uo τf τf OT C t ^ c O -- : ( N CM- - : σ ) <-. C - N ( N χ - : - : JJ J. N τt τf τf τf ) lO lΩ in iΛ τt τt τf τf τf xf τf J LΩ LΩ lΩ τf τf τf τf τ ιO U0 lΩ lΩ in in iΩ lΩ in in i^ x- x- CM CM CM CM x- x- X X X X x- CM x- CM CO DO x- CM x- CM x- CM X X X X X X X X < 00 Ω Ω LU LU NJ X < χ χ Ω Ω LU LU X oo O < OO O Ω L X __ < cxoxxx Ωx Ωx_u x- CM x- CM O X X υooυoozUoN Xzz X X X X < OOOOO O X X X- CM X X X X X X- CM X- CN X- CM X x- CM x- CM Z oo OO Oo_ o:Q: -t Qi Q_ __ Q. Q Q Q_ Q: Q; Q Q: Q. Q:Q: c_:Q_ O OO OOO O O LQ.Q. o_ α_α_ __:>- >->- >- >- >- >- >- - >- >- >- >->- >->- >- - -Eα_: Q:Q_: Q:Q κ < < < < - l- l- l- l- H - l- r- l- l- r- - l- l- l- l- l- l- l- H < < < < < < < < < < < < < < < < < < < < < < < < < < < © o CD O χ - CM CO τf uθ (θ N OO CD O χ - CM (O xf UO CD N CO Cn θ χ - C CO τf lΩ CD CO CJ) O χ - CM CO τf u CD N CO CJ ) O χ^ x- CN CN CN CN CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO xf τf τf τf τf τf τf τf τf τf Ln in iO lO lΩ LΩ J [v. ι-. r-- N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N x- OO O O O O O 0) UJ χ - 0 O O O O O O O CD x- 00 x- O O O O O N N C0 C0 O CD O O O O O O O UJ N d cM d d d d d c 9 o co Tf O O T dd dd dd d co ' c x- CN CM CN CM CM CO x- x- CJ) CM CM CM CM CM CM CM x- x- CO CD CD x- N CD CO CO CM CO O N CM x- CD N CO CD O CJ) CO CN U0 CJ) C0 τf O τf O UJ CJ) CM O U0 O N τf r-. U0 C0 CM C0 τf |v- ir) 00 C0 CD CM τt CM Tf O CM x- Tt N CM CM UJ O CD CD lΩ CM CD CO UO CO OO OO N N CD UJ CO UJ lO N LO UO CD CD x- Tt CO in N x- x- OO O x- CM CD CJ) UO CM CO CD CJ) Tf CD cD N CN CJJ cq cq in q N co χ- CJ) 0O U0 CD τf CM U0 CD LO τf CD OO N CO N CD O CM O CD N N N CM CD O Tf UO O x- x- CD N x- O q c N q CD dsbiriirisoci oos dcM CMCMCMco O CM CM t co χ^ c χt co cb t cN o t t t τ- : N oo co co j. ∞ CN CM CN CM CN CN CN CN CN CM CM CM CM CM CN CN CN CN CM CM CM CM CN CM CN CM CM CM CM CN CM CM CM CM CN CM CM CO CM CN CM CN CM CM σ. o Tt x- CO O lΩ CD LΩ CO UO CM CO N CM UO O CO LO O C CD C C UJ CD x- CO C x- x- O CO CJ) O x- CO τt o CN O lΩ C CJ ) Cθ m θO χ - CO O CΩ χ - N CΩ CN CO N O Tf r- CN D N CD CO U) CD Tf N O lΩ O N O O x- OO Tf oO in CD CD CO N OO N τf CM CM O τf O θ σ ) τf UO O C O τf cθ χ - χ - χ - CM CN x- CO CM O x- U) CN CO O CD N O N CD CM x- τf θ N CM C0 CD τf θ CD UJ O x- N CN τf CJ) CD CO N CM CO CD CD CN CM O CO τf CJ) CD in c UJ CD in χ χ χ - : d x- : CD CD CM χ - σ) d OO _ N χ - χ - CM CJJ O CM O O χ - χ - CM CO CO N CO C-) CD CD CJ) CD lΩ N CD N N CD U CD UJ CD CO CD UJ τt t cD UO N N τf τf τf τf τf c C τf τf c τf C C ^ ^ ^ CO ^ xT xf xr ^ - N- ^ C C C C C C C C t C C C C C C C C C C C C C C C C C C CM N O O CO lΩ CO χ - χ - CD CO in θ UJ CD τf CD χ- O χ- lΩ CD CD N CJ) CD xt CD CO lΩ UJ x- x- CM x- CM O CJ) τf r-. CM CO CM CO CJ) LO τ^ LΩ C CM xf O CO CO O CO N N UJ U σ) CO CM CM CM CD τf |v_ o UJ O CD O C CJ) in θ O C t N CO x- CO CM CM CO C CD τf O N CM N τf C^ τt ( » cM q τf c uo cq cq ιn τf uj uJ CD θ co u cM CM CJ) χ - cM co ιn uo cθ χ- N χ- cj) χ^ d Lb N O T LD d Tf Tf T T ' c c cN cd xf f cd x^ cM lΩ O UO in lΩ UJ lΩ tΩ lD lΩ lO lΩ UJ lΩ J iΩ lΩ lΩ lΩ lΩ lΩ lO UJ lΩ lO in iO in iΩ LO lΩ lΩ in in iΩ x- x- x- CM CM CM x- CN CQ CQ x- CM _. OOOOOO ^ fT , ^ ωcα,.. DQ CQ Ω Ω DQ Ω Ω <xx < O Q <ωχχχχχχ < _ ωO <χχO < CO Ω O OO oo X x- CM OOOOO x X X X X- CM CO X- CM CO Z O O O O O X X X- CM X O O O O OO X <xX-xCMxX-xCM X-xCM Z<O D- Q.a. l Q- D- D- D- J J -J J -J _l J _l J J J J _J _i _i _i Q.D. t:Q_ Q_Q Q. Q_ Q_ Q. Q O OOOO OO OO OO OOO lU -J (O(0t. (O(Λ(j. (O(0W < < < < < < < < < < < < < < << _lllJ liJ l_ lilU l_ llJlU l_ l_ (_ Q.(Ϊ Q: Q_ Q_0_ __ ^ < < < < < < < < < > > > > > > > > > > > > > > > > (Λ ( ) ω W cy3 (ΛCOCO (O CO Q- Q_ _ CL Q. CL CL Q- CL CL CL CL CL CL CL Q_ © O χ - CN CO τf UJ CD N Cθ σ ) O χ - CM C τf _ D N CO C O χ - CN C τf uθ CD N CO CJ) O χ - CN CO τf UJ CD N CO CJ ) 0 CN Cθ τf ιr> CO N CO OO O χ - CN N S S S S S N S S C0 (D C000 C0 (0 C0 (000 C0 (J) (3) 0) (J) (]) (J) (!) (J) (J) (3) O O O O O O O O O O x- x- x- x- x- x- x- x- x- CM CN CM N N N N N N N N N N N N N N N N N N N N N N N N N N N N N CO CO CO CO CO CO CO CO CO CO CO CO 00 00 00 C0 CO CO 00 C0 CO CO C0 LO © © UI H U α. x- CO CD CO CM O O O O O O O O O CM N N x- O UJ CM CJ ) O O O O CD x- CM x- UO O CD CJ) O O O O O O O O CO CO CD N CD CO CD χ - O CO χ - CM O τf θ O O O O O O O O CD O CM CM t CM N N O O O O x- N O CD O CO CO CO CO CO O O O O O O O xt T- N CO x- CM CM • CO Q xf Q Q Q Q Q Q Q Q Q Q Q ^ CM CN UO CO Tf lΩ CM O O O O CM CM CO UO CM O -: co O O O O O O O CO CM CN CO O x- x- CD <J ) CJ ) x- x- CO CM CN CM CM CN CN CN CN CN x- x- x- x- x- x- x- x- CM CM CN CN x- x- x- x- x- x- CD CM CM CM CM CN CN CM x- x- x- x- x- CO CN LO CO CM CM O CD CO N CM CO O x- CD O Tf Tf Tt N CD CM Tf oO CO C LΩ LΩ CO 00 CN CO O N CM CO CO CN Tf CΩ CN CD O CN CΩ CD C0 C0 CD C0 τt O 00 τf r-- C0 O CD CD CD O N τf CD τf -- c0 CM CD C0 lΩ CM CM τf O τt τf x- N 00 χ- CD CM O CD U0 O C0 CM C0 O x- C0 CD C0 τf LΩ CN cq q cq cq q N L cθ N cq τf N cq co c χ- co cM CD CD CJ) LΩ χ- cD CD θ CD θ χ- LΩ CM Tf CD τf τf c0 C_ N C0 CJ) O CD Cq τf τf U0 CM 00 cq cq d cb o N C cb c d x^ - x^ d cb d x^ c c d cb x^ ^ x-^ c Tt Uj τf τf UJ cd τf cd cM τf τf U) cN UO τf UO τf . τt C CO CO CN CN CO CM CN CN CN CN 00 C CN CO CN CO CN CO C CO C CO CN CN CN CN C CO CO 00 CO C CO CO CO τf |v. cM CJJ CD N CJ ) CM CD CJ ) CO UJ χ - CM x- CJ ) x- Cθ αj CD CM CO CJ ) CD N x- CD - x- cθ N O O O O CD CO CD ∞ CM τf cO O lΩ CJ) CJ) C CJ ) CO x-- CO CO lΩ CD LΩ C τf CO CD CN CO C lO x- N UO N C CD C τf CJ) N x- N LΩ CJ) O UO O O C x^ CM x- CD CD θ χ - cq c0 N CM CN N O O CN CM C0 CM O τf |v_ CM in x- τf C0 τf τf 00 τf |v- χ- c) N x- σ ) O c cb x^ x- cM CM od cb cb x^ x^ c ' c uO Tf Tf ' c ^ CO CO CO CO CO τf τf τf τf c CO CO CO CO f τf τf τf cθ CO CO CO CO CO CO C CO CO CO CO CO CO CO CO CO CO C CO τf τf C^ τf CJ ) O CO χ - N CJ) CO τf |v. cD N CD N χ f ιn θ CJ) N CD CD χ- CO N O Cθ CM O C U UJ CD CM CD x- C O CD x- N CJ) UO O x- x- C O C^ CD χ - CO N N UJ OO τf uJ UJ Oθ LD χ - τf CJ ) χ - x- CO O CD σ) CM x- CJ) N O CD χ - CO O τf O CM CM x- CD CO CM C- ) CO ∞ N CD N N x- UJ τf CD oq χ^ τf r-- N cq x^ N CD N N N x- x- O CJ) CM CO CJ) CM O CD CJ) CD τt x- cd d d ^ d τ : d ^ d ^ d τ d : d ^ d d d d (\ N d ro c ri r' d d (. UJ UO CD CD CD CD CD CD CD UJ CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD UO CD CD LD CD CD CD CD LD CD C^ ,„ - CM T- CM OQ CQ T - CM X- CM x- CM CQ CQ .„ ■ «- ζ_ ■ «- CM OQ CQ τ_ M x- 00 Ω Ω LU LU N <χχΩΩLULU N < CQ Ω Ω <xx < ωOΩΩLU LU < X X Ω Ω LU < OQ OOOOOOOOO X X X- CM X X X X X O OOOO O X X X- CM Z O O O O O Z O O Z X X -- CM X X X OOOO LU LU LU UJ UJ UJ UJ UJ UJ UJ UJ LU LU UJ UJ LU UJ UJ Q_ CL QL 0_ CL CL CL 0.0. CL Q. Q. , n , Λ rn (n fn tn (n (n (n fn cn (n (n DL DL CL CL 0L X X X X X X X X X X X X X X X X X X CO W CO W f-O C ω W CO C ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ LU L LU LU LU Q- Q- CL CL CL C CL CL Q- Q- CL CL CL Q_ _L CL CL CL < < < < < < < < < < < < X X X X X X X X X X X X X X X X X CO CO CO CO C © o C0 τf U0 CD N C0 CD O χ - CM C0 τf J CD N 00 σ ) O χ - CN C0 xf L0 CD N 00 CJ ) O χ- CM CO τf UJ CD N CO CJ) O χ- CM CO τf ιn cθ N CO (J) O x- CN CO τf CM CM CM CN CM CM CM C C CO C C CO C C C C Tf xf - - Tf Tf Tf Tf Tf Tf Tf u-) U0 LO U0 Ln U0 uO U0 U0 LΩ CD Lθ CD Lθ Lθ Lθ D CD CD Lθ N N N N N CO OO OO OO CO CO OO OO OO OO OO CO OO OO CO OO OO CO ∞ CO OO OO CO OO OO OO CO CO CO CO CO CO OO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO LO t- JN © © UI H U α. Tf o o o o O CO N UO CD CD x- O CO O CM Tf O O O O O O O O O O O O O χ- OO χ- CD CO CD τt o O O O O O O O O O O O CM CO O CO O O O O O N oq oq cD cq cM N q oq CD O O O O O O O O O O O O O CM LO CD CN UJ CM LD CO O O O O O O O O O O O CO CJJ CD d d d d d d τ÷ c c x^ cM c c Tf L x^ N o d o ' o ' d d d d d d d τf cN ' χ t ιb .d oό .d cd d d d d d d d d d d d ιb ιb N CM CM CM CM CM CN CM CM CM CM CM CM CM x- x- x- x- x- x- x- x- CM CM CN CM CM CM CM CM CM CM CM x- - x- x- O CM CM O CN CM 00 χ- C0 O τf C0 τf CD τf uJ C000 UJ C0 CJ) in N C0 CD C0 O O ) x- x- CD CM U) O CM UO x- x- UJ CD CN CJ) τf CM LO CD UJ N UO CD 00 O O 00 CM O CN O O τ- 00 lΩ CN N N N C0 O CD χ - χ - τf c0 N CN N CM O N CO N Tf O N CO N CO CM x- CM O OO CM N N UO CD x- CD N CO CO cq cq CM Tf N O UO CD LO CM CD Tf cq O OO J N x- CD N CM CN N CO O O (D N N CO CM N UJ CO CD CO x- CD CN T f x- CM CO O T f CD CD x- CD Tf CJ) b b b ιri ιri c f t ' j: ιri cM CM , τ- : τ : cM c b b τ- - J b b b b cM , - CM CM τf . τf uJ Lri d cd τf lri lri N ' N N N U U co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co c^ xt CD CD CO CO C CD LO C UJ N χ - CJ ) χ - CD N CO N θ LD C CN O CD x- CM U x- UO CD τf x-- u CD C τf CjO C» CN O CO CO CD ω χ - CD N CD O CO O N O CJJ N CD CO CO CO CO CM CD CD in N τf iΛ CD CO CO CD CM lΩ CM τt CJ) N CO O O CD χ- N UJ UJ CM OO CD Lθ CD τ^ θ χ - c co o cq c D CJ) τf θ χ^ c» τf | . f cM CJ) cθ Ln χ - cD CJ) oo ιn cN co co ^ N CJ- σ- od ιb ιri t c t c (N < ιb D t t cM ' c CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CO CO CO CO CO CO CO CO CO CN CO CN CN CO CO CO CO CO CO CO CO CO CO CO CO C^ ( s ^ τ- ( r ^ ro . c M (O CM f ( co c co co co ro co ιn D ■ f ro c ro t ιn . τ- c ^ s ro o τ- N ιo o (D ^ N c ro . o oo - UO U N τ f τf θ) τf cθ lΩ τf N O x- C CD CM C CM CD CO τf u CO τf CM x- τf CM CD x- CM χ- CO χ- CJ) χ- C χ- lΩ CJ) χ- 00 τf |v. cjJ CM CJ) χ- N x- N q cD O CO CO χ- CO CO CM CJ) UO N x- CD τf CM CO CO CO O N CO CD CJ) CD CO τf τ^ α lΩJσiniuoόOfflUJsUOsUOisUJiUriiUriOiUriOcUdOcUbOsUOsUO ' sUJiUriOsUJ ' ωUOilriΩtlDΩiinriiinrisLΩ ' sLO UωO UodOwUO UO UJ UO UJ UJ UJ UO LO LO in LO LΩ LO UO UO UJ U^ x- x- CM CM x- x- CN CN CN x- x- x- o DO CO x- cN ω cα O O Ω Ω X X X X . x- CM x- OOOOOΩ ΩΩ <XXO o < DQ Ω LU N LU X X X X < CO OO Q < CQ χ χ χ χ χ χ χ χ < X X x- CN X O O O O O Z O Z Z X X x- CM x- CM x- CM X x- CM x- CM ooooooo X X X x- CM x- CM CO x- CM CO Z O O a. a._£ _£0: _£ O OO OOOO OOOOOOOOO cococo U m θl CLCC O LQL fc LCLCLLLιΥ. LlL L LLO^ C0 CO CO CO CO C < < < < < < < < < < < < < < < < < < < < < < < < d d d d d d d d d d d d d d d d d d d _ _l _J © o LΩ CD N CD σ ) O x- CM Cθ τf J CD N CO CJ ) O χ - CM O τf iΛ Lθ N CO CJ) O x- CN C τt LΩ CD N αθ Cn θ x- CM C τf U) C.^ N N N N N CO CO CO CD CD Cθ αθ CO CO CO CD <_J CJ) CD CJ) CJ) σ) CJ) CJ) CJ) O O O O O O O O O O χ- χ- χ- χ- χ- 'r- x- χ- χ- χ- CM CM CM CM CM CM CM CO CO CD CO CO CO CO CD CO CD CO C CO CO CO CO OO CD C» CO CO CO OO CD CO O) CJ) CJ) CD CD CO <J) CJ) CJ) CJ) CJ) OT LO © © UI H U α. LO CO Tf x- lΩ CD O O O O O O O O O O O O O UJ CJJ xt O CO CD CO CO O O O O O O O O O O O CD CD LO CM CM CM CD x- CM CO O O O O q cM CM c o cq q q q o q q q q q o o o cM CM co N CM CD x-- CD O O O O O O O O O O O co co o co x- x- N OO in co o o o o s N tN io ^ d d d d d d d d d d d d d N ffl d ffl cό s ^ d d d d d d d d d d d iN io d ^ χ - χ - χ - CN CN CO CN CN CM CN CN CN CN CN CN CN CN CN CN x- χ - CN χ - χ - χ - χ - χ - CN CN CN CN CN CN CN CN CN CN CN CN C^ D x- CO OO CO C_ N CM τf CM UO CO x- CJ) N χ- χ- C Uj αθ x- L θ O ιn N UO Cθ LD CO x-- CM CJ) τf χ- UJ CM CD O τf CD N CM O CD CM N CM CN CO CO O CN CD CD N χ - CN N O N CD CO CO τf C CO CD CD O χ - χ - Cθ σ ) lΩ O CJ ) CO θ σ ) N CM UO N CJ ) CM CD τt CM O N O UO CD CD Tf LO O CO N UO CN O Tf τf lΩ τf θO CM CD CJ ) CJ ) UO CD O CJ ) τf x- O CO CM CD CJ ) CM N N x- CO χ - CM CD UO CM CO CD N O CO CM CD CD CM C Cθ Lθ N τf CM CM LO D CD CD CD d Tf J N Tf uO N ri N u U u cb cb - 1 ^ ' σ. τ ; b si od b σ. CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ xt TT CJJ τf CD τf O χ - CD CN χ - O CJ ) lΩ lΩ CM O LO CN CO CD N CO CJ) χ - ιn LΩ UO OO CD CD C σ) τf cθ N τf O τf c CD O CJ) CD ∞ Tf CD CM UO CN CD N C Tf cO Tf O CO CD C Tf cO CJ) CJ) CM CN CO Tf u Tf O) O in CM Tt x- UO C x- C LO UJ x- N CO OT CO CN O x- CO Cq N N CN x- CD CO χ - σ ) N O C_ Lθ CM CO θ Lθ CN τf CN CJ) N N CD τf τf |v. OT d cb x^ c j - cd d d od cb d d N cb cb cd d N cb N cb cb d CM CN CO CN CN CN CO CN CN CN CO CO CN CM CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CO CM CO CN CN C^ N Tf O O C CN x- x- O lO O CN N CD x- LO x- CO N UJ x- t CD CJ) C CJ) CO τf c CO (J) N f CD CM x- CM N OO CO N N UJ CO O Tf CD CD O x- CM CO UO LΩ CO CM O C τf xt τf τf |v. c O UO N CD CD χ - 00 0 CD UO CD UJ OO CM CD CD CD CM UO CD CO CD Tt x- CD OJ CO O O CN CO CM N CD CO 00 CD CN CM x-; τj u (JJ θ oq q CM q τf UO UO UO O CJ ) CO CD CJ ) OO N cD cq cq q χ-; q cq q N τf x- τf rv. CM CD CD CD UJ UO LO OO Tf τ χ ιri N ro c co χ . co ιri ιri d (D cd N c (D b d b ^ tjicoNs od ω ∞fflNωNN ∞ Bcd O CD O CO O CD CO LΩ UO UO UO UO UO UO UJ UO UJ UO UO UJ UJ UJ LΩ. LO UO UO U Tf UJ UJ Tf τf t t UO τt τt UO τf τt τf τf τf τt τf τf τf f τf τf τf τf UO Tf LΩ Tf UJ Tf Tf - >- ^ >- ^ ^ ^ >- ^ ϊ- ^ ^ LU LU LU LU J LU LU UJ UJ UJ UJ UJ LU _U LU LU _ _J J ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ _ _J _J ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ _J .J ^ ^ ^ ^ ^ ^ ^ J ^ _J _J _J _I ___ __ ._J X X X X X X X X X X X X © o N C CJ ) O χ -- CM CO τf ^ cD N CD CD O χ - CM C τf uθ CD N CO CJ) O x- CM C xt ιn CD N CO CJ) O x- CM C τf CD N CO CN CN CN CO CO CO CO C CO C C C C τf τf τf τf τf τf τf -^ τf τf ι_. J lΩ lΩ lΩ 0 UJ UJ in UJ CO C CJ ) CJ ) CJ ) CJ> 0 ) CJ ) CJ ) 0 ) CJ ) CJ ) CJ ) CJ ) CD CJ ) CJ ) CJ ) CJ ) C_. CJ ) CJ ) CD CJ ) CJ) CJ) CJ) CJ) CJ) CJ) OT LO © © UI H U α. UO O O CM CM x- CM Tf x- CM CJ) x- x- OO CM CD CN CM x- CN O x- O UJ UJ UJ N lO C τf x- CO C CO CN x- C N CN CO CΩ CO τf x- τf CD τf cO τf O N CD χ - N CJ ) τf UJ O U0 CM CN CM xf Tf c OO N x- x- xf CJ) LΩ x- CD UO Tf CO χ - O τt UO CM O O CM CO CD CO τf CD CD CD CO CM Lθ CD τr N UO O x- Lθ N O Tf cO CO CO CO CO O O COO x- CCDD CCDD CCOD xxtt CCMN CCOD CCDO OCDJ CCNM OO CCDO CCO CCDO CCDD xx-- OO xx-- CCΩD CC CCNM CCOO ιlnΩ ττff ττft UlΩO O O l LΩΩ χ- τ Tff C OD) CO CC σ CD) NN COD- CCDD NN CCNM CCMN CCO OCOO x^ OO CM CD lri uό uJ Tf Tf cM CN CN b b Tf xt ^ c iri Tf cM uO N co cb cb Lri ib Lb x^ d o d cb cb oo M o x-^ x^ o Tt CO Tf cO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CN CN CN CO CO CO CO CO CO CO C^ o xt xt CD UO N CO UO CD CD UO CO CD CM N x- CD CO O UJ CJ) CJ) OO f CO CD N UO τt x- O C CO CO O CM O N CO CM OO CJ) C0 x- UJ U0 CM CO x- CD x- O CO Cp φ lfi M- O ω θ - - 0) 0 ∞ (O Q χ - ro - r uJ N C (0 (M CO O C CO CN CO O N O) Tf Tf x— UO OO U) CO x- x- O ) CO x- x- CM CJ) τf σ) CD CJ) lΩ CO O CO CD N CD CD CJ) OO CM CD UJ τf CD C0 N CD U0 0D CJ) CO CJ) CM CO 0O x- CO N N N CO N CO " O Tf CO 00 N CD CJ) O x- CM UJ CO N N O- CO CM x^ CM CM T f cd cM T f T f ' x^ CM x^ T f f xf ' ιri b bσ) roc bN cobbdN σ. (dσ) σ)dd _)d σid rø dcd cMcb 'xrTf co ' CN CN CM CM CM CM CN CM CM CN CN CM CM CM CM CM CN CN CM CN CN x- x- x- x- x- x- x- x- CN CM x- x- x- x- x- x- CM CM x- CN x- CM x- x- CN x- CM CM CM CM CM Tf Tf O CD N N CO x- UO OO CD x- CD CO CD CO CD t CO OO CO CO O N CO CM CO CM cO OO CO N N CO LΩ UJ x- CO C LO'J x X-— x X-— xX-— U UO C LJJ)J τ XfT N I— • τ XfT U UJJ C LDU L-J C IM O L-J C COJ - L 14Ω J N I -- C VOJ C LDU CO CD Tt CD N UJ CM Tt Tf τf τt r-. r-. cθ N CJ) CO τt cθ CD CO C CO CO x- CD CM O O X- CN X- X- O CJ) X- CJ> CM CM O X- CM O O X- CM CJ) CD O C0 CJ) X- C0 C0 X- X- X- O in ιΛ in LΩ UJ τt U0 τf UJ U0 U0 lΩ LΩ U0 UJ LO UJ τf τf U0 τf τf UJ τf τf UJ UJ in UJ uo ,„ . _ CM CM x- CM x- x- CM 00 OQ LU LU x- CM CO DO T - CM OQ CQ Ω Ω U < CO O Ω LU UJ < X X X X X X < 00 Ω LU LU < X X X X < C0 Ω Ω < χ χ < 00 X XX ZOOOOOOO Z X X x- CM x- CM x- CM OϋOϋϋϋOOl X x- CM x- CM O O O O O O O X X X- CN Z O O O O 2 C,Λ Λ CΛ Z^ Z^ ^Z Z^ Z^ Z^ ^Z Z^ Z^ Z^ Z^ Z j Z^ Z^ Z^ Z^ Z^ 3 j 3^ 3^ 3^ 3^ 3^ 3^ 3^ 3^ 3^ 3 j 3^ 3^ 3^ 3^ w Q_ c CL w CL w CL C w L Q w L. w CL C w L c CL w CL C ω L c CL w Z w Z w Z ω Z c Z / - XXX O OO <<<<<<<<<<<<<<<<< © O x- CM C0 Tf Ln CD N 00 CJ) O x- CM C0 Tf L0 L0 N 00 CJ) O x- CM C0 Tf U0 (0 N CO CJ) O o CJ) O χ- CM CO τf lΩ CO N CO CJ) O χ- CM CO τf Ln cD N CD CJ) O O O O O O O O O O x- x- x-- x- x- x- x- χ-- x- x- CM CM CN CM CN CM CM CM CM CM Cθ N αO OO CO CO CO CO CO CO CO OO CD CD CD CD CD CD CD CD CD CD O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O CD CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) CJ) ( ) CJ) CJ) CJ) (J) CJ) CJ) x- x- x— x— x— x- x- x— x— x- x— x- x— x— x- x- x— x- x— x— x- x- x- x— x- x— x— xτ- x— x— x— LO © © UI H U α. Tf LΩ CD O O O O O O O CO UJ x- OO O UO CO o o o o LΩ OO N x- CD CM UJ O CD x- CD O O O O O O O O O CD x- CM CJJ CO x- O O q c o q o q q q q N cq oo Tf x- CO LΩ O O O O lΩ CD CM CO CO Tf uO CO N N N CD O O O O O O O O O O Tf cO x- CD CD OJ CO O O cd d uό d d d d d cd co N cd cd xf d d d d d d cM CM CM d cM d -_ -l CD O O O O O O O O O O CO CM CM CN N r Oi ∞ w . O O x- x- x- CM CN CM CM CM CM x- x- x- x- x- CM CM CM CM CN CN CN x- x- x- x- x- x- x- CJ ) χ - CM CM CM CM CM CM CM CM CM χ - χ - χ - χ - CO x- OO CM CM CM CD N CM UO N N CO CD Tf CM CO CO CD LO CD CJJ CD N CO CO Tf r^ CD Tf CN Tf CM LO O x- Tf CO OT Tf CM N UO CO O CD CO CO CO CM CO CD N CD CM UO N O N CD CM x- CD CO CD OO N CM Tf N CD CD UO N x- CM 00 UJ LΩ UJ CM LO CO Tt CD CD O CN Tf x- cO LΩ N CO CO x- OO CO CD CO CJ) x- x- x- N J) Tf CD OJ CN CD CO x- CM N N O CD CD O CO N Tf o J CD OO CO O UJ N N iΩ CM iΩ cM τt q N cθ χ t c q - CD CM CO N x- CM x- CD N N cd cb d d cd cd cb cb x-^ CN CM CM co co x- co CO Tf Tf O CD CD CD CO N cob s dt cbdds cdcdcDs ' iri irid C CJ) CJ) O O CN x- O CO CN CN CN CO CO CN CM CN CM CO CO CO CO CO cO CO CO CO CO CO CO CO CN CN CN CN CN CN CN CN CN CN CN CO CO CN CN CN CN CN CN CM C^ xt xt xt CM τf c CJ) N <3J CJ ) O N τf c CJ ) χ - αJ N OO CJJ CM CD CN CO CO N CM CO CO C CJ) CO CO CO CO χ - CD CN lΩ CM CM CD CN τ^ O UO CO N τf O OO O in cO CO C C» τf - CJ) O UJ CM τf x- <O xf cO O O CO CM N CO in CD O CD Lθ N Lθ CO x- τf CO O in CM x^ CM CJJ O CO τ- N cq CO CO CD O CO CO O UO N CO CD C3) O CD CM LO C CJ) cq ^ Tf Tf Tf ' x-^ c c cN Tt co Tt N ro xt b ib N ∞ C ώ CM CM CM CM CM CM CM CM CN CN CM CN CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CO CO CO CO CO CO CM CM CM CM CO CM CO CO CO CO CO z zzzz zz zz _- [ i iD-_-_-i Q .ι _-_- _- α(ϊ Q_D_Q Q: [_:κQ_ Q:Q:-CQ_(_:(£ Q-Q- [ϊQ: D_α: 1 , l , ll ll , ,,, ,,, ,,, C CΛC COC0WCΛCOCΛ<_0<_0COW CΛC ωCΛCΛCOC >->- >->- >-.>- > < << << << << < < < < < <<< < < < < HI- l-l- l-h- l-l- l- l- -- -h-l-l- l- l- l- h- l- l-d dd dd dd d dd © x- CM C0 xf lΩ L0 N CO CJ) O x- CM C0 τf 0 CD N CD CJ) O '^ CM C0 τf UJ CD N 00 CJ) O x- CM C0 τf U0 CD N C0 CJ) O x- C^ o C C C C C C C C CO τf xf τf xf ^ τf τf τf τf τf UJ UO U lΩ U LO UJ U UO LΩ CD CD CD CD CD Lθ Lθ O OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO O OO OOOO OO N N ( D O O O O O O lΩ 00 CM O O O O O x- CO UO OO UO O O O O O OO CO UO UO OO CO UJ O O OO OO OO OO CD UO CO O CO Tf (J ) CD O O O O O O x- O LΩ CJ) O O O O O O UJ CM CO f U0 τf θ O O O O τf UJ x- CD x- U0 τf cJ) ddddddddd^. 10 . 0 . 1 ". o dddd d'^o CN " " . O O O O o o O CM J O O O O O O x- CM CO CO CO UO UJ UJ CN CN CN CN CN CN CN CN CN CD CD x- x- CD CD x- CD CM CM CN CM CM CM CD N CN CN CM CM CM x- x- CN CN CN CN CN x- x- x- x- x- x- x- x- OO O CO x- N UJ χ - χ - τf CM x- N CM τf UJ τf N CD U0 τf CD C0 x- τf χ - o CD O CM Uj Tf r-- O CJ) O N LO CJ) N U O CD CJ) N x- CO O CO CD CJ) N CO xt x- x- N CO CM CO UO CD UJ N CD C CO x- N CD CD Tf N C CD O UO CM τf U) CD lΩ CO N CD LΩ U) CO N O UJ τf cθ CO N C N x- CO CO x- CM OO CN O CM UJ OJ O xf CD CN CD CD N LO CD CD N CD LO CO CM CO x- CM N C_D. - cM o N co N θ τf cM iΩ uo co c) oo iΩ oo ιn ιn iΩ co N N cq cq cq d d cN CM CN CM x^ d cb N c cb ib Tf ^ cb O r xt ^ x^ cM c^ CO CN CO CO CO CO CO CO CO CN CN CN CN CN CN CN CN CM CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CD CM CO N N LO x- C0 C0 lΩ τf c0 C0 CD CM C0 CM χ- lΩ C0 C0 τf τf χ- χ- CM C0 CD C0 N O O (» CM x- τf C0 τf C0 C0 N CM C0 N τf 00 N 00 CD χ - O N CO CD C CO N Tf CN N O CJ) x- C CO χ- N χ- CO CD τf 'xf Ln CJ) O O CO CJ) N lO CO N CD UJ CD O CM N UJ CM CD τf CD θ CO χ - N CM CO χ - CO CM CD O N CD x- Tf Tf CO τf q N σ) N iΩ in cM c co N o c o q cM CM cq cM <q τf f θ x- 1 CM CO CO cN co cN τ CO CO CO O 00 CO CO CO cCO cCOd Cf C CO uCO CO NCO CO cC τCθf Cθ τCOf dCO uCO dCθ CO NCO ' CO dCO COO NCO uCOJ CbO NCO ώCO CO CO τf cO CO CO CO τf τf cO CO τf τf x^ c^ O CJ) Tf x- CM Tf CO O O τf x- cθ CD O CD CO CN χ - CΩ x- χ - N N CN O OO C C Nr-- τr x- x- N CO CM CO LΩ CO CO τf CO CM τt CD CD CJ) N lΩ CD CJ) O CD CO O LO 00 N Tf Tf Tf CM UO x- UO CO OO Tf UJ CO O CD CM CM CO N Tf N CD O CJ) O CM CO N CO CM CD CO CN CJ) τf cθ CJ) CD CD N CO CJ) N O O UJ N CO LO CD UJ CM CN CO CN τf x- CD CM CO CO N UJ N x- C0 CO N CD CD CJ ) τf x- τt C "N> ■ ' N CD CN CD lΩ CO CN Tt CO lΩ N CN CO CD N O CD CO x- Uj q q x-; cd r-i cb d d oo N " C LOU C LOU O L-J xx-- O LJ C UDJ O L-J xx-— x— C CNN C UDJ C LMN C UDJ O L-J C CMN x— - x— C IMN C COJ O LJ C IMN O L-J L-J d UJ UJ c IMN c CoJ c CoJ c IMN τ XfT ' X^T ' xr-^ τ XfT U.J c CJ c CdJ XT c CoJ τ XtT LU τ XfT XT ' c Lo'J ι ubj Tf Tf Tf UJ UO Tf Tf Tt Tf UJ UJ UJ Tt UO UJ UJ U Tf Uj Tf UJ UO UJ UO UJ UO UO UO UO UJ UJ Tf Tf UJ UJ UJ UO UO UO UJ UJ LΩ UJ UJ UJ UO UO UJ UJ UJ UO UO x- x- CM CM CM x- CM CM OO OO O Ω Ω Ω _ <N OQ 00 Ω Ω 00 OQ DO CQ DQ x- CN C Q X X X X X X X X < CQ Ω Ω < χ χ X X < GO < X X X < DO < X x < CO Ω Ω X x- CM x- CM CO x- CN CO OOO OO O Z X X x- CM x- CM O OOOX X x- CM CO Z OOO OO X X x- CM X oo ooooυ Z Z Z Z Z Z Z Z Z Z Z Z Z Z < < < < < < < < < < C__ _E _£ _£ C__ C__ Ω_ 0_ Q - Q _ Q _ 33333333 L-J LU LlJ L_J LU LlJ U-I LU UJ cy s l t y) c7_ <y. COtø d d d d d d d d d < < < < < < < < < < < < < < < < < < < < < < < < COCOCOCO CO CO COC0 COCO C _J _J _l _J -J -l _l _l © o CO τf ιn CD N CO CJJ O χ- CM CO τf ιn CD N CO CD O χ- CM C τf Ln CD N CO CD O x- CM CO τf LΩ CD N CO CJ) O x- CN C τf UJ CD N C^ CO CO CO CO CO CO CO CJ) CJ) CJ) CJ) CD CJ) CJ) CJ) CJ) CD O O O O O O O O O O x- x- x- x- x- x- x- x-- x- x- CM CM CM CM CM CM CM CM CM CM C^ O O O O O O O O O O O O O O O O O X - X- X - X- X - X - X - X - X - X - X - X- X - X - X - X- X - X- X- X- X- X- X-- X- X- X-- X- X- X- X- X- X- X- X- T- LO © © UI H U α. O O O O O O O O O O O x- N N CO UJ CM N UO O O O O O O O O O O O CO CO CJ) CJ) CD O IΩ CD CD O O O O O O O O O O O O O O O O O O O O O O O O O CO Tf N UJ CO CO N O O O O O O O O O O O CO O N CO CO N CO CO CM O O O O O O O O O O O O O dddddddddddcN(θ dco( d(Mdd dd ddddddd© (oαi -) (o CM CM CM CM CM CM CM CM CM CM CN χ - x- -^ χ - χ - χ - χ - χ - CM CM CM CM CM CM CM CM CM CM CN x- x- x- x- CM CO τf τf LO CM CM CM CM CM C^ Tf UJ CM CM UJ OO Tf cO CD τf χ - O CO CO τf CM N CO CJ ) CD N N χ - CM CJ) UO CJ) CD x- lΩ τf τf O τf CD CD χ- O O CD CO CD CN CD CM N OO CJ) CN CD CO τf Tf O N OO N LΩ UO N CO x- CD N CO O CD CO CO CJ ) N CM CJ ) χ - x- CD CO τf CM x- N 00 θ σ) CΩ C0 CN C0 lΩ CΩ CD C0 CN C0 C0 CN N N τt r-- C0 N N O Tf O CO CO m CM CO CO x- CN CO CO x- N CO CO OO N CM CO CO CD UJ CO CD CO CM CD τf x- CM UJ CO CO CD τf O UJ CM UJ x- UJ τf rv. CO N CD N CD x- CO CO LΩ N N N CJ ) CJ ) CJ) O O O χ - CD N CO CD CD χ t CD χ t CD CD CD χ t τt CD N CD τf τf c CJ) O O O O CM CO Tf LΩ OO χ - O O CN CN CM CM τf τf LΩ τf cD C C C C CO C CO τf τf τf τf CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tf Tf Tf Tt f Tf Tf Tf cO Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf CO UJ CO τt CD CO CJ) CO CD CO CO χ - τf UJ CM τf CD O τf cθ x- CM N N O N τt N UJ UJ CM CO CD x- CD CD CO CM N CN CN CO x- CO CN CO m CJJ O CM UJ O cococMCMτ- χ f - coroc τ- rococo o f coιn roroωτ-N rocMcoroNcocoιnooτ-roιθ (θcoσ)(θ (θθ 00 CO CJ) CO CM x- Tf CO CD CN cθ O x-; Cq CN Cq CM CJJ CM CM τf r-- O CM CJ) N CM CO CO CD O O τf CM τt O CJ) CD τf O x- UJ UJ CJ) CO ιn c^ CD CN O O O CO CO N CJ) IΩ CN LD UJ od d cb cb d χ -- : d cb cjJ cM cd τ f '^ 'xf τf ' cb cd cM cb ιri b u d C Tf cb cN cb cb x-^ O x^ CM O CJ- O " CO τf c CO CO τf τf τf cO CO C τf τf τf τf τf τf τf τf τf τf τf τf -^ - - τf τf τf τf τf τf τf τf τf τf f τf f τf τf τf τf f xf xf χ ^ τf τf τf τf cO f CO IΩ CO X- CΩ CD CD CN LO CO CO CO CD CO OO CN O O CO O U0 N C0 O CD C0 CD CD τf CD χ- U0 C0 U0 CD CM C0 CD C0 U0 CJ) χ- N O C0 f x- UO O UO UJ Tf OJ UJ CD 00 CO τf CO x- in τf c CJ) τf CD U0 CO 00 Tf O O CD χ - CO O CM U UO UJ O x- CD UO τf _ CD CO xτ- CM CO C τf CD CD CD x- CO N UO x- x- qιθ -xf τ- f ooq 00 χ- C0 N CM CO CJ) χ- CM C -O- C-M- C0- -N O- -N U -0 x- -D O- (-J) x- C0 O_ C_J) C_J) CO_ χ- LΩ _ . N χ- C - CD x- N C J) τf - σ> Tt CO N x- N UO O CO Tf CM LO Tf C CM 00 CM U UJ ^ ^ ^ ^ c ^ ^ ^ ^ cό ή d ^ d d χ t ^ c ^ ^ ό d d d d d \^ \^ \^ d \^ d UO N CO cb cb N CO N N UO UJ UJ UO UO UJ UJ UJ UO UJ UJ UJ LΩ lΛ LΩ lΛ UJ UJ LΩ UJ UJ UJ UO UO UO UO UJ UO UJ UO UO UJ UJ UO UJ UO UO UO UO UO UO UO UJ LΩ in in in UO UO UO U^ x- x- x- CN CM CM x- x- CM CM CM x- x- x- 0Q CO,_ ΩΩ ΩΩ ΩΩ x- CM x- OOOOOΩΩ Ω CO OO O O Ω Ω LU UJ N N N _<X X χχ χχ χ χ < DO Ω < CQ χ χ χ χ χ χ χ χ < X- CN CO X- CN CO υooooυo X X X x- CM x- CN CO x- CM CO oooυ DO Ooo Ωo LU Nz _ <x X X X- CN X X X x-xCMxx-xCNxx-xCNxx-xCMxx-xCNxCO 33333333333............ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO LU LU LU LU LU LU UJ UJ UJ UJ LU L I L1J . ^ ^ ^ W W LU L ^ LIJ UJ UJ W U-I IU IU LU ^ _) _ _l _J _l _J _J _ι _ι _ι _ d d d d d d d d d d d d d d d d d d d _l _J _J _J _l _J _J _J _J _J _l _J _l _ι _J _l _J _J _l _J _l _l © o LΩ CD N CO CJ ) O x- CM CO τf lΩ CD N CO CJ ) O χ - CM CO τf LΩ CD N CO CJJ O χ - CM CO τf LO CD N CO CJJ O χ - CM CO τf lΩ CD N CO OT CO CO CO CO CO τf τf τf τf τf τf τf -^ τf τf ir) lΩ lΩ LΩ LΩ in LO LO LO lΩ CD CD CD CD CD CD CD CD CD N N N N N N N N N N CO CO CO rø LO © © UI H U α. Tf N Tf N CD N x- CD O O O O O O O O O N f CO CO CD UJ O UO τf O O O O O O x- x- xt N CD CJ) CD CM CD O O O O O O N τf CD UO CO Tf O O 00 Tf Tf N OO O O O O O O O O O CM UJ CO O CO CM O χ - U0 O O O O O O τf 00 N N CJ) N O C0 CD O O O O O O χ - CD τt O LΩ N N N CD lb UO CD CN o d d d d d d d o o cN CN Tf co iri d cb cd d c Tf Tt T b uJ Lri cb d d d cM x^ cM Tf o x- CN CM CM CM CM CM CN CM CN CN CM CM CM CM CO τf Tt Tf CN CM CM CM CM CM CM CM CM CM CN CO Tf Tf Tf CM CM CM CM CM CM CN CN CM CM CM UJ N N U0 CJ) CD 00 CD N 00 C O CD CD CJ) x- CD CD τf CD in τf |v. O CD UO CD OO O CD CJ) CO τf CD σ ) CO CD N CN O CO CO τf CO N CD O Cq N CO lΩ CD cq iric tib t τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf N CD CJ ) lO N τf σ ) lΩ τf x- τf | v_ 00 CM x- C U0 C CD CM UJ CJ ) CM O N CM xf CM CD N CO lΩ LΩ N UJ CM x- x- OO UJ CD C CD Tf f CM CO CM N CD C CM CO Tf CM CJ) O CO CM <J) L D LO CO CM CO CD CM UJ Ln CD CM CO Tf cD xf O N CM CM χ- xt τf τf xf uJ τf UO τf CM O CO CO CD UO O CJ) τf CD CO UO UJ O CM O in C0 00 q 00 N in x-; Tf (J ) C0 CD iq C0 N CD CN N N O x- C0 l0 τf c C U CD CN N lΩ O O C N x- CO CO CΩ C N CO C CN CJ ) CO χ - CΩ O O x- CN b - - od cd cd cd D ' n cd j ) N N <j> σ. b ώ τf τf τf τf τf τf τf UO Tf τf τf τf τt τf UJ IΩ U τf τf τf xf τf τf τf τf 'τf xf τf '^ 'sf τf τf LΩ in UO UJ UJ UO UO U^ N T f N N in x- CO O CN CD CO CM OJ CO CJJ CM CJJ x- CO UJ x- x- CM CD N CO CD U Tf r^ CO Tf CD Tf CJJ x- LO O CM CJJ N CO CM ra CN CO O τf N CJ) UO OJ CO τf cθ N O x- CO N CD x-- N LΩ in CD LO O O CD τf cθ σ) in θ CD N CD N in CD x- CM CD τf N CM N N CO LO N τf UJ CD q q q x- q CM N q q UJ x-- N N CD CO x- CO CO N τf uJ CM N CO O N CO CM CO τf cθ τt x- σ) τf O N CO CM CD N CJ) xt CO N UJ CO CD CM cq d s ' iri iri ω s ' iri s d ^ ^ ^ N d s ∞ ro od s d d c C tN co ∞ in in UJ UJ UO UJ UJ LΩ LO UJ UJ LΩ UO UJ UJ UJ UJ lΩ LΩ Ln u CD CD CD CD CD lΩ UO CD CD CD CD UJ UJ UJ UO UO UO CD UJ CD UJ UO UO C^ ω ω LU LU LU x- CM DQ DO OO τ - <N OO OO OO < ω o Ω LU _ <xxxxxxx < CO Ω LU LU < χ χ χ χ < DQ Ω LU LU < X X X X < CQ ϋϋOϋϋtnϋ X X x- CM x- CM x- CM CO OOOOOOO X X- CM X- CM Z O O O O O O O O X X X- CM X- CM Z O O O O I— r— \— - — r— 1— I— I— I— I— I- I— I— I— I— I— 333333333333333333333333333333 <r< <-<< UJ IIJUJ UJ UJ IIJUJ UJIJ UJ UJ IIJUJ LJ UJ IU IIJ J J J J J JJ J J J J J J J J J J J J J J J J J J J ^_≥-> -≥-≥_>^^^ .>.≥^:>^SOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO<<<<:< © N C0CJ) O x- CMC0 τf UJ CD N αj σ) O χ- CM C0 τf UJ CD N ∞CJ) O x- CM C0 τf ιn cD N 00 CJ) O x-- CM C0 τf U0 CD N ∞ o CO OJ CD CJJ CJJ CJ) CJ) CD CJ ) CJ) CJ) CJ) CJ) O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM CO CO CO CO CO C^ x- χ - χ - χ - x- χ - χ - χ - x- χ - χ - χ - χ- CM CM CM CM CM CM CN CM CN CM CM CM CN CM CM CN CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CN CN C^ LO © © UI H U α. O O O O O Tf O CM x- CO CO CD Tf CD O O O O O O O O CO x- Tf CD CO CD O CD Tf OO O O O O O O O O O O O O O O CM CO N CD CD T- O O O O O N OO OO N OO CO x- CO UO O O O O O O O O τf OO CO CD UJ CO N CM CJ) CD τt O O O O O O O O O O O O O Cq τf cq x-; Cq q ddddd !. (_ NtNdNrN(dobd dddddc. ob(_ NiB( NNu.t. (odddddd CN CM CM CM CM CM CM CM CM CO τf τf τf CN CM CM CM CM CM CN CM CM x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM CM C^ N CD CD UJ N U Tf cO UJ OO O O CO UJ UJ O CO x- CO CO N CO xt x- Tf cD CD UJ UJ N CD x- UJ CM CM CM UJ CD N CM N χ- τf cN UJ CJ) CO C N N O CJ ) CD CD CM χ - x- CJ ) τf UJ CJ ) CO CD N CD CD OO x- N x- UJ UJ O CD UO CJ) x- N CJ) O CM O CJ) N O CD N CM CM CJ) UJ Tf N O CJJ Tt CO CO CO CM UJ O CJ ) O) CO CJ) C0 CO CD CD C0 τf x- χ - N CD CN CD UJ UJ x- CJ) U0 N LO Tf |-- CO CD O CO C lO OO CO CD O Tf cO CO CD CO Tt CM x- c N x^ x^ co CO IO CM CM CO UO CD UJ CD CO CD CD CD IΩ CD CO CO O CO OO cb T cO CN x-^ c CM CM c cM Tt Tf ^ ' ci cO CM x-^ x- 1 CM Tf ' cb x-^ uό uj CM x- O x^ CN CM Tt Tf Tt f Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf Tt Tf Tf Tf Tf Tf Tf Tt Tf Tf Tf f f Tf f Tf Tf Tf Tf Tf CO CO CO lΩ τf τf θ χ- CD N CD CM CM CD CD CM N CM in θ O CJ) x- CO CD N N N CM CD τf cθ N CD lΩ N CO C CJ) CM C_J CO CO CJ) τf O CM N CD τf cD C_ CO CD O CO CJ) τf CM CM χ- O C CO CJ) COCD x- CM UJO lΩCM τt CN O x- x-- CO x- ιn θ σ) UJ x- OO CM OOO CJ. cM θ CN N qco co q cM θ cM uj cq o N cθ N o cθ N N θ co cM co cq τf τf τt q x- T^ c tN CN co ' od N ro d N s d co cd io cd s sffl ) LΩ in iΩ lΩ f τf τf xt τf xf τf τf τf τf τt τf lΛ τf τf τf τf τf τf τf τf τt τf τf τt lΩ lΩ IΩ τ^ C τf CD CM CJ ) O x-- U CJ ) O CD CM χ - CM τf ι CM CD CO τf c N CD N CO CO O CO τf CO x- N O OO N CD CO CO CO CM CD CO UJ CM CD CO CD CM Tf N N CO LΩ N LO CM CM CO O) CM τf τ CNj x- CN x- CD CO CO χ- CD CD O C CD LΩ U x- CN CJ) CO O τf O0 x- x- CM N UJ 00 U0 N Tf U0 U0 UJ CD CJ) CD CD CO CO x- CM N . U _J. CO O CO χ - CO CM τf O CD O C .M- C„O C.O. C.M_ C_J. ) . C_D q Tt co cq q q CM xt CM- o~q s θ tcnoco co coτt cNN NCM cqN CDτtcNjcqq N Lθ τt ιb cd ό τf c cM τt ιb ιb τt d ό ιb cb cd ιb ιb d cb cN d σJ cb r-i N cb τf ' x-^x- J χ orøcj. cbcb NicD cbχ- : χ- oσ. χ-- : cb lΩ UO UJ UJ UJ UJ UO UJ UJ UJ UJ UJ UO UO UJ UO U LO LΩ LO LΩ LΩ LO UO UO UJ UJ UO Tf t τf τf in u UO UJ τf UJ τf xf f τf τf τt τf UJ UJ UO τt UO UJ ,_ .„ CM CM x- x- CM CN DO GO DQ GO GQ LU UJ ,„_ "- M ωωOOΩΩ xxxx _ .„ _ <XXX < GQ Ω LU UJ < X X X X X X < CO Ω UJ N X X < X X X X X X LU x x x X < Λ CQ X X x- CM CO ooooυoozxx x- CM x- CM x- CM OO OO OO Z O Z Z X X X- CM X- CM - CM X X- CM X- CM Z OO O O O < << << 2z zz z zzzz z z z zzzz z Q_ α:ct_ Q_Q_Q_ i ^^ —iLi -l-i -l-i -i-i-i-i-i -i -i-i-i-i-i-i -i L L CCGL L L ttLL^ < << <<00000000000000000<<<<<<<<<<<<<<<<<<< << << <cococococoω © CJJ O x- CN CO τf LΩ CD N Cθ σ) O χ - CM CO τf ιn CD N OO <_D O χ - CM CO τt in CD N CO CJ) O x- CM CO τf UO CD N CO CJJ O x- CM C^ O C τf τf τf τf τf τf τf τf τf τf LΩ lΩ lΩ U0 UJ U0 U0 UJ UJ U0 CD CD CD CD CD CD CD CD CD CD N N N N N N N N N N CO CO CO CO CO CO CO CO CO CN CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM C^ LO © © UI H U α. O O O O O OO CM CM CM CD OO LΩ CO O O CO CM O O O O O O O O O UO O OOOOOOO OOOO O O) CO C O O O O O CD x- CD CO CO O UO UJ OJ x- x- CN O O O O O O O O O N CO CM UO CM N CO OOOOOOO OOOO CO CO x- Tf UJ UJ x- d d d d d τ^ d d -r^ d d d d (N C . o. d d d d dd d d dd °l | : d9 d ^ (, l d d d d d d d dd d d N . !D . CM CD CM CN CM CN CM x- x- x- x- x- x- x- x- τ- x- x- χ - CM CN CN CM CM CN CM CM CM χ- N CJ) x- σ> x- CO CO CM CM CM CM CM CM CM CM CM CM CM CO CO σi CD N CM CM UJ CM O Cn τ^ c CD O τt CM x- N CD O x- τ^ CJJ x- OJ CN CJJ UJ CM OJ Tf T- cM CM CD x- CJ ) CD CO χ - CJ ) in θ CO N CO CM CO CO CO CD CD CD CM Tf Tf O UJ CO CD x- UJ N CO O Tf CD CD CO CO CO OO Tf N x- N UJ N CD CO O UO CO Uj Tf UO x- x- CO O CO C CJ) CJ) τf Tf x- Tf Lf) CM x- UJ N CJ ) CO N UJ CO N CD UJ x- CM x- CO UO O Tf CD CO UJ CM xt O UJ Tt oq uj cM CM O N in x- uo cD Tt CM CD x- Tf x- N O O CM x- CM CO N O O CD OO N x- N OO CM OO OO OJ x- CD N O CO IΩ CO CO O CN CO OO CO UO Tf CM CM cb Tf Tf CM CM uό cb cD cb cb CJ. d Tf ( ' lri iri cD s od ro c N ^ CD CD CO N CN O CJ) CD CD CO CJ) N N N N x- CM x- O CO Tf UJ τf τt τt τt τf τf τf τf τf τf τ^ τf τf τf τf x LO τf τf τf τf τf τf f τf J Tt τt τt τf cO CO CO CO τf τf CO CO CO CO CO Tf Tf Tf Tf Tf t Tf N CO O T f oO N CM CD OJ CM Tf cO UO UJ UJ O CJJ x- CM CM UJ cO O CO CO CJ) CM C N τt o CJ) CD N lΩ CN τf cO CD CO CO N χ- χ- OO CD N x- UJ CM N CO CD CM LO O CD CO CO Tf CM CD CD CD CD O CD CO OO UO OO OO CO N CO CO UJ N CM O CO x- CD CD N C N N σ) τf m τf τf cθ CM CD CM CO CO CD CD in UJ CM χ -; LΩ CD CD x^ N N χ ^ cq UJ N O CD cq cq x- x- N N U0 CM C0 CD co q ro c UJ q N CM CJ) N CM UJ CD O CO O UJ UO O CD x- O N q UJ cq Uj χ - : CM χ - o oo d d χ - J cb cj. χ - : od χ - : cb d d χ- cb cd d χ- : N CM CO d oό d sod co»dds ' ddd(ό ω s dσ. σidσd - : lΩ U0 UJ UJ UJ U0 τf U0 UJ τf τf UJ τf UJ τf ιr> LΩ U0 τf τf LΩ τf in Tf UJ Tf Tf Tf -vt Tf -^ Tf Tf Tf UO Tt Tf UJ Uj Tf Tf Tf Tf Tf U Tf Tf UJ UJ UJ UO x- x- CN CN CN x- x- x- DO 00 x- CM x- CN CQ 00 *~ CM x- CM x- CM x- _ OOOOOΩΩΩ < χ χ < cα O Ω Ω LU UJ rxj X < X X Q Q LU LU X < 00 Ω X X X- CM X Z O O O O O O O O O O O X <coχxxxxxxx < ω Q X x- CM X X X X X OO ooooo X X x- CM x- CM CO x- CM CO OOOOO Q i Q mi Q m-IΪQm.I>Ϊ-D>.-D^.i>r-Ci^rK^K>-D^.α>-KQ>.-Q.-Q^.Q>-.-Q.-Q.-Q.K^α>-Q:.,Ll,J.,UJLlJ iJ LiJ LiJLiJLUmm ,.,,., , 3333333 WWCOWWI-|- l-h- h- h- l- l-H -h-l-l-l-l-h- h-h- l-l- l-ddd d d dddddddddd dd dd --J_J _l_l _l_l_l © o χ- CN CO τf uJ CD N CO CJ) O x- CN C τf LΩ CD N CO CD O χ- CM CO τf uJ CD N CO CJ) O x- CN Cθ τf UO CD N CO CJ) O χ- CM CO τf U^ CD CJ) CJ) σ) CJ) CJ) CJ) CJJ CJ) O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CM CN CM CM CM CO CO O CO CO CO CO CO CO CO τf τt τ^ CN CN CN CN CN CN CN CN CN OO CO CO CO OO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ LO © © UI H U α. N O O O O O O O O O O O CO N O O O O O O O LΩ O O O O O O O O OJ CD O O O O LΩ Tt O O O O O O O O O O O CO CD CO N CM CO O O O O O O O uo . LΩ CD CM CO Tf CD CD O O O O O O O O O LO CO UJ O O O CJJ Tf CM O O O O O O O O O O O O O x- LO CO __coD O O O O O O O o uo CN N Tf UJ CO O O O O O O O O N CD O CM O O O x- x- CM CM CM CM CM CM CM CM CM CM CM x- CO CD CO CO O OOO dCCNM dCCMM dCCMM dCCMM dCCMM dCCMM C d u CMM NN NN CCOO CCDD NN NN NN CO CN CN CN CN CN CN CN CN CO CO x- x- CM CM CM x- UJ CJ) Tf O CD CD CO C0 x- C CJ ) C0 C0 CD U0 O UJ C CJ ) 00 CO N N Tf CJ) Tf CO O CJ) O CM CO CD O UJ xt CD N O LO OO CO N CD CO o N CO CD O CD J N UJ UO UO O O OO CD CM CD CM CM CN x- CM O CO CO CD CJ) Tf OO CO CD CD U) x- C CJ) U O CD CJ) CO CD CD CO CD τf xf |-- CN CD CD UJ CD CM UO O Tf UJ q c) q cq CO N OO Tt CM Cq CM CO CO N N CO O CO Tf Tf CO O CO τf τf CJ) CD CD OO χ - UO CN N CD τf cθ O χ - CO τf CM CO CD CO CO M O CM x- 1 O CM Tf co cb d c- cb cd d d d d cD x^ CD CD N CO CD N U) UJ τf τf cθ N U) τf τf uJ CD CO CO U0 UJ UJ τf τf τf CD U0 U0 CO CO CO CO CO CO CO CO CO OO OO CO CO CN CN CN CO CO CO CO CN CO CM CM CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN o Tf Tf CM x- UO O O Tf Tf CM N UO CO O x- σ) τf θ CM CD CJ) CM CD CJ) τf cθ lO O O CD τf τf CM C CM N N C τf τf CM CM CM N CO CM CJ) OO lΩ O CD x- CM CM CD CO CO CO N CD CO CD Tf 00 UO UO Tf C CM U0 CJ) x- CD τf 0O x- N N x- 00 x- CO CD τf UJ CO CD CO LΩ CD N CD CD LΩ CD CO Tf x- CD CO CD O CD CD x- uq co cM O O cq u oq iΩ co cD oo cD O x- CD CM O LΩ CN CD CD x- CJ) CO χ - CD τf CD N cMCMθiocM CD CJ) J qo f c_)i_) σ)τt o Nx-;N τt x^ cM c co ιb ιb uό τf τf Lri d cj. O ^ CO N OJ m oo(orocn ∞c_ roσ) ooωN ' ιo o d(oraωN ifiN d NNdd θ)Niri τf τf τf τf τf τf τf τf τf τf τf τf τf cθ τf τf cO C C τf cO CO CO C C C Cθ CO CO Cθ CO CO CO CO CO CO τf c CO CO CO CO CO τf τf LΩ CO N U) τf σ) CD τf cO O C0 χ - CD CD CM C0 CD τf c0 UJ CD C0 C0 CD UJ O χ - τf C0 CM N CD x- CD CO x- LΩ CM Tf CO CO CN O x- N N O CO IΩ CO CN CM CJ) x- CD τf cθ τf OO CD CD Tf N CO CD CD CM CO UO CO CO CD CM UO CO CD CO CD N CO O CD O OO CO x- CD CO x- CM N N CN OO O CO τf x- x- CN CN O O cq oo co co cD N LΩ co x- τf x- lΩ CM CD CM C τf 0O C0 CM N CM CM N CO N O UO UJ τf CJ) UJ x- O CM CD O Cθ CJ) LΩ τf N C τf x- x- CD Cq N N b b od d ^ o. - cN Oό d cb cO N N N N lb N CD CO N CD N CD CD τf CO cb τf uO CM CM CM CM LΩ LΩ τf LO LΩ xf lΩ UJ LO UJ τf UJ τf τf τf τf τf τf τf τf τf sτf ' τsf ' iτrif τirif iτrif τsf sτf ' iτrif i T rif sTfsTf sTfsTf oTfioTdfsTf Tf Tf Tf Tf Tf Tf Tf T f f Tf Tf Tf Tf Tf Tf x- x- x- CM CM CM CM CM CM . „ ,„ CM CM M' 0Q 0O „, Ω Ω Ω Ω Ω Ω "- CM Z OO ■ «- CM OQ 00 LU LU α < X X U χ χ χ χ χ χ < ooOO < DQOxx x < 00 Ω LU LU < X X X X X X < _ X X < O X X X- CM X X- CM CO X- CM CO OOOOOO X X X X x- CM CO OOOOOO Z X X x- CM x- CM x- CM O O O X X- CM Z O LO © © UI H U α. O) O x- CD O O O O O O O CD CN CO UO CD CD CO x- O O O O O O O O O O O x- Tf lΩ Tf CM N UJ O O O O O O O O CD CD Tf CO CO CO UJ CO UO CO N O O O O O O O x- O CD CJ ) CO CΩ CM CN O O O O O O O O O O O CO CO CO CM x- Tf Tt O O O O O O O CO CO CO OO Tf O CD CM CM O O O O O O O O O cb xt ' cd cN cb xT cb cN O O O O O O O O O O O CD N CD CO N CD CD O O O O O O O LΩ Tf J UJ Tf CD CD CD CN CM CM CM CM CM CM CM CN CM CM CM CN CM CM CM CM CM x- x- x- x- x- x- x- CM CM CM CM CM CM CM CD CO O CM CO CD CO CO Tf O CD O CO x- CO CM CO UO CD Tt Tf CD O x- CM Tf CO Tf Tf x- x- N N CO CD CD CD CM CO CO UJ CO OO Tf O N N CO CO O O x- CD CO CM CM C 0O CM CD CO N N CO 0O CM C0 UJ N OO O LΩ CM CD Tf CO CO O CO CM UJ O CD x- χ- COOO NN CCMM x- CO τf CO CM CO N x- x- C CO CM UO CD CD CJ ) O χ - CM CO CD LΩ N τf [^ σ. r s - χ - CD CO χ - N CD CM co co cq cq q Cq q N CD N CM U q CM Tf f CM UJ CD CD N Tf N Tf cD O CM Tf CO CΩ N CD CD N ∞ ∞ N cO CM CM cb x-^ x^ x^ O Tf d CM d oi CM x^ x^ cM cb σ- cM o cb c O CD CM CO Tf LΩ CM CM x- CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN x- C CN CM CM CM CM CM CN CM x- x- CM x- CM CN CM CM CM CM CM _. xt CN τf cθ O CD CO τf θ CM σ) CD CN CJ) x- x- CJ) CO χ- χ- CM UO UJ CO N τf x- LΩ CM OO τf cθ UJ CM CM O CM UJ τf CM χ- O OO τf D C χ- CO N CO CJ) τf LO CM O LΩ τf c CJ ) O τf CD CD CM CD CO UJ τf |-- CD χ - ( » CD τf σ ) N UJ CO CO τf CO CM σ ) O τf r-- τt OO CD O CO UJ O CO CD uo CM C CM cq τf CO χ - cq x- cq q χ ^ τf τf x- CD xt CO CD CJ ) x- x- N N CO O CD lΩ UJ CJ ) CO O CO CM Tf CM CO " CO " " U " J CO CM u ό ιb N τ c cb τ c cM CM CM b cb τ cb τf c^ CJ) 00 CO N N cb oό CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CO CO CO CO CO CN C^ 000000000000333333333333333333300000000000000ZZZZZZZ Q CLLιCYL.CCLLLCLL CCLLLCLLθCLlCQL-CCLLCCLLιCΥL.CQL\n I -_J .-J --J\-n-J\_nJ -u-J --J --Ju-- ^ ^ ^ ^ J ^ ^ ^ ^ Q_ Q. Q. CL CL CL Q. CL Q. CL C CL Q- Q- < < < < < < < © o LΩ CO N CO CD O x- CM CO τf ιr) CD N CO CJJ O x- CN C τf ιn cD N CO CJJ O x- CM C τf UJ CD N OO CJ) O x- CN CO τf Ln CD N ∞ CJJ (J) CJ) CJ) CJ) O O O O O O O O O O χ- χ- χ-- x- χ- χ- χ- x- x- χ- CM CM CM CM CM CM CM CM CM CM CO CO CO CO CO CO CO CO CO CO τf τf τf τf χϊ τ^ CO OO CO CO CO Tf 'rf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tt xt xf xt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf 's^ N O O O O O O CM CJ) CD CJ) N CM CJ) O O O O O O O τf |v. rv- θ CD τf O O O O O U0 x- N x- O O O τf CD CO CD CD CO CO lΩ CO N O O O q q q q q q q q cM q cD cq oo τf c ) o o o o o o θ χ - CD c) χ - cM θ θ o o o cM χ- N N O O O O τt cO χ- CO CD τf LO CO CO O O O uό dd dd d d uό cM x^ x-^ o d d d d o d d O xf T cMc c u o o d d cb Tt tuόd ouόcb xtuόcMTf cbcb Ttuόddd x- CM CM CM CN CM CM x- x- x-- x- χ - x- χ - CM CM CM CM CM CM CM χ - x- x- χ - x- x- CM CM CM CM CM x- x- x- x- CM CM CM x- x- x- x- x- x- x-x- x-x- CM CM CM τf CoD) CCMN UUO. N CD O O O CO N ^ M N CM x- CJ) N UJ CJ) χ- CM C0 UJ Tf Tf UJ CJ) UJ CO CO CM UJ CO UJ CM χ - CJ) CO x- CD CD α CO C τf CD CN x- UO CN CO UO N CO CM N CO O CD O CO x- UJ U CM C Ln cD CD τf cθ χ- O OT CD CB xf ON CN:( Nro ( N O xf N(D CO <J) N αD τ- xf NCD CO O) ^( Nro (M CM Cβ xr cθ ( - NCD(M ^N c CB U)xf lI)σ) inM CD COCn cq cq q x-^ ιn χ ^ CJ ) CM O τf O CO CM CD C CJ) CD O CO OO O CD CD τf CD OO N CD CO CD CM CD N CO CD CM rø N ffl N tD t N ffl r ^ r o d oi d N d oi d ^ ^ d^ N d cN ^ d t ffl o ffl CN CN CN CN CN CN CN CN CO CO CO CO CO C CO CN CO CO CO CN CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CN CN CN CN C^ CJ) CM cq uό Tf CM CM CN CM CM CM CQ CO Ω Ω "- CM DQ DQ < < .-. τ_ ^ ' I- CM DO Q < XX XX < DQ OO < ωOχχχ < CO < X X < XX < DO Ω Ω LU LU <χ Z X X x- CM x- CM OOOOO X X X X x- CM CO O O O O CO X X ^ CM X Z O O O X X- CM Z O O O O O Z O O Z X X X- CL t L L L L L L L cciL L CL L W TiWUiwww O O O CO O CO CO χχχ χ χ χχ >- >->- >->- >->- >-->->-^^_j^^-- -j _2^^^^^^^^-_25_ ^ -_ < << << << ι-f-i-ι-ι-ι-ι-ι-H-ι-ι-ι-i-ι-υυoυooυoooooooooooχχχχxχχχxxχχχ © N CD CD O x- CM C τf uJ CD N CO CD O χ - CM CO xf LΩ CD N CO CJJ O χ - CM CO τt UO CD N CO C_ O x-- CM CO τf LΩ CD N Cθ σ ) O χ - C o τf τf τf ι_. U0 UJ UJ UJ UJ U0 lΩ U0 lΩ CD CD CD CD CO CD CD CD CD CD N N N N N N N N N N 00 CO CO 000000 CD CO CO C0 σ) CJ) OT ^ r r t xr ^ "f ^ ^ ^ ^ ^ ^ ^ ^ ^ "t ^ τ. xf xf r x. ^ xf ^ ^ χ t f ^ x. x. xf xf xf ^ ^ ^ ^ ^ x. . ^ ^ ^ f ^ x. ^ x. xr "f © © UI H U α. O O O O CM CO CN CM CN CD CO O O O O O O O O O O N lΩ N OO OO CO O CD CO x- Tf CD CD x- O O O O O O O O O O CO CO Tf CΩ O O O O N CO CM x- CO O CO T f N O N O O O O O O O O O x- χ - N 0O CN τf CJ ) CD N CM UO f T CD o o o oo oo oq oτt ιv.ι uj O O O O CN CM CO CM CM CD x- UO O O O O O O O O O O CN CM CM CN CO CO CO CM CO CM CM d d d dd dd dσ dcb cMcdcb CM CM CM CN x- x- OO CO CO X - CN CN CN CN CN CN CN CN CN T- X- X- X- X- X- X- X- X- X- CM CM CN CN CN CM CN CM CM CM x- x- x- x- x- CD CD χ- χ- N χ- C τf c (J) CJ) CO N C0 N N CO xt CO N CO CD O CO x- UO CD x- CD lΩ x- O O CO LΩ N CD CM CO CM LΩ UO UJ CD N CD CD CO CD Tf CM O CO OJ OO x- CO O O N OO N O CD CD x- UO xf CD x- OO xf LΩ CO CD N x- CD l UΩ O l_J C UJ)J C LDU U U0J O L-J C UDJ O L_J x X-- x X-- ( UJ)J O L-J C L0U C LDU C UJ)J T XTf 00 C IMN C LU0 C UJ)J N I— - N CJ ) C0 C0 UO CO Tt c COO CCOO OOOO CCNN CCNM NIv- xx-- COOO CαDJ COO CCOO xx-- xxff CCDD ULnO OoOO OO CC CCDD xx—- ττff xx-- ττff LLOΩ "N ~O Cθ O O CJ) O C xt CD CD CO N CO CM CO O O CD LΩ CJ ) x- CCJn ) LiΩ-) Nl- CD N O " ~tb *- - : c t O - " x- ' θ ' cM x- CM " θ .- : θ cM O CM x- CM CO τt tb ώ CN CM CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M o cn t CO τf O lΩ UO CM CD UJ CJ) LΩ N τf CD UJ UJ O N CO CM CJ) CO O χ- lΩ σ) CM CO CO N CO τf c LΩ x- CJ) N O O LΩ CD C CO UO τf x- UJ O CJ) C^ CO N O N CJ ) N O τf θ C CM CO UO CD τf x- CD lΩ χ - τf CO CD CM CO CO CM CO χ - O UO CD x- CJ) CO CO χ - O O CD CO χ- N UO N N CO O CJ ) CM C^ τf CM N CD q q Uθ σ ) C cθ cq cD CD xf xf xt CD CO χ- O UJ OO CN CN τf CO N OO CJ) x- χ- CD UJ CM C^ d d x- c c cd uό c N N ^ c c co f N cb rø CM CM x^ CO CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ CM O N CD O) CD tΩ CM UJ CN UJ CJ) Cθ τf uJ C CO Ln χ- OO τf UO x- N CO O CO C lΩ CD xt CM O τt CJ) CO CN lΩ χ- CD CN τf O N τf c^ CJ) Cθ σ ) τf in C0 χ - N χ - C0 N χ - lΩ LΩ C0 f O L0 xt LΩ CM CD CO x- N U0 x- τf x- CM CM U0 C0 x- N UJ CM CD χ -- CJ) N O CD O CD U0 OT cq c j) q χ - o τ f oq cq q cq σ ) cD CD iΩ N χ - co co χ - co N CM co cM τf x- o o cN N C ) χ - co cM ro T f l b T u cb cO CM CN CM CN O CM O CN x^ CN T f x-^ CN O τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf c τf τf τf τf x^ f cO C CO CO Cθ CO CO CO CO CO τf τf cθ C^ OQ ^- CM x- x— CM x- CM DO 00 ^ CM x- CM „ "- CM χ- CM C CN Cθ CN OO DQ '- x- CO CM CO CM X Ω Ω LU < ωOΩΩuJLUN < χ χ Ω Ω LU UJ N < DO Ω Ω LU LU LU N N X < X XΩ UJUJ NN X < CN X X X Z O O O O O O O O O O X X- CM X X X X X υυoυooozoooooxx X- CN X X X X X X Z O O , n rn , n . n liJ lil_JUJLJliJUJ llJlJJ_JlJJLlJ llJLU-J-JllJ llJllJm(L iQ._-(LD.Q._-l i. !.i_!.ιιι ιιιιιιι ι ι ι ιιιι ιιiQ: κQ;[i;κQ:Q:κD:(i:ιι: [. Q: Q:D:tt:Q: (ϊϊ (i:tt:Q;QiD:j j j IIIIQ.Q.Q. Q.Q.ILILQ.Q.Q. ILQ. Q-αQ. D. Q.Q.D.hhh h hh h h h h H C- ϋ © ro o σ) ιτnf θ Tf UJ LO © © UI H U α. CO x- CO CM x- O O O O O O x- CO CO Tf cθ τf o o o o o o o o o CO N CD CO CO O O O O O O O O O CM CJ) Tf CM N CD x- CJ) CO x- Tf x- cq O O O O O O N CM CD CM CM CD O OOOOOOOOO CD N CM UJ CN Tf O O O O O O O O O U UJ O CM CD Tf CD N χ-- : uONC) ' cj)ddd odχ- : cMχ χ- 0C lχ Lb 000000000 cM co f " o ^- d d d d d dd o ' o Tf UO CD CM N x- 1 CJ) x- χ- x- x-x- CMCM CM CN CM CM x- χ- χ- x- CJ) x- x- CN CM CM CM CM CM CN CM CM x- x- x- x- x- OOx- CM CM CM CM CM CM CN CN CMx- x- x- x- x- x- CM T- CD O CO OO OO OO CD -— - r COr. n O mOO iUnJ rCDn CO CO CM CO CM C θ N N ιθ C(DDio cri T- T- 1 CO C CO τf CO τf τf τf x- x- Tf CD CD x- Tf UJ O CM Tf CM O N CO CM N UO O C0 O N lΩ CJ) N CO N CJ) U0 CM N τf N N τf τf uJ C N CD τf U) N O O O τf O N O CO N UO CO CD CO O CM CM UO CO Tf CO O N O CD O CO N UJ CO Tf O O Tf CM N x- CM CN UJ N CJ) CN N χ- N τf O O CJ) CD CM CJ) χ- N xf CM CJ) τf UJ N N CD O O CN σ) CO CN τf τf cθ τf N- χt c - C q τ x- x- rv. q N CO N CJ Tf cM x- o cD uo Tf cD O uo cD Tf u cD N q o uq cq cq CO N CO CO CO O OJ CO N N CO x- CM c cb cO χf uό cb χ- χ - cb cM τf ib b uό cb cb co Tf Lb c iΩ Tf ib N b b d cM x^ x^ cM d c c. CN CN CN CN CN CO CN CN CN CN CN CO CO CO CO CO CO CO CO OO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ 00 CD CM CD CD Tf O Tf CD CO OO CD Tf r-. Tf CO CD CM CM CD σ) UJ xf CJ) Cθ O OO τf c τf -- x- τf x-- τf |v. τf N CO N CO CM τf x- τf OO O N CD CM 00 CO 0 CO N CM Tf CM CM CD O τf x- CM CM t CM N O τf UO UJ N UJ UJ OO CN O CO Tf uJ cO CO CM N N CM x- UJ N CO x- CM CM O CD CM Tf CD O O O Tf CM CJ) O CD CM CO D CD CO CO N CO x- CO CD x- CO O T —t α — -iΩ- x- c —D _t .u-q —u N u N τt σ) u χ- co σ) cD τf o o χ-; N CM q cM cq cq cq cb Tt u Tf CD CM CO CM CO ib Tf uό τf ib b co N cb τt cb ib N cb lb uό c cO CM CM CM x- 1 c cb d cM CM χ- : χ- : d cbcM CMcb cbχ- J χ-- ' σJ Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf Tf Tf Tf Tf Tf Tf f Tf Tf f xf Tf Tf xf Tf Tf Tf Tf Tf τt - τf τf τf τf τf τf τf τf τf τf cθ τf τf τf τf τf τf τt cO x- x- x- CM CM CM OQ CO ω 00 LU UJ LU x- CM x- CM DO Ω LU LU < X X X X < DO Ω LU < X X X X X X X < 00 OO < CQ x x x x x x < 00 Ω Ω OO OO X X x- CM x- CM z OOOOOCOO X X x- CM *- CM x- CM CO OOOOOX X X x- CM CO x- CM CO OO OOOOO D D D D D D D D D D D l- r- 1- l- l- r- r- l- l- r- l- l- r- l- r- l- j j j j j j j j j j j j j j j j O. ll D. D. Q. l Q. l -J -J -J -J -J -J -J -_J -J --J -J IU LU LU IJJ LU UJ 1JU LU .U LU LU UJ LU UJ IJU LU UJ < < < < © x- CM CO xf lΩ CD N CO O x- CM CO τf J CD N C CJ) O x- CM C xt UJ CO N CO CJ) O x- CM C τf UO CO N CO CD O x- CM CO τ^ O IΩ IΩ U0 UJ UJ U0 U0 U0 UJ CD CD CD CD CD CD CD CD LO CD N N N N N N N N N N CO CO CO C0 CO CO CO CO CO 00 CJ) CJ) CD CJ) CJ) CJ) LO lΩ UJ UJ UJ LΩ UO UO UJ UO LΩ LΩ LΩ lΩ UJ UJ UJ UJ UO UJ UJ LO LO LO UJ UO LΩ lΩ UJ UO UO UJ UO UJ UJ UJ in iΩ LO in UJ UJ UO UO UJ UJ UJ U^ LO © © UI H U α. UO O CD CD UO CO O O O O O O O O O O CD UJ O N CO N CO N X- OO OOOOO) CJ) CO Tf N CM LΩ x- O O O O O O O O Tf x- CD x- OO N O N x- CM O O O O O O O O O O O O lO CO Tt r- Tf cO CD OOOOOOO) N O CO N x- 00 x- O O O O O O O O CM O CD CO cd cM x^ x-^ x- x^ d d ib d cb c Tf Lri Lri o τ f ' f ' τt ' CO Tf O x-^ 00 O O O 0 " τ lb cN c CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM x- x- x- x- x- x- x- x- x- CN CM CM CM CM CM x- x- x- x- x- x- CM CM x- CN CN CN CN CN CN CN CN x- x- ''- x- CD N x- CO CO τf τf τf cθ CO CD CO O τf τf LD CM CD x- CD in τf CJ) N χ- CD CJ) N in in CJ) UJ x- CD UJ UO UJ CO Tf CD cO CM O CO CD CM x- CD CO Tf CO lO CO N N Tf cq CM CM o cjJ M c c d cM c cb Tf f τf τf cθ τf τf cθ τf τf τf cO C C τf cO τf τf τf τf CD UJ UJ UO CM O CM CM CD Tf CM Tf CO O CD UJ UO CD Tf O CO N CM UJ Tf CD O N CD x- CM CO CO CO N CO O O Tf cO CN Tf O O CO UO CO CN lΩ x- lΩ LΩ CD O OJ x- N O CO J CO x- UO x- UO CD CM CO CN CD CO OO Tf CD N CO CD τf CJ) CD in θ x- O CM CD CO CD χ- χ- CO lΩ χ- UJ O χ t CO UJ CM CD t O CD CO Tf UJ cO CO O) N CO CO CM CM CJ ) Tf OO CD CJ) CO O LΩ CO CO N lΩ CJ) O UO LO CJ) O CM x- x- χ- τf CD N CD O O O τf x- ι τf CD CD C C CO CD θ " CO O CJ) CM CM CJ) O OO N CO O CD O O CO N cb d d d d cb N ' cb τf ib ό τf ' cd τf ' cM- cd τf ' uό uό cb cM CN CN CO CN CO CN CO CO CN CO CN CN CO CN CO CN CO CO CO CO CO CN CN CN CN CO CN CO CO CN CN CO CO CO CO CO CO CO CO CO CO C^ CJ) CO Tf CD O CO f Tf O N CO O N N N LΩ CD CM CO CO N CO CO CO Tf CM CM Tf UO O) Tf x- CM τf x- x- CO O CN O O N CJ) CD O x- CO O O U0 CD LΩ CD N CD x- N O) CO CO CM O CD CO LΩ O CD CM CO N LO UJ UO x- CM CM CD CJ) CJ) CD x- Tf CD N O OO Tf Tf OO CM CD UJ CD CO CO x- OO CM C f CO CD Tf Ω CO Tf q CM q Tt CD CM Tf CD Tf UJ CM UJ CM CO xf CD Uj Tf x- Tf U) CO 00 x- OO N CO CM q q cM cq N iΩ CD LΩ x- cM uq iΩ Tf UO N CO CM O CB CO COS N CM χ CM O CM x^ oo cb cb cb t ib cb cb cb uό cb N cb Tf lb N CD Tf CO U0 CD UO CD s cd ro ro ro iri s s co co r-i o a. Tt cb co c Tf CO CO CO CO CO Tf Tf Tf Tf Tf Tf C CO CO CO τf xf xf τf τf τf τf τf τf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf f Tf Tf Tf Tf Tf Tf Tf Tf T f U0 T t Tf Tf Tf Tf x- CM CO CN CO CM CQ CQ '<- χ - cO CN Cθ CN x- CN O Q 00 OQ DQ LU LU LU LU LU N N X < χ χ Ω LU LU txJ N X < 00 Ω LU UJ < OQ Ω LU LU < X X X X X Z OOOO OX X X- CM X X X X X X OOOOOOOO T X- X x- I CM x- CM ^ Z υυooooozxx X x- CM x- CM x- CM OO CL CL CL CL CL CL CL CL CL CL CL CL Q- Q- CL CL 333333333333333Z O CO CO O CL CL CL CL CL CL CL CL CL CL CL CL CL CL CL CL r-r-r-r-r- I- I- r-H HHHr-r-r-r- OOOOOOO O OOOO OOOOOOOOOOOO O OOOOO © o CO τf LO CD N CO CJ) O x- CCNM CC0O ττff iiΛΛ CCDD NN C∞O CCDD OO χ χ -- CCMM CC0O ττff LLΩΩ CCDD NN CC0O CCDD OO xx-- CCMM CC0O ττff Uu0O CCDD NN 0O0O CCDD OO xx-- CCMM CC0O ττff UU0O CCDD NN CCO0 COTD O x-- CM C0 τf O O O O O O O x- x- χ- χ- χ- x- χ- χ- χ- χ- CM CM CM CM CM CM CM CN CN CM Cθ CO CO CO CO CO CO CO CO CO τf τf τf τf τf τf ^ τf τf τf ιn iΩ LΩ L^ CD CD CD CD CD CD CD CD CD CD CD CD —I CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD x- CM CJ) CN CJ) O O CD CJ) O O O O O O O O O O O O cN N co o τt cM CJ) co τf o o o o o o o o o q q q d σ) (cO. TNf ; (cO. iNsbO (C)D. τx- : dO dO dO dO dO dO dO dO dO dO dO dO dO x- x- CM CN CO CM CO CO CM CM CM CM CN CM CM CM CM CM CM CM CD x- OO LΩ CO OO LΩ CO O CJJ UJ CN CN CM CO CD CD CO CM CD O CO CO C _D CO CM O x- CJ) lΩ N χ - CD CO x- O UJ CD CM x- CD 00 CD x- CO N N x- N UJ CM CM O CD UJ O CO O CO CM UJ CO UJ UJ N CO CO CJ ) N N CJ ) N UJ C0 CD CD CD CO C LDU C LDU C UDJ x X- — T XfT C LMN N 1^- T XTf O »— ' U UjJ Tf x- Tf LO x- CO CD CO N UJ 00 CM UJ CM lO q CN CD CN CD CJJ Tf q x^ iΩ Tt oJ cq N x- CD c cM N LΩ Tf CO N CN UO CO x- OO UJ O O O Tf UO Tf N CD U UO CO O O CD CO x- Tf UO O N cb CM CO UO UO Tf lb d oO N Lri O CM x- x^ x^ σ. - 1 CM ro oi b CM CM χ- χ- CO τf τf U0 UJ τf LO CM CN CO τf ιr) τf c Tf LΩ Tf T J Tf Tf Tf Tf Tf Tf Tf Tf Tf τf τf τf τt τf τf τf τf τf τf τf τf τf τf c Tf Tf CO CO Tf Tf Tf Tf Tf Tf Tf Tt Tf xf xf Tf Tf Tf Tf Tf Tf Tf t T f Tf Tf Tf Tf CD N x- CCMM UU00 NN ττff CCDD UU00 χχ -- xx-- CroD CCOO CCDD CCMM CroD CroD UuJ UU00 ττff ττff xx-- σro ) ττft cCθ0 CCNM LCDD CCDD τf cθ τf U0 x- x- ro CD C0 CN CJ ) χ - C N N Tf x- Tf O CO x- CD CO N CO Tf O CM x- CO O N CO OO CM CM CM CD O O CD OO CN Tf CO T Tff o COO C CDO C COO C COD xx-- N Tt |v. CM CO UJ CD N CO x- Tf O Tf CO CO Tf N Tf LΩ x- CD UJ N N χ - iΩCN raq rocD incD CMθ τf cj- d cD co co cD θ CD N CD CO CO x- UJ OJ N ro cO x- O CM CM CO UJ x- CD CJJ Uj Tf CM N CO CO CM CO CO N CM UJ ι LriO CcOocCOoVx- xτ- cCO χT fr LιriΩιlriO CcO CcO CcOo CcOoVx- xτ-- : CCNN xχ- : dONN ∞ ∞ N ro ∞ cJJ ro N CO ro O x^ x^ x^ C CO CO CO CO C CO CO CO C C CO C CO C C C C C C CO CO CO Cθ C CO CO CO CO CO τf τf f τf τf τf τf τf τf τ^ τf C τf τf τf τf τf τf τf τf τf τf 0D N O C0 CO CD U0 x- U ro C0 τf c0 C0 CD χ - UJ O CN xt ro c0 CM ro χ - τf χ ^ c0 lΩ τf CD O N lΩ C0 N χ- O UJ O CO CO C0 τf U0 O xt N CD ro x- CM CO T f uO T f - CD CO CD CO Tf ro UJ U T f CD C ro Tf CD UO CM ro O CN OO UO Tf ro cO x- C CO Tf N O N x- CD CO CM UJ CM CD U^ CN τf lΩ q cq CN N τf x- CN UJ CD CM C0 χ - O CN N CN ro τf C0 CN J J τf C0 J τf x- ω cN T f Tf T to J f M ^ ^ lb b cd LΩ Tf U N ' cb c cN x- ' Tf T f -xf -^ ^ T f T f T f T f Tf Tf Tf Tf T f Tf Tf Tf Tf Tf Tf ^ Tf Tf Tf Tf Tf Tf Tf T ^ Tf cO CO CO CO CO CO C^ ^ . O Q ω O O Ω Ω LU UJ N N N ω 00 00 x- CN ooωOOΩΩ xxx 00 Ω LU N N X CM x- CM x- CM x- CM x- CM CO o <o oo o <xχO O Ω __ <xxxxxx_uχxx o oo oz __ <xxxxxxxxxxx X X x- X X x- CN X o <υoυ DOooLUυzXz X X X- CN X- CM X- CM X X- CM X- co cococo cocococo oocococococo coo Q:Q Q__tQ_Q_Q_Q_Q_Q.OOOOOOOOOOOOOOOO OOOOOOO r- >- >- >- >- L . L . L . L . L . L J > _ L . L . > . L L U J U J 1 lJ J 1 J 11J 11J UJ | lJ llJ Q: D. K [ϊ fI Q: K _ -J _I -I -I -I _I _I -J _I _I _I _J _I -J _I _I _I C C C C L CO CO CO CO CO CO < < < < < < < < < < < < < < < < < < < < < < < © o LΩ CD N OD ro θ χ - CN CO xt UJ CO N Cθ ro θ x- CM CO τf LΩ CD N Cθ ro θ χ - CM CO τf ι_. CD N Cθ ro θ x- CM CO τf UJ CD N Cθ ro θ x^ LΩ LO UO UO UJ CD CD CD CD CD CD CO CD CD CD N N N N N N N N N N CO CO OO CO CO OO OO CO CO CO ro ro ro ro ro ro ro ro CD CD O O O O O O O CO CD CD CD CO CD CO CD CD CΩ CD CΩ CO CD CD CΩ CΩ CO CO CO CO CD CΩ CΩ CΩ CD CO CD CD CO CD CO CO CD CΩ CO CD CO CO CO CD CO Φ o N O co 00 O O O CO N Tf CO CM CM OOOOOOOOO O O O O O O O O O J ) O O O O o O O O CO oo CD O N N N OOOOOOOOO x- CD Tf O CN O O O O O O O O O CN CO CD CO CO CN IΩ O O O O O d ib co ¬ CM CM dd dr d CD O O x- O O O O O O O O O O ; UJ CD O N N CO O O O O O O O O O 00 UJ CM CD CD O CO °°. O O O O CM CM CM CM x- CD x- x- x- CM CM CM CM CM CM CN CM CM CO N CO ro CD N CO CM CM CN CM CM CM CM CM CM OO CO CD CD OO CD N CM CM CM CM CO x- α Cθ N τf CD CM CO CO CM LD CM CM N CM CO CJ ) CD CM CJ ) CM LΩ CM LD UJ U0 x- CJ) τf UO UO CM CM CJ) CN τt r-. χ- θ (J) LΩ CD LΩ χ- UJ CO UJ CM χ- N UO N CD OJ N CD CM x- CO CD CD N O CO x- CO CO LO CM x- OO CD CN CN CO O CO N CO N CO ro CD x- O CO CO LO Tf CD CO CD CM x- CM N O CD CD CD UO CD x- CD N in cM CM τ- cq τf χ - r v . χ --. χ -- cj ) cD uj co co ro cD CD ro uo ro o cD N CM co cM N co co cjJ CM co co o co co N Tf o cM CM q cM co q ro N q cq O d ro ra b τ- : ro ro s ιri ιri ιri f u) b s ιri N- ω ιri ; b cM b i : b (M τ : ^ ιri cb τt cb τt uJ d cb cM cθ χ^ d ro ro cj. cb N χ-- CD d d Tf Tt CO CO CO Tt cO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M r- LO t CD CO CO CM CD CO CM C N 0q N C CO χ - : CM CM τf τf τf τf O C0 ro χ - CD O CD lΩ τff ' d O ro d CCOO τ Tff cO τf CM x- x- x- CM CM CM x- x- x- CM CM CM X x- CM _. OOOOO x- CN 00 DQ < < <: < O Q O O _<co χ χ χ χχ χ < ω OO _. OOOOOO < cθ χ χ χ χ χ χ < DQ O Ω LU <χχ CN OOOOOO X X X x- CM CO x- CM CO OOOOOO X X X x- CM CO x- CM CO OO OO OCO OX X X- CM Cϋ) >— >— >— >— >— >— >- 1 I I I I I I I I I I I i I I I 1 I I I 1 I I I I I i I I I I I r- r- r- r- r- h- r- H r- r- r- r- UJ LU LU LU UJ LU LU LU LU LU LU LU © <O OO o5^^5>:>5i>5>>5^ :^5^5^^5^ i 5 - -> o N αθ ro θ χ- CM CO τf LΩ CD N Lθ ro θ χ- CM C τf LΩ CD N Cθ ro θ χ- CM CO τf LΩ CD N Cθ ro θ x- CM CO τf LΩ CD N Cθ ro θ x- CM CO τf ιn c^ O O O χ- χ- χ- χ- χ- χ- χ- χ- χ- χ- CM CM CM CM CM CM CM CN CN CN CO CO CO CO CO CO CO CO CO CO τf τf τf τf τf τf τf τf τf τf UJ U U UO UJ UJ UJ UJ U^ r-. (v_ iv. (v. rv. tv. N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N LO © © UI H U α. o o o o o O O O O O O O O O O O lΩ CD CN CΩ CO O O O O O O O x- Tf CD CM CD CO CD CM CD CD O O O o o o o o in ro ro N CM CO Cp CD O O O O O O O O O O O lΩ CO CD lΩ UJ x- CO xt O O O O O O OO CO O N O N UJ Tf CD CO O O O d d d d d O N CM OO CO CD CD O O O O O O O O O O O CO O O x- O O Cθ O~O O O O O O O CN CM Cθ CO lΩ CO τf τf x- τf cθ O O O CM CM CM CM CM CO CD CO 0O CO CD CD CO CM CM CM CM CM CM CM CM CM CM CN CO CD CM CM CM CM CM CM x- CN CO Tf UJ UJ UJ CM CM CM CD UJ C0 UJ CN O CD CJ ) N UO UO CD CM CM CO O N N f N C -) o CM CN UJ N d cdcMcoV CO ro CD CO CD CO CD O Tf oO CD CO CN O N CM Tf UO N CO O LΩ χ - 00 N C0 UJ τf CD τf CD CD N CM N τf Iv_ 00 C0 00 CN C0 τf χ- c 00 χ - CD N O χ - O CO O τf c CD CM CD CO CO CD CO O UJ lΩ N CO CD χ- LΩ CJ) τf OO Tt , C .O . CM CO CM CM CD CO Tf Tf oO OO LΩ CD O LΩ Tf O f CD CO CD O CD CD CO N CM CO CD CM N Oθ θ cq τf Uθ ro CJ) (X) C τf CD CJ) CO CD CO N CD Tf OO x- CO CD CO x- CD CO CO N O CO x- CO ro iΩ CO LΩ CO CD O OO N Tf CO CO CO CD x-; cd ib cN co cM N cb cb ro cb cb ro ro cri ro cb N CD d σ. do o CD co τt cb cd τf cb uό τf τf cD c» cb αJ c θ CD ιb cb Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf xr UJ UJ Tf Tf N Tf N Tf Tf c Tbf Tcbt Tf Tf Tf Tf Tf Tf f Tf Tf xf Tf Tf Tf Tf Tf Tf Tf Tf Uj Tf Tf Tf Tf CD O CJ ) CO CO CO χ - 00 N x- x- UJ CD τf UJ C0 00 N CD CD N x- C0 CD OO x- N O CM CO CD CN N CD N UO O N O CO N O CO CD xt CM CD CO CO UO CO CM T f x- CM O CD N CM CO UJ CN CO x- O Tf h- O CM UJ CM CO CO CO C UO CM CD CD CO O N CO N N UO τf θO CM UO O χ- O θ ro τf x- Tf CD UJ CD LΩ CO CD CO O χ-- cq q UιoJ OcOo CcOo CcNN CσD) τt- q— C-M- C—O C—O -N x- CO- C-J) C-D- τf x- CD " O ~ CO τf CM CJ) x- x- CM O τf x- CD CO lΩ CD N CD UJ CO x- CO N Tf CJ) CD CO CO N N x^ x^ O x-÷ CM CM x^ Tf ' x-÷ o CN cb cN O x^ CM Tf Tf Tf O O ' cb cd O O x- ro θ CN x- x- x- CO CO N CO lΩ lO τf τf LΩ CD lΩ CO CΩ τf CO CO CO CO CO τt τf τt τf f τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf c CO τf xt τf τf CO τf xf τf τf τf cθ CO CO CO CO CO C CO CO CO CO CO CO CO x- x- x- CM CM CN CM CM LU LU LU x- CM 00 DO Ω Ω Ω Ω Ω Ω T <N DO CO Ω Ω x- CN OQ X X X X X < CO Ω Ω < X X X X X X X X < CQ Ω Ω O Q OΩ L X x- CM x- CM CO oooooυυxx x- CM X x- CM CO x- CM CO OOOOOO ^ Z - Xr X x- X CM x- X CN o <oooυυzUυN Xzzx <xXx- . 7 .. 7 .. 7 .. 7 .. 7 . 3333333333333333333ZZZZZZZZZZZZZZ00000000000000 r- ->-≥- -≥- _J_J_l_l _J_J_J_l_l _J_l_J_J_l_J_l _J_J _J< <<<<<< <<<<<<<<<<<<<< <<<< <<< © o ro θ x- CN CO xt UJ CD N Cθ ro θ x- CM C τf Ln CO N (» ro θ x- CM C τf UO CD N Cθ ro θ x- CM C xt UJ CD N C» ro θ x- CM CO τf UJ UO CD CD CD CD CD CD CD CD CD CD N N N N N N N N N N OO CO CO CO CO OO CO CO OO CO ro CD CD CD CD CD CD CD CD CD O O O O O O O O O O x- N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N OO CO OO CO CO CO OO CO CO CO CO O O O O O O O O O O CO CM CO CD CD O CO O O O O O O O O O CM x- CM χ- CO τf c CO O O O O O O O O O CD τf OO CM τt CM τf CM CO O O O O O O O O O O Tf x- Tf LΩ N CO lΩ O O O O O O O O O CD Tf CM Tt UJ Tf Tf CM O O O O O O O O O Tt CD OO CO LΩ Cq ro uq ro O O O O O O O O O O CO CD CD Tf Tf Tf d d d d d d d d dN Q N f iN dc tN d d d d d d d d d Ncό N co iri iri iri CM CN CM CM CM CM CM CM CM CM x- x- x- χ- CM CM CM CM CM CM CM CM CM x- x- x- χ- CN CO C CO CM CM CM CM CN CM CM CM CM x- x- x- x- x- τ- x- x- x- CO CD xt CO CO UJ CO N UJ CJ) CO Tf N OO CM CO CO CM N O CD CO O N O Tf oO UJ CM lΩ CD CM CM CO N CD CD UO UJ CD UJ CO N CD N Tf Tf CO O CO x- O CO N CΩ x- O N CO Tf CD O CD UJ CD C0 C0 τf C0 CD C0 CM CD O C0 χ- τf C N τf CM CO N 0O U0 x- N x- τf cθ τf CD O CO LΩ CJ) N CD CD CO 00 t UO O O CO Tf O N N O Tf CO CM N x- CD U0 C0 N CJ ) CN CO LO CD CJ) CM CJ ) N CN x- CΩ N CO C0 lΩ Cq iΩ τf C\J C0 CN Cq O CD τf 00 CD C0 CM CM -«- O CM CO CM CM CD CD x- N N CM CJ) CD CO O CN CO CO CO O CD O CD N N o N iri Tf T O- N N ib u co ib c b u Tt N ro O O x- CN CN CM CM CM CM x- CM CM x- x- CM CM CM CM CM CN CM CM CM CN CM CM CM CM CO O O N CD C χ - LΩ xt CO CM x- χ - χ - τf N O N CD xf t Cθ ro f CM CO N x- CD χ- N CD CD CJ) CM N CN CO τf CD O CD x- χ- CO Cθ ro cθ CM UJ CD N O CD CD x- N CM CJ ) lΩ xf τf CM CM τf O CD ro θ CO O O UO CM O ro o x- 00 χ- N C CD CD τr τf r- CD CJ) CM C0 CM f x- c0 UJ CM 00 O C0 x- O c D CJ) ro τf o ro τf σ) cD θ CM co uj co cD co cD co o τf x— o C D c No x C D- T f N x- O CM CM CM N O x- ro CM LD CM U0 CM UJ UJ CD χ - CM τt cq cq q x- d c N ro cb cd o d ro od c cM CM x^ x- d d cb x^ cM x-^ d d ro d ro cb co uj cD co co cM co Tf c cb cM CM Tf Tf Tf cO ib cb N cb N ' cb N N cb Tt Tf Tf xf Tf Tf UJ U Tf Tf Tf Tf Tf Tf Tf Tf Tf f Tf Tf Tf Tf Tf CO τf cθ τf τf τf τf τf τf τf f τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf O CD CD CM CO UJ CD LO CO x- CM CO CD CO CD N CM χ t xt x- Lθ χ- N Cθ CD τf CD CD x- τt cθ ro CD CO χ- τf CD N OO UJ CD UO UO O O CO UJ x- CO τf |v. CO CD CM CO CD Tf x— τf CO CM CJ ) x- N CO O χ - O CM τt r L _ c x- c COj OO iCNN UCD CO_J <O-ι iCM LO_J CD UJ CD UJ CO CM CJ) CO CM CD CO τf cθ x- N O x- ro N CD τt ^ N CN CD τt UJ CD O CD χ - CD N τf CD CJ ) LΩ τf U0 CM UJ U0 UJ U0 τ _t- ,cDn _τ- C m J) τ-f 1 . τ-t ,CD ro- -. n (D - f ^. c - -f i n o m (D O O (00) C CO C N CM Tf CO d τf cb f d uj τf ' d d N uό ό b τf j τt τf ' τ^ oό co co co co co co co co co co co co co co co co co co co co co co co co co co co co co oo co co co co co co co co c^ co CM CM CM CM CM 00 OO Ω Ω X X X X x- CM 0000 LU LU LU x- CM X X X X X LU X X X X < oo < _.00 χOχOχOχOχOχ < 00 O Ω LU <xxxxxxx < 00 O Ω LU LU CN x- CM x- CM X x- CM x- CM OOOOOO X X X x- CM CO x- CM CO OOOOOCOOX X x- CM x- CM x- CM CO OOOOOOOO O O O O O O N Tf Tf CD O x- CM O CO O O O O O O O O O O O O O ro CO CN O O O O CO CD N O CN UJ O O O O O CJJ CM O O CD CD O O O O O O x- x- N CO UJ x- ω cθ m θ O O O O O O O O O O O O N CO O CO O O O O N O CO Cθ ro θ O O θ q χ - CM CD cq χ -; CD d d d d d d d ocd c ^xf ( d ( d d d d d d d d dd d d d c N o6 d d d N d ιnV (). dd dd d CM CM CM CM CM CM x- CN τ- x- CN CN CN CO C CN CN CN CN CN CN CN CN CN CN CN CN CN x- x- x- x- CN CN CM x- x- τ- χ- CN CN CN CN CN CN CN x- x- χ - x- x- τ- x- τf cD C0 ro ro τf τf τt O L0 CD C0 τf c0 C0 lΩ CO N CM τf ro cD U0 N x- N CD CN CO C0 U0 CN CD ^- CM O U0 CM O CM τf O CD τt C0 UJ CD CD O τf c0 ro N C0 CN N x- C0 N ro C0 CD UJ CD x- C0 CO CD N CD N U0 UJ C00000 ro N N C0 θ ro CD O O x- CD C0 CM x- O CD C0 τf rv. O C0 ro N ro χ - cD cq N c τf q f σ) LΩ co ro τf x- co ro N χ- c f θ N c - θ N ro cM CD τf ro - CM CD o ro τt c cb N- ro ro Tf cd cM x^ co cd Tf T x^ Lb c cM c Tf co co ^ o Tf ro CJ ) CO x- x- O CM N CN CO O τt cM CJ) x- CD O CD CO CO O CM O N τf CM CO N N x- N OO CM CO CO O CD CD CO C x- CM UO CM Tf x- ro oO xf UJ O N CD O CD CO Cθ χ - CO N CN N τf LΩ LΩ O χ - CM CO CO CD N ro τf CO CD τf τf τf cθ ro O x- χ- τf UJ N CN UO OO CO N x- CM N CD τf ro cθ O CO CM ro cθ N UJ UJ CO N q cO N UJ x- CM CD UJ OO x- O UO x- Tf ro cO ro ro cO CD x- CM CO N CD Cθ CO χ- CO C CO O χt CM O CM CM CM O CD CJ) χ-; τf Lθ cq c f r-i 00 N J NcoωNNrobbτ J bro rorocobτ : roσ)τ- : -- : bcobcoιn Tf cb N uo uO Tt cb cM cb cb cb ib cM CM co cb x-^ d d d cb cb τf τf τf τf τf τf τf f τf 'τf τf LO U0 U0 U0 τf '^f τf τf UJ U) τf τf ιn LΩ UJ UJ UJ Tf τt τf τt τt τf τf τf τf xf τf τt τt τf τf τf τf t τf - v t χ !f xf cθ CO CO CM x- O N CJ ) CD N O CO CO CM χ- ro c lΩ CO CO CM xt τf CM CD x- χ- θ ro χ- τt ro u UJ τf τf UJ |v- cD UJ τf cθ x- ro cθ UJ N τf ro CD o co co O N N CJ) CD C0 τt |v_ CN N O N CM x- N x- CO CD CO N CD LO CO CD UJ O O CO CD CO Tf O CD O O O CD CD x- CD CO CO CD CO x- UJ N CM O UJ x- CD CO x- CM CM T- xf S lO CO CM S T- O ~ CO " ro " CD CO O CD N χ- N CD N N O τt x- ro CD CO CO x-; ro CD CM ro x-; τf CM x- τf CD CM Cq x- Tf UJ ro CD od s ' ro d CJ ) cb cb c cb ro d d CM co CM N cb o cM CM cd cd χ- : N- N- N N d Ni cb ro ro αj χ- : χ c- ro χ χ- : χ- : ro ro b ^ c N CO CO CO Tf cO CO CO CO CO CO τt τf τt τt τf CO CO τf τf xf τf τf τf τf τf τf τf x^ c CO CO CO C Cθ CO C CO CO CO τf τf Cθ CO τf f t O CO Tf Tf CO CO CQ DO ^ CO OO O O Ω Ω UJ UJ N N N _. < < _. _ , n 0000 __ < X X X X < 00 Ω LU N < X X X X XX XX XX X < Λ X X < Λ ω 3 <xχO X X x- CM x- CM OOOOOOOZ X X X- CM X- CM X- CN X- CM X- CM CO Z O O O X X- CM Z O O O O O X X x- CM X o <oo ωoo CO CO CO LO CO CO LO LO x- CN CO χt UO CD N Ccθo roro θo x- C CNM C COO τ Ttf o o o o o o o o o O χx-- χ- χ-- χ- χ- ro ro ro ro ro ro ro ro ro ro ro ro ro ro CO CO O O O O O O O O O O O O CD x- Tf O CN CD CD UJ. O O O O O O O O O O O O O UO CN Tf x- f CD O O O O O Tt N O N O τt co o q o q q o o o o o o cθ χ- uo cM ro cN co cN τf o o o o o o o o o o o o o co χ- co cD θ θ θ θ θ o o c τf csj cq o q uό cb d d d o d d o d o Tf ^ o x^ x^ Ln d cb o d d d d d d d d d d d d o ' cb cb cb x^ d d d d x- x- CM CM CM CM CM CM CM CM CM CM CM x- x- x- x- x- x- x- CM x- CM CM CM CM CM CM CM CM CM CM CM CM CM x- x- x- x- x- x- CM CM CM CM CM -^ x- x- x- ro ro χ - CD ro τf ro CD CM U0 ro U0 x- N C0 CN ro c0 C0 ro τf C0 CD CN C0 cM CM cq cM q τf x- o τf C q u τf cbN ib τf c N J τf x- x-x- x-x- x-x- x-x- x- x- x- CM T _T x- CM UO Tf N LΩ ) CCMM τf O x- CJ) N x- O χ- O x- CD CD Cθ ro CD O UJ O CD x- CD O CN CO UJ C CD O CO CO UJ x- UO CO O CO CO CO CO N O O N Tf CM O) x- CD x- Tf o > U " J " CD τf xt N N UJ CM CM CD O χ- CD 00 N UJ CJ) CD CD lΩ CN N N τf C0 ro θ C0 O CD N τf N CO UJ N . O x .- f U .J. C _D x- N N N N Tt; x- CO q Tf Tf rq u χ-; cq u qc) χ-Nro χ-cM q q cq NCN uouo coχ-; Nθ t ro τf cqcq UJ CO CO CM CJ) CO ro x- co ro N ro o ro NO d cb c . CCD_ riu OfoJr))i CU_J)J(CcoDri tC(Dori rCDUΩ τx-- : -x-- : riO -χ-- : rCO xτrf ' xxtr ' xτfr xτf. ^χ- τ x-- : rOoO rCO_USJ CO CO Tt Uj Tf cO UJ UJ O o oo o co dc- dcb dx- 1 -ςf τf τf τf τt τf ro N cb cb N " t N CO CO Tt Tf CO CO CO Tf CO CO CO CO CO Tt Tf Tf Tf Tf Tf f Tf f Tf τt τt τf τf τ f τf CO C CO τt CO τf cθ τf τf co co co co co co co ro θ CN lΩ CN CO CO χ - CO τf |s - o Cθ CO τf τf x- r-. '^ ( N CD CD O CN CO Cθ ro CN ro CN CN lO CN N CO rø N θ ro N CO CcOoU τ tJ croqcroθ cNDτNt ιUnOcxo- roτtιCnMcxo- C χ CM- χ CM- cτNf roτf cCND CroM∞N χ τ-f cCoOiCΩMNOiτnf NoθCroD CcθNO χ t Nx-CxN-cxo-rox- cτo-cτDf Ncθθcqτx-f roχ-roro τ ^ N OJ cb cb ro N u N cb x^ x^ cM d x^ cN cd T^ c CM x^ ro CO CO C CO CO CO CO CO CO CO CO CO Cθ τf τf τf τf τf τf xt -xf τt C τf τf c τt τf τf t τt τf f τ rO χ O D χ 3333333333333<y)WC cθC0CO<OCΛC0WC0C0COWCOC>G0CΛCOCθWωC0W r- IIJ IIJ IIJ IIJ IIJ IIJ IIJ IIJ IIJ IIJ IIJ UJ IIJ >- >- >- > ). >- >. >. > >. >- >- >- >- >- >. >. >. >- >- ^ - _-j -j -- -_j - --j -_j -- --j --j --j -j --j --j --j --j --j -j j --j -- _j -j -j __j --j --j -_j __j --j j -j _j -J O O OO OO O < © UJ CD N Cθ ro θ x- CM C τt UO CD N Cθ ro θ χ- CN CO t UJ CD N Cθ ro θ x- CN CO τf UJ CD N Cθ ro θ x- CN CO τt UJ CD N Cθ ro θ x- CN CO τ^ o χ - x- x- x- x- CM CM CM CM CM CN CM CM CM CM CO CO CO CO CO CO CO C CO CO τf τf τf τf ^ τt τf τf τt τf lO LO UO UO LΩ LΩ LΩ UJ UJ UJ O ro roro roro roro roro ro ro ro rororororo roro ro ro roro roro roro roro ro ro ro rororororororororo roro roro roro roro roro ro O O O O LΩ CO x- CN τf CD C0 CN CJ) O O O O O O O O CD Tf CM x- O CD x- CD N CO CJ) O O O O O O O O O O xt xt ro N UJ LO OO CO CM CO O O O O CM x- N ro D x- N lO UJ O O O O O O O O N CD N x- CM x- CO CO O N O O O O O O O O O ro CO lΩ lΩ OO CO UO Tt O CO O O O O CM CO CO Tf CO Tf Tf O CO O O O O O O O O CM x- O CM O CM O x- CM O x- x- O O O O O O O O O T- CM Tf Tt CM CO Tt CM Tt CM CM CM CM CM x- x- x- x- x- CM x- CM CN CN CN CN CM CM CM CM CM CM CN CM CM CM CM CM x- N OO O CD lΩ CM τf cθ CM CM χ- LO CM lΩ CO CD CD CD CJ) CM C CO C CM τf N CO CM CD N Tf N N O OO UO N CO x- N CO CO N N CD xf N CM CO CD O x- CO x- CM O x- CM N C CD -r- UJ CM Tf cO x- N OO CD N Tf CD CM x- CO CO N OO OO N CO Tf cO CM O O Tf x- o O N lΩ OO N CD CD CO x- CD O O UJ O OO UO ro cD Tf Tf CD N UJ x- UJ N U " J CD " N CO LO ro cO CO UJ CD CD CO N C0 τf 00 CD τf CM CD τ- U0 CM ro U0 UJ CD LΩ in x- C0 C0 CN x- N O τt O U0 N τt cM cb cd τf uό uό cb τ f ' ιb cb cM Tf CO CM Tf cO CO CM CD N CO CD N CO CD N O CO ro O CD N LD CO O CD Nooororocoooororoco CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CO CM CM CO CN CM CN CM CO CM CO CM CO CM C^ CM CD xt CD CM Tt rs- CM O OO O Tf x- rs- x- CD CD CM N N CD CD LΩ CO CD CD O CO N Tf C CD x- LΩ CO LΩ N CJ) N LΩ 0O χ- C CM τf LΩ χf ro N CM OO CO CM O UJ CD Tf CN UJ CM CO O O UJ CM CO Tf oO x- CO CO x- CM CM ro UJ CD N O CO UO CD χ- τf χ- N U) x- CD CD N N ro cθ U0 C UJ τf τf . CN CO x- χ - CO CO τt O χ- τ- ιn rM in co ro ω ιn q ^ N C ro co ^ o σ) τ- q ( c χ f ir) in θ χ- ro cθ χ- co cD CM co τf r s - cM co co ro o co Tf cO LO N CD Tf CD l-J N φ l0 ^ xf (D CD ^xr ■ ((dD NN o(Dd (o0. ( o»i iιnri s iirin s d(O cCdD O d O (O iirin iiflri MM' , i-ri) ωCO N N CMO dU Ud ud sr» ^v. iuri x^: u. |s ωiJ oUjJ i- ' ω cb i cibJcωDcωbNι χ ιcbuouόroUJ d CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M CO CO CO Tf CO CO CO CO cO CO CO CO CO CO CO CO xf CO M Tf Tf N CO τf cM LΩ LΩ CJ ) CD τf cJ. CJ ) χ - CM CM CO CD τf CD CO LO χ f N O OO CM χ - τf CD τf O UJ CM x- CD ro CD CD CO OO CO UJ O C O UO CD UJ N CO N CO CD CM Tf cO CM CM Tf oO O CM Tf CM UO CD O CM LO LO CO CO OO O CD CD CD CD UO x- CO CD CD CM UO τt O UJ O τf cθ C0 CM N CJ) τf CD CJ ) CD LD C0 CM U0 χ - CM N ro cq N N q N cq τf χ-- cN χ- χ- N co uj co cq cD cq uo o χ- CM Uj oq N χ- o uo τf N O CJ) χ- ro τf CM O CO CO CM CM N UO CD O CO CD CD N N cb ro N UO Tf Tf Tf cO CM CM CN CM lb f c cd x^ x^ x^ CM lb d uO UJ oo co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co ._ .„ CM CM CQ CO CQ - CM CQ OQ O O LU LU x- CM x- CM 00 00 ■ *- CN x- CN ^ x- CM x- CM < X X X < CQ Ω LU LU < X X X X X X < OQ O Ω Ω UJ LU N X < χ χ Ω Ω LU UJ X < ω O Ω Ω LU UJ X x- CM co Z O O O O O O O Z X X x- CM x- CM x- CM O O O O O O O O O O O X X X- CM X X X X X υoooυoozo < < < < Z Z Z 2 Z 2 Z Z Z Z Z Z Z Z Z 2 Z Q. (T Q. D: (ϊ (r Q. Q: [K Q: K D. Q- Q: D_ D: Q: Q: Q_ D_ Q: D- l -. CL _. _. _. D- CL Q. r- -J -J -J .-J -I -I -I -J -J -J -J -J -I -I -I ^ ^ ^ ^ ^ -I >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- >- ^ <<<< OOOOO OO OO Of-i-f-f-f-f-f-f-i-HI-f-Hf-f-H © o N Cθ ro θ x- CM CO τf iΛ CD N Cθ ro θ χ - CM CO τf LΩ CD N Oθ ro θ χ- CM Cθ τf LΩ CD N Cθ ro θ χ- CM CO τf UJ CD N Cθ ro θ χ - CM CO CD CD CD N N N N N N N N N N CD CO CO CO CO C OO CO OO CO CJ) CJ) CJ) CD ro ro CD CJ) CD CD O O O O O O O O O O χ - χ - x- χ - χ - x- x- χ - x- rororororororororororororororororororororororororororororororororoooooooooooooooooooo X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- T- X- X- X- X- X- X- X- X- X- X- X- X- X- X- CM CM CN CN CM CN CM CM CM CN CM CM CM CM CN CN CM CN CN CM x- CD CD O O O O O O O O O O x- CD CD LΩ O O O O O O O CD U Tf CD O χ - N CO N O O O O O O O θ ro θ CO CO CJ ) τf cO CO CO Tf O O O O O O O O O O O oo CD O N Tf UO O N N o o o o o o o ro co x- Tf o N UO CM OO O O O O O O O O CO x- Tf UJ Uj ro UO 00 CM x- 1 Tf o o o o o o o o o o CcDD UinJ CcDD CαOj CcMM LLΩO LuΩo o o o o o o o co x- CM O CD C u o d d d d d d d d ro d cN Tt d CM CM CN CN CN CM CM CM CM CM x- x- x- χ - x- x- x- CM CM CM CM CM CM CM x- CM CM CM CM CO CO CO τf CM CM CM CN CN CM CM CM CM χ - χ - x- CM CM N CD UO N O UJ CO ro cO UJ CN UJ O O 00 CO J D 00 D x- N CM O τf U N 00 CD CD τf rv- τt x- CD C0 C0 O CM χ - O 00 N C0 CD C0 C0 τf CD CM CJ) o co o co ro ιn o co τf x- x- ro f N ro CN ro ro co x- CM ro cθ in CD CO CM CD τf CD CJ) UJ CD CD UJ CD CO CD UO CM N N CO O CJ ) O CO CO CO CD CJ ) CM cq N cq o q io cq N x- uo uj Tf N CM O CD CO x- CD C Tf cD τf co co cD co o cM ro τf uj τf o u ro ro uj χt cM ro cq τt q uj ro N N uo ro χ- cM OO t— N N CO O O X- X— 0 ) 00 N CD CD L O-J UCDJ UCDJ CO—J LO-J X— Xx—- L0U0 LO—I LO-J LCMN CCMN X τ—- : LCM LcUb Is—- ' UcdJ LcbU LbU LbU ^XT L('J Lc'.J sI— , raLU ωLU UbJ bLU LdU bL'J XJ ; ωLU LroJJ bL_ Ud bLU LcUd sI—- CN CN CN CN CN CO CO CO CO CN CN CN CN CN CO CN CN CO CO CO CO CN CO CO CO CO CO CO CN CN CN CN CN CN CN CN C Tf CO CD τf cθ CO N lΩ lΩ O τf θ lΩ CO CO CO CO CO CD LΩ τf |v_ o ro cθ CO CD CM U ro θ CO χ- CO N τf r- cθ CD Cθ L D ro N CM τf x- L^ C ro c ro iΩ N x- lΩ O CN x- CD ro ∞ O CO CD x- α_ CN ro x- x- N ro CO rø CD τf CN ∞ IΛ CO CO O τf CD CO CO O U0 U0 τf τf cJ) in 00 CD χ- O N C0 CM χ- ro C0 χ- χ- O C CM C O C0 CM U0 CM CO CM U0 UJ CD N C0 CO CM τf UJ C0 U0 CO N C0 lΩ ro ^ O x^ lb N N CJJ x^ cb cM cM U U N cb u U UJ U f J d f Tf ^ OO Tf -N' Tf cO CO CO CO CO Tf cO Tf Tf Tf cO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tf cO CO C^ ro N N CO N CJ ) O N LΩ CO CM CO CO τf x- σ ) χ - CN CO UJ N χ- CD χ- CD UJ CO χ- CM χ- x- CO θ ro τf O CD CO CO CM χ - θ σ) x- UJ OO UJ CO O CO x- O o CD CO N CD UO UO CO Tf uO CO CD Tf uO N N x- N τf cθ CO CO τf O τf CO CN CD U CJ ) ro θ τf r-- N N CD O CN CO O CN CO τf x- O lΩ χ- CO τf σ) τf CO O x- CN CO N CM x- N Tf cO O LΩ N CO N CO CD LΩ CJ) CO CD CD CO CO CO lΩ CD CM CO CO CM UO τf CM UJ x- OO τf O τf |v. Tf CO Tf CN CM OO O CD CO Tf cb ib Tf Tf co Tf CO O LO CN CD Tf O CD CO OO CO CD O CD CO N CD ro N N UJ UJ N CO CO CO OO CD N CD N CD CO CO CO UO Tf Tf f cO CM CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CN CN CN CN CN CO CN CN CN CN CM CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ CO CM CO CM GQ CO ^- x- CO CM CO CM DQ GQ O O LU LU LU N N X < X X L_ LU LU N N X < _ ωOΩ <χ χχ χχ χ < 00 Ω LU LU < X X X X X X < DO Ω OO OX X x- CM X X X X X X Z O O O O O O X x- CM x- CM x- CM OOO O O O O Z X X x- CM x- CM x- CM OOOOOO CL CL CL CL CL CL CL Q- CL Q- Q- CL CL CL O O O O O O O O O O O O O O CO O O O CO O O r- CL CL CL CL CL CL CL L CL VΥ. CL CL I Υ. CL CL CL CC CL CL CC ΙΥ. CL >-> >> > >- l- l- l- l- H H H r- r- l- H I- r- r- Q- Cu CL α Q- CL CL Q. Q. α. Q. CL CL θ OO O O O O O O O O OO OO OO _J _l _l _J _l _J _J © o ro θ χ- CM CO τf uO CD N Cθ ro θ χ- CM C xf LO CD N σj ro θ χ- CM CO τf UJ CD N C ro θ χ- CN CO χt UJ CD N Cθ ro θ χ- CM C τf lΩ CD N ∞ x- CM CM CM CM CN CN CM CM CM CM CO CO CO C CO CO CO CO C CO Tf τf '^ '^ 'xf τf '^ τf τf τf UJ UJ UJ U0 UJ UJ UJ lΩ U^ O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O CN CM CN CM CM CM CM CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CN CN CN CM CM CM CM CM CM CM CM CM CM CM CN CN C^ 4o 2071 LYS CE 21.248 37.656 27.135 32.07 2072 LYS NZ 19.951 37.638 26.450 40.14 2073 LYS H 25.913 36.568 28.818 20.00 2074 LYS HA 24.207 38.466 30.286 20.00 2075 LYS 1 HB 23.084 38.21 1 28.385 20.00 2076 LYS 2HB 22.156 37.389 29.639 20.00 2077 LYS 1 HG 22.886 35.151 28.800 20.00 2078 LYS 2HG 23.896 35.943 27.603 20.00 2079 LYS 1 HD 21.052 35.524 27.493 20.00 2080 LYS 2HD 22.158 35.907 26.237 20.00 2081 LYS 1 HE 21.938 38.332 26.616 20.00 2082 LYS 2HE 21.014 38.102 28.1 1 1 20.00 2083 LYS 1 HZ 19.364 37.019 27.058 20.00 2084 LYS 2HZ 20.056 37.233 25.501 20.00 2085 LYS 3HZ 19.574 38.608 26.433 20.00 2086 GLU N 23.400 36.776 31.841 15.88 2087 GLU CA 23.136 36.1 18 33.1 1 1 15.37 2088 GLU C 22.807 34.620 32.974 15.69 2089 GLU O 23.432 33.804 33.626 13.68 2090 GLU CB 22.083 36.964 33.900 16.72 2091 GLU CG 22.625 38.280 34.481 14.29 2092 GLU CD 22.320 39.420 33.579 18.80 2093 GLU OE1 22.205 39.180 32.359 21.62 2094 GLU OE2 22.216 40.551 34.077 21.27 2095 GLU H 22.923 37.629 31.683 20.00 2096 GLU HA . 24.072 36.180 33.655 20.00 2097 GLU 1 HB 21.726 36.367 34.740 20.00 2098 GLU 2HB 21.182 37.117 33.295 20.00 2099 GLU 1 HG 23.692 38.268 34.620 20.00 2100 GLU 2HG 22.172 38.502 35.438 20.00 2101 GLU N 21.816 34.259 32.125 18.42 2102 GLU CA 21.276 32.842 31.945 20.95 2103 GLU C 22.156 31.928 31.090 20.76 2104 GLU O 21.994 30.705 31.057 20.49 2105 GLU CB 19.952 32.834 31.234 20.78 2106 GLU CG 19.309 34.201 31.354 25.93 2107 GLU CD 19.642 35.143 30.246 25.99 2108 GLU OE1 19.653 34.697 29.122 28.63 2109 GLU OE2 19.906 36.310 30.524 25.53 21 10 GLU H 21.335 35.045 31.723 20.00 21 1 1 GLU HA 21.174 32.451 32.958 20.00 2112 GLU 1 HB 19.298 32.082 31.685 20.00 2113 GLU 2HB 20.022 32.547 30.179 20.00 2114 GLU 1 HG 19.417 34.671 32.332 20.00 2115 GLU 2HG 18.245 34.072 31.265 20.00 2116 LYS N 23.11 1 32.603 30.414 21.38 2117 LYS CA 24.125 31.842 29.692 21.50 2118 LYS C 25.526 31.935 30.345 21.97 2119 LYS O 26.347 32.738 29.892 22.57 2120 LYS CB 24.088 32.258 28.172 22.92 2121 LYS CG 22.714 31.845 27.594 27.23 2122 LYS CD 22.552 31.376 26.144 35.59 ro cθ O O O O O O O O O O O O O CD τf r-- CO CO CM CM N Tf O O O O O O CO Tf l— CO N CD CO O O O O O O O O O O CO O N UJ x- CO τf O O O O O O O O O O O O O CM CJ) N CO CO CO x- Cθ Tf O ~ O O ~ O ~ O O ~ 00 UJ O U) CM U0 C0 N O O O O O O O O O CD CD c o q co d d d d d d d d d d d o d x^ cM x^ cb cM cb cD cb cό d d d d d d cb N ro d cb cb cD cd d d d d d d d d d od d d cb Tf Tt Tf CM CM CM CM CM CM CN CM CM CN CN CN CM CM CM CM CM CM CM CM CO CM CM CM CM CM CM CM x- x- x- CM x- x- x- x- CM CN CM CM CM CN CM CM CM x- CM CM CM CM O O O _. N N ro ro x- CM CO (O (N 0) . T- (D (D C0 MD (O O MD 000) \- 0. C0 m N T- CO CD CD O O O CN O lΩ CO lΩ N O Tf cO lΩ CN O lΩ CO CO f J CO x- OO N ro CD Tf O N Tf cO x- ro cD CD CO ro CO N Tf rv- ro CD CM UJ CM N N O CO ro cO O ro N O CO Tf CD x- OO UJ CD CO N CD UJ N CM Tf LO x- x- CM τf CN CD N N CO CD ro cN CO O χ- lΩ τf t s - θ ro θ CN f LΩ τf cM ro xt ro cθ O CM O CM CD lΩ ro CD N Cq cθ CO '^ x- χ- CM CN UJ CJ) τf cθ τf cO CM d cj. cb x- ' co cM d cM O ^ o cb ro cb x-- o ro ro cb cb d x x- d d cD CO CM O LO CO CO CO CO CO CO CO CO CN CN CN CO CO CO CN CO CN CN CN CN CO CO CO CO CO CN CO CN CN CN CO CO CO CO C^ ∞ N O LΩ N ro UJ CO CD CO O CO O CO τf c ro CM UJ χ- LΩ O CD ro ro CM χ- CD τf lO χ- CD Cθ χ- N O N C ro CO χ- τf cθ χ- xt CD N ro x- C ro θ CM O O O O CD N UJ ro ro cθ N χ- lΩ UO N C ro χt C O N C CN UJ CO (O O Uj ro ro χ- CM ro CM N CO CN CO N CN τf CM CM τf O χ- CO x- ro θ CO N O χ - ro ro CN ro c τf UJ CD UJ CM x- CO N x- O CD CN CM CO U xt O UJ CM CM τf UJ C τf x- τf τf cθ x- CN UJ CJ) CO N q UJ N ^ Cθ ' τf cb c τ 'x --^ CM CM x- τf c cd τf τj ' i ; | v αO N N- ^ CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CM CN CN CO CO CO CO CO CO M CN CM CO CO C^ ^ OO O Q O O Ω Ω LU LU N N N _ _,,. . -. rr; . > . ^ . O Q oo ^ OQ OOOOUJ UJLU ^ _ L N <XXX XXXXXXXX < _ 00 Ω LU LU <χχχχ < _ ω O Q U <χχχxxχx < _ C Q O ZX Xx- CMx- CMx- CM x-CM x- CM CO ZOυOOOOOOX Xx- CMx- CM υoooocoυxxx-cNx-cNx-cNcozυυoo r- lil l l]li l] l ] ^S2-≥-≥^S_≥SS^^S^^_ ^dd dd © CO τf LΩ CD N Cθ ro θ χ- CN CO τf LΩ CD N Cθ ro θ χ- CM CO τf UJ CD N Cθ ro θ χ- CM CO τf UJ CD N Cθ ro θ χ- CN CO τf Ln CD N ∞ O CN CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO τf - " τf - " τf τϊ τf ^ τf τf U0 lΩ lΩ CM CM CM CN CN CN CM CN CN CM CN CN CN CN CM CN CN CN CM CM CM CM CM CN CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM C^ x- O CO O O O O O O O O O O O N CD CO τf uJ |v. LΩ Tt CM CO CM O O O O O O O O O CN Tf N N xt CD CD CD N O O O O O O N N CM cq cD cq q q q q σ q q q q o o ro τf rv_ cD co co iΩ x-N CDOJ Oo oo oooooTf ocDNco u co cDq oq qq qq cM N co uό τf |v. o d d d d d d d d d cD cb cj) cb cb τf cb xt τf τf O O O O O O O O O cb N cb N " cM c cN τt lb θ O θ " d θ O l τf τf CM CM CM CM CM CM CM CN CM CM CN CM CN CM T- X- X- X- T- X- χ- x- x- x- x- CM CM CM CN CM CM CM CM CM CM CM CM CM C τf LΩ UJ UJ CN CM CM CM CM CN CM CM CM CD CD N O C CD0 T^- CCMM x- CD χ - x- CO O τf 00 ro C0 τf 00 U0 ro N ro C0 CJ) ro θ U0 U0 τt UJ N χ t x- CM Cθ C0 ro CD CJ) C0 CD O C CJJ)) CD x- UJ N N χ- CJ) N x- CO CM UO CCOθ CCDD UUO0 O CD N CM O x- N CD O χ - τf θ CN N ro CD UJ N τf C0 τf C0 C0 N CD χ t C0 x- C0 C0 C0 CD CD 00 C0 CJ ) CM O x- UO ro CM CO CD N x- CO CD O cD " ~ T ocM "n Tf Nc ro c Tf cM O N Ouo co j u co Tf M roouocDcOT iv.c N Nu^ N O N CD N O CM CD COj CiM CiMN O CM x^ cd T cd x^ CM CM x^ cd x^ x- CM x^ x^ ro CN CJ) χ- O CM ro θ CN OO CO CO CM O O O O χ- CJ) CD CO N Cθ ro x- O CO CJ) O O O x- CO Cθ CO CO C CO Cθ C CO Cθ CO CO CO C CO CO C CO CO C CN CO CM CO CO CO CM CO CO CM CO CM CO CO CO CO CO OO CM CM CM CM CM CM CO CO CM CM CO OO CO CO CM CD CN Tf UO xt CN xf τf CJ) Cθ ro τf cθ CM x- U0 CD N CO CJ) O χ- CN CM lΩ N CM Cθ ro CN CO xf UJ O CJ) CD x- UJ ro θ U O CD C CD χ - N O τf CJ ) CD CD CM O ) N 00 O O UO O N x- CM CO Tf UO CM Tf O OO CO CD x- CD ro U) CM ro cθ lΩ τf τf C CO N ro cO N χ- τf cθ CD x- CO CO N O τf x- o ro f UO CO O O O oq cq τf N cq N χ -; q cD C CO τ- N tΩ CM CD CM o Tf O LΩ O CM co co co ro ro ro N cq ro cM cq T r^ x-i αq o x^ cq LΩ iΩ x- u cq N u) τf iri N cd τf ri ' τt cb c τt ιb . d τt τf N cb cD ro d x^ b N- N d co- o x- ' cb cM x^ x- x^ x^ x^ ro Tf cM x^ cM x- cM c^ CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO CN CN CN CN CN CN CO CO OO CN CM CN CN CN CN CN C^ CO LΩ LΩ τt LΩ LΩ CO CM CD x- x- x- CD CO Tf Tf o Tf UO CM C0 x- N 00 C0 CD lΩ x- oO LΩ OO ro CJ) O Tf CD CO Tf τf τ o ro τt σ ) τf cD q cD Noo roo ro N UJ ro UJ d cMrodcM dddco ' CO O CO CD d CO CO CN CO CO CO CO CO CO C O C O C O C O Tf CM CM CM x- x- π CM x- CM CQ DQ O . ftO PΩI < .^ COO x x x Q xΩ xΩ _, x- CM x- CM DQ CO T CM x- < DQO Ω Ω LU LUN < χχΩΩ_U LU N < OQ O Ω UJ LU < χ χ 00 X X < O O O X X X x- CM x- CM CO x- CM CO ooooooooυυ X X- CM X X X X X oooooυooχ χ χ-cM x- CM 00 LU LU LUUJ LU UJ LU LUUJ LULU LUUJ LUUJ UJUJ LU LU LU 333333333333333 Q- Q. α. r- m LULU LUu j m Lu u j m χ χ χ χ χ χ χ χ χ ^ j _ j ' _ j _ι_ι_ι _i-- j _ι_ι _i-_ι _ j _i c co ddddddd dddddddCLCLCLQ.Q-Q.Q. Q.CLCLα- CLQ.Q.CLCLCLQ-Q-Q.OOOOOOOOOOOOOOO<<< © LΩ CO N Cθ ro θ χ- CN CO τf u LD N C ro θ χ- CM C τf U. CD N αD ro θ x- CN CO τf lΩ CD N Cθ ro θ χ- CM Cθ τf UJ CD N Oθ ro θ χ - CM C^ o ιv. r-N NN coco cooo oo coco co cD co ro rororororo rocD rocj) θθ oo ooo o o o χ- χ-χ-χ- χ-χ- χ-χ- χ-χ- cMCM CMCM CM CM CM x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CN CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C CD N UO CD O O O O ro o o UO N CD O r O O O O O O O CO CO UJ CO N CD CN Tf o o o o o o Tf r v - xt ro t r v - co cM O O O O O O O CD CO o o o o o o CD x- x- UJ O O O O O O O CO CM CO CM CD x- τt O O O O O O N CD CD CO CO CM x- CD O O O O O O O cD i o d d d d cM d rø ib cb d d d d d d d x- cb co ' t N CM t x^ d d d d d d cM x- 1 CO N x- 1 d d d d d d d CM CM CM CM CO CM CN CN CN CN CN CM CM χ - χ - χ - CM CM CN CM CM CM CM CN CM CN CM CM CO CO CO CM CM CN CM CM CM CM CM CN CM C^ ro ιn ro τf -xf c0 L0 U0 N U0 CM CM UJ N O x- ro N χ - UJ O χ - L0 τf !v. c0 C0 O χ - O CN L0 C0 x- CD L0 lΩ N L0 CO C0 CM χ - u0 τf 00 x- x- CM x- CD CM 00 C0 in uJ CM UJ CM ro cD O N UJ C0 C0 x- ιn N C0 U0 CM CM C0 O x- ro CM C0 UJ C0 O C0 τf U0 ro uj O C0 U ) χ - C0 τf x- O UJ CJ ) 00 O x- CO CM x- Tf χ ^ χ - CM N CJ ) τf cM χ - o cq q N cq uj χ - o ro q cM o co ro τf τf cq uθ 'xf rø x- CD N CO U CM oJ ro ro cb c j - c ro cM cd Tf Lri c cb cM x^ cd Tf M x^ iri xt co Tt io CO CM CN CN CN CN CO CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ r- xt CO CN O CO CN CD CD CD ro τf -Lf ro c CO O CO τf O N ro cθ CO χ - N τf x- CM θ ro τf CD O χ - ro CM τf cO CO CM CD ro c ro iΩ CM ro CD O χ - ro U^ CD UJ UJ UJ x- χ - N N N CO τf |v- cθ C CO CD CD χ - χ - CD θ ro UJ χ - CD x- χ - Cθ ro uθ χ - CD N τf N χ - τf 'Lt CD N θ ro N CO C O CO CO CD x- CO CD q q iΩ χ - χ - co cM N cq χ - ro cM CΩ τf N xt Ln ro χ - τf q N iΩ χ ^ cq cM χ - χ cM cb T f Lri uό c x^ cM CM cd T f c f Lri d iri T f d iri d iri iri c^ CM CM CM CM CM CN CM CM CM CN CN CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CN CM CM CN CN CM CM CM CM x- CM CM CM CM CM CN CN C^ CD ro xf LΩ τf τf ro ro CJ ) τf θ LΩ CO LΩ N τf uJ C0 x- O C0 N C0 O C0 N χ - ro CJ ) CM ro C0 CD C0 O τr 00 |- N. LΩ CO CD N 00 N CM x- x- CD cD uo N χ - q u CD Tf oO μ d d ro x- 1 oo o O C _J). C _D. o cM Cj- Tf Tf Tf CO Tf CO Tf o Tf μ O Tf Tf τf c0 CO τf τf -xf cO CM CM CM CM CM x- CM co ω *- CM TZ OO .- Z p* 0000 Ω Ω x- CM 0000 Ω Ω 00 Ω Ω < DQ OO < oα χ xx < 00 Ω Ω < X X < ω O Ω Ω OOOOO τ X- X x- CM OOOOOO X X X X x- CM co oυoooozxx X X x- CM x- CM OOOOOOO X x- CM X x- CM CL CL CL CL CL C C CL CL Q _ C_: __: Q _ Ct: C_: Q __: _r __: Q _ Q _ __: __: Z Z Z Z Z Z Z Z Z Z Z Z Z Z 333333333333333 r- CO CO CO CO c .o. ωcococ _o. x xxx x xxxxxx x xxcocococococoωwcowcocococoLumωm m Lu ujuj uJ UJ Uj < << < << <<<< <<<< r- r- l-|- l- l- -H-|-|-|- l- |-|- << << << < < < <<<<< _l _l _l -J _l- _J_J _J_J _J_J _J _l -J © N Cθ ro θ χ - CN CO τf uo cD N Oθ ro θ χ - CM OO τf ιo CD N Cθ ro θ χ-- CM CO τf LΩ CD N Cθ ro θ χ- CM CO τf LΩ CD N Oθ ro θ x- CM Cθ τf u ω O CN CM CM CO CO CO CO CO CO CO CO CO CO T f T f - L f -Lf - L f ' L f T f 'Lf 'Lf Tf UO UO UJ UJ UO UO UO UO UO UJ CD CD ω CN CN CM CN CM CM CM CM CM CN CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CN CM C^ CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CM CN CN CN CN CN CN O O O O O CO Tf CM Tf r s - N CD t O O O O O O O O O O O O O x- x- CD x- ro oO CM UO O O O O O O O O O O O UJ x- UJ O Tf CO N q q q q χ - uo cq cN ro cq cM χ - cq q q o o o o o o o o o o o τf τt oo N o ro τf rv.00000000000 CD UJ CD x- C N CD d d d d -r d d d c d c d d d d d d d d d d d d d d d d d y ό d ό d d d d d d d d d d d N N CO cb iri iri CN CN CN CM CM x- x- CM CN CN CN CO CO CM CM CM CM CN CN CN CN CM CM CM CN CM x- x- x- x- x- x- x- x- CM CM CM CM CM CM CN CM CM CM CM CO O O CO N OJ CM CO τ-; in ro N LΩ CD CD O CO Tf x- UJ N ro CM OO CM O N CD CO ro O N χ - τf cθ CO τf CD τf O UJ O CO UJ O O CO O CM O CD CJ) UJ CO x- CO x- UJ N τf O CM x- CM UJ CJ ) χ - CO O O CJ ) LΩ O CO CM CO χ - OO OO N CO CO CD CD τt ro cθ CD x- CD τf x- oθ CM CD CM CD CO x- CO CO N χ- τf O CD CD CO CO CM CD N O N O CD τf CD CD CD χ - CD O τf 00 C0 C0 UJ C0 00 CD C C0 N τf ro x- co N in ro cM N co ro co co cM co co o o oo co co co co co x- Tf x- r-- x- cD cq cq cq ro N N dσJdN is ' (d (b N (θN (o ' (bιri N c d ^ cM ^ CM c Tf 'sf .o cM CM ^ Tf c cb d c xt uo c ^ CM CM CM CN CN CN CN CO CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CO CO CO CO CO CO CO CO CM CO CO CO CO CO CO CO C^ x- τf ro ro cθ lΩ O N CO CM UJ UJ x- N CD CO CM CD CO O CM χ- O CM CD CO O CD τf x- CD C Cθ ro θ τt O C O CO x- O τt CM UJ CM x- x- CO CD OO CM CO UJ O Tf oO CD CD CO CO CM N U Tf CD UO x- UJ N CO CD N x- CD CM CO CO UJ x- x- CD UJ CD O CD x- Tf cO x- CO ro CM CD CO O CD CO LΩ CM ro O N N CN τf .χf x- rv- ^f t o CO CJ) CD UJ CN O CO τf τf |v. iv. τf oθ CO LΩ O χ- CO CO CO τf OO CO O OO CO Tf O UO OO x- CN OO OO CO CO O OO UJ CD Tf CD N x- O CO N ro c0 CM CN CO χ - ro C0 N N τf CN x- x- ro ro ro c0 CD N C0 N CD x- x- θ ro CM C0 C0 C0 x- CM CM 00 CM CO τf cθ τf c0 τf ro CO Cθ ro N N CD Tf CO CO CO CO CO CO CO CO CN CN CN CN CO CO CO CO CN CN CN CN CN CN CN CN CN CO CO CO CM CO CO CO CO CO CO CO CO CO CO C^ x- CN CN CM x- x- x- CM CM CM Ω Ω Ω Ω ^ D Q DO O O Ω Ω LU LU N N N x- CM 00 00 ,_ Ω Ω x Ω x Ω x Ω Ω -<- CM X X X X < DQ O Ω LU N < CO Ω Ω x x x < CO OO CO x- CM CO OOOOOOOZ _ <xxxxxxxxxxx X X x- CM x- CN x- CN x- CM x- CM CO OOOOOOO - Xr X x- CM X x- CM CO x- CM CO OOO OO r- D3DD(nW(ΛtntflCOWC. (Λ(fl(Λ(fl(ΛCfl(ΛWC tΛ(Λ(/)(Λ(ΛD DDDDD DD DD DDDDD L-_: tt I UIJI iUl-Il iLUll iLUl l S^__ S^__ S^__ N^__ ^__ S^__ S^__ S^__ S^__ N^__ S^__ *^s__ S^__ X^__ ^__ S^__ S^__; ^ ^ _ __ , ^_ s._ S__ ■■■ ■■■ i ■ i i ■ i i ■ i 11 i 11 i 11 i 11 i 11 i i i i 11 i i i i i ■ i 11 i 11 i i ι i "T * T" T" T T~ T X T X~ © O ro θ χ - CM CO τf LΩ CD N Cθ ro θ χ - CN CO τf LΩ LD N Cθ ro θ χ- CN C τf ir. cD N Oθ ro θ x- CM C τf LΩ CD N Cθ ro θ χ- CM C τf uJ C^ N CD CO OO CD CO CO CO OO CO CO ro ro ro ro ro ro ro ro ro ro O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CN CN CM CM CM CM CM CM CM CM CO CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CN CN CM CO C CO C C C CO C C C C C CO C CO C CO C C C CO CO CN CN CN CN CN CN CN CN CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CN CN CN CN CM C^ M M W N) M M M M M M M M M M I M M M M M M N) M M N) M I I. W M M W M M M M M I. M M M M M M M CO CO C CO CO CO W CJO CO CO W CJ- CO CO CO CJO CJO CJ- CO CO CO CO CO CJJ CO CO W CJ- CO CO CO CO CJO W ro ∞ ∞ -M -vi - - -Li -j -vi - i '-j -M ro ro ro ro ro ro ro ro ro ro cji ci j. cj. cjo c^ cji c^ w -' O co ro M ro w ω J -^ o co oo M ro w Λ ω M -i O (D ro ro c^ ω -i o ω (» N ro ol ω ^) - ι o (o ω M ro ro ^ ω w -i J cy ω o Λω JFFFFFFFFFFFFFFFFFFFr-r-i-r-r-r-r-r-r-r-r-r-i-r-r-r-r-i-r-HHHHHHH mmmmmmmrτιmmmmmmrτιmmmmmmmmmmm 73737373737373 CCCCCCCCCCCCCCCCCCC JJ JJJTJΛ . OO OO coro-»-coro- ι .r -».χχ OOOOOOO r -j.c r -L sj- ^ OOOOOO ω ro -^ O∞ > XXXXXXXXθD> OOO σ. > XXXXXX XX> D O O DD > II Ifl O] > OOOOOOOO -> ■ ro ->■ O O O O O D LTJ O- ro ->■ _-___-roror ->-->- ro ro ro -»■ -L -L ro ro ro ro r r ro M t r w . M ro M . M M N) r ro W M M r r r M . w w -vi cD cn -vi ro cn ro -vi n co ro n 4 s - co -vi --j cι ∞ σ) uι -N ro 4- c ro -vi -vi ro ∞ cjι ro cjι ro -j ro ∞ -vi ∞ ro ro -vi cn ro -vi -vj n cn cj) oo -vl co o d d d cn co it^ d CD __ ro co ->■ i Λ b i vi ώ is ^ ώ d co αi co ώ ϋi o -»■ CD ro cn o O CO -> ■ CO CJI cn 4 s - co o CJ) 4 s - ->. 4- co co --j cn -vi co co CD o (D vJO CO -". Cn 00 -^ 00 O -J- Cn 4 s .4 s - 4 s - 4 s - ro ->- CD _. -J o ro -L -si ro -j n c» cn cn co cn oo ro - l 4 s - O 00 -vi n ro θ r o co *. i θ r *. N v) ω oo (θ θ ^ ϋi oι ω cn to M co -vi -J co ω co co ro co -vj r ∞ ro Nj ro co o co -vi oo cD ro cn ωωωωωωωω^. CO 4 s - 4>- 4- CO 4 s - ω co co co -P_. CO C C CJO C) CA) CO C C C C G ) C C C C C C C CO C CJO C C CA) CO CO CO C C CO C -vi po po O) ro o) -vi co p 00 -L O O CD O O CCDD 0000 --vv|| CCDD oO cCDD cCo0 --vvil --ssil o0o0 --vvi| cCo0 44 ss -- rroθ tto -»- rroo 4 4 ss .- M ro rroo cnn 44 ss -- ωco rιo_ ωco ωω cιjnι ucnι ^4 s . j4_ s - rocD c(-ni cuni -vji -svji ^j-. σcD) ro i_j io ^ d cD co c» cn . co cjθ i- j - ^ i^. d d ro cn -vi i^ io -j d d ro ro n iχ> d ro — o c ∞ cD -j σ : vj : j -->. -- 4!- it_ D co -^ -^ -^ -^ 4^ -vi ∞ D o ro - i M -vi Cjθ c o to co cD 4- o cn cD ro c -vi n o CO CD CD -si o CD -j cn 4 s - ιo ->- o co cD -vi cD 4- 4 s - r '-si cn -»- cn co cn co 4- ro cn oo cD co cjo ro co - i oo cD - j - r -vi -^ c c -si c ^ c»owco co.. oo co o cD cD ro ro -vi CD Cn CD 4 s .4 s . CD CD -». O -v| -vi rO CJ) 004- ro ro ro ro ro -^ -»- ro r ro ro ro ro fo ro ro ro to -^ ->- ->. _- _- _- _L _v ro to ro ro rLj ro ro ro o ro ro _- _- _- -- ro -». -». -»- ro ro fo r r ro r o ^ - j - ro -'- cD Oo o o p o o o o o p p o cn -vi ro -si co po oo oo p p o p o o p o o o o cn co cn n p co ro cn o o o o o o o d cn ro O) co it_ d d d d d d d d d d d d f co i->. 4-. j_. bo co i&. d d d d d ' d d d d d d v! ^ oi bi a) bi (» o o o o o o o O -^ 00 4 s - CX) O I O O O O O O O O O O O CJ) -vi ro 4-. ->- o ro o o o o o o o o o o o ϋi ro oo ro co ω -Oi o o o o o o o O O O O x- N x- CM ro O CM N O O O O O O x- UO O UJ CN C x- N O O O O N CO x- UJ x- CM CO OOOOOOOOOOO LΩ O O O O CD UO x- x- CM CO O Cq o p O O O O CO N CO CO CJ) x- O N O O O O Tf ro iO x- UO CO N CD OOOOOOOOOOO Tf d d d d CM iri iri od s (N K coV d d d d d d d cd s ^ cd cb co d o d d σJ o cM uό cM CM cb CM d d d d o d d d d d x- d CM CM CM CM CM CN CM CM CM CO CO xf Tf CM CM CN CM CM CM CN x- CM CM CM CO CN CM CM CN x- CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CD 00 CD CO CM CO x- OO UJ CM x- UO CD CD N CO CO LD CD CO x- O N OO CM Tf cO CD Tf CM CO O CD CO CD CM N CO Tf CO x- lΩ CO OO O N CO N Tf x- ) CO CΩ lΩ CN N CN OCOO LLΩΩ LlΩΩ CCNM CCOO OO xx-- CCOO TTff NN C CMM OO NN x- C CMM OO OO CCDD CCDD NN U UJJ CCMM NN CCOO NN TTff UuOO NN Tf CcOO OO O x- TTff ro cO OO OO N CO x- N Tf cO x- CO O O CM CM CD OJ CD x- CO CD UJ CM CD CM O N Tf N O CJ) C LΩ N Tf CM x- O CD CM CO CD N x- UO C CM O τf θO CM χ- lΩ CM CD CM χ- χ- CO τf cb ro co co UJ Tf Tf -^ cO CN O O O Tf LΩ CO CM CN CM Ln UJ CO CO CD CD CO N LO LΩ N CM x- x- CM O O ro ro c x- O x- O CO ro cO CO ro CD x- x- CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CO CO CO CO CO CN CN C^ o r- xt O Tf UJ O CM J uo Tf CD Tf UJ Tf CD χ - τf τf τt cD O τt CD τf τf x- τf θ CM N O CD CD N N o UO O N Tf o 00 LΩ CM Tf o Tf CM 00 LΩ UJ CM O CM CD Tf x- OO UO UJ CD x- τf CM τf cO CO O CD x- CO x- x- O CM O o oo O CD ro δ O UO f ro CD CM N Tf CD CM CM O O CD CD O CO CO O χ- CN CO N O O CO CN ro τf CN CO CO CO CD O Tf Tf Tf i cb uό CD r-i ό Tf N N J O r-i N 00 N r-i CD CO CO UJ 00 CD N ιb d d uό uό cd ιb u N cb cb uό uό τf UJ N CO CN CN CN CN CM CN CM CM CN CM CM CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CM CM x- x- CM CM CM x- x- OQ 00 00 DO OO OO Ω Ω OQ O Ω LU LU < Ω Ω < X X < X X X X < 00 Ω < X X < < X x- CM X Z OO OO O OOO X X x- CM x- CM zυooooooxx Z υoooDQoooΩ < CQ χ χ χ χ χ χ χ X X X X x- CM x- CM CO x- CM CO o C_:__:__:Q_333333333333333Q_Q_Q-Q-CLO.Q-Q-Q-Q-a-Q- r- llJLUllJm-JJJJJJ-J-JJJ-JJ-J-JJ(Λ(/.(/.(/ c/)C/3()(Λ(/.(/.(Λ cococo << <<<<<<<<<<ddddddddddddddddddd__i__i © o CO xt UJ CD N CO ro O x- CN CO - - J CD N CD ro O x- CM C Tf UJ CD N CO ro O x- CM CO Tf iΛ CD N CO ro O x- CM CO Tf CD N ∞ αj co co co co αD c» ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o χ - χ- χ- χ- χ- χ- χ- χ- χ- χ- cM CM CM CM CN CM CM CM CM CM co co co co co 0 C C CO CO CO CO 00 CO CO CO Cθ C CO CO C CO τf -^ τf τf '^ τf 'xf '^ τf τf τf τf ' N s τf ' ^ τf τf '^ CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CN CN CM CN CN CN CM CM CN CM CM CM CM CM CN CM CM CM CM CM CM CM O CD N CM CO LΩ CM O O O O O O O O O O O O O CM CD CO ro cO CO Tf O O O O O O O CO N CD CD UJ CD O co co ro co x- o o o o o o cq C CO CD CO O CO O O O O O O O O O O O O O CO UO OO UO x- N Tf O O O O O O O N CJ) Tf 00 UJ UJ N OO Tf CD CD N O O O O O O d (\ N ifl (. u. d d d d d d d d d d d d d τ d ( ' ' N ; d d d d d d d d N iri ιri ιri N ' y ή d d d d d d CM CM CM CM CN Cθ CO CN CN CM CM CM CM CM CM CM CM CN CM CM χ - CM CM CM CM CM CO CM CN CN CN CN CN CN x- x- x- χ - χ - χ - χ - χ - χ - χ - χ - x- CM CM CM CM CM CM N CM O CD CM CO UO CO UO C χ - χ - OO OO C OO CO τf c τf cD C CD CD CO C O τf ro c N CD CM CD N CM N Tf CM CD CD OO CD O UJ O OO N ro CD τf x- O CO CM CD τf CD CM τf x- O CO UO CD χ- N CM N LΩ OO CD τf CM CO CM CD O O CM τf UJ CJ) CD UJ CD CO CO CJ) CO O CM CO OO UJ χ - CD CM ro τ- xf ro N τ- q ro q c χ - ( cM ifi N CM ro q ιn q vj ιo c q ιθ N CO N ro CD CO τf τf τf CD lΩ x- x- τf c N UJ CD CD χ- CM CO O C x- x- ro ro cM c ' ] : cD d τ- : M (M τ. . ^ χ. ιri s ro (o s od (D oo ' bs ' (oωroωcoros ' roω©ro b roVbτ-bro (θoό sbro CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CN CN CN CM CO CN CN CN CN CN CN CN CN CN CN CN CN CO CN CO M θ ro θ Cθ ro iΩ CO CO τf cO χ - x- CN O lΩ lΩ O CO O τf CO UO CN CN N CN OO CO CN CN N N ro CO τf x- Cθ α. _D N CO x- O CΩ CO N ro cO CΩ ro CN CN CD ro χ- O O CM τf CD N N C C CD xf Ln uθ C C N χ- x- x- χt N τf r^ CM CO CO χ- UJ UJ N O N CD UJ N CM CO θ ro u CD x- CO τf cO N N UJ N cM cq cM ra ro N p co cN CM N cD co χ- co τf ro τf |v. θ LΩ co co ro co ro co cM co co ro N χ- co co o N χ- τf r^ cD χ- ro LΩ τ^ τf co τf cb τf τf --^ '^ ιri cd co cM Lri τf b d d Lri Lri Lri τf h^ UO UJ in UJ UJ UJ UJ UJ UJ UJ UJ lΩ lΩ in UJ UJ LΩ LO LΩ lΩ lΩ LΩ lΩ LΩ lΩ lΩ LO UJ UO UO UJ UO UO UO LΩ LΩ LΩ LΩ LΩ LΩ Ln iΩ LΩ lΩ τf lΩ τf CD CD χ - O OO CD O CO UO N N O τ- CO OO CO χ - UJ CJ ) N CM x- χ t CD τf N τf cθ CO CD U0 UJ CO χ- CO τf -. τf CD CO UO CD Tf O CD x- CO ro CM UO CN ro CM CD CO CD O CN CO χ - x- CO χ - χ f CM CO CM UJ CD CD C O UJ CO CD O ro x- CM CO CD O χ- O N τf CM CO CD CD O O CO CM D ro x- x- x- CO CD τf CD θ ro CM CJ) CO N O CO O CD CO CO CO CD x- N χ- CO CD CO CM CM N ro τt cq q UJ o co q co oq co CM ro cq CM CD N x- CD O CD LΩ CO T CO roodroraoo ' ssωsrobrobsrarasbrobbωbdcdros cb cb cd d N N ^ CM cO Tf cb cd cd ib cb iri uo ' Lri CM CM cb CM iri CM CM CM CM CM CM CM CM CM CM CO CM CM CM CM CM CN CM CM CN CM CM CO CO CM CM CM CM CM CM CO CM CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO O CO CO CM CM CM T - CM OO χ - CM τ- CM CQ DQ ' r - CN ω Ω LU N cαωOOΩΩujuJNNN < OQ OO < OO O Ω Ω LU LU N X <χ χΩ Ω OOOO z ___<xxxxxxxxxxx < GO X X X X X x- CM x- CM x- CM x- CM x- CM CO OOOOOO X X X X x- CM CO O O O O O O O O O O O X X X- CM X X mm mmmmmm mmmmmmCL CLCL CLCL CLCL CL^ r- ^ ^^ ^^ ^^ ^^ ^^^^^ ^^ ^ ^^ V XX X XX XX XXXX X^^ ^^Ϊ-^ ^ ^V ^^ ^^ ^^ ^ ^V ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ -J ^ _J - J _ι _ _J _l - h- h- h- l- l- l- l- l- h- l- h- h- l- l- l- l- l- l- l- - l- H I- l- l- |- |- l- l- h- l- © o UO CD N CD ro θ x- CN C xf UJ CD N Cθ ro θ χ- CN CO τf u-) CD N Cθ ro θ χ- CN CO τf UJ CO N Cθ ro θ χ- CM CO τf J CD N Cθ ro θ χ- CM CO τ^ CO CO CO CO CO τf τf τf τf -^ τf τf τf τf -^ u0 Ln iΩ LO lΩ LΩ UJ U0 UJ U0 CD CD CD CD CD CD CD CD CD CD N N N N N N N N N N CO CO C ro τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf -xf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τ^ CM CM CM CM CM CM CN CN CN CM CM CM CN CN CN CN CN CN CN CM CN CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM C^ O O O Tf cO CN CN Tf O N CO x- Tf CD CM O O O O O O O O O x- CM Tf Tf lΩ UJ x- O O O O O O O lΩ x- CO N CΩ CO Tt O O O O O O O O O O N O x- CO N Tf N OO OO CD CD O O O O O O O O O CM Tf Tf x- x- N CN q o q o o q o cM CD N co LΩ Oo co o o q o o o o O O O Tf Tf CD N CM LΩ CO OO UO N CD CO O O O O O O O O o τf ' u. u Lri cb cD Lri d d d d d d d τt ιri ιb cb ιri N Lri d d d d d d d CM CM CM x- x- x- x- x- x- x- x- x- x- x- x- CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CD O O O CN CM in UO CD CO xf CO CD CD CD O CO CD CJ ) N CO CJ ) CD τf CO UJ CD CM CM CO τf cD CO UJ χ - χ - N CO UJ O CD O UJ χ - χ - CM CO CJ ) CM O CD Tf LΩ UO CD x- N N LΩ Tf oO xt CD 00 J O χ- O χ- O UJ N CD CO τf UJ ro cO CD CM UJ O x- UO CD CD CO x- CM UJ CD N CO CD O τf x- cθ CD Tf CM OO CD CO CO ro cO UO N UO OO CD 00 00 CD OJ N CO CD OO CO x- x- CO O CD CO CD UJ O CM CO x- CD CO OO x- CO CD O CD UJ UJ x- O x- O O UJ O CM x- CO CD O O O x- CM C0 CM τf c0 τf cD ro ro θ χ - C0 τ- LΩ C0 CD χ - χ - C0 CM O CJ ) x- x- CN O CD χ - CM O τf U0 UJ CD CD CD N τf uJ N CD CD N N CO CO CO CM CO CO CO CO CO C^ CO CO CO CO CO CN CN CO CO CO CO CO CO CO CO CO CO CO CO CN CO CO CO CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CN r- Tt CM τf τf CO O CD O CM τf -- O OO x- UJ τ- OO CO CD O N Cθ ro uθ CD CM CO O τf rv- CM CO τf cθ CO τf x- O x- CO CD x- X- LO N X- X- LΩ CN N CΩ O O Tf N CM Tf LΩ LΩ CO x- CO CO ro N CD CO N OO CO CM χ - CD χ - C UO CD CJ) ro τf τf rv- τf CD ro θ _ C.M, .N (θ σ> ιn ιn ro ro CM x- CD CD O CM CM O x- CD N CO χ - χ - CM O C ro τf x- τf f θ Tf OO CD CO o uo cq o uj χ- N θ χ- uq cq o τf χ - N 00 CO CM N UJ τf CM τf CM τf CN LO χ- N χ - τf cθ τf CJ) 00 CO C CDD N CO CN x- x- CCMM CCOO CCMM Tτff CcO UlΩ0 Tτft Tτff cd0 μx- cCd μx- μx- ilbΩ cCNM CD iLbΩ dO roCD c0b0 c0b0 cCbO cCbO N roro ' roCJ) NN " ro N CO CD CO N CD d cb cD N c N cd d cD CJJ cb J U0 UJ U0 U0 UJ UJ UJ LΩ UO U0 UJ U0 UJ UJ UJ U0 UJ UJ UJ UJ UJ UJ UJ UJ τf τf ' τf τf τf τf τf τf roτf Tf Tf Tf Tf Tf ^ xf Tf Tf Tf Tf Tf Tf LΩ Tf Tf Tf CM CM CM O N CD xt x- CO UJ CD U Tf O O O OO CD CO CD CN Tf LO τf CD UJ CJ ) CO CM τf UJ CO O OO N CD τf CD CJ ) τf UJ N τf xf rv. ro ro UJ CD x- CJ ) CD Tf CO N CN CD O CM LO CN N N x- xt Tf Tf UJ CM x- Tf UO CO UJ CD CD CM CO CM N CD CM CO CM O CD CD CO ro N CO x- N ro LO CO N UO CO N CD N O CO N Tf N x- CD Oq C N Tf Tf O CD N CN OO CD O N CO CD CO CD OO O 00 x- UJ C0 UJ O C0 τt O CD CJ) O O UJ N U0 N UJ UJ x- UJ C0 CJ) τf N UJ 00 CD CM CO τt cb cb cd cb cN CN CN μ cb τ cd cd cM CM χ- CN CO O CD CD CO O O 00 CD CJ) O CD CN CN O CN O CO CN CO C CO CO CO C CO CO C CO Cθ 00 CO CO CO CO C CO CO C CO CO CO Cθ CO CO CO CO CO CO CM CN CO Cθ CO CO CN C^ CM CM CM x- x- x- CM x- CM x- CM x- CM 00 OQ x- CM x- CM CM x- CM OOO LU UJ X < 00 Ω Ω LU LU N X < χ χ Ω Ω LU LU X < DQ OO < OQ x x x < ω OO < Q X X X X xxxzoυooυoυoooox X X- CM X X X X X OOOOOO X X X X x- CM CO OOOOOOXX X x- CM CO x- o_ o_ _i_ _. -E c__ Q_ Q_ __: Q_ _t: __: c_: o_ Q_ o_ c_: __: __: __: _t r- >- ^ ^ ^ ^ s __ s _- s >- s J- s _-. s - s _- s _- s - s _- s _- s >- s - s >- s _- s >- s > - s _- χ χ χ χ χ χ χ χ χ χ χ χ χ < < < < <; <: <. < < <. < l- t- l- l- l- r- r- r- 1 r- r- r- r- r- r- - r- l- l- I- I- I- I- h->>>>>>>>>>>>>> © N C LOU C LJDJ —> X— C INN C L'OJ T XTf U UOJ C LUD N 1^ C UOJ ro UJ O l_J xX-— C INN C CO'J T XTf u UOJ C LOU N I-- O LUO C UDJ O C_J X— IN L'J XT UJ LU I— - LU UJ l_J X— IN L'J XT UJ LU I—- CJU UJ L-J X— IN L'J XT U J LU I—- UJ o CO co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM co co co co co co co co co f Tf Tf -^ f ^ ^ ^ 'xf Tf ^ ^ LΩ lO LO lΩ lΩ lΩ lΩ lΩ lO lΩ u u LΩ u J u U^ CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ r- © © Ui P H U α. O O CO O N x- CN CM CO O CM LΩ O O O O O O O O O O O O O O UJ O OO CD CD CD CD OO O O O O O O O O O O O UJ CD N CD CN UJ O O O CM ro iΩ UJ CM CM τt | s _ θ N Cθ O O O O O O O O O O O O O ro CM CD x- CJ) CO CM x- CM O O O O O O O O τf LO UJ χ - CO x- CD τf O d uό cN Tt Tf ' cM Tt ' ro c o- C CMM d d u u Tf Uj σ) τf cθ CD CM O O O O O O O O τf CD N CO CD CD 00 ro o CN CN x- x- T- x- x- T- x- x- CM CM CM CM CN CM CM CM CM CM CM CN CM CM CM x- x- CM CO C C CM CM CM CM CM CM CM CM x- x- x- x- x- x- x- CM O CN CD C0 CN CO CD τf CM CO CM C0 τf r-~ ro N N N CD UJ C CO χ - UJ Tf CM O CD UO CO CO CM UJ Tf cO O ro UJ CO CO CM UO CD x- CD CM CM CO N ro rom roco cMco coro roco χ f ro cD UO χ - CD O CD ro CM CD CD xt τf CM CD N lΩ UJ CD CN N CJ) O CO O θ ro ro ro θ ro θ N LΩ UJ N CO N τf τf rv. χ - CD cθ CO CM O CM UO CM C -M - C -- ■ N OO χ - C lΩ o ~ CD CD CM UJ CM CD CD O τf rv. θ χ- ro θ CN O τf θ τf θO CD CO CM CO O ro f 00 CO N OO UJ UJ N N Tt cO CM x- O O ro u U Tf Tf CO CO CM CM θ ro χ - OO CJ) N C CO N ro χ- CM χ- C N ro ro o x- o co co oo N ro CD UJ UJ Tf 00 CO CO C CO CO CO C CO C Cθ C CO CM CO CO C CO C C C C CO CM CO CN CM CO CO C C CO τf '^t τf τf CO CO CO τf τf τf τf τf CO CO CO CO CO CO CO CO r- xt N CM χ - ro ro c CM CM N τf x- UJ CD N χ - CM CO CN CD χ- CN O LO CO N CO N ro cθ CD ro χ- CO χ- CD CO χ- N N O LΩ O CD CD CM CM τf LΩ θ ro ro θ ro — C -M O — C " D- x- CM CM χ - ro CD CD xt ro τf CD C CD CM C» O N O O N N O CM N Cθ ro cθ CO N τf x- CM τf UJ x- CO O CD x- CM CO τf CM χ- χ - UJ CM CD ro CM ro u τf x- (» o τf x- o χ- c χ- χ- N oθ χ- q LΩ θ co τf Lq χ- N N ro co co τf uo cD u oo cM ro uo cq cq θ '^ τr ro CO N UO CO CO CO CM CO CM CO CO Tf f - L -O Tf CM CM Tf Tf f Tf T f T μ μ cb τ cd u τ cM μ or μ μ cM θ cM χ- : μ cM μ cj) cj) CJ- cb N N cb cb cj- Tf+- Tf+- Tf TTft- τTf+- TTf+- Tf+- Tf+- - T«-fl- ^T+f- T*f- Tf+- Tf Tf Tf Tf Tf Tf xt '^ Tf '^ Tf Tf '^ ' ' CO Tf Tf xf x^ 'xf Tf '^ xf xf xt cO Tt CO CO CO CO CO CO CO CO CO CO N C0 C0 CD CD x- C0 τf c0 C0 in c0 O C000 U0 UJ χ- CJ) x- CD O τf c0 CM χ- N U0 UJ χ- CO CJ) O lΩ CM UJ CM ro CM CM χ- θ ro χ - τf O Cθ ro CD CM χ - N χ - CO τf r s -' X- LΩ ro CM CM CO Lθ CD CD τf cθ CO CD CM χ- CM N O O τf x- N 00 l0 C0 C0 U0 CM χ- ro CD UJ τf CD τf τf x- θ 00 τf O CD τf x- N O q OcqO CcOq CD xx-- CcMM roro ocqO CqD CcMN CroJ ) xx-- CcOq CcNM UiΩJ xx-- C∞O NN OroO CroJ ) CcDD CCNM NN UiΩJ CCDO CcOo CcNM Txft CcNM x- Tt ' CcoD UiΩJ 0ra0 Tt CO Tt Tf xf CD CD CD -»- CM C C CJ) CD UJ 00 Tt CD cM CM μ χ - cN θ o cM θ ' cM σ- μ - ro ro χ- C M CN ro ro cj ro CO CO OO CO CO OO CO C CO CO CO CO CO CO CN CO CO CO CN CN CO CN CO CO CO CN CO CO CO CN CN CN CN CN CN CN CO CN CN CO CN C^ , n T } _ C0θ ΩΩ O O O O O O X _ι _ιO OOOOOOOOOOOOOOOOOOOOOOOZ ZZ Z Z Z Z ZZ Z Z Z Z ZZ ZZ 33 3333 33 3 r- < < O_ C_: __: __: -_: Q_ C_: __: Q. Q_ C_: __: Q C_: Q_ __: C_: Q_ __: __: __: __: _^ >><<<<<<<<<<<<<<<<<<<<<<<<ooooooooooooooooo LU LU LU LU LU LU LU LU LU © o ro θ χ- CM C0 τf LΩ CD N C0 ro θ x- CN C τf LΩ CD N 00 ro θ χ- CM C0 τf U0 CD N αD ro θ χ- CM C0 χf UJ CD N αj ro θ χ- CM C0 τf UJ C0 N C» C N- ^ ^ ^. M' - M- , * - ^ ιn -) ιn ιfi ιn ιn ifi lO lfi CO (O 0 (D _ CO (O (O CO (O N N N N N N N N N N B CO 0O (D ra (O (D ra cθ (θ ro ininin i minininL ininin inmin mm ininin in inininin inininin inin ininininininininin in inininin ininmmmmin CM CM CM CM CN CM CN CN CM CM CM CN CN CM CM CM CM CN CM CN CN CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM C^ r- © © Ui H U α. O O O O O O O O O O CD CO f UO CO LΩ CD uO CO O O O O O O x- O χf χ- UJ UJ CO UJ O O O O O O O O O O O O O τf CD UJ CD N UJ O O O O O O O O O O CM CD OO CO CO CD uO CM CD O O O O O O CO O UJ CO UJ CD CO CO O O O O O O O O O O O τf θO CD τf LO τf CD UJ O O O O O O O O O CD CO UJ N N CO O x- CM O O O O O O N C χ- CD N ro θ N O O O O O O O O O O O τf τf UO τf τf CD CO CO CN CN CM CM CM CM CM CM CM CM x- x- CN CO CO CO CM CM CM CN CM CM CM x- x- x- CM x- CM CM CN CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CO CM N ro CN O CD CD C0 CD ∞ ro ro c0 N in N C0 τf c0 O O O τt CD C0 CD ro θ CM N N τf τf C0 N CM C0 C0 C0 C0 C0 UJ χ - C C0O x- CD Tf OO CM UO O UJ CO CM C _D Cθ ro U0 CD τf CD ro cD CO lΩ C0 χ - τf x- x- ro c0 O C0 N N ro CD τf ro c0 CM CM O UJ N UJ O CD C0 x- CN C0 UJ UJ UJ C CM O T T ff ro CM N O CO O N OO N O x- T f cO x- ro cO O CD CD ro O N UJ CO CO U CO O CO CO CM CO CN Tf CM CD O Tf cO CM CD ro cD UoO UooJcoO UTfO O T f CrvM. N N NN τTff LLΩΩ llΩΩ τTff ULOO UUJJ CCO CCθO roro roro coθO OO χ x-- CCMN CCMN x'.-- CO θ ro Uθ ClNN OU UCD) roUJ θU τχ-- UroJ ClUO NMCUO UO lCUO θU roU) |Ns CilDJ ttCOJ ttCDJ CUDJ 0COU N|s 0) O O 00 O τ- τ- O CO CO C COO CCOO CCO CCOO CCOO CCOO CCOO CCOO CCOO CCOO CCθθ CCOO τxff ττff ττff ττff -τ^f cθ xt CO τ χff xxft -x^t cC CCOO ττft ττff ccO CCOO CCOO CCOO ττff ccθθ ττff ccθθ CCOO CCOO CCO CCOO CC^O CO CO CO χt τf cθ τf τf τf τf xt r- Tf N CO O CM ro x- x- CD UJ CJ) CJ) C0 C0 O xr 00 CD C0 C0 CD xt x- CJ) 00 C0 U0 CD CM C0 x- O x- CD N Tf Tf Tf O ro CD CO CD Tf CD CO CD O O CD CO x- x- CD f CO Tf O χ - CD O N CD CO τf CM C0 O CM χ - N lΩ CN CJ) CJ) ro f 00 CJ) N CD O UJ UJ N O l_Ω. C _J). τf CJ) CD χ - C .M. U_J. C.M_ U_J. l_Ω. xt _ ro _ x- Tf N OO UJ CM CN N CM O Lθ x- ro αj N χ - CO CM CD N N CM ro χ- UJ CO UJ τf CM CO CD CD CO CJ) CM O CD O CO χ - τf x- |v- θ τf x-- oθ CD CD O Tf ro N CDco Nco roro o OO ro UO Tf cO CO Tf cO CM CO x- U) U0 C0 UJ C0 CM C CM χ- χ- CM CM x- CM τf CM CM τf C0 x- O χ - CM τf CM O C0 N N 00 N CD CD CO CO CO CO CO CO CO Tf CO CO CO CO CO CO CO CO CO CO CO CO C CO CO O CO C CO CO CO CO CO CO CO CO CO CO C CO CO CO CO C CO CO CO CM CM CN CM CM CM CM N CM x- ro LΩ CM Tf cD -r- CM C CO Tf O x- iΩ Ln oO O ro O CO UO CO C CD O O CD CD CM x- O N C O O O CD ro O x- U Tf cD in UJ CO ro iΩ CD U^ χ - (D C0 03 00 ro \f N ro CM ( CO M θ ro (0 N O τ- m 00 (0 τ- ( !\ ^ ^ O ^ ^ C m c0 ^ t m c CM t r ( θ σ) N (D C0 ^ ( O N τf ro o UO CD ro CO CO τf τf cO CM O CD O τf CM CO N CO CO CN τf CM ro cθ x- ro CM CD τf CM ro UO CO χ - CD χ - CM τf ro CM χ - CD τ^ O CM CO CM τf cθ CO x- O χ - O x- CM x- O θ ro cθ OD O x- ro ro x- O CO τf cθ τf UO CD CD N CO CO CD UO CD UJ CD CD CD CO CO CO CO τ^ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CO CO CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ x- x- x- CM CM CM x- x- x- CM CM CM CQ GO ,_ Ω Ω Ω Ω Ω Ω x- CM DQ CQ x- CN ιQnDQ Q < X χ χ χ χ χχ χ < GO Ω LU LU < X X X X < 00 Ω Ω ι < 00 Ω LU X X- CM X X- CM CO X- CM CO OOOOOOOO <ι mmιϋ,. QιQ X x- CM x- CM OOOOOOO X X X- CN X X- CN CO X- CNιCO OOOOOO 3333333333333333333333333333333333333333333 333333333 r- LU LU LU LU LU LU UJ UJ LU LU — ' — ' — ' — J — ' — ' — J — ' — ' — J — ' — ' — J — ' — ' LU UJ LU LU LU LU LU LU UJ UJ UJ LU LU UJ LU LU LU UJ UJ — ' — ' — ' — ' — ' — J — ' — ' -J -J ^ ^ __J ^ ^ __J !_J _J O -J --I _J -J --I _J _J -J © χ- CM ( s 0 τf LΩ CD N C0 ro θ χ- CM C0 τf LΩ CD N C0 ro θ 'r- CM C0 τf LΩ CD N C0 ro θ x- CN 00 τf U0 CD N CD ro θ χ- CM C0 τ^ o ro ro or ro ro ro ro ro ro o o o o o o o o o o χ- χ- χ- χ- χ- χ- χ- χ- χ- χ- cM CM CM CM CM CM CM CN CN CM co co co co co co co co co co τf τf τf m m m m m m m m ω (D (θ (D (θ co (θ (D (D ω co cD CD co co cD co (θ co cD (θ co co cD co co co co (θ cD cD cD co co (D co co cD (θ (D (D (θ (D CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM C^ r- © © Ui H U α. CM O O O O O O CO CΩ O Tf cO x- CN CO O O O O O O CD O OO CM UJ OO UO O O O O O O O O O O O O x- CD N 00 CD LO Tf O O O O O O O O O O O co cq cD co ro cN CD N O O O O O O UO CO CM CD CD CO CO O O O O O O O O O O O O N xt N o o o o Oo CN b d d d d d (D (θ d ^ is d κ) τ : d d o d d d d τ ifi iri o. σJ N o o " O O O O O O O O N X- ' CO UO Tf lb Tf CO CN CM CM CM CM CM CM CN CN CO CM CO CM CO CM CM CM CM CM CN CO CO CO CO CM CM CM CO CM CM CN CN CM CM CM CM CM CM CM CO Tf Tf Tf Tf xt Tf d d d d d CM CM CN CM CM τt CO NI—" UUJJ CLDU CCNN OL-J roUJ OL-J OO x— CCDD CCOO xx—— NN CCNN CCOO COD) X- CDJ CLDU x-- NI— ■ CN CO CN xt CO CD CO N O CD CD CO CO UJ CD CO CM CD x- CD CO CO x- O CJ ) ; C .M O CM - O _ x -- C _D. C.M- T-f C_D. .N UO O CD Tf O CO CM x- CD Tf CM N ' ω CO CO CO CO CD lΩ CO CD N O x- CO CO x- O CN O x- x- CD CM τf CO CO CO CO CO CO CO s C ~~ C CO xt - τf τf τf τf xf τf τf τf τf CO r- Tf χ- CM N Cθ ro uθ O CM UO UJ UO CD CO CM N O O CD N N UJ CO CO U CO N CO CM ro CD UJ N ro x- UJ N CO τf N N O J CO CM N C τf θO UJ CM CD ro C χ - UJ τf x- c OO CN N O C CD t χ - CM O C C xf τf r^ CD O C» CM CD CO CO τf O CN N τf τf ro LΩ τf CN χ - N ro LΩ τf o ro N C CD ro C^ CO χ - O CD CO τf x- uJ CO χ - CD CD t C N ro cN C CM ro cD UJ C χ- CO x- C τf CD x- CO χ- CO UJ τf CM UJ UJ CO N χ- χ - χ - χ - χ - CM χ - ∞ ro N cb ' N " d uO τ c lb τf Lb N cb N N ' τ^ ι j f cd cM CM CO CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CN CN CN CN CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CN CN CM CN C^ τf C x- x- CM CN N CJ) N τf CD CM N τf U0 CM CD f O CD UJ UJ χ- CO O CM CO CD ro iΩ OO τf r- τf r s - x- lΩ N CD CO CN UJ τf CD N χ- τf CM Tf CO τf CO N χ - χ - τf cθ CM CM UJ CO χ - CD Cθ O CO O O CM O OO CD CM CO 00 O χ- τf CM CD CM τf oθ CO N N N C N τf CD O CM τf cθ N O CJ) CO CJ ) ro N C x- N CM f O CD τf CM τf U UO τf x- UJ CM UJ Tf CM x- N ro o T • N- ^ CO ^ O ^ O ^ CO Tf N O CM Tf oO CD CO O Tf M C D N -r- Tf ro c CD Tf O O CO CO CM x- CM CM UJ CD UJ UJ N OO OO ro UJ CD N CO CD τf τf LΩ τf τf CM CM CM LΩ CO τt τf CM CO CO χ - CM ^ CD s bbco roro cDco cororo O CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CM CM x- x- x- CM CM CM CN N 00 CQ _T ^ ^ CO 00 Ω Ω x- CM j .C0CO,-ΩΩΩΩΩΩ ■ <- CM w < χχ χχ < OQ Ω Ω < ω Ω Ω <χχOχχχχχχ < CQ OO < ooO "- ox O X X x- CM x- CM OOOOOZ X < X x x- x CM x x- x CM OOOOO O OOOOOO X X X X x- 3 33 33 33 Z Z Z Z Z Z Z Z Z Z Z Z Z Z 33 33 33 33 333 3 3 3 3 33 3 3 _: L. C_: Q_ C_: __: __: Q: Q_ Q_ __: __: r- r_ 7 . WW WW ( Λ ( / ) ( fl ( 0 ( Λ ( / ) () (β W ( / ) lJUJ llJ IJ _J llJ _J _J llJ _J 0000000 < < < < < < < < < < < < < < --J .-J --J _J --J --J --J ^ - --J --J _J --J --J --J --J _J --J _l r- r- r- l- r- r- r- r- r- r- r- r- © CO Tf lΩ Tf UJ CD N CO ro O x- CM CO Tf o Tf Tf Tf oooo coco ooco roro ro ro ro CO CD CD CD CD CD CD CO CD CD CD LD CD CD CM CM CM CM CM CM CM CM CM CM CM CM CN CN r- © © Ui H U α. o o x- CO τf CN lΩ CJ) CN O O O O O O O τf θ O CO N x- Tf Tf CD O O O O O O O O CD CO Tf CO x- O CO o o O O O O O O T f r-. T f CN LΩ N CO O CM O CD O O O O O O O CD CM N x- CO UO Tf O O O O O O O O O O CM N N C O x- N CM O O O O O O Tf CD CO CD O O CO o CO CD CM N O O O O O O O O x- CO OO lΩ χ - CO CO χ - O O O O O O O O NN NN ULOO Tτft CcOθ χ x-- NN OCDO CCDD OO OO OO OO OO OO C CO x x-- OO x- CM CN Tf Tf t Tf CO Tf CO (M CM CM (M N CM CM ^ xf c C N- m m m (D CM CM (M (M CM CM CM CM ( C CO C - m m m m (N (M CM CM (M (N C C C C CO CO O O x- UJ x- N N Tf CM CD O UJ x- CM CD N CJ ) CD N O N τf r s - OO O CO CJ) CD τf ro cθ CD CO OO Cθ ro σ) N τf CD CO CD Tf UO CM CD Tf CM Tf x- x- O CM CO O CO CD CO N O χ - OO CN C x- O N UJ CD Tf cO CO CD CO O LO CO OO OO CM ro x- O UJ CM CM CM CO x- CN CD Tf rv- OO N UJ O N Tf CD N x- Tf Tf cD O in CD UJ OJ CO O CD CD CM CO CD CO Tf UO CM UO O ro CN CN Tf LO in x- ro ro CD Tf r^ CD O CD N Tf O Tf UJ UO N OO CD CN ro CM Tf iΩ OO O CO CN CO LΩ LΩ CD LO xf LO CO UJ CD Tf Tf U LO Tf Tf LΩ LΩ LΩ CO Tf UJ CO CO CO LΩ UJ CO CN CO CM UJ CD Tf CO CD N N N N UJ CD UJ N N CD U Tf Tf CD xt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf xf Tf Tf Tf Tf xt xt xf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf T f Tf Tf Tf f Tf Tf Tf CD r- xt O OO N CN OO CO CM CM N IΩ ro cN xr cθ O χ - UJ lΩ τf ro c ro LD CN lΩ CD τf cθ CM τf ' f x- CM τf τf ro τf r-- CD CO CM CO OO CD N χ - Tf C D CO Tf |^ CM UJ UJ ro CM N ro CM CO CD CD CN 00 O τf ( O τf CD χ - τf CM LΩ CM N CO UJ CO CD O CJ) UJ N CD χ - LΩ O LΩ CM CD CM CD χ - χ - N CD CO UO CD x- CO CM CO x- CO Tf O x- CD O Tt UJ CD x- CM UO CM τf c0 CD τf LΩ LΩ CD CM CM x- CD CM O N CJ) N CD O u0 τf CM ro τf C0 O O τf CD 00 CM UJ x- UJ CD O) CM O O CM CN CO CO CO UJ CO CO x- CO LΩ CO CM Tf C τf Uθ LD CO CM χ - χ - CM C τf τf cθ x- CN χ - CM CD N OO OO N CJ) CJ ) ro χ - lΩ N N N ro O CD O x- CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C U0 00 in ro UJ ro CM CM C0 N UJ τf cO UJ U0 C0 CD CN U0 CD ro CD τf θ CD χ- O O (» lΩ C0 UJ x- CM x- N N N N ro N C0 N x- O UJ N O χ- O N UJ m ro m (θ ^ r m o co cD co ( θ N (θ N m '' co ^ co τ- N c - (D τ- m ro ∞ θ (θ τ- N C τ- ro co oco co (M ∞ , t θ(D m co co x- T f ^ in CN ro Tf x- OT CO CO lΩ CN -r- T f C lΩ LΩ x- N Tf CN Tf r^ x- cO CO Tf r-^ ro O CD CD LΩ Tf r^ N CO CD N CD ro ro ro Tf cO CO CM CM x- O O ro Tf cO x- CM CM x- OO ro T f Tf Tf Tf cD CD N CO CO lΩ Tf CO τf cO CO CO CO CO CO CO Cθ 00 C C CO CO CO CO CO CO CO C C C CO CN CO CO CO CO CO C CN CN CO CO CO CO CO CO CO C CO CN CM CM CM CM o o ->- CM _. TZ OQ GO LU LU x- CM 0000 O X X < oo OO < oo x x x < CQ Ω LU UJ < X X X X X X < 00 Ω LU LU < X X X X CM CO O O OO X X X X x- CM CO O O O OO O Z X X x- CM x- CM x- CM OOOOOOO X x- CM x- CN OO 01 Q: Q: Q: Q: Q. t Q_ _ Q_ 01 Q: Q- Q. Q. C-: Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z 333333333333333 t: Q: Q: Q: r- X X X X X X X X X X X X X X X X -1 -l -l — I — l -J — 1 — I — I — I — I — I — l _J _J _J _J _J _J _J _J _J _J _J _J _J _J _J _J _J _J _l χ χ χ χ r- h- r- l- l- l- l- l- l- l- h- h- l- l- l- l- O O O O O OO OO OO O O O O O O OO O O O O O O OO OO OO O l- H H H © o UJ CD N Cθ ro θ χ - CN CO τf UJ CD N CD ro θ χ - CM C τf UJ CD N ∞ ro θ χ - CM CO τf uO CD N Cθ ro θ χ - CM C τf UJ CD N Cθ ro θ χ - CM CO Tf UJ CD ro ro ro ro ro θ O O O O O O O O O χ- χ- χ- χ- x- x- χ- χ- χ- χ- CN CN CN CN CN CM CM CM CM CM C C C C C CO Cθ C CO CO τf τf τf τf T _f, T -f, T _f CD CD CD CD CD N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N CM CM CM CM CM CM CM CM CM CN CN CN CM CM CM CM CN CM CN CM CN CN CM CM CN CM CN CN CM CM CM CM CN CM CM CM CN CN CM CN CM C^ r- © © Ui H U α. CM CO O O O O O O O O CD O CO CM CD Tf oO N x- N O O O O O O O O O O O O O x- CD UO O CO CO N x- UO O O O O O O x- Tt cO UJ Tf 0O0O O O O O O θ p τf ro cD O O O C O CM O N O O O O O O O O O O O O O CD τf c LΩ N UO CO CJ) CD O O O O O O C τf O d^NdddddddNt oicoN-Nd ^ cόco^dddddd ddddddd dtd rtd CM CO CM CN CM CM CM CM CN CM CN CM x- x- CN CM C 00 CO CM CO CM CN CN CM CN CM CM CM CN CM CM CM CM x- CM x- x- CM C CO xf CO C^ Tf CO x- LΩ CM Tf CO CO x- O CO O N O CD N N CO N CN CN Tf CD N CN N N CN iO Tf CD N O CM CO CO Tf O CO CD N Tf O f CO O x- 00 CJ) N N O CO N O C τf O U CO CJ) CD CD CN CM xr θO CO Tt O τf CD τf θO CJ) UJ CD N CO CO Tf O LΩ Tf CO Tf CO N CO Tf UJ N CO CM O CO Tf CO CD CM c LUo ro UJ ro UJ C LDU c Lo'J o L-J T XfT C LOU x T- ^ N I N O U O U N is C lM\ C IMN U UJJ C LDU C IMN O LUO C IMN T XTf CO CM O x- C IO'J U UJJ XT XT- T XTf C LDU N I s - C LUO C IMN T XTf C IMN C CDU C tO'J C LDU C LDU C LDU T XfT CMN X- C LOU C UDJ T XtT ^ T X7f O L-J C LO'J d ro μ ro o Oo O d CCMM CCMM CM Txtf UlΩO Tτff Tτff CcO CCO CCMM CCMM CCMM ^χ- CCMM τf U0 τf cN_cd ττ _ c . d c . CM . c . d . d_ o_ . d_ N . i cd cb cb ro d μd dN cbN ' rod cb cj) d CO CM CO CM Cθ CO CO CO CO CO CO CO C CO CO CO CO CO CO CO CO CO CO CO CO Cθ CO CO CO CO CO CO CO Cθ CO CO CO CO CO CO τf τ^ χ - CM τf OO CM UJ N CM CO CO N CO CJ) CM OO τf UJ CO O τf cM CM τf r-- CM CD N χ - UJ τf U lΩ CO CN CjO ro cO CD CD x- Tt rs CD CN OO lΩ CD CO x- CN CO CD O χ - CJ) τf c0 ro c0 CN N CD O C L0 CM N UJ 00 C0 N UJ τt C0 C0 C0 τt O C0 CM C0 U0 O — CD O UO LO CD σ) O lΩ UJ CJ) τf N τf τf N χ - N CD CO O N O O O τt CD τf x- cD O χ - UO CJ) N O CO CM χ - CO O N N χ - CO CO CD CD UJ τf θO CD CCDD CCDD xx-- CCOO TTff CCDD CCDD CCDD CCOO CCDD CCOO UUJJ OO OOOO N N CCDD CCMM inJ uUqO c0q0 . . . τf C χ- O χ- χ- O τf τf CO CO CD CD CO CD O O CO Tf CD CD CO CO CO OO CO O OO CCOO CCOO T Tff U U) C CNM CCMM xx-- CCMM OO '' T Tff CCNN CCOO μ CO Tf lb Tf CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO Tf xf Tf CO CO CO CO CO CO CO CO CO τf xt τf τf C0 C C0 CO C0 CO C0 C CO CO C CO C0 C0 C C0 C0 CO co N ro x- ro OOOOOOOOOOO lΩ lΩ CN CN CD CΩ O O O O O O O O O O O O co UJ ro o LΩ Tf CM x- OOOOOOO N N ro oo co OOOOOOOOOOO CN CO Tf rv. lΩ N OO CD O O O O O O O O O O O CD UO N N O 00 CN CD CD CM OOOOOOO CO Tf CO CO CO O O O O O O O O O O O ^ O CM CO x- N Tf UO O O O O O O O O O O O O x- CM f CD O O CM x- O O O O O O O T- x- x- CM CM CM CM CN CN CM CN CM CM CM CD x- x- x- x- x- x- x- CM CM CM CM CM CM CM CM CM CN CN CN CM CN CN CM CN CM N CD CO x- CD CO CO UJ O CM CM CO CO 00 CO J CO CO CN CM CO N N UO UO x- CO CM ro cD UO ro N Tf O xt ro CO N N Tf CO ro CJ) N CO N CM O x- O χ - χ - CO U τf τf oθ CO UO CD N UJ CO O CD CO CD lΩ N CN CO CO CO CO ro CN Tf 00 OO o Tf x- CD CN 00 Tf CO O CΩ CO Tf CO CN CO CO O CO OO UO CD CO O CD ro cO x- O N UJ O ~ OO OO " C -M - C -J ) -N CO CO τf N CM χ - CJ ) ro N χ - CD CM CM ro τf OO CD CD CD CM x- N O Tf O lΩ CO O CO CO O roro x CD 00 N O O ro ro N N O x- CM x- O ro CD O O CM CM CO CM O CN CD UJ UJ τf τf cθ CN CM x- x- N UO τf LΩ CM CO O CO COroCOcCOooTf oTf T-f ocOocCOooTf CO CO Cθ τf τf τf c C CO CO τf τf τf τf τf cO CO Tf Tf -vr Tf Tf Tf Tf Tf cO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO r— xr ro x- N x- x- CO (O x- Cθ ro c τf CN C x- x- ' - 'χt- < CD N U ro x- CN xt τf CN CD O CN UJ N x- CN τr iΩ CN Φ CD CO χ- CO C θ ro ro CD χ- CM CD τf N CM C τf cθ CO τf UJ UO lΩ CM O τf ro N CD in Ln ro N CD χ- ro N N CD CO C CM CO χ- O CM τf ' ^ CM O N N N χ - CO CO O CM χ - x- CN CN N xf CD ro ∞ CD ro N N f co iΩ CN lΩ N CM C» ro CN O CO τt ( » CM τf cθ CO N lΩ ro c^ O OO CD CO CD Cθ ro N CD Cθ ro ro <X) N N UO x- CM CM CM CO CO τf CN x- CM τf CO τf ιO τf ' s x- CM CO CO CO τf ^ τf CO C CO CO CO CO CO CO CO CO C C C C C τf τf τf τf x^ τf τ^ τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τ^ uo Tf ro CD N CO Cθ CO τf CD CD CO x- χ - C CD N τf cjJ C U0 CO CO CO τf ro ro CD ∞ χ - CO U0 τf 00 N CO U0 CO τf <» cθ CD ro CM x- CD U0 N ro N N CO CO N UJ N UJ CO CM CO CO CO CM ro cθ O O τf UJ CO UJ x- CM CN x- τf CM τf cθ τf CM ro CD CD CM CM CO CM CO O τt UJ N O N N o Tt x- r-. CD CO x- CD CD ro N lΩ CD UO x- Tf ro CD CO CO CM N lΩ CO CO N CM LO O UO ro x- ro N ro u CO x- N CN U Tf x- cO ro CD N ∞ CD CM CO 00 CD CD N N CO CD U0 CD U0 N CD N N CO C0 UJ τf UJ CD U0 τf τf cθ CD CO U0 CD 0O U0 U0 CO τt CM CM τf U0 U0 τf τf UJ τf cD U0 CD C^ CO CO C CO CO CO CO C CO CO CO CO CO CO CO C CO CO CO CO O C CO CO C CO CO CO C CO CO CO CO CO CO CO CO CO CO C C CO x- x- CM CM CM x- x- x- x- x- x- CM CN CM x- CN x- O O O O O Ω Ω Ω x- CM OQ CQ Ω Ω Ω Ω Ω Ω x- CM x- CM OQ CQ τ_ C x- COO Ω < CQ O Ω Ω < χ χ O o oo oo < C Q X X X X X X X X X X X X X X < CQ Ω Ω LU UJ < X X Ω Ω LU X X x- CM x- CM CO x- CM CO O O O O O O O X X X- CM X x- CM CO x- CM CO oυoυυzoυz X X x- CM X x x r- m __j _ϋ UJ LLJ LU __l _J LlJ LU LU LU L_J W ^ d d d d d d d d d d d d d d d d _i _i _j _i _J _j _j _i _j _j _i _j _j _i _i _i _i _i _i X X X X X X X X X X X X X X X X X © o ro θ χ - CM O τf LΩ CD N Cθ ro θ x- CM C τf LΩ CD N Cθ ro θ χ - CN CO τf UJ CD N Cθ ro θ χ - CM CO τf LΩ CD N Cθ ro θ χ - CM C τf L^ ro θ O O O O O O O O O x- x- χ- χ- χ- χ- χ- χ- χ- χ- CN CM CM CM CM CM CN CM CM CM CO CO CO CO CO CO CO CO CO CO τf τf 'sf ' " τf '^ τf τf τ^ N co co co co co co co co co co co co co co co co co αo co co oo co co oo co oo α co rø oo co co co oo oo ra CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C LO r- © © Ui H U α. co ro Tf UO O Tf o CO x- CD O O O O O O O O O O CO CD CO CJ) CO τt U N O O O O O O O CO CO UJ τf χ - χ - CM N CM N N CO O O O CM co co J 00 CO CD τf ro CD τf O O O O O O O O O CD CD CN N N CM τf CD CD CJ) O O O O O O O χ- LΩ N CD CJ) τt CD CD CM N LΩ O O O O CM d cb c d Tt cM uό b d d d d d d d c O Tf CM O O O O O O O O CN CM Tf N Tf Tf ' u-j cb d d d x- x- x- x- CN CM CN CN CM CM CM CN CM x- x- x- x- x- x- x- CD CO x- CN CN CN CM CN CM CM x- x- x- x- T- x- x- CN CN CN CD N 00 C0 χ - N CM N CD CN x- CN O τf τf CD CO U0 00 CN O CM CJ) CO CO N CM CD Tt cO Tf UJ CO lO O x- ro ro x- CO N UO N ro CD N Tf rs- Tf CM CD CO CO CM Cp τf τf θ CD p CD CO LΩ CJ ) O τf LΩ O CN CN N CO O χ - . . N- ,CO. -UO. CO CD UJ CD CO ro cO O N CO N O N CO O O CD CM CD N CO CD CD CM CM ro in o uo Tt ro s-UJJ o C —O . _J. CD - C-M C-M C-M O- iUnO cCOO LUΩJ CCMM cCoO cCoO cCoO cC -MM " cCoO roro x- NN CC0O CCDD UUJJ CC0O CC0O x- xxtt 0O0O 0O0O χx-- llΩΩ CC0O τTff CCMM CCDD CCMM NN OO C 0O0 NN C OJO) U UJJ NN x χt cb cM UO N N ro cb cj) U τf lb uO N N CD CD o cN O O o o oo N co co co cN O O o oo co in ro ro N co ro ro N O N O co co ro cD co co co co co co co co co co co co co co co co co co co co Tf CO CO CO CO CO CM CM CM CN CM CO CO CO CO CM CM CM CM CM CM CM CM CM CM CO CM CO CM CM CM CM CM OO CO CO UJ CO N x- O CO N N CD Tf CM xf CM xf O UO Tf N UO O N co cD ro ro cM N ro cM co ro ro cD CM Tf uo uJ N O oo uj co cD CM x- x- ro ro N O CM x- CD UJ x- Tf CM ro cO CD N OO CM CD x- CO CD x- N CO N CM N x- 00 ro c0 C0 C0 O LΩ ro N CD CD U0 N τf x- τf c0 x- CM O O 00 CM CM CO CM N q p x^ ro co N N u Tf cM CM x- cq ro u x- co cD CD O co cq cq Tf UJ x- N CM CN CM lΩ ro ro LΩ τf U. U0 CM UJ CO UJ χ - x- UJ UJ cq τf cq cD CM. q UJ N N ' ( _ d d ιb N τf ' cb ro cM cd cb τf f uό cb b Tf Tf Tf Tdfs Tf s Tfb Tf bTfbTf bTfsTf ' iTrifsTf ' oTdfsTfbTf T-fiiTrifωTfsTf ' sTfsfoTdf σTfJbTf dTfbTf iTofbTf iTrif.Tf τf τf τf τf τf τf τf LΩ UJ xt UJ UJ UJ UJ UJ UJ UJ UO τf UJ UJ OO CN UO x- Tf CO UJ xf Tf ro χ- o uj uo cD co τf uo ro o ro ro ro co χ- ro cM co τf rs> o χ- ro cN co τf cM χ- ro ro cD iΩ o co cD CN τf oo co ro ro co CO UO CO x- CO UJ UJ CO CD Cθ ro x- CO N CD χ - CD χ - ro cθ C CN O N CO x- CO N UO CO N O CD x- U CN N CD U CD CD CD O O x- CM CO O CO Cθ x- CO Tf co cD cq cq o cD x- CM N CN cq cq CN CO xt CO N ro ro CO CO N N ro N x- lΩ lΩ N CD N N Tf Tf ro ro O N xt xt lΩ CO ∞ Tt ω cΩ UO c b cb N N N N c r-: uό d N Lri N cb cb Lb N τt ιb ι uό uό τ τ uj τf L τf τt c f CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M x- CM x- CM OQ CQ ^ CM x- CN x- CM x- CM CQ CQ T- CM x- x- CM x- CM GQ < GO O Ω Ω LU LU N < 00 Ω Ω LU UJ < X X Ω Ω UJ < CQ Ω Ω LU LU N X < X oooooooooox < χ χ Ω Ω LU LU N X X- CM X X X X X ooooozooz X X x- CM x x x O O O O O O O O O O O X X x- r- © © Ui H U α. O O O O O O CD N N Tf CM x- CO O O O O O O O CD x- CM CD O N CD O O O O O O O Tf CM CO OO CD CD CO OO CD CO CD O O O O O O O O O O CO CO CO N CD CN χ - O O O O O O O N N CM τf O UJ C0 O O O O O O O CM τf CM C0 LΩ C0 CN CO IΩ N CΩ CO CO O O O O d o d d d o " cb Tf cb ro " cb Tf Tf ooo o o o oN N roo cM Oo dddodcb ' o o x- CM o -o O O O O CM CM CM CM CM CM x- x- x- x- x- x- x- CM CM CM CM CM CM CM x- x- x- x- CM CM x- CM CM CN CM CM CM CM x- x- x- x- x- x- O ) CD CM CM CM CM CD CD CO χ - τf uJ CO CO O C CD CO τf σ) LΩ ro ιn ro ro τf l s _ oθ χ - N N χ - CM O UO CO N CD τf CD CO N O N lΩ O N lΩ CD O UJ N C CO CO CD OO CM x- N x- O CD N UJ O CO CD CO CO x- CO x- CO N UJ CD O CD N O O LO Tf J x- UO CM CN x- CO x- OO CO CD O CM N CD N N x- O CM CM x- x- UJ Tf N CD O O N N lΩ N CO CΩ CO CO N N CΩ x- lΩ x- θ ro UJ τf N UO O χ t ro cθ CD C0 CO CM CJ) ro τf CD CD C0 x- U) x- CD CN CD C0 CN UJ CO N χ- cb N iri τf cb iΩ Lb N uj τf N d d u τ ' cb cd f u. ^ CO CN CO CN CO CN CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ o τf CM τf CD θ ro x- ro iΩ UJ N O CO Cθ ro χ- ro θO CD N χ- ro CO N CD UO CD UO τf CD CO τf O N CD CO C ro UJ CO CD τf cD O CO τf θO O χ - N N N ω ro θ '- m c ^ τ- θ (D (D N ro co N o m co τ- ro N (D c D ro (θ co (o ro co co , * ro N c D C ( (o ro - ( (θ ro o N c cq τ o q u CM ro iΩ q c p cM c» iΩ CD q D co o LΩ N o cM cq q τf q o χt cD CM ro cM . cM χ τ U N θ b σ- σ- cd b cb cN c τf ό u u τf cd cb uό m m m m m m m m ^r m χ i- χ m ^. '* - m m m m m m m m m m m m m m m m m m m m m m m m m m m (M IO O) (O O N - N CD x- co o co ro CO CM CM CO O x- CD x- ro N x- O CD x- χ- CD CM ιUnO ro CM CM CO cq c odro cbro cbib ib co Tt od d d d co coco coco coco co Tf Tf CO Tf Tf Tf CM CN CN CM CM CM co x- CM x- CM ■ «- CM TZ CQ Ω Ω LU UJ X OO x- CM x- CM CO CN CO CM CO < co < ooO x x x < co < 0Q χ x x < CO Ω Ω LU LU LU N N X < X X CN X X X X X OOOOOO X X X X x- CM CO OOOOO X X X x- M CO ooooooυz υoυooxxx-cM __ __Q_ ____ __Ω_ Ω_Q_ 0_ LY__C_____ Ω_ _£: _-: rc r- >>->->->->-xxxxxxxxxxxxxxxxxxxxxxxxxxxx__:__:__:__:__:__:__:__:__:__:__:_£^ r- r-l- r-l- l-l- l-H- l- l-l-l-l-l- H H h- l- l- l- l-l- Hh- l-H I-l- l-l-l-HH-l-l-H I- l- l- l- l-l- l-l- l-h- l-l- l-J- l- © o CO xf ) CO N ∞ ro θ χ - CN CO τf LΩ CO N rø ro θ χ - CN CO τt LΩ CΩ N ∞ ro θ x~ CN CO τf LΩ CD N CD ro θ χ - CN CO τ^ O O O O O O O x- χ- χ- χ- x- x- x- χ- χ- χ- CN CN CN CN CM CM CM CM CM CM CO CO CO CO CO CO CO CO CO CO τf τf τf τf τf ' t τt τf 'xf '^ rorororororororororororororororororororororororororororororororororororororororororororororororororororo CM CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM CN C^ r- © © Ui H U α. O O O O O O CO CO x- Tf UO CM O. O O O O O O O O CN LΩ CD CO Tf O O O O CO CM UO CO CO N UO Tt Tf CM CO O O O O O O O O O q q q q q q cq o oo N τf CJ) τf O O O O O O O CO UJ τf x- χ- CO OO O O O O co cM CD x- o co oo o uo co cD o o o o o o q q q d d d d d d ^ tN d ^ iri d d d d o d ^ cd uj cb Tf N cb cb d d d d uό cd cd Tt ib cb cM ib d cM CM d d d d d d d d CN CM CM CM CM CM x- x- x- x- x- x- x- CM CM CM CM CM CM CM CD x- x- x- x- x- x- x- CM CM CM CM x- x- x- x- x- x- x- x- x- x- x- CN CN CM CM CM CM CM CM CM N O x- O xt CJ ) N N O CM ro CM CD C O CD O. CD Tf CM x- CO N CM CJ) x- 0 CD N χ- χ- CO τ- θ LΩ CD O CO CO CD CO N LO CO χ- CM O UJ CD CJ) CO N LD Lθ CO CO C0 O x- lΩ CM UJ CJ) 00 CM τt CD τf σ C0 CO C0 x- τf rv. r-. - CM U0 N N ro UO CO LΩ UJ U UJ CD CO O CM O O O x- CM O CO CO CD CJ) N x- uo q cq cq cN N ro cD cD cq uo co N uo N χ - ro τf τf N s . cD θ χ - oo cN χ - cD CN q N o cD τf io ro cM CM cq u co t χ--; χ- co cq cq cq q cM c χ- C0 τf 00 N O CD x- O O ro d μ d cb ro ro d cM μ ro ro ro cb od ro d cd ro d N ro ro ro ro cb cd cd co N co N cb d d cD N ro N ro d cb CM CM CM CM CO CM CN CM CM CM CM CM CM CM CM CM CM x- x- CM x- x- x- x- x- x- x- x- x- x- x- x- x- CM CM x- - x- x- x- x- x- Tf CM CD CO CD CO N CM Tt cO CD CO O CO CD O LΩ CO OO Tf cO CO O CO x- θ LΩ CO Cθ ro UJ N CO O CO CN UO χ - N xt CJ) x- CD UJ x- CM CO χ - CJ ) CD CM CD N CD CD CM C0 ro cD CM C0 CN C0 CD C0 τf CM C0 CD 00 τf CM C0 N O CN xt τf LΩ x- CM x- CM CN C CM CM N CJ) ro CM ro ιn τt CD O χ- LΩ CD CO CD O x- O xt N CO O CO UO OO CM UJ CD O O O UJ CO O CO UJ UO CM U Tf CM CM CM UO x- OO CO τf N UJ UJ θ ro CM OO LΩ ro CM q cθ CD τf q τt cq x- CJ) ro cθ τt τf CM τf CO CO CO CM CM CM CO UO UO CN CO τf cD τf UO UJ χ - O χ - (CMM θro) cCoOcCOo iNsidO dθ θro) ccdθ τ χ - : (CMN τf 'xf CM O θ ro ro c CO O CM Cθ CM O CO N N m m m m in m m m m m m m m m m m f ''Tr xt f ^. m m m m - ^ 'r N- m m m UJ UJ Tf Tf Tf τt CO τf cθ N τf τf x- CM Tf CM CO O x- CD x- ro CO CΩ CO CO x- O CN LO CO N O N CD lΩ O CD CD x- Tf cO CD O CD CD O CD CD UJ CM CM O O x- x- C N ro τf cθ CM CM LΩ τf cD N O x- CO Tf |s x- CM UJ CD x- CD N CO O CD UJ N N N Tf cO CM CM Tf CM O— C.O. τf . lΩ O N CO CN τf | s , CN CO CJ) N CO O CD CD x- CD CM CO CD O CO N CD O CO CD CD C CJ) τf CN CN ro oq CO O x- CO CM O τf x- x- cθ Cθ ro uj CM N CD O CO Tf CD UJ CD O CD Tf O CM ro CJ ) CM UJ x- CD CO UJ x- i coV d ddd ^ d ro i CM Tt UJ j τt . t . ' ι ι ιb c t " ^ c b < N c od ro cd cd σ. cb N- σi N N N CD Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf CO τf τf τf τf τf h τff -τf. t xf f f f j' f x xr xr xr xt xf xf xj- in ^ ^ f xf xf t in ^ Tf i UnO Tf Tf - x- CO CM CO CM ,„ _. GO GO O O Ω Ω ,_ TT Sϋ 0000 ,_ T- CM T- CM CO 00 ■ «- CN x- CM Ω LU LU N N X < _. ωO Ω < χ χ χ χ χ χ < 00 Ω Ω < χ χ < ω OΩ Ω LU UJN < χ χ Ω Ω LU LU N X X X X X X υ O O OO X χ - CM x- CM χ - CM OO OO OO OX X x- CM 0000000000 X X X- CM X X X X X 0- Q. CL CL Q- CLθ OO O O O O O O O O O O O o. cL CL CL Q- CL CL C D. o. L -u m m uj m Lu m iju Lu uj uj uJ UJ LU r- o_ c_: c_: Q_ Q_ __: --: _t: __: __: -r: Q _ o_ __: __: __: _£: _-: __: __: w h l-H h h H-- --_- -- -- -- _. - - - _ _ - < < < < < < < < < < < < _ Q- Q. Q. _ _ _ Q. _ _ _ _ Q. Q_Q_ __ _ _ _ © o LO CD N Cθ ro θ x- CM Cθ τf LΩ CD N Cθ ro θ χ - CM C τf LΩ CD N Oθ ro θ χ - CM CO τf LΩ O N C» ro θ χ - CM CO τf LΩ CD N Cθ ro θ χ - CM C^ lΩ uo uj uo uo cD cD cD CD co cD CD cD cD cD N N N N N N N N N N co co co co co oo co co co co ro ro ro ro ro ro ro ro ro ro o o o o o o o ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro o o o o o o o CN CN CN CN CN CM CM CM CN CN CM CN CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CN CM CM CM CM CN CM CM CM CM C^ ϋ_-_^_=_XXOOOOOOOO _^_ _^=__^r_X OOOO co r_ -^ co ro -»- χ χ OOOO xxx > m m o co > ιιιιιι>ooα] > XXXXXXco> r ^XOOO OO DD > co co ro -»• ro ->■ >> ro ro ro -»■ -L -L Cj. co cj. A) ω ω ω CA ω ω ω ω ω ω » 4- ^ ^ 4i j- ^ j- ^ 4- 4- ^ 4- ^. Ji. ^_ J_ 4_ J_. ^ J_. *_ J_.4i.45> *_ ^_ ^_ 4i. ^. ^_ .t_ j_. j_..(_. ^_ ^_ ro vj j i (D (o oι j ro j vj _ © © co ^ ^ M ( N) -^ p 4- ω ι - ι : ^ - i ro -vi -vi -vi cn c .4_ cn cn 4 s - -si cn cn r co 4 s - 4 s - n 4». n oo cn n n i-^ j co t c co ro -g c» d ro co -j i-^ do bj b) o c» ro ro (D3 d c o ^ ι r ro - j - c j θ -. l_D bo in --^ _ -^ i^ ro bo 4 s . Cn M M ro θ O CO -^ CO Ol 4 s - 04- C04 s .4 s . ->.4 s . ∞ CO ∞ -^ ro C .O. C» CO C _D. C_J). 0_0_ -v .| CD O -sl vi ro cO -' vJ O vl r ^. '^ O CD vl OO W CJ ^ OJ ■ vj -_ j oi -t_ -J co r oo cn ro ro ->- cD O NJ O cn 4 s - oo CD cn cD O c'n ^ --j ■ c —o o -o c-o- -to- α-) cn 'vi oo -»- -- -^ -^ oo -^ co oo cD r oo C " D co ro ro o -J cn ϋi ro ro ro ui cn oi cji cn ro ro cjo ro cn cn cn cn cn cn cn cn cn c cnι conι croD con. cn cji cn oι cn ro cj. ro cjι cn cn σi cj. cjι cn cn oi cn cn cn cn cn cn cn cn © (O o ^ o fSM Mco ωp r ^p ω po ro ro xi tti xi xi xi x siiα fn o n mfo si s J (O v| m oo n o '°D °O 'p n m ro v-Jl rcno cDn mO) —s4 i ssji ssji mcj) mro icnn Mco IcnII icjn. ccnn Λ4 s - v- i-^ bj nbo ro io3 -4ro i^ ro o c» -44 s - r i^ -^ i^. -i -j ^ w to co co cn co ro o _ sj . _n ^ r bo ω ^ ∞ ^ co bi cn o o ro co ro bo ir- CO 4 s - ro co co -vi co o cji co co -t- -vi co co ro -vi c» co co cD co c .o. o _ o _ -svii jj_.. ccoo ->- co co cn 4 s - co co co O 4 s - 4 s - 4 s - 0000 O CO oo -»• n cn co n 4 s - OO O ro ^ l C D ro r O -' C D C O vl ϋ l D ro NJ W vl J- i JL f CDn mOO rCnD O fCnr. fC!D. -vJ sl sl CD CO sJ CO rO W 4- 0000 CO CO 00 si n o co ro co M I I. -»■ ro to ro to ro to 4- co p p to ro p p c -o - co n si co i-» ro 4 s - ro c3 ∞ c o c -. ∞ M cn cn ro ro -vi co s - θ 4 s - ro ro ro ro ro ro co co co co ro ro ro r ->- ro to ro ro ro ro ro -^ -' -' -' -' -' -k l. r f l. r r. r NJ -i -' -i -i -i -i -i f rO t -i -i -J. -i o o o o o o oi ^ ro ^ w i p oo O O O O O O O ^ ^ ro iji ro ^ ro o o p p o p p p ro ω ro ro oi ω ^ o p o ro co ro to d d d d d d ^ k) b) -i oi k) d co w d D M ^ si i iji b bi α α ώM d co oi - 1 O O O O O O s| 00 CD O 4 s - 00 ->- CD -vl b b d d d d d O O O O O O O CD C04- sl O CDCD O O O O O O O O O CJ ) CJ) 4 s - 4 s . Cn ro cO O O OO C04 s - sl LO r- © © Ui H U α. CO CO CO N Tf IΩ O O O O O CN Tf CO Tf CO CM CM OOO OO OO CO CM CO CO CD O O O O O CM CJ ) lΩ OO LΩ CO O O O O O uo CD O ro o CO 00 O O x- N O O O O O O Tf UJ N UJ N N OOO OO OO CD x- CM UO CM O O O O O CO N Tf O ro cO O O O O O CO N x- N δ r CO O N Uj Tf CD CO O O O O O N CD CD UO CD CO CD O O O O O O O CO CD IΩ IΩ ' UO dddo iriuόcdcbNcb dddd CO CN CN Tf Tf CM CM x- x- x- x- x- CM CN CN CM CM CN CM CM CM CM CM CM x- x- x- x- CN CN CN CN CN X- X- X- T- X- CN CN CN CN CN CN ro o co χ- χ- ro cD τf CD N χ - N CM CM CD χ t χ - ro ro xf CN C O χ- ro cθ CO C O CO N CO x- N O O N UO N CO x- xf p CD CO N O LΩ τt c χ - ro co o N co co cM uo CM CO C _D .N C.O. C_D C.O. C_D CO N O C CMN CCOJ Oj Nrs C cO) x- O O OC-J CCDD roOJ xx-— O O CCDϋ TTff cςxOj CCNM Nr— C UDJ C CMN TTff x— x— L UΩ) UO UO (CM (CMN UCD) O O N cq o cq q Tf cq N Tf o ro cN ro cM c x- cD CN Tf x- CO Tf CO CO CD CN CN x- O CD UJ CM CJ) CM CD CD CO x- OO τf CD χ - UJ τf CM τf N O CD Tf O |X i c0qU roO) σϋ)> c» roO) N|X N|s. N|X c0dO cOx)i roO) μτ- CCNM " cnb r- dJ roOJ x- CCMN CCMM OO COD) COOO COD. CCMM CCO CCO Tτff CCNM x— Tf x- CCO CCO xx-- xx-— C CMM CCMM OO roO. xx-- CCNM OO Oa CCJJ ) . x- CCMM CCO r ) TTff x- CCNM CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO CO CO CN CO CO CO CO CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CO C^ ro co t o Tf rs Tf CO O N UO CM CD CD CO UO x- CD OO N CO xf CM N x- OO N UO C CO τf rs ro ro cO O CO CO CM LD CN x- τf |v. cj) θ LD O LΩ CO CO CM x- lΩ N O x- CD UJ UJ O O lΩ CD CD CD N UJ OO N N N ro OO CO CM CD x- x -t .N CJ) χ- CM CM χ- ro UJ C0 C0 N τf C0 CD CM χ - U0 O CD ro CM O χ - CJ ) ro θ O CD CD N x- O CO Tf N O xt uq CD UO CO xf UJ CM '^ UO x- CO CM N x- O x- co χ- cocoχ-τf cMCMτto oo ro ro cD θo coσ) to rooq co cq τt x- C CNM CCNN x- CC cCdO O cCOd xxTf τff ' ccsMj cCMM CCN CC^M ^x- cC ff Tτff x- cCO xxTt UJ CO ττff iLriΩ cCdOcCdO x-μx- τff cC cCbOττff " ιLriΩττff x-oOcObONNroCD O CMM b roNN cbN- CD CD CO CD CD CD CO CD CD CD CD CD CO CD CD CD CD CD CD CD O CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD UO UJ UJ CD CD CD CD UJ CD UJ UJ UJ UJ UO UJ O N N ro CD τf cθ χ - CD N CO CD CM N CD CO C CD τf O CD τt τf cθ UJ CD CD CD ro CJ) OO CD O CD CD N CO CN Tf CD O Tf O O O CD Tf 00 x- CO OO CD CD Tf CD 00 CD O N CD 00 x- Tf Tf CD CN CD UO CD x- Tf cO UO N ro CD x- CO CD N x- Tf N O N CO O CD CO O O CO N CM x- T CD N 00 CO CD 00 UJ CJ ) CO x- N CD CD CD Tt cq CM q p U LO UJ CO CJ ) N O UJ CM C N CJ ) x- τf cθ UJ CO Tf Tf 00 ro UJ CM lΩ τf χ - χ - 0 CO N x- CD CD N N CO CO x- CM CD O O CD CO CD ro Tf CO Tf Tf CMCN O ro cbcb cO O CD CO CO N CO N CO CO N CO CO CΩ CΩ CΩ 00 CD ddd(Mco O CO CO τf Cθoτf ccbOcτf CτMf τf τf cτbf c CO Tf Tf Tf C τdf cτMf τf Tf Tf Tf Tf Tf Tf Tf cO CO CO CO Tt CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tf Tf Tf Tf Tf ,-. CQ 00 CQ OQ O O Ω Ω 0Q CQ 0O -„ 0O CQ < CQ < χ χ < CQ θ Ω < χ χ χ χ χχ < 00 < X X X < CQ < χχ < 00 O O O O O X X X- CM X Z O O O O O O X X- CM X- CM X- CM Z O O O O X X X- CM CO Z O O O O O X X X- CM X Z O O O O O CL CL lΥ. ιΥ. CL Ql CL CL 0L (Z LL θ O O O O O O O O O OO OO <{ < < < < < < < < < y* C L fc r- iΩiΩvuiΩL iϋinm iuc LL LC crc OLCLCL rLKfc σ)mmmm mm CLCLΩ-CLCLθ-CLCl.C iZL. (^ © ro θ χ- CM C0 τf U) CD N ∞ ro θ x- CN C0 τf u0 CD N ∞ ro θ χ- CN C0 τf uJ CD N C0 ro θ χ- CM C0 τf U0 CD N C0 ro θ χ- CM C0 τf UJ CD N C^ o UO CO CO CD CD CD CD CD CD CD N N N N N N N N N N CO CO CO CO OO OO CO OO CO CO ro ro CD CD CD ro CD CD ro ro O O O O O O O O O O x- O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- x- CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO r- © © Ui H U α. O CO IΩ OO OO O O O O O O O O O N OO CD CD CD U Tf O O O O O O O O O O O CM O OO CO x- Tf N N OO OO OO N O x- UO Tf N CO CD CO CO O O O O O O O O O x- C CD CO Tf CD CO O O O O O O O O O O O LΩ N CD Tf CO O CD N OO OO OO CM CD CD x- CD O UJ C Cθ τf O O O O O O O O O O χ- χ- ' CN CN O O O O O O O O O O O CO Tf CO CO J CD N UJ O O O O O O CM CO x- x- x- x- x- CM CM CM CM CM CM CM CM CM x- x- x- CD x- x- CM CN CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM Tf N O N χ - x- τt 00 C0 τf ro cθ LΩ U0 τf cθ CO CD UJ UJ CM UJ U0 N UJ N xt O CM CO τf τf CD CD N χ- CD CO χ- UJ CD χ- τf CO CD CO x- OJ CD CO O Tf τt τf CM CM UJ CM CO CO CO CO CD CO CD N χ - χ - CO χ - N N UO OO CO x- N CM CO Tf ro cO CM CM CO CO UO O x- O CO CD CD x- C0 x- C0 CJ) x- x- CJ) CD C -N ■ 00 - CO - x- N UJ CO ~ C0 τt C0 CΩ N CN N lD CO N CO UJ CD CD cD co co co uj τt r-. χ- χ- Lr) τt τf oo co m τf τf LΩ N Cθ CO τf CM x- CM O N CD N UJ UO N Tf CD Uj Tf UJ UJ CD N CO N CM O χ- xt UJ ro cθ x- χ- CD C τf θ ro θO O χ- N UO xf OO UJ CD CN CO N CD χ- O θ ro θ CD O CN CN C O χ- χ- CN N O OO Tf x- N N OO Tf UJ U0 CD ro CD C0 O C0 UJ χ - UJ N ro CN CD N xf N CN N N O O N τf τf i0 CM χ- N C0 C0 LΩ C0 τf ro c0 τf r-- Uj ro U0 O O CO UJ N x- UO UO CM CO CO ro cθ χ - CO CO O CO χ - N ro cθ LΩ CM O CM ∞ O CO O lΩ CD CO lΩ OD C CD τf co r-- χ- CJ) ro τf θO CO N CD χ- O N CM OO CO CO CO CD x- UJ CD N cD N uo N uo ro N ro co u co τf rs uo ro ro co oo o χ- o cM ro co o χ- o ro o o ccoo ccMM CCNN roro ccθo NN CCDD roro roro roro ccoo oo roro roro o c» oo cD uj Tτff CcOo Tτff m m m m m m m m m m m m m m m (D (D CD (D m (θ (θ (θ m (θ co co co co m m m m m m m m co m m (o m m m m m m m ro cD UJ CM CO x- O CO CO UJ CO CO CO Tf N N CD 00 CM C D τf x- CD N UJ χ- ro uθ χ- τf x- CM τf CD CO CO CO CO N U0 τf σ) τf x- CD x- CO CD N N UJ CM UJ CD O x- CN CN Tf CO N lΩ CN CO Tf Tf CN CN CO T τff CD τf θO UJ O CM CO CM CD N CO χ - CO N N UJ CO CM CO x- CM CD Tf O CO CM xt N Tf CM O x- Tf O Tt ro CM O Tf Tf x- CO CO CO lΩ CD CD CN O x- CΩ OO χ - O CO O UJ CD CM x- CJ) x- CO CO O C0 lΩ τf CM τf O 00 χ- CJ) U0 U0 τf c0 CM CD C0 00 U0 C0 CO Tf Tf Tf U) O O CN CN CN CO τf UJ lΩ O x- O O χ- CO τf c O CM x- O CO τf cθ UO CM CM τf CO N N N CD UO Tf Tf oO N CD CD CO Tf rv- rs cO CO CO Tf Tf Tf Tf Tf Tf Tf Tf Tf xt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO x- x- x- CM CM CM CM CN x- CM x- CM CO OQ x- CN x- CN x- CM cα_0,_ΩΩΩΩΩΩ T CN 00 CQ Ω Ω Ω Ω LU LU N < χ χ Ω Ω UJ UJ N < DQ Ω Ω <XXθχχχχχχ < coOQΩ <χχχχ < Λ ω OOO OO X X X- CM X X X X X OOOOOO O X X X- CM X X- CM CO X- CM CO O OOOO O Z X X X- CM X- CM Z O O O O UU LU LU LU L LU LU LU LU LU LU LU 3333333 333333333333 Z Z Z Z Z Z Z Z Z Z Z Z Z Z J LU LU LU UJ r- X X X X X X X X X X X X X X UJ UJ LU UJ LU LU LU LU LU LU UJ LU LU LU LU LU LU LU LU CO CO CO CO W Q- Q. Q. CL CL Q. CL CL O. CL CL Q. Q.0 I _J _J _ _ _J _ _J _ _J _J _J _J _ _J _J _J _J _J < < < < < < < < < < < < < < 0 ^ © o x- CN CO τf LΩ CD N Cθ ro θ χ - CN CO τf uJ CD N Cθ ro θ χ - CN CO τf UJ CD N Cθ ro θ x- CM CO τt UO CD N Cθ ro θ χ - CM C τf u CD N χ - χ - χ - χ - χ - χ - χ - χ - χ - CN CM CM CM CM CM CN CN CM CM CO C CO Cθ CO C CO CO CO CO τf τf τf τf 'st τf τf τf τf 'vf LΩ U0 U^ CO CO CO CO CO CO C^ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M r- © © Ui H U α. OO O Tf x- rs Tf O O O O O O O O O CM CD x- Tf O O O O O O O O O O O N CO O CD ro oO CD CD UJ N O O O O O O O O N O CD CD O CN O O O O O O O O O N CO Tf CN O CN N OO O O O O O O O O O O O CO x- χ- τf u co cD τf oo ooo oq oo q o q T^ ^t -r^ d ci d d d d d d d d d d d d -r- ^ ^ μ ^. d o d dd d d d o'co Tf Tf ' ( ^NN ONVoidd ddddd x- x- x- x- x- x- CM CM CM CM CM CM CN CM CM x- x- x- 0O CD χ - CD CO CM CM CM CM CN CN CM CM CM CM CM x- x- χ - x- x- x- x- CN x- CN x- CM CM CM CM CM CM CM CD τt cθ CM CD CD UJ UO CM 00 N CD O CN UJ UO O C CO CO CO CN N CO Tf ό ~ CN CO N CD O CO O X-; LΩ ro CM O cN N cd c ro cN d τf τf cO τf τf cO CO τf τf T f OO UJ OO CM CD CM x- CD lΩ Tf UJ UJ CD x- OO OO O UJ U Tf O CD CN N UJ CO UJ N CO N lΩ N ro CN CO Tf CN O OO OO x- J CO CO CM CO CD O CO UJ N UJ O CM CO O 00 O τf oθ τf cθ UJ CM CD CN UO CO CJ) CD CD χ- CM CD . uo Tf UJ CN Tf O CD N CO CD Tf Tf UJ Tf ro uo x- ro x- ro CM UJ Tf f CM N ro CD U0 C0 CD τf U0 U0 C0 O C0 CD CD τf c0 Tf ro N CD CN O UJ N CD O Tf Tf Tf OO OO CD CD ro o co ro o ( (M χ-τ-os sf m c θθ ()) ^^ sr c mm < m( (Dmm(D mm c c c mmm sf scoco (Dco co(j) (Dm NNωoo(θ m m m m mm xr m mm m mmmmm mm mm m m mm mm m mm m mm m mm mm mmm N τf CN C0 O lΩ χ- τf m C0 C0 O C0 N CN O CD χ- τf |S x- CD O O CD f x- τf LΩ x- ro ro cθ UJ N C0 CD χ- C000 CD CJ) CN CM O UJ C0 CJ) 00 N 00 χ- χ - τf CD χ - N CD τf C0 C0 N UJ UJ N U0 O C0 CM N C0 U0 C0 χ- O„O C.O. O_ x -- C -O_ OO O CD CO CO CO CM CM O x- CM N O CM Tf O Tf oO x- UJ CO N OO N CD Tf CD CM N CO LO CO CO CN CD UJ CO CO Tf CD O x- CD N Tf iO OO OO CM CO C -M C—O O CO CO Tt cO O CD CN CD Tf Tf cO CD N CD ro co ro cO CO LΩ O CD N N OO CD N CD N OO N CD CD N O O CD CO O χ - O O CM CO τf cθ O x- CM CN CO τf UJ UJ τf cθ τt θ ro θO OO CD O x- O CM χ- CM O O CO CD χ- CD CO CO CO CO CO CO CO CO CO CO CO Tf Tf CO CO xt Tf xt Tf Tf Tf Tf Tf Tf Tf Tf τf τf f τf τf τf τf τf τf cO CO CO C τf τf τt τf τf τf τf τf cO CO τf cO τf x- x- x- CM CM CM _ x- CM x- CM co co CM x- CM x- CM OQ CQ ,„Ω Ω Ω Ω Ω Ω x- CM x- CM CQ CQ ■ "- CM x- Ω Ω LU LU N < χ χ Ω Ω LU LU N < 00 Ω Ω X X X X X X < OOOΩ ΩLU LUN < Ω Ω LU O O OO OX X X- CM X X X X X OOOOOO - Xτ- X x- CN X x- CM CO x- CM CO OOOOOO OOOO X X x- CM X X X r- LUU in nini n mi u j inininiΩ iZ Z Z Z ZDZ Z ZDZD I II II II II I I IIII_ __ l_ _ _ __l __ _l_ __ _ l_ __l_ II II IIII III Q- QL Q. CL Q_ CL O. Q. Q. Q. Q. Q. Q_ Q_ 0 I _J _I _I _I _I _J _I _ _I _I _I _I _J _J _J _I _J _I CL Q. Q. Q. 0. CL CL Q- CL QL Q- Q. Q. Q. 0. Q. Q. 0_ © o CO τf LΩ CD N ∞ ro θ χ- CM C τf LΩ CD N Cθ ro θ χ- CN CO τf LΩ CD N Cθ ro θ χ- CN CO τf ιn CD N Cθ ro θ χ- CM CO τf uJ CD N Cθ ro CD CD CD CD CD CD CD N N N N N N N N N N OO CO CO CO OO OO CO CO CO CO ro ro CD CD CD CD CD CD CD ro O O O O O O O O O O x- x- x- x- x- X- X- X- X- -Γ- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- X- -Γ- X- X- CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CO CO CO CO CO CO CO CQ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ r- © © Ui H U α. O O CO OO CD N Tf ro CM UJ CO O O O O O O O O O O O O O ro cD CD CO O OO N OOOOOOOOO CO OO UJ CM CD CN N CO x- x- CO O o p q N x- N cq Tf x- p q o o o p o o o o q o q cq cq co ro o co co OOOOOOOOO ro xt Tf CM N CN CD CD CM CD q O τf cb cd cb N cM τf ro o o co M cM ddddddddd CM Tf cb N cb cM cb lb Tf CN CM O CN CN χ - χ - χ - χ - χ - CM CO C C CN CM CM CM CM CM CN CM CM CN CM CM CM χ - χ - χ - χ - χ - x- χ - CN CN CM CM CM CM CM CN CM x- x- x- x- x- x- x- T- x- x- x- CM N 00 CD CD CO ro x- N CO N UO N CO CD CO Tf CD N Tf OO UO CD ro cD UJ CO CD CO CN Tf x- CD CO UJ O CD N CM CM Tt O UJ CO O co Tf ro UO Tf OJ CM CM CM CN OO CD CM CM UO CO Tf UJ Tf CM N x- Tf CD CD τf c0 τf O LΩ CD 00 UJ N CD UJ C0 C 00 00 τf τf CO N Tf CN CO CD CO CO x- CO ro ro UJ CD CD CN x- C CDD CCDD xx-- TTff CCOO OCOO N N CM CO CD CN O Tf |s Tf ro cq uj Tf cD x- cq iΩ o ro iΩ q N ro cq ro ro cM co CD oq CM Tt p CM ro cq p c CM ro cj) d CO CO CD CD CD CO O oo N N CD O co co o o _o • c_o- • ro_ • ro_ ■ ro_ ■ ' oo s-i cd oo ro cb cb cb cb cb cj) oo CM CO sf C CM CM CM CM CMV o Tf Tf CO CO Tf Tf CO CO CO CO CO CO Tf CO CO CO CO Tf C CO τf c C C C C τf τf cO CO 00 CO CO CO CO CO CO CO CO CO τf Tf xf Tf xt Tf Tf Tf Tf Tf Tf Tf CM N UJ N x- CO Tf U0 CO x- C Tf x- UJ OO CN CD CO x- O CD x- CD O CO Tf CD O N N Tf x- lΩ N x- x- CM O x- O x- UJ CO N CO CD Tf CD N x- Tf CD Tf UJ CD τf UJ ro ro Tf cO CM x- CO CO CN CO CM UJ CO CN Tf -sf uO CD UO CM m mm mmm x- OO CM CO CM O O x- CM CO CD x- CO CN Tf Tf x- CD N CD N O U UJ x- N CO CN CN τt CN xt N O xt χ- χ- x- CO N CD CO UO CD N CJ) CM C C O τf cθ Tf OO N CO CO CD x- Tf J O OO ro u CO CD O O lΩ OO Tf cD CM xt UO xf x- CD OO CM χ - OO τf τf CO CO χ - CM τf c UJ O N CN CD CD CO UJ CO O CD CM CD OO CO Tf UO cO O N CM CN N UO Tf OO N - θ χ - N τ cq τt τf χ-- cD q cN N co cD co ro coro uoχ- co cD τf oqoo cj)τt cq oo N CLj LΩ χ - CO N cCDb NN NN ilriΩ -τft ccbθ μ χ - O NN uUόO uUό CD ττff ττff ccd cCdO χ - χ - O dθ σro) ccdθ oCDό oCJό) cCDD dO CCJD) OO OOOO OOO Oθ CroD CcOθ OO OO x χ -- χ - d dσ τf τf cO CO CO 00 CO CO C C CO CO CO C C C C C CO CO CO C CO CM CO CO CO CO τf cO τf cO C τf cO C τf - ' τf τ^ τf τf cO) θCO)Vτf cτMf cτof ιτrif (τf ιτrif Nτf dτf CM CM CM CN CO CQ O O Ω Ω J N N N x- CM O LU N < O Q Ω LU N < ω <pQχχχχχχ < CQ O Ω LU N X X X X oυoooυυzx <x x U U X x-x L CM x-xCMxx-xCMxx-xCNxx-xCNxCO OOOOOO X X x- CM CO x- CN CO oυoooozυzzx LU LU r- coco c cococo cocococococooococo ωcoco COCO O -j - J -! -j - J -J- _! _! _! _! - - _! - - ^5 55 5 5 5S5 5 2 2 5S5 0- -L _l _l _l _l _J _l _l _l _J _J _l _l _l _l _l _l _J _J _l _l _l _l > > > > > > > > > > > > > > > > < < < < < < < < < < < < © o lΩ CD N Cθ ro θ χ - CM CO xf LΩ CD N αj ro θ χ - CM CO τf LΩ CD N Oθ ro θ x- CM CO τf LΩ CD N αθ ro θ χ- CM CO τf LΩ CD N CD ro θ χ - C^ χ - CM CM CM CM CN CM CM CM CN CM CO CO CO CO CO CO C CO CO CO τf 'Lf '^ τf τf '^ xf τf τf τf U0 U0 UJ U0 UJ U0 UJ UJ U0 UJ C^ CN CM CN CN J CM CN CM CM CM CM CM CN CN CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM C^ CO CO CTJ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ r- © © Ui H U α. O O O O O O O O O O O O CO CN CO m N x- CN LΩ LΩ O O O O O O O CO x- O Tf CN O O O O O CN uO CN uO O O O N N O Tf N O O O O O O O O O O O O O CN CD CD O N x- CD N CM O O O O O O UO CD Tf ro oO CD O O O O O N N CD N O O O N CO CO ro CM x- O O O O O O O O O O O O O CD CD CD N x- O N CN CD O O O O O O CD N O x- Tf cO O O O O O O O CM UO O O O O O CM CM N CD O CM CM CM CN CM CN CM CN CN CN CM CM χ - x- CM CO CO τf cO CM CM CM CM CM CM CM CM x- CM CM CM CM CM CM CM CM CN CM CM CM CN CM CM CM x- CM UO CM CM CD O CM UO N χ - CJ ) xf N N CO O CD CN τf CM τf O N O τf CD N N CO CN UJ CD CM LΩ CO O 00 OO CD Tf UJ CD O O CO x- CD Tf OO O N CO CO O UJ CM x- CD O CD CD Tf rs O O x- OO OO ro cO x- N CM O O CD O O OJ x- Uj Tf CM CD CD O UJ UJ N OO CO OO UJ CD CO CO CO CO CO CO CD O OO CN CN N lΩ CJ ) τt CN x- χ - CN ro θ CO τf uJ CD CD N O CM J ) Tt OO CM UJ CM x- x- UJ N UO CO UJ O N CO CO CM CD CM O ro ~ ro ~ cM CD in c χ - χ - co CJ ) N OO N χ - CO CD CN UO CM N UJ CD CD CO χ - UJ N χ - O Uθ ro θ xf x- τf τf CD CJ) CO CD N CM O CD ro CM CM UJ χ- UJ CO O O CJ) OO χ - CJ) CO CJ) CD χ - CO CD N τf cD τt cD x- χ - τf CD Uθ LD τf N τf O CD CD N CD CO UJ O CO CΩ CJ) CD O O lΩ O x- CO x- x- UJ CD L _Ω. C _D. χ - _τf- .LΩ~ C~M. C-b~ ~θ ~CM. N τf CD CM LΩ O CN CM N O CD CO CM CO O CD CO N CO CD LΩ CD CD O CD UJ x- CD O CM OO LΩ CN CO CO N ro O Tf UJ CM UJ CD UJ OO Tf x- cO UJ UJ N N CO Tf χ - τf τf cθ CM UO UO CO N CO CD τf CM CM χ- O CO τf uJ r N s ~ uUJj CD UJ UJ Tf UJ UJ N LΩ UO UJ UO UJ UO UJ UO UJ UJ UJ UO UJ UJ LΩ LΩ LΩ UJ UJ U ιnJ UιnJ χf xf xf xf ' " Nt xf CD UJ x- CO x- Tf CM O CM CM O CM Uj Tf CM CD f CD N CO CO CN Tf CO χ - ro CD lΩ CD CD CN CO O CO CN UO CD O τf τf CD CN CO CO CM N CD CO τf O CD x- CM ro cO UJ in cD x- CM O CM CO N Tf oO UJ x- Tf CD CN U) N N O Tf x- Tf U Tf oO N UO Tf t s - ro N UJ CO O CM CD CO ro O O CN CM CM UJ UJ CM UJ CM CD τt CO CO τf cD CM CO UJ Cθ ro τf |s CD CN ro τf N CD U0 CD CD χ - N ro O N CM U0 CM N U0 N UJ UJ x- CD N U^ O N x- CO CM N CO χ - χ - O CM C0 C0 C0 lΩ CD τf |s ls c0 N N CD CD CD N CD N 00 00 UJ U0 CD N N CD N CD CD N N UJ CD UJ 00 00 ro θ O 00 C0 ro O O CM CM O 00 CD Tf Tf Tf -xf -f Tf Tf Tf Tf Tf Tf f cO CO CO CO CO C^ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ f Tf Tf f Tf CO CO x- x- CM CM CO CQ Ω Ω X X X X x- CM co oo GO GO < < < X X X X X X LU χ χ χ χ < 00 Ω LU LU < X X X X < CQ < x χ X X < 00 X X- CM X- CM X- CM X X- CM X- CM O O O O O O O X X x- CM x- CM O OOO X x- CM X OOO x- CM OO OOX O OO O OO O 333333333333333 Q_ 0_ Q_ Q_ 0_ Q_ Ω_ 0_ Ω_ 0_ Ct >- >- >- >- >- : s - >- _ Q_ Q_ K r- 0_ 0_ Q_ Q_ Q_ 0_ Q_ Q_ C_: Q_ Q_ Q_ — I — I — I — I — l — I — I — l _l _l _J _J _J _J -J LU m LU UJ LU LU LU LU LU — ' -I — I — I — I — I — I LU LU LU LU LU LU LU < < < < < < < < < < < < O COCO COCOCO COCOCOCO C CO COC COC COCO CO © o N ∞ ro θ χ - CN C τf LΩ CO N Cθ ro θ x- CN C τf Ln CO N ∞ ro θ x- CN C τf LO CΩ N ∞ ro θ x- CN CO τf J CO N ∞ ro CD CD CD N N N N N N N N N N ∞ ∞ CO CD CO CD CD CO CD C» ro CD ro CD CD CD ro ro ro CD O O O O O O O O O O χ - χ - χ - χ - x- x- x- χ - χ - CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CO CO CO CO CO CO C^ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ r- © © Ui H U α. O O O O Tf OO oo Tf CM CD CO CD O O O O O O O O O O O CO 00 N CO CD CM o o o o o ro U Tf co x- N oo oo oo oro ro o ro O O O O Tf UO x- UJ CO CD CD UO O O O O O O O O O O O co ro x- CM UJ oo o o o o o CJ) x- CO τf . C ..D. , N- O--. O_ ^O O_. O_. O_. O_, w OO . o _ c _o_. O O O o cN uό ro τf cb cN cb uJ d d d d d d d d d d d N od ro ro ro cb d d d d o cb cb N c CbO ro CD 00 CO d d d d d d d ι t- (Ω ya CM CM CN CN CN CN CN CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CN CN CN CN CN CN CN CN CN CN C^ τf C0 N τf c0 χ - χ - CM CM UJ CM x- ro CD CD CM C0 χ - τf CD O UJ CD ro τf U0 U0 C0 x- C0 CM θ ro ro CD CD O C0 χ- x- τf θ UJ χ- ro N χ- U^ co o ro ro N O N Tf co ro oo ro co OO Tf ls CD C0 C _D CM C _D τf ro c0 τf O _ UJ U0 χ- τf CM O _ C0_ O_ ιn τf C _D 00_ τf |s o CD C0 N N CD CJ) O U0 CJ) x- ro cq iΩ CD CD ro x- q uo cD CO CD O CD Tf cO OO C "D C ~ M ' C "O x- C ~D CM Uj ro - C-M- C-O- N- Tf CM x- CD _ CO_ CD_ U_O OO_ CM O_ cD LΩ 00 CJ) CO τf CD CJ) CD U0 00 Tt μ μ cN co cb τf ' ιri cb μ d χ- co cM co c χ- o o x- o in N N CO CO N in N CD CO N 00 CO CD CD CD Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf f f Tf Tf Tf Tf Tf Tf b ro N ' b rob dco bro bffiCJ) Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf UO τf τf τf τf UJ UJ Tf τf τf J τf f oo oo xt CM CO UJ O OO x- CO CM x- CO CD O CM UO O Tf cO N Tf N Tf O CD CM UJ CO O O 00 O O Cθ UJ CM CJ) N CM τf CD CD CM CJ) CD τf CN τf CO O 00 CM CD OO x- N N CD UJ N N UO x- O CO ro CM CD CD O CO x- UO CO x- UJ CD x- CM O N. T ,t N. ro _. O _O CO OO CM O Tf cO CD OO O CM N N ro cO Tf UJ UJ 00 x- x— U0 CO CO CD x- CD Tf UJ CD ro O CO Tf OO CM CN OO CO O Tf C -D~ CO CO O O Tf CD CD O Tf uo uo ororocDNcouoorocouj N x- ro o ro Tf Tf uUoO cCDO CCDD NN CCDD N c cb N d N cb cJ cb d cb cb d d _ d _ CD CD UJ Tf CD N u N o u τf cN τ j cd ι b u. c N c ' CD τt τf τf τf τf τf τf τf τf τf τf UJ xf τf τf τf τf τf τf τf ιr) UJ U Tf Tf Tf Tf Tf Tf Tf τf τf τf τf τf xf τf xf ^f ^f τf τf τf f τf τf f τf τf τf t CO Tf x- CM O O x- OO LΩ N x- O CD O N CM C0 C0 C0 N CO O CM O N N C0 C0 τf χ - CN CM O τf O O LΩ UJ CM O 00 CM N 00 χ - O C0 ro χ - N x- C0 CM CD x- CO O CO CM UJ CO CN N ro cO CM UJ . N C _D C_D C ro CN CO CD ro τf CM CD CM ro CJ) τf C0 C0 O CD U0 C0 CD CJ) C0 CM CD O CD CM 00 CD ro c0 U0 N CD τf UJ UO CO CM UO O N CO CN N N N CD Tf CCM CCDO NN C CO NN U U0O NN O COO O U CM ro CN CO x- CM CD N CD Cθ CM CD CM τf CO N UJ O O CO UJ χ- C CD τ Tff θ COO C CθO C CJD) O O O CO CM Tf Tf uO Tf cO Tf cO x- Tf UO CO CM Tf . UO T Tf c c τf τf ' uό τf co cM cb uj cb cM CM cb r-i cb N cb Tf Tf Tf CO xt τf τf τf τf τf τf τf xf xf xf f χ3- τf τf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf s s σ UJ U f f d Tf CO Tf Tf Tf Tf T Tf TfiNTf oTfdsTf Tf Tf Tf Tf Tf x- x- x- CM CM CM OQ OQ x- CN CO 0O ,_ Ω Ω Ω Ω Ω Ω OQ CQ CQ CO O O Ω Ω < X X _> < 00 Ω Ω < X χ O χ χ χ χ χ χ < _ ω O < X X θ < _. CΩ Ω < χ χ χ χ χ χ < X x- CM X OO O O O O O X X X- CM X X- CN CO X- CM CO Z O O O O O X X- CM X Z O O O O O O X X- CM X- CM X- CM Z O O O Q_ Ql C_: Q: iD 333333333333333333 Qi Qi 0_ Q_ Q __: Q_ Q_ Q_ 0_ Q_ OO O O O O O OO OO OO θ 3333 r- LU LU W W W W W W W W W W W W W LU LU W W W W W W LU LU UJ LU LU W W W W W CO CO CO O — I — I — I — I — l _J _ l _ l _l — I — I — I _l _ I — I I I l _ I CO CO CO CO CO CO CO CO CO CO CO CL CL CL CL Q- Q- _L Q- Q- CL CL Q- CL Q- 0000 © o ro θ χ - CM C τf ιn cD N Cθ ro θ χ - CN C τf UJ CD N Cθ ro θ x- CN C τf LΩ CD N CD ro θ x- CM CO τf uJ O N C ro θ χ - CN CO τf LΩ CD N C^ x- CM CN CM CN CM CM CM CM CM CM CO C C C C C C CO C C τf τf τf τf τf '^ τf '^ 'xf 'xf UJ UJ UJ UJ U0 UJ UJ U0 U^ C C CO CO C CO CO CO C CO C C CO C C C C C CO C C CO CO CO C CO CO CO CO CO CO CO 00 CO C CO C C CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO C CO r- © © Ui H U α. LΩ CN τt m τf O O O O O O CN CΩ C N τf O CN σ) N C O O O O O O O χ- N LΩ CO O O O CD CD O CO CM CM O O O O O O O O x- CD uo q N CM q q q q q o o ro ro cq o ro N f co ro cD o o o o o o o co o co Tf o o o UO O N CD CO Tf O O O O O O O N OO x- cd μ N ' ro cb cN ro cb ro d o τf M c c cb cM d d d d d d cM CM cb CO xf Tf Tf in CN CN CM CN CM CM CM x- x- x- CN CN CN x- x- x- CM CM CM CN CN CN CM x- x- x- x- CM CM CN x- x- x- x- x- x- CM CM CN CM CN CM CM x- x- x- OO CM Tf uO O OO Uj Tf oO CM x- OO OO O UO CD O O CD CM x- CD N CO CO CM Tf CD CD CD CD CO CD χ- τf cθ χ- CD N CO CD UJ O CM τf τf f CD CO CM N UO 00 CD UJ CM N N CO Tf Tf Tf O CD CM x- CO CD N N OO O CD CD lΩ O lΩ x- lΩ Tf cO CD N CM x- x- CD CO N x- x- ro oO N OO C CO CO UO N CO CD CD O N Tf CM CM N CM O CN Tf N O CM LΩ CD O C τ- C0 C0 x- C0 cq cθ τf U0 CM N 00 τf cD cD x- oo x- co cM CM N cq cM CN CN cq cq ro CD x- CM CM ' CN O CO N cb cb cb cb N N N N cd N UO Uj N N UO τf cb cb uO CO τf CM τ d d d τ N ( , τ- oJ d : (. (N d σ) N L •^Ω ^UO dUJ dUO dUJ Tf UJ LΩ UO UJ LΩ Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf xt Tf τf τf τf τf τf τf cθ τf τf τf τf τf cO CO Tf UO UJ UJ x- UO N N CD N UJ CD UJ x- O UJ CD OO UJ CO OO UJ O CM N O Tf ro O x- Tf CN N CM CO CM xt CO CM O CD CD OO Tf O O O N CO N ro CO o CN χ - O Cθ CN xt x- UJ x- CD CD x- C O τf τf θO CO CD O χ - N CM θ ro CD χ- C CM UO UJ x- O CD UJ UJ CD N N OO O_ x- x- CON CO UJ CO CD Tf CO x- Tt - U O p ro Tf O in CM T -^ D CN N Tf is o C O CO OJcq cocq NCM OCMCMc x- rocMcqin uj x- cCqO cCqOcCOq CO CO x-; D CO CM CO oq in CM cb χf ib cd cd c cM c cM ^ cM C ro cb cb CD CJ) CJ) CO CM CM CM τf τf f f τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf c xf cNf cxdf CO τf rocO roCO Tf τf cOcCOcCO τf τf τf τf τf rocO roCO-cτNf Tf Tf CO CO CO CO Tf Tf Tf x- O U N CM C OO N in ro oO x- N N O CM Tf O CO N x- CM CO O CO Tf CO Tf CN UJ O N N CO CO N CD x- CO τf LΩ χ- O χ- O O τf CN CO CD -0 χ- LΩ O τf θ CN CN UJ CD UJ UJ N CN CD UJ CM CD CM χ - τf CD CM UJ 00 χ- O CD 00 O CO UO 00 o Tf x- UO x- ro ro CD O CM CO O UJ N x- UO N CM OO ro uO N OO N CD CD Tf CD CD CD Tf CO xt C ro Tt ro CM CO CD CD CD CD CD O in T- o to q CM T- CM C 0 τf c0 N N x- τf U0 U0 N C0 CM O p ro ro τf b cM CM cb τf ιb τf ' cb t - uό b cd o cD xt cM c CD ib CD CD U Tf D N N N cb iri cb ro cb N ro cd od d ro cd iri Tt iri Tt Tf Tf Tf Tt Tf Tf Tf Tf τt τf τf τf τf τf τf τf τf τf τf cθ τf τf τf τf τf τf CO Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf U Tf Tf Tf Tf Tf x- CM OQ 00 x- CN x- CM ω co x- CM x- ,„ Λ CO OO OO Ω Ω CO O Ω LU LU < X X X X < co Ω Ω LU LU < x Ω Ω LU < < X < x < _ C0 Ω < x x x x x x < O OOOO X X x- CM x- CM υυooo Z O O Z X X x- CM xxxzυoox x- CM O O O O O O X X- CN X- CM X- CM Z O O r- _J -J _J _J _J JJ J J _jW (ΛW (j2W WW WW «W(β (ΛW >->->- Λ >->->-OOOOOOOOOOOOOOJJJ 0_ Q_ << < O O O O O O O O O O O X X X X X X X X X X X X X X X X X O O O O O O O -L Q- Q- Q- O- Q- Q- Q- CL CL CL Q. O-O- > > > © o x- CN CO τf LΩ CD N Cθ ro θ χ- CM CO τf LΩ CD N Cθ ro θ χ- CM CO τf LΩ D N Cθ ro θ χ- CM CO τf LΩ CO N Cθ ro θ '^ CN CO τf UJ CD N ∞ rs r^ N N N N N N N oo co co co oo oo oo co oo co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- CN CM CM C (0 (0 ( ( C C ( C C (O C ( C C C CO C CO CO C C n ( CO C CO C C ^ ^ co co co co oo co oo co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co c^ r- © © Ui P H U α. Tf cD in ro o o o o o o o o o ro co co Tf CD O O O O O O O O O x- UJ N CN O O O O O O O O O OO CO CD O CM CO O O O O O O O O O UJ CD CO CN CD O O O O O O O O O O UJ x- O x- τf rs θO O O O O O O O O O CO CO O CD x- τf τf CO Tf OO O O O O O O O O O CN CM UO LO Tf d d d d d d d d d d d ^ ^ N i o iN 00000 00 000 ^ 0 °. °. ^ ^ x- CN CM CM CN CN CN CM CN CM x- x- CD CD x- CM CM CM CM CM CM CN CN CM x- x- x- x- ro oO ro CM CM CM CM CM CN CM CN CM x- OO x- ro cO OO N O CO OO N Tf CN CO O UJ CD UO OO Tf Tf CM CJ ) U ) τf uJ O O χ - N CO N CM UJ CM CN χ - x- CO N CN N C CO O O CD O CD N O CO CJ ) xf CD O CO N CD CN UO Tf O CO CO UJ CO x- UJ CD ro cO Tf uj xr co N co x- Tf N ro oo xt o o uj o N ro χ- N τf r r j χ - oo cj) τf r x- cN c ro cM CD co χ- co uo CD CM CM N CO CD CM UO CM CM CD CM N N CO N C x- ro UJ CD UO x- O S- CD CM N x- O OO CD CO CD lΩ CM χ - O χ t CN θ ro UJ N θq U Uq CO cq CJ ) q N ro cb cb o ro o co N cb N ro cb N u T f '^ Lb cb N Lri uj N cb uj CO CO CO CO Tf CO xf CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Λ o Tt 00 x- x- ro ro UJ N CM O x- CD N x- N N 0000 CM ro UJ C0 C0 ro O U) C0 C0 O CD CJ) x- ro UJ C0 O UJ 00 O UJ CD CD xt CM xt N CO UO Tt CO xt CO CO CM CM C N N χ - UJ O CO O N UJ τf CM N N UJ N UO CM x- χ- N τf cD x- CN CD N UO CM τf OO UJ χ- CO x- ro ro cO CO O O CO CM O Tf UO UJ CM Tf x- N τf N CM u j cq N CM χ t cq o χ - co ro ιn N χ - cM o ro N τf ( r) χ - ro χ - co cD ro co co iΩ co ιn ro co o ιn cM χ- o oq cM q p N cq τf x- cD ro ro CM xt t uj c cM Tt Tf Tf ' uό u uό cM ro ro μ ro c ro o ' ∞ ' Lb uό cb c N c cb c xf iri Tf τt τf τf τf τf τf xf xf τf τf τf τf τf τf τf τf τf cO C xt τf τf cO C CO CO τf cO xt τt xf τt τf τf τf τf τ ro O O CN CO CO CN x- x- N CO CO x- CJ) Tf UO CD Tf UJ O ro cO CJJ CO O UJ CD OO CM N CD O Tf OO CN O CO x- OO CO N UO N Tf O CO N CM CN N CO O CO CO CD N Tf CD O UJ x- N CM CN x- CD N N x- CM Cθ ro UJ CD O LΩ CM -- τf τf CM OO CM CO Tf UO OO OO CM N τf LΩ χ - CJ ) U0 xf CD 0q U0 C x- N C N CD x-; Tf CO CO Tf cq oθ τt CM UO UJ O O CD τf x- x- UJ O CD N UJ χ t UO CO CM CN CM CO CO CN cd cb uό u τf τf τf ' cb τf τf τf cb UJ CO Tf UJ Tf UJ cd cb ιb uj uό d cb j τf ' N cd ό cb τf uό cD Tf Tf T f cb xt CM CM Tt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf T t T f Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf f Tf Tf x- x- x- CM CM CM x- x- x- CN x- x- x- CM CM CM x- CN O x- CN _. OOOO OO x- CM O 00 < 00 X X X X X X < CD OO < co x x x x < CQ χ χ χ χ χ χ < 00 Ω O OO O X X X X X _., co OO x- CM CO x- CM CO υ o o υ υ o x X X x- CM CO x- CM CO Z OOO OOO X X X x- CM CO x- CM CO O OO OO z I I I I I I I I < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < < O CO O CO O O O r- © C0 τf U0 CD N C0 ro θ x- CN C0 τf UJ CD N C0 ro θ χ - CM C0 τf U0 CD N C0 CJ) O χ - CN C0 τf U0 CD N C0 ro θ . CM CO Tf UO CD N CO CD O x- CM CO Tf O CM CM CN CM CN CM CM CO CO CO CO CO CO CO CO CO OO Tf Tf -xf Tf -^ Tf -sf Tf Tf -^ UJ UJ UJ UO UJ UO UJ UO UO UJ CCDD CD CD CD CD CD CO CD CD CD N N N N N τf τf τf τf τf τf τf τf -ςf τf τf τf xf xf τf τf τf τf τf '^ τf τf τf τf τf τf '^ τf τf τf τf τf τf τf ^- τf τ Tf τTff Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf CO C CO CO CO CO C CO C C CO C CO C CO CO C CO CO C CO C C CO CO CO CO CO CO CO CO CO CO CO C C CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO LO r- © © Ui H U α. CD O O O O O O O x- f O O O O O O O O O O UO O O O O O CM O O O Tf N CO CJ ) τf O O O O O O O CO CM x- Tf CD O O O O O U0 C0 UJ UJ . C .-, CD_ O _. O — • O — O O . CO CN N O O O O O O CO CN CD x- O O O x- O N UJ x- O l_J Ol_J OLJ O>_J OC— > Ol_J OL_J Ol_J C—D xt . x- . CD. O O c_ O L_J O L_J O ι_> O c_ . N. UO. . s ^ . c ^ . ud ud ud ud ud s . s ° . O .. ^χ- ° . uo ' ud ud ud υd s P . c . , ^ • u uo- υd ud χ-cM ' o ' oo ro CM CN CN CM CM CN CN x- CO CD ro CD CM CN CM CM CN ro oO CO CO N CO CM CM CM CM CM CO N CO x- N CN CN CM CM CM CO OO CD x- CM CM CM CO CO Tf xf rv- LΩ CM x- CO LΩ O CD CN O CO CD CN CO CO O lΩ τf θ CJ) N CO τ- x- τf rs χ- CO CO CM θ ro cθ ro ro O CO CD CD x- O UJ N OO χ - CJ ) CO CD UJ OO O N CO CO N OO CO CO τf CO C CM CO τf L CD_J CM ro CN N CD Tf CO CO N N CJ) χ - CO CM UJ 00 CO co τf x- χ - τf N αJ τf cq CN N CD ro χ- CM C CD CD CD τf uq cD Tf CO Tf s CD UJ x — ro N co ro o oo co o CO N uό uό uόu N cb χτ τf cbcd cbcd μd cdcb μ CN CN CN CO CN CO CN CN CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN uj ujN θCM NN θχ- ιnrorocMro cM θ χ- χ- u co co cDro roco roτf cocN corocMcocDCD ro co τf u cθ χ- cMτf coro Nco NUJ CD N ro x- C N C0 CN CM CM 00 C0 C0 τf C0 τf CD UJ C0 UJ CD N x- χ- CO U0 CM ro cθ O CO τf cθ ro CD U0 CM x- τf |s UJ N CO x- N CN τf x^ c» χ -cN cqτf roN LΩ uo χ- o o cq χ- ro τf cM cΩ o cθχ- o χ- cDΦ μ τf cri τf u. τf N c u N ' τf cd cM o cM ibcM ^ τt τf τf τf τf x^ xf τf ^ ^ τf τf τf τf τf τf τf τt τf τf τf τf τf τf τf τf 'ςf τf τf xtf τf τf τf τf τf '^ τf τf τf co CM o ro Tf CM CO CO x- UO CO CO x- CO ro cO Tt cO CN LΩ N CD CN O x- CN O UJ T xfi - u CuO L CiDj u UJ -"— O CJ) x- χ- χ- OO O O CD CO CN ro cθ τf 00 CO CO xt CM CM x- CM ro ro O CO UJ CO UJ CM CD CD Tf CD CD CM O x- OO CO UO ro _. O __ T _f — ~ C0-ι N xf θ ro θ 00 τf CM C0 in c0 CM UJ χ- χ- CD O CJ) O N O N N CD xt CO CD N C- ro- cθ ' C " χ - χ - O ~ CD ' C N OO UJ CD N CM co co co co χ- τf cM CM in o ro τf x- u τt cM in τf oo o N N χ- ro cM cq χ- c lΩ Tf Tf CN x- d τt ' τt τf ' τf lΩ N Lb cd t τt N " τt " t " (b cb τf -^ -xt co uό cd τf rs od ro ro ' ro N αj ro ro d cb cb d N cj. N d Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf f f f τf τf τf τf τf τf τt xt τf τf UJ τf τf UJ UJ τf τf τf UJ UJ UO CM x- CN CQ OQ ^ CN x- 0000 CQ 00 m DQ OQ Ω LULU < χχ ΩΩ LU < co < X X < ωO < xχO < CO X X X X X < O O Z X X X- CM X X X υooυco X x- CM X OOOOO X X x- CM X OOOO X x- CM CO OO OX x- CM Z O O >> >> r- _2^__!__>__?_2_2 __>__> __!>->- >->- >~: s - s >- s - >- >- >- iiJw wu^ xxxxxxxxxxoooυυooooυocθLθLθLθL Lθcocococ co<<<<<<<<<< θ =_ © o LΩ CD N Cθ ro θ χ - CM CO τf LΩ CD N ∞ ro θ χ - CN CO τf UJ CD N Cθ ro θ x- CM CO τf UO CD N Cθ ro θ χ - CM CO τf uJ CD N C» ro θ χ - CN C^ is r^ N N N co co co co cD co co co oo oo ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cM CN CM CM CM CM CM ^ ^ ^ ■ ^ ^ ■ ^ ■ ^ ^ ■ ^ ■ ^ ^ ^ ^ ■ ^ ■ ^. t xf f χf χf χ . χr ^ ^ m m m m m m ι ιn m m m m m m ιn co co co co co co crj c co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co c^ r- © © Ui H U α. UJ o o o o o o o o o o o co CD O O O O O O O O O O O O O N OJ τf CO CO N CO CD O O O O O O O O O O O CO cD uo x- co o o o o o o o q q o o p o p cD x- cq cj) cM c 'r . G*. " . dd dd d d d d ddd d °9 ". d"!ddddddd r O> n O r O , r O' r O' r O' r O' r '" O" O ιn x- OO OO OO N CN CN CN CN CN CN CN CN CN CN CN x- oo ro ro CN CN CN CN CN CN CN CN CN CN CN CN CN 00 OO CD UJ O CD CO N Uj Tf rs CO OO CO CM OO CM O N UJ UJ O OO OO CO OO CO CO CO in CD N CO CO N CD ro CD N x- CD CN LD UJ CO ro CD CO N CO CO O O CN Tf CO CM CM O O Tf Tf CD O x- CO CN 00 τf O τf -^ c CD N ro x- τf CO Uj ro θ N CN N αj τf ιθ x- CM OO OO χ- τf CD CD τf CD CD CD C ro N CN CM co ro co co oo O O N UJ CD CO O N N CD τf |s D CD U0 θ ro θ N χ- C0 UJ τf cO CD U) N N ro θ U0 ro -- 00 ro c CD cq CD C 0 00 d ιb τf cb ιb N cb τr u cb cb cM τf u b τf ' od ' " uό cb CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CD N CD x- CD UJ N O χ - χ - CD UJ χ - OO CD C» lΩ CD O N ro θ ro uθ CM τf x- O O CD CO CM χ- CO N CD CO χ- N τf CD N θ ro CM C τf ro CD CM O CO Uθ ro cD O x- x- O χ- CM CO CO N χ- CM CD O CO N CD CO CD τf uO CM τf cθ N CO CM CO C CN CO τf O CM CM CM CM ro χ- ro ro θ x- ro CO O CD τf c^ N N iΩ cq cq uj τf '^ ι cD τf ro cq o cθ χ- uj cM θ co u o ro τf c N θ co τf cN U ro u τf uj cM θ co ro χ^ cd uό uό τf uό uό τf cd τf ' cb τf ' b od ro d N ro d ro d ro- d d d ro ^ ^ ^ ^ - ^ N- ^ ^ ^ ^ ^ ^ ^ f xf xf m ^ - _) ^ m ^. m m ^ ^ f ^ ^ m ^ ^ ^ ^ ^ N- ^ ^ ^ , t CO UO CO UJ x- UJ CD CD CM CM O CO N CD UJ CM N x- ro N CO OO CM UO O O OO N τf cθ CD CD CM O CO Cθ x- χt O CN τt CO N CD O CO CN τf c UJ x- C 00 CO CM CM 00 CO Tf O CN CO CO lΩ O O CΩ CD x- D CO O CN O χ- χ- O lΩ CN O τf |S xf CD N τt O O CO CO O CO CO CO O CD CD CD Cθ ro χ- CO O CO Tf U0 CN OJ Tf U0 N τf CO τf x- χ- 0θ ro CN CM τf x- CM N CO N χ- O O CN χ- CD x- N O x- ro UJ N O OO CD CJ) x- CO O O C UJ N τf UO CJ) θ ro θ x- CM CM CM CO CJ) ^ CM b c c τf cd O CD CD O CJ ) r 0) N N lri lri ; CθV cO N N l : lri lri lri ( C. lri τ : CM ^ UJ UJ UJ UJ UJ Tf UJ LΩ UO UJ UJ UJ UJ UO UO UO UO UJ t Tf UJ τf UJ τf τf τf τf τf τf τf -^ τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf x- x- CN CN CM x- x- x- x- x- x- CM x- OOOOOΩ ΩΩ m co O Ω Ω xx OQO Ω < C Q X X X X X XX X < O Q O Ω LU N X X O O O X X X x- CM x- CM CO x- CM CO OOO X Ϊ CM OOOOOZOZZ - XrX X- CM X- CM X- x CM X X- CM ^ ^ ^ ^ ^ ^^ O O O O O Ooict oiQlQ- r- LU LU LU LU LU UJ UJ UJ LU LU LU ULJ UJ LU LU UJ — i— i — i — i — i — i — I Q: Q. Q: O_ __: Q: Q_ Q_ Q_ Q_ Q. __: Q_ Q_ __: __: __: __: __: __: Q. Q- __: C_: LU LU LU LU LU 0000000 < < < < < < < < < < < < < < < < < < < < < < < < CO CO CO CO CO © o N C0 ro θ χ - CM C0 τf LΩ CD N Cθ ro θ χ - CM C0 τf UJ CD N 00 ro θ χ- CM C0 τf LΩ CD N C0 ro θ x- CN 00 τf U0 CD N 00 ro θ x- CM C0 τf UJ (N tN tN co c co c c c co c ^ t '^ ^ ^f ^ '. ^ 'f ^f m m m m m m o o cD o co o co fO co o N N N N N N N N N m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO O CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ LO r- © © Ui H U α. UJ O O O O O Tf OO O O O N CN O O O O O O O O 00 τf Tf CO O O O O O O O O O O CM CJJ CM N O O O O O O Tf O CM CO O O O CO O CM CO CO O O O O O O O O CD UJ CN CO CO UJ CM Tf Tf rs O O O O O O O O O N O CO CO x- T^ d d d d d d ^ 0 . ^ - d d d 00 UO d ' N". d dd dd dd "^. d d ^ ∞ . " "^ OT . " . d d d dd dd dd dd d oi oi x- CM CM CM CM CM x- OO CD x- CM CM CM CD CD CO CN CN CN CN CM CM CM CJ) χ - x- x- Cθ ro χ - χ - CD CD CD CM CM CM CM CM CM CN CM CN x- x- x- x- x- x- CD CO CO N UJ CM UJ CO N CO CD CO CD CO CO N oq N N 00 CO x- CO Tf cb cb cb -xt LO cb Tf ro cθ N CO CO θ ro c Cθ ro ro χ- ro UJ N χ- O CCDO ττff CroD Oθ OO CCOO CCMM UUOO CCMM NN CCNN CCNN CCNN CCθθ roro uujj NN OO NN OO CCOO ττff ττff ccDD CCOO CCDD CCJJ)) χ- U UJJ CCMM UUJJ NN C COO C CMM C CJD) O N U) τf CD CD CM UJ N N CJ) CJ) C χ- CD O C C CMN NN NN xx-- CCDD CCNN iUnJ ττff CN Cθ ro CN OO x- CD Cθ αj UJ N χ- CO CO CM UJ CO N CO CN CM CJ) ro τf θ ro cθ oq q iΩ τf cM x- cM ro cq c» oq ro τf o o u cq NN NN χχ -- CcDD Oθ CCNN roro NN τf UJ UJ χ t CM O x- O CD CM lΩ χ - N N CCDD CCOO CCMM CCMM CCMM N x- UJ CD CN CD O CN CD ιri c od ro ro cb ro ro cM cb c τ o cb uj τf cM uό uό uό N N ^ d χ - ' cθ d - CN (D CM CI) 0 - '* s t , !. f ^. ^. ^. m ^ " N- ιn m m m m m m m m m m m m m ' m χ . - CM Uj ro ro C0 ro CN UJ CD ro τt Cθ ro U0 CM CD χ- C0 τf CM χ- UJ 0000 O x- CD CD 00 C0 C0 N CM C0 U0 C0 N UJ O UJ O N O Tf CO LO N CO x- CD UO CD CM CD CO CD CD N CO CM ro c CN O xf UJ C τf x- UJ ro χ- CD N CO CO CJ) x- CM C ro CD CD O CM CD CM CJ) O N τf ro CO OO N CO CD Uj Tf O CO ro CD N ro θ O O CM χ - CO CO χ- CM χ- CD χ- CD CO χ- CD CO CN O τf cD CD O CD N CO CD N τf x- CM CD CD x- CO UJ N co cD Tt D UJ CM x- CD N q q cq m d ^ d ^ d ^ d ffl cd ffl od m ffl d d ffi N ' N iD io n w cb cb ib cd cb CM uό CM c ro d o ^ - ^ ^ ^ ^ m ^ ^ ^ ^ ^ ^ xf i- f }- χ t ^ τf χ t )' χ t i- χf . j- f N" Tf Tf Tf xf Tf xf xf xf xf Tf UJ UJ UO CM CM CM T- CM o OQ 00 < < TZ OO x- CM x- CM CQ CO • "- CM x- CM < ooOO τ- o -. X X <oo χ xx Ω LU LU N < OQ o X X x- CM X OOO X x- CM OOOOO I I I I r- ( C o <ooo GOOooΩΩooLULυUυN < χ χ Ω X X X- CM X X X X X Z O O O O o_ c_:__: c_:Q: Q;>- >->- >- >- : s - : s - Q_α_ Ω: Q_ Q_ Q_ _£ Q_ Q_Q_ Q-_^ r- uj mw wm w-^ -^-J ^-^-J -Jxx x xx x x x xx xx xx xx xx xxxx xxxxxx x xx xx >-^ >->->- (fltO(OWCflM(DϋOϋϋϋ(Dhh hh hh h hh Q.Q.l _ __-l-l_ ___D. _. © ro θ χ- CN CO χ t lΩ CΩ N ro ro θ x- CN C τf J CO N ∞ ro θ χ- CN CO τf iΛ CO N rø ro θ x- CN CO τf U) CD N ∞ o N co co co oo co co co co co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cN CM CM CM CM CM CM CM CM CM co m m m m m m m m m m m m m m m m m m <θ (D (θ (D (D (θ co co cD cD co co co co co cD (θ cθ (θ co co co co cD cθ (θ cD co (D (θ <o CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO W r- © © Ui P H U α. CD N CJJ O -r- T- 1 T- X- CD τf O N CD ro CM C0 CO x- U0 U0 N CD CO UJ CD CN CJ) UJ CM CO τf CO CO Uj Tf OO x- CM OO CD CO CD CD CO UJ CJ) x- O CO CM x- UJ OO N CO x- CO CO CM ro CD CO OO x- CN lO x- N Tf io CD O N CO CN CN CO CO x- O CO CD Tf x- N CM OO CD N N x- UJ CO x- x- CM x- N CN UJ UJ x- CO Tf UO UO CD UJ OO Tf CD UJ q ro N χ - τf τf x- CM χ - O CO CM ro θ CM CO CM CO CO lΩ CM χ- UJ O x- N CN N CO CM CD Cθ q cθ CD O τf cO Tf CO N CD O cM oo co N ro N ro o x- τt cN Lri Lri cb cb τf -^ . d cM cb τ cd τf cN M cb CM CO lb τf τf b d N τt c uj τf cd τf θd CD d c ro o cb cb rs N cd ro cj μ ro C CO CO CO CO CO CO C CO C CO CO CO CO C CO CO CO C CO C CO CO CO C CO C CO CO C CO CO CO CO CO CO C CO Tf CO CO Tf Tf CO CO CO CO CO CO CO Tf CO J N UO ro cD ro CD CO CO CO O N CO UJ LΩ τf θ N LΩ CD CD C ro CD CJ) CD τf σ cθ C _D CO O _ C.. ro_ . C_J) . χ - 0 _0_ O τf N CD OO O CO N CM UJ τf rs CD UO x- CM O CD N CO x- CO CM CJ ) x- C τf oθ N O CD CO τf CD N CO CD . N CD τf ro UJ x- C C x- CM CD CD τf UJ CO O CD CJ ) θ ro ro θO CO CM CO N N UJ N O UO CD CO CO x- cq O ∞ CO CN UJ CO x- U Tf OO CD Tf U. CN Tf C0 00 00 χ- O x- N ro τf UJ χ- CD τf x- CM τf O CN O C0 ' N' O Λ — Tf - CO~ 0 O0D O θ ro ro CO CM Cθ τf UJ ττff uuόO CD ττff CCNN cCb ττff ccd cCbD cCDb uUJj COocCbO τf uJ UJ CD CD CO CD τf rs CD N N xf τf τf uJ CN CM CO χ - τf UJ CM C^ ^ m m xf N- ^ m m m m m m in m m m m m m m m m m m m m m m m m m m m m m in m m m m m m m m m m m C0 CD LΩ 00 C0 Tf O UJ O CD CN N O CN N ro LJJ CO OUJJ xx-- OC- . χ t t m χ)- , <" ^r ' ^. - - , ! - , t " , ' x- x- x- CM CM CN 00 OQ x- CM ^ CO OO .- Ω Ω Ω Ω Ω Ω ffl CD OQ x- CM CQ CQ < xχ O < 00 Ω Ω < x χ χx xx xx < ^ C Q <xxx < 00 Ω Ω < CQ CO X X x- CM X OOOOOOO X X X- CM X X- CM CO X- CN CO Z O OO O X X X- CM CO OOOOOOO - Xr X x- CN OOOO ωw WWW3333333333333333333 << << < < < <<<Q- Q-Q-CLQ-0_ _LQ. Q-Q- CL_L Q_Q_ 0_ __: _-: r- >->- >- >-llJ _Jl_l_l_UJl. l_l_l__Jt_lJl_llJ l_l_ l_llJJJJJ JJJJJJW(ΛW(/3(ΛW 000000-J -J_l _l _l _J _J_J_l_J _l _J _l_l _l _l_l _l_J << << <<<<<<<<<<<< << << <<|-r-r-r-r- © . C .M- C.O- T-f UJ CD N Cθ ro θ χ - CM C τf LΩ CD N Cθ ro θ χ - CM C τf uJ CD N CO CD O χ - CM CO τf UJ CD N CO CD O x.- C * M„ C.O- T-f, -.- ^ ■ - __ - O -- x . » - CO CO Cθ CO CO CO CO Cθ C τf τf τf τf τf τf -^ τf -f τf Lθ UO UO UO UJ UJ UO UJ UJ UJ CD CD O CO CD CD CD CD CD CD N N N NN NN sNsUJsCD N CsOsrooooo- CoN o o CD O CD CD CD CD CD CD CD CO CD CD CD CO CD CO CD CD CD CO CD CD CD CD CD CD CD CD CD CD O CD CD CO CO CD CD CD CO CO OO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ LO r- © © Ui H U α. O CD O O O O O O O UJ CO CD CD CO CM O O O O O O UO Tf C0 C0 O O O O O O O O O O O τf O CΩ O O χ- O χ - O O O O O CO CO O O O O O O O CD CD CD Uj Tf Tf O O O O O CM CD Tf CD N CD Tf O O O O O O O O O O O CM CD CO O ro cO ro ro O O O O O x- O O O O O O O O O O CN CO O co σ o o o o O x- CM Tf Tf UJ x- O O O O O O O O O O O CO CM CO UO CM N N N O O O O O x- x- CN CN CM CN CM CM CM x- x- x- x- x- x- CM CM CM CM CM x- ro oo X- CN CM CM CM CM CM CM CM CM CM CM T- X- X- X- T- X- X- X- CN CN CM CM CM CO CD O UJ CM CM CO xt CO o ro ro cD N Tf co xt co co O CO CM UJ O Tt CN CD CD x- CO CD CO CN UJ CO CN xt CO CO OO x- N O CΩ CO O LΩ CO CΩ OO xt ro cO CD CD LΩ CΩ CO CN oo o o ro ro co oo cN co Tf uJ co co u co Tf OO CM CO CO Tf τf cO CO CO Cθ τf - - τf τt τf τf τf τf τf τf f xf τt CO CD CM O CO CD CD CD CD Tf CD N CD xt O CO ro cO UJ CM CO CM CO CD O ro in CO CN CD O Tf Tf OO UJ CD O O Tf x- cD CD CD UJ CD CD τf τf c0 τf x- θ N x- O CN UJ N τf C0 ro CD C0 C0 τf c0 N C0 τf x- r-. CM CD N N lΩ CN CO Tf rs CN lΩ CΩ O UJ O O CD CD CM OO LΩ CO CM CO Tf UJ CO UO CO CM x- UJ ro cO CM O OO O UO ) x- O O UJ N UJ CJ) UJ Uj Tf CJ) O x- UJ - in cN o p Tf Tt j u ro cM x- CM CO CO CO x- CM C x- UJ N OO CO CO N UJ N C roD OcOo CdD N ∞ ro co ro o ro N ro ro N ro ro co ro b xT cb cb cN UO UJ O O UJ in in uo u uj uj uo uj uj uo uj uj in UO UJ UJ UJ UJ UJ UJ UO CD UO UO UJ UJ UJ UJ CD CD CD UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UJ LΩ UJ CN CN CM x- x- x- CM CN CN ■ <- CM x- x- CM x- CN DQ OQ O O < co O χ χ χ < ωo < Cx Q Cχ Q O ,„ < CO Ω Ω <XχOχχχχχχ < C0 ΩΩ < χ χ O OX XX X x- CN co O O O O C X X X- CM X O OO OO O X X- CM X X- CM CO X- CM CO Z O O O OO OO X X X- CN X Q_ Q_ C_: Q_ Q Q Q_ Q O_ ( -0 W CO -O C C C0 C C C CO Z) 33 33 33 33 333333 33 3 3 3 3 33 33 33 33 333 r- ι ιι ι ι iι ιι >- >- >- >- > >- >- _ _ _ _ _ ijj _ _ _ _ _ ι_ _j _j m ι_ LU_j_J i_ _JUJ UJ_j m r- r- r- r- r- r- r- |- r- 00000000000 _J _l _J _l _J _J _J _l _J _J — I I I I I I — I I I — I — I — I — I — I — I — I — I — I — I — I — I — I © C τf LΩ CD N C» ro θ χ - CN CO τf LΩ CD N Cθ ro θ χ - CN CO τf UJ CD N OO CJ) O x- CN CO τf UJ CD N CO CD O CM CO Tf UJ CO N OO ro O x- CN CO Tf o co co ∞ co co co cD ro ro ro ro ro ro ro cD CD ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- CM CM C -M C-M C-M C-M CN CN CN CN CO CO CO CO CO CO CΩ CO CD CO CO CΩ CD CO CD CO CO CO CO CΩ CD CD N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N CO OO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M co co co co co co co co co r- © © Ui P H U α. O O O O O O CD CO CD CO x- CD CO CO O O O O O O O O O O O CD O N CM O CO CO x- O O O O O O O O O CD CM CM CD N CO O CO O O O O O O O O O CO OO Tf CD CN CO CM O O O O O O O O O O O O x- CO CO ro OO ro O O O O O O O O O O CD N N Tf rv- N CO O O O o o o o σ o T f m UJ UJ UJ co o CD O O O O O O O O O O O Tf CD OO N N CN N x- O O O O O O O O O N CO O CO UJ UJ UJ CN O O CM CM CM CM CM CM x- CM CM CM CM CM CM CM CM CM CM CM x- x- x- x- x- CM CM CM CM CM CN CN CM CM CM CN CN x- x- CM x- x- x- x- x- CM CM UJ O CD CO CD CO O O CO LΩ CO UJ CO CD x- CN Tf CN OO O CD CD x- τf [s x- |s τf 00 O UJ Tf N lΩ CD O OO CO CD CO CJ) CD CD CJ) N CJ) O Uj σ ) τf CN N x- x- N UO ro CD CM CD OO CM CO CO OO N CD CO N CM Tf cO CO χ - CJ) N CD χ - CO τf 0O N OO Tf lΩ CO Tt ro CD CO x- Tf O UO Tf x- OO CN CO Tf LΩ CD CM O CO UJ CD CO N CM N D C -D O- U--O C-J) N- ro UJ x- CN CD CM Tf CD O CO CO x- UJ CO CO OO CM Tf ro cq u j p cM UJ O x- (O N ro cN CO N N co co ro q U0 CD UJ τf CM τf cO τf τf U0 CM CO x- CO CN f CM CM cb τ cb uj cb cb τf ib cb cM CM CN f CN CM cd cd biri bαJ ro ' cD sscd ^s Tt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf μ Tf d Tf Tf Tf Tf Tf Tf Tf Tf Tf o M- ■ * - f t ^ ■ * f ■ N" ■ * CD O. Tt O CD x- τf UJ CO O CO O CM O O UJ <» ro in cθ CD χ- CM ro CD O CM x- CN CD CO N N τt CM CM ro N τf CM N CN CO CN CN LΩ N N O CO CO CO LΩ UJ τ^ C CD C» τf O CD CM CM O CO N O UJ CM N N τf τf CJJ Cθ O UJ CD UJ CD τf θ CO τf cJ) CO CM CO CO CO χ - CO x- ro cθ O OO τf x- x- x- cθ CM ro τ^ cq CN χ - CN ro τf ( q θ τf CD ro cM N O CD CM ro u OO CD O CM xt CO CO CM CD N UO O U x- OO CO χ - U ro χ - CD CO χ - UO τ mf τf ' cmb cmM m m m Nm cmb cmb m m uJ j dm m N m m md um j mτ bm τmf mCD oco co 'c^o ^(θ cD CD CD co (θ (θ cθ (D (D co cD m m (om (D mm(θ _D Z)Z) _D Z) 33333333333333333333 t — •— •— •— •— •— ^ *— •— I- •— •— ^ I- I- ^ ^ Q- Q- Q- Q- Q- CL Q- Q- CL Q_ r- LU LU LU ω UJ LU LU LU W LU LU UJ UJ LU LU LU LU IJ_ LU LU ω iU UJ LU ω ! y !_- !_^ — i — i — ι _j _J — i — i — 1 _ i — i i i — i — i — i — i i i i i i ι _ι _ι _j -_: __: __: _≥ --i -≥ -≥ __: __: __: __: __: __: __: _-: __: _ < < < < < < < < < < © UJ CD N C0 ro θ x- CM CO τf UJ CD N ∞ ro θ x- CM C0 τf UJ CD N C0 ro θ x- CN C0 τf UJ CD N C0 ro θ χ - CM C0 τf U0 CD N C0 ro θ χ^ o 00 CO C C0 CO τf τf τf τf '^ '^ xf τf τf '^ LΩ U0 UJ UJ U0 UJ U0 UJ UJ UJ CD CD O CD CD CD CD CD CD CD N N N N N N N N N N C CD CD ∞ NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN oo co co coco co co co co co co co co co co co co co co co co co co co co coco co co co co co co co co co co co co oo co r- © © Ui H U α. O O N OO x- UO CO x- UJ CO CM O O O O O O O O O O O O O CO UJ x- CO CD O CM CM CD UO N O O O O O O O O O O O O O CO CD CD xf O O q N ro CM CM x- c uj p p O O O O O q o p O O O x- CM UJ CO ro CD N N Tf UO CM O O O O O O O O O O O O O O CD x- UJ o ' cM N Nμ χ - Lri oo ' d d o d d d d d d dd dro d cb rouJ uό roτf rocbτf d d CN CN CN CN CN CN CO C xt xt τf CN CN CN CN CN CN CN CN CN CN CN CN CN CN CO CN CN CO CO CO τf τf τf UJ CN CN CN CN CN CN CN C^ 00 CO x- 00 x- CO CD CO UJ oόo. cd xf Tf Tf CN x- O UO O CD Tf Tf CM CM CD x- x- CM O O OO UJ CD Tf CD O CD CM CM CM CD O CD CN O O cM x- x- co ro co ro ro o o co N OO x- CO LΩ UJ CO CO ro Tf CD Tf CM Tf CO N CO N O CM CO CM O O O CM x- O CO x- CD CO CD N N O CM O Tf Tf lΩ N -O ro iΩ LΩ x- CD CO O CO N CD O CD CO N N CD N CO N x- CD Tf CD x- N CD Uj Tf CM CM CM CO CM N Tf cO x- CO CD CO x- O Tf xt N N x- N O UJ CO CO CD N Tf CD O N x- CM ro uj τf q ro o cM 00 CO CO CO CO CD CD τf cθ CM C0 C0 CD CD CD CD τf xf cO τf CM x- O CN CO O O O CO CO CO CO O O CD O O O cdN OJ cbcM cbib cb m m m mm m m mmmmm mmmm mmmcD coco cDCD cocoinin mcDCD cDCDCD CDco m cococo co CO CO CO τf x- CN χ- χ- τf CN CN CO x- N CO CM CN τt CO Cθ ro χ- CO CO CO O CM CO CD lΩ χ- CM CD χ- x- CN N τf CM N N CO τf rs τ^ τf CM CO N CO UO O CM CD O CO CD N CO N N τf CJ ) CM CO χ - CO N CO CD CM χ - CO CO CM N τf ιn cθ CO CM CM x- lΩ N Uj ro CD N χ- CN τf CM ro χ - uoro qro roro cMuj uq cq χ- ro ooo θ χ- cD uoN uj χ-cM CDN ro τf roχ- co roco cMNcD ro cM uo ro uo ro cDCD roco o ro cM cb τf Lri cb ιb τf τf cd cM cb cb d ιb u τf cb τf uό cb m - m m m m m m m m m m m m m m m m m m m m m m m m m m mm m m m m m co mco m m m m m < Λ Z O O O Q-C mm mm m mm mmm mmm mmO OOOO OOOOOOOOOOOO OOOO OOOcocococo r- ^^ > l-LCL t LTL CC L^ < <—I —l-l—l-J-J—I —1—1—I—I—l-J-J—I —1—1—I—I —I—! _)< << << <<<<<<<<<<<<<<<<<< <_I —l_J_l © o N 00 ro θ x- CN C0 τt U0 ( D N 00 ro θ χ - CN C τf UJ O N Cθ ro θ χ- CN C0 τf UJ CD N Cθ ro θ χ- CM C 'xt lΩ CD N C0 ro θ χ- CM C^ oo co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cM CM CM CM CM CM CM CM CN CM co co co co co co co co co N N N NN N N NN N N N N C0 CO Cθω ω 00 ω (O (O C0 (O ∞ C0 (θ ω (O (O (O (O(O COC000 (D COC00000 C0C0 C0 C000 C0000D 00 (D (D CO CO CO CO C 00 CO C CO CO CO CO CO CO CO CO C CO CO CO CO CO CO CO CO CO C CO CO CO CO CO CO CO CO CO CO CO CO CO M r- © © Ui H U α. UJ O x- Tf CM O O O O O O O O O O O O O CO IΩ x- OO 00 Tf N x- O O O O CO CM N CN CD N O O O O O O O CD x- CD CO CD N O O Tt x- N CJ) N O O O O O O O O O O O O O Tf oO Tf Tf U) CD N Tf O O O O UJ CM N CO N x- O O O O O O O Tf CM x- CD CO UJ O O CO O O N N O O O O O O O O O O O O O x- CN x- χ- lΩ CJ) χ- O O O O O O CN τf C CMN COOO CCNN CCNM OO OO OO OO OO OO OO CCθD roOJ COOO OO CCNM NN OO OO CN CN CN x- CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN U0 O 00 ro x- CD CD τf h> UJ CM ro UJ O C0 χ- ∞ CM O CM U0 C0 CD CD τf ro C0 N CD ro τf U0 N CM CM CD τf |s cD U0 CD τf CM N O O C0 θ ro τf LΩ N N O θ τf x- S oθ CO UJ CD CO N CO OO OO τf CD CD f CD UJ UJ CM τf ro τf rs LΩ lO C0 UJ N C0 UJ τf CD U0 χ- CD χ- CD CJ) 00 C0 O CD CO τf O O CM CO CD N CO CD τf CM ro c Cθ UJ τf cD OO C N τf UJ ro UJ N O Uj Tf rs CM CO CO OO x- CN x- x- CN O CO x- UO CO ro CD CO UJ CM N CJ) rooroorocoNCDOx-ococDoocoooroNC D uoT f rs CD UO CD N N N OO τf c CN x- CM τf LΩ CO CM CN τf xt CD UJ CM χ- χ- O CM CM CO O τf UO τf UJ τf .sf τf τf ιn UJ UO τf τf UJ UJ τf τf τf τf τf τf τf τf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf Tf Tf Tf Tf Tf Tf Tf CM CM CM CN CO O CO CM O CO τf CM x- O C C N ro CM x- τf c OO N ro τf θO UJ Oθ ro CO CD N N CO O τf C X j O N O CM CO CD N C» Cθ ro CD C τ^ 0_ x- O CO UJ CO N τf CD CN J χ- CD N ∞ χ- χ- θ α_ J τf O CQ CΩ χ- τt O O χ- CD CO χ- O τt iΛ lΩ CN ∞ CO CO CO C^ CO Tf CM CM ro cO CO CO UJ CD Tf oO x- CD CN CO CO Tf - - CM ro x- ro N CO CO UO CO ro cO CD Tt c UJ CD CO CO Tf c^ τf CO CO CM χ- χ- CO U0 τf cθ CM CM τf CM χ- χ- CN χ- τf U0 τf '«ϊ '^ U) CD LΩ C CD CO UJ UJ UJ UJ τf CD N CO t CD N ∞ CΩ CO CO CO O CD CD CD CΩ CD CΩ CO CΩ CO CΩ CD CO CO CO CO CD CΩ CD CO CΩ CD CO CD CΩ CD CD CO CD CO CD CD CD CΩ CD CΩ CO Φ C0 C0 CM U0 O 00 χ- C0 τf τf CD τf CM CJ) CM O 00 N σ) CD C0 00 CD τf CM C0 O CJ) UJ N CJ) CO CJ) CM CO x- τf cθ CN CD UJ CM CD τf τf CM χ - τf rs O CD CN O CO O UJ CD N CD ro O CO OO Uj Tf uJ x- O Tf oO O Tf CD x- Tf CD O CD O CD N CO O CD N Tf UJ CD CO τf CM CD τf ro cθ τf τf cθ O O CO CO CM CO N UJ UJ xt ro O CO Tf cO x- CO O O CD CO x- CD OO CO UJ x- CM CM CO xt O CD Tt CM UO CO UO UO Tf ro cO N CD O ro CD CN UJ CD N N CO CO CD CD Tf CM χ- θ ro CD CO CO CM CO χ- CM O θ ro ro c CO N lΩ CD N C» ro cθ O CD CD CO CO lΩ UJ CD CD τf cθ τf 'xf c UJ CO CM τf UJ N ∞ m - - m m m - ^- - N- N- m m m m m m to m m m m m m m o m m -~ /r» rv _. _0C Q Ω Ω LU LUN NN x- CM coco ,„ ωcoOOΩΩ C Q OΩ LUN < xx x x x χχ xx x x < GQ O Ω Ω <X X < Λ CO Ω< χ χ χ χχ χ < ω O < O O O O Z X X x- CM x- CM x- CM x- CM x- CM CO OOOO OOO X X- CN Z O O O O O O X X- CM X- CM X- CM OO OO OX X wcocococococowcoσjcocow cΛωωωQ- Q- α- Q-Q- Q-Q- O-Q- Q-Q- Q-OOOOOOOOOOOO r- _l ^ ^ _l _l _l _l ^ ^ ^ _J _J _l _l _J _l -J ^ < < < < < < < < < < < < CL Q- CL CL CL CL Q- _L CL O- CL CL CL CL < 5 C C C W © o ro θ χ- CM CO τf UJ CD N Oθ ro θ χ- CM CO τf ι_. CD N Cθ ro θ χ- CM CO τf UJ CO N Cθ ro θ χ- CN CO τf L Ω CD N Cθ ro θ χ- CN C τf ι^ CO τf -τf '^ τf τf τf '^ 'r τf 'xf J UO UJ UO lΩ UO U UO UJ UJ Cθ Lθ CD CD CD CD O CD CD CD N N N N N N N N N N ∞ 00 CO CO 00 CO ∞ 00 00 C0 C» C0 CO CO CO CO Cθ αj CO 00 CO CO CO CO CO CO CO CO <X) C0 C0 CO CO C0 C0 CO ∞ CO CO CO CO CO CO OO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO rt r- © © Ui P H U α. O O O τf | s | s x- c000 O O O O O lΩ O C0 CJ ) C0 C0 N O O O O O O O O O CN 00 x- x- CJ ) x- C0 C0 O O O O O N O x- ro N CO J O O q q q ro ro q τf U j χ - o o o o o τf cM CM τf LΩ N χ - o o o o o o q o o ro ro cD LΩ co co uj o o o o o θ χ - cM N CD O x- CO O O d d d ιb cb cb cb τ f cri d d d d d cM μ μ cM CM θ N o d o o d d d ro ro N ∞ μ ιb cb cN CM CM CM CM CM CN CN CN CM CM CM CM CM CM CM CM CM CM CM CM x- CM CM CM CM CM CN CM CM CM x- x- x- x- CM CN CM CO CM CM CN CN x- x- x- x ^ CN CM O CO ro CO OO UJ CD OO CO CO O OOO CCDD CCDD x- N CM CM O O CO OO CD Tf CD CD CD CD UJ OO CM C —O C —O O — CD τf OO CD χ- UJ cM co o o ro ro co co oo oo N cqiΩcq τf CD CN c N cb cM τf τf ' b CN lΩ « ■ f+ ■ x χ_t+- x - —- 0 i — CO .cθt «τ+f iU"0. UJ Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf CO CO CO CO CO τf τf rs co cD co ro uo χ- θ χ- CO CJ ) CO χ - N CD C τf CD CD O CO O N χ- CJ) x- CO CD O CD CJ) x- OO CM x- CD x- N CD CO O CM x- CM CD CJ) Tf OO ro UJ ro uJ CD x- CD O x- Tf cO O x- Tf Tf x- CO CN Tf CD CO CO CM Tf cO CO OO OO x- O O UJ N CO OO ro ro UJ N CO O OO CD N CD x- CM CD UJ O Tf CD UJ N CD τf θ CD τf cq τf oq τf CD OO Tf CD O CN O CM x- Tf CO O O CN Cq N CO ro χ - OO LΩ C τf τf CM CM τf cD CO N τf cθ O O CM χ - CD O O χ - xt O CD N i Ni CDi Txfr CO CiMN x— C CM CiMN TXf C'J tC'jV— o tiMN ^x— T x—- ' t CNNi dCJ dC J xX—- C-J d-J OJ oC-JJ X— ro CM O O O O CJ) C0 O O O O CJ) χ- ro χ— O ro cO CD O x— CJ) χ— x— OO cD (0 (D (D (0 (D CD cD (o cD (D CD co (D (0 (0 (0 (o co cD co co cD m m cD co co (D (D (o m m (D CD CD CD m cD m cD co m m m cD co co co m χ - x- θ LΩ CJ) N x- UJ UJ CJ) O x- C0 τf CD τf CN UJ χ- χ- UJ 00 O UJ CO CM CO ro CN ro xt CN CO O CO CM CD LD CM x- N OO x- UJ N OO CN CN CO xt CO Tf UJ CM N CM O O UJ CD CM UJ x- CO -Ω x- N CO CO N ro iΩ CD CO O CO OO UJ OO CO UJ CM CO CM CD x- CD CO O Tf CD CO CD O τf x- UJ UO OO CD CO CD τt uj CO UJ CD CD OO xt CM CD OO Tt OO CO CO UO x- CO x- CD CO xf CD U UJ UJ CO CN τf U0 CN N O τf U000 CD CD O 00 xf χ - CM Tf CD N Tf x- CD CO CD t x- d oON ' rod dx- dro ro x- CO ro co ro CO N CD CD CO CD N CD CD in CD N lΩ O O ro CD CM CM CO O O CM cM cb r-i cd od cb uό uό xt o N co m m m co (O CD cD m (o cD (o m m m m m m m -j m m m m m m cD CD m cD co co co co cD CD co m m m m m m m m m x- x- x- CM CM CM CQ GQ CO CQ x- CM O x- CM CO CQ - CM x- χ χ < ω < X X θ < OQ < CQ χ χ χ χ χ χ < DQ Ω Ω < X X < GO O O Ω < X- CM X Z O O O O O X X x- CM X O O O X X X x- CM CO x- CM CO OOOOOO X X X- CM Z O O O O O O O X X C_: __: __: Q: O; OI _C __: __: Q QI Q_ Q_ Q _ J ^ ^ ^ ^ ^ ^ ^ ^ _J ^ ^ ^ ^ _J ^ CL Q- 0- 0. O- CL Q- Q- Q. _L Q- CL , r- u j _ j m _ j ι_ιm u j _J ii j _Ju j < << <<< <<< << << << <(/ wc/)wwwwwwwww L 4 ^^ cococococ cococococococococo>> > > > > > >> >> >> >> > < < <<< < < < < < < <__! __! __!__! __! __!__!__! © χ - CM CO τf UJ CD N Cθ ro θ χ- CM C τf LΩ CD N Oθ ro θ χ- CM CO τf LΩ CD N CD ro θ χ- CM CO τf UJ CD N CD ro θ χ- CM CO τf UJ CO N Cθ ro θ χ^ o ro ro ro ro ro or ro ro ro o o o o o o o o o o χ- χ- χ- χ- χ- χ- χ- χ- χ- χ- CM CM CM CM CM CM CM CM CM CM co co co co co co co co co co f τf τf (X) oo co co co co co co co ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro cJ) CJ) CJ) co co co co co co co co oo co co co co co co co co co co co co co co co co co co co co co co co co co co co cθ co co co cθ c^ OOOOOOOOO x- CM CM CM f x- CO O CD O O O O O O O O O O O O O ro N x- CO N x- UJ x- Tf O O O O O O O O O O O O OOOOOOOOO CD x- CD x- CO CO N xt O O O O O O O O O O O O O O χ - χ - CO CO τf τf N O τf O O O O O θ q θ O O O O dodo od do y d ή d -^ ^ d \^ d d d d d d d d d d d d d \^ y ό d 1 d ^ tJ- 'r - d d d d d d d d d d d d CM CM CM CM CM CM CN CM CM χ - x- χ - χ - χ - CO Cθ τf τf CM CM CM CM CM CN CM CM CM CM CM CN CM x- x- χ - χ - CM CM CO CO τf CM CM CM CM CM CM CM CM CM CM CN CM χ - χ - CD τf c0 CD CD O LΩ C0 C0 O CD CD C0 UJ N UJ CD O x- CJ ) τf cD U0 τf CD C0 CD ro θ UJ O x- O O OO UUO0 NN Tf CD CO CD O CD Tf N UJ UO Tf O ro cO O N Tf O N CO CD UJ CO CO ro cD UJ CO OO UJ UJ OO N O N O CM CO x- UJ UO x- N CM O N OO CM CO O CO Tf Tf cN co in ro ro cN N Tf co co ro O O N N τf '^ <q cM CO x^ CM χ - N χ - U UJj ro 00 θO C CNM CCNN N CO CD CO CO CM Cθ ro θ τf τf O CN CM CD N τf CM CO N τf N O O CD O τf τf U0 N Cθ ro c i' L ubj u uj c Lb'J c IMN C INN c L'J c Lb' T XTf c CdJ c IMN c CbJ c INN x— O ι_ C LJDJ χ ~ x~ c Lb'J x~ O χ ~ x— CJ ) CD i CJ) O CM x- O CN T LΩ UJ UJ CD N CO r-i t Tf N CQ cb cO CO CO CO UJ N N CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CO CO CO CO CO CO CO CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO rt o o u. ro co χ - co cD ro τf cD M- CM C N CO N M- N CM N O CM τf τf c0 CD UJ CD UJ τf c0 O CD CD CM O N χ - ro CN CD 00 00 CD CM ro θ UJ UJ N C0 χ - 00 CM Tf UJ N N Tf CD CD CO O CD O CM CD UJ CD N C0 N τf r s - U0 CD O C0 CM N CD χ- N τf cD C0 τt x- UJ CM N N τf r s - CD C0 CD O C0 00 CD χ - x- x- N CD CO CO Tf LΩ Tf cO CO O χ - LΩ N N UJ τf rs UJ χ - UJ U. O N CD CO UJ CO CO N N ro x- CO x- CM O CO O χ - O CO O x- N CO CJ ) CO CD τt OO Cq cθ x- CD cbcb ro cMCM cb N Jcd ro x- c ro cb ro ro cN cbcM (D(Dω mm m(θ (D<ommmm mcDcocD mm ω cDmcDcocDcocommm mmmmm mm m mm CD Tf OO CO OO CM CO O Tf OO CD CO OO N O UJ CD Tf CD CO Tf Tf CO τf cθ σ) O CM CD χ- CO N CO O x- UJ τf χ- UJ N N χ - N CJ) N UJ CO UJ ro C0 CM N CM O N CO x- x- CM 00 x- N CM τf O CD τf UJ CD CD CJ) x- CM CO χ- N N CD CJ) CO CD Uj ro UJ CM Cθ ro τf O CM CO CO CM τf U0 UJ N CM x- τf CN Tt CD p x- ro CO N CJ) τf cθ χ - CM x- CD N N N CD UJ CO x- CO CD mCO iNs- x-tρ rN- — nO N t — rCMsi C ~M.ι rNs ιNs_ rCD rNs_ rO-» ιNs_ _ m CO r CsMi ,— x- Tf CO x- CO UJ O N CD U UJ CD Tf CO Tf CO CD O x- O x- CM CM ro ro χ- cM θ C ' cN cM cM cM cd τf N cd - c cb τ Tff cCO )J τTrf J uUJ. N N m m m m m m m m m (θ cD co co co co co cD m m (D co cD m co (θ (D co (θ CD cD CD co cD co cD CD CD (θ (θ (D (θ (D CDco co cD CD co co x- x- CM CM CM x- x- x- OOOOOΩ ΩΩ ^ ω o Q O OΩ Ω LU LU N N N O Q O Q O O Ω Ω LU LU N N C Q X X X X X X X X < OQ Ω LU N __ < X X X X X X X X X X X < Λ GO O Ω LU N < X X X X X X X X X X X x- CM x- CM CO x- CM CO O O O O O Z X X x- CN x- CM x- CM x- CM x- CM CO O υ υθO Z X X x- CM χ- CM χ- CM χ- CM χ- CM σ)Wσ) σ)σ)σ)mmmmmmmmmm mmm mm mmmmmmm m r- LU LU LU LU LU LU LU LU LU O O > I I I I I I I I I I I I I I I ■ I I I I I I I I I i I I ■ I I I I I I — I — I I I I I © o Cθ τf iΛ CO N rø ro θ χ - CN CO τf ιo c~ rs ( X_ CJ ) O χ - CN CO τf J O N ∞ ro θ x- CN CO τf ιO CO N ∞ Tf Tf Tf Tf -^ -sf Tf LΩ UO U UJ UJ UJ UJ U LΩ in CD CD CD CD CD CD CD CO CD CD N N N N N N N N N N CO CO CO CO CO CD CO CO rø ω ro roro roro roro roro rororororo ro ro ro ro ro ro ro roro roro roro roro roro rorororo ro ro ro ro ro ro roro roro roro roro rororo CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO O CO O CN CD CM O CD O O O O O O O O O C CN χ- U τf x- cD τf O O O O O O UO CM CD CD UJ O O O O O O O O o q τf τf x- Dr M o o o o o o o o o u xf ro co ro uj oo cD OO OO O O x- CD CD N x- O O O O O O O O d uό cb cM CM N cb τf o cN M Tf T ' cj d CN CM CN CM CM CM CM CM CM x- x- x- x- x- x- x- x- d d ή cό co d d d d d d d d CMdCM CdMdCMdCM CdM x- x- x- x- CM CM CM CM CM CM CN CM CM CM ro x- CJ) τf cθ O O τf rs CD x- CJ) χ- CD x- x- CJ) CO U0 CD τf τf CM CO x- O CO O O ro O CO Tf m UJ O UJ ro CM x- CM CN CN N N CO CO CM O CO Tf CO UJ UO CO CD CO CN x- CM U Tf Tf Uj Tf CD CN CO CD CM Tf CD CM O OO O - O) x- UJ O τt CD τt CD τf 00 CM ro N C0 N C0 CD C0 UJ UJ O C0 N LΩ CD O CO CD CM O O CO CM CJ ) CD N CM CD τf x- O _. C.- CD CO N . - τ -f C.O-. C„D " C.O. x-- U -J, C-D.. C_D. τf cJ) O O C0 CM αj CM LΩ τf C0 τf O τf χ - O 00 τt τf x- O x- CD O CM cD uό cD uj uo N N N u cb d cb oq N od cb od cM CM CM μ d ro o cd c^ o co co co co co co co co co co co co co C CO CO CO CO CO CO CO CO CM C CO CO CO CO C CM CM CM C C CM CO CO CO CO CO CO CO CN CO CO CO CO CO CO CO CO o UJ CO Uj Tf LO CO Tf oO CO x- Tf O ι_> U ujj T XfT c cO") C UDJ N r C cOi TfT cDD ι Ns- u O c CoO CcDa c (oD cOo cCOo Txfr oθ c(_o ro0) CcoJ Oro) - C CMN (CN CCM CO N OO Tf cD CO O CO O N UO N N CM CD CM x- CO CO CD O CO O CO Tf N CD CD Tf cO CO CO UJ UJ x- O OO CO CD O x- CO N O CM CD C N LO CD N UO CD CN CM CO ro cO N UJ CN UO CO CM Tf CM UO ro OO CO UJ O CD UO O CO CM x- O CM CM O Tf Tf cO O CD CO CO O O CO CD CD CO N CO N CD i N- x- CD CD N CO CO CD CD CD CM ro CO Uj Tf CO CM Tf cO UJ CD CO Tf CN T xT C b cb xt cb cM Tf CO Tf CM UJ CM Tf CM UJ UJ CO CM CM O O CCDD CCMM CCOO TTff CCMM CCOO ' C CMM bCO CMM Ttf LLOΩ ■ T!f. m m m m m m m m m m m m m m m m m m m m m m m m m m mm x m m m m m m m m m UO UJ N CM O Tf cO CD O N CO N CM O UO N OO CO CO CΩ CΩ O N CO CO x- CM CO O CD CD xf CO Tf O x- CN CO CO Tf OO OO UJ CD CO CO x- CM xf T τft OCOO OO CCMM NN UUJJ CCDO CCDD UUJJ CCMM CCMN NN Tff CroD UUJJ CCO '^ Cθ τf rs UJ τf CM 0CO0 CCOO CCOO UUOθ CroD Tτff C(3Dj CCDD Tτff CroD NN Oθ CroD oθ roro co OO xχ-- aCOo cCN NN Oro UiΩJ CCDD UUJJ UUJ^ CM x- O UuJ CroD Oo CD UuOo roroUuJ CroD NN CcDDCcOqUinJ Oo CroD NN CroD CcNN xtx-CM O Nco ^o —x- TTff CcMM UuJ CroD xx-- Oro) CcMM CcoO CcNM TTtf CcOo UuJ CcDD NN Oo roro CcDD OO OOUuJ CωD CD CO CD CD N ro ' ro cb∞ N ' ro ro cbd cb b N cd N cb od ro ro ' NN N ∞ co mm m m m mm mm mm mm mm m mm mm mm mm mmm mmm mco cDCDCD co cDCD coco tDco cococo cocD . . - CM CM CM CM CM CM N " " " ^ x- CM _o_a, Ω X < CQOO < _ΩΩΩθao x- CN GO OQ ,_ Ω Ω co X X X X X X < CQ Ω Ω <XXθχχχχχχ < ω Ω Ω < X χO χ χ χ cozoυooυυxx X x- CN CO x- CM CO oυooooυx X X- CM X X- CM CO X- CN CO OOOOOOO X X X- CM X X- CM CO 3333333333333333333333333 _JUJ _J _J UJ l_I LU l_ _J _J _J llJU U UJliJ _J _J _J llJ l_ lU _J — I — I — I — I — l —l — I — I — I — I — l —l — l _J — I — l _l — I — l —l — l _J — I — I CCMM CCOM TCMjuCMjCCDMNCM CCDM roCM COO CxO- CCNO CCOO CTOf CUOJ CCDONCO CCOOroCθ τOf xτ-f -CM"CτOf τf rO-) rO-> πO rO-ιO-_ oOOOOOOOOO OO O τf τf τf τf τf τf τf τf τf τf τf τf τt τf τf τf τf τf τf Tf Tf Tf Tf r- © © Ui H U α. O O O CD O Tf CD UJ OO OO CM O O O O OO ro CD CO UJ UJ UJ O O O O O O O O O x- ro OO N N x- CO O N O O O O O O O O O O O O O N Tf O O CO ro O O O O O LΩ N CD x- OJ CN x- O O O O O O O O O CO O x- CO CM Tf CO CO Tf O O O O O O O O O d d d cb CM UJ CO CM Tf O O O O CO CN cq Tf O Uj Tf O O O O O O O O O x- Tf Tf UO UO O CN x- d fJ- y d d d d d d d d d CM CM CM - x- x- x- CN CN CN CN CN CN CM x- x- CD x- CM CM CM CN CM CN CM CM CM CM CM CM x- x- x- CM CM CM x- x- x- CN CM CM CN CM CN CN CM CM UJ N CO N x- CO Uj Tf CM O ro CM CD O CD Tf CO CO CD CD O lΩ CΩ CO CD N CO CO CO O N CΩ CD O CM CJ) CM x- N CO CM xf CM UJ CD N UO CM CD CO O O N O CO O CO o LΩ N CD Tf O CO x- xt CD x- UJ O N CO N N O CD CO CM CO UO CJ) τf cθ τf CD o cM N co ro ro uj co Tf CD CO CO N OJ CO CO Tf Tf CO O O CD x- CO CO Tf O) Tf t co ro co ro σ) CM O Tf UJ UJ CN N ro τf CN τf U0 CD CJ) CD τf co co uo ro o ro cM co N CO CO C OJi CO Tf UJ UO UJ N cd od cd Lb uO N N Tf Tf oo cd cb τf τ f ' ιri τf LΩ cd cb uj uj cb cb uό cM o ro ro co N co uo iΩ CN O CD CD O O OO OO N CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CN CN C^ O Cθ ro CN LΩ CO lΩ τf θO CN ro CD τf CM UJ CD CD CD UJ CO OO N CO lΩ CO CO O O CM CO O UJ τf ro CM CD χ- CD CD N CO χ - x- CO CD Cθ ro CN ω UJ χ - CD CO O CM ro τf cθ CD N ro χ - N χ - x- LΩ UO UJ Cθ ro iΩ τf x- UJ O UO UO τf τf CM CD χ- χ- lΩ CM χ- UJ CD χ- ro cθ CO N CO CN ro ro CN x^ ro co -_ q ro ro D cq cM CM cq ro cq cq c iΩ cD co τf t cD cq q ιn q q t τt cq N CM cN c ro co N d ro ro cb ro ro cb N ro ro cb ro cb cb N d ib cb ro lΩ in U UJ τf τf '^ UJ τf 'sf xt UJ Tf lΩ in τf τf τf τf τf τf Lθ in uθ τf τf UJ UO τf UJ UJ UJ τf ' τf τf τf ' ^ CN CJ) UJ O O x- x- CO cO xf CD x- x- UJ CM CO x- CN CO Tf CO O CM ro cD OO ro CD Tf oO UO CD CM CM N UJ CO CO CD O CD CM CD x- CD CO CD CD Tf cO CD N CM UO Tf CD OJ CO CM N CN CD CO ro O UJ CO CD O CD x- O O σO CO CN CD CD CM CO CO CO Tf CM CO Tf cO CM Tf CD N O CO LΩ N CO O CO ro CM ro O O O O x- UJ UJ CO CM CO CM x- CO j f cq cM O o xr x- ro cj) C\| O χ- (D CO ( (O N ω θ τ- (N (D (D O) -) O CO C\| CO Cθ m m N N Ci) N (M qq τ- (M CO COV T- O OV CM C. cN d ro co cb cd cb uό f τf ro N N ιb τf τf cb ro ro d d ro ro od ro cd N ro ro cb ro d ro (D CD co co co cocD co co cD CD co co cD co m m m m m m m m mm m m co io in m m m m m m m m mto mm m tD CM CM CM Ω Ω Ω _ ,. ^ N co oo CQ CQ LU LU LU CM OQ CQ Ω Ω X X X < 00 Ω Ω < χ χ < _ 00 O Ω LU __. < x x x x x x x < O Q Ω LU N X < X X X X X X LU χ - CM co Z O OO θυ θ O X X χ- CM o υ o o o co o X X x- CM x- CM x- CM CO υυoooo zυ Z X X X- CM X- CN X- CM X Z Z> z> Q- CL CL CL Q. Q_ _L Q_ CL Q- a_ CL H I- h- l- l- l- l- l- l- l- H I- l- h- l- l- l- 00000000000000000000 r- UJ llJ lij WtΛ Wtn cnW WWtO tflt/JVj LU LU LU ^ ^ ^ ^ LU ^ ^ ^ LU LU LU ^ _j _j _ι < < < < < < < < < < < < _≥ _> _> _≥ _≥ _≥ _≥ _≥ _≥ _> -> __: _≥ __: __: __: __: < < < < < < < < < < < < < < < < < < < < © o N C0 ro θ χ - CM C0 τf U0 CD N 00 ro θ χ - CM C0 τf UJ CD N 00 ro θ x- CM C0 τf U0 C0 N C0 ro θ x- CM CO Tf UJ CD N CO ro O x- CN CO Tf uO CD N CO o TfoTfoTf UJ UJ UJ UJ UJ UJ UO UO UJ UJ CD CO CD CD CD CD CD CD CD CD N N N N N N N N N N CO CO CO oo co co oo oo oo co ro ro ro ro ro ro ro ro ro O O O O O O O O O O O O O O O O τf τf τfoτf τofoτf τofoτfoτfoτfoτfoτfoτfoτfoτfoτfoτfoτfoτfoτfoτfoxfoτfoτfoτfoτfoτfoτfoτfox^-oτfoτfoτfoτfoτfoτf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf r- © © Ui P H U α. O O O O O O O O d d d CN CN CM CM CN CM CM CD CO CD O x- UJ x- UJ τf O CJ) τf f τf CN CM τf CD c _ N UJ CO OO CO N Tf cO N x- CO O Tf Tf x- CD CM CM Tf OO OO CD CO CD CO CM O CM CO 0O τf UJ τf rs UJ χ - CM CM O CO OO CM x- α CO CD CM t CO xf N CD O OO J ' C WJ) τ XfI C VM N ■ - C CO CJ) N CO CD x- U ro θ N CO χ- CO CM CN O N UO (N CO OO UO CO CD N CN Tt Tf CO CD CD CO CM τf τf CJ ) CO χ - O UJ UJ τf cM N N CM .U.J, NN CCDD CCDD OOOO x- ro τt O UJ CO CD χ- O UJ CD CO N CO CM N xf CM χ t τf CM τt CD τf U0 CM C C CO τf -^ LO LΩ N CO CN χt U0 τf xf CD CD UJ UJ N N N CO CO CM CN τf cD CD CD CO N CO C τf UJ τf CD U0 CO CN CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ σ Tf CM O OO Tf x- cO N CD N CM CO CM OO CM UO CO CO x- CO CD x- CO Tf CD CO CD CN O Tf CN CD O N CD CM CN CO CD CN UO O CN Tf Tf O Tf x- ro cO O CM ro N τf UJ x- τf x- rv. CM N x- CJ) x- UJ CO χ- N CO CD CO CD τf N. C _J)- xt - CM N N UJ N τf x- τf O U) τf τf c ro cθ OO O χ- CD 0000C0 N C0 CD C0 x- CN CO ro O x- ro N UO x- CN N N O CO N CM CO x- CD OO O N T ^f Or-. ULnJ τf CD CO CO x- CO N N O O CO CO CJ) CD UJ χ- s oo cMco m cM ro ro τ- o c ro ro τf cb cM ib N σ3 b τf ' xf u u N- bN Ncb cb c cN CO CO CM UJ . c .O . Uj . Tf . Tf C CNN T Tf uό cM cb τf cd cM cb uό cb cM lΩ in τt τf τf τf ' f τf τf τt ' t τf xf τf τf xt τf τf xf xf τf τf τf τt τf ' t τf τf ' ^ τ^ Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf Tf Tf τt CD τf U0 U0 CO x- CO C0 ro cO τf x- Uθ O OO O O UJ χ- O CO CD N τf O x- O x- CN OO CO CO CD x- CO CJ) τf cD CD x- CN CM CO N ro N τf O O O CD CM xt CD CO CO CD Tf x- uj O O N CO OO LO O CD CD CO τf r-. O UO OO CD N χ- τf O CJ) τf CN O CO CD τf τt UJ CM τf CJ) CD CO C CD CO LΩ UJ CN C CiDJ CCNN UJJ CCMN xx-— C CJD O_J UUJ) CCiDJ CC_OJ OC_J xx—- C C_D CUDJ CtD_J x— O OUO Tx-- L UΩJ TTff xx-— r |Vs ϋCD) C «DJ ro UJ UJ) IN s - O UOJ O U C COO C UJ)J I N s - Tx-- CJD υCDj rNv iCMN TTjf- TTf lCM CCOJ CO-J Uin CCMN UCO CO CD CJ) UJ N Tf N N N ro cN cb τ f J ό o cM μ od f 'xf ' cd χ f u j u τf cD θ ∞ O N CD N N UO Tf ' m m m co cD co co co co co cD co co co - tD cD to co co cD co co cDco com m m m m to m m m m mm co m CD UJ UJ UJ UO UJ UJ CN CM X X X X C Q CO O O Ω Ω LU LU NN N x- CM x- CM m CQ J" M x- CM X X X X < CQ Ω LU N <xxxxxxxxxxx < χ χ Ω Ω LU LU N < ω O x- CM x- CM υooυoυozx < ooo Co Q OoΩoΩυoLU LU N X x- CN x- CM x- CM x- CM x- CM CO oo X X X- CM X X X X X OOOO OOOOcocococococow w cocoωcow c Λ cococoωωω r- < < < < — l —l — I — I — I I I I I I I _l — I — I — l —l — l —l -J — l _l — | Q- Q- Q. Q- Q_ 0_ Q- Q. CL Q- Q- CL Q_ CL Q. O. Q- CL CL CL < < < < < < © ro θ χ- CM CO τf LΩ N.Cθ ro θ χ- CM CO τf ιn CD N C» ro θ x- CN Cθ τf UJ O N CD ro θ χ- CN C τf UO CD N Cθ ro θ χ- CM CO OT O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CM CM CN CM CM CO C CO C CO CO CO CO CO CO Tf Tf Tf Tf -sf Tf Tf Tf -^ -^ O O x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- τf τf τf -f τf τf ' t τf ^ τf τf τf τf τ^ τt τt τf τf τf τf τf τf τf τf τf ' t τf τf ^ τf τf τf τ LO r- © © Ui H U α. O O O O O O O O O O O O O O CN x- CD O CN CD CN O O O O O O O O O CN CD O x- O O O CO ro O xt CO CO O O UJ UO Tf Tf xf O O O O O O O O O O O O O τ- LΩ CM CD τf x- τf UJ O O O O O O O O O CO CD OO CO O O O τf cθ CM CM OO N CD CO O O c ? ' s . "^. ^ ". O O O O O O O O O O O O O O CN x- CM CO CM Tf O O O O O O O O O O x- x- O O O CM CM O . O O O CO CO CO OO ro CN CN CM CM CN CN CM CM CM CM CM CN CN x- CM CM CN CN CM CM CM CM CN x- x- x- CM CM CM CD CJ ) x- CM CM CN CO CJ ) lΩ O N x- .M x- CD CN CN CO lΩ CN CJ ) CD lΩ lΩ CN O χ - CΩ Tt N x- CD CN UJ UO CO CO OO CD O x- τf τf CD N CD CO x- CD ro cθ CD x- CD CO τf N x- x- CN τf O N τf τf CM CO CM τf CO x- O CM CD N CD O N ro CN xt CM N Ln oO CO OO CD UJ CM x- o oχ- ujcq o co uj τf θχ- χ- cD τf o ro uj τ f rs x- x- CO Tf CO CM CD CD CD N CO CD N N CO CO τf τtro τf r CM N CM CD CO x- ro CD ro xt Tt o o N q cq cM CD O co cq co cq cq cM cq uj ro odN rød cMd dμ ro cbro d cb αD ro c b cd cb cb cbuό uoco ' t N N cb t Tf UJ UJ f uό uj uό τf τf - N N N ro ro cj) N N CN CM CM CN CN CO CO CO C^ CM CM CM CO CM CM CM CM CM CN CN CN CM CM CM CM CN CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM Tf O CO CO O N CD CD CM CD CO CD CO N CO CD CD CM Tf cO xf O CO CO CM CD CD O CD CD x- x- x- x- CO O CO O x- OO N CO CO CN τf ro θ τf rs θ N CJ ) CN ro θ UJ CM UJ CD CD UJ CM UJ O τf τf θ 00 x- x- 00 O CD CM U) CO CO Tf OO CO x- CO CD UO N 00 UJ C0 τf τf O C0 CD 00 lΩ UJ O O CD N CJ ) C0 CM U0 x- N τf UJ x- x- CD O U) C0 CJ ) CM C0 τf LΩ 00 CM C0 T f CM CN CO CO Tf CD CD UJ OO N OO O N O CM ro τt cM ro τr u iΩ ro o oo co o cD χ- co ro τf 'τf CM x- O O τf x- τf CM x- CM CO x- CN Cθ ro cJ) O CO τf UJ Tf c CM x- O CM Tf CM CO CO x- O ^ ro d N td Nffl od d x- ' oci Ncd N od Tf xt xf τf τf τf τf τf τf τf τf τf τf c CO CO Tf Tf Tf Tf Tf Tf Tf f Tf Tf Tf Tf Tf Tf Tf Tf τt CO τf τf τf τf τf τf τf τf τf UJ U0 τf τf τf τf τf x C0 ro θ ro cθ O τf cD τf θ ro cθ xf CM CD CN CM 00 CD CD xt CO CD τf uJ CD N C0 x- N N C0 ro C0 ro 00 CD UJ UJ Uj ro ro τf CM CO CD LΩ OO ro CD LΩ LO N CM τf cθ x- CD ∞ x- lΩ θ ro CD CO CM O O χ- N x- CO CM τf O Cθ ro cθ UJ CO CN χ- CO UJ CJ) CM CD xf CJ) O O CJ) N CD τt CD OJ x- CN UO N O UJ CD χ - Cθ CM ro τf Cq CM x- x- CN C» cq cq N CD CD CO q N χ - O CO CD τf θO CM τ- O τf O l^ N N Cq τ- χ -- ro x-; CN N CO tM t V N N lri lri lri ^ M C V C. ^ d N ' lri ∞ N N Tt ' Tf iriuόuόcoujcbcb mm mm m inm m inm m m m m m mmm mm mmm commm minm mm mm mm mmmmm x- x- CM CM _ - CM cαco OOΩ Ω X X X X CQ CO LU LU LU x- CN Ω LU N X X < X X X X X X L X X X X < CO Ω LU __.<xxxxxxx < < < < OQ Ω Ω < O Z υ Z Z X X x- CM ^ CM x- CN X x- CM x- CM oυoυoco υ X X x- CM x- CM x- CN CO OOOX ϊ CN υυoυoooxx 000000000000000000h-l-l-HI-h-l-l-l-HHr-l-l-l-l-l->- ->->->- ->--3- 3 -)3 3 333 33 r- 0_ Q_ Q_ C_: __: Q- Q_ Q_ Q_ Q_ Q_ Q_ Ω_ Q_ Q_ Q_ __: Q- LU LU LU W W W W W UJ W W < << << << << <<<< < < < < < -≥ _≥ _≥ _≥_≥ _≥_≥ _≥_≥ _ © o x- CN CO Tf UJ CD N CO ro O x- CM CO Tf UJ CD N CO ro O x- CN CO -t UJ CO N CO ro O x- CN CO Tf lΩ CD N CO ro O x- CM CO Tf uO CD N ω inuoujujujuououjuocDCDCDCDcDcDCDCDO NNNNNNNNNNcocoα cococococococororororororororororoooo x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- 'T- x- 'r- x- x- x- x- 'r- x- x- x- x- CN CM CM Tt Tf Tf Tf 'sf ' " τf τf τf τf 'χt '^ τf τf Tf Tf τf Tf τf τf ' " τf 'f τf τf Tf Tf '^ Tf '^ 'X^ r- © © Ui H U α. o o o o o o o o o τf rs uj χ- χ- CO O O O O O O O O O O O CO x- x- CO O 00 CO UJ N O O O O O O O O N CM x- x- Tf Tf O O O O O O O O O O lΩ x- N CD x- CO CO lD O O O O O O O O O O O x- CO lΩ CJ ) x- O CO Tf CJ) O O O O O O O O Tf oO CO CM Tf CO CO d d d d d d d d d d co cd μ . Tf C U D-I O O O O O O O O O O O CO CN Tf Tf CN CO Tf CD d d d d d d o Tf CO UO UO CN CO CM CM CM CN CM CM CM CM CN CM x- x- x- x- x- CD x- CO CM CM CM CM CM CM CN CM CM CM CN x- x- χ - x- x- x- x- CM CM CN CM CM CM CM CN x- CO O OO UO O CM CN CM CN UJ CO Tf x- N CO CO x- CD U Tf UO UO CO x- UO UJ OO O OO UJ N CN CD xt x- UO UO CO ro OO ro Tf cO CM N O CN CM CD N O CN UJ Uj Tf cO CO x- CM CO CM N x- Tt OO CO N CO N CD lΩ N CD x- O O U0 χ - CM CJ) N CD CD CO N τf CD CM σ) τf CD CM CO CD N τf CD CM O τf CD O ro cq τf χ- cq cq co co co ro O CD CO N CM CD N O CO CO CO CO O CD Tf O N N CD CN CO CM N CM CM O O χ - CD O x- Cθ τf O CO x- O CM UO τf ro ro ro ro cd ro ro i — CO CO T f Tf cO CO lΩ CO N UJ CD CO CO CΩ Tt b cd c ro c cM d cM O CN Tf CM O CM CM CO CO CM CO O x- CD CN CN CN CN CN CN CO CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C ion N N χ- O CO CN ro cθ x- N τf rs LΩ ro CM ro cθ θ ro τf cO χ- χ- Cθ CM χ- N CN τf CD CD O O O N O τf CD CM N CO CN OO N τf ro CM N CO χ - N CO CO N CO N LO O CO N CO τf θ O CM ro cθ O CO χ- τf Ln iΩ τf (s CM UJ x- N τf cJ) O χ- CD CD CD τf τf CN χ - CO O O CO CM N CO CO x- N N CN χ - χ - N CM CJj τf x^ cθ ro N ro N in x- CM U0 q x- CO χ - N CD N τ cq p CM CD N in N U0 U0 x^ UJ cq cq ^ o ro d d ιb N N u χ^ -d τf 'χf θ χ^ c cN CM τr s N~ uJ uj ^ • N- , ϋ- " - " ^ - ^- m ιn m m m m m m ιn m ιn m m m ιn m - , ^ ' cr m m ^ , f "<f m m m CL CL 01 CL CL CL CL r- iuϊumiu iu uϊu^^^ω^H^^H^^^^^^^^^H X X X X X X X d OOO Or-r-r-r-r-l-l- © CO Tf LO CΩ N CO ro O x- N CO CD CM CO Tf o OO OO OO OO OO OO OO xχ-- xx-- CM CN CM CM CN CM CM CM CM τf τf τf τf τf ' f τf τf τf 4255 THR H 52.517 53.881 22.722 20.00 4256 THR HA 54.032 54.925 20.382 20.00 4257 THR HB 52.313 56.216 19.551 20.00 4258 THR HG1 51.470 57.060 22.111 20.00 4259 THR 1 HG2 50.910 53.814 20.510 20.00 4260 THR 2HG2 51.562 54.409 18.964 20.00 4261 THR 3HG2 50.153 55.136 19.640 20.00 4262 ALA N 54.477 57.213 21.304 16.12 4263 ALA CA 54.775 58.515 21.914 17.15 4264 ALA C 53.591 59.401 22.373 17.06 4265 ALA O 53.789 60.142 23.290 16.84 4266 ALA CB 55.595 59.324 20.904 15.40 4267 ALA H 54.845 56.937 20.420 20.00 4268 ALA HA 55.376 58.310 22.799 20.00 4269 ALA 1 HB 55.020 59.526 19.991 20.00 4270 ALA 2HB 56.466 58.733 20.623 20.00 4271 ALA 3HB 55.932 60.276 21.309 20.00 4272 ASP N 52.372 59.361 21.793 16.67 4273 ASP CA 51.253 60.1 17 22.425 16.05 4274 ASP C 50.459 59.397 23.628 14.16 4275 ASP O 49.950 60.007 24.564 13.25 4276 ASP CB 50.285 60.449 21.279 16.36 4277 ASP CG 49.302 61.573 21.733 18.91 4278 ASP OD1 49.622 62.439 22.570 19.27 4279 ASP OD2 48.176 61.536 21.255 19.47 4280 ASP H 52.169 58.892 20.940 20.00 4281 ASP HA 51.675 61.041 22.821 20.00 4282 ASP 1 HB 49.700 59.570 21.004 20.00 4283 ASP 2HB 50.796 60.835 20.398 20.00 4284 GLN N 50.509 58.059 23.612 12.74 4285 GLN CA 50.357 57.350 24.885 12.47 4286 GLN C 51.372 57.732 25.883 13.42 4287 GLN O 50.983 57.853 27.01 1 13.68 4288 GLN CB 50.268 55.796 24.870 10.94 4289 GLN CG 49.003 55.278 24.131 10.93 4290 GLN CD 49.169 53.862 23.674 1 1.89 4291 GLN OE1 50.245 53.338 23.823 13.27 4292 GLN NE2 48.120 53.148 23.278 10.17 4293 GLN H 50.220 57.686 22.728 20.00 4294 GLN HA 49.410 57.687 25.306 20.00 4295 GLN 1 HB 50.120 55.691 25.933 20.00 4296 GLN 2HB 51.199 55.298 24.622 20.00 4297 GLN 1 HG 48.722 55.880 23.275 20.00 4298 GLN 2HG 48.157 55.324 24.814 20.00 4299 GLN 1 HE2 48.192 52.170 23.170 20.00 4300 GLN 2HE2 47.274 53.670 23.184 20.00 4301 LEU N 52.632 57.962 25.482 15.21 4302 LEU CA 53.622 58.317 26.460 13.64 4303 LEU C 53.221 59.639 27.103 14.41 4304 LEU O 53.197 59.793 28.299 15.65 4305 LEU CB 55.040 58.373 25.963 12.86 4306 LEU CG 55.940 58.940 27.044 13.02 r- © © Ui H U α. CN O O O O O O O O O O O CO CO CO Tf CD CD CM N ro cO CM O O O O O O O O O O O O O x- O CM Tf N CO CN CO OO x- OO O O O O co cq o o q o o o o o o o o Tf co x- CD τf CM UJ χ- τf 00 C0 O O O O O O O O O O O O O τf O τf 00 C0 O C0 τf C0 N τf O O O O rM CM o d d d d d d d d d d cb cb Tf Tf CO CO CD O C O χ- O O O O O O O O O O O O O CO CO CM τf CN Cθ UJ CO τf τf CO O O O O x- x- CM CM CM CM CM CM CN CN CN CM CM x- x- CM CN CM CM CM CM CM CM CM CN CN CM CN CM CM x- x- x- x- x- x- - x- x- x- x- CM CM CM CM UJ UJ CD CN ro CM N CM O O x- τf OO CM O O CM x- CD O N Cθ ro CJ) N CJ) CO mCCDD roC~D _ilΩΩi xττfft xx--- xττftr CιCDDn rCCMM. rCCMM. (CCDDn iNNs xττffi- mccOO mCCO0 Tx-- mC COO rCCNM. C_Oi NN mOO mCD ~CD nCD) nO nCD) iLrΩ) r- CCMM OO CCDD CD OO UUJJ TTff CCDD xx-- OO UUJJ CCDD CCDD UUJJ x- CCOO CCOO UO CM CD O Tf x- x- Tt r- ' CO N N cd cb ro oJ cb N cb uό CM CM CN CN CM CN CN CN CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM τf cθ CO UJ O OO CD τf UJ CO O χ- CM χ- CJ) N ro co o oo ro cM CD uo u co co ro cD co ro co ro ro co x- co co N N CM co cM x- co o x- x- uj cD co cM x- ro x- N CD N u ro uj ro co co co co x- CO x- O CO CD CD O Tf CD CD O CD O N O CM UJ CM UJ UO OO N CO x- N ro ro CM CO CD x- CD N CO CM O CD x- O N τf ro cq ro N χ - τf O x- τf UJ ro CD N C " D O - C " O CN O τf CM CO τf O CD UJ x- UJ N Cθ ro τf CO CD O O N UJ O O OO χ- CJ) χ- O CD O χ- τt ro oo N N oo N ro ro cb ro N cb cb M CN Tf xf b N CD OO O CN CN CN Tf Tf Tf Tf CD CD UO OO OO x- d ^ d d d o d oJ d d cM cri d m m m m m m m m m m m co cD CD CD CD co co _ co co cD CD CD CD co co co co co co co cD CD CD co co co (D -) <o cD m (o (θ co co m co CO CO CO N ro CO CO CO CD CD Tf cO O CO UO CO χ- CM CD CN N CD CO N CO CD O τf CO CD N OO CO OO Cθ ro UJ x- CM CO CO OO χ- UJ N τf O CM UJ CD UO o UJ ro o CD Tf O CM CD CO CM CM Tf x- Tf cO UJ CD N CM ro x- CD CO CO O N CM Tf x- cO UO N CO ro oO CO O x- O ro CM O O CD N Tf CD CO CO x- Tf CO CO CD x- CO CD UJ CO " q ro c uj ro j cM θ CM N in iΩ c cM τf x- cq uj χ-; uq o N τf M N lb cN CO uό uό u N N c j Tf b cM N cM ro c cd cd cM cM CM cb ro ' ro ro ro b o m m m m m i- m m m m m 'f N- '<. m - ^ - - N- ^ " - f f - " - x- x- x- CM CM CN x- x- CM CM x- CM CQ OQ Ω Ω Ω Ω Ω Ω x- CM ω cα Ω Ω xx xx x- CM x- CM CO OQ Ω Ω <χ χO X X X X X X < CO Ω LU N X X _ < X X U X X X X < OQ O Ω Ω LU LU N < X X O OX X x- CM X x- CM CO x- CM CO oooυoozo X X X X L Z Z X X X- CN X- CM X- CN X X- CN X- CM oooυυoυυυoxxx-cM Z Z)Z Z)Z 33333333 _)00000000000000000000000-ULULULU LULU UJLU LULU UJUJ UJLULU r- ι_uϋajLu_ι_jι__ii_ι_ι_ι_ι__:_--_---------_________-iιιιιιιιιιιιιιι _I _I _I -J _I _I -J _J _J _I _I _I _I < < < < < < < < < < < < < < < < < < < < < < < < Q- QL Q_ Q_ _L Q. Q- CL CL CL Q- CL CL Q_ CL © o N ∞ ro θ x- CM CO τf ι_) CD N C0 ro θ χ- CM C0 τf UJ CD N C0 ro θ χ- CN C0 τf UJ CD N C0 ro θ x- CN C0 τf U0 CD N C0 ro θ x- CM C0 τf U^ O O O x- x- x- x- x- x- χ- χ- χ- χ- CM CN CN CN CM CM CM CM CM CM C C O O C Cθ CO CO CO CO τf τf '^ τf τf τf τf τf τf 'τf ιn Ln U^ co coco coco coco coco cococo coco coco co oo co co co co co coco coco coco co co co cococococo co cococ^ Tt Tt Tf Tf Tt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf -sf Tf Tf Tf Tf Tf - - Tf Tf Tt Tf Tf Tt Tf Tf LO r- © © Ui H U α. O O O O O CD CM CD CD O N O O O O O N CO CM CM CD O x- OJ CD ro x- CO O O O O O O O O O O O Tf CM CM x- CD OO O O O O O O O O O O O O CO CO O OO UJ O O q p O O cq CD N CD UO x- O CD CN N ro O O O O O O O O O O CD CO CO CM CM CD CO CO O O O O O O O cMc uόuό rod τf cd τf ιb Lriu N N b c M d d ddo-d τ f CN CM CM CM CM χ - χ - χ - χ - χ - χ - CM CN CM CN CN χ - x- χ - χ - x- χ - x- x- x- x- x- CM CM CM CM CM CM CM CM CN CN χ - x- x- x- χ - χ - χ - χ - CN CN CM CN C^ 00 O CD θ ro τf θ CD τf CD C0 N CM CD τf 00 τf CD 00 UJ N τf x- CD χ - CO lO ro O Tf CN CO UO N CO Tf O CN CO x- O N CD CM χ- N UJ x- CD CD χ- τf CM Tt , Tf - C _D CD CD x- in N x- Tf CD O CM UO UO CM CD CD O x- in N Tf Tf ro CN CO UJ CO O N CO UJ CD N Tf ls cO x- O τf CD τf τf x- CD CM O CD τf O Tf CD CO CO N Tf oO CD OO N OO CO Tf ls cD CO O N CD O ro ro CM UJ x- Tf N Tf O N CN CO N O UO O CD O CM CO x- co ro uo cM CM uo ro cN x- co co CD OO N θ ro ro θ χ- CM θ ro cθ χ - χ - O CD χ - χ - x- CO O O O χ- O x- O O O CN x- ro ro CN ro CN CD χ- χ- CM CO CD CO N CD O χ- ro CJ) CD N N CN CN CN CO CN CN CO CO CO CO CN CN -O CO CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CO CN CO CN CO CO CO CO 00 o C UDJ τ x-- - UUJJ 0CU0 C CO') C CMN CCUO τ- τ- ClNM χ -- N|x cCUO Xτ/f υcJ)J Cl'J CCDU ι χ -- N|s OU τXff τXfr CCNM COθϋ υro) Ccϋθ τ- U lΩJ CCO) xx—- CCNN x- CO UJ N N O CD CD CO CO ro N CD N N CO UJ CO UO CO CO CD CO CO N CD τf CD O CN CO CO C CJ ) OO CN CJ ) CD CO CO O N C CO C x- CO N Tf NN UUJJ CCDD CD CO CD CO Tf CO Tf cO x- CM CD CD CD CO CD CO N O CO CM in τf ιn UJ O N UJ CD N N CD χ - O CM CM N UJ N q c0 CD CM χ - χ - C000 CD CM Tf Tf • CD UJ Tf o ro Tf CD N Tf rv- Tf Tf CD CM CO CM Tf co r^ O f ro cb cd ro ro o ' d co N ro ro cb ro ' J cN cd τf cb cN τf ' cb cM CM τ- CM Tf CO UJ O Tf cN c Tf Tf ^ i Lb c ib cd cb c Tf f CD UJ CD UJ CD UO UJ CD CD UJ UJ UJ UJ UJ UJ UJ CD CD CD CO CD CD CD CD CD CD CD CD CO CD CD CO CD CD CD CD LD LD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CM CM CD CD CM CD N x- χ - 00 CD CN CD O CM O C0 N 00 N CJ) CN CM O x- UJ CJ) Tf ro CD ro CN N O x- O UJ CD N CD CD CO CD Tf CN CD CN OO ro x- O CO CO x- lΩ O τt CD CO τf S- lΩ x- τf χ - χ - lΩ N χ - CO lD CΩ CN Uθ m CN CN θ ro x- CD N CD O CM O x- in Tf x- Tf rs- N CN CO CO C ro UJ N x- x- CO N cq in α uq q ro u O N co uo cM oq o oq cM co cM O CD CM CD O CD Tf o co N CD CD x- CJ) CO CO N CD x- χ- CO CJ) CO x- Cθ ro N CN O χ- N Cq CM ro uo N co UJ co ro ' μ ro cM CM cM c τf ib uj cb N N τ : (M C. (M x. lΛ d N d ∞ N N 00 N N ro d N ω (. N CCi Tf Tf Tf Tf Tf -r - m m m m m m m m m m j- j- t j' r xf i- - - N- - - N" x- CM x- CM ,_ 00 CQ _ χ - CM χ - CN OQ CO τ- CM x- CM x- CM ^ 0000 Ω Ω Ω Ω LU LU N < CO O < X χ < OO O Ω Ω LU UJ N X < χ χ Ω Ω LU LU X < 00 O Ω Ω X X X X X Z O O O O O X X X- CM X Z O O O O O O O O O O O X X X- CM X X X X X OOOOOOO X X x- CM X - CM UJ LU LU LU LU Α_ Q_ Q_ Q_ Q_ Q_ Ω_ G_ Q_ Q- Q_ Q_ K Q: Q^ Q Q_ CT __: _^ r- X X X X X LU W W W W W W LU W W W ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ UJ W W W W W W _. l _. l l t/ ) C/) ( /) ( )(β COW ( ΛCθ ) CO h hh h h H h hH h h h h J J J J JJ J J J J JJ J J J © o ro θ χ- CM CO τf uO CD N Cθ ro θ x- CN C τf LΩ CO N Cθ ro θ χ- CM CO τf LΩ CD N Cθ ro θ χ- CM Cθ τf LΩ CD N Cθ ro θ 'r- CN CO τf LΩ ω uj co co co co cD CD CD cD cD cD N N N N N N N N N N co co co co co cD co co co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o -- CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tt Tt τf τf τf τf τf τf τf τf τf τf Tf τf Tf Tf Tf Tf τf τf τf τf τf τf τf ^ Tf Tf Tf x^ Tf Tf τf τf Tf Tf τf Tf Tf τf τf τf τf LO r- © © Ui H U α. O O O O 00 UJ CD O CN O O O O O CO CO CN CO CΩ Tf O O O O O O O O O CD Tt iΩ CD O x- Tf OOOOOOOOOOO N ro CM O O O O x- CD x- O O O O O O O N lΩ CO CO CΩ CN CN O O O O O O O O O CM CJ ) x- O U0 CD N OOOOOOOOOOO CM N CN O O O O CO CM Tf Tf CO O O O O O CM CO CM CD CO ". O O O O O O O O O CM CO f Tf CO Tf CM CO O O O O O O O O O O O O CN Tf CM CM CM CM x- x- x- x- CM CN CM CM CN x- CD CM CM CM CM CM CM CM CN CM x- x- x- x- x- CM CM CM CM CM CM CM CN CN CN CN x- x- x- OO CΩ CO N x- Tf Tf lΩ CD CD O Tf cO N CO CΩ N O ro uO O CN CD CD τf O τf C0 N CD CD O C0 ro CD O C0 τf x- O x- O CM τf CM N CN τf x- τf O CD CO O CO CO ro O CO CD UJ O Tf ro CD UJ CD UJ CD ro cO UJ Tf CO Tf rs CD N Tf LΩ CM CD CD N UO ro cD CM CO UJ CM CO O x- lΩ N CO U N CO x- Tf CO CM CM τf cθ CO CO N O CD τf O O N CD CM CD N x- ro τf x- CO O N N CO UJ CO N O CD N ro N x- CO OO CD O O U ' O x- x- CO x- UJ x- OO C CD CD ro θ ∞ CM CO τf UJ CO χ - CO CO CN CO τf CD CD N CD UJ N τf r s - UJ UJ CD UJ CO N N UJ CD N τf 'sf UO CO τf CD τf lΩ CN CN CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ o cn CN N N UJ CD CN θ σ) τf CJ) UJ CM UJ Oθ ro θO OO τf UJ O CD CD O O CO CD CM CD CO CD CO CD O Tf xf CM CD CD 0 —0 C _D CM . N ro ro CD ro N D χ - τf CM τf rs cO CD CD CD OO τf rs rs θ CD CM OO UJ N i MCM mCO T.f UinO mCO T.f nO iUnO raCD mOO rx-- iUnJ iNs mCD iUnJ ^ .- j- N N . i _fi. W.. O_ O_ .iK. _D N TfO O CO CO CO Tf x- UO CO CD CO N OO x- CM OO CM N x- CO CD CD CO CD ro CO CO CO CD CD Tf CD Tf oO CO CO N x- CD CD UJ N O OO CO J CN UO CO N OO Tf CO CO O CO < c N " N " c - cN d cN θ o " ro " c co " C x— x- x- ro ro ro CN Tt UJ CD CD CD CD CO T CD CD CD CD CD CD CD CD CD CD CD UO CD UJ CD CD CD CD UJ CD CD CD CO UJ * -~ - -~ ,~ * ~ * ~ C * D~ -~f u ,~O C ,D~ U ,~J N -~ O -~O C -~O C ,~O N r ~ C -D~ C ,D~ U * ~J C * D~ U * ~J UJ UO CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CO CO CD CD CD CD CD CD CD τt x- x- CO CO O N τf CD Tf CD OO N N CO OO ro CD O x- Tf UJ N UJ N N CO Tf cO CO CD N CD N τf τf CD UJ x- χ- N CM 00 N CM χ - O Tf o ro ro N CO CD O CD CM N Tf CM CD O O Tf CM UJ CD CO CN O CD x- CO O CD CM UJ CD CN CO CN N UJ N CO x- ro τf N O CM UJ CM CM xf UJ O O CO N CM U0 CO O N N UJ UJ CD O CD CD CO Tf x- CO Tf CM CD CD UJ x- O O CO UO O Uj Tf UO O f O 00 CO N CO τ- CO CD O τf CN τt ro CM τf τf O UO UO N τf cq ro CD N ro cO OO N N N CO CD CO CD N CD CO OO ro CD CD x- ro ro cM cM CM ro ro cd cd d cM ro cM CM ro M c N in uό Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf J UJ Uj Tf Tf UJ UJ UJ UJ UJ UJ UJ xt Tf Tf Tf UJ UJ UJ UJ UJ UO Tf UJ UJ UJ Tf UJ UJ UO UO Tf Tf Tf x- CN CM CN x- x- x- CM CM CM x- x- CM CM CM x- x- x- Ω Ω Ω Ω oo ω CQ x- CM x- CM x- OOOOOΩΩΩ X X X X < CO < ω _. OOOOO _<pQχχχχχχ < 00 Ω - <_o.χχχχχχχχ--,<: CO x- CM CO OOOO _ X < X x x-x CMx CO z υ υ o oo o X X X x- CM CO x- CM CO OOOOOOO X X X x- CM x- CM CO x- CM CO Z O O [_ D[uDi2Dω<_ J <_ J _< J <_-<_ J <_ J <_ J <_ J <_- <_ J -<IJ<J<J< J< J<<J-<JJ< J<<J <JJ< J<J<<JLiJLU _J_J_J_J_J-J 333 r- _ι_ι_ι_ι<<<<<<<<<0>>>>>>>>>>>>>>>dddddddddddddddddddOOO © o CM CO τf UJ CD N OO CD O O χ x-- CCNM CCO τTff Ui-Jj CCoD Nrs CraO CcDD OO χ x-- CCMM CCθO τTff UUJJ CCDD NN CCOO CroD OO x- CM CO Tf UJ CD N OO CD . C vM - C .O , T -f, U -J C _D- N,- C«O. C .D.- O - ^ x -- C «M - (M rN ( CMN( < ( Nc c ( c c ( c ( c c χi- χtχt tχtχ χt t χ t m m m m m ococo ^ ^ ' ^ ^ ^ ^ ^ ^ ^ t N " v' ^ ^ f xf xt ^ ^ ^ ^ * * ^ * τr ^ ^ ^ ^ ^ '* ^r ^f '* '* '* ^- ^ J J _ __. __. __. __ ^ -^ - -. -. τf τf -sf τf τf τf τf x τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τt τf τf τt τf τf - - χ t ^ r- © © Ui H U α. OO OO ro x- OO N O O O O O O O UO CM CD O O O Tf O Tf uJ O O O O O CO N N CM CD CD UO UO OO OOO OOOO OO OO O O CD ro cq c co co o o q o o o o x- CO Tf O O O O CM UO N CO O O O O O τf CD x- N CO OO Cθ τf UJ OO O OO OO OO OOOO O ' N oo cD τf CM τf o d cM cd τf uό cM θ d d d o u- N cd N d ro x- cd d d d d d d d o ' d d d d N x- x-x- x-x- CMCM CNCM CMCNCMx- τ- CN CN CN χ - χ - x- χ - χ - CN CN CN CN CN x- x- x- χ - x- CN χ - CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN x- x- O O CO N UO x- O O CD N UO O CD χ - CM UJ O CO CO CM N τf τf CM x- CO N CD CD CD UJ τf CD UJ OO CD CD CM χ - _ C .O . x- O _ C.O. CO N CO CD CD IΩ O Tf CN Tf N CD CD CD x- N CO CM CD CD N ro CD Tf CM N x- OO N ro CD CD CD N UO Tt ro ro CM x- CO CO UO CD x- O N CO O CM ro CD N CD CM CO - C _D. C -O . UO x- Tf 00 CM N CD UJ 00 CM CM UJ N CO χ - CM CJ ) CD CD O O CD χ - τf θ CD ro N CM CM CO x- CN N N O CO CD CO CN CM xt O x- N CD CO CO CO UJ O CO CO lΩ lΩ lΩ lΩ CD τf CD τf τf CD τt rs cθ O x- CD OO CO O x- x- 00 O CJ ) x- ro CJ ) x- x- x- CO τf O CD CD N CD O CN x- O CD O ro OO N CO N CD CD CM CO CO CO CO CO CO CO CO CO CO CO CO CO CO τf τf c C C τf τf τf τf τf CO τf CO CO τf τf τf τf τf τf CO Cθ CO CO Tf Tf Tf Tf CO Tf cO CO CO CO CO CO CO Tf O x- CO CM UJ x- CD CO CD CO CM O CD CN co cM co co N Tf . c .o . cM ro co c .o c_D ro ro .. N. c _o u_j. ro_. - CO N N CO x- N N CO Tf CD CM U Tf cD ro CD x- x- CO C0 N CM x- CD C0 N τt C0 χ - 00 00 N CM CD CJ ) CN O τf τf CM O _ C —0 O CM . C —0 N CO CM τf τf r-- UJ CD O U N CD CO LΩ CO N O CO τf UJ CD CD UJ O CM CO ro UJ cOϋ OU lUΩJ C τ O) N|v- Tτfr x'r-- cOL> CXNj CrO) C»O Oσ CN liΩn CNN N-S C(N4 CN CCN C»O N lΩ N CO CD UJ x- O LΩ CO N CO CD UJ CO CM lΩ UJ CM CM N CD ro co N x- cq co x- cq uό uj N αD N uJ N τf cb u uό τf cd cb cd cd cM b τ ' τ^ u^ u^ u^ μ o ro μ ib CO CD CO CO CO CO CD CDCO CO CO CD CD Cθ ω (00 (0 (D (D CD CD Φ (OCO CO CD CO (O CD CO (D (DCO CO CD S S CO (0 (D CO CO (O CD CD (0 N N CO N CD CD CJ ) N ro N τf CD C ro ro UJ CO UJ τf x— u CM CD x— CD τf CN CD O lΩ χ- N 00 CM CD τf x- CD x- C0 x- x- τf O τf CD χ- O χ- τf C0 O O N N τf x- χ - CD - 00 ro C0 CO CM N χ - τf uJ CM χ - χ - τf r-- χ - ι N~ 0 J L0/ Lro Lro χ ^- LC0_. χ - LO O χ - CM C0 ro τf N x- τf uJ N CJ ) CM C0 C0 ro CD N U0 C0 U0 C0 CO C0 O O CD Tf x- CD UJ CD x- CO CM CD O CD CO OO UJ CD UO UO CO UJ Uj Tf cO N O CM CO N CD CO N τf τf CD OO CJ ) χ - CJ ) CM O χ - CO CD N CO CD CD x- CN UJ UJ CO CO τf CM N ιn U UJ CO CM CD U CD UJ CD UJ τf ^ cθ N N ro N C ro θ O CD UJ τf '^ 'sf UO τf τf cθ CD CD CO τf CD CD CO CO -^ τf τf τf χ f xf -^ τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf ' - τf τf τf uO UJ τf τf τf '^ τt 'xt τt τf τf '^ ,_. . - . - C oo oo < < cQ cαω ^ CO COOOΩ ΩLU LUN N N CO O Ω LU LU <χ χ χ χ < x < oo <χ χχ < 00 Ω LU N O O O O O O X X ^ CN ^ CM Z O O O X ^ CM Z O O O O X X ^- CM CO ooooυooz < x xx xx xx xx x x X x- CN x- CM x- CN x- CM x- CN CO r- 3 — I 3 — I3 — I 3 — I3 — I — l3—l — I3— I 3— I — I3— I — I — I >—-; I >— I >— l —l >—- I < _ I < _ I < _ I< _ | <_J<_ 1 <_J<_ I < _ I< _ | cso_ csows cso s s s s s s s s s s_ χ 0000000000000000000<<<<<<<<<< _J_J_J_J_J_J_J_J_J_J_J_J_J_J_JQ- © O Tf lΩ CD N CO ro O x- CM CO Tf UJ CD N CO ro O x- C CMM CC^0 xxff UUO0 CCDD NN CCO0 CCDD OO xx-- CCNN CCO0 τTff UUO0 CD NN O0O0 CD o C CD CD OO χ- CM C τf U0 CD N C0 ro θ x- CM C0 τf CD CD CD CD CD CD CD N N N N N N N N N N OO OO OO OO OO OO CO CO CO CO ro _ ro _. ro _. ro _. ro_. ro_. ro_. C_D. C_D. ro _ OO O O O O O O O O O x- x- x- x- x- Tf Tf ^ Tf Tf f Tf Tf Tf Tf Tf Tf Tf ^ Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf T τff Tτff Tτff Tτff Tτff Tτff Tτff Tτff xff Tτff Tτff Tτff UuOO Ln LΩ LΩ LΩ LΩ UJ LO UJ UJ UJ UJ UJ UJ UJ Tf Tf f Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tt xf τf τf τf τf Tf Tf τf Tf Tf τf τf Tf τf τf ^ Tf τf τf τf τf Tf τf τf τf Tf Tf ^ Tf τf τf Tf τf ^ Tf τf τf τf r- © © Ui H U α. CD UJ Uj Tf ls rs cD CD CD CO O O O O O O O O O CD UO CN CO UO O CO O O O O O O O O O O O O CD UJ CD CN CO O CO Tf O O O O O O CM CD CO O x- N Tf UO CM N O O O O O O O O O x- ro CM LΩ CD CM CO O O O O O O O O O O O O N x- UJ CD CO x- ro x- O O O O O O N N N CD OO CO N CO N CD O O O O O O O O O N CD CO OO CD UJ N CD O O O O O O O O O O O N N OO CO CO OO CM CM O O O O O O X- X- X- X- X- X- X- X- X- X- CM CM CN CM CM CM CM CN CN X- X- X- X- X- X- X- X- CN CM CM CN CM CN CN CM CM CM CN - 'Γ- X- X- X- X- CM CM CM CM C^ C O UJ N CN O CD CO N CD CO χ- CO χ- CD CD N CD CM τf τf Tf , N CD UO Tf cD UJ CO x- N CO x- O N N CO CO UO CO ro CM CO CO UJ x- CM O CD CO CD T f CM O CN CD CN N x- CO N O Tf T f cO CD UJ x- CO UO 1C-DJ CCNNl CCDD CO CO x- CD OO N CO CD xt χ- CO O CN CD UO CD ro τf τf cθ CD CM UJ CN CD O CO O Cθ ro 00 CD τ- x- O N τ xf UC0LJ ulΩj iCN LCjD iC0'j uinj τxτf ic'0j CjD iC0'j 0jL0J χ - τf τf cθ UO CD N CD Cθ τf O O CM ro cθ CM x— ro O CD N lO UJ UJ CD O x- O CO CN CM CJ ) CO CO CO Tf CD CO Tf Tf τf lΩ U0 O χ - τf CN CM τf CO CD U0 N τf U0 CD N τf cO UJ τt c0 CD xt C0 CM CD CD IΩ τf UJ CO UJ CD N C0 U0 U0 LD N τ^ Tf Tf Tf Tf Tf Tf τf τf τf τf x^ τf τf τf τf τf τf τf τf τf τf τf τf -^ τf τf τt τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf τf CD CO OO x- CO N O CO CO x- O U -O. C _J ) χ - CN CM CO O Oθ ro θ _ χ -- C „D N. τf |s CJ) O O O O C0 00 CM CD τf O N O x- C0 x- 00 CO T _t O_ C.O. . C _D. T ,f C.O. CO x- CO OO N x- CD CD O UJ N UJ ττtf xx-- τ-r-- CCO 0COO NN CCMM UUJJ xx-- ττff CCMM UUJ CroD τf τf CM CO CN O x- O O x- CD UJ x- CO x- O CO UJ CD CM x- CO UJ CJ ) CO CO CD OO UJ N UJ UJ CD CD CO CD O C.M- T -f —O ro_- _iΩ. C.O. x .- ro „- -u.O- O ^ _ ^ ■N UJ , O __ -OO_. ^CD ,N - O -^ .C-O, ~CO_- -UJ, C.O, C-D.. .U.J, »CM- -O_• C.M- _O C-.D, ^O_ C ^D O _. ro -. x ,- T -f C _.D- O ^ _ UJ N CO CO CO τf τf τf c CM x- CM O x- x- UO UO CO C x- C O x- O τf c τf xf c x- CM O τf CM CO x- CM x- CO CM x- O O in N N CO N N CD N CD CD ∞ CD CO CD CD CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD CO CD CD CO CD CD CO CD CD CD CD CD CD CO O CD CO CD CO O CD Tt CM N UJ CD O N N f Tf CM O UJ Tf CO N O CD τf cθ C τf c N χ- τf UJ CO CD CN CD CN CM ro N x- ro τf cθ O τf cθ ro χ - UJ UJ τf u N N N τf χ - Cθ ro θO CN Cθ CD N Tf Tf CD UJ CO Tf CD Tt Tf ro O CD O CO CO N CO CM OO CO ro cO CD UJ CO CM CD x- N CO CM CO CO x- OO ro O N N OO UJ O CO CD N Tf CD CO CM O N UO Tf Tf 00 N CN CM CO τf UJ θ ro ro τf rs cM CO CO x- O UJ CO N CM O N CM CM OO N τf x- x- CD ro θ Cθ ro x- CO CM CM CD CD CO Tf Tf CN CM CO x- CN O x- Tf CM CO CM Tf O CO CD x- LΩ CD N N CO N ro N CD CD CO CO N CJ) ro θ CO N CD N OO N N CO O x- x- N CO CD CO O CD T f Tf Tf Tf Tf xf xf τt τf τf τf τf τf τf τf τf τf CO Tf Tf Tf Tf f Tf Tf Tf Tt Tf Tf Xf xf -^ xf Tf UO Tf Tf Tf Tf Tf Tf Tf Tf J UO UJ T f Tf Tf Tf UJ Tf x- x- CM CM CN x- x- x- x- CM x- CM OQ OQ x- CN x- CM x- CM x- O O OOO Ω Ω Ω co co O < CO O Ω Ω LU UJ N < χ χ Ω Ω LU LU N < 00 Ω < oυoooooooo D Q x x x x x x x x < CO Ω LU X X X- CM X X X X X ooooυυυxx X χ - CM τ- CN CO x- CM CO υ o oo υco υ < X X X X X x- CM x- CM LU LU LU LU LU LU LU LU LU LU LU LU LU LU LU LU LU LU LU r- I— ~ \- — H I— I— — \— \— H I— I— x x x x x x x x x x x x x x x u Lu m L m L Lu m m m m m m Lu uj Lu uj uJ LU LU LU LU uj r- α Q- Q. CL Q- CL Q- CL C L 0- CL Q- Q- Q. Q. Q. Q. Q- d d d d d d d d d d d d d dd d d d d _> _> _≥ _> _≥ _≥_5 _ ^ _≥ _> S __i _> O UO CD N Cθ ro θ χ - CM CO τf U CD N Oθ ro θ χ - CM C τf UJ CD N C» ro θ χ- CM C t lΩ CD N Cθ ro θ χ- CN CO τt ιn CD N Oθ ro θ χ- CM CO rt x- x- x- x- x- CM CM CM CM CM CM CN CM CM CN CO C C C CO CO CO CO C CO τf τf τf τf '^ τf x^ τf '^ τf LΩ LΩ U0 UJ U0 UJ UJ jr mmmmm mmmmmmmmmm mmmm m m mmmmmm mm mmm mmmmmmmmm τf -^ τt τf τt τf τf τf τf τf τf - - χt τt xf τf τf τf τf ' " τf τf 't τf τf τf τf τf τf x τf τf τ^ LO r- © © Ui H U α. O O O x- Tf CM x- O O O CO O CO CD CM CM x- CD O O O O CO CD CD CO CO UJ O O O O O O Tf uJ OO N CO O O O O O N CN CO CO ro ro O O O O O CO CM x- CO O O O UJ O x- O CO CN UJ UJ O O O O N CD CO CO x- CM O O O O O UJ N N CD CD CO O O O O O CM CN N q q N N q d d Noό cbcbdd d CD N CO CD CO O CD O O O Oid 00 CD CO CO N Tt d d d d d N o ro μ d d d o cbcb ro d N c o ' CM CM CN x- x- x- x- CN CM CM x-x-x-x-x- CN x- CM CM CM CN CMτ- x-x- x-x- x- CM CM CM CM CM x- x- x- x- x- CM CM CM CM CN CM x- x- x- x- CM x- CM CM N CD ro CN N C CM ro σKD τ- -) -) CO O τ- CO C σ) τ- N -) co co o cOTf cDN cqoq Ncq rouqcM c Tbf uTfJ TfJ UTfOτTff c T df CTMf Tf dTf roCO Tf Tf Tf Tf O CO CO co o CM ro CN χ - CN CD CD N N τf cθ CN N O CΩ CO χ - τt r- CO O CN CD CO CO N O O CO τf UJ CD CD τf τf cO CM CD CO CO χ- O CD χ- CO CM xt CM O N N CM CO Tf CD τf C0 CD CM O O x- CM CJ) x- x- CD CM CD CD CD N O CD ro N x- CD CO CD CM CN χ- O τf CJ) CM CO UO CM N θ ro N O x- N CM CO Tt co CD cq co ro x- CD CO CN CO CO CO CN N ro cO CO CN CO CN CD CD N x- C N CM CN CM CO CM τf in θ N t ιn τt CM τt CO CO C N τ- ro CJ) σ> q CM τ-; OO 00 N N N N CO cb N cb cb cd N N ro ro ro d cb ro ro bcd ιri ιn ' τr τ. s ' ιri ri ιri : s oo s s ' σ) d o s ro ro ds sm ' ιri (D CD od b CO CO CΩ CD CO CD CΩ CO CD CΩ CD CO CΩ CO CO CD CΩ N CO CO CΩ NCO CΩ CΩ CD CΩ CD CO CD CO CD CO CO CD CD CO CO N CD CO CD CD NCO CO CO CΩ CO CO CO CD UJ CD N CM O τf τf CM CJ) CD O x- UO UJ CO CO O CO CM CO Tf CD N Tf OO CO CO CD CD CJ) N N CD χ- CD C0 C0 N O N χ - lΩ τf τf c0 O O CM CM τf C0 N CO CO N UJ N CO N CD x- CD CD CO UJ CO CO CM CD x- N τf τf CM CO CO UJ τf C -D_ O_ x- C .M_ χ -- x- CD χ- CO CO τf θ ro cθ O N CO N OO x- N CO CO CD O O CO CD Cq cq τf CD CD CM N CM ro θ OO χ- CO N CJ) O τf o ujTf DTf Nuq r Nv-qCD cCNMroCJ)oOqO N x- O x- x- N UJ N χ - CD CD τf τf cD ro τf x- OO CO CM μ M CM iri τf cd cM Lri uό τ cb cM cD τf (M CMd σJcd soJ o ' dd cdcd CO N N CD CD N CO CD CD UO CO CO CO N N O O O CJ) UJ UO U Tf -^ Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf cO Tf -^ Tf Tf - T f Tf cO CO CO CO Tf Tf Tf cO CO Tf CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tf Tf xf CO LU LU LU < < - CM DO DQ 00 CO CO 00 χ ~ CM X X X X X < COOΩ Ω <χ χ < 00 <χχ < ωO <χχO < 00 O x- CM CO OOO x- CM O O O O O O O X X ^ CM O O O O O X X X- CM X Z O O O O O X X X- CM X Z O O O O O O X >->- >- Ω- Q - Q - Q - θ- Q - Q - Q - Q - Q - θ- θ- L Q _o_ r- J J J CβW(/)W(/)tO(ΛCO(ΛCflCO(/)l_l_l_l__J l__J_Jl__Jl_l_llll_ω 000<<<<<<<<<<<<cocococococococoωcococococococococococococo>>>>>>>> © N Cθ ro θ x- CM CO τf uJ CD N Cθ ro θ χ- CM CO τf LΩ CD N Oj ro θ χ- CM CO τf u CD N Cθ ro θ χ- CM Cθ τf UJ CD N (X) ro θ χ - CM C^ o CD CD CD N N N N N N N N N N CO CO CO CO C» α3 C» CO C» Cθ ro ro ro CD CD CD CD CD CD ro θ O O O O O O O O O x- x- x-- x- χ- χ - χ - x- χ - m m m m m m m m m mm m m m m m m mm mm mm m m m m cD _ co co <o iD (θ (θ co (θ (θCD (D(D CD(D CDCD CD τ Tf+ τT*f τT-ft xT_f' τTf τT*f τTif- τTf* τTf*- τTf+- Tft τTfi- τf ' ^ τf τf τf τf 'xf τf τf τf τf τf τf xf τf τf τf τf τf τf τf τf τf τ^ Tt Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf xf r- © © Ui H U α. O O O O O O O O OO OO UJ CN CD Tf CD Tf CM O O O O O O O O CM CD CM CO CM T O O O O CO CN CD N O CM CO N CM O O O O O O O O O O O O O O CM N CM x- UO OO CM O Tf O O O O O O O O CO O N CO N CD O O O O O CO CO x- CM O N χ - UJ C0 O '~' '~> O O O O O O O O CO ro cO UJ O Tf rs x- CD O O O O O O O O UO N UJ UJ UJ Tf O O O O O O CO Tf cO x- OO UJ CO CO CO O O O O O O CN CM CM CM CM CN CN CN x- x- CM CN CN CN CM C CM CM CM CN CN CM CM CM CM CM CM CM CN CO Tf UO UO CM CM CM CN CN CM CN CM CM CO Tf Tf Tf CM CM CM CM CM CM O N CD UO Tf UJ CD x- OO CO O O CN N OO N UO Tf CD CO ro cD CD x- N UJ CO x- xf CO CN CN CN CO CO ro cO N Tf CD lΩ CO N CD Tf CD O CM CM Tf x- CD CD Tf Tf UO O CD x- x- 0O 0O 0O x- x- τf CM N CO x— ro uo o ujc) x- x- CD N UJ CO N UJ x- O CO UO CN Tf O OO CD CD x- Tf O x- UO D CN CD CJ) O x- CD ro o co CD Tf CD χ - N cq ro o f ro ro N N N Tf cO CD CD OO Tf O CD O OO CO x- CM O UO UJ τf ro χ - CO τf CM x- UJ CD OO CO O CD CM UJ UJ CD Tf O OJ CM CM CD o cM M cb cM CM O cb cM CO CM CD CO CN CM CM CM CM cd ro CD N b CD C cd O CO N CO O CD Tf CO Tf Tf Tf Tf CO Tt Tf Tf f Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf Tf CO CO τf τf τf τf τf τf τf τf cO CO CO CO CO CO CO CO Tf Tf CO CO CO Tf CO θ ro cO O UJ CO CO τf rs τf τf O CN C CD N O CO O CD N CM N C τf O CM UJ τf cO OO τf CD Tf ro x- CD CN x- CD Tf o -O_ C-O. τf CD τf τf OO τf CM N ro OO N O OO CO UO OO CO ro cD CD N x- CO UO LΩ x- O CO CD CD N CO ro UO CD Tf x- cO CD Tt CM CM Tf CD CO O CO N CM Tf Tf CO OO CD OO UJ CD CO ro uO N ro cO x- U j ro N OO O ro CD in cO CD CM x- CO O CM Tf cO UO ro x- CM CO CO LΩ UJ CM CO CO ro CD N CO CD N UJ x- CM Tf CM CM O Tf cO N CD N N N OO s is ' b uj ι UnJ ( LU ι UJ ( CΛbJ © UJ o UdJ ^ XT b CJ b CJ c IM C INN τ x-- b U U Uro) UιriJ b f) c (NNi CcMN b U τ r-- c CoU bOU TT xT UJ UJ Tf C x— C J τTf cCd) τTff ττfχ ' cib£j N| cbL> cbU cαbj cUDJ o_> dC_> _> cCbIj Nr cαbj Nr cαbj roJ CD CO CD CD CD CD CD CO CD CD CD CD CD CD CD CD UJ CD CD CD CD CD CD UJ UO CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CD ω LΩ CD O N O CM xt CD N N N U Tf x- 00 N UJ UJ C0 ro CM χ - N CJ) UJ CM τf τf θ C0 CM O τf 00 CD χ - τf CD C0 ro ro ro LΩ Tf CD UJ CJ) x- O Tf CM O CΩ x- ro CN Tt o cO CN O lΩ CO OO N CM OO O UO OO CD U Tf rs oO CO CO ro x- x- CM CO CD x- CM O N O CM O O CO CO CD x- ro O D O N N CM CO x- Tf cO CD O CO CO CO Tf ro cO CD x- CD τf O χ - CJ ) χ - N UJ O χ - CO x- N N O N CM O O τf CD OO χ - CD CD CM CD CD N co co x- ro o ro uo ro 00 ' d d d T^ -r- d N N ιn iO N N N ω s ' ∞ N N (O N ' d N ' d m ' c. (. ( (M CN t V lθ d UO UJ N N N UJ CO CD cb iri Tf CO Tf Tf Tf Tf Tf Tf Tf CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M x- x- x- CN CN CM _ OOOO OQ ω LU LU T CM 00 OQ U < OQ O Ω Ω < χ χ < CO Ω LU LU co oo O < CQ X X X X X X < CO O Ω LU L X X x- CM CO x- CM CO oooooυoz _<xxxxxx < X X X X X X x- CN x- CM x- CM υoooυooxxx-cM υooooυoz X X x- CM x- CM -J _ι _J _J _J _l _J _j Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z CL CL CL CL CL CL Q- Q- Q- CL Q_ _L Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z r- < < < < < < < < — i — i — i — i — i — i — i — i — i -J — i — ι _i — i — i —i — i m m m m m m m m m m — 1 _ ι _ ι _ ι _ι _ ι _ι _ι _ i — i — i — i — i — i — i >>>>>>>>00000000000000000<<<<<<<<<<<<000000000000000 © o ro θ χ - CN CO τf U0 CD N α0 ro θ χ - CN C0 xf UJ CD N C0 ro θ χ - CM C0 τf U0 CD N C0 ro θ x- CM C0 τf U0 CD N C0 ro θ x- CM C0 τf UJ CD N CD CJ) O χ - CM CM CM CM CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO xt xt τf xf τf τf ' " τf '^ τf UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ CD C^ O CD O CD O CD CD CD CO CO LD LD LD CD CD CD CD CD D CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD CD C^ t xf Tf ^ T Tf ^ Tf τf τf T T τf τf '^ f τf f τ Tf ^ ^ T τf ^ T τf τf ^ Tf xf f ^f ^ '^ O O CJ ) x- N O CD U0 τf UJ τf CD CD C0 N CD O O O O O O O O O O CD N C0 UJ C0 O N N τf O O O O O O O O O O O O O CM N C0 CM O O CM cq θ CM CM ro cq iΩ CD CO N O UJ O O O O O O O O O O χ- x- CM x- τf O CO τf N O O O O O O O O O O O O O CM CO UO τf d o roro roro ιb τf ibιbuότf cb τf b d d o do dd dμ τf uό cN cb uj μ d CM CM CM x- χ - χ - x- χ - χ - x- χ - χ - x- x- x- χ - CM CM CM CM CM CM CM CM CM CN CN CN CN CN CN CO CO τf UJ CM CM CN CM CN CM CM CN CM CM C^ co co co to m c tD co o ro ' co o o co cD ro o r- ro - o ro to o co co co N O CM ro N c ro ^ m tN co ts ^ m ro N ro ro to CD CM CD _ CD _ O 00 UJ Tf o cO CO O CO Tf CO J o O CO CD CD Tt N O UJ uJouorororox-ocDuococo O N OO CO CD T- X- O CD CD CD o ro τf cq ro N o cN χ- cM χ- ro oo N N co u χ- N CD o ro co Tf co ro N N CD τ- O χt CD O CD Cθ iΩ N CD τt ro O Tf CD CM N CO CM CO CO CO N ' d uj xf ' ^ cb N cb cb cb cD ro c u cb N uό N 00 d d ib Tt oo cd ro CD N cb CO 00 N N CJ) d cJό od τ- μ μ cb uό cb cM τf τf CO C CO CO Cθ CO CO CO CO CO C Cθ C CO CO CO CO CO CO CO CO Tf Tf cO CO CO CO CO CO CO CO Tf cO CO CO CO CO CO CO Tf CO CO Tf Tf Tf CO CO CO CO ra iΩ N τf N co ro co ro ro ro ∞ j cN x- uo co ro N co co χ- oo -o ro cD co χ - τf cN N iΩ co co o cN CN uo ro χ - cN co cD ω x- τf O CD Oθ ro CD N O O CO CO χ- CM CD CO Uj ro CN CO f χ- O N O CM C CM CD ro cθ ro θ χ- τf O UJ UO C UJ CO N N ro ro τf CD ro CM CO N CD ro x- CM CM Tf x- x- rs ro CM O O x- N N UJ x- N Tf cD UJ CD UJ CO ro cO x- Tf CNj cO x- O ro ro O CO Tf O N x- Tf cq iΩ o ιb cd cb cb cb τ b u τf CM cN U τf ' j cM u τf ^ N N CD CO CD (D (0 <O CD CO CO CD CO (D CD (θ ω (0 (O CO <0 (D CD lO (O CD (D (O CD (0 (D (O CD CD CO (O CD CO CD CO CO CD m CO CD m CD CO CD CD m roN roroτ-c ffico co(M roo roro - ∞cMCM romroo τ-comcocM - (θcororo N rocθ -τ-ffi ~ m moocθNcococoo cocM τf CDCD x-CO CD CD CO CO CO x- x- ro ro N CO O CN UO τf f UJro N CO COCO (n UO C U CM O CD N τf Cθ O CO N ro x- CD Cθ τf cθ θ ro U^ CN roo cqq cqcM u χ - τf χ f cD cq τ D u f co N θ f u. τ τf co θχ- τ co ro d d uj Tf ' ∞rji D o d ro d ∞ c M N Tf C CO CO CO CO CO Cθ CO CO CO τf τf cθ τf τf τf cθ CO CO CO CO τf cθ τf -^ χ ^ o CO CO Cθ CO CO CO CM CM CO Cθ CO CN CM LU LU , r , r £. , '- CN CO CN Cθ CN 0Q ω τ- τ- C CM C M ^ CQ OOOO ΩΩ LULU NN N X X < C Q OΩ Ω LU LU LU N N X < χ χ Ω LUUJ NN X < 00 O Ω LU N < XXXX XX XX XX X__, <C _ x- CM ooooooozoooυo X X X- CM X X X X X X OOOOOOO Z X X X- CN T- CN X- CN T- CN X- CN CO Z O O O CO C CO C ω c ) C CO W r- © x- CNCO Tf LΩ CDN ∞ro O x- CN CO Tf uJcO N ro ro O x- CNC^ Tf U CON ωro O x- CN C Tf UO CDN ∞ o r- N N N N N N N N co co co co oo oo co co co oo ro ro ro ro ro ro cD ro ro ro o o o o o o o o o o χ - χ - χ - χ - χ - χ - χ - χ - χ - χ - cM CN CM CD CD CD CD CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CD CD CO CD CD CO CD N N N N N N N N N N N N N N N N N N N N N N N N τf τf 't ' ' τf τf τf 'f τf '^ τf τf τf τf τf τf τf τf τf τf f τf τf τf τf τf 'ςf τf τf τf τf τf τf '^ Tf Tf Tf Tf Tf Tf LO r- © © Ui H U α. O x- CO CD CO O O O O O O CD C CO UJ CN CD CO O O O O O O O O O O O O CM C N N CM Cθ O O O O O O C τf O χ - χ - N CO O N O OO cO N O O O p p O O x^ T f o αD O CO O Tf O O O O O O O O O O O CM UJ CO Tt ro cO O O O O O OO x- CD CO UO N ro CD CD CD O τt N iri ro μ d d d d d d τf cb τf CNi uό u N od d d d o d d d d d d cb τf d cb N d d d d CO T f UJ UJ CD CM CN CN CN CM CM CM CM CM CN CM CM CM CN CM CM CM CM CM CM CM CN CN CN CN CM CM CM CM CM CN CM CM CM CM CM C^ CO lD CN OO CO CO x- CO N N CO CO O O N CΩ CO lΩ CO O ro CN CΩ OO N Tf x- UO CO CD CD ro U Tf oO Tf UJ CO N CO x- lΩ N x- CD CO O CO ro CΩ x- x- CD CO CD CD CM N N CD Tf x- ls CD Tf x- Tf LO N O CO ro Tf r^ N CO ro CO τf O N N τf r- | |sS x x-- c l θ- J x x-- O L _ J C I O 'J O L - J C C OJ O CO UJ CD CJ) CD Tf Tf x— 00 UJ Tf CM UJ Tf ro oo x— C iM CUD UuJ xx—- C IN NΓS lUΩJ CUDJ TTfΓ ro UJ OoOϋ ClDϋ UUJJ 1CD1) C UD) TCOJ UCDJ C CUO UO ( COϋ C (ϋD C CDD O O ( CDD X- C CMN T Tft TTff CCMN COOO xx-- CC-OJ roO. CUD COJ OC lUOJ COOU roIJJ oCJ roOJ CCN UUOJ COO xx-— C 0Oϋ CD N N cb N NuJ uόcb cb cd cd cM o ' CM CM b cd τf x-^ cN co cd τf τf d cd cM ro M M b cM o c roo o ro cb o CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CO CO CO CO CO CO CO CO CO CO CN CN N UJ CO CJ ) τf CM x— x- ro CN C C τf cO UO N UJ LΩ UJ x- CN N ro c CM O Uθ ro τf CM x- O τf CD OO CM OO CN C CD CO CD O CD OO CJ ) N N CM Tf ro O CM ro CM CO χ - lΩ CD O N ro χ- O N OO N CN O χ- N CO O CM CO O UJ CM N τf τf CJ) CO τf cθ CD τf CD x- CO x- CD τf uJ UJ CD Tf UJ OO CO CO N ro ^ ^ ' '^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ 0 . p cM τf cq cM u χ f χ -^ u cM ro ιn ιn cq τf J O ro UJ CD CM x— D x- CD CD dCD NN uUJ Tτff iubo Nrs Nrs ls uLΩ uLΩj dCD Tτff xff CD NN NN cObO ilbΩ dCD UJ uUjJ cCbO NN NN- cCbO raCO Cθ ro c CN CM x- x- CD CD i cCoO cCDo CcoD cCoD cCoD cCoD cCDo cCDo cCDo cCDo cCDo cCDo cCoD cCnD CDo CoD CoO CDo CDo CDo CoD cCoD CcDo cCoO CDo CDo CDo CDo CDo cCDo cCD^ CD CD CM CO x- CM CO CO O x- Tf CO O CO oo C0 ro C0 N CD ro τf C0 CD CD τf CM CD CM N CM C0 CD C0 C0 χ - 00 O τf O CJ ) CM N C0 UJ O C0 CD C0 τf rs CN Tf ro x- CM CO Tf x- OO CD O OO 00 O τf UJ CO UJ τf u ro N ro CO O C» τf cD CO O τt CM CM UO CD U τf O N CN x- CO UJ N CD UJ CO τf θ ro x- CO UJ CO CM Tf oO CN Tf x- uj N O o uq CD CO CD N CD CM O x- CN N N CD CO Cό O N N OO in ro O UO CM U CM N x- x- CD N x- OO ro CO x- dθ cro cCOb cCOb cCMM dO x- cCMM O χ - CO Tτff Tτft Tτff LLriΩLLriΩ N Tτff ccdθ cCO CDuUJ cCDcCbD N-iNN Tτff cb uUόJcCOd τf CM CM xt CM Cθ xt UJ xt CM x- O CJ) CD O O x- O x- O x- CO CO CN CN CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO C^ 00 CO CO CO CO ,_ ■ >- CM x- CM < CQ O Ω Ω LU LU Z O O O O O Z O O Z X XX XX XX XX X X X τf Ln CO N Cθ ro N N N N N N N N N N N ^ r- © © Ui H U α. O O O O O O ro O O CO CM O CD O Tf O O O O O O CO O ro cO CO UJ O CM N O O O O O O O O O O x- N CD UJ OO CN OO CD x- O O O O O O CD Tf x- cO CD CO UJ O UJ O O O O O O O O O O O O O O O O O O O O O O d d d d d d uό cb cb r-i uj cb cb cb d d d d d d CM cb N " cb d N d cb d d d d °. PPPPPPPPP PPPPPP rM CN CM CM CM CM CO CO CO CO CO CO OO CO Tf CM CN CM CM CM CM Tf -^ Tf -^ u UO CD CD Tf CM CM CM CM O O O O O O O O O O O O O O O O O O N Tf CM CD N CN x- U Tf O x- CO ro CD N CM CO CD CD N CM CD CM CO CO x- CO OO CD ro ro cO CD CD CM x- CM CM CO CO CD CO CN O x- CD CO UJ O CM θ ro ro CO lΩ CM CD ro CD CM CM CM L ■ Ω" CroD CCMM UU0θ CroJ ) ττft UuJ ULbJ CcMM CθOO CCDD ττff O_ CN CO τf O _ C.M. C .O. T -f O CO x- C .N. O_O O_ T .f C.N. O_ CO CO CM Tf ro Tf oo Tt co N. C __O~ N .- x _- ro ^ x- Tf - x__-_- r-s o __O x- Tf x_t_. c-o~ o-q~ N^ oq _. oo CCMM τf CM . :N CM . U " J :N N C _D_ C.M. ro__ C.M. τf._ C_D O__ N. _ C_D_ CO UJ τf - θO x- C COO _ C_D_ Tf__ C_D CM CM Tf ro CO o od N O N CM CM CM x^ C- lri c tD N CM μ b cb uj uό M CM θ c τ '^ ιb d M M cd c τf f '^ τf c c cd c^ CO CN CN CN CO CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO co CO N OO N Tf O OO UJ CO x- x- τf OJ N N CD N N UJ OO O x- UO UO ro x- CD CD x- CD CM CM UJ CO O) UJ Tf [s x- 00 O UO ro CM O CO UJ CD x- CM CO N N CD CD CD CM Tf CM CD N N CN UJ CM CO ro cD N CD Tf O CD χ - CJ ) N CN CO τf CM N O CM x- CD x- CD CD Tf O x- CM χ- CD N τf CM CM C0 O CD U0 N Tf CD CD x- CM x- N CM x- x- CD ro UJ OO N x- CO O Tf tv. x- N O x- x- CO x- O CM O CD CO x- N Tf CO O N N co Tf cM Uj D D ro cM o rv- cN CM μ cb uό b cb c N OO CO N N N O CO OO N CO ro CD CO CD O CD CO N ro cO O N OO O N CO ro O O CO CD O O x- x- C CMN CCDD NN CDD CM CO CD CD CD CD CD CD CD UJ UJ UJ lΩ UJ lΩ UJ UJ CD UJ UO UO UJ UO UJ UJ UJ CD UJ UO UO UO UO CD UJ UJ CO CO CO CO Tf Tf CO CO Tt Tf Tf Tf Tf ■ C " O- C -O C -O Tf Tf ro τf rs x- -xf CD ∞ CN UJ N UJ UJ U0 τf τf σ) CM C0 U) N 00 UJ N C0 C0 CD N τf CM CM ro θ 00 C0 O N OO Tf CO CM N CD x- CD CO CO CO CO OO Tf CM CD CD CM CD lΩ τf σ) CO χ- CD CO OO CO OO CM C O χ- UJ O χ- O UJ τf cθ CD UJ UJ CN ro cθ x- UJ χ- CO τf OO O UJ UJ OO CO CN CN OO CN CN CD CD x- ro O CO J N CO CM CO O OO CO x- CO CD co Tf oq f -^ co co CD co ro cq q x- N N CN uo UJ ro x- x- N O x- O N x- Tf CD o N CD O CD I s - CD CD ro roro cMrocNdrocdcodoόd ro d d μ cb ro N uό uό uj uj uό uό τf N- u_ τf uό ro d μ d ro cb cD CO N CM O O CM CM CM CM CO CO CM CO CO CM CM CM CO CM CO CO CM CO CO CO CO CN CN CN CM CM CM CM CM CM CM CM CM CM CM CM xt U " J U " J U " J Tf Tf Tf Tf Tf LΩ LΩ LΩ UJ IΩ UJ UJ UJ UO 0000 ■ "- CM x- x- CM oo OQ TT CN h- 00 DQ O χ- CM CO τf UJ cD N CO < X X Ω Ω UJ < 00 Ω LU LU < X X X X < DO Ω Ω X < X X x- CM CO Tf J CO X X X x- CM X X X OOOOOOOO X X x- CM x- CM Z O O O O O O O O X X X- CM O O O O O O N 00 xδzoδδδxυυ ^^ 2^^ 2_ι_j_ι_ι-ι_ι_ -j-j-ι-ι-ι_ι-i-icocococo ()cocococococoθθθoυυooooooooυυoo © χχχχχχooooooooooooooo<<<<<<<<<<<<<oooooooooooooooooo O in cD N Cθ ro θ χ - CM CO τf UO CD N OO CD O χ - CN CO τf LΩ CD N CO CJ) O χ - CN CO τf U CD N CO rsisNNNcocooocooocococococorororororocDrorororoooooooooo i Tsf iTsf rTsf iTsf rTsf rTf rTf rTf rTf rTsf iTsf iTsf rTf iTsf rTsf Tf NTf NTf NTf Tf NTf NTf NTf NTf NTf oTof cTof oTof c CM CO xf UJ CD N CO Tof cTof oTof cTof cTof oTof CM CO Tf LΩ CD N CO CD ro ro ro ro ro ro ->. -»- - j . (θ θo Mro n j- ω ι ^ ^ j- Λ CA) ωωω ω ω ω ω w ω ι r w w ι. ι N) i t N) -i cn 4 s - co ro -^ o co oo si ro cn 4- co ro cn 4- co ro - » - θ D c_o si ro cn 4 s - co ro -^ o cD C_o -v! cj) cn ^. co ro -^ o cD d d dd dd OOOOOOOOOOOOOOOOOOOOOOOOOOO I " 0 " D ' U -O I I I " 0 " O I ) " □ " D TI I TI I I I I I I -O l OO OO OO OO O O O O O O OOOO OO OO OO OO O I I I I I I I I I I I I I I I I I I I I I I I I I I I °._x O X 0!_X OX=_O _±OX O ro to X j ;Xto X X O X X ^ O OO O O O O O Z O O O O cD x x ro oo oO OX X x Ό ro X ro X X ^ -^ 4 s - 4 s - X j^ 4 s _.4 s . co oo co co co co co co co χ χ tLj ro X ro ro to ro r rLj -». to ro x ^ -" o x x ro ro ro ro ro ro j^ cji 4 s .4 s - r ->- o co oo si CD cn 4 s - oo ro - i co io oo sj rLj cn 4- co _o -- o cD co 4- 4>- 4- cn cn cn 4_. j_. -fc- cn c ..n.c ~n.- _N4-_ s -4- s --ι.o_ι.o_r .o_cnoιoιcncncn4 s .4-4 s -4 s .4-4 s -4-4 s -4 s -4 s -4 s -4 s -4 s -4 s -cnc^ co co coco co co co oo ooo moomoo ( cnnfcnnfcnBcconmcomp_o.--iO(Jl (_lWNC«ro fflN(DO)(J)slOOOO(DfflOO(I. WWMOO-'I MWW cnroip-coioJC-ocD- .O_ _._- ro ' θ _ > d rθ 4- fθ l cθ - CD -». CD CO cnj-.ωrocorororoi^- ^ s.o s ..odi-- i- -ιborow CoO - i _- -- co o tωO cCoO c s»j rCoO WOAsj ' s - cn ro o ro cn ro sj cn cn s C_0-^C CDLθ-^Cn Ds _ι.^.rooC OOOCO-^-^->-COOOsJOCD- ^ rθ4 s -CJ) J-O M O -vi co o si o ro 4 s - co co ro o ro oro- ^ ro4 s .osjs4rocD-^cjιror DcnMsioo Dcosj-_v^.__. - ^ r cn c cj oo cj Cjθ Cj co cj co 4 s .4- 4. ω o- ω c c c co o c . .^ 4 s .4 s - .4- 4 s - 4^ p w i- M W MM Mro ro ^ ro i-i ui -^ fo po fB CJi ^ ro ro co^ ^ ω co co co io -^ t d d d -j -Ni -j bo oj o- ro ro -j d d d -j bo ∞ ^ ro fif N) O CDO 00 W N)O 0D W O O) W - i (0 ^ N)O ^ N) C0 ro 00 N) ro w CJiro ro M W (0 W ro w ro A - l ffiM xl S -' (0 (» O 0 (J C C ^J^ -.O M oo roM ω ω (O C)l ^) ω o M oo ^) ω cD cn (D CD Oo o ow (D Λ ω - ι M ω - ι oo (Λ oω (o ro QO M cD (D ro c_l AM ffi to ro ro to co co co -- ro -^ r ro ro ιo ιo ιo co co co to to to -». ->. -». r ro -^ -^ -'■ -'■ ro ro ro ro ro ro -'. ro ro -N ro i ro oo CD oo co o co c» co co co cD Co oo cD po r co ro ro _si ro o co _sj -vi co oo ro co co ro ro ->. cQ o o -j ro oo ro sj oo p oo sj ro cn co 4 s - cn σ) 4s- cn cD - j - ro co -^ r ro ro si oo o -^ ro d - » - - ι -». co co cn -»- d -i o n oo o co oo ro o ->- ro cD vi ro J>. bώ ώ ' ϋi J.i-) co j- j . cn cD co u _i o_o oo 4 s - ro σ _) t.o. r.o. .ro_ c_o cn cn ro sj sj 4 s . - i - i -vl CJ) 4- 00 CO 00 CD sJ xJO W A CO OD N) U ls ) x| N) A W Ul ro oo si o o co co ro oo o 4- 4- cn co ro co ro ^ M cjι cD CD Cθ ∞ co ro ro co cθ 4 s - ro co cD 4. ro 4- o o o ro co cD O *>. c) ro ro cn cD oo - » . -t- co cn s - o cn co CD M M M I. M M I. MI t N) l. N ) I I M I I M I ι\ ) M ι\ ) Mr O O O O O O O O O O O O O O O O O O O O O O O O OO O O O O O O O O O O O O O O O O O O O O O O O O O O ^ ^o r -,o^ ^ ^ ^ ^ ^ r -o^o^o^ ^ ^ ^ ^ ^ ^ ^ ^ ^ „ -, -, ^ , ooooooooooooooooooooo O_O_O oooooooooooooooooo o o oooooo ooooooooooooooooooooooooooooooooooooooooooooooooo OqOqOqOqOoOqOqOqOoOoOpOoOoOoOpOoOoOoOoOoOooOOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOoOooOOooOOoOoOoOo dddddddddddddddddddddddddddddddddddddddddddddddddddd CM CM CM CM CM CM CM CM CN CM CM CN CN CM CM CN CN CN CM CM CM CM CM CM CM CM CM CN CN CM CM CM CM CM CM CM CN CM CM CM CN CM C^ Tf Tf Tf O O N CO CO CO N CO LΩ Tf N Tf CO CO O CD CM CO N CM CD CO x- N N CO O ro x- CO N CO U Tf Tf O O CD CN CN O CD CD x- CO N O N ro roc N coco oT f T f r O O O O O O Tf Tf x- l.Ω_, f Tf rs r ro N CN N O o CO CM x- UJ OO CO x- lΩ UO x- UJ U CD O O CO x- x- O) CM CM O CO CM x- Tf CO CM CD U) Tf N N CD N S- CD O CD CO CO N CD O CD OO O O O C Tf Tf cO x- O ro cO N CD CO CM x- N N CD CM CM x- CM CM x- N CD UJ Tf CM CO CM CM N c6s ' (- N-co ro o. coV cM CM CM CN N CO CD N CO N O x- CD UJ CD UJ OO CD CO C -O. Tf c.O OO CM CO CM Tf uj CN CN τf τf τf CN CN CM CO CO CO CN CM CM τf ' " τf CN CN CM τf ' " τf CM CM CM CO C C CM. CM. C CO CO τf τf cO CM CM C^ CM T.f. roTf cTof CM CM CM Tf Tf oo CO N lΩ ro cθ N x- O N x- O χ- UO τf |v. o CD x- UJ CO τf CO N CO N UJ O xt C OO CN χ- CM CD UO CO N UJ χ- τf cθ CD O roN x-O CON U0 τf 00 OO O CO lΩ N ro CM τf CJ) CM xf UJ N ro u Cθ ro CO O τf CD C» CO O CM N ro x- O C in CM τf CD x- CO UJ x- CO in cθ x- CM N O CM CD x- CO N CJ) cN cq χ- o o ro ro ro ro ro ro cq cM CM U τf τf o ro o co cM CN in uj u o uj cD N N χ- o o τt x- CO CO CO CO CO CO CO CM d cM CM co ro ro μ Tf Tf i cM CM c d ro μ -^ cM uό u d d cN CM cb ib cb co Tf N CM cd UJ UJ τf τf τf f -^ U0 CO CO CO CM CM CM C CO CO lΩ τf UJ U0 U0 UJ CO CO 00 τf -sf τf cθ CO CO τf τf uJ CM CM CM UJ U^ Tf OO lΩ N x- LΩ αj x- CM U ro o ro CM UJ CO x- ro CN UJ CO x- U Tf lS x- Tf r^ x- CM Uj ro CM Tf cO UO N x- N ro cO N O CO x- Tf N x- CO N CD CO x- O O CO CO τt CN CM lΩ CO CM CM O θ ro N N x- θ ro τf Cθ CM CO x- x- O CO CO UO CO CM χ- CJ) CO UJ CO CO N UJ UJ N CD UJ N LΩ Tf LΩ CO CN Tf CM N in cM cq χ- cq ιn co co iΩ cq uo N uo oq o oo iΩ N τf co o co co o co cD N in cM τf cM ro p co χ- cθ χ- τf q co o ~~ c " o o cN o ro x- ro ro x- c co cd co ' cd cb cb c cb cd cd cd cb cb d μ d od cd cb N cb N ^ cO Tf cb c cb N c N cb Tf CO C τf '^ 'xf cO CO CO τf xt τf '^ xf ' - 0 CO CO τf τf τf LΩ U0 UJ UJ UJ U0 CM CM CN CD CD CD CD CD CD CM CM CM U^ CN CN CM CN X X x- CM X CM X XO CM O X XO X θ r- __: __: __: __: __: __: !__ Q_. _ Q. __L Q- Q- 0- 0- Q- 0- Q- O. l Q- Q- Q- Q- ^ 0- Q- ^ Q- Q- Q. ^ ^ I- h I- h h H I- H r- l- l- l- r- r- l- r- - H r- r- l- l- l- l- l- l- l- l- l- l- l- l- H I- l- H h- l- H I- l- l- l- l- l- h- l- l- l- l- © o CD N Cθ ro θ χ- CN CO τf u CD N CD ro θ χ- CN CO τf UJ CD N Cθ ro θ x- CM CO τf UJ CD N CD ro θ χ- CN CO τt UJ CD N Cθ ro θ x- CN CO Tf UJ CD N CM CM CM CN CO CO CO CO CO CO CO CO CO CO Tf x ^ -f Tf '^ ' ' Tf 'st ' ' Tf in UJ UO UO UJ UJ UO UO UJ UO N N N N OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO 0 0000 00 00 00 00 0 0 0 0 0 0 0 0 00 00 00 00 0 00 000000000 00 00 00 00 0 0 0 CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CD N τf cθ CD CO CM x- N N O O CO N CO CO τf O O CM CD CO CO LΩ τf oθ τf τf 'sf O O τf O O CO ιn τf χ- |s |S x- <X) r- (O xf τf OT CO CD O O CO N N N O O 00 O τf τf τf 00 00 C0 ro ro θ τf τf τf C0 C0 N x- cd CN CM Cb d O x- τt τf CD CJ) ro ro cθ CO U ro CD C0 CN CN UO p O ro CO N CD Tf Tf CO OO CO N CN T- oO oO roro 0o0O uUOo Tff cCoO Tf CO CM CO N CD CO CO N * -N N - C "D- χ- χ- O θ ro θO CM χ-^ O CD CD UJ τf cθ CM O θ ro Tt cd Tf CM N CD CD d ro N cd N μ μ ro rocb τ f cb roo cDτ f ' UJ Tf Tf i Tf o roc cdcbN-cb Tf cd μ cb Nc cMc x- 1 τf cO CO CO τf τf τf x- CM χ- CM CM CM xf xt τf UJ U0 UJ CM CO CN CO CO CO CO τf cθ τf τf τf cO Cθ CO x- x- x- x- x- x- CO C CO τf τf τf τf τf τf CM CM CM CD N N x- O χ- UJ CO τt oO N ro cθ x- ιn CD N O τf CN O τf cθ CD CO CM O τf cθ ro CM χ- UJ OO N O O τf cθ ro cO χ- τf θO N N χ- O O τf CM O τf cO CD ro x- x- CO UJ CM xt CD C CD OO O CM Tf CM Tf CD CO O CM CO CD CO CM xt CD Tt r- ro Tf CD CO ro Cθ ro CN τf CO O CM CO -- CO UJ N CD O CM τf O N CD N τt CO CO ιn τf ^ cD U0 U0 τf cθ CO CN χ - x- C0 C0 C0 CO CM CM C0 N N Cθ CM CM CO CM CM χ - x- CN CM CM UJ UJ UJ CM CM CN CD UJ UO Tf cO CO o o ro cb d N ro ro N N ro ro μ N N cb τf xt Lri N N cd ι^ μ N c o cdo τf τf iri CO τf τf f cO CO CO U0 U0 CD CM CM CM τf τf 'τf CM CM C τf 'sf xt CM CM CM CN CM CM UJ U0 UJ τt χ t '^ U0 U0 ω CM Tt CD O UJ CO x- CO UJ CD Tf N O ro CM CD CM UJ CO UJ CO CN O CO CD N O CO UO N x- x- τt N CD C0 CM CO CD CD U0 C0 CM τf rs x- cD CD CM CM CO CD CD CD Tt Tf CO CD UJ ro N N Tf cO CM UJ CO CM CO CD CD ro N CD CO N CD CO cDCDNUjTf x- ro ro oocDujx- roro cNO oro NN ro cN τf cM τt cD τf x- cθ χ-; χ- cq χ- N CJ) N ro χ -; ro ιn N UJ CD cq q co iΩ cq OO CD O CN O x- CN O CN τt CN xt UJ cq θ CN q x- cq χ -_ CO CO CO CO Tf Tf Tf N N N cb cb cb cb cb cb cb ro cb cN CM CM θ d d τf τt τt r-: N ' N ' N ' N rsiri ifl iόd d d dd d N N ' rs ' τrt -SJ -Sj rsι rO -O r τ_' τ_' Trt ro ro ro ( CO cn m ro ro rsi rsj rsj m ro tn xrt τ_t ■_ ■ χ_r xr KΠ m cn r xr * m cn to co co co to co co co co o CM CN CM CM CM CM CM CM CM CN CM CM CN CM CM CM CM CM X CM X _ X. CM X C X X- X X X CM X x- (Ml X CM X X- X X x- X X x- X X x- X X X (M l x- X X "- X X O χ - XO X o X C M OΪ XOx- XO xox CM O x- X O X XO X O X CM ox CN OX CM OX CM 0 XO X CM O X CN Q- CL CL CL CL r- O. CL CL Q- Q- CL CL CL - © o O χ - CM CO τf LΩ CD N CO CD O CM CO Tf lO CD N CO ro O x- CM CO Tf uJ CD N CO ro OO ro O x- CM CO Tf UJ CD N CO CD O x- CM CO Tf UJ CD N CO ro O O O O O O O O O O x- x- x- x- x- x- x- x- x- CM CM CN CN CM CM CM CM CN CM N N αj oo co co co oo oo co oo co ro ro ro ro ro ro ro ro cj ) ro χ - χ - χ - χ - χ - χ - χ - χ - χ - χ - χ - OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO qoqoqoqoooooooooooooooooooooooooooooooo 000000000000000000000000000000000000000 CM CM CM CM CM CN CM CN CM CM CM CN CM CM CM CM CM CM CN CM CN CM CM CN CM CM CM CN CN CN CN CM CM CM CM CM CM CM CM UJ CM - CD CO CM CM ro cO UO CN x- N x- - oo cM CN UJ co oo uj ro co ) uo uo τf iq χ t cq N t uo f . ro m ' o ' c CJr ) i C_JD ) dθ ro_-i cCbD N Tf CM CM CM CO CO CN CO CM CO CO Tf cn m ro co o Tf CM C0 CM x- O τf C0 CD θ ro 00 CM x- O τf c0 O Tf co cD o ro in ro oo m ro co uj ro N ro co x- Q) x- CO CM Tf cD co co oo cN Tf co ro cN co ro cM Tf rs ro CO UO N OO x- CM x- CO UJ CD CO O CD CO O UJ OO O O O O O ro ro CM x- x- CO CM CM x- Tf Tf Tf U) Tf UJ CO CM CN ro ro ro xt CO CO CM x- CM CO N CO N CD N CM CM cb uj τf Lri uό uό b τf τf ' ιri d d μ Tf Tf UO CD CD O N N rø -st τf lb uO lb d τf τf lri cD CD O cb cb τf ' Tf Tf Tf CM CM CM CD CD CO CN CM CM CM CM CM τf τf τf τf τf UJ U0 U0 UJ τf τf τf CN CM CM CM CM CM CM CM CO τf τf τf CD CJ ) CM O CD CD O CO N CO U ro cθ O τf τf CD θ ro CM CD x- τf 00 x- 00 N UJ N x- x- C0 N τf N O C0 CD O CJJ N N CO x- O Tf CN x- UJ CO CM CN x- O N UJ UO CM x- O CD τf CO ro N CD CO x- x- CO CD UO Tf CM CM CM O O CM Tt CM x- cq x- ro χ-; ro ro χ- ro N σ N θ CM o ro χ- ro cM τt CM Tf CD Tf CN Tf CM UJ N UJ CD CO CD cq UJ CO CM CM CM UJ UJ UJ CO Tt c cM cb cM μ μ cd b b N- oo N N N N ' roro ' ro ' cb j CO CO CO CM CM CM CD CD CD Tf Tf Tf cO CO CO CD CD CD UJ UO UO OO CO CO τf τt τf lΩαinciΩdroCOroCOroCOcCbN CNbcCNbcτbf cτbf cτbt CM CM X x- X X X 9_ __:_-: __:_-: __:_L __.__: __.9___: __:Q-__: [i __:__:__: ^ l-l-l-l-H HI-l-h-l-h-l-l-l-l-h-l-h-l-μ-l- l-l-l-l-l-l-l-l-l-l-l-l-l-l-l-l-h-l- © O O x- CN C0 τf UJ CD N C0 ro θ x- CM C0 τf UJ CD N C0 ro θ x- CM C0 τf UJ CD N 00 ro θ χ- CM C0 t UJ CD N 00 CO CO CO CO CO CO C CO CO CO τf τf τf ' - τf - < ^ τf τf '^ ' - U0 UJ U0 UJ UJ UJ UJ UJ UJ U0 CD CD CD CD CD CD CD CD CD TABLE D Table of the orthogonal three dimensional coordinates in Angstroms and B factors (A 2 ) for Protein Tyrosine Phosphatase 1 B complexed with 2-(oxalyl-amino)-7-(1 ,1 ,3-trioxo-1 H- benzo[d]isothiazol-3-yloxomethyl)-4,7-dihydro-5r.-thieno[2,3-c]pyran-3-carboxylic acid and the water molecule which forms hydrogen bonds with the pyran oxygen atom, the side chain oxygen atom and aspartic acid 48 (Example XX). No Amino * acid X Y Z B 1 GLU N 21.703 70.01637.889 44.68 2 GLU CA 20.47369.20637.78243.88 3 GLU C 20.31368.401 36.43842.17 4 GLU O 20.96368.69635.441 41.34 5 GLU CB 19.33370.22737.98646.14 6 GLU CG 17.91369.69438.16953.54 7 GLU CD 17.72368.47939.08861.73 8 GLU OE1 16.69368.36339.73564.31 9 GLU OE2 18.581 67.61839.17063.66 10 MET N 19.36667.43236.41639.32 11 MET CA 18.89366.68435.22634.55 12 MET C 18.08867.58934.29732.30 13 MET O 18.04667.44433.09332.26 14 MET CB 17.971 65.501 35.62734.25 15 MET CG 16.76365.88436.52532.80 16 MET SD 15.64264.52536.91829.12 17 MET CE 16.78063.48537.83328.64 18 GLU N 17.44468.54534.94332.02 19 GLU CA 16.66069.56834.28235.48 20 GLU C 17.56570.54533.47834.80 21 GLU O 17.32470.861 32.32834.07 22 GLU CB 15.84370.22635.37737.66 23 GLU CG 14.63871.01634.85941.16 24 GLU CD 13.64071.22836.01044.68 25 GLU OE1 14.01871.06637.16843.98 26 GLU OE2 12.48871.54035.73447.38 27 LYS N 18.70470.90934.09835.30 28 LYS CA 19.74971.591 33.31836.1 1 29 LYS C 20.29770.75032.11533.14 30 LYS O 20.33771.20630.97832.17 31 LYS CB 20.88772.02334.25840.81 32 LYS CG 20.52473.20935.17447.76 33 LYS CD 21.621 73.49536.22653.62 34 LYS CE 21.051 73.90837.58755.86 35 LYS NZ 21.88573.36838.67756.39 36 GLU N 20.701 69.50032.40431.78 37 GLU CA 21.11268.59731.321 30.77 38 GLU C 20.05368.48930.19430.69 39 GLU O 20.35368.59229.02029.85 LO © © Ui H U α. CO ro CM N CN CO UJ Uj Tf UJ CO O CM UJ UJ CO OO CO O O N CM CO CN lΩ UJ x- ro CM CM CO LΩ CN CM x- x- N CM CD τf ro |s UJ Tf cO CM CD N Tf oO CO CO x- O CD Tf x- Cq τf CD CDCD x- CM C _q- i .Ω~ N _ C —D CO CO CO O Tf θO CD lΩ CO CO CD CO CD τf τf CM x- CM N ∞ CM O O CM Tf CO O CO UJ CM Tf ccoO cCdO cCbO cCMM OO cCbO cCbO roro NN CCMM CroJJ ccbO roro cCbD NN cCOb x- N CM ro cO CO N N N UJ TTtf cCoO NN co O Cθ CO τf τf CO CO CO CO CO CM CM CM CN CM CM CO τf τf cO τf UJ N CD Cθ CO CO CO τf UJ UO CD UJ CO CM CM CM CM CN CN CM CM Tf Tf CO O N N CO CM CO O O UJ CO N O CD N UJ UJ CO CD N CD CN C0 τf τf c0 CD C0 CD N τf x- 00 O lΩ O τf rs UJ C0 N CD τt CO Tf CD Tf CD Tf N N O CD CO O Tf UJ CN UJ OO CO Tf xf IO CJ) UJ O O OO x- CO O O CM UJ CO OO CD CO OO τt cθ CM τt CO CO CD x- τf CD N CM CO τ- N CD Tf Tf CO UO UJ CM OO OO x^ CCOO CCMM UUJJ OCD CCDD ττfr ccθθ cCOq θO CCDD xx-- NN τf CM τf τf cq cO CO CD UJ x- O CO CM CM τf O CM CM τf τf τt CM x- ro N CD CO N CD CD O ' d T^ cN d d ffi ∞ N d ro ro d ∞ N N ' cd N ' ω ro d do N ' d io co f Tt <b Tf O CO CO CO 00 CO CO CM CN CN CO CM CM CM CM CM CM CM CN CM CM CM CO CN CN 00 CM CM CM CM CM CM CN CM CO CM CM CM CM CM CM CM Tf OO cO CD x- CD O OO CO O CO O CO OO CD CO N N Tf oO CD CD CD O - N . ro _. C_O ro_. C_O_ CM CO UO ro O x- xt ro CD CO x- CD Tf UJ CO N Tf CM Tt CO CO CO OO CO N CM N CO CO CM N CO CD N O CD CD CM N CD CM Tf O OO CO OO N _ C -N-, N - U "J- C'M- ■ xf cO UJ N CD CM ro CD xt CD UJ Tf CO lΩ O O UJ O CO CD CD CM x- C0 xt CO CO CM Tf CCMM CCMM CC00 UUJJ 0000 xx-- UUJJ χx-- CCDO roro roro C CMM xx-- CCMM CCO0 CCOO CCOq CCOO CCOO CCDD CCOO ττff CM CO ττff roCD τ'xfr ττtt roσ) ooθq Oθ Uin) Oθ CCMM CCOO CCOO OO x- COO τ Ttf ff C cOo C oDo x- - d xt Tf Tf c cd ro ro cd N cb cd cb od N d cM cd c cb xr cb μ μ d d ro c cb c N d ib cJ ro d ro c oό cb CD CD CO CD CD CD CD CD LO LD CD CD CD CO LD CD N N N N N N N N N N N N N N N N N N CD CD CD CO CD CD CO CO CD CD N N N CD CD CD N N CD xf CO CD LΩ τf |s O τf x- τf x- CM CO CD x- O CO CM CM CO CD O τf 't CO CM UJ O O O τt CM N τf cO τf cJ) ro N O N CD ro cθ O o co N o α ro cM in o σj ro cM co co ro uo o x- oo uj co cD O N CM CD ro cM O O cM CD co Tf cD in cocN x- roroco ro in cM ro ∞ τt cθ x- CM N N N N ro cθ CM O UJ O CD C CD CD CO N N UJ CO UO CM ro x- CM ro x- τf UJ N CD UJ CD ro CM CO x- OO τf UJ θ ro cθ O x- O N CN x- x- CM CN CM CO N N N CD UJ UJ Tf Tf cO CO N N CO CO N CD UJ U Tf CD x- x- x- CM CO τr UO CO O O CD CJ) O x- O O CO N OO N CD in iΩ τf Cθ ro CM CM CM CM CN x- x- x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM x- x- CM CM CM CM x- x- x- x- x- x- x- x- x- 1- x- CM x- CM x- CM x- CM x- CM DQϋQ UUJ < CO Q Q LU LU N < CQ Q LU LU < CO Q LU LU < 00 Q < co Q Q < oυooozooooυooooo OOOOOOOO OOOOOOZZ O OO OOOOOOZO D D D D D LU - _ _ - _ _ _ LU _ l_I D D D D D D D D Z Z Z 2 Z Z Z Z Z Q. Q. Q_ Q. Q_ Q.0_ . C C _J -J _J _J _J X X X X X X X X X X X -J ^ _J _J ^ ^ _ _J _J _ _J _J _J ^ _J _J _J _J _U LU LU LU LU LJ LlJ LlJ cy) ^ OOOOOQ- Q. CL Q-Q.Q. CL_LQ- Q-Q-OO OOOOOOOOOOOOOOOddddddd d<<<<<<<<_j _j © o C0 ro θ x- CM C0 τf UJ CD N 00 ro θ x- CM CO τf UJ CD N C0 ro θ x- CM C0 τf UJ CD N C0 ro θ x- CM C0 τf UJ O - N-miniommi ioiniΛintDtDtotDtDωtotoJocoNN NNNNNNωcotD∞ωootooooooroσ) 92 LYS C 20.201 72.782 21.859 38.28 93 LYS O 20.020 73.189 20.713 41.49 94 LYS CB 20.015 74.041 24.063 43.91 95 LYS CG 19.071 74.819 25.012 52.90 96 LYS CD 19.799 75.829 25.904 58.71 97 LYS CE 18.834 76.499 26.900 60.27 98 LYS NZ 19.587 77.453 27.717 61.96 99 SER N 21.163 71.912 22.177 35.28 100 SER CA 22.098 71.545 21.090 33.50 101 SER C 21.511 70.377 20.261 33.89 102 SER O 22.246 69.714 19.554 35.89 103 SER CB 23.342 70.937 21.788 32.34 104 SER OG 22.978 69.903 22.780 34.77 105 GLY N 20.201 70.097 20.417 32.04 106 GLY CA 19.593 68.985 19.695 31.04 107 GLY C 20.362 67.670 19.728 31.12 108 GLY O 20.378 66.986 18.724 34.31 109 SER N 20.977 67.282 20.858 29.06 110 SER CA 21.777 66.031 20.725 26.56 11 1 SER C 21.199 64.762 21.398 25.00 112 SER O 21.940 63.835 21.667 26.10 113 SER CB 23.233 66.335 21.115 28.79 114 SER OG 23.361 67.063 22.382 32.58 115 TRP N 19.855 64.639 21.554 22.56 116 TRP CA 19.293 63.388 22.093 19.31 117 TRP C 19.786 62.100 21.381 18.55 118 TRP O 20.083 61.102 22.013 20.55 119 TRP CB 17.751 63.440 22.080 17.74 120 TRP CG 17.247 64.345 23.180 17.53 121 TRP CD1 16.779 65.654 23.022 14.15 122 TRP CD2 17.312 64.085 24.605 16.03 123 TRP NE1 16.593 66.177 24.251 16.66 124 TRP CE2 16.887 65.268 25.251 17.66 125 TRP CE3 17.675 63.004 25.350 11.39 126 TRP CZ2 16.898 65.347 26.623 18.08 127 TRP CZ3 17.676 63.059 26.745 10.09 128 TRP CH2 17.279 64.235 27.383 15.36 129 ALA N 19.871 62.143 20.056 17.72 130 ALA CA 20.202 60.910 19.307 17.15 131 ALA C 21.652 60.428 19.547 15.94 132 ALA O 21.895 59.243 19.607 16.09 133 ALA CB 20.042 61.212 17.815 15.04 134 ALA N 22.583 61.369 19.645 15.86 135 ALA CA 23.953 61.087 20.057 16.56 136 ALA C 24.062 60.639 21.520 17.32 137 ALA O 24.632 59.609 21.781 18.09 138 ALA CB 24.761 62.357 19.906 14.93 139 ILE N 23.417 61.377 22.433 17.87 140 ILE CA 23.245 60.832 23.789 19.03 141 ILE C 22.763 59.345 23.796 18.11 142 ILE O 23.305 58.438 24.409 18.57 143 ILE CB 22.216 61.696 24.560 21.02 LO © © Ui H U α. CO CD N τf CO θ ro CN lΩ x- CΩ O O CO UO N τ- τf τf τf is ro 00 C0 N CJ) O CM x- CD τf c0 CD O CM C0 UJ x- ro C0 C0 ro Q0 τf UJ N τf UJ τ CD O CO x- CN CO CN x- CD CO CO ro O CM x- Tf CO τf co uj cD U χ- cocq cq χ- τf iq cθ N inιnrororo χ--; χ- τt o τf co uj τf co cqι^ O O CO CD N ro ro UJ Uj Tf CD CO Tf Tf τf T - d τf ro cM - c b τf c μ τf '^ d d ro ro cb cb cb cM cb τf r CM cd CN CM x- x- x- x- x- x- x- x- x- x- CN CM CM CM C τf CO CO CD CM CM CM CM CM CO CO CO CN CN CM x- x- x- x- CM CM CM CN CM CN CM CO Tf τt τf CO-C N CM θ cM co N co o τf LΩ N ro cr) τf τf co cθ χ- co co uo ro cM χ - ro co ro ro ro χ - co cD ro cM co uj ro co χ- u o co τt co χ ^ Tt ro CM OO CO N O OO OO CO CO x- N CD Tf ro CO ro cO UJ N CD CO N CD C0 CM 00 N CJ) CD τf r s - x- ro CD C0 ro θ τf xf C0 C0 CM C0 CM O UJ CD Uj ro x CD ro χ - O O Cθ ro cO CN τf O τf CJ) x- CJ) χ - UJ U) CD CO N UJ CD x- CO CO CO τf O x- O CD CO N ro uθ x- CM N CO N ro θJ O UJ UJ x- x- x- ro cθ C Tt u u cb cb cM CM CN CM cb μ c cM μ c od N cb N- CN CO τf τf xf cθ CM CO τf UJ τf UJ CD N CD N CO CM CM CO x- x- O O CJ) N OJ C CM CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM x- x- x- C ro O CO CN Tf ro CΩ x- x- CN N CO CO rø ro O x- x- O CN lΩ CD CO Tf CN CN CO ro O lΩ ID ro ∞ lΩ x- Tf r^ x- ro Tt IΩ OO CO Cθ ro CO O UJ O OO CD UO CO O UJ CD CO O CO OO CO lΩ Oθ ro θ CO x- τf τf O O τf CM τf CO CO UJ CM O O τf ro CO UJ O O CM CO CM N τt -- ^ cM ^ c N CJ) UJ O N x-; q cq c ro o u co cq ra cb c ro uO N cb uό uό τf τf τ " cM N τf uJ N ιb τf CD CD CD UJ UJ UO UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UO UJ UJ UJ CD UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UO UJ UJ UJ UJ UO UJ U lΩ CM N τf θ C0 O τf ro c0 O N ro iΩ U0 x- U0 C0 τf C0 x- CD N C0 UJ τf C0 O x- C0 C0 x- N τf O τt CM CD CM N x- UJ x- CD C0 CN CM O UJ C^ CDx- ro N CN t O IDx- l θ ro C OID O τf c_) O x- ωτf CN C O N x-ωNUJOin θ O O CN CN l Ω C NCD C Nτt O CN x- τ-τtωω cq o o cD χ- o cq χ- cq N C M χ- c) co μj cD N χ- CN cq χ-; ro oq cq χ-; cq cD τf x- cN CM τ μ cM CM ro ro od cb c cb N N CN c τf uό τ uJ uό uό uό CM CM CM CM CM CM CM χ - x- x- x- χ - χ - x- χ - CM CM CM CM CN CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM C^ x- CN x- x- CM x- CM x- CM x- OO Q x- CM x- CM < CQ O O Q LU LU N X < CQ Q LU LU < CQ Q Q < CQ Q < CQ O Q LU N OOOOOOOOOO OOOOO OOZ O OO O OO O zoυooυozoXzXz LO o_c_:__:Q___:Q_θ-_r_o_c_:o_Q_zzzzzzzzzc_.α-Q-Q.Q-Q-Q.-_. , eiϋOOOϋOϋϋgϋ, LU LU LU J J J >- .>. >. ^ >. >. _ _ >. _ J J J J J J J J COW ( O WCO W W W ^ W ^ ^,^ ^ ^ ^ ^ ^ ^ K^ ^ ^^ l-l-l-l-HI-h-l-K-l-l-l-000000000<<<<<<<<dddddddd<<<<<<<<<<< © O Tf LΩ CO N ∞ ro O x- CN CO xf in O N rø ro O x- CM CO xf in CO N ∞ ro O x- CN CO xt UJ N CO ro O x- CN CO Tf UO CO N CO ro O x- CN CO Tt U Tf Tf Tf Tt Tf ^ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO CO CO CO CD CO O CO CD CD CD N N N N N N N N N N CO CO CO CO CO CO CO CO CO ra ro ro ro ro ro LO © © Ui H U α. Tf Tf N CM CM O CD f CD O C0 C CN N CD CM CD N C0 x- 00 00 CM x- O UJ CM CD τf t xf C000 x- χ - C0 xt CD ro UJ CO U UJ x- N CO N CM CD N 00 CO N CD x- UJ OO CD x- N ro cq UJ O CM cq xt lΩ τt CD O τf N CD τf CM CO x--; CO CM O UJ UJ CO Tf CO Tf CM CJ) ro d ib u d cb b μ ro d u uό ro d cM od cM CN ro N cb J uό T cd rø θ N- θ rό rxi CO Tf x- UJ CD ( CM CO CO CO xt UJ τt UJ UJ CM CM CM CM CM CO τf τf τf cM x- χ - x- x- x- x- χ - x- x- CN x- x- x- x- CM CM CM CO x- x- ro CD ro J N N D ro ιo CO x- N O CD OO O CD CO OJ CO CD xt OO CD OO Uj Tt O N Tf CD CM CD ro CN CO O O CD τf UJ CD CJ) CO CO O CO UJ x- τf N CN CO O D CO CO ro C O O CM UO N CD CO CM x- UJ CM UO CM UJ x- CO lO CO CO CO CD CM CD N CD CO N in cO O xf UJ CO CO CO OO CM CM CO CO O Tf CM CD N CD ro cO ^ C N O _ O x- C0 ro C0 N CD O τf ro C0 CM C0 CM x- CD τt O O CM CM O CM CM U0 CD N CM C0 O C0 θ ro x- O C0 ro θ C0 C0 CM C0 τt N cq θ CN τr CD CM Tt Tf cM ro ro c ∞ Lb cb N ' ' d c cd N ro N CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CO CM CM CM CM CM N CM CM CM CM CM CM CM CO CO CO CO CO CO CM CM CM C CD CO OO UJ CD CD CO CO CD O CO τf N O CD 00 ro cD O C0 UJ CM CM O x- xf O UO Cθ CM UJ τt CJ N UJ τf |s ro CD 00 τf x- x- U0 O 00 C0 CD N N τt N N O x- C0 O N CD Tf cO CD CD CD N ro C oo cq co oo cO N cq o co x- N iΩ N ro x-; UJ CO ιn cM χ- CO UJ O O CD CD cθ CJ) CM O N CD CO U μ cM CM c cM cbcM ' rocN τf uό ro roN uότf x- O CM CM CD UJ UJ U UJ UO UJ UJ UO UJ UJ UJ UJ UJ UJ UJ τf UJ U0 U0 UJ U0 UJ τf τf τf τf τf τf τf xt Tf Tf Tf cO CO CO C ω N N C (M _ <0 (D N- O N τ- 00 lΩ ro N lfi C0 ^ - N N in (0 (D S N 00 (0 \- N 0) C0 CN N r- N IO N (0 ω ω N (0(θ rN' l0 τ-τ- l0 N CO CO CN CO τt CO CN CN ro iΩ x- CD lO CO xt CN x- CO CN CN ro cN x- CO O CΩ lΩ CN N x- CO N CO N CO O CO N x- ro N O N O CO O τt UO xt lΩ N x UJ x- CO xt CM xt N O Uq oq CM τf ro cθ N CM τf CD CM τt 'r- O x--; CO τt O O CJ) θ ro CD O CM Cq cq s ' b o cD cd cό s od s s ' c s s s ' od oό s oό cD iΛ td s ' Tf iri tD ω iri i ώ CM CM CN CN CN CN CN CM CM CM CM CM CN CM CM CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CN CM CM CM x- CM x- CM x- CM x- CM x- CM < ω Q Q LU LU < C0 Q LU LU < CQ < CO O < D.C5QQ < ω O Q Q LU U N < υooυozυoz υooooooozυυoozooooo O OOOOO OOOOOOOOOZOO mmm r nmmm f n r n3323DDDDD<<<<<l__:_:QlKtt:_._.ll_.l_.ia.l--ll--l_J-l_l-l_l-Jl-000 _2_2_2_2_2_2_2_2_2- j - j - j - j -_ - j - j j - j _j_j_ _j_iιummLumω X X X X X X X X X < < < < < W C C CΛ W CO < < < < < < < < Q- Q_ C _ CL O_ 0_ CL O_ Q. Q_ Q_ Q. CL Q © o C0 N C0 ro θ χ - CM C0 τf LΩ CD N 00 ro θ χ - CM C0 τf UJ C0 N C» ro θ x- CM 00 τf ιO O N C0 ro θ x- CN C0 τf UJ CD N C0 ro θ x ^ ro ro ro ro θ O O O O O O O O O x- x- x- x- x- x- x- x- x- x- CN CM CM CM CN CM CM CM CM CM CO CO CO CO CO CO CO CO CO τf τf f τf f τf x τ χ - x- x- χ - CN CN CN CM CM CN CN CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CN CM CM CN CM CN CM CM CM CN CM CM CM C^ LO © © Ui H U α. CD UO CJ) N UJ CO CD τf CM CD τf cO CD UJ O CD UJ τt CD CM CM O CD x- x- ^- CM UJ N x- N τf O O x- 00 xf CD x- O τf τf rs ro x- co CO CO UJ CO CD x- Tf cO Tf Tt cO O UJ CM CM CO CD CN UJ UO ro cO CD CM χf cqcDcqcDχ- ιncqcqcqNcqτto χ-;τtoiΩχ-cM N lO O N ro CO CM UJ CM CM xf N CD CO UJ OO ro CD O xf xt CM N N CD Tf rs- CD CD O Tf b cbcM-cMd cMcbN-cMoόNCMu cbcbcbTr ' Tf O CO CO o CO Tf CO x- x- x- x- x- x- x- x- x- CN CN Cθ τf f τf τf τf x- x- x- CN x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM CM x- x- x- x- x- 00 CM UJ x- CM CM CO N ro COO OO ττff Uu roro CCOO UUJJ OO CCOO UUJJ NN xx-- OCOO OO OO xx-- ττff τ'f" UUJ τt uj ccoO cND COM CχM- uCDj χCD- ro x- CD Cθ χ - oO N τCDf χCO^ oO N C J τt ccθθ roro CCMM CCOO NN OCθθ ro ro ro CD τ τf oo uo o r CD τ^t CD xt CD CM ro — τf - CD- τt • C —D τt - o — O OO CO CO OO LΩ CM ro CD CD in cθ OO CM lO Tf . C-M. U . _J O__ ιτ- CO CD N . C —D N - O —O CO O x- UJ N x- CN O CO UJ CD x- CM Uj ro CO CM CO τt c0 C0 τf |s r-. CM C0 C0 τf O x- τt C0 τt x- O x- 00 O CO N x- 00 C0 CD x- x- CD τt ro ro τf d cd od u uj uό τf uJ uό u τf ' uό τf b τf u N- od od raro rn m iιbn <τ*t iN — ' mcd mod LΠ o o ro co CM o o co Tf co io ro co ro CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ C C0 CM CM C0 CN C0 τf N ∞ x- UJ C0 O τf x- O 0000 N N CN CM x- ro c0 CD O x- CM C0 lΩ 00 x- N 00 x- τf 00 UJ CN τf C0 N CO C0 O τ^ O CM CM Oθ ro θ CO lΩ Cθ UJ CM UJ ro ro x- CO x- ro CO x- x- UJ CO CD O O N τt CM LΩ O UJ τt O x- Uj ro c» ro CO CO N UJ CO CO CD CO x- Cθ ro θ x- UJ CJ) τf ro τf 'r^ N τf CM CM ro '^ UJ x- CD UJ UJ Uq UJ N x-; CM N ro N O O O N cq t CM O N CM ∞ xt Tt Tf T ' y j -xj ^ ^ cM d ro μ μ μ ro ro cb cd ro ro cb μ ro CO CO CO CO CO CO CO CO CO CO CO CO CM CO CO CO CO CO CO CO CO CM CM CM CM CM CM CO CO CO CO CO CO CO CM CM CO CO CO CO N N CD CO x- CM CM O CM ro τf UJ θ ro τf CD N CM UJ x- CD CD O CO CO x- N CD in θ O O CO N CM CD CO CM xt CO CO CO xt ro N UJ CM CM C^ O CO CD (N CO N xt O OO CM N CD CD CO CO O CD CO CM x- τt xt N CM O O CM CD ro cθ CD CO O x- ro CD CM N ro τf lO CM UJ UJ O CM CO UJ x- CM C^ cq τt cq cD (N χ- co cq cq χ- χ- cq cq cq cD uj o c» χ-^ cq cM θ cq cM N cθ N C^ d N cd cM CM μ co c μ τf uJ d cb c c ro cb c N cb N b ro CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN x- x- x- x- CN x- x- x- x- x- x- x- x- x- CN CN x- x- x- x- x- x- CM x- CM x- CM CQ Q < C Q < C Q Q LU N X X < CQ < CQ < C Q Q LU N < CQ Q O < O O O O O CO O O O O O Z O Z Z Z OOOOOO ZOOOO υoooυooz oυooooυzoo __: __: __: >_- > . - >_- L >_- Q_ CL _L OOOO © o Cθ ro θ x- CM CO τf LΩ CO N Cθ ro θ x- CN CO τf LΩ CO N Cθ ro θ x- CM CO τf UJ CD N Cθ ro θ x- CN CO τf LΩ CD N Cθ ro θ x- CM CO xf Tf UJ UJ UO UJ UO UJ UJ UJ UJ UJ CD CD O CD CD O CD CD CO CD N N N N N N N N N N ∞ OO CO CO CO CO OO CO CO CO ro ro ro ro ro ro ro ro ro CJ CM CM CM CM CM CM CM CN CN CN CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM C^ 300 PRO O 15.028 25.094 18.853 23.12 301 PRO CB 18.053 23.970 18.312 22.01 302 PRO CG 19.544 24.226 18.419 20.31 303 PRO CD 19.693 24.935 19.760 21.95 304 LYS N 16.032 24.245 20.703 20.72 305 LYS CA 14.730 23.878 21.253 20.41 306 LYS C 13.860 25.101 21.665 22.87 307 LYS O 12.648 25.010 21.812 25.57 308 LYS CB 14.945 22.949 22.437 19.35 309 LYS CG 15.755 23.579 23.575 18.95 310 LYS CD 15.710 22.689 24.822 21.88 311 LYS CE 16.801 23.034 25.823 28.88 312 LYS NZ 16.535 22.399 27.128 34.05 313 ASN N 14.556 26.233 21.841 20.66 314 ASN CA 13.870 27.431 22.279 18.39 315 ASN C 13.486 28.352 21.122 18.29 316 ASN O 12.970 29.444 21.354 16.34 317 ASN CB 14.739 28.164 23.298 16.54 318 ASN CG 14.821 27.389 24.621 18.02 319 ASN OD1 13.969 26.599 24.993 18.28 320 ASN ND2 15.875 27.678 25.307 15.54 321 LYS N 13.754 27.923 19.857 19.25 322 LYS CA 13.464 28.846 18.745 20.87 323 LYS C 12.043 29.452 18.860 18.97 324 LYS O 11.823 30.654 18.781 18.79 325 LYS CB 13.693 28.184 17.377 25.70 326 LYS CG 14.211 29.179 16.316 33.55 327 LYS CD 14.555 28.542 14.949 41.05 328 LYS CE 15.066 29.579 13.926 44.78 329 LYS NZ 14.971 29.087 12.537 44.25 330 ASN N 11.091 28.544 19.113 15.61 331 ASN CA 9.708 28.969 19.134 14.25 332 ASN C 9.210 29.512 20.495 13.55 333 ASN O 8.012 29.666 20.711 11.55 334 ASN CB 8.855 27.796 18.681 14.58 335 ASN CG 8.704 26.756 19.791 18.11 336 ASN OD1 9.204 26.857 20.899 19.64 337 ASN ND2 7.912 25.772 19.462 22.97 338 ARG N 10.163 29.703 21.400 12.38 339 ARG CA 9.830 30.375 22.640 12.69 340 ARG C 10.255 31.846 22.554 11.47 341 ARG O 10.045 32.608 23.480 10.92 342 ARG CB 10.492 29.633 23.827 12.58 343 ARG CG 9.840 28.263 24.143 7.25 344 ARG CD 10.452 27.622 25.391 6.96 345 ARG NE 9.754 26.378 25.717 10.56 346 ARG CZ 9.591 25.939 26.964 12.63 347 ARG NH1 10.049 26.621 27.978 13.70 348 ARG NH2 8.970 24.830 27.205 13.18 349 ASN N 10.877 32.231 21.416 11.45 350 ASN CA 11.276 33.639 21.283 10.48 351 ASN C 10.479 34.359 20.189 10.61 LO © © Ui H U α. Tf CO Tf CO N Tf CM CD CM CM ro x- ro θ O CO lΩ UJ N ro CM O CO τf O CJJ CD CO O lΩ UJ CO CO CO N ro UJ CO N UJ O UJ CO O Tf x- CD N CD O OO CN CD UJ CO CO O CO UJ CN N x- CN CD CM CJ) x- τt cq cM in U0 τf CM CO N τf CD x-_ Cq CD N c CN U "O ^ CO; , UAJ CO -^ . N OO UJ τf |s oθ CO N CD τf O CN r ■ N CN 0 CM ^ CM CN CN χt uJ N dτr ιbτt ujτt cM roτt N uJc c c dτ x- CD x- x- x- CD N CD CD N UJ N N CD CO CO CO N UO N CO CO x- x- x- x- x- CM CN CO CO CO CO x- x- x- x- x- CM CM CM x- x- x- x- x 00 Tf cO Tf UJ CN N UJ O CD CO OO O Tf CD lO CM CM x- N Tt CD CO CM x- x- Tf x- N CD O CO O CM Tf O ro ro O CD CO N O CO Tf CD OO ro x- OO CO CD T )l UJ CM x- τf O CO O τf r-. oθ CM LΩ ro x- N x- CO CM ro CO CO CO x- τf UJ N 0) CD CO Tf X— N I — T XfI c LO'J O *— N I-- U UJJ O V_ C LMN O LLOJ T XfJ c LO'J C MOJ Tt lΩ x- CD CD N ro UJ 10 O CD x- CN CO UJ CO lΩ CO CO τf χ - cθ CO O θ ro θ O x- CO CO CN lΩ x- χt CM CM CO N UJ O CM CD CD _ CD UO xf . C . O- τt . ro_ τf . ro_ f- Tf CD O xt CO CO ro O CM CO x- O CD OO N o CJ) o o o CD 0O CO CO O0 CO CO N CD N CJ) 00 CO CD CD N C0 UJ xt cO CO CM x- CM N N CJ) ro N lΩ UJ Tf O x- CM CM x x- CN CM CM CM CM x- x- x- CM x- CM CM CM CM x- CM CM CM CM C xf lΩ CO CO OO OO O N N N x- CM CD x- x- CM N UJ U0 C0 O C0 CN τf C0 CD C0 τf x- CJ) N CD ro x- τf O CJ) CM CM UJ N x- UJ CO N UJ x- xf x- CD CN ro CM x- N OO xf xt x- x- O OJ CO x- Tf CN CO N UO CM CM CO CD CD CN O CN O ro CO CO CJJ O CO CO xt xt CN CM Tf O O coro co co co xf x- co c roro cCDD CCMM CCDD cCOo xxtt cCMM roCD oO CM OO OO CCOO OO CCOO UUJJ UUJJ U UJJ TTtt CCDD CCOO CCOO CCOO OOOO UUJJ CCDD CCMM CCOO NN UUJJ roro NN OO CCOO NN TTtt CCOO NN roro roro ccOO OO C CMM x- C CMN x- C COO x- ro roO o x bbbbcMbωbss ' ωrocbcoc s ' s co N - ro d d μ μ c D N D cb i σi od σi r- x- O CM CD O CO CO OO CO CO CO CO CO Cθ CO CO CO CO CO CO CO CO CO CO CO CO C CO τf τf τf τf xf τt f cO CO Cθ CO CO Cθ CO CO C CO CO CO CO xt xt xt xt xt Tt CO Tf cO CO in rocN inco O Tt oo x- CD ro cO ro O UJ CM LO O CD CO CD CO C CM xt x- UJ CD CO CM O CO CN CO UJ O CD CO CD x- CD ro CO CM CM CD CO CO CN O O UJ CO CM lΩ N x τf N UJ CM τf O CO CO CM CO O CJ) CM U) CD CD x- CD CO τt - o cj) N cq iΩ CM cq oq cD Uj cq ι CJ) x- CD CD CN τf UO UO CO O τf O CM OO CO Tf (. c od b b b N oo j i ui t T ro ro ro ro co N co iΩ Tt t co x- ■ <- CN x- CM x- CM x- CM x- CM T- CM OQ Q O < CO Q LU N X X < CQ Q O LU LU N X < C Q Q LU N X X < CQ O O O < C O O O O Z oooυoozo Z Z O O O O O O O O O O O Z O O O O Z O Z Z Z O O O O O O O Z O O O Q_c_:OOOOOOOOOOOo.Q_Q__ C Q_o.Q__i_i_i_i_ l-l-<< < < <<<<<<<<< < << << <>>>> © o CM C0 τf UJ N ∞ ro θ x- CM C0 τt U0 O C0 ro θ x- CN C0 t UJ CD N C0 ro θ x- CM C0 τf U0 CD N 00 ro θ x- CN C0 xt U^ uj uj u uj u uj u uj cD CD CD cD o cD cD co cD N N N N N N N N N N co oo co co co co co co co oo ro ro ro ro ro ro ro ro ro ro o o o co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co co c^ CO CJ) CD CM CD O CD CO CD UJ CN CM Tf UJ CO UJ CM CM CM N O) CD x- O x- O τf CO x- O CO CO OO CD CO Uj Tf O CO UJ CM CO CD N Tf CM O O O O CJ) O CD Tf Tt CD x- xf O Tf ro UJ xt UJ CD O xt CO CO UO ro CD UJ CM Tf O CD O CM Tf ^. CM O 0 CO Tf CO CM CM r r o CD cq o ■ cM O Tt c N N c ^ ^ cM ^ ^ ∞ ^^ ∞ d ^ dc x- ro co UJ x- N OO N ro o oo x- C u O. dx- CD Tf CM cb cb CM M x- x- x- x- x- x- x- CD N x- x- Tf UJ OO lΩ UJ N x- x- x- x- CO x- x- x cn CM CO N N N N CO x- x- CM x- CO CO x- τf (s θO CO τf LΩ O CO x- τf CD CN τf O CJ) UO O CD τt CN in cθ CM x- N N ro - CM N CJ) x- CD CM UJ CO τt 0 CN x- CD U) CM OO N CD N Cθ ro CM O χ - CO CM O CM UO CO CN ro N τf x- rs CD CD CN CM UO CD CM O CD CO CO ro ro UJ CO x- ro UJ N CM O N CM O Tt N C 10 O Tf CM x- Tf cO Tf O Tf rs ro UJ UJ UJ CM UJ CD CO CD N O N CO CN CM ro N CD x- ro CN CO Tt x- Tt ro CO CO x- x- CM O CO UJ OJ CD - CD O UJ CM CO O Cθ τf lΩ UO CO CM CD N N N CO N CD CO Cθ ro θ ro ro N ro N ro N ro θ CN CM O CO CO CO CM CO xt UJ τf τf uJ CO τf cO CO τt τf t τf CM C^ CN CM CM CM CM CM CN CN CM CN CM CM CM CM CN CM CM CM CO CM CM CM CM CM CM CM CM CO CO CO CO CM CN CM CO CO CO CO CO CO C^ τf O CM U) ro θ ro CM C0 CM UJ χ- x- N CD C0 N x- ro u0 x- C0 C0 xt N CD C0 C0 τt τf CD ro CN CN UJ CM C» xt τr ro CD UJ x- OO N CM CO UJ N CO τf CO lΩ O UJ CO CD N CD UO O CM UJ N τf CD ro c» ro CM CD UJ x- ro CD τf iΛ CO τf CD CO CD θ ro τt x- CM CM x- ro cθ CJ) N CM τf τf CN CD ro τt x- x- ro CD N x- CM C» τf cN Cθ ro CO CO CN O N x- ro cθ CN lΩ CD N Oθ ro θ O CO CN ro τf σ) U) CM τf CD N CO N τf CD N ro CD CO N x- N N N x μ co N cb c N N d uj b ' N uό uό c ro ro cN ib cb τ od cM τf τf CO CO CO CO CO CO CO CO CO CO CO Cθ CO CO Cθ CO CO CO CO CO τf τf τf τf cO CO CO Cθ CO CO CO CO Cθ CO CO Cθ CO Cθ C^ U x- CM x— CN x- M „ x- CM x- CM δ o < CQ o < CO Q < CQ Q Q LU LU N < C Q Q Q < CQ Q Q LU LU < CQ oozooooo OO oooooooooozoυooooo oooooz υzz OOOO _:ι__:[_(__:0000000_j_ι_ι_j_ι_ιι__ιiJL__JiQ.iD.[LiιiQ., n fΛ fn , n , n ,^ 33 ωwL_JWL__w__:o_o_o_c_:o_c_;xxxxxxxxxxxcoc/)co wtoωw-2_2_2_2_^ WWWWC (Λ_.-._.l lQ.-.-.-._._._.DL _._._.i © o Tf UJ D oo ro o CN CO Tf UJ CD N CO C roD OO x- CCMN CCOO τTfr UUJJ CCDO NN CCOO CCJD) 0O x- CCNM CCOO TTff uUDJ CCDΩ NN OCOO CCDD OO x- C CNM CO Tf in CD N OO CD O x- CM CO Tf U O O O O O O x- x- CM CM CM CM CM CM CM CM CM CM CO CO CO O CO Cθ CO Cθ CO CO τf τf f xt xt xt xt Tf Tt xt UJ UJ UJ UJ UJ U f t Xt T Tt t f f Tf Tt t T Tf Tf Tt Tt -^ ^ f Tf xt xt Tf xf Tf t Tt t Tf t Tt t ^ f f t xt t Tt xt Tf Tt Tt Tf Tt Tf Tf Tt T f Tt T 456 ARG C 16.139 34.506 33.898 14.39 457 ARG O 16.647 33.926 34.844 12.31 458 ARG CB 17.292 34.168 31.637 12.58 459 ARG CG 17.894 32.846 32.135 14.19 460 ARG CD 18.073 31.815 31.023 15.27 461 ARG NE 18.531 30.520 31.560 15.37 462 ARG CZ 17.720 29.463 31.683 15.74 463 ARG NH1 16.468 29.566 31.330 13.61 464 ARG NH2 18.150 28.339 32.167 13.65 465 ILE N 14.811 34.584 33.745 16.19 466 ILE CA 13.964 33.837 34.671 13.97 467 ILE C 13.863 32.356 34.253 13.70 468 ILE O 13.599 32.046 33.119 15.22 469 ILE CB 12.583 34.496 34.725 14.29 470 ILE CG1 12.697 35.981 35.109 14.68 471 ILE CG2 11.695 33.761 35.745 14.23 472 ILE CD1 12.768 36.193 36.625 11.53 473 LYS N 14.079 31.452 35.184 15.41 474 LYS CA 13.901 30.039 34.865 16.79 475 LYS C 12.555 29.531 35.391 17.35 476 LYS O 12.222 29.772 36.539 19.31 477 LYS CB 14.952 29.273 35.664 17.97 478 LYS CG 16.348 29.641 35.224 20.00 479 LYS CD 17.342 28.756 35.923 21.07 480 LYS CE 18.757 29.183 35.586 25.86 481 LYS NZ 19.661 28.132 36.065 29.41 482 LEU N 11.827 28.807 34.546 17.14 483 LEU CA 10.659 28.096 35.026 16.17 484 LEU C 11.101 26.982 35.997 18.46 485 LEU O 12.139 26.361 35.815 16.31 486 LEU CB 9.925 27.512 33.820 16.73 487 LEU CG 9.241 28.474 32.838 16.01 488 LEU CD1 9.233 28.140 31.340 18.22 489 LEU CD2 9.174 29.942 33.208 19.99 490 HIS N 10.307 26.720 37.031 20.86 491 HIS CA 10.504 25.539 37.856 22.12 492 HIS C 9.967 24.256 37.160 26.50 493 HIS O 9.214 23.488 37.729 29.06 494 HIS CB 9.795 25.710 39.208 20.80 495 HIS CG 10.244 26.940 39.961 18.49 496 HIS ND1 9.650 27.355 41.096 18.74 497 HIS CD2 11.279 27.836 39.657 17.16 498 HIS CE1 10.306 28.462 41.471 16.79 499 HIS NE2 11.293 28.776 40.626 15.80 500 GLN N 10.416 24.000 35.928 31.86 501 GLN CA 9.989 22.769 35.260 36.18 502 GLN C 11.226 22.046 34.724 37.67 503 GLN O 12.153 22.676 34.251 38.03 504 GLN CB 8.969 23.068 34.141 38.37 505 GLN CG 9.413 24.118 33.110 45.32 506 GLN CD 8.538 24.115 31.844 51.67 507 GLN OE1 8.913 23.628 30.781 53.74 Tf Tt x- cO UJ UJ CN O CD UJ CO Tf UJ UJ CM CD CO OO UJ CD UO CM CO N CO Tf O N UJ UJ UO OO O CD ro O Tf in C O CO τf O x- ro CO CM CD N CO OO N C x- CM x- UJ CO CO O CO CM CO CO CM UJ CO CD CO N N O CD N UJ UJOJCO N O O OOO Tf N UJ CO CD C O x- O OO UJ CM O CO x- ro N x- CN UJ CO N CD CO x- O x- OO UO CD "J. N UJ CO CD ro Tf uJ N x- CD CO CD Tf N C WO C VMι U *+J C ^O 00 UJ T f T f Tf CO Tf LΩ CO CΩ CD CO CO CO CO Tf UJ UJ UJ CM CN CM CN x- x- x- UJ x- x- x- x- x- CM CN CN x- ro co ro N UJ CD CD UJ CO CO CO x- CD UJ Tf CO x- Tf O CO O CM N UJ UJ CD CO CD O CD Tf CO CO τf CO O CD CD Cθ τf CJ) O OO CO OO τf OJ x- ro cO N CN lO x^ lO N CO UJ CO O N CN f2 x- CN CO ro oO UJ OJ CO N CM O CO N CO UJ CM Tf Tf UJ N CN σJ x- CO x- CD CO 00 CO N N x- CM τt ro N CD x- CO OO O CM CO UJ N CM ro N O Tt 10 O CO Tf OO CO O UJ x- CO cO CM N O Tf cM N O CN CM CD Uj Tf CN UO CM CM CM O CO ro x- N CO Tf ro CM O CD ro x- CD x- O UJ O CO CO O N CO C cM Tf Tf ' cM CM ib d c cM o cD d cb cb cb C roD Oo Oo CcOo NN CoOo CcDD x- CM x- x- co cM x- co ro cD ro co N N N CD N UJ CD U ro ro co ro CO CO CO CO CO CO CO CO CO CO CO CO CO CM CO CM CN CM CO CM CO CO CM CM CM CM CO CO CO CO CO CO CO CO CN CM CN CM CM CM CM CM CN CM CM CM CM CM CM CM C x- x- N CD CO UJ OO UJ CN x- ro UJ CO CM Tf cO UO CD CM CJ) UJ N UJ CM UJ O UJ CD x- CN xt Tf UJ N C0 N xt N O x- C0 x- O 00 m O O N ro C x- x- x- O CD CO CD χ - Cθ ro N CM CD σ) N UJ CD CO N O τf CM χt CM CO N ro UJ x- CD x- x- UJ UJ x- N N xt x- CJ) τf CD CM CO τf uJ N CO0 cq N ro cq N iΩ uo cq cq cN N N oo cD N CD χ- σ) θ CM τf O CO τf CM CO CO O τr τf θ UJ O CO τf CO xf ro τf CD UJ O CO CO CM UJ N CO . x-;(T0f x Tf o ro ro ro o co N N ro ro d d ro ro ro d cM < CO τff UJj oCO τtf ιUJ τff τtf CO NN oOOd CDb <CDb NN <CDb N cCdO roCD cOOd cCOci <CjDi O O x- x- C CCMMM cCCObO 0OO xx-- CCCOOO CCCOOO CCC CM CM x- x- x- x- x- x- x- x- x- x- CM CM x- x- x- CM CN CN CM CM CN CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CO CO CO CO CO CO CO CO CO CO C UO Tt UJ O CD CO χ- co co ro co σ) co oo ro ro χt u) N CM χ- ro χt u) CM χ- co ro co cD θ co ro χ- UO CJ) N τf CD CD x- ιn N CM OO CO CO CO CD χt UO τt CM U OO CO N τr cθ CO CD CO Oθ ro ro Uθ ro CD CO C CM x- cq UJ CO O O ro N cq cq χ- ro ro ro p τt c τt p cN ro ro p cN CN τt cq iΩ τt p p cq cq C __ CM CM CM CM μ μ cM cb cM cb cM CM CM τf ib uό cb cd μ d τt τf ' uό cb uό cd τf τt ' C-M : x- ■ C_M.: CN T- CM x- CM x- CM x- CM x- CM UJ < ω Q LU LU < ω O Q Q < muQ _:Q < CQ Q Q < CQ Q Q LU LU N X < C Z Z OOOOOOOO OOOOOO o o O o OOz zυυooooo 00000 υoo oozυoo Z D D D D D D D D D _. Q. Q.1 _. _. _. _. Z Z Z Z Z Z Z Z Q. O. _L Q_ O_ Q_ Q. O_ Q_ Q: C_: O_ __: __: Q_ Q_ Q_ Q_ Q_ Q_ —o Io— I —o ' —o I —o I —o I —o J —o I —o Io— I D<C<Λ C<JO C<Λ C<C<C<C<C< c <w<c<c<w<c<c<w<c<ow<<w<w<w<w<H>l-->l-->l-->l-->l-->l-->l--l->l-->l-->l--HdHd L dH L dH © o CO OO O x- CN CO τf U ) CΩ N OO CD O x- CN CO τf LΩ CΩ N CO CD O x- CM CO Tf l CD N CO CD O x- CM CO Tf UJ CD N CO ro O x- CM CO Tf uJ CO N C O O x- x- x- x- x- x- x- x- x- x- CM CM CM CN CN CM CM CN CM CM CO CO CO CO Cθ CO CO CO CO CO xf xt τt τt τf xt τf τf f τf U0 UJ UJ UJ UJ UJ UJ UJ U UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UJ U 00 OO CO CD CM CΩ CO CN CO CD Tf ro co o CN O ro UJ CM CM UJ CM N N CO CD N CO OO CO N CN CΩ CD CΩ CD CD CM N J) CJ) 00 UJ CD CO O UJ O OO CD Tf Tf cO CD CO CD Tf oo Tf o N lO CN CD Cθ ro ro x- x- lΩ CD O τt CD CO o o N Tf oO CD CO O CD CO x- UJ UJ CD CO O UJ O CM CD CM CD ,-; CD O O CO CM CM d o CO UJ CD Tf O U u J- lO UJ UJ UJ OO xt CM CD τt UJ CD N N τf OO OO CO CO CD N N CD Tf rs cO CD CD OO OO CD N CO CD CD CO CD UJ x- x- x- x- x- CM CO Cθ τf x- x- x- x- x- CO UJ x- UJ CD UJ C0 ∞ C0 N τf UJ C0 CM χ- CO CM CD O UJ τf τt ro CD τf r s - ro θ CD N C0 CD ro U0 C000 CD CM CD x- 00 x- C000 ro CO CN ro CD x- τf CM N ∞ LΩ CD UJ O UJ N CM x- N x- CM Ln τf τt cθ Cθ N τt ro CN CM x- UJ N θ ro N N CD CO in CM CO CO CO CD N x- UJ N CD Cθ O N LO UJ CO CO x- CD cq θ x- f CD τf UJ UJ O CO x- χ- O CD x- cq cθ CO Uθ ro CN O CM_ CO CO UJ UJ O O τt χ CO CM x- CO CO CM p ro cb c uJ b τf ro μ cMCM τf τf cM uό d N cb ro d dN CM CO CO CM CM CM CM CM CM CM CM CM CO CO CO CO CO CO CO Cθ CO C CO CO CO CO CO CO CO τf cO CO CO Cθ CO CO CO CO C x- C CD CN LΩ x- CM CO lΩ- τιnf τχ-f;χc- coD Uχ-J Oσ)CτM f θ ro CM CO N CO τf CJ) CO cbcMcbcbibdduJ CO CO CO CO CO CO CO CO CD O C0 C0 UJ CD CD C0 τf 00 O CD N C0 CO C0 CD CD τf O CD x- C0 χ- C0 U0 C0 τf C0 x- C0 O C000 τf UJ CD O CD C0 C0 N UJ O UJ N C0 θ ro C0 O χ - τf rs oθ CO CN N O CM CO CM CO UJ N CN O N CO N N CJ) N CM CM τt τf O x- x- UJ N τf N CM CM CO UJ CO CO N CJ) CM CO CO O CM ro cθ O N CD O N O τf O CD N CD UJ N CD τf x- χ t CM x- CD N CO τf UJ CD x- θ ro x- CO O OO x- CM CD O O CM Tf N x- CM CO x- CO x- O CO ro CM CO CJ) Tt UJ ro N CM x- O CM CM CM CN CM CO Tf CO Tf Tf cO LΩ UJ UJ UJ UJ N UJ UJ CO CD UJ UJ CD UJ UJ UJ UJ UJ N N CO ro cO CO CO N CO N N CO N CO CD N x- CM x- x- CM x- CM x- CM x- O < CQ Q Q < CO < CQ < CQ Q Q < CO Q < CQ Q LU N < CQ oυozooooυozzoooozoυooo O O o oooo υ o OOOOOOZ OOOO z Ud^U^J<%<e$e<$Z<Z<e<7>e<3>e<7)<5<55<5<<5m)^(Λωω ) ^^^^^^^^=^^=i= ^zi=i^LiL LιΩΩLiL ΩL ΕΕΕΕ^ © o ro θ χ- CM C0 τf LΩ CD N ∞ ro θ x- CM C0 τf io CD N C0 ro θ x- CM C0 τf UJ N C0 ro θ x- CM C0 τt U0 N C» ro θ x- CM C0 τf uJ C0 N ra UO CO O CD CD CD CD CD O CD N N N N N N N N N N CO CO CO OO CO CO ∞ CO CO CO ro ro CD ro CD ro CD CD CD ro O O O O O O O O O O x- LO UJ UJ UO UJ UJ UJ UJ UO UJ UJ UJ LO UJ UJ UJ UJ UJ UO UO UO UO UO UO UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UJ CO CD CO CD CD CD CD CD CO O © © Ui H U CD O O Tf O CN CD CΩ Tf cO CO UJ O x- CO O O UJ CD CD N N CD x- CM UJ CM CO CO OO O Tt N CD CO CD x- OJ CD CM CO O C CD O x- CO N N CM CM UJ O CO O UJ CD CO O UJ CM UJ CO CO UJ CD UJ N CD x- N CJJ N CO OO UJ CD CD CO CD UO Tf CM UJ UO O x- UJ N N c cόs ' ^O) r- x- Tf x— CO CD O CN CM CM CO CO ro UO CD CO OO x— O χ — L O) i CNN i CO'j x— L CO'j LOLO iN uUJj CDJ LCOJ ro UJ UJ CD CN UJ N xf O f Tf CO x- co x- ro τf x- CN CM CM CM Cθ CO CO τt CM CM CM CM CM CM CO CO CO CM CM CM CM x- <N CM CM CM CN CO τf τt f c x- co oo ro ro N CD- ro oO N τ- ro cθ lO CM U CD ro ro CD CO CN lO C UU UJ ro CM Tf ' C Tf Tf Tf Tf Tf T C COO CCOO CCOO C COO O 00 C N N CCOO C COD CCMM ιn iD cq co coroc oo < θ N Tf Tf UJ Tf xf f T CO x- Tf CO x- O x- CM CO O UJ N O CD CD O x- UJ x- CO CD OO OO x- CO CM UJ CD N CO x- O CM CM CM CM CN O OJ O CD UJ UJ N CO N CD O CO lO ro CM CD CN CO Tt x- oO UJ N x- UO UJ t τf oo ro o co cM CO x- τf CO CM O UJ CD CM N UJ χ - UJ τf O CD CO τf ro cθ Cθ CM N O O x- UJ OO Tt UJ N O x- ro CN dcocb roddro μ cM cb τt τf dd rocb T- T- x- CM OO CD CD UJ CD CD UJ Trbiri NN bN x- x- x- x- CN CN x- CM CN CM CM CM CM CN CM CM CM CN CN x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM x- CN ■ «- CN O Q LU < CQ Q LU LU < CQ O Q LU LU < CQ < CQ Q LU LU < CQ Q LU N X X < CQ C O OOOOOOO υυoooooozoooo zooooυooz zoυoooozo Z Z Z O O O O 1 — 1 — 1 — =) 3 D D =) 3 __ ) Z ) Z ) 3 33 3 3 3 3 3 3 < < < < < Z Z Z Z Z Z Z Z Z _-: Q_ C_: __: Q_ __: IΛ U UJ LU _J _J _J _J _J _J _J _J -J _J _J _J _J _J _J ._J _J _J _J _J J _J _J _J __ _J _J ._J _J _J ._J J t- _≥ _≥ _≥ 000000000000000000 < < < < < 000000000 < < < < < < < < < < < W C W C CO C © o x- CM CO Tf UJ co N co ro O x- CM C0 τf U0 CD N C» ro θ x- CM CO τt UJ CD N C0 ro θ x- CM C0 τf UJ CD N C0 ro θ x- CM C0 τf UJ C0 N 00 CJ) O x- CM CM CM CM CM < CM CM CM CM CM CO CO 0 CO CO CO CO CO Cθ CO Tf τf xf xf τf x^ x^ xf f τf UJ UJ UJ U0 UJ UJ UJ U0 UJ U0 CD cb cb cb co co co cΩ co cΩ CD CD CD O CD CD CD CD CD CD CD CD CD CD CO CD CD CD CD CD CD CD CD CD CD CD CD CO CO CD CD CD CD CD CD CO CO CD CO CD CD C 663 TYR N 12.149 44.304 38.838 10.99 664 TYR CA 11.059 43.986 37.924 11.25 665 TYR C 11.428 42.738 37.134 11.69 666 TYR O 12.600 42.426 36.947 12.93 667 TYR CB 10.855 45.145 36.944 11.85 668 TYR CG 1 1.048 46.504 37.543 11.61 669 TYR CD1 12.330 46.990 37.697 13.15 670 TYR CD2 9.974 47.284 37.928 10.09 671 TYR CE1 12.574 48.223 38.239 12.30 672 TYR CE2 10.189 48.561 38.453 11.52 673 TYR CZ 11.477 49.041 38.615 11.57 674 TYR OH 1 1.518 50.318 39.128 16.85 675 ILE N 10.411 42.065 36.626 10.13 676 ILE CA 10.683 41.103 35.561 10.15 677 ILE C 10.210 41.646 34.208 1 1.23 678 ILE O 9.017 41.882 34.001 14.10 679 ILE CB 9.984 39.783 35.918 8.65 680 ILE CG1 10.575 39.226 37.221 5.54 681 ILE CG2 10.1 17 38.788 34.758 4.72 682 ILE CD1 9.885 37.981 37.750 3.41 683 LEU N 11.171 41.837 33.292 8.83 684 LEU CA 10.757 42.279 31.952 8.27 685 LEU C 10.642 41.089 31.042 9.63 686 LEU O 11.563 40.274 30.925 10.20 687 LEU CB 11.754 43.266 31.361 6.64 688 . LEU CG 11.554 44.667 31.933 5.33 689 LEU CD1 12.441 45.790 31.363 7.20 690 LEU CD2 11.164 44.814 33.411 7.37 691 THR N 9.476 41.020 30.372 9.19 692 THR CA 9.353 39.941 29.424 7.94 693 THR C 8.748 40.395 28.068 7.09 694 THR O 8.236 41.487 27.941 6.68 695 THR CB 8.633 38.725 30.140 7.51 696 THR OG1 8.460 37.446 29.475 10.84 697 THR CG2 7.202 39.098 30.532 4.90 698 GLN N 8.895 39.560 27.025 5.28 699 GLN CA 8.176 39.853 25.785 4.05 700 GLN C 6.657 39.538 25.856 8.34 701 GLN O 6.182 38.810 26.707 9.07 702 GLN CB 8.778 38.943 24.733 4.35 703 GLN CG 8.435 37.461 24.941 3.62 704 GLN CD 9.043 36.521 23.968 7.57 705 GLN OE1 8.588 35.441 23.735 13.92 706 GLN NE2 10.151 36.927 23.436 7.22 707 GLY N 5.886 40.050 24.882 8.61 708 GLY CA 4.495 39.635 24.802 6.03 709 GLY C 4.380 38.143 24.529 6.11 710 GLY O 4.839 37.652 23.504 6.83 711 PRO N 3.737 37.417 25.464 7.87 712 PRO CA 3.639 35.977 25.333 7.10 713 PRO C 3.212 35.542 23.927 8.95 LO © © Ui H " U O CO CM CO CD UJ N CO Tf Tf x- τt Cθ CO x- τf ro cθ C0 CD O x- CO N UJ N 0O N x- CJ) τf cθ CO τt C0 CO x- ro τt co O CM UJ CD OJ x- x- O xf CD N O UJ x- UJ CO OO xt x- CO O ro ro cO N ro CM CO x- UO CM χt τt x- ro cθ N U) p co p uq ro p τf x- cq ro x- CD CO CM CM O O CM O CO CO CN CO UJ O O CO CO cb cb CM cd ^ ". J Tf CO cM CN cM χt ~ "r . d cb χt ' x χt d d CD N CO 00 CD 00 CD - CM x- ro ro - CO uό m ro N O UJ CM CM N UJ O N UJ x- CO CO CO CO O CO CO C CDD Tτff x- ULΩO CCDD NN x- CCOO CCMM CCNM OO LUΩJ CCDD CCNN x- UuoJ CCNN roroccθox- roro UUJO OO CCDD CCMM CCDD OCOO CCMM TTtt CCDD TTff roro Txff co O CN lΩ CΩ CN CO N CO N OO UJ O N CO CO CN UJ CO CJ) τf τf ro cθ CO CO τf CM τf cJ) OO CJ) x- CM O CO τf f rs m Tt O co N co u co o uj oo ro ro in CM CO CO CD τf CM UO CD CD CD O N UO N τf x- CO ^ CM CD CN CO O UJ x- N N O O ro CO CN UJ OO OO x- x- CO CO ro x- CJ) x- CN 0O UJ UJ N CO UJ cb N d c cM CM c μ cD μ cM cb cN CM f τf ' cM τf c N N uό u τf c N ro N- uό cd d cM d cN ro c N- ro CN CM CM CM CM CM CM CM CM CM CM x- CM CM CM CM CM CN CM CM CM CM CM CM CM CN CM CM CN CM CN CN CM CN CN CM CO CM CM CM CO CO CO CO CO CO CO CM CM CM CM O CO CD CD x- CN UJ CD N τf τf CD χt 00 x- CM τt CD CD τt c) τf ro N C0 O UJ N N UJ xt UJ UJ N CD CO CO t N Tt xt xt CD 0O xt 0O xt CM τf -- CD x- CO x- CO UJ N CM CD x- O CM τf CD UJ UJ τf UJ x- N C0 UJ N ro CD C0 CM CD N . - xt CO CD Tt cO N ro N CM O ro UJ x- Lo ro ro co co xt oo co uj N CM UJ N ro Tf NN CO xtf roro CCDD CCDO NN TTff T Ttt x x-- u lΩO CCNN TTtt roro Nis liΩq CcOq CroD NN CCDD NN x- o CcNM xx-- N N x x-- UUJJ UUOO x- N NCroJJ UinJoO roroCcDqCcOo Opxx--xx--iinnroroCcNNNNliOnCcDq cb uό cb N Tt cb cM M CM cb θd τf CM ro cM CM ro cb co N N cd oό cb d d ' CM d ' b - cMCNroωrorororodτ- : cric c. s CO CO CO CO CO > C CO CO CO CO CO CO CO CO CO CN CO CO CO CN CN CN CN CN CN CN CN CO CO CO CO CO CO CO 00 CO CO CO CO CO CN CN CN CN CN CN CO C^ CM N CM CD CD CO Tf CD CO OO O O CO O O CJ) CM CO N CM O IO T ,t CM CD N C .O. ro_. C_D N. O CM CM CD CM N N N x- Jsj ^ CD CO CD Tf ro cO Tt CM UJ CD Tt CM CO x- lO N CM UJ OO CD in uO CO CM CD x- CO OO N N O CO cCNN CCDO roro iinΩ oO cCoO cCoO cCoO x- u N Tt co O Tt rv- ^ L io ro co oo x- rox- cococDro in Tt CO Tf O CO Tf CM O CD CD x- CM Tf Tf oO O CM UJ x- UJ CO ro xf CD UJ CO CM O cM N cM ro x- oo o ro N ^. . χ- cM in uj N ro ro τt o χ- τt ro N CN CM cb cd cb cN CM Tf u N uό μ d d d ' μ cM CM d b od t '^ ό x- CN T ^ — ■ CM —- CM ω o Q < CQ Q Q < CO Ω < CQ Q Q < CO < CQ < < OQUQQ OOOO OOOOOOO OOOOOO O OOOO O Z oooooozoooυw ooozoooooz O O O θ 33 _D D 333 _D θ O O O O O O Z Z Z Z Z Z Z Z C_: 0- Q_ __: 0_ __: __: (Λ W ω W W W >- >- >- >- fΛ fn fΛ fΛ c_:-_:__:c_:Lu_u_u w _uω_u w Q_α- α- α. _r: Q- ^ _L_ Q_ 0- JJ JJ_J_J-JQ_CL_LQ_ Q_ Q_ Q_ << <<<<<<|-I-|-I-|-I-I--OOOOOOOOOOXXXXXXXX © o Tf UJ CD N OO ro O x- CM CO Tf UJ CD N OO CD O x- CM CO f. LΩ CD N CO CD O x- CM CO τf uJ CD N Cθ ro θ x- CM CO τr uJ CD N OO CD O x- CM Cθ τf U) x- x- x- x- τ- x- CM CM CM CM CN CM CM CM CM CM CO Cθ CO Cθ CO CO CO C CO Cθ τf τf xf xf xf xf xf x τf f ιr) lΩ UJ U^ |s |v. rs r- N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N © © Ui H U α. O O CO O O CD O x- N Tf CD UJ N CN UO UJ CO Tf UJ CO CO x- N O CM Tt OO CO CD N CO CO CO CN CO x- OO CΩ xt LO N O> CN c -_ CN N __: CO N x- ro iO Tt CM C « O. O O CO CD CO CD ro ro ro od cj) τ- N r~- CD J) 00 UJ CJ) CD x- CO x- CD CO C- CO CO . co xt N UJ O CM ro CD CD xt CO O UJ N O N N xt CM CM O x- O O xt UJ CD N OO UJ N OO CM N N CD CO UJ ro cO CD N ro CD CO CO CO CD CM CD CN CD in UJ N x- N CO O OO CD CD CD UJ CO N x- CO UJ CO — uo co ro o CM OO O CO CO Tf ro x- CO CM O O CO x- CO UJ x- CD xf OO CO N CD OJ CO CD UJ O CD OO CO N N CO OO CO UJ CD N N O O CM CD OO N CΩ N O x- CO CO CO Tf c CoJ c LoU c LoU c UoJ c UoJ T XTf c CoJ cuojroUJ roUJ cUoJ N C CMN CUDJ VOU UroJ OU OJ CcuO uO CO N N NN OO x- CCMM CCOO OO OO χ - OO CCMN OO x- CCMM ττff iUbJ CD CO cCO x- cCdO μx- cCMM uUόJ cCbO uUJ ττff ττff uUόJ cCDD NN τf UO Tf cO UJ UJ UJ CO N Tf UJ CO CO CD N CO O N UJ CO OO CM CM CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO rCoO mOO O CO CO OO CO CO CO CO CO CO CO CO CO CO CO CO Tf cO CO CO CO Cθ ro iΩ x- ( UJ C0 (N N CO U0 00 CO UJ N ro N N U0 U0 ∞ CD N C0 χ - CM ro cN UJ τf cθ x- τf cD ro ro UJ CO CM Cθ ro N x- CO CM N ro x ^ CO CM CM O N ∞ x- χ - ro ∞ ro cθ τf CJ) cO Cθ CM O θ ro N CM O N O CO O O τf χ f cO CO CO CM x- x- CO CM CO x- OO CO in ro ro x- CO N C IΛ ra τf ιn ro cO CM N CM CD CO CD x- ro cM UJ τf uJ CO O CM CM τf UJ ro CD CN x- UJ N CD O CD N N CO O τf τf cθ CO x- τf cq cM CO s d ^ ( . ( . C. ; j ' lri d N ' s c6 (N (Λi τ CN C. ( f xf CM CN CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CM CO CO CM CM CM CM CM CO CO CO OO CO UJ CO CD Tf uJ CD UJ CO ro io ro CM θ o ω 'f c ro N x- co co ro cD oo uj O OO O ro CD t O N UJ x- Tt x- cN O cq cq co o ro ro p cD τf cΩ cb τf " τf cb cb cb cb μ c j-d— i — _ rt CO-i . CvMi ■T-f «--tH #cOx CvO. /CsMi *CxMi CO x- CM _ T- CM x- CM T- CM T- CM CO CM CO CM x- CM x- CM LU LU < CO O α O -U LU N < CQ O Q Q LU LU LU N N X < O Q UJ U < O Q LU < ωOO υzzoυoυυυoooozoυooooo zoooυozoυ OOOOOO OOOO OC o OOOOOO CO CO l_ llJ l j J l_ l_ _lllJ l_ _I U _l lL l l D. _. l l l l l Q . _. _. _. DDD D D DD Q Dr- l . f . J J J-l JJ J Q - X X X X X X X X X X X C_: Q_ O_ __: __: __: _t __: __: __: __: _-: Q: -_: -ι -ι -J -J -J -J - - - - u m LU ω m ω m ω < < < < < < < --: X X . Q- Q_ Q_ Q- Q_ Q- Q_ Q- Q- Q- |- |- l- l- © o C0 N C0 ro θ x- CM CO τf UJ CD N ∞ ro θ χ- CN C0 τf UJ CD N C0 ro θ x- CM C0 τf U0 CD N Cθ ro θ x- CM C0 τf UJ CD N C0 ro θ x- CN C0 τf U^ cD o cD CD N N N N N N N N N N oo co co ∞ co co co oo co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- - x- x- x- x- rs rs rs N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N CO OO OO CO CO CO CO OO CO OO CO CO OO CO CO CO CO CO LO © © Ui H U α. CM O Tf CM CO CO N CN UO in O CO Tf cO xt CO CN xf xf CM CO lΩ N CO x- CN O CJ) τf UO N CO UO τf CN x- Uj ro Tf N ro oO N O UJ x- O x- Tf O N UJ Tf 00 O CO N x- O CO O Cθ CN τf τt O CO CD N CO CN N x- N CO CD CN O N CN CN O N CO N CO τt N oqcMcqcMrocqcMcqroop CN x- CM O CM τf τf UJ UJ UJ CD τf |s CM CO UJ CO CO O CO CM UJ UO CD CD CD CD CD CD UO UJ CO CO O CD O CO CD O Tf cb xt cd cd cb uό ib xf μ cb CD CM CN CM CO x- r- CO Tf Tf o x- ro CN CD UJ CO ∞ N CO O CO CN τf in iΩ CN τf |s -χ. CN x- lΩ CO CN CN CN ro N xt cθ lO CN N ro CN ro x- x- CO IO UJ Tf CO x- O Cθ N CO CO UJ UJ N CM τt cθ UJ τf CO CM ro cθ x- x- χt UJ CD O CM UO CD ro CM LΩ ro ro CM N xt CM x- O UJ CM CO CM CD CD UJ OO x- CM τt O CO O N O N N 0q ro LΩ ∞ τt p x- N C0 τf |s l0 CM CD θ p θ O CD C0 C0 U0 C0 CM CM CM ro C0 p cq c0 Uj p N C^ d O CM C x- μ c CNN CM μ cd cM cb cM ro ro cb N- cb cM CM ro c ro d ro cM c cM c Tf Tf Tf CO Tf τTff τTff -Tff τTff τTff -^ '^ ' " τf τf xf 'f CO CO Cθ CO CO τf τf τf τr cO CO CO τf cO τf τt τf '^ τf '^ τf ^ CO CD Tf CM UJ UJ N τf σ) co o cM χ- uj cN N co ιn co ro u ro ro cD co co o χ- τf is cM ro uj cD σ> ro N co ro uj ro N N N ro u cM co CD Tf CO N UJ O N x- N x- τf 00 CM ro θ CM U0 τf CJ) O 00 CO τf C0 ro ∞ in 00 C0 N C0 N ro τf U0 τf ro ro CM CD CD x- ro x- x- CD CO N U0 UJ CD Nι- O*_j CuO CuD ^ L o_j Nι-_ CM Ni CN L C ∞ χ - p x-; N O Cθ ro CN τf CN χ - CN lΩ O N ∞ μ cM o ro ro o co ro o ro o ro cM CN o ω ∞ ∞ b τf ib o uό τt τf χ ^ M τf ib d CO CO CO CO CM CM CO CM CN CO CM CO CM CO CO CO CO CO CM CN CN CM CTJ CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tf Tf Tf Tf ro N CD N CO CD xt CM O O x- τ χ- Tfr N| N- Ns. Tfr lrs CcxMj CLMX| x- Tτ3f- LuOj roc_ CCN o_J C- - LUO 0 iό'? O M C '- O CB ' C f T - ,-- ι.s «-H *vs _ N CO UJ CM CD CO ro N Tf UJ UJ OO UJ Tt oO CM ro S 'Λ r ro CM CO CM CO CD lO O OO 000 N ro CD UJ UJ N O N ro UJ x- CD CO N CO O CO . O . CM Tf Tf CM CM O CN O UO f χ f xf UJ u N- τf -f CN uO CM C C ? x- CN x- CM CO CM CO CM x- CM < ωO Q O LU LU LU N N X < CQ Q LU UJ < CQ Q LU LU < C Q Q LU N < CQ < 00 ooooυoozooooo O O O O O O O O O O O O O Z O O O O O O O Z O O O O O O O O O O t:α:_-:-_:Q___:Q-Q_Q-c_:Q_Q_o_-J-J-J— '— '---J--— i— '— i-J-^-J-J— i— '— 1>- ι-ι-ι-h-Hh-ι-ι-ι-Hh-ι-ι-ooooooo ooooooooo-j_-_j_j-j-j-j-j_-i (-. co wco<<<<<< © o Cθ ro θ x- CM CO xf LΩ CO N Cθ ro θ x- CM CO τf LΩ CD N Cθ ro θ x- CM CO τf uJ CO N Cθ ro θ x- CM CO τf u. cD N Cθ ro θ x- CM CO τ^ x- x- CM CM CM CM CM CM CM CM CN CM CO CO CO CO CO CO CO CO CO CO τf ^ τf τf 'τf τf τf τf τf '^ ιO LΩ LO UJ U0 UJ UJ UJ UJ UJ CD ω CO OD CO CO OO CO rø OO CO ∞ CO CO CO CO CO CO CO CO CO CO CO CO OO OD OO OO CO CO CO CO CO CO CO CO OD OO LO © © Ui H U α. x- OO CD OJ Tf CN CD f O O O N CN O O CN Tt cO N Tf cO C N CD xf N N CD x- CM Tf x- Tf CM CM x- O CD CO N UJ CD N CD CM UJ CN O Tf CD CD UJ O O CO CD CD CO CM N UJ CM CO N CD CM UJ Uj Tf x- rs CD Uj CO U) UJ CN N CN O O N ro U CN Tt x- CD O CM CN UO UJ O x- CD CD Tf UO o τt r-- τf σ) co τt m cM χ- N O O CO x- CM CM CO CM CM CM CN CN OO CD N CO N cb cd uό uό cb τf ib uό cd cd uό cb cb ιb CN IΩ UJ N N CO CO CO IΩ CO OO oo O UJ O Tf CD x- CO CD UJ O UJ N N CD CO OO O UJ x- co cMχ-LΩθcorococooNrorocDCDujcooτtrsrs-cDNUjujroχ- NUJcoro IO CO CO CO CD CM O CD UJ CD τf CD ro x- N x- UJ U0 ro 0O UJ CCMN xx-- xx-- UUDJ CuO Nι- C LMN C COJ C LMN O L_J x- ro UJ ro UJ C LDU N ro UJ C UDJ C COJ τ XTt C IMN C LMN O l_J C VAOJ N , _ O O N x- O τf τ ro CD Cq x- UJ CO CM CD CD OO UJ OO N N CO CM CO UJ O CO O _UJ) (C<Oι cCO O_Oι -- ( CO. xxti- σroi (COn _COι mCO rNs pCMj (CDn nO _UJ) cCO _OOι iNs ιCO. nO mCD (CnO -. _ UJi x TMf ss c CO N - x- ' C θd τt τf ' τf ' u d (J. N N uO τt τf ' τf ' uO cb τf cb cM μ τf UJ cb ro ro ro ro N N uo oo N CD UJ co ro o ro uj τr τf τf co τf co u cM CM χ - χ- χ " τtf Tτff Tτff Tτff 'τf' ff CCOO CCOO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CM CM CM CM CM CM CM CN CM CM CM CN CM CO C^ σ) UJ OO Tf O CO τf Is oθ τf CD τf ro θO O CO O τf rs C CDD CCOO ττfr UUJJ OO τTff τTff UUJJ CCOO CC O ro Tf N CO CO OO ro CO O N CO m CN CD CO Tt O CD τf - C-D C- _D-J C L-θ'-J CCOO N N N N x X-— τ Tff CC cq o τf cq ro ro uo uj ro cM τf θ χt uJ N τf χ- o _o_ x.- x .- UUJJ ττtf CC00 roro CCMM roro NN CC CM b (M τ J CMV ' τ : ( CM ( - τ : d τ J ; iθ b lri ( d- N c ib ib t t t t T t xt T t xt xt t - xt f t t t t t Tf Tf Tf Tf Tf Tf Tt Tt Tf f T Tf UJ UJ 0000 t CO CO Tf |s CO w _ o - OT _.. CM CD τr ro x- UJ x- CO UJ CN τf τf CM N x- ro -, wC O CD x- CN x- N CJ) CO CD O UJ CO CN UJ τf O CM O O CD τf CM CM CM OO p N CD UJ x- O CD N M CM O CM CM CD CD CO C -Mτ O - O μ CO CO T x- μ cM μ μ cM CM CN cd cM CN CM x- x- x- CM x- CM x- CM x- CN _T CM " Q LU N X X < < CQ < CQ < CO Q LU < CO O Q < CQ O Q Q < C ozozzzooozoooooozoooooo O CO O O O O Z O O O O Z O O O O x- CM CO τf UJ CO N C» ro θ x- CN CO τf UJ CD N Cθ ro θ x- CN CO τt lO CD N Cθ ro θ x- CN CO τt LO CD N Cθ ro θ x- CM C τt UJ CD N N N N N N N N N N co co c» cχj co co co oo co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o χ- χ- χ- χ- χ- χ- χ- χ- χ- χ - cM C ∞ co co ∞ ∞ co co co co co co co co co ∞ αo co oo co co co oo co co co co co co co co ro ro ro ro ro ro ro LO © © Ui H U α. o cD uo co ro ro o co Tt Tf O UJ N CD N CO CO CO UJ ro O N Tf UJ CD O CD CM CO N x- CO CD N UJ x- O O CO N CD CN O CO CO O x- CM CO Tf CM CM Tf UJ CM CM CO Tf CD x- o τf ro f x- c c ro χ-; p ro cM χ-; χ- c cM ro N c o ιn t ιs is o co cq τf c^ cb cN T ' μ c cM CM τf ^ cd cb uό uό ro uό d cb uJ cd d uJ N cb uόcM cbμ μ τf cb ιb cb CM CO xf UJ UJ UJ x- x- x- x- x- x- x- χ - x- x- x- x- CM CO CM χ - x- x- CM x- x- x- χ - x- CN CM CM CN CM CM CM CM CM CM x- '-- x- x- x- x- x- x- CO x- x- x- CD CD O CD N CO O N CD O O CO O O ro O CO CD ro in N OO xt O O ro ro N O CN x- N CO ro CD CM N CO CM CO CM ro CD CO UJ CD CM O CO CD O xt co IO CD ro CM xt N xt ∞ UJ CO UJ CO Cθ ro cθ CO O N ∞ N C» CO xt O CO N O Cθ ro N N CM θ ro cθ CM τt x- x- x- CM x- CD N CO CO CM CO Cθ ro θ x- O xt O CM N ro N O UJ CO cq N x- O CD O N CM x- CM ro cD CM CO x- x- ro θ UJ CM CO in cθ CO OO x- CM τt lΩ ro CM ro c^ CM d ro ro N ro c cN ro N N cb d b τf c L τf r ' cD d ro τt cd c^ CM CO Tf in cO CM Tf CO N CM CM CM x- x- x- CM CM x- x- CM CM CM x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM x- CM x- x- x- x- x- x- x- x- x- x- CO CO O τf CD O UO CD lΩ CO N _ C.O. UJ UJ UO CO CO xf UO CO UJ O CO UJ N Tf x- CO CD UJ Tf O CM x- x- O x- N τf U) CM CD N CD OO CD UJ N OO Tt ro τt x- Oθ ro iΩ τf CM OO τf O OJ CO CO N τf x- O CO τf cθ x- O N N CM Tf s CO CD CM T UJ O CM CO OO O lΩ Tf x- CD CO O ro iΩ CM UJ CO CN CN UJ lO co co io s cp ro co rocM q cM s oj τf 0O CO CO CO CD x- OJ CM x- x- UJ CO N τf τf cθ τf CM N N x- co cq uj oq cq cO Tf cNcqιnτf rococNcqcq cd ro ro ro ro ro o cN CN CM μ μ d cb τf uό d τf τt cb uJ uό . N . N C _D . N N N N 00 CO 00 N cb od d d μ cM cb ιb τf ' cb "^ Tf 'f Tf '^ ' - Tf Tf 'f Tf Tf Tf '^ Tf Tf Tf T Tft- TTft- T Tf. T CM CM '^ xf Tf Tf cb CM Tf cb d d f T -f " Tti- T'^T-- T Tif- x^f t Tf Tf Tf Tf Tf UJ UO UJ Uj Tf Tf Tt Tf Tt xt xt Tt Tf xt xt Tt xt J CN Tf CN OO CO O τf τf CD x- C CO CN τf CJ) U) XfI U UJJ V_J LN T XfT C CNN C LNN C UDJ N I— • X— X— T XfT C LO'J ∞ LU O L-J C COJ C COJ C COJ x X-- O L_J o CM CO CM O CO UO x- O xf CO UJ N N UO ro UJ N CO UJ CO Tf Tf cO CN CO CN CN CM x- CO CO CO CN CM x- CN CO CO Tf x- CN x- CM Q LU N X X < CQ O < CQOQ LU < CQOQLULU < CO Q LU N < < CQ < O O z o z z oooυυυzoo OOOC OZOOOOOOOOZOO OO OOO z z OZOOOOOZOO 000000_j _ι _j_j _j _j _j l- l- l- l- - l- l-H _£ __ _ __ __ __: < < LU W I_JIJJIJJLU I-J LU Z2Z Z Z ZDZDZZiZ Z (j mmm m > > CL lCL01DLCL-DZZιZZι >:>->:>->->->->- -J -J -J -J UJ UJ UJ LU UJ UJ LU HI LU <<<<<<>>>5>55_≥_≥-≥_≥_≥:___≥_≥ OOOOOOOO UOCDOWWWWWW © o CM CO τf UJ CD N CD ro θ x- CM CO τf UJ CD N Cθ ro θ x- ( N CO τf UJ O N Cθ ro θ x- CN CO τt UJ CO N C» ro θ x- CM CO τf ιO CD CM CM CM CM CM CM CM CN CO CO CO C CO CO CO CO CO CO Tf τf τf -^ τf τf τf τf τf τf ιn in LΩ UJ U0 UJ UJ U0 UJ UJ Cθ ω rorororororororororororororororororororororororororororororororororororororororororororororororororororo 974 LEU O 2.026 39.930 16.888 12.03 975 LEU CB -0.717 39.195 16.092 13.63 976 LEU CG -2.160 39.215 15.545 10.24 977 LEU CD1 -3.226 40.017 16.301 10.97 978 LEU CD2 -2.646 37.927 14.916 9.61 979 LYS N 1.105 41.571 18.084 11.18 980 LYS CA 2.290 41.882 18.858 8.96 981 LYS C 2.390 41.095 20.161 7.30 982 LYS O 3.376 41.101 20.884 6.49 983 LYS CB 2.258 43.376 19.126 12.36 984 LYS CG 2.527 44.152 17.844 14.52 985 LYS CD 3.978 44.105 17.484 16.12 986 LYS CE 4.345 44.924 16.271 20.42 987 LYS NZ 5.804 45.081 16.202 23.02 988 CYS N 1.319 40.356 20.402 6.54 989 CYS CA 1.256 39.673 21.686 10.66 990 CYS C 0.100 38.668 21.635 14.07 991 CYS O -0.882 38.889 20.936 18.36 992 CYS CB 1.133 40.710 22.839 9.20 993 CYS SG 0.873 40.094 24.504 5.00 994 ALA N 0.214 37.548 22.367 13.71 995 ALA CA -0.970 36.706 22.498 11.28 996 ALA C -2.054 37.332 23.451 13.57 997 ALA O -1.787 38.061 24.405 13.87 998 ALA CB -0.506 35.347 22.988 5.96 999 GLN N -3.315 36.986 23.148 13.22 1000 GLN CA -4.355 37.267 24.134 11.86 1001 GLN C -4.194 36.315 25.338 9.90 1002 GLN O -4.748 35.227 25.329 8.51 1003 GLN CB -5.696 36.958 23.442 11.64 1004 GLN CG -6.901 37.307 24.331 12.96 1005 GLN CD -6.930 38.782 24.786 15.38 1006 GLN OE1 -7.275 39.155 25.885 18.48 1007 GLN NE2 -6.501 39.645 23.923 10.76 1008 TYR N -3.353 36.690 26.311 10.20 1009 TYR CA -2.959 35.652 27.305 11.34 1010 TYR C -3.874 35.622 28.587 10.00 1011 TYR O -3.692 34.809 29.480 12.22 1012 TYR CB -1.451 35.764 27.671 9.57 1013 TYR CG -1.092 37.093 28.295 10.61 1014 TYR CD1 -1.112 37.261 29.674 11.35 1015 TYR CD2 -0.748 38.189 27.492 10.24 1016 TYR CE1 -0.865 38.489 30.277 10.01 1017 TYR CE2 -0.500 39.429 28.066 8.22 1018 TYR CZ -0.564 39.588 29.448 8.65 1019 TYR OH -0.317 40.841 29.935 7.28 1020 TRP N -4.815 36.557 28.642 9.43 1021 TRP CA -5.714 36.690 29.792 10.16 1022 TRP C -7.175 36.690 29.287 10.75 1023 TRP O -7.442 37.154 28.187 8.67 1024 TRP CB -5.341 37.945 30.612 8.10 1025 TRP CG -5.788 39.222 29.929 8.50 1026 TRP CD1 -6.970 39.931 30.199 9.41 1027 TRP CD2 -5.138 39.917 28.835 8.04 1028 TRP NE1 -7.089 40.994 29.356 8.02 1029 TRP CE2 -5.979 41.032 28.508 8.86 1030 TRP CE3 -3.990 39.680 28.138 6.23 1031 TRP CZ2 -5.626 41.863 27.469 7.39 1032 TRP CZ3 -3.641 40.518 27.068 8.40 1033 TRP CH2 -4.457 41.614 26.747 8.65 1034 PRO N -8.137 36.145 30.127 11.94 1035 PRO CA -9.538 36.107 29.746 11.58 1036 PRO C 10.158 37.512 29.637 14.25 1037 PRO O 10.022 38.396 30.486 14.80 1038 PRO CB 10.225 35.238 30.819 8.41 1039 PRO CG -9.31 1 35.278 32.027 5.08 1040 PRO CD -7.939 35.615 31.474 10.33 1041 GLN N 10.892 37.626 28.524 15.45 1042 GLN CA 11.657 38.851 28.328 18.38 1043 GLN C 13.068 38.858 28.949 19.02 1044 GLN O 13.747 39.861 28.892 20.54 1045 GLN CB 11.682 39.166 26.841 20.69 1046 GLN CG 10.255 39.453 26.327 27.58 1047 GLN CD 10.336 39.675 24.835 28.97 1048 GLN OE1 10.447 38.767 24.036 27.29 1049 GLN NE2 10.375 40.949 24.506 28.60 1050 LYS N 13.516 37.738 29.523 19.10 1051 LYS CA 14.764 37.856 30.269 18.50 1052 LYS C 14.946 36.717 31.217 15.91 1053 LYS O 14.342 35.680 31.035 16.84 1054 LYS CB 15.921 37.842 29.309 24.10 1055 LYS CG 15.932 36.706 28.297 25.36 1056 LYS CD 16.993 36.968 27.238 29.33 1057 LYS CE 17.243 38.464 27.014 37.08 1058 LYS NZ 18.344 38.699 26.095 42.94 1059 GLU N 15.801 36.951 32.206 14.50 1060 GLU CA 15.976 36.171 33.393 14.90 1061 GLU C 16.338 34.709 33.088 18.20 1062 GLU O 15.719 33.790 33.632 21.55 1063 GLU CB 17.056 36.856 34.217 15.32 1064 GLU CG 16.575 38.151 34.874 13.30 1065 GLU CD 16.724 39.424 34.004 16.29 1066 GLU OE1 16.616 39.376 32.782 16.80 1067 GLU OE2 16.964 40.491 34.568 16.60 1068 GLU N 17.317 34.475 32.183 19.29 1069 GLU CA 17.820 33.133 31.855 19.57 1070 GLU C 16.760 32.233 31.213 21.30 1071 GLU O 16.888 31.007 31.232 20.15 1072 GLU CB 18.964 33.205 30.827 18.63 1073 GLU CG 19.852 34.414 31.027 16.44 1074 GLU CD 19.393 35.654 30.276 16.06 1075 GLU OE1 19.651 35.750 29.079 17.52 1076 GLU OE2 18.763 36.522 30.864 15.56 1077 LYS N 15.763 32.878 30.564 21.95 __ __. __. __. __. _A __. __. _A _-. __. __. __ _A __. __. -_L __. __. _A __. .__. .__ __ __. _-- _i M MMM I M M W M -» - - -» -» - --» J JO OOO O O O OOO (0 (0 (O (0 (0 (D - (D(0 _ 00 (D C0 (II0000000000 ffl co ro ^ ro cn 4- ω ro _^ o co ∞ -v! ro cn 4i ω ro _- o cD ∞ ->ι ro αι 4- co M -i θ CD ∞ sj ro cn -t s - ω OO OOO O OQ TJ Ti Ti ^ - ^ X TiτTJ TJ F Fr F F F F F ^ S^ S ^ S S S OQO li O O OΩ O r ^ r r ccccccccmrnmmmmmmmmm HHHHHHHHCCccccccccv. cococococo ω OOOOOOO OOOOOO OOOO OOOO o oo o o o OOOOOOOO ZOOOOOOO mDOOD > Nmmooocσ > oOQro > m rπ o co > N m o o co > ro -— ro — - m o o DD > — - ro -»■ ro -i n •t- IV) cn 4- co co to ro ro ro -- oo ro ro -^ -- -- -- -- -- co co co co ro --. ro ro ro cn 4-. co co ro ro ro ro ro oo cD -- θJ 4- cn -- to o ^ p ro p cD ro ro 4 s « sj ω po co -vi ro cj. co cn -i i- CD ro cfl M θi [- ω i- ro (o o (Λ) ^ r » M (o _. ro ^ j- J_ o ro co o co oo ro oo 4 s - cn 4 s - cn co ioo- i_n ro ώ o " 4-. d co ^ c cn _--i. " 4ii. oco 4 s - ώ c» ) 4-.4^ k) c co r bo d ^ bι -- 4 s . (_- ^ cn 4- 4 s - -vi co 4_ CD ro oo -vi ro cn si ro co oo cn ro -J > ro ∞ ro cn cD M ∞ o ro cn cn ro oo co oo oo o -j ro o cn cn 4-. cn co ro co o cj) -i crι 1130 GLU OE2 -5.724 19.507 28.772 51.99 1131 ASP N -0.697 22.914 30.136 23.00 1132 ASP CA 0.712 22.482 30.155 22.21 1133 ASP C 1.446 22.782 31.508 20.47 1134 ASP O 2.261 22.031 32.033 19.77 1135 ASP CB 1.332 23.130 28.915 21.00 1136 ASP CG 1.430 24.643 29.079 22.61 1137 ASP OD1 0.486 25.282 29.556 26.49 1138 ASP OD2 2.454 25.190 28.734 21.60 1139 THR N 1.068 23.914 32.079 19.14 1140 THR CA 1.645 24.175 33.404 16.22 1141 THR C 0.561 24.054 34.479 18.50 1142 THR O 0.848 24.327 35.628 20.38 1143 THR CB 2.051 25.710 33.412 14.66 1144 THR OG1 0.989 26.641 33.065 13.92 1145 THR CG2 3.261 25.983 32.480 11.30 1146 ASN N -0.686 23.637 34.105 19.33 1147 ASN CA -1.730 23.331 35.094 19.95 1148 ASN C -2.154 24.539 35.987 21.85 1149 ASN O -2.161 24.482 37.214 22.33 1150 ASN CB -1.180 22.269 36.021 24.72 1151 ASN CG -2.334 21.494 36.646 27.53 1152 ASN OD1 -3.342 21.190 36.060 30.68 1153 ASN ND2 -2.193 21.200 37.881 26.04 1154 LEU N -2.484 25.635 35.297 22.78 1155 LEU CA -2.886 26.899 35.936 22.24 1156 LEU C -4.265 27.315 35.376 22.59 1157 LEU O -4.561 27.167 34.194 23.95 1158 LEU CB -1.875 28.025 35.599 21.01 1159 LEU CG -0.701 28.404 36.548 17.04 1160 LEU CD1 0.610 28.303 35.804 13.07 1161 LEU CD2 -0.612 27.764 37.930 14.04 1162 LYS N -5.087 27.901 36.222 20.53 1163 LYS CA -6.322 28.485 35.725 17.91 1164 LYS C -6.339 30.003 35.942 17.68 1165 LYS O -5.903 30.515 36.958 16.29 1166 LYS CB -7.441 27.691 36.368 17.25 1167 LYS CG -8.807 28.050 35.869 18.58 1168 LYS CD -9.895 27.178 36.443 22.19 1169 LYS CE 11.140 27.885 36.932 22.34 1170 LYS NZ 11.879 26.984 37.836 24.46 1171 LEU N -6.846 30.705 34.934 17.39 1172 LEU CA -7.006 32.157 34.943 15.35 1173 LEU C -8.477 32.621 34.637 16.31 1174 LEU O -9.075 32.259 33.636 16.43 1175 LEU CB -5.961 32.752 34.009 12.86 1176 LEU CG -5.853 34.284 34.126 9.27 1177 LEU CD1 -5.021 34.787 32.956 8.45 1178 LEU CD2 -5.200 34.687 35.454 9.53 1179 THR N -9.012 33.479 35.526 13.25 1180 THR CA 10.363 34.063 35.463 12.10 1181 THR C 10.355 35.563 35.597 13.46 LO © © Ui H U α. ro D CO CD x- O CO OO CD N x- CD x- N CO N CO x- τf OO ro cO x- O CO CD UJ O N CO CN CM CO Tf OO O O x- OO Tf UO x- CM UJ oo OO x- N CD CM CO CO N CD U Tf ro UJ CD CO Tf CN UJ OO O CO CM CM O x- cM ro co p cq uj Tf cM O x- co N CD oo in N ro co ro cq x- O O CO o UJ CM CO CM CO CD N CM ro o o CD CD UO CD Tf CO 00 CD ro rod d c ( co s χr ' ιo τ J C bτ- ' s (o d cM (δ s ' c. (6 m d dd dσJ x- CM ro uo co CN χ - x- CM CM CM CM CN CM CN CN CO Cθ CO CM x- x- CM CN CM CM CO x- x- CM CM CM CM x- CN CM τl- ro τf U0 O N θ ro 00 N τf θ C0 ro θ τf r- ∞ ∞ ro θ ro c0 N N C0 τt O in c0 N CD CD τt x- ro x- in cθ τt τ CD N CM C0 LΩ N C0 CD N C0 C lO ro ro τf CO O O O Cθ ro N CM CD x- O N CN CD x- UJ CO x- Uj ro UO CN O CO τf cO Cθ ro ro CM UJ UJ N τf CN O x- CO Cθ ro CO O CM CO N UJ O CO CO xt p N Lq N ro x- x- p N UJ 0q x- CM ro CM UJ N p UJ τf C» CN in θ O CD x- CM CM CD CO τt O CD CN τt CM x- ω τf χ cb cb cd cM cθ N cb N cb ro ro d ro N cb ro CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO Tf cO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO M 00 x- C0 CO C0 O O N O O CJ) τf x- -f UJ C0 CO N τf Tf CO x- CO CD O x- CO O CO x- τt rs CO x- UJ τt O τr x- O CM CM CD O τf ro-.. - C .O . O CD N . - OO CO x- N lΩ CO xt CO CO ro CO N CO x- CD CO N CN CM O UO OO Cθ τf CD τ- CD CO CO CD CM x- CO CM τf cO CO CO UJ CO CO O Cθ CO UJ CD CO UJ Tf ro cθ O Tf O CO CM CD OO CO CM N x- UJ UJ OO O x- CD CM x- O χ - χ - CJ) ro u x- CM CD CO CJ) N lΩ N CO CD O N O τf ro CD τr CD UJ O N O U UJJ CCDO C CJD) CO CO CO CM CO CD N N N CO CD O O OO OO O O OO N ro CD x- CN C CM CM CO τt UJ CD CD τf τf -f τf τf r-- ro CD θ ro θ x- x- ro θ CM CM O CO O N C CO OO OO CO CO CO Cθ CO CO CO τt τf cO CO τf τf cO CO CO CO Tf τf τf τf τf τf τf τt τf τf τf τf xf τf τf τf f τf _r) ^f UJ UJ UJ τf UJ UJ UJ UJ τf UJ f U co N CO OJ N x- CO CO UJ UO CO Tf r s - x- CO N CO x- N O OJ CN CD CD N CO CD CM N τf x- x- x- CM CO x- UJ UJ O CO CD τt CM CD CO τf O CD CO CM CM r. CD τf CO CD CD CO OO O UJ x- CO CD x- 00 N UJ CM UJ N CD O) Tf N O CM CO OO LO UO O CD OO O CO N ro CD O Tf O UJ x- O CO N U Tf UJ CD CM O o ro uo o co CN co CO O N N Tf CD O UJ O UJ N Tf Tf cM x-^ x- co ro LO N N ro Tt t cD ro co cM Tf T co ro cq o ro c N N N ^ x- O CN x- x- CN CO CM CM CO x- x- CM CO T f CM x- CO CM CM CO CN x- Tf cO CM x- CM CO x- CM CM x- CO x- x- x- O x- x- CM O CM CM CM CM CM CO ■ <- CM x- CM x- CN x- x- CM x- CM x- CM x- CQ < CQ O Q < CQ Q < CO O < CQ O LU LU < co O - < OOO O O OO OO O O O O O O OOOOO OOOOOOOO OOOOOOO OOOOOO Q _ Q - Q _ 0_ D 3 Z 3 D =) Z) Z) 1 ,..,, Q _ Q _ Q_ Q_ Q _ Q_ 3 = ) D D 3 D D Z ) Z ) Q_ Q_ 0. Q_ _ Q. Q_ Q_ |ιl m X X X X L _U W m i_J W m ω W LU LU LL^ L_J L_J LU _jj |_j |_j w h- h- - h- _ι _i -J -J -J _ι _i -j d d d d d d d d w c C W W C < < < < < < < < d d d d d d d d _ © O CM CO τf l CO N Cθ ro θ x- CM CO τf UJ CD N Cθ ro θ χ - CM CO τf UJ O N Cθ ro θ x- CN CO τt UJ CD N Cθ ro θ x- CM CO τf UJ CD N Cθ ro oo co oo co co co co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o o o x- x- x- x- x- x- x- x- x- x- cN CN CM CN CN CM CM CM CM CM co co co c -- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM LO © © Ui H U α. CD Oθ ro N CD x- CN x- CM OO τf c χ- N CD UJ CM τf CD CO ro O UJ CM UJ Tf CD x- CO CO CM O N OJ CO CO O UJ CD x- x- UJ Tf OO Tf CD O CD CD CO CM N N CM Cθ ro τf UJ CO CD OO CD τf ro x- CM N τf CN CO O CO Tf CM CD CM O CD CD Tf oO x- O CD O O N CO N O UJ UJ CM 00 O CM CO CM CO CO f μ d cM CM CN UJ od d ro d d cN ro cM Tf d cd cb d cb cb Tf CO N ro ro o UJ Tf LO N LΩ CJ) CD CN O O CO Tf CO CM U UJ CM CO ¬ ' Tf Tf CO ∞ . CM CM CM CM CM CM CM CO x- CM CM CM x- CM CM CN x- x- CM x- x- x- x- CN x- CN CM CM CM CM x- x- x- x- CO io O CO Cθ cθ O CM ro cθ N CM N ro τf CD CD N CM CO CN τf x- x- x- τf CD x- x- CO CM O τf cθ CO CO UJ CO CM UO CO CO τf CD CM CO UJ N τt ro ro rø Tiin θ CD CO O CO CO CO CO UJ O x- CO τf θ O O τf x- cθ CM x- N ro θ ro CM CO CM Cθ τt CM O UO CM O CM x- CD CM CO CN UJ x- τf θ CD O τf CO to in x- CM CO CD O lΩ N CM N CD CO OO CD p θ CD CM O CO O N Cq cq cθ CO UJ CM ro cq x- τf Uq CO N Cq ro --; CM μ d ro c τt ' d d ro cb N d cb ro cb cb cd cb cd cd ro d ro " μ d μ cN ro d d CO CO CN CO CO CO CO CN CN CN CN CN CN CN CN CN CN CN CN CN CO CN CO CO CO CO CN CO CO CO CO CO CO CO CO CO CO CO OO CO CO CO ro θ C C0 ro N C0 CM C0 ro θ CM ∞ CD C0 C0 ro CN C0 τf C0 τf Is x- CD in 00 x- x- C0 CM in ro x- C0 C0 UJ CD C0 CD x- UJ CD x- x^ CO CO CO CO O N x- UJ OO UJ x- CM CD O τf x- x- CM N ro ∞ CD CM ro cθ x- N UJ UJ OO in CM x- Cθ ro x- O CO τt O CM in cθ CO τf ro CM Cθ ro τf x- lO o τf in τf θ χ - ro o co o uj χ- uo co co uJ CM ro τf τf co co τf x- cq N θ co χ - cq ro ιn χ -^ cM τt cq o χ - N τ^ f ; b -. τ ιri ; ώ ιri b ιo ιn s s co ιri ιri b b D D N U0 UJ UJ UJ UJ UJ UJ UJ U0 U0 UJ UJ UJ UJ UJ UJ LO LΩ UJ U0 U0 U0 UJ UJ UJ UJ UJ UJ UJ U0 U0 U0 U0 UJ UJ UJ UJ U0 UJ UJ τf τf τf xf xt τf τf τf τf x^ x τ^ Oo θ CrN CO CD lΩ O co ro oo ro co o o co x- N Tf OO O OO UJ CO CD CD Tf N N CM LN n L C —D OO OO O UJ N N UJ CM CD O N CD x- . x- UJ N CO O CD CO OO x- CD CD N CO x- x- CM x- x- Tf io oO OO OO CM N N CD UJ CD x- N CO N CM x- CO N N CO CO N t N CD CD OO t Cq p O N O f ro O O N x- Tf T- CO UJ CO CN N N O O CO x- CM CD O O CN OO CO c oό c II N ιb ' f uό τt ιb cb ιb <b ro cb cb ιb N co Tf ' ib ib ib ib ib ib cb cb N- N cb cd ro ro N N ' od ro cb cD J- CM x- CM x- CM _^ x- CM x- CM __, — ■ CM < ω Q LU N < coOO < C Q O O O LU LU N X < C Q O O O LU UJ N X < CQ < CQ OOOOOOOZZOO oooozooooooooooozoo OOOOOOOOO O OO OOOO mmm m cLoioicLo cLoioioioioicLCLCLoicLcLo^ >- >- - >->- X X XX>-ϊ>- >->- >- >- - - - >->->- >- >- >- XXXX XX < ^ -J -J -J -J -J -J -J -J h- l- l- l- l- l- l- l- l- h- l- l- l- l- l- h- h- l- h- - l- l- l- l- l- l- l- l- l- l- l- l- l- l- l- l- l- l- > > > > > > © xt lΩ CΩ N ∞ ro θ x- CN CO τf lΩ CD N ∞ ro θ x- CN CO τf UO CO N ∞ ro θ x- CN CO τt UO CD N (» ro θ x- CN CO τf U^ o CO CO CO Cθ CO CO τf τf τf τf χ f xf τf τf χ f τf LΩ UJ UJ UJ UJ UJ UO UO UO UO CD O CO CO CO CO CD CD CD CD N N N N N N N N N N CO OO CO ∞ Cθ ω CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ O O O O co ω co co co co co co co ω ω ω co ω co co co co co co co c- co co ω co co ω co co ω co ω O O CO O U ωωWMM M M MMMM M M-ι -> -i -i_v_>-ι -> -i -J- O OO O O OO O O O(0(0 (D (0 (0 (0 (0 (0(0 (D 000000 α) si CD cn 4i ω Nj -iO to∞ vj ro ωw -i O co α M rocj. ω w ^ o tD ∞ M ro r ji ω NJ ^ o ω ∞ M ro w Λ ω M -' o ω ∞ vi σ) r O-i-rQ-r-Or-i-[n=nEmEm£m£mEm£mEmi-rO-rO-iO-i-rO-Or-i-i-£rn£[=[I££|Z 0 >>>>>>>>>>>< CCCCCCCCCCCCCcCCCCCCCC C ZCCCC C CCzzzzZZZZZOOOOOOOOOOO 1- OOOOO OOOOOOOZOOOOOOOO O OOOO OOOOOOOZZ OZOOOOOO o Ω CO > D > O O CO > m m o c X N m α o co > roD-> ■ Oro > m r-π O ro ω σα o -i ro -_ o > ro o ro C0 i^ W W p M M ω ^ ^ ^ W o o αC0M _3)M N M ^ (BM l N ^ o CD CD CD p000 p000 ro _vJ 0O O0 OD O0 CD _vJ oo si O) v sj iσroiM ir ιιo(ω_ (∞_ σroi (ω_ ωω j4- i (ro_ s s i j (ro- Λ « ϋ(n) C_jπιcioO ^ f oW_o mroO) c(OnD Λ4- ccDon ιrNo_ MMro nOo 4J>i. J44_i- cWcnn _ l _. s iWo cWo roC) roCJ) JAi -Nvi ^- roO) (cDO -Nvi rroL) rNo) d0 σ _j sj. ro 4- i ∞ ri f j oo co oi ocD Oi oo Moi- c ^- v c - - n ii ϋ θo 1 C _ D ι » ω -' co (θ A ^ o o ω(o ω m n θ) θo ji θ w ω ro cD θo oo σ oo j- ro s ro ro co sJ O CO CD tO CD Cn CO O CD O o ro 4- ro co cD CD io ro ro ro ro co co ω c» !^ 03 ^ M io si o -vi o c» ro cjι ro -- CD cn o o CD cn sj ro io io ro ro co co co co co oo CO CO O CO CO CO o co co co co co co co co CO CO W CO Cθ 4 s - 4i 4.4 s .4- 4 s .4 s - 4i 4 s - 4 s . 4 s . 4 s - 4i 4i.4- 4i.4 s .4- 4- 4-.4- sj oo si po p !θ -i. ιo co -- -- ro co -- co ro ω A ω Ji oi ro to oc- oo oo vi M ω o -' _- -i i- o o ^ w ^ ^ ω w ω ω ω ω *. oi ι o_ ' j_ cn _ j . ^-- co cD 4- -vi co cn 4- ro -J si n bo co 4- cn d d ^- io cD cn -- ro co ro ro ro ώ cj d d d c -j -N co ro j cji (_j όo -_. c ω d j 4-. sj cn co -- -- ιo co cD -- o -vi ■ vl si o o oo 4- ■t- oo to o cn o o co si sj co ro oo ro -si cn 4- oo sj sj - i cn -^ ro co si cD 4i. cn co co cD co co cn oo sj cD θ cn ιo 4i.4i. ιo -- Cjθ -- CO 0000 CD CO oo o -i oo co -— -- -— cn ro 4i M 4-. o cn sj si co o ro o -- ro 4i. oo oo o 4 s . co co ro ιo cn 4- cn -t_ .t_ CO CO -l s - CO CO CO CO Cθ 4i.4i. CO CO 4- 4- 4 s - 4- 4- CO CO C CO CO C C o O CO CO C 4i- 4i. 4i. 4i. CO CO CO CO CO IO CO rO CO CO CO CO CO CO CO CO CO _-- p p0 CO p p0 sl p0 CD _-- p co co ro co ro _-- o si oo co oo 4.4- cn CD CO 00 icoω_--'θ9 α(»sifflopo_-u^sio)oιoι i 4i. co " si o co cJ 4 s - co --. --. ro __ _- cn d d -- r ω D D σ> -vi o i . CD CO CD " 1 vl ■ d 4 s - bo bo si c _n. d n bi co ■ C*O~ sl ■ c'θ~ ->- 4i. C.O. C:_O • C—D • 4_i. :sJ. y , vi cnoo oo o o ro o oi ω oo __ CO si __ J_ sj vi roo cn vi -Oi co ω O CO -i -- CO co -_- cn -ii. ro co cD si co cD ro cD co cn to co 4i. ro co *. O 4i co σ)θ) -» co o r -i co co -vi oo o sj C0 C0 O IO O -- -VJ O 4-. ωj_ M00 - co ro co 4- co -- o cn co ro cD cn cn co co o o o A o oo σ> M-J-J -i-i--i-iJiiiC M->---> ro ro ro to ro p coN ffl W 4- —- ro co o ro ro ro co co _-> c sj sj _- ιo cn ro c cn sj o ro sj --v ro ro o M cjι 1338 GLU CD -8.058 26.570 41.332 22.37 1339 GLU OE1 -8.995 26.977 40.666 21.04 1340 GLU OE2 -8.108 25.474 41.879 25.85 1341 ASN N -3.345 27.828 40.804 22.37 1342 ASN CA -2.546 26.649 40.584 25.92 1343 ASN C -3.387 25.377 40.755 25.53 1344 ASN O -3.572 24.897 41.861 25.67 1345 ASN CB -1.325 26.765 41.500 27.66 1346 ASN CG -0.601 25.427 41.717 27.77 1347 ASN OD1 -1.077 24.341 41.436 27.56 1348 ASN ND2 0.571 25.533 42.244 29.56 1349 LEU N -3.807 24.821 39.627 23.83 1350 LEU CA -4.652 23.629 39.641 22.45 1351 LEU C -4.106 22.430 40.435 24.96 1352 LEU O -4.848 21.603 40.937 26.15 1353 LEU CB -4.919 23.245 38.197 16.54 1354 LEU CG -6.200 23.824 37.584 15.77 1355 LEU CD1 -6.355 23.781 36.061 13.72 1356 LEU CD2 -6.966 24.930 38.291 12.99 1357 THR N -2.783 22.364 40.547 26.74 1358 THR CA -2.184 21.257 41.276 27.87 1359 THR C -2.387 21.269 42.779 29.27 1360 THR O -2.324 20.235 43.438 30.62 1361 THR CB -0.656 21.271 40.960 28.76 1362 THR OG1 -0.222 21.276 39.580 28.70 1363 THR CG2 0.076 20.197 41.798 28.43 1364 THR N -2.626 22.437 43.328 28.69 1365 THR CA -2.904 22.402 44.775 28.99 1366 THR C -4.201 23.179 45.033 32.17 1367 THR O -4.673 23.210 46.146 34.29 1368 THR CB -1.808 23.352 45.374 25.58 1369 THR OG1 -1.906 24.712 44.893 24.80 1370 THR CG2 -0.413 22.844 44.960 21.97 1371 GLN N -4.726 23.838 43.975 34.19 1372 GLN CA -5.903 24.683 44.149 36.02 1373 GLN C -5.651 25.904 45.068 34.54 1374 GLN O -6.560 26.502 45.630 34.82 1375 GLN CB -7.056 23.797 44.633 40.16 1376 GLN CG -7.447 22.737 43.605 46.76 1377 GLN CD -8.777 22.111 44.000 50.73 1378 GLN OE1 -9.050 21.806 45.145 50.25 1379 GLN NE2 -9.586 21.893 42.985 53.71 1380 GLU N -4.364 26.264 45.184 33.22 1381 GLU CA -4.084 27.590 45.723 33.18 1382 GLU C -4.526 28.672 44.740 30.34 1383 GLU O -4.574 28.507 43.524 28.93 1384 GLU CB -2.597 27.807 45.960 37.35 1385 GLU CG -2.029 27.073 47.151 45.79 1386 GLU CD -0.503 27.118 47.092 53.23 1387 GLU OE1 0.090 28.186 47.253 54.41 1388 GLU OE2 0.110 26.083 46.854 58.44 1389 THR N -4.771 29.824 45.341 27.29 1390 THR CA -5.321 30.882 44.519 21.75 1391 THR C -4.702 32.231 44.866 20.39 1392 THR O -4.480 32.572 46.024 21.88 1393 THR CB -6.901 30.855 44.831 20.91 1394 THR OG1 -7.887 30.317 43.926 18.30 1395 THR CG2 -7.402 32.239 45.242 22.13 1396 ARG N -4.478 33.010 43.805 17.74 1397 ARG CA -3.917 34.344 44.023 15.94 1398 ARG C -4.593 35.365 43.131 15.58 1399 ARG O -4.922 35.078 41.994 14.33 1400 ARG CB -2.434 34.314 43.653 16.13 1401 ARG CG -1.673 33.304 44.487 18.13 1402 ARG CD -0.197 33.503 44.382 18.87 1403 ARG NE 0.471 32.485 45.132 20.71 1404 ARG CZ 1.666 32.149 44.780 21.27 1405 ARG NH1 2.351 32.800 43.866 19.60 1406 ARG NH2 2.163 31.120 45.349 22.46 1407 GLU N -4.737 36.564 43.664 16.20 1408 GLU CA -5.232 37.648 42.820 17.96 1409 GLU C -4.066 38.466 42.226 18.25 1410 GLU O -3.223 39.023 42.925 19.75 1411 GLU CB -6.054 38.623 43.649 20.78 1412 GLU CG -6.513 39.851 42.845 23.52 1413 GLU CD -6.777 40.984 43.840 31.18 1414 GLU OE1 -5.867 41.331 44.491 35.95 1415 GLU OE2 -7.849 41.495 43.990 33.07 1416 ILE N -4.131 38.557 40.902 16.64 1417 ILE CA -3.169 39.310 40.109 12.04 1418 ILE C -3.880 40.515 39.527 11.07 1419 ILE O -4.862 40.403 38.819 11.62 1420 ILE CB -2.704 38.444 38.926 9.49 1421 ILE CG1 -2.292 37.027 39.359 8.19 1422 ILE CG2 -1.679 39.155 38.027 6.71 1423 ILE CD1 -1.062 36.953 40.271 8.86 1424 LEU N -3.314 41.663 39.796 12.20 1425 LEU CA -3.765 42.894 39.153 11.34 1426 LEU C -3.068 43.084 37.797 10.98 1427 LEU O -1.855 43.017 37.679 11.20 1428 LEU CB -3.376 43.996 40.135 11.87 1429 LEU CG -4.459 44.428 41.136 14.45 1430 LEU CD1 -3.851 45.049 42.374 13.48 1431 LEU CD2 -5.510 43.382 41.494 14.58 1432 HIS N -3.887 43.335 36.774 11.21 1433 HIS CA -3.409 43.599 35.405 10.35 1434 HIS C -3.599 45.056 35.037 11.82 1435 HIS O -4.720 45.529 34.960 13.04 1436 HIS CB -4.223 42.719 34.475 10.25 1437 HIS CG -3.735 42.604 33.061 5.26 1438 HIS ND1 -4.371 43.183 32.017 4.31 1439 HIS CD2 -2.622 41.907 32.605 3.49 1440 HIS CE1 -3.660 42.851 30.935 4.28 LO © © Ui H U α. o co co o Tf r . CN CN N CM OO x- UO CM x- CO x- CO τt UJ τf τf cθ τf CD CD CO UO O CD CM N N CO xt N CD ro cθ CD CM CO τt Tf OO O CD CO CD CO N O Tf Tf O CN OO CD CN OO ro CM O CO x- CM x- O O UO τ τ r- χ- ιn τ ro ) χ- ro LΩ χ- p χ- uj N CM c cN p p N χ-- ro p O O O CM CO O -^j CO U "~ J O ~ J o o O o CD CN CO CN τt uό cb uό c cM cb cb uό d od uό d uό τf u. uό τt ' od cM μ τt CO ro co N co CD CD x- x- x- x- x- x- x- x- x- x- CM x- x- x- x- x- x- x- x- x- x- x- x- x- x- o. Tf UJ Tf CD CO Tf Tf N N τf |s oO O CD N O O N C» x- N x- N ro UJ x- OO CD τt r- CN x- CO x- CD CO OO CD CD CM CM O O τf |s oO x- CN UJ x- τf TT IO CD 00 CM UO UJ UJ τf UJ C0 x- χ - lΩ CM in UJ CM UJ CD C0 UJ 00 ro ro c0 N C0 N x- CD C0 τf C0 ro x- x- C0 O O O CD τt 00 τf C0 N C0 x- C0 τt ιn θ CM N Tf CD UJ CM N τf c N N τt x- N o ro cM N ro ro N CD u oo co cD χ - o ro χ - cθ χ- ro ro ro uouJ τf CDCM τf ro ∞ ro cD τt co τt cocM ro ro Tf Tt cN CM uJ N cd cb ro cN ro c N ro cb N d ro ro CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CO CN CN CN CN CN CN CN CN CN CN CN CN CO CN CO CN CN CN CN CN CN CN CN CN CN C^ CD CM CM lΩ C» OO CD CO UJ CM τf rs uθ CO ( CD ro CM UJ UJ CD ro CO x- ro UJ UJ ro ro N O x- C» ro UJ CO N O τt CM x- CM τ^ OO CO ro O UJ x- UJ UO O CN CD N Tf N N roCnθcO. (CN (CM Tf- CCDn CCM-x- O0x-- C(DOOO roC»ωco (roB C(O- NN NNCCOOCCOO NN (O- iLΩn NN -x-' CCMN CCOO -x- CCNN C( , O)x-- OO CM CJJ N N LΩ O N χ- τf cM O co cθ N N UJ UJ N O c o- . ccDo rNs ιU_j_ ro_n o_oθ τTf*- c_q_ι iuΛjocro) cpo o_oo ccoo hN^ τTft Tfr c_qo c_or) u-o ro — c -M- c —o p — ro — ■ u-j p — c —o x- C -M- (N C-O- -N .u- C jp —O .u_ O c.o_). N ro _ N c -N. l_O CN U N N N co N co co ∞ N ro ro d d uό uό ro d ro cM c cb τf ' ι d cM ' d ro c^ τf τf τf τf τf τf τf ^ xf τf f 'N- τt τf xf ^f '^ τf τf 't τf ' " τf _r5 UJ τt UJ UJ UJ UJ UJ UJ U^ CO CD N CO O ,- , O 00 N x- N CD τf UJ CM O .£ CN i cM CM CN μ x—- CN x- CM x- CM x- CM x- CM x- CM x- CM - CM -- CM LU < C Q O Q Q LU LU N < CQ O Q O LU LU < CO O O Ω LU LU N X < CQ O O < CQ < zzoooooυooυυ O O O O O Z O O Z Z O O OOOOOOOOO O O O O O O O O O cn cn cn ro cji cn cn ro cn cn cn cfl ro cn ro cji cn cn cn cn cn ro cn cn cn cji cn cn cn cti cn cn cn cn cn ui cn cn cn cn c^ 4i 4- 4i 4-.4- ω co co ω co co co co co co ro M ro M W io ro M SJ io -- --- -- -- -i -- -- -i -- 4- ω ro -^ o ∞ si ro uι 4- ω sj -- o co ro -j ro cn 4i Cj M -- o co ∞ ^ ro cji 4- co ro ^ o co ∞ si ro uι ^ JT)Xττ<<<<<< <0( OO~ ~~~T3~~'ϋ' 1 D'0>>>>> >>>'0'σ~ -D-. 'O-θHHHHHH HH HH 7373737373 > > OOOOO i — i — i — i — i — — < — ^rτιmmfτιrn rπmrnrτιrπ rn " D ' θ " . " D " D " - ' . " θoOOOOO O ' D " D " D ' D " ti " D " στ3 " D " D αi αi o CD -vl si si sj CO O co oo 4- cn o o o CO si 00 00 -»■ CD 00 co oo sj ro cn ro o Cn 4- C04- 4- CO O -- o 4- oo ro ro 4 s - - J . ro ro ro ro ro o n ro o cn .&. co ro 4- cn co oo o cn . co . cn o co ro o co -_ o o si s4 o ω cn ro cΩ co ro o- θo oo ro oo cn ro o ro -χi sj ro 4_.4_ o ro -- co cn 4_ sj CD D si ro -»■ cn ro cD CD co cn co -^. cD *- co cn 4- -- cj) co to *- cn cn -i ^. si oo -- --. o co ro o 4_. o co ro o cD o 4- si cn sj o 1545 PRO CG 4.528 57.385 27.893 12.41 1546 PRO CD 5.346 57.630 26.643 13.69 1547 GLU N 1.202 59.808 25.668 20.58 1548 GLU CA 0.652 61.098 25.215 24.47 1549 GLU C 1.250 62.298 25.940 22.91 1550 GLU O 1.492 63.361 25.390 25.20 1551 GLU CB -0.850 61.158 25.409 32.07 1552 GLU CG -1.590 60.311 24.379 47.45 1553 GLU CD -3.087 60.502 24.517 58.57 1554 GLU OE1 -3.532 61.222 25.432 65.04 1555 GLU OE2 -3.790 59.928 23.682 61.51 1556 SER N 1.500 62.076 27..234 18.37 1557 SER CA 2.197 63.131 27.944 15.28 1558 SER C 2.757 62.537 29.222 14.24 1559 SER O 2.365 61.449 29.650 14.09 1560 SER CB 1.096 64.150 28.335 16.36 1561 SER OG -0.038 63.590 29.064 13.71 1562 PRO N 3.694 63.279 29.870 16.15 1563 PRO CA 4.138 62.933 31.224 15.80 1564 PRO C 3.004 62.717 32.253 14.92 1565 PRO O 3.058 61.827 33.071 16.83 1566 PRO CB 5.050 64.111 31.635 15.53 1567 PRO CG 5.523 64.712 30.308 13.98 1568 PRO CD 4.387 64.458 29.31 1 14.91 1569 ALA N 1.938 63.509 32.155 13.73 1570 ALA CA 0.888 63.387 33.176 11.80 1571 ALA C 0.126 62.067 33.107 12.67 1572 ALA O -0.162 61.442 34.116 15.33 1573 ALA CB -0.118 64.507 32.976 10.12 1574 SER N -0.196 61.656 31.875 13.30 1575 SER CA -0.925 60.382 31.746 13.82 1576 SER C -0.019 59.148 32.010 13.05 1577 SER O -0.412 58.220 32.690 15.15 1578 SER CB -1.429 60.366 30.317 14.32 1579 SER OG -0:511 60.907 29.312 19.74 1580 PHE N 1.239 59.221 31.521 12.50 1581 PHE CA 2.228 58.251 32.002 12.76 1582 PHE C 2.343 58.176 33.577 11.82 1583 PHE O 2.186 57.121 34.169 11.88 1584 PHE CB 3.615 58.605 31.431 13.14 1585 PHE CG 4.637 57.656 32.013 16.05 1586 PHE CD1 4.686 56.327 31.585 14.24 1587 PHE CD2 5.489 58.064 33.038 13.37 1588 PHE CE1 5.556 55.424 32.196 13.11 1589 PHE CE2 6.349 57.150 33.644 11.48 1590 PHE CZ 6.383 55.827 33.237 9.34 1591 LEU N 2.617 59.319 34.219 11.77 1592 LEU CA 2.708 59.367 35.689 11.73 1593 LEU C 1.410 58.893 36.391 10.70 1594 LEU O 1.438 58.216 37.408 10.38 1595 LEU CB 3.025 60.798 36.167 9.36 1596 LEU CG 4.478 61.159 35.960 5.68 © © Ui H U α. CN Tf CM Tf Tf CD CO CO O Tf o CD N CO Tf cO CO O CO CO Tf CM CM CO N Uj Tf - UJ CM Tf ls CD CD N N o CM x- ro CN UJ CO CM Tt CM OJ CD CO N OO CN O N Tf CO CD O x- CO UO CD U) O OO UJOOCO N O Cq o cOro CD Uj pCMOOUJ CN CM Tf CM O O Tf O CD CM CO P cM cd c ro ro c b μ cM f d d . ιb τ f f- C CO CD x- CD CD CO N d d CD CO O x— CD- x— x— CO O CM xt x- x- x- x- x- x- x- CM x- CM CM x- x- x- x- x- CM CM CM CO x- x- x- O Tf cO CO Tf UJ N ro O CO CD O CM OO CN x- CD CD CO CO CM N CO N N CD O N x- CD Tf ro cO N Tf CO CM CD UJ CM O CO CO CO O UJ O OO CD Tt O co IO CD x- CM CM χ - O τf x- cθ CM χ - CO x- OO CO CO O UO τf x- UJ CO CD CO CM CO UJ xt Tf x- CD ro cO O N Tf CO Tf CM x- UJ O ro N x- O O N CO ro N CD CO OO τf cθ CO N CM cO τf x- O O CD UJ CO τf O x- 00 00 ro τf . CM N C _D CD OO OO CN τf τt UO O x- CM UJ CO OO UJ CD O CO CO LΩ ro UJ τt cO CD O ib ib d cb N ib N uό uό uό cb co cb rd cd cb cM CM cb ∞ ro cb N- N N o o CO CO CO CO CO C0 C0 CO CO C0 C0 CO CO C0 C0 CO CO CO CO CO CO C0 C O CO CO C 0 C θ CO CO oo C O τf cN cM ro ro cbo c rorororo τf τt τt τf τf xf f f ^f cO Cθ τf τf cO CO CO CO CO CO CO τf CD OO x- CN O O CD CO CM OO x- C N x- x- CO ro O O CM Tf oO CN CO CD x- τf O CD CO N CD CD CD ro τf UJ τf x- x- CO CO CO CD O CM x- CJ) x- CN N O CO N CJ ) τf OO CD OO N ro N 0) CD O 00 C0 CM N- (O N C0 (O - 00 ^ N CO >CM> ,N- O>. -UJ, -UO, Tf, x .- .c_O. CO CO UJ CO CD ro ro CD CD CO CO Tf CD N CM CM N cq cO CN N CN lΩ UJ x- Tf Tf p ^ in N io iq c T- io r' ffl xr q io co 't -; CM N 0O τf f 0O N τf r-- Uq x- x- N N x- 0q cq d cM ro ∞ N cb ro ro cD cb cb b τf cb τf cb cM CM μ μ d uj τt ' τf ' cd ιb b cb uό uό uό τf r od od cd od cD ro bcM c Ttc c cMCMdd CD CD UJ UJ UJ UJ UO UO UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UO UJ UJ UJ UO UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ ro UJ CO CJ ) CM CD CO CD CD U Tf cD Tf .. . CO CO UJ CO x- CD O O UO CO CN ffl O rO O IO OO CO OD UO Tf o x- CM CO CO Tf O N o x- CM - CM x- CM x- CM x- CM _ , T- CM x- CN o Qo Qzo <ooυ CQoo Oz Q o <ooυ CαυOoQoOo-UoLUoN < ffiOQQ < COOQQLULUN < CO Q LU N < OOOOOOO O OOOOOOOOO OOOOOOOZZOO 33Z zz L umω L m m L um3333333^ L um L uω ω ωm LUc oww o ww ωι_jwww<OWwωwxxxxxxxxxxxwωωwLUwωωxxxxxxxxxxx>- >- JJ<<<<<<<<lQ.D.ll_._._.LD.αjJJJjJJj|LLαQ.lIII_Q.lQ.lJJJJJJJJJ>>> © o N ro ∞ro roro θθ χ O- CON COO O χ t UO0 COΩ NO 0O0 roO θx- χ x-- CxN- CxO- xτ-f χ-J Cx0- Nx- røx- rox- θCM χ CM- CCNM CC0M CτMf CUM0 CM NCM ∞CM roCM θCO χ CO- CCON CC0O CτOf lCΛO CCO0 NCθ C∞O roCO θτf xτf τf τf '^ '^f x^- '^f τf in uO UO CD CD CD CD CD CD CD CO CD CD CO CO CO CD CD CD CD CO CD CO CD CD CD CD CO CD CO CD CD CD CO CD CD CD CO CD CD CD CO CD C^ y o t- -t © © i υ _5 CD CD Cθ x- C M N C O CN C N τf CD UJ O τf UJ N UJ UJ UO CO CO CM x- CM ro cθ O C θ O x- CD ro τf uJ CM O CD CM UJ CM x- x- τf O CO τf CO o CD O CO CD x- ∞ ro cθ O CO CO O x- UJ CM τf UJ O UJ x- x- CM CO N cq cθ ro θ p CD p p cθ N C» CN lΩ N Uq CM CM O N CN τ^ N CO x- ro CD τt cM d τf u τf -^ |v. cb f i ^ f cb uό uO N N d od τ o ιb uό ro CM CO CO CO x- x- χ - x- x- x- x- x- CM CM CM x- CM CM x- x- CM CM CM CO CM CM CM CM CO CO CO Cθ CD CM ro x- C CDD CCOO CO N CM Uj ro CD O x- CD x- OO CM UO CN O CM Tf UJ CO UJ x- x- co N x- ro CM UJ ro CO CO CO Tf OO CD Tf CD OO CD CO x- N CO N UJ CM N CD CO O Tf UJ UJ CO x- CD CM CD x- OO CO N O ro . ro χ- χ- co o N co co χ- co cD co ro co oo CM O CN ro O CM N ∞ N in CD UJ ro UJ CM CD N CO UO N xf Tf CM CM OO CD N N CO O Tf cO UJ xf UJ CM O _ ro N UJ Tf CD CO CD N CO LΩ N N Tf rs Tf ro Tt p x- p cN - cq u ■ u-j ro ~ ro ~ " u c " q Tf ' ro ro UJ CM N CM ro θ τf |s τf τf cO N x- CO CO OO x- CO N CO N CO UJ O CM CD x- CD CO ro CN CD CO CO CO ro _ O θ roro cCNN CCMN CCMN μx- cCOd cCb τft Tτtf LLbn CO uUj- cCMN CCNN x- x- c COj uUJJ uUJ iN ,U_J., (O_, LCJDJ uCOj N CO CO OO N CD CO CD UJ UJ Tf UJ UJ N N CD N OO CO N O CD CD UJ Tf Tt UJ UJ xt UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ U UJ U Tf Tf τf τf τf τf τf τf f τf τf τf xf τf τf τt τf τf τf τf τf f ) τt τf τf τf N N N ro UJ CD x- CD CM CO CD CO CM 00 CD N τf c0 C000 UJ N x- x- UJ |,s T -∞ O N ®N O 0) W ,f OJ CN CJ) x- CD x- O O CO CN CO CM x- (MCJ)r-l --0( r' N ' M μ cN cM μ cM Tf xf ιriιrisιoιri©bιribω x- CM x- CM x- CM x- CM CQ O < CO O LU N X X < CO O UJ LU < O < < O < CQ O Q < OO O υooooozo zzzoooooooozooooozooozoυooo O OOOOO ZOOO _J _J _J _J O O O O O O 3 3 3 3 3 3 3 3 3 O: Q __: __: __: Q_ >- - __: -£ __: C_: _^ < < < < C_: O- _-: --: O __: __: __: _-: __: Q- -J -J -- -J -I -J 'J >>>><<<<<<<<<<<OOθO OOOOc c c c c coOOOOw c c ωω_ι-j-j-j-j_j-j_ιcocoωco © o ro θ x- CM CO xt UJ O N Cθ ro θ x- CM Cθ τf UJ CD N ∞ ro θ x- CM CO τf uJ CD N C» ro θ x- CM OO τf ιn CO N Cθ ro θ x- CM CO Tf UJ UJ UO UJ UJ UJ UO UJ UO UJ CD CD CD CD CD CD CD CD CO CD N N N N N N N N N N CO CO CO CO CO OO CO CO CO CO ro ro ro ro ro ro ro CJj ro ro O CO CΩ CO CO CΩ CΩ CO CO CΩ CD CO CD CO CO CΩ CD CD O CO CO CO CO CD CΩ CO CO CΩ CO CO CO CD CO CD CΩ CO ω LO © © Ui H U α. τf -t OO CD τf O CM x- O O O x- CM C CO CM N _ C .O . _ UO. CO CD CO CM x- CM O τf x- CN CO x- CQ CO CN N ro CO CO Tf CO xf 00 CD CO UJ CD UJ CM CD CD OO O O CO O O CO χ t x- x- CD CD CD U00O f ' Tf - 00 x- CO C0 N CD CM x- CM CO N UJ CD ro ro τt UJ ro CM CO CO CO CM 00 OO N CM 0O CD lΩ UJ UJ N CD lΩ lΩ CO CO CM U0 CO N τf ro CD τf 0O CD CD CJ) N N x- CO UO x- O O CM O CO CD CM CO Tf CO O O Tf CO CO CO τf CM CM CM CM CM CN CM CM CM CM CM CO τf LΩ UJ UJ x- x- x- x- x- x- x- x- x- ( xo-d x-' CO.o x-o x- x- CO UJ 00 N CO Tf CO CM CO Tf N CO LΩ CM CM CD CO O CO CN f CO CO CO UJ N N CO x- UJ UJ CO CD CM CM CO ro O Tf CD CM N N O CO CM O CO CM O lO UJ O O CO τf uJ x- τf IO O CD τt UJ CD x- x- CJ) τf CM x- UJ CO CO O CO x- N CO OO O CD O CO CO N OO O N τf τt ro iΩ UJ x-- lΩ CM CM Tf UO CN CO Tf CM Tf OO CO N CJ) O OO UJ N x- τf CΩ O O χ- χ- CN Cθ τt ro CD N ro τ- O N lΩ O τf CO CJ) m cθ lΩ CM x- cb cb cbodoό ro rod roro d CD UJ CD UJ CD CD N N N ' uότt ' cbcbcM ' μdroddμdro N N ' rocdcb uότf τf uJ cb Tf Tt Tf Tf Tf Tf Tf uj Tf Tf UJ Tf Tf T f f Tf Tf T f Tf τt τf τf τf τt τf τf τf cθ τf τf τf τf CO CO CO CO CO CO Cθ CO CO CO CO CO x- CO N O CD CM N CM O x- CO O τf UJ χ - x- τt x- O CO OO UJ CJ) CJ) CM O N O CO CM x- Tt UJ OO N CO O UJ CO CO CO O CN CO CD CD CD O N UJ CO UJ CM C0 N CO N CD τf U0 CM Cθ ro cθ N N ro CM U0 τf cO x- x- CO τf x- UJ C0 N C0 x- N N O o co ro uj N CM CD CM O Tf Tf ro co ro x- cN CM N ro oo ro cq χ t χ t χ - χ - o o uJ CM ro o c» cθ χf χ - CD θ uj N co ro uj co o co co i-J co o cN CM cq χf in uj cM cq cN cq o u) N χf α τf ro p N ro cM θ cb uό t cb cM uo c μ μ ro cN c cb μ τ μ μ c cM μ cj) ro μ ro ro cM b cM CM Tt x ib μ M CM ro τf τf τf τf τf τf τf τf ^ τf τf τf cθ τf τf τf χ f xf xf xf τf τf τf τf τf τf τf τf cO CO Tf τf τf xt Tf τf τf cO CO τf τf τf τf τf xf x«f τf f τf τf τf cO x- UJ CD CM x- O N UJ O CM UO CO N CO CM UJ O UJ UO UJ N CM OO N CD CD UJ UJ Tt oO x- O CD CM CM x- CO UJ N CO UJ N ro cO CO Tf UJ N N CD N ro OO O Tf CO CD CD N CO Tf O CM Uj Tf ls cM UJ O CO O CM UJ C0 O U0 C0 C0 O x- CD O τf 00 Cθ τf rs CD C0 x- O τt UJ CD CD ro N x- CM x- UJ CD N 00 C0 ro lΩ CN τf τf CD CO UO CO CO N τ- CO CO O x- CO CO OO N CO CO CO Tf N CO UJ CO Tf Tf CD OO CD N UO x- O O CO O O CO CO N CO CO CO CM N UJ U N τt τf N cd N cd oό cb N ' cb cb ιb uj uό τf CN CM μ UJ J c N f cb CM CN CO N N CO CO OO N N x- roNddNuότf cbuόcbujτtιbuj x- CM T- CM x- CM x- CM CQ < CQ O Q < CO O Q LU LU < CO OO O LU LU < < co o o < ω < CQ oozoooooυzoυoooooo υooυozoυzzooo OOOOOO OOOO O OOO O _CC_:OOOOOOθ333333333 fΛfn fnfnfn fnfn ->->->-0000000_j_ι_j_ι_J_ι_ι_J_j_ι_l_ι_ι iij _j _ D Q: (_ _ _ (_ j j j j j j j -? _? _? ^ _^ _! _! i_ _! _i j _: c_ [_ _ _ _: _: < < < < < < < < < < << < - C Q-Q-Q.Q-CLQ_CLOOOOOOOOOXXXXXXXXXXOOOOQ-Q-Q.Q.Q___.Q_>>>>>>>>>>>>> © o x- CM CO xf UJ CD N C» ro θ x- CM C^ τf LΩ C_. rs αj ro θ x- CM CO τf in CD N C» ro θ x- CM CO τt UJ CD N Cθ ro θ x- CM CO τt UO O O O O O O O O O O x- χ - x- x- χ - x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM CO Cθ CO CO Cθ CO CO CO CO Cθ τf χ f -^ τf' τf τf τf τf τt τf lΛ UJ UJ NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN LO © © Ui t_ H " U . UO Tf Tt CM ro CD N O Tf CD N CD N ro CO OO OO O N x- CD CO CD UO CD O CO N O O CD N CD T f CD ro uj UJ CO CN CΩ x- Tt ro co ro cO CN O lΩ CO CO CD CO N CO CN x- O O CN Tt CO UJ N x- CO CO OJ CO UO CO N N CO CM Tf CD x- CO O x- Tf x- τf cθ CD τf x- UJ x- CO τf ro CD 00 O O C000 CJ) UJ C0 C0 ro C0 CM τt x- UJ C0 C0 O τt C0 CM τf O τt Tt CO CM UJ CO O CM O p CD cq xt LΩ x- CD O co ro o co co o x- CD N N r O-x - x- i UrOs i UOs r CsM, , UrOx ^ CD o _ • o ' (M N o -J _ -j N ^ ,η CO ^ ^ ^ d ^ uό cb cb cD N N N rs uό uό uό xt UO Tf CO CO CM CD UJ UJ UJ CD N UJ UJ N N U UJ CO OO OJ ro ro x— x— x— x— x— x— x— x— x— x— x— ro CM x- CM < ω o < co o δ Q LU LU < CQ o < ωO < CQ < < ω Q < ozυooυυυ oooυozoozzooooc zooooozoooozooozoooυooozυoo <S$< g <§§ n fΛ m ΓΛ w rn cn cn m w W w W W ( O l_ (_ [_ (_ _: [_ < < < < < _- _2 _2 _ _2 -_! _2 _2 -_! __! >- >- >- >- >- >- LU LU LU _L_U, LU i_j ' ' ' ' __,' _j _j _j _j LU UJ UJ LU LU LU UJ UJ _j _j _J _J a; xx xxxxxxxxυooooθcocowc c c <<<<<0000_-!__!__!__!__!__!__!__! < © O CO τf if5 CO N OO CJ) O x- CM CO f UJ CD N Cθ ro θ x- CM CO xf lΩ CD N C» ro θ x- CM CO τf UJ CO N Cθ ro θ x- CN CO τf UJ CO N Cθ ro θ x- CM CO τf UJ UJ UJ UJ UJ UJ UO CD CD CD CD CD cD co co cD N N N N N N N N N N co co oo co co co co co co oo ro ro ro ro ro ro cD ro ro ro o o o o o r- h- N N N N N N N N N N rs rs rs rs rs N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N OO CO CO CO CO ω∞ cnro roro rrrrrr rrθθnθOOT3"D "D O"D"- l "D"D1J"D H HHHHH HOO _)OWC CnCn C Cn> >>>>>> > > > mmmmmmmm-<-<-<-<-<-< i-r-r-i-mmmmmm^ ]^ J7]^ 3 ] 3^O c cc cco ωω wmmmmmmmmmmm^ i ] 737- 3π-<^^-< -^ ) 3 i7. ] O O OOO W O o O O OOOOOOOOOO OOOOOO O O OOO o o z z ozoooooo DDOOD > CD > Nmmαoo o > > 03 > X X N m o DO > ro -- ro -i ro ->■ ro __. ∞ > to -L 4i. CJ) 4- CD Cn CJ) sl CO CO 00 CD CO co oo co oo oo j_. co 4 s - cn 4- ro c) θo oo c» rocncn4-corocoroo ro o o oo o *. oo M J- ω o -^ ω o w c coo ov o oy - r!o y r!o^ ! ro y - rwo r ro o !- , oco sicn -- ro -- co co si roco-- co ro -». -- 4- co o.4i. cn ro ro cD CD O to -- -vi w co -J W sj ro o ro co cji -- 4- -- oo co ro -i 4- ro co oi ----coocoo 4i. ro rocn cocn4- -- o 4i Cn si cn ro -- co co ro cD ϋi -- o ro _- rθ C04i 4- CD -vl _-. --. CD CD O C000 rθ s| sJ C000 CD CD 00 -- CO CD OO *_ CD O CD CO C Cn Cn 4i CO CD oo -_ ro cD 4-.4-. ro o o. ro oo cn oo o o oo oo coo co cn cn cn 4- LO © © Ui H U α. τf CM τf cθ CM 00 CO x- CO 00 N CD CD Cθ 00 UJ CO τ N Lnroco O CN Tf Tf Tf oO OO OO CO CD N N UJ CD O O N τ C r lj C CD M C ( N CO C cb cb T xtf- - x CD ro x- CO CD CO Tf N NN σCD) UUJj OO UJ UJ CD N O O O C CO O CD x- O CD CO CM OO x- O CCOO CM CO ro cO x- CD CO CO Tf CD CO CD N CO CO p cq cM N CO N CD CM UJ O C u c UπόJ ι«uJ uuUό)) cl_.J ctbϋ_> χ τTT;f " x-Tff' ' χ τxfTr cb _μ _b U -J U ■ -J U ■ -J U -J U -J UJ U -J U -J UJ UJ UJ UJ UJ UJ UJ UO UJ UJ UJ C UJ uo ro CM co o UJ CO CD O x- O N O ro CN x- UO CM UO N CO O CO CO N CO OO O CO LΩ O CO Tf |v. τf CD N U) CJ) θ ro CJ) U CD Tt UJ UJ CO O CM CM CM UO N CO CD 00 O CO CM CD N Tf CD UJ N CD Tf UJ CO CO CD O UJ CO O OO CO CD CO UJ Tt rs- N x- U Tf ro O CO T- UJ CO CO T N x- OO CM CO CM CO x- x- CO N CM CD x- Tf O Tf CO 00 CO O U0 N 00 U0 CD τf C0 C0 O x- O τf O CD CM CD N τf O UJ N C0 CD C0 τf C0 00 x- C0 CM μ o μ °~> ∞ __: ,__: x- cq x- oq OO Q Tf CN CO xt xt xt CO UO xt xt CO Tf Tf i CM CM O CM O CO CM CM x- CM Tf J UJ CD CD N CO N UJ U x- ro x- CD x- x- CD CO CO 00 ro co x- CM -- CM x- CM x- CM x- CM < CQ < CQ O Q < ω o < co o < ω o o o < CQ O O Q < CQ O Q O oooozoυooυoo υooooozoooooD OOOOOO O O O O O O O O Z O O O O O O O < < < < < Ω_ _L _L Q _ Ω_ Q - Q . Q _ 0_ Q _ Q _ Ω_ Ω_ Q _ Q _ W W W ω W W 3333333 _J _J -J _J _J C0 C C C/ ) C C C/5 CD X X X X X X X >- >- >- >- >- >- U LU LU LU LU LU LU UJ LU UJ LU LU UJ UJ ω < < < < < < < < < < < < < - l- l- l- l- l- - 000000 -J -J -J -J -J -J -J -J -J -J -J _J -J -J -J -J -J -J -J _i -J -J -J -J -≥ _ © O N Cθ ro θ x- CM C O τf UJ C O N ∞ ro θ χ- C M C O xf UJ CD N Cθ ro θ x- CM C O τf UJ C D N C θ ro θ x- C M C O τf UJ CO N Cθ ro θ x- CN C O τf u. c^ uj uo uj co cxj co cD CD CD co cD CD N N N N N N N N N N co co co co co co cD ∞ co co ro ro ro ro ro ro ro ro ro ro o o o o o o o o OO CO CO OO OO CO CO CO CO CO CO CO CO CO αj CO CD CO ∞ CO CO CO CO CD CO CO ∞ CO CO CO CO CO αO CO OO ∞ 1909 MET C 14.356 60.343 45.749 20.59 1910 MET O 14.705 61.087 46.653 19.57 1911 MET CB 14.202 61.069 43.311 15.42 1912 MET CG 14.045 62.573 43.556 22.27 1913 MET SD 13.221 63 451 42.216 26.88 1914 MET CE 14.257 62.910 40.846 20.89 1915 ASP N 13.406 59.399 45.879 21 .94 1916 ASP CA 12.588 59.263 47.068 20.62 1917 ASP C 13.373 58.964 48.367 22.12 1918 ASP O 13.158 59.545 49.428 21.16 1919 ASP CB 11.560 58.168 46.825 17.54 1920 ASP CG 10.247 58.505 47.525 17.97 1921 ASP OD1 10.130 59.552 48.186 16.33 1922 ASP OD2 9.323 57.702 47.398 16.58 1923 LYS N 14.304 58.014 48.244 24.18 1924 LYS CA 14.838 57.506 49.461 30.25 1925 LYS C 15.855 58.477 50.159 31.26 1926 LYS O 16.11 1 58.474 51.360 31.16 1927 LYS CB 15.431 56.139 49.330 34.06 1928 LYS CG 16.631 56.140 48.175 37.83 1929 LYS CD 16.505 54.826 47.413 40.81 1930 LYS CE 15.165 53.967 47.642 45.68 1931 LYS NZ 15.491 52.600 48.093 49.67 1932 ARG N 16.448 59.284 49.291 32.87 1933 ARG CA 17.298 60.331 49.838 34.54 1934 ARG C 16.556 61.652 49.897 32.47 1935 ARG O 16.969 62.544 50.607 35.59 1936 ARG CB 18.529 60.438 48.950 40.97 1937 ARG CG 18.224 60.378 47.464 42.29 1938 ARG CD 19.440 59.951 46.685 46.58 1939 ARG NE 19.789 58.566 46.787 51.13 1940 ARG CZ 20.305 57.917 45.732 51.55 1941 ARG NH1 20.573 58.530 44.593 50.19 1942 ARG NH2 20.556 56.659 45.871 52.57 1943 LYS N 15.477 61.744 49.085 28.06 1944 LYS CA 14.887 63.034 48.739 23.26 1945 LYS C 15.871 63.979 48.006 22.95 1946 LYS O 15.846 65.185 48.145 24.32 1947 LYS CB 14.280 63.666 49.994 20.64 1948 LYS CG 13.096 62.885 50.574 17.75 1949 LYS CD 11.829 63.028 49.746 16.37 1950 LYS CE 10.610 62.496 50.484 18.59 1951 LYS NZ 9.607 61.996 49.547 18.19 1952 ASP N 16.744 63.378 47.216 22.49 1953 ASP CA 17.804 64.139 46.613 22.01 1954 ASP C 17.837 63.901 45.057 22.36 1955 ASP O 18.396 63.068 44.529 20.34 1956 ASP CB 19.135 63.784 47.280 22.14 1957 ASP CG 20.281 64.530 46.551 24.82 1958 ASP OD1 20.036 65.282 45.596 27.44 1959 ASP OD2 21.408 64.386 46.894 28.31 1960 PRO N 17.129 64.817 44.351 22.38 LO © © Ui H U α. Tf UJ CD O CM ro OO CD O O N N UJ N CD N UJ CM CO Tf UJ CO N Tf OJ N O xt CO CO CN Tf CD CO CO CO CO CO N x- N Uj Tf O UJ CO x- CO N CO CO x- N Tf O CD O x- CO CD N Tf Tf CD Tf CM τtcqo cq N χ- LΩCNpcMχ-χ- LΩp cq χ- ocMroχ- cqcqro τtcM LΩ uj u pcq cM cd cb cM d cM uό cb o τf ' cN cb τf CNj τf ' od ro ro cb μ μ 'r- cM ro ro ro ra Ttrocdodcboόcbib CM CM CM CM CM CM CM CM CM CO CO CO CM CM CM CM χ - x- CN CN CM CM CM x- χ - x- x- x- χ - x- CN x- CM CM co co co x- x UJ . ~. CM CO CO CO oocq Tt (O I_ CO CM Tf cO CO UJ UJ CO CO CO lΩ N OO CD CM CO CM ro N CO O CD UJ xt CM CM CM O roχ-cooχ- ujocococoocomcoo χtτf tooroχ-cocDCD oo ro cD o ro N θ Lθ oo ro oo N co cM θ co ro τf ro χ- ro o χ- ro τt o o _ O C0 τf C0 C0 N x- C0 τf U0 UJ N C0 O τt N CM CM O UJ C000 x- C0 τt O CO UJ CM Tf CO CO UJ UJ UJ ro O CN x- Tf CD OO Tf Tf x- CD UJ CD CD CD Tf ro x- co co x- cD oo x- x- ro cD x- oo x- Tf oj in co co cD O x- x- cM ro cD N OO CO CD UO CD ro O x- CM O O x- CM x- x- x- O O O O O CO N N x- x- x- x- CO xf CO UJ O ro ro ro oO N N CD O x- CN CM CM CM Cθ τf τf CM CO x- x- x- x- x- x- x- CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM x- CM CM CM CM CM CM CM CM CM x- x- x- x- x- x- x- CN CM CM CM CM CM CM CM CN CN CM x- CN x- CM < ω Q < CQ CO < ω o < CDOQQ < co δ o S < CO O LU N < υ o O o o < OOO o OOO υ υ O O OOOOOOO OOOOO υoooooozzo O O O O O O Q _ Q_ Q_ Q; Q_ Q: Q_ C_: Q_ __: C_: Q_ _J _I _J _J _J _J _J Q_ Q_ Q_ Q_ CL Q_ CL CL w c c c c wωc c K Q : I_ KO Q ; U _I _I I_ I_ U I_ I_ _I _I I_ I_ < < < << < < WWWWW W W(O^ ^ ^^^ O. Q_ _L Q_ Q- Q_ C/ C/) C0 W C/. C0 W <Y. C0 C0 W C0 > > > > > > > < < < < < < © o x- CN Cθ τf ιo cD N ∞ ro θ x- CN CO τf UO CO N ∞ ro θ χ- CN CO τf lΩ CO N ∞ ro θ χ- CN CO τf iΛ O N rø ro θ x- CN CO τ CD CD CO CD CD CD CD CD CD N N N N N N N N N N ∞ CO CO CO CO C» CO CO CO Cθ ro ro ro ro CD ro ro CJ) CD ro θ O O O O O O O O O x- x- x- rororororo ro ro rorororo ro rorororororo ro ro ro ro roro rorororo rororo ro ro rorororororooo ooooooooooo x- x- x- x- x- x- x- x- x- x- x- x- x- x- -r- x- x- x- x- x- x- x- χ - x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM CM CN CN CM CM CM CM CM CM CM CM CM LO © © Ui H U α. Tf O UJ x- OO CM x- CO CD x- Tf OO CO CM CD xf N UJ Tf CM CO N CD CO O OO CD CD UO N x- O xt CM xf lO CO N CO CM N CO UJ CD Tf N O CM CD O x- UJ O O OO CO Uj Tf CN N Tf CO CO CD O N ro cO CM UJ x- OO CD UJ N CO Tf ro N CO CD UJ ro UO CO CO CO UO UJ CO CO CO CO CN O CD N CO Tf x- CO CO UJ CM o o O O O C u D! Tf. 0~0 O CM (N CM O O CM Tt cO CO O CM CM CO CM CD CO CO CO CN CM UJ N x- CM Tf ∞ O CM CO CO CO x- x- x- x- x- CO OO CO x- x- x- x- CO OO CD x- x- x- CM x- CN x- CM x- CM x- CM ω Q LU N < CQ O < m o O Q < CD O O < m . QQ < CO Q LU < O oooooυzzoo O O O ooooooυzooooooυzυoooooo o o o o υ w o O O O O © o CO xf UJ CD N Cθ ro θ x- CM CO τf UJ CO N C» ro θ x- CN CO τf LΩ O N Cθ ro θ x- CM CO τf- ιo N Oθ ro θ x- CM CO τf UJ CD N rø x- x- x- x- x- x- x- CN CN CN CN CN CN CN CN CN CN CO CO CO CO CO CO CO CO CO CO Tf Tt Tf Tf T Tf ^ Tt Tf Tf UJ U^ ooooo oo oo oo oo o o oo o o o o o ooo ooooooooooooooooooooooooooo CN CM CM CM CM CM CM CM CM CM CM CM CN CM CN CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CN CM CM CN CN CN CN CN CM CM CN CM C^ LO © © Ui H U α. ocooroco r. Nχ- CD CO O CD CO N CD CD x- N CO CD Tf O c .o. N. O _ CO CD CM CO x- CD CO CD N CD CM CD τf τt CD CO Cθ x- CM in o m ro 0 g0o CcMM co oo cM cO Tf ro p cq dcbcdτf τf ' σ) . r Ho o C0 __ x- x- UJ 00 N O x- CO - p ro cO Q lΩ CO N CM x- O Tf cq T f UJ x- p O r d-. C0.CO N C0 τt N CJ) τf x- x- x- x- x- ro ro x- χ- cd χ- cd od cD cb N " cD N " χ- N CD CD χ- cb uό cb cb cD τf <b N N ib cd ιb cb CO IO .C ' D .N .CO .N ' .N .O . x- CD O x- C0 N CD CM O CJ ) ro τf r s - x- τf O N UJ CM x- CO N Tf C.M. UJ UJ CO N CD CO Tf oO CO CO N OO CO CM CO ro O UJ O x- CD Tt UJ ro x- o Tt OO ro UJ CN CO UJ x- CM CO Tf UJ CO N N N CO CO CO IO CO O CM Tf Tf Tf x- N O x- τf cθ lΩ CO CD O O x- CN x- N ro CN O x- CD CO CO x- τf τf rs Cθ p τf cO τf O UJ N N ro CD CO CO N OO x- CJ) 00 O J CO CO UJ O CO x- O—O N. O ro N. x.- O CD C.M, CD UJ C.O. CO ro C.M. N. C.M- O-_ C.O. U_J- C.M, CO UJ.. C.O. ro_. N uό uό τf (~N CN CN CM cb cb ιb uJ cb cM cb μ μ f incdbssNVrorororobrobs ' ωbs ' bbiriiri^b^b^ CN CM CM CM CM CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CM CD UJ CO lΩ O Tf cO CO UO CO N O CO CD CD CO CO Tf CM OO O O CD CO CD U) UJ CO x- CD x- CM CM CO x- N CD θ ro x- CD CO τf x- cθ CO CM N N UJ O x- 00 CD N C0 x- τf UJ CO C0 O C0 O 00 CD τf c0 CD N CJ) N x- τf CD CD CD CO C CN UJ N O CO OO x- x- τf O CO x- Oθ ro cθ CO O UJ O O UJ CO CO (O N x- o p x- ro co m cM t N co ro oo N cq τf τf θO N O O CM CD CD x- CD CO CM CO UO CD C τt cθ CM O CO τf ιO τf τf x- O CO O CO CM ro ro d d d τt cb cM ib cb cD N N cb cN CM x- CO CO CM xt CN UJ Tf cO CM CO UJ CM CM CM x- O O CO Tf uJ UJ CO CM x- O CD N CO CO CO CO O Tt Tt UJ UJ Uj Tf Tf xf Tt Tf Tf Tf Tf Tf Tf Tf Tt Tf Tf τf τf τf τf ' - τf f τf τf τf τf τf x^ τf t Tf xt Tf Tf Tf Tt Tf Xt Tf Tf Tf Tt Tt Tt Tt UJ O x- O CO CM OO CD UJ x- Tf N CN O UJ OO ro cO CO xf UJ O C0 N CJ) C0 CM 00 CD C0 C0 CM C0 in CM O τf C0 τt N τf cM O CM CM C0 lΩ UJ N CO ro cO xt Tf CM CD OJ N CD CO x- O CM N CD CM o in ro oco cocN x- N Tt ro ocN CD N 00 UJ C0 N CD N UJ O O UJ o ro co o - ro Tt CD Tt O OO N xt x- CN N N N CN CO N CD O CN CO CM O Tt cM x- ro cq ro cq N CJ N O UJ CD Tt p co ro cq cN O N CD x- cq N N N cq ro ro cq CD O O 00 o cM co cM CM cd τf uJ cb cb d d oό CO ro " d d d μ d μ od cd od cd c cb xt cb cb Tf CM cb ro cb N ro cd cD d co N co in cb ib in CM CM CN CM CM CM CM CM CM CM CM CM CN CM x- CM CM CM CM CM CM x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM x- CN x- CM x- CM x- CM O LU N X X < CO Q LU N < CQ O O LU LU N O Z O Z Z OOOOOOOZ OOOO O OOO OO z <oυoo C Q Ooo Q LzUNυXzXz < DQOQLU < oo O OO WO OOO O OO OOcy. coco c coc / oc / . c / . _uujωwuj LUUJLUUJ LU LU I-l-l-H I-l-l-l->->->->-3--)--, xxxxxxo_o:_CQ_Q_Q_Q_Q_o_Q__r:yωωyyωyω- -J- -Jiij[u_j < < < < < — l —l — l -J — l -J — 1 -J -J θ- Q. Q- CL Q- Q_ 0_ Q_ Q.0_ Q_ < < < < < < < < < < < _≥ _≥ _≥ _≥ _≥ _≥ _≥ _≥ -J -J _l © o UO CO N CO ro O x- CN CO Tf UJ CO N OO ro O x- CM CO Tf UJ CD N OO CD O x- CM CO Tf u CD N OO ro O x- CM CO xt UJ CD N CO CD O x- CN CO Tt UO CO CD CD CD CD N N N N N N N N N N CO OO OO OO OO CO OO CO CO CO CD CD CD ro ro ro CD CJ) CJ) ro O O O O O O O O O O x- x- x- x- x- x- O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- x- CM CM CM CM CM CN CM CN CM CM CN CM CM CM CN CN CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CN CM CM CM CM CM CM CM CM CM CM CM CM CN CM CD ro ro UJ CO CD UJ UJ CN CM CO CD CO CN CD CO N o CM 00 N ro CO CO O UO UJ ro X — ro CO CD CO O CO O ro CD CD O Tf cM CJ) N O CD CD CO OO CD N Tf CJ ) OO CO CO x- CM CM Tt N CD Tf O Tf CO Tf CJ) CD CO CΩ CN O O CN p N Cq N Cq CN O r o CM N CO CO O CM O Tf CO CO CO N N N xf O O O CO O o CM CM CM CO O CO T - Tf UJ o UJ CD o CO x— Tf LΩ CO o CD o ib cb cM cb cb cd cjJ ro N UJ cb N ib x— x— x— CD x— x— x— x— x— x— CM x— CO CD CJ) x— CD N CO x— LO x— CM in UJ τf cO CO UJ τf x- cθ x- CO CN CO CD ro C» τf τf cJJ τf CO τf CD τf CM CD in cθ N CD CO O Oθ ro cθ θ ro N CO τt ιn τ^ UJ UJ CO CD ro N UJ τf UJ CO CO N CO CO CD CO UJ U ro cθ CM ro uθ N CO x- CO τf O τf ro ro cθ τf cJJ τf CD CM in N x- O CD CN τt ro ro co τf ro ro τf is c χ - iΩ ro c ro o p τf |s o c τf p ιq o p o j oό ro cd b ιb τ b i -d ro N σ- - c c b μ CM CM CM CM CO CN CN CN CM CM CM CM CM CM CM CN CM CM CM CM x- CN CM CM CM CM CM CM x- CM CM CM CM CM CM CM CM CM CM CM CM C^ lΩ ro x- τf τf |s ^ cθ χ - C^ χ - CO τf τf c» O x- CM UO CD CO CN UJ x- ro θ x- ro UO O CO CO N UO O N CO N CO N CO CO τf O N CO N ro CM UJ x- CD CO χ - N O CN O CM C» CO CN N CO UJ UJ CD CO O O τf '^ cO τf o ro θ ro iΩ CO x- ro τf x- x- CD N CO CM N CO O CO ιn x- CM τ^ O N Tf CD CM CD CO CD CO CO CO O CD CO N OO CO N CO τf O CN τf τf cθ τf CD τf CD LΩ CO τf xf CM lΩ x- CO UO CD τf x- UJ CO O O τf CJ) τf cθ O ro CO N^ C^UD N U O - ■ - ^ C (0 ^ xf CN ■ C I N O σ) (O 00 0D xt U^ (0 (0 lfi (0 t N 00 σ) O σ) 0 O σ) O O - CM ^ • l CJO N|s N|s CuO C^Du ^UJ CO' C^O C^O'J O^wO UO Tf ^ xf Tf UJ UJ UJ UJ UJ UJ UO UJ UJ UJ UJ UJ UJ Tf Tf Tf x^ uj UO UO UJ UJ UJ UO UJ UJ UJ O in UJ CD UJ CD CD CD O CO UJ UO UJ UJ U^ x- U Tf UJ CO U T f -^ cD N N x- O CN ro cO N O CO CO x- CO CO CO UJ CN CD CD CN CD O CM CO Tf CJJ N ro cO CO CO N x- N τf CD CO O OO CO CD x- CO x- N x- CO CM x- x- O CM x- x- ro χ - UJ Cθ ro θ χ - N CO τf CM x- N O O CO CM τf cM CM CO Cθ CN ro CD CO x- N τf x- σ) O CM x- x- x- CO CD N C0 τf x- 00 τf CD Tf O CM ro τf UJ N O CO CD C0 x- τf cD O CD x- U0 O C0 CM τt C0 UJ θ ro x- C» N p ro CD U0 N CM O d d τf τf τf U τf τf ' τf ' τf τf '^ τf uO cb cb τf τf uO τf τ^ x- x- x— x- x- x- x— x- x— x- x- x- x- x— x- x- x- x- x- x- x- x— x- x- x— x- x- x- x— x— x— x— x- x— x- x- x— x- x- x- x- CJJ x— x- x- x- x- x- x- x- CJJ x— x- CM ~" CM -- CM x- CM CQ O O < CQ δ o o < CQ O LU LU < CQ O < CQ < co o o o < CO Q LU LU OOOOO O OOOOO OOOOOOOZ OOOOOO OOOO OOOOOOO OOOOOOZZ 3 i 3333 I , I , 1I 1 1 I 1 Z Z Z Z Z Z Z Z Z 0_ C_: Q_ Q- Q_ Q_ __: < < < < < 0_ 0_ O. Q_ Q_ Q. 0_ Q_ Z Z Z Z Z Z Z Z Z 3 _iJji_.Ji_iJji_.Ji_iJj^^^ωω j j j jj-O'j j OJiiiiiiijjjj<jww<w<ωwwwcoJ- J © o CΩ N ∞ ro θ x- ( N C χ t lΩ CO N CD ro θ x- CN CO τf UO CD N rø ro θ x- CN CO τt lΩ O N ω ro θ x- CN CO τf LΩ CD N CD ro x- x- x- x- CN CM CM CM CM CM CN CN CN CM CO CO CO Cθ CO CO Cθ CO CO CO τf τf τf τf τf τf τf τf τf x^ UJ UJ UJ U0 UJ UJ UJ UJ U^ CN CN CN CN CN CN CN CN CN CN CN CM CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN CN C^ owroio oroi sjroi wiowi MroMrororoior roio jr roMroior Mr^ rororoN rowroioioroio rowroioM ro row ro--. _- --. ---L-i-- ->- --v - ^ _- _- _- _- _A --. _-. _- _-L -- O O O O O O O O O O CD CO CD CO CD CO CO CD CD CD ro ω ∞ ∞ ∞ ro ∞ ro ∞ ∞ ^ ^ - sJ sj sJ sJ sJ sJ s^ o∞siroro 4i oM--o o∞-virooi 4 s -co ro -i θ o ∞ ^rocn 4i C M -i θcD ro sj ro cji 4i oM -^ ocD ∞ s^ rrrrr-mHHHH-m-H(/)(/)tO()()0n!-D-DT0-DT]-cn)-ou>>>>>>>>>>>rrrrrrr mmmmm-<^-<-<-<-<^-<-<^-<^mmmmmmxxxxxxxxxxx;B;O;E;E <Zl CZ ZZ y ZZ Z ZO ZO 7373 ZO 737373 ZJ37373 ZO 737373737373 rπ oooozooooooooooozooooo z z ozoooooo o o o o oo o CD > x N m m o o cσ > DO > zoNomomo o X X N m o o co > O O CD > ro —_ o —- ro oooooooσ oo> z -i ro -- ro -i ro -L e O ro CD CO -i. -- -L -i -- -- --. --. CO - CD ro co co n D co co -ϋ. o co ro oo cn ro 4i co si 4- co ro co ω nι coj _--. __- 1 ω cn 4 c -t ω M c o p ^ 4i i_ ι_- 4 s - -^ o qι r 4 s - co μ ro ro ro ∞ sj sj ro cD cD ro ro co -^ -i ro cD -i si c o ι co D -^ ro i i w -i ro ι -- -i 4 s - -vl ro cD oo ro co co ro ro ro oo o 4i. oo ro -i ro oo ro 4i n -- -- co co oo cD ro o oo cn co cn o co o oj -t- cn sj ro co sj oo ro r M r M M W MW r M r M r r r I M N) N) W M W N) M N) l- M W N W W M M M M NO i ro iOM io M M r M M M io ro io r io Nj r M ro ro ro r M M M M M ro io NJ i ro M sj sj ro ro ro ro ro ro ro ro ro ro cjι cn cn cn cn cn cn cn ui cn 4i 4i 4- 4i 4- 4 s .4i 4- 4- 4i. co co co co co co co co co co M -- o o ∞ - 4 ro cn 4i Co r _-. o D ∞ si ro cjι 4i C M -^ o co ∞ sj ro cj s 4 C NJ -i θ o ∞ sj ro cji i C M -i o ω • OT j r- r- r- ^ r- r-r- r- r; > > > > > _; 00 _) (-.00000 χ χ -< -< -< -< -< -< -< -< - |— ι— r- r- |— (— j— ι— i— r— r- |— I— r- ι— ι— r- r— m m m m m m m m > > > > > ' — r- r- r- ^ rπ m rπ o >zz No mo OooDooo > o C ooozooozoooooooozooooo OOZOOOO OO Z OOO O Z OO O D > > m m o CD > o o CD > Q CD > CD > ro -- -i ro __ ro -A σ ro σ ->. o c -t ro _. __. __. _i __. _-. _i __. __. _i __. __ __ _i __. __. ro ιo ro -- (D (0 -> o co G —i —i -— (O 00 - - - -i -— -— -i j- ^ j oι ^ N φ N oo i, q ^ M ( ι ω |. ι. _- o si do ro r^ ^vl ro r° CD [. U ^ ^ O O J O M O O o co co ro co - cn cn bι cD b. co ω co --. co ^ co ^ ro ro ι d uι -v! ro d co do --- -ro o -i o co cn sj bi si cn co do co bo io ro iχ) co oi si -- όj co co d d cn cn ro cD CD CD io cn ro cD si co sj ro si sj cn co co co co ro ro -i co ro cn ro o cn cD -fc- o co ro co oo co ro co cn -- o o 2272 PHE C 6.529 64.115 44.923 15.10 2273 PHE O 6.356 64.173 46.135 14.00 2274 PHE CB 4.737 63.652 43.197 14.81 2275 PHE CG 4.063 62.700 44.139 15.08 2276 PHE CD1 4.788 61.680 44.744 16.62 2277 PHE CD2 2.722 62.833 44.438 14.90 2278 PHE CE1 4.201 60.834 45.687 14.26 2279 PHE CE2 2.122 61.981 45.359 13.81 2280 PHE CZ 2.854 60.983 45.992 11.28 2281 ILE N 7.602 63.516 44.369 15.29 2282 ILE CA 8.620 62.994 45.271 14.87 2283 ILE C 9.098 64.058 46.323 18.20 2284 ILE O 9.269 63.810 47.523 18.22 2285 ILE CB 9.781 62.450 44.423 13.45 2286 ILE CG1 9.314 61.364 43.436 10.62 2287 ILE CG2 10.886 61.886 45.294 11.70 2288 ILE CD1 8.566 60.206 44.086 4.61 2289 MET N 9.239 65.281 45.809 18.52 2290 MET CA 9.792 66.326 46.640 18.33 2291 MET C 8.732 67.081 47.515 19.20 2292 MET O 8.959 68.195 47.962 19.72 2293 MET CB 10.605 67.243 45.721 17.77 2294 MET CG 11.851 66.555 45.143 19.38 2295 MET SD 12.907 65.705 46.383 20.87 2296 MET CE 13.821 67.149 46.923 16.05 2297 GLY N 7.574 66.434 47.745 18.14 2298 GLY CA 6.695 66.952 48.792 18.26 2299 GLY C 5.452 67.686 48.275 20.47 2300 GLY O 4.563 68.022 49.049 22.07 2301 ASP N 5.356 67.942 46.965 20.50 2302 ASP CA 4.108 68.483 46.437 17.37 2303 ASP C 3.162 67.337 46.013 17.32 2304 ASP O 2.919 67.081 44.841 18.62 2305 ASP CB 4.439 69.421 45.276 19.62 2306 ASP CG 3.154 70.077 44.730 24.90 2307 ASP OD1 2.113 69.959 45.386 26.11 2308 ASP OD2 3.181 70.716 43.684 25.14 2309 SER N 2.580 66.630 46.985 16.61 2310 SER CA 1.600 65.618 46.540 16.15 2311 SER C 0.437 66.083 45.684 16.64 2312 SER O -0.191 65.274 45.017 19.31 2313 SER CB 1.018 64.974 47.843 16.12 2314 SER OG 1.977 64.473 48.858 18.84 2315 SER N 0.137 67.393 45.713 16.18 2316 SER CA -1.081 67.847 45.042 14.76 2317 SER C -1.003 67.619 43.503 14.88 2318 SER O -2.019 67.519 42.820 15.72 2319 SER CB -1.161 69.349 45.254 13.96 2320 SER OG -0.260 70.137 44.401 22.60 2321 VAL N 0.253 67.507 43.003 13.31 2322 VAL CA 0.437 67.281 41.570 14.74 2323 VAL C -0.202 65.960 41.092 15.66 2324 VAL O -0.608 65.824 39.951 13.81 2325 VAL CB 1.896 67.243 41.083 15.18 2326 VAL CG1 2.814 66.190 41.711 12.54 2327 VAL CG2 2.515 68.549 40.598 15.63 2328 GLN N -0.243 64.979 42.006 16.96 2329 GLN CA -0.793 63.684 41.636 18.92 2330 GLN C -2.226 63.773 41.066 21.43 2331 GLN O -2.521 63.253 39.993 24.69 2332 GLN CB -0.734 62.761 42.839 17.47 2333 GLN CG -1.288 61.371 42.515 18.74 2334 GLN CD -0.938 60.331 43.569 18.38 2335 GLN OE1 -0.084 60.526 44.399 19.34 2336 GLN NE2 -1.630 59.234 43.514 18.40 2337 ASP N -3.081 64.507 41.797 23.31 2338 ASP CA -4.435 64.639 41.265 24.99 2339 ASP C -4.498 65.555 40.036 24.90 2340 ASP O -5.371 65.464 39.191 27.85 2341 ASP CB -5.359 65.090 42.386 30.46 2342 ASP CG -5.898 63.864 43.139 38.34 2343 ASP OD1 -6.096 62.796 42.538 41.41 2344 ASP OD2 -6.133 63.968 44.331 40.64 2345 GLN N -3.481 66.421 39.920 24.19 2346 GLN CA -3.341 67.176 38.686 24.10 2347 GLN C -3.036 66.310 37.465 22.53 2348 GLN O -3.619 66.479 36.402 22.16 2349 GLN CB -2.236 68.189 38.854 27.88 2350 GLN CG -2.519 69.162 39.994 35.96 2351 GLN CD -1.452 70.219 39.986 41.70 2352 GLN OE1 -1.042 70.696 38.939 46.03 2353 GLN NE2 -0.989 70.532 41.190 41.69 2354 TRP N -2.111 65.357 37.651 20.33 2355 TRP CA -1.847 64.398 36.574 17.39 2356 TRP C -3.136 63.679 36.183 17.81 2357 TRP O -3.426 63.468 35.016 19.79 2358 TRP CB -0.830 63.332 36.993 13.77 2359 TRP CG 0.516 63.940 37.335 10.55 2360 TRP CD1 1.046 65.159 36.878 9.50 2361 TRP CD2 1.470 63.387 38.256 8.89 2362 TRP NE1 2.254 65.372 37.454 9.63 2363 TRP CE2 2.563 64.307 38.309 9.34 2364 TRP CE3 1.485 62.233 38.992 7.20 2365 TRP CZ2 3.624 64.047 39.152 6.71 2366 TRP CZ3 2.570 61.964 39.836 8.42 2367 TRP CH2 3.652 62.866 39.910 6.38 2368 LYS N -3.920 63.356 37.205 19.50 2369 LYS CA -5.171 62.681 36.902 22.56 2370 LYS C -6.181 63.495 36.071 23.90 2371 LYS O -6.735 63.007 35.084 23.96 2372 LYS CB -5.799 62.361 38.218 24.50 2373 LYS CG -7.008 61.458 38.044 28.26 2374 LYS CD -7.501 61.118 39.433 34.93 >>>>>>>> O X XXXXXX XXX 7Jω ωωω<- r- r-r-r- r- r- _^ ωωωω ωωωr-r-ι-ι-r-ι-ι-r-ι-^_> j ^^^^^^^^mmmmmmπ]mmmm OOOOOOO OOOOOOOO > zrπomozooCDooo O O OOOOZOOOOOO OO Z Z O O O D o > m m o CD o o ocD > mm oo cD > N m ro -i H ro -- ro -» ■ oro o- o > OOO O v ro > ro - ro ->■ © © Ui H U α. N x- lO CΩ N CΩ O x- UJ UJ CO CM CD CD N CO UJ CO ro N Tf Tt CD OO N CO ro cO CM CM CD CO x- CO CO x- CM Tt cO CO UO N CD CM CO CD Tf xf x- CD OO Tf x- CO O CM CD CM UJ CM CM CM UJ CM CM N CM x- CO CM τf UJ x- τf rs CD CO τt CO UJ x- x- N N O CO UJ UJ τf O τt O ro CD O N O N O UJ Tf Tf CM OJ CD N CD CO Tf CO O CN Tf O) CM CM O N N N CD CD CJ ) x- CO CM x- UJ UJ CD O UJ CN CO O CM CO CO τf r-- rs cθ N O CJ ) CD CD O N CD N CO Tf CM CO x- x- CM CM CM CM CM CM x- τt τf x- x- CM CO x- CM CM CM CM x- CM CM CN x- CN CO 0O x- CM x- CO τt x- CO CM x- U0 CO τt CM CM x- CO x- oo Tf CD CO T xfi Tf C vO- CM U -J ■ * UJ Tf CM CD U) C0 O O 00 N CD x- O CD C0 x- ro τ -f UJ CD N Tf CO CM OO LO CO CD OO LO CO UO CO x- UJ CO CM fg CO CM ro-. CN CO CM Tf Tf CD CO CO CJ) CO CJJ O UJ OO UO ro O CM UJ O O _ O CO OO N UO CD OO CO x- O CO O CO CD CO UJ CD N N 10 oo oo in ιUoJ x- x- Tf OO UJ OO x- Tf O N o ro cN θ χ - ro cq τf cq τf - Tff c) N " cq co uo cq N O O N N Uj cM uj p uJ co cq cM U ro d CD- α ιo s ' σi c . χ- : cci σ) σ _i τ- c. N O _J. . τt o N " o ιb τt c τf σ) " c τf .o " N " iΩ o cjj " d o CO x- CsM CMiCidN CM xo-iCM CtM- sCM CM CM CM Tf CO UJ x- CO CM CM CO Cθ CO τf τf UJ x- CM τf τf cM CO x- x- τf cθ CO τf CM τf cO CM CM τt N N 00 x- Tf CD N CO CO x- UJ OO CO OO Tf rs τf x- CO τf O UO N τf CO O CO CO CO CO O O OO CO CO CO N τf τf CM τt UO UJ O CO UJ CO x- x- CD CO CO Tf UJ N N N CO x- CO N O CM CM UJ ro UJ N O _ N CD x- OO CD x- CO CO ro ro cO x- CO CO CM x- UJ CO N UO CO Tf O CN Tf O LΩ O CD N x- CD N Tt x- CM x- Tf ro co co oq rorororo ττff rNs ττff ccqD CroD CcDooooq OoCoOoCcOoCroD luΩj NN ττff CcΩD NN NNCCΩD ττft ccθq ττff rt s --- luΩ roro CcOD CpO Oo CcOo CcOq CcJ)) x χ -- x χ -- ττtt CcOo Tτff ooOq CcMM CCDD Op CcDD NN oό cb uό d μ co uό cb cM τf ro c cb N uj CN roμN o roro ro CJ) τf b μ o d ιb o ιb N d τt ' d ro co τf θ N CN " ιb N c τf " UO CO xt UJ CO CO Tf CO CO τt CM lΩ CD CM CM CO τf CD τf cM CD CM UJ U0 UJ UJ τf τf CO Tt CD UJ CO CO in cO UJ UJ CO CM CM CO Tf cO CO UO Tf f xf UO CD CO CO CN O CD O CM ro CD N _ j u cM CM x- x- CO ro CM υ OOOOOOOO OOOOO OOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO© Q_XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX (OOOOOOOO OOO OOO OOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOO <XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX © o N ∞ ro θ χ - CN CO -f UO CΩ N ∞ ro θ χ - CN CO τf iΩ CO N ∞ ro θ χ - CN CO τt LΩ CΩ N ra ro θ x- CN CO τf lΩ N ∞ ro θ x CM CM CM CO CO Cθ CO CO Cθ CO CO Cθ CO τf τf τf τf -^ f τf τf -^ τf U UJ UJ UO UJ UJ UJ UJ UJ UO CO CD CO O CO CO CD CO τf τf τf - - τf τf τf τf τf τf τf τf τf -^ τf '^ τf τf τf τf τf 'ςf τf τf τf τf τf τf '^ τf τf τf τf '^ xf τf '^ CN CM CN CM CM CM CM CM CM CN CN CN CM CN CN CN CM CN CN CM CN CN CN CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM C^ LO © © Ui H U α. CM CM CO x- Tf LΩ ro oo cM ro uj uo o co O x- UJ f x- N CD O N N x- O CO CO CO UJ N UJ UJ O CD UJ CM OJ UJ UJ N N OO x- CO o x— O) UJ O D O N UJ τf uq ro χ- cq cq ro Op Tτff p τf x- p N CD UJ CM O O N UJ N UJ O) N CM ro cO O O N ro O CD O CO O UO Tt OO N O χt α τ σ. co cM ro ιb ro τf cM c χ- d u c cM ro N c x- CN O CN ro x- CO CO τf CD x- χ- τf LΩ τt lΩ x- CO CN x- CO τf x- O xt 00 N CN CO CM CO CM CO x- CM CM x- CO in cO CM CN CM x- x- CM CO x- CO τf CO τf Cθ CO Tf CM Cθ τf cO CO CO Cθ UJ CM CM CO CM CM CO τf UJ τt xf τf CM xt Tf CD CD N OO UJ ro τf cθ O N N CN CN CO CJ) N Cθ ro CN CO CN f Tf CD N O CN N O CO N Tt N O CD Tf CD O x- N N O CM CO CO O UJ O ro J 0O x- 0O CO CO x- CD x- ro N U0 CN xf x- CJ) x- 0O x- U " J CO " OO O OO CO CM X- UO O CO CD LO CO CM O CO O CM CD O X- CO x- CD Tf CD N Tf O CD CD O N ro UJ O CM Tf O CM N UJ OO OJ O CM CD N O O Tt CD CN OJ CM O O CM CO Uj Tf CN CM CO CM CD CO O CO CM N OO Tf CD CO x- CO CD N N CO ro CD cb ro cb ro uj cb cN N- μ μ c) cb C_J). x _t x _t C.N. x,t _UJ. O N N Tf N O Tf Tf rs oO CD N ro cO N UJ OO cd oό cb cb co cd cD N cb in CD x- x- τf CO xf CO xt τf CM CM τf xt CM UJ CO x- CM τf τf τf UJ CO Tf CM Tf CO CM CO CO CO CM Tf CM CO CM CM CO CM Tt CM CO CM CM x- x- CM CM x— CM O x- CN τf CD ro U0 C0 C0 τf |s xf rs τf τf CM UJ τf 00 O 00 O τf N CN x- CD τf cθ O x- CO τf CD O CD CO x- CO O O CN CO N τf ro ro CN Tf N CO CO N ro CO Tf O CD x- N UJ CD O O CM Tf CM CO CD CO ro CO CO CM x- UJ Tf OO OJ CD CD UJ UJ OO O x- CN Tf CO CM CO CM O CM UJ UO CM Tf Tf Tf p ro ro χ-; co cq τf τf cD N cq co o χ-; u cM cq cM N cq χ- O CM OO OO UJ OO O N Tf LΩ O CM CM O CN N O O O CM CM 00 UJ CD N UJ UJ x— 00 ιb μ μ χf ro cd c N b c ιb ro χt c CMM cCθ ττff c00 cCDD x- CCOO CCOO CCMM CCMM 0000 x- x- CCOO NN CCOO CCOO x- τf r s - ro ro 00 τt UJ UJ τf CD CM CM O Tf CM CM CO CO CO CN CM xt Tf CM Tf Tf cO UJ UJ CM Tt UJ Tt Tf cO CD CN N Tf cO UJ CD Tf cO UJ CD LO Tf CD UJ CD CN CO CD CO CO CM CM Tf CM CO N CO UJ Tf ooooooooooooooooooooooooooooooooooooooooooooooooo oo LO © © Ui H U α. N T f OO CO O N CM T f T f cO O O CO Tf CD CM CD CO Tf UJ x- lΩ O CO CN O CO CD CΩ CN CN N χ - τf uj ro co N θ CD ro co ro ro χ - cθ N ro co χ - o CO OO CD O O CN CD CO N N x- CD UJ x- Tf CO UO x- CD x- UO ro ro CM N O O UO CO N CM Tf 00 O CO CO CO ro ro N N ro cO CN CN LΩ x- CO x- LΩ CD CO UO τf UJ N O CD CD CD τf CO O τf CM CO CO N τf x- CO x- τf UJ UJ x- 00 N Tf O CM CD UO x- 00 x- N UJ τf τf cM CD CO τf CO τf cD x- UJ CO CO τf cθ CN CO CO UJ CO CO UJ CO UJ UJ τf cO CO Tf cO τf τf τf τf τf τf LΩ τf cO Tf UJ UJ UJ T f CO Tf Tt CO x- CO o CM UJ 00 CD Tf Tf cO CO CO CO UJ CM CO x- x- CM x-_ CO θ p co ro τt co ro c N N CNi c C CO x- x- x- CM CM CM CM N N CO CD CD CO CO N CN O OO N CM O CO O OO CD CD OJ O O CO ro cO x- OO CD x- ro oO xt OO O CO Tt CM CD x- N UJ CM ro co ro x- uj cM f Tt r ro o CO CM x- ro CD UO CO CO N CD O τf τf cθ O UJ CM CO τf τf CM CO N O x- Cθ ro τf rs cO x- N N O CO CN UJ UJ s tpoqcM iNcpc s oo N p θ CD N N CO O OO CO CD τf CM CO x- CO O CJ) O τf τf CD UJ x- O CO O CM CO p xt Tf UJ LO CO N cb UJ cd cb cb co ¬ ∞ θ χ - N N u. μ c c ro f μ χf c χτ ro cM c μ τr iΩ uό uJ LΩ τf LΩ UO CD UJ O UJ UJ N CM CO τf cM UO τf CD τf cθ CM N τf cθ O CO CO CO UJ CO CM CD τt cθ Cθ τf 'st τf τt Tτft cτbf cτbf u τfo NcbcbN- CO UJ OT N J5 CO CD O τ- CM cθ τf UJ CD N OO ooooooooooooooooooooooooooooooooooδoooδowoδoδδzδδδδδ xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxx oooooooooooo O,O _OOOOOOOOOOOOOOOOOOOO DCDOOOOOOOOOOOOOOOO © o O x- CM CO τf UJ CD N C» ro θ χ - CM C τf UJ CD N Cθ ro θ x- CM CO τf in CD N CO ro θ x- CM CO τf ιn N Cθ ro θ x- CN CO τf U CO N Cθ ro CO CO CO CO CO CO CO CO CO CO Tf Tf Tf Tf Tf Tf -^ Tf -^ xf UJ UJ UJ UJ UJ UJ UJ UJ UJ UO CD CD CD CD CD CD CD CO N N N N N N N N N N CO UO UJ UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO UO UJ UJ UO UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UJ UO CM CM CN CN CM CN CN CM CM CM CM CN CM CM CM CM CM CM CN CN CN CN CN CN CM CN CM CM CM CN CN CN CM CN CM CM CM CM CM CM CM C^ 2582 LIG C19 14.63846.212 18.060 13.64 2583 LIG O20 15.87745.679 17.667 12.90 2584 LIG C21 16.71345.231 18.698 11.97 2585 LIG C22 17.94944.543 18.423 14.27 2586 LIG C23 18.63544.315 19.609 13.98 2587 LIG S24 17.78044.78421.023 15.89 2588 LIG N25 16.601 45.291 20.050 12.72 2589 LIG C26 18.46244.268 17.177 16.50 2590 LIG C27 19.67043.576 17.086 13.27 2591 LIG C28 20.39643.313 18.253 13.47 2592 LIG C29 19.871 43.620 19.501 12.46 2593 LIG O30 18.42045.87921.625 15.41 2594 LIG O31 17.37643.60321.782 15.88

Claims: CLAIMS 1. A method of inhibiting at least one intracellular or membrane- associated PTPase that has aspartic acid (Asp) in position 48 using the numbering for PTP1 B, the method comprising exposing the PTPase to an inhibitor compound which fits spatially into the active site and the vicinity thereof, said compound comprising the following features and moieties: I. a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and a hydrogen bond with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles X 0 - 0H X S'V OH X N ' V OH X N 'N SH u N- N ^ OH HN' ° H ^V 0H ^ 0H « N Y° ^-S =N -0 -S -H / / ' / H p HN' S 0 wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 wherein the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said Lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of features IV through V: IV. a hydrophobic group that interactswith the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and one or more of the following features VI-XXXVII: VI. an amino group which forms a salt bridge to the site chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said site chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; and VII. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond or forms a salt bridge with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 is 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 is 2 ranges from.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that interacts with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that reaches a proximity interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7- 4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV.a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7- 4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX.a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXI 11. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV.a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV.a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and (i) the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, (ii) the centroid of said glycine 259 ranges from 4.7-7.7 A, and (iii) the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; 2. A method for inhibiting at least one intracellular or membrane- associated PTPase that has an aspartic acid (Asp) at position 48 using the numbering for PTP1 B, the method comprisingexposing the PTPase to an inhibitor compound which fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising the following features and moieties: I. an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles H -N. 0 - N OH s - N γOH HN ' V 0H ° - N OH N Vs SH H pr 0H HN ' -^ OH pr pr / H wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid group or carboxylic acid isostere group and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of the following features IV through V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and/or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and one or more of the following features VI through XXXVII: VI. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; and VII. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond or forms a salt bridge with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7- 4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV.a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7- 4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 is 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX.a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine, 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 is 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV.a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV.a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 ranges from 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A. A method of inhibiting at least one PTPase selected from the group consisting of PTP1B, TC-PTP andother PTPase that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity therof , said compound comprising the following features and moieties: I. a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; and (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or acid isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and one or more of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and/or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and one or more of the following featuresVI through XXXVII: VI. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; and Vll. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a salt bridge with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVI 11. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7- 4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV.a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7- 4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX.a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV.a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV.a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 ranges from 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; 4. A method of inhibiting at least one PTPase selected form the group consisting of PTP1 B, TC-PTP and other PTPase that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising the following features and moieties: I. an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) carboxylic acid isostere group selected from the following 5-membered heterocycles H O N' N '8-0 θ ' V OH S'V 0H N' N OH K SH -6 )= X ^ό X u N- N -o H HN 'N OH < O i N Y OH < Y° s ) =N X / ~s H wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said Lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and/or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and at least one of the following features VI through XXXVII: VI. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; and VII. two oxygen atoms which forms hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the - centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7- 4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV.a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7- 4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX.a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV.a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV.a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 ranges from 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; 5. A method of inhibiting a PTPase selected from the group consisting of PTP1B, TC-PTP and other PTPases that are structurally similar to PTP1B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising the following features and moieties: I. a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said Lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at lest one of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 3.55.1 A; and/or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 is 4.4-6.5 A; and one or more of the following features VI-XXXVII VI. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; VII. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 is 3.4-4.1 A; VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7- 4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXIII. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 1 18 ranges from 2.7-4.0 A; XXIV.a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7- 4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVI I. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX.a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV.a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV.a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVI I. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 is 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; 6. A method of inhibiting a PTPase selected from the group consisting of PTP1 B. TC-PTP and other PTPases that are structurally similar to PTP1B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising the following features and moieties: I. an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles H ,N. o'V OH s' N y O HN' ^ OH ° s 9 H ' o N S-° .SH μ s 'N v OH _V OH N wherein said acid or said isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said Lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of the following features IV and V IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; and V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and at least one of the following features VI through XXXVII: VI. two oxygen atoms which form hydrogen bonds via a water molecule to the side chain carboxylic acid group of aspartic acid 48 such that the distance between each of the two oxygen atoms and the centroid of said water molecule ranges from 2.5-3.6 A and that the distance between said water molecule and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 2.5-3.6 A and that the distance between said two oxygen atoms ranges from 2.5-3.0 A; and Vll. an amino group which forms a salt bridge to the side chain carboxylic acid group of aspartic acid 48 such that the distance between the nitrogen atom of said amino group and the centroid of said side chain carboxylic acid group of aspartic acid 48 ranges from 3.4-4.1 A; VIII. a hydrophobic group that interacts with the side chain methylene groups of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the methylene groups of said tyrosine 46 ranges from 4.4-5.1 A; IX. a hydrophilic group that forms a hydrogen bond with aspartic acid 181 such that the distance between the centroid of said hydrophilic group and the centroid of the carboxylic acid of said aspartic acid 181 ranges from 4.4-5.1 A; X. a hydrophobic group that interacts with tyrosine 46 and the methylene side chain atoms of arginine 47 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.7-5.2 A and the centroid of the methylene side chain atoms of said arginine 47 ranges from 4.5-5.5 A; XI. a hydrophilic group that forms a hydrogen bond with the one or more hydrogen atoms donated by the guanidinium group of arginine 47 such that the distance between the centroid of said hydrophilic group and the guanidinium group of said arginine 47 ranges from 2.7-3.5 A; XII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of arginine 47 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said arginine 47 ranges from 2.7-4.0 A; XIII. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said aspartic acid 48 ranges from 2.7-4.0 A; XIV. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of asparagine 44 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said asparagine 44 ranges from 2.7-4.0 A; XV. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XVII. a hydrophobic group that interacts with the side chain methylene groups of arginine 45 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XVIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of arginine 45 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said arginine 45 ranges from 2.7- 4.0 A; XIX. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of tyrosine 46 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said tyrosine 46 ranges from 2.7-4.0 A; XX. a hydrophilic group that forms a hydrogen bond with the side chain amino group of lysine 41 such that the distance between the centroid of said hydrophilic group and the amino group of said lysine 41 ranges from 2.7-4.0 A; XXI. a hydrophobic group that interacts with the side chain methylene groups of lysine 41 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said lysine 41 ranges from 4.4-5.1 A; XXII. a hydrophobic group that interacts with the side chain methylene groups of leucine 88 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said leucine 8 ranges from 4.4-5.1 A; XXI 11. a hydrophilic group that forms a hydrogen bond with the side chain hydroxy group of serine 118 such that the distance between the centroid of said hydrophilic group and the hydroxy group of said serine 118 ranges from 2.7-4.0 A; XXIV.a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of leucine 119 such that the distance between the centroid of said hydrophilic group and the amide carbonyl group of said leucine 119 ranges from 2.7- 4.0 A; XXV. a hydrophilic group that forms a hydrogen bond with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glutamine 262 ranges from 2.7-4.0 A; XXVI. a hydrophilic group that forms a hydrogen bond with the hydrogen atom donated by the backbone amide group nitrogen of glycine 259 such that the distance between the centroid of said hydrophilic group and the amide nitrogen group of said glycine 259 ranges from 2.7-4.0 A; XXVII. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the side chain guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXVIII. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 254 ranges from 2.7-4.0 A; XXIX.a hydrophobic group that interacts with the side chain methylene groups of arginine 254 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 254 ranges from 4.4-5.1 A; XXX. a hydrophilic group that forms a hydrogen bond with one or more hydrogen atoms donated by the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXI. a hydrophilic group that forms a salt bridge with the guanidinium group of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the guanidinium group of said arginine 24 ranges from 2.7-4.0 A; XXXII. a hydrophobic group that interacts with the side chain methylene groups of arginine 24 such that the distance between the centroid of said hydrophilic group and the centroid of the methylene groups of said arginine 24 ranges from 4.4-5.1 A; XXXIII. a hydrophilic group that forms a hydrogen bond with the backbone amide carbonyl group of aspartic acid 48 such that the distance between the centroid of said hydrophilic group and the backbone amide carbonyl group of said aspartic acid 48 ranges from 2.7-3.5 A; XXXIV.a hydrophobic group that interacts with the side chain atoms of methionine 258 such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.5-6.2 A; XXXV.a hydrophobic group that interacts with glycine 259 such that the distance between the centroid of said hydrophobic group and the centroid of the alpha-carbon atom of said glycine 259 ranges from 4.5-6.2 A; XXXVI. a hydrophobic group that interacts with phenylalanine 52 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic group of said phenylalanine 52 ranges from 4.1-9.1 A; or XXXVII. a hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket such that the distance between the centroid of said hydrophobic group and the centroid of the side chain of said methionine 258 ranges from 4.1-7.2 A, the centroid of said glycine 259 ranges from 4.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A; 7. A method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1 B (PTP1 B) and/or T-Cell Protein Tyrosine Phosphatase which (TC-PTP) and/or other PTPases that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof , said compound comprising: I. a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; and (a) a carboxylic acid group or (b) acarboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of the following features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A. 8. A method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1 B (PTP1 B), T-Cell Protein Tyrosine Phosphatase and other PTPases that are structurally similar to PTP1 B comprising exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity therof, said compound comprising: I. an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide nitrogen ranges from 2.7-3.5 A; and II. (a) a carboxylic acid group or (b) acarboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and a hydrophobic group that interacts with the aromatic ring of tyrosine 46 wherein the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and at least one of the features IV and V: IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A. 9. A method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1 B (PTP1 B), T-Cell Protein Tyrosine Phosphatase (TC-PTP) and other PTPases that are structurally similar to PTP1 B which comprises exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising: I. a phosphate isostere which forms a salt bridge to the guanidinium group of arginine 221 and interacts with a hydrogen atom donated by the backbone amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the phosphate isostere group and (I) the centroid of said guanidinium group-ranges from 3.50-4.20 A, (II) said arginine 221 backbone amide nitrogen ranges from 3.5-4.2 A, and (III) said glycine 220 backbone amide nitrogen ranges from 2.7-3.5 A; and (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; wherein the distance between the centroid of the phosphate isostere and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said amino group ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said amino group ranges from 4.8-5.8 A or wherein the distance between the centroid of the phosphate isostere and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said oxygen atoms are ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said oxygen atoms are ranges from 5.0-7.9 A. 10.A method of inhibiting at least one PTPase selected from the group consisting of Protein Tyrosine Phosphatase 1 B (PTP1 B), T-Cell Protein Tyrosine Phosphatase (TC-PTP) and other PTPases that are structurally similar to PTP1 B which comprises exposing said PTPase to a compound that fits spatially into the active site of said PTPase and the vicinity thereof, said compound comprising: I. an oxalylamide which forms a salt bridge to the guanidinium group of arginine 221 and forms a hydrogen bond with a hydrogen atom donated by the amide nitrogens of arginine 221 and glycine 220 such that the distance between the centroid of the carboxylic acid group of said oxalylamide group and (I) the centroid of said guanidinium group ranges from 3.50-4.20 A, (II) said arginine 221 amide nitrogen ranges from 3.5-4.2 A and the distance between the amide carbonyl group of said oxalylamide group and the said glycine 220 amide . nitrogen ranges from 2.7-3.5 A; and (a) a carboxylic acid group or (b) a carboxylic acid isostere group selected from the following 5-membered heterocycles H ° -N. -N. OH .N. oμ -N . O H °.S N N O V S V HN V OM HN r, ___ \__y i- P -N N ' -s r - OH H μ N' V OH <rV OH μ c N ≠ 0 wherein said acid or isostere group forms a salt bridge to the side chain amino group of lysine 120 such that the distance between the centroid of said carboxylic acid or carboxylic acid isostere and the side chain nitrogen atom of said lysine 120 ranges from 3.4-4.1 A; and III. a hydrophobic group that interacts with the aromatic ring of tyrosine 46 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said tyrosine 46 ranges from 4.4-5.1 A; and IV. a hydrophobic group that interacts with the aromatic ring of phenylalanine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said phenylalanine 182 ranges from 4.4-5.1 A; or V. a hydrophobic group that interacts with the imidazole ring of histidine 182 such that the distance between the centroid of said hydrophobic group and the centroid of the aromatic ring of said histidine 182 ranges from 4.4-6.5 A; and wherein the distance between the centroid of the carboxylic acid group of said oxalylamide group and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said amino group ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said amino group ranges from 4.8- 5.8 A or wherein the distance between the centroid of the carboxylic acid group of said oxalylamide group and the centroid of (I) said carboxylic acid or carboxylic acid isostere ranges from 4.9-5.9 A, (II) said oxygen atoms are ranges from 8.0-14.0 A and between the centroid of said carboxylic acid or carboxylic acid isostere and said oxygen atoms are ranges from 5.0-7.9 A. 11. The method of claim 1 to 6 wherein said hydrophobic group that interacts with the aromatic group of tyrosine 46 and/or the aromatic group of phenylalanine/histidine 182 is an aryl group optionally substituted. 12. The method of claim 11 wherein said aromatic group that interacts with tyrosine 46 and/or phenylalanine/histidine 182 is phenyl optionally substituted. 13. The method of claim 1 1 wherein said aromatic group that interacts with tyrosine 46 and/or phenylalanine/histidine 182 is thiophenyl optionally substituted. 14. The method of claim 12 wherein said phenyl optionally substituted that interacts with tyrosine 46 and/or phenylalanine 182 is naphthyl. 15. The method of claim 13 wherein said thiophenyl optionally substituted that interacts with tyrosine 46 and/or phenylalanine/histidine 182 is thieno[2,3-c]pyridyl optionally substituted. 16. The method of claim 1 to 6 wherein said hydrophobic group that interacts with tyrosine 46 and arginine 47 is an aryl group optionally substituted. 17. The method of claim 16 wherein said aromatic group that interacts with tyrosine 46 and arginine 47 is phenyl optionally substituted. 18. The method of claim 17 wherein said phenyl optionally substituted that interacts with tyrosine 46 and arginine 47 is isoindolyl-1 ,3-dione optionally substituted of which one of the isoindol carbonyl oxygen atoms interacts with a hydrogen atom donated by the backbone amide nitrogen of aspartic acid 48 such that the distance between these two atoms ranges from 2.7-3.5 A. 19. The method of claim 18 wherein said isoindolyl-1 ,3-dione optionally substituted that interacts with tyrosine 46 and arginine 47 is 4- hydroxy-isoindolyl-1 ,3-dione of which the hydroxy group interacts with a hydrogen atom donated by the backbone amide nitrogen of arginine 47 wherein the distance between the hydroxy group and the amide nitrogen of arginine 47 ranges from 2.7-3.5 A. 20. The method of claim 1 to 6 wherein said hydrophobic group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket is an aryl group optionally substituted. 21. The method of claim 20 wherein said aryl group that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket is phenyl optionally substituted. 22. The method of claim 21 wherein said phenyl optionally substituted that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket is isoindolyl-1 ,3-dione optionally substituted wherein the distance between the centroid of the phenyl ring of said isoindolyl-1 ,3-dione and the centroid of the side chain of said methionine 258 ranges from 6.1-7.2 A, the centroid of said glycine 259 ranges from 6.7-7.7 A, and the centroid of the side chain of said phenylalanine 52 ranges from 4.1-9.1 A. 23. The method of claim 22 wherein said isoindolyl-1 ,3-dione optionally substituted that interacts with methionine 258, glycine 259 and phenylalanine 52 being part of a hydrophobic pocket is 5-methoxy- isoindolyl-1 ,3-dione of which the methoxy group interacts with the side chain atoms of methionine 258 wherein the distance between the centroid of said methoxy group and the centroid of the side chain of said methionine 258 ranges from 4.4-5.6 A. 24. The method of claim 1-6 wherein said hydrophilic group that interacts with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 is 1 ,1 -dioxo-1 ,2-dihydro-1 H- benzo[o]isothiazol-3-one. 25. The method of claim 1-6 wherein said hydrophilic group that interacts with the one of the hydrogen atoms donated by the side chain amide nitrogen of glutamine 262 is 2,3-dihydro-benzo[d]isothiazol 1 ,1- dioxide. 26. The method of claim 1 wherein the compound is selected from the following: 5-(4-Chloro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(2,4-Dioxo-thiazolidin-3-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid; 5-(4,5,6,7-Tetrachloro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(1 ,3-Dioxo-1 ,3-dihydro-benzo[f]isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; Oxalic acid (3-carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3- c]pyran-5-ylmethyl) ester methyl ester; Oxalic acid (3-carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3- c]pyran-5-ylmethyl) ester; 7-Hydroxymethyl-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran- 3-carboxylic acid; 7-(((Benzo[1 ,3]dioxole-5-carbonyl)-amino)-methyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(3-lmidazol-1-yl-2,5-dioxo-pyrrolidin-1-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-5-phenylcarbamoyl-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3,7-dicarboxylic acid 7-ethyl ester; 7-Benzylcarbamoyl-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3- c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-b]pyrazin-6-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4_(4-Chloro-phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihydro- pyrrolo[3,4-c]pyridin-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid; 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yloxymethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-b]pyridin-6-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(3-(2,4-Dimethoxy-phenyl)-ureidomethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-((3-Carboxy-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-5- ylmethyl)-carbamoyl)-nicotinic acid; 5-(4-Fluoro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Benzyloxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5,7-Dioxo-5,7-dihydro-[1 ,3]dioxolo[4,5-f]isoindol-6-ylmethyl2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(2,4-Dioxo-5-pyridin-2-ylmethylene-thiazolidin-3-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(2,4-Dioxo-5-pyridin-2-ylmethyl-thiazolidin-3-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(4-Methoxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(4-Acetylamino-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(3,5-Dimethoxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(5-(1 H-lmidazol-4(5)-ylmethylene)-2,4-dioxo-thiazolidin-3-ylmethyl)- 2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-(4-Methanesulfonyl-phenyl)-acetylamin,o)-methyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(1 ,3-Dioxo-4,7-epoxido-1 ,3,4,5,6,7-hexahydro-isoindol-2-ylmethyl)- 2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Amino-3-phenyl-propionylamino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(((2R)-2-Amino-3-phenyl-propionylamino)-methyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino)-methyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Acetylamino-3-methyl-butyrylamino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Acetylamino-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Acetylamino-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-b]pyridin-6-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5,7-Dioxo-5,7-dihydro-pyrrolo[3,4-c]pyridin-6-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Nitro-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(5-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-Nitr o-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-7-(1 ,1 ,3-trioxo-1 ,3-dihydro-1 H-benzo[d]isothiazol-2- ylmethyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 2-(Oxalyl-amino)-7-(3-oxo-3H-benzo[d]isoxazol-2-ylmethyl)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-ethyl ester; 5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; (L)-5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; or a pharmaceutically acceptable salt thereof. 27. The method of claim 1 wherein the compound is selected from the following: 5-(5-Methoxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-(((Benzo[1 ,3]dioxole-5-carbonyl)amino)methyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(4-(4-Chloro-phenylsulfanyl)-6-methyl-1 ,3-dioxo-1 ,3-dihydro- pyrrolo[3,4-c]pyridin-2-ylmethyl)-2-(oxalyl-amino)-4,7-dihydro-5H- thieno[2,3-c]pyran-3-carboxylic acid; 7-(3-(2,4-Dimethoxy-phenyl)-ureidomethyl)-2-(oxalyl-amino)-4,7- dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-(4-Methanesulfonyl-phenyl)acetylamino)methyl)-2-(oxalyl- amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 7-((2-Acetylamino-3-(4-hydroxy-phenyl)propionylamino)methyl)-2- (oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid; 5-(S)-(1,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(4-Hydroxy-1 ,3-dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(S)-(1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-methyl-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-((1 , 1 -Dioxo-1 /-/-benzo[d]isothiazol-3-ylamino)methyl)-2-(oxalyl- amino)-4, 5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-((1 , 1 -Dioxo-1 H-benzo[d]isothiazol-3-ylamino)methyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Methoxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Hydroxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Benzyloxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(7-Hydrpxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy- benzyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid; 5-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(7-Hydroxy-1 -oxo-1 ,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl-amino)- 4,5, 6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(7-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy- benzyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid; 7-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(((5-Benzyloxy-1/--indole-2-carbonyl)amino)methyl)-6-(4-methoxy- benzyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid; 7-(((6-Bromo-2-p-tolyl-quinoline-4-carbonyl)amino)methyl)-6-(4- methoxy-benzyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 6-(4-Methoxy-benzyl)-7-(((5-methyl-2-phenyl-2H-[1 ,2,3]triazole-4- carbonyl)amino)methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 7-(((1 H-lndole-3-carbonyl)amino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-((4-Ethoxy-2-hydroxy-benzoylamino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-((4-Benzoylamino-benzoylamino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(((Biphenyl-4-carbonyl)-amino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(((1 H-lndole-2-carbonyl)amino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-((3-Biphenyl-4-yl-acryloylamino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c)pyridine-3-carboxylic acid; 6-(4-Methoxy-benzyl)-7-(((5-methoxy-1 /- -indole-2- carbonyl)amino)methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 7-((4-Benzyl-benzoylamino)methyl)-6-(4-methoxy-benzyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 6-(4-Methoxy-benzyl)-7-(((naphthalene-1-carbonyl)amino)methyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 6-(4-Methoxy-benzyl)-5-((2-naphthalen-2-yl-ethylamino)methyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-((2-Benzo[1 ,3]dioxol-5-yl-acetylamino)methyl)-2-(oxalyl-amino)- 4,5,6, 7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-((2-Dibenzofuran-2-yl-ethyl)amino)methyl)-6-(4-methoxy-benzyl)-2- (oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 6-(4- ethoxy-benzyl)-5-((2-(5-methoxy-2-methyl-1/-/-indol-3-yl)- acetylamino)methyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 5-(f.)-(7-Methoxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-(7-Methoxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-(4-Hydroxy-1 -oxo-1 , 3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(S)-(Oxalyl-amino)-5-((4-phenoxy-benzylamino)methyl)-4,5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-((4-Acetylamino-benzylamino)methyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(S)-((Acetyl-(4-phenoxy-benzyl)amino)methyl)-2-(oxalyl-amino)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 7-(S)-((Acetyl-benzyl-amino)methyl)-2-(oxalyl-amino)-4, 5,6,7- tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(S)-((1 , 1 -Dioxo-1 /-/-benzo[d]isothiazol-3-ylamino)methyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(4-Benzyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-(oxalyl- amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 5-(6-Methoxy-4-methoxycarbonyl-1 -oxo-1, 3-dihydro-isoindol-2- ylmethyl)-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3- carboxylic acid; 2-(Oxalyl-amino)-5-(1 ,1 ,3-trioxo-1 ,3-dihydro-1/-/-benzo[d]isothiazol-2- ylmethyl)-4,7-dihydro-5/- -thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-7-(1 ,1 ,3-trioxo-1 ,3-dihydro-1H-benzo[d]isothiazol-2- ylmethyl)-4,7-dihydro-5 - -thieno[2,3-c]pyridine-3-carboxylic acid; 7-(f.)-Carbamoyl-2-(oxalyl-amino)-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(S)-(2-oxo-tetrahydro-thiophen-3-ylcarbamoyl)- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-5-(S)-phenylcarbamoyl-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 2-(Oxalyl-amino)-7-( c ?)-phenylcarbamoyl-4,5,6,7-tetrahydro-thieno[2,3- c]pyridine-3-carboxylic acid; 5-(R),7-(R)-Bis-benzyloxymethyl-2-(oxalyl-amino)-4,5,6,7-tetrahydro- thieno[2,3-c]pyridine-3-carboxylic acid; 6-Benzyl-2-(oxalyl-amino)-5-(1 , 1 ,3-trioxo-1 ,3-dihydro-1 ,6- benzo[d]isothiazol-2-ylmethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine- 3-carboxylic acid; or a pharmaceutically acceptable salt thereof. 28. The method of claiml wherein said compound is of the Formula 1. 29. The method of any one of claims 1 to10 wherein said exposing step is effected by administering said compound to a mammal including a human in need of said inhibition. 30. The method of claim 29,wherein said mammal has a disease selected from the group consisting of autoimmune diseases, acute and chronic inflammation, osteoporosis, various forms of cancer and malignant diseases, and type I diabetes, type II diabetes, and obesity. 31. A pharmaceutical composition comprising a compound according to any of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form together with one or more pharmaceutically acceptable carriers or diluents. 32. A pharmaceutical composition suitable for treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising a compound according to any of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form together with one or more pharmaceutically acceptable carriers or diluents. 33. A pharmaceutical composition suitable for treating immune dysfunctions including autoimmunity, diseases with dysfunctions of the coagulation system, allergic diseases, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases comprising a compound according to any of the claims 1 to 28 or a pharmaceutical acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form together with one or more pharmaceutically acceptable carriers or diluents. 34. The pharmaceutical composition according to claim 31 , 32, or 33 in the form of an oral dosage unit or parenteral dosage unit. 35. A pharmaceutical composition according to claim 31 , 32, or 33 wherein said compound is administered as a dose in a range from about 0.05 to 1000 mg, preferably from about 0.1 to 500 mg and especially in the range from 50 to 200 mg per day. 36. A compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form for therapeutical use. 37. A compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form for therapeutical use in the treatment or preventing of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity. 38. A compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form for therapeutical use in the treatment or preventing of immune dysfunctions including autoimmunity, diseases with dysfunctions of the coagulation system, allergic diseases, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases. 39. The use of a compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form as a medicament. 40. A method of treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising administering to a subject in need thereof an effective amount of a compound according to any of the claims 1 to 28 to said subject. 42. A method of treating immune dysfunctions including autoimmunity, diseases with dysfunctions of the coagulation system, allergic diseases, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases comprising administering to a subject in need thereof an effective amount of a compound according to any of the claims 1 to 28 to said subject. 43. A process for the manufacture of a medicament, particular to be used in the treatment or prevention of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity which process comprising bringing a compound according to any of the claims 1 to 28 or a pharmaceutically acceptable salt thereof into a galenic dosage form. 44. A process for the manufacture of a medicament, particular to be used in the treatment or prevention of immune dysfunctions including autoimmunity, diseases with dysfunctions of the coagulation system, allergic diseases, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases which process comprising bringing a compound according to any of the claims 1 to 28 or a pharmaceutically acceptable salt thereof into a galenic dosage form. 45. A pharmaceutical composition suitable for treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising a compound according to any of the claims 1 to 28 or a pharmaceutical acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form together with one or more pharmaceutically acceptable carriers or diluents and an insulin sensitizer, such as a thiazolidinedione eg. troglitazone, ciglitazone, pioglitazone, rosiglitazone, 5-[[4-[3-Methyl-4-oxo-3,4- dihydro-2-quinazolinyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione or a pharmaceutically acceptable salt thereof, preferably the potassium salt, or (-) 3-[4-[2-Phenoxazin-10-yl)ethoxy]phenyl]-2- ethoxypropanoic acid or a pharmaceutically acceptable salts thereof, preferably the arginine salt. 46. The use of a compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form and an insulin sensitizer, such as a thiazolidinedione eg. troglitazone, ciglitazone, pioglitazone, rosiglitazone, 5-[[4-[3-Methyl-4-oxo-3,4- dihydro-2-quinazolinyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione or a pharmaceutically acceptable salt thereof, preferably the potassium salt, or (-) 3-[4-[2-Phenoxazin-10-yl)ethoxy]phenyl]-2- ethoxypropanoic acid or a pharmaceutically acceptable salts thereof, preferably the arginine salt for the preparation of a medicament suitable for the treatment or preventing of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity. 47. A method of treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising administering to a subject in need thereof an effective amount of a compound according to any of the claims 1 to 28 and an insulin sensitizer, such as a thiazolidinedione eg. troglitazone, ciglitazone, pioglitazone, rosiglitazone, 5-[[4-[3-Methyl-4-oxo-3,4-dihydro-2- quinazolinyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione or a pharmaceutically acceptable salt thereof, preferably the potassium salt, or (-) 3-[4-[2-Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or a pharmaceutically acceptable salts thereof, preferably the arginine salt to said subject. 48. A pharmaceutical composition suitable for treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising a compound according to any of the claims 1 to 28 or a pharmaceutical acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form together with one or more pharmaceutically acceptable carriers or diluents and an agent stimulating insulin release from β cells such as repaglinide. 49. The use of a compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form and an agent stimulating insulin release from β cells such as repaglinide for the preparation of a medicament suitable for the treatment or preventing of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity. 50. A method of treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising administering to a subject in need thereof an effective amount of a compound according to any of the claims 1 to 28 and an agent stimulating insulin release from β cells such as repaglinide to said subject. 51. A pharmaceutical composition suitable for treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising a compound according to any of the claims 1 to 28 or a pharmaceutical acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form together with one or more pharmaceutically acceptable carriers or diluents and an antiobesity agent such as orlistat. 52. The use of a compound according to any one of the claims 1 to 28 or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form and an and an antiobesity agent such as orlistat for the preparation of a medicament suitable for the treatment or preventing of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity. 53. A method of treating type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising administering to a subject in need thereof an effective amount of a compound according to any of the claims 1 to 28 and an antiobesity agent such as orlistat to said subject.

Inventors: ANDERSEN HENRIK SUNE, AXE FRANK URBAN, GE YU, HANSEN THOMAS KRUSE, HOLSWORTH DANIEL DALE, IVERSON LARS FOGH, JONES TODD KEVIN, JUDGE LUKE MILBURN, LAU JESPER, MOELLER NIELS PETER HUNDAHL, OLSEN OLE HVILSTED, RIPKA WILLIAM CHARLES, SHAPIRA BARRY ZVI, UYEDA ROY TERUYUKI, ANDERSEN, HENRIK, SUNE, AXE, FRANK, URBAN, GE, YU, HANSEN, THOMAS, KRUSE, HOLSWORTH, DANIEL, DALE, IVERSON, LARS, FOGH, JONES, TODD, KEVIN, JUDGE, LUKE, MILBURN, LAU, JESPER, MOELLER, NIELS, PETER, HUNDAHL, OLSEN, OLE, HVILSTED, RIPKA, WILLIAM, CHARLES, SHAPIRA, BARRY, ZVI, UYEDA, ROY, TERUYUKI
Applicants: NOVO NORDISK AS, ONTOGEN CORP, NOVO NORDISK A/S, ONTOGEN CORPORATION
Application year: 2000
Main classification: A61K31
IPC codes: A61K31, A61K45, C07D495, C07D519