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CARLTON warmed up for an AFL season-defining month with a commanding 94-point victory over Greater Western Sydney at Etihad Stadium on Saturday.The Giants were at least competitive in much of the first, second and fourth quarters, but cannon fodder in the third, as the Blues won 22.16 (148) to 8.6 (54) to improve their win-loss record to 6-4.Once again, it was the Blues' speedy flotilla of small forwards who did most of the damage, with Jeff Garlett, (four), Chris Yarran (three), Dennis Armfield (two) and second-gamer Troy Menzel (two) combining for half of their side's tally of 22 goals.At the other end, Andrew Walker and Michael Jamison anchored a rock-solid Blues defence, while Matthew Kreuzer relished the opportunity to ruck all day in the absence of the injured Robbie Warnock.After a slow start to the Mick Malthouse era, the Blues have won six of their past seven games as they become better attuned to the requirements of their new coach."I had to find out what the playing group were equipped to do and what they enjoy because football is about enjoyment as well - and what can they achieve or tell me about the best way they play," said Malthouse."It's give and take on both sides and what we've done over the last few weeks is start to cut off bits and pieces that I had and bits and pieces that perhaps I didn't like."What's happened is we've got a game structure which meets the criteria and, so long as we don't stray from it now, we can be a good football side."But it all gets much harder in a hurry for the Blues, who face a month of tough games against Essendon, Hawthorn, Sydney and Collingwood either side of the bye.The winless Giants tackle mission impossible at home against Geelong next week, having lost each of their past four matches by margins between 83 and 135 points. Malthouse was not that impressed with his forward line, despite a return of 22 goals but lauded Walker's 34 possession game."What he brings to the side is versatility and he generally uses the ball pretty well both sides of the body," he said. Coach Kevin Sheedy felt GWS should have been much closer than 22 points at quarter-time on Saturday had Stephen Coniglio not butchered a golden opportunity, allowing Lachie Henderson to score at the other end as the siren sounded.His young side struggled most in the third term when they were outscored 6.4 to three points."We're going to get inconsistent performances at times," said Sheedy."I thought we played well in a lot of different patches in the game, but to sustain it for 100 to 120 minutes has been very awkward."I've got to not like it, but to cope with it".GWS were best served by co-captain Callan Ward and fellow onballers Toby Greene and Dylan Shiel.With former Port Adelaide premiership ruckman Dean Brogan (back) a late withdrawal, the Giants featured one of their most-inexperienced line-ups, averaging just 28 games per player.Carlton had an even more-important late absentee, with dual Brownlow medallist Chris Judd pulling out with a sore hamstring.6.4 12.6 18.12 22.16 (148)3.0 6.2 6.5 8.6 (54)Garlett 4, Waite 3, Yarran 3, Armfield 2, Menzel 2, Henderson 2, Armfield 2, Gibbs, Curnow, Casboult, KreuzerCameron 2, Coniglio 2, Hampton, Whitfield, Palmer, WardWalker, Garlett, Yarran, Kreuzer, Gibbs, ArmfieldWard, Whitfield, Adams, GreeneChris Judd (hamstring) replaced in the selected side by Troy MenzelO'hAilpin (knee)Michael Jamison replaced by Tom Bell at three-quarter timeSetanta O'hAilpin replaced by Jacob Townsend at half timeNilMcBurney, Burgess, Pannell25,008 at Etihad Stadium

Review of the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction. Topical capsaicin is known to be a safe and effective pain management adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, and diabetic neuropathy. However, studies and case reports in the literature have indicated that other conditions may also benefit from capsaicin: painful or itching cutaneous disorders from operations, injuries, or tumors; neural dysfunction; or inflammation of the airways and urinary tract. To determine the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction, the authors analyzed data from 33 reports (MEDLINE search of 1966-96) on the efficacy of capsaicin. Outcome measures consisted of the response rate and degree of pain relief. Results from placebo-controlled trials were pooled when possible; effect of treatment was estimated by the method of DerSimonian and Laird. Pain relief for postmastectomy syndrome and cluster headache was greater with capsaicin than with placebo; also, psoriasis and pruritus responded better to capsaicin. Uncontrolled studies and case reports have indicated that pain or dysfunction was less at the end of capsaicin therapy for neck pain, loin pain/hematuria syndrome, oral mucositis, rhinopathy, reflex sympathetic dystrophy syndrome, detrusor hyperreflexia, and cutaneous pain due to tumor of the skin. Capsaicin is effective for psoriasis, pruritus, and cluster headache; it is often helpful for the itching and pain of postmastectomy pain syndrome, oral mucositis, cutaneous allergy, loin pain/hematuria syndrome, neck pain, amputation stump pain, and skin tumor; and it may be beneficial for neural dysfunction (detrusor hyperreflexia, reflex sympathetic dystrophy, and rhinopathy). A universal problem for many of the studies analyzed was the absence of a "burning placebo" such as camphor.

Increased occurrence of PGP 9.5-immunoreactive epidermal Langerhans cells in rat plantar skin after sciatic nerve injury. This study examines the occurrence and distribution of epidermal dendritic cells (DCs) in cryostate sections from plantar skin in normal rats and in rats with a crush injury or neurotomy and suture of the sciatic nerve. The dendritic cells were visualized with antibodies against protein-gene product 9.5 (PGP 9.5). Counts under the fluorescence microscope showed that the occurrence of dendritic cells is increased and that the proportion of dendritic cells in the basal layer is elevated 3 months after sciatic neurotomy and suture but not after a crush lesion. The countings also revealed that the number of cells is elevated as soon as 1 week after neurotomy and suture. Labelling with specific antibodies showed that the dendritic cells examined represent Langerhans cells (LCs). These observations show that there is a neural influence on the occurrence and distribution of PGP 9.5-immunoreactive epidermal Langerhans cells. Whether this influence is direct or indirect remains to be ascertained.

Pipettes and automatic aspirators are constructed preferably with disposable tips or containers, means for mounting the tips or containers, and means for pressurizing or evacuating the contents of the tips or containers. The pressurizing means then comprise a piston chamber, a piston, and means for reciprocating the piston. Most commonly, the piston uses sealing rings that rub against the inside wall of the piston chamber or outside wall of the piston. Because such rings are subject to wear, bellows have been suggested as an alternative since they have a much longer wear capability. Such bellows can be prestressed and simply compressed manually, as shown in U.S. Pat. No. 4,296,071, or they can be driven by a motor as shown in U.S. Pat. No. 4,041,995, FIGS. 6 and 8. In either case, some manufacturing difficulties are encountered. In the case of a simple bellows that is of the type shown in the '995 patent, it is difficult to attach the base portion of the bellows to the bottom of the piston chamber, simply because of inaccessibility. A solution would be to assemble the chamber housing in several parts, but it is preferred, e.g., for convenience, to have such a housing be one integral part. One approach to this problem has been to use a flat elastomoeric membrane in place of a bellows, for example, as shown in U.S. Pat. No. 4,444,062, since such a membrane can be secured to the top of the piston chamber. As the piston is advanced, FIG. 4 of the '062 patent, the membrane (68) is stretched into a cylindrical shape. However, such a design encounters the following disadvantages: the elastomeric membrane tends to crack under the high stress that is delivered, and is therefore short-lived. Furthermore, it provides a non-linear displacement since the cross-sectional shape changes as the piston is advanced. A bellows does not suffer these disadvantages. Thus, such a flat membrane is not a suitable substitute for a bellows. Therefore, prior to this invention there has been a need to provide a more readily manufacturable bellows design as a piston ring replacement. Yet another problem exists with such bellows construction. Many pipettes have a disposable tip ejector comprising a rod extending from the tip mounting surface, back into the end of the piston chamber nearest to the disposable tip. Such rods need to be pushed at the appropriate moment, such as by extending the piston until it contacts the rod. However, when a bellows is disposed in between the piston and the end of the chamber at which the rod is located, excessive power is required to activate the rod. That is, not only must the piston push against the resistance of the rod and tip, but also it must collapse the bellows. For the above reasons, bellows have had limited utility in use as replacement of piston seals, in spite of their advantage in wearing.

The present invention relates to spinal implant devices and associated techniques for promoting fusion of two or more vertebrae. It is known that when an intervertebral disc degenerates or is damaged, there is often a compression of the disc and a reduction in the normal intervertebral height. Typically, this condition results in abnormal motions that become a source of pain. In order to treat a pathology of this type, the disc is often stabilized to eliminate the abnormal motions caused by disc disorders or injuries. Generally, one approach is to prevent articulation between the two vertebrae situated on each side of the damaged disc by bone fusion. This fusion fixes the vertebrae to each other, eliminating the relative mobility causing the pain. Various spinal implants to promote fusion between adjacent vertebrae have been proposed. It has been proposed to interconnect the two vertebrae by a kind of rigid U-shaped stirrup which restores the discal height with a bone graft material disposed inside the stirrup. However, one drawback of this proposal is its diminishing effectiveness over a period of time. An spinal cage is also known which consists of a cylindrical member provided with a series of openings and provided with anchoring points. This implant is placed in a recess formed in the intervertebral disc and penetrates the opposite cortical plates of the two vertebrae which were previously hollowed out to receive the implant. This penetration forms openings in the sub-chondral plates to place spongy bone of the vertebrae in contact with bone graft material placed inside the implant, facilitating bone fusion. U.S. Pat. No. 5,015,247 provides one example of this approach. FR 2,736,538 discloses an intersomatic cage formed by a body having inclined upper and lower surfaces and parallel lateral walls, provided at their end portions with anti-backward movement teeth. In such a structure the central and end surfaces are in the same plane so that the major part of the bearing surface is provided by the central part, that is in contact with the spongy bone, of which the strength is lower than the strength of cortical plates. Hence such structure is not entirely satisfying. Proper performance of a spinal implant of this type requires balancing the need to promote fusion between the spongy bone and the need to form a reliable load bearing relationship with the stronger cortical bone. As a result, the spinal cage must be neither engaged too far into the openings provided in the cortical plates to provide a sufficiently dense load bearing surface, nor insufficiently inserted, in which case the bone fusion between the two vertebrae would be adversely affected by a poor anchorage. Thus, there is a demand for devices and techniques that facilitate attaining the proper balance between fusion and load support. The present invention meets this demand and provides other significant benefits and advantages. The present invention relates to spinal fusion implants and techniques. Various aspects of the present invention are novel, nonobvious, and provide various advantages. While the actual nature of the invention covered herein can only be determined with reference to the claims appended hereto, certain forms which are characteristic of the preferred embodiments disclosed herein are described briefly as follows. According to one form of the invention, the spinal implant comprises a body having a central part arranged to allow arthrodesis and at least one terminal part for bearing against the cortical bone of the vertebral end plates. The central part is adapted to penetrate the vertebral end plates, transversely projecting from the terminal bearing part. Thus the invention achieves a separation between the end parts constituting the load bearers, and the intermediate part of the implant which permits fusion. In addition, the central part may include at least one cavity for receiving a bone graft material. In another form of the present invention, an implant for insertion between a first vertebra having a first cortical bone plate and a second vertebra having a second cortical bone plate includes two terminal parts. The first terminal part defines a first bearing surface to bear against the first cortical bone plate and a second bearing surface opposite the first surface to bear against the second cortical bone plate. The second terminal part opposes the first terminal part and defines a third bearing surface to bear against the first cortical bone plate and a fourth bearing surface opposite the third surface to bear against the second cortical bone plate. The implant has an elongated central part defining an upper projection extending past the first and third surfaces, and a lower projection extending past the second and fourth surfaces. These projections correspondingly pass through openings in the first and second cortical bone plates when the first and third surfaces bear against the first cortical bone plate and the second and fourth surfaces bear against the second cortical bone plate. The terminal parts are dimensioned to facilitate restoration of the natural geometry of the intervertebral space (lordosis, cyphosis, and parallel discs). Thus, the first and second surfaces may be separated by a first distance, and the third and fourth surface may be separated by a second distance greater than the first distance to accommodate a natural curvature of the spine. In a further form of the present invention, an implant with two terminal parts also has an elongated central part that includes a pair of longitudinal walls defining a cavity. The walls define a first edge projecting past the first and third surfaces and a second edge projecting past the second and fourth surfaces. The first and second edges correspondingly penetrate the first and second cortical bone plates when the first and third surfaces bear against the first cortical bone plate and the second and fourth surfaces bear against the second cortical bone plate. According to another form, the bearing surfaces of the terminal end parts are defined by flanges extending from opposing ends of the implant along its longitudinal axis. Preferably, the bearing surfaces are generally flat for bearing against the cortical bone of the vertebral end plates of the two adjacent vertebrae. It is also preferred that openings be cut into the cortical plates in their central regions corresponding to the length of a central part of the implant along the longitudinal axis and leaving a region of the cortical bone plates around the periphery of the openings. The length of the remaining peripheral plate corresponds to the length of the bearing surfaces along the longitudinal axis. When the implant is placed in position, the edges of the walls of the central part engage the openings cut in the cortical plates and consequently do not substantially bear against the remaining peripheral portion of the plates. A cavity may be defined by the central part that holds bone graft material in contact with the spongy bone of the two vertebrae. In contrast, the bearing surfaces of the flanges are disposed adjacent the edges of the openings of the cortical plates and bear against the remaining portions of the plates to establish a strong load bearing relationship. Thus, both bone fusion and support are distinctly accommodated by different parts of the implant structure, which permits obtaining a satisfactory support of the vertebral bodies on the implant and an excellent arthrodesis. Yet another form of the present invention includes a cutting tool accessory to prepare the cortical plates of two adjacent vertebrae for insertion of an implant. This tool comprises a proximal handle connected to an elongate shaft configured to rotate about a longitudinal axis of the tool. The tool also includes a first non-cutting portion with the shaft extending therethrough and being configured to rotate relative thereto. A cutting portion is fixed to the shaft to rotate therewith and is positioned distal to the first non-cutting portion. The cutting portion includes a first pair of generally parallel opposing faces and a second pair of opposing faces each extending between the first pair of faces. The second pair of faces each define a number of cutting teeth. A second non-cutting portion is fixed to the cutting portion that includes a distal head. The first non-cutting portion, the cutting portion, and the second non-cutting portion have a rotatably selectable alignment that presents a generally constant height corresponding to the intersomatic space defined between the cortical bone plates to facilitate insertion therein. Once inserted, the cutting portion may be rotated out of this alignment to cut a first opening in the first cortical bone plate and a second opening into the second cortical bone plate. The cutting portion and to non-cutting portions may be arranged to provide uniform, symmetrical cutting of these openings with a predetermined length corresponding to the dimensions of a given implant device. In an additional form, a technique of spinal fixation includes cutting adjacent vertebrae and inserting an implant therebetween to promote fusion and provide suitable support. The implant may be inserted by anterior or posterior surgical approaches. The cutting may be performed by the cutting tool of the present invention and may include initially inserting the tool so that a first pair of faces are in contact with a respective one of the first and second cortical bone plates, turning a handle to rotate the cutting portion to remove cortical bone with cutting teeth defined by a second pair of faces, and withdrawing the tool. The tool may be used to form openings readily positioned in the central region of the adjacent vertebrae that leaves cortical bone plate about the openings. The insertion of the implant may include positioning the implant of the present invention between the first and second vertebrae and turning the implant about one quarter of a turn. It is envisioned that the implants of the present invention may be used with other tools and procedures, that the tools of the present invention may be used with other implants and procedures, and that the procedures of the present invention may be used with other implants and tools as would occur to those skilled in the art without departing from the spirit of the present invention. Accordingly, one object of the invention is to provide a spinal implant arranged to facilitate proper fusion of two or more vertebrae. The implant may be arranged to have at least one structural part to promote bone fusion through contact with spongy vertebral bone and one or more other structural parts adapted for contact with cortical bone to provide load support. Another object is to provide a tool accessory to facilitate implantation of devices suitable to promote fusion. Still another object is to provide a technique for preparing a site between two vertebrae to be fused and inserting an implant. Other objects, features, benefits, forms, aspects, and advantages of the present invention will become apparent from the description and drawings herein.

Improved dietary treatment with low protein and phosphorus restriction in uremic rats. The independent effect of low-protein or low-phosphorus diets in chronic renal failure were studied. The following four isocaloric diets, which contained various amounts of protein (24%, 6%) and phosphorus (0.5%, 0.12%) were fed to chronically uremic rats: high protein and no phosphorus restriction (HPrNP), high protein and phosphorus restriction (HPrRP), low protein and no phosphorus restriction (LPrNP), and low protein and phosphorus restriction (LPrRP). Adult male rats were made chronically uremic by electrocoagulation of one kidney and contralateral nephrectomy. Two grades of renal damage were produced, one of which was mild and the other severe. The mean number of days of survival in the severely uremic animals was 7.5 +/- (SEM) 2.5 with the HPrNP diet, 17.6 +/- 2.4 with the HPrRP diet, 20.3 +/- 2.3 with the LPrNP diet, and over 41.8 +/- 2.5 with the LPrRP diet during a 50-day period of observation. The BUN, serum creatinine (SCr), calcium (SCa), phosphorus (SP), urea and creatinine clearances (Curea, CCr), and plasma PTH levels before and 3 weeks after the diets were compared in the surviving rats with mild and severe uremia. There were marked reductions in the BUN and SP concentrations with the low-protein diets, whereas the SCa increased with all diets. Curea remained practically unchanged with the low-protein diets, whereas CCr decreased with all diets. Plasma PTH levels varied with each diet, but those rats with elevated PTH levels before dietary therapy experienced a fall in plasma PTH after the low-phosphorus diets were administered, with or without protein restriction.(ABSTRACT TRUNCATED AT 250 WORDS)

The present invention relates to a process for purifying amino acid-containing solutions by electrodialysis, an amino acid-containing solution being employed which is obtained from a fermentation. Amino acids can be produced from a carbon source such as, for example, molasses and raw sugar by means of fermentation. The solutions generally accumulating in the fermentation contain in addition to about 10% by weight of amino acid large amounts of contaminants such as, for example, also biomass. According to the processes used up until now in accordance with the prior art numerous process steps are necessary for purifying this solution obtained from a fermentation in order to produce the amino acid in the commonly marketed form, for example as lysine hydrochloride. Usually, large amounts of salts such as, for example, ammonium sulfate accumulate, approximately 1 kg of ammonium sulfate per kg of amino acid being generated as a product of value. Additionally, large amounts of wastewater accumulate and have to be worked up and disposed of. A preferably commercially used process for working up discharges from amino acid fermentation is essentially based on ion exchange treatment. The discharges from the fermentation are mixed with acid and then loaded onto a cation exchange column or an anion exchange column. The amino acid in its ionic form displaces the corresponding ions of the cation or anion exchange column and thus is retained by the column. The biomass can be filtered off before or after the ion exchange treatment. The mother liquor obtained after passage still contains approximately 0.1% by weight of amino acid and a load of about 1 metric ton of salt, for example ammonium sulfate, per metric ton of amino acid. This solution can be disposed of by dumping at sea which is objectionable, in particular ecologically, owing to the high salt load of the solution to be dumped at sea. As an alternative to this, the mother liquor which contains essentially ammonium sulfate and biomass may be worked up in numerous evaporation and filtration stages, it being possible for ammonium sulfate to be retrieved. However, the accumulating mother liquor has still to be disposed of. Moreover, this procedure is very labor-intensive and has a high energy consumption. The amino acid retained on the ion exchange resin is eluted, for example, with aqueous ammonia. Ammonia is stripped off the accumulating eluate, large amounts of aqueous ammonia having to be evaporated. The eluted amino acid is then mixed with acid, for example hydrochloric acid, crystallized and dried. The amino acid obtained in this way is greater than 98.5% pure and is called xe2x80x9cfeed-gradexe2x80x9d amino acid. In order to obtain even less contaminated, so-called xe2x80x9cfood-gradexe2x80x9d or xe2x80x9cpharma-gradexe2x80x9d amino acid, feed-grade product has to be subjected to a further purification procedure, for example active carbon treatment and/or repeated crystallization. Further details with respect to the purification processes in accordance with the prior art described above can be found in the PERP report 5357. The specifications food-grade and pharma-grade used here refer to the relevant purity requirements according to the US FDA, where the appropriate standard for lysine HCl is to be understood correspondingly or analogously. According to this, the term xe2x80x9cwith high purityxe2x80x9d used here also refers to the food-grade or pharma-grade standard for lysine according to the US FDA and is in this context also used either correspondingly or analogously. Electrodialysis is a very elegant purification or separation process which can fractionate, inter alia, mixtures of amino acids. A process of this type is described, for example, by Sandeaux et al. in J. Chem. Technol. Biotechnol. 71 (1998), pp. 267 ff. According to this scientific publication, protein hydrolysates obtained by acidic hydrolysis of animal residues or human residues such as, for example, feathers or hairs are initially neutralized and decolorized by activated carbon and then subjected to a multistage electrodialysis, various fractions of the individual amino acids being obtained. WO 91/02584 describes a process for removing amphoteric compounds from aqueous solutions by means of 3-cycle electrodialysis with bipolar membranes. U.S. Pat. No. 5,002,881 describes a fermentation process for producing lactic acid by a combination of microfiltration, reverse osmosis and electrodialysis. U.S. Pat. No. 4,882,277 discloses a further process for removing organic acids from fermentation broths by means of anion exchange membranes and producing the free acid by bipolar membranes. The above summary of the prior art reveals that the purification of amino acids from discharges from fermentations has up until now merely been carried out by means of ecologically disadvantageous and/or costly processes. It was an object of the present invention to provide an improved process for purifying amino acid from discharges from fermentations. This object was achieved by applying electrodialysis to this problem. Accordingly, the present invention relates to a process for purifying amino acid-containing solutions by electrodialysis (d), an amino acid-containing solution being employed which is obtained from a fermentation for producing at least one amino acid. Using this process it is possible to avoid numerous process steps which are indispensable according to the processes of the prior art. Large amounts of ammonium sulfate or other extraneous salts are not generated inevitably in this case. Electrodialysis carried out in a suitable way makes it further possible to produce amino acid as free base or free acid. It is further possible to obtain high amino acid yields of preferably greater than 90%, further preferably greater than 95%, based on the employed amount of amino acid at high current densities and therefore correspondingly high capacities of the electrodialysis. Accordingly, the present invention also relates to the use of electrodialysis for purifying amino acid-containing solutions obtained from the fermentation up to an amino acid content of greater than 98.5% (% by weight). As stated above, the process according to the invention relates to the purification of amino acid-containing solutions which are obtained from the fermentation. It is possible to employ here generally all amino acid-containing solutions obtainable by the various fermentation processes. Further stages such as, for example, ion exchange treatment and/or crystallization may be carried out between the actual fermentation process and the electrodialysis, merely the resulting mother liquor then being treated by means of electrodialysis. Therefore the present invention also relates to a process comprising the following additional stages (a) to (c): (a) treatment by means of an ion exchanger of an amino acid-containing solution obtained from the fermentation for producing at least one amino acid, (b) crystallization of an amino acid-containing solution obtained in (a), where an amino acid-containing mother liquor is obtained, and (c) introduction of the amino acid-containing mother liquor obtained in (b) into an electrodialysis apparatus. Besides the mentioned process stages, further stages such as, for example, filtration before stage (a) may be carried out.

A nursing home rotation in a family practice residency. A nursing home rotation can be a complementary component of geriatrics education in a family practice residency curriculum. Using nursing homes in teaching geriatrics has been done for some time but has of late received more emphasis. This increasing emphasis has been brought about by the growing health care needs of an aging population and a concomitant focus on education in geriatrics. If implementation of a nursing home rotation is contemplated, both the positive and negative aspects of such action as it relates to the residents, the nursing home, and the nursing home patients should be explored. The rotation as incorporated into the geriatrics curriculum of the Family Practice Residency, Knoxville Unit, University of Tennessee College of Medicine, involves all second-year and third-year residents in the medical care for patients of a 222-bed long-term care facility. From an educational standpoint, overall evaluation of the rotation reflects satisfaction. The experience exemplifies personal and comprehensive continuity of patient care. Other educational benefits include desensitization to the nursing home environment, understanding the kinds of medical care that can be delivered in this setting, and appreciation for the cost not only to the patient and the family but also to the medical care system as well.

Reports estimate that over 90% of all human genes are subject to mRNA splicing. RNA splicing occurs in highly specialized structures termed nuclear spliceosomes. Spliceosomes consist of a few key proteins that catalyze the excision of target introns/exons, plus 100's of co-factors that regulate the activity/efficiency of these enzymes. Spliceosome co-factors direct many facets of splicing dynamics including distribution of different protein variants throughout the body. Brain injury and disease disturb splicing. Pathological changes in spliceosome mechanics alter splice variant expression of different survival and death proteins. An upregulation of maladaptive protein variants may exacerbate neuronal death and impair CNS recovery. RNA Binding Motif 5 (RBM5) is a splicing co-factor. It is highly expressed in the CNS and testis but its function in the healthy or injured brain is unknown. RBM5 briefly localizes to the spliceosome, very early during spliceosome assembly around pre-mRNA targets. A zinc finger domain (RanBP2-Type), and several other RNA binding domains, coordinate its highly selective interaction with spliceable exons in pre-mRNA targets. In cancer cells, RBM5 regulates splice variant selection of caspase-2 (pro-death) and c-FLIP (pro-survival) genes. It promotes the exclusion of exon 9 from caspase-2, and exon 7 from c-FLIP mRNA. This induces caspase2L and c-FLIPL protein expression, respectively. Caspase2L is a pro-death splice variant. The c-FLIPL splice variant also has pro-apoptotic functions. In contrast, RBM5 inhibition causes exon 9/7 retention, respectively, and forces caspase-2s/c-FLIPs expression. Caspase-2s and c-FLIPs are both potent pro-survival variants. Thus RBM5 promotes cell death by upregulating the ratio of pro-death to pro-survival splice variants. RBM5 has not been studied in the brain. High expression in the CNS suggests that it may play a key role in splicing-mediated cell death mechanisms. To the best of our knowledge, no drug has ever been developed to specifically target pro-death splicing mechanisms in the brain - thus the therapeutic value of splicing directed therapies is completely unknown. Our preliminary data show that RBM5 is highly enriched in the hippocampal CA3 formation - a neuron population that is especially vulnerable to traumatic brain injury (TBI). Furthermore, we show that anthraquinone-2-sulfonic acid (AQ2S), the world's first small-molecule RBM5 inhibitor (that blocks the RanBP2-Type domain), decreases neuronal death after TBI in vitro and in vivo. This grant proposal seeks to test our hypothesis that RBM5 is a potent pro-death splicing factor in rat/human neurons (i.e. show that it upregulates caspase-2L and c-FLIPL splicing in these cells), and further confirm our preliminary data showing that AQ2S is the first viable drug to block pro-death splicing mechanisms in the brain.

The present invention relates to a fixture suspension bracket assembly for suspending a lighting fixture directly from a drop ceiling assembly. Modular suspended linear fixtures are typically assembled in place by connecting and mounting individual modules. Typical linear fixtures are suspended from an overhead structure above a drop ceiling that is also suspended from the overhead structure. The linear fixtures support linear fluorescent lighting systems such that the lighting fixtures may radiate light upwardly against the drop ceiling or downwardly towards the work area. Typically these assemblies are suspended at heights of 7 ft. or more from the floor and the installer has to work above the drop ceiling to install connections that connect the fixtures to the ceiling structure which may involve driving securing bolts directly into ceiling joists or through ceiling framework. In any event, the installer has to work above the drop ceiling resulting in movement of lay in tiles. Further, when the fixtures are being installed, the placement of the fixtures is limited to where there may be an upper support beam in the ceiling. This limitation becomes more apparent when the working space is redesigned and lighting patterns have to be changed in the workspace. Clearly there is a need to improve the suspension of these fixtures that improves flexibility in deployment and re-deployment of the fixtures to accommodate lighting in the work space and does not require the installers to work above the drop ceiling. The present invention relates to a fixture suspension bracket assembly for suspending a lighting fixture directly from a drop ceiling assembly. In particular, the suspension bracket supports a screw and a wire to suspend a linear fixture. The suspension bracket has a base plate and at least one pair of legs extending from bendable relative to the base plate. The legs are adapted to bend about a runner to mount the bracket directly to the runner with the base plate below the drop ceiling runner. In accordance with an aspect of the present invention there is provided a fixture bracket suspension assembly mounted directly to an inverted T shaped drop ceiling tile supporting member. The assembly comprises a screw having a head portion and a stem portion for supporting a suspension wire adapted to be mounted to a fixture. The assembly comprises a bracket having a base plate with an opening through which the stem portion of the screw passes. The base plate has a top surface for supporting the head of the screw. The bracket has at least one pair of bendable legs adapted to be wrapped around the runner to present minimal encumbrance to the runner and to support the base plate and the screw below the runner.

Series capacitor installations are used to increase the transmission capability of power lines for transmission of electric power and for stabilizing the operation of such power lines, especially in the case of long high-voltage transmission lines. For high system voltages, typically exceeding 145 kV, the components included in the installation are usually arranged on a platform insulated towards ground potential. A known design of such a series capacitor installation and, in particular, protective equipment for such an installation is described in IEEE Transactions on Power Delivery, Vol. 4, No. 2, April 1989, pages 1369-1376: EHV Series Capacitor Banks, a new approach to platform to ground signalling, relay protection and supervision (M Adolfsson et al). The protective equipment comprises a number of relay protection devices to which measured values of currents sensed in the installation are supplied and which, in dependence on these measured values and on criteria chosen and set in the relay protection devices for evaluation of the measured values, initiate protective measures in the event that these measured values indicate an abnormal operating condition for the installation. The relay protection devices are placed in a control room at ground potential. The series capacitor is normally designed comprising a number of capacitor units. As is clear from FIG. 3.1 in the cited document, the capacitor units are divided into two parallel-connected capacitor groups, whereby each one of these groups is built up of a plurality of capacitor units. In addition thereto, the installation comprises a non-linear voltage-limiting resistor, connected in parallel with the series capacitor, in the form of a varistor, a bypass breaker and a spark gap capable of being fired, the last two components being connected in parallel with the series capacitor via a damping inductor D. A current transformer senses the current that flows through the series capacitor up to the point where this is connected in parallel with the varistor, and a measured value of this current is supplied to a relay protection device of inverse-time type to protect the series capacitor against thermal overload. In this case, the criterion is the current/inverse-time characteristic of the relay protection device. Another current transformer senses the current which flows through the series capacitor installation out into the power line, that is, the line current, and a measured value of this current is supplied to a relay protection device for detecting subsynchronous oscillations in the current flowing through the power line. Here the criterion is the presence of oscillations in the line current of a frequency considerably lower than the system frequency of the power line. Another current transformer is connected in a bridge connection between series-connected parts of the two capacitor groups for monitoring their mode of operation. A measured value of current sensed by this current transformer is supplied to a relay protection device for detecting unbalance in the series capacitor, caused, for example, by the triggering of an internal fuse in the capacitor units. In this case, the criterion is a current of a certain level through the current transformer, usually put in relation to the actual line current such that the criterion consists of a quotient between these currents. The components included in the installation are placed on insulators on the platform, whereby one side of the above-described parallel connection of the components, in FIG. 3.1 in the cited document the right one, is galvanically connected to the platform. For example, a flashover across an insulator causes a current to flow through this connection. A current transformer senses this current and a measured value thereof is supplied to a relay protection device for detecting flashover against the platform. The criterion is here a chosen current level. A further current transformer senses a current flowing through the spark gap and a measured value thereof is supplied to the relay protection device for detecting any remaining current through the spark gap. In this case, the criterion is a chosen current level that remains for a chosen period of time. In all of the above-mentioned cases, the respective relay protection device initiates, as protective measure, a closing of the bypass breaker by generating an order signal therefor. An additional current transformer senses a current flowing through the varistor and a measured value of this current is supplied to a relay protection device for the combined protection of the varistor against overcurrent and against thermal overload. Here the criteria are both a current level and a calculated thermal heating of the varistor. The relay protection device initiates, as protective measure, firing of the spark gap as well as closing of the bypass breaker. The above-mentioned criteria in some cases also include chosen time delays and the protective measures also include, depending on which relay protection device initiates these, such measures as temporary or definite blocking of the by-pass breaker, automatic reclosing of the installation through reopening of the bypass breaker, etc. Further details about the performance of these protective functions, however, fall outside the scope of this patent application. They are known per se to the person skilled in this technical field and are described in greater detail also in the article referred to here. In the same article, a so-called optical current transformer suited for the purposes described above, is also described. The current transformer has a magnetic core surrounding a connection bar, which bar is intended to be connected in the conductor whose current is to be measured. Further, the current transformer comprises, in a known manner, a secondary winding with a burden as well as an optoelectric converter for conversion of the voltage, formed across the burden, into an optical signal corresponding to the amplitude of the voltage. The optical signal is transferred to ground potential via light guides connected between the optoelectric converter at the current transformer and an optoelectric converter, arranged at ground potential, which converts the optical signal into a shape and level adapted to the respective relay protection device. Although not shown in FIG. 3.1 in the cited document, the light guide from the respective current transformer is usually passed via a so-called platform link to a common joint box located on the platform, and from this all the light guides are then passed to ground potential via a common insulator in a so-called high-voltage link (FIG. 2.1 in the cited document). Thus, the protective equipment comprises a large number of measuring points for current-measuring devices, and for each one of these there is required, in addition to the current transformer itself, a platform link for passing the respective light guide to the joint box. Each current-measuring device with its associated platform link entails, in addition to a material cost, also a cost for installation and commissioning. To this is added the fact that each component in an installation in principle increases the risk of a fault arising in the installation.

Endometrial changes with tamoxifen: comparison between tamoxifen-treated and nontreated asymptomatic, postmenopausal breast cancer patients. Endometrial thickness, as evaluated by vaginal ultrasonography, and endometrial histologic findings, as well as demographic characteristics, health habits, and risk factors for endometrial cancer, were compared between 93 asymptomatic postmenopausal breast cancer patients who had been on tamoxifen treatment and 20 patients who had not. The mean ultrasonographic endometrial thickness in the women on tamoxifen treatment was 13.1 +/- 10.4 mm, which was significantly thicker than the 4.0 +/- 3.2 mm found in the nontreated women (P = 0.001). The frequency of endometrial pathological findings was remarkably high (35.5%) among the tamoxifen-treated patients, compared with nontreated patients (20.0%), with a P value of 0.058 and an odd ratio of 4.6. Thus, it is suggested that the remarkably high prevalence of pathological endometrial changes was due to the continuous and unopposed exposure of the endometrium to tamoxifen.

This invention relates to a liquid handling system used in chemical analyses, and, more particularly, to such a system suited for automated operation with multiple functions. Modern analytical chemical techniques often utilize a series of liquid handling steps that must each be applied to a large number of samples. For example, in solid phase extraction, columns of absorbent are used to separate the components of a liquid sample, and particular components are removed for further analysis. In a typical case, the column is first conditioned with the addition of a fluid. The sample is applied, possibly after being filtered, and the column is washed with a solvent to separate the component of interest. The component of interest is then eluted with yet another solvent and transferred to further analytical apparatus. Some analytical laboratories process hundreds of samples using solid phase extraction or other techniques. Since the steps are highly repetitive, automated systems have been developed to reduce the manual labor involved in the liquid handling and processing. Such systems are commercially available and widely used. Existing systems have shortcomings that limit their usefulness, however. One important problem arises in the wide variety of samples studied and the absence of a single standard size for the various columns, tubes, and vessels utilized in liquid handling operations. For example, an analytical laboratory may receive samples for analysis in a number of different-sized sample containers. It may be necessary to pour the sample into a single-size container that can be handled by the automated analytical apparatus. If a range of sizes are used in the analytical apparatus, there may be safety risks from splashing and spraying of fluids into the air, particularly when pressure is applied to the sample containers or columns in certain procedures. The result of this problem is that hand operations may be required that reduce the efficiency of the otherwise-automated analytical system. There is a need for improved automated apparatus for performing analytical procedures without the need for operator intervention and minimizing the manual tasks required before, during, or after the analytical procedure. The present invention fulfills this need, and further provides related advantages.

Kinetic modelling of acrylamide formation during the finish-frying of french fries with variable maltose content. In light of a recent update in EU regulations governing levels of acrylamide in foodstuffs, further understanding of the role of different precursors is fundamental to extending mitigation strategies into a wider product range. Kinetic modelling was used to investigate the role of maltose in the formation of acrylamide during the finish-frying of french fries. The maltose concentration of raw white potato strips was systematically increased from 0 to 1.4% to observe the effect of this reducing disaccharide on acrylamide formation. A mathematical model, incorporating glucose, fructose and maltose and based on known Maillard reaction pathways, was developed which showed that acrylamide formation from maltose only contributed <10% to the total acrylamide. An additional kinetic model allowed for the formation of acrylamide directly from sugar-asparagine glycoconjugates. This model suggested that under these conditions, it is unlikely that acrylamide is formed directly from the maltose-asparagine conjugate.

Efficacy testing of visible-light-curing units. This study evaluated (1) the effect of known reductions in the output of curing lights on the depth of cure of various resins as determined by hardness measurements, and (2) the ability of the clinician to detect reduced light output by use of an explorer to compare the hardness of the top and bottom surfaces of resin specimens. Curing light output was reduced stepwise from 10 to 70% with neutral density filters. Hardness values indicated polymerization of the top surface to be generally unaffected by light blockage. Bottom surfaces were greatly affected: more with a 30-second than a 60-second cure time. Three clinicians utilized an explorer to compare the tops and bottoms of specimens of known hardness. Evaluators were unable to routinely detect differences of less than 20 to 30 Barcol numbers. The data indicate that a light meter is a more efficacious means of monitoring curing light performance than is a tactile test of resin surface hardness.

The invention relates to a mobile electric appliance comprising an appliance housing having at least one battery bay for accommodating a battery with at least one voltage-generating cell and a battery-side charge status indicator, an electric consumer, a power connector as well as a charging device for charging the at least one battery. In addition, the invention relates to a battery comprising a battery housing, at least one voltage-generating cell arranged in the battery housing, a battery-side electronic circuit arranged in the battery housing for determining the charge status of the at least one cell, a battery-side charge status indicator arranged on the battery housing and a switch arranged on the battery housing for activating the battery-side electronic circuit and/or the battery-side charge status indicator. Finally, the invention relates to a set comprising at least one mobile electric appliance and an appropriate battery for it. One thing users of mobile, battery-operated devices desire is the most convenient possible display of the charge status of an accumulator (also known colloquially as a “battery”) provided for operating the device. Most of the time, the charge status is determined and displayed by the device itself. However, batteries deviating from this are also known that are able to display the charge status independently. A battery for a hand power tool is disclosed in German Patent Document No. DE 10 2005 000 135 A1. This battery features a housing accommodating several battery cells and on which coupling means, which are externally accessible and electrically connected to the battery cells, are provided. In addition, the battery includes a charge status indicator, which can be activated by an externally accessible switch and which displays the charge status of the battery cells. The switch in this case is formed by actuating means of a locking mechanism of the battery. Moreover, a portable computer is known from U.S. Pat. No. 6,078,164 A, which comprises a battery bay and a battery situated therein. The battery has a charge status indicator which is also visible through a viewing window in the computer's housing when the battery is inserted. The battery has a switch to activate the charge status indicator, which may also be actuated externally with the aid of a knob arranged on the computer. As a result, the charge status of a battery situated in the bay may be determined without the battery having to be removed from the bay. Finally, a set is known from European Patent Document No. EP 1 419 723 B1 comprising a vacuum cleaner, which may be operated both when connected to the power supply system as well as with batteries. In addition, the batteries may also be used in different electric hand-held devices. The disadvantage of the known solutions, for example the solution in accordance with U.S. Pat. No. 6,078,164 A, is that the viewing window provided there as well as the knob must be aligned precisely with the charge status indicator and the switch on the battery. On the one hand, incorrect operation can easily lead to a situation where the charge status cannot be queried, for example if the knob in question is not precisely aligned with the switch. On the other hand, the design of the battery must be precisely coordinated with the design of the device being operated. As a result, these types of batteries are not universally useable. Therefore, the object of the invention is creating an improved mobile electric appliance, an improved battery, and an improved set. In particular, the interchangeability of the batteries is improved and querying the charge status of the same is facilitated. According to the invention, this object is attained with a mobile electric appliance of the type cited at the outset comprising means for detecting the charge status of the at least one battery and a device-side charge status indicator arranged on the mobile electric appliance. The term “mobile electric appliance” is understood as an electric appliance which can be moved or displaced from one workplace to another workplace even when in operation. The object of the invention is also attained with a battery of the type cited at the outset comprising an interface, which is prepared to relay the charge status determined to an external processing unit. Finally, the object of the invention is attained by a set comprising at least one mobile electric appliance according to the invention and an interchangeable, advantageously inventive battery. This is achieved according to the invention in that the charge status may be displayed both independently on the battery itself as well as by the device being operated. In doing so, the disadvantages mentioned, such as, for example, malfunctions with incorrect alignment of the battery in the device being operated and poor interchangeability of batteries, are overcome. In contrast to this, the arrangement of battery-side switches and battery-side charge status indicators in the case of the invention is independent of the device being operated, because the latter has an its own additional charge status indicator. The user of the mobile device is also immediately able to see whether a battery is inserted into the battery bay without having to open a cover of the battery bay. The display of the charge status may be accomplished with the use of illuminating means or even mechanically as a bar representation. The illuminating means may be designed to be both round as well as square, rectangular and triangular. The term “battery bay” should be understood within the scope of the invention as any type of device in which a battery may be inserted or introduced for the purpose of transferring energy. Advantageous embodiments and further developments of the invention are disclosed in the description in conjunction with the figures. It is especially advantageous if the means for detecting the charge status are formed by a device-side electronic circuit arranged in the mobile electric appliance, which is connected electrically to the at least one voltage-generating cell. In the case of this variant of the invention, no other connectors are necessary besides those that are present anyway to supply the device in question. Thus, it is possible to implement the invention in reality in an especially simple manner, in particular because existing batteries may continue to be used unchanged. It is also especially advantageous if the means for detecting the charge status are formed by an interface to a battery situated in the battery bay, wherein the battery includes a battery-side electronic circuit for determining the charge status of the at least one cell and wherein the interface is prepared to receive the charge status determined by the cited first electronic circuit. In the case of this variant of the invention, the device-side electronic circuit may be kept relatively simple, because the charge status of the battery is determined per se by the battery-side electronic circuit. For example, electrical interfaces, optical interfaces or radio interfaces may be used for data transmission (i.e., for transmitting the charge status determined) between the device-side electronic circuit and the battery-side electronic circuit. It is beneficial if the mobile electric appliance includes a controller, which is prepared to activate the device-side charge status indicator when the electric appliance is being operated by the battery. In this way, a user is always able to read the charge status, or the remaining run-time of the device being operated. For example, the controller may be integrated into a central device controller or into the charging device. It is also beneficial if the mobile electric appliance includes a controller, which is prepared to deactivate the device-side charge status indicator when the electric appliance is being operated by the power supply system. In this way, electrical energy may be saved, because the charge status is less relevant during operation by the power supply system. A button may be provided as an option which may be used to query the charge status also manually as needed. It is also beneficial if the mobile electric appliance includes a controller, which is prepared to deactivate the device-side charge status indicator when the electric appliance is switched off. In this state as well, the charge status of the batteries is normally of less interest, which is the reason why the charge status indicator is deactivated for the purpose of saving energy. In this case as well, an optional button may be provided which may be used to query the charge status also manually as needed. It is also advantageous if the mobile electric appliance is configured as a vacuum cleaner. This is an advantage in particular if the vacuum cleaner is part of a set, which also includes at least one electric hand-held device as well as several batteries that are interchangeable between the at least one electric hand-held device and the at least one mobile electric appliance. Most of the time, a vacuum cleaner is made of a movable base part and a suction nozzle connected therewith via a suction hose. Because the base part normally does not have to be lifted during vacuuming but is merely pulled along behind, a vacuum cleaner is very well suited as a central charging station for the relatively heavy batteries. In this way, it is possible for batteries to be charged conveniently at the construction site or in the household. On the one hand, an empty battery of an electric hand-held device (e.g., cordless screwdriver, cordless drill, cordless saw, cordless grinder, cordless planer, cordless table vacuum cleaner, cordless search lamp, cordless radio, etc.) may be interchanged for a fully charged one from the vacuum cleaner. On the other hand, the vacuum cleaner may also be operated independently, i.e., without being connected to the electric supply system. Because of the measures according to the invention, the charge status of a battery is always visible, both when it is inserted into the mobile electric appliance as well as when the battery is removed. The advantage of the invention is especially striking in this case. However, these advantages are not limited to vacuum cleaners, but also apply to additional displaceable or moveable devices or devices whose base part is only moved comparatively seldom. Another example of such a device is a high-pressure cleaner. It is noted at this point that the variants listed for the mobile electric appliance according to the invention and the resulting advantages also apply correspondingly to the battery according to the invention as well as to the set according to the invention and vice versa. The above-mentioned embodiments and further developments of the invention may be combined in any manner. The present invention is explained in more detail in the following on the basis of the exemplary embodiments indicated in the schematic figures.

Caring in nursing: investigating the meaning of caring from the perspective of cancer patients in Beijing, China. The aims of the study were to develop an understanding of caring in nursing from the perspective of cancer patients and attempt to identify the concept of caring in the Chinese cultural context. Caring as a concept remains elusive, the acceptable definitions of the term care have not been reached. The expressions, processes and patterns of caring vary among cultures, but there is a lack of Chinese culture-based study about caring in nursing. A qualitative research design was used and 20 cancer patients were interviewed using a semi-structured interview guide. A qualitative content analysis was used to identify themes in the data. Three themes emerged from the data, which suggested that caring is delivering care in an holistic way: nurses' caring attitudes and their professional responsibility for providing emotional support, nurses' professional knowledge and their professional responsibility for providing informational support and nurses' professional skills and their professional responsibility for providing practical support. The caring behaviour of nurses as perceived by cancer patients involved the provision of emotional, informational, and practical support and help based on patients' needs. A model of caring in nursing was formulated. Caring in nursing as perceived by cancer patients involves nurses having qualified professional knowledge, attitudes and skills in oncology and providing the informational, emotional and practical supports and help required by cancer patients. Caring is manifested in nursing actions through nurse-patient communication process. Patients have their inner expectation for nurses' caring behaviour and attitudes and nurses' performance of caring or uncaring behaviour has a direct influence on the feelings of patients. It is necessary for all nurses to continue improving their oncology professional knowledge, attitudes and skills as well as their abilities of offering informational, emotional and practical support and help for their cancer patients.

Is nonperforated pediatric appendicitis still considered a surgical emergency? A survey of pediatric surgeons. To describe the beliefs and preferences of pediatric surgeons regarding the emergent nature of nonperforated appendicitis. An electronic mailing was sent to all 1052 members of the American Pediatric Surgical Association (APSA) inviting participation in a 26-item survey, which was administered by Survey Monkey (www.surveymonkey.com). Chi-square and Mann-Whitney tests were used for bivariate analysis. Spearman's rho was used for nonparametric correlation. Four hundred eighty-four pediatric surgeons (46%) responded to the survey. Few respondents (4%) considered nonperforated appendicitis to be a surgical emergency. A minority (14%) would come in from home to perform an overnight appendectomy. Most (92%) believe that postponing overnight appendectomy until daytime does not result in a clinically significant increase in perforation. Respondents endorsed surgeon fatigue (56%) and limited operating room availability (56%) most often among factors that would make them more likely to postpone surgery. Sixty-eight percent reported no departmental guideline regarding delay of overnight appendectomy. Most pediatric surgeons in our study believe nonperforated appendicitis is not a surgical emergency and prefer to postpone overnight appendectomy.

Rho GTPases mediate diverse pathways in the cardiovascular system, including smooth muscle Ca 2+ sensitization and cell migration phenomena critical for the vasculogenesis. The primary objective of the project is to define the molecular mechanisms that control Ca sensitization pathways upstream of RhoA. These pathways involves activation of the RhoA GTPase by a family of nucleotide exchange factors, including PDZRhoGEF and LARG, which contain domains coupling these proteins to G and receptors of the plexin family, although their direct participation in smooth muscle physiology has not been proven. Structures of the individual domains, as well as of the multi-domain fragments of these GEFs will be determined by a combination of NMR and X-ray crystallography, as well as other complementary biophysical methods. The function and mechanism of the PDZ domain which binds the C-terminus of plexins will be assayed by isothermal titration calorimetry and phage display to determine specificity and affinity of interactions. The strategic aim is to understand how signals transduced membrane receptors ultimately activate the DH-PH domain tandem, which catalyzes the nucleotide exchange on RhoA. The selectivity of the latter reaction will also be probed by site-directed mutagenesis and X, ray crystallography. The functional properties of isolated domains and multi-domain fragments of GEFs, as well as their cellular localization, will be studied in collaboration with Project 1 and 3 within this PPG. The project will also focus on the structural biology of plexins and neuropilins, which function upstream of PDZRhoGEF and LARG in many tissues, and which are of primary importance to vasculogenesis. The central domain of plexin is believed to sequester the active form of Rac through a putative CRIB domain, although the boundaries of structural domains have not been determined. Crystallographic and/or NMR studies will determine the molecular architecture of these proteins and the interaction with Rac. Finally, structures of isolated domains of neuropilins, and the regulatory mechanisms of these receptors will also be probed by a synergistic combination of NMR and X-ray crystallography to determine interdomain communication patterns. This work will provide a model for the PDZRhoGEF activation, and will yield data directly relevant to cardiovascular biology.

I just want to be normal: a qualitative study exploring how children and adolescents view the impact of intractable epilepsy on their quality of life. This qualitative study explores how children and adolescents with medically refractory seizures experience the impact of epilepsy on their quality of life (QOL) within the domains of physical, emotional/behavioral, social, and cognitive/academic function. Semi-structured, open-ended interviews were conducted with 49 participants (7-18 years old). These narratives constituted our data source. Analyses involved inductive generation of themes/subthemes and connection of these themes to generate a theoretical representation of their relationships. These themes reflected the negative impact of epilepsy on QOL: physical-excessive fatigue as a barrier to academic and social pursuits; emotional/behavioral-intermittent emotional distress heightened by epilepsy-related factors such as unpredictability of seizures; social-profound social isolation; and cognitive/academic-discontinuous, fragmented learning. Youths perceive seizures as the major barrier to their sense of normalcy, setting them apart from others. Findings provide direction for assessment and evidence for developing or enhancing clinical interventions and community/school-based programs that might mitigate some of these negative experiences.

Traumatic damage to the nodal axolemma: an early, secondary injury. Electronmicroscopical investigations were made in a model of optic nerve damage in guinea-pigs on the development of acute axonal damage on an ultrastructural basis. It was expected to obtain thereby further information on mechanisms underlying axonal damage in traumatic brain injury. For that purpose an injury apparatus was employed to deliver defined elongation and/or tensile strains to the optic nerve. Transmission electronmicrographs were examined of longitudinal and transverse nerve sections throughout its entire length. The most severe abnormalities were identified in the prechiasmatic portion of the nerve. Among others, elongations of the nodes of Ranvier were encountered, swollen axons with accumulation of organelles, and even disrupted axons having a morphology similar to retraction balls. In all instances, abnormal axons were found together with axons having a normal structural appearance. Nodes of Ranvier demonstrated outward dilatations of the nodal axolemma and of the adjacent axoplasm, which are named as nodal blebs. Nodal blebs occurred already 15 min after injury, and were fully developed at 6 or 24 hrs. The blebs had disappeared again after 5-7 days. The axoplasm in the blebs demonstrated considerable disorganization of cytoskeletal elements with an array of amorphous material appearing as granular degeneration. Taken together, the present experimental model is a useful approach to analyse axonal damage at the ultrastructural level as it may occur in white matter of the central nervous system.

TropshaOs group has made excellent progress with a novel approach in the area of protein folding, which applies methods of statistical geometry to the analysis and prediction of protein structure from primary sequence. In the past year, this work has led to new algorithms for sequence-structure compatibility (fold recognition) searches in multi-dimensional sequence-structure space. Individual amino acid residues in protein structures are represented in this work by their Ca atoms; thus each protein is described as a collection of points in three-dimensional space. Delaunay tessellation of this set of points generates an aggregate of space-filling, irregular tetrahedra, or Delaunay simplices. Statistical analysis of residue compositions of all Delaunay simplices in a representative dataset of protein structures have produced a four-body residue contact potential (expressed as log likelihood factor q) for the full set of 20 amino acids as well as for several reduced sets. Two independent sequence-structure compatibility (threading) functions have been defined in terms of these q factors: 1) the sum of q factors for all Delaunay simplices in a given protein, and 2) Delaunay tessellation profiles where the sum of q factors for all simplices that share the vertex residue is plotted as a function of residue number. Both threading functions were used as criteria to answer the two questions, "does structure recognize sequence?" and "does sequence recognize structure?" We find that threading functions based on either a profile or a total score can distinguish the native fold from incorrect folds for a given sequence, and the native sequence from non-native sequences for a given fold. Figure 1. Comparison of 3D-1D Delaunay tessellation profiles for native and deliberately misfolded structures. Of the two three-letter abbreviations in each legend, the first corresponds to the PDB code for the sequence and the next corresponds to the PDB code for the structure. In each case, the "self" matching produces a profile with higher scores, indicating that the interioirs of these molecules are "packed" according "rules" followed also by other proteins. These protocols can effectively deal with nongapped threading and find an immediate application in selecting the most plausible conformation among alternative structures predicted on the basis of homology model building or molecular simulations. The Figure illustrates the efficiency of Delaunay tessellation profiles in discriminating between native and deliberately misfolded structures, obtained by assigning a native sequence to a protein structure with the same sequence length. membranes. (M. Berkowitz, U. Essmann).

In a typical ink jet recording or printing system, ink droplets are ejected from a nozzle at high speed towards a recording element or medium to produce an image on the medium. The ink droplets, or recording liquid, generally comprise a recording agent, such as a dye or pigment, and a large amount of solvent. The solvent, or carrier liquid, typically is made up of water, an organic material such as a monohydric alcohol, a polyhydric alcohol or mixtures thereof. An ink jet recording element typically comprises a support having on at least one surface thereof an ink-receiving or image-recording layer, and includes those intended for reflection viewing, which have an opaque support, and those intended for viewing by transmitted light, which have a transparent support. Medical images, such as radiographic images, are typically viewed on a blue transparent support. While a wide variety of different types of image-recording elements for use with ink jet devices have been proposed heretofore, there are many unsolved problems in the art and many deficiencies in the known products which have severely limited their commercial usefulness. The requirements for an image recording medium or element for ink jet recording are very demanding. It is well known that in order to achieve and maintain photographic-quality images on such an image-recording element, an ink jet recording element must: Be readily wetted so there is no puddling, i.e., coalescence of adjacent ink dots, which leads to nonuniform density PA1 Exhibit no image bleeding PA1 Provide maximum printed optical densities PA1 Exhibit the ability to absorb high concentrations of ink and dry quickly to avoid elements blocking together when stacked against subsequent prints or other surfaces PA1 Provide a high level of gloss and avoid differential gloss PA1 Exhibit no discontinuities or defects due to interactions between the support and/or layer(s), such as cracking, repellencies, comb lines and the like PA1 Not allow unabsorbed dyes to aggregate at the free surface causing dye crystallization, which results in bloom or bronzing effects in the imaged areas PA1 Have an optimized image fastness to avoid fade from contact with water or radiation by daylight, tungsten light, or fluorescent light PA1 Provide image stability under high-humidity conditions PA1 a) providing an ink jet recording element as described above, and PA1 b) applying liquid ink droplets thereon in an image-wise manner. Image stability is an important concern for inkjet prints. In particular, dyes used in the printing process may continue to migrate over time during storage of a printed image. The migration process typically occurs more quickly under conditions of high relative humidity since inkjet dyes are water soluble and materials used to manufacture inkjet media are often easily plasticized by water. Within a given dye set, the individual dyes may migrate or bleed at different rates due to differences in solubility or molecular dimensions. As a result, areas which are originally printed as neutral densities may acquire a colored tint over time. Such a phenomenon is especially objectionable in a medical application such as a radiographic image, since a neutral gray scale is expected and a colored tint is typically unacceptable in any area of the print. U.S. Pat. No. 4,547,405 relates to an ink jet receiver comprising an ink jet recording layer which contains a polymeric latex of a block copolymer of polyvinyl alcohol and polyvinyl (benzyl ammonium chloride). However, there is a problem with this material in that, under high humidity conditions, the image stability is not as good as one would like. Other prior art references such as U.S. Pat. No. 5,916,673 discloses that trivalent salts or ions of Group IIIb metals may be added to ink jet recording sheets for the purpose of improving waterfastness of images without compromising lightfastness. However, it has been found that such salts or ions of metals in reality actually contribute to poorer color stability under high humidity conditions. It is an object of this invention to provide an ink jet receiver in which the color does not shift under high humidity conditions.

The present invention relates to video games, and more particularly to video game competitions. Video games are enjoyed by many, often allowing video game players to virtually participate in otherwise unavailable activities, whether due to requirements of skill, experience, or equipment availability, or simply due to inherent dangers of the activities. In many games a video game player may compete against another player either in person or via an online game. Many online games offer leaderboards which allow a player to judge how a particular game play session compared against other game players. However, it is often difficult to compare the player's skill to another player's since many conventional leaderboards measure a level achieved or certain standard statistics, but may not consider the amount of time played to do so. Further, many players are driven by and desire to compete at all levels of game play, for example a player may desire to not only be the player with the highest score but also to be the best player with a particular game weapon or accessory or combination thereof. Managing a competition with numerous players based on such non-standard statistics may be labor intensive. It may also be extremely difficult to ensure rules compliance in a multiplayer online game environment.

Clinical and biological significance of never in mitosis gene A-related kinase 6 (NEK6) expression in hepatic cell cancer. Nek6 is a cell cycle regulatory gene, which can control cell proliferation and survival. Recent studies suggested that desregulation of Nek6 expression plays a key role in oncogenesis. This study was aimed to investigate the potential roles of Nek6 in hepatocellular carcinoma (HCC) development. Immunohistochemistry and Western blot analysis was performed for Nek6 in 80 hepatocellular carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were performed to determine the prognostic significance of Nek6 in HCC. In addition, Nek6 expression vector was used to detect its role in cell cycle control. Nek6 was overexpressed in hepatocellular carcinoma as compared with the adjacent normal tissue. High expression of Nek6 was associated with histological grade and the level of alpha fetal protein, and Nek6 was positively correlated with proliferation marker Ki-67. Univariate analysis showed that Nek6 expression was associated with poor prognosis. Multivariate analysis indicated that Nek6 and Ki-67 protein expression was an independent prognostic marker for HCC. While in vitro, following release from serum starvation of HuH7 HCC cell, the expression of Nek6 was upregulated. Overexpression Nek6 in Huh7 cell could promote the cell cycle. In conclusion, Nek6 is involved in the pathogenesis of hepatocellular carcinoma. It may be a favorable independent poor prognostic parameter for hepatocellular carcinoma.

Needlestick injuries among German medical students: time to take a different approach? Medical students are at risk of occupational exposure to blood-borne viruses following needlestick injuries (NSIs) during medical school. The reporting of NSIs is an important step in the prevention of further injuries and in the initiation of early prophylaxis or treatment. The objective of this study was to describe the mechanisms whereby medical students experience occupational percutaneous blood exposure through NSIs and to discuss rational strategies for prevention. Incidents of exposure to blood-borne pathogens among medical students at a large German university were analysed. Year 6 medical students completed a written survey immediately before the clinical part of their training began, describing incidents that had occurred during the previous 5 years. In our study, 58.8% (183/311) of participating medical students recalled at least one NSI that had occurred during their studies. Overall, 284 NSIs were reported via an anonymous questionnaire. Occupational exposure to blood is a common problem among medical students. Efforts are required to ensure greater awareness of the risks associated with blood-borne pathogens among German medical students. Proper training in percutaneous procedures and how to act in the event of injury should be given in order to reduce the number of injuries.

The present invention relates to recording apparatuses for intermittently recording picture data of a monitor camera or the like at a constant interval and, more particularly, to time lapse recorders, which comprise a motion correcting circuit, typically MPEG2 (xe2x80x9cGeneric coding of moving pictures and associated audio information: videoxe2x80x9d, ISO/IEC IS 13818-2), provided in a picture coding part and an HDD (hard disc drive) or a VCR (Video Cassette Recorder) provided in a recording unit part. Time lapse VCRs (video tape recorders) using VTRs are well known in the art as an apparatus for intermittently recording an extracted part of a picture signal from a camera at a constant interval. With the recent development of digital signal processing techniques, time lapse recorders are also used, in which image signal is digitized and data compressed by using a still image coding system, typically JPEG (xe2x80x9cDigital Compression Coding of Continuous-Tone Still Imagesxe2x80x9d, ISO/IEC IS 10918-1) for recording of the compressed data in a recording medium, such as HDD or an optical disc. The time lapse recorder currently in practical use, has a problem that in the case of an analog VTR it is difficult to record high quality picture signal. In the digital system case, it is possible to obtain high quality picture signal recording owing to the use of a still picture cording system. However, for executing abnormality detection and automatically reducing the picture signal recording interval when the abnormality is detected, an exclusive abnormality detector is necessary, so that the apparatus is increased in scale, complicated and increased in cost. The present invention was made in view of the above problem, and it has an object of providing a time lapse recorder, which uses a motion picture coding system having a motion compensating circuit typically MPEG2 and thus can detect abnormality without exclusive abnormality detector, and in which when the abnormality is detected the recording interval is adaptively changed or the recording picture quality is improved to permit accurate recording of the abnormal phenomenon. According to an aspect of the present invention, there is provided a time lapse recorder comprising: a dividing means for dividing an input picture signal into signals corresponding to small area blocks each consisting of a plurality of pixels; a motion estimate means for retrieving motion vectors of blocks most similar to each other in picture frames of different times; a motion compensating means for obtaining a difference between a coding subject frame and a motion vector computation frame for each of the blocks on the basis of the motion vectors; an orthogonal transform means for executing orthogonal transform of the blocks; a quantizing means for quantizing transform coefficient values as the output of the orthogonal transform means; a code quantity control means for controlling picture quality and quantity of codes generated per frame in accordance with the complexity of the input picture; a variable length coding means for variable length coding quantized coefficient data outputted from the quantizing means; an abnormality detecting means for detecting abnormality of input picture; a recording interval control means for changing recording frame number at a constant interval in the normal state and in unit times in the abnormality detection state; and a recording means for recording the variable length coded data in a recording medium under control of the recording interval control means, wherein the abnormality detecting means computes the coding bit number of the variable length coding means for each frame, compares the difference of this coding bit number from the coding bit number of the immediately preceding frame having the same predicted structure and executes abnormal detection when the compared difference is above a predetermined threshold value. According to another aspect of the present invention, there is provided a time lapse recorder comprising: a dividing means for dividing an input picture signal into signals corresponding to small area blocks each consisting of a plurality of pixels; a motion estimate means for retrieving motion vectors of blocks most similar to each other in picture frames of different times; a motion compensating means for obtaining a difference between a coding subject frame and a motion vector computation frame for each of the blocks on the basis of the motion vectors; an orthogonal transform means for executing orthogonal transform of the blocks; a quantizing means for quantizing transform coefficient values as the output of the orthogonal transform means; a code quantity control means for controlling picture quality and quantity of codes generated per frame in accordance with the complexity of the input picture; a variable length coding means for variable length coding quantized coefficient data outputted from the quantizing means; an abnormality detecting means for detecting abnormality of input picture; a recording interval control means for changing recording frame number at a constant interval in the normal state and in unit times in the abnormality detection state; and a recording means for recording the variable length coded data in a recording medium under control of the recording interval control means, wherein the abnormality detecting means computes statistical value of the distribution or amplitude values of the motion vectors for each frame, compares the statistical value of the motion vectors with a predetermined threshold value, and executes abnormality detection when the statistical value is above the threshold value. The recording interval control means adaptively controls the recording frame number according to a multiple-valued output of the abnormality detecting means. When the output of the abnormality detecting means is abnormal, the recording interval control means controls the recording frame number such as to permit recording of all frames. The abnormality detecting means provides a multiple-valued output, and the recording interval control means decodes the value of the output of the abnormality detecting means, selects a recording time interval corresponding to the output value among a plurality of different recording times shorter than a recording time in a normal state and causes the recording means to record frames at the selected recording time interval. The code quantity control means executes code quantity control on the basis of the output of the abnormality detecting means such as to provide an improved recording picture quality when the abnormality is detected. According to other aspect of the present invention, there is provided in an image processing apparatus of moving picture coding type for detecting motion vectors from an input picture, variable length coding a motion corrected signal, and recording the coded signal in recording means, a time lapse recorder comprising: means for comparing a unit time mean coding bit number of past frames and the coding bit number of the present frame and executing abnormality detection on the basis of the difference between the compared coding bit numbers; and means for controlling the number of frames recorded in the recording means such that the recording interval per unit time is reduced when the abnormality is detected. According to still other aspect of the present invention, there is provided inn an image recording apparatus for detecting motion vectors from an input picture, generating an inter-frame difference value between the input picture and a predicted frame from the motion vectors, executing orthogonal transform of the inter-frame difference, quantizing coefficients obtained by the orthogonal transformation, coding the quantized coefficients and recording the quantized coefficients in a recording means, a time lapse recorder comprising: an abnormality detecting mean for comparing a unit time mean coding bit number of past frames and the coding bit number of the present frame and executing abnormality detection on the basis of the difference between the compared coding bit numbers; and a recording interval control means for controlling the number of frames recorded in the recording means such that the recording interval per unit time is reduced when the abnormality is detected. According to further aspect of the present invention, there is provided in an image recording apparatus for detecting motion vectors from an input picture, generating an inter-frame difference value between the input picture and a predicted frame from the motion vectors, executing orthogonal transform of the inter-frame difference, quantizing coefficients obtained by the orthogonal transformation, coding the quantized coefficients and recording the quantized coefficients in a recording means, a time lapse recorder comprising: an abnormality detecting means including means for computing the unit time least mean coding bit number on the basis of the frame coding bit number of each frame, and means for comparing the coding bit number of the present frame and the least mean coding bit number and determines that the frame is abnormal when the difference is greater than a predetermined threshold value; and a recording interval control means for controlling the number of frames recorded in the recording means such that the recording interval per unit time is reduced when the abnormality is detected. According to still further aspect of the present invention, there is provided in an image recording apparatus for detecting motion vectors from an input picture, generating an inter-frame difference value between the input picture and a predicted frame from the motion vectors, executing orthogonal transform of the inter-frame difference, quantizing coefficients obtained by the orthogonal transformation, coding the quantized coefficients and recording the quantized coefficients in a recording means, a time lapse recorder comprising: an abnormality detecting means including means for computing the unit time least mean coding bit number on the basis of the frame coding bit number of each frame, and means for comparing the coding bit number of the present frame and the least mean coding bit number and determines that the frame is abnormal when the difference is greater than a predetermined threshold value; and a recording interval control means for controlling the number of frames recorded in the recording means such that the recording interval per unit time is reduced when the abnormality is detected, wherein a plurality of threshold values are provided, and abnormality detection is executed by a multiple-valued state detection as a result of comparison between the difference and the plurality of threshold values. The abnormality detecting means includes: means for selecting a frame having a predetermined predicted structure among input frames; means for receiving frame coding bit number of the selected frame and computing the unit time least mean coding bit number; and means for executing abnormality detection and providing an abnormality detection signal when the quotient of division of the mean coding bit number by the least mean coding bit number is greater than a predetermined threshold value and also when the quotient of division of the coding bit number of the selected present input frame by the unit time least mean coding bit number is greater than a predetermined threshold value. The frame coding bit number is inputted when P picture frames alone or P and B picture frames are inputted. The abnormality detecting means includes: means for analyzing the motion vector over one frame; and means for comparing the motion vector value distribution with a predetermined value, executing abnormality detection when it is larger than the predetermined value, and generating an abnormal detection signal. The abnormality detecting means includes: means for converting the motion vector amplitudes to corresponding scalar values; means for accumulating the scalar values for each frame; and means for comparing the accumulation value with a predetermined threshold value and outputting an abnormality detection signal when the accumulation value is greater than the threshold value. The recording interval control means normally executes a control for recording frames at a predetermined recording time interval in the recording means; and when the abnormality detecting means detects abnormality, the variable length coding means is controlled on the basis of the value of the output of the abnormality detecting means such that all frames are recorded continuously or at a recording time interval shorter than the recording time interval in the normal state. An abnormal detection signal is outputted when it is determined from a motion vector value and coordinate data of a base block of the motion vector that motion coordinates of the motion vector are in a predetermined monitoring area. When the abnormality detecting means detects abnormality, the code quantity control means controls the quantizing means and the variable length coding means for recording frames in the recording means at an increased coding rate and a reduced compression factor compared to the normal state. Other objects and features will be clarified from the following description with reference to attached drawings.

Deficits in attention and working memory, the abilities that allow individuals to selectively attend to and mentally maintain and manipulate information to guide behavior, are considered to be central components to the cognitive dysfunction in schizophrenia. While advances in antipsychotic pharmacotherapy have resulted in important gains for treating symptoms of hallucinations and delusions, cognitive deficits have been far less responsive to standard treatments. Developing novel pharmacological agents to target these persistent cognitive deficits is an important goal of ongoing schizophrenia treatment research. This is a broad and multidimensional problem involving drug development and translational animal models. In the end, success will depend on the ability of trained investigators who have the expertise and tools to evaluate drug effects on neurocognitive systems in the clinic. The aim of this proposed career development program is to facilitate the candidate's efforts to become a successful independent clinical investigator in this area. Primary objectives of this career development program are to provide the candidate with advanced training in three main areas: (1) functional brain imaging;(2) cognitive neuroscience and neuropharmacological models of working memory;and (3) clinical trial design and methodology. Research activities will focus on designing and conducting behavioral and event-related functional neuroimaging studies of working memory and attention using paradigms translated from animal models to examine antipsychotic treatment effects on these core cognitive deficits in schizophrenia. These activities will prepare the candidate for an independent program of research examining disturbances in functional brain systems that underlie cognitive impairments in schizophrenia and how these are impacted by antipsychotic treatments. The knowledge and skills gained from proposed training and research activities will be important for the Pi's career objective to use integrative approaches to investigate the effectiveness of pharmacological treatments developed to reduce cognitive impairments in schizophrenia. PUBLIC HEALTH RELEVANCE Schizophrenia is a debilitating psychiatric disorder. With a prevalence of 1% of the population and billions of dollars expended annually in direct costs and lost productivity, it is a major public health concern. Cognitive symptoms, which are not adequately treated, account for much of the long-term functional disability, and the need to understand the brain basis of these deficits is imperative to advance treatments for this disorder.

The invention generally relates to a rack for stowing leaders of the type employed in the fishing industry, and more particularly to a rack which can readily be mounted aboard a fishing vessel and employed in rapidly stowing leaders, as fishing lines are retrieved, and from which leaders can rapidly be broken-out and deployed during fishing operations. In the fishing industry, it is common practice to deploy or pay-out fishing lines having a plurality of leaders attached thereto in predetermined spaced relation. Of course, each leader normally is made up by hand and includes a fastener, often referred to as a snap, secured to one end of the leader and a lure secured to the opposite end thereof. As the fishing lines are paid-out during trolling operations, the leaders are serially fastened to the fishing lines. These operations must be rapidly performed. Similarly, as the fishing lines are retrieved or taken-in, each of the leaders must be detached from the fishing lines and rapidly stowed. Further, for reasons fully understood by those familiar with the fishing industry, it is desirable that the leaders be washed-down and stowed upon retrieval. Currently, it is common practice, upon retrieval, to coil the leaders into small coils and deposit them in pails containing fresh water. Of course, a great deal of time is lost in coiling the leaders. This loss of time should be avoided, where possible, in the interest of economy and efficiency. In a similar manner, a great deal of time may be lost in breaking-out the leaders, particularly in the event a fouling of the leaders is encountered, due to the tendency of leader material to retain its coiled configuration. It is, therefore, the general purpose of the instant invention to provide a practical rack for use in stowing leaders of the type employed in the fishing industry, which can readily be mounted aboard a fishing vessel and easily employed for facilitating expeditious deployment and retrieval of fishing lines during the performance of fishing operations such as trolling and the like.

Music and nonmusical abilities. Reports that exposure to music causes benefits in nonmusical domains have received widespread attention in the mainstream media. Such reports have also influenced public policy. The so-called "Mozart effect" actually refers to two relatively distinct phenomena. One concerns short-term increases in spatial abilities that are said to occur from listening to music composed by Mozart. The other refers to the possibility that formal training in music yields nonmusical benefits. A review of the relevant findings indicates that the short-term effect is small and unreliable. Moreover, when it is evident, it can be explained by between-condition differences in the listener's mood or levels of cognitive arousal. By contrast, the effect of music lessons on nonmusical aspects of cognitive development is still an open question. Several studies have reported positive associations between formal music lessons and abilities in nonmusical (e.g., linguistic, mathematical, and spatial) domains. Nonetheless, compelling evidence for a causal link remains elusive.

1. Field of the Invention This invention relates to a polynucleotide or vector for expressing short interfering RNAs (siRNAs) to inhibit the expression of a target gene. The invention also relates to cells and non-human transgenic animals comprising the polynucleotide or vector and their various uses including in target drug validation and in human therapeutics. The ability to inhibit or disrupt the function of a specific gene is highly desirable both from the point of view of studying gene function and also from a therapeutic perspective. Many diseases arise from either the expression of a mutated gene or from abnormal, and in particular elevated or inappropriate, expression of a particular gene. Such mutations may be inherited, such as in the case of autosomal dominant disorders, or occur in the somatic or germ line tissues of an individual, such as in the case of cancer. The ability to modulate the expression of a mutated allele or of an inappropriately expressed wild type allele in various diseases or disorders may therefore be used to provide therapies to treat the disorders. In addition, in various infectious diseases, such as viral infection, the ability to inhibit the expression of viral genes in the host cell, or of a gene encoding a host cell protein involved in the life cycle of the virus, may also lead to possible treatments for infectious diseases. The ability to inhibit gene expression has also been used to study gene function. Techniques such as classical mutagenesis have provided great insights into gene function, but such techniques are labour intensive, expensive and may take long periods of time. Such techniques simply may not be practical in higher organisms and require a means to identify the desired mutant. They also do not offer the possibility of mutating a specific gene of choice. Although various methods for targeted gene disruption have been developed, where a gene of choice can be inhibited or disrupted, these also suffer from limitations. Techniques such as gene targeting are highly costly, expensive and time consuming often taking several years to obtain a homozygous mutant. Gene targeting also requires detailed knowledge of the structure of the gene to be disrupted. As well as gene targeting antisense technology has also been developed to try and disrupt a specific gene. However, antisense RNA is unstable and it is often difficult to achieve high enough levels of antisense RNA in cells to achieve effective inhibition of a target gene. Recently, it has been found in organisms such as C. elegans, Drosophilia melanogaster and plants that double stranded RNA molecules (dsRNA) are capable of inhibiting the expression of a target gene that they share sequence identity or homology to. The observed phenomena, sometimes referred to as post transcriptional gene silencing (PTGS), are thought to represent a possible cellular defence mechanism against viruses or transposons. Typically, in the studies carried out in these organisms the dsRNA has been introduced into cells by techniques such as microinjection or transfection and the inhibition of a target gene such as a reporter gene been measured. The mechanism by which the dsRNA exerts its inhibitory effect on the target gene has begun to be elucidated. It is thought that the dsRNA is processed into duplexes of from 21 to 25 nucleotides in length. These short duplexes have been detected in plants where PTGS is occurring as well as in extracts of D. melanogaster schenider-2 (S2) cells transfected with a dsRNA molecule. It has been found that the processing reaction of a dsRNA can be carried out in vitro using extracts from these S2 cells. This provides an in vitro model system in which both the processing, targeting and transcript cleavage mechanisms involved in gene silencing can be studied. In the S2 lysate it was observed that the target mRNA was cleaved at 21 nucleotide intervals and that synthetic 21 and 22 RNA duplexes added to the lysate were able to guide efficient sequence specific mRNA degradation. Larger duplexes of 30 bp dsRNA were found to be active. The 21 nucleotide RNA products in the system were therefore named small interfering or silencing RNAs (siRNAs). Factors from the target cell are also necessary for gene silencing. In D. melanogaster a ribonuclease III enzyme, dicer, is required for processing of the long dsRNAs into siRNA duplexes. It is thought that genes homologous to dicer exist in other organisms including mammals and humans as well as homologs or counterparts to the other host factors necessary. The initial steps in silencing involve the generation of a siRNA containing endonuclease complex. The endonuclease may be dicer or a gene homologous to dicer. The complex then specifically targets the mRNA transcript by a mechanism involving the exchange of one of the strands of the siRNA duplex with the region of sequence identity in the target transcript. Following this strand exchange, cleavage of the mRNA transcript occurs. The cleavage of the target mRNA may occur at the ends of the duplexed region so, in effect, regenerating the siRNA endonuclease complex with one of the two strands of the regenerated siRNA coming from the original siRNA molecule and the other from the target transcript. Multiple cycles of transcript mRNA cleavage and hence siRNA regeneration may mean that each initial siRNA molecule can inactivate multiple copies of the target mRNA. Once the target mRNA transcript has been cleaved, the cleavage products not in the regenerated siRNA are rapidly degraded as they either lack the stabilising cap or pol(A)tail. Although experiments investigating gene silencing in lower organisms have offered promising results it is thought that they may not be applicable to higher organisms such as mammals. It is thought that in higher organisms, such as mammals, cellular defence mechanisms operate which are triggered by dsRNA. It is believed that dsRNAs activate the interferon response which leads to a global shut-off in protein synthesis as well as non-specific mRNA degradation. This can lead to cell death and hence prevent selective gene inhibition. The presence of such defence mechanisms means that the applicability of gene silencing employing dsRNA in higher organisms has been questioned. Experiments which have claimed to have demonstrated the efficacy of dsRNA in inhibiting the expression of a target gene in higher organisms have either been in non-mammalian systems, such as zebra fish or chicks, or alternatively in mammalian systems such as early embryos where the viral defence mechanisms are not thought to operate. Preliminary experiments transfecting and/or microinjecting synthetic siRNAs, rather than longer dsRNA molecules which can be processed to give rise to a siRNA, have led to speculation that it might be possible to overcome the problems of the viral defence mechanisms in higher organisms. It may be that there is a threshold for the length of dsRNA necessary to activate the cell's defence mechanisms. The size of the synthetic siRNAs, and in particular the double stranded regions in them, introduced into the target cell may be small enough that they are below this threshold and hence do not activate the defence mechanisms.

The impact of personalized medicine on survival: comparisons of results in metastatic breast, colorectal and non-small-cell lung cancers. Breast, colorectal and lung cancers represent the three most incident forms of cancer worldwide. Among these three "big killers", lung cancer is considered the one with the worst prognosis due to its high mortality even in early stages. Due to their more favorable prognosis, breast and colorectal cancers might appear to have benefited from major advances. Most oncologists who are faced with metastatic non-small cell lung cancer (NSCLC) find the reported results very frustrating when compared with those for metastatic breast (MBC) and colorectal cancers (MCRC). The aim of this analysis was to quantify and compare the relative magnitude of overall survival (OS) improvements in the first-line approaches in metastatic NSCLC, MBC and MCRC through the analysis of the main landmark meta-analyses and randomized clinical trials (RCTs) of commercially available drugs. Five items were considered and analyzed for each cancer. Moreover we evaluated the real clinical impact of the results reported by each item on the entire population; for each "big killer" an overall hazard ratio (HR) was estimated: 0.88 (95%(+) CI: 0.72-1.07) for MBC, 0.94 (95%(+) CI: 0.82-1.07) for MCRC, and about 0.80 (95%(+) CI: 0.73-0.90) for advanced NSCLC. We showed that, in the last decades, these three tumors had important and constant OS improvements reached step by step. The relative magnitude of OS improvement seems higher in metastatic NSCLC than MBC and MCRC.

This invention relates generally to the construction of concrete walls, slabs or other structures adjacent to or inclusive of spaces. More particularly, this invention pertains to void forms for creating spaces beneath concrete structures to separate and protect the structures from underlying expansive soils. Expansive soils are prevalent in many areas of the United States, as well as in other countries. Such soils typically contain much clay, and expand and contract considerably as a result of cyclical changes in moisture content and/or as a result of natural freezing-thawing cycles. A common method of construction in such expansive soils uses spaced drilled piers or spread footings for supporting the walls and floors. In this method, the concrete walls or beams supported by the piers or footings must be provided with a substantial spacing from the expansive underlying soil. Otherwise, the upward expansion of the soil may contract and force the beams or walls upward, causing cracking and deformation of the concrete. Without the required spacing, the integrity of the concrete structure is eventually lost. Excavation of soil from beneath a concrete structure after it has "set" is a labor-intensive, very expensive method for resolving the problem with expansive soils. Where the structure has a lower edge below grade, a trench sufficiently wide to permit hand removal of soil below the structure must be provided. Furthermore, it is desirable to remove any forms of wood, metal or plastic used to form the lower surface of the structure. Such forms have a long life and should be removed after the concrete has set to provide further expansion space below the structure, and for re-use. The use of integral corrugated paper form voids is known. In one application, such form voids are placed at the bottom of wall forms and trenches to separate the subsequently poured concrete from the ground. The corrugated paper form voids have sufficient temporary strength to support the wet concrete at a distance above the ground, but gradually absorb water and deteriorate to a condition where they no longer provide support. However, by this time the concrete has set and needs no support other than that provided by the piers. During periods of upward expansion of the underlying soil, the soil occupies the space left by the deteriorated or weakened form voids. Form voids are available in various cross-sectional configurations. The generally rigid form voids are prepared by forming the desired structural shape of panels of corrugated paper and joining the panels together with adhesive. An internal cellular grid structure may be used within the form void to increase the strength of the form void as required. It has been common practice to abut square-ended form voids to round piers, resulting in the flow of wet concrete downward between the pier and form void. While the quantity of this misdirected concrete is relatively small, it has been found that it nevertheless may provide a lower surface against which expanding soils may apply upward forces to distort or damage the concrete structure.

1. Field of the Invention The present invention is directed to memory management. It particularly concerns what has come to be known as “garbage collection.” 2. Background Information In the field of computer systems, considerable effort has been expended on the task of allocating memory to data objects. For the purposes of this discussion, the term object refers to a data structure represented in a computer system's memory. Other terms sometimes used for the same concept are record and structure. An object may be identified by a reference, a relatively small amount of information that can be used to access the object. A reference can be represented as a “pointer” or a “machine address,” which may require, for instance, only sixteen, thirty-two, or sixty-four bits of information, although there are other ways to represent a reference. In some systems, which are usually known as “object oriented,” objects may have associated methods, which are routines that can be invoked by reference to the object. They also may belong to a class, which is an organizational entity that may contain method code or other information shared by all objects belonging to that class. In the discussion that follows, though, the term object will not be limited to such structures; it will additionally include structures with which methods and classes are not associated. The invention to be described below is applicable to systems that allocate memory to objects dynamically. Not all systems employ dynamic allocation. In some computer languages, source programs must be so written that all objects to which the program's variables refer are bound to storage locations at compile time. This storage-allocation approach, sometimes referred to as “static allocation,” is the policy traditionally used by the Fortran programming language, for example. Even for compilers that are thought of as allocating objects only statically, of course, there is often a certain level of abstraction to this binding of objects to storage locations. Consider the typical computer system 10 depicted in FIG. 1, for example. Data and instructions for operating on them that a microprocessor 11 uses may reside in on-board cache memory or be received from further cache memory 12, possibly through the mediation of a cache controller 13. That controller 13 can in turn receive such data from system read/write memory (“RAM”) 14 through a RAM controller 15 or from various peripheral devices such as communications interface 16 through a system bus 17. The memory space made available to an application program may be “virtual” in the sense that it can actually be considerably larger than RAM 14 provides. So the RAM contents will be swapped to and from a system disk 18. Additionally, the actual physical operations performed to access some of the most-recently visited parts of the process's address space often will actually be performed in the cache 12 or in a cache on board microprocessor 11 rather than on the RAM 14, with which those caches swap data and instructions just as RAM 14 and system disk 18 do with each other. A further level of abstraction results from the fact that an application will often be run as one of many processes operating concurrently with the support of an underlying operating system. As part of that system's memory management, the application's memory space may be moved among different actual physical locations many times in order to allow different processes to employ shared physical memory devices. That is, the location specified in the application's machine code may actually result in different physical locations at different times because the operating system adds different offsets to the machine-language-specified location. Despite these expedients, the use of static memory allocation in writing certain long-lived applications makes it difficult to restrict storage requirements to the available memory space. Abiding by space limitations is easier when the platform provides for dynamic memory allocation, i.e., when memory space to be allocated to a given object is determined only at run time. Dynamic allocation has a number of advantages, among which is that the run-time system is able to adapt allocation to run-time conditions. For example, the programmer can specify that space should be allocated for a given object only in response to a particular run-time condition. The C-language library function malloc( ) is often used for this purpose. Conversely, the programmer can specify conditions under which memory previously allocated to a given object can be reclaimed for reuse. The C-language library function free( ) results in such memory reclamation. Because dynamic allocation provides for memory reuse, it facilitates generation of large or long-lived applications, which over the course of their lifetimes may employ objects whose total memory requirements would greatly exceed the available memory resources if they were bound to memory locations statically. Particularly for long-lived applications, though, allocation and reclamation of dynamic memory must be performed carefully. If the application fails to reclaim unused memory—or, worse, loses track of the address of a dynamically allocated segment of memory—its memory requirements will grow over time to exceed the system's available memory. This kind of error is known as a “memory leak.” Another kind of error occurs when an application reclaims memory for reuse even though it still maintains a reference to that memory. If the reclaimed memory is reallocated for a different purpose, the application may inadvertently manipulate the same memory in multiple inconsistent ways. This kind of error is known as a “dangling reference,” because an application should not retain a reference to a memory location once that location is reclaimed. Explicit dynamic-memory management by using interfaces like malloc( )/free( ) often leads to these problems. A way of reducing the likelihood of such leaks and related errors is to provide memory-space reclamation in a more-automatic manner. Techniques used by systems that reclaim memory space automatically are commonly referred to as “garbage collection.” Garbage collectors operate by reclaiming space that they no longer consider “reachable.” Statically allocated objects represented by a program's global variables are normally considered reachable throughout a program's life. Such objects are not ordinarily stored in the garbage collector's managed memory space, but they may contain references to dynamically allocated objects that are, and such objects are considered reachable. Clearly, an object referred to in the processor's call stack is reachable, as is an object referred to by register contents. And an object referred to by any reachable object is also reachable. The use of garbage collectors is advantageous because, whereas a programmer working on a particular sequence of code can perform his task creditably in most respects with only local knowledge of the application at any given time, memory allocation and reclamation require a global knowledge of the program. Specifically, a programmer dealing with a given sequence of code does tend to know whether some portion of memory is still in use for that sequence of code, but it is considerably more difficult for him to know what the rest of the application is doing with that memory. By tracing references from some conservative notion of a “root set,” e.g., global variables, registers, and the call stack, automatic garbage collectors obtain global knowledge in a methodical way. By using a garbage collector, the programmer is relieved of the need to worry about the application's global state and can concentrate on local-state issues, which are more manageable. The result is applications that are more robust, having no dangling references and fewer memory leaks. Garbage-collection mechanisms can be implemented by various parts and levels of a computing system. One approach is simply to provide them as part of a batch compiler's output. Consider FIG. 2's simple batch-compiler operation, for example. A computer system executes in accordance with compiler object code and therefore acts as a compiler 20. The compiler object code is typically stored on a medium such as FIG. 1's system disk 18 or some other machine-readable medium, and it is loaded into RAM 14 to configure the computer system to act as a compiler. In some cases, though, the compiler object code's persistent storage may instead be provided in a server system remote from the machine that performs the compiling. The electrical signals that carry the digital data by which the computer systems exchange that code are examples of the kinds of electro-magnetic signals by which the computer instructions can be communicated. Others are radio waves, microwaves, and both visible and invisible light. The input to the compiler is the application source code, and the end product of the compiler process is application object code. This object code defines an application 21, which typically operates on input such as mouse clicks, etc., to generate a display or some other type of output. This object code implements the relationship that the programmer intends to specify by his application source code. In one approach to garbage collection, the compiler 20, without the programmer's explicit direction, additionally generates code that automatically reclaims unreachable memory space. Even in this simple case, though, there is a sense in which the application does not itself provide the entire garbage collector. Specifically, the application will typically call upon the underlying operating system's memory-allocation functions. And the operating system may in turn take advantage of various hardware that lends itself particularly to use in garbage collection. So even a very simple system may disperse the garbage-collection mechanism over a number of computer-system layers. To get some sense of the variety of system components that can be used to implement garbage collection, consider FIG. 3's example of a more complex way in which various levels of source code can result in the machine instructions that a processor executes. In the FIG. 3 arrangement, the human applications programmer produces source code 22 written in a high-level language. A compiler 23 typically converts that code into “class files.” These files include routines written in instructions, called “byte codes” 24, for a “virtual machine” that various processors can be software-configured to emulate. This conversion into byte codes is almost always separated in time from those codes' execution, so FIG. 3 divides the sequence into a “compile-time environment” 25 separate from a “run-time environment” 26, in which execution occurs. One example of a high-level language for which compilers are available to produce such virtual-machine instructions is the Java™ programming language. (Java is a trademark or registered trademark of Sun Microsystems, Inc., in the United States and other countries.) Most typically, the class files' byte-code routines are executed by a processor under control of a virtual-machine process 27. That process emulates a virtual machine from whose instruction set the byte codes are drawn. As is true of the compiler 23, the virtual-machine process 27 may be specified by code stored on a local disk or some other machine-readable medium from which it is read into FIG. 1's RAM 14 to configure the computer system to implement the garbage collector and otherwise act as a virtual machine. Again, though, that code's persistent storage may instead be provided by a server system remote from the processor that implements the virtual machine, in which case the code would be transmitted electrically or optically to the virtual-machine-implementing processor. In some implementations, much of the virtual machine's action in executing these byte codes is most like what those skilled in the art refer to as “interpreting,” so FIG. 3 depicts the virtual machine as including an “interpreter” 28 for that purpose. In addition to or instead of running an interpreter, many virtual-machine implementations actually compile the byte codes concurrently with the resultant object code's execution, so FIG. 3 depicts the virtual machine as additionally including a “just-in-time” compiler 29. The arrangement of FIG. 3 differs from FIG. 2 in that the compiler 23 for converting the human programmer's code does not contribute to providing the garbage-collection function; that results largely from the virtual machine 27's operation. Those skilled in that art will recognize that both of these organizations are merely exemplary, and many modern systems employ hybrid mechanisms, which partake of the characteristics of traditional compilers and traditional interpreters both. The invention to be described below is applicable independently of whether a batch compiler, a just-in-time compiler, an interpreter, or some hybrid is employed to process source code. In the remainder of this application, therefore, we will use the term compiler to refer to any such mechanism, even if it is what would more typically be called an interpreter. The arrangement of FIG. 3 differs from FIG. 2 in that the compiler 23 for converting the human programmer's code does not contribute to providing the garbage-collection function; that results largely from the virtual machine 27's operation. Although the FIG. 3 arrangement is a popular one, it is by no means universal, and many further implementation types can be expected. Proposals have even been made to implement the virtual machine 27's behavior in a hardware processor, in which case the hardware itself would provide some or all of the garbage-collection function. In short, garbage collectors can be implemented in a wide range of combinations of hardware and/or software. As is true of most of the garbage-collection techniques described in the literature, the invention to be described below is applicable to most such systems. By implementing garbage collection, a computer system can greatly reduce the occurrence of memory leaks and other software deficiencies in which human programming frequently results. But it can also have significant adverse performance effects if it is not implemented carefully. To distinguish the part of the program that does “useful” work from that which does the garbage collection, the term mutator is sometimes used in discussions of these effects; from the collector's point of view, what the mutator does is mutate active data structures' connectivity. Some garbage-collection approaches rely heavily on interleaving garbage-collection steps among mutator steps. In one type of garbage-collection approach, for instance, the mutator operation of writing a reference is followed immediately by garbage-collector steps used to maintain a reference count in that object's header, and code for subsequent new-object storage includes steps for finding space occupied by objects whose reference count has fallen to zero. Obviously, such an approach can slow mutator operation significantly. Other approaches therefore interleave very few garbage-collector-related instructions into the main mutator process but instead interrupt it from time to time to perform garbage-collection cycles, in which the garbage collector finds unreachable objects and reclaims their memory space for reuse. Such an approach will be assumed in discussing FIG. 4's depiction of a simple garbage-collection operation. Within the memory space allocated to a given application is a part 40 managed by automatic garbage collection. In the following discussion, this will be referred to as the “heap,” although in other contexts that term refers to all dynamically allocated memory. During the course of the application's execution, space is allocated for various objects 42, 44, 46, 48, and 50. Typically, the mutator allocates space within the heap by invoking the garbage collector, which at some level manages access to the heap. Basically, the mutator asks the garbage collector for a pointer to a heap region where it can safely place the object's data. The garbage collector keeps track of the fact that the thus-allocated region is occupied. It will refrain from allocating that region in response to any other request until it determines that the mutator no longer needs the region allocated to that object. Garbage collectors vary as to which objects they consider reachable and unreachable. For the present discussion, though, an object will be considered “reachable” if it is referred to, as object 42 is, by a reference in the root set 52. The root set consists of reference values stored in the mutator's threads' call stacks, the CPU registers, and global variables outside the garbage-collected heap. An object is also reachable if it is referred to, as object 46 is, by another reachable object (in this case, object 42). Objects that are not reachable can no longer affect the program, so it is safe to re-allocate the memory space that they occupy. A typical approach to garbage collection is therefore to identify all reachable objects and reclaim any previously allocated memory that the reachable objects do not occupy. A typical garbage collector may identify reachable objects by tracing references from the root set 52. For the sake of simplicity, FIG. 4 depicts only one reference from the root set 52 into the heap 40. (Those skilled in the art will recognize that there are many ways to identify references, or at least data contents that may be references.) The collector notes that the root set points to object 42, which is therefore reachable, and that reachable object 42 points to object 46, which therefore is also reachable. But those reachable objects point to no other objects, so objects 44, 48, and 50 are all unreachable, and their memory space may be reclaimed. This may involve, say, placing that memory space in a list of free memory blocks. To avoid excessive heap fragmentation, some garbage collectors additionally relocate reachable objects. FIG. 5 shows a typical approach. The heap is partitioned into two halves, hereafter called “semi-spaces.” For one garbage-collection cycle, all objects are allocated in one semi-space 54, leaving the other semi-space 56 free. When the garbage-collection cycle occurs, objects identified as reachable are “evacuated” to the other semi-space 56, so all of semi-space 54 is then considered free. Once the garbage-collection cycle has occurred, all new objects are allocated in the lower semi-space 56 until yet another garbage-collection cycle occurs, at which time the reachable objects are evacuated back to the upper semi-space 54. Although this relocation requires the extra steps of copying the reachable objects and updating references to them, it tends to be quite efficient, since most new objects quickly become unreachable, so most of the current semi-space is actually garbage. That is, only a relatively few, reachable objects need to be relocated, after which the entire semi-space contains only garbage and can be pronounced free for reallocation. Now, a collection cycle can involve following all reference chains from the basic root set—i.e., from inherently reachable locations such as the call stacks, class statics and other global variables, and registers—and reclaiming all space occupied by objects not encountered in the process. And the simplest way of performing such a cycle is to interrupt the mutator to provide a collector interval in which the entire cycle is performed before the mutator resumes. For certain types of applications, this approach to collection-cycle scheduling is acceptable and, in fact, highly efficient. For many interactive and real-time applications, though, this approach is not acceptable. The delay in mutator operation that the collection cycle's execution causes can be annoying to a user and can prevent a real-time application from responding to its environment with the required speed. In some applications, choosing collection times opportunistically can reduce this effect. Collection intervals can be inserted when an interactive mutator reaches a point at which it awaits user input, for instance. So it may often be true that the garbage-collection operation's effect on performance can depend less on the total collection time than on when collections actually occur. But another factor that often is even more determinative is the duration of any single collection interval, i.e., how long the mutator must remain quiescent at any one time. In an interactive system, for instance, a user may never notice hundred-millisecond interruptions for garbage collection, whereas most users would find interruptions lasting for two seconds to be annoying. The cycle may therefore be divided up among a plurality of collection intervals. When a collection cycle is divided up among a plurality of collection intervals, it is only after a number of intervals that the collector will have followed all reference chains and be able to identify as garbage any objects not thereby reached. This approach is more complex than completing the cycle in a single collection interval; the mutator will usually modify references between collection intervals, so the collector must repeatedly update its view of the reference graph in the midst of the collection cycle. To make such updates practical, the mutator must communicate with the collector to let it know what reference changes are made between intervals. An even more complex approach, which some systems use to eliminate discrete pauses or maximize resource-use efficiency, is to execute the mutator and collector in concurrent execution threads. Most systems that use this approach use it for most but not all of the collection cycle; the mutator is usually interrupted for a short collector interval, in which a part of the collector cycle takes place without mutation. Independent of whether the collection cycle is performed concurrently with mutator operation, is completed in a single interval, or extends over multiple intervals is the question of whether the cycle is complete, as has tacitly been assumed so far, or is instead “incremental.” In incremental collection, a collection cycle constitutes only an increment of collection: the collector does not follow all reference chains from the basic root set completely. Instead, it concentrates on only a portion, or collection set, of the heap. Specifically, it identifies every collection-set object referred to by a reference chain that extends into the collection set from outside of it, and it reclaims the collection-set space not occupied by such objects, possibly after evacuating them from the collection set. By thus culling objects referenced by reference chains that do not necessarily originate in the basic root set, the collector can be thought of as expanding the root set to include as roots some locations that may not be reachable. Although incremental collection thereby leaves “floating garbage,” it can result in relatively low pause times. The invention to be discussed below is directed to garbage collectors that collect incrementally, and it addresses the problem of long pause times that can result even when that approach is employed. It will become apparent that it is applicable to most types of incremental collection. For the sake of concreteness, though, we will consider as an example a particular type of incremental collector, one that divides the garbage-collected heap into “generations” and employs the “train algorithm” on one but not all of the generations. In many collectors, different portions, or generations, of the heap are subject to different collection policies. New objects are usually allocated in a “young” generation, and older objects are “promoted” from younger generations to older or more “mature” generations. Collecting the younger generations more frequently than the others yields greater efficiency because the younger generations tend to accumulate garbage faster; newly allocated objects tend to “die,” while older objects tend to “survive.” For the sake of example, consider FIG. 6, which depicts a garbage-collected heap as divided into a relatively small young generation 58 and larger old generation 60. Let us assume that mutator execution is interrupted from time to time for collection intervals in each of which the entire young generation 58 is collected but not the entire old generation. The operation of collecting the young generation 58 by itself may be more or less the same as that described in connection with FIGS. 4 and 5 for the entire heap, with one major exception: the root set must be considered to include not only the call stack, registers, and global variables represented by set 52 but also objects in the old generations 60, since such objects may themselves may contain references to objects in the young generation 58. So pointers must be traced not only from the basic root set 52 but also from objects within the old generation. One could perform this tracing by simply inspecting all references in the old generation 60 at the beginning of every collection interval, and it turns out that this approach is actually feasible in some situations. But it takes too long in other situations, so workers in this field have employed a number of approaches to expediting reference tracing. One approach is to include so-called write barriers in the mutator process. A write barrier is code added to a write operation to record information from which the collector can determine where references were written or may have been since the last collection interval. A reference list can then be maintained by taking such a list as it existed at the end of the previous collection interval and updating it by inspecting only locations identified by the write barrier as possibly modified since the last collection interval. One of the many write-barrier implementations commonly used by workers in this art employs what has been referred to as the “card table.” FIG. 6 depicts the old generation 60 as being divided into smaller sections, known for this purpose as “cards.” Card table 62 contains an entry for each card. When the mutator writes a reference in a card, it makes an appropriate entry in the card-table location associated with that card (or, say, with the card in which the object containing the reference begins). Most write-barrier implementations simply make a Boolean entry indicating that the write operation has been performed, although some may be more elaborate. The mutator having thus left a record of where new or modified references may be, the collector can thereafter prepare appropriate summaries of that information, as will be explained in due course. For the sake of concreteness, we will assume that the summaries are maintained by steps that occur principally at the beginning of each collection interval. Of course, there are other write-barrier approaches, such as simply having the write barrier add to a list of addresses where references where written. Some collectors collect the entire young generation in every interval and may thereafter perform old-generation collection in the same interval. It may therefore take relatively little time to scan all young-generation objects remaining after young-generation collection to find references into the old generation. As the drawing indicates, the illustrated example use a card table to help find old-generation objects but does not them for finding young-generation references that refer to mature-generation objects. A card table is shown for the old generation, though, since laboriously scanning the entire old generation for references to young-generation (or old-generation) objects would ordinarily take too long. Now, although it typically takes very little time to collect the young generation, it may take more time than is acceptable within a single garbage-collection interval to collect the entire old generation. So some garbage collectors may collect the old generation itself incrementally. That is, the collection set may consist of only a portion of the old generation; an object in the collection set is considered reachable if it is referred to from outside the collection set, even if the reference is in the same, old generation. This is true because objects outside the collection set are not so processed during the collection increment as to enable them to be recognized as unreachable. To reduce the adverse effect this would otherwise have on collection efficiency, workers in this field have employed the “train algorithm.” A generation to be collected incrementally is divided into sections, which for reasons about to be described are referred to as “car sections.” Conventionally, a generation's incremental collection occurs in fixed-size sections, and a car section's size is that of the generation portion to be collected during one cycle. The discussion that follows will occasionally employ the nomenclature in the literature by using the term car instead of car section. But the literature seems to use that term to refer variously not only to memory sections themselves but also to data structures that the train algorithm employs to manage them when they contain objects, as well as to the more-abstract concept that the car section and managing data structure represent in discussions of the algorithm. So the following discussion will more frequently use the expression car section to emphasize the actual sections of memory space for whose management the car concept is employed. According to the train algorithm, the car sections are grouped into “trains,” which are ordered, conventionally according to age. For example, FIG. 7 shows an oldest train 73 consisting of a generation 74's three car sections described by associated data structures 74, 76, and 78, while a second train 80 consists only of a single car section, represented by structure 82, and the youngest train 84 (referred to as the “allocation train”) consists of car sections that data structures 86 and 88 represent. As will be seen below, car sections' train memberships can change, and any car section added to a train is typically added to the end of a train. Conventionally, the car collected in an increment is the one added earliest to the oldest train, which in this case is car 74. All of the generation's cars can thus be thought of as waiting for collection in a single long line, in which cars are ordered in accordance with the order of the trains to which they belong and, within trains, in accordance with the order in which they were added to those trains. As is usual, the way in which reachable objects are identified is to determine whether there are references to them in the root set or in any other object already determined to be reachable. In accordance with the train algorithm, the collector additionally performs a test to determine whether there are any references at all from outside the oldest train to objects within it. If there are not, then all cars within the train can be reclaimed, as will be explained below, with much less effort than is usually required to prepare cars for reclamation. And the train algorithm so operates that inter-car references tend to be grouped into trains, as will now be explained. To identify references into the car from outside of it, train-algorithm implementations (and other incremental collectors) typically employ “remembered sets.” As card tables are, remembered sets are used to keep track of references. Whereas a card-table entry contains information about references that the associated card contains, though, a remembered set associated with a given region contains information about references into that region from locations outside of it. In the case of the train algorithm, remembered sets are associated with car sections. Each remembered set, such as car 74's remembered set 90, lists locations in the generation where references into the associated car section have been found at some time or another. The remembered sets for all of a generation's cars are typically updated at the start of each collection interval. To illustrate how such updating and other collection operations may be carried out, FIGS. 8A and 8B (together, “FIG. 8”) depict an operational sequence in a system of the typical type mention above. That is, it shows a sequence of operations that may occur in a system in which the entire garbage-collected heap is divided into two generations, namely, a young generation and an old generation, and in which the young generation is much smaller than the old generation. FIG. 8 is also based on the assumption and that the train algorithm is used only for collecting the old generation. Block 102 represents a period of the mutator's operation. As was explained above, the mutator makes a card-table entry to identify any card that it has “dirtied” by adding or modifying a reference that the card contains. At some point, the mutator will be interrupted for collector operation. Different implementations employ different events to trigger such an interruption, but we will assume for the sake of concreteness that the system's dynamic-allocation routine causes such interruptions when no room is left in the young generation for any further allocation. A dashed line 103 represents the transition from mutator operation to collector operation. In the system assumed for the FIG. 8 example, the collector collects the (entire) young generation each time such an interruption occurs. When the young generation's collection ends, the mutator operation usually resumes, without the collector's having collected any part of the old generation. Once in a while, though, the collector also collects part of the old generation, and FIG. 8 is intended to illustrate such an occasion. When the collector's interval first starts, it first processes the card table, in an operation that block 104 represents. As was mentioned above, the collector scans the “dirtied” cards for references into the young generation. If a reference is found, that fact is memorialized appropriately. If the reference refers to a young-generation object, for example, an expanded card table may be used for this purpose. For each card, such an expanded card table might include a multi-byte array used to summarize the card's reference contents. The summary may, for instance, be a list of offsets that indicate the exact locations within the card of references to young-generation objects, or it may be a list of fine-granularity “sub-cards” within which references to young-generation objects may be found. If the reference refers to an old-generation object, the collector often adds an entry to the remembered set associated with the car containing that old-generation object. The entry identifies the reference's location, or at least a small region in which the reference can be found. For reasons that will become apparent, though, the collector will typically not bother to place in the remembered set the locations of references from objects in car sections farther forward in the collection queue than the referred-to object, i.e., from objects in older trains or in cars added earlier to the same train. The collector then collects the young generation, as block 105 indicates. (Actually, young-generation collection may be interleaved with the dirty-region scanning, but the drawing illustrates it for purpose of explanation as being separate.) If a young-generation object is referred to by a reference that card-table scanning has revealed, that object is considered to be potentially reachable, as is any young-generation object referred to by a reference in the root set or in another reachable young-generation object. The space occupied by any young-generation object thus considered reachable is withheld from reclamation. For example, it may be evacuated to a young-generation semi-space that will be used for allocation during the next mutator interval. It may instead be promoted into the older generation, where it is placed into a car containing a reference to it or into a car in the last train. Or some other technique may be used to keep the memory space it occupies off the system's free list. The collector then reclaims any young-generation space occupied by any other objects, i.e., by any young-generation objects not identified as transitively reachable through references located outside the young generation. The collector then performs the train algorithm's central test, referred to above, of determining whether there are any references into the oldest train from outside of it. The process of actually inspecting all remembered-set-identified locations for references into the remembered set is conventionally performed for only a single car section in any increment. In the absence of features such as those provided by the train algorithm, this would present a problem, because garbage structures may be larger than a car section. In such structures there would always be objects that (erroneously) appear reachable, since they are referred to from outside the car section under consideration. But the train algorithm additionally keeps track of whether there are any references into a given car from outside the train to which it belongs, and trains' sizes are not limited. As will be apparent presently, objects not found to be unreachable are relocated in such a way that garbage structures tend to be gathered into respective trains into which, eventually, no references from outside the train point. If no references from outside the train point to any objects inside the train, the train can be recognized as containing only garbage, and its memory space can be reclaimed without inspecting all of the memory locations identified by all of the remembered-set entries associated with all of its cars. This is the test that block 106 represents. The question of whether old-generation references point into the train from outside of it is (conservatively) answered in the course of updating remembered sets; in the course of updating a car's remembered set, it is a simple matter to flag the car as being referred to from outside the train. The step-106 test additionally involves determining whether any references from outside the old generation point into the oldest train. Various approaches to making this determination have been suggested, including the conceptually simple approach of merely following all reference chains from the root set until those chains (1) terminate, (2) reach an old-generation object outside the oldest train, or (3) reach an object in the oldest train. In the two-generation example, most of this work can be done readily by identifying references into the collection set from live young-generation objects during the young-generation collection. If one or more such chains reach the oldest train, that train includes reachable objects. It may also include reachable objects if the remembered-set-update operation has found one or more references into the oldest train from outside of it. Otherwise, that train contains only garbage, and the collector reclaims all of its car sections for reuse, as block 107 indicates. The collector may then return control to the mutator, which resumes execution, as FIG. 8B's block 108 indicates. If the train contains reachable objects, on the other hand, the collector turns to evacuating potentially reachable objects from the collection set. The first operation, which block 110 represents, is to remove from the collection set any object that is reachable from the root set by way of a reference chain that does not pass through the part of the old generation that is outside of the collection set. In the illustrated arrangement, in which there are only two generations, and the young generation has previously been completely collected during the same interval, this means evacuating from a collection set any object that (1) is directly referred to by a reference in the root set, (2) is directly referred to by a reference in the young generation (in which no remaining objects have been found unreachable), or (3) is referred to by any reference in an object thereby evacuated. All of the objects thus evacuated are placed in cars in the youngest train, which was newly created during the collection cycle. Certain of the mechanics involved in the evacuation process are described in more detail in connection with similar evacuation performed, as blocks 112 and 114 indicate, in response to remembered-set entries. FIG. 9 illustrates how the processing represented by block 114 proceeds. The entries identify heap regions, and, as block 116 indicates, the collector scans the thus-identified heap regions to find references to locations in the collection-set. As blocks 118 and 120 indicate, that entry's processing continues until the collector finds no more such references. Every time the collector does find such a reference, it checks to determine whether, as a result of a previous entry's processing, the referred-to object has already been evacuated. If it has not, the collector evacuates the referred-to object to a (possibly new) car in the train containing the reference, as blocks 122 and 124 indicate. As FIG. 10 indicates, the evacuation operation includes more than just object relocation, which block 126 represents. Once the object has been moved, the collector places a forwarding pointer in the collection-set location from which it was evacuated, for a purpose that will become apparent presently. Block 128 represents that step. (Actually, there are some cases in which the evacuation is only a “logical” evacuation: the car containing the object is simply re-linked to a different logical place in the collection sequence, but its address does not change. In such cases, forwarding pointers are unnecessary.) Additionally, the reference in response to which the object was evacuated is updated to point to the evacuated object's new location, as block 130 indicates. And, as block 132 indicates, any reference contained in the evacuated object is processed, in an operation that FIGS. 1A and 1B (together, “FIG. 11”) depict. For each one of the evacuated object's references, the collector determines whether the location that it refers to is in the collection set. As blocks 134 and 136 indicate, the reference processing continues until all references in the evacuated object have been processed. In the meantime, if a reference refers to a collection-set location that contains an object not yet evacuated, the collector evacuates the referred-to object to the train to which the evacuated object containing the reference was evacuated, as blocks 138 and 140 indicate. If the reference refers to a location in the collection set from which the object has already been evacuated, then the collector uses the forwarding pointer left in that location to update the reference, as block 142 indicates. Before the processing of FIG. 11, the remembered set of the referred-to object's car will have an entry that identifies the evacuated object's old location as one containing a reference to the referred-to object. But the evacuation has placed the reference in a new location, for which the remembered set of the referred-to object's car may not have an entry. So, if that new location is not as far forward as the referred-to object, the collector adds to that remembered set an entry identifying the reference's new region, as blocks 144 and 146 indicate. As the drawings show, the same type of remembered-set update is performed if the object referred to by the evacuated reference is not in the collection set. Now, some train-algorithm implementations postpone processing of the references contained in evacuated collection-set objects until after all directly reachable collection-set objects have been evacuated. In the implementation that FIG. 10 illustrates, though, the processing of a given evacuated object's references occurs before the next object is evacuated. So FIG. 11's blocks 134 and 148 indicate that the FIG. 11 operation is completed when all of the references contained in the evacuated object have been processed. This completes FIG. 10's object-evacuation operation, which FIG. 9's block 124 represents. As FIG. 9 indicates, each collection-set object referred to by a reference in a remembered-set-entry-identified location is thus evacuated if it has not been already. If the object has already been evacuated from the referred-to location, the reference to that location is updated to point to the location to which the object has been evacuated. If the remembered set associated with the car containing the evacuated object's new location does not include an entry for the reference's location, it is updated to do so if the car containing the reference is younger than the car containing the evacuated object. Block 150 represents updating the reference and, if necessary, the remembered set. As FIG. 8's blocks 112 and 114 indicate, this processing of collection-set remembered sets is performed initially only for entries that do not refer to locations in the oldest train. Those that do are processed only after all others have been, as blocks 152 and 154 indicate. When this process has been completed, the collection set's memory space can be reclaimed, as block 164 indicates, since no remaining object is referred to from outside the collection set: any remaining collection-set object is unreachable. The collector then relinquishes control to the mutator. FIGS. 12A–12J illustrate example results of using the train algorithm. FIG. 12A represents a generation in which objects have been allocated in nine car sections. The oldest train has four cars, numbered 1.1 through 1.4. Car 1.1 has two objects, A and B. There is a reference to object B in the root set (which, as was explained above, includes live objects in the other generations). Object A is referred to by object L, which is in the third train's sole car section. In the generation's remembered sets 170, a reference in object L has therefore been recorded against car 1.1. Processing always starts with the oldest train's earliest-added car, so the garbage collector refers to car 1.1's remembered set and finds that there is a reference from object L into the car being processed. It accordingly evacuates object A to the train that object L occupies. The object being evacuated is often placed in one of the selected train's existing cars, but we will assume for present purposes that there is not enough room. So the garbage collector evacuates object A into a new car section and updates appropriate data structures to identify it as the next car in the third train. FIG. 12B depicts the result: a new car has been added to the third train, and object A is placed in it. FIG. 12B also shows that object B has been evacuated to a new car outside the first train. This is because object B has an external reference, which, like the reference to object A, is a reference from outside the first train, and one goal of the processing is to form trains into which there are no further references. Note that, to maintain a reference to the same object, object L's reference to object A has had to be rewritten, and so have object B's reference to object A and the inter-generational pointer to object B. In the illustrated example, the garbage collector begins a new train for the car into which object B is evacuated, but this is not a necessary requirement of the train algorithm. That algorithm requires only that externally referenced objects be evacuated to a newer train. Since car 1.1 no longer contains live objects, it can be reclaimed, as FIG. 12B also indicates. Also note that the remembered set for car 2.1 now includes the address of a reference in object A, whereas it did not before. As was stated before, remembered sets in the illustrated embodiment include only references from cars further back in the order than the one with which the remembered set is associated. The reason for this is that any other cars will already be reclaimed by the time the car associated with that remembered set is processed, so there is no reason to keep track of references from them. The next step is to process the next car, the one whose index is 1.2. Conventionally, this would not occur until some collection cycle after the one during which car 1.1 is collected. For the sake of simplicity we will assume that the mutator has not changed any references into the generation in the interim. FIG. 12B depicts car 1.2 as containing only a single object, object C, and that car's remembered set contains the address of an inter-car reference from object F. The garbage collector follows that reference to object C. Since this identifies object C as possibly reachable, the garbage collector evacuates it from car set 1.2, which is to be reclaimed. Specifically, the garbage collector removes object C to a new car section, section 1.5, which is linked to the train to which the referring object F's car belongs. Of course, object F's reference needs to be updated to object C's new location. FIG. 12C depicts the evacuation's result. FIG. 12C also indicates that car set 1.2 has been reclaimed, and car 1.3 is next to be processed. The only address in car 1.3's remembered set is that of a reference in object G. Inspection of that reference reveals that it refers to object F. Object F may therefore be reachable, so it must be evacuated before car section 1.3 is reclaimed. On the other hand, there are no references to objects D and E, so they are clearly garbage. FIG. 12D depicts the result of reclaiming car 1.3's space after evacuating possibly reachable object F. In the state that FIG. 12D depicts, car 1.4 is next to be processed, and its remembered set contains the addresses of references in objects K and C. Inspection of object K's reference reveals that it refers to object H, so object H must be evacuated. Inspection of the other remembered-set entry, the reference in object C, reveals that it refers to object G, so that object is evacuated, too. As FIG. 12E illustrates, object H must be added to the second train, to which its referring object K belongs. In this case there is room enough in car 2.2, which its referring object K occupies, so evacuation of object H does not require that object K's reference to object H be added to car 2.2's remembered set. Object G is evacuated to a new car in the same train, since that train is where referring object C resides. And the address of the reference in object G to object C is added to car 1.5's remembered set. FIG. 12E shows that this processing has eliminated all references into the first train, and it is an important part of the train algorithm to test for this condition. That is, even though there are references into both of the train's cars, those cars' contents can be recognized as all garbage because there are no references into the train from outside of it. So all of the first train's cars are reclaimed. The collector accordingly processes car 2.1 during the next collection cycle, and that car's remembered set indicates that there are two references outside the car that refer to objects within it. Those references are in object K, which is in the same train, and object A, which is not. Inspection of those references reveals that they refer to objects I and J, which are evacuated. The result, depicted in FIG. 12F, is that the remembered sets for the cars in the second train reveal no inter-car references, and there are no inter-generational references into it, either. That train's car sections therefore contain only garbage, and their memory space can be reclaimed. So car 3.1 is processed next. Its sole object, object L, is referred to inter-generationally as well as by a reference in the fourth train's object M. As FIG. 12G shows, object L is therefore evacuated to the fourth train. And the address of the reference in object L to object A is placed in the remembered set associated with car 3.2, in which object A resides. The next car to be processed is car 3.2, whose remembered set includes the addresses of references into it from objects B and L. Inspection of the reference from object B reveals that it refers to object A, which must therefore be evacuated to the fifth train before car 3.2 can be reclaimed. Also, we assume that object A cannot fit in car section 5.1, so a new car 5.2 is added to that train, as FIG. 12H shows, and object A is placed in its car section. All referred-to objects in the third train having been evacuated, that (single-car) train can be reclaimed in its entirety. A further observation needs to be made before we leave FIG. 12G. Car 3.2's remembered set additionally lists a reference in object L, so the garbage collector inspects that reference and finds that it points to the location previously occupied by object A. This brings up a feature of copying-collection techniques such as the typical train-algorithm implementation. When the garbage collector evacuates an object from a car section, it marks the location as having been evacuated and leaves the address of the object's new location. So, when the garbage collector traces the reference from object L, it finds that object A has been removed, and it accordingly copies the new location into object L as the new value of its reference to object A. In the state that FIG. 12H illustrates, car 4.1 is the next to be processed. Inspection of the fourth train's remembered sets reveals no inter-train references into it, but the inter-generational scan (possibly performed with the aid of FIG. 6's card tables) reveals inter-generational references into car 4.2. So the fourth train cannot be reclaimed yet. The garbage collector accordingly evacuates car 4.1's referred-to objects in the normal manner, with the result that FIG. 12I depicts. In that state, the next car to be processed has only inter-generational references into it. So, although its referred-to objects must therefore be evacuated from the train, they cannot be placed into trains that contain references to them. Conventionally, such objects are evacuated to a train at the end of the train sequence. In the illustrated implementation, a new train is formed for this purpose, so the result of car 4.2's processing is the state that FIG. 12J depicts. Processing continues in this same fashion. Of course, subsequent collection cycles will not in general proceed, as in the illustrated cycles, without any reference changes by the mutator and without any addition of further objects. But reflection reveals that the general approach just described still applies when such mutations occur. As was mentioned above, incremental collection is helpful in keeping pause times low. Still, it exacts some efficiency costs, since many unreachable objects cannot immediately be recognized as such. The resultant inefficiency tends to be less when collection sets are larger, so it is helpful to choose a collection set whose size is the greatest value that is not inconsistent with the desired pause-time limit. Unfortunately Unfortunately, the time required to collect a given-size collection set varies greatly. There are a number of reasons for this, but a principal reason is the variability in remembered-set size. At any given time, there may be a relatively large number of references to objects in one car section and a relatively small number of references to objects in a different car section. Moreover, different rates of mutation result in different numbers of “stale” remembered-set entries. A remembered-set entry is made whenever, as a result of a reference modification, the collector finds a reference into the car with which the remembered set is associated. But an entry is not removed from a given car section's remembered set when a reference is so modified as no longer to refer to an object in that car section: the entry becomes stale. When a car section comes up for collection, the collector must inspect all of the locations that the car section's remembered set entries identify. Even if there currently are not many references to objects in a given car section, therefore, the operation of inspecting all of the remembered-set-identified locations can take a long time, because the remembered set may contain a great many stale entries.

Alterations in neural cardiovascular control mechanisms with ageing. AGEING AND MECHANISMS OF BLOOD PRESSURE CONTROL: Ageing is associated with functional and structural alterations to the cardiovascular system. Evidence is accumulating, however, that ageing also determines major changes in the effectiveness of mechanisms involved in blood pressure control and that this represents an important determinant of the cardiovascular changes that can be observed in the elderly. DIFFERENCES SEEN IN ELDERLY SUBJECTS: It has been observed that compared to young subjects, in the elderly (1) baroreceptor control of the heart rate and cardiac function is impaired; (2) baroreceptor modulation of the sympathetic drive to the peripheral circulation is impaired, particularly the speed of reflex adjustments to normal and abnormal stimuli; and (3) cardiopulmonary stretch receptors, which tonically inhibit sympathetic tone, the renal release of renin and vasopressin secretion, are impaired. These three factors may account, at least in part, for the raised blood pressure and sympathetic activity in the elderly. They certainly explain the reduced ability of elderly people to maintain blood pressure and blood volume homeostasis, and their increased blood pressure variability over 24 h. ASSOCIATION WITH HYPERTENSION: All these problems are exacerbated if ageing is associated with hypertension, and are highly relevant to antihypertensive treatment. Care should be taken that any antihypertensive drugs selected for treatment in the elderly do not aggravate these basic homeostatic problems.

The Leishmania spp. protozoa have a profound effect on the host cell that they invade. These parasites reside intracellularly usually in macrophages, a cell type with the capacity to kill intracellular microbes. Rather than succumb, Leishmania paralyze the microbicidal pathways of the host cell, changing the macrophage from a lethal cell to an intracellular safe haven which allows the parasite to survive, replicate and ultimately spread to neighboring cells. The mechanism(s) through which the parasite paralyzes the host microbicidal function is incompletely understood. It has recently come to light that most eukaryotic organisms utilize short noncoding RNA sequences to globally regulate expression of a wide variety of genes. Indeed short RNA sequences of 18-30 bp in length, called microRNAs, are critical for regulating expression of an estimated 30% of the human genome. The hypothesis underlying this proposal is that microRNAs are the upstream trigger(s) determining which pattern of macrophage activation will occur after Leishmania infection. We will address the following questions. (1) What microRNAs does the parasite usually induce or suppress during infection of macrophages? (2) Which microRNAs are induced in response to stimuli that activate macrophage toward different polar phenotypes? (3) Is there overlap between the microRNAs discovered in Aims 1 and 2, and what is the effect of experimental manipulation of these microRNAs on Leishmania-infected macrophages? Specific aims of the proposal are: 1. To perform a global profiling of changes in microRNA expression induced in response to phagocytosis of L. chagasi by human macrophages. 2. To use a similar profiling approach to determine which microRNAs are induced in response to macrophage activation toward different polarized phenotypes. Of primary interest will be the microRNA changes that occur during M1 (classical) activation with reciprocal changes in other forms of macrophage activation, since classically activated macrophages can kill intracellular Leishmania. 3. To correlate the results of Aims 1 and 2, and to selectively either overexpress or suppress macrophage expression of selected microRNAs that may change in the pattern of macrophage activation or intracellular parasite growth.

Medical student illness and impairment: a vignette-based survey study involving 955 students at 9 medical schools. Physician impairment is defined by the presence of a physical, mental, or substance-related disorder that interferes with the ability to practice medicine competently and safely. The seeds of impairment may be sown early in adulthood, and medical students experience health issues that may receive insufficient attention in the context of a rigorous training period. Few empirical studies have examined the attitudes of medical students toward recognizing and acting upon signs of potentially impairing illnesses in peers. Medical students at 9 medical schools were invited to participate in a written survey exploring personal health care issues during training. As part of this larger project, students were asked to imagine their response in 3 situations to a medical student who is discovered to have serious symptoms and potential impairment secondary to mental illness, substance abuse, or diabetes. Responses were gathered from 955 students (52% overall response rate). For all of the vignettes, "tell no one but encourage him/her to seek professional help" was the most prevalent reaction (45%, 53%, and 49%, respectively) as opposed to seek advice (37%, 35%, and 42%) and notify the Dean's office (18%, 12%, and 9%). Willingness to report varied by school, and women were somewhat less likely to formally report medical student illness. This study suggests that medical students attach great importance to preserving the confidentiality of fellow medical students who may experience even very severe symptoms. This pattern may have important implications for the early recognition and treatment of potentially impairing disorders. Greater attention to these issues may help assure the health of early career physicians as well as the many patients whose safety and well-being are entrusted to their care.

Highly sensitive and robust peroxidase-like activity of porous nanorods of ceria and their application for breast cancer detection. Porous nanorods of ceria (PN-Ceria), a novel ceria nanostructure with a large surface area and a high surface Ce(3+) fraction, exhibited strong intrinsic peroxidase activity toward a classical peroxidase substrate in the presence of H2O2. Peroxidase-like activity of ceria originated from surface Ce(3+) species as the catalytic center, thereby explaining the high performance of PN-Ceria as an artificial enzyme mimicking peroxidase. Compared with the natural enzyme horseradish peroxidase (HRP), PN-Ceria showed several advantages such as low cost, easy storage, high sensitivity, and, prominently, chemical and catalytic stability under harsh conditions. Importantly, the enzymatic activity of PN-Ceria remained nearly constant and stable over a wide range of temperature and pH values, ensuring the accuracy and reliability of measurements of its peroxidase-like activity. A PN-Ceria based novel diagnostic system was developed for breast cancer detection with a higher sensitivity than the standard HRP detection system. Our work has laid a solid foundation for the development of PN-Ceria as a novel diagnostic tool for clinical use.

In the manufacture of integrated circuits (chips) it is well known that it is desirable to encapsulate the chip in order to protected the chip from mechanical damage and contamination. Encapsulation techniques are also known to passivate the chips an enhance their long term performance. There are a variety of well known techniques available for encapsulating chips. These techniques include mounting chips within a cavity of a substrate or a die structure, wire bonding chips to a lead frame and then enclosing the package with a lid. Another technique includes mounting chips to a lead frame, wire bonding the chips to the lead frame and then passivating the chips and a portion of the lead frame in a molded plastic or plastic epoxy body. Yet another technique for packaging and passivating chips includes “flip-chip” bonding to a printed circuit board and then covering the chips with a plastic resin. There are several applications where the above mentioned packaging and passivation techniques are inadequate because the materials used to form the packaging are opaque and/or do not provide an optical window of suitable quality for optical applications. For example, such packaging is unsuitable for EPROM devices. An EPROM device is a read-only memory device. The program or data which is stored in an EPROM can only be erased through optical radiation (ultraviolet and/or visible) impinging on the surface of the EPROM. Conventional opaque chip packaging does not allow for such a device to be erased optically and, therefore, is unsuitable for packaging these devices. To solve this problem, makers of EPROM devices mount EPROM chips within the cavity of a ceramic package and hermetically seal the assembly with an optically transparently lid. Micro-electro-mechanical devices (MEM devices) are another class of silicon semiconductors devices. MEM devices are useful for a variety of applications including strain gauges, accelerometers, electronic levels, and also for display light valves or other optical applications. Because of their extremely small moving parts, MEM devices are particularly susceptible to ambient conditions. Accordingly, MEM devices are traditionally sealed within the cavity of a hermetic package to control the operating environment to which the MEM is subjected. When the MEM device is an optical MEM device, as for example in the case of display applications, the MEM device is required to be accessed optically through the packaging, wherein optical energy penetrates the package, impinges on a surface of the MEM device, and where the optical energy is reflected and/or modulated and then escapes from the package forming the optical image or signal. Though conventional ceramic packages can be hermetic, they also tend to be opaque and are, therefore, unsuitable for use with a variety of optical MEM devices. A package which includes an optically transparent window can represent a considerable portion of the manufacturing cost for making an optical MEM device. Under certain circumstances it is important to provide a package which has an optical window of suitable optical quality which has a controlled physical relationship relative to another portion of the MEM device, such as a mechanically active portion of the MEM device or the substrate of the MEM device. Specifically, in some applications it is important to position a transparent lid at an angle relative to an optical element or elements of the MEM device to reduce surface reflections from the optically transparent window, where reflections can interfere with the intended image and/or signal. Conventional silicon semiconductor chip packaging technology does not provide for the ability to control the physical relationship of a transparent window/lid with respect to other portions of a MEM device. Therefore, there is a need for a MEM device with an optical widow that can be controllably positioned at an angle relative to other portions of the MEM device, and in particular at an angle relative the reflective surface(s) of one or more encapsulated optical elements of the MEM device, and a method for making the same.

The present invention relates to a communication apparatus and a communication method of a multi carrier transmission system, and in particular, to a communication apparatus and a communication method using a multi carrier transmission method (Digital Wavelet Multi Carrier-transmission system, hereinafter, described as “DWMC transmission system”) which carries out data transmission by digital modulating and demodulating processing with the use of a real coefficient wavelet filter bank. In a terrestrial digital broadcasting system etc., wide band data transmission is enabled by a multi carrier transmission system with the use of OFDM (Orthogonal Frequency Division Multiplexing). As a data transmission system depending on this type of the multi carrier transmission system with the use of OFDM, a multi carrier transmission method depending on digital modem processing with the use of a real coefficient wavelet filter bank (DWMC transmission method) has been proposed. In the DWMC transmission method, a plurality of digital modulated waves are combined by use of the real coefficient filter bank, and thereby, transmission signals are generated. As a modulation system of each carrier, PAM (Pulse Amplitude Modulation) etc. are used. Data transmission, which depends on the DWMC transmission method, will be described by use of FIGS. 15 to 18. FIG. 15 is a view which shows an example of an wavelet wave form, and FIG. 16 is a view which shows an example of a transmission wave form in the DWMC transmission method, and FIG. 17 is a view which shows an example of a transmission spectrum in the DWMC transmission method, and FIG. 18 is a view which shows a configuration example of a transmission frame in the DWMC transmission method. In the data transmission which depends on the DWMC transmission method, as shown in FIG. 15, impulse responses of each sub carrier are transmitted over being overlapped in each sub carrier. Each transmission symbol becomes such a time wave form that impulse responses of each sub carrier were combined, as shown in FIG. 16. An example of an amplitude spectrum is shown in FIG. 17. In the DWMC transmission method, approximately several dozen through several hundred of transmission symbols in FIG. 16 are collected to configure one transmission frame. A configuration frame of the DWMC transmission frame is shown in FIG. 18. In this DWMC transmission frame, a symbol for frame synchronization, a symbol for equalization etc. are included in addition to a symbol for information data transmission. FIG. 19 is a block diagram which shows a conceptual configuration of a communication apparatus as a past example, which is configured by having a transmitting device and a receiving device in case that the DWMC transmission system was adopted. In FIG. 19, a receiving device 199 is configured by having an A/D converter 110 which carries out analog-digital conversion, a wavelet transform unit 120 which carries out discrete wavelet transformation, a parallel/serial (P/S) converter 130 which converts parallel data into serial data, and a decision unit 140 which carries out judgment of received signals. A transmitting device 299 is configured by having a symbol mapper 210 which converts bit data into symbol data to carry out symbol mapping, a serial/parallel (S/P) converter 220 which converts serial data into parallel data, an inverse wavelet transform unit 230 which carries out inverse discrete wavelet transformation, and a D/A converter 240 which carries out digital-analog conversion. An operation of the communication apparatus with the above-described configuration will be described. Firstly, in the transmitting device 299, bit data of transmission data is converted into symbol data by the symbol mapper 210, and symbol mapping (PAM) is carried out in accordance with each symbol data. Then, serial data is converted into parallel data by the S/P converter 220, and thereby, a real number value di (i=1˜M, M is a plural number) is given to symbol data with respect to each sub carrier. After that, this real number value is inverse discrete wavelet transformed on a time axis by the inverse wavelet transform unit 230. By this means, sample values of time axis wave forms are generated, and a sample value series, which represents transmission symbols, is generated. Then, this sample value series is converted into analog base band signal wave forms which are continuing in terms of time by the D/A converter 240, and then, transmitted. Here, the number of sample values on a times axis, which are generated by the inverse discrete wavelet transformation, is normally 2 to the n-th power pieces (n is a positive integer). In the receiving device 199, analog base band signal wave forms, which are obtained from received signals, are sampled with the same sample rate as that of a transmitting side by the A/D converter 110, to obtain a sample value series. Then, this sample value series is discrete wavelet transformed on a frequency axis by the wavelet transform unit 120, and parallel data is converted into serial data by the P/S converter 130. Finally, an amplitude value of each sub carrier is calculated in the decision unit 140, and judgment of a received signal is carried out to obtain reception data. In addition, as an example of the communication apparatus with the use of the DWMC transmission method, proposed is a power line carrier communication apparatus which carries out data transmission by utilizing a power line which were disposed in a house etc., as communication medium (e.g., see, JP-A-2003-218831). In the meantime, in the multi carrier transmission system, there is a case to dispose a pilot symbol for transmitting a pilot signal by use of a sine wave signal in a predetermined symbol, in order to carry out adjustment etc. of a phase of transmission data. By information of this pilot symbol, it becomes possible to adjust an amplitude and a phase of transmission data, and to improve an equalization characteristic of a channel characteristic (compensation of a transmission characteristic, etc.) between a transmitting device and a receiving device. A past multi carrier transmission system with the use of FFT (Fast Fourier Transform) based OFDM is one which carries out FFT as complex number conversion, and therefore, it is possible to generate a pilot symbol having complex information which represents an amplitude and a phase, only by transmitting a known signal (e.g., a signal in which identical data such as all 1 continues) by use of one symbol, in case of disposing a pilot symbol (e.g., see, JP-A-2000-278237). In contrast to this, a multi carrier transmission system, which depends on wavelet transformation based OFDM to be used in the DWMC transmission method, is one which carried out wavelet transformation as real number conversion, and in addition, even if a pilot symbol, which was simply configured by one symbol, is demodulated, it is not possible to obtain complex information since a filter length is longer than a symbol length, and therefore, in the multi carrier transmission system which depends on wavelet transformation based OFDM, a pilot symbol was not used.

This invention relates to a method for the preparation of emulsions of oil in water and more particularly the preparation of high internal phase ratio (HIPR) emulsions of viscous oils in water. Many crude oils are viscous when produced and are thus difficult, it not impossible, to transport by normal methods from their production location to a refinery. Several methods have been suggested for the transportation of such crudes by pipeline. These include (1) heating the crude and insulating the pipeline, (2) adding a non-recoverable solvent, (3) adding a recoverable solvent, (4) adding a lighter crude oil, (5) forming an annulus of water around the crude and (6) emulsifying the crude in water. Methods (1)-(4) can be expensive in terms of added components and capital expenditure and method (5) is technically difficult to achieve. Method (6) whilst superficially attractive presents special difficulties. The dispersion of a highly viscous oil in a medium of much lower viscosity is an unfavorable process on hydrodynamic grounds. This problem is further complicated by the economic requirement to transport emulsions containing relatively high oil phase volumes without sacrificing emulsion fluidity. Mechanical dispersing can lead to the formation of polydisperse or multiple emulsions, both of which are less suitable for transportation. In the case of a system comprising dispersed spheres of equal size, the maximum internal phase volume occupied by a hexagonally close-packed arrangement is ca 74%. In practice, however, emulsions are rarely monodisperse and it is therefore possible to increase the packing density without causing appreciable droplet distortion. Attempts to increase further the internal phase volume results in greater droplet deformation and, because of the larger interfacial area created, instability arises; this culminates in either phase inversion or emulsion breaking. Under exceptional circumstances, it is possible to create dispersions containing as high as 98% disperse phase volume without inversion or breaking. Emulsified systems containing 70% internal phase are known as HIPR emulsions. HIPR oil-in-water emulsions are normally prepared by dispersing increased amounts of oil into the continuous phase until the internal phase volume exceeds 70%. Clearly, for very high internal phase volumes, the systems cannot contain discrete spherical oil droplets; rather, they will consist of highly distorted oil droplets, separated by thin interfacial aqueous films. A useful state-of-the-art review of HIPR emulsion technology is given in Canadian Patent No. 1,132,908. British Patent Specification No. 1,283,462 discloses a method for producing an oil-in-water emulsion comprising beating up a mixture of the oil and water together with emulsifying agent in a vessel having a bottom exit to disperse the oil in droplets of an average size of not more than 10 microns in diameter throughout the water to form a concentrated emulsion, continuously withdrawing concentrated emulsion from the bottom exit of the vessel while simultaneously introducing components of the mixture into the top of the vessel to form further concentrated emulsion. The oils are synthetic polymers or thickened animal or vegetable oils. The action of the beater results in particle sizes in the dispersed phase of not more than 10 microns in diameter, usually from about 0.5 to 2 microns in diameter. The concentration of surfactant used is relatively high, 4-10% by weight of the total composition. This results in concentrated, thick, extremely stable emulsions which have thixotropic properties and are useful as vehicles for paints or other coatings. While U.S. Pat. No. 1,283,462 discloses that the concentrated emulsions are discharged through a short conduit from the emulsifying vessel to a tank in which they are further diluted, the concentrated emulsions are not suitable, nor are they intended, for transportation over long distances through relatively large diameter pipelines such as those used for the transportation of crude oil. Furthermore, because of their extreme stability these emulsions cannot be, and are not intended to be, readily broken. Thus, they are unsuitable for applications where it is desired eventually to resolve the emulsions into their constituent parts, such as the treatment of crude oil where water must be removed before fractionation in an oil refinery distillation unit.

1. Field of the Invention The present invention relates to an embedded semiconductor device substrate having a semiconductor device buried in an insulating resin layer of a printed wiring board, and a method of producing the same. 2. Description of the Related Art In recent years, the semiconductor package having a semiconductor device mounted therein has been continuously reduced in size and weight. Therefore, there has been increasing adopted a structure in which an electrode portion of a semiconductor package is formed into an area array, such as BGA (Ball Grid Array) and CSP (Chip Scale Package). Furthermore, not only a two-dimensional size reduction such as the BGA and CSP, but also a multi chip package in which a plurality of semiconductor devices are stacked in a single package has been proposed such as disclosed in Japanese Patent Application Laid-Open No. H11-3970. On the other hand, in addition to such size reduction of semiconductor packages, an embedded semiconductor device substrate having a semiconductor device buried inside of a printed wiring board has been proposed such as disclosed in Japanese Patent Application Laid-Open No. H09-321408. In the embedded semiconductor device substrate disclosed in Japanese Patent Application Laid-Open No. H09-321408, a semiconductor device having stud bumps formed thereon is mounted in a recessed portion formed beforehand on a printed wiring board, and an insulating layer is then formed so as to cover the semiconductor device. However, in the embedded semiconductor device substrate described in Japanese Patent Application Laid-Open No. H09-321408, since a routering is necessary for forming a recessed portion in a printed wiring board, which increases the processing time remarkably. In addition, in order to bury a semiconductor device, it is necessary to form a holding surface for holding the semiconductor device at a bottom of the recessed portion, and an insulating layer is needed for the holding surface. In consequence, the thickness of the embedded semiconductor device substrate having the semiconductor device varied therein becomes very large, which makes the size reduction difficult. So, there has been proposed a method which does not form a recessed portion beforehand in a printed wiring board but buries a semiconductor device during production of a printed wiring board to thereby produce an embedded semiconductor device substrate, in Japanese Patent Application Laid-Open No. 2004-335641. The production method disclosed therein will be explained with reference to FIGS. 10A to 10F. First, as shown in FIG. 10A, a semiconductor device 101 is mounted through an insulating epoxy resin 104 on a Cu foil 103. Next, as shown in FIG. 10B, a prepreg material 105 is disposed at such a location that an opening 105a of the prepreg materiel 105 contains the semiconductor device 101. The prepreg material 105 has approximately the same thickness as the thickness of the semiconductor device 101, and the opening 105a having a shape corresponding to the shape of the semiconductor device 101 is formed with a punching press. In addition, on the prepreg material 105, there is put an RCC (Resin Coated Cupper) material 107 having an epoxy resin 106 as an insulating resin coated on a Cu foil 103a. The Cu foil 103, prepreg material 105, and RCC material 107 (epoxy resin 106/cupper foil 103a) are disposed by stacking in this way, and are subjected to thermocompression bonding in a vacuum atmosphere as shown in FIG. 10C. Next, as shown in FIG. 10D, a part of the Cu foil 103a corresponding to an electrode portion 102 on the semiconductor device 101 is removed by ordinary etching to form a hole portion. Then, a part of the epoxy resin 106 which is exposed via the hole portion is removed by a laser such as a CO2, YAG, or excimer laser to form an opening 108, whereby the electrode portion 102 of the semiconductor device 101 is exposed therethrough. Next, as shown in FIG. 12E, while a Cu layer 103b is formed on the entire surface by plating, the opening 108 is filled with the Cu layer 103b. Subsequently, a resist material is coated on the Cu layer 103b, and a wiring pattern is formed in an exposure step through a mask and a development step, so that the embedded semiconductor device substrate having the semiconductor device 101 integrated therein as shown in FIG. 10F is obtained. In the embedded semiconductor device substrate disclosed in Japanese Patent Application Laid-Open No. 2004-335641 above, by forming an opening accurately by use of a laser, electrodes of a semiconductor device are exposed outside. Furthermore, by etching a Cu layer formed on a printed wiring board by use of a mask, a wiring pattern connected to the electrodes is formed. Hence, there is required an etching accuracy of such an extent as to surely connect the electrodes of the semiconductor device and the wiring pattern on the printed wiring board to each other. On the other hand, since a large number of semiconductor devices are produced from a single semiconductor wafer, there are differences between individual semiconductor devices obtained therefrom, and there are positional errors between the individual semiconductor devices also with regard to electrode positions. Furthermore, there will be necessarily generated a mounting error within a predetermined range in the mounting position of a semiconductor device to a printed wiring board. Therefore, there is generated a displacement with respect to a design position between the patterning position of a wiring pattern, and the position of an electrode of a semiconductor device. Generally, in prospect of this displacement, the patterning using a mask is made so as to provide a pattern shape with a predetermined amount of margin. Nevertheless, as the pitch of electrodes of a semiconductor device is reduced, it becomes impossible to take a sufficient margin to avoid interference with an adjacent wiring pattern. That is, it becomes difficult to allow the above described errors when mounting semiconductor devices to a printed wiring board and positional errors of electrodes between individual semiconductor devices, by means of a margin of a pattern shape. Thereby, the electrodes of the semiconductor devices and the wiring on the printed wiring board will not be connected. Such a situation becomes significant as the pitch between electrodes of a semiconductor device is reduced, and it is believed that it will become a more serious problem in the future.

The prognostic significance of DNA ploidy in clinically localized prostate cancer treated with radiation therapy. To determine the prognostic significance of deoxyribonucleic acid (DNA) ploidy in comparison to pretreatment prostate specific antigen (PSA) and other prognostic factors for patients with adenocarcinoma of the prostate treated with external beam radiotherapy. Paraffin-embedded prostatic adenocarcinoma material was obtained from patients treated from 1987-1991. Sufficient histologic material for flow cytometric DNA content analysis was obtained from 86 patients and adequate histograms were obtained from 76 of these. The DNA histogram profiles were classified as diploid, tetraploid, or aneuploid. Median patient follow-up was 36 months. There were 54 patients with diploid tumors, and 22 with nondiploid tumors (11 tetraploid and 11 aneuploid). Since the disease outcome for tetraploid and aneuploid tumors was the same, these were pooled (nondiploid tumors). The distribution of diploidy and nondiploidy correlated with pretreatment PSA (p < 0.0005) and grade (p = 0.055), but not with stage, pretreatment prostatic acid phosphatase, transurethral resection, pretreatment serum testosterone, or age. In actuarial univariate analyses, DNA ploidy was a significant predictor of outcome for local failure, distant metastases, any clinical relapse, rising PSA, and rising PSA and/or relapse. Ploidy was not a significant predictor of overall survival, although there were only six deaths. Diploidy predicted for improved outcome, for example, 34.6% incidence of a rising PSA and/or relapse at 4 years compared to 76.9% with nondiploidy (p < 0.0001). An actuarial univariate analysis of other potential prognostic factors using the composite endpoint of rising PSA and/or relapse also revealed pretreatment PSA, grade, pretreatment prostatic acid phosphatase, stage, and serum testosterone to be significant predictors of outcome. In Cox proportional hazards analysis, pretreatment PSA, DNA ploidy, and grade were the only independent prognostic factors for disease outcome using the composite endpoint. DNA ploidy is an independent predictor of outcome in patients with Stages T1-T3 prostate cancer treated with definitive external beam radiotherapy.

Thinking and caring about cognitive inconsistency: when and for whom does attitudinal ambivalence feel uncomfortable? The relation between conflicting evaluations of attitude objects (potential ambivalence) and associated unpleasant feelings (felt ambivalence) was investigated. Participants indicated their potential and felt ambivalence about capital punishment (Studies 1 and 2) and abortion (Studies 1-3). The simultaneous accessibility (J. N. Bassili, 1996) of participants' potential ambivalence (i.e., how quickly and equally quickly conflicting evaluations came to mind) was measured using response latency (Studies 1-3) and manipulated by repeated expression (Study 3). The relation between potential ambivalence and felt ambivalence was strongest when potential ambivalence was high in simultaneous accessibility (Studies 1-3). This pattern was most pronounced for participants who were high in preference for consistency (Study 3; R. B. Cialdini, M. R. Trost, & T. J. Newsom, 1995). Similarities of ambivalence and cognitive dissonance constructs are discussed.

Genes and their associated enzymatic complexes govern the main pathways of autophagy. Macroautophagy is the pathway for removal of degraded or damaged proteins and organelles at a cellular level. Modulation of this highly specific process has been a general approach toward the treatment of diseases associated with cellular over-accumulation of some misfolded proteins. Whereas the other major protein clearance pathway, the ubiquitin proteasome pathway, is unable to degrade aggregated proteins (normal or misfolded), autophagy can engulf and clear protein aggregates as well as monomeric proteins. Misfolded proteins, as monomers or in aggregates, can cause neurodegeneration by using up critical components of the chaperone-protein folding processes and protein clearance pathways, leading to additional protein misfolding and the loss of function of a variety of essential proteins. Aggregates may also cause direct damage to organelles and interfere with an array of cellular functions such as transcription and axonal transport. Likewise, abberant autophagy is implicated in various cancers. Thus, compositions and methods which stimulate the autophagic clearance of misfolded proteins and/or protein aggregates is of considerable interest. An illustrative example of neurodegenerative disorders related to cellular over-accumulation of misfolded proteins is Huntington's disease. Huntington's disease is categorized as a trinucleotide repeat disorder and caused by expansion of a repeated section of the gene, HTT, that encodes the protein HUNTINGTIN. Normal HUNTINGTIN protein contains a region referred to as the “PolyQ region”, which has a repeated sequence of the DNA triplet base cytosine-adenine-guanine (CAG), which codes for the amino acid glutamine (Q). A mutant HUNTINGTIN gene, mHTT, generates a mutant HUNTINGTIN protein with a PolyQ region containing greater than 36 glutamine residues. This mutant protein is misfolded and is also cleaved to produce numerous fragments. Both the misfolded protein and the fragments are contemplated to be particularly toxic. Accordingly, areas of the brain possessing cells with the mutant gene and correspondingly high likelihood and/or presence of misfolded protein are found to show a correspondingly higher incidence of adverse effects. Another example of a misfolded-protein associated disorder is Parkinson's disease. In Parkinson's patients, over-expression of the protein, α-SYNUCLEIN, can result from duplication or triplication of the SNCA gene locus and occurs for unknown reasons in the vast majority of Parkinson's patients, who develop the disease without any identifiable mutation. In addition, A53T and A30P point mutations of the gene have been demonstrated to trigger the early onset of Parkinson's. Further, over-expression of the wild type protein in transgenic mice and flies has been shown to cause progressive neuronal defects. The accumulation of α-SYNUCLEIN in misfolded and aggregated forms, is strongly associated with neuronal dysfunction and death. Clearly, the homeostatic removal of misfolded proteins and/or protein aggregates is a prime therapeutic target for the treatment of Huntington's, Parkinson's, and other such related disorders. Examples of other disorders and diseases categorized as proteopathies include, but are not limited to: Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia of types 1, 2, 3, 6, 7 and 17, spinobullar muscular atrophy; dentatorubral-palli-doluysian atrophy, peripheral neuropathy, and dementia. Treatment of these types of diseases can be affected by the administration of an active pharmaceutical ingredient, which is capable of inducing autophagic removal of the particular toxic misfolded proteins and/or protein aggregates. Some bacterial and viral infections are treatable by autophagic upregulation, as well. Pathogens can be engulfed by autophagosomes and further disposed of by lysosomes. Streptococcus (Group A) and Herpes virus (Type I) are important examples of pathogens, although not limiting, that are susceptible to this kind of capture. There remains a need for compounds that are effective stimulants of autophagic removal of misfolded proteins and/or protein aggregates and such compounds can be used in treating neurodegenerative disorders. Compounds that induce neuronal autophagy and can be used to treat and prevent neurodegenerative disorders characterized by misfolded proteins and/or protein aggregates are provided herein.

The delivery of radio frequency (RF) energy to target regions within solid tissue is known for a variety of purposes of particular interest to the present invention. In one particular application, RF energy may be delivered to diseased regions (e.g., tumors) for the purpose of ablating predictable volumes of tissue with minimal patient trauma. RF ablation of tumors is currently performed using one of two core technologies. The first technology uses a single needle electrode, which when attached to a RF generator, emits RF energy from an exposed, uninsulated portion of the electrode. The second technology utilizes multiple needle electrodes, which have been designed for the treatment and necrosis of tumors in the liver and other solid tissues. U.S. Pat. No. 6,379,353 discloses such a probe, referred to as a LeVeen Needle Electrode™, which comprises a cannula and an electrode deployment member reciprocatably mounted within the delivery cannula to alternately deploy an electrode array from the cannula and retract the electrode array within the cannula. Using either of the two technologies, the energy that is conveyed from the electrode(s) translates into ion agitation, which is converted into heat and induces cellular death via coagulation necrosis. The ablation probes of both technologies are typically designed to be percutaneously introduced into a patient in order to ablate the target tissue. In the design of such ablation probes, which may be applicable to either of the two technologies, RF energy is often delivered to an electrode located on a distal end of the probe's shaft via the shaft itself. This delivery of RF energy requires the probe to be electrically insulated to prevent undesirable ablation of healthy tissue. In the case of a single needle electrode, all but the distal tip of the electrode is coated with an electrically insulative material in order to focus the RF energy at the target tissue located adjacent the distal tip of the probe. In the case of a LeVeen Needle Electrode™, RF energy is conveyed to the needle electrodes through the inner electrode deployment member, and the outer cannula is coated with the electrically insulative material to prevent RF energy from being transversely conveyed from the inner electrode deployment member along the length of the probe. The procedure for using the ablation probe requires the insulative coating to have sufficient durability. To illustrate, when designing RF ablation probes, it is desirable to make the profile of the probe shaft as small as possible, namely to have a smaller gauge size, in order to minimize any pain and tissue trauma resulting from the percutaneous insertion of the probe into the patient. Thus, it is advantageous for the electrically insulative material applied to the probes be as thin as possible. However, RF ablation probes are often introduced through other tightly toleranced devices that may compromise the integrity of the thinly layered insulation, thereby inadvertently exposing healthy tissue to RF energy. For example, probe guides are often used to point ablation probes towards the target tissue within a patient. A typical probe guide takes the form of a rigid cylindrical shaft (about 1-2 inches in length) that is affixed relative to and outside of a patient, and includes a lumen through which the ablation probe is delivered to the target tissue. To maximize the accuracy of the probe alignment, it is desirable that the guide lumen through which the probe is introduced be about the same size as the outer diameter of the probe, thereby creating a tight tolerance between the probe and the probe guide. As another example, ablation probes are also often used with co-access assemblies that allow several different devices, such as ablation probes, biopsy stylets, and drug delivery devices, to be serially exchanged through a single delivery cannula. To minimize pain and tissue trauma, it is desirable that the profile of the delivery cannula be as small as possible. To achieve this, the lumen of the delivery cannula will typically be the same size as the outer diameter of the ablation probe, thereby creating a tight tolerance between the probe and the delivery cannula. As a result, during the initial introduction of the probe through a delivery device, such as a probe guide or cannula of a co-access system, it is possible that a portion of the insulation may shear off as the probe is introduced through the delivery device. Consequently, the attending physician will either have to replace the probe with a new one or risk ablating healthy tissue. Thus, the durability of the insulative coating is critical to prevent damaging healthy tissue and/or having to discard the probe. Besides providing the insulation on the ablation probe with the necessary durability, it is also necessary to ensure that the distal end of the ablation probe, where the RF energy will be directed, is in contact with the target tissue. This may be achieved with an imaging device located outside the patient's body, such as an ultrasound imager. The echogenicity of the probe determines how well the probe may be located using ultrasound techniques. That is, the more echogenetic the ablation probe, the easier it is to determine the location of the probe with ultrasound imaging and to ensure accurate contact with the target tissue. To achieve greater echogenicity, it is known in the art, for example, to make marks or nicks along the shaft in order to increase the amount of edges and surfaces on the shaft, thereby creating a non-uniform surface profile. Echogenicity increases as the number of edges and surfaces for reflecting the ultrasound is increased. This technique may also be applied to insulative coating on the probe shaft. It is also known in the art to have air bubbles interspersed throughout the insulative coating in order to increase echgenicity. However, the inclusion of air bubbles may degrade the integrity of the insulative coating, which may also occur when marks or nicks are made in the insulative coating. Therefore, there is a need in the art for an ablation probe with an insulative coating having improved echogenicity for properly positioning the ablation device relative to the target tissue, while also having sufficient durability and size to remain intact during insertion and use of the ablation probe.

The S region of the murine histocompatibility complex (H-2) was defined almost 25 years ago as a genetic locus controlling the quantity of Ss (serum substance) in mouse serum. Subsequent work from a number of laboratories established that Ss is composed of two distinct proteins: C4, the murine fourth component of complement, and sex-limited protein (Slp), a protein that shares extensive structural and biochemical identity with C4 but which lacks C4 activity. Slp is notable in that its expression is testosterone-dependent and hence limited to males in some strains while in other strains expression is either independent of testosterone or conversely completely undetectable. Recent nucleic acid cloning and sequencing studies in our laboratory and others have demonstrated that C4 and Slp are encoded by distinct structural genes that lie in the S region and are doubtless the products of gene duplication. The goals of the proposed program are (a) to determine and compare the structural organization of the C4 and Slp genes; (b) to understand the structural and evolutionary relationships between these genes and other genes, in particular the class I and class II genes of the H-2 complex and the genes for the related complement proteins C3 and C5; and (c) to characterize the molecular mechanisms controlling sex-, tissue-, and strain- specific expression of the C4 and Slp genes. We propose to use recombinant DNA cloning and sequencing methods (a) to sequence the entire transcribed regions of the C4 and Slp genes; (b) to extend our study of upstream regions of the C4 and Slp genes by mapping restriction enzyme cleavage sites and by DNA sequencing; (c) to sequence regions upstream of the transcription initiation sites of C4 and Slp genes from mouse strains that exhibit varied C4 and Slp expression phenotypes; and (d) to use site-specific mutation and DNA reconstruction methods, together with methods for expression in cell culture to identify the gene segments responsible for regulating C4 and Slp expression.

Current handheld plasma cutting systems use a power supply coupled to a handheld cutting torch that has a trigger mechanism for initiating or stopping the cutting operation. However, this trigger mechanism is simply an “on/off” mechanism and when it is engaged the power supply activates to its set output. In many instances, users of handheld cutting systems “overuse” the system to cut workpieces of a thinner or weaker material than the system is designed for. For example, users would use a 100 amp cutting system to cut thin sheet metal, or thin aluminum but do not bother to reduce the output of the power supply. This usage typically results in very poor quality cuts, as the cutting energy is too high. Further limitations and disadvantages of conventional, traditional, and proposed approaches will become apparent to one of skill in the art, through comparison of such approaches with embodiments of the present invention as set forth in the remainder of the present application with reference to the drawings.

Utilization and effectiveness of medical rehabilitation in foreign nationals residing in Germany. In Germany, the proportion of foreign national residents receiving an invalidity pension is higher than that of Germans. Lower utilization and effectiveness of medical rehabilitation are presumed to be the main reasons. We aimed to examine whether differences in utilization and effectiveness of medical rehabilitation between Germans and foreign nationals are attributable to differences in socio-demography, socio-economic background and health status. Utilization of rehabilitation was analyzed for household members aged 18 years or above enrolled in the German Socio-Economic Panel in 2002-2004 (n = 19,521). Effectiveness of rehabilitation was defined by the occupational performance at the end of rehabilitation. It was examined by using an 80% random sample of all completed medical rehabilitations in the year 2006 funded by the German Statutory Pension Insurance Scheme (n = 634,529). Our study shows that foreign nationals utilize medical rehabilitation less often than Germans (OR = 0.68; 95%-CI = 0.50; 0.91). For those who do, medical rehabilitation is less effective (OR for low occupational performance = 1.50; 95%-CI = 1.46; 1.55). Both findings are only partially attributable to socio-demographic, socio-economic and health characteristics: After adjusting for these factors, ORs for utilization and low occupational performance were 0.66 (95%-CI = 0.49; 0.90) and 1.20 (95%-CI = 1.16; 1.24), respectively. It can be concluded that differences in the utilization and effectiveness of medical rehabilitation between Germans and foreign nationals cannot be explained only by socio-economic differences or poorer health before rehabilitation. In addition, factors such as the ability of the rehabilitative care system to accommodate clients with differing expectations, and migrant-specific characteristics such as cultural differences, seem to play a role.

By By Andrew Moran Nov 2, 2012 in World Calgary - Canadian universities received a failing grade in the annual Campus Freedom Index by the Justice Centre for Constitutional Freedoms (JCCF). The report claims that these post-secondary institutions have desecrated free speech. It also looks at security fees to see if these can be utilized by officials as an indirect method from banning certain speech that they don’t approve of. The Calgary-based centre noted that “actions speak louder than words,” which is why it only awarded three top “A” grades. At the other end of the scale, 28 “F” grades were given to 12 universities and 26 student unions for their policies and actions. “Universities justify their censorship on grounds of safety and security, believing that people have a right not to be offended by what they see or hear on university campus, and believing that would-be violent protests must be appeased by censoring unpopular messages,” said John Carpay, study co-author and president of the JCCF, in a What universities received an “F” grade? The universities of McMaster, McGill, York, Carleton, Simon Fraser, Western Ontario, Concordia, Dalhousie, University of Toronto, Saint Mary’s and others were given “F” grades for these actions: - Threatened Ann Coulter with civil and criminal penalties if she iterates her views incorrectly and did not provide proper security for, which forced the organizers to cancel the event (University of Ottawa). - Cancelled campus events for Jared Taylor and British Member of Parliament George Galloway, who were deemed “too controversial.” (Dalhousie University). - Prohibited the issue of a campus newspaper that featured images of the Prophet Mohammed (University of Prince Edward Island). - Banned the expression “Israeli Apartheid” (McMaster University and Wilfrid Laurier University). - Ordered a pro-life club to hold their activities in an isolated room so they would not offend anyone (University of Toronto, University of Western Ontario and Carleton University). Meanwhile, student unions at Carleton University, Memorial University, McGill University, Lakehead University, University of Calgary and others were provided with an “F” grade for either banning campus pro-life groups or not certifying them. Also, the Students’ Society of McGill University Equity Committee can end funding for a club if it is in violation of its Equity Policy. The University of Toronto did get an “A” for its policies and principles, while St. Thomas University got an “A” for its actions and policies and Mount Allison University’s Students’ Administrative Council was given an “A” for its student union actions and practices. The 2012 Campus Freedom Index looks at the state of free speech at Canadian universities. This year’s study assigned grades to 35 universities and student unions. Grades are given based on human rights and anti-discrimination policies. Higher grades are given if there is a clear anti-disruption policy, which prohibits students and other people from obstructing, blocking, suppressing or interrupting speech that these individuals disagree with.It also looks at security fees to see if these can be utilized by officials as an indirect method from banning certain speech that they don’t approve of.The Calgary-based centre noted that “actions speak louder than words,” which is why it only awarded three top “A” grades. At the other end of the scale, 28 “F” grades were given to 12 universities and 26 student unions for their policies and actions.“Universities justify their censorship on grounds of safety and security, believing that people have a right not to be offended by what they see or hear on university campus, and believing that would-be violent protests must be appeased by censoring unpopular messages,” said John Carpay, study co-author and president of the JCCF, in a news release What universities received an “F” grade? The universities of McMaster, McGill, York, Carleton, Simon Fraser, Western Ontario, Concordia, Dalhousie, University of Toronto, Saint Mary’s and others were given “F” grades for these actions:- Threatened Ann Coulter with civil and criminal penalties if she iterates her views incorrectly and did not provide proper security for, which forced the organizers to cancel the event (University of Ottawa).- Cancelled campus events for Jared Taylor and British Member of Parliament George Galloway, who were deemed “too controversial.” (Dalhousie University).- Prohibited the issue of a campus newspaper that featured images of the Prophet Mohammed (University of Prince Edward Island).- Banned the expression “Israeli Apartheid” (McMaster University and Wilfrid Laurier University).- Ordered a pro-life club to hold their activities in an isolated room so they would not offend anyone (University of Toronto, University of Western Ontario and Carleton University).Meanwhile, student unions at Carleton University, Memorial University, McGill University, Lakehead University, University of Calgary and others were provided with an “F” grade for either banning campus pro-life groups or not certifying them. Also, the Students’ Society of McGill University Equity Committee can end funding for a club if it is in violation of its Equity Policy.The University of Toronto did get an “A” for its policies and principles, while St. Thomas University got an “A” for its actions and policies and Mount Allison University’s Students’ Administrative Council was given an “A” for its student union actions and practices. More about 2012 Campus Freedom Index, Justice Centre for Constitutional Freedoms, Canada, Universities, Free speech More news from 2012 Campus Freedom ... Justice Centre for C... Canada Universities Free speech

Contemporary, flash memory-based Solid State Drives/Disks (SSDs) have grown enormously both in data storage capacity and popularity as a design feature of many electronic devices (“hosts”). Indeed, NAND flash-based storage devices (“NAND devices”) are current available in multiple Terabytes (TBs) and the future promises greater data storage capacity and higher performance. Current market trends indicate that PCIe based NAND devices are in great demand in enterprise as well as data center applications. In certain enterprise applications, storage domain multi-path and virtualization are two important features of storage devices. That is, a storage device should be useable (or accessible) by multiple host entities capable of using the storage device for different purposes. The term Quality of Service (“QoS”) is used to characterize the operating performance of a storage device in relation to one or more hosts. For example, QoS may be expressed as a minimum time within which the storage device responds to a request received from a host. For multi-function storage devices being accessed by multiple hosts, this minimum time should ideally be fixed and consistent across the range of hosts, regardless of the type of requests being issued by the respective hosts. In this context, each host may be understood as creating a virtual environment within which the storage device is accessed. This virtual environment may define, sequence and execute a number of “tasks” respectively corresponding to requests received from one or more hosts. Certain hosts (e.g., hosts running one or more multimedia applications) may generate a large number of data I/O operations, while other hosts may run Online Transaction Processing (OLTP) or even a full blown database. If the storage device is unaware of the number and type of tasks being generated by each host, the QoS relative to different hosts may vary dynamically, dramatically, and in an unpredictable manner. Under such conditions, the storage device manufacturer will be unable to ensure a fixed and acceptable QoS for each host request. However, a predictable and reliable QoS is very important to the proper execution of OLTP and similar operations. Accordingly, there is need to provide methods and systems capable of providing a fixed QoS across a range of hosts accessing a storage device using protocols and approaches specified by the PCIe.

The present invention relates to a mold tool for forming an electronic component having a semiconductor chip sealed on a substrate by resin, a method for forming the electronic component, and a lead frame on which a semiconductor chip can be put and thereafter the chip on the frame is sealed by resin. Referring to FIGS. 6-8, a known semiconductor sealing method will be described hereinafter. FIG. 6 is a schematic cross-sectional view of a known resin-molded electronic component 21 and FIGS. 7 and 8 show example phenomena caused by molding in the known semiconductor sealing method. In FIG. 6, a substrate 23 for attaching a semiconductor 22 is flat. The chip 22 is sealed on the substrate 23 by resin, resulting in a difference between the distance (c) from the upper surface of the chip 22 to the upper surface of a sealing portion 27 and the distance (d) from the lower surface of the substrate 23 to the lower surface of the sealing portion 27. However, since the configuration elements such as the sectional area and the thickness of the molded product have a great effect on the flow of the molten resin, the above construction causes the resin to firstly flow in the lower mold having a cavity with a larger depth than the depth of the upper mold as shown in FIG. 7 and then flow to the upper mold after the lower cavity of the lower mold is filled with resin. As a result thereof, the resin flow forces gas in the cavities to be held in the upper mold having the cavity with the smaller depth, forming voids in the upper cavity, thus causing disadvantages such as poor insulation properties of the product. As shown in FIG. 8, if the substrate 23 is easily deformed, the substrate 23 is easily deformed by the resin flow. The forward ends 28a and 28b of the two resin flows entering the upper and lower cavities after passing through a gate 24 are difficult to coincide with each other. Therefore, after the lower cavity is filled with the resin, the pressure caused in the lower cavity by the resin is applied to the substrate 23 to deform, resulting in a poor quality of the electronic component molded by resin.

Evaluation of virulence factors profiles and antimicrobials resistance of Escherichia coli isolated from bulk tank milk and raw milk filters. Data on the presence of pathogenic Escherichia coli in bulk tank milk (BTM) and raw milk filters (RMF) are not available in Italy and there are few studies worldwide. Therefore, a study under field condition was conducted to assess the presence of E.coli pathogenic and commensal (CoEC) strains in BTM and RMF samples and their associated AMR pattern. One hundred forty-nine E.coli isolates were characterized. Among all the isolates, 53 (35.6%) were classified as pathogenic while the other ones were classified as CoEC. Among the pathogenic ones, 23 (54.7%) were classified as enterotoxigenic E.coli (ETEC), 6 (11.3%) as enteroinvasive E.coli (EIEC), 2 (3.8%) as enteroaggregative E.coli (EAEC), 12 (22.6%) harboured virulence factors (VF) common to ETEC+EIEC, and 2 (3.8%) common to ETEC+EAEC. To our knowledge, it is the first time that ETEC isolates harboring VF associated with EAEC or EIEC are observed in raw milk. These data support the presence of transmission of VFs genes among isolates. None of the isolates showed resistance to three or more antimicrobials. The CoEC role as a vector of AMR was confirmed by the presence of 18% ampicillin- and cephalexin-resistant isolates. The presence of AMR in CoEC supports the role of these bacteria as source of resistance genes. Monitoring raw milk by either BTM or RMF analysis, and the relatively cheap procedure applied to identify E.coli pathotypes can be useful to identify hazards related to the spread of enteric diseases and antimicrobial resistance.

The prevalence of AIDS, AIDS related complex and HIV seropositivity in a large population of patients with congenital clotting disorders. We have investigated up to the beginning of 1987 114 patients with congenital clotting disorders. 84 had received plasma and/or clotting factors concentrates. 18 out of 84 (21%) had leukopenia, thrombocytopenia, or both. 64 out of 84 (76%) had been infected by hepatitis B virus. The great majority of them (62 out 64) developed adequate immunity (anti Hbs antibodies). Despite this, 47 out 84 (57%) showed persistently elevated transaminases. 17 out of 84 (20%) had HIV-seropositivity. Among them, 7 are free of symptoms related to such a virus up to present time, 8 developed AIDS-related complex and 2 had the full-blown AIDS and died. Non significant difference in HIV seroconversion or its clinical manifestations was noted depending on the administration of factor VIII concentrates versus prothrombin complex concentrates. In contrast, plasma administration appeared to be associated with a lower risk of viral transmission. No abnormality was observed in patients who had never received haemoderivatives, except the presence of anti Hbs antibodies in 1 of them.

The invention relates to a method to turn over print products which are transported in a conveyed flow along a conveying path while clamped in along one edge by the clamps of a circulating first conveyor in order to suspend the print products. Following the movement through a turning section, the print products are gripped along the opposite edge by the clamps of an additional, synchronously driven conveyor and are transported further while suspended from the clamps. The invention furthermore relates to an arrangement to turn over print products, transported in a conveyed flow along a conveying path while gripped and suspended, along one edge by the clamps of a circulating transporter or conveyor, the arrangement comprising a first conveyor having successively spaced apart clamps attached to a traction device that is guided around a reversing wheel. The clamps transfer the print products to the clamps of a following, synchronously driven conveyor. The arrangement furthermore comprises a turning section that operatively connects the conveyor and the additional conveyor. In addition to the conveyors, the print products are turned over with the aid of a transfer device and are transferred to the clamps of the additional conveyor with the opposite-arranged edge pointing forward. In contrast, European patent document EP 1 547 950 A1 discloses a method and an arrangement for stabilizing and positioning flat objects, in particular print products, for which the print products, supplied while suspended from one edge so as to be suspended, are stabilized at the exposed, opposite-arranged edge, are turned over and are then transferred to the clamps of a different conveyor.

Notes: Video begins after Officer Ann Carrizales reports in after being injured. Carrizales catches up to them at the 1:30 mark, and gets close enough that the suspects continue shooting at her at the 4:40 mark. Backup arrives to check her condition at the 7:30 mark.A Stafford police officer was recovering Saturday after being shot twiceby a suspect during a traffic stop. Amazingly, the shooting did not stop her from going after the suspects and helping to capture the gunman.Two other men remain at large. We're learning more about one of them, including his possible involvement with a dangerous gang. According to the Stafford Police Department, the whole thing started when Officer Ann Carrizales stopped a vehicle around 3:30am in the 12700 block of Murphy Road.Inside were three males. "She approached and was speaking with the driver when the passenger inside the vehicle shot her once in the chest and once in the face," SPD Lt. Dustin Claborn said.In spite of her injuries, Carrizales returned fire as the vehicle fled. She then managed to make it back to her patrol car and follow the suspects, chasing them into Houston. "I think it speaks highly of her character, her fortitude," Claborn said.The chase ended outside an apartment complex on Greenfork at Concourse near the Northwest Freeway. The 21-year-old shooter -- identified as Sergio Francisco Rodriguez -- was located and taken into custody by Missouri City police officers, who came to assist with the chase, along with DPS, Sugar Land and Houston officers. Rodriguez is charged with aggravated assault on a peace officer and was being held without bond Saturday night.An active warrant for aggravated assault on a peace officer has been issued for the driver, 28-year-old Freddy Henriquez. Police said Henriquez should be considered armed and dangerous. He is also reportedly a Honduras native wanted by Immigration and Customs Enforcement for illegally re-entering the United States as a violent felon.According to ICE, Henriquez is believed to be a member of a violent gang called Sureno 13 -- a prison gang affiliated with the Mexican Mafia. If you see him or have information on his whereabouts, you're asked to call SPD at 281-261-3950, SPD Detective Henry Garcia at 281-208-6991, or call 911. Investigators are working to identify the third suspect.Carrizales was taken to Memorial Hermann Hospital and was released Saturday night. According to police, her bullet-proof vest saved her life. "Her ballistic vest stopped almost all the shot to the chest, some minor injuries there," Claborn said."Without a doubt, it saved her life. It just illustrates how quickly something can go bad forany officer at any time." Carrizales has been a member of the Stafford Police Department since August of 2010. abclocal.go.com/ktrk/story?section=news/local& ;amp;id=9308510

The invention relates to a two-port cartridge type seat valve. For approximately thirty years, two-port cartridge valves have been widely used in hydraulic control technology as pressure-control, directional or check valves. Such cartridge valves are described in detail, for example, in the article "Cartridge check valves: New option for hydraulic control" by David C. Downs, in "Machine Design", Vol. 52, No. 28, of 11th Dec., 1980, Cleveland USA, pages 143-147. A positive-seating, two-port cartridge valve is likewise described in German Offenlegungsschrift DE-A-36 19 927. Such two-port cartridge valves are used in a manifold that has a stepped bore and first and second main flow channels. The stepped bore has a first bore step that is connected to the first main flow channel and a second bore step, with a larger diameter than the first bore step, that is connected to the second main flow channel. The typical two-port cartridge type seat valve includes a valve sleeve that is inserted into the stepped bore, a poppet fitted in the sleeve for sliding axial displacement, a closure spring that biases the poppet into sealing engagement with a valve seat in the valve sleeve, and a valve cover. The valve sleeve has first and second ends, with a first cross-sectional portion at the first end that sealingly fits axially into the first bore step, and a second cross-sectional portion that sealingly fits axially into the second bore step. A central cross-sectional portion between the first and second cross-sectional portion defines an annular chamber within the second bore step, into which the second main flow channel opens when the valve sleeve is inserted into the stepped bore. The sleeve also has an axial main flow bore that forms a first main port in the first end of the valve sleeve and lateral second main ports in the central cross-sectional portion for connecting the main flow bore with the annular chamber. The valve seat is disposed in the main flow bore between the first and said second main ports. The poppet has first and second ends, with the first end having a closure cone that sealingly engages the valve seat in the valve sleeve. The poppet is biased closed by the closure spring. To make the two-port cartridge valves interchangeable, the diameters and depths of the stepped bore, the position of the lateral second main flow channel in the manifold, and the dimensions of the valve cover and the position of its fastening screws and pilot connections, are set out in standards for the different nominal valve sizes. In Germany, for example, the relevant standard is DIN 24342. As a result, the external shape of the valve sleeve is substantially predetermined and the person skilled in the art has little scope for adapting the valve to different functions. Known valves have a cylindrical guide bore that extends from the valve seat axially through the valve sleeve to the second end of the valve sleeve. The poppet is fitted in the guide bore for axial displacement in the valve sleeve. Within the guide bore, a pilot chamber is defined axially by the second end of the poppet. The second end of the poppet accordingly forms a pilot pressure area, S.sub.X, equal to the cross-sectional area of the guide bore. The maximum possible cross-section of the guide bore is dictated by the minimum necessary wall thickness of the valve sleeve in its central cross-sectional portion and the necessary free cross-section of the annular chamber in the region of the second main port. Accordingly, the maximum possible pilot area S.sub.X, the maximum possible cross-section of the poppet, and therefore the maximum possible free cross-section S.sub.A of the valve seat are also fixed. The free cross-section S.sub.A of the valve seat must, of course, be smaller than the cross-section of the poppet's closure cone which, in turn, cannot be larger than the cross-section of the guide bore. Such two-port cartridge valves with a maximum free cross-section S.sub.A for the valve seat are used as pressure-control valves. In this application the valves should have a maximum flow capacity. Therefore, the pilot area S.sub.X (which is fixed by the cross-section of the guide bore) is preferably approximately equal to the free cross-section S.sub.A of the valve seat. However, two-port cartridge valves can also be used as pilot-controlled two/two-port directional valves for switching applications. For such applications, the maximum free cross-section SA of the valve seat is reduced by about 35% to 50%, to reduce the hydrostatic force acting on the poppet in the opening direction, rendering the switching behavior of the valve as much as possible independent of pressure fluctuations in the first main flow port. Consequently, the flow capacity of the valve is reduced by about 35% to 50%, or the valve produces a greater pressure loss. There is thus a need for a two-port cartridge valve that provides a switching function with a high flow capacity.

The invention is directed to an angle measurement with a graduation carrier which is connectable to a shaft by a hub, and which is scanned by a stationary scanning arrangement, installation means being provided for defining the positional correlation of the graduation carrier and scanning arrangement. Such angle measurement apparatus are also designated as "built-in rotary encoders", which comprise no support of their own (for instance company publication of the DR. JOHANNES HEIDENHAIN GmbH, Traunreut: Rotary Encoder, issued 2/88). A preassembled angle measurement device without its own support is known U.S. Pat. No. 4,689,595. In a preassembled state, a clamping spring causes the cohesion of the scanning arrangement with the hub to which the graduation carrier or support is fastened. A stop is provided at the hub, which contacts the scanning arrangement during the preliminary assembly and which fixes the hub in the radial and the axial direction. In this state the angle measurement apparatus is placed on the drive shaft and the scanning arrangement is fastened at the mounting surface of the drive unit. Subsequently, the clamping spring is moved out of engagement and the hub is shifted in the axial direction onto the drive shaft. This shift is required in order to cancel the contact of the stop of the hub with the scanning device and in order to assure a friction-free rotation of the hub relative to the scanning arrangement. In this angle measurement apparatus there exists, in the preassembled state, a defined correlation between the hub and the scanning device in the radial and axial directions with respect to the hub axis, this correlation must however be removed during the installation at the drive unit. Because of the required axial displacement of the hub and of the graduation carrier relative to the scanning device, no defined correlation can be achieved without additional auxiliary means, and indeed neither in the radial nor in the axial direction. The measures disclosed in the U.S. Pat. No. 4,639,595 assure only security during transport. Additional angle measurement devices are described in the U.S. Pat. No. 4,556,792 and German Offenlegungsschrift 37 40 744. Expensive adjustment instruments are required for the axial and radial adjustment of the hub with respect to the scanning device. The fixation of the hub with respect to the scanning device occurs by means of a plurality of elements, which must all be laboriously removed by the recipient which requires a great deal of time.

[Acute venous liver circulatory disorder caused by blunt abdominal trauma: is it a compartment syndrome?]. Authors describe the case of a 37-year-old female patient who had been operated on for a subcapsular haematoma of the liver that had developed following a blunt abdominal trauma. This manifested as a Budd-Chiari syndrome-like phenomenon that was not recognized until an exploratory operation was performed, when we found that the liver was hard and dark purple in colour and there was considerable ascites in the abdominal cavity. After aspiration of the haematoma, which contained about 1 l of a mixture of fluid and clotted blood, the circulation of the liver rapidly improved. On the basis of the findings, a posttraumatic Budd-Chiari syndrome seems unlikely, since the symptoms caused by the rise in intracapsular pressure are similar to those of a compartment syndrome. No literature data can be found to define such a posttraumatic failure of the liver circulation. Subcapsular and intrahepatic haematomata can be successfully monitored by ultrasonography and managed conservatively if they are asymptomatic. Operation is restricted to lesions with worsening symptoms or increasing danger of haemorrhage.

This Program Project grant is designed to enhance our understanding of the basic mechanisms responsible for gastrointestinal (Gl) motility. Knowledge of mechanisms that generate normal motility patterns will help explain what goes awry in motility disorders and develop novel approaches to therapies. In this Program we are investigating smooth muscle cells, Interstitial cells of Cajal (ICC) and PDGFRa+ cells of Gl muscles, which through electrical coupling, form a syncytial tissue we refer to as the SIP syncytium. Cells of the SIP syncytium generate electrical pacemaker activity and provide what has been known as 'myogenic' regulation of motility. SIP cells also receive and transduce inputs from enteric motor neurons, so they are key participants in neural regulation of motility. We have developed techniques to isolate and purify each class of cell in the SIP syncytium, and we have performed deep sequencing of the gene transcripts in these cells. Hypotheses in this proposal were developed from this unprecedented knowledge of the cell-specific transcriptomes of SIP cells. Four projects will investigate questions regarding the mechanism of pacemaking and propagation of electrical slow waves, integration of excitatory responses by ICC and smooth muscle cells in generation of propulsive colonic contractions, bioactivity and targets of purines released and metabolites produced in colonic muscles, and the fate and recovery of ICC in patho-physiological conditions causing loss of ICC. Three Core laboratories will support these projects. Core A will provide informatics support and aide investigators with experimental planning and data management. Core B will provide transgenic animal, isolate and sort cells by fluorescence activated cell sorting, and support organ cultures. Core C will analyze expression of genes and proteins in cells and tissues. Experiments will utilize transgenic mice as model organisms to test novel hypotheses. Ideas developed in rodent studies will be tested on cells and muscles of non-human primates and human patients. The research team is highly synergistic and collaborative and has a long track record of productivity and innovative contributions to neurogastroenterology.

Protein kinase A and its role in human neoplasia: the Carney complex paradigm. The type 1 alpha regulatory subunit (R1alpha) of cAMP-dependent protein kinase A (PKA) (PRKAR1A) is an important regulator of the serine-threonine kinase activity catalyzed by the PKA holoenzyme. Carney complex (CNC) describes the association 'of spotty skin pigmentation, myxomas, and endocrine overactivity'; CNC is in essence the latest form of multiple endocrine neoplasia to be described and affects the pituitary, thyroid, adrenal and gonadal glands. Primary pigmented nodular adrenocortical disease (PPNAD), a micronodular form of bilateral adrenal hyperplasia that causes a unique, inherited form of Cushing syndrome, is also the most common endocrine manifestation of CNC. CNC and PPNAD are genetically heterogeneous but one of the responsible genes is PRKAR1A, at least for those families that map to 17q22-24 (the chromosomal region that harbors PRKAR1A). CNC and/or PPNAD are the first human diseases to be caused by mutations in one of the subunits of the PKA holoenzyme. Despite the extensive literature on R1alpha and PKA, little is known about their potential involvement in cell cycle regulation, growth and/or proliferation. The presence of inactivating germline mutations and the loss of its wild-type allele in CNC lesions indicated that PRKAR1A could function as a tumor-suppressor gene in these tissues. However, there are conflicting data in the literature about PRKAR1A's role in human neoplasms, cancer cell lines and animal models. In this report, we review briefly the genetics of CNC and focus on the involvement of PRKAR1A in human tumorigenesis in an effort to reconcile the often diametrically opposite reports on R1alpha.

Intraoperative positioning during cesarean as a cause of sciatic neuropathy. Sciatic nerve compression has been well documented as a cause of perioperative sciatic neuropathy but rarely during cesarean. A parturient complained of left foot drop after cesarean delivery for twins performed under spinal anesthesia. Intraoperatively, her right hip was raised with padding under the right buttock to tilt the pelvis approximately 30 degrees to the left. Postoperatively, the patient had weakness, sensory changes, and diminished reflexes in the left lower extremity. Electrodiagnostic studies supported a diagnosis of neurapraxia and partial denervation in the distribution of the sciatic nerve. By postpartum week 6, she had full recovery. Elevating the right buttock during cesarean can cause compression of the underlying structures of the left buttock and result in sciatic neuropathy. Decreasing the duration of time the patient is in the left lateral position may reduce the risk of this uncommon but debilitating complication.

1. Field of the Invention The present invention relates to a tire chuck apparatus and method for gripping a tire from the inner side of the bead portion. 2. Description of the Related Art Unprocessed tires and vulcanized tires (finished products) are generally gripped for various reasons. Tires are gripped in order to insert or take out a tire in a vulcanizing mold in a tire manufacturing process, or in order to collect and ship tires in a physical distribution process, or in order to be shipped in or out in a sales process. A known conventional chuck apparatus for gripping tires in these types of processes is one provided with, for example, a supporting member capable of moving in the central axial direction of the tire and at least two gripping claws supported by the supporting member such that the gripping claws can expand and contract in the radial direction of the tire. In this chuck apparatus, by moving the supporting member in the central axial direction of the tire when each of the gripping claws is contracted in the radial direction of the tire, each gripping claw is inserted within the tire bead portion of a tire placed horizontally on a roller conveyor, loading stand, or the like. By then expanding each of the gripping claws in this state in the radial direction of the tire, the tire bead portion is gripped from the inner side. However, in this type of conventional tire chuck apparatus, the problem arises that the tire is sometimes gripped in a state in which the center of the tire is out of position. The reason for this occurring is described below. Namely, if the central axis of the tire and the center of the chuck apparatus gripping the tire (the center of a single circle running through all the gripping claws) are not aligned, when the gripping claws expand in the radial direction of the tire, the gripping claws contact the internal periphery of the tire bead portion one after the other with a small time difference between each contact. If, at this time, the amount of friction resistance between the tire and the roller conveyor or loading stand is large enough that the tire is unable to move, the tire bead portion is pushed by the gripping claw which makes contact first and is slightly deformed in portions. As a result, the tire ends up being gripped by the gripping claws in a state in which the central axis of the tire is not aligned with the center of the chuck apparatus. Furthermore, because the above described gripping claws only hold the tire as it is and cannot rotate the tire, when performing an inspection over the entire periphery of the tire, it is necessary to rotate the inspection apparatus or the like around the periphery of the tire which results in the problem that the apparatus as a whole is large and expensive. The aim of the present invention is to provide a tire chuck apparatus and method in which the size of the apparatus can be reduced and the cost thereof decreased and at the same time gripping of a tire by gripping mechanism at a misaligned position can be reduced. In order to achieve the above objectives, the first aspect of the present invention is a tire chuck apparatus for holding a tire having a tire bead, the apparatus including a gripping mechanism with at least two gripping members movable in tire radial direction from a retracted position to an extended position for pressing against the inner side of the bead portion of the tire and thereby holding the tire, gripping rollers as the gripping members adapted to be rotatable around an axis substantially parallel to a central axis of the tire, and a rotation drive mechanism for rotating the tire around the central axis of the tire. In the above aspect, when gripping a tire, firstly, each gripping roller (gripping member) which has been moved to the inner side in the radial direction of the tire is inserted along the central axis of the tire into the inner side of the tire bead portion. From this state, each gripping roller is then expanded to the outer side in the radial direction of the tire. If the central axis of the tire is not aligned with the central axis of the chuck apparatus (the center of a single circle passing through all of the gripping rollers) at this point, the gripping rollers make contact one after another with the inner periphery of the tire bead portion with a short time difference between the contact by each roller. If the tire is unable to move at this time, the tire bead portion begins to undergo slight partial deformation as it is pushed by the gripping claw which makes the first contact. In the present invention, however, by rotating the tire around its central axis using the rotation drive means, the tire is shifted to a position in which all of the gripping rollers make contact with the inner periphery of the tire bead portion. At this point, because the gripping rollers contacting the tire bead portion rotate around an axis parallel to the central axis of the tire, the gripping rollers do not hinder the rotation of the tire. As a result, a movement of the tire such as that described above can take place easily and smoothly. Because of this, the above described deformation is prevented and the result of this is that mispositioning between the central axis of the tire and the center of the chuck apparatus is reduced. In short, the tire is gripped from the inside by the gripping rollers in a state in which the central axis of the tire has been accurately positioned relative to (coincided with) the center of the chuck apparatus. Furthermore, after the tire has been gripped by the gripping rollers, if the tire is rotated around the central axis thereof by the rotation drive mechanism, it is possible to perform an inspection or the like over the entire periphery of the tire even if the inspection apparatus is stationary. As a result, there is no need to rotate the inspection apparatus or the like around the periphery of the tire enabling the size of the apparatus overall to be reduced and the production costs to be decreased. The inspection apparatus mentioned above may be a tire information reading mechanism, a surface condition reading mechanism, an internal condition reading mechanism, and the like. In the second aspect of the present invention, a tire is rotated by at least one gripping roller being rotated by the rotation drive mechanism. The structure of the second aspect enables the gripping rollers to also be used for the rotation of the tire which allows the structure to be simplified. Moreover, because the rotation force in the peripheral direction is applied from the gripping rollers to the bead portion which is the portion of a tire with the highest rigidity, the rotation of the tire can be accurately controlled. In the third aspect of the present invention, a tire is rotated by all gripping rollers being rotated by the rotation drive mechanism. The structure of the third aspect enables rotation force to be continuously applied to the tire from the time the first gripping roller makes contact with the tire bead portion. The result of this is that the alignment of the central axis of the tire with the center of the chuck apparatus is smoothly carried out. In the fourth aspect of the present invention, the drive source of the rotation drive mechanism is placed in a central space (position) surrounded by gripping rollers. The structure of the fourth aspect allows effective use to be made of empty space. In the fifth aspect of the present invention, the tire information reading mechanism, the surface condition reading mechanism, the internal condition reading mechanism, or the like is attached to a member which moves in the central axial direction of the tire integrally with the gripping roller.

Sexual orientation and mental health: results from a community survey of young and middle-aged adults. Community surveys have reported a higher rate of mental health problems in combined groups of homosexual and bisexual participants, but have not separated these two groups. To assess separately the mental health of homosexual and bisexual groups compared with heterosexuals. A community survey of 4824 adults was carried out in Canberra, Australia. Measures covered anxiety, depression, suicidality, alcohol misuse, positive and negative affect and a range of risk factors for poorer mental health. The bisexual group was highest on measures of anxiety, depression and negative affect, with the homosexual group falling between the other two groups. Both the bisexual and homosexual groups were high on suicidality. Bisexuals also had more current adverse life events, greater childhood adversity, less positive support from family, more negative support from friends and a higher frequency of financial problems. Homosexuals reported greater childhood adversity and less positive support from family. The bisexual group had the worst mental health, although homosexual participants also tended to report more distress.

Ca2+ current in rabbit carotid body glomus cells is conducted by multiple types of high-voltage-activated Ca2+ channels. Ca2+ current in rabbit carotid body glomus cells is conducted by multiple types of high-voltage-activated Ca2+ channels. J. Neurophysiol. 78: 2467-2474, 1997. Carotid bodies are sensory organs that detect changes in arterial oxygen. Glomus cells are presumed to be the initial sites for sensory transduction, and Ca2+-dependent neurotransmitter release from glomus cells is believed to be an obligatory step in this response. Some information exists on the Ca2+ channels in rat glomus cells. However, relatively little is known about the types of Ca2+ channels present in rabbit glomus cells, the species in which most of the neurotransmitter release studies have been performed. Therefore we tested the effect of specific Ca2+ channel blockers on current recorded from freshly dissociated, adult rabbit carotid body glomus cells using the whole cell configuration of the patch-clamp technique. Macroscopic Ba2+ current elicited from a holding potential of -80 mV activated at a Vm of approximately -30 mV, peaked between 0 and +10 mV and did not inactivate during 25-ms steps to positive test potentials. Prolonged ( approximately 2 min) depolarized holding potentials inactivated the current with a V1/2 of -47 mV. There was no evidence for T-type channels. On steps to 0 mV, 6 mM Co2+ decreased peak inward current by 97 +/- 1% (mean +/- SE). Nisoldipine (2 mu M), 1 mu M omega-conotoxin GVIA, and 100 nM omega-agatoxin IVa each blocked a portion of the macroscopic Ca2+ current (30 +/- 5, 33 +/- 5, and 19 +/- 3% after rundown correction, respectively). Simultaneous application of these blockers revealed a resistant current that was not affected by 1 mu M omega-conotoxin MVIIC. This resistant current constituted 27 +/- 5% of the total macroscopic Ca2+ current. Each blocker had an effect in every cell so tested. However, the relative proportion of current blocked varied from cell to cell. These results suggest that L, N, P, and resistant channel types each conduct a significant proportion of the macroscopic Ca2+ current in rabbit glomus cells. Hypoxia-induced neurotransmitter release from glomus cells may involve one or more of these channels.

Association between early advanced life support and good neurological outcome in out of hospital cardiac arrest: A propensity score analysis. Out-of-hospital cardiac arrest (OHCA) is an important public health problem. The French organization, combining OHCA basic life support (BLS) and advanced life support (ALS), has been recently questioned. The study was conducted to evaluate the association between early ALS (E-ALS) arrival and good neurological outcome at 1 month in nontraumatic OHCA patients. Retrospective cohort study using data from RéAC, multicentre OHCA database since June 2011. Adult patients with nontraumatic cardiac arrest were identified, and firefighters' (BLS) arrival time was recorded. The main analysis was performed after multiple imputation, using propensity score matching with a variable ratio. Sensitivity analyses were also performed. The exposure was early ALS (E-ALS), start of ALS before. or simultaneously with BLS. The primary outcome was the cerebral performance category (CPC) at day 30 after the cardiac arrest (1-2 vs 3-5), while cumulative incidence of return of spontaneous circulation (ROSC) defined secondary outcomes. Between January 2013 and January 2016, a total of 30 672 adult nontraumatic OHCA with resuscitation were identified, from whom 20 804 were included, 2711 in the E-ALS group and 18 093 in the control group. Based on the matched sample, patients in the E-ALS group had a significantly lower rate of good neurological outcome than those in the control group (OR, 0.95; 95% CI, 0.93-0.96). Sensitivity analyses were mostly consistent with this result. Cumulative incidence of ROSC was higher in delayed ALS (D-ALS) group. This study showed that patients in the E-ALS group were less likely to have a good neurological outcome. One explanation of this unexpected result could be the total duration of resuscitation performed, which may be interrupted prematurely in cases of E-ALS.

Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-null cells are unrelated to DNA repair defects. While the Ku complex, comprised of Ku70 and Ku80, is primarily involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type or Ku80-null (Ku80(-/-)) mice with various stress agents revealed that hydrogen peroxide (H(2)O(2)) was markedly more cytotoxic for Ku80(-/-) MEFs and led to their long-term accumulation in the G2 phase. This differential response was not due to differences in DNA repair, since H(2)O(2)-triggered DNA damage was repaired with comparable efficiency in both Wt and Ku80(-/-) MEFs, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and G2-progression are not only dependent on the cell's DNA repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.

Pipes containing fluid under pressure are prone to leak from a number of causes, including corrosion, freezing, deterioration of fixtures, etc. This is of particular concern in a household residence where protracted leakage of plumbing pipes can cause much property damage to the structure and contents. A number of systems have been devised to automatically shut off water in a plumbing system in the event of a leak. One example is found in U.S. Pat. No. 5,038,820 to Phillip Ames, et al. This system uses a "pivotal flapper" positioned within a pipe, which flapper is pivoted upward due to water flow in the pipe. The flapper then operates a switch which starts a timer which, in turn, operates a motor to control a valve after the expiration of a preset time period. Another example is found in U.S. Pat. No. 4,589,435 to Aldrich, which is very similar in that it uses a probe positioned within a pipe and which is moved by fluid flow to trigger a timing circuit. The timer, in turn, controls a solenoid which closes off a valve to shut down fluid flow after a preset time period. Neither the Ames or the Aldrich patent allows their systems to be set to be triggered at different flow rates. This is a problem, for example, where it is desirable to allow a certain minimal flow volume for humidifiers, ice makers, etc., but to shut off in response to a larger flow volume. In addition, both Ames or Aldrich are relatively complex systems which makes them expensive. It is clear, then, that an improved automatic shut-off device for closing plumbing or other fluid carrying pipes is needed. Such a device should preferably be simple and inexpensive, but be capable of adjustment to allow for different flow thresholds upon installation.

Electric vehicles and electric-hybrid vehicles are gaining in popularity with consumers. The electric motors in these vehicles are typically powered from multiple storage batteries disposed in a battery pack in the vehicle. If the battery needs to be recharged while the vehicle is parked, a wired coupling device is connected to the vehicle, typically by the vehicle operator. However, some operators object to having to ‘plug-in’ their vehicle each time the vehicle is parked. Wireless or connector less battery chargers have been proposed, see U.S. Pat. No. 5,498,948 issued Mar. 12, 1996 to Bruni et al. and U.S. Pat. No. 8,008,888 issued Aug. 30, 2011 to Oyobe et al. A known wireless battery charger includes a source resonator or charging pad lying on a parking surface under the vehicle being charged, and a corresponding capture resonator mounted underneath the vehicle. Such wireless battery chargers are most efficient when the vehicle is parked such that the source resonator and capture resonator are horizontally (i.e. laterally and longitudinally) aligned. However, as the source resonator and the capture resonator are underneath the vehicle and/or out of the vehicle operator's view, it is difficult for the vehicle operator to judge where to park the vehicle so that the source resonator and the capture resonator are aligned. Some current wireless charging systems rely on methods to align the capture resonator attached to the undercarriage of a vehicle with its corresponding source resonator using trial and error positioning of the vehicle relative to the source resonator. These methods are time intensive, with poor repeatable results. Other wireless charging systems utilize wheel stops to align the capture resonator on the vehicle with the source resonator. While these systems may provide precise alignment for one particular vehicle configuration, they are unlikely to provide adequate alignment for a wide variety of vehicles wherein the spatial relationship between the wheels and capture resonator differ. Still other wireless charging systems provide a magnetic beacon signal to guide the vehicle to align the capture resonator with the source resonator. Examples of such systems are described in U.S. patent application Ser. No. 13/677,362 and U.S. patent application Ser. No. 13/677,369, both filed Nov. 15, 2012. The subject matter discussed in the background section should not be assumed to be prior art merely as a result of its mention in the background section. Similarly, a problem mentioned in the background section or associated with the subject matter of the background section should not be assumed to have been previously recognized in the prior art. The subject matter in the background section merely represents different approaches, which in and of themselves may also be inventions.

There are a number of applications where it is desirable to be able to identify an unknown location of an object which emits a signal. One example occurs when planning an indoor wireless local area network (LAN) having one or more RF or microwave emitters. Of course precisely defining an object's location requires specifying coordinates in three dimensions (e.g., longitude, latitude, and altitude). In the discussion to follow, for simplicity of explanation it is assumed that the third coordinate (i.e., altitude) is either known or is otherwise easily determined once the other two coordinates (e.g., latitude and longitude) are identified. Those skilled in the art will be able to extrapolate the discussion to follow to the case where all three coordinates are to be determined. There are a few known methods to locate signal emitters using a plurality of distributed sensors, or receivers, which are spaced apart from each other. Among the most common of these methods are: Time Difference of Arrival (TDOA), Time of Arrival (TOA), Angle of Arrival (AOA), and Received Signal Strength (RSS). The TDOA method, also known sometimes as multilateration or hyperbolic positioning, is a process of locating an emitter by accurately computing the time difference of arrival (TDOA) of a signal emitted from the emitter to three or more sensors. In particular, if a signal is emitted from a signal emitter, it will arrive at slightly different times at two spatially separated sensor sites, the TDOA being due to the different distances to each sensor from the emitter. For given locations of the two sensors, there is a set of emitter locations that would give the same measurement of TDOA. Given two known sensor locations and a known TDOA between them, the locus of possible locations of the signal emitter lies on a hyperbola. In practice, the sensors are time synchronized and the difference in the time of arrival of a signal from a signal emitter at a pair of sensors is measured. With three or more sensors, multiple hyperbolas can be constructed from the TDOAs of different pairs of sensors. The location where the hyperbolas generated from the different sensor pairs intersect is the most likely location of the signal emitter. In the TOA method, a signal emitter transmits a signal at a predetermined or known time. Three or more sensors each measure the arrival time of the signal at that sensor. The known time of arrival leads to circles of constant received time around each sensor. The locations where the circles from the three or more sensors intersect are the most likely location of the signal emitter. In the AOA method, the angle of arrival of the signal is measured with special antennas at each receiver. This information is combined to help locate the signal emitter. In the RSS method, the power of the received signal at each sensor is measured, and this information is combined to help locate the signal emitter. There are a few different emitter location procedures that employ RSS. For example, one commonly used method in planning indoor wireless LAN systems in a building of interest is to map the received signal strength at various locations around the building during a setup phase. From this map, a variety of algorithms can be used to locate the signal emitter based on computed received power at three or more sensors. A more detailed explanation of principles employed in an RSS method of locating a signal emitter will now be provided, particularly illustrating a case involving an RF emitter and RF sensors. FIG. 1 illustrates a general case of an RF emitter 110 and two RF sensors 122 and 124. In free space, the received power of a signal transmitted by RF emitter 110 decreases with the square of the distance from RF emitter 110. For indoor or dense urban environments the power fall-off is even steeper, for example r−3 or r−4, where r is the distance from RF emitter 110. In general, given a transmitted power P0 measured at distance r0, the power P1 received at first RF sensor 122 is: P 1 = P 0 ⁡ ( r 0 r 1 ) n , ( 1 ) where r1 is the distance between RF emitter 110 and first RF sensor 122, and n is the exponential rate at which the power decreases with distance. Likewise the received power P2 at second RF sensor 124 is: P 2 = P 0 ⁡ ( r 0 r 2 ) n , ( 2 ) where r2 is the distance between RF emitter 110 and second RF sensor 124. This leads to: P 1 P 2 = ( r 2 r 1 ) n ( 3 ) With a bit of manipulation this yields: 10 ( log ⁡ ( P 1 P 2 ) n ) =  r 2 r 1  = const = α ( 4 ) It can be shown that this leads to a circle of a given radius and centered on the line defined by the two RF sensors. FIG. 2 illustrates an exemplary circle generated by power measurements of a signal transmitted by RF emitter 110 and received at RF sensors 122 and 124. With at least three RF sensors, three such circles are generated, and the location of RF emitter 100 can be found where the three circles intercept. With many sensors, it is possible to increase the accuracy by determining the point where most of the generated circles intersect. However, the addition of measurement uncertainty and noise makes this a difficult problem to solve analytically with a high degree of accuracy. Moreover, using just the measured signal power, as it typical in most RSS methods, multiple emitters transmitting from different locations at the same time with the signals having the same characteristics (e.g., frequency, bandwidth, etc.) leads to confusing results for the emitter location. Furthermore, with existing equipment, it is often difficult for a troubleshooter to easily and efficiently view all of the relevant data of interest to allow a clear picture of any coverage and interference issues. More robust data analysis and data presentation capabilities are needed. In particular, methods are needed that are robust when multiple emitters are present that transmit signals at the same time and on the same frequency. What is needed, therefore, is a method and system for locating signal emitters that addresses one or more of these shortcomings.

"Brought to you by WITH S2 Written In The Heavens Subbing Squad" "Episode 24" "Notice Suspension of Business" "We weren't prepared for this at all." "We never even dreamed this could happen." "Aigoo." "People's lives are so unpredictable." "A person's life is truly nothing." "Those people that came and went like this was their home when Father was alive, how could they just completely sever ties like that?" "Hey Seo Tae Jo!" "How dare you come here!" "What the hell are you thinking stepping in here again!" "Gap Soo Ahjussi!" "Hey, you punk." "How do you think Master got that way?" "Because of who?" "He died because of everything you caused!" "What are you going to do now?" "What are you going to do about it, punk?" "Huh?" " What are you going to do about it?" " Calm down." "Even ingratitude has its limits!" "Aigoo, Master!" "Aigoo, Master!" "Aigoo, Master!" "Stop it, all of you, and calm down." "Tae Jo, come in." "You should at least pay your last respects to the Master." "What are you doing?" "Why don't you come in to pay your final respects?" "Tae Jo." "Come on in." "I didn't know it would be so barren when Father made his final journey." "Over a few lines printed in the newspapers, how could people cut him out so completely?" "It makes me fear that humanity is really like this." "It may be that people are late because it was such a sudden announcement." "He was a man that only ever knew bread." "To think that he had to suffer such a disgrace in his final days... truly, there are no words that can describe my feelings." "The Master said this, that the truth will always prevail." "I'm sure the people who knows our teacher still respect him as always." "It's time for the funeral procession, Boss." "Oh, right." "But, Il Jung Hyungnim, do you really think it will be all right?" "He is forever my Master." "It is just proper that I escort him on his final journey." "I am truly so sorry." "We just received the announcement." "We ran like mad from all over to get here on time and only just arrived." "Reverently, we pray, may the Master rest in peace." "Even though we're considered merely as bread guys baking bread worth a couple hundred Won," "we are master artisans that spend our lives in the pursuit of creating the taste of that bread." "Don't ever forget that, Tak Gu." "Here is today's schedule, President." "Are you all right?" "President." "Yes, I'm all right." "My arm is just a little sore." "Let's resume last night's new product development meeting." "Yes, all right." "Starting the day you went for the funeral services, for 3 days straight, he's been having meetings with the Board of Directors." "I believe President Il Jung's judgment is getting more and more cloudy." "At this rate, it looks like our Geosung managerial rights will be passed on to mere little bakeries." "Does that make any sense?" "At next week's Board of Director's Meeting," "I think we'll need to show him exactly where we stand." "[Fermentation Journal]" "Tae Jo," "If you are reading this letter, it probably means you've taken my fermentation journal, right?" "Did you want to see me, Boss?" "Yeah, come in." "Okay." "How are you feeling?" "Don't worry." "I'm okay." "I called you in here because I have something to give you." "It looks like Father left this for you." "This is the task" "I gave you all for the 3rd round of the competition." "[The world's happiest bread]" "Finding the world's most filling bread was in the spirit of thinking of others." "Finding the world's most interesting bread... was in the spirit of enjoying yourself." "Finding the world's happiest bread... is in the spirit of finding the bread you are to make for all the days of your life." "This is the final task I will give to you, so I hope in earnest that you will carry it out." "Master." "Master." "Master!" "What you asked me before..." "Does your request still stand?" "Are you saying you'll help me?" "You said that if I couldn't do it for you, do it for Tak Gu." "Then, will it also be a revenge against the people who hurt the Pal Bong Bakery?" "It can also be dangerous." "What is it I need to do?" "What are you saying?" "You haven't been able to obtain that 8% of stocks?" "It appears that there's some nervousness in supporting Ma Jun." "What do I need to do?" "The marriage you mentioned to Seo Chang Produce family's daughter," "I think it would be a good idea to move that along more quickly." "I understand what you're saying." "I'll give it priority." "So, Na Jin, when do you return to the US?" "Next week." "Ah, I see." "This may sound sudden, but our Ma Jun has returned and all..." "I'm wondering, how about an engagement in the fall?" "Of course right now, Na Jin, school is probably more important to you, right?" "That doesn't matter." "If we agree on a date, I can come out briefly in the middle of the session." "Then, shall we plan on it, Na Jin?" "What do you think, Madam Lee?" "Well, if our Na Jin wants to, well..." "I'm sorry, but I can't." "Na Jin," "I'm not going to marry you." "I won't go through with this marriage." "Then, I'll be leaving now." "Ma Jun." "Ma Jun." "You stop right there." "What on earth are you doing?" "Why throw ash on a completely set dinner table!" "Can you please stop doing this!" "Did I ever agree to that marriage?" "I never agreed to it!" "Is this marriage bad for you?" "This is all for your benefit." "This is to lay the foundation for your support!" "I told you, it's not just one or two people that have staked their lives for you." " So, why can't you come to your senses?" " Who asked them to do that for me!" " I never asked for that!" " Gu Ma Jun!" "I love that girl!" "What?" "I love Shin Yu Kyung, Mom." "I can't live without her." "If even for a moment, she's not with me," "I get anxious and it drives me crazy." "If I don't see her, I miss her so much I can't breathe, and at that moment, it feels like I'm dying." "Now, I don't have anyone left." "Yu Kyung is the only one I have left." "You know that?" "What do you mean she's all you have?" "You have a mother." "You have Geosung!" "Other than you, other than Geosung, I have no one left." "You little half-wit." "Are you really going to disappoint your mother like this?" "Up to now, I've believed in you and you only." "I lived all my life for this moment, and you... you betray me like this?" "Mom, please!" "I don't want to hurt you." "So, please leave me alone." "Let me breathe, please!" "You're the one that needs to let go of this cowardice and focus on what you need to do!" "There's no way, I'm going to lose you to a worthless girl like Shin Yu Kyung!" "I absolutely can't, I won't!" "Mom!" "The more you act this way," "Shin Yu Kyung's life will become more miserable, Ma Jun." "And you, you will never win over this mother of yours." "Understand?" "We'll plan for an engagement with Na Jin before the end of September." "That's how it's going to be." "I'll take you home." "Get in." "That's okay." "You can just go." "It's 15 minutes by bus." "What do I need to do to become happy?" "What can I do to obtain that so called happiness?" "Do you know?" "You want to become happy?" "If I live with you, could it happen?" "I don't know." "But you and I are people who can't hope for happiness, aren't we?" "After all, I'm someone who's using you to win against your mother, and you're using me to hurt Tak Gu, and take me away from him." "We are together for reasons that's so far from happiness." "Could we actually ever attain happiness?" "That's true." "Hearing you say that, I see that's the case." "I have something to give you." "This weekend when you come to dinner, make sure you wear this bracelet." "What meaning does it hold?" "It means that I'm going to marry you." "Perhaps it means, it may cause the beginning of misery." "And, if knowing that, you will continue on this path with me," "I'll take it to the very end." "It means something like that." "I'll see you this weekend." "I'll come and pick you up." "Mi Sun." "Why... didn't I know when he was around?" "How great his presence was." "I miss Grandpa." "My grandpa..." "I miss my grandpa so much." "I miss my grandpa so much, Tak Gu!" "Grandpa!" "[The world's happiest bread]" "[Baker King, Kim Tak Gu]" "Isn't that the smell of bread baking?" "Excuse me?" "Uh." "It is." "It smells like it's coming from our bakery." "Who in the world is it?" "So early in the morning?" "Come and eat, everyone!" "Breakfast is here!" "Hmm?" "What is all this?" "Fresh baked breads." "I brought it for your breakfast." "I don't know how it will taste." "But, I made it just as Master made it for me last." "Aigoo, the bread is really moist." "Is this bread or collagen?" "It's so soft." "It's really good, really good, eh?" "I think the kneading must have been perfect." "The flavor is just right, and the outside has a nice crisp sheen and color." "And the individual shapes came out really nicely, Boss." "Looks like we can eat these now without jam or cream." "So, I guess it means you're now making some proper edible bread." "Boss..." "It's not just edible." "It's tasty." "It's really good, Tak Gu." "It's a lot like the bread Father used to make." "Thank you." "Why are you just standing there?" "Come sit, huh?" "Sit down and eat with us." "Yes, Boss." "Now then." "What?" "Jin Gu Hyungnim left?" "Mmm." "He said it would be awkward saying goodbye if everyone knew, so he just said goodbye to my father and left early this morning." "Still, how could he leave without a word to any of us?" "So, where did he go?" "What bakery?" "I don't know." "He didn't say anything to Dad either." "He just said he couldn't return for a while." "That's all he said." "Where on earth has he gone?" "It's good you came." "The real fight begins now." "I'm looking forward to what you can do." "Madam, you've come." " Where's the President?" " He's not in right now." "He's out for a dinner appointment." "Where did he go?" "We don't really know." "Place a call to him." "Excuse me?" "Driver Yoon must have taken him." "Call him." "Yes, Madam." "President." "No, don't stand up." "So, what did you want to see me about?" "There's no reason." "I just wanted to see you and have dinner with you, like this." "What just happened?" "14 years ago, when I was in an accident," "I hurt my eyes a bit." "Occasionally, I have problems with my vision." "I'm sorry." "I am so very sorry." "If words like that could make me forget all of the past, how nice that would be." "What should I do?" "If I ask you to do something, could you even do it?" "In regards to what you are planning right now," "I can't do anything." "The reason suddenly dawned on me, the reason, why you suddenly stunned me about my mother's death," "You thought I wouldn't know the reason?" "This kind of revenge isn't right." "Your hurt will only deepen." "Oh, how grateful I should be." "You're not possibly showing concern for me, are you?" "Can't you forgive what happened in the past?" "Starting now, I'll rectify the things that have gone wrong." "Is it not possible?" "Why didn't you take care of him?" "Our Tak Gu..." "You promised to look after him, so why didn't you?" "Why?" "Look..." "Those people, do you know what they did to our Tak Gu?" "They tried to send him off onto a deep sea fishing boat." "They tried to send off a 12 year old child onto a fishing boat, the young Madam and Manager Han!" "What are you saying?" "Living under the heavens, people can't do such dreadful things." "As a human being, those are things one absolutely mustn't do!" "Are you... really saying, my wife did those things?" "Forgive what's happened in the past?" "For the past 14 years, my heart's been pierced and resentment has been festering in my blood, and you ask me to forget all those years?" "I can't do that." "I absolutely won't forgive." "If you leave like this, what am I supposed to do?" "Follow them." "Excuse me?" "What are you waiting for?" "Follow that car immediately." "Ah, ah, yes." "President!" "Are you all right?" "I'm all right." "My hand is just a bit sore." "Um, but President..." "Actually, outside..." "Madam was here." "What are you talking about?" "She followed the woman you were with earlier." "The President's wife's car is still following us." "Shall I lose her?" "Let's go there." "Excuse me?" "Let's take her there." "All right, I understand." "Hello." "Ah yes, President." "We're headed toward Cheongsan." "[The world's happiest bread]" "You must be tired following such a long way." "Let's talk." "I had something to talk to you about as well." "Shall we walk?" "I have some place to show you too." "Where in the world are you going?" "We're almost there." "Follow me just a little longer." "They went towards the cliff." "What?" "It was here." "What?" "This is where" "I fell and died, 14 years ago." "Did you bring me all this way to complain about that?" "What could I do to make your life difficult?" "What could I do to take revenge on you painfully?" "For the last 14 years, that's all I thought of, again and again." "Then, you've succeeded somewhat." "Because right now, I'm seriously upset by you." "If you insist on crossing a line you shouldn't with my husband, then I won't leave you alone any longer." "Let's end it here." "A heart full of hate for a person has no end." "The more pain you cause, the more painful things happen." "You..." "What are you thinking right now?" "You wouldn't..." "Let's end it right here, Madam." "You're crazy!" "What the hell are you doing?" "Let go!" "Let go!" "With the two of us gone, everything will be fine." "Let's go together." "Even if I were to die, do you think I'll die with you?" "Let go of me." "Let go immediately!" "I can't do that." "Let's go!" "Stop it right now!" "Honey!" "Let go of that hand." "I don't want to." "Please let it go." "The person you need to punish is not this person, but me." "All of this was my fault." "It happened because of my order." "It was me that sent someone to protect you." "The person who sent someone to separate you and Tak Gu was also me." "So the person you need to punish is not her, but me." "Why... why..." "Tak Gu, that child," "I wanted to bring him up solely as my legitimate son." "I wanted to separate you from that child, and make him solely the eldest son of Geosung." "All of it was my fault." "So, please stop." "Even though it's only but an empty shell, but to me," "it's a family I must protect." "She is my wife, and they are my children." "So, please stop now." "Even if it's only for Tak Gu, whom you miss so much, please stop now." "What?" "Tak Gu... your son." "You think you'll deceive me again with those words?" "Do I look like I'm deceiving you right now?" "Is it true?" "Is my Tak Gu... truly, is alive?" "He's grown up to be a fine young man." "He's now an excellent baker." "My..." "Tak Gu?" "Tak Gu." "Tak Gu." "President!" "President!" "President, what's the matter?" "What's the matter, President?" "President!" "Ahjumma, I'll get it." "Hello?" "Mom." "Why's your voice sound like that?" "What's going on?" "What?" "The President?" "Yes." "They are currently headed to the hospital." "I think you should go, Manager." "Honey!" "Open your eyes." "Honey, what's the matter?" " Cerebral hemorrhage?" " Yes" "Then, when will he wake up?" "We can't guarantee anything." "Even if he regains consciousness, he may be paralyzed on one side." "Right now, all we can do is wait..." "You're a doctor." "Is that all a doctor can say?" "My husband is lying there unconscious, and you say, all we can do is wait?" "All we can do is wait!" "Mom, calm down." "We understand what you're saying for now, Doctor." "We'll wait." "What do you mean we'll wait!" "Immediately, bring my husband back to consciousness." "Bring my husband back to consciousness!" "Doctor, you can go." "Save my husband first." "Where are you going?" "Where are you going?" "Stop it, Mom!" "The doctor has done everything he can." "If all we can do is wait, we have to wait!" "Please, calm down." "If you act like this, it becomes harder for all of us." "Please, let's just pray that Dad can wake up safely, huh?" "Save him!" "Save him!" "Save him!" "Why didn't I stop?" "It's all my fault." "This is all happening because of me." "Doctor, please save the president." "Will you?" "No matter what, he has to wake up." "Only then... only then, can I face the senior Madam after I'm gone." "Only then, can I look for Tak Gu." "Is this guy living okay?" "You look exhausted." "Yeah, a little." "How did you know?" "I'm supposed to return to the secretary's office on Monday." "I was in the office talking about that." "That secretary's office, do you have to go back there?" "How's the President?" "Is he okay?" "I don't know." "What about you?" "Are you okay?" "And what's this now?" "Are you being polite, or are you really concerned about me?" "Go on and check in on the President." "I better go and catch the last bus." "Just stay 5 minutes." "Just 5 minutes." "You, what are you doing here right now?" "I'm asking you." "What are you doing here!" "It's gone." "What?" "It's not at the office and it's not here." "What's not?" "I can't find the President's company stock shares certificate." "Are you in your right mind?" "He's lying there, and we have no idea when he may wake up, and you can look for that sort of thing right now!" "Because the President is on his sick bed, of course, we need to get our hands on it first." "Have you forgotten that his eldest son according to the family registry is Tak Gu?" "If by any chance, the President's stocks are passed on by a will or default order, the beneficiary is not Ma Jun, but Tak Gu." "We have to block that situation." "What brings you here, sir?" "Are you President Gu Il Jung's eldest son, Kim Tak Gu?" "Yes, that's right." "But, who are you?" "I'm Geosung Foods' legal counsel, Park In Taek." "It's not here." "Where is it?" "Mom, we have to go see Father at the hospital..." "Mom!" "Where the hell did he put it?" "What happened here?" "Did you do this?" "It's not here." "Excuse me?" "Where on earth did he put it?" "Where'd he put it?" "What is this?" "It's something that the President asked me to keep, about a month ago." "He told me that if by chance, any problems arise with his health or life, that I should find Kim Tak Gu at Pal Bong Bakery and deliver it myself to you." "What are you saying?" "What do you mean any problems with his health or life?" "Then, are you saying..." "Last night, President Gu Il Jung suddenly collapsed due to cerebral hemorrhage." "*(bleeding into the brain tissue)*" "[Power of Attorney]" "Tak Gu, if by any chance, something happens to me, the only one who could act in my place is you." "[Register of Geosung Shareholders]" "[Title Deed, Gu Il Jung]" "[Stock Certificate]" "All my deeds and stocks I'm entrusting to you, so please, look after Geosung, Tak Gu." "How's his condition?" "In these last few days, his vital signs have improved quite a bit." "The issue is still the uncertainty of when will he regain consciousness." "I see." "Then, for now, his life is not in danger." "Is that correct?" "Yes." "We've passed the critical phase for now." "Then, that's fine." "Then, I think we'll be taking the President home." "Mom." "Your father absolutely hates hospitals." "If we take him home and he's comfortable, his recovery will be much faster." "I'll inform Chief Ju of that plan, so please get everything ready, Doctor Jung." "Yes, well..." "But anyhow, have you seen the papers?" "I took a glimpse, and it looks like Il Jung's condition is really critical." "Do you think we should go and see him?" "What's the matter, Tak Gu?" "Aren't you eating?" "Oh." "I had some bread earlier, and I feel full." "Then, if you'll excuse me..." "I'm sorry, President." "I can't return to Geosung." "I don't have many people around me I can trust, Tak Gu." "Now, I'm not sure who to trust and who to be suspicious of." "It looks like Il Jung's condition has gotten really critical." "He suddenly collapsed due to cerebral hemorrhage." "Why... didn't I know when he was around?" "How great his presence was." "Who are you?" "Who are you?" "Whoa." "Oh my gosh!" "I didn't know there were houses so big!" "It's really big!" "Wow!" "Let's go in." "Who's house is it?" "Is it someone you know?" "It's your father's house." "Who are you?" "I'm Kim Tak Gu," "Geosung Food President Gu Il Jung's eldest son." "Please let them know Kim Tak Gu is here." "Yes." "Let him in." "They say a guest has arrived." "Who is it?" "You came?" "Yeah." "I came." "Brought to you by WITH S2 Written In The Heavens Subbing Squad" "Main Translator: meju" "Spot Translators: ai*, serendipity" "Timer: julier" "Editor/QC:" "PTTaT" "Coordinators: mily2, ay_link" "Watch dramas legally at dramafever. com | crunchyroll. com"

An estimated 142,000 men and women died of lung cancer in 1990. The majority of patients present with locally advanced, unresectable disease for whom the 5 year survival is 5-7%. New strategies are urgently needed to improve the therapeutic ratio. Frequently, advanced non-small cell (NSC) lung cancer will produce endobronchial obstruction. High dose rate (HDR) brachytherapy combined with external beam irradiation has the advantage of providing improved localization so that the portion of the tumor most responsible for the obstruction receives the highest dose, while sparing the normal surrounding lung tissue. The lung is one of the most sensitive structures to irradiation and is a major dose-limiting organ to the delivery of optimal therapy. The acute and late effects of radiation therapy, pneumonitis and pulmonary fibrosis, are of particular concern and the ability to predict for these side effects could allow early intervention and thus, reduce the morbidity of lung cancer therapy. We propose to identify the optimal dose schedule for concurrent external radiation therapy and HDR brachytherapy in terms of symptom relief and local disease response in patients with locally advanced NSC lung cancer. Because HDR brachytherapy requires bronchoscopy, it provides a unique opportunity, via bronchoalveolar lavage (BAL), to study the effects of irradiation in vivo, and to correlate laboratory findings to date in several animal models with clinical outcome in humans. Serial BAL will provide cellular material to: identify and quantify the production of specific growth factors for fibroblasts by alveolar macrophages induced by radiation; measure production of extra cellular matrix (ECM) proteins and expression of ECM mRNA in vitro by fibroblasts in response to specific growth and inhibitory factors produced by alveolar macrophages; identify changes in cellular responses outside the radiation volume due to the release of biochemical messages from within the irradiated volume. Serum samples will be analyzed to measure the release of biochemical messages into the vascular system after irradiation as monitors/predictors of radiation injury. These laboratory findings will be correlated with each patient's clinical outcome. The information obtained could contribute significantly to our understanding of the pneumonitic and fibrotic processes secondary to lung irradiation in humans. This could enable the development of early interventions and would impact on our ability to lower the morbidity in future clinical trials for all disease sites where the lungs may be irradiated.

The use of oil bottles or other recipients containing oil for dressing salads and the like is a common operation, which is widely known in the current state of the art. The recipients used for these purposes incorporate some kind of outlet conduit which generally consists of a hole of reduced diameter allowing the user to control as far as possible the amount of oil poured during the salad dressing operation. Oil bottles have some practical disadvantages, for example the fact that the outlet conduit has a reduced diameter and hence a very limited flow rate. An oil bottle or dispenser is practical when it is used to dress an individual salad or the like, which requires a relatively small amount of oil, but is not so practical when in comes to dressing salads intended for a number of people, in which case the limited flow rate requires a greater amount of handling and time; another drawback consists of the fact that the single outlet with a limited flow rate means that the air drawn into the recipient as the product is extracted also has to circulate through the same conduit as the oil being poured; this shakes the pouring intermittent, with continuous interruptions which hamper the extraction operation by causing the oil to come out in spurts. The state of the art shows different valves or rotating mechanisms to modify the pouring flow rate. However, these devices have the disadvantage that the number of parts required for manufacture increases, with the subsequent cost and, on the other hand, residues of the liquids, in particular when viscous liquids are poured, accumulate in the joins, and may compromise the quality of the stored liquid. The problem solved by the invention is to find a multi-flow dosage cap with the minimum number of parts, which produces a uniform flow of the liquid. The solution found by the inventors is a cap with a lower part with the means to adapt it to the recipient, a pouring channel and an upper part which comprises pouring means. The pouring means are two “U”-shaped channelled tracks with different radii. The channelled tracks are located at diametrically opposed points. The lower part and the upper part of the cap are separated by a partition. The partition contains a slit which ends in two holes with different areas, and the aforementioned channelled tracks are aligned with the holes, i.e. the track with the larger radius is aligned with the hole with the larger area. The cap produces two different flow rates of oil. This allows the user to choose which of the two holes should be used at each moment, depending or whether, for example, the salad to be dressed is individual or is a larger salad intended for consumption by more than one person. This cap construction also has the feature that the flow of oil provided is continuous, without interruptions, given that, because only one of the conduits for the oil is used at any one time, the other conduit acts as an air inlet, thus facilitating the extraction of oil. The present multi-flow dosage cap has the advantage of being perfectly adjustable to the necks of the current recipients. In a preferred embodiment, the adjustment involves a screw thread or by pressure. According to the invention, the design of the presently proposed cap allows various forms of embodiment. In a first embodiment, the interior space of the cap is divided by means of an internal central partition, with a slit in the central partition and two holes. The pouring channel ends in two “U”-shaped pipes or conduits, with different radii, and the pouring conduits are aligned with the holes in the central partition. This means that, by tilting the bottle to one side or another, the desired outlet conduit can be selected, and thus the volume of oil in the chosen flow. The slit allows air to enter and gives a continuous flow. In other embodiments of the inventive cap, the internal division may contain an integrated partition running lengthways to the centre of the cap, which determines at the outlet end two conduits or pipes with very different respective flow capacities; one or other of the outlets is selected as described above, i.e. by tilting the bottle to one side or the other. In a preferential embodiment, the central partition is sloping. In addition to the formation of a sloping internal partition, the profile of the partition may either be straight or curved, arched. In another particular mode, the cap contains a skirt ring which projects outwards in a radial direction, and is adapted to be coupled to the edge of the neck or the recipient. The skirt prevents any dripping liquid from staining the table. The cap may be manufactured with any material compatible with the liquid to be poured. In a preferred mode, it is made of polypropylene and injection-moulded. The cap is suitable for the manufacture of oil holders or bottles containing oils.

Published data show that beta amyloid vaccination can markedly reduce amyloid burdens, apparently by activating microglia to degrade amyloid. Vaccinations may also prevent certain behavioral deficits. The overall impact on the AD phenotype remains vague. Vaccination might be expected to reduce amyloid but activate microglial inflammatory cytokine production, NADPH oxidase and reactive oxygen species. This may lead to a net decrease or possibly even an increase in oxidative damage and synapse loss. In this proposal, Aim 1 will address unanswered questions about the impact of vaccination at different timepoints on aspects of inflammation while aim 2 will investigate the impact on oxidative damage and synaptic pathology that we have documented in aging APP transgenic mice. Present data suggests that vaccination may not reduce Abeta 40 and vascular amyloid. There is also a real danger that vaccination may induce vascular damage and possibly even hemorrhage. Aim 3 will assess the impact of vaccination on amyloid and soluble Abeta in different compartments, vascular amyloid and vessel damage. Finally, there are unanswered questions about the mechanisms of amyloid reduction induced by vaccination. Available data strongly support an increase in amyloid phagocytosis by microglia, but data on enhanced degradation are inconsistent with some reports showing increases and some showing no change in amyloid degradation. Aim 4 will investigate hypotheses about the mechanisms involved in vaccine induced amyloid reductions. If successful, these experiments would be expected to lead to small molecule approaches to mitigate potential harmful effects of vaccination and to conceivably enhance amyloid removal.

A novel model to predict the risk of readmission in patients with renal colic. Abstract Purpose: To identify the clinical, laboratory, and imaging parameters that may increase the risk of readmission in patients with renal colic that is managed by active surveillance and to produce a novel model to predict the risk for this. We retrospectively reviewed patients with renal colic secondary to ureteral calculi admitted to our hospital from March 2009 until September 2010. The colic was managed with active surveillance for 6 weeks. Patients were divided into those who were not readmitted to the hospital within the follow-up period (group A) and those who were (group B). From the 452 studied patients, 82 (18.1%) were readmitted to the hospital. Stone size (P<0.001) and location (P<0.001) and serum white blood cell count (P=0.009) were statistically significantly different between groups. These parameters were found to be independent predictors for readmission. A predictive model was produced to calculate the risk of readmission. Stone size and location and white blood cell count are independent predictors for potential readmission in patients with renal colic. Using these parameters, we may calculate the risk for readmission, and the latter may assist physicians in identifying the best treatment option.

The present invention generally relates to optical transmission networks and more particularly to the establishment of dedicated LAN connections in optical transmission networks. In optical transmission networks, information is transmitted between network elements (NEs) via optical fibers. As is well known, the majority of the transmission capacity available in each fiber is typically used for transporting client information (hereinafter referred to as payload) while some capacity (hereinafter referred to as overhead) is set aside for transmission management and control. In the majority of optical transmission networks, it is common to provision dedicated connections between NEs which do not use any of the optical fiber capacity used for payload transmissions. These connections are highly desirable because they can provide some additional and separate connectivity between NEs without using any transport capacity which could otherwise serve for transmitting payload information and generate revenues. Dedicated connections are often provisioned in optical transmission networks to provide remote access to or interconnect local area networks (LANs). For example, dedicated connections will be established between NEs of an optical transmission network where different NEs are located in close proximity of separate LANs or where a user connected to one NE wishes to access a LAN located in proximity of another NE. By using dedicated connections, LANs can be interconnected or remotely accessed through an optical transmission network without using any of the payload capacity available therein. Dedicated connections in an optical transmission network can also be used to monitor equipment for maintenance, administration, provisioning or simply to monitor data transmissions. Typically, the monitoring is performed remotely from a central monitoring unit installed in proximity to a particular NE, and connected to other NEs in the network via dedicated monitoring connections. Presently, various methods are used to provide dedicated connectivity between NEs of an optical transmission network. However, these methods all present a number of disadvantages. Considering in particular the equipment monitoring usage, one traditional approach is to use a standard telephone connection between the monitoring unit and each NE in the network where equipment is to be monitored. In this approach, each telephone connection is terminated at its ends with a respective modem. At each NE, the modem terminating the telephone connection is connected directly to the monitored equipment by way of a serial connection such as, for example, RS-232. For NEs with multiple pieces of equipment to monitor, a pool of modems connected in parallel must be used where each modem provides a connection between the monitoring unit and a particular device or element to monitor in a one to one (1:1) arrangement. Apart from the inherent bandwidth restrictions of conventional telephone lines, this approach has a number of drawbacks. First, telephone network connectivity is required at both the monitoring site and each of the NEs where equipment is to be monitored. For NEs with many devices or elements to monitor where, as noted above, a large number of modems is required, this approach could be quite prohibitive, particularly for NEs in remote areas. In addition to being prohibitive, this method increases the complexity of the monitoring equipment. More specifically, with the need to establish at least one telephone connection and use at least one modem at each NE where equipment is to be monitored, data collection cannot be easily automated unless a sophisticated-monitoring unit is used. Further, because the modems and telephone connections used at each NE are external to the optical transmission network, they must be managed separately. Apart from the obvious resulting high cost, maintaining a separate network of telephone connections and modems would also have a considerable impact on the overall complexity of the monitoring equipment. Another conventional method used to provide dedicated connectivity for remotely monitoring equipment at NEs without using the available network capacity consists of deploying a dedicated network of data connections linking the monitoring unit with each monitored NE site. According to this method, each data network connection is terminated at its ends with a respective bridge. At each NE, the bridge terminating the network connection is connected directly to the monitored equipment by way of a multi-access link such as Ethernet. Similarly to the telephone method described above where at each NE, modems must be connected to the monitored equipment in a 1:1 configuration, a bridge can also be connected in a 1:1 arrangement. In contrast however, bridges can also be connected in a 1:N arrangement if a large number of devices must be monitored. An obvious advantage of dedicated data network connections over telephone lines is that the capacity provided by data network connections is considerably higher and with possible 1:1 or 1:N connection arrangements, the connectivity provided at each NE is more flexible. However, despite offering a higher transmission capacity and a more flexible connectivity at each NE, this approach requires that a separate data network be deployed and maintained separately from the optical transmission network. Similarly to the telephone line approach described above, the provisioning and maintenance of a separate data network substantially increases the overall cost and complexity of the optical transmission network. In synchronous optical networks (SONET), another conventional method for remotely monitoring equipment without using any of the available payload transport capacity consists of using an audio channel in the SONET overhead. This channel typically referred to as the orderwire (OW) channel is normally provisioned for voice communications in the network. According to this method however, the OW channel is provisioned instead to establish a monitoring connection between NEs and a monitoring unit. According to this method, the monitoring unit is connected to a nearby NE with a modem and a telephone line to access to OW channel. At NEs with equipment to monitor, a telephone line terminated with a modem is also used to connect to the OW channel. For NEs with multiple pieces of equipment to monitor, a pool of modems connected in parallel must also be used where each modem provides a connection between the monitoring unit and a particular device or element to monitor. The main benefit of this approach is that it does not require a separate telephone network. However, because modems and telephones lines are still necessary, the disadvantages associated with their use also apply to this method. This includes low capacity, limited connection flexibility at the NEs (limited to 1:1 configurations and not 1:N configurations), complex data collection at the monitoring unit and the need to manage a network of modems separately from the optical transmission network. Therefore, in view of the shortcomings of conventional dedicated connection schemes, it would be desirable to provide optical transmission networks with dedicated connections between NEs which are cost-effective, simple and can offer increased capacity, flexible connectivity without the need for managing or maintaining external network components. The present invention provides a method and apparatus for establishing dedicated local area network (LAN) connectivity between network elements (NEs) in an optical transmission network without using any of the payload transport capacity available. In order to provision dedicated LAN connections in an optical transmission network without using the available payload transport capacity, the invention reallocates overhead functionality to provide dedicated bandwidth between NEs. At each NE, a respective LAN interface unit provides access to this dedicated bandwidth and allows the NEs or LAN networks or devices connected thereto such as personal computers (PCs), servers and monitoring equipment to communicate without consuming any payload transport capacity available in the network. According to a broad aspect, the invention provides a method of transmitting LAN data in an optical transmission network wherein information is transmitting frames, each frame containing a first plurality of bytes for transmitting payload data and a second plurality of bytes for transmitting overhead data, the method comprising allocating in each frame one or more bytes of the second plurality of bytes for LAN data transmissions, for each LAN data transmission, transmitting frames with LAN data in the one or more allocated bytes until the LAN data transmission is complete. According to another broad aspect, the invention provides an optical transmission network formed of multiple NEs interconnected with optical links where each link has a defined payload transmission capacity allocated for payload data transmissions and a defined overhead transmission capacity allocated for overhead data transmissions of which a portion is reallocated for LAN data transmissions, the optical transmission network comprising at each NE a LAN interface connected to receive LAN data from one or more LAN devices for transmission in the reallocated portion of the overhead transmission capacity and an optical transmitter connected to the LAN interface and operable to transmit the received LAN data using the reallocated portion of the overhead transmission capacity. According to yet another broad aspect, the invention provides an apparatus for a first NE in an optical transmission network for transmitting LAN data to a second NE via an optical link interconnecting the first and second NE wherein the optical link has a defined payload transmission capacity allocated for payload data transmissions and a defined overhead transmission capacity allocated for overhead data transmissions of which a portion is reallocated for LAN data transmissions, the apparatus including a LAN interface connected to receive LAN data for transmission with the reallocated portion of the overhead transmission capacity and an optical transmitter connected to the LAN interface and operable to transmit the received LAN data using the reallocated portion of the overhead transmission capacity. According to yet another broad aspect, the invention provides a LAN interface connecting a LAN device to a NE in an optical transmission network of a defined payload transmission capacity allocated for payload data transmissions and a defined overhead transmission capacity allocated for overhead data transmissions of which a portion is reallocated for LAN data transmissions, the LAN interface being operable to receive LAN data from the LAN device and process the LAN data received for transmission using the reallocated portion of the overhead transmission capacity. Preferably, the reallocated portion can either be an optical channel such as the optical service channel (OSC) or overhead bytes in an optical channel. In the latter case, the overhead bytes could be one or more overhead bytes. The invention can be incorporated in any optical transmission network topology or configuration such as for example, synchronous optical networks (SONET) or optical transport networks (OTN) where it is desirable to establish dedicated connections between NEs without using any of the payload transport capacity available. In a preferred embodiment, the invention is used to provide dedicated layer 2 Ethernet connectivity between NEs in a SONET network. In order to provide this Ethernet connectivity, the invention uses F1 bytes in the SONET overhead to establish dedicated bandwidth for Ethernet communications between NEs. When the SONET overhead is not visible, it is possible to use other overhead functionality to establish dedicated bandwidth. In another preferred embodiment, an optical service channel is used to provide this dedicated bandwidth. In both embodiments, an Ethernet wayside (EW) unit is used at each NE to provide access to this dedicated bandwidth. The EW unit can be used to attach multiple Ethernet devices or networks. By using overhead bytes (e.g. F1 bytes) or optical channels which are conventionally allocated for overhead, the invention can be used to support various LAN communications across the NEs without using any of the payload bandwidth available. For example, the dedicated bandwidth could be used for software download of loads to each NE. Alternatively, a network administrator at a monitoring unit could remotely monitor equipment at or in proximity of the NEs in the network without consuming any of the payload transmission capacity available and adversely affect transport revenues. Another advantage of the invention is that the dedicated LAN connections provided by the present invention can provide in excess of 10 megabits per second of transport capacity. In addition, the dedicated LAN connections are provisioned internally to the optical transmission network therefore eliminating the need for deploying and maintaining any additional telephone or data network external to the optical transmission network. Therefore, the overall cost of providing dedicated connections in an optical transmission network is considerably reduced. Yet another advantage of the present invention is that multiple LAN devices can be connected at each NE via a single LAN interface unit (e.g. a EW unit). With this ability, the invention can advantageously be used to establish point-to-point or point-to-multipoint LAN connections between NEs of an optical transmission network. In addition to equipment monitoring, these point-to-point or point-to-multipoint LAN connections can also be used for LAN applications such as for example, connectivity between LANs or as a further example, remote access by one or more users to a LAN.

Over the years, a number of ways have developed for the design and construction of control devices using mechanical and electromechanical equipment that have proved to be safe and reliable in operation. These types of devices have been used for many years in the control of equipment that can create unsafe conditions if a failure occurs. An example of this type of equipment is a burner control system that is operated under the supervision of units that generically are referred to as flame safeguard systems. In this burner control art it is essential that upon certain types of failures that the fuel valve to a fuel burner be closed. The failure of a flame safeguard control system to operate properly can lead to a situation in which a fuel valve is left open when no flame exists, and a fuel-burning chamber can be loaded with fuel. This fuel can then accidentally be ignited causing an explosion. This type of failure can generally be guarded against in the existing technology of flame safeguard systems by utilizing safety checking types of circuits that repetitively simulate the absence of flame and then check for the presence of flame. These types of systems then repetitively charge and discharge a capacitive series arrangement to hold in a control relay that in turn energizes the fuel valve. This type of closed loop safety system has been used for a number of years, and is generally considered to be quite reliable. In recent years, the conventional electromechanical and electronic types of control systems, including flame safeguard control systems, have been displaced by electronic control systems of the digital type that utilize microprocessors or microcomputers as the heart of the condition responsive control circuit means. The use of digital logic including microcomputers and microprocessors leads to many benefits in that more sophisticated and fuel efficient types of control systems can be developed. The detriment of the use of digital logic and microcomputers or microprocessors is that circuit failures within the digital equipment can occur and result in an unsafe mode of operation of the overall control system. The normal technique for verifying the operation of a computer-type of microprocessors or microcomputer arrangement is in the use of dual processors. In this case, one computer or processor is programmed to check up on the other processor or computer, and vice versa. This redundancy allows for the detection of a malfunction, and allows the healthy processor or microcomputer to take the necessary corrective action in the event of a failure of the other of the dual elements. The use of dual microcomputers or microprocessors is a very expensive and complex technique for generating a safe operating control system. It is essential for the practical application of safety control systems, such as the flame safeguard control systems, that a reliable and less expensive approach be developed.

With the development of radio networks, data services play a more and more important role in the radio networks, and accordingly require a broader and broader transmission bandwidth. The data services demand a broader bandwidth than voice services do. Especially after the introduction of High Speed Downlink Packet Access (HSDPA), High Speed Uplink Packet Access (HSUPA) and Code Division Multiple Access (CDMA) 1X Do, the transmission rates of the data services that may be provided for the terminals have become higher and higher, and development of the data services has also become faster and faster. Consequently, the traffic load on a base station grows increasingly, and a broader transmission bandwidth is demanded by the base station. In the conventional radio networks, the base stations having three sectors are generally used. After the introduction of HSDPA, HSUPA or CDMA 1X Do, the downlink throughput of the base station may be up to 9 megabits per second (Mbps) and the uplink throughput thereof may be up to 1 Mbps, so as to ensure the data service transmission for the terminals. Plus the overheads of the lower layers, the resulting rate of the physical layer is proximately 15 Mbps in the downlink direction and 1.5 Mbps in the uplink direction. The fees for the data services are relatively low, and thus the income from the data services is greatly less than that from the voice services. In this case, if operators go on to implement the access and data transmission of the base station by using the E1/T1. with expensive rent, their profit is reduced severely. The x Digital Subscriber Line (xDSL) is a family of technologies that provide very high-bandwidth digital signal transmission over conventional telephone lines and have advantages in convenient access, abundant transmission resources and low transmission cost. At present the xDSL technologies are generally applied in the radio networks. Compared with the accessing of base station by use of E1/T1, the accessing of base station by use of xDSL may reduce the cost in base station access significantly. It is primarily the Very high speed Digital Subscriber Line (VDSL) and the Asymmetric Digital Subscriber Line (ADSL) in the xDSL family that are used to implement the base station access in the prior art. The two application scenarios are described respectively as below. FIG. 1 shows a schematic diagram of a networking structure for implementing base station access by use of VDSL in the prior art. It may he seen from FIG. 1 that a base station is connected to a VDSL Modem via an Ethernet line, the VDSL Modern is connected to a Digital Subscriber Line Access Multiplexer (DST AM) via a twisted-pair, and the DSLAM is connected to a Broadband Access Service (BAS) via a fast Ethernet network. The BAS transfers the traffic on the DSLAM to a radio network controller (RNC) via an IP network, The transmission rate of VDSL in the uplink direction may be up to 1.5 Mbps and in the downlink direction may be up to 12 Mbps. Thus, the bandwidth of VDSL may meet the requirements for data transmission in base station access. However, the valid transmission distance of VDSL is 1 kilometer(km) beyond which the rate of VDSL decreases rapidly. Therefore, VDSL may be only used in short-distance base station access and thus can not be applied widely. FIG. 2 shows a schematic diagram of a networking structure for implementing base station access by use of ADSL in the prior art. This figure is basically the same as FIG. 1, except that the base station is connected to an ADSL Modem via an Ethernet line and ADSL access technologies are employed therein. ADSL is applied widely. ADSL has a valid transmission distance up to 3 km and thus is applicable to long-distance base station access. However, because the bandwidth of ADSL is too narrow, i.e. proximately 0.5 Mbps in the uplink direction and proximately 6 Mbps in the downlink direction, the base station access by use of ADSL is unable to meet the requirements of most base stations for transmission bandwidth.

U.S. Pat. No. 3 976 577, assigned to the assignee of the present invention, shows a prior high pressure liquid filter system for industrial use in which plural side-by-side filter units are spaced along an array of vertically spaced horizontal conduits, for example backwash, filtered liquid outlet, process liquid inlet, and drain (blow off) conduits in descending order. A set of four valves, namely respective backwash, filtered liquid outlet, process liquid inlet, and drain valves, connect the respective backwash, filter liquid outlet, process liquid inlet and drain conduits to a filter unit or pair of filter units. Each of the four valves is equipped with its own individually controlled pneumatic actuator. The backwash and filtered liquid outlet valves are mechanically linked and connected to the top of the filter unit and the process liquid inlet and drain valves are mechanically linked and connected to the bottom of the filter unit. A given mechanical link assures that both of its valves are not simultaneously in the full open position and such links are mere synchronizers, actuation of the valves being by the individual pneumatic actuators. A link interconnects the pneumatic actuators for the process liquid inlet valve and drain valve and a second link interconnects the pneumatic actuators for the filter liquid outlet valve and backwash liquid inlet valve. The connections of such links to such pneumatic actuators are exposed. In normal operation, process liquid from the process liquid inlet conduit passes up through all of the filter units simultaneously and thence appears as filtered liquid in the filtered liquid outlet. Eventually back pressure in the filter units rises due to build up on the filter of solids filtered from the process liquid. This is cured by shifting the valves connecting one or a pair of the filter units to terminate process liquid flow (filtering flow) therethrough and instead permit backwash liquid flow from the backwash conduit through the filter unit to the drain conduit while the rest of the filter units continue filtering flow. In this way the filtering operation of the system as a whole is continuous and yet the filter units are backwashed one or a pair at a time. Filter systems of this kind are usable for filtering of various process liquids including hot and/or abrasive process liquids. For example, systems of this kind are usable in chemical plants, pulp mills, refineries etc. In one particular example, process liquid temperatures in the range of 400.degree.-550.degree. F. are frequently encountered in refinery installations. To avoid loss of process liquid heat and to reduce the need to reheat process liquid, it is known to locate a heat retaining (insulative) box around the major portion of the filter system, the four pneumatic actuators per filter unit, or filter unit pair, being outside the heat retaining box to avoid heat damage to their internal seals. In the prior patent, each of the actuators was controlled by a solenoid valve, the solenoid valves being located outside the heat retaining box along a bottom frame member of the apparatus. The system disclosed in above mentioned U.S. Pat. No. 3,976,577 has proven satisfactory in service, but a continuing effort to improve systems of this general kind has resulted in the present invention. The objects of the present invention include provision of: (1) a filter assembly in which there is a substantial reduction in the number of pneumatic actuators as well as a change in the type of pneumatic actuator, in which there is only one actuator per filter unit (or filter unit pair) rather than one per valve, and wherein all four valves (backwash, filtered liquid output, process liquid input and drain valves) are positively mechanically interlinked for both (1) positive mechanical actuation of each and (2) simultaneous synchronization of opening and closing of all four valves, wherein the number of valve actuating parts susceptible to wear or damage is reduced by a factor of four wherein the likelihood of down time due to failed actuators is correspondingly reduced, and wherein the number of pressurizable air lines leading to actuators is correspondingly reduced so as to reduce clutter and complexity and cost in the air circuitry; (2) an assembly as aforesaid, in which the valve actuator levers and their pivot connections to links are protected in which the drive motor is supported on actuator housings fixed to ones of the valves and not on the filter units, conduits or frame supporting the latter, wherein the motor and actuator housings are installable as a unit and are substitutable on existing field installations for actuators of earlier type, and wherein tolerance and alignment problems that may result from variations in location of the filter units, valves, conduits and frame members with respect to each other are minimized; (3) an assembly as aforesaid, in which the number of pneumatic lines susceptible to damage is substantially reduced, and in which pilot valves previously located on the lower portion of the frame are now located to be less susceptible to damage; (4) an assembly as aforesaid, wherein pivotable valve actuating levers are enclosed to more readily avoid contact with persons or objects moving therepast; (5) an assembly as aforesaid, in which any tendency for the motor driven actuator to twist its housing, upon actuation by said motor, is minimized; (6) an assembly as aforesaid, which is usable with liquids containing abrasive particles in which a tendency for abrasive particles to collect on and prematurely wear the drain valve seat is minimized. (7) an assembly as aforesaid, which is usable with hot liquids wherein a temperature drop across the drain valve is minimized, so as to minimize temperature differential induced dimensional changes and distortions and thereby avoid valve malfunction or failure resulting therefrom; and (8) an assembly as aforesaid, in which the major portions of the apparatus are enclosable in a heat insulating box with the drive motor and a control therefore located outside the box so as to be free of elevated temperatures within the box, the insulated box helping to reduce heat loss from preheated process liquid. Other objects and purposes of the invention will be apparent to persons acquainted with apparatus of this type upon reading the following specification and inspecting the accompanying drawings.

The invention relates to an apparatus and method of trading electric energy between utility companies and others. Specifically, the invention is a software product that, when coupled to a communications network, creates a trading environment for the electronic purchase and sale of electric energy, the scheduling and usage of the transmission system, and the automated invoicing and electronic funds transfer for the settlement of transactions. Electric energy is generated for public consumption by utility companies. Each utility company has a service area in which it enjoys near-monopoly status. The utility company is obligated to supply the electric energy needs of individual customers within the service area. Of course, the demand for electricity can vary according to a number of factors. In the long run, the demand for electricity is a function of the population and industries within the service area. In the short run, electrical demand varies according to many factors. Extreme weather, in particular, can significantly strain the generation capacity of the utility company. An electric energy grid exists which connects each utility""s generating facilities to those of adjacent utilities. Each circle represents an individual utility company. Each line represents high-voltage lines which form the grid between the various utilities. Electric energy is traded between utility companies and other market participants to meet shortfalls in capacity during unit outages, to achieve cost savings, or to increase revenues. xe2x80x9cBulk transactionsxe2x80x9d refers to the wholesale buying and selling of electrical energy. Typically, the parties involved in these trades are traditional electric utility companies. These companies wish to meet their obligations to provide reliable service to their customers in the most economically feasible manner. Often it is possible for a utility to purchase electricity from a neighboring utility more economically than it could produce it for itself. At other times, the power generator can sell excess generation at a price higher than its cost of generation. To determine which trades are economic, utilities produce sophisticated forecasts of load (required generation) so that they can schedule their generators to run efficiently. The system dispatcher then determines if demand is likely to be over or under projections during various times of the day. The dispatcher is also interested in the associated cost with each level of generation. Even though the load forecasts are sophisticated, actual conditions usually deviate from them. This may be due to a number of circumstances, such as having generating units go off-line unexpectedly, differences between forecast and actual weather conditions, or changes in the price of available fuel to run the generators. All of these events affect the costs to produce electricity. Because of changes in these forecasts, the dispatcher telephones neighboring utility companies to determine prices and quantities of energy available for upcoming hours. These calls occur many times a day, sometimes hourly. At the same time, dispatchers for other utilities are also making phone calls. If the dispatcher finds what he considers to be a good deal, a trade is consummated. The result is that deals are often struck before the phone surveys are complete. It is rare for a dispatcher to call beyond his direct neighbors, and almost never farther out than two companies. This means that the opportunity for more economic transactions may have been overlooked simply because the dispatcher did not know about them. A need exists for a system which creates substantial efficiency gains by automating this trading process over the current method of using the phone. This method of trading energy should allow utilities to simultaneously view real-time market prices and energy availabilities and to quickly consummate the best opportunities. The system should consider available transmission capacity, and calculate and schedule the least cost path for the energy. It should also report the transactions, invoice the participating parties, and facilitate rapid collection and disbursement of funds. Lastly, the system should allow for anonymous trading required of a true market. The present method, also known as CPEX, establishes a nationwide electronic information system that assists buyers and sellers of electricity to conduct business by providing a common marketplace. CPEX is an easy to use windows-based software and hardware system that enables Participants to gather market information and make energy transactions decisions based on the best available opportunities. CPEX involves a software application, a computer and communications network, and a central server. CPEX allows users to enter quantity and price information on energy that they have available to sell, wish to buy, or both. These offers are then sorted and presented to other CPEX Participants. These offers are sorted by lowest price to highest for purchase opportunities and sorted highest price to lowest for sale opportunities. Each Participant sees delivered price for purchases and total revenue for sales from its unique location in the electric grid. The purchase price of the energy is shown inclusive of any transmission charges, known as xe2x80x9cwheelingxe2x80x9d. Wheeling is a term used to refer to the transfer of electricity across a Participant""s transmission system. A Participant who provides wheeling services is referred to as a wheeler, and receives monetary compensation for providing this service. CPEX also allows the buyers and sellers of electrical energy to offer different degrees of firmness for their energy. Interruptible energy may be curtailed, or cut off, for any reason. Non-interruptible energy may only be curtailed to avoid or remedy an unreliable condition. Both types of energy have a distinct market. CPEX assists in maintaining the reliability of the electric grid by using a conservative method to schedule available transmission capacity. Each Participant maintains the amount of transmission capacity made available for CPEX transactions each hour. As transactions are consummated, this capacity is consumed and is no longer available for use by others. This helps assure that the transmission systems do not become unintentionally overloaded. Reliability is augmented by allowing simultaneous, electronic notification of all parties to a transaction upon a transaction""s curtailment. The current method of phone notification is inadequate when multiple parties are involved, as is common in buy/resell types of transactions. CPEX provides monthly billing and Electronic Funds Transfer (EFT) services for payments and disbursements to all Participants as part of the basic CPEX package. This feature allows Participants to trade with more companies than they would otherwise and to manage their invoicing and collections with their current levels of staffing.

Thermostatic mixing valves commonly employ a valve shuttle movable between hot and cold seats to control the relative proportions of hot and cold water supplied to an outlet in accordance with user selection of the outlet water temperature and a thermal control system to adjust the position of the valve shuttle to compensate for changes in the temperature and/or pressure of one or both supplies tending to change the set temperature. The known valve shuttles typically have a very small stroke, for example movement of the valve shuttle from full cold to full hot is generally less than 1 mm and is typically only 0.6 mm. As a result, misalignment of the valve shuttle affects the flows of hot and cold water and this can have a significant effect on the operation of the valve. For example, if the valve shuttle lifts off the hot seat unevenly, more of the hot water flows through one side of the valve and vice versa more of the cold water flows through the opposite side of the valve giving rise to asymmetric streams of hot and cold water producing incomplete mixing of the streams that affects the response of the thermal control system to correct any deviation in the outlet water temperature from the selected temperature. It has been proposed to employ close fit sliding guides to keep the valve shuttle aligned with the seats but the sliding parts add complexity, increase manufacturing costs and are susceptible to corrosion and lime-scale causing friction. Misalignment of the valve shuttle may also result in vibrations of the valve shuttle generating noise, especially under high pressure operating conditions. Thus, the water velocity at the edge of the valve shuttle produces a low pressure region that tends to pull the valve shuttle towards its seat and any misalignment of the valve shuttle causes the pull to be uneven and this can start vibration of the shuttle valve against its seat in what we believe is a nutating motion generating noise. Typically, the valve shuttle is mounted on a thermostat and the thermostat is displaced against the biasing of a return spring. Traditionally, the return spring is a helical coil spring of wire of circular cross-section and this may contribute to misalignment of the valve shuttle. In particular, the final turn of wire at either end of the spring coils around, not as desired in a plane perpendicular to the helical axis, but at an angle to the perpendicular. As a result, the valve shuttle mounted on the thermostat can be forced out of line with the valve seats by the inclination of the final turn of the helical wire at the ends of the spring causing the thermostat, and thus the valve shuttle carried by the shuttle, to be tilted slightly relative to the axial direction. This problem persists even if the best quality helical wire springs are used. Generally, thermostatic mixing valves can correct for inlet water temperature changes much better than inlet pressure changes. If the flow rate is reduced by restricting the valve outlet, then inlet pressure changes become much more severe for the valve to correct. FIG. 6 shows a graph of pressure loss ratio versus temperature of the mixed water at the outlet of a typical thermostatic mixing valve for a set temperature of 40° C. typically chosen for showering. Pressure loss ratio is the ratio of the higher inlet pressure drop to the lower inlet pressure drop across the mixing valve. Normally, higher hot water pressure results in increases in the temperature of the mixed water at the outlet and higher cold water pressure results in decreases in the temperature of mixed water at the outlet. The temperature deviations for pressure loss ratios tending to increase the set water temperature are higher than those tending to reduce the set water temperature because the set temperature is usually closer to the hot water inlet temperature than the cold water inlet temperature. As shown the overall spread of temperature variation is about 6° C. This is unacceptable for many applications, for example in healthcare installations, and currently the performance requirements for these applications are met by skewing the response of the valve to reduce the size of hot deviations which may give rise to a risk of scalding with a consequential increase in the size of cold deviations which although noticeable to the user present less risk. The hot and cold water streams are often incompletely mixed as they flow past the thermostat and changes to the waterway geometry can alter the temperature at the thermostat. As a result, skewing the response is usually done on a trial and error basis until a response is achieved that meets the standard. This is inefficient and there is still a possibility that a valve could be used under conditions in which the cold water and hot water pressures are not equal resulting in hotter temperature deviations than intended. Moreover, it may not always be possible to meet the performance requirements by skewing the response of the valve.

While mucins are found on normal cell surfaces, and are proposed to have multiple roles such as providing protection from environmental exposures and carcinogens, and involvement in cell adhesion and migration, altered forms of the MUC1 glycoprotein have been found heavily expressed in human breast cancer tissue, and other tumors. In our laboratory mammary tumor cells expressing the transmembrane isoform of MUC1 develop tumors in vivo and lead to death of the host. In contrast, tumor cells expressing a MUC1 secreted isoform fail to develop tumors by an immunologically regulated mechanism. Furthermore, MUC1 secreting mammary tumor cells confer protection in mice against the parental mammary tumor line, which does not secrete MUC1, and other highly tumorigenic cell lines unrelated to the mammary tumor line. The following proposal aims to dissect some of the molecular mechanisms involved in this phenomenon. The first aim will examine characteristics of the MUC1 secreting tumor cells which may lead to rejection in vivo or failure to grow. Immunological surface molecules, and production of tumor derived factors, such as chemoattractant molecules and extracellular matrix degrading proteins, will be screened by various assays such as flow cytometry, ELISA, and zymography assays. These techniques will identify if there is a variable expression of these molecules by the tumor lines, which may aid in immunoregulation of tumor growth or elimination. The second aim will dissect the effect of these tumor cells differing in MUC1 expression on various immunological parameters including among others migration and activation of different types of lymphoreticular cells, dendritic cell maturation and function, monocyte migration, expansion of immature myeloid suppressor cells and their ability to inhibit anti-tumor immune responses, and induction of immunological tolerance to tumors. This aim will be achieved by different assays including but not limited to flow cytometry, gel matrix cellular recruitment in vivo, T cell activation and proliferation, and use of cellular migration chambers. Furthermore, the purified secreted isoform of MUC1 or an Immuno Enhancing Peptide (IEP) only found in the secreted isoform will be used in parallel experiments to test the ability of changing the parameters analyzed in the two aims. The objective of this proposal is to investigate the immunological and cellular mechanisms involved in the growth of tumors, and examine the immunoregulatory characteristics of the MUC1 glycoprotein, which may have immunoenhancing and anti-tumor properties. Understanding how MUC1 is involved in tumor immunoregulation may potentially lead to its use as an immunotherapeutic agent against various cancers.

Identification, induction and localization of cytochrome P450s of the 3A-subfamily in mouse brain. Several cytochrome P450 subfamilies are inducible by specific exogenous compounds like the antiepileptic drug phenytoin. Some of these P450 enzymes are involved in the metabolism of gonadal hormones also contributing to neuronal differentiation. CYP3A enzymes have the capacity to catalyze the hydroxylation of testosterone and a wide variety of therapeutic agents, but little is known about the expression and potential function of this subfamily in mouse brain. Here, we report the identification of mouse CYP3A isoforms, their induction and localization in mouse brain. Western blot analysis with anti-CYP3A1 antibodies revealed the phenytoin-inducible expression of CYP3A in brain microsomes, and also a constitutive expression of members of this subfamily in brain mitochondria. Using RT-PCR with a consensus primer pair for known mouse liver CYP3A-isoforms we could demonstrate the expression of CYP3A11 and 3A13 mRNA in mouse brain. Finally, using double immunofluorescence labeling we analyzed the histoanatomical distribution of CYP3A throughout the brain with confocal laser scanning microscopy. We found strong immunoreactivity in neurons of hippocampus and hypothalamic areas which are sensitive to steroid hormones. CYP3A immunoreactivity was apparent also in neurons of the cerebellum, the thalamus and the olfactory bulb. Non-neuronal expression of CYP3A could be found in some astrocyte populations and in vascular as well as ventricular border lines. The presence of CYP3A predominantly in neurons but also in cells contributing to the blood-brain and blood-liquor barrier suggests important roles of this subfamily in mediation of steroid hormone action in mouse brain as well as in preventing the brain from potentially cytotoxic compounds.

The invention relates to a piezoelectric actuators and their application within fuel injector valves. Such a piezoelectric actuator may be to actuate a control valve such as a servovalve within fuel injection valve for controlling flow of a medium. These kind of valves can be used for the direct control of an injection needle within an fuel injection valve or indirect control of a needle by means of a control valve. These kind of valves usually comprise a housing having an inlet duct and an outlet duct and, a movable body which can reciprocate in order to control communication between the inlet and the outlet ducts, and drive means for the reciprocating movement of the body. A known valve of this kind includes a piezoelectric actuating member supported in a valve housing, the housing having an inlet duct and an outlet duct and a movable body which can be displaced by the actuating member in order to control in operation a flow of pressurized fluid through a connection between the inlet and outlet ducts, the surfaces of the movable body on which pressurized fluid can produced hydrostatic force being arranged to minimize any resulting hydrostatic force in a direction tending to oppose movement of the actuating member. The possible extension of the piezoelectric element of such a valve and thus the potential stroke of the valve is usually small, for example, of the order to 10 or 20 micrometers. It is therefore essential to minimize the effect of thermal expansion on the valve parts so that the flow through the valve will vary only slightly with changes of ambient temperature. One solution to the problem is to choose a material for the valve housing which material has a similar thermal expansion coefficient to that of the piezoelectric element. An example of such a material is a nickel-iron alloy having a low coefficient of thermal expansion. A possible disadvantage to the use of this material is the high cost of the alloy. U.S. Pat. No. 4,284,263 discloses a control valve having an actuating member supported within and between a closed end and a seat end of a housing, the actuating member has a fixed end connected to the close housing end and a free end connected to a movable valve body. The actuating member includes an elongated piezoelectric element which has a relatively low thermal coefficient of expansion. The housing is made from common, inexpensive materials having moderately higher thermal coefficient of expansion, and the actuating member includes a spacer having a high thermal coefficient of expansion, arranged between the closed housing end and the piezoelectric element. By proper dimensioning of the spacer and housing with respect to the piezoelectric element, temperature compensation may be achieved without the use of exotic materials. However, as shown in FIG. 2 of U.S. Pat. No. 4,284,263, the compensating structure elongates the device significantly.

Drilling at very great sea depths, for example above 2000 meters and notably up to 4000 meters, requires a riser architecture that is different from that of current risers. What is referred to as a riser is an assembly consisting of a central tube, peripheral lines and possibly other equipments. Such a riser allows fluids to be transferred between the water bottom and an installation that is situated at a higher level, i.e. that can be situated substantially at the water surface or underwater, for example just below the surface. In fact, these risers are subjected to various modes of vibration, such as lateral, axial or torsional modes. The present invention concerns more particularly the axial modes of vibration and the term "natural period" defines the axial natural period of the riser, or that of an element of the riser. The invention is particularly well suited for a riser connected by its upper part to a floating installation and whose lower end is free, for example after being disconnected from a blowout preventer or BOP, or from a manifold. When a riser of great length hangs from a drillship and is free at its lower end, the heave of the ship due for example to the wave motion communicates an excitation thereto in the substantially vertical direction. This excitation can induce high stresses in the riser which can damage it significantly and even lead to its breaking. This excitation phenomenon, which can be maintained and increased, becomes particularly critical when the natural period of the riser becomes at least equal to the minimum value of a period range for which the floating installation could be excited significantly by the heave. For example, for a conventional drillship, the period range for which such an excitation has strong repercussions on the riser is above 6 seconds. The risk of excitation of the ship also exists for the 4 to 6-second range, but it is slighter. The natural period of a riser notably depends on the following parameters: its linear density m or mass per unit of length, its axial rigidity ES corresponding to the product of the Young's modulus E by the structural section S, and its length L. The calculation of the natural period of the riser also depends on the geometry and on the dimensioning of the riser, and it is for example described in the article OTC 4317, Offshore Technology Conference, 14th Annual OTC in Houston, Tex., May 3-6 1982. For a water depth of 4000 meters, the "natural" period of a riser of a conventional type used in the petroleum sphere can reach values of the order of 7 seconds, which are within the period range for which a conventional drillship can be significantly excited by the wave motion. The excitation phenomenon can increase for example with the number of peripheral lines whose mass contributes to increasing the natural period of the assembly consisting of the riser and the lines. The prior art thus describes risers comprising notably a central tube and peripheral lines consisting of several elements linked together by slip joints, each one of the elements being immovably fastened to the central tube. The mass of each of the lines thus participates in the mass of the whole riser without participating in its rigidity ES, which leads, in case of great depth, to a value of the natural period of the riser that is great enough for the above-cited problems to be encountered. Furthermore, the increase in the mass of the riser when the water depth increases leads to the emergence of two phenomena which are of little importance and often disregarded for slight and average water depths but which, in the case of great water depths, become much more important and can condition the dimensioning and the characteristics of the risers. The causes and the effects of these phenomena must be carefully studied. The increase in the supertensions due to the inertia of the riser during strong storms can lead to a tension decrease and/or to a compression, notably in the upper part of the riser, and induce therein, in correlation with the other motions (surge, sway) and the direct action of the wave motion, crippling bending stresses. The rise in the natural period of longitudinal or axial vibrations towards values for which the heave amplitude cannot be disregarded can limit considerably, even in relatively calm weather, the operations intended for manoeuvring the riser because of the risks they would present.

Differences between cough and Valsalva leak-point pressure in stress incontinent women. The aim of the study was to evaluate the relationship between Valsalva leak-point pressure (VLPP) and cough leak-point pressure (CLPP). Sixty women with stress urinary incontinence were included. One woman was excluded from evaluation because of detrusor instability. At a bladder volume of 200-300 mL (mean, 284; standard deviation, 29) CLPP and VLPP were measured in the sitting position. Intra-abdominal pressure was recorded with a rectal balloon catheter. A standardized pad test and multi-channel urodynamics were performed. VLPP was significantly lower than CLPP (58.9+/-27.6 versus 112.5+/-46.9 cm H(2)O, P<0.0001). Although CLPP was negative in two women only, VLPP was negative in 24 of 59 women (40.1%). If intrinsic sphincter deficiency was defined as a leak-point pressure of 65 cm H(2)O, 16.9% of women fulfilled this criterion using the CLPP compared to 35.6% if the VLPP is used. In conclusion, coughing and Valsalva seem to result in a different reaction of the pelvic floor.

It is known to make caskets for the final disposal of human remains by scoring and cutting a flat blank of corrugated fiberboard and then folding it up to form a casket body for receiving the corpse. Such caskets and methods for making them are disclosed, for example, in U.S Pat. No. 4,967,445, issued Nov. 6, 1990 and U.S. Pat. No. 4,773,134, issued Sep. 27, 1988. The casket body is preferably covered interiorly with a liquid-impervious liner, and its exterior provided with a decorative covering. Such caskets require substantial finishing work after the precursor blank has been folded up into casket form, to install the interior lining and the exterior covering. This constitutes a substantial and commercially important drawback, especially in certain situations. For example, it is often desirable to be able to ship the flat precursor blank to a remote point of use, which may be in a foreign country, where unskilled persons can take the blank and convert it into a completed casket body. According to the prior art, one must either ship and store the casket in final assembled form, which because of its substantial volume is very costly and inconvenient, or provide skilled workmen at the point of use to apply the liner and decorative covering, which is also expensive and inconvenient. A principal object of the present invention is to provide a casket, casket precursor and method for converting the precursor into a casket, which permit shipment and storage of the precursor as a flat blank, and permit easy, quick conversion of the precursor blank into a casket body with liner and exterior covering, without requiring skilled labor or expensive tools.

In recent years, in an outdoor unit for an air-conditioning apparatus installed at a building, a commercial facility, or other similar structure, heat exchangers are disposed at the back side and the right and left sides of the outdoor unit. A fan is installed at an upper portion of the outdoor unit. A negative pressure is produced in the outdoor unit by driving the fan, so that the ambient air around the outdoor unit is sucked into the outdoor unit, and heat is exchanged between the air and refrigerant in the heat exchangers. Each heat exchanger is configured such that heat-transfer pipes penetrate fins in a direction perpendicular to the fins. Each heat-transfer pipe is, for example, a circular pipe, and the fins reject heat transmitted from the circular pipe by the refrigerant moving in the circular pipe. Here, each heat-transfer pipe is described as a circular pipe, but may be, for example, a flattened pipe having a flattened shape. In the related art, an outdoor unit for an air-conditioning apparatus having a structure in which, in the case where a plurality of heat exchangers are provided, the number of rows of heat-transfer pipes of the heat exchangers is increased by stacking the heat exchangers in the height direction, has been proposed (see, for example, Patent Literature 1). In the plurality of heat exchangers stacked in the height direction, a sheet metal for preventing the heat exchanger at the upper side from falling downward is disposed at an upper portion of the heat exchanger at the lower side. The heat exchanger at the lower side supports and fixes the heat exchanger at the upper side using the sheet metal. In the heat exchangers disclosed in Patent Literature 1, a bottom plate for supporting a lower end portion of the heat exchanger provided at the lower side is disposed. However, dew condensation water (drain water) generated from the heat exchangers remains on the bottom plate, and thus the fins and the heat-transfer pipes of the heat exchangers may be frozen or corroded by the dew condensation water. Consequently, an outdoor unit for an air-conditioning apparatus has been proposed in which a plurality of drain water outlets are provided in a bottom plate of the outdoor unit, dew condensation water generated at a heat exchanger is drained through the drain water outlets to prevent freezing and corrosion of fins and heat-transfer pipes of the heat exchanger (see, for example, Patent Literature 2). In an existing outdoor unit for an air-conditioning apparatus, a slope is provided to a bottom plate of the outdoor unit, and a drain water outlet is provided at the downstream side of the slope so that dew condensation water remaining on the bottom plate is drained through the drain water outlet by using the slope. For example, an outdoor unit for an air-conditioning apparatus has also been proposed in which a plurality of louver-like cut-and-raised parts are provided on a bottom plate of the outdoor unit for an air-conditioning apparatus at a position at which a heat exchanger is placed so that the strength of the bottom plate is enhanced while the efficiency of draining dew condensation water generated at the heat exchanger is improved (see, for example, Patent Literature 3). Furthermore, an outdoor unit for an air-conditioning apparatus has been proposed in which heat pipes are disposed at the lowermost stage of a heat exchanger provided in the outdoor unit for an air-conditioning apparatus so that dew condensation water generated at the heat exchanger is heated to avoid freezing of the dew condensation water (see, for example, Patent Literature 4).

Barcode scanners are known to be effective tools in sales environments. Prior to barcode scanners, labels (e.g., numbers, letters, or a combination thereof) were placed upon individual products that identified such products. A compilation of the labels and their corresponding products was utilized by a salesperson to determine which items were being sold in order to accurately determine inventory. Upon arrival of new products to the sales establishment, a new compilation of labels and products required generation to effectively determine available inventory. For example, each new product was manually counted and typically entered into a table. A summation of the products was added to remaining products having substantially similar labels. Compiling inventory data included laboriously reviewing products and labels and creating a table that illustrated a number of products represented by particular labels. Such a system is time consuming and susceptible to human error, as labels can be easily misread or entered incorrectly into a table. Barcode scanners were introduced to help mitigate some of the above deficiencies related to inventory maintenance. Each product was delivered with a barcode (e.g., a graphical object that encodes information as alternating dark and light portions) that identified a particular product. Via scanning the barcodes of products sold, products could automatically be deducted from inventory through utilization of a barcode scanner and a computing component. Furthermore, products brought to a particular store could be scanned and automatically added to a list of inventory. However, those barcode scanners were stationary due to their size. Thus double-checking inventory still required manually counting products in the sales area. Furthermore, entering products into an inventory database required moving products to an area with a barcode scanner. Today, barcode scanners have a wide range of applications. For instance, examples of barcode scanners can be found in almost every department store, grocery store, and convenience store and are utilized in connection with selling products (e.g., price determination) and maintaining inventory. Furthermore, barcodes and barcode scanners are currently employed in factory and warehouse settings that utilize barcodes in connection with inventory and production control. Moreover, barcodes have been added to drivers' licenses and other identification cards, wherein the barcodes contain data relating to the person being identified (e.g., age, height, weight, birth date, . . . ). As technology has advanced, barcode scanners have become portable and include memory and a display. For example, a couple engaged to be married can go to a department store to generate a gift registry and simply be given a portable barcode scanner. Thereafter, the couple can scan items that they wish to be added to their registry, and a display within the barcode scanner will illustrate which item(s) they have added. Moreover, typical barcode scanners are equipped with memory that can store the registry list, which can later be transferred to a more permanent data store. Wearable barcode scanners have also been developed, wherein a user that typically requires use of both hands can still utilize a barcode scanner. For example, the barcode scanner can be associated with a strap that wraps around a user's arm and secures such barcode scanner to the arm. Therefore, the user has ability to use both arms when the employment of the barcode scanner is not required. These wearable barcode scanners, however, are designed to be worn on a particular arm, as a keypad for entering data into the barcode scanner is associated with such scanner. However, if a user desires to utilize the scanner on the other arm, the keys and display will be approximately 180 degrees displaced from a desirable orientation. Furthermore, a user utilizing the keypad will have at least part of the display blocked by a hand when the barcode scanner is not on an arm that the scanner was particularly designed for. These barcode scanners are subject to errors in entering and/or reviewing data, as the keypad is not desirably oriented and a display can be partially blocked and/or not oriented desirably. In view of at least the above, there exists a strong need in the art for a system and/or methodology that enables a keypad and display to be adjusted as desirably by a user.

Mouse γ-butyrobetaine dioxygenase is regulated by peroxisome proliferator-activated receptor α through a PPRE located in the proximal promoter. Convincing evidence from studies with peroxisome proliferator-activated receptor (PPAR)α-deficient mice suggested that the carnitine biosynthetic enzyme γ-butyrobetaine dioxygenase (BBD) is regulated by PPARα. However, the identification of BBD as a direct PPARα target gene as well as its exact regulation remained to be demonstrated. In silico-analysis of the mouse BBD promoter revealed seven putative peroxisome proliferator response elements (PPRE) with high similarity to the consensus PPRE. Luciferase reporter gene assays using mutated and non-mutated serial 5'-truncation BBD promoter reporter constructs revealed that one PPRE located at -75 to -87 relative to the transcription start site in the proximal BBD promoter is probably functional. Using gel shift assays we observed in vitro-binding of PPARα/RXRα heterodimer to this PPRE confirming that it is functional. In conclusion, the present study clearly shows that mouse BBD is a direct PPARα target gene and that transcriptional up-regulation of mouse BBD by PPARα is likely mediated by binding of the PPARα/RXR heterodimer to one PPRE located in its proximal promoter region. The results confirm emerging evidence from recent studies that PPARα plays a key role in the regulation of carnitine homeostasis by controlling genes involved in both, carnitine synthesis and carnitine uptake.

Self-perceived motivation for benzodiazepine use and behavior related to benzodiazepine use among opiate-dependent patients. Clinical observations have shown a high prevalence of benzodiazepine use among opiate-dependent patients. Our objective was to identify if distinct patterns of behavior could be associated with three different self-perceived motivations for benzodiazepine use: (a) exclusive self-therapeutic motivation, (b) exclusive hedonic motivation, and (c) combined self-therapeutic and hedonic motivation. Data were collected through a self-administered questionnaire in 92 opiate users in treatment in France (Aquitaine). The behaviors associated with exclusive self-therapeutic motivation included the search for an anxiolytic effect, oral administration, use within the context of a medical prescription, and use without other substances. The behaviors associated with exclusive hedonic motivation were use in combination with other substances, the obtaining of benzodiazepines by the black market, and use of other routes of administration in search of a "blackout." Among patients who reported both motivations, there were distinct trends of behavior according to motivation.

Time trends in the incidence and disease location of Crohn's disease 1980-1995: a prospective analysis in an urban population in Germany. To determine the incidence and clinical pattern of Crohn's Disease in a defined area in Germany, a prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995. All patients newly diagnosed with Crohn's disease within the respective study period who were resident in the study area were included in the study. The results from both study periods were then compared to detect time trends. Altogether 288 (156 and 132, respectively) incident cases were identified yielding an almost unchanged incidence over the years (1980-84: 4.9/10(5); 1991-95 5.2/10(5)). While the peak of incidence is still in the 15-24-year-old group, 1 out of 5 incident patients is now age 50 years and older. Median age at onset of symptoms increased to 30 years (20 years in the former period). Time from onset of symptoms was reduced from a median of 20 months in the 1980s to 5 months. Symptoms did not change significantly, although there seems to be less complicated disease recently. Distal migration of the inflammation in the intestinal tract was observed with significantly more involvement of the sigmoid and rectum in the recent period.

Results of treating Hodgkin's disease without a policy of laparotomy staging. Results of the treatment of 780 primary patients with Hodgkin's disease at the Princess Margaret Hospital (PMH) between 1968 and 1977 are analyzed. Treatment decisions were based on the evaluation of the extent of disease by clinical methods. A marked improvement in relapse-free survival and overall survival was observed for 1973-1977 as compared to 1968-1972. This improvement did not result from differences in the distribution of important prognostic attributes (clinical stage, pathology, and age) between the two periods, and there was no improvement in our ability to rescue relapsed patients. Improved relapse-free and overall survival during the second period was observed for all stages in patients less than 50 years of age, but not in the older group. The improved survival of patients treated between 1973 and 1977 is attributed to more effective initial therapy, which reduced the fraction of patients who relapsed. These observations provide indirect evidence that relapse has a negative effect on prognosis, and that the initial treatment of patients with Hodgkin's disease should be designed to reduce the risk of relapse to a minimum without causing an unacceptable increase in late complications. The observed/expected incidence of acute leukemia and non-Hodgkin's lymphoma in the PMH series was increased to 41.9 and 13.9 respectively. The question of whether a policy of doing routine staging laparotomies improves the results of treatment of patients with Hodgkin's disease is considered only in general terms by comparing the total PMH series with the total Stanford Medical Center series of patients treated between 1968 and 1977. Relapse-free survival at 10 years is 48.9% and 66.8% respectively, at the two institutions, while overall survival at 10 years is identified.

Family perspectives on integrated child health information systems. The perspectives of families, and especially parents of children with special health care needs, need to be better understood by the government agencies, health care providers, associations, and information systems vendors that are integrating child health information systems. To date, research on children with special health care needs has not included the perspectives of parents on integrated child health information systems. Interviews were conducted with a limited number of parents of children with special health care needs and a young adult with special health care needs about their perspectives on integrated health information systems needs. The interviews revealed common themes: (1) parents have experienced the benefits of information technology for health care purposes, (2) parents believe integrated health information systems could help to coordinate their children's health care, (3) parents believe information technology can help improve accuracy and timeliness of information, (4) parents of children with special health care needs believe their children's health information should be available to those who need it, but safeguards must be in place, (5) parents believe health information systems can improve health care, but it is not the highest priority health care issue for them, and (6) parents believe that their involvement in issues related to children with special health care needs, including information technology, is critical. Parents of children with special health care needs hold strong opinions about their children's health care, including health information systems. Parents need to be central to discussions about development of integrated child health information systems if we are to develop information systems that serve the needs of children with special health care needs and their families.

Generally, in the semiconductor industry the most difficulty and/or problems occur with the formation of external electrical connections and with interconnections to different components on a single substrate. Semiconductor devices are typically fabricated on a planar substrate by sequentially growing or depositing several different layers of material and then patterning or etching one or more of the layers to expose a lower surface. Metal is then deposited on the exposed surfaces for interconnections or external connections. One problem in this process is that the etching requires masking which adds several complicated steps to the process and, consequently, a large amount of labor and cost. Also, the metal contacts require a relatively large amount of real estate and, consequently, many semiconductor devices are limited in size by the ability to provide external connections to them. Accordingly, it would be highly advantageous to provide semiconductor devices and methods of manufacture which do not include additional etching steps for the formation of interconnections and external connections. It is a purpose of the present invention to provide novel ultra-small semiconductor devices and methods of fabrication and connection. It is another purpose of the present invention to provide novel ultra-small semiconductor devices and methods of fabrication and connection in which at least some of the interconnections are formed automatically during the formation of the various layers. It is still another purpose of the present invention to provide novel ultra-small semiconductor devices and methods of fabrication and connection in which external terminals and interconnections are formed without requiring additional masking and etching steps. It is a further purpose of the present invention to provide novel ultra-small semiconductor devices which are smaller than previously possible with standard external terminals. It is still a further purpose of the present invention to provide novel ultra-small semiconductor devices using simplified methods of fabrication and connection.

Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes. To quantify adverse events (AEs) associated with the use of metformin (MET), sulphonylureas (SUs) and thiazolidinediones (TZDs) in a usual care setting, and to assess the relationship of AEs to treatment patterns and glycaemic response in patients with type 2 diabetes. An electronic medical record database was used to identify patients with type 2 diabetes age >or=18 years from 1996 to 2005. Patients naïve to oral antidiabetic therapy were followed for 395 days postinitiation of MET, SU or TZD treatment. AEs related to study drugs were evaluated during the follow-up period. Baseline and follow-up A1C levels were compared by drug regimen. Associations between the change in A1C, drug regimen changes and AEs were evaluated. A total of 14,512 patients (mean age 60.8 years, 52.9% female) were identified. During the follow-up period, 12.7% of patients experienced an AE (8.6% MET, 15.9% SU and 19.8% TZD patients). SU and TZD patients were more likely to experience an AE than MET (p < 0.001) patients. AEs did not significantly influence A1C outcomes, although MET and SU patients experiencing an AE were more likely to add-on therapy (odds ratio (OR) = 1.34 and OR = 1.37, respectively; p < 0.05) than those without an AE. MET patients with AEs were more likely to switch therapy (OR = 1.91; p < 0.05) than those without an AE. The occurrence of AEs did not significantly impact glycaemic response to therapy. However, AEs may lead to greater treatment switches for patients receiving MET and add-on therapy for MET-treated and SU-treated patients.

Influence of lactose concentration of milk and yogurt on growth rate of rats. Growth rates of rats fed lyophilized diets of yogurt, milk, 100% lactose-hydrolyzed milk, and 100% lactose-hydrolyzed yogurt were compared. No differences were significant in weight gains between the animals fed lactose-hydrolyzed diets over 3 wk. Further more, rats fed the lactose-hydrolyzed diets had significantly larger weight gains during the 1st wk than those fed unhydrolyzed diets. This may have been from the deleterious effect of lactose, which was in concentrations of 43% in milk and 36% in yogurt. However, by the 2nd wk, rats fed yogurt had growth rates similar to those fed lactose-hydrolyzed diets, and by the 3rd wk, no differences of growth rates were significant. Continued consumption of high concentrations of lactose improved digestion of lactose. Yogurt fermentation produced growth benefit as compared to the milk from which it was made by reducing the lactose content and by supplying microbial lactase activity.

Gastric stasis occurs in spontaneous, visually induced, and interictal migraine. To evaluate and compare gastric motility and emptying during spontaneous migraine to previous observations from induced migraine. We have previously demonstrated a delay in gastric emptying both during the interictal period and during an induced migraine. A limitation noted in these studies was whether there are differences gastrointestinally during a visually induced migraine compared to spontaneous migraines. To address this, 9 additional studies have been performed to ascertain if there is a similar delay during spontaneous migraine Gastric scintigraphy using a standard meal was performed in 3 subjects during 3 periods: spontaneous migraine, induced migraine, and interictal period. On average, the time to half emptying was delayed during spontaneous migraine (124 minutes), during induced migraine (182 minutes), and during the interictal period migraine (243 minutes) compared to normative values established at our center (112 minutes). On average, similar gastric slowing was seen in all 3 groups when the percentage of nuclear material remaining in the stomach at 2 hours was measured. This study provides additional evidence of gastric stasis in migraineurs interictally during induced and spontaneous migraine.

A cysteine in the repetitive domain of a high-molecular-weight glutenin subunit interferes with the mixing properties of wheat dough. The quality of wheat (Triticum aestivum L.) for making bread is largely due to the strength and extensibility of wheat dough, which in turn is due to the properties of polymeric glutenin. Polymeric glutenin consists of high- and low-molecular-weight glutenin protein subunits linked by disulphide bonds between cysteine residues. Glutenin subunits differ in their effects on dough mixing properties. The research presented here investigated the effect of a specific, recently discovered, glutenin subunit on dough mixing properties. This subunit, Bx7.1, is unusual in that it has a cysteine in its repetitive domain. With site-directed mutagenesis of the gene encoding Bx7.1, a guanine in the repetitive domain was replaced by an adenine, to provide a mutant gene encoding a subunit (MutBx7.1) in which the repetitive-domain cysteine was replaced by a tyrosine residue. Bx7.1, MutBx7.1 and other Bx-type glutenin subunits were heterologously expressed in Escherichia coli and purified. This made it possible to incorporate each individual subunit into wheat flour and evaluate the effect of the cysteine residue on dough properties. The Bx7.1 subunit affected dough mixing properties differently from the other subunits. These differences are due to the extra cysteine residue, which may interfere with glutenin polymerisation through cross-linkage within the Bx7.1 subunit, causing this subunit to act as a chain terminator.

Brain tissue volumes and small vessel disease in relation to the risk of mortality. Brain atrophy and small vessel disease increase the risk of dementia and stroke. In a population-based cohort study (n=490; 60-90 years) we investigated how volumetric measures of atrophy and small vessel disease were related to mortality and whether this was independent of incident dementia or stroke. Brain volume and hippocampal volume were considered as measures of atrophy, whereas white matter lesions (WML) and lacunar infarcts reflected small vessel disease. We first investigated all-cause mortality in the whole cohort. In subsequent analyses we censored persons at incident dementia or incident stroke. Finally, we separately investigated cardiovascular mortality. The average follow-up was 8.4 years, during which 191 persons died. Brain atrophy and hippocampal atrophy, as well as WML increased the risk of death. The risks associated with hippocampal atrophy attenuated when censoring persons at incident dementia, but not at incident stroke. Censoring at either incident dementia or stroke did not change the risk associated with brain atrophy and WML. Moreover, WML were particularly associated with cardiovascular mortality.