bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalation
Authors: Aswania Osama , Chrystyn Henry
Published: August 2002

The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4×5 mg from an Intal® metered dose inhaler (MDI), (ii) 4×5 mg from an MDI attached to a large volume spacer (MDI+SP) and (iii) 20 mg from an Intal Spinhaler® (DPI). Urine samples were provided at 0, 0.5, 1, 2, 5 and 24 h post dose. The mean (S.D.) amount of sodium cromoglycate excreted in the urine during the first 30 min post inhalation was 38.1 (27.5), 222.3 (120.3) and 133.1 (92.2) μg following MDI, MDI+SP and DPI, respectively. The mean ratio (90% confidence interval) of these amounts excreted in the urine over the first 30 min for MDI+SP vs MDI, DPI vs MDI and MDI+SP vs DPI was 801.0 (358.0, 1244; p<0.002)%, 457.0 (244.0, 670.0; p<0.02)% and 262.4 (110.2, 414.5)%, respectively. Similarly for the 24 h cumulative amount of sodium cromoglycate excreted over the 24 h post inhalation the ratios were 375.4 (232.9, 517.9; p<0.005)%, 287.5 (183.4, 391.6; p<0.02)% and 211.4 (88.3, 334.5)%, respectively. The results highlight better lung deposition of sodium cromoglycate from a metered dose inhaler attached to a large volume spacer. Copyright © 2002 John Wiley & Sons, Ltd.
A pH‐dependent variation in α‐helix structure of the S‐peptide of ribonuclease A studied by Monte Carlo simulated annealing
Authors: Nakazawa Takashi , Ban Sumiko , Okuda Yuka , Masuya Masato , Mitsutake Ayori , Okamoto Yuko
Published: August 2002

Low‐energy conformations of the S‐peptide fragment (20 amino acid residues long) of ribonuclease A were studied by Monte Carlo simulated annealing. The obtained lowest‐energy structures have α‐helices with different size and location, depending distinctively on the ionizing states of acidic amino acid residues. The simulation started from completely random initial conformation and was performed without any bias toward a particular structure. The most conspicuous α‐helices arose from the simulation when both Glu 9 and Asp 14 were assumed to be electrically neutral, whereas the resulting conformations became much less helical when Asp 14 rather than Glu 9 was allowed to have a negative charge. Together with experimental evidence that the α‐helix in the S‐peptide is most stable at pH 3.8, we consider the helix formation need the carboxyl group of Asp 14 to be electrically neutral in this weakly acidic condition. In contrast, a negative charge at Asp 14 appears to function in support of a view that this residue is crucial to helix termination owing to its possibility to form a salt bridge with His 12. These results indicate that the conformation of the S‐peptide depends considerably on the ionizing state of Asp 14. © 2002 John Wiley & Sons, Inc. Biopolymers 63: 273–279, 2002; DOI 10.1002/bip.10055
Establishing structure–function relationships for eumelanin
Authors: Nofsinger J. Brian , Weinert Emily E. , Simon John D.
Published: August 2002

The aggregation‐dependent optical properties of eumelanin from human hair are examined. When aggregation is increased, the absorption spectrum extends to lower energy. The absorption spectra of oligomers isolated from black human hair and Sepia officinalis are comparable and are in quantitative agreement with the reported action spectra for photoinduced oxygen consumption and free‐radical generation by eumelanin. The agreement between the optical properties of human hair and squid eumelanins suggests the fundamental molecular constituents of the pigments are similar and aggregation‐dependent photophysical behavior is a general feature of all eumelanins. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 302–305, 2002
Mobility measurements of immunomagnetically labeled cells allow quantitation of secondary antibody binding amplification
Authors: McCloskey Kara E. , Comella Kristin , Chalmers Jeffrey J. , Margel Shlomo , Zborowski Maciej
Published: August 2002

Magnetic cell separation methods commonly utilize paramagnetic materials conjugated to antibodies that target specific cell surface molecules. The amount of magnetic material bound to a cell is directly proportional to the magnetophoretic mobility of that cell. A mathematical model has been developed which characterizes the fundamental parameters controling the amount of magnetic material bound, and thus, the magnetophoretic mobility of an immunomagnetically labeled cell. In characterization of the paramagnetic labeling, one of the parameters of interest is the increase in magnetophoretic mobility due to the secondary antibody binding to multiple epitopes on the primary antibody, referred to as the “secondary antibody binding amplification,” Ψ. Secondary antibody‐binding amplification has been investigated and quantitated by comparing the mobilities of lymphocytes directly labeled with anti‐CD4 MACS™ (Miltenyi Biotec, Auburn, CA) magnetic nanoparticle antibody with the mobilities of lymphocytes from the same sample labeled with two different indirect antibody‐labeling schemes. Each indirect labeling scheme incorporated a primary mouse anti‐CD4 FITC antibody that provides both FITC and mouse‐specific binding sites for two different secondary antibody‐magnetic nanoparticle conjugates: either anti‐FITC MACS magnetic nanoparticle antibody or anti‐mouse MACS magnetic nanoparticle antibody. The magnetophoretic mobilities of the immunomagnetically labeled cells were obtained using Cell Tracking Velocimetry (CTV). The results indicate that an average of 3.4 anti‐FITC MACS magnetic nanoparticle antibodies bind to each primary CD4 FITC antibody, Ψ1,2f = 3.4 ± 0.33, and that approximately one, Ψ1,2m = 0.98 ± 0.081, anti‐mouse MACS magnetic nanoparticle antibody binds to each primary mouse CD4 FITC antibody on a CD4 positive lymphocyte. These results have provided a better understanding of the antibody‐binding mechanisms used in paramagnetic cell labeling for magnetic cell separation. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 642–655, 2001.
Simultaneous degradation of organophosphorus pesticides and p‐nitrophenol by a genetically engineered Moraxella sp. with surface‐expressed organophosphorus hydrolase
Authors: Shimazu Mark , Mulchandani Ashok , Chen Wilfred
Published: August 2002

Moraxella sp., a native soil organism that grows on p‐nitrophenol (PNP), was genetically engineered for the simultaneous degradation of organophosphorus (OP) pesticides and p‐nitrophenol (PNP). The truncated ice nucleation protein (INPNC) anchor was used to target the pesticide‐hydrolyzing enzyme, organophosphorus hydrolase (OPH), onto the surface of Moraxella sp., alleviating the potential substrate uptake limitation. A shuttle vector, pPNCO33, coding for INPNC–OPH was constructed and the translocation, surface display, and functionality of OPH were demonstrated in both E. coli and Moraxellasp. However, whole cell activity was 70‐fold higher in Moraxellasp. than E. coli. The resulting Moraxella sp. degraded organophosphates as well as PNP rapidly, all within 10 h. The initial hydrolysis rate was 0.6 μmol/h/mg dry weight, 1.5 μmol/h/mg dry weight, and 9.0 μmol/h/mg dry weight for methyl parathion, parathion, and paraoxon, respectively. The possibility of rapidly degrading OP pesticides and their byproducts should open up new opportunities for improved remediation of OP nerve agents in the future. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 318–324, 2001.
Zeolite molecular sieves have dramatic acid–base effects on enzymes in nonaqueous media
Authors: Fontes Nuno , Partridge Johann , Halling Peter J. , Barreiros Susana
Published: August 2002

Zeolite molecular sieves very commonly are used as in situ drying agents in reaction mixtures of enzymes in nonaqueous media. They often affect enzyme behavior, and this has been interpreted in terms of altered hydration. Here, we show that zeolites can also have dramatic acid–base effects on enzymes in low water media, resulting from their cation‐exchange ability. Initial rates of transesterification catalyzed by cross‐linked crystals of subtilisin were compared in supercritical ethane, hexane, and acetonitrile with water activity fixed by pre‐equilibration. Addition of zeolite NaA (4 Å powder) still caused remarkable rate enhancements (up to 20‐fold), despite the separate control of hydration. In the presence of excess of an alternative solid‐state acid–base buffer, however, zeolite addition had no effect. The more commonly used Merck molecular sieves (type 3 Å beads) had similar but somewhat smaller effects. All zeolites have ion‐exchange ability and can exchange H+ for cations such as Na+ and K+. These exchanges will tend to affect the protonation state of acidic groups in the protein and, hence, enzymatic activity. Zeolites pre‐equilibrated in aqueous suspensions of varying pH‐pNa gave very different enzyme activities. Their differing basicities were demonstrated directly by equilibration with an indicator dissolved in toluene. The potential of zeolites as acid–base buffers for low‐water media is discussed, and their ability to overcome pH memory is demonstrated. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 296–305, 2002.
The simultaneous biosynthesis and uptake of amino acids by Lactococcus lactis studied by 13C‐labeling experiments
Authors: Jensen Niels Bang Siemsen , Christensen Bjarke , Nielsen Jens , Villadsen John
Published: August 2002

Uniformly 13C labeled glucose was fed to a lactic acid bacterium growing on a defined medium supplemented with all proteinogenic amino acids except glutamate. Aspartate stemming from the protein pool and from the extracellular medium was enriched with 13C disclosing a substantial de novo biosynthesis of this amino acid simultaneous to its uptake from the growth medium and a rapid exchange flux of aspartate over the cellular membrane. Phenylalanine, alanine, and threonine were also synthesized de novo in spite of their presence in the growth medium. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 11–16, 2002; DOI 10.1002/bit.10211
Community College Faculty and Professional Staff: The Human Resource Challenge
Authors: Gibson‐Harman Kim , Rodriguez Sandria , Grant Haworth Jennifer
Published: August 2002

To assemble the cadre of educated professionals needed to carry out their evolving mission, community colleges must take an active role in recruiting and training qualified faculty and staff.
PLS score–loading correspondence and a bi‐orthogonal factorization
Authors: Ergon Rolf
Published: August 2002

It is established industrial practice to use the correspondence between partial least squares (PLS) scores and loadings or loading weights as a means for process monitoring and control. Deviations from the normal operating point in a score plot are then related to the influences from major process variables as shown in a loading or loading weight plot. These relations are often presented in a bi‐plot, i.e. appropriately scaled scores and loadings or loading weights are displayed in the same plot. As shown in the present paper, however, the orthogonal PLS algorithm of Wold gives no direct theoretical and graphical correspondence, i.e. the bi‐plot will show an angle deviation that causes an interpretational problem. The alternative non‐orthogonal PLS algorithm of Martens gives direct correspondence, but the correlated latent variables may then cause another interpretational problem. As a solution to these problems, this paper presents a PLS factorization where both scores and loadings are orthogonal (BPLS), and we show how the Wold and Martens factorizations can easily be transformed to this solution. The result is independent latent variables as well as direct score and loading correspondence. It is also shown that the transformations involved do not affect the predictor found by PLS regression. The score–loading correspondence properties for the different PLS factorizations are discussed using principal component analysis (PCA) as a reference case. An example using industrial paper plant data is included. Copyright © 2002 John Wiley & Sons, Ltd.
Immobilization of difunctional building blocks on hydroxysuccinimide activated silica: Versatile in situ preparation of chiral stationary phases
Authors: Kosjek Birgit , Uray Georg
Published: August 2002

Several brush‐type chiral stationary phases (CSPs) based on undecanoyl‐ or butanoyl‐bound (R,R)‐1,2‐diphenylethane‐1,2‐diamine (DPEDA) as chiral selector were prepared by an innovative, fast, and less expensive kind of preparation. The key to this method is the immobilization of the enantiomeric pure diamine with only one amino function in a simple substitution reaction on hydroxysuccinimide ester‐activated silica. No excess chiral material is lost. Loading can be easily monitored analyzing the filtrate. The free second amino function can subsequently be acylated with different acyl halogenides. Examples with benzoyl‐ and 3,5‐dinitrobenzoyl (DNB) amides show that, based on our new approach, a library of differently acylated Pirkle‐type CSPs can easily be obtained. A benzoylated analog of the commercially available ULMO CSP is shown to be very effective in separating enantiomers of N‐acyl amino acids. Chirality 13:657–667, 2001. © 2001 Wiley‐Liss, Inc.
Immunohistochemical localization of DARPP‐32 in the brain of the lizard, Gekko gecko: Co‐occurrence with tyrosine hydroxylase
Authors: Smeets Wilhelmus J.A.J. , Lopez Jesus M. , González Agustín
Published: August 2002

To assess the relationship between dopaminergic neuronal structures and dopaminoceptive structures in a reptile, single and double immunohistochemical procedures with antibodies directed against DARPP‐32 (dopamine‐ and cAMP‐regulated phosphoprotein with an apparent molecular mass of 32,000 daltons),a phosphoprotein related to the dopamine D1‐receptor, and tyrosine hydroxylase (TH) were applied to the brain of the lizard, Gekko gecko. The DARPP‐32 antibody yielded a well‐differentiated pattern of staining in the brain of Gekko. In general, areas that are densely innervated by TH‐immunoreactive, putative dopaminergic fibers, such as the nucleus accumbens, striatum, dorsal ventricular ridge, and amygdaloid complex, display strong immunoreactivity for DARPP‐32 in somata and neuropil. Distinct cellular DARPP‐32 immunoreactivity was also found in the lateral cortex, ventral hypothalamus, habenula, central nucleus of the torus semicircularis, midbrain tectum, parvicellular isthmic nucleus, raphe nuclei, caudal rhombencephalic tegmentum, and spinal cord. Striatal projections to the midbrain and their target, i.e., the substantia nigra pars reticulata, were found to be strongly immunoreactive. Double immunofluorescence staining revealed that dopaminergic cells generally do not stain for DARPP‐32, except for cells in the ventral hypothalamus and at caudal rhombencephalic levels. In conclusion, the distribution of DARPP‐32 in the brain of the lizard Gekko gecko largely resembles the pattern observed in birds and mammals, at least as far as basal ganglia structures are concerned. On the other hand, there are several specific features of DARPP‐32 distribution in the gekkonid brain that deserve further attention, such as cellular colocalization of DARPP‐32 and TH immunoreactivity in hypothalamic and caudal rhombencephalic areas, and cellular DARPP‐32 immunoreactivity in the tectum and central nucleus of the torus semicircularis of the midbrain, the superior and inferior raphe nuclei, and the spinal cord. J. Comp. Neurol. 435:194–210, 2001. © 2001 Wiley‐Liss, Inc.
Accurate analytical approximation for normalized diode characteristic
Authors: Le Bihan J.
Published: August 2002

An analytical function is proposed as an approximation of the generalized normalized diode equation. This function is simple, has a right asymptotic behaviour and achieves very good accuracy. Copyright © 2001 John Wiley & Sons, Ltd.
Concurrent measurement of the survival of two populations of rabbit platelets labeled with either two PKH lipophilic dyes or two concentrations of biotin
Authors: Rand M.L. , Wang H. , Mody M. , Chu I. , Treutiger I. , Nguyen A. , Packham M.A. , Freedman J.
Published: August 2002

Background

To avoid radioisotopic labeling and permit comparison of the survival of two platelet populations concurrently in one animal, we compared simultaneous recoveries and survival times of homologous rabbit platelets labeled in vitro with the lipophilic dyes PKH26 (red fluorescing) and PKH67 (green fluorescing) and with two levels of biotin (low, 1 μg/ml; high, 10 μg/ml).

Methods

Blood samples were drawn up to 96 h postinfusion and analyzed by flow cytometry. Biotin‐labeled samples were incubated with phycoerythrin‐streptavidin before analysis.

Results

Recovery of PKH26‐labeled platelets at 1 h was lower (37.5%) than that of PKH67‐labeled platelets (47.3%; P < 0.001). Platelet survival times were 62.4 and 61.9 h. Recoveries at 1 h of platelets labeled with two levels of biotin were similar (86.6% and 84.6%) and greater than those of PKH‐labeled platelets (P < 0.001). Survival of platelets labeled with biotin did not differ (low, 83.3 h; high, 85.2 h) and was longer than for PKH‐labeled platelets (P < 0.01). Labeling methods did not activate platelets (measured by P‐selectin expression), nor did they affect platelet responses to adenosine diphosphate (ADP), collagen, or thrombin.

Conclusions

Labeling with two levels of biotin is superior to labeling with PKH dyes, and is useful for measuring concurrently the survival of two differing platelet populations. Cytometry 47:111–117, 2002. © 2002 Wiley‐Liss, Inc.
Simultaneous blockade of Fcγ receptors and indirect labeling of mouse lymphocytes by the selective detection of allotype‐restricted epitopes on the kappa chain of rat monoclonal antibodies
Authors: Balogh Péter , Tew John G. , Szakal Andras K.
Published: August 2002

Background

Incubation of mouse hemopoietic cells with rat monoclonal antibodies (mAbs) of the IgG class sometimes results in Fc‐region mediated binding of immunoglobulins by Fc‐receptors. This unwanted binding can be prevented by preincubation of target cells with the rat anti‐mouse anti‐CD16/32 (2.4G2) mAb.

Methods

To avoid the cross‐reactivity of fluorochrome‐conjugated secondary anti‐rat antibodies with the Fc‐receptor blocking 2.4G2, direct fluorochrome‐conjugated immunoglobulins need to be used. However, we report that a mouse mAb (MRC OX12) with a strong rat Igka allotype preference can be used for flow cytometric measurements in conjunction with unlabeled rat mAbs with the simultaneous blockade of Fcγ receptors by the 2.4G2 mAb.

Results and Discussion

This lack of reactivity of OX12 against the 2.4G2 mAb is remarkable, as it could efficiently detect another Sprague‐Dawley–derived rat mAb. This staining procedure (unlabeled rat mAb of the appropriate strain detected by OX12 mAb in the presence of 2.4G2 IgG) is an attractive alternative to using direct antibody conjugates, while satisfying the need for an effective Fcγ‐receptor blockade. Cytometry 47:107–110, 2002. © 2002 Wiley‐Liss, Inc.
Allosteric modulation of the rat adenosine A1 receptor: Differential effects on agonist and antagonist binding
Authors: Kourounakis Angeliki P. , Visser Corine , de Groote Miriam , IJzerman Ad P.
Published: August 2002

The interaction of 2‐amino‐3‐benzoyl‐thiophene derivative, PD81,723, as well as other G protein‐coupled receptor (GPCR)‐modulating agents such as suramin (SUR), N‐ethylmaleimide (NEM), GTP, and NaCl with the rat adenosine A1 receptor was investigated using kinetic, saturation, as well as displacement experiments of various agonists, partial agonists or antagonists. PD81,723 enhanced agonist (CPA, R‐PIA, NECA) binding ∼2‐fold, while its effect on CPA binding was increased (4–11‐fold) with other modulators present. In contrast, binding of antagonists (DPCPX, CPT, N‐0840) was inhibited, while binding of partial agonists (8BCPA, MeSCPA) remained uninfluenced. The effect of PD81,723 is consistent with shifting A1 receptors to an “active” (R*) state with high affinity for agonists and low for antagonists. Further, all described allosteric modulators influenced both agonist and antagonist binding. The IC50 values observed for the agonist CPA, ranging from 4.7 nM in the presence of PD81,723 to a high value of 2.9 μM in the combined presence of NEM, NaCl, and GTP, represented a greater than 600‐fold affinity shift. We suggest that the latter micromolar IC50 value may approximate CPA’s “true” affinity (KA) for the rat adenosine A1 receptor. Drug Dev. Res. 51:207–215, 2000. © 2001 Wiley‐Liss, Inc.
Chronic neuropathic pain: Pathomechanism and pharmacology
Authors: Urban L. , Nagy I. , Bevan S.J.
Published: August 2002

Neuropathic pain syndromes form a group of loosely connected diseases linked by the common presence of injury/damage to the peripheral sensory system and the resulting effect: chronic pain. Treatment of patients suffering from neuropathic pain is one of the most challenging clinical tasks as classical painkillers such as opioids and nonsteroidal anti‐inflammatory drugs lack antinociceptive effect in these syndromes. The recent development of various animal models aided our understanding of neuropathic pain and provided targets for analgesic intervention. The discovery of abnormal, ectopic activity in injured primary afferents, sprouting of large calibre primary afferent fibres to the superficial dorsal horn, and changes in protein expression in DRG (dorsal root ganglion) cells after injury has highlighted differences between the pathomechanisms of nociceptive and neuropathic pain and explained the lack of efficacy of commonly used analgesic drugs. Recent clinical trials based on considerations from animal studies have proved, at least partly, that targeting these mechanisms could lead to more efficacious antinociceptive agents for neuropathic pain syndromes. There are three major sites of interventions: (1) abnormal, ectopic activity of the injured afferents, (2) increased release of transmitters in the spinal cord, and (3) enhanced neuronal activity in the spinal dorsal horn. To date, there has been no breakthrough in the clinical treatment of neuropathic pain; however, data from recent preclinical studies and clinical trials with anticonvulsants, gabapentin‐like molecules, Ca (calcium)‐channel blocking agents, GABAB (γ‐amino butyric acid) receptor agonists, and NMDA (N‐methyl‐D‐asparate) receptor antagonists promise the development of effective pain relief for patients suffering from neuropathic pain. Drug Dev. Res. 54:159–166, 2002. © 2002 Wiley‐Liss, Inc.
Differential tissue growth and patterns of cell death in mouse limb autopod morphogenesis
Authors: Salas‐Vidal Enrique , Valencia Concepción , Covarrubias Luis
Published: August 2002

Programmed cell death (PCD) is considered one of the most important cellular processes in the morphogenesis of organs and tissues during animal development. Although the embryonic limb has been established as a classic model for the study of PCD, detailed studies on this process' contribution to morphogenesis are still lacking. In the present work, using modern computer‐aided techniques, we estimated the contribution of PCD to mouse limb morphogenesis. For the detection of apoptotic cell death, we stained whole embryonic limbs with acridine orange or, in some instances, used the TUNEL technique, and visualized the tissues by confocal laser scanning microscopy. We found that cell death patterns are dynamic during limb development, and occur in gradients oriented with the main limb axes, anteroposterior, dorsoventral and distoproximal. Interdigital apoptosis in the autopod was initially detected at the most distal region, and then more proximally as development proceeded. Interestingly, we found that digit separation is more pronounced on the dorsal side, contrary to what is expected from the apoptotic cell distribution, which shows more abundant cell death in the ventral region. Using 2‐D and 3‐D models, we found that most digit individualization occurs rather by digit growth than by interdigital cell death. Therefore, digits do not mainly individualize by degeneration of preformed interdigital tissue, but probably by a dynamic balance between proliferation and cell death, reducing interdigital growth, which results in protrusion of digits. We determined the expression pattern of fgf‐8 during the period of digit individualization, as the product of this gene could participate in defining the limb growth pattern. Initially, fgf‐8 expression was coincident with the apical ectodermal ridge, but when cell death was first detected in the interdigits, fgf‐8 expression became restricted to the tip of the growing digits. Therefore, FGF‐8 could be one of the factors responsible for differential digit‐interdigit growth, and might also act as a survival factor on interdigital tissue. We also found that the expression patterns of rar‐β, bmp‐2, bmp‐4, bmp‐7, msx‐1, and msx‐2 genes, proposed to be involved in the activation of interdigital cell death, did not overlap with, or were not highly expressed in the major zones of cell death in the developing limb. © 2001 Wiley‐Liss, Inc.
EM‐MODE in high‐resolution DOA estimation for nonuniform array
Authors: Nakazawa Tatsuya , Yamada Hiroyoshi , Yamaguchi Yoshio
Published: August 2002

Recently, the superresolution method has attracted significant attention as a high‐resolution method of estimation of the electromagnetic wave propagation environment for mobile communications as well as various kinds of wireless communications. With regard to the array shape used in the estimation problem of direction of arrival, various array configurations in addition to equally spaced arrays have been studied. Weiss and colleagues have proposed a method of realizing a virtual equally spaced array by applying the EM method and the IQML method to nonuniform arrays. In this paper, the EM‐MODE method based on this algorithm is proposed for estimation of the direction of arrival of the coherent wave by a nonuniform array and for improved processing. It is shown that improvement of the estimation success rate is possible by applying the improved processing in cases where estimation by the conventional EM‐MODE method is difficult. The errors in estimation of the direction of arrival when this method is applied are studied. It is shown that much better characteristics can be obtained than when real elements are equally spaced. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 85(8): 47–56, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1117
A high‐capacity switching method for IP datagrams with multistage networks
Authors: Saito Tadao , Aida Hiroshi , Aoki Terumasa , Nishimura Norihisa , Shinbo Kenichi
Published: August 2002

The rapidly spreading use of the Internet and the general use of video communication through the Internet have caused a rapid increase in Internet traffic. It is highly probable that the Internet will be used as the network for future multimedia communications. In that case, the capacity of IP routers for the Internet must be enlarged. At present, an IP router capacity of several gigabits per second can be realized, but ATM technology must be applied if a still larger capacity is to be achieved. The IP traffic is of variable length, and the packets are long, which can be handled by ATM. If a high‐capacity switch that can handle packets of variable length is created, performance will be improved compared to high‐capacity switches based on ATM. The purpose of this paper is to achieve a capacity of 1 Tbps order. Several IP datagram switching methods are proposed and evaluated. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 85(8): 57–65, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1118
Use of a gaas microprobe tip pumped by circularly polarized light as a source of spin‐polarized tunneling electrons
Authors: Shinohara Ryoichi , Yamaguchi Koichi
Published: August 2002

We have studied the feasibility of using GaAs microprobe tips fabricated by anisotropic wet chemical etching followed by sulfur passivation as a source of spin‐polarized tunneling electrons. In our experiments, we studied the magnetic state of a nickel thin film by spin‐polarized STM, using a GaAs microprobe tip illuminated by circularly polarized light. We observed that the tunneling current was different depending on the sense of rotation of the circular polarization (and hence was proportional to the number of spin‐polarized tunneling electrons). We then made measurements of the thin film's hysteresis characteristics by the same technique and by the magnetic Kerr effect. We confirmed by time‐resolved photoluminescence measurements that surface states located at the surface of the GaAs microprobe tip can mediate the tunneling, which shortens the lifetime of electrons within the tip. This indicates that these surface states can affect the spin‐polarized tunneling signal. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 85(5): 21–28, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.1103
A blueprint for making the prospective Mediterranean free trade zone an environmental role model
Authors: Neumayer Eric
Published: August 2002

If not accompanied by strong environmental provisions, the prospective Mediterranean Free Trade Zone (MFTZ) is bound to increase existing pressures on scarce natural resources in the region. This article argues that the existing bilateral association agreements between the European Union and Southern Mediterranean countries are clearly insufficient from an environmental perspective. If the MFTZ were to be based upon those agreements, then it would represent a free trade agreement environmentally inferior to the North American Free Trade Agreement and even the World Trade Organization. To turn the MFTZ into an environmental role model instead, a number of provisions are indispensable: environmentally friendly preambular language, upward harmonization of environmental standards, a comprehensive general exceptions clause, a prominent role given to the precautionary principle and the allocation of the burden of proof on the party challenging an environmental measure. Equally importantly, the European Union needs to step up financial, technical and other assistance as part of a wider regional environmental strategy and partnership. Doing so would ensure that the prospective MFTZ becomes a promoter not only of trade and economic growth, but also environmental protection in the Southern Mediterranean region. Copyright © 2001 John Wiley & Sons, Ltd and ERP Environment
Environmental carcinogens and p53 tumor‐suppressor gene interactions in a transgenic mouse model for mammary carcinogenesis
Authors: Medina Daniel , Ullrich Robert , Meyn Raymond , Wiseman Roger , Donehower Larry
Published: August 2002

Mouse mammary tumorigenesis is greatly influenced by a variety of exogenous agents, such as MMTV, chemical carcinogens (i.e., polycyclic aromatic hydrocarbons), and radiation, as well as by endogenous/physiological factors, such as steroid hormones, tumor‐suppressor genes (i.e., Brca1/2, p53), and gene products of modifier genes. In the mouse model, the most frequently used chemical carcinogen has been 7,12‐dimethylbenz[a]anthracene (DMBA), which activates the Ha‐ras gene but does not alter the p53 tumor‐suppressor gene. However, on an existing background of p53 gene alteration, low doses of DMBA are strongly cocarcinogenic. Using a transgenic model system, in which the p53 gene was deleted in the mammary gland, we examined the carcinogenic effects of a variety of external agents and internal factors given at either low doses or physiological doses. These agents/factors included DMBA, γ‐radiation, Brca2 heterozygosity, and steroid hormones. All agents/factors increased the tumorigenic response of the p53 null mammary cells, even under conditions where no tumorigenic response was observed in the p53 wildtype mammary cell. The strongest cocarcinogenic effect was observed with the steroid hormone progesterone. The majority of tumors were highly aneuploid and composed of nuclear igh‐grade cells. The mechanism for the aneuploidy and secondary events associated with high tumorigenicity were examined using array technology. These results demonstrate that, on a background of underlying genetic instability, very low doses of environmental mutagens and mitogens can produce strong cocarcinogenic effects. Environ. Mol. Mutagen. 39:178–183, 2002. © 2002 Wiley‐Liss, Inc.
Tumor formation in Brca1 conditional mutant mice
Authors: Deng Chu‐Xia
Published: August 2002

BRCA1 is the first breast cancer–associated gene, whose mutation predisposes women to breast and ovarian cancers. Targeted mutations of Brca1 in the mouse result in embryonic lethality primarily attributed to cellular proliferation defects, raising questions about the mechanisms by which Brca1 represses tumor formation. To overcome the early lethality, we engineered Brca1 by flanking its exon 11 with loxP sites. We showed that deletion of the exon by EIIA‐Cre, which expresses Cre in the germline, causes p53‐dependent lethality at late gestation. On the other hand, MMTV‐Cre, which expresses Cre in mammary epithelium, resulted in tumorigenesis at low frequency after a long latency, accompanied by increased epithelial cell apoptosis and abnormal ductal development. Mammary tumor formation was significantly accelerated in a p53+/− genetic background; however, it still appeared in a stochastic fashion, suggesting the involvement of additional factors. Notably, the tumors were highly diverse in histopathology and displayed extensive genetic/molecular alterations, including overexpression of ErbB2, c‐Myc, p27, and Cyclin D1, and downregulation of p16 in the majority of tumors. This observation suggests roles for these proteins in Brca1‐associated tumorigenesis. Environ. Mol. Mutagen. 39:171–177, 2002. Published 2002 Wiley‐Liss, Inc.
Variation of micronucleated erythrocytes in peripheral blood of Sciurus aureogaster in relation to age: An increment of micronucleated polychromatic erythrocytes after the administration of colchicine
Authors: Zúñiga‐González G. , Torres‐Bugarín O. , Ramos‐Ibarra M.L. , Zamora‐Perez A. , Gómez‐Meda B.C. , Ventura‐Aguilar A.J. , Ramos‐Mora A. , Ortíz G.G. , Álvarez‐Moya C. , González‐Rodríguez A. , Luna‐Aguirre J. , Gallegos‐Arreola M.P.
Published: August 2002

In some species, in which the human is included, the influence of age in the variation in the number of micronucleated erythrocytes (MNE) is known. In the present work we show how the process of aging influences the number of spontaneous MNE in the gray squirrel (Sciurus aureogaster). Because of the difficulty of knowing the age of each animal, 69 animals were weighed at their arrival to the laboratory and at the start of sample taking, with the supposition that the heaviest animals were the oldest and those with the lightest weight were the youngest. The major number of MNE was found in the younger animals, whereas the adults displayed less MNE (P < 0.0001). A group of 11 animals were sampled every 15 days over a period of 6 months, and the number of MNE were found to decrease with an increment in the weight in conformity with the time elapsed. These results showed that in the gray squirrel, the number of spontaneous MNE in peripheral blood depend on age. An additional interesting datum about the increment of MNE after the administration of colchicine is shown. Environ. Mol. Mutagen. 37:173–177, 2001 © 2001 Wiley‐Liss, Inc.
Response of unbounded soil in scaled boundary finite‐element method
Authors: Wolf John P.
Published: August 2002

The scaled boundary finite‐element method is a powerful semi‐analytical computational procedure to calculate the dynamic stiffness of the unbounded soil at the structure–soil interface. This permits the analysis of dynamic soil–structure interaction using the substructure method. The response in the neighbouring soil can also be determined analytically.

The method is extended to calculate numerically the response throughout the unbounded soil including the far field. The three‐dimensional vector‐wave equation of elasto‐dynamics is addressed. The radiation condition at infinity is satisfied exactly. By solving an eigenvalue problem, the high‐frequency limit of the dynamic stiffness is constructed to be positive definite. However, a direct determination using impedances is also possible. Solving two first‐order ordinary differential equations numerically permits the radiation condition and the boundary condition of the structure–soil interface to be satisfied sequentially, leading to the displacements in the unbounded soil. A generalization to viscoelastic material using the correspondence principle is straightforward. Alternatively, the displacements can also be calculated analytically in the far field.

Good agreement of displacements along the free surface and below a prism foundation embedded in a half‐space with the results of the boundary‐element method is observed. Copyright © 2001 John Wiley & Sons, Ltd.
Investigations regarding Alpine talus slopes using ground‐penetrating radar (GPR) in the Bavarian Alps, Germany
Authors: Sass Oliver , Wollny Klaus
Published: August 2002

The applicability of ground‐penetrating radar (GPR) for the investigation of loose debris was tested at two sites (Viererkar and Zugspitzplatt). A pulseEKKO 100 GPR system equipped with 25 MHz antennae was utilized. The aim of the investigation was to record the base of the debris layer, and thereby acquire an estimation of the backweathering rates of the adjacent rockwalls. The study areas are situated in the Northern Alps near the German–Austrian border. The sites are characterized by steep limestone rockwalls and extensive talus accumulations. A total of six profiles was surveyed.

The method is suitable and effective for a quick survey in this dry, high‐ohmic substrate. The GPR system was able to deliver information about the subsurface stratigraphy to c. 70 m depth. The boundary line to the bedrock was discovered – depending upon the profile surveyed −5 to 25 m below the surface. The base of the debris material sometimes shows no distinct reflection. Buried features (V‐shaped furrows, zones overdeepened by ice action, geological structures) could be detected. Arched structures well below the talus–bedrock interface can be interpreted as drainage systems in the karstic bedrock. A thick scree layer of Late Glacial age was separated from a thinner layer on the talus surface, which was related to the Holocene.

The backweathering rates were fixed by a calculation of talus volume to c. 100 mm/103 a during the Holocene (Viererkar) and 150–300 mm/103 a (Zugspitzplatt). The detrital formation in north‐exposed sites is twice as intense as in south‐exposed sites. These results match the rates of recent rockfall in the same area of investigation. The calculated backweathering for the late glacial period is 150–730 mm/103 a.

The magnitude of the calculated rockwall retreat lies well within the range of previous measurements. The discrepancy between some weathering rates highlights the fact that recent and past relief formation must be differentiated. Otherwise recent removal rates may be overestimated. Copyright © 2001 John Wiley & Sons, Ltd.
Acknowledging different needs: Developing a taxonomy of welfare leavers
Authors: Julnes George , Hayashi Kentaro , Anderson Steven
Published: August 2002

This chapter uses cluster analysis to distinguish three groups of leavers of Temporary Assistance to Needy Families in terms of their self‐reported well‐being after exit, verifies these clusters, and then uses classification tree analysis to isolate some of the factors that may be responsible for these differences in post‐exit outcomes.
Finite element analysis of vortex shedding using equal order interpolations
Authors: Jan Y. J.
Published: August 2002

An operator splitting and element‐by‐element conjugated gradient solver, and equal order interpolations are applied for solving time dependent Navier–Stokes (NS) equations to simulate flow induced vortex shedding in the present study. In addition, the convection term is corrected by balanced tensor diffusivity, which can stabilize the numerical simulation and overcome the numerical oscillations. The evolution of the interested flowing properties with time is analyzed by using spectral analysis. The developed code has been validated by the application of two examples: a driven cavity flow and a flow induced vortex vibration. Results from the first example for Reynolds number Re=103 and Re=104 are compared with other numerical simulations. Results from the second example, uniform flow past a square rod over a wide range of high Reynolds numbers from Re=103∼105, are compared with experimental data and other numerical studies. Copyright © 2002 John Wiley & Sons, Ltd.
Genomic imbalances in human lung adenocarcinomas and squamous cell carcinomas
Authors: Pei Jianming , Balsara Binaifer R. , Li Wu , Litwin Samuel , Gabrielson Edward , Feder Madelyn , Jen Jin , Testa Joseph R.
Published: August 2002

Comparative genomic hybridization analysis was performed on 67 non‐small‐cell lung cancers (NSCLCs), including 32 squamous cell carcinomas (SCCs) and 35 adenocarcinomas (ACs), to identify differences in the patterns of genomic imbalance between these two histologic subtypes. Among the entire tumor set, the chromosome arms most often overrepresented were 1q, 3q, 5p, and 8q, each detected in 50–55% of cases. The most frequently underrepresented arms were 9q, 3p, 8p, and 17p. The number of imbalances was similar in SCCs and ACs (median number/case: 12 and 11, respectively). Moreover, many imbalances, such as gains of 1q, 5p, and 8q, occurred at a high frequency in both histologic subgroups. Several statistically significant differences, however, were found. The most prominent difference was gain of 3q24‐qter, seen in 81% of SCCs compared with 31% of ACs (P < 0.0001), with amplification at 3q25‐26 being detected in eight of 32 (25%) SCCs but in only two of 35 (6%) ACs. Gain of 20p13 and loss of 4q also were seen at a significantly higher rate in SCCs than in ACs, whereas overrepresentation of 6p was more common in ACs. Gains of 7q and 8q each were associated with higher‐stage tumors and either positive nodal involvement or higher tumor grade. These data suggest that genes located in several chromosomal regions, particularly 3q25‐26, may be associated with phenotypic properties that differentiate lung SCCs from ACs. Furthermore, certain imbalances, prominent among them gains of 7q and 8q, may be indicative of tumor aggressiveness in NSCLCs. © 2001 Wiley‐Liss, Inc.
Uncommon TGFBRI allele is not associated with increased susceptibility to colon cancer
Authors: Samowitz Wade S. , Curtin Karen , Leppert Mark F. , Slattery Martha L.
Published: August 2002

Previous studies have suggested that an allele of the transforming growth factor‐beta type I receptor (TGFBRI) gene that codes for six instead of the usual nine alanines in a polyalanine repeat is associated with an increased susceptibility to colon cancer, and that the six‐alanine homozygote is seen only in individuals with some form of cancer. We evaluated this TGFBRI polymorphism in a population‐based sample of 252 individuals with colon cancer and 362 age‐ and gender‐matched controls from the state of Utah. TGFBRI genotypes were determined by PCR amplification and length determination of the polyalanine repeat. In addition to the common nine‐alanine (9A) allele, we identified six‐ (6A), eight‐ (8A), ten‐ (10A), eleven‐ (11A), and twelve‐alanine (12A) TGFBRI alleles. 6A/9A heterozygotes were seen in similar percentages of colon cancer cases (18.3%) and controls (16.0%). 6A/6A homozygotes were slightly more common in controls than in colon cancer cases (1.4% vs. 0.8%), and none of the controls with the 6A/6A genotype had any of the non‐colonic cancers reported in previous studies. We conclude that the 6A TGFBRI allele is not associated with an increased susceptibility to colon cancer at the population level, and that the 6A/6A homozygote is not restricted to individuals with some form of cancer. © 2001 Wiley‐Liss, Inc.
Activation of astrocyte intracellular signaling pathways by interleukin‐1 in rat primary striatal cultures
Authors: Dunn Sarah L. , Young Elizabeth A. , Hall Matthew D. , McNulty Shaun
Published: August 2002

The striatum has been implicated as the site of action mediating neurotoxic effects of interleukin‐1 (IL‐1) during ischemia. However, the molecular mechanisms underlying these events have yet to be fully addressed. In the present study, primary cultures of rat striatal cells were used as a model for the study of IL‐1 signaling pathways in the striatum. Immunocytochemical analyses revealed that these cultures consisted of a mixture of neurones and astrocytes and demonstrated expression of the IL‐1 type I receptor (IL‐1RI) on both cell types. Treatment with IL‐1 (3 units/ml) for 10 min increased phosphorylation of p38 MAP kinase in striatal cells. The endogenous IL‐1RI inhibitor IL‐1Ra (24 ng/ml) and the p38 MAP kinase inhibitor SB203580 (10 nM) both inhibited this response. Analysis of the effects of IL‐1 on nuclear translocation of the transcription factor NF‐kB revealed that NF‐kB became activated in a time‐dependent manner. Immunocytochemistry revealed that IL‐1 stimulated p38 phosphorylation and NF‐kB translocation in astrocytes only. TaqMan real‐time quantitative PCR analysis revealed that IL‐1 stimulated gene expression of tumor necrosis factor‐α (TNF) in striatal cultures. The p38 MAP kinase inhibitor SB203580 failed to inhibit the effects of IL‐1 on NF‐kB translocation or gene transcription. These studies have demonstrated significant aspects of the IL‐1 signaling cascade in cultured striatum. Of particular interest is the finding that IL‐1 stimulated activation of p38 MAP kinase and NF‐kB in striatal astrocytes exclusively. GLIA 37:31–42, 2002. © 2002 Wiley‐Liss, Inc.
Using benchmarking to influence tuition and fee decisions
Authors: Loomis Hubbell Loren W. , Massa Robert J. , Lapovsky Lucie
Published: August 2002

This chapter examines how benchmarking can be used to assist in making decisions about tuition and fees. Emphasis is placed on generating sufficient tuition income to fund institutional operations.
Penn State joins the Big Ten and learns to benchmark
Authors: Secor Robert
Published: August 2002

Joining the Big Ten wasn’t just about football. Since it became part of the alliance, Penn State has learned to benchmark to great effect, particularly in regard to faculty and academic issues.
Benchmarking by state higher education boards
Authors: Barak Robert J. , Kniker Charles R.
Published: August 2002

Benchmarking provides increasingly useful information for state higher education boards. This chapter provides information on how boards use benchmarking in their operations.