bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractNeuropathic 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

AbstractProgrammed 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

AbstractRecently, 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

AbstractThe 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

AbstractWe 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

AbstractIf 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

AbstractMouse 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

AbstractBRCA1 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

AbstractIn 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

AbstractThe 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

AbstractThe 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

AbstractThis 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

AbstractAn 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

AbstractComparative 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.