bluuebunny/crossref_metadata_2025_split huggingface dataset:
Narcotic Analgesics
Authors: Aldrich Jane V. , Vigil‐Cruz Sandra C. 
Published: November 2003

AbstractNarcotic analgesics such as morphine have been the mainstay for the treatment of severe pain, although these drugs are associated with serious adverse effects, most notably addiction liability and respiratory depression. Therefore there has been an intensive effort to find new therapeutic agents that retain the effectiveness of morphine, but do not have its undesired side effects. Compounds have been identified from a wide variety of chemical classes, from the rigid morphinan alkaloids to the flexible phenylpiperidines and the opioid peptides, which have affinity for opioid receptors. In recent years considerable effort has focused on identifying ligands, both agonists and antagonists, with affinity for delta (δ) and kappa (κ) opioid receptors as pharmacological tools and as potential therapeutic agents that would not have the side‐effect profile of morphine and other agonists that interact with mu (μ) opioid receptors. After the identification of the closely related opioid receptor‐like (ORL1) receptor and its endogenous ligand orphanin FQ/nociceptin, there has been considerable effort directed toward identifying agonists and antagonists for this receptor as well. This review discusses the structure‐activity relationships for each of the major classes of compounds that interact with the opioid receptors, along with ligands for the ORL1 receptors.
Cognition Enhancers
Authors: Eid Clark N. , Wu Yong‐Jin , Kinney Gene G. 
Published: November 2003

AbstractVery little can be done to abate or control the progression of dementia, a clinical syndrome most commonly encountered later in life and manifested by impairments in cognition, language, and memory. The percentage of the world's elderly population is increasing, and so too is the need for effective pharmaceutical interventions for dementias such as Alzheimer's disease (AD), age‐associated memory impairment (AAMI), multi‐infarct dementia (MID), vascular dementia, and Parkinsonian dementia. Advances have been made in understanding the etiology of these diseases, but much remains to be discovered. In this chapter we have focused on the development of several therapeutic approaches that have in common the ability to modulate gated ion channels, and as such, have the potential to affect multiple neurotransmitter systems. Specifically, we discuss the structure‐activity relationship (SAR) and behavioral outcome for ligands interacting with the (1) γ‐aminobutyric acid subtype A benzodiazepine receptor (GABAA/BzR); (2) nicotinic acetylcholine receptor (nAChR); (3) serotonin subtype 3 receptor (5‐HT3R); and (4) the potassium M‐channel.
Familial cryptic translocation (2;17) ascertained through recurrent spontaneous abortions
Authors: Bruyere Helene , Rajcan‐Separovic Evica , Doyle J. , Pantzar Tapio , Langlois Sylvie 
Published: November 2003

AbstractWe report a young woman who presented with a reproductive history of three recurrent spontaneous abortions (RSA) and two neonatal deaths. Comparative genomic hybridization (CGH) was used to determine the chromosomal composition of the patient's last miscarriage. It showed the presence of monosomy for the distal end of chromosome 2 long arm (segment 2q37.2 to qter) and trisomy for the distal end of chromosome 17 long arm (segment 17q25 to qter). The mother was found to be a carrier for a cryptic translocation between chromosomes 2 and 17 long arms by fluorescence in situ hybridization using a subtelomeric probe for 17q. Retrospective CGH analysis on one baby who died neonatally showed that he had inherited the maternal translocation in the same unbalanced state as the last pregnancy loss. His detailed postmortem examination is reported. © 2003 Wiley‐Liss, Inc.
Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome
Authors: Johnston Jennifer J. , Olivos‐Glander Isabelle , Turner Joyce , Aleck Kyrieckos , Bird Lynne M. , Mehta Lakshmi , Schimke R. Neil , Heilstedt Heidi , Spence J. Edward , Blancato Jan , Biesecker Leslie G. 
Published: November 2003

AbstractGreig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes. © 2003 Wiley‐Liss, Inc.
Expression of class μ glutathione‐S‐transferase in human liver and its association with hepatopathies
Authors: Engracia V. , Leite M.M.B.S. , Pagotto R.C. , Zucoloto S. , Barbosa C.A.A. , Mestriner M.A. 
Published: November 2003

AbstractWe studied the distribution of GSTM1 phenotypes in 611 individuals from an ethnically mixed sample of the Brazilian population who died from various causes. No influence of age, gender, or ethnicity was detected on the phenotypic distribution. In a sub‐sample of 66 alcoholic individuals compared with 399 non‐alcoholics there was almost a doubling of the odds ratio for GSTM1(0) individuals in the alcoholic category. The incidence of hepatopathies was higher in this group as well, and we observed a significant association of the null phenotype with cirrhosis. An excess of null phenotypes (374/611) was observed, and the allelic distribution was: GSTM1*A = 0.168, *B = 0.089, and *0 (null) = 0.743. © 2003 Wiley‐Liss, Inc.
Neuroarchitecture of the color and polarization vision system of the Stomatopod haptosquilla
Authors: Kleinlogel Sonja , Marshall N. Justin , Horwood Julia M. , Land Mike F. 
Published: November 2003

AbstractThe apposition compound eyes of stomatopod crustaceans contain a morphologically distinct eye region specialized for color and polarization vision, called the mid‐band. In two stomatopod superfamilies, the mid‐band is constructed from six rows of enlarged ommatidia containing multiple photoreceptor classes for spectral and polarization vision. The aim of this study was to begin to analyze the underlying neuroarchitecture, the design of which might reveal clues how the visual system interprets and communicates to deeper levels of the brain the multiple channels of information supplied by the retina. Reduced silver methods were used to investigate the axon pathways from different retinal regions to the lamina ganglionaris and from there to the medulla externa, the medulla interna, and the medulla terminalis. A swollen band of neuropil—here termed the accessory lobe—projects across the equator of the lamina ganglionaris, the medulla externa, and the medulla interna and represents, structurally, the retina's mid‐band. Serial semithin and ultrathin resin sections were used to reconstruct the projection of photoreceptor axons from the retina to the lamina ganglionaris. The eight axons originating from one ommatidium project to the same lamina cartridge. Seven short visual fibers end at two distinct levels in each lamina cartridge, thus geometrically separating the two channels of polarization and spectral information. The eighth visual fiber runs axially through the cartridge and terminates in the medulla externa. We conclude that spatial, color, and polarization information is divided into three parallel data streams from the retina to the central nervous system. J. Comp. Neurol. 467:326–342, 2003. © 2003 Wiley‐Liss, Inc.
Distribution and colocalization of cholecystokinin with the prohormone convertase enzymes PC1, PC2, and PC5 in rat brain
Authors: Cain Brian M. , Connolly Kelly , Blum Alissa , Vishnuvardham Daesety , Marchand James E. , Beinfeld Margery C. 
Published: November 2003

AbstractDuring posttranslational processing to generate CCK 8, pro‐cholecystokinin (CCK) undergoes endoproteolytic cleavage at three sites. Several studies using endocrine and neuronal tumor cells in culture and recombinant enzymes and synthetic substrates in vitro have pointed to the subtilisin/kexin‐like enzymes prohormone convertase (PC) 1, PC2, and PC5 as potential candidates for these endoproteolytic cleavages. In these experimental models, they all appear to be able to cleave pro‐CCK to make the correct products. One rodent model has provided information about the role of PC2. PC2 knockout mouse brains had less CCK 8 than wild‐type, although a substantial amount of CCK was still present. The degree to which CCK levels were reduced in these mice was regionally specific. These data indicated that PC2 is important for normal production of CCK but that it is not the only endoprotease that is involved in CCK processing. To evaluate whether PC1 and PC5 are possible candidates for the other enzymes involved in CCK processing, the distribution of PC1, PC2, and PC5 mRNA was studied in rat brain. Their colocalization with CCK mRNA was examined using double‐label in situ hybridization. PC2 was the most abundant of these enzymes in terms of the intensity and number of cells labeled. It was widely colocalized with CCK. PC1 and PC5 mRNA‐positive cells were less abundant, but they were also widely distributed and strongly colocalized with CCK in the cerebral cortex, hippocampus, amygdala, ventral tegmental area, and substantia nigra zona compacta. The degree of colocalization of the enzymes with CCK was regionally specific. It is clear that PC1 and PC5 are extensively colocalized with CCK and could be participating in CCK processing in the rat brain and may be able to substitute for PC2 in its absence. These three enzymes may represent a redundant system to ensure production of biologically active CCK. J. Comp. Neurol. 467:307–325, 2003. © 2003 Wiley‐Liss, Inc.
Expression of L1 decreases during postnatal development of rat spinal cord
Authors: Akopians Alin , Runyan Steve A. , Phelps Patricia E. 
Published: November 2003

AbstractL1 is a cell adhesion molecule that is highly expressed on developing axons and is associated with neurite outgrowth, guidance, and fasciculation. In this study we systematically examined L1 expression at all spinal levels across eight postnatal ages to detect regional and developmental differences. We observed striking changes in the developmental pattern of L1 expression between birth (P0) and adult ages, with intense L1‐immunopositive axons prevalent throughout the funiculi at P0 compared with predominantly L1‐immunonegative funicular axons in adults. At all ages and spinal levels examined, some L1‐positive dorsal root afferents entered the spinal cord, coursed in Lissauer's tract, and projected into the superficial dorsal horn and the dorsal columns, as well as across the dorsal commissure. Additional L1‐positive axons were detected consistently around the perimeter of the spinal cord, in the dorsolateral funiculus, and adjacent to the central canal. While specific L1‐labeled axons were detected at all ages, a pattern of segmental variation was observed within animals, with the highest levels of L1 expression detected in lumbar and sacral segments and the lowest in cervical spinal cord. The pattern of L1 immunoreactivity was compared to that of the growth‐associated protein GAP‐43 and the results indicated colabeling of most axons. These observations demonstrate that L1 is expressed on immature axons well into postnatal development, possibly until they have completed their differentiation. Furthermore, the L1‐positive axons that continue to be detected in adults are likely to be either unmyelinated or sprouting axons. J. Comp. Neurol. 467:375–388, 2003. © 2003 Wiley‐Liss, Inc.
Cytotoxicity of normal and activated rat monocytes analyzed by flow cytometry
Authors: Stehling Oliver , Grau Veronika , Steiniger Birte 
Published: November 2003

AbstractBackgroundThe cytotoxic potential of activated monocytes might play an important role during severe systemic immune reactions and thus needs further elucidation. As established cytotoxicity tests are not suitable for this purpose, we developed a flow cytometry–based method.MethodsDuring acute renal allograft rejection in the rat, monocytes were harvested by vascular perfusion and then purified by Percoll density gradient centrifugation and subsequent immunomagnetic negative selection. For comparison, natural killer (NK) cells were similarly isolated from spleen homogenates. Cytotoxicity was determined by flow cytometry using the fluorescein isothiocyanate–labeled NK‐sensitive lymphoma Yac‐1 as target. Necrotic cells were identified by propidium iodide, and apoptotic cells were identified by MC 540. Cytotoxicity was determined by the calculation of a cytotoxicity coefficient, ζ. The ζ coefficient describes the interrelation between the reciprocal proportion of target cells in a sample and the specific cytotoxicity, simultaneously allowing estimation of the contribution of contaminating NK cells.ResultsThe method showed a substantial cytotoxicity of activated monocytes and indicated different or additional cytotoxic mechanisms compared with NK cells. Our assay permitted a detailed study of effector and target cells and took cytotoxicity of contaminating cells into account.ConclusionsThe method is nonradioactive, easy to perform, and thus helpful in investigating the role of monocytes in several diseases. Cytometry Part A 56A:81–88, 2003. © 2003 Wiley‐Liss, Inc.
Inclined load capacity of suction caissons
Authors: Aubeny C. P. , Han S. W. , Murff J. D. 
Published: November 2003

AbstractA simplified method of analysis for estimating lateral load capacity of suction caisson anchors based on an upper bound plasticity formulation is presented. The simplification restricts the analysis to caissons in uniform and linearly varying undrained strength profiles; nevertheless, its computational efficiency permits quick evaluation of a number of parameters affecting load capacity. The validity and limitations of the simplified formulation are demonstrated through comparisons to more rigorous finite element solutions. A series of sensitivity studies demonstrate the effects of various soil conditions and loading parameters. Copyright © 2003 John Wiley & Sons, Ltd.
Two zebrafish mutants, ebony and ivory, uncover benefits of neighborhood on photoreceptor survival
Authors: Goldsmith Paul , Baier Herwig , Harris William A. 
Published: November 2003

AbstractZebrafish offer a tractable system for the study of retinal development and degeneration, to provide insights into human retinal degeneration. We have begun to dissect the question of neighborhood effects on photoreceptor differentiation and survival through the isolation and characterization of mutants with retinal degeneration. We describe two mutants, ebony and ivory, isolated through a behavioral screen for blind mutants induced by ethyl nitrosourea mutagenesis. Chimeric analysis was conducted to attempt to rescue the photoreceptor degeneration. In ebony, the photoreceptor cell death was both cell autonomous and nonautonomous in nature, whilst the photoreceptor cell death was strikingly nonautonomous in ivory. The rescue at a distance is in keeping with a putative diffusible survival factor. We propose a density‐dependent nonautonomous neighborhood effect to explain these findings. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 235–245, 2003
Finite element analysis and evaluation of design limits for structural materials in a cyclic state of creep
Authors: Boulbibane M. , Ponter A. R. S. 
Published: November 2003

AbstractIn this paper a direct non‐time stepping method derived from the minimum theorems given by the authors (European Journal of Mechanics – A/Solids 2002; 21:915–925) is outlined. This method can be used in the prediction of the deformation and life assessment of structures subjected to cyclic mechanical and thermal loadings. It produces accurate predictions of failure modes based on material behaviour incorporated into constitutive equations. It also can be used to define limit loads related to certain design criteria.Generally, for complex geometries and load histories, the identification of load histories that correspond to predefined design conditions, in the form of time or number of cycles to failure, can only be achieved by extensive and repeated calculations. For the Linear Matching Method, however, the representation of materially non‐linear stress and strain fields by linear behaviour with spatially varying moduli, indicates the possibility that direct evaluation of loads and temperature ranges that correspond to a design restriction may be evaluated directly through the construction of the exact cyclic state and via sequence of approximations. The technique employs the finite element method combined with the cyclic state solution. The description of the material behaviour is given by a non‐linear viscous model (Norton's law). It can also apply to any class of material behaviour that includes internal state variables. This technique has been applied successfully to a set of characteristics problems (Bree problem and plate containing a circular hole and subjected to radial temperature gradient). Copyright © 2003 John Wiley & Sons, Ltd.
On the numerical implications of multiplicative inelasticity with an anisotropic elastic constitutive law
Authors: Sansour Carlo , Bocko Jozef 
Published: November 2003

AbstractThe statement that theories of inelasticity at finite strains have arrived at a high level of development is only true in conjunction with isotropic material behaviour. From both points of view (theoretical and computational), the extension to anisotropic material behaviour seems to be a complicated task. The statement is especially true when the multiplicative decomposition of the deformation gradient is considered a basis for the formulation. Of special interest are questions related to the mathematical form of the stored energy function or, equivalently, of the constitutive relation for the material stress tensor as the thermodynamical force. This paper deals with the above issues. The anisotropic formulation is accomplished using the notion of structural tensors. Here we suggest that the privileged directions of the material should be transformed in a specific way under the action of the inelastic part of the deformation gradient. The inelastic behaviour is assumed to be governed by evolution equations of the unified type.Numerically, we deal with the full multiplicative structure of the theory. The numerical treatment is developed in full detail. Expressions concerning the local iteration as well as the tangent operator are derived. Various numerical examples with applications to shells are presented which demonstrate the influence of anisotropy and the applicability of the theory. Copyright © 2003 John Wiley & Sons, Ltd.
Extending the functionality of the general‐purpose finite element package SEPRAN by automatic differentiation
Authors: Bischof C. H. , Bücker H. M. , Lang B. , Rasch A. , Risch J. W. 
Published: November 2003

AbstractFrom an abstract point of view, a numerical simulation implements a mathematical function that produces some output from some given input. Derivatives (or sensitivities) of the function's output with respect to its input can be obtained—free from truncation error—by using a technique called automatic differentiation. Given a computer code in a high‐level programming language like Fortran, C, or C++, automatic differentiation generates another code capable of computing not only the original function but also its derivatives. Thus, the application of automatic differentiation significantly extends the functionality of a simulation package. For instance, automatic differentiation enables, in a completely mechanical fashion, the usage of derivative‐based optimization algorithms where the evaluation of the objective function comprises some given large‐scale engineering simulation. In this paper, the automatic differentiation tool ADIFOR is used to transform the general‐purpose finite element package SEPRAN. In doing so, we automatically transform the given 400000 lines of Fortran 77 into a new program consisting of 600000 lines of Fortran 77. We compare our approach with a traditional approach based on numerical differentiation and quantify its advantages in terms of accuracy and computational efficiency for a standard fluid flow problem. Copyright © 2003 John Wiley & Sons, Ltd.
SIMS: from research to production control
Authors: Werner Helmut W. 
Published: November 2003

AbstractIn 1958, when I joined the Philips Research Laboratories, there were a number of technological problems related to the analysis of solids within Philips that needed analytical support. Because the available (bulk) techniques did not give sufficient results, a new technique, later called secondary ion mass spectrometry (SIMS), was launched that involved the bombardment of a solid target with (primary) energetic ions, followed by mass analysis and ion detection of the sputtered (secondary) target ions.The restrictions of the available infrastructure for such an analytical technique were many: there was no PC for data handling, no internet or database for literature search, the photocopying machine was not yet invented, communication with other scientists had to be done by mail (there was no fax, no E‐mail, no mobile phones) and, what was worse, SIMS was not considered to be a useful analytical technique compared with established techniques!In the years that followed there were many advances:

The SIMS instrumentation was improved by better ion optics, advanced electronic equipment and was extended from sector type to quadrupole and finally to time‐of‐flight (TOF) mass spectrometers.
The methodology of SIMS was developed step by step (parameters such as lateral and depth resolution, detection limit and quantitative analysis were all optimized in turn).
The SIMS technique then made its entrance to solve problems in technology development.
In the last two decades SIMS has become an indispensable, reliable, quantitative analytical technique for production control in integrated circuit technology and the after‐sales care of integrated circuits. The philosophy of the provision of an analytical service at the Philips Research Laboratory (hereinafter referred to as ‘our laboratory’) is discussed. After the initial period, where every method (SIMS, AES, ESCA, RBS, etc.) was claimed to be ‘the only one’ (the panacea), we learned how to organize analytical service cost efficiently and for the optimum benefit of the ‘customer’. The core analytical techniques were concentrated in one department and the customer would profit from synergy by using several appropriate analytical techniques for the same problem.Today, the latest developments in SIMS instrumentation keep pace with the latest challenges of the ultra‐large‐scale integration (ULSI) roadmap for integrated circuits, which indicates the dimensions of the circuits that are predicted for the years to come. Copyright © 2003 John Wiley & Sons, Ltd.