bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between noradrenaline and nonlinear indexes of blood pressure dynamics in normotensive and spontaneously hypertensive rats
Authors: Dabiré Hubert 
Published: November 2004

AbstractRecent studies in normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats show that some nonlinear indexes derived from the recurrence plot method may be better markers of sympathetic activity than the spectral powers of blood pressure (BP). We herein investigated the relationships between nonlinear indexes and plasma noradrenaline concentration in conscious WKY rats and SHRs. Blood pressure was recorded for 30 min after intravenous injection of saline (0.9% NaCl, 100 μL/kg), hexamethonium (20 mg/kg), atropine (0.5 mg/kg), atenolol (1 mg/kg) or prazosin (1 mg/kg). Spectral power in the low‐frequency (LF) band and the nonlinear index (Lmax), calculated on diastolic (DBP) and systolic blood pressures (SBP), were used to analyse the BP signal. Noradrenaline concentration was determined by radioenzymatic technique. A robust stepwise regression analysis – using noradrenaline concentration as dependent variable, and LF, Lmax and treatment, as independent variables –shows that treatment is the main variable explaining the variance of noradrenaline level in WKY rats, excluding the use of the pooled data to explore the relationship between noradrenaline concentration and LF or Lmax. In contrast, in SHRs, treatment has no effect on the variance of noradrenaline concentration and the pooled data were then used. In this group, no correlation was observed between noradrenaline concentration and LF. In contrast, very high positive correlation was observed between noradrenaline level and Lmax‐DBP (r = 0.59; P = 0.0005) or Lmax‐SBP (r = 0.53; P < 0.002). The results strengthen our previous suggestion that nonlinear indexes may be better tools than spectral powers to investigate the sympathetic nervous system.
ACCELERATING WILSON FERMION MATRIX INVERSIONS BY MEANS OF THE STABILIZED BICONJUGATE GRADIENT ALGORITHM
Authors: FROMMER ANDREAS , HANNEMANN VOLKER , NÖCKEL BERTOLD , LIPPERT THOMAS , SCHILLING KLAUS 
Published: November 2004

The stabilized biconjugate gradient algorithm BiCGStab recently presented by van der Vorst is applied to the inversion of the lattice fermion operator in the Wilson formulation of lattice Quantum Chromodynamics. Its computational efficiency is tested in a comparative study against the conjugate gradient and minimal residual methods. Both for quenched gauge configurations at β=6.0 and gauge configurations with dynamical fermions at β=5.4, we find BiCGStab to be superior to the other methods. BiCGStab turns out to be particularly useful in the chiral regime of small quark masses.
NONLINEAR DYNAMIC EXCITATIONS AND PHONONS IN NANOSYSTEMS
Authors: SCHOMMERS W. , KLANN H. , POLITIS C. , PAPANIKOLAOU P. , ATHANASIOU N. 
Published: November 2004

The phonon density of states for nanoclusters has been studied theoretically using molecular dynamics; in this way, anharmonic effects could be fully considered. Comparisons are made with results obtained from bulk calculations. The cluster properties have been studied for several particle numbers and temperatures. It turned out that the properties of clusters are sensitive to small variations in the interactions between the particles. Therefore, in the calculation of cluster properties, the precise knowledge of the interaction is necessary. In our study, we have chosen krypton nanosystems because for this substance, a reliable interaction potential is available. First estimations have also been performed for metal (Al, Pb) systems.
PT VIOLATION AND ORIENTABILITY IN THE EARLY UNIVERSE
Authors: MAGNON ANNE 
Published: November 2004

We recall that the “Sagnac Effect” can be viewed as a clock converting rotation (torsion) into a lapse of time. It is shown that the two available helicities can be used to show that PT invariance can be experimentally confirmed within the framework of General Relativity. These clocks are rather similar to those proposed by de Broglie (the particle-clocks) to convert (right or left) rotation into a quantum of energy. The Quantum analogue of this PT invariance is analyzed for zero rest-mass fields and related Mass and Spin Casimir operators. We suggest that Quantum PT invariance could have been violated in the monopole phase, due to mixing of homotopy classes of the Lorentz Lie Group along a spacetime track, appearance of superselected Mass and Spin Casimir operators, and spontaneous breaking of their proportionality. We suggest that this could be viewed as an evidence of the asymmetric flow of time, (arrow of time) in the Early Universe. Existence (non existence) of spinor structure and orientability of space, is discussed.
Direct Observation of Anion‐Mediated Translocation of Fluorescent Oligoarginine Carriers into and across Bulk Liquid and Anionic Bilayer Membranes
Authors: Sakai Naomi , Takeuchi Toshihide , Futaki Shiroh , Matile Stefan 
Published: November 2004

AbstractThe recent hypothesis that counteranion‐mediated dynamic inversion of charge and solubility might contribute to diverse functions of oligoarginines in biomembranes was tested with two fluorescently labelled oligomers, FL‐R8, one of the most active cell‐penetrating peptides, and its longer version, FL‐R16. We report evidence for counteranion‐mediated phase transfer from water into bulk chloroform and anionic lipid‐bilayer membranes as well as reverse‐phase transfer from bulk chloroform and across intact lipid‐bilayer membranes into water. The differences found between FL‐R8 and FL‐R16 with regard to location in the bilayer and reverse‐phase transfer from bulk and lipid‐bilayer membranes into water implied that the reported results may be relevant for biological function.
Applying pharmacogenomics in drug development: Call for collaborative efforts
Authors: Gurwitz David 
Published: November 2004

AbstractPersonalized medicine remains the long‐awaited next revolution in medicine. So far, progress towards this change has been much slower than hoped, given that our entire DNA sequence has been publicly available since April 2001. Three years down the road, it has become clear that the expectations for fast progress in medicine were excessive, and that our genome is by far more complex than originally perceived. Moreover, it seems that both the medical profession and health care systems, as well as pharmaceutical companies, are too conservative for modifying diagnostic and treatment protocols following the gain of new pharmacogenomics knowledge that has the potential to drastically reduce the incidence rates of adverse drug reactions. The next few years may well be a crucial turning point for the use of pharmacogenomics data in drug development. The transformation will hopefully begin with the availability of FDA approved rapid and reliable diagnostic screening tools for CYP450 alleles, along with new FDA guidelines favoring the approval process for drug applications supported by valuable genomic information related to toxic reactions. The current theme issue, a focused snapshot for mid‐2004, highlights some of the vital topics in clinical genetics and informatics that together will hopefully form a platform for future joint efforts to identify the most valuable genotype/drug response phenotype correlations. Dialogue and collaboration between regulatory agencies and the pharmaceutical industry, as well as within the pharmaceutical sector, will be indispensable for advancing beyond this turning point towards genuine personalized medicine. Drug Dev. Res. 62:71–75, 2004. © 2004 Wiley‐Liss, Inc.
An “Omics” view of drug development
Authors: Altman Russ B. , Rubin Daniel L. , Klein Teri E. 
Published: November 2004

AbstractThe pharmaceutical industry cannot be blamed for having a love/hate relationship with the fields of pharmacogenetics and pharmacogenomics. At the same time that pharmacogenetics and pharmacogenomics promise to save pipeline drugs by identifying subsets of the population for which they work best, they also threaten to increase the complexity of new drug applications, fragment markets, and create uncertainty for prescribers who simply do not understand or have time to master “personalized medicine.” Most importantly, the logical case for genetics‐specific drug selection and dosing is much more mature than the practical list of drugs for which outcomes are demonstrably improved. Understandably, pharmaceutical developers and regulators have been careful in creating strategies for using genetics in drug development, and only recently has the FDA begun to establish preliminary rules for pharmacogenetic testing. A growing public academic effort in pharmacogenetics and pharmacogenomics is helping flesh out the basic science underpinnings of the field, and this should combine with extensive efforts of industry to create a solid foundation for future use of genetics in drug development. Two grand challenges to accelerate our capabilities include the characterization of all human genes involved in the basic pharmacokinetics of drugs, and the detailed study of the genes and pathways associated with G‐protein‐coupled receptors and how they are affected by genetic variation. Drug Dev. Res. 62:81–85, 2004. © 2004 Wiley‐Liss, Inc.
Application of expression genomics in drug development and genomic medicine
Authors: Chin Khew‐Voon , Selvanayagam Zachariah E. , Vittal Ragini , Kita Tsunekazu , Kudoh Kazuya , Yang Chung S. , Wong Yick Fu , Cheung Tak Hong , Yeo Winnie , Chung Tony Kwok Hung , Lin Yong , Liao Jason , Shih Joe Weichung , Yap Sook Fan , Lin Albert W. 
Published: November 2004

AbstractExpressed sequence tags and genome sequencing have virtually uncovered all the genes and transcripts in the human genome. Functional genomic analysis of these genes will undoubtedly reveal their physiological roles in cells in the near future. Coupled with the advent of DNA microarray, cellular response to perturbation can now be examined at genome‐wide levels in a single analysis, yielding clues to the network of pathways and interacting pathways that underlie a comprehensive systems response to exposure to small molecule perturbants. This post‐genomic information will be the foundation for knowledge‐based in silico systems biology. It is envisioned that querying such relational databases will generate testable hypotheses as well as revealing information on networks of regulatory genes and pathways that could further fuel and shape molecular and drug target discovery, and ushering in a new era in genomic medicine. In this review, we will first discuss examples of laboratory results generated from high‐throughput microarray analyses that illuminated previously unrecognized networks of regulatory genes and pathways that point to the mechanisms of action for the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate, and the green tea polyphenol, epi‐gallocatechin gallate. We will then focus on the application of gene expression profiles in genomic medicine for predicting treatment response in cancer, using clinical specimens obtained from patients. These studies and others point to an increasing trend in modern biology in which high‐throughput genome scale comprehensive biological information is incorporated into databases for constructing and reconstructing pathways and networks of interacting pathways that constitute a physiological response to environmental perturbation at the organism or systems levels. Drug Dev. Res. 62:124–133, 2004. © 2004 Wiley‐Liss, Inc.
Adrenocortical response to stress in fasted and unfasted artificially reared 12‐day‐old rat pups
Authors: Ward Glenn , Xing Hua Cheng , Carnide Nancy , Slivchak Jane , Wainwright Patricia 
Published: November 2004

AbstractRecent studies have compared artificially reared (AR) rats with dam‐reared rats on behavioral outcomes but, despite the fact that they are deprived of their mothers during the stress hyporesponsive period (SHRP), little is known about the effects of AR on the development of the stress response. In this study, the corticosterone (CORT) response to a stressor (saline injection ip) on postnatal Day 12 was assessed in rat pups that had been either dam‐reared (DR) or artificially reared since Day 5. In the preceding 24 hr, half the pups in the DR group were maternally deprived (DEP). To control for the food deprivation consequent to maternal deprivation in these groups, half the pups in the AR groups also underwent 24‐hr food deprivation (DEP). In the nondeprived condition AR pups did not differ from DR pups on untreated CORT levels or on levels at 1‐hr poststress (i.e., all rats demonstrated low levels of CORT characteristic of the SHRP). In contrast, both maternally deprived DR pups and food‐deprived AR pups exhibited increased untreated CORT levels as well as a significant increase at 30‐min poststress, but CORT elevations were lower in the AR groups than in the DR groups. Thus, long‐term maternal deprivation through artificial rearing in rats does not affect the reduced CORT levels and reduced CORT responsiveness associated with the SHRP; however, if animals are food deprived, then all show increased basal CORT levels and a greater CORT response to stress, although this response is lower in AR groups than in DR groups. These results suggest that rat pups artificially reared with adequate nutrition will still exhibit the SHRP. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 45: 245–250, 2004.
Intraocular injection of tamoxifen‐loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis
Authors: de Kozak Yvonne , Andrieux Karine , Villarroya Henri , Klein Christophe , Thillaye‐Goldenberg Brigitte , Naud Marie‐Christine , Garcia Elisabeth , Couvreur Patrick 
Published: November 2004

AbstractIn this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non‐steroidal estrogen receptor modulator, in retinal soluble antigen (S‐Ag)‐induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)‐coated nanoparticles (NP‐PEG‐TAM). The localization of the nanoparticles within the eye was investigated using fluorescent‐labeled PEG‐coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP‐PEG‐TAM performed 1–2 days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP‐PEG‐TAM injection significantly reduced EAU compared to injection of NP‐PEG‐TAM with 17β‐estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class II+ inflammatory cells and low expression of TNF‐α, IL‐1β, and RANTES mRNA were noted in eyes of NP‐PEG‐TAM‐treated rats. Intravitreal injection of NP‐PEG‐TAM decreased S‐Ag lymphocyte proliferation, IFN‐γ production by inguinal lymph node cells, and specific delayed‐type hypersensitivity indicative of a reduced Th1‐type response. It increased the anti‐S‐Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP‐PEG‐TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen‐loaded nanoparticles may represent a new option for the treatment of experimental uveitis.
Inhibition of mast cells by interleukin‐10 gene transfer contributes to protection against acute myocarditis in rats
Authors: Palaniyandi Suresh S. , Watanabe Kenichi , Ma Meilei , Tachikawa Hitoshi , Kodama Makoto , Aizawa Yoshifusa 
Published: November 2004

AbstractProgression of acute myocarditis involves a variety of inflammatory events. Mast cells have been implicated as the source of various cytokines, chemokines and histamine in acute inflammation and fibrosis. Interleukin (IL)‐10 has well‐known immunomodulatory actions that are exerted during the recovery phase of myocarditis. In this study, 9‐week‐old male Lewis rats were immunized with cardiac myosin. A plasmid vector expressing mouse IL‐10 cDNA (800 μg per rat) was then transferred three times (7, 12 and 17 days after immunization) into the tibialis anterior muscles of the rats by electroporation. Microscopic examination of mast cells was carried out on toluidine blue‐stained transverse sections of the mid ventricles. Mouse IL‐10 gene transfer significantly reduced mast cell density, cardiac histamine concentration and mast cell growth, and prevented mast cell degranulation. Furthermore, improvement in both myocardial function and the overall condition of the rats was evident from the reduction in the heart weight‐to‐body weight ratio and inflammatory infiltration as well as improvement in hemodynamic and echocardiographic parameters. These findings suggest that IL‐10 gene transfer by electroporation protected against myocarditis via mast cell inhibition.
Distal regulatory elements play an important role in regulation of the human IL‐5 gene
Authors: Urwin Debra L. , Schwenger Gretchen T. F. , Groth David M. , Sanderson Colin J. 
Published: November 2004

AbstractEosinophil infiltration of the lung is a feature of both allergic and nonallergic asthma, and IL‐5 is the key cytokine regulating the production and activation of these cells. Despite many studies focusing on the IL‐5 promoter in both humans and mice there is as yet no clear picture of how the IL‐5 gene is regulated. The aim of this study was to determine if distal regulatory elements contribute to appropriate regulation of the human IL‐5 (hIL‐5) gene. Activity of the –507/+44 hIL‐5 promoter was compared to expression of the endogenous IL‐5 gene in PER‐117 T cells. The IL‐5 promoter was not sufficient to reproduce a physiological pattern of IL‐5 expression. Further, functional analysis of the 5′ and 3′ intergenic regions revealed a number of novel regulatory elements. We have identified a conserved enhancer located approximately 6.2 kb upstream of the hIL‐5 gene. This region contains two potential GATA‐3‐binding sites and increases expression from the hIL‐5 promoter by up to ninefold.
Interleukin 1 plays a major role in the development of Th2‐mediated immunity
Authors: Helmby Helena , Grencis Richard K. 
Published: November 2004

AbstractExpulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th)2‐type response, involving interleukin (IL)‐4, IL‐9 and IL‐13. Here, we show that Th2 response‐associated resistance is dependent on the presence of IL‐1α and IL‐1β. When lymph node cells from naive IL‐1α‐ or IL‐1β‐deficient mice were subjected to Th2 polarization in vitro, they failed to polarize in the presence of IL‐4 alone, but required the addition of exogenous IL‐1α or IL‐1β. Furthermore, we demonstrate that both IL‐1α‐ and IL‐1β‐deficient mice are susceptible to chronic T. muris infection and that the inability to expel the worms is associated with a defect in the development of a Th2 response in the mesenteric lymph nodes. These results provide the first demonstration of the critical role of IL‐1 in regulating Th2 responses during gastrointestinal nematode infection.
Down‐regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation
Authors: Kobayashi Naoki , Takata Hiroshi , Yokota Shumpei , Takiguchi Masafumi 
Published: November 2004

AbstractMulti‐color flow cytometric analysis on human CD8+ T cell subsets revealed that CXCR4 is predominantly expressed on CD8+ T cells with the naive CD27+CD28+CD45RA+ phenotype, and is down‐regulated during differentiation into those with an effector phenotype. The down‐regulation of CXCR4 expression during peripheral differentiation was supported by the fact that the expression of CXCR4 on CD8+ T cells was negatively correlated with that of perforin. The analysis of CCR5, CCR7, and CXCR4 co‐expression further showed that CD8+ T cells expressing a high level of CXCR4 are CCR7+CCR5− naive or central memory subsets, and those expressing a low level of CXCR4 were included in the CCR7−CCR5+/− memory/effector and effector subsets. Epstein Barr virus‐specific CD8+ T cells, which mostly express the memory phenotype, expressed CXCR4, while human cytomegalovirus‐specific CD8+ T cells, which mostly express the effector phenotype, partially expressed this receptor, showing that the expression of CXCR4 is also down‐regulated during differentiation of viral antigen‐specific CD8+ T cells. The classification of human CD8+ T cells based on the expression of these chemokine receptors should prove useful for studies that clarify the differentiation of human CD8+ T cells.
Leader visioning and adaptability: Bridging the gap between research and practice on developing the ability to manage change
Authors: Zaccaro Stephen J. , Banks Deanna 
Published: November 2004

AbstractThe construction of organizational vision and the ability to manage the change engendered by visions represent core organizational competencies that foster competitive advantage for organizations. However, while a significant body of conceptual and empirical research studies supports these as core competencies, high numbers of HR professionals are either not aware of this research or still dispute the utility of these skills. In this article, we discuss three gaps between leadership research and practice. The first refers to the value of organizational visions. The second reflects beliefs about the importance of change management skills for HR managers. The final gap concerns the utility of training and development programs that target visioning and change management skills. We discuss some reasons for these gaps between leadership research and HR practices. We also describe some components of visioning, adaptability and managing change, and provide some supportive conceptual and empirical research. We suggest the use of developmental work assignments as a leader development strategy that we believe is most appropriate for growing these core competencies. © 2004 Wiley Periodicals, Inc.
The importance of pay in employee motivation: Discrepancies between what people say and what they do
Authors: Rynes Sara L. , Gerhart Barry , Minette Kathleen A. 
Published: November 2004

AbstractA majority of human resources professionals appear to believe that employees are likely to overreport the importance of pay in employee surveys. However, research suggests the opposite is actually true. We review evidence showing the discrepancies between what people say and do with respect to pay. We then discuss why pay is likely to be such an important general motivator, as well as a variety of reasons why managers might underestimate its importance. We note that pay is not equally important in all situations or to all individuals, and identify circumstances under which pay is likely to be more (or less) important to employees. We close with recommendations for implementing research findings with respect to pay and suggestions for evaluating pay systems. © 2004 Wiley Periodicals, Inc.