bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining variable latency pipeline with instruction reuse for execution latency reduction
Authors: Sato Toshinori , Arita Itsujiro 
Published: September 2003

AbstractOperand bypass logic is likely to be one of the critical structures for future microprocessors to achieve high clock speed. The logic delay causes the execution time budget to be reduced significantly, so that the execution stage is divided into several stages. The variable latency pipeline (VLP) structure has the advantages of pipelining and pseudo‐asynchronous design. According to the source operands delivered to arithmetic units, VLP changes execution latency and thus achieves both high speed and low latency for most operands. In this paper we evaluate VLP with dynamically scheduled superscalar processors, using a cycle‐by‐cycle simulator. Our experimental results show that VLP successfully reduces the effective execution time, and thus relaxes the constraints on the operand bypass logic. We also evaluate the instruction reuse technique in order to support VLP. © 2003 Wiley Periodicals, Inc. Syst Comp Jpn, 34(12): 11–21, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10498
IBCD: a fast collision detection algorithm based on image space using OBB
Authors: Fan Zhaowei , Wan Huagen , Gao Shuming 
Published: September 2003

AbstractImage‐based collision detection algorithms make efficient use of the graphics rendering hardware and reduce the computational cost of CPU. In this article, a fast collision detection algorithm based on image space is presented, which combines graphics hardware capabilities with a simplified geometric representation (oriented bounding box) in order to rapidly detect collisions between complex objects. The method can deal with arbitrary polyhedra, while preserving the merits of image‐based collision detection algorithms. This is achieved by decomposing the surfaces of an object into a list of convex pieces. High efficiency of the algorithm is obtained by organizing the convex pieces into a binary tree with each node representing a convex piece, and by adopting triangle strip compression. The algorithm has been implemented and compared with related algorithms. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluation of Laryngeal Function after Implantation of the Vagus Nerve Stimulation Device
Authors: Santos Perry M. 
Published: September 2003

OBJECTIVESThe vagus nerve stimulation device (VNS) is used for the management of seizures. This study evaluated what effect the diameter of the vagus nerve helical electrode might have on true vocal cord (TVC) mobility. The study was prompted after 2 cases of TVC immobility. Electrode nerve compression was suspect.METHODSEighteen patients underwent intraoperative vagus nerve measurement and electrode placement with subsequent voice and TVC evaluation. Electrode selection was based on vagus nerve measurements.RESULTSSeven patients had vagus nerves measuring less than 2 mm diameter and received the 2‐mm inner diameter electrode. Eleven patients had vagus nerves measuring more than 2 mm in diameter and received the 3‐mm inner diameter electrode. No patients experienced transient or permanent hoarseness or paresis/paralysis.CONCLUSIONPrecise vagus nerve measurements and electrode selection appear to decrease the incidence of nerve compression injury and TVC immobility.
Degranulation in RBL‐2H3 cells: regulation by calmodulin pathway
Authors: Funaba Masayuki , Ikeda Teruo , Abe Matanobu 
Published: September 2003

AbstractInvolvement of the calmodulin pathway in Ca2+‐induced degranulation was evaluated in RBL‐2H3 mast cells. Pretreatment of RBL‐2H3 cells with a calmodulin antagonist, W‐13, blocked ionomycin‐dependent release of β‐hexosaminidase into the supernatant, although W‐13 treatment alone slightly but significantly increased the release. Ca2+/calmodulin activates various protein kinases and phosphatases including myosin‐light chain kinase (MLCK), calmodulin‐dependent protein kinases (CaMKs), and calcineurin. When RBL‐2H3 cells were pretreated with a MLCK inhibitor, ML‐7, or a CaMKs inhibitor, KN‐93, the ionomycin‐dependent release of β‐hexosaminidase into the supernatant was inhibited. In addition, pretreatment with calcineurin inhibitors, cyclosporin A and FR901725, resulted in blockage of the ionomycin‐dependent release of β‐hexosaminidase into the supernatant. Our results indicate that Ca2+/calmodulin, activated calmodulin, is indispensable for Ca2+‐induced degranulation, and that within the calmodulin pathways, at least MLCK, CaMKs and calcineurin positively regulate the release of granules initiated by increasing cytosolic Ca2+concentrations in RBL‐2H3 cells.
Evaluation of nutritional status and pathophysiology of growth retardation in patients with phenylketonuria
Authors: Dobbelaere D. , Michaud L. , Debrabander A. , Vanderbecken S. , Gottrand F. , Turck D. , Farriaux J. P. 
Published: September 2003

AbstractSummary: Recent European studies have shown that growth retardation is common in people with phenylketonuria (PKU) during the first years of life while they receive a low‐phenylalanine (Phe) diet. The aims of the present study were to assess the growth of our PKU patients and to search for nutritional and hormonal explanations for the growth delay. Twenty PKU patients aged 8 months to 7 years entered the study. The design was cross‐sectional, a longitudinal study having already been performed in our centre. The following data were recorded: weight/height (W/H), height/age (H/A), and weight/age (W/A) Z‐scores; fat‐free mass (measured from bioelectrical impedometry (FFM1), and skinfold thickness (FFMA). Thyroid hormones, insulin‐like growth factor I (IGF1), insulin‐like growth factor binding protein (IGFBP3), selenium, zinc, and Phe blood levels were measured. Dietary intake was also recorded over 4 days. PKU patients were moderately but significantly shorter (H/A Z‐score varied from −2.12 to 1.61; mean −0.49) and lighter (W/A Z‐score varied from −2.58 to 1.49; mean −0.71) than the French reference population. Body composition was not different from that of controls matched for age and sex. IGF1, IGFBP3, and thyroid hormone levels were within normal range. All children received more than two‐thirds of the recommended daily allowances for energy (91%±18%) and for proteins (146%±26%). The mean daily intake of our patients was sufficient in selenium, but markedly deficient in zinc (2.4±2.2 mg/day). No correlation was found between zinc daily intake or zinc plasma levels and growth retardation. Moreover, no relation was found between the plasma Phe concentrations, protein or caloric intake and the presence of growth retardation. Our results show that growth retardation in PKU patients is not related to hormonal or caloric deficiencies. Further studies are needed to investigate the effect of various nutrient supplementation regimens (especially zinc) on the growth of PKU patients.
Esomeprazole administered through a nasogastric tube provides bioavailability similar to oral dosing
Authors: Sostek M. B. , Chen Y. , Skammer W. , Winter H. , Zhao J. , Andersson T. 
Published: September 2003

SummaryAim : To determine if nasogastric tube administration of the enteric‐coated pellets from an opened esomeprazole capsule provides bioavailability similar to oral dosing with the intact capsule.Methods : A randomized, single‐centre, open‐label, two‐period crossover pharmacokinetic study consisting of two 5‐day dosing periods separated by a 7‐ to 14‐day washout period was conducted. Healthy subjects between the ages of 18 and 50 years received esomeprazole 40 mg once daily either orally as an intact capsule, or as a suspension of the enteric‐coated pellets from an opened capsule in water through a nasogastric tube.Results : In 47 evaluable subjects, the 90% confidence intervals were 0.87–1.08 and 0.93–1.25 for the geometric mean of the ratio of nasogastric tube administration relative to administration of the intact capsule for the area under the plasma concentration–time curve and for maximum plasma concentration, respectively, on day 1, demonstrating bioequivalence. Oral and nasogastric administration also demonstrated similar bioavailabilities on day 5. Esomeprazole was well tolerated regardless of the mode of administration.Conclusions : Nasogastric tube administration of the enteric‐coated pellets from an opened esomeprazole 40 mg capsule provides bioavailability similar to oral dosing. Administration of the contents of an opened esomeprazole 40 mg capsule in water through a nasogastric tube is a practical alternative for patients with feeding tubes who require effective gastric acid suppression, but cannot swallow an oral preparation.
Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome
Authors: Corazziari E. , Bytzer P. , Delvaux M. , Holtmann G. , Malagelada J. R. , Morris J. , Muller‐Lissner S. , Spiller R. C. , Tack J. , Whorwell P. J. 
Published: September 2003

SummaryAppropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations.This consensus report highlights the following points.(a) A 4‐week period is considered to be adequate to assess drug efficacy for the control of symptoms.(b) For the cyclic and non‐life‐threatening nature of the disease, a long‐term study of 4–6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients.(c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow‐up period prolonged for a sufficient time (4–8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post‐treatment benefit.(d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on‐demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome.(e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome.(f)  The main efficacy outcome of the treatment should be based on one primary end‐point.(g) The primary efficacy end‐point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms.(h) A 50% improvement in the primary efficacy end‐point seems to be a reasonable definition of a responder.
Meta‐analysis: comparative efficacy of different proton‐pump inhibitors in triple therapy for Helicobacter pylori eradication
Authors: Vergara M. , Vallve M. , Gisbert J. P. , Calvet X. 
Published: September 2003

SummaryBackground : It is not known whether certain proton‐pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication.Aim : To compare the efficacy of different proton‐pump inhibitors in triple therapy by performing a meta‐analysis.Methods : A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton‐pump inhibitor were included in a meta‐analysis using Review Manager 4.1.Results : Fourteen studies were included. Intention‐to‐treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69–1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58–1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58–1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48–1.22) in 550 patients.Conclusion : The efficacy of various proton‐pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.
Inter‐individual variability in levels of human microsomal protein and hepatocellularity per gram of liver
Authors: Wilson Z. E. , Rostami‐Hodjegan A. , Burn J. L. , Tooley A. , Boyle J , Ellis S. W. , Tucker G. T. 
Published: September 2003

Aims  To determine levels of microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of human liver and their interindividual variability.Methods  Triplicate liver samples were used to determine values of MPPGL (n = 20) and HPGL (n = 7) after accounting for the fractional loss of microsomal protein or hepatocytes during processing. Repeated measurements from each liver sample allowed the estimation of true interindividual variability in MPPGL and HPGL using ANOVA.Results  The value of MPPGL ranged from 26 to 54 mg g−1 (meangeo= 33 mg g−1). The value of HPGL ranged from 65 to 185 × 106 cells g−1 (meangeo= 107 × 106 cells g−1).Conclusions  There is significant interindividual variability in MPPGL, which has implications for the accurate extrapolation of in vitro data on drug metabolism to predict in vivo metabolic clearance.
Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions
Authors: Kokwaro Gilbert O. , Ogutu Bernhards R. , Muchohi Simon N. , Otieno Godfrey O. , Newton Charles R. J. C. 
Published: September 2003

Aims  Phenobarbital is commonly used to treat status epilepticus in resource‐poor countries. Although a dose of 20 mg kg−1 is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15‐mg kg−1 intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus.Methods  Twelve children (M/F: 11/1), aged 7–62 months, received a loading dose of phenobarbital (15 mg kg−1) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg−1 at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx® fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to predict the optimum dosage regimen that would maintain plasma phenobarbital concentrations between 15 and 20 mg l−1 for 72 h.Results  All the children achieved plasma concentrations above 15 mg l−1 by the end of the infusion. Mean (95% confidence interval or median and range for Cmax) pharmacokinetic parameters were: area under curve [AUC (0, ∞) ]: 4259 (3169, 5448) mg l−1.h, : 82.9 (62, 103) h, CL: 5.8 (4.4, 7.3) ml kg−1 h−1, Vss: 0.8 (0.7, 0.9) l kg −1, CSF: plasma phenobarbital concentration ratio: 0.7 (0.5, 0.8; n= 6) and Cmax: 19.9 (17.9–27.9) mg l−1. Eight of the children had their convulsions controlled and none of them had recurrence of convulsions. Simulations suggested that a loading dose of 15 mg kg−1 followed by two maintenance doses of 2.5 mg kg−1 at 24 h and 48 h would maintain plasma phenobarbital concentrations between 16.4 and 20 mg l−1 for 72 h.Conclusions  Phenobarbital, given as an i.v. loading dose, 15 mg kg−1, achieves maximum plasma concentrations of greater than 15 mg l−1 with good clinical effect and no significant adverse events in children with severe falciparum malaria. A maintenance dose of 2.5 mg kg−1 at 24 h and 48 h was predicted to be sufficient to maintain concentrations of 15–20 mg l−1 for 72 h, and may be a suitable regimen for treatment of convulsions in these children.
Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma
Authors: Currie Graeme P. , Lima John J. , Sylvester Jim E. , Lee Daniel K. C. , Cockburn Wendy J. R. , Lipworth Brian J 
Published: September 2003

Aim  Cysteinyl leukotrienes are important pro‐inflammatory mediators in the pathogenesis of asthma, while leukotriene C4 synthase is a key enzyme in their biosynthesis. Our aim is to evaluate whether responsiveness to leukotriene receptor antagonists was determined by expression of the variant (C) or wild‐type (A) polymorphism of this enzyme.Methods  We carried out a retrospective analysis of 8 randomised, placebo‐controlled trials performed in our department in mild‐to‐moderate asthmatics. In all trials, effect of leukotriene receptor antagonist was compared to placebo, where the primary outcome was bronchial hyperresponsiveness to adenosine monophosphate or methacholine. Secondary outcomes were forced expiratory volume in 1 second, exhaled nitric oxide and peripheral blood eosinophils.Results  For the primary outcome of attenuation of bronchial hyperresponsiveness by leukotriene receptor antagonist vs placebo, there were significant effects within each genotype on adenosine monophosphate (AMP) (n = 78): 2.21 and 2.07‐fold improvements for AA and AC/CC, respectively; while for methacholine (n = 81) there were 1.39 and 1.36‐fold improvements, respectively. There were no significant differences between genotypes (i.e. AA vs AC/CC): geometric mean fold‐differences of 1.07 (95%CI 0.63–1.81) and 1.02 (95%CI 0.70–1.50) for AMP and methacholine, respectively. There were also no differences between genotypes for all secondary outcomes.Conclusion  Polymorphisms of leukotriene C4 synthase did not determine responsiveness, in terms of attenuation of bronchial hyperresponsiveness, to leukotriene receptor antagonists in mild‐to‐moderate asthmatics. Further prospective large pharmacogenetic studies are required in more severe patients, where there may be greater improvements in pharmacodynamic outcome measures such as bronchial hyperresponsiveness and exhaled nitric oxide.
Blood‐mediated scavenging of cerebrospinal fluid glutamate
Authors: Gottlieb Miroslav , Wang Yin , Teichberg Vivian I. 
Published: September 2003

AbstractThe maintenance of brain extracellular glutamate (Glu) at levels below its excitotoxic threshold is performed by Glu transporters present on glia and neurons as well as on brain capillary endothelial cells which remove brain Glu into blood. The feasibility of accelerating the naturally occurring brain‐to‐blood Glu efflux was studied using paradigms based on the fate of Glu present in the cerebrospinal fluid or infused into the brain ventricles and monitored before, during, and after decreasing blood Glu levels with pyruvate and oxaloacetate, the respective Glu co‐substrates of the blood resident enzymes glutamate–pyruvate transaminase and glutamate–oxaloacetate transaminase. Results from cerebroventricular perfusions with [3H]Glu, intracerebroventricular injections of [3H]Glu, and measurements of the basal CSF Glu levels point out to the same conclusion that the intravenous administration of pyruvate and oxaloacetate which decreases blood Glu levels accelerates the brain‐to‐blood Glu efflux. We conclude that the brain extracellular Glu levels can be controlled in part by the blood Glu levels. The results may provide not only a rational explanation for the inhibition of Glu release and neuroprotective effects of parentally administered pyruvate in hemorrhagic shock and forebrain ischemia but could also outline a potential strategy for the removal of excess Glu in various neurodegenerative disorders.
Signal transduction pathways in mouse microglia N‐11 cells activated by advanced glycation endproducts (AGEs)
Authors: Dukic‐Stefanovic Sladjana , Gasic‐Milenkovic Jovana , Deuther‐Conrad Winnie , Münch Gerald 
Published: September 2003

AbstractDeposition of cross‐linked insoluble protein aggregates such as amyloid plaques is characteristic for Alzheimer's disease. Microglial activation by these extracullar deposits has been proposed to play a crucial role in functional degeneration as well as cell death of neurones. A sugar‐derived post‐translational modification of long‐lived proteins, advanced glycation endproducts (AGEs), activate specific signal transduction pathways, resulting in the up‐regulation of various pro‐inflammatory signals such as cytokines [interleukin‐6 (IL‐6), tumour necrosis factor‐alpha (TNF‐α)] and inducible nitric oxide synthase (iNOS). Our goal was to study AGE‐activated signal transduction pathways involved in the induction of pro‐inflammatory effectors in the murine microglial cell line N‐11. Chicken egg albumin‐AGE (CEA‐AGE), used as model AGE, induces nitric oxide (NO), TNF‐α and IL‐6 production. The AGE receptor, RAGE, and the transcription factor, nuclear factor kappa B (NF‐κB), appear to be involved in all pathways, since a neutralizing RAGE antibody and a peptide inhibiting NF‐κB translocation down‐regulated NO, TNF‐α and IL‐6 production. NO and TNF‐α, but not IL‐6 production appear to be regulated independently, since NOS inhibitors did not decrease TNF‐α secretion and a neutralizing TNF‐α antibody did not reduce NO production, while employment of NOS inhibitors reduced significantly the secretion of IL‐6. Inhibition of the MAP‐kinase‐kinase (MEK) and phosphatidylinositol 3‐kinase (PI3K) pathway, but not that of mitogen‐activated protein kinase‐p38 (MAPK‐p38), reduced NO, TNF‐α and IL‐6 significantly, suggesting that simultaneous activation of the first two pathways is necessary for the AGE‐induced induction of these pro‐inflammatory stimuli.
Dopamine‐dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum
Authors: Chartoff Elena H. , Papadopoulou Maria , Konradi Christine , Carlezon William A. 
Published: September 2003

AbstractChronic morphine leads to compensatory up‐regulation of cAMP signaling pathways in numerous brain regions. One potential consequence of up‐regulated cAMP signaling is increased phosphorylation of cAMP response element binding protein (CREB), a transcription factor that may regulate neuroadaptations related to morphine dependence. Altered gene expression within the nucleus accumbens (NAc), a ventral component of the striatum that receives substantial dopaminergic input, may play a role in some of the motivational aspects of opiate withdrawal. To determine if morphine withdrawal leads to increased CREB phosphorylation in striatal tissues, we examined the effects of naloxone‐precipitated morphine withdrawal on CREB phosphorylation in primary cultures of rat striatal neurons. Precipitated morphine withdrawal was associated with enhanced dopamine‐, SKF 82958 (D1 receptor agonist)‐, and forskolin‐induced CREB phosphorylation. During precipitated withdrawal, D1 receptor‐mediated CREB phosphorylation was dependent on cAMP‐dependent protein kinase (PKA). Precipitated withdrawal also led to up‐regulation of c‐fos mRNA in response to SKF 82958. CREB protein levels were not altered by acute or chronic morphine. These results suggest that D1 receptor‐mediated signal transduction is enhanced during morphine withdrawal. Furthermore, they are consistent with in vivo evidence suggesting that increased CREB activation in portions of the striatum (e.g. the NAc) is related to dysphoric states associated with drug withdrawal.