bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cross‐fostering on blood pressure and renal function in the New Zealand genetically hypertensive rat
Authors: Ashton Nick , Kelly Philip , Ledingham Janet M 
Published: November 2003

Summary1. The severity of hypertension displayed by adult spontaneously hypertensive rats (SHR) and Dahl (SS/Jr) rats can be reduced by 20–30 mmHg if the hypertensive pup is cross‐fostered to a normotensive mother within the first 2 weeks of birth. In the SHR, at least, this blood pressure‐lowering effect arises through programming of the neonatal kidney to excrete sodium more effectively. Thus, cross‐fostering may only be effective in lowering pressure in salt‐sensitive hypertensive strains. Accordingly, the aim of the present study was to determine whether cross‐fostering is effective in lowering adult blood pressure in the salt‐resistant New Zealand genetically hypertensive (GH) rat.2. Genetically hypertensive and control normotensive (N) rat pups were reared by either their natural mothers or a foster mother of the opposite strain (NX and GHX). Blood pressure was tracked from the age of 6–18 weeks, at which time renal function was assessed using standard clearance techniques in anaesthetized rats. Renal function was also assessed in a separate group of young rats at 5–6 weeks of age.3. Cross‐fostered GHX rats had lower blood pressure than GH rats, but this difference was only apparent until 9 weeks. The NX rats had higher blood pressures than N rats, but again pressure converged at 10 weeks. Basal renal function did not differ between GH and GHX rats or between N and NX rats at either age. However, young GH rats had lower renal blood flow, glomerular filtration rate, urine output and sodium excretion than N rats.4. These data show that cross‐fostering is effective in lowering blood pressure in GH rats, albeit transiently. The kidneys do not appear to play a role, because renal function did not differ under the current experimental conditions between GH and GHX rats. However, the kidney may play a greater role in the onset of hypertension in the GH rat than previously thought.
Cerebral vascular effects of reactive oxygen species: Recent evidence for a role of NADPH‐oxidase
Authors: Paravicini Tamara M , Sobey Christopher G 
Published: November 2003

Summary1. Reactive oxygen species (ROS) are a diverse family of molecules that are produced throughout the vascular wall. Many ROS, such as the superoxide anion (·O2–) and hydrogen peroxide (H2O2), are now known to act as cellular signalling molecules within blood vessels. In particular, these molecules can exert powerful effects on vascular tone.2. Cerebral arteries are relatively unusual in their responsiveness to ROS. Unlike in many systemic vessels, both ·O2– and H2O2 can cause vasodilatation in the cerebral microcirculation.3. Reactive oxygen species can be produced in the vasculature via a variety of mechanisms; however, it appears that the primary source of ·O2– within blood vessels is the enzyme NADPH‐oxidase.4. In cerebral vessels, activation of NADPH‐oxidase causes both ·O2– production and vasodilatation, indicating that NADPH‐oxidase‐derived ROS may have a functional role in the regulation of cerebral vascular tone.5. Elevated levels of NADPH‐oxidase activity and expression occur in cardiovascular disease states such as hypertension, atherosclerosis and subarachnoid haemorrhage.6. Thus, ROS may contribute to the regulation of cerebral vascular tone during both physiological and pathological conditions.
In silico insights: Chemical and structural characteristics associated with uridine diphosphate‐glucuronosyltransferase substrate selectivity
Authors: Smith PA , Sorich MJ , McKinnon RA , Miners JO 
Published: November 2003

Summary1. Undesirable absorption, distribution, metabolism, excretion properties are the cause of many drug development failures and this has led to the need to identify such problems earlier in the development process. This work highlights computational (in silico) approaches used to identify characteristics influencing the metabolism of uridine diphosphate (UDP)‐glucuronosyltransferase (UGT) substrates. Uridine diphosphate‐glucuronosyltransferase facilitates conjugation between glucuronic acid and a nucleophilic site within a substrate and is one of the major drug‐metabolizing enzymes.2. An understanding of the relevant structural and chemical characteristics of the ligand and the enzyme active site will lead to greater utilization of metabolically relevant structural information in drug design. However, an X‐ray crystal structure of UGT is not yet available, little has been reported about important structurally or catalytically relevant amino acids and only recently has the reported substrate profile of UGT isoforms reached an interpretable level.3. A database of all the known substrates and non‐substrates for each human UGT isoform was assembled and a range of modelling approaches assessed. Currently, pharmacophore models developed using Catalyst™ (Accelrys, San Diego, CA, USA) indicate that substrates of the UGT1A family share two key hydrophobic regions 3 and 6–7 Å from the site of glucuronidation in a well‐defined spatial geometry. Furthermore, two‐dimensional quantitative structure‐activity relationship models show significant reliance on substrate lipophilicity and a range of other descriptors that are known to capture information relevant to ligand–protein interactions.4. In conclusion, substrate‐based modelling of UGT appears both useful and feasible, with significant potential for determining aspects of chemical structure associated with metabolism and to quantify the nature of the relationship for UGT substrates. The development of a novel, user‐defined ‘glucuronidation feature’ for alignment was crucial to the development of pharmacophore‐based UGT models.
Responses to ischaemia and reperfusion in the mouse isolated perfused heart and the phenomenon of ‘contractile cycling’
Authors: Sutherland Fiona J , Baker Kathryn E , Shattock Michael J , Hearse David J 
Published: November 2003

Summary1. The aims of the present study were to examine the response of the murine heart to ischaemia and reperfusion and to determine whether these responses are influenced by the strain of mouse.2. Isolated, paced (600 b.p.m.) murine (T/O mice) hearts were perfused aerobically (2.6 mL/min) with buffer for 40 min before being subjected to whole‐heart (global) ischaemia (37°C) for 20, 30, 35, 40 or 50 min prior to 90 min reperfusion. Contracture was measured during ischaemia and the reperfusate was collected and assayed for creatine kinase.3. With increasing durations of ischaemia, there was a progressive decline in postischaemic recovery such that left ventricular developed pressure (LVDP) after 20, 30, 35, 40 or 50 min ischaemia was 75 ± 4, 65 ± 4, 38 ± 6, 18 ± 2 and 18 ± 2% of pre‐ischaemic controls, respectively.4. There was a reciprocal increase in creatine kinase leakage, indicative of a time‐dependent increase in tissue injury.5. To compare the ischaemic vulnerability of different strains, hearts from Swiss and C57BL/6 mice were perfused for 20 min, followed by 40 min global ischaemia (37°C) and 60 min reperfusion. Functional recovery of LVDP in Swiss mouse hearts was significantly higher than in C57BL/6 mouse hearts (39 ± 7 vs 20 ± 4%, respectively; P < 0.04, t‐test; 10 d.f.).6. During our investigations, we encountered and characterized the phenomenon of ‘contractile cycling’ (cyclical patterns of declining and increasing left ventricular systolic pressure of variable severity and duration).7. We have shown that this confounding phenomenon is a manifestation of an underlying metabolic disturbance of unknown origin that can be attenuated by the addition of substrates, such as pyruvate or acetate, to the standard glucose‐containing perfusion buffer.
Population pharmacokinetics of imipenem in burn patients
Authors: Dailly Eric , Kergueris Marie France , Pannier Michel , Jolliet Pascale , Bourin Michel 
Published: November 2003

AbstractThe interindividual variability of imipenem pharmacokinetic parameters in burn patients suggest that these parameters have to be estimated with a large number of patients. The aim of this study is (i) to estimate these parameters with a population pharmacokinetic approach, and (ii) to test the influence of factors on pharmacokinetics parameters. Data are provided by therapeutic drug monitoring (n = 47, 118 samples) and analysed by a nonlinear mixed effect modelling method. Among the tested covariates (age, gender, body weight, height, size of burn and creatinine plasma level) creatinine plasma level affects imipenem pharmacokinetic parameters substantially. The best fit is obtained with a two‐compartment model integrating a linear–inverse relationship between imipenem clearance and creatinine plasma level. The estimates of imipenem clearance (16.37 ± 0.204 L/h) and of the distribution volume of the central compartment (0.376 ± 0.039 L/kg) are higher in the population of burn patients than the estimates in healthy subjects. This result is connected with high values of glomerule filtration rate and confirms the interest of therapeutic drug monitoring of imipenem in burn patients and particularly for patients with extreme values of creatinine clearance.
Short‐ and long‐term effects of treatment of chronic hepatitis B and delta virus by IFN
Authors: Örmeci Necati 
Published: November 2003

AbstractChronic hepatitis B virus (HBV) infection is a common infectious disease in the world. Two percent of the patients with chronic HBV infection will develop cirrhosis each year, and will die prematurely from cirrhosis or hepatocellular carcinoma. So far interferon alfa and lamivudine are the only effective drugs. Interferon alfa can be used at the dosage of 9–10 million units thrice a week for 4–6 months either intramuscularly or subcutaneously for standard treatment. Interferon provides sustained response in 1/3 of the patients when HBe Ag is (+). Response rate to interferon therapy in HBe Ag(−) patients was similar to that reported in HBe Ag(+) ones. However the responses were not sustained in many patients, serum HBV‐DNA reappear in most after stopping the treatment. Extension of therapy to 1 year may be needed in patients who are unresponsive to therapy and having HBV‐DNA levels <10 pg/ml and ALT >100 IU. Establishment of unresponsiveness in early phases of the therapy is important and careful follow up of serum HBe Ag may be helpful. Interferon alfa treatment of chronic HDV infection may result in temporary normalization of ALT values. Disappearance of HBV‐DNA and HBs Ag from the serum upon completion of therapy dictates sustained response in chronic HDV infection. The long term effect of interferon with respect to virological and histopathological responses is poor in HDV infection and longer periods of therapy in higher doses may be beneficial.
Vasorelaxant effects of grape polyphenols in rat isolated aorta. Possible involvement of a purinergic pathway
Authors: Mendes Anne , Desgranges Claude , Chèze Catherine , Vercauteren Joseph , Freslon Jean‐Louis 
Published: November 2003

AbstractThe purpose of this study was to investigate the mechanism of the vascular relaxation produced by polyphenolic substances from red wine, with a particular focus on the possible involvement of purinoceptors. With this aim, relaxing responses induced by procyanidin from grape seeds (GSP), anthocyanins, catechin and epicatechin were assessed in rat isolated aortic rings left intact (+E) or endothelium‐denuded (−E). In preparations precontracted with noradrenaline, incubation with NG‐nitro‐l‐arginine methyl ester (100 μm, 30 min) fully inhibited the GSP‐induced relaxations. Concentration–effect curves to these substances (from 10−7 to 10−1 g/L) were determined in depolarized (60 mm KCl) preparations in control condition, after incubation with reactive blue 2 (an antagonist of P2Y purinoceptors, 30 μm), with apyrase (an enzyme which hydrolyses ATP and ADP, 0.8 U/mL) or with α,β‐methylene ATP (an inhibitor of ecto ATPases, 10 μm). In (+E) rings, relaxations (expressed as percentage of initial contraction) were 41 ± 2 and 37 ± 3 for GSP and anthocyanins, respectively. Only modest relaxations (ca. 10%) were observed in (−E) rings, as it was the case for catechin and epicatechin in (±E) rings. Reactive blue 2 or apyrase inhibited the GSP‐ and anthocyanin‐induced relaxations in (+E) rings, while α,β‐methylene ATP shifted to the left the relaxation curves obtained with GSP. These data confirm that modest relaxations observed with catechin and epicatechin are not endothelium‐dependent but that GSP and anthocyanins induce a relaxing effect, which is related to the integrity of the endothelium and the synthesis and release of nitric oxide (NO). Furthermore, the inhibition by apyrase and the increase by ecto‐ATPase inhibition of the GSP‐ and anthocyanin‐induced relaxation suggest that these substances could act via an initial release of nucleotides, which in turn could activate P2Y1 and/or P2Y2 purinoceptors of endothelial cells, trigger the synthesis and release of NO and then lead to relaxation.
MGraph: graphical models for microarray data analysis
Authors: Wang Junbai , Myklebost Ola , Hovig Eivind 
Published: November 2003

Abstract
Summary: This paper introduces a MATLAB toolbox, MGraph, which applies graphical models as a natural environment to formulate and solve problems in microarray data analysis. MGraph with its graphical interface allows the user to predict genetic regulatory networks by a graphical gaussian model (GGM), and to quantify the effects of different experimental treatment conditions on gene expression profiles by a graphical log-linear model (GLM). The power of graphical models was explored and illustrated through two example applications. First, four MAPK pathways in yeast were meaningfully reconstructed through GGM. Second, GLM was used to quantify the contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster. This application may provide a valuable aid in the prediction of genetic regulatory networks, as well as in investigations of various experimental conditions that affect global gene expression profiles.
Availability: The MATLAB program MGraph is freely available at http://www.uio.no/~junbaiw/mgraph/mgraph.html for academics.
In silico analysis reveals substantial variability in the gene contents of the gamma proteobacteria LexA-regulon
Authors: Erill Ivan , Escribano Marcos , Campoy Susana , Barbé Jordi 
Published: November 2003

Abstract
Motivation: Motif-prediction algorithm capabilities for the analysis of bacterial regulatory networks and the prediction of new regulatory sites can be greatly enhanced by the use of comparative genomics approaches. In this study, we make use of a consensus-building algorithm and comparative genomics to conduct an in-depth analysis of the LexA-regulon of gamma proteobacteria, and we use the inferred results to study the evolution of this regulatory network and to examine the usefulness of the control sequences and gene contents of regulons in phylogenetic analysis.
Results: We show, for the first time, the substantial heterogeneity that the LexA-regulon of gamma proteobacteria displays in terms of gene content and we analyze possible branching points in its evolution. We also demonstrate the feasibility of using regulon-related information to derive sound phylogenetic inferences.
Availability: Complementary analysis data and both the source code and the Windows-executable files of the consensus-building software are available at http://www.cnm.es/~ivan/RCGScanner/
Parametric alignment of ordered trees
Authors: Wang Lusheng , Zhao Jianyun 
Published: November 2003

Abstract
Motivation: Computing the similarity between two ordered trees has applications in RNA secondary structure comparison, genetics and chemical structure analysis. Alignment of tree is one of the proposed measures. Similar to pair-wise sequence comparison, there is often disagreement about how to weight matches, mismatches, indels and gaps when we compare two trees. For sequence comparison, the parametric sequence alignment tools have been developed. The users are allowed to see explicitly and completely the effect of parameter choices on the optimal sequence alignments. A similar tool for aligning two ordered trees is required in practice.
Results: We develop a parametric tool for aligning two ordered trees that allow users to see the effect of parameter choices on the optimal alignment of trees. Our contributions include: (1) develop a parametric tool for aligning two ordered trees; (2) design an efficient algorithm for aligning two ordered trees with gap penalties that runs in O(n2deg2) time, where n is the number of nodes in the trees and deg is the degree of the trees; and (3) reduce the space of the algorithm from O(n2deg2) to O(n log n · deg2).
Availability: The software is available at http://www.cs.cityu.edu.hk/~lwang/software/ParaTree
A simple and efficient algorithm for gene selection using sparse logistic regression
Authors: Shevade S. K. , Keerthi S. S. 
Published: November 2003

Abstract
Motivation: This paper gives a new and efficient algorithm for the sparse logistic regression problem. The proposed algorithm is based on the Gauss–Seidel method and is asymptotically convergent. It is simple and extremely easy to implement; it neither uses any sophisticated mathematical programming software nor needs any matrix operations. It can be applied to a variety of real-world problems like identifying marker genes and building a classifier in the context of cancer diagnosis using microarray data.
Results: The gene selection method suggested in this paper is demonstrated on two real-world data sets and the results were found to be consistent with the literature.
Availability: The implementation of this algorithm is available at the site http://guppy.mpe.nus.edu.sg/~mpessk/SparseLOGREG.shtml
Supplementary Information: Supplementary material is available at the site http://guppy.mpe.nus.edu.sg/~mpessk/SparseLOGREG.shtml
Early bioinformatics: the birth of a discipline—a personal view
Authors: Ouzounis Christos A. , Valencia Alfonso 
Published: November 2003

Abstract
Motivation: The field of bioinformatics has experienced an explosive growth in the last decade, yet this ‘new’ field has a long history. Some historical perspectives have been previously provided by the founders of this field. Here, we take the opportunity to review the early stages and follow developments of this discipline from a personal perspective.
Results: We review the early days of algorithmic questions and answers in biology, the theoretical foundations of bioinformatics, the development of algorithms and database resources and finally provide a realistic picture of what the field looked like from a resources and finally provide a realistic picture of what the field looked like from a practitioner's viewpoint 10 years ago, with a perspective for future developments.
Normality of oligonucleotide microarray data and implications for parametric statistical analyses
Authors: Giles Peter J. , Kipling David 
Published: November 2003

Abstract
Motivation: Experimental limitations have resulted in the popularity of parametric statistical tests as a method for identifying differentially regulated genes in microarray data sets. However, these tests assume that the data follow a normal distribution. To date, the assumption that replicate expression values for any gene are normally distributed, has not been critically addressed for Affymetrix GeneChip data.
Results: The normality of the expression values calculated using four different commercial and academic software packages was investigated using a data set consisting of the same target RNA applied to 59 human Affymetrix U95A GeneChips using a combination of statistical tests and visualization techniques. For the majority of probe sets obtained from each analysis suite, the expression data showed a good correlation with normality. The exception was a large number of low-expressed genes in the data set produced using Affymetrix Microarray Suite 5.0, which showed a striking non-normal distribution. In summary, our data provide strong support for the application of parametric tests to GeneChip data sets without the need for data transformation.
PreP: gene expression data pre-processing
Authors: García de la Nava Jorge , van Hijum Sacha , Trelles Oswaldo 
Published: November 2003

Abstract
Summary: PreP is a versatile, powerful, standalone application that aims at pre-processing gene expression data.
Availability: Documentation and executable file for MS-Windows are available at http://chirimoyo.ac.uma.es/bitlab/services/index.htm
NCL: a C++ class library for interpreting data files in NEXUS format
Authors: Lewis Paul O. 
Published: November 2003

Abstract
Summary: The NEXUS Class Library (NCL) is a collection of C++ classes designed to simplify interpreting data files written in the NEXUS format used by many computer programs for phylogenetic analyses. The NEXUS format allows different programs to share the same data files, even though none of the programs can interpret all of the data stored therein. Because users are not required to reformat the data file for each program, use of the NEXUS format prevents cut-and-paste errors as well as the proliferation of copies of the original data file. The purpose of making the NCL available is to encourage the use of the NEXUS format by making it relatively easy for programmers to add the ability to interpret NEXUS files in newly developed software.
Availability: The NCL is freely available under the GNU General Public License from http://hydrodictyon.eeb.uconn.edu/ncl/
Supplementary information: Documentation for the NCL (general information and source code documentation) is available in HTML format at http://hydrodictyon.eeb.uconn.edu/ncl/
MetaGeneAlyse: analysis of integrated transcriptional and metabolite data
Authors: Daub Carsten O. , Kloska Sebastian , Selbig Joachim 
Published: November 2003

Abstract
Summary: New techniques in sample preparation allow high throughput analysis of samples on the transcriptional as well as on the metabolic level. We present a service accessible via the web that allows the analysis of integrated data sets that combine gene-expression data and metabolic data. After uploading, data sets can be normalized, clustered by various methods and results can be graphically visualized. All calculations are carried out on a server, so even time- and memory-consuming analyses can be done independently of the performance of the client.
Availability: The service is accessible via web-interface at http://metagenealyse.mpimp-golm.mpg.de/
Missing-value estimation using linear and non-linear regression with Bayesian gene selection
Authors: Zhou Xiaobo , Wang Xiaodong , Dougherty Edward R. 
Published: November 2003

Abstract
Motivation: Data from microarray experiments are usually in the form of large matrices of expression levels of genes under different experimental conditions. Owing to various reasons, there are frequently missing values. Estimating these missing values is important because they affect downstream analysis, such as clustering, classification and network design. Several methods of missing-value estimation are in use. The problem has two parts: (1) selection of genes for estimation and (2) design of an estimation rule.
Results: We propose Bayesian variable selection to obtain genes to be used for estimation, and employ both linear and nonlinear regression for the estimation rule itself. Fast implementation issues for these methods are discussed, including the use of QR decomposition for parameter estimation. The proposed methods are tested on data sets arising from hereditary breast cancer and small round blue-cell tumors. The results compare very favorably with currently used methods based on the normalized root-mean-square error.
Availability: The appendix is available from http://gspsnap.tamu.edu/gspweb/zxb/missing_zxb/ (user: gspweb; passwd: gsplab).