bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetrandrine induces apoptosis in hepatic stellate cells
Authors: Zhao Yu‐Zhe , Kim Ji‐Young , Park Eun‐Jeon , Lee Sung Hee , Woo Sun‐Wook , Ko Geonil , Sohn Dong Hwan 
Published: May 2004

AbstractWe have previously reported that tetrandrine reduced hepatic stellate cell activation and collagen accumulation in liver ﬁbrosis induced by biliary obstruction. In the present study, we examined the apoptosis‐inducing effect of tetrandrine on activated hepatic stellate cells, as the therapeutic goal in hepatic ﬁbrosis is to eliminate the activated hepatic stellate cells by apoptosis. We used rat hepatic stellate cells transformed by Simian virus 40 (T‐HSC/Cl‐6) to overcome the limitations inherent in studying primary cultures of hepatic stellate cells. Tetrandrine treatment at doses of 25 and 50 µg/ml for 12 h induced apoptosis as conﬁrmed by DNA fragmentation and increased sub‐G1 DNA content as detected by ﬂow cytometric analysis. Tetrandrine also induced the activation of caspase‐3 protease and subsequent proteolytic cleavage of poly(ADP‐ribose) polymerase. In conclusion, our results demonstrate that tetrandrine induces apoptosis of T‐HSC/Cl‐6 cells, and these results should contribute to the development of new agents for the treatment of hepatic ﬁbrosis. Copyright © 2004 John Wiley & Sons, Ltd.
Advances in chemistry and bioactivity of the genus Uncaria
Authors: Laus Gerhard 
Published: May 2004

AbstractThe alkaloids of the pantropical genus Uncaria (Rubiaceae) were reviewed extensively by Phillipson et al. in (1978) Since then a host of papers with new results has been published. The compounds discovered are from three major groups: (1) alkaloids; (2) terpenoids; and (3) ﬂavonoids. Some highly unusual structures have been reported. Although there are at least 35 species of Uncaria known, recent research focussed on a relatively small number of species. During recent years bioactivity of extracts and pure compounds isolated from Uncaria species have been increasingly investigated. These include anticonvulsive, antiinﬂammatory, antimutagenic, antioxidant, cytoprotective, hypotensive, and immunoregulatory effects. The literature since 1978 is reviewed and 133 references are given. Copyright © 2004 John Wiley & Sons, Ltd.
Structure of stable double‐ionic model water clusters of quaternary alkylammonium surfactants with some monovalent counterions as derived by the DFT method
Authors: Zieliński Ryszard , Szymusiak Henryk 
Published: May 2004

AbstractWe have performed DFT calculations on stability of model water clusters of alkylammonium surfactants with different monovalent counterions, such as fluoride, chloride, bromide, hydroxide, nitrate, perchlorate, and tetrafluoroborate. We have found that stable water clusters are formed if they contain at least three molecules of water. We can distinguish two types of stable water clusters of ammonium salts: stable neutral water clusters and double‐ionic water clusters. According to the results of our DFT calculations, the first type of cluster is more stable by ca. 3–7 kcal/mol. We have found several types of stable double‐ionic water clusters of alkylammonium salts with different counterions. In each case, the stable structures have some element of symmetry and they are stabilized by hydrogen bonding. The computed energy of double‐ionic cluster formation of hydrated alkylammonium salts with different counterions correlates quite well with experimental data of the critical micelle concentration (CMC), indicating a role of hydration phenomena in the process of micelle formation. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Density functional theory for superconductors
Authors: Lathiotakis N. N. , Marques M. A. L. , Lüders M. , Fast L. , Gross E. K. U. 
Published: May 2004

AbstractTwo recently proposed exchange‐correlation functionals describing the superconducting phase of matter are reviewed and further explored: Whereas the first is a generalization of the local density approximation dealing with purely electronic correlations, the second is a functional derived from Kohn–Sham perturbation theory that includes electronic and phononic correlations on the same footing. Superconducting properties of simple metals obtained with the latter functional agree rather well with experimental results. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
The (100), (110), and (111) Cu surfaces revisited by the semiempirical LCAO method
Authors: Cortona Pietro , Sapet Christophe 
Published: May 2004

AbstractThe electronic properties of surfaces covered by adsorbates are often investigated by means of the semiempirical LCAO method. This implicitly requires the existence of parameters that correctly account for the bulk as well as for the surface electronic structure of the substrate. We will show that, in general, such parameters cannot be found by fitting just the available experimental data for the bulk band structure: some results for the surface states must also be taken into account. We have found that very few data, for just one surface, are sufficient to select a set of parameters that give electronic bands in good agreement with experiment for the bulk as well as for the three low‐order surfaces that we have investigated. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
A comparison of goodness of fit tests for age‐related reference ranges
Authors: Pan H. , Cole T. J. 
Published: May 2004

AbstractAge‐related reference ranges based on cubic spline or kernel‐based smoothing methods lack a parametric framework with which to assess goodness of fit, as the distribution of the log‐likelihood ratio comparing models with different degrees of smoothing is not known in general. Several methods have been proposed to assess goodness of fit in this case: Healy's grid test, Royston's Q tests and van Buuren's worm plot. Here we compare the performance of the various methods, including an extension of the Q tests, and show how they can be used, with other information including the appearance of the fitted curves, to inform the choice of model for age‐related reference ranges of height and weight in a large Dutch data set. Copyright © 2004 John Wiley & Sons, Ltd.
Simultaneous inference for longitudinal data with detection limits and covariates measured with errors, with application to AIDS studies
Authors: Wu Lang 
Published: May 2004

AbstractIn AIDS studies such as HIV viral dynamics, statistical inference is often complicated because the viral load measurements may be subject to left censoring due to a detection limit and time‐varying covariates such as CD4 counts may be measured with substantial errors. Mixed‐effects models are often used to model the response and the covariate processes in these studies. We propose a unified approach which addresses the censoring and measurement errors simultaneously. We estimate the model parameters by a Monte‐Carlo EM algorithm via the Gibbs sampler. A simulation study is conducted to compare the proposed method with the usual two‐step method and a naive method. We find that the proposed method produces approximately unbiased estimates with more reliable standard errors. A real data set from an AIDS study is analysed using the proposed method. Copyright © 2004 John Wiley & Sons, Ltd.
Minimization of sample size when comparing two small probabilities in a non‐inferiority safety trial
Authors: de Boo Theo M. , Zielhuis Gerhard A. 
Published: May 2004

AbstractIn clinical trials success rates of two treatments to be compared often range from 10 to 90 per cent. When the comparison probabilities are (much) smaller than 10 per cent, standard methods for sample size and power calculations may provide invalid results. This situation may occur when there is interest in safety rather than in efficacy. In such trials, no more patients should be included than strictly necessary. We compared the results of maximum likelihood methods for the computation of sample sizes in a non‐inferiority trial, including exact procedures and considered unequal sample sizes for experimental and reference treatment. An exact, unequal sample size maximum likelihood procedure is advocated when the specified non‐zero risk difference under the null hypothesis is not too large. Such a procedure is also indicated when the parameter of interest is the relative risk, rather than the risk difference. Copyright © 2004 John Wiley & Sons, Ltd.
Gene expression profiling for prognosis using Cox regression
Authors: Pawitan Y. , Bjöhle J. , Wedren S. , Humphreys K. , Skoog L. , Huang F. , Amler L. , Shaw P. , Hall P. , Bergh J. 
Published: May 2004

AbstractGiven the promise of rich biological information in microarray data we will expect an increasing demand for a robust, practical and well‐tested methodology to provide patient prognosis based on gene expression data. In standard settings, with few clinical predictors, such a methodology has been provided by the Cox proportional hazard model, but no corresponding methodology is available to deal with the full set of genes in microarray data. Furthermore, we want the procedure to be able to deal with the general survival data that include censored information. Conceptually such a procedure can be constructed quite easily, but its implementation will never be straightforward due to computational problems. We have developed an approach that relies on an extension of the Cox proportional likelihood that allows random effects parameters. In this approach, we use the full set of genes in the analysis and deal with survival data in the most general way. We describe the development of the model and the steps in the implementation, including a fast computational formula based on a subsampling of the risk set and the singular value decomposition. Finally, we illustrate the methodology using a data set obtained from a cohort of breast cancer patients. Copyright © 2004 John Wiley & Sons, Ltd.
Sample size determination for comparing several survival curves with unequal allocations
Authors: Halabi Susan , Singh Bahadur 
Published: May 2004

AbstractAhnn and Anderson derived sample size formulae for unstratified and stratified designs assuming equal allocation of subjects to three or more treatment groups. We generalize the sample size formulae to allow for unequal allocation. In addition, we define the overall probability of death to be equal to one minus the censored proportion for the stratified design. This definition also leads to a slightly different definition of the non‐centrality parameter than that of Ahnn and Anderson for the stratified case. Assuming proportional hazards, sample sizes are determined for a prespecified power, significance level, hazard ratios, allocation of subjects to several treatment groups, and known censored proportion. In the proportional hazards setting, three cases are considered: (1) exponential failures–exponential censoring, (2) exponential failures–uniform censoring, and (3) Weibull failures (assuming same shape parameter for all groups)–uniform censoring. In all three cases of the unstratified case, it is assumed that the censoring distribution is the same for all of the treatment groups. For the stratified log‐rank test, it is assumed the same censoring distribution across the treatment groups and the strata. Further, formulae have been developed to provide approximate powers for the test, based upon the first two or first four‐moments of the asymptotic distribution.We observe the following two major findings based on the simulations. First, the simulated power of the log‐rank test does not depend on the censoring mechanism. Second, for a significance level of 0.05 and power of 0.80, the required sample size n is independent of the censoring pattern. Moreover, there is very close agreement between the exact (asymptotic) and simulated powers when a sequence of alternatives is close to the null hypothesis. Two‐moment and four‐moment power series approximations also yield powers in close agreement with the exact (asymptotic) power. With unequal allocations, our simulations show that the empirical powers are consistently above the target value of prespecified power of 0.80 when 50 per cent of the patients are allocated to the treatment group with the smallest hazard. Copyright © 2004 John Wiley & Sons, Ltd.
Cure fraction estimation from the mixture cure models for grouped survival data
Authors: Yu Binbing , Tiwari Ram C. , Cronin Kathleen A. , Feuer Eric J. 
Published: May 2004

AbstractMixture cure models are usually used to model failure time data with long‐term survivors. These models have been applied to grouped survival data. The models provide simultaneous estimates of the proportion of the patients cured from disease and the distribution of the survival times for uncured patients (latency distribution). However, a crucial issue with mixture cure models is the identifiability of the cure fraction and parameters of kernel distribution. Cure fraction estimates can be quite sensitive to the choice of latency distributions and length of follow‐up time. In this paper, sensitivity of parameter estimates under semi‐parametric model and several most commonly used parametric models, namely lognormal, loglogistic, Weibull and generalized Gamma distributions, is explored. The cure fraction estimates from the model with generalized Gamma distribution is found to be quite robust. A simulation study was carried out to examine the effect of follow‐up time and latency distribution specification on cure fraction estimation. The cure models with generalized Gamma latency distribution are applied to the population‐based survival data for several cancer sites from the Surveillance, Epidemiology and End Results (SEER) Program. Several cautions on the general use of cure model are advised. Copyright © 2004 John Wiley & Sons, Ltd.
An object model and database for functional genomics
Authors: Jones Andrew , Hunt Ela , Wastling Jonathan M. , Pizarro Angel , Stoeckert Christian J. 
Published: May 2004

Abstract
Motivation: Large-scale functional genomics analysis is now feasible and presents significant challenges in data analysis, storage and querying. Data standards are required to enable the development of public data repositories and to improve data sharing. There is an established data format for microarrays (microarray gene expression markup language, MAGE-ML) and a draft standard for proteomics (PEDRo). We believe that all types of functional genomics experiments should be annotated in a consistent manner, and we hope to open up new ways of comparing multiple datasets used in functional genomics.
Results: We have created a functional genomics experiment object model (FGE-OM), developed from the microarray model, MAGE-OM and two models for proteomics, PEDRo and our own model (Gla-PSI—Glasgow Proposal for the Proteomics Standards Initiative). FGE-OM comprises three namespaces representing (i) the parts of the model common to all functional genomics experiments; (ii) microarray-specific components; and (iii) proteomics-specific components. We believe that FGE-OM should initiate discussion about the contents and structure of the next version of MAGE and the future of proteomics standards. A prototype database called RNA And Protein Abundance Database (RAPAD), based on FGE-OM, has been implemented and populated with data from microbial pathogenesis.
Availability: FGE-OM and the RAPAD schema are available from http://www.gusdb.org/fge.html, along with a set of more detailed diagrams. RAPAD can be accessed by registration at the site.
Dblox: a genome-wide test for ancient segmental duplication
Authors: Friedman Robert , Ekollu Vikram , Rose John R. , Hughes Austin L. 
Published: May 2004

Abstract
Summary: Dblox and RDblox provide a simple statistical test for duplicated genomic structure; the same programs can also be used to identify putatively duplicated regions. The method focuses on ancient duplication events involving protein-coding genes.
Availability: http://www.biol.sc.edu/~austin/
An efficient algorithm for optimizing whole genome alignment with noise
Authors: Wong Prudence W. H. , Lam T. W. , Lu N. , Ting H. F. , Yiu S. M. 
Published: May 2004

Abstract
Motivation: This paper is concerned with algorithms for aligning two whole genomes so as to identify regions that possibly contain conserved genes. Motivated by existing heuristic-based software tools, we initiate the study of an optimization problem that attempts to uncover conserved genes with a global concern. Another interesting feature in our formulation is the tolerance of noise, which also complicates the optimization problem. A brute-force approach takes time exponential in the noise level.
Results: We show how an insight into the optimization structure can lead to a drastic improvement in the time and space requirement [precisely, to O(k2n2) and O(k2n), respectively, where n is the size of the input and k is the noise level]. The reduced space requirement allows us to implement the new algorithm, called MaxMinCluster, on a PC. It is exciting to see that when tested with different real data sets, MaxMinCluster consistently uncovers a high percentage of conserved genes that have been published by GenBank. Its performance is indeed favorably compared to MUMmer (perhaps the most popular software tool for uncovering conserved genes in a whole-genome scale).
Availability: The source code is available from the website http://www.csis.hku.hk/~colly/maxmincluster/. Detailed proof of the propositions can also be found there.
Correcting log ratios for signal saturation in cDNA microarrays
Authors: Dodd Lori E. , Korn Edward L. , McShane Lisa M. , Chandramouli G.V.R. , Chuang Eric Y. 
Published: May 2004

Abstract
Motivation: Pixel saturation occurs when the pixel intensity exceeds a threshold and the recorded pixel intensity is truncated. Microarray experiments are commonly afflicted with saturated pixels. As a result, estimators of gene expression are biased, with the amount of bias increasing as a function of the proportion of pixels saturated. Saturation is directly related to the photomultiplier tube (PMT) voltage settings and RNA abundance and is not necessarily associated with poor array or poor spot quality. When choosing PMT settings, higher PMT settings are desired because of improved signal-to-noise ratios of low-intensity spots. This improved signal is somewhat offset by saturation of high-intensity spots. In practice, spots with saturated pixels are discarded or the biased value is used. Neither of these approaches is appealing, particularly the former approach when a highly expressed gene is discarded because of saturation.
Results: We present a method to correct for saturation using pixel-level data. The method is based on a censored regression model. Evaluations on several arrays indicate that the method performs well. Simulation studies suggest that the method is robust under certain model violations.
Supplementary material: Supplementary tables and figures can be found at http://linus.nci.nih.gov/Data/doddl/saturation/extras.pdf
TigrScan and GlimmerHMM: two open source ab initio eukaryotic gene-finders
Authors: Majoros W. H. , Pertea M. , Salzberg S. L. 
Published: May 2004

Abstract
Summary: We describe two new Generalized Hidden Markov Model implementations for ab initio eukaryotic gene prediction. The C/C++ source code for both is available as open source and is highly reusable due to their modular and extensible architectures. Unlike most of the currently available gene-finders, the programs are re-trainable by the end user. They are also re-configurable and include several types of probabilistic submodels which can be independently combined, such as Maximal Dependence Decomposition trees and interpolated Markov models. Both programs have been used at TIGR for the annotation of the Aspergillus fumigatus and Toxoplasma gondii genomes.
Availability: Source code and documentation are available under the open source Artistic License from http://www.tigr.org/software/pirate.
FigSearch: a figure legend indexing and classification system
Authors: Liu Fang , Jenssen Tor-Kristian , Nygaard Vegard , Sack John , Hovig Eivind 
Published: May 2004

Abstract
Summary: FigSearch is a prototype text-mining and classification system for figures from any corpus of full-text biological papers. The system allows users to search for figures that contain genes of interest and illustrate protein interactions. The retrieved figures are ranked by a score representing the likelihood to be of a certain type, in this case, schematic illustrations of protein interactions and signaling events. The system contains a Web interface for search, a module for classification of figures based on vector representations of figure legends and a module for indexing gene names. In a preliminary validation, the FigSearch system showed satisfactory performance according to domain experts in providing the most relevant graphical representations. This strategy may be easily extended to other figure types. Moreover, as more full-text data become available, such a system will find increased usefulness in identifying and presenting compressed biological knowledge.
Availability: A searchable Web interface, FigSearch, is accessible via http://pubgeneserver.uio.no/figsearch/ for all figures from the available corpus.
Transcription/replication collisions cause bacterial transcription units to be longer on the leading strand of replication
Authors: Omont Nicolas , Képès François 
Published: May 2004

Abstract
Motivation: The costs of head-on versus codirectional collisions between the replication complex and the much slower transcription complex on the circular bacterial chromosomes are much debated. Although it is established that the number of genes on the leading strand is higher than on the lagging strand of replication, the consequences of collisions on the length of transcription units are unknown.
Results: Here, we show that transcription units are generally longer on the leading strand, in rough proportion to the bias in number of units between the two strands. We propose a statistical physics model, based on the assumption that the proportion of interrupted transcripts for each unit is the major factor contributing to these biases. Its main prediction is that a large replication/transcription speed ratio implies a low leading/lagging bias for transcription unit length and number. This model is validated by an analysis of proven and predicted units in Escherichia coli and Bacillus subtilis. The results are consistent with an equal cost of head-on versus codirectional collisions.