bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model-based optimization framework for the inference on gene regulatory networks from DNA array data
Authors: Thomas Reuben , Mehrotra Sanjay , Papoutsakis Eleftherios T. , Hatzimanikatis Vassily 
Published: July 2004

Abstract
Motivation: Identification of the regulatory structures in genetic networks and the formulation of mechanistic models in the form of wiring diagrams is one of the significant objectives of expression profiling using DNA microarray technologies and it requires the development and application of identification frameworks.
Results: We have developed a novel optimization framework for identifying regulation in a genetic network using the S-system modeling formalism. We show that balance equations on both mRNA and protein species led to a formulation suitable for analyzing DNA-microarray data whereby protein concentrations have been eliminated and only mRNA relative concentrations are retained. Using this formulation, we examined if it is possible to infer a set of possible genetic regulatory networks consistent with observed mRNA expression patterns. Two origins of changes in mRNA expression patterns were considered. One derives from changes in the biophysical properties of the system that alter the molecular-interaction kinetics and/or message stability. The second is due to gene knock-outs. We reduced the identification problem to an optimization problem (of the so-called mixed-integer non-linear programming class) and we developed an algorithmic procedure for solving this optimization problem. Using simulated data generated by our mathematical model, we show that our method can actually find the regulatory network from which the data were generated. We also show that the number of possible alternate genetic regulatory networks depends on the size of the dataset (i.e. number of experiments), but this dependence is different for each of the two types of problems considered, and that a unique solution requires fewer datasets than previously estimated in the literature. This is the first method that also allows the identification of every possible regulatory network that could explain the data, when the number of experiments does not allow identification of unique regulatory structure.
Availability: The implementation of the algorithm in AMPL is available on request from the authors.
Accuracy improvement for identifying translation initiation sites in microbial genomes
Authors: Zhu Huai-Qiu , Hu Gang-Qing , Ouyang Zheng-Qing , Wang Jin , She Zhen-Su 
Published: July 2004

Abstract
Motivation: At present the computational gene identification methods in microbial genomes have a high prediction accuracy of verified translation termination site (3′ end), but a much lower accuracy of the translation initiation site (TIS, 5′ end). The latter is important to the analysis and the understanding of the putative protein of a gene and the regulatory machinery of the translation. Improving the accuracy of prediction of TIS is one of the remaining open problems.
Results: In this paper, we develop a four-component statistical model to describe the TIS of prokaryotic genes. The model incorporates several features with biological meanings, including the correlation between translation termination site and TIS of genes, the sequence content around the start codon; the sequence content of the consensus signal related to ribosomal binding sites (RBSs), and the correlation between TIS and the upstream consensus signal. An entirely non-supervised training system is constructed, which takes as input a set of annotated coding open reading frames (ORFs) by any gene finder, and gives as output a set of organism-specific parameters (without any prior knowledge or empirical constants and formulas). The novel algorithm is tested on a set of reliable datasets of genes from Escherichia coli and Bacillus subtillis. MED-Start may correctly predict 95.4% of the start sites of 195 experimentally confirmed E.coli genes, 96.6% of 58 reliable B.subtillis genes. Moreover, the test results indicate that the algorithm gives higher accuracy for more reliable datasets, and is robust to the variation of gene length. MED-Start may be used as a postprocessor for a gene finder. After processing by our program, the improvement of gene start prediction of gene finder system is remarkable, e.g. the accuracy of TIS predicted by MED 1.0 increases from 61.7 to 91.5% for 854 E.coli verified genes, while that by GLIMMER 2.02 increases from 63.2 to 92.0% for the same dataset. These results show that our algorithm is one of the most accurate methods to identify TIS of prokaryotic genomes.
Availability: The program MED-Start can be accessed through the website of CTB at Peking University: http://ctb.pku.edu.cn/main/SheGroup/MED_Start.htm
Effects of pooling mRNA in microarray class comparisons
Authors: Shih Joanna H. , Michalowska Aleksandra M. , Dobbin Kevin , Ye Yumei , Qiu Ting Hu , Green Jeffrey E. 
Published: July 2004

Abstract
Motivation: In microarray experiments investigators sometimes wish to pool RNA samples before labeling and hybridization due to insufficient RNA from each individual sample or to reduce the number of arrays for the purpose of saving cost. The basic assumption of pooling is that the expression of an mRNA molecule in the pool is close to the average expression from individual samples. Recently, a method for studying the effect of pooling mRNA on statistical power in detecting differentially expressed genes between classes has been proposed, but the different sources of variation arising in microarray experiments were not distinguished. Another paper recently did take different sources of variation into account, but did not address power and sample size for class comparison.
In this paper, we study the implication of pooling in detecting differential gene expression taking into account different sources of variation and check the basic assumption of pooling using data from both the cDNA and Affymetrix GeneChip microarray experiments.
Results: We present formulas for the required number of subjects and arrays to achieve a desired power at a specified significance level. We show that due to the loss of degrees of freedom for a pooled design, a large increase in the number of subjects may be required to achieve a power comparable to that of a non-pooled design. The added expense of additional samples for the pooled design may outweigh the benefit of saving on microarray cost. The microarray data from both platforms show that the major assumption of pooling may not hold.
Supplementary information: Supplementary material referenced in the text is available at http://linus.nci.nih.gov/brb/TechReport.htm
MyWEST: My Web Extraction Software Tool for effective mining of annotations from web-based databanks
Authors: Masseroli Marco , Stella Andrea , Meani Natalia , Alcalay Myriam , Pinciroli Francesco 
Published: July 2004

Abstract
Motivation: High-throughput technologies create the necessity to mine large amounts of gene annotations from diverse databanks, and to integrate the resulting data. Most databanks can be interrogated only via Web, for a single gene at a time, and query results are generally available only in the HTML format. Although some databanks provide batch retrieval of data via FTP, this requires expertise and resources for locally reimplementing the databank.
Results: We developed MyWEST, a tool aimed at researchers without extensive informatics skills or resources, which exploits user-defined templates to easily mine selected annotations from different Web-interfaced databanks, and aggregates and structures results in an automatically updated database. Using microarray results from a model system of retinoic acid-induced differentiation, MyWEST effectively gathered relevant annotations from various biomolecular databanks, highlighted significant biological characteristics and supported a global approach to the understanding of complex cellular mechanisms.
Availability: MyWEST is freely available for non-profit use at http://www.medinfopoli.polimi.it/MyWEST/
A computational search for box C/D snoRNA genes in the Drosophila melanogaster genome
Authors: Accardo M. C. , Giordano E. , Riccardo S. , Digilio F. A. , Iazzetti G. , Calogero R. A. , Furia M. 
Published: July 2004

Abstract
Motivation: In eukaryotes, the family of non-coding RNA genes includes a number of genes encoding small nucleolar RNAs (mainly C/D and H/ACA snoRNAs), which act as guides in the maturation or post-transcriptional modifications of target RNA molecules. Since in Drosophila melanogaster (Dm) only few examples of snoRNAs have been identified so far by cDNA libraries screening, integration of the molecular data with in silico identification of these types of genes could throw light on their organization in the Dm genome.
Results: We have performed a computational screening of the Dm genome for C/D snoRNA genes, followed by experimental validation of the putative candidates. Few of the 26 confirmed snoRNAs had been recognized by cDNA library analysis. Organization of the Dm genome was also found to be more variegated than previously suspected, with snoRNA genes nested in both the introns and exons of protein-coding genes. This finding suggests that the presence of additional mechanisms of snoRNA biogenesis based on the alternative production of overlapping mRNA/snoRNA molecules.
Availability: Additional information is available at http://www.bioinformatica.unito.it/bioinformatics/snoRNAs
SARGE: a tool for creation of putative genetic networks
Authors: Shaw O. J. , Harwood C. , Steggles L. J. , Wipat A. 
Published: July 2004

Abstract
Summary: SARGE is a tool for creating, visualizing and manipulating a putative genetic network from time series microarray data. The tool assigns potential edges through time-lagged correlation, incorporates a clustering mechanism, an interactive visual graph representation and employs simulated annealing for network optimization.
Availability: The application is available as a .jar file from http://www.bioinformatics.cs.ncl.ac.uk/sarge/index.html
DAGchainer: a tool for mining segmental genome duplications and synteny
Authors: Haas Brian J. , Delcher Arthur L. , Wortman Jennifer R. , Salzberg Steven L. 
Published: July 2004

Abstract
Summary: Given the positions of protein-coding genes along genomic sequence and probability values for protein alignments between genes, DAGchainer identifies chains of gene pairs sharing conserved order between genomic regions, by identifying paths through a directed acyclic graph (DAG). These chains of collinear gene pairs can represent segmentally duplicated regions and genes within a single genome or syntenic regions between related genomes. Automated mining of the Arabidopsis genome for segmental duplications illustrates the use of DAGchainer.
CSB.DB: a comprehensive systems-biology database
Authors: Steinhauser Dirk , Usadel Björn , Luedemann Alexander , Thimm Oliver , Kopka Joachim 
Published: July 2004

Abstract
Summary: The open access comprehensive systems-biology database (CSB.DB) presents the results of bio-statistical analyses on gene expression data in association with additional biochemical and physiological knowledge. The main aim of this database platform is to provide tools that support insight into life's complexity pyramid with a special focus on the integration of data from transcript and metabolite profiling experiments. The central part of CSB.DB, which we describe in this applications note, is a set of co-response databases that currently focus on the three key model organisms, Escherichia coli, Saccharomyces cerevisiae and Arabidopsis thaliana. CSB.DB gives easy access to the results of large-scale co-response analyses, which are currently based exclusively on the publicly available compendia of transcript profiles. By scanning for the best co-responses among changing transcript levels, CSB.DB allows to infer hypotheses on the functional interaction of genes. These hypotheses are novel and not accessible through analysis of sequence homology. The database enables the search for pairs of genes and larger units of genes, which are under common transcriptional control. In addition, statistical tools are offered to the user, which allow validation and comparison of those co-responses that were discovered by gene queries performed on the currently available set of pre-selectable datasets.
Availability: All co-response databases can be accessed through the CSB.DB Web server (http://csbdb.mpimp-golm.mpg.de/).
Defining chronic conditions for primary care with ICPC-2
Authors: O'Halloran Julie , Miller Graeme C , Britt Helena 
Published: July 2004

AbstractBackground. With the increasing prevalence of chronic conditions, there is need for a standardized definition of chronicity for use in research, to evaluate the population prevalence and general practice management of chronic conditions.Objectives. Our aims were to determine the characteristics required to define chronicity, apply them to a primary care classification and provide a defined codeset of chronic conditions.Methods. A literature review evaluated characteristics used to define chronic conditions. The final set of characteristics was applied to the International Classification of Primary Care-Version 2 (ICPC-2) through more specific terms available in ICPC-2 PLUS, an extended terminology classified to ICPC-2. A set of ICPC-2 rubrics was delineated as representing chronic conditions.Results. Factors found to be relevant to a definition of chronic conditions for research were: duration; prognosis; pattern; and sequelae. Within ICPC-2, 129 rubrics were described as ‘chronic’, and another 20 rubrics had elements of chronicity. Duration was the criterion most frequently satisfied (98.4% of chronic rubrics), while 88.2% of rubrics met at least three of the four criteria.Conclusion. Monitoring the prevalence and management of chronic conditions is of increasing importance. This study provided evidence for multifaceted definitions of chronicity. While all characteristics examined could be used by those interested in chronicity, the list has been designed to identify chronic conditions managed in Australian general practice, and is therefore not a nomenclature of all chronic conditions. Subsequent analysis of chronic conditions using pre-existing data sets will provide a baseline measure of chronic condition prevalence and management in general practice.
What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions
Authors: Avenell A. , Brown T. J. , McGee M. A. , Campbell M. K. , Grant A. M. , Broom J. , Jung R. T. , Smith W. C. S. 
Published: July 2004

AbstractBackground  Evidence is needed for the effectiveness of interventions given with reducing diets for obese adults: drug therapy, exercise, or behaviour therapy.Methods  We systematically reviewed randomized controlled trials in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted data and a second checked data extraction. Trial quality was assessed.Results  Adding orlistat to diet was associated with weight change for up to 24 months (−3.26 kg, 95% CI, −4.15 to −2.37 kg), and statistically significant beneficial changes were found for total and LDL cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was associated with a 12 month weight change of −4.18 kg (95% CI, −5.14 to −3.21 kg), and statistically significant beneficial effects on high density lipoprotein cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood pressure.Adding exercise to diet, or to diet and behaviour therapy, was associated with improved weight loss for up to 36 months and improvements in HDL, TGs and blood pressure. Adding behaviour therapy to diet, or to diet and sibutramine together, was associated with improved weight loss for up to 18 months. Adding drugs, exercise or behaviour therapy to dietary advice was each associated with similar weight change.Conclusions  Adding orlistat, sibutramine, exercise, or behaviour modification to dietary advice can improve long‐term weight loss.
What are the long‐term benefits of weight reducing diets in adults? A systematic review of randomized controlled trials
Authors: Avenell A. , Brown T. J. , McGee M. A. , Campbell M. K. , Grant A. M. , Broom J. , Jung R. T. , Smith W. C. S. 
Published: July 2004

AbstractBackground  Evidence is needed for the best long‐term diet for weight loss, and improvement in cardiac risk and disease in obese adults.Methods  We systematically reviewed randomized controlled trials (RCTs) in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted the data and a second checked data extraction. Trial quality was assessed.Results  Low fat diets (LFDs) produced significant weight losses up to 36 months (−3.55 kg; 95% CI, −4.54 to −2.55 kg). Blood pressure, lipids and fasting plasma glucose improved with these diets after 12 months. Four studies found that LFDs may prevent type 2 diabetes and reduce antihypertensive medication for up to 3 years. A very low calorie diet (VLCD, <4.2 MJ day−1) was associated with the most weight loss after 12 months (−13.40 kg; 95% CI, −18.43 to −8.37 kg) in one small study with beneficial effects on asthma. There was no evidence that low carbohydrate protein sparing modified fasts (PSMFs) were associated with greater long‐term weight loss than low calorie diets (LCDs, 4.2–6.7 MJ day−1) or VLCDs. PSMFs were, however, associated with greater lowering of fasting plasma glucose and HbA1c than LCDs.Conclusions  Little evidence supports the use of diets other than LFDs for weight reduction. With the increasing prevalence of morbid obesity, long‐term follow‐up in RCTs is needed to evaluate the effect of LCDs, VLCDs and PSMFs more fully.
A critical evaluation of the relationship between serum vitamin B12, folate and total homocysteine with cognitive impairment in the elderly
Authors: Ellinson M. , Thomas J. , Patterson A. 
Published: July 2004

AbstractBackground  Serum homocysteine increases with age and is also considered a marker for low serum vitamin B12 and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B12/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people.Aim  To systematically review published studies on the relationship between serum vitamin B12, folate and total homocysteine and cognitive function in the elderly.Design and data sources  A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B12/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. ‘The Cochrane Non‐Randomized Studies Methods Group’ guidelines were used for assessment and extraction of data from these studies.Results  All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B12 and folate in both groups of participants. The relationship of serum folate and vitamin B12 status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B12.In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B12 and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B12 levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B12 at baseline.Conclusion  Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B12 or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B12 or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double‐blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.
Dietetic guidelines: diet in secondary prevention of cardiovascular disease (first update, June 2003)
Authors: Hooper L. , Griffiths E. , Abrahams B. , Alexander W. , Atkins S. , Atkinson G. , Bamford R. , Chinuck R. , Farrington J. , Gardner E. , Greene P. , Gunner C. , Hamer C. , Helby B. , Hetherington S. , Howson R. , Laidlaw J. , Li M. , Lynas J. , McVicar C. , Mead A. , Moody B. , Paterson K. , Neal S. , Rigby P. , Ross F. , Shaw H. , Stone D. , Taylor F. , Van Rensburgh L. , Vine R. , Whitehead J. , Wray L. ,   UK Heart Health and Thoracic Dietitians Specialist Group of the British Dietetic Association
Published: July 2004

AbstractAim  To update dietetic guidelines summarizing the systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention).Methods  The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to November 2002 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomised controlled trials relating to diet and secondary prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review. The quality and results of each review were discussed and summarized in a meeting of the whole group.Results  Providing evidence‐based dietary information (including increasing omega‐3 fat intake) to all people who have had a myocardial infarction will save more lives than concentrating dietary advice on just those in need of weight loss or lipid lowering. The practice of prioritizing dietetic time in secondary prevention to those with raised lipids is out of date since the advent of statin therapy. However, effective dietary advice for those with angina, stroke, peripheral vascular disease or heart failure is less clear.Conclusion  There is good systematic review evidence that dietary advice to those with coronary heart disease can reduce mortality and morbidity as well as modify some risk factors. Dietary advice that does this most effectively should be prioritized.