bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintaining data integrity in a rural clinical trial
Authors: Van den Broeck Jan , Mackay Melanie , Mpontshane Nontobeko , Kany Kany Luabeya Angelique , Chhagan Meera , Bennish Michael L. 
Published: October 2007

Background Clinical trials conducted in rural resource-poor settings face special challenges in ensuring quality of data collection and handling. The variable nature of these challenges, ways to overcome them, and the resulting data quality are rarely reported in the literature. Purpose To provide a detailed example of establishing local data handling capacity for a clinical trial conducted in a rural area, highlight challenges and solutions in establishing such capacity, and to report the data quality obtained by the trial. Methods We provide a descriptive case study of a data system for biological samples and questionnaire data, and the problems encountered during its implementation. To determine the quality of data we analyzed test—retest studies using Kappa statistics of inter- and intra-observer agreement on categorical data. We calculated Technical Errors of Measurement of anthropometric measurements, audit trail analysis was done to assess error correction rates, and residual error rates were calculated by database-to-source document comparison. Results Initial difficulties included the unavailability of experienced research nurses, programmers and data managers in this rural area and the difficulty of designing new software tools and a complex database while making them error-free. National and international collaboration and external monitoring helped ensure good data handling and implementation of good clinical practice. Data collection, fieldwork supervision and query handling depended on streamlined transport over large distances. The involvement of a community advisory board was helpful in addressing cultural issues and establishing community acceptability of data collection methods. Data accessibility for safety monitoring required special attention. Kappa values and Technical Errors of Measurement showed acceptable values. Residual error rates in key variables were low. Limitations The article describes the experience of a single-site trial and does not address challenges particular to multi-site trials. Conclusions Obtaining and maintaining data integrity in rural clinical trials is feasible, can result in acceptable data quality and can be used to develop capacity in developing country sites. It does, however, involve special challenges and requirements. Clinical Trials 2007; 4: 572—582. http://ctj.sagepub.com
Policing diversity in the digital age
Authors: Wall David S. , Williams Matthew 
Published: October 2007

Members of `terrestrial' communities are migrating in ever-increasing numbers to a new `Third Space' that manifests outside traditional geographical physical boundaries. This online space consists of purely social relations where interaction and community are performed at-a-distance. The diversifying populations of these virtual villages, towns and cities now constitute very real communities. Online non-gaming spaces such as Ebay, Active Worlds and Secondlife, for example, deliberately utilize the discourse of community in an attempt to instil a sense of communal space and shared responsibility among their members. While the majority subscribe to the rhetoric of `netizenship' others find alternative means to participate online. The avocations of these few have resulted in the endemic deviance/crime problem that exists online. As a result, online communities have developed their own distinct history of control and regulation. This article explores the ways that online social spaces maintain orderly `communities'. It contrasts `proximal' (online) forms of governing online behaviour, such as online reputation management systems, `virtual' police services and vigilante groups that employ `online shaming', with `distal' (offline) forms such as offline policing and criminal justice processes. The central theme of the article is a critical account of how these, often contradicting, nodes of governance interact.
TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts
Authors: Bossen Claudia , Cachero Teresa G. , Tardivel Aubry , Ingold Karine , Willen Laure , Dobles Max , Scott Martin L. , Maquelin Aris , Belnoue Elodie , Siegrist Claire-Anne , Chevrier Stéphane , Acha-Orbea Hans , Leung Helen , Mackay Fabienne , Tschopp Jürg , Schneider Pascal 
Published: October 2007

Abstract
The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R–dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons.
The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity
Authors: Petersen Steen V , Valnickova Zuzana , Oury Tim D , Crapo James D , Chr Nielsen Niels , Enghild Jan J 
Published: October 2007

Abstract

Background
Human extracellular superoxide dismutase (EC-SOD) is a tetrameric metalloenzyme responsible for the removal of superoxide anions from the extracellular space. We have previously shown that the EC-SOD subunit exists in two distinct folding variants based on differences in the disulfide bridge pattern (Petersen SV, Oury TD, Valnickova Z, Thøgersen IB, Højrup P, Crapo JD, Enghild JJ. Proc Natl Acad Sci USA. 2003;100(24):13875–80). One variant is enzymatically active (aEC-SOD) while the other is inactive (iEC-SOD). The EC-SOD subunits are associated into covalently linked dimers through an inter-subunit disulfide bridge creating the theoretical possibility of 3 dimers (aa, ai or ii) with different antioxidant potentials. We have analyzed the quaternary structure of the endogenous EC-SOD disulfide-linked dimer to investigate if these dimers in fact exist.

Results
The analyses of EC-SOD purified from human tissue show that all three dimer combinations exist including two homo-dimers (aa and ii) and a hetero-dimer (ai). Because EC-SOD is a tetramer the dimers may combine to generate 5 different mature EC-SOD molecules where the specific activity of each molecule is determined by the ratio of aEC-SOD and iEC-SOD subunits.

Conclusion
This finding shows that the aEC-SOD and iEC-SOD subunits combine in all 3 possible ways supporting the presence of tetrameric enzymes with variable enzymatic activity. This variation in enzymatic potency may regulate the antioxidant level in the extracellular space and represent a novel way of modulating enzymatic activity.
Investigations into the relationship between feedback loops and functional importance of a signal transduction network based on Boolean network modeling
Authors: Kwon Yung-Keun , Choi Sun Shim , Cho Kwang-Hyun 
Published: October 2007

AbstractBackgroundA number of studies on biological networks have been carried out to unravel the topological characteristics that can explain the functional importance of network nodes. For instance, connectivity, clustering coefficient, and shortest path length were previously proposed for this purpose. However, there is still a pressing need to investigate another topological measure that can better describe the functional importance of network nodes. In this respect, we considered a feedback loop which is ubiquitously found in various biological networks.ResultsWe discovered that the number of feedback loops (NuFBL) is a crucial measure for evaluating the importance of a network node and verified this through a signal transduction network in the hippocampal CA1 neuron of mice as well as through generalized biological network models represented by Boolean networks. In particular, we observed that the proteins with a larger NuFBL are more likely to be essential and to evolve slowly in the hippocampal CA1 neuronal signal transduction network. Then, from extensive simulations based on the Boolean network models, we proved that a network node with the larger NuFBL is likely to be more important as the mutations of the initial state or the update rule of such a node made the network converge to a different attractor. These results led us to infer that such a strong positive correlation between the NuFBL and the importance of a network node might be an intrinsic principle of biological networks in view of network dynamics.ConclusionThe presented analysis on topological characteristics of biological networks showed that the number of feedback loops is positively correlated with the functional importance of network nodes. This result also suggests the existence of unknown feedback loops around functionally important nodes in biological networks.
On the detection of functionally coherent groups of protein domains with an extension to protein annotation
Authors: McLaughlin William A , Chen Ken , Hou Tingjun , Wang Wei 
Published: October 2007

AbstractBackgroundProtein domains coordinate to perform multifaceted cellular functions, and domain combinations serve as the functional building blocks of the cell. The available methods to identify functional domain combinations are limited in their scope, e.g. to the identification of combinations falling within individual proteins or within specific regions in a translated genome. Further effort is needed to identify groups of domains that span across two or more proteins and are linked by a cooperative function. Such functional domain combinations can be useful for protein annotation.ResultsUsing a new computational method, we have identified 114 groups of domains, referred to as domain assembly units (DASSEM units), in the proteome of budding yeastSaccharomyces cerevisiae. The units participate in many important cellular processes such as transcription regulation, translation initiation, and mRNA splicing. Within the units the domains were found to function in a cooperative manner; and each domain contributed to a different aspect of the unit's overall function. The member domains of DASSEM units were found to be significantly enriched among proteins contained in transcription modules, defined as genes sharing similar expression profiles and presumably similar functions. The observation further confirmed the functional coherence of DASSEM units. The functional linkages of units were found in both functionally characterized and uncharacterized proteins, which enabled the assessment of protein function based on domain composition.ConclusionA new computational method was developed to identify groups of domains that are linked by a common function in the proteome ofSaccharomyces cerevisiae. These groups can either lie within individual proteins or span across different proteins. We propose that the functional linkages among the domains within the DASSEM units can be used as a non-homology based tool to annotate uncharacterized proteins.
Genetic determinants of hyaloid and retinal vasculature in zebrafish
Authors: Alvarez Yolanda , Cederlund Maria L , Cottell David C , Bill Brent R , Ekker Stephen C , Torres-Vazquez Jesus , Weinstein Brant M , Hyde David R , Vihtelic Thomas S , Kennedy Breandan N 
Published: October 2007

Abstract
Background
The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish.

Results
We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO), subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development.

Conclusion
Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.
Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research
Authors: Hirunsatit Rungnapa , Ilomäki Risto , Malison Robert , Räsänen Pirkko , Ilomäki Essi , Kranzler Henry R , Kosten Thomas , Sughondhabirom Atapol , Thavichachart Nuntika , Tangwongchai Sookjaroen , Listman Jennifer , Mutirangura Apiwat , Gelernter Joel , Lappalainen Jaakko 
Published: October 2007

Abstract

Background
GABA transporter-1 (GAT-1; genetic locus SLC6A1) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in SLC6A1 in five populations representing three continental groups.

Results
We resequenced 12.4 kb of SLC6A1, including the promoters, exons and flanking intronic regions in African-American, Thai, Hmong, Finnish, and European-American subjects (total n = 40). LD in SLC6A1 was examined by genotyping 16 SNPs in larger samples. Sixty-three variants were identified through resequencing. Common population-specific variants were found in African-Americans, including a novel 21-bp promoter region variable number tandem repeat (VNTR), but no such variants were found in any of the other populations studied. Low levels of LD and the absence of major LD blocks were characteristic of all five populations. African-Americans had the highest genetic diversity. European-Americans and Finns did not differ in genetic diversity or LD patterns. Although the Hmong had the highest level of LD, our results suggest that a strategy based on the use of tag SNPs would not translate to a major improvement in genotyping efficiency.

Conclusion
Owing to the low level of LD and presence of recombination hotspots, SLC6A1 may be an example of a problematic gene for association and haplotype tagging-based genetic studies. The 21-bp promoter region VNTR polymorphism is a putatively functional candidate allele for studies focusing on variation in GAT-1 function in the African-American population.
The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
Authors: Newrzella Dieter , Pahlavan Payam S , Krüger Carola , Boehm Christine , Sorgenfrei Oliver , Schröck Helmut , Eisenhardt Gisela , Bischoff Nadine , Vogt Gerhard , Wafzig Oliver , Rossner Moritz , Maurer Martin H , Hiemisch Holger , Bach Alfred , Kuschinsky Wolfgang , Schneider Armin 
Published: October 2007

AbstractBackgroundThe different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization.ResultsProfiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types.ConclusionThe differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research.
A motif-based search in bacterial genomes identifies the ortholog of the small RNA Yfr1 in all lineages of cyanobacteria
Authors: Voß Björn , Gierga Gregor , Axmann Ilka M , Hess Wolfgang R 
Published: October 2007

Abstract

Background
Non-coding RNAs (ncRNA) are regulators of gene expression in all domains of life. They control growth and differentiation, virulence, motility and various stress responses. The identification of ncRNAs can be a tedious process due to the heterogeneous nature of this molecule class and the missing sequence similarity of orthologs, even among closely related species. The small ncRNA Yfr1 has previously been found in the Prochlorococcus/Synechococcus group of marine cyanobacteria.

Results
Here we show that screening available genome sequences based on an RNA motif and followed by experimental analysis works successfully in detecting this RNA in all lineages of cyanobacteria. Yfr1 is an abundant ncRNA between 54 and 69 nt in size that is ubiquitous for cyanobacteria except for two low light-adapted strains of Prochlorococcus, MIT 9211 and SS120, in which it must have been lost secondarily. Yfr1 consists of two predicted stem-loop elements separated by an unpaired sequence of 16–20 nucleotides containing the ultraconserved undecanucleotide 5'-ACUCCUCACAC-3'.

Conclusion
Starting with an ncRNA previously found in a narrow group of cyanobacteria only, we show here the highly specific and sensitive identification of its homologs within all lineages of cyanobacteria, whereas it was not detected within the genome sequences of E. coli and of 7 other eubacteria belonging to the alpha-proteobacteria, chlorobiaceae and spirochaete. The integration of RNA motif prediction into computational pipelines for the detection of ncRNAs in bacteria appears as a promising step to improve the quality of such predictions.
BACTIBASE: a new web-accessible database for bacteriocin characterization
Authors: Hammami Riadh , Zouhir Abdelmajid , Ben Hamida Jeannette , Fliss Ismail 
Published: October 2007

Abstract

Background
Bacteriocins are very diverse group of antimicrobial peptides produced by a wide range of bacteria and known for their inhibitory activity against various human and animal pathogens. Although many bacteriocins are now well characterized, much information is still missing or is unavailable to potential users. The assembly of such information in one central resource such as a database would therefore be of great benefit to the exploitation of these bioactive molecules in the present context of increasing antibiotic resistance and natural bio-preservation need.

Description
In the present paper, we present the development of a new and original database BACTIBASE that contains calculated or predicted physicochemical properties of 123 bacteriocins produced by both Gram-positive and Gram-negative bacteria. The information in this database is very easy to extract and allows rapid prediction of relationships structure/function and target organisms of these peptides and therefore better exploitation of their biological activity in both the medical and food sectors.

Conclusion
The BACTIBASE database is freely available at http://bactibase.pfba-lab.org, web-based platform enabling easy retrieval, via various filters, of sets of bacteriocins that will enable detailed analysis of a number of microbiological and physicochemical data.
Prevalence of heroin and methamphetamine male users in the northern Taiwan, 1999–2002: capture-recapture estimates
Authors: Chiang Shu-Chuan , Chen Chuan-Yu , Chang Yuan-Ying , Sun Hsiao-Ju , Chen Wei J 
Published: October 2007

Abstract

Background
Illegal drug use and related problems have been emerging as an important public health issue in Taiwan. Via the capture-recapture approach, the present study aimed to offer insights into the size of heroin and methamphetamine male user population in the northern Taiwan during the period from 1999 to 2002.

Methods
Annual lists of male subjects were collated from both judiciary and medical systems in Taoyuan County, Taiwan. A total of 2809, 2486, 1661, and 1440 local male illegal drug users aged 15 to 54 years were identified in Taoyuan County from 1999 to 2002, respectively.

Results
An estimated number of 16192, 14532, 16844, and 11783 local male methamphetamine or heroin users were found in each of the four consecutive years in the region. From 1999 to 2002, the annual prevalence rate for heroin use was 0.27% (95% CI = 0.20%, 0.38%), 0.33% (95% CI = 0.25%, 0.44%), 0.63% (95% CI = 0.44%, 0.92%), and 0.72% (95% CI = 0.54%, 0.97%), respectively, suggesting a trend of significant increase (chi-square for linear trend = 1677.76, d.f. = 3, p < 0.0001). In contrast, a decreasing trend was found for methamphetamine (2.38%, 1.91%, 2.47%, and 1.24%), with a modest rebound in 2001. The prevalence rates of illegal drug use for male residents in Taoyuan County were approximately 2–3% during this period, and the scale of problem shows no sign of diminution.

Conclusion
By taking advantage of existing datasets that were incomplete by each alone, the approach of capture-recapture model may be ultimately considered as a tool to estimate the scale of illegal drug use problems. The population of heroin-using males apparently is stably expanding in the northern part of Taiwan in the first years of 21st century.