bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA1-mediated repression of select X chromosome genes
Authors: Jazaeri Amir A , Chandramouli Gadisetti VR , Aprelikova Olga , Nuber Ulrike A , Sotiriou Christos , Liu Edison T , Ropers H Hilger , Yee Cindy J , Boyd Jeff , Barrett J Carl 
Published: September 2004

AbstractRecently BRCA1 has been implicated in the regulation of gene expression from the X chromosome. In this study the influence of BRCA1 on expression of X chromosome genes was investigated. Complementary DNA microarrays were used to compare the expression levels of X chromosome genes in 18 BRCA1-associated ovarian cancers to those of the 13 "BRCA1-like" and 14 "BRCA2-like" sporadic tumors (as defined by previously reported expression profiling). Significance was determined using parametric statistics with P < 0.005 as a cutoff. Forty of 178 total X-chromosome transcripts were differentially expressed between the BRCA1-associated tumors and sporadic cancers with a BRCA2-like molecular profile. Thirty of these 40 genes showed higher mean expression in the BRCA1-associated samples including all 11 transcripts that mapped to Xp11. In contrast, four of 178 total X chromosome transcripts showed significant differential expression between BRCA1-associated and sporadic tumors with a BRCA1-like molecular profile. All four mapped to Xp11 and showed higher mean expression in BRCA1-associated tumors. Re-expression of BRCA1 in HCC1937 BRCA1-deficient breast cancer cell resulted in the repression of 21 transcripts. Eleven of the 21 (54.5%) transcripts mapped to Xp11. However, there was no significant overlap between these Xp11 genes and those found to be differentially expressed between BRCA1-associated and sporadic ovarian cancer samples. These results demonstrate that BRCA1 mediates the repression of several X chromosome genes, many of which map to the Xp11 locus.
A knowledgebase system to enhance scientific discovery: Telemakus
Authors: Fuller Sherrilynne S , Revere Debra , Bugni Paul F , Martin George M 
Published: September 2004

Abstract
Background
With the rapid expansion of scientific research, the ability to effectively find or integrate new domain knowledge in the sciences is proving increasingly difficult. Efforts to improve and speed up scientific discovery are being explored on a number of fronts. However, much of this work is based on traditional search and retrieval approaches and the bibliographic citation presentation format remains unchanged.

Methods
Case study.

Results
The Telemakus KnowledgeBase System provides flexible new tools for creating knowledgebases to facilitate retrieval and review of scientific research reports. In formalizing the representation of the research methods and results of scientific reports, Telemakus offers a potential strategy to enhance the scientific discovery process. While other research has demonstrated that aggregating and analyzing research findings across domains augments knowledge discovery, the Telemakus system is unique in combining document surrogates with interactive concept maps of linked relationships across groups of research reports.

Conclusion
Based on how scientists conduct research and read the literature, the Telemakus KnowledgeBase System brings together three innovations in analyzing, displaying and summarizing research reports across a domain: (1) research report schema, a document surrogate of extracted research methods and findings presented in a consistent and structured schema format which mimics the research process itself and provides a high-level surrogate to facilitate searching and rapid review of retrieved documents; (2) research findings, used to index the documents, allowing searchers to request, for example, research studies which have studied the relationship between neoplasms and vitamin E; and (3) visual exploration interface of linked relationships for interactive querying of research findings across the knowledgebase and graphical displays of what is known as well as, through gaps in the map, what is yet to be tested. The rationale and system architecture are described and plans for the future are discussed.
Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells
Authors: Nandakumar Kutty Selva , Bäcklund Johan , Vestberg Mikael , Holmdahl Rikard 
Published: September 2004

AbstractAntibodies against type II collagen (anti-CII) are arthritogenic and have a crucial role in the initiation of collagen-induced arthritis. Here, we have determined the dependence of T and B cells in collagen-antibody-induced arthritis (CAIA) during different phases of arthritis. Mice deficient for B and/or T cells were susceptible to the CAIA, showing that the antibodies induce arthritis even in the absence of an adaptive immune system. To determine whether CII-reactive T cells could have a role in enhancing arthritis development at the effector level of arthritis pathogenesis, we established a T cell line reactive with CII. This T cell line was oligoclonal and responded to different post-translational forms of the major CII epitope at position 260–270 bound to the Aq class II molecule. Importantly, it cross-reacted with the mouse peptide although it is bound with lower affinity to the Aq molecule than the corresponding rat peptide. The T cell line could not induce clinical arthritis per se in Aq-expressing mice even if these mice expressed the major heterologous CII epitope in cartilage, as in the transgenic MMC (mutated mouse collagen) mouse. However, a combined treatment with anti-CII monoclonal antibodies and CII-reactive T cells enhanced the progression of severe arthritis.
Analysis of HLA DR, HLA DQ, C4A, FcγRIIa, FcγRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcγRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility
Authors: Jönsen Andreas , Bengtsson Anders A , Sturfelt Gunnar , Truedsson Lennart 
Published: September 2004

AbstractDysfunction in various parts of immune defence, such as immune response, immune complex clearance, and inflammation, has an impact on pathogenesis in systemic lupus erythematosus (SLE). We hypothesised that combinations of common variants of genes involved in these immune functions are associated with susceptibility to SLE. The following variants were analysed: HLA DR3, HLA DQ2, C4AQ0, Fcγ receptor IIa (FcγRIIa) genotype R/R, Fcγ receptor IIIa (FcRγIIIa) genotype F/F, mannan-binding lectin (MBL) genotype conferring a low serum concentration of MBL (MBL-low), and interleukin-1 receptor antagonist (IL-1Ra) genotype 2/2. Polymorphisms were analysed in 143 Caucasian patients with SLE and 200 healthy controls. HLA DR3 in SLE patients was in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7–4.5). Analysis of combinations of gene variants revealed that the strong association with SLE for HLA DR3-DQ2-C4AQ0 remained after combination with FcγRIIa R/R, FcγRIIIa F/F, and MBL-low (OR>2). Furthermore, the combination of the FcγRIIa R/R and IL-1Ra 2/2 genotypes yielded a strong correlation with SLE (OR 11.8, 95% CI 1.5–95.4). This study demonstrates that certain combinations of gene variants may increase susceptibility to SLE, suggesting this approach for future studies. It also confirms earlier findings regarding the HLA DR3-DQ2-C4AQ0 haplotype.
Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement
Authors: Trysberg Estelle , Blennow Kaj , Zachrisson Olof , Tarkowski Andrej 
Published: September 2004

AbstractSymptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8 – two cytokines that are known to upregulate MMP-9 – both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.
A comprehensive transcript index of the human genome generated using microarrays and computational approaches
Authors: Schadt Eric E , Edwards Stephen W , GuhaThakurta Debraj , Holder Dan , Ying Lisa , Svetnik Vladimir , Leonardson Amy , Hart Kyle W , Russell Archie , Li Guoya , Cavet Guy , Castle John , McDonagh Paul , Kan Zhengyan , Chen Ronghua , Kasarskis Andrew , Margarint Mihai , Caceres Ramon M , Johnson Jason M , Armour Christopher D , Garrett-Engele Philip W , Tsinoremas Nicholas F , Shoemaker Daniel D 
Published: September 2004

Abstract
Background
Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22.

Results
The combination of microarray data with extensive genome annotations resulted in a set of 28,456 experimentally supported transcripts. This set of high-confidence transcripts represents the first experimentally driven annotation of the human genome. In addition, the results from genomic tiling suggest that a large amount of transcription exists outside of annotated regions of the genome and serves as an example of how this activity could be measured on a genome-wide scale.

Conclusions
These data represent one of the most comprehensive assessments of transcriptional activity in the human genome and provide an atlas of human gene expression over a unique set of gene predictions. Before the annotation of the human genome is considered complete, however, the previously unannotated transcriptional activity throughout the genome must be fully characterized.
Genome-wide mutagenesis of Zea mays L. using RescueMu transposons
Authors: Fernandes John , Dong Qunfeng , Schneider Bret , Morrow Darren J , Nan Guo-Ling , Brendel Volker , Walbot Virginia 
Published: September 2004

AbstractDerived from the maize Mu1 transposon, RescueMu provides strategies for maize gene discovery and mutant phenotypic analysis. 9.92 Mb of gene-enriched sequences next to RescueMu insertion sites were co-assembled with expressed sequence tags and analyzed. Multiple plasmid recoveries identified probable germinal insertions and screening of RescueMu plasmid libraries identified plants containing probable germinal insertions. Although frequently recovered parental insertions and insertion hotspots reduce the efficiency of gene discovery per plasmid, RescueMu targets a large variety of genes and produces knockout mutants.
A Distal Region Involving Hepatocyte Nuclear Factor 4α and CAAT/Enhancer Binding Protein Markedly Potentiates the Protein Kinase A Stimulation of the Glucose-6-Phosphatase Promoter
Authors: Gautier-Stein Amandine , Mithieux Gilles , Rajas Fabienne 
Published: September 2004

AbstractGlucose-6-phosphatase (Glc6Pase) is the last enzyme of gluconeogenesis and is only expressed in the liver, kidney, and small intestine. In these tissues, the mRNA and its activity are increased when cAMP levels increased (e.g. in fasting or diabetes). We first report that a proximal region (within −200 bp relative to the transcription start site) and a distal region (−694/−500 bp) are both required for a potent cAMP and a protein kinase A (PKA) responsiveness of the Glc6Pase promoter. Using different molecular approaches, we demonstrate that hepatocyte nuclear factor (HNF4α), CAAT/ enhancer-binding protein-α (C/EBPα), C/EBPβ, and cAMP response element-binding protein (CREB) are involved in the potentiated PKA responsiveness: in the distal region, via one HNF4α- and one C/EBP-binding sites, and in the proximal region, via two HNF4α and two CREB-binding sites. We also show that HNF4α, C/EBPα, and C/EBPβ are constitutively bound to the endogenous Glc6Pase gene, whereas CREB and CREB-binding protein (CBP) will be bound to the gene upon stimulation by cAMP. These data strongly suggest that the cAMP responsiveness of the Glc6Pase promoter requires a tight cooperation between a proximal and a distal region, which depends on the presence of several HNF4α-, C/EBP-, and CREB-binding sites, therefore involving an intricate association of hepatic and ubiquitous transcription factors.
Fuzzy-Systeme mit inhärenter Dynamik: ein Überblick (A Survey on Fuzzy Systems with Inherent Dynamics)
Authors: Adamy Jürgen , Kempf Roland 
Published: September 2004

Abstract
Fuzzy-Systeme sind im Allgemeinen statische Systeme. Des Weiteren lassen sich aber auch dynamische Systeme direkt durch Fuzzy-Funktionen und Regeln beschreiben. Ihre Dynamik ist dabei inhärent und wird nicht durch das Gewichten von dynamischen Modellen wie im Falle von Takagi–Sugeno–Kang-Systemen erreicht, sondern durch direkte Rückführung der Ausgangsgrößen eines Fuzzy-Systems. In diesem Beitrag werden vier verschiedene, zentrale Ansätze für Fuzzy-Systeme mit inhärenter Dynamik behandelt: rekurrente Fuzzy-Systeme, dynamische Fuzzy-Systeme, iterierte Fuzzy-Mengen und Fuzzy-Automaten.
Multi Device Portals (Multi Device Portals)
Authors: Hänel Walter 
Published: September 2004

Summary
In the last few years, Internet Portals have evolved from proprietary solutions to frameworks supporting open standards for portal applications, commonly called portlets. Despite this evolution, portals supporting data access on multiple devices are still in their infancy. The differences in the capabilities of the supported devices and the used protocols are significant. While there are some answers on the horizon for presenting applications on multiple devices, such as JSR 188 and new markup languages like RIML, we are still missing solutions supporting multi modal devices on portals.
Verifix: Konstruktion und Architektur verifizierender Übersetzer (Verifix: Construction and Architecture of Verifying Compilers)
Authors: Glesner Sabine , Goos Gerhard , Zimmermann Wolf 
Published: September 2004

Zusammenfassung
Übersetzer (Compiler) sind das Herzstück bei der Erstellung von Software, erlauben sie es doch, Programme in höheren Programmiersprachen zu schreiben, die dann mithilfe von Übersetzern in Maschinencode transformiert werden. Um zuverlässige Software zu erstellen, ist es daher unbedingt erforderlich, dass Übersetzer nachweislich korrekt arbeiten. Das DFG-Projekt Verifix, das gemeinsam in den Arbeitsgruppen von Prof. Goos (Universität Karlsruhe), Prof. v. Henke (Universität Ulm) und Prof. Langmaack (Christian-Albrechts-Universität zu Kiel) durchgeführt wurde, hat Methoden entwickelt, mit denen formal korrekte Übersetzer konstruiert werden können, ohne dass dabei Leistungseinbußen entstehen. In diesem Artikel stellen wir diese Methoden sowie unsere im Projekt erzielten Ergebnisse im Überblick vor.
Relation between cell disruption conditions, cell debris particle size, and inclusion body release
Authors: van Hee Pim , Middelberg Anton P.J. , van der Lans Rob G.J.M. , van der Wielen Luuk A.M. 
Published: September 2004

AbstractThe efficiency of physical separation of inclusion bodies from cell debris is related to cell debris size and inclusion body release and both factors should be taken into account when designing a process. In this work, cell disruption by enzymatic treatment with lysozyme and cellulase, by homogenization, and by homogenization with ammonia pretreatment is discussed. These disruption methods are compared on the basis of inclusion body release, operating costs, and cell debris particle size. The latter was measured with cumulative sedimentation analysis in combination with membrane‐associated protein quantification by SDS‐PAGE and a spectrophotometric peptidoglycan quantification method. Comparison of the results obtained with these two cell debris quantification methods shows that enzymatic treatment yields cell debris particles with varying chemical composition, while this is not the case with the other disruption methods that were investigated. Furthermore, the experiments show that ammonia pretreatment with homogenization increases inclusion body release compared to homogenization without pretreatment and that this pretreatment may be used to control the cell debris size to some extent. The enzymatic disruption process gives a higher product release than homogenization with or without ammonia pretreatment at lower operating costs, but it also yields a much smaller cell debris size than the other disruption process. This is unfavorable for centrifugal inclusion body purification in this case, where cell debris is the component going to the sediment and the inclusion body is the floating component. Nevertheless, calculations show that centrifugal separation of inclusion bodies from the enzymatically treated cells gives a high inclusion body yield and purity. © 2004 Wiley Periodicals, Inc.
Improved recanalization of chronic total coronary occlusions using an optical coherence reflectometry‐guided guidewire
Authors: Hoye Angela , Onderwater Emile , Cummins Paul , Sianos Georgios , Serruys Patrick W. 
Published: September 2004

AbstractSuccessful percutaneous therapy of chronic total occlusions is limited predominantly by the inability to cross the lesion. We report our experience of 29 chronic total occlusions (CTOs) that could not be crossed with conventional wires and subsequently underwent attempted recanalization facilitated using a wire navigated with optical coherence reflectometry. Mean length of occlusion was 22.1 mm (range, 4.5–88.7 mm). Successful recanalization was achieved in a further 15 (51.7%), with no complications of tamponade, myocardial infarction, or death. These results demonstrate that this wire can be a useful tool in addition to conventional wires in the treatment of CTO. Cathet Cardiovasc Intervent 2004;63:158–163. © 2004 Wiley‐Liss, Inc.
Real‐world bare metal stenting: Identification of patients at low or very low risk of 9‐month coronary revascularization
Authors: Ellis Stephen G. , Bajzer Christopher T. , Bhatt Deepak L. , Brener Sorin J. , Whitlow Patrick L. , Lincoff A. Michael , Moliterno David J. , Raymond Russell E. , Tuzcu E. Murat , Franco Irving , Dushman‐Ellis Sandra , Lander Katherine J. , Schneider Jakob P. , Topol Eric J. 
Published: September 2004

AbstractThe high cost of drug‐eluting stents (DESs) has made identification of patients who are at low risk for subsequent revascularization after treatment with bare metal stents (BMSs) highly desirable. Previous reports from randomized trials suffer from biases induced by restricted entry criteria and protocol‐mandated angiographic follow‐up. Between 1994 and 2001, 5,239 consecutive BMS patients, excluding those with coil stents, technical failure, brachytherapy, staged procedure, or stent thrombosis within 30 days, were prospectively identified from a large single‐center tertiary‐referral‐center prospective registry for long‐term follow‐up. We sought to identify characteristics of patients with very low (≤ 4%) or low (4–10%) likelihood of coronary revascularization 9 months after BMS. Nine‐month clinical follow‐up was obtained in 98.2% of patients. Coronary revascularization was required in 13.4% and did not differ significantly by stent type. On the basis of multivariate analysis identifying 11 independent correlates and previous reports, 20 potential low‐risk patient and lesion groups (228 ± 356 patients/groups) were identified (e.g, patients with all of the following: native vessel, de novo, reference diameter ≥ 3.5 mm, lesion length < 5 mm, no diabetes, not ostial in location). Actual and model‐based outcomes were analyzed. No group had both predicted and observed 9‐month revascularization ≤ 4% (very low risk). Conversely, 19 of 20 groups had a predicted and observed revascularization rate of 4–10% (low risk). In the real‐world setting, the need for intermediate‐term revascularization after BMS may be lower than expected, but it may be very difficult to identify patients at very low risk. Conversely, if the benefits of DESs are attenuated in routine practice, many groups of patients treated with BMSs may have nearly comparable results. Catheter Cardiovasc Interv 2004;63:135–140. © 2004 Wiley‐Liss, Inc.
Patient tolerance and resource utilization associated with an arterial closure versus an external compression device after percutaneous coronary intervention
Authors: Juergens Craig P. , Leung Dominic Y.C. , Crozier John A. , Wong Adelina M. , Robinson Jacqui T.C. , Lo Sidney , Kachwalla Hashim , Hopkins Andrew P. 
Published: September 2004

AbstractWe assessed patient tolerance and resource utilization of using the AngioSeal closure device versus assisted manual compression using the Femostop device after percutaneous coronary intervention (PCI). Patients undergoing PCI with clean arterial access and no procedural hematoma were randomized to receive the AngioSeal or Femostop device to achieve femoral arterial hemostasis. Times from procedure end to removal from angiography table, hemostasis, ambulation, and hospital discharge were recorded. Bedside nursing/medical officer care time, vascular complications, and disposable use were also documented. Patient comfort was assessed using Present Pain Intensity and Visual Analogue scales at baseline, 4 hr, 8 hr, and the morning after the procedure. One hundred twenty‐two patients were enrolled (62 AngioSeal, 60 Femostop). Patients in the AngioSeal group took longer to be removed from the angiography table (11 ± 4 vs. 9 ± 3 min; P = 0.002) compared with the Femostop group. Time to hemostasis (0.4 ± 1.1 vs. 6.4 ± 1.7 hr; P < 0.001) and ambulation (17 ± 8 vs. 22 ± 13 hr; P = 0.004) were less in the AngioSeal group, although time to discharge was not different. Nursing and medical officer time was no different. Disposables including device cost were higher in the AngioSeal group ($209 ± 13 vs. $53 ± 9; P < 0.001). On a Visual Analogue scale, patients reported more pain at 4 hr (P < 0.001) and 8 hr (P < 0.001) in the Femostop group. The worst amount of pain at any time point was also more severe in the Femostop group (P < 0.001). Similar results were found on a Present Pain Intensity scale of pain. There were no differences in ultrasound‐determined vascular complications (two each). Femoral access site closure using the AngioSeal device resulted in a small delay in leaving the angiography suite and a higher disposable cost compared to using the Femostop device. However, patients receiving the AngioSeal were able to ambulate sooner and reported less pain, which may justify the increased costs involved. Catheter Cardiovasc Interv 2004;63:166–170. © 2004 Wiley‐Liss, Inc.