bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of the Ubiquitin-Proteasome System in Human Carotid Atherosclerosis
Authors: Versari Daniele , Herrmann Joerg , Gössl Mario , Mannheim Dallit , Sattler Katherine , Meyer Fredric B. , Lerman Lilach O. , Lerman Amir 
Published: June 2006

Objective—The ubiquitin-proteasome system is the principal degradation route of intracellular and oxidized proteins, thus regulating many cellular processes conceivably important for atherosclerosis. The aim of this study was to evaluate the activity of ubiquitin-proteasome system in human carotid artery plaques in relation to oxidative stress and clinical manifestation.Methods and Results—In carotid endarterectomy specimens from 83 asymptomatic and 94 symptomatic patients, content of ubiquitin, ubiquitin conjugates, matrix metalloproteases, and NADPH-oxidase-p67 was evaluated by immunoblotting; proteolytic proteasome activity by fluorometric assay; single and double immunostaining for ubiquitin conjugates, 3-nitrotyrosine, apoptosis, smooth muscle α-actin, and macrophage CD-68, as well as Sirius Red staining for collagen were performed. Compared with asymptomatic patients, symptomatic patients showed a more unstable plaque phenotype, an increased degree of apoptosis, a significantly higher ubiquitin conjugates content (17.72±1.36 versus 10.99±1.04;P<0.001), and lower proteasome activity (5.01±0.70 versus 9.41±1.19 nmol AMC/mg protein/min;P<0.01). Ubiquitin conjugates content was directly correlated to NADPH-p67 and degree of apoptosis. Immunostaining revealed colocalization of ubiquitin conjugates and 3-nitrotyrosine, and accumulation of ubiquitin conjugates in smooth muscle cells and macrophages.Conclusions—In human carotid plaques increased oxidative stress is associated with inhibition of the proteasome activity and accumulation of ubiquitin conjugates, particularly in symptomatic patients. These results suggest a possible role of the ubiquitin-proteasome system in influencing plaque stability.
Kernel Projection Classifiers with Suppressing Features of Other Classes
Authors: Washizawa Yoshikazu , Yamashita Yukihiko 
Published: June 2006

We propose a new classification method based on a kernel technique called suppressed kernel sample space projection classifier (SKSP), which is extended from kernel sample space projection classifier (KSP). In kernel methods, samples are classified after they are mapped from an input space to a high-dimensional space called a feature space. The space that is spanned by samples of a class in a feature space is defined as a kernel sample space. In KSP, an unknown input vector is classified to the class of which projection norm onto the kernel sample space is maximized. KSP can be interpreted as a special type of kernel principal component analysis (KPCA). KPCA is also used in classification problems. However, KSP has more useful properties compared with KPCA, and its accuracy is almost the same as or better than that of KPCA classifier. Since KSP is a single-class classifier, it uses only self-class samples for learning. Thus, for a multiclass classification problem, even though there are very many classes, the computational cost does not change for each class. However, we expect that more useful features can be obtained for classification if samples from other classes are used. By extending KSP to SKSP, the effects of other classes are suppressed, and useful features can be extracted with an oblique projection. Experiments on two-class classification problems, indicate that SKSP shows high accuracy in many classification problems.
Understanding Diabetes Medications From the Perspective of Patients With Type 2 Diabetes
Authors: Hayes Risa P. , Bowman Lee , Monahan Patrick O. , Marrero David G. , McHorney Colleen A. 
Published: June 2006

Purpose The purpose of this qualitative study was to explore diabetes medication experiences of patients with type 2 diabetes. Methods Study participants were recruited through newspaper advertisements and letters from primary and specialty clinics in Indianapolis, Indiana. The same professional facilitator conducted 18 focus groups (7 male, 11 female) at a Veteran Affairs facility in Indianapolis, Indiana. Participants were 138 socioeconomically diverse individuals with type 2 diabetes (68% female, 74% [.greaterequal] 50 years old, 61% non-Hispanic Caucasian). Participants were on a variety of diabetes medication regimens (61% injectable insulin monotherapy or in combination with orals). Content analysis of focus group transcripts was used to establish themes. Results Three major themes emerged across the focus groups: (1) the inconvenience and inflexibility of the timing and frequency of administration of many diabetes treatments on participants' lives, (2) the desire to avoid injections and/or insulin therapy, and (3) the physical and emotional side effects of diabetes medications. Assuming equivalent effectiveness of 2 medications, participants would weigh the convenience and flexibility, route of administration, side effects, and cost of the medications to arrive at a treatment preference. Participants believed they currently had no opportunity to express their treatment preference to their health care provider. Conclusions The best therapeutic option for a patient with type 2 diabetes will be one that is clinically effective and consistent with the patient's needs and preferences. The challenge for diabetes educators is to support patients in articulating and incorporating their needs and preferences into the treatment decision-making process.
Interferon-γ therapy in two patients with progressive chronic pulmonary aspergillosis
Authors: Kelleher P. , Goodsall A. , Mulgirigama A. , Kunst H. , Henderson D. C. , Wilson R. , Newman-Taylor A. , Levin M. 
Published: June 2006

Infection by Aspergillus species causes a wide spectrum of pulmonary disease in humans.In two patients with semi-invasive Aspergillus-induced lung disease, significantly reduced levels of interferon-γ secretion by peripheral blood mononuclear cells were found afterin vitrostimulation with the T-cell mitogen phytohaemagglutinin. Despite anti-fungal therapy, both patients exhibited progressive disease, and adjunctive interferon-γ therapy was associated with significant clinical improvement.The data suggest that impaired production of interferon-γ can be seen in patients with chronic pulmonary aspergillosis. Adjunctive cytokine therapy with interferon-γ may be useful in patients with progressive disease despite adequate anti-fungal therapy.
Beyond the dogma: novel β2-adrenoceptor signalling in the airways
Authors: Giembycz M. A. , Newton R. 
Published: June 2006

β2-Adrenoceptor agonists evoke rapid bronchodilatation and are the mainstay of the treatment of asthma symptoms worldwide. The mechanism of action of this class of compounds is believed to involve the stimulation of adenylyl cyclase and subsequent activation of the cyclic adenosine monosphosphate (cAMP)/cAMP-dependent protein kinase cascade.This classical model of β2-adrenoceptor-mediated signal transduction is deeply entrenched, but there is compelling evidence that agonism of β2-adrenoceptors can lead to the activation of multiple effector pathways, which now compels researchers in academia and the pharmaceutical industry alike to think beyond the traditional dogma. Therefore, the regulation by β2-adrenoceptor agonists of responses, including airways smooth muscle tone and the secretory capacity of the epithelium and pro-inflammatory/immune cells, may be highly complex, involving both cAMP-dependent and -independent mechanisms that, in many cases, may act in concert.In this article, the current status of β2-adrenoceptor-mediated signalling in the airways is reviewed in the context of understanding mechanisms that may underlie both the beneficial and detrimental effects of these drugs in asthma symptom management.
Marked stem cell factor expression in the airways of lung transplant recipients
Authors: Da Silva Carla A , Adda Mélanie , Stern Marc , de Blay Frédéric , Frossard Nelly , Israel-Biet Dominique 
Published: June 2006

Abstract

Background
Airways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF) could play a role in this setting.

Methods
We studied 9 lung transplant recipients (LTx recipients) during their first year postgraft, and evaluated SCF mRNA expression in bronchial biopsy specimens using on-line fluorescent PCR and SCF protein levels in bronchoalveolar lavage (BAL) and serum using ELISA. The expression of SCF receptor Kit was assessed using immunostaining of paraffin-embedded bronchial sections.

Results
SCF mRNA was highly expressed during the early postgraft period [Month (M)1-M3] (300% increase vs controls: 356 vs 1.2 pg SCF/μg GAPDH cDNA, p < 0.001) and decreased thereafter (M4-M12: 187 pg/μg), although remaining at all times 10–100 times higher than in controls. While SCF protein levels in BAL were similar in LTx recipients and in controls, the SCF serum levels were at all times higher in LTx recipients than in controls (p < 0.05), with no relationship between these levels and the acute complications of the graft. Finally, Kit was strongly expressed by the mast cells as well as by the bronchial epithelium of LTx recipients.

Conclusion
SCF and Kit are expressed in bronchial biopsies from lung transplant recipients irrespective of the clinical status of the graft. A role for these factors in tissue repair following lung transplantation is hypothesised.
ROKU: a novel method for identification of tissue-specific genes
Authors: Kadota Koji , Ye Jiazhen , Nakai Yuji , Terada Tohru , Shimizu Kentaro 
Published: June 2006

AbstractBackgroundOne of the important goals of microarray research is the identification of genes whose expression is considerably higher or lower in some tissues than in others. We would like to have ways of identifying such tissue-specific genes.ResultsWe describe a method, ROKU, which selects tissue-specific patterns from gene expression data for many tissues and thousands of genes. ROKU ranks genes according to their overall tissue specificity using Shannon entropy and detects tissues specific to each gene if any exist using an outlier detection method. We evaluated the capacity for the detection of various specific expression patterns using synthetic and real data. We observed that ROKU was superior to a conventional entropy-based method in its ability to rank genes according to overall tissue specificity and to detect genes whose expression pattern are specific only to objective tissues.ConclusionROKU is useful for the detection of various tissue-specific expression patterns. The framework is also directly applicable to the selection of diagnostic markers for molecular classification of multiple classes.
Analysis of circular genome rearrangement by fusions, fissions and block-interchanges
Authors: Lu Chin Lung , Huang Yen Lin , Wang Tsui Ching , Chiu Hsien-Tai 
Published: June 2006

Abstract

Background
Analysis of genomes evolving via block-interchange events leads to a combinatorial problem of sorting by block-interchanges, which has been studied recently to evaluate the evolutionary relationship in distance between two biological species since block-interchange can be considered as a generalization of transposition. However, for genomes consisting of multiple chromosomes, their evolutionary history should also include events of chromosome fusions and fissions, where fusion merges two chromosomes into one and fission splits a chromosome into two.

Results
In this paper, we study the problem of genome rearrangement between two genomes of circular and multiple chromosomes by considering fusion, fission and block-interchange events altogether. By use of permutation groups in algebra, we propose an

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MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFoe=taaa@383D@

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2) time algorithm to efficiently compute and obtain a minimum series of fusions, fissions and block-interchanges required to transform one circular multi-chromosomal genome into another, where n is the number of genes shared by the two studied genomes. In addition, we have implemented this algorithm as a web server, called FFBI, and have also applied it to analyzing by gene orders the whole genomes of three human Vibrio pathogens, each with multiple and circular chromosomes, to infer their evolutionary relationships. Consequently, our experimental results coincide well with our previous results obtained using the chromosome-by-chromosome comparisons by landmark orders between any two Vibrio chromosomal sequences as well as using the traditional comparative analysis of 16S rRNA sequences.

Conclusion
FFBI is a useful tool for the bioinformatics analysis of circular and multiple genome rearrangement by fusions, fissions and block-interchanges.
Array2BIO: from microarray expression data to functional annotation of co-regulated genes
Authors: Loots Gabriela G , Chain Patrick SG , Mabery Shalini , Rasley Amy , Garcia Emilio , Ovcharenko Ivan 
Published: June 2006

AbstractBackgroundThere are several isolated tools for partial analysis of microarray expression data. To provide an integrative, easy-to-use and automated toolkit for the analysis of Affymetrix microarray expression data we have developed Array2BIO, an application that couples several analytical methods into a single web based utility.ResultsArray2BIO converts raw intensities into probe expression values, automatically maps those to genes, and subsequently identifies groups of co-expressed genes using two complementary approaches: (1) comparative analysis of signal versus control and (2) clustering analysis of gene expression across different conditions. The identified genes are assigned to functional categories based on Gene Ontology classification and KEGG protein interaction pathways. Array2BIO reliably handles low-expressor genes and provides a set of statistical methods for quantifying expression levels, including Benjamini-Hochberg and Bonferroni multiple testing corrections. An automated interface with the ECR Browser provides evolutionary conservation analysis for the identified gene loci while the interconnection with Crème allows prediction of gene regulatory elements that underlie observed expression patterns.ConclusionWe have developed Array2BIO – a web based tool for rapid comprehensive analysis of Affymetrix microarray expression data, which also allows users to link expression data to Dcode.org comparative genomics tools and integrates a system for translating co-expression data into mechanisms of gene co-regulation. Array2BIO is publicly available athttp://array2bio.dcode.org.
Identification and characterisation of human apoptosis inducing proteins using cell-based transfection microarrays and expression analysis
Authors: Palmer Ella L , Miller Andrew D , Freeman Tom C 
Published: June 2006

Abstract

Background
Cell-based microarrays were first described by Ziauddin and Sabatini in 2001 as a powerful new approach for performing high throughput screens of gene function. An important application of cell-based microarrays is in screening for proteins that modulate gene networks. To this end, cells are grown over the surface of arrays of RNAi or expression reagents. Cells growing in the immediate vicinity of the arrayed reagents are transfected and the arrays can then be scanned for cells showing localised changes in function. Here we describe the construction of a large-scale microarray using expression plasmids containing human genes, its use in screening for genes that induce apoptosis when over-expressed and the characterisation of a number of these genes by following the transcriptional response of cell cultures during their induction of apoptosis.

Results
High-density cell-based arrays were successfully fabricated using 1,959 un-tagged open reading frames (ORFs) taken from the Mammalian Gene Collection (MGC) in mammalian expression vectors. The arrays were then used to screen for genes inducing apoptosis in Human Embryonic Kidney (HEK293T) cells. Using this approach, 10 genes were clearly identified and confirmed to induce apoptosis. Some of these genes have previously been linked to apoptosis, others not. The mechanism of action of three of the 10 genes were then characterised further by following the transcriptional events associated with apoptosis induction using expression profiling microarrays. This data demonstrates a clear pro-apoptotic transcriptional response in cells undergoing apoptosis and also suggests the use of common apoptotic pathways regardless of the nature of the over-expressed protein triggering cell death.

Conclusion
This study reports the design and use of the first truly large-scale cell-based microarrays for over-expression studies. Ten genes were confirmed to induce apoptosis, some of which were not previously known to possess this activity. Transcriptome analysis on three of the 10 genes demonstrated their use of similar pathways to invoke apoptosis.
Verification of predicted alternatively spliced Wnt genes reveals two new splice variants (CTNNB1 and LRP5) and altered Axin-1 expression during tumour progression
Authors: Pospisil Heike , Herrmann Alexander , Butherus Kristine , Pirson Stefan , Reich Jens G , Kemmner Wolfgang 
Published: June 2006

Abstract

Background
Splicing processes might play a major role in carcinogenesis and tumour progression. The Wnt pathway is of crucial relevance for cancer progression. Therefore we focussed on the Wnt/β-catenin signalling pathway in order to validate the expression of sequences predicted as alternatively spliced by bioinformatic methods. Splice variants of its key molecules were selected, which may be critical components for the understanding of colorectal tumour progression and may have the potential to act as biological markers. For some of the Wnt pathway genes the existence of splice variants was either proposed (e.g. β-Catenin and CTNNB1) or described only in non-colon tissues (e.g. GSK3β) or hitherto not published (e.g. LRP5).

Results
Both splice variants – normal and alternative form – of all selected Wnt pathway components were found to be expressed in cell lines as well as in samples derived from tumour, normal and healthy tissues. All splice positions corresponded totally with the bioinformatical prediction as shown by sequencing. Two hitherto not described alternative splice forms (CTNNB1 and LRP5) were detected. Although the underlying EST data used for the bioinformatic analysis suggested a tumour-specific expression neither a qualitative nor a significant quantitative difference between the expression in tumour and healthy tissues was detected. Axin-1 expression was reduced in later stages and in samples from carcinomas forming distant metastases.

Conclusion
We were first to describe that splice forms of crucial genes of the Wnt-pathway are expressed in human colorectal tissue. Newly described splicefoms were found for β-Catenin, LRP5, GSK3β, Axin-1 and CtBP1. However, the predicted cancer specificity suggested by the origin of the underlying ESTs was neither qualitatively nor significant quantitatively confirmed. That let us to conclude that EST sequence data can give adequate hints for the existence of alternative splicing in tumour tissues. That no difference in the expression of these splice forms between cancerous tissues and normal mucosa was found, may indicate that the existence of different splice forms is of less significance for cancer formation as suggested by the available EST data. The currently available EST source is still insufficient to clearly deduce colon cancer specificity. More EST data from colon (tumour and healthy) is required to make reliable predictions.
Persisters: a distinct physiological state of E. coli
Authors: Shah Devang , Zhang Zhigang , Khodursky Arkady B , Kaldalu Niilo , Kurg Kristi , Lewis Kim 
Published: June 2006

Abstract

Background
Bacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understanding persisters is encouraging, but the main obstacle in understanding their nature was our inability to isolate these elusive cells from a wild-type population since their discovery in 1944.

Results
We hypothesized that persisters are dormant cells with a low level of translation, and used this to physically sort dim E. coli cells which do not contain sufficient amounts of unstable GFP expressed from a promoter whose activity depends on the growth rate. The dim cells were tolerant to antibiotics and exhibited a gene expression profile distinctly different from those observed for cells in exponential or stationary phases. Genes coding for toxin-antitoxin module proteins were expressed in persisters and are likely contributors to this condition.

Conclusion
We report a method for persister isolation and conclude that these cells represent a distinct state of bacterial physiology.
Does updating improve the methodological and reporting quality of systematic reviews?
Authors: Shea Beverley , Boers Maarten , Grimshaw Jeremy M , Hamel Candyce , Bouter Lex M 
Published: June 2006

Abstract

Background
Systematic reviews (SRs) must be of high quality. The purpose of our research was to compare the methodological and reporting quality of original versus updated Cochrane SRs to determine whether updating had improved these two quality dimensions.

Methods
We identifed updated Cochrane SRs published in issue 4, 2002 of the Cochrane Library. We assessed the updated and original versions of the SRs using two instruments: the 10 item enhanced Overview Quality Assessment Questionnaire (OQAQ), and an 18-item reporting quality checklist and flow chart based upon the Quality of Reporting of Meta-analyses (QUOROM) statement. At least two reviewers extracted data and assessed quality. We calculated the percentage (with a 95% confidence interval) of 'yes' answers to each question. We calculated mean differences in percentage, 95% confidence intervals and p-values for each of the individual items and the overall methodological quality score of the updated and pre-updated versions using OQAQ.

Results
We assessed 53 SRs. There was no significant improvement in the global quality score of the OQAQ (mean difference 0.11 (-0.28; 0.70 p = 0.52)). Updated reviews showed a significant improvement of 18.9 (7.2; 30.6 p < .01) on the OQAQ item assessing whether the conclusions drawn by the author(s) were supported by the data and/or analysis presented in the SR. The QUOROM statement showed that the quality of reporting of Cochrane reviews improved in some areas with updating. Improvements were seen on the items relating to data sources reported in the abstract, with a significant difference of 17.0 (9.8; 28.7 p = 0.01), review methods, reported in the abstract 35 (24.1; 49.1 p = 0.00), searching methods 18.9 (9.7; 31.6 p = 0.01), and data abstraction 18.9 (11.7; 30.9 p = 0.00).

Conclusion
The overall quality of Cochrane SRs is fair-to-good. Although reporting quality improved on certain individual items there was no overall improvement seen with updating and methodological quality remained unchanged. Further improvement of quality of reporting is possible. There is room for improvement of methodological quality as well. Authors updating reviews should address identified methodological or reporting weaknesses. We recommend to give full attention to both quality domains when updating SRs.