bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronary Calcium Score and Prediction of All-Cause Mortality in Diabetes
Authors: Agarwal Subhashish , Morgan Timothy , Herrington David M. , Xu Jianzhao , Cox Amanda J. , Freedman Barry I. , Carr J. Jeffrey , Bowden Donald W. 
Published: March 2011

OBJECTIVE
In diabetes, it remains unclear whether the coronary artery calcium (CAC) score provides additional information about total mortality risk beyond traditional risk factors.

RESEARCH DESIGN AND METHODS
A total of 1,051 participants, aged 34–86 years, in the Diabetes Heart Study (DHS) were followed for 7.4 years. Subjects were separated into five groups using baseline computed tomography scans and CAC scores (0–9, 10–99, 100–299, 300–999, and ≥1,000). Logistic regression was performed adjusting for age, sex, race, smoking, and LDL cholesterol to examine the association between CAC and all-cause mortality. Areas under the curve with and without CAC were compared. Natural splines using continuous measures of CAC were fitted to estimate the relationship between observed CAC and mortality risk.

RESULTS
A total of 17% (178 of 1,051) of participants died during the follow-up. In multivariate analysis, the odds ratios (95% CIs) for all-cause mortality, using CAC 0–9 as the reference group, were CAC 10–99: 1.40 (0.57–3.74); CAC 100–299: 2.87 (1.17–7.77); CAC 300–999: 3.04 (1.32–7.90); and CAC ≥1,000: 6.71 (3.09–16.87). The area under the curve without CAC was 0.68 (95% CI 0.66–0.70), and the area under the curve with CAC was 0.72 (0.70–0.74) (P = 0.0001). Using splines, the estimated risk (95% CI) of mortality for a CAC of 0 was 6.7% (4.6–9.7), and the risk increased nearly linearly, plateauing at CAC ≥1,000 (20.0% [15.7–25.2]).

CONCLUSIONS
In diabetes, CAC was shown to be an independent predictor of mortality. Participants with CAC (0–9) were at lower risk (0.9% annual mortality). The risk of mortality increased with increasing levels of CAC, plateauing at approximately CAC ≥1,000 (2.7% annual mortality). More research is warranted to determine the potential utility of CAC scans in diabetes.
Retrospective Analysis of Use of Empiric Anit Tuberculosis Treatment in Smear Negative Pulmonary Tuberculosis Patients in Central Sri Lanka
Authors: Madegedara D , Kulathunga KMCN , Nakandala SC 
Published: March 2011

Objective: To critically analyze the outcome of sputum negative pulmonary TB patients who were managed in the Respiratory unit, Kandy Sri Lanka. Setting: Respiratory Unit, Teaching hospital, Kandy. Method: The subjects were between age 12 years or older and visited chest clinic Kandy, between January -December 2008 with a suspicion of pulmonary TB. 84 patients were reviewed with admission note, microbiology results and chest radiography. The characteristics of patients such as age, sex, clinical features, laboratory and radiographic findings were analyzed. Results: The diagnosis of definite or probable smear negative pulmonary TB was made on treatment outcome at one month with ATT medication. At this endpoint, 67 (79.76%) had clinical and radiological improvement, 7(8.33%) had clinical improvement and 3 (3.57%) had radiological improvement. Mantoux test was positive in 46(78%) of definite cases and 6(85.7%) in probable cases. Mycobacterial culture was positive in 5 patients. 7 (8.3%) cases were diagnosed as ‘non-TB’ based on absence of clinical / radiological improvement or discovery of another cause at or before this study end point. In non TB group 3 had carcinoma, 2 had pneumoconiosis, 1 had bronchiectasis while in 1, cause was indeterminate. Mantoux became positive in 6 (83.3%) in non Tuberculosis group. There was no association between positive Mantoux and presence of active pulmonary TB. Conclusion: Our findings suggest that empirical anti TB treatment is an acceptable practice if clinical suspicion of tuberculosis is high and patients show supportive radiological evidence of active TB. Keywords: Smear negative pulmonary tuberculosis; empirical anti tubercular treatment DOI: 10.3126/saarctb.v7i2.4400SAARC J. TUBER. LUNG DIS. HIV/AIDS 2010 VII(2) 15-18
Application of the Taguchi approach to investigate the softening kinetics of AISI 304 stainless steel during hot deformation
Authors: Rasti Javad , Meratian Mahmood , Najafizadeh Abbas 
Published: March 2011

Abstract
The Taguchi approach was employed to determine the softening kinetics of AISI 304 stainless steel during post-dynamic recrystallization. Analysis of variance was done to evaluate the effectiveness of parameters quantitatively. Using regression analysis, four equations for the time corresponding to softening of 50 % during pass intervals were obtained. The equations were related to the four strain regions ranging from 0.25 to 2 times the peak strain. With mathematical manipulation of some equations, relations for the transition strain and the corresponding time of 50 % softening were derived and explained by considering microstructures evolved during dynamic recrystallization.
La crise : levier strategique d'apprentissage organisationnel
Authors: Boumrar Julie 
Published: March 2011

Résumé : Dans la littérature managériale, il existe une dichotomie concernant le concept de crise : elle est, soit considérée comme un événement, soit comme un processus. En considérant la crise comme un processus, il est possible de constater qu’elle a une histoire. En amont, il est important de savoir repérer les signaux déclencheurs pour préparer l’organisation et ainsi minimiser les effets néfastes de la crise. La gestion aval permet de gérer les conséquences en maximisant les effets positifs et minimisant les effets négatifs. De cette manière, il est possible de capitaliser sur le processus de crise qui représente une opportunité d’amélioration de l’organisation. Dans ce contexte, les questions de gestion de crise et d’apprentissage organisationnel paraissent centrales.
Une analyse critique du traitement de la crise des subprimes par la Big Bank et le Big Government de Minsky
Authors: Diop Samba 
Published: March 2011

Résumé : Dans l’analyse de Minsky, les mesures contra-cycliques de l’État sont les seules à même de permettre au système économique en crise d’échapper à une déflation par la dette. Le spectre de la Grande Dépression ne pourra s’éloigner que si les économies capitalistes se dotent de Big Bank et de Big Government de taille suffisamment importante pour contrecarrer les forces du marché. Ces deux institutions sont des équivalents de ’’stabilisateurs automatiques’’ qui permettent d’enrayer les spirales négatives et de faire redémarrer l’économie sur de nouvelles bases. Les limites inférieures sur le prix des actifs que l’intervention de la Big Bank instaure et la substitution d’une demande privée par une demande publique que l’action du Big Government organise introduisent des forces de rappel. Et ces dernières combattent les effets récessifs du marché qui ont tendance à pousser le système vers l’enlisement dans un processus de déflation à la Fisher. Cet article essaie d’analyser dans une perspective minskyenne les plans d’action mis en œuvre pour venir à bout de la crise des subprimes.
Banks as creators and transmitters of information in historical perspective
Authors: Di Caprio Debora , Santos-Arteaga Francisco J. 
Published: March 2011

Résumé : Cet article soutient que les banques commerciales ont eu recours aux principaux développements en NTIC des trente dernières années pour se spécialiser à la fois dans la création et la transmission de l’information. La capacité à créer de l’information financière confère aux banques un avantage stratégique important qui s’accroît avec les innovations technologiques permettant une plus grande concentration industrielle et informationnelle des grandes banques. Ce processus de concentration se réalise au détriment des plus petites banques qui ne peuvent faire face à l’assimilation et au développement des technologies de l’information récentes. Cet article présente une analyse descriptive, illustrant comment ce type de processus de transformation structurelle est survenu au sein de l’évolution de l’industrie bancaire états-unienne, et étudie le lien avec la crise des subprimes.
Innover dans la recherche publique en France : la responsabilite sociale de la recherche est-elle mesuree ?
Authors: Dou Henri 
Published: March 2011

Résumé : Cet article montre comment l’innovation et l’intelligence économique peuvent être introduites en France dans les laboratoires publics de recherche. L’utilisation sans discernement des indicateurs d’évaluation peut conduire à une distorsion de la perception des activités de recherche d’une part et d’autre part à éloigner les laboratoires de recherche d’un de leurs objectifs : l’utilisation d’une partie de leurs compétences et savoirs pour résoudre des problèmes liés au développement de la société et pour accroître la cohésion sociale. Des exemples sont fournis et une solution est présentée passant par l’intégration des méthodes et des outils de l’Intelligence Economique : les UMSR 1 . L’importance du rôle de telles structures au sein des universités et des centres de recherche est analysée en détail. Un concept nouveau est ensuite évoqué, celui de la RSR (Responsabilité Sociale de la Recherche), qui rejoint l’idée de participation des entités de recherche et d’enseignement à la création de richesses locales et nationales.
Liver X Receptors Inhibit Macrophage Proliferation through Downregulation of Cyclins D1 and B1 and Cyclin-Dependent Kinases 2 and 4
Authors: Pascual-García Mónica , Carbó José M. , León Theresa , Matalonga Jonathan , Out Ruud , Van Berkel Theo , Sarrias Maria-Rosa , Lozano Francisco , Celada Antonio , Valledor Annabel F. 
Published: March 2011

Abstract
Macrophages serve essential functions as regulators of immunity and homeostasis, and their proliferation contributes to pathogenesis of certain disorders. In this report, we show that induction of macrophage proliferation by the growth factor M-CSF is negatively modulated by agonists that activate the nuclear receptor liver X receptor (LXR), both in vitro and in vivo. Both isoforms LXR α and β are involved in the antiproliferative actions of LXR ligands in macrophages. In contrast, M-CSF does not exert negative effects on LXR-mediated gene expression. Treatment with LXR agonists results in the accumulation of macrophages in the G0/G1 phase of the cell cycle without affecting ERK-1/2 phosphorylation. The use of small interfering RNA or genetically modified mice revealed that, in contrast to other cellular models, functional expression of either the cyclin-dependent kinase inhibitor p27KIP1 or the cholesterol transporters ATP-binding cassette A1 or ATP-binding cassette G1 was not required for the antiproliferative effects of LXR agonists in macrophages. Western blot analysis revealed that protein expression of key molecules that regulate progression through the cell cycle, such as cyclins D1 and B1 and cyclin-dependent kinases 2 and 4, was downregulated upon LXR activation. These observations suggest a role for LXR agonists in limiting macrophage proliferative responses associated to pathogenic disorders.
CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry
Authors: Specht Sabine , Frank Jutta K. , Alferink Judith , Dubben Bettina , Layland Laura E. , Denece Gaelle , Bain Odile , Förster Irmgard , Kirschning Carsten J. , Martin Coralie , Hoerauf Achim 
Published: March 2011

AbstractFilarial parasites have to trespass many barriers to successfully settle within their mammalian host, which is equipped with mechanical borders and complex weaponry of an evolved immune system. However, little is known about mechanisms of early local events in filarial infections. In this study, bone marrow-derived dendritic cells not only upregulated activation markers CD40 and CD80 upon in vitro stimulation with filarial extracts, but also secreted CCL17, a chemokine known to be produced upon microbial challenge. Mice deficient for CCL17 had an up to 4-fold higher worm burden compared with controls by day 10 of infection with the murine filaria Litomosoides sigmodontis. Also, numbers of mast cells (MCs) invading the skin and degranulation were significantly increased, which was associated with enhanced vascular permeability and larval establishment. This phenotype was reverted by inhibition of MC degranulation with disodium cromoglycate or by blockade of histamine. In addition, we showed that CCL17-mediated vascular permeability was dependent on the presence of Wolbachia endosymbionts and TLR2. Our findings reveal that CCL17 controls filarial larval entry by limiting MC-dependent vascular permeability.
Histone Deacetylase 7 Regulates Cell Survival and TCR Signaling in CD4/CD8 Double-Positive Thymocytes
Authors: Kasler Herbert G. , Young Bryan D. , Mottet Denis , Lim Hyung W. , Collins Amy M. , Olson Eric N. , Verdin Eric 
Published: March 2011

Abstract
CD4/CD8 double-positive thymocytes express the transcriptional repressor histone deacetylase (HDAC)7, a class IIa HDAC that is exported from the cell nucleus after TCR engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in mouse thymocytes and that it regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR Jα segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAPK activity that contributes to the observed loss of viability. Remarkably, the activity of protein kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining autoexcitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions.
Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10
Authors: Mellett Mark , Atzei Paola , Jackson Ruaidhri , O’Neill Luke A. , Moynagh Paul N. 
Published: March 2011

Abstract
TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR adaptor-induced activation of NF-κB and the IFN regulatory factors have been intensively studied, there is a dearth of information on the role of TIR adaptors in regulating CREB. In this paper, we describe a role for the TIR adaptor Mal in enhancing activation of CREB. Mal-deficient murine bone marrow-derived macrophages show a loss in responsiveness to TLR2 and TLR4 ligands with respect to activation of CREB. Mal-deficient cells also fail to express the CREB-responsive genes IL-10 and cyclooxygenase 2 in response to Pam2Cys-Ser-(Lys)4 and LPS. We reveal that Mal-mediated activation of CREB is dependent on Pellino3 and TNFR-associated factor 6, because CREB activation is greatly diminished in Pellino3 knockdown cells and TNFR-associated factor 6-deficient cells. We also demonstrate the importance of p38 MAPK in this pathway with the p38 inhibitor SB203580 abolishing activation of CREB in murine macrophages. MAPK-activated protein kinase 2 (MK2), a substrate for p38 MAPK, is the likely downstream mediator of p38 MAPK in this pathway, because Mal is shown to activate MK2 and inhibition of MK2 decreases TLR4-induced activation of CREB. Overall, these studies demonstrate a new role for Mal as a key upstream regulator of CREB and as a contributor to the expression of both pro- and anti-inflammatory genes.
Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice
Authors: Nel Hendrik J. , Hams Emily , Saunders Sean P. , Mangan Niamh E. , Smith Philip , Atzberger Ann , Flavell Richard A. , Akira Shizuo , McKenzie Andrew N. , Fallon Padraic G. 
Published: March 2011

Abstract
Parasitic-infection studies on rhesus macaque monkeys have shown juvenile animals to be more susceptible to infection than adults, but the immunological mechanism for this is not known. In this study, we investigated the age-dependent genesis of helminth-induced type 2 immune responses using adult (6–8-wk-old) and juvenile (21–28-d-old) mice. Following infection with the parasitic nematode Nippostrongylus brasiliensis, juvenile mice had increased susceptibility to infection relative to adult mice. Juvenile mice developed a delayed type 2 immune response with decreased Th2 cytokine production, IgE Ab responses, mouse mast cell protease 1 levels, and intestinal goblet cell induction. This innate immune defect in juvenile mice was independent of TLR signaling, dendritic cells, or CD4+ cell function. Using IL-4–eGFP mice, it was demonstrated that the numbers of IL-4–producing basophil and eosinophils were comparable in young and adult naive mice; however, following helminth infection, the early induction of these cells was impaired in juvenile mice relative to older animals. In nonhelminth models, there was an innate in vivo defect in activation of basophils, but not eosinophils, in juvenile mice compared with adult animals. The specific role for basophils in this innate defect in helminth-induced type 2 immunity was confirmed by the capacity of adoptively transferred adult-derived basophils, but not eosinophils, to restore the ability of juvenile mice to expel N. brasiliensis. The defect in juvenile mice with regard to helminth-induced innate basophil-mediated type 2 response is relevant to allergic conditions.
CD5 Promotes IL-10 Production in Chronic Lymphocytic Leukemia B Cells through STAT3 and NFAT2 Activation
Authors: Garaud Soizic , Morva Ahsen , Lemoine Sébastien , Hillion Sophie , Bordron Anne , Pers Jacques-Olivier , Berthou Christian , Mageed Rizgar A. , Renaudineau Yves , Youinou Pierre 
Published: March 2011

Abstract
B lymphocytes from chronic lymphocytic leukemia (CLL) display some CD5 transcripts for CD5 containing the known exon 1 (E1A) and other CD5 transcripts containing the new exon 1 (E1B). These malignant B cells, as well as B cell lines transfected with cDNA for E1A-cd5 or with cDNA for E1B-cd5 produce IL-10, raising the possibility that CD5 participates in the secretion of IL-10. We identified transcription factors involved in this production in CD5+ B lymphocytes from CLL patients and in E1A-cd5–transfected or E1B-cd5–transfected Jok cells. STAT3 is activated via phosphorylation of serine 727 but also NFAT2 through its translocation into the nucleus. Chromatin immunoprecipitation experiments confirmed the role of STAT3 and allowed the discovery of a role for NFAT2 in IL-10 production. Both transcription factors bind not only to the enhancer of the Il-10 gene but also to the promoter of the Il-5 and Il-13 genes. Furthermore, transfection of B cell lines with E1A-cd5 or E1B-cd5 established that activation of STAT3 and NFAT2 is regulated by CD5. The same holds true for the production of IL-10, IL-5, and IL-13 and the expression of the receptors for these cytokines. This interpretation was confirmed by two experiments. In the first, downregulation of CD5 by small interfering RNAs lowered the production of IL-10. In the second experiment, transfection of the GFP-NFAT2 gene into B lymphocytes induced nuclear translocation of NFAT2 in CD5+ but not in CD5− B cells. Thus, CD5 expression is associated with NFAT2 activity (and mildly STAT3 activity), indicating that CD5 controls IL-10 secretion.
Cutting Edge: Ku70 Is a Novel Cytosolic DNA Sensor That Induces Type III Rather Than Type I IFN
Authors: Zhang Xing , Brann Terrence W. , Zhou Ming , Yang Jun , Oguariri Raphael M. , Lidie Kristy B. , Imamichi Hiromi , Huang Da-Wei , Lempicki Richard A. , Baseler Michael W. , Veenstra Timothy D. , Young Howard A. , Lane H. Clifford , Imamichi Tomozumi 
Published: March 2011

Abstract
Cytosolic foreign DNA is detected by pattern recognition receptors and mainly induces type I IFN production. We found that transfection of different types of DNA into various untreated cells induces type III IFN (IFN-λ1) rather than type I IFN, indicating the presence of uncharacterized DNA sensor(s). A pull-down assay using cytosolic proteins identified that Ku70 and Ku80 are the DNA-binding proteins. The knockdown studies and the reporter assay revealed that Ku70 is a novel DNA sensor inducing the IFN-lambda1 activation. The functional analysis of IFNL1 promoter revealed that positive-regulatory domain I and IFN-stimulated response element sites are predominantly involved in the DNA-mediated IFNL1 activation. A pull-down assay using nuclear proteins demonstrated that the IFN-λ1 induction is associated with the activation of IFN regulatory factor-1 and -7. Thus, to our knowledge, we show for the first time that Ku70 mediates type III IFN induction by DNA.
Reference Intervals for Serum Alpha-Fetoprotein and Carcinoembryonic Antigen in Chinese Han Ethnic Males from the Fangchenggang Area Male Health and Examination Survey
Authors: Qin Xue , Lin Liwen , Mo Zengnan , Lv Hui , Gao Yong , Tan Aihua , Yang Xiaobo , Li Shan , Zhao Jinmin 
Published: March 2011

Objectives We calculated upper 95% reference limits for serum alpha-fetoprotein (AFP)and carcinoembryonic antigen (CEA) according to the CLSI/NCCLS C28-A3 guideline. Material and methods Serum samples from 1400 healthy male subjects were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum AFP and CEA values were measured by electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers. Results Serum AFP and CEA values were not normally distributed but log normally distributed. The upper 95% reference limits of the reference intervals were ≤4.76 IU/mL (nonparametric) or ≤4.56 IU/mL (parametric) for AFP and ≤5.57 ng/mL (nonparametric) or ≤5.82 ng/mL (parametric) for CEA. The distribution of AFP levels was found to be consistent between the non-smoking and smoking (p=0.740) and non-drinking and drinking groups (p=0.698). The distribution of serum CEA levels was significantly higher in the smoking than the non-smoking group (p<105), whereas there was no significant difference in this respect between the non-drinking and drinking groups (p=0.147). A significant increase with age was found both for serum AFP and CEA levels, and the age-dependent reference intervals were calculated. Conclusions The reference intervals for serum AFP and CEA show a slight deviation compared to previously reported reference levels. Distinct reference intervals of serum CEA must be established for smoking and non-smoking populations. In addition, age-dependent reference intervals should be implemented in clinical laboratories.