bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering, Expression, Purification, and Characterization of Stable Clade A/B Recombinant Soluble Heterotrimeric gp140 Proteins
Authors: Sellhorn George , Kraft Zane , Caldwell Zachary , Ellingson Katharine , Mineart Christine , Seaman Michael S. , Montefiori David C. , Lagerquist Eliza , Stamatatos Leonidas 
Published: October 2011

ABSTRACTThe envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is composed of two noncovalently associated subunits: an extracellular subunit (gp120) and a transmembrane subunit (gp41). The functional unit of Env on the surface of infectious virions is a trimer of gp120/gp41 heterodimers. Env is the target of anti-HIV neutralizing antibodies. A considerable effort has been invested in the engineering of recombinant soluble forms of the virion-associated Env trimer as vaccine candidates to elicit anti-HIV neutralizing antibody responses. These soluble constructs contain three gp120 subunits and the extracellular segments of the corresponding gp41 subunits. The individual gp120/gp41 protomers on these soluble trimers are identical in amino acid sequence (homotrimers). Here, we engineered novel soluble trimeric gp140 proteins that are formed by the association of gp140 protomers that differ in amino acid sequence and glycosylation patterns (heterotrimers). Specifically, we engineered soluble heterotrimeric proteins composed of clade A and clade B Env protomers. The clade A gp140 protomers were derived from viruses isolated during acute infection (Q168a2, Q259d2.17, and Q461e2), whereas the clade B gp140 protomers were derived from a virus isolated during chronic infection (SF162). The amino acid sequence divergence between the clade A and the clade B Envs is approximately 24%. Neutralization epitopes in the CD4 binding sites and coreceptor binding sites, as well as the membrane-proximal external region (MPER), were differentially expressed on the heterotrimeric and homotrimeric proteins. The heterotrimeric gp140s elicited broader anti-tier 1 isolate neutralizing antibody responses than did the homotrimeric gp140s.
The Hepatitis B Virus X Protein Elevates Cytosolic Calcium Signals by Modulating Mitochondrial Calcium Uptake
Authors: Yang Bei , Bouchard Michael J. 
Published: October 2011

ABSTRACT
Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduced HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication.
miRNA Expression Profiling Enables Risk Stratification in Archived and Fresh Neuroblastoma Tumor Samples
Authors: De Preter Katleen , Mestdagh Pieter , Vermeulen Joëlle , Zeka Fjoralba , Naranjo Arlene , Bray Isabella , Castel Victoria , Chen Caifu , Drozynska Elzbieta , Eggert Angelika , Hogarty Michael D. , Iżycka-Swieszewska Ewa , London Wendy B. , Noguera Rosa , Piqueras Marta , Bryan Kenneth , Schowe Benjamin , van Sluis Peter , Molenaar Jan J. , Schramm Alexander , Schulte Johannes H. , Stallings Raymond L. , Versteeg Rogier , Laureys Geneviève , Van Roy Nadine , Speleman Frank , Vandesompele Jo 
Published: October 2011

Abstract
Purpose: More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples.
Experimental Design: Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples.
Results: The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P &lt; 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples.
Conclusions: In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material. Clin Cancer Res; 17(24); 7684–92. ©2011 AACR.
ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category
Authors: Metzeler Klaus H. , Becker Heiko , Maharry Kati , Radmacher Michael D. , Kohlschmidt Jessica , Mrózek Krzysztof , Nicolet Deedra , Whitman Susan P. , Wu Yue-Zhong , Schwind Sebastian , Powell Bayard L. , Carter Thomas H. , Wetzler Meir , Moore Joseph O. , Kolitz Jonathan E. , Baer Maria R. , Carroll Andrew J. , Larson Richard A. , Caligiuri Michael A. , Marcucci Guido , Bloomfield Clara D. 
Published: October 2011

Abstract
The associations of mutations in the enhancer of trithorax and polycomb family gene ASXL1 with pretreatment patient characteristics, outcomes, and gene-/microRNA-expression profiles in primary cytogenetically normal acute myeloid leukemia (CN-AML) are unknown. We analyzed 423 adult patients for ASXL1 mutations, other prognostic gene mutations, and gene-/microRNA-expression profiles. ASXL1 mutations were 5 times more common in older (≥ 60 years) patients (16.2%) than those younger than 60 years (3.2%; P < .001). Among older patients, ASXL1 mutations associated with wild-type NPM1 (P < .001), absence of FLT3-internal tandem duplications (P = .002), mutated CEBPA (P = .01), and with inferior complete remission (CR) rate (P = .04), disease-free survival (DFS; P = .03), overall survival (OS; P = .006), and event-free survival (EFS; P = .002). Within the European LeukemiaNet (ELN) genetic categories of older CN-AML, ASXL1 mutations associated with inferior CR rate (P = .02), OS (P < .001), and EFS (P < .001) among ELN Favorable, but not among ELN Intermediate-I patients. Multivariable analyses confirmed associations of ASXL1 mutations with unfavorable CR rate (P = .03), DFS (P < .001), OS (P < .001), and EFS (P < .001) among ELN Favorable patients. We identified an ASXL1 mutation-associated gene-expression signature, but no microRNA-expression signature. This first study of ASXL1 mutations in primary CN-AML demonstrates that ASXL1mutated older patients, particularly within the ELN Favorable group, have unfavorable outcomes and may be candidates for experimental treatment approaches.
BioN∅T: A searchable database of biomedical negated sentences
Authors: Agarwal Shashank , Yu Hong , Kohane Issac 
Published: October 2011

Abstract

Background
Negated biomedical events are often ignored by text-mining applications; however, such events carry scientific significance. We report on the development of BioN∅T, a database of negated sentences that can be used to extract such negated events.

Description
Currently BioN∅T incorporates ≈32 million negated sentences, extracted from over 336 million biomedical sentences from three resources: ≈2 million full-text biomedical articles in Elsevier and the PubMed Central, as well as ≈20 million abstracts in PubMed. We evaluated BioN∅T on three important genetic disorders: autism, Alzheimer's disease and Parkinson's disease, and found that BioN∅T is able to capture negated events that may be ignored by experts.

Conclusions
The BioN∅T database can be a useful resource for biomedical researchers. BioN∅T is freely available at http://bionot.askhermes.org/ In future work, we will develop semantic web related technologies to enrich BioN∅T.
Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus
Authors: Costa Sofia Santos , Falcão Celeste , Viveiros Miguel , Machado Diana , Martins Marta , Melo-Cristino José , Amaral Leonard , Couto Isabel 
Published: October 2011

Abstract

Background
Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones.

Results
Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds.

Conclusions
The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role played by efflux systems in the development of resistance to fluoroquinolones in clinical isolates of S. aureus.
A large sustained endemic outbreak of multiresistant Pseudomonas aeruginosa: a new epidemiological scenario for nosocomial acquisition
Authors: Suarez Cristina , Peña Carmen , Arch Olga , Dominguez M Angeles , Tubau Fe , Juan Carlos , Gavaldá Laura , Sora Mercedes , Oliver Antonio , Pujol Miquel , Ariza Javier 
Published: October 2011

Abstract

Background
Studies of recent hospital outbreaks caused by multiresistant P.aeruginosa (MRPA) have often failed to identify a specific environmental reservoir. We describe an outbreak due to a single clone of multiresistant (MR) Pseudomonas aeruginosa (PA) and evaluate the effectiveness of the surveillance procedures and control measures applied.

Methods
Patients with MRPA isolates were prospectively identified (January 2006-May 2008). A combined surveillance procedure (environmental survey, and active surveillance program in intensive care units [ICUs]) and an infection control strategy (closure of ICU and urology wards for decontamination, strict compliance with cross-transmission prevention protocols, and a program restricting the use of carbapenems in the ICUs) was designed and implemented.

Results
Three hundred and ninety patients were identified. ICU patients were the most numerous group (22%) followed by urology patients (18%). Environmental surveillance found that 3/19 (16%) non-ICU environmental samples and 4/63 (6%) ICU samples were positive for the MRPA clonal strain. In addition, active surveillance found that 19% of patients were fecal carriers of MRPA. Significant changes in the trends of incidence rates were noted after intervention 1 (reinforcement of cleaning procedures): -1.16 cases/1,000 patient-days (95%CI -1.86 to -0.46; p = 0.003) and intervention 2 (extensive decontamination): -1.36 cases/1,000 patient-days (95%CI -1.88 to -0.84; p < 0.001) in urology wards. In addition, restricted use of carbapenems was initiated in ICUs (January 2007), and their administration decreased from 190-170 DDD/1,000 patient-days (October-December 2006) to 40-60 DDD/1,000 patient-days (January-April 2007), with a reduction from 3.1 cases/1,000 patient-days in December 2006 to 2.0 cases/1,000 patient-days in May 2007. The level of initial carbapenem use rose again during 2008, and the incidence of MRPA increased progressively once more.

Conclusions
In the setting of sustained MRPA outbreaks, epidemiological findings suggest that patients may be a reservoir for further environmental contamination and cross-transmission. Although our control program was not successful in ending the outbreak, we think that our experience provides useful guidance for future approaches to this problem.
Sequential thrombosis and bleeding in a woman with a prolonged activated partial thromboplastin time
Authors: Spencer Akpan , Pearce Michael I , Ames Paul RJ 
Published: October 2011

Abstract
Simultaneous or sequential haemorrhage and thrombosis in the presence of a prolonged activated partial thromboplastin time (aPTT) is a rare occurrence: we describe the case a 37 year old lady who developed post-delivery deep vein thrombosis treated with low molecular heparin and warfarin followed a week later by extensive bruising over legs and forearms, a significant drop in haemoglobin and a very prolonged aPTT. Further tests revealed an acquired factor VIII inhibitor at 35 Bethesda Units. We discuss the clinical and laboratory implications and provide a literature review of simultaneous thrombophilia and haemophilia in the presence of a prolonged aPTT.
Dynamic Behavior of Sand/Rubber Mixtures, Part II: Effect of Rubber Content on G/GO-γ-DT Curves and Volumetric Threshold Strain
Authors: Senetakis Kostas , Anastasiadis Anastasios , Pitilakis Kyriazis , Souli Argiro 
Published: October 2011

Abstract
This paper examines the strain-dependent dynamic properties (G/GO-logγ-DT curves) of dry and saturated sand–recycled rubber mixtures in a range of shearing strain amplitudes from (5 × 10−4) % to (6 × 10−1) % using a fixed-free torsional resonant column device. The effect of the rubber content on the pore water pressure buildup and volumetric threshold strain γtv of saturated mixtures, as well as the effect of specimens’ geometry on the experimental data, are also presented and discussed. Based on a comprehensive set of experimental results, a modified hyperbolic model, frequently used in practice, has been proposed. An increase in the rubber content leads to a more linear shape of the G/GO-logγ and DT-logγ curves and a reduction in the pore water pressure buildup. Damping is expressed in terms of DT-DTO, which eliminates the effect of the rubber content and the mean confining pressure. The final aim is to propose appropriate design G/GO-logγ-DT curves for sand–rubber mixtures currently used in practice.
Pilot Evaluation of a Biopsychosocial Integrated Standardized Patient Examination in a Family Medicine Clerkship
Authors: Morley Christopher P. , Flad Jennifer R. , Arthur Melissa , Recker-Hughes Carol , Barzee Kathleen A. , Bailey R. Eugene , Manyon Andrea T. 
Published: October 2011

Objective: A new biopsychosocial Integrated Standardized Patient Examination (ISPE) was implemented to assess communication skills for medical students participating in a family medicine clerkship. Method: Mixed method, multi-level evaluation. Results: Pilot ISPE scores were significantly higher than previous Objective Structured Clinical Examination (OSCE) ( p < .01). Family Physician and Social/Behavioral Scientist rater scores were correlated ( p < .001), and Cronbach's a statistics were acceptable (FM: α = .837; BH: α = .768). Preceptor scores on “relations with professionals” (β = .694, p = .008) significantly predicted ISPE scores, but other clerkship assignment grades were inversely associated with ISPE. Qualitative focus group themes included lack of readiness, divergence in beliefs on scope of physician practice, and focus on grade. Conclusions: This pilot project describes the process and demonstrates the possibility of implementing a complex standardized patient case to assess students' management of complicated primary care patients with medical, psychological, and social issues.
Les femmes qui accouchent sous le secret en France, 2007-2009
Authors: Villeneuve-Gokalp Catherine 
Published: October 2011

Résumé Chaque année en France, 600 à 700?femmes demandent le secret de leur accouchement. Cette étude, réalisée dans 83 des 100?départements, a permis de rassembler des informations administratives sur 835?accouchements secrets ayant eu lieu de juillet 2007 à juin 2009, et de connaître les caractéristiques sociodémographiques ainsi que le contexte de la grossesse de 739?femmes. À la naissance, 10?% des femmes établissent la filiation, 13?% indiquent leur identité dans le dossier de l’enfant et 29?% y laissent un pli fermé qui, si plusieurs conditions sont remplies, permettra à l’enfant de connaître son identité. Trois «?profils?» principaux de femmes ont été définis : les «?jeunes femmes dépendantes de leurs parents?» (25?% des femmes), les «?femmes indépendantes?» (25?%), et les «?femmes seules en situation de précarité?» (15?%). L’accouchement secret n’est donc pas seulement le fait de très jeunes femmes «?abandonnées?» par leur partenaire ou en situation de précarité, même si elles sont effectivement surreprésentées. Dans le délai légal de deux mois après la naissance, 14?% des mères reprennent l’enfant. Les femmes qui reviennent le plus souvent sur leur décision sont celles qui ont dû se séparer de l’enfant sous la pression de contraintes familiales ou économiques. L’accouchement secret étant plus rare chez les femmes qui ont acquis leur indépendance économique ou qui vivent en couple, celles qui y ont recours seraient plus déterminées et se rétracteraient moins souvent.
Quand l'humour contribue à la performance de la relation
Authors: Barth Isabelle 
Published: October 2011

Résumé Les situations où l’humour est mobilisé en entreprises sont très nombreuses : on observe qu’elles sont souvent liées (mais sans obligation) à des moments de tensions et visent à les dénouer : tensions entre individus (situations de conflits), tensions situationnelles (problèmes liés au contexte de travail). Nous faisons l’hypothèse dans cette recherche que l’humour peut contribuer à la performance de la relation, de nature commerciale et/ou managériale (nous limitons notre champ aux services commerciaux). Une observation participante de plusieurs situations en entreprise nous permet de proposer une retranscription et une analyse de ce processus très complexe : double processus à la fois cognitif et affectif qui se met en place entre les partenaires de l’interaction. La littérature mobilisée est empruntée à la linguistique, la sociologie, la psychologie et la littérature car les sciences de gestion se sont encore peu intéressées à ce sujet, qui nous semble pourtant riche de potentiel explicatif et argumentatif dans le champ de la relation. La méthodologie mobilisée est l’approche énonciative issue de la socio-linguistique.
L'être-sujet
Authors: Leymarie Stéphane , Muller Renaud 
Published: October 2011

Résumé Quelle place reconnaît-on au sujet dans la conception des organisations ? On pourrait penser que l’introduction des sciences humaines dans les sciences de gestion ait été l’occasion de le faire. Il convient bien naturellement de s’interroger sur les exigences que suppose la considération de l’individu en tant que sujet dans un contexte organisationnel. Nous prendrons appui sur le travail de la notion de sujet chez Lacan, au carrefour de la tradition philosophique et de son expérience clinique. Cet examen de notion nous amènera à considérer le sujet comme la posture de l’individu qui accède à une représentation de soi au travers de son environnement, et qui, en même temps a besoin de s’en différencier. Le sujet peut ainsi être considéré comme une posture interstitielle entre l’individu et son organisation qui contribue autant à lui donner une image qu’il doit s’en détacher pour exister en propre. Forts de cette définition, nous examinerons comment les conceptions de l’organisation, au regard de la classification théorique en métaphores proposées par Morgan, ménagent un espace à cette posture. Nous constatons l’apport des sciences humaines dans les théories des organisations et du management pour reconnaître le rôle structurant de l’identité. Nous soulignerons toutefois les carences majeures dans la prise en compte des besoins de différenciation entre l’individu et son organisation, le besoin d’une prise de distance avec le miroir organisationnel, l’identité professionnelle. Cette nécessité est à mettre en rapport avec le développement de risques psychosociaux qui témoignent de ce besoin de distanciation.
Comprendre les femmes au foyer, des intermittentes du travail ?
Authors: Dieu Anne-Marie , Delhaye Christine , Cornet Annie 
Published: October 2011

Résumé Il peut sembler étonnant de proposer un article sur les femmes au foyer un numéro spécial consacré à la GRH. En effet, les femmes au foyer ne sont a priori pas concernées par le marché du travail, elles sont d’ailleurs reprises dans les statistiques dans la catégorie des « inactives. » Pourtant, dans le cadre d’une recherche qualitative que nous avons menée pour le compte de la Région Wallonne de Belgique auprès de femmes ayant cessé pendant plus de deux ans de travailler pour des raisons familiales, nous avons pu constater que le rapport au travail et au marché de l’emploi des femmes dites « inactives » est bien plus complexe que ce que les représentations communes laissent apparaître. Les femmes au foyer développent en effet, lors de leur période de vie « au foyer », une série d’activités productives, de service et créatives, qui sortent de la simple sphère familiale et qui contribuent à leur procurer une série de gratifications sociales, psychologiques et symboliques, tout en leur assurant des revenus occasionnels ou plus réguliers. Elles développent un « rapport en pointillé » au monde du travail dont elles ne sont pas toujours conscientes elles-mêmes. Ces activités, des « impensés de la GRH » leur permettent pourtant de développer des compétences transposables sur le marché du travail mais encore trop peu prises en compte par elles-mêmes comme par les employeurs potentiels.