bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited Effects of Bile Acids and Small Heterodimer Partner on Hepatitis B Virus Biosynthesis
In Vivo
Authors: Reese Vanessa C. , Moore David D. , McLachlan Alan 
Published: December 2011

ABSTRACT

Multiple nuclear receptors, including hepatocyte nuclear factor 4α (HNF4α), retinoid X receptor α (RXRα) plus peroxisome proliferator-activated receptor α (PPARα), RXRα plus farnesoid X receptor α (FXRα), liver receptor homolog 1 (LRH1), and estrogen-related receptors (ERRs), have been shown to support efficient viral biosynthesis in nonhepatoma cells in the absence of additional liver-enriched transcription factors. Although HNF4α has been shown to be critical for the developmental expression of hepatitis B virus (HBV) biosynthesis in the liver, the relative importance of the various nuclear receptors capable of supporting viral transcription and replication in the adult
in vivo
has not been clearly established. To investigate the role of the nuclear receptor FXR and the corepressor small heterodimer partner (SHP) in viral biosynthesis
in vivo
, SHP-expressing and SHP-null HBV transgenic mice were fed a bile acid-supplemented diet. The increased FXR activity and SHP expression levels resulting from bile acid treatment did not greatly modulate HBV RNA and DNA synthesis. Therefore, FXR and SHP appear to play a limited role in modulating HBV biosynthesis, suggesting that alternative nuclear receptors are more critical determinants of viral transcription in the HBV transgenic mouse model of chronic viral infection. These observations suggest that hepatic bile acid levels or therapeutic agents targeting FXR may not greatly modulate viremia during natural infection.
Emergence and Dissemination of a Swine H3N2 Reassortant Influenza Virus with 2009 Pandemic H1N1 Genes in Pigs in China
Authors: Fan Xiaohui , Zhu Huachen , Zhou Boping , Smith David K. , Chen Xinchun , Lam Tommy T.-Y. , Poon Leo L. M. , Peiris Malik , Guan Yi 
Published: December 2011

ABSTRACT
The 2009 pandemic influenza virus (pdm/09) has been frequently introduced to pigs and has reassorted with other swine viruses. Recently, H3N2 reassortants with pdm/09-like internal genes were isolated in Guangxi and Hong Kong, China. Genetic and epidemiological analyses suggest that these viruses have circulated in swine for some time. This is the first evidence that swine reassortant viruses with pdm/09-like genes may have become established in the field, altering the landscape of human and swine influenza.
Serious neck injuries in U19 rugby union players: an audit of admissions to spinal injury units in Great Britain and Ireland
Authors: MacLean James GB , Hutchison James D 
Published: December 2011

ObjectivesTo obtain data regarding admissions of U19 rugby players to spinal injury units in Great Britain and Ireland and to compare this with a recent peak in presentation in Scotland. To assess the current state of data collection and subsequent analysis of serious neck injuries. To analyse the mechanism of injury in this group of at-risk players.DesignRetrospective case series.ParticipantsSpinal injury units in Great Britain and Ireland.Outcome measuresAnnual frequency of serious neck injuries. Analysis of injury types, neurological deficit and mechanism of injury.Results36 Injuries were recorded. 10 Of these occurred in Scotland since 1996 of which six have occurred in the past 4 years. This compared with 14 in Ireland over the same period. 12 Cases were traced in England and Wales since 2000; records were not available before this date. No prospective collation of data is performed by the home unions and inconsistency of data collection exists. The mean age was 16.2 years. 16 Of the 36 admissions had complete neurological loss, 9 had incomplete neurological injury and 11 had cervical column injury without spinal cord damage. The mechanism of injury was tackle in 17 (47%), scrum in 13 (36%), two each due to the maul and collision, and one each due to a kick and a ruck. Some degree of spinal cord injury occurred in 92% of scrum injuries (61% complete) and 53% of tackle injuries (29% complete).ConclusionU19 rugby players continue to sustain serious neck injuries necessitating admission to spinal injury units with a low but persistent frequency. The recent rate of admission in Scotland is disproportionately high when the respective estimated playing populations are considered. While more injuries were sustained in the tackle, spinal cord injury was significantly more common in neck injury sustained in the scrum (p<0.001). No register of catastrophic neck injuries exists despite repeated calls over the past three decades, and a study such as this has not been reported before. Data collection of this serious category of injury is incomplete and very variable across the home unions, as a consequence a large proportion of the serious neck injuries that have occurred in U19 players over the past 14 years have not been analysed. Rigorous data collection and analysis have to be established so that problem areas of the game such as scrum engagement and the tackle can be made safer.
Monitoring performance, pituitary–adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players
Authors: Schmikli Sándor L , de Vries Wouter R , Brink Michel S , Backx Frank JG 
Published: December 2011

ObjectiveTo verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR).DesignA prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones.SettingSporting field and sports medical laboratory.ParticipantsNinety-four young elite soccer players were monitored during the 2006–2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease.Main outcome measuresPerformance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol.ResultsPlayers with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control.ConclusionsPerformance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.
[18F]FLT–PET Imaging Does Not Always “Light Up” Proliferating Tumor Cells
Authors: Zhang Cathy C. , Yan Zhengming , Li Wenlin , Kuszpit Kyle , Painter Cory L. , Zhang Qin , Lappin Patrick B. , Nichols Tim , Lira Maruja E. , Affolter Timothy , Fahey Neeta R. , Cullinane Carleen , Spilker Mary , Zasadny Kenneth , O'Brien Peter , Buckman Dana , Wong Anthony , Christensen James G. 
Published: December 2011

Abstract
Purpose: [18F]FLT (3′-Fluoro-3′ deoxythymidine)–PET imaging was proposed as a tool for measuring in vivo tumor cell proliferation. The aim of this article was to validate the use of [18F]FLT–PET imaging for measuring xenograft proliferation and subsequent monitoring of targeted therapy.
Experimental Design: In exponentially growing xenografts, factors that could impact the outcome of [18F]FLT–PET imaging, such as nucleoside transporters, thymidine kinase 1, the relative contribution of DNA salvage pathway, and the ratio of FLT to thymidine, were evaluated. The [18F]FLT tracer avidity was compared with other proliferation markers.
Results: In a panel of proliferating xenografts, [18F]FLT or [3H]thymidine tracer avidity failed to reflect the tumor growth rate across different tumor types, despite the high expressions of Ki67 and TK1. When FLT was injected at the same dose level as used in the preclinical [18F]FLT–PET imaging, the plasma exposure ratio of FLT to thymidine was approximately 1:200. Thymidine levels in different tumor types seemed to be variable and exhibited an inverse relationship with the FLT tracer avidity. In contrast, high-dose administration of bromdeoxyuridine (BrdUrd; 50 mg/kg) yielded a plasma exposure of more than 4-fold higher than thymidine and leads to a strong correlation between the BrdUrd uptake and the tumor proliferation rate. In FLT tracer-avid models, [18F]FLT–PET imaging as a surrogate biomarker predicted the therapeutic response of CDK4/6 inhibitor PD-0332991.
Conclusions: Tumor thymidine level is one of the factors that impact the correlation between [18F]FLT uptake and tumor cell proliferation. With careful validation, [18F]FLT–PET imaging can be used to monitor antiproliferative therapies in tracer-avid malignancies. Clin Cancer Res; 18(5); 1303–12. ©2011 AACR.
Temperature–Moisture Dependence of the Deep Convective Transition as a Constraint on Entrainment in Climate Models
Authors: Sahany Sandeep , Neelin J. David , Hales Katrina , Neale Richard B. 
Published: December 2011

AbstractProperties of the transition to strong deep convection, as previously observed in satellite precipitation statistics, are analyzed using parcel stability computations and a convective plume velocity equation. A set of alternative entrainment assumptions yields very different characteristics of the deep convection onset boundary (here measured by conditional instability and plume vertical velocity) in a bulk temperature–water vapor thermodynamic plane. In observations the threshold value of column water vapor above which there is a rapid increase in precipitation, referred to as the critical value, increases with temperature, but not as quickly as column saturation, and this can be matched only for cases with sufficiently strong entrainment. This corroborates the earlier hypothesis that entraining plumes can explain this feature seen in observations, and it places bounds on the lower-tropospheric entrainment. Examination of a simple interactive entrainment scheme in which a minimum turbulent entrainment is enhanced by a dynamic entrainment (associated with buoyancy-induced vertical acceleration) shows that the deep convection onset curve is governed by the prescribed minimum entrainment. Results from a 0.5° resolution version of the Community Climate System Model, whose convective parameterization includes substantial entrainment, yield a reasonable match to satellite observations in several respects. Temperature–water vapor dependence is seen to agree well with the plume calculations and with offline simulations performed using the convection scheme of the model. These findings suggest that the convective transition characteristics, including the onset curve in the temperature–water vapor plane, can provide a substantial constraint for entrainment assumptions used in climate model deep convective parameterizations.
Self-Stratification of Tropical Cyclone Outflow. Part II: Implications for Storm Intensification
Authors: Emanuel Kerry 
Published: December 2011

Abstract
Tropical cyclones intensify and are maintained by surface enthalpy fluxes that result from the thermodynamics disequilibrium that exists between the tropical oceans and atmosphere. While this general result has been known for at least a half century, the detailed nature of feedbacks between thermodynamic and dynamic processes in tropical cyclones remains poorly understood. In particular, the spatial relationship between surface fluxes and the radial entropy distribution apparently does not act to amplify the entropy gradient and therefore the surface winds. In previous work, this problem was addressed by accounting for the radial distribution of convective fluxes of entropy out of the boundary layer; this led to the conclusion that a radial gradient of such convective fluxes is necessary for intensification.
Part I showed that the assumption of constant outflow temperature is incorrect and argued that the thermal stratification of the outflow is set by small-scale turbulence that limits the Richardson number. The assumption of Richardson number criticality of the outflow allows one to derive an equation for the variation of outflow temperature with angular momentum; this in turn leads to predictions of vortex structure and intensity that agree well with tropical cyclones simulated using a full-physics axisymmetric model. Here it is shown that the variation of outflow temperature with angular momentum also permits the vortex to intensify with time even in the absence of radial gradients of entrainment into the boundary layer. An equation is derived for the rate of intensity change and compared to simple models and to simulations using a full-physics model.
Ocean Surface Impacts on the Seasonal-Mean Precipitation over the Tropical Indian Ocean
Authors: Chen Mingyue , Wang Wanqiu , Kumar Arun , Wang Hui , Jha Bhaskar 
Published: December 2011

Abstract
This study analyzes factors affecting the predictability of seasonal-mean precipitation over the tropical Indian Ocean. The analysis focuses on the contributions from the local sea surface temperature (SST) forcing in the Indian Ocean, the remote SST forcing related to ENSO in the tropical eastern Pacific, and the role of local air–sea coupling. To understand the impacts of the individual factors, the prediction skill over the tropical Indian Ocean for four model simulations, but with different treatments for the ocean, are compared. The seasonality in precipitation skill, the local precipitation–SST relationship, and prediction skill related to Indian Ocean dipole mode (IODM) are examined. It is found that the importance of the accuracy of local SST and the presence of local air–sea coupling in the Indian Ocean has a strong seasonal dependence. Accurate local SSTs are important during the boreal fall season, whereas the local air–sea coupling is important during the boreal spring. The precipitation skill over the Indian Ocean during boreal winter is primarily from ENSO. However, ENSO impacts are better realized with the inclusion of an interactive ocean. For all four seasons, the simulation without the interannual variations of local SST in the Indian Ocean shows the least precipitation skill and a much weaker seasonality. It is also found that, for the simulation where the global SSTs are relaxed to the observations and hence maintain some level of active air–sea coupling, the observed seasonal cycle of precipitation–SST relationship is reproduced reasonably well. In addition, the analysis also shows that simulations with accurate SST forcing display high precipitation skill during strong IODM events, indicating that IODM SST acts as a forcing for the atmospheric variability.
Les matrones et la réduction de la mortalité maternelle, une contribution au débat
Authors: Petitet Pascale Hancart 
Published: December 2011

Résumé Avec le présupposé que la biomédecine était capable de prévenir la majorité des morts maternelles, l’une des recommandations formulées en 1987 par l’Initiative Maternité Sans Risque était de former des matrones. Ces formations réalisées durant trois décennies sont souvent décrites comme étant un échec. Néanmoins, elles n’ont guère pris en compte l’hétérogénéité des statuts sociaux et pratiques des matrones, ni remis en question certaines méthodes pédagogiques essentiellement didactiques et souvent inappropriées. Ainsi, le débat relatif à la pertinence de ces formations est loin d’être clos. Dans cette perspective, l’ouvrage collectif L’art des matrones revisité. Naissances contemporaines en question dirigé par Pascale Hancart Petitet (2011) rassemble neuf contributions d’auteur(e)s dont l’objectif n’est nullement de remettre en cause les effets bénéfiques de la biomédicalisation de l’accouchement mais de montrer, comment, et pourquoi, se construisent les pratiques des matrones et les discours dont elles sont l’objet actuellement.
Functional heterogeneity of human effector CD8+ T cells
Authors: Takata Hiroshi , Naruto Takuya , Takiguchi Masafumi 
Published: December 2011

AbstractEffector CD8+ T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF-γ and TNF-α. We investigated the difference between CXCR1+ and CXCR1− subsets of human effector CD27−CD28−CD8+ T cells. The subsets expressed cytolytic molecules similarly and exerted substantial cytolytic activity, whereas only the CXCR1− subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1+ subset. These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1− subset and that of pro-apoptotic death-associated protein kinase 1 (DAPK1) in the CXCR1+ subset. The IL-2 producers were more frequently found in the IL-7R+ subset of the CXCR1− effector CD8+ T cells than in the IL-7R− subset. IL-7/IL-7R signaling promoted cell survival only in the CXCR1− subset. The present study has highlighted a novel subset of effector CD8+ T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8+ T cells.
R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming
Authors: Singh Gobind , Hashimoto Daigo , Yan Xiaocai , Helft Julie , Park Patricia J.-Y. , Ma Ge , Qiao Rui F. , Kennedy Colin R. , Chen Shu-Hsia , Merad Miriam , Chan Andrew M. 
Published: December 2011

AbstractR-Ras is a member of the RAS superfamily of small GTP-binding proteins. The physiologic function of R-Ras has not been fully elucidated. We found that R-Ras is expressed by lymphoid and nonlymphoid tissues and drastically up-regulated when bone marrow progenitors are induced to differentiate into dendritic cells (DCs). To address the role of R-Ras in DC functions, we generated a R-Ras-deficient mouse strain. We found that tumors induced in Rras−/− mice formed with shorter latency and attained greater tumor volumes. This finding has prompted the investigation of a role for R-Ras in the immune system. Indeed, Rras−/− mice were impaired in their ability to prime allogeneic and antigen-specific T-cell responses. Rras−/− DCs expressed lower levels of surface MHC class II and CD86 in response to lipopolysaccharide compared with wild-type DCs. This was correlated with a reduced phosphorylation of p38 and Akt. Consistently, R-Ras–GTP level was increased within 10 minutes of lipopolysaccharide stimulation. Furthermore, Rras−/− DCs have attenuated capacity to spread on fibronectin and form stable immunologic synapses with T cells. Altogether, these findings provide the first demonstration of a role for R-Ras in cell-mediated immunity and further expand on the complexity of small G-protein signaling in DCs.
Responses to second-line tyrosine kinase inhibitors are durable: an intention-to-treat analysis in chronic myeloid leukemia patients
Authors: Milojkovic Dragana , Apperley Jane F. , Gerrard Gareth , Ibrahim Amr R. , Szydlo Richard , Bua Marco , Reid Alistair , Rezvani Katayoun , Foroni Letizia , Goldman John , Marin David 
Published: December 2011

AbstractSecond-generation tyrosine kinase inhibitors (2G-TKIs) are effective at inducing complete cytogenetic responses (CCyRs) in approximately half of chronic myeloid leukemia patients treated while still in the chronic phase and after failing imatinib. It is less clear whether these responses are durable. In the present study, we report the clinical outcome of 119 patients who received a 2G-TKI as second-line treatment while still in the chronic phase. In an intention-to-treat analysis, the 4-year probabilities of overall and event-free survival were 81.9% and 35.3%, respectively. Sixty-two patients discontinued the initial 2G-TKI because of resistance or intolerance. To further explore the durability of cytogenetic responses, irrespective of the need for a third-line TKI, we used the concept of “current CCyR-survival” (c-CCyRS). The c-CCyRS at 4 years was 54.4%. After introduction of a 2G-TKI, 77 patients had a 3-month BCR-ABL1/ABL1 transcript ratio of ≤ 10% and had significantly superior overall survival (91.3% vs 72.1%, P = .02), event-free survival (49.3% vs 13.0%, P < .001), and c-CCyRS (67.2% vs 11.2%, P = .0001) compared with the 33 patients with ratios > 10%. The 3-month molecular response was the only independent predictor for overall survival. Using an intention-to-treat analysis, we have shown that the responses to second-line therapies are durable. Patients destined to fare poorly can be identified early during therapy.
A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes
Authors: Doherty Kathleen M , Nakka Priyanka , King Bracken M , Rhee Soo-Yon , Holmes Susan P , Shafer Robert W , Radhakrishnan Mala L 
Published: December 2011

AbstractBackgroundGreat strides have been made in the effective treatment of HIV-1 with the development of second-generation protease inhibitors (PIs) that are effective against historically multi-PI-resistant HIV-1 variants. Nevertheless, mutation patterns that confer decreasing susceptibility to available PIs continue to arise within the population. Understanding the phenotypic and genotypic patterns responsible for multi-PI resistance is necessary for developing PIs that are active against clinically-relevant PI-resistant HIV-1 variants.ResultsIn this work, we use globally optimal integer programming-based clustering techniques to elucidate multi-PI phenotypic resistance patterns using a data set of 398 HIV-1 protease sequences that have each been phenotyped for susceptibility toward the nine clinically-approved HIV-1 PIs. We validate the information content of the clusters by evaluating their ability to predict the level of decreased susceptibility to each of the available PIs using a cross validation procedure. We demonstrate the finding that as a result of phenotypic cross resistance, the considered clinical HIV-1 protease isolates are confined to ~6% or less of the clinically-relevant phenotypic space. Clustering and feature selection methods are used to find representative sequences and mutations for major resistance phenotypes to elucidate their genotypic signatures. We show that phenotypic similarity does not imply genotypic similarity, that different PI-resistance mutation patterns can give rise to HIV-1 isolates with similar phenotypic profiles.ConclusionRather than characterizing HIV-1 susceptibility toward each PI individually, our study offers a unique perspective on the phenomenon of PI class resistance by uncovering major multidrug-resistant phenotypic patterns and their often diverse genotypic determinants, providing a methodology that can be applied to understand clinically-relevant phenotypic patterns to aid in the design of novel inhibitors that target other rapidly evolving molecular targets as well.