bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced MCMV Δm157 viral clearance in the absence of TSAd
Authors: Moussa P. , Abrahamsen G. , Fodil N. , Gopalakrishnan R. P. , Mancini M. , Dissen E. , Sæther P. C. , Wiltshire S. A. , Boivin G. A. , Caignard G. , Spurkland A. , Vidal S. M. 
Published: March 2015

AbstractThe T cell specific adapter protein (TSAd) is expressed in activated T cells and NK cells. While TSAd is beginning to emerge as a critical regulator of Lck and Itk activity in T cells, its role in NK cells has not yet been explored. Here we have examined susceptibility to virus infections in a murine model using various viral infection models. We report that TSAd-deficient mice display reduced clearance of murine cytomegalovirus (MCMV) that lack the viral MHC class I homologue m157, which is critical for Ly49H-mediated NK cell recognition of infected cells. In this infection model, NK cells contribute in the early stages of the disease, whereas CD8+ T cells are critical for viral clearance. We found that mice infected with MCMV Δm157 displayed reduced viral clearance in the spleen as well as reduced proliferation in spleen NK cells and CD8+ T cells in the absence of TSAd. Though no other immunophenotype was detected in the infection models tested, these data suggests that in the absence of the Ly49H ligand activation, NK cell and CD8+ T cell responses may be compromised in TSAd-deficient mice.
CASP7 variants modify susceptibility to cervical cancer in Chinesewomen
Authors: Shi Ting-Yan , He Jing , Wang Meng-Yun , Zhu Mei-Ling , Yu Ke-Da , Shao Zhi-Ming , Sun Meng-Hong , Wu Xiaohua , Cheng Xi , Wei Qingyi 
Published: March 2015

AbstractPolymorphisms in Caspase-7 (CASP7) may modulate the programmedcell death and thus contribute to cervical cancer risk. In this case-controlstudy of 1,486 cervical cancer cases and 1,301 controls, we investigated associationsbetween four potentially functional polymorphisms in CASP7 and cervicalcancer risk and evaluated their locus-locus interaction effects on the risk.The genotype-phenotype correlation was performed by a generalized linear regressionmodel. We found that the rs4353229 polymorphism was associated with cervicalcancer risk (under a recessive model: crude OR = 1.20, 95% CI = 1.02–1.40).Compared with the TT genotype, the rs10787498GT genotype was associated withan increased cervical cancer risk (adjusted OR = 1.19, 95% CI = 1.00–1.41).Combination analysis showed that subjects with four putative risk genotypeshad a 1.54-fold increased cancer risk, compared with those who carried threeor less putative risk genotypes. We also observed significant locus-locusjoint effects on the risk, which may be mediated by the polymorphisms regulating CASP7mRNA expression. Subsequent multifactor dimensionality reduction and classificationand regression tree analyses indicated that the CASP7 genotypes mighthave a locus-locus interaction effect that modulated cervical cancer risk.Out data suggest that CASP7 polymorphisms may interact to modify cervicalcancer risk by a possible mechanism of regulating CASP7 mRNA expression.
Beyond EUV lithography: a comparative study of efficient photoresists' performance
Authors: Mojarad Nassir , Gobrecht Jens , Ekinci Yasin 
Published: March 2015

AbstractExtreme ultraviolet (EUV) lithography at 13.5 nm is the main candidate for patterning integrated circuits and reaching sub-10-nm resolution within the next decade. Should photon-based lithography still be used for patterning smaller feature sizes, beyond EUV (BEUV) lithography at 6.x nm wavelength is an option that could potentially meet the rigid demands of the semiconductor industry. We demonstrate simultaneous characterization of the resolution, line-edge roughness and sensitivity of distinct photoresists at BEUV and compare their properties when exposed to EUV under the same conditions. By using interference lithography at these wavelengths, we show the possibility for patterning beyond 22 nm resolution and characterize the impact of using higher energy photons on the line-edge roughness and exposure latitude. We observe high sensitivity of the photoresist performance on its chemical content and compare their overall performance using the Z-parameter criterion. Interestingly, inorganic photoresists have much better performance at BEUV, while organic chemically-amplified photoresists would need serious adaptations for being used at such wavelength. Our results have immediate implications for deeper understanding of the radiation chemistry of novel photoresists at the EUV and soft X-ray spectra.
Genetic variations in sites of affinity between FVIII and LRP1 are not associated with high FVIII levels in venous thromboembolism
Authors: Bittar Luis F. , Siqueira Lucia H. , Orsi Fernanda A. , De Paula Erich V. , Annichino-Bizzacchi Joyce M. 
Published: March 2015

AbstractIncreased factor VIII (FVIII) levels are a prevalent and independent risk factor for venous thromboembolism (VTE). The low density lipoprotein receptor-related protein 1 (LRP1) has been associated with FVIII catabolism. After a median of 10 years of the first thrombotic episode, we evaluated FVIII activity levels in 75 patients with VTE and high FVIII levels and in 74 healthy controls. Subsequently, we evaluated the regions of F8 and LRP1 genes coding sites of affinity between these proteins, with the objective of determining genetic alterations associated with plasma FVIII levels. After a median time of 10 years after the VTE episode, FVIII levels were significantly higher in patients when compared to controls (158.6 IU/dL vs. 125.8 IU/dL; P ≤ 0.001]. Despite the fact that we found 14 genetic variations in F8 and LRP1 genes, no relationship was found between FVIII levels with these variations. We demonstrated a persistent increase of FVIII levels in patients with VTE, but in a much lower magnitude after 10 years when compared to 3-years after the episode. Moreover, we observed no relationship of genetic variations in the gene regions coding affinity sites between LRP1 and FVIII with FVIII levels.
Quantum Interference Induced Photon Blockade in a Coupled Single Quantum Dot-Cavity System
Authors: Tang Jing , Geng Weidong , Xu Xiulai 
Published: March 2015

AbstractWe propose an experimental scheme to implement a strong photon blockade with a single quantum dot coupled to a nanocavity. The photon blockade effect can be tremendously enhanced by driving the cavity and the quantum dot simultaneously with two classical laser fields. This enhancement of photon blockade is ascribed to the quantum interference effect to avoid two-photon excitation of the cavity field. Comparing with Jaynes-Cummings model, the second-order correlation function at zero time delay g(2)(0) in our scheme can be reduced by two orders of magnitude and the system sustains a large intracavity photon number. A red (blue) cavity-light detuning asymmetry for photon quantum statistics with bunching or antibunching characteristics is also observed. The photon blockade effect has a controllable flexibility by tuning the relative phase between the two pumping laser fields and the Rabi coupling strength between the quantum dot and the pumping field. Moreover, the photon blockade scheme based on quantum interference mechanism does not require a strong coupling strength between the cavity and the quantum dot, even with the pure dephasing of the system. This simple proposal provides an effective way for potential applications in solid state quantum computation and quantum information processing.
A novel composite conductive microfiltration membrane and its anti-fouling performance with an external electric field in membrane bioreactors
Authors: Huang Jian , Wang Zhiwei , Zhang Junyao , Zhang Xingran , Ma Jinxing , Wu Zhichao 
Published: March 2015

AbstractMembrane fouling remains an obstacle to wide-spread applications of membrane bioreactors (MBRs) for wastewater treatment and reclamation. Herein, we report a simple method to prepare a composite conductive microfiltration (MF) membrane by introducing a stainless steel mesh into a polymeric MF membrane and to effectively control its fouling by applying an external electric field. Linear sweep voltammetry and electrochemical impedance spectroscopy analyses showed that this conductive membrane had very good electrochemical properties. Batch tests demonstrated its anti-fouling ability in filtration of bovine serum albumin, sodium alginate, humic acid and silicon dioxide particles as model foulants. The fouling rate in continuous-flow MBRs treating wastewater was also decreased by about 50% for this conductive membrane with 2 V/cm electric field compared to the control test during long-term operation. The enhanced electrostatic repulsive force between foulants and membrane, in-situ cleaning by H2O2 generated from oxygen reduction and decreased production of soluble microbial products and extracellular polymeric substances contributed to fouling mitigation in this MBR. The results of this study shed light on the control strategy of membrane fouling for achieving a sustainable operation of MBRs.
CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction
Authors: Tabeling Christoph , Yu Hanpo , Wang Liming , Ranke Hannes , Goldenberg Neil M. , Zabini Diana , Noe Elena , Krauszman Adrienn , Gutbier Birgitt , Yin Jun , Schaefer Michael , Arenz Christoph , Hocke Andreas C. , Suttorp Norbert , Proia Richard L. , Witzenrath Martin , Kuebler Wolfgang M. 
Published: March 2015

Significance
Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism that protects against systemic hypoxemia by redistributing blood flow from poorly to better ventilated areas of the lung, thereby minimizing ventilation-perfusion mismatch. However, in chronic hypoxemia-associated lung disease, HPV contributes to pulmonary hypertension. In this study, we provide novel evidence for a dual role of sphingolipids as important signal mediators in HPV, which critically depends on the presence of functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR). CFTR gene mutations cause CF, which is associated with profound pulmonary ventilation-perfusion mismatches. The present findings propel our current understanding of HPV, establish a previously undescribed mechanism for hypoxemia in CF disease, and identify CFTR as a functional contributor to the pathologic changes in hypoxia-associated pulmonary hypertension.
Combinatorial proteomic analysis of intercellular signaling applied to the CD28 T-cell costimulatory receptor
Authors: Tian Ruijun , Wang Haopeng , Gish Gerald D. , Petsalaki Evangelia , Pasculescu Adrian , Shi Yu , Mollenauer Marianne , Bagshaw Richard D. , Yosef Nir , Hunter Tony , Gingras Anne-Claude , Weiss Arthur , Pawson Tony 
Published: March 2015

Significance
Intracellular signaling during complex cell–cell interactions, such as between immune cells, provides essential cues leading to cell responses. Global characterization of these signaling events is critical for systematically exploring and understanding how they eventually control cell fate. However, proteome-wide characterization of intercellular signaling under physiologically relevant conditions involving multiple interacting receptors during cell–cell interactions remains challenging. We developed an integrated proteomic strategy for quantitatively profiling intercellular-signaling events mediated by protein phosphorylation and protein–protein interaction. We applied this approach to determine the influence of a single receptor-ligand pair during T-cell stimulation by blocking the interaction of the CD28 costimulatory receptor with its ligand. This approach is generally applicable to other transmembrane receptors involved in signaling during complex cell interactions.
The coreceptor CD4 is expressed in distinct nanoclusters and does not colocalize with T-cell receptor and active protein tyrosine kinase p56lck
Authors: Roh Kyung-Ho , Lillemeier Björn F. , Wang Feng , Davis Mark M. 
Published: March 2015

SignificanceImmune cell signaling is heavily associated with the spatial organization of molecules. Here, we examined the nanoscale organization of coreceptor CD4 and its relative spatial localization to the T-cell receptor and the active form of Src kinase p56lck (Lck), using two different superresolution microscopy techniques photoactivated localization microscopy and direct stochastic optical reconstruction microscopy in both living and fixed cells. With concurrent spatial analyses, we show that neither CD4/T-cell antigen receptor nor CD4/active Lck nanoclusters colocalize but only overlap at the interfaces. In activated T cells, the enhanced clustering of each kind results in increased seclusion from each other. Our observations here in molecular resolution may reveal the general roles that are played by nanoscale organization of critical components in immune cell signaling.
Doppler tomography by total variation minimization
Authors: Uemura Makoto , Kato Taichi , Nogami Daisaku , Mennickent Ronald 
Published: March 2015

Abstract
We have developed a new model of Doppler tomography using total variation minimization (DTTVM). This method can reconstruct localized and nonaxisymmetric profiles with sharp edges in the Doppler map. This characteristic is emphasized in the case where input data are small in number. We apply this model to natural data for the dwarf nova WZ Sge in superoutburst and TU Men in quiescence. We confirm that DTTVM can reproduce the observed spectra with high precision. Compared with the models based on the maximum entropy method, our new model can provide Doppler maps that little depend on the hyperparameter and on the presence of the absorption core. We also introduce a cross-validation method of estimating reasonable values of a hyperparameter in the model from the data themselves.
Site Selection Bias in Program Evaluation
*
Authors: Allcott Hunt 
Published: March 2015

Abstract
“Site selection bias” can occur when the probability that a program is adopted or evaluated is correlated with its impacts. I test for site selection bias in the context of the Opower energy conservation programs, using 111 randomized control trials involving 8.6 million households across the United States. Predictions based on rich microdata from the first 10 replications substantially overstate efficacy in the next 101 sites. Several mechanisms caused this positive selection. For example, utilities in more environmentalist areas are more likely to adopt the program, and their customers are more responsive to the treatment. Also, because utilities initially target treatment at higher-usage consumer subpopulations, efficacy drops as the program is later expanded. The results illustrate how program evaluations can still give systematically biased out-of-sample predictions, even after many replications.
Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect
Authors: Mattusch Corinna , Kratzer Stephan , Buerge Martina , Kreuzer Matthias , Engel Tatiana , Kopp Claudia , Biel Martin , Hammelmann Verena , Ying Shui-Wang , Goldstein Peter A. , Kochs Eberhard , Haseneder Rainer , Rammes Gerhard 
Published: March 2015

AbstractAbstract
In thalamocortical slices, xenon evoked hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channel-dependent impairment of neuronal excitability and reduced thalamocortical signal propagation. In HCN2 knockout mice, the sedative effect of xenon was not observed. The data suggest that depression of thalamocortical signal propagation that is in part mediated by HCN2 channels might contribute to the anesthetic action of xenon.

Background:
The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined.

Methods:
The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels.

Results:
Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated I
h current amplitude by 33.4 ± 12.2% (at −133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V
1/2) from −98.8 ± 1.6 to −108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2−/− mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo.

Conclusions:
Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon.
Pancreatic Enzyme Replacement Therapy and Coefficient of Fat Absorption in Children and Adolescents With Cystic Fibrosis
Authors: Woestenenk Janna W. , van der Ent Cornelis K. , Houwen Roderick H.J. 
Published: March 2015

ABSTRACTObjectives:Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the PERT and CFA in a large cohort of pancreatic insufficient pediatric patients with CF.Methods:We retrospectively studied 1719 completed 3‐day dietary food records, including the pancreatic enzyme intake registrations, and 1373 CFA assessments of 224 patients with CF, ages 0–17 years. The clinical characteristics, PERT, expressed as an intake of lipase unit (LU) per gram of fat per day and LU per kilogram per day, and the CFA were described for the group as a whole and separately for those on enteral tube feeding. Cross‐sectional relationship between the CFA and the LU per gram of fat per day and LU per kilogram per day were determined for each year of age. We also addressed the effect of the interventions done in patients with CFA outcomes <85%.Results:The LU per gram of fat per day was relatively stable throughout the age groups, whereas the LU per kilogram per day fell markedly with age. The median CFA in the age group 17 varied between 86% and 91%, however, with a CFA below 85% in 325 of 1373 (24%) of the measurements. No relationship was found between PERT and CFA. The patients with persistent CFA less than 85% had significant lower z scores weight for age and weight for height (P = 0.01) than those with CFA at least 85%.Conclusions:In this study population, no correlation between an enzyme dosage and the degree of fat malabsorption was found; however, a CFA below 85% was found in 24% of the measurements.
A Comprehensive Program to Reduce Rates of Hospital-Acquired Pressure Ulcers in a System of Community Hospitals
Authors: Englebright Jane , Westcott Ruth , McManus Kathryn , Kleja Kacie , Helm Colleen , Korwek Kimberly M. , Perlin Jonathan B. 
Published: March 2015

Objectives
The prevention of hospital-acquired pressure ulcers (PrUs) has significant consequences for patient outcomes and the cost of care. Providers are challenged with evaluating available evidence and best practices, then implementing programs and motivating change in various facility environments.

Methods
In a large system of community hospitals, the Reducing Hospital Acquired–PrUs Program was developed to provide a toolkit of best practices, timely and appropriate data for focusing efforts, and continuous implementation support. Baseline data on PrU rates helped focus efforts on the most vulnerable patients and care situations. Facilities were empowered to use and adapt available resources to meet local needs and to share best practices for implementation across the system. Outcomes were measured by the rate of hospital-acquired PrUs, as gathered from patient discharge records.

Results
The rate of hospital-acquired stage III and IV PrUs decreased 66.3% between 2011 and 2013. Of the 149 participating facilities, 40 (27%) had zero hospital-acquired stage III and IV PrUs and 77 (52%) had a reduction in their PrU rate. Rates of all PrUs documented as present on admission did not change during this period. A comparison of different strategies used by the most successful facilities illustrated the necessity of facility-level flexibility and recognition of local workflows and patient demographics.

Conclusions
Driven by the combination of a repository of evidence-based tools and best practices, readily available data on PrU rates, and local flexibility with processes, the Reducing Hospital Acquired–PrUs Program represents the successful operationalization of improvement in a wide variety of facilities.
Dimensionality and the statistical power of multivariate genome-wide association studies
Authors: Márquez Eladio J. , Houle David 
Published: March 2015

AbstractMutations virtually always have pleiotropic effects, yet most genome-wide association studies (GWAS) analyze effects one trait at a time. In order to investigate the performance of a multivariate approach to GWAS, we simulated scenarios where variation in ad-dimensional phenotype space was caused by a known subset of SNPs. Multivariate analyses of variance were then carried out onktraits, wherekcould be less than, greater than or equal tod. Our results show that power is maximized and false discovery rate (FDR) minimized when the number of traits analyzed,k, matches the true dimensionality of the phenotype being analyzed,d. When true dimensionality is high, the power of a single univariate analysis can be an order of magnitude less than thek=dcase, even when the single trait with the largest genetic variance is chosen for analysis. When traits are added to a study in order of their independent genetic variation, the gains in power from increasingkup todare much larger than the loss in power whenkexceedsd. Simulations that explicitly model linkage disequilibrium (LD) indicate that when SNPs in disequilibrium are subjected to multivariate analysis, the magnitude of the apparent effect induced onto null SNPs by SNPs carrying a true effect weakens askapproachesd, such that the rank of P-values among a set of correlated SNPs becomes an increasingly reliable predictor of true positives. Multivariate GWAS outperform univariate ones under a wide range of conditions, and should become the standard in studies of the inheritance of complex phenotypes.