bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Nuclear Export Sequence in the MHC CIITA
Authors: Chiu Emily , Gold Theresa , Fettig Veronica , LeVasseur Michael T. , Cressman Drew E. 
Published: May 2015

Abstract
Initiation of an immune response through expression of MHC class II and related genes is under the control of the CIITA. Normally found in both the cytoplasm and nucleus, CIITA is tightly controlled by a variety of posttranslational modifications as well as interactions with other nuclear and cytoplasmic factors, whereas disruption of this dual subcellular localization impairs CIITA functioning and expression of target genes. Although CIITA has well-defined domains necessary for its nuclear import, the region responsible for the translocation of CIITA from the nucleus has not been characterized. In this study, we identify a leucine-rich motif at residues 717–724 that bears strong homology to known nuclear export sequence (NES) domains. Mutation of this region renders CIITA insensitive to treatment with leptomycin B, an inhibitor of nuclear export, whereas fusion of this domain to a heterologous GFP is sufficient to induce its export to the cytoplasm or cause its retention in the nucleus following leptomycin B treatment. Point mutations of specific leucine residues within the NES disrupt the normal subcellular distribution of the full-length CIITA, impair its ability to interact with the nuclear export factor CRM1, and enhance CIITA-induced gene expression from an MHC class II gene promoter. IFN-γ stimulation of class II genes is further enhanced by inhibiting the nuclear export of endogenous CIITA. Collectively, these data demonstrate the first identification of a specific NES within CIITA and place it among the other protein domains that contribute to the posttranslational regulation of CIITA activity.
A Population Response Analysis Approach To Assign Class II HLA-Epitope Restrictions
Authors: Paul Sinu , Dillon Myles B. C. , Lindestam Arlehamn Cecilia S. , Huang Huang , Davis Mark M. , McKinney Denise M. , Scriba Thomas Jens , Sidney John , Peters Bjoern , Sette Alessandro 
Published: May 2015

Abstract
Identification of the specific HLA locus and allele presenting an epitope for recognition by specific TCRs (HLA restriction) is necessary to fully characterize the immune response to Ags. Experimental determination of HLA restriction is complex and technically challenging. As an alternative, the restricting HLA locus and allele can be inferred by genetic association, using response data in an HLA-typed population. However, simple odds ratio (OR) calculations can be problematic when dealing with large numbers of subjects and Ags, and because the same epitope can be presented by multiple alleles (epitope promiscuity). In this study, we develop a tool, denominated Restrictor Analysis Tool for Epitopes, to extract inferred restriction from HLA class II–typed epitope responses. This automated method infers HLA class II restriction from large datasets of T cell responses in HLA class II–typed subjects by calculating ORs and relative frequencies from simple data tables. The program is validated by: 1) analyzing data of previously determined HLA restrictions; 2) experimentally determining in selected individuals new HLA restrictions using HLA-transfected cell lines; and 3) predicting HLA restriction of particular peptides and showing that corresponding HLA class II tetramers efficiently bind to epitope-specific T cells. We further design a specific iterative algorithm to account for promiscuous recognition by calculation of OR values for combinations of different HLA molecules while incorporating predicted HLA binding affinity. The Restrictor Analysis Tool for Epitopes program streamlines the prediction of HLA class II restriction across multiple T cell epitopes and HLA types.
Immunobiology of Fibrin-Based Engineered Heart Tissue
Authors: Conradi Lenard , Schmidt Stephanie , Neofytou Evgenios , Deuse Tobias , Peters Laura , Eder Alexandra , Hua Xiaoqin , Hansen Arne , Robbins Robert C. , Beygui Ramin E. , Reichenspurner Hermann , Eschenhagen Thomas , Schrepfer Sonja 
Published: May 2015

Abstract

Different tissue-engineering approaches have been developed to induce and promote cardiac regeneration; however, the impact of the immune system and its responses to the various scaffold components of the engineered grafts remains unclear. Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis (Lew) rat heart cells and transplanted onto the left ventricular surface of three different rat strains: syngeneic Lew, allogeneic Brown Norway, and immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed similar degrees of systemic immune activation in the syngeneic and allogeneic groups, whereas no systemic immune response was detectable in the immunodeficient group (p &lt; .001 vs. syngeneic and allogeneic). Histological analysis revealed much higher local infiltration of CD3- and CD68-positive cells in syngeneic and allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and immunofluorescence experiments revealed matrix-directed TH1-based rejection in syngeneic recipients without collateral impairment of heart cell survival. Bioluminescence imaging was used for in vivo longitudinal monitoring of transplanted luciferase-positive EHT constructs. Survival was documented in syngeneic and immunodeficient recipients for a period of up to 110 days after transplant, whereas in the allogeneic setting, graft survival was limited to only 14 ± 1 days. EHT strategies using autologous cells are promising approaches for cardiac repair applications. Although fibrin-based scaffold components elicited an immune response in our studies, syngeneic cells carried in the EHT were relatively unaffected.

Significance
An initial insight into immunological consequences after transplantation of engineered heart tissue was gained through this study. Most important, this study was able to demonstrate cell survival despite rejection of matrix components. Generation of syngeneic human engineered heart tissue, possibly using human induced pluripotent stem cell technology with subsequent directed rejection of matrix components, may be a potential future approach to replace diseased myocardium.
The Clinical Efficacy and Safety of Paclitaxel in Adjuvant Therapy of Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Hua-Qing Chen  , Yi-Si Li  , Si-Chao Huang  , Ya-Hua Lin  , Qiu-Tong Tan  , Shu-Ting Ao  , Jun Xu  , Shao-Hui Cai  
Published: May 2015

Purpose: To systematically review the clinical efficacy and adverse reactions of Paclitaxel for the treatment of mammary cancer. Math: We searched Web of knowledge, PubMed, VIP information and CNKI (to October 2013) on randomised controlled trial about Paclitaxel for the treatment of mammary cancer and retrieved relevant reference and research material by hand. Two authors independently screened document, extracted data and assessed the quality according to inclusion and exclusion criteria, we finally used the software RevMan 5.2 from Cochrane for Meta-analysis. Result: 18 randomized controlled clinical study were brought into our study according to inclusion and exclusion criteria, including 10712 patients. The result of meta-analysis showed that the odds ratios of Paclitaxel for adjunctive therapy [OR = 1.64, 95% CI (1.40, 1.92), P <0.00001] was better than conventional drugs, while the overall survival was no significant difference between Paclitaxel and conventional drugs. The further Subgroup analysis showed that the efficacy of Paclitaxel for adjunctive therapy was better than cyclophosphamide [OR = 1.41, 95%C I (1. 07, 1.85), P =0. 01] and NVB [OR = 2.10, 95% CI (1.33, 3.30), P =0.001]. The adverse reactions analysis results showed the ratio of myelosuppression and alopecia by treated with Paclitaxel was improved, while the occurrence of gastrointestinal reaction rate was decreased. Conclusion: The current evidence showed Paclitaxel was effective for the adjuvant treatment of breast cancer, but the above conclusions still need future expansion of more samples, high quality RCT verify. Keyword: Paclitaxel, Breast cancer, efficacy, adverse reactions, systematically review, Meta-analysis, randomized controlled trial.
Les modèles et la modélisation vus par des enseignants de sciences et technologies du secondaire au Québec
Authors: Roy Patrick , Hasni Abdelkrim 
Published: May 2015

Cet article présente les résultats d’une étude exploratoire menée auprès de cinq enseignants de sciences et technologies (S & T) québécois du secondaire sur l’enseignement des modèles et de la modélisation. Le cadre conceptuel et méthodologique vise l’analyse de leurs pratiques d’enseignement sous l’angle de deux dimensions : la dimension épistémologique (quelles significations attribuent-ils aux modèles et à la démarche de modélisation ?) et la dimension fonctionnelle (pourquoi recourent-ils aux modèles et à la démarche de modélisation en classe ?). L’analyse de leur discours révèle que ceux-ci ont une compréhension partielle de ces objets et de leurs finalités dans l’enseignement et l’apprentissage des sciences et souligne la nécessité d’assurer leur formation continue sur ces questions.
Aeolian process and climatic changes in loess records from the northeastern Tibetan Plateau: Response to global temperature forcing since 30 ka
Authors: Wang Xianyan , Yi Shuangwen , Lu Huayu , Vandenberghe Jef , Han Zhiyong 
Published: May 2015

AbstractThe response of surface processes to global climatic changes since the last glacial is critical to understanding the mechanism of climatic changes on the Tibetan Plateau. In this study, loess from the northeastern Tibetan Plateau (NETP) was closely spaced dated to provide an independent high‐resolution record of dust accumulation processes and millennial‐scale climatic changes. Optically stimulated luminescence ages reveal episodes of rapid dust deposition at approximately 12.3 ka, 16 ka, 21–23 ka, 25–28 ka, and possibly also at 30–33 ka. These episodes are broadly correlated with high‐latitude and marine records cold climatic events, such as the Younger Dryas, Heinrich event 1, and the Last Glacial Maximum. This correlation implies that dust storms in the NETP represent episodic aridification and wind strengthening, which is ascribed to the southward shift of the polar front and the intensification of the Siberian high‐pressure cell that was forced by millennial‐scale cooling in high northern latitudes.
Flood response for the watersheds of the Fernow Experimental Forest in the central Appalachians
Authors: Bates Naomi S. , Smith James A. , Villarini Gabriele 
Published: May 2015

AbstractWe examine flood response of high‐gradient, forested central Appalachian watersheds through analyses of rainfall, streamflow, and piezometer observations from the Fernow Experimental Forest near Parsons, West Virginia. Analyses focus on hydrologic processes that control the “upper tail” of flood distributions. The largest flood peaks in the Fernow are an order of magnitude smaller than record floods in the central Appalachian region (for basins of comparable drainage area). We examine flood distributions in the Fernow using extreme value distributions (Generalized Extreme Value and Generalized Pareto distributions) and compare them to other watersheds in the central Appalachians. To examine the role of antecedent soil moisture on flood response, we installed a network of 415 crest‐stage piezometers on two headwater watersheds (0.30 and 0.14 km2) of the Fernow. Observations show pronounced heterogeneity of subsurface saturation even within the unchannelized swales of headwater watersheds. Shallow perched water tables over large portions of a watershed occur infrequently in forested central Appalachian basins, but may play an important role in extreme flood response. Fernow watersheds include “treated” and control watersheds with stream gaging records extending back to 1951. We examine nonstationarites in flood frequency in the Fernow and show that forest management practices have had relatively minor impacts on flood frequency.
Long‐term deformation driven by small ambient tectonic stresses and strong oscillating tidal within Enceladus with analogy to rock behavior near the San Andreas Fault
Authors: Sleep Norman H. 
Published: May 2015

AbstractStrong tidal stresses brought much of the icy shell of Enceladus into frictional failure at past times of high orbital eccentricity. The frictional behavior of shallow terrestrial rock exposed to repeated episodes of strong seismic waves provides analogy. Frictional failure produces cracks that lower the shear modulus. Seismic regolith develops where the shear modulus increases linearly with depth. Imposed peak strains barely cause frictional failure within self‐organized regolith. With regard to Enceladus, eccentricity could continue to build up in the past since little anelastic strain, and hence tidal dissipation occurred within the self‐organized regolith and within the underlying cold ice. A frictional instability analogous to the formation of weak major faults on the Earth likely occurred once the regolith was many kilometers thick. The effective coefficient of friction dropped to low levels along major faults within the deep cold ice. Tidal dissipation on these faults heated the ice starting thermal convention within the South Polar Terrain. Once thermal buoyancy produced stresses, the oscillating stresses from tides nonlinearly enhanced the rate of tectonic convection. Warm ice that dissipates tides now exists within Enceladus. The eccentricity will likely decrease and the object will then freeze.
Distribution of large‐scale contractional tectonic landforms on Mercury: Implications for the origin of global stresses
Authors: Watters Thomas R. , Selvans Michelle M. , Banks Maria E. , Hauck Steven A. , Becker Kris J. , Robinson Mark S. 
Published: May 2015

AbstractThe surface of Mercury is dominated by contractional tectonic landforms that are evidence of global‐scale crustal deformation. Using MESSENGER orbital high‐incidence angle imaging and topographic data, large‐scale lobate thrust fault scarps have been mapped globally. The spatial distribution and areal density of the contractional landforms are not uniform; concentrations occur in longitudinal bands and between the north and south hemispheres. Their orientations are generally north‐south at low latitude to midlatitude and east‐west at high latitudes. The spatial distribution and distribution of orientations of these large‐scale contractional features suggest that planet‐wide contraction due to interior cooling cannot be the sole source of global stresses. The nonrandom orientations are best explained by a combination of stresses from global contraction and tidal despinning combined with an equator‐to‐pole variation in lithospheric thickness, while the nonuniform areal density of the contractional features may indicate the influence of mantle downwelling or heterogeneities in lithospheric strength.
The upstream‐propagating Alfvénic fluctuations with power law spectra in the upstream region of the Earth's bow shock
Authors: Wang Xin , Tu Chuanyi , Wang Linghua , He Jiansen , Marsch Eckart 
Published: May 2015

AbstractBased on theories, the beam instability induced by shock‐accelerated ions can generate upstream‐propagating Alfvén waves (UPAWs) with a power spectral bump near 0.03 Hz, while the nonlinear wave‐wave interaction favors an inverse cascade to create a power law spectrum. Here we present the first observational evidence for the upstream‐propagating Alfvénic fluctuations (UPAFs) with power law spectra. We utilize a new criterion to identify the upstream‐propagating Alfvénic intervals: the propagation direction is opposite to that of solar wind strahl electron outflow. Besides 35 UPAWs, we find 47 UPAFs with power law spectra, and ∼47% of these UPAFs are associated with energetic ion events (>30 keV). These UPAWs and UPAFs are mostly observed in the slow solar wind. However, their occurrence rate and power behave differently in dependence on the radial distance from the Earth. These results provide new clues on understanding the dynamic equilibrium between the nonlinear inverse cascade and the linear ion beam instability.
Biocatalytic Imine Reduction and Reductive Amination of Ketones
Authors: Schrittwieser Joerg H. , Velikogne Stefan , Kroutil Wolfgang 
Published: May 2015

AbstractChiral amines represent a prominent functional group in pharmaceuticals and agrochemicals and are hence attractive targets for asymmetric synthesis. Since the pharmaceutical industry has identified biocatalysis as a valuable tool for synthesising chiral molecules with high enantiomeric excess and under mild reaction conditions, enzymatic methods for chiral amine synthesis are increasing in importance. Among the strategies available in this context, the asymmetric reduction of imines by NAD(P)H‐dependent enzymes and the related reductive amination of ketones have long remained underrepresented. However, recent years have witnessed an impressive progress in the application of natural or engineered imine‐reducing enzymes, such as imine reductases, opine dehydrogenases, amine dehydrogenases, and artificial metalloenzymes. This review provides a comprehensive overview of biocatalytic imine reduction and reductive amination of ketones, highlighting the natural roles, substrate scopes, structural features, and potential application fields of the involved enzymes.magnified image
Fluorescence‐Based Kinetic Assay for High‐Throughput Discovery and Engineering of Stereoselective ω‐Transaminases
Authors: Scheidt Thomas , Land Henrik , Anderson Mattias , Chen Yujie , Berglund Per , Yi Dong , Fessner Wolf‐Dieter 
Published: May 2015

Abstractω‐Transaminases are a valuable class of enzymes for the production of chiral amines with either (R)‐ or (S)‐configuration in high optical purity and 100% yield by the biocatalytic reductive amination of prochiral ketones. A versatile new assay was developed to quantify ω‐transaminase activity for the kinetic characterization and enantioselectivity typing of novel or engineered enzymes based on the conversion of 1‐(6‐methoxynaphth‐2‐yl)alkylamines. The associated release of the acetonaphthone product can be monitored by the development of its bright fluorescence at 450 nm with very high sensitivity and selectivity. The assay principle can be used to quantify ω‐transaminase catalysis over a very broad range of enzyme activity. Because of its simplicity and low substrate consumption in microtiter plate format the assay seems suitable for liquid screening campaigns with large library sizes in the directed evolution of optimized transaminases. For assay substrates that incorporate structural variations, an efficient modular synthetic route was developed. This includes racemate resolution by lipase‐catalyzed transacylation to furnish enantiomerically pure (R)‐ and (S)‐configured amines. The latter are instrumental for the rapid enantioselectivity typing of ω‐transaminases. This method was used to characterize two novel (S)‐selective taurine‐pyruvate transaminases of the subtype 6a from thermophilic Geobacillus thermodenitrificans and G. thermoleovorans.magnified image
Medical therapy vs surgery for recurrent acute rhinosinusitis
Authors: Costa Milena L. , Psaltis Alkis J. , Nayak Jayakar V. , Hwang Peter H. 
Published: May 2015

BackgroundTreatment indications for recurrent acute rhinosinusitis (RARS) remain poorly defined. We studied outcomes of medical vs surgical treatment of RARS, anatomic variants associated with RARS, and factors predicting crossover from medical to surgical treatment.MethodsA total of 220 RARS patients treated between 2006 and 2014 were retrospectively divided into 3 cohorts: medical only (MED); surgical only (SURG); or medical crossing over into surgical (CROSS). Twenty‐two item Sino‐Nasal Outcome Test (SNOT‐22) scores, modified Lund‐Kennedy endoscopy scores, and prevalence of anatomic variants by computed tomography (CT) were compared. A total of 220 CT scans obtained for non‐sinus indications served as controls. A logistic regression model was used for analysis.ResultsThe mean baseline SNOT‐22 scores for all cohorts were similar (MED = 48, SURG = 49, CROSS = 45, p < 0.0001). The SURG cohort showed greater reduction of SNOT‐22 scores compared to the MED cohort at 3, 6, and 12 months follow‐up (p < 0.0001). The crossover cohort converted to surgery after escalation of SNOT‐22 score by a mean of 15 points (p < 0.03), and showed significant reduction postoperatively (p < 0.0001). Haller cell (odds ratio [OR] 3.9; p < 0.0001), concha bullosa (OR 3.7; p < 0.003), and accessory ostium (OR 2.2; p < 0.01) were more common in the entire RARS group vs controls; however, there were no inter‐cohort differences in prevalence.ConclusionRARS patients can benefit from both medical and surgical treatment strategies, but surgical treatment results in greater symptomatic improvement compared to medical treatment. Patients cross over from medical to surgical treatment when SNOT‐22 scores escalate by a mean of 15 points. Haller cell, concha bullosa, and accessory ostium are associated with RARS but are equally common in medical, surgical, and crossover cohorts.
Sinonasal extramedullary plasmacytoma: a population‐based incidence and survival analysis
Authors: Patel Tapan D. , Vázquez Alejandro , Choudhary Moaz M. , Kam David , Baredes Soly , Eloy Jean Anderson 
Published: May 2015

BackgroundSinonasal extramedullary plasmacytoma (SN‐EMP) is a rare plasma cell neoplasm. Published literature on this tumor largely consists of case reports and case‐series with small sample sizes. This study analyzed population‐based data on SN‐EMP patients to understand demographic and clinical features as well as incidence and survival trends.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was queried for SN‐EMP and other head and neck EMP (HN‐EMP) cases from 1973 to 2011. Cases were analyzed to determine patient demographics, initial treatment modality, and survival outcomes.ResultsOf 778 patients identified with EMP in the head and neck region, 367 patients had SN‐EMP and 411 had other HN‐EMP. There was a strong male predilection found, with a male‐to‐female ratio of 3.65:1 in the SN‐EMP group and 1.87:1 in the other HN‐EMP group. The majority of the patients presented with localized disease in both SN‐EMP (84.4%) and other HN‐EMP (81.0%) groups. The most common treatment modality reported in this database was surgery with adjuvant radiotherapy in both SN‐EMP (46.3%) and other HN‐EMP (38.9%) groups, followed by radiotherapy alone (SN‐EMP: 40.7%; other HN‐EMP: 34.2%). Five‐year and 10‐year disease‐specific survival rates were comparable between SN‐EMP (88.2% and 83.3%, respectively) and other HN‐EMP (90.0% and 87.4%, respectively) (p = 0.6016 and p = 0.4015, respectively).ConclusionThis study analyzed the largest cohort of SN‐EMP patients to date. There was no statistically significant survival advantage found for any 1 particular treatment modality over other treatment modalities in both SN‐EMP and other HN‐EMP.
The Stabilizing Effects in Gold Carbene Complexes
Authors: Nunes dos Santos Comprido Laura , Klein Johannes E. M. N. , Knizia Gerald , Kästner Johannes , Hashmi A. Stephen K. 
Published: May 2015

AbstractBonding and stabilizing effects in gold carbene complexes are investigated by using Kohn–Sham density functional theory (DFT) and the intrinsic bond orbital (IBO) approach. The π‐stabilizing effects of organic substituents at the carbene carbon atom coordinated to the gold atom are evaluated for a series of recently isolated and characterized complexes, as well as intermediates of prototypical 1,6‐enyne cyclization reactions. The results indicate that these effects are of particular importance for gold complexes especially because of the low π‐backbonding contribution from the gold atom.