bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Large Groove Found in the gH/gL Structure Is an Important Functional Domain for Epstein-Barr Virus Fusion
Authors: Chen Jia , Jardetzky Theodore S. , Longnecker Richard 
Published: January 2013

ABSTRACT
Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins—gB, the gH/gL complex, and gp42—and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells.
Reevaluation of the Requirement for TIP47 in Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Incorporation
Authors: Checkley Mary Ann , Luttge Benjamin G. , Mercredi Peter Y. , Kyere Sampson K. , Donlan Justin , Murakami Tsutomu , Summers Michael F. , Cocklin Simon , Freed Eric O. 
Published: January 2013

ABSTRACTIncorporation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into assembling particles is crucial for virion infectivity. Genetic and biochemical data indicate that the matrix (MA) domain of Gag and the cytoplasmic tail of the transmembrane glycoprotein gp41 play an important role in coordinating Env incorporation; however, the molecular mechanism and possible role of host factors in this process remain to be defined. Recent studies suggested that Env incorporation is mediated by interactions between matrix and tail-interacting protein of 47 kDa (TIP47; also known as perilipin-3 and mannose-6-phosphate receptor-binding protein 1), a member of the perilipin, adipophilin, TIP47 (PAT) family of proteins implicated in protein sorting and lipid droplet biogenesis. We have confirmed by nuclear magnetic resonance spectroscopy titration experiments and surface plasmon resonance that MA binds TIP47. We also reevaluated the role of TIP47 in HIV-1 Env incorporation in HeLa cells and in the Jurkat T-cell line. In HeLa cells, TIP47 overexpression or RNA interference (RNAi)-mediated depletion had no significant effect on HIV-1 Env incorporation, virus release, or particle infectivity. Similarly, depletion of TIP47 in Jurkat cells did not impair HIV-1 Env incorporation, virus release, infectivity, or replication. Our results thus do not support a role for TIP47 in HIV-1 Env incorporation or virion infectivity.
The impact of the built environment on health across the life course: design of a cross-sectional data linkage study
Authors: Villanueva Karen , Pereira Gavin , Knuiman Matthew , Bull Fiona , Wood Lisa , Christian Hayley , Foster Sarah , Boruff Bryan J , Beesley Bridget , Hickey Sharyn , Joyce Sarah , Nathan Andrea , Saarloos Dick , Giles-Corti Billie 
Published: January 2013

IntroductionThe built environment is increasingly recognised as being associated with health outcomes. Relationships between the built environment and health differ among age groups, especially between children and adults, but also between younger, mid-age and older adults. Yet few address differences across life stage groups within a single population study. Moreover, existing research mostly focuses on physical activity behaviours, with few studyingobjectiveclinical and mental health outcomes. The Life Course Built Environment and Health (LCBEH) project explores the impact of the built environment on self-reported and objectively measured health outcomes in a random sample of people across the life course.Methods and analysisThis cross-sectional data linkage study involves 15 954 children (0–15 years), young adults (16–24 years), adults (25–64 years) and older adults (65+years) from the Perth metropolitan region who completed the Health and Wellbeing Surveillance System survey administered by the Department of Health of Western Australia from 2003 to 2009. Survey data were linked to Western Australia's (WA) Hospital Morbidity Database System (hospital admission) and Mental Health Information System (mental health system outpatient) data. Participants’ residential address was geocoded and features of their ‘neighbourhood’ were measured using Geographic Information Systems software. Associations between the built environment and self-reported and clinical health outcomes will be explored across varying geographic scales and life stages.Ethics and disseminationThe University of Western Australia's Human Research Ethics Committee and the Department of Health of Western Australia approved the study protocol (#2010/1). Findings will be published in peer-reviewed journals and presented at local, national and international conferences, thus contributing to the evidence base informing the design of healthy neighbourhoods for all residents.
Human Carboxylesterase-2 Hydrolyzes the Prodrug of Gemcitabine (LY2334737) and Confers Prodrug Sensitivity to Cancer Cells
Authors: Pratt Susan E. , Durland-Busbice Sara , Shepard Robert L. , Heinz-Taheny Kathleen , Iversen Philip W. , Dantzig Anne H. 
Published: January 2013

Abstract
Purpose: The oral prodrug of gemcitabine LY2334737 is cleaved systemically to gemcitabine; the mechanism responsible for hydrolysis is unknown. LY2334737 cytotoxicity was tested in the NCI-60 panel; mining of microarray expression data identified carboxylesterase (CES) as a top hydrolase candidate. Studies examined whether CES is responsible for hydrolysis and whether cellular CES expression confers prodrug sensitivity.
Experimental Design: Human recombinant CES isozymes were assayed for LY2334737 hydrolysis. Stable CES-overexpressing HCT-116 transfectants and a SK-OV-3 knockdown were prepared. Cell lines were tested for drug sensitivity and CES expression by quantitative real time-PCR (qRT-PCR), Western blotting, and immunohistochemical staining. Bystander cytotoxicity studies were conducted with GFP-tagged PC-3 cells as the reporter cell line. Therapeutic response of the HCT-116 transfectants was evaluated in xenografts.
Results: Of 3 human CES isozymes tested, only CES2 hydrolyzed LY2334737. Five cell lines that express CES2 responded to LY2334737 treatment. LY2334737 was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells. The drug response of CES2-transfected HCT-116 cells correlated with CES2 expression level. Bystander studies showed statistically greater PC-3–GFP growth inhibition by LY2334737 when cells were cocultured with CES2 and not mock transfectants. Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days showed greater tumor growth inhibition of CES2 transfectant than the mock transfectant (P ≤ 0.001).
Conclusions: CES2 is responsible for the slow hydrolysis of LY2334737. Because intact prodrug circulates at high plasma levels after oral LY2334737 administration, improved response rates may be observed by tailoring LY2334737 treatment to patients with CES2 tumor expression. Clin Cancer Res; 19(5); 1159–68. ©2012 AACR.
Long-Term Simulations of Thermally Driven Flows and Orographic Convection at Convection-Parameterizing and Cloud-Resolving Resolutions
Authors: Langhans Wolfgang , Schmidli Juerg , Fuhrer Oliver , Bieri Susanne , Schär Christoph 
Published: January 2013

AbstractThe purpose of this paper is to validate the representation of topographic flows and moist convection over the European Alps in a convection-parameterizing simulation (CPM; Δx = 6.6 km) and two cloud-resolving simulations (CRM; Δx = 1.1 and 2.2 km). All simulations and further sensitivity experiments are validated against a large set of observations for an 18-day fair-weather summer period. The episode considered is characterized by pronounced plain–valley pressure gradients, strong daytime upvalley flows, and weak nighttime down-valley flows. In addition, convective precipitation is recorded during the late afternoon and is preceded by a phase of shallow convection. The observed transition from shallow to deep convection occurs within a 3-h period. The results indicate good agreement between both CRMs and the observed diurnal evolution in terms of near-surface winds, cloud formation, and precipitation. The differences between the two CRMs are surprisingly small. In contrast, the CPM produces too-early peaks of cloud cover and precipitation that are due to a too-early activation of deep convection. Detailed sensitivity experiments show that the convection scheme, rather than the underresolved small-scale topography, is responsible for the poor performance of the CPM. In addition, observations and simulations show that late-morning mass convergence does not correlate with afternoon precipitation. Rather, it is found that enhanced convective activity is related to increased conditional instability.
Intralesional Injection versus Mouth Rinse of Triamcinolone Acetonide in Oral Lichen Planus
Authors: Lee Young Chan , Shin Seung Youp , Kim Sung Wan , Eun Young Gyu 
Published: January 2013

ObjectiveTo compare the efficacy, relapse, and adverse effects between intralesional injection and mouth rinse of triamcinolone acetonide (TA) in patients with oral lichen planus (OLP).Study DesignA randomized controlled study.SettingCollege medical center.Subjects and MethodsForty consecutive patients, who had been diagnosed with OLP, were recruited. Participants were randomly divided into 2 groups using intralesional injection or mouth rinse of TA. The severity of pain and burning sensation on a 10‐cm visual analog scale (VAS) and the Oral Health Impact Profile–14 (OHIP‐14) were assessed at weeks 0, 1, 2, 3, 4, and 6. The signs of OLP were quantified using a special scoring system for OLP. The rate of relapse and the adverse effects were compared between both groups.ResultsThe VAS scores for pain and burning mouth sensation and objective scoring for OLP were significantly improved at 1, 2, 3, 4, and 6 weeks in both groups. The changes in the VAS for burning mouth sensation, OHIP‐14, and objective scoring for OLP were similar between both groups. The change in the VAS for pain from baseline to week 1 in the intralesional injection group was significantly higher than in the mouth rinse group. The rate of adverse effects was significantly higher in the mouth rinse group than in the intralesional injection group (44.4% vs 5.0%).ConclusionThe efficacies of both treatments were similar. The rate of adverse effects was significantly lower for intralesional injection of TA than mouth rinse of TA.
Preoperative MRI Underestimates Articular Cartilage Defect Size Compared With Findings at Arthroscopic Knee Surgery
Authors: Campbell Andrew B. , Knopp Michael V. , Kolovich Gregory P. , Wei Wendo , Jia Guang , Siston Robert A. , Flanigan David C. 
Published: January 2013

Background: Magnetic resonance imaging (MRI) is widely used as a preoperative tool to estimate the size of articular cartilage defects to optimize treatment selection. However, the reliability of MRI sizing of cartilage defects is not well understood. Hypothesis/Purpose: The purpose of this investigation was to compare the size of knee articular cartilage defects on MRI to arthroscopic visualization after debridement. It was hypothesized that MRI sizing would produce measurements that were no different than those made during arthroscopic knee surgery. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Seventy-seven patients (age [mean ± SD], 38 ± 10.7 years) who met inclusion criteria underwent preoperative knee MRI of at least 1.5 T within 1 year of arthroscopic knee surgery for a high-grade cartilage defect. Postdebridement defect sizes were obtained from intraoperative surgery notes and compared with retrospective MRI estimates. Results: Ninety-two total cartilage defects were analyzed with an average of 1.2 high-grade defects per knee and average postdebridement defect area of 2.99 cm2 per lesion (95% CI, 1.63-2.26 cm2). Preoperative MRI analysis estimated a lesion area that was an average of 1.04 cm2 smaller (95% CI, 0.70-1.39 cm2; P < .0001). In 74% of the lesions analyzed, defect size was larger on arthroscopic visualization than was estimated by MRI sizing. On average, MRI underestimated the defect area by 70% compared with arthroscopic visualization. Conclusion: Magnetic resonance imaging underestimates the size of articular cartilage defects compared with final postdebridement size as measured during arthroscopic knee surgery. Thus, before arthroscopic surgery, orthopaedic surgeons should consider treatment strategies that are appropriate for a larger defect than predicted by preoperative MRI.
Curing behavior and dielectric properties of amino-functionalized polyhedral oligomeric silsesquioxane/cyanate ester resin hybrids
Authors: Zhang Zengping , Liang Guozheng , Wang Xiaolei , Adhikari Sanjeev , Pei Jianzhong 
Published: January 2013

In order to improve the dielectric and overall properties of cyanate ester (CE) resin, octa(aminopropyl)silsesquioxane (POSS-NH2) was used to modify CE. A series of POSS-NH2/CE hybrids containing different contents of polyhedral oligomeric silsesquioxane (POSS) were elaborated by melt casting and then curing. The curing kinetics and reaction mechanisms of the resin systems were studied using Fourier-transform infrared (FT-IR). Dielectric properties, thermal stability, and hot/wet resistance of the hybrids have been investigated. FT-IR results show that both temperature and POSS content may influence the curing reaction of CE. POSS-NH2 mainly displays the catalytic effect at higher temperature (220°C). Dielectric results indicate that NC1 containing 1 wt% of POSS displays not only the lowest dielectric constant but also the lowest dielectric loss. The increase in POSS content leads to significant increase in glass transition temperature ( Tg) at lower POSS content (≤5 wt%). However, further increase in POSS content (>5 wt%) does not lead to great increase in Tg. Besides, all the POSS-NH2/CE hybrids show lower water absorption than that of CE.
Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis
Authors: Bozzali M , Spanò B , Parker GJM , Giulietti G , Castelli M , Basile B , Rossi S , Serra L , Magnani G , Nocentini U , Caltagirone C , Centonze D , Cercignani M 
Published: January 2013

Background: Brain disconnection plays a major role in determining cognitive disabilities in multiple sclerosis (MS). We recently developed a novel diffusion-weighted magnetic resonance imaging (DW-MRI) tractography approach, namely anatomical connectivitity mapping (ACM), that quantifies structural brain connectivity. Objective: Use of ACM to assess structural connectivity modifications in MS brains and ascertain their relationship with the patients’ Paced-Auditory-Serial-Addition-Test (PASAT) scores. Methods: Relapsing–remitting MS (RRMS) patients ( n = 25) and controls ( n = 25) underwent MRI at 3T, including conventional images, T1-weighted volumes and DW-MRI. Volumetric scans were coregistered to fractional anisotropy (FA) images, to obtain parenchymal FA maps for both white and grey matter. We initiated probabilistic tractography from all parenchymal voxels, obtaining ACM maps by counting the number of streamlines passing through each voxel, then normalizing by the total number of streamlines initiated. The ACM maps were transformed into standard space, for statistical use. Results: RRMS patients had reduced grey matter volume and FA, consistent with previous literature. Also, we showed reduced ACM in the thalamus and in the head of the caudate nucleus, bilaterally. In our RRMS patients, ACM was associated with PASAT scores in the corpus callosum, right hippocampus and cerebellum. Conclusions: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.
Image-Guided Techniques Improve the Short-Term Outcome of Autologous Osteochondral Cartilage Repair Surgeries
Authors: Kunz Manuela , Devlin Steven M. , Hurtig Mark B. , Waldman Stephen D. , Rudan John F. , Bardana Davide D. , Stewart A. James 
Published: January 2013

Objective: Autologous osteochondral cartilage repair is a valuable reconstruction option for cartilage defects, but the accuracy to harvest and deliver osteochondral grafts remains problematic. We investigated whether image-guided methods (optically guided and template guided) can improve the outcome of these procedures. Design: Fifteen sheep were operated to create traumatic chondral injuries in each knee. After 4 months, the chondral defect in one knee was repaired using (a) conventional approach, (b) optically guided method, or (c) template-guided method. For both image-guided groups, harvest and delivery sites were preoperatively planned using custom-made software. During optically guided surgery, instrument position and orientation were tracked and superimposed onto the surgical plan. For the template-guided group, plastic templates were manufactured to allow an exact fit between template and the joint anatomy. Cylindrical holes within the template guided surgical tools according to the plan. Three months postsurgery, both knees were harvested and computed tomography scans were used to compare the reconstructed versus the native pre-injury joint surfaces. For each repaired defect, macroscopic (International Cartilage Repair Society [ICRS]) and histological repair (ICRS II) scores were assessed. Results: Three months after repair surgery, both image-guided surgical approaches resulted in significantly better histology scores compared with the conventional approach (improvement by 55%, P < 0.02). Interestingly, there were no significant differences found in cartilage surface reconstruction and macroscopic scores between the image-guided and the conventional surgeries.
On Subregional Analysis of Cartilage Loss from Knee MRI
Authors: Jørgensen Dan R. , Lillholm Martin , Genant Harry K. , Dam Erik B. 
Published: January 2013

Objective: Understanding how knee cartilage is affected by osteoarthritis (OA) is critical in the development of sensitive biomarkers that may be used as surrogate endpoints in clinical trials. The objective of this study was to analyze longitudinal changes in cartilage thickness using detailed change maps and to examine if current methods for subregional analysis are able to capture the underlying cartilage changes. Materials and Methods: MRI images of 267 knees from 135 participants were acquired at baseline and 21-month follow-up and processed using a fully automatic framework for cartilage segmentation and quantification. The framework provides an anatomical coordinate system that allows for direct comparison across cartilage thickness maps. The reproducibility of this method was evaluated on 37 scan–rescan image pairs. Results: In OA knees, an annualized thickness loss of 3.7% was observed in the medial femoral cartilage plate (MF) whereas subregional measurements varied between −9.0% (loss) and 1.6%. The largest changes were observed in the posterior part of the MF. In the medial tibial cartilage plate (MT), a thickness increase of 0.4% was observed whereas subregional measurements varied between −0.8% (loss) and 1.6%. In addition, notable differences in the patterns of cartilage change were observed between genders. Conclusions: This study indicated that the spatial changes, although highly heterogeneous, showed distinct patterns of cartilage thinning and cartilage thickening in both the MF and the MT. These patterns were not accurately reflected when thickness changes were averaged over large, predefined subregions as defined in current methods for subregional analysis.
A highly conserved sequence associated with the HIV gp41 loop region is an immunomodulator of antigen-specific T cells in mice
Authors: Ashkenazi Avraham , Faingold Omri , Kaushansky Nathali , Ben-Nun Avraham , Shai Yechiel 
Published: January 2013

Key PointsA motif associated with the gp41 loop region of HIV interacts with the T-cell receptor complex and inactivates antigen-specific T cells.
SRAdb: query and use public next-generation sequencing data from within R
Authors: Zhu Yuelin , Stephens Robert M , Meltzer Paul S , Davis Sean R 
Published: January 2013

Abstract

Background
The Sequence Read Archive (SRA) is the largest public repository of sequencing data from the next generation of sequencing platforms including Illumina (Genome Analyzer, HiSeq, MiSeq, .etc), Roche 454 GS System, Applied Biosystems SOLiD System, Helicos Heliscope, PacBio RS, and others.

Results
SRAdb is an attempt to make queries of the metadata associated with SRA submission, study, sample, experiment and run more robust and precise, and make access to sequencing data in the SRA easier. We have parsed all the SRA metadata into a SQLite database that is routinely updated and can be easily distributed. The SRAdb R/Bioconductor package then utilizes this SQLite database for querying and accessing metadata. Full text search functionality makes querying metadata very flexible and powerful. Fastq files associated with query results can be downloaded easily for local analysis. The package also includes an interface from R to a popular genome browser, the Integrated Genomics Viewer.

Conclusions
SRAdb Bioconductor package provides a convenient and integrated framework to query and access SRA metadata quickly and powerfully from within R.
Endoscopic large-balloon dilation alone versus endoscopic sphincterotomy plus large-balloon dilation for the treatment of large bile duct stones
Authors: Hwang Jae Chul , Kim Jin Hong , Lim Sun Gyo , Kim Soon Sun , Shin Sung Jae , Lee Kee Myung , Yoo Byung Moo 
Published: January 2013

Abstract

Background
Endoscopic sphincterotomy (EST) combined with large-balloon dilation (LBD) has been proposed as an alternative to manage large bile duct stones. However, recent reports indicate that LBD without EST may be safe and effective in this setting.

Methods
One hundred thirty-one patients with large common bile duct (CBD) stones 12 mm in size or larger underwent LBD alone (n = 62) or EST plus LBD (n = 69) for lithotripsy. The therapeutic outcome and complications were reviewed and compared.

Results
There were no differences between the two groups with regard to age, size and number of stones, or bile duct diameter. The LBD alone group (mean age, 70.4 years) and the EST plus LBD group (mean age, 68.2 years) had similar outcomes in terms of overall successful stone removal (96.8% vs. 95.7%, P = 0.738) and complete stone removal without the need for mechanical lithotripsy (80.6% vs. 73.9%, P = 0.360). Complications in the LBD alone and EST plus LBD groups were as follows: pancreatitis (6.5% vs. 4.3%, P = 0.593), impaction of basket and stone (0% vs. 1.4%, P = 0.341), and perforation (0% vs. 1.4%, P = 0.341).

Conclusions
LBD alone may be a simple, safe, and effective alternative to EST plus LBD in relatively aged patients with large CBD stones, and it can simplify the procedure compared with EST plus LBD.