bluuebunny/crossref_metadata_2025_split huggingface dataset:
Water exchange between the continental shelf and the cavity beneath Nioghalvfjerdsbræ (79 North Glacier)
Authors: Wilson N. J. , Straneo F. 
Published: August 2015

AbstractThe mass loss at Nioghalvfjerdsbræ is primarily due to rapid submarine melting. Ocean data obtained from beneath the Nioghalvfjerdsbræ ice tongue show that melting is driven by the presence of warm (1°C) Atlantic Intermediate Water (AIW). A sill prevents AIW from entering the cavity from Dijmphna Sund, requiring that it flow into the cavity via bathymetric channels to the south at a pinned ice front. Comparison of water properties from the cavity, Dijmphna Sund, and the continental shelf support this conclusion. Overturning circulation rates inferred from observed melt rates and cavity stratification suggest an exchange flow between the cavity and the continental shelf of 38mSv, sufficient to flush cavity waters in under 1 year. These results place upper bounds on the timescales of external variability that can be transmitted to the glacier via the ice tongue cavity.
Generation of large postinjection‐induced seismic events by backflow from dead‐end faults and fractures
Authors: McClure Mark W. 
Published: August 2015

AbstractInduced seismicity is common during hydraulic stimulation in fractured crystalline rock. Fluid injection pressurizes preexisting fractures, triggering slip and seismicity. Often, the largest induced events occur after the end of injection, which complicates efforts to manage seismic risk. In this study, a three‐dimensional discrete fracture network simulator that couples fluid flow with earthquake simulation was used to investigate a novel hypothesis for why large postinjection seismic events occur. Fractures that form dead‐end pathways differentially pressurize during injection. After injection is stopped, fluid backflows through the well from the dead‐end fractures into larger fractures, inducing additional seismicity and potentially causing events larger than occurred during injection. Our simulations indicate that flowing fluid back to the surface immediately after injection could mitigate this effect and reduce postinjection seismicity.
Seasonal drought predictability and forecast skill over China
Authors: Ma Feng , Yuan Xing , Ye Aizhong 
Published: August 2015

AbstractUnder a changing environment, seasonal droughts have been exacerbated with devastating impacts. However, the understanding of drought mechanism and predictability is limited. Based on the hindcasts from multiple climate models, the predictability and forecast skill for drought over China are investigated. The 3 month standardized precipitation index is used as the drought index, and the predictability is quantified by using a perfect model assumption. Ensemble hindcasts from multiple climate models are assessed individually, and the grand multimodel ensemble is also evaluated. Drought forecast skill for model ensemble mean is higher than individual ensemble members, and North American Multimodel Ensemble grand ensemble performs the best. Predictability is higher than forecast skill, indicating the room for improving drought forecast. Drought predictability and forecast skill are positively correlated in general, but they vary depending on seasons, regions, and forecast leads. Higher drought predictability and forecast skill are found over regimes where ENSO has significant impact. For the ENSO‐affected regimes, both drought predictability and forecast skill in ENSO years are higher than that in neutral years. This study suggests that predictability not only provides a measure for selecting climate models for ensemble drought forecast in ENSO‐affected regimes but also serves as an indicator for forecast skill especially when in situ and/or remote sensing measurements for the hindcast verifications are considered unreliable.
The influence of marine microbial activities on aerosol production: A laboratory mesocosm study
Authors: Alpert Peter A. , Kilthau Wendy P. , Bothe Dylan W. , Radway JoAnn C. , Aller Josephine Y. , Knopf Daniel A. 
Published: August 2015

AbstractThe oceans cover most of the Earth's surface, contain nearly half the total global primary biomass productivity, and are a major source of atmospheric aerosol particles. Here we experimentally investigate links between biological activity in seawater and sea spray aerosol (SSA) flux, a relationship of potential significance for organic aerosol loading and cloud formation over the oceans and thus for climate globally. Bubbles were generated in laboratory mesocosm experiments either by recirculating impinging water jets or glass frits. Experiments were conducted with Atlantic Ocean seawater collected off the eastern end of Long Island, NY, and with artificial seawater containing cultures of bacteria and phytoplankton Thalassiosira pseudonana, Emiliania huxleyi, and Nannochloris atomus. Changes in SSA size distributions occurred during all phases of bacterial and phytoplankton growth, as characterized by cell concentrations, dissolved organic carbon, total particulate carbon, and transparent exopolymer particles (gel‐forming polysaccharides representing a major component of biogenic exudate material). Over a 2 week growth period, SSA particle concentrations increased by a factor of less than 2 when only bacteria were present and by a factor of about 3 when bacteria and phytoplankton were present. Production of jet‐generated SSA particles of diameter less than 200 nm increased with time, while production of all particle diameters increased with time when frits were used. The implications of a marine biological activity dependent SSA flux are discussed.
Isolation of Undifferentiated Female Germline Cells from Adult Drosophila Ovaries
Authors: Lim Robyn Su May , Osato Motomi , Kai Toshie 
Published: August 2015

AbstractThis unit describes a method for isolating undifferentiated, stem cell–like germline cells from adult Drosophila ovaries. Here, we demonstrate that this population of cells can be effectively purified from hand‐dissected ovaries in considerably large quantities. Tumor ovaries with expanded populations of undifferentiated germline cells are first removed from fly abdomens and dissociated into a cell suspension with the aid of protease treatment. The target cells, which express Vasa‐green fluorescent protein (GFP) fusion protein under the control of the germline‐specific vasa promoter, are specifically selected from the suspension via fluorescence‐activated cell sorting (FACS). These protocols can be adapted to isolate other cell types from fly ovaries, such as somatic follicle cells or escort cells, by driving GFP expression in the respective target cells. © 2015 by John Wiley & Sons, Inc.
Regional Cell Specific RNA Expression Profiling of FACS Isolated Drosophila Intestinal Cell Populations
Authors: Dutta Devanjali , Buchon Nicolas , Xiang Jinyi , Edgar Bruce A. 
Published: August 2015

AbstractThe adult Drosophila midgut is built of five distinct cell types, including stem cells, enteroblasts, enterocytes, enteroendocrine cells, and visceral muscles, and is divided into five major regions (R1 to R5), which are morphologically and functionally distinct from each other. This unit describes a protocol for the isolation of Drosophila intestinal cell populations for the purpose of cell type–specific transcriptome profiling from the five different regions. A method to select a cell type of interest labeled with green or yellow fluorescent protein (GFP, YFP) by making use of the GAL4‐UAS bipartite system and fluorescent‐activated cell sorting (FACS) is presented. Total RNA is isolated from the sorted cells of each region, and linear RNA amplification is used to obtain sufficient amounts of high‐quality RNA for analysis by microarray, RT‐PCR, or RNA sequencing. This method will be useful for quantitative transcriptome comparison across intestinal cell types in the different regions under normal and various experimental conditions. © 2015 by John Wiley & Sons, Inc.
TALEN‐ and CRISPR/Cas9‐Mediated Gene Editing in Human Pluripotent Stem Cells Using Lipid‐Based Transfection
Authors: Hendriks William T. , Jiang Xin , Daheron Laurence , Cowan Chad A. 
Published: August 2015

AbstractUsing custom‐engineered nuclease‐mediated genome editing, such as Transcription Activator–Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA‐guided Cas9 nucleases, human pluripotent stem cell (hPSC) lines with knockout or mutant alleles can be generated and differentiated into various cell types. This strategy of genome engineering in hPSCs will prove invaluable for studying human biology and disease. Here, we provide a detailed protocol for design and construction of TALEN and CRISPR vectors, testing of their nuclease activity, and delivery of TALEN or CRISPR vectors into hPSCs. In addition, we describe the use of single‐stranded oligodeoxynucleotides (ssODNs) to introduce or repair point mutations. Next, we describe the identification of edited hPSC clones without antibiotic selection, including their clonal selection, genotyping, and expansion for downstream applications. © 2015 by John Wiley & Sons, Inc.
Hepatocyte‐Based Metabolism, Drug–Drug Interaction, and Toxicity Assays in Drug Discovery and Drug Development to Minimize Attrition
Authors: Li Albert P. 
Published: August 2015

AbstractPrimary human hepatocytes are generally considered the “gold standard” forin vitroevaluation of human drug metabolism, drug‐drug interactions (DDIs), and hepatotoxicity. Successful cryopreservation to retain high viability and plateability (ability to be cultured) allows human hepatocytes to be used routinely for experimentation. Assays developed with human hepatocytes include metabolic stability, metabolite profiling, P450 inhibition, P450 induction, andin vitrohepatotoxicity. These assays are routinely used in drug development to minimize metabolic and safety liability of new chemical entities (NCEs).
Longitudinal Course of Physical Function in People With Symptomatic Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative
Authors: Øiestad Britt Elin , White Daniel K. , Booton Ross , Niu Jingbo , Zhang Yuqing , Torner Jim , Lewis Cora E. , Nevitt Michael , Lavalley Michael , Felson David T. 
Published: August 2015

ObjectivePain and functional decline are hallmarks of knee osteoarthritis (OA). Nevertheless, longitudinal studies unexpectedly reveal stable or improved physical function. The aim of this study was to impute missing and pre–total knee replacement (TKR) values to describe physical function over time among people with symptomatic knee OA.MethodsWe included participants from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) with incident symptomatic knee OA, observed during the first 30 months in MOST and 36 months in OAI. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (WOMAC‐PF), the 5‐times sit‐to‐stand test, and the 20‐meter‐walk test were assessed at 4 and 5 years in MOST and at 6 years in OAI. We used a multiple imputation method for missing visits, and estimated pre‐TKR values close to the time of TKR, using a fitted local regression smoothing curve. In mixed‐effect models, we investigated the physical function change over time, using data before and after imputation and calculation of pre‐TKR values.ResultsIn MOST, 225 (8%) had incident knee OA, with corresponding 577 (12.7%) in OAI. After adjusting for pre‐TKR values and imputing missing values, we found that WOMAC‐PF values remained stable or slightly declined over time, and the 20‐meter‐walk test results changed from stable in nonimputed analyses to worsening using imputed data.ConclusionData from MOST and OAI showed stable to worsening physical function over time in people with incident symptomatic knee OA after imputing missing values and adjusting pre‐TKR values.
Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials
Authors: Combe Bernard , Furst Daniel E. , Keystone Edward C. , van der Heijde Désirée , Luijtens Kristel , Ionescu Lucian , Goel Niti , Emery Paul 
Published: August 2015

ObjectiveAnti–tumor necrosis factor (anti‐TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti‐TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients.MethodsA pre‐specified subgroup analysis comparing 2 MTX dosage categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials, Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) and RAPID 2, according to treatment group: CZP 200 mg, CZP 400 mg, or placebo, every 2 weeks. Inclusion criteria required MTX dosage ≥10 mg/week. Efficacy end points included week 24 American College of Rheumatology criteria for 20%, 50%, and 70% improvement (ACR20/50/70) responses analyzed by logistic regression, and changes from baseline in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) and the modified Sharp/van der Heijde score (SHS) were analyzed by analysis of covariance. Incidence rates of treatment‐emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post hoc sensitivity analysis investigated 3 MTX dose categories: ≤10 mg/week, >10 and ≤15 mg/week, and >15 mg/week.ResultsA total of 638, 635, and 325 patients received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline MTX dose category, and were superior to the placebo group for all investigated end points: ACR20/50/70, DAS28‐ESR, and SHS. TEAE incidence rates were higher in patients receiving MTX ≥15 mg/week for most TEAE types across treatment groups.ConclusionCZP efficacy was not affected by background MTX dose category. It can be hypothesized that to minimize TEAEs, background MTX doses could be tailored to individual patient tolerance without affecting CZP efficacy.
Post‐Traumatic Stress Disorder and Risk for Incident Rheumatoid Arthritis
Authors: Lee Yvonne C. , Agnew‐Blais Jessica , Malspeis Susan , Keyes Katherine , Costenbader Karen , Kubzansky Laura D. , Roberts Andrea L. , Koenen Karestan C. , Karlson Elizabeth W. 
Published: August 2015

ObjectiveTo examine the association between symptoms of post‐traumatic stress disorder (PTSD) and rheumatoid arthritis (RA) risk in a prospective cohort and to characterize the role of smoking in this relationship.MethodsA subset (n = 54,224) of the Nurses’ Health Study II, a prospective cohort of female nurses, completed the Brief Trauma Questionnaire and a screen for PTSD symptoms. Participants were categorized based on trauma exposure and number of PTSD symptoms. Incident RA cases (n = 239) from 1989 to 2011 were identified. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) between PTSD symptoms and incident RA. To identify the impact of smoking, secondary and subgroup analyses were performed. In all analyses, PTSD and smoking were lagged 2 years before the development of RA.ResultsCompared to no history of trauma/PTSD symptoms, the HR for ≥4 PTSD symptoms and incident RA was 1.76 (95% CI 1.16–2.67) in models adjusted for age, race, and socioeconomic status. The risk for RA increased with an increasing number of PTSD symptoms (P = 0.01). When smoking was added to the model, the HR for RA remained elevated (HR 1.60 [95% CI 1.05–2.43]). In a subgroup analysis, excluding women who smoked before PTSD onset, results were unchanged (HR 1.68 [95% CI 1.04–2.70]).ConclusionThis study suggests that women with high PTSD symptomatology have an elevated risk for RA, independent of smoking, adding to emerging evidence that stress is an important determinant of physical health.
Design of robust fault isolation observers for linear systems with bounded uncertain parameters
Authors: Wahrburg Arne 
Published: August 2015

SummaryIn this article, a design procedure for robust fault isolation observers for linear systems is proposed. It allows to detect and isolate faults by means of a single, specifically parametrized observer, yielding a small implementation effort compared with standard bank‐of‐observers approaches. A design based on parametric eigenstructure assignment for nominal system dynamics is presented. The main contribution is to show how the remaining degrees of freedom can be utilized to optimize robustness of the fault isolation observer with respect to uncertain system parameters. Therein, the uncertainties are assumed to belong to a polyhedral domain. The application of the design to two examples verifies the results for systems defined by nominal dynamics and known bounds on the uncertain parameters. Copyright © 2015 John Wiley & Sons, Ltd.
Oxidative Coupling between Methylarenes and Ammonia: A Direct Approach to Aromatic Primary Amides
Authors: Zhao Zhenguang , Wang Tao , Yuan Lin , Hu Xu , Xiong Fei , Zhao Junfeng 
Published: August 2015

AbstractA direct oxidative amidation between methylarenes and aqueous ammonia using a tert‐butyl hydroperoxide and tetrabutylammonium iodide (TBHP/TBAI) oxidation system with co‐catalysis of iron(III) chloride has been developed. Both coupling partners were used in their native form to render prior functionalization unnecessary and afford a facile approach to aromatic primary amides.magnified image
Rapid and Efficient Acylative Active Transport on a Rotaxane
Authors: Nishiyama Junya , Makita Yoshimasa , Kihara Nobuhiro 
Published: August 2015

AbstractBiased Brownian movement, a key process of biological molecular motors, was achieved by the neutralization of a rotaxane consisting of a secondary ammonium salt, in which the ammonium group is located next to the terminal group, and crown ether. Active transport occurred kinetically upon fixation of the transient pseudorotaxane by the rapid acylation of the amino group. The bulky terminal group enhanced the biased Brownian movement, although it suppressed the formation of the pseudorotaxane. Efficient active transport was possible when a large excess of acylation agent and triethylamine were used at 0 °C with 1.5 equivalents of crown ether. The efficiency of active transport increased as the electrophilicity of the acylation agent increased. The highest efficiency of active transport was observed with the cyclopentyl terminal group with one methylene spacer. A simple, two‐step, unidirectional transport was carried out using the active transport system based on the cyclopentyl terminal group.
Successful conservative management of a case of caustic esophagitis based on computed tomography assessment
Authors: Yonemaru Hiroki , Karimata Hiroyuki , Shimoji Hideaki , Yamamoto Kei , Hanashiro Kazuhiko , Fukami Masataka , Ouchi Gen , Tamaki Yuichiro , Kondo Yutaka , Kukita Ichiro 
Published: August 2015

CaseWe describe the case of a female patient who ingested approximately 100 mL of toilet bowl cleaner containing 9.5% hydrochloric acid in a suicide attempt. Upon admission for hematemesis and epigastric pain, she was alert and oriented with stable vital signs. Initial contrast‐enhanced computed tomography (CT) demonstrated edematous changes with no evidence of upper gastrointestinal tract perforation. Endoscopy was not performed owing to the high risk of perforation. We managed this patient conservatively. Repeat contrast‐enhanced CT revealed mediastinal emphysema on day 2, which resolved by day 6. The patient was subsequently discharged with no apparent strictures of the upper gastrointestinal tract.OutcomeSurgical interventions are frequently required following the ingestion of large amounts of highly concentrated hydrochloric acid; however, this patient was successfully managed conservatively.ConclusionContrast‐enhanced CT is useful in the assessment of the respiratory and digestive systems and the prediction of potential complications.
Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque
Authors: Frischer Josa M. , Weigand Stephen D. , Guo Yong , Kale Nilufer , Parisi Joseph E. , Pirko Istvan , Mandrekar Jay , Bramow Stephan , Metz Imke , Brück Wolfgang , Lassmann Hans , Lucchinetti Claudia F. 
Published: August 2015

ObjectiveAn extensive analysis of white matter plaques in a large sample of multiple sclerosis (MS) autopsies provides insights into the dynamic nature of MS pathology.MethodsOne hundred twenty MS cases (1,220 tissue blocks) were included. Plaque types were classified according to demyelinating activity based on stringent criteria. Early active, late active, smoldering, inactive, and shadow plaques were distinguished. A total of 2,476 MS white matter plaques were identified. Plaque type distribution was analyzed in relation to clinical data.ResultsActive plaques were most often found in early disease, whereas at later stages, smoldering, inactive, and shadow plaques predominated. The presence of early active plaques rapidly declined with disease duration. Plaque type distribution differed significantly by clinical course. The majority of plaques in acute monophasic and relapsing–remitting MS (RRMS) were active. Among secondary progressive MS (SPMS) cases with attacks, all plaque types could be distinguished including active plaques, in contrast to SPMS without attacks, in which inactive plaques predominated. Smoldering plaques were frequently and almost exclusively found in progressive MS. At 47 years of age, an equilibrium was observed between active and inactive plaques, whereas smoldering plaques began to peak. Men displayed a higher proportion of smoldering plaques.InterpretationDisease duration, clinical course, age, and gender contribute to the dynamic nature of white matter MS pathology. Active MS plaques predominate in acute and early RRMS and are the likely substrate of clinical attacks. Progressive MS transitions to an accumulation of smoldering plaques characterized by microglial activation and slow expansion of pre‐existing plaques. Whether current MS therapeutics impact this pathological driver of disease progression remains uncertain. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696
Mechanical detection of ultraslow, Debye‐like Li‐ion motions in LiAlO single crystals
Authors: Langer Julia , Wohlmuth Dominik , Kovalcik Adriana , Epp Viktor , Stelzer Franz , Wilkening Martin 
Published: August 2015

Single crystalline LiAlO is known as a very poor ion conductor. Thus, in its crystalline form it unequivocally disqualifies itself from being a powerful solid electrolyte in modern energy storage systems. On the other hand, its interesting crystal structure proves beneficial to sharpen our understanding of Li ion dynamics in solids which in return might influence application‐oriented research. LiAlO allows us to apply and test techniques that are sensitive to extremely slow Li ion dynamics. This helps us clarifying their diffusion behaviour from a fundamental point of view. Here, we combined two techniques to follow Li ion translational hopping in LiAlO that can be described by the same physical formalism: dynamic mechanical relaxation and electrical relaxation, i.e., ionic conductivity measurements. Via both methods we were able to track the same transport mechanism in LiAlO. Moreover, this enabled us to directly probe extremely slow Li exchange rates at temperatures slightly above 430 K. The results were compared with recent insights from nuclear magnetic resonance spectroscopy. Altogether, an Arrhenius‐type Li diffusion process with an activation energy of ca. 1.12 eV was revealed over a large dynamic range covering 10 orders of magnitude, i.e., spanning a dynamic range from the nano‐second time scale down to the second time scale.
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