bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligand‐based Modeling for the Prediction of Pharmacophore Features for Multi‐targeted Inhibition of the Arachidonic Acid Cascade
Authors: Saroj Devi Nisha , Shanmugam Rajasekar , Ghorai Jayanta , Ramanan Meera , Anbarasan Pazhamalai , Doble Mukesh 
Published: October 2017

AbstractThe single‐target drugs against the arachidonic acid inflammatory pathway are associated with serious side effects, hence, as a first step towards multi‐target drugs, we have studied the pharmacophoric features common to the inhibitors of 5‐lipoxygenase‐activating protein (FLAP), microsomal prostaglandin E‐synthase 1 (mPGES‐1) and leukotriene A4 hydrolase (LTA4H). FLAP and mPGES‐1 shared subfamily‐specific positions (SSPs) and four mPGES‐1 inhibitors binding to them mapped onto the pharmacophore derived from FLAP inhibitors (Ph‐FLAP). The reactions of mPGES‐1 and LTA4H had high structural similarity. The pharmacophore derived from two substrate mimic inhibitors of LTA4H (Ph‐LTA4H) also mapped onto three mPGES‐1 inhibitors. Screening of in‐house database for Ph‐FLAP and Ph‐LTA4H identified one compound, C1. It inhibited the production of the mPGES‐1 product, prostaglandin E2 (PGE2) by 97.8±1.6 % at 50 μM in HeLa cells and can be a starting point for designing molecules inhibiting all three targets simultaneously.
A truly complementary approach: A qualitative exploration of complementary and alternative medicine practitioners' views of treating ankylosing spondylitis
Authors: Family Hannah , Jordan Abbie , Blaxall Kelly , Sengupta Raj 
Published: October 2017

AbstractObjectiveAnkylosing spondylitis (AS) is a chronic inflammatory rheumatic disease in which individuals experience a long delay to diagnosis. Prior to diagnosis, individuals report frequent use of complementary and alternative medicine (CAM) therapies. While popularly used, there is a dearth of knowledge concerning the experiences of CAM practitioners in terms of treating individuals with AS. Addressing this knowledge gap, the present study provides a detailed exploration of how UK‐based CAM practitioners treat individuals with AS.MethodsSemi‐structured telephone interviews were conducted with eight UK‐based CAM practitioners, (four males), aged 45–69 years. CAM practitioners were recruited across a range of CAM therapies and years of CAM practice experience (8–46 years).ResultsThematic analysis resulted in the identification of three themes to characterize the data. Themes comprised: (i) the whole picture; (ii) alarm bells; and (iii) a common language. Themes highlighted CAM practitioner adoption of a holistic, yet individualized approach to treating individuals with AS, despite a general sense of lack of knowledge concerning AS among CAM practitioners. Notably, results indicated a desire of CAM practitioners to work more collaboratively with mainstream health providers to provide more joined‐up care for individuals with AS.ConclusionCAM practitioners emphasized the benefits of CAM to focus on providing effective symptom management when used in conjunction, rather than in opposition to, mainstream healthcare. Adoption of a more holistic approach to AS management by CAM practitioners may empower clients to become more aware of symptoms, thus potentially reducing delays in receiving a formal diagnosis of AS.
Psychosocial co‐morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review
Authors: McKernan Lindsey C. , Walsh Colin G. , Reynolds William S. , Crofford Leslie J. , Dmochowski Roger R. , Williams David A. 
Published: October 2017

AimsPsychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self‐management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment.MethodFollowing PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics.ResultsThirty‐four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta‐analyses shows mean Mental Component Score of the Short‐Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES‐D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS‐A 8.15, SD 4.85, N = 465).ConclusionThe psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self‐management intervention may be helpful.
Optimizing usage and maintenance decisions for k‐out‐of‐n systems of moving assets
Authors: Eruguz Ayse Sena , Tan Tarkan , van Houtum Geert‐Jan 
Published: October 2017

AbstractWe consider an integrated usage and maintenance optimization problem for a k‐out‐of‐n system pertaining to a moving asset. The k‐out‐of‐n systems are commonly utilized in practice to increase availability, where n denotes the total number of parallel and identical units and k the number of units required to be active for a functional system. Moving assets such as aircraft, ships, and submarines are subject to different operating modes. Operating modes can dictate not only the number of system units that are needed to be active, but also where the moving asset physically is, and under which environmental conditions it operates. We use the intrinsic age concept to model the degradation process. The intrinsic age is analogous to an intrinsic clock which ticks on a different pace in different operating modes. In our problem setting, the number of active units, degradation rates of active and standby units, maintenance costs, and type of economic dependencies are functions of operating modes. In each operating mode, the decision maker should decide on the set of units to activate (usage decision) and the set of units to maintain (maintenance decision). Since the degradation rate differs for active and standby units, the units to be maintained depend on the units that have been activated, and vice versa. In order to minimize maintenance costs, usage and maintenance decisions should be jointly optimized. We formulate this problem as a Markov decision process and provide some structural properties of the optimal policy. Moreover, we assess the performance of usage policies that are commonly implemented for maritime systems. We show that the cost increase resulting from these policies is up to 27% for realistic settings. Our numerical experiments demonstrate the cases in which joint usage and maintenance optimization is more valuable. © 2017 Wiley Periodicals, Inc. Naval Research Logistics 64: 418–434, 2017
Novel enriched pathways in superficial malignant peripheral nerve sheath tumours and spindle/desmoplastic melanomas
Authors: Jour George , Andeen Nicole K , al‐Rohil Rami , Aung Phyu P , Mehrotra Meenakshi , Duose Dzifa , Hoch Benjamin , Argenyi Zolt , Luthra Rajyalakshmi , Wistuba Ignacio I , Prieto Victor G 
Published: October 2017

AbstractSuperficial malignant peripheral nerve sheath tumour (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle/desmoplastic melanoma (SDM). Herein, we sought to identify molecular targets for therapy by using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin‐fixed paraffin‐embedded tissue were extracted and processed. Massive high‐throughput deep parallel sequencing was performed with the Oncomine comprehensive panel, enabling detection of relevant single‐nucleotide variants, copy number variations, gene fusions and indels for 143 unique genes on the Ion torrent sequencer for clinical trial research programmes. Gene expression analysis was carried out with a customized 770‐gene expression panel combining markers for 24 different immune cell types and 30 common cancer antigens, including key checkpoint blockade genes analysed with the Ncounter system. Fifty‐one patients (SDM, 16/11; MPNST, 24; male, n = 37; female, n = 16) had sufficient DNA and RNA for testing. NF1 deleterious mutations and/or deep/homozygous deletions were identified in 73% of MPNSTs and 67% of SDMs, with 50% of the mutations involving the RAS‐binding domain. Inactivating/deleterious mutations of TSC1/TSC2 were identified in 40% and 41% of MPNSTs and SDMs, respectively. Activating mutations affecting the EGFR‐like and the negative regulatory domains of NOTCH1 and KDR (VEGFR2) were identified in 45% and 40% of SDMs and in 30% and 8% of MPNSTs, respectively. Differential gene expression and gene clustering analysis showed significantly perturbed immune pathway components, including nuclear factor‐κB (NF‐κB), JAK–STAT, and CXCL12–CXCR4, and differentially expressed CD274 and CTLA4, in both SDM and MPNST. Angiogenesis (KDR and NOTCH1) and mammalian target of rapamycin complex (mTORC) pathways offer a rationale for anti‐angiogenic and selective mTORC inhibition as treatment strategies for MPNST and SDM. Cytokines and the JAK–STAT, TNF and NF‐κB axes were perturbed in both SDM and MPNST. These pathways have been targeted in haematological malignancies and present promising targets for these tumours. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Erosion and sediment transfer processes at the front of rapidly moving rock glaciers: Systematic observations with automatic cameras in the western Swiss Alps
Authors: Kummert Mario , Delaloye Reynald , Braillard Luc 
Published: October 2017

AbstractWhen connected to torrential channels, the fronts of active rock glaciers constitute important sediment sources for gravitational transfer processes. In this study, a 2013–16 time series of in situ webcam images from the western Swiss Alps was analyzed to characterize the erosion processes responsible for sediment transfer at the front of three rapidly moving rock glaciers and their temporal behavior. The main erosion processes comprised rock fall, debris slide, superficial flow and concentrated flow. These processes were induced by (i) changes of the frontal slope angle produced by rock glacier advance, and (ii) increases in water content of the sediments at the rock glacier front due to melt processes and rainfall. Erosion almost ceased during winter, when the front was frozen and snow‐covered. The onset of snowmelt triggered an active period of high‐frequency erosion events. After the melt period, sediment transfer continued as occasional rock falls, while other erosion processes occurred only during or following rainfall events. Intense regressive erosion phases that triggered debris flows were rare and occurred when enhanced snowmelt and/or recurring rainfall induced substantial groundwater flow on the debris slopes directly below the rock glacier fronts.
Resistance to cycloxaprid in Laodelphax striatellus is associated with altered expression of nicotinic acetylcholine receptor subunits
Authors: Zhang Yueliang , Han Yangchun , Yang Qiong , Wang Lihua , He Peng , Liu Zewen , Li Zhong , Guo Huifang , Fang Jichao 
Published: October 2017

AbstractBACKGROUNDCycloxaprid is a new oxabridged cis‐configuration neonicotinoid insecticide, the resistance development potential and underlying resistance mechanism of which were investigated in the small brown planthopper, Laodelphax striatellus (Fallén), an important agricultural pest of rice.RESULTSA cycloxaprid‐resistant strain (YN‐CPD) only achieved 10‐fold higher resistance, in contrast to 106‐fold higher resistance to buprofezin and 332‐fold higher resistance to chlorpyrifos achieved after exposure to similar selection pressure, and the cycloxaprid selected line showed no cross‐resistance to the buprofezin and chlorpyrifos‐selected resistance strains. Moreover, we identified 10 nicotinic acetylcholine receptor (nAChR) subunits from the transcriptome of L. striatellus, and six segments had open reading frames (ORFs). While we did not find mutations in the nAChR genes of L. striatellus, subunits Lsα1 and Lsβ1 exhibited, respectively, 9.60‐fold and 3.36‐fold higher expression in the resistant strain, while Lsα8 exhibited 0.44‐fold lower expression. Suppression of Lsα1 through ingestion of dsLsα1 led to an increase in susceptibility to cycloxaprid.CONCLUSIONThe findings indicate that resistance to cycloxaprid develops slowly compared with resistance to other chemicals and without cross‐resistance to chlorpyrifos or buprofezin; over‐expressed Lsα1 is associated with low cycloxaprid resistance levels, but the importance of over‐expressed Lsβ1 and reduced expression of Lsα8 could not be excluded. © 2017 Society of Chemical Industry
Abiotic factors controlling the seasonal and spatial patterns of phytoplankton community in the Tigris River, Turkey
Authors: Varol M. , Şen B. 
Published: October 2017

AbstractIn this study, the seasonal and spatial dynamics of the phytoplankton community in the Tigris River (Turkey) and the relationships with environmental factors were analysed. Bacillariophyta were the most important taxonomic group both in terms of abundance and species number. Phytoplankton abundance increased from winter to autumn associated with a decline in discharge and an increase in nutrient concentrations and water temperature. There was a downstream increase in phytoplankton abundance and species number in the river. Similar spatial and seasonal patterns were observed in chlorophyll‐a concentration and phytoplankton abundance. Redundancy analysis and correlation analysis revealed that chemical variables, mainly nutrients were the most important abiotic factors controlling phytoplankton abundance in the Tigris River.
Helenos: A realistic benchmark for distributed transactional memory
Authors: Kobyliński Paweł , Siek Konrad , Baranowski Jan , Wojciechowski Paweł T. 
Published: October 2017

SummaryTransactional memory (TM) is an approach to concurrency control that aims to make writing parallel programs both effective and simple. The approach has been initially proposed for nondistributed multiprocessor systems, but it is gaining popularity in distributed systems to synchronize tasks at large scales. Efficiency and scalability are often the key issues in TM research; thus, performance benchmarks are an important part of it. However, while standard TM benchmarks like the Stanford Transactional Applications for Multi‐Processing suite and STMBench7 are available and widely accepted, they do not translate well into distributed systems. Hence, the set of benchmarks usable with distributed TM systems is very limited, and must be padded with microbenchmarks, whose simplicity and artificial nature often makes them uninformative or misleading. Therefore, this paper introduces Helenos, a realistic, complex, and comprehensive distributed TM benchmark based on the problem of the Facebook inbox, an application of the Cassandra distributed store.
Cyclic‐di‐GMP regulation of virulence in bacterial pathogens
Authors: Hall Cherisse L. , Lee Vincent T. 
Published: October 2017

Signaling pathways allow bacteria to adapt to changing environments. For pathogenic bacteria, signaling pathways allow for timely expression of virulence factors and the repression of antivirulence factors within the mammalian host. As the bacteria exit the mammalian host, signaling pathways enable the expression of factors promoting survival in the environment and/or nonmammalian hosts. One such signaling pathway uses the dinucleotide cyclic‐di‐GMP (c‐di‐GMP), and many bacterial genomes encode numerous proteins that are responsible for synthesizing and degrading c‐di‐GMP. Once made, c‐di‐GMP binds to individual protein and RNA receptors to allosterically alter the macromolecule function to drive phenotypic changes. Each bacterial genome encodes unique sets of genes for c‐di‐GMP signaling and virulence factors so the regulation by c‐di‐GMP is organism specific. Recent works have pointed to evidence that c‐di‐GMP regulates virulence in different bacterial pathogens of mammalian hosts. In this review, we discuss the criteria for determining the contribution of signaling nucleotides to pathogenesis using a well‐characterized signaling nucleotide, cyclic AMP (cAMP), in Pseudomonas aeruginosa. Using these criteria, we review the roles of c‐di‐GMP in mediating virulence and highlight common themes that exist among eight diverse pathogens that cause different diseases through different routes of infection and transmission. WIREs RNA 2018, 9:e1454. doi: 10.1002/wrna.1454This article is categorized under:

RNA in Disease and Development > RNA in Disease
Ethics of Fallibility
Authors: Kvalnes Øyvind 
Published: October 2017

AbstractAn ethics of fallibility can have a normative and a descriptive dimension. The normative traditions of consequentialism and duty ethics provide conflicting advice about what is the morally right response to different kinds of mistakes. The chapter outlines some theoretical resources available to formulate a normative platform for coping with fallibility, both with regard to what from a moral point of view should happen ahead of critical events where people are likely to make mistakes, in the midst of such events, and in their aftermath. The descriptive dimension of an ethics of fallibility addresses alternative explanations to why people become involved in moral misbehavior, and often continue to be so once they have habituated a certain behavioral pattern. In the final section of the chapter, the normative and descriptive dimensions are combined in a stance on forgiveness. Considerations of whether a person who has made a moral mistake ought to be forgiven (a normative issue) can be informed by knowledge about why people make such mistakes (a descriptive issue).
A paired training curriculum and internal monitoring program for clinical research regulatory compliance in the emerging era of the single Institutional Review Board
Authors: Jarrell T. Che , Hamblin Frances , Ford Daniel E. , Powell Sylvia R. , Ellen Jonathan M. , Goldenberg Neil A. 
Published: October 2017

BackgroundAcademic health systems and their investigators are challenged to systematically assure clinical research regulatory compliance. This challenge is heightened in the emerging era of centralized single Institutional Review Boards for multicenter studies, which rely on monitoring programs at each participating site.ObjectiveTo describe the development, implementation, and outcome measurement of an institution-wide paired training curriculum and internal monitoring program for clinical research regulatory compliance.MethodsStandard operating procedures (SOPs) were developed to facilitate investigator and research professional adherence to institutional policies, federal guidelines, and international standards. An SOP training curriculum was developed and implemented institution-wide. An internal monitoring program was launched, utilizing risk-based monitoring plans of pre-specified frequency and intensity, assessed upon Institutional Review Boards approval of each prospective study. Monitoring plans were executed according to an additional SOP on internal monitoring, with monitoring findings captured in a REDCap database.ResultsWe observed few major violations across 3 key domains of clinical research conduct and demonstrated a meaningful decrease in the rates of nonmajor violations in each, over the course of 2 years.ConclusionThe paired training curriculum and monitoring program is a successful institution-wide clinical research regulatory compliance model that will continue to be refined.
THE MIXED LEGACY OF MAGNA CARTA FOR AMERICAN RELIGIOUS FREEDOM
Authors: Green Steven K. 
Published: October 2017

AbstractIn 2015 Magna Carta celebrated its 800th anniversary. The Great Charter has been widely heralded as a fount of many rights that are highly valued in British and American law. One right that people have identified in the Carta is that of religious freedom. Magna Carta contains two provisions guaranteeing freedom of the church from government authority. In 2013, the United States Supreme Court relied on that authority in a ruling that affirmed the principle of religious autonomy. This article argues that relying on the legacy of Magna Carta for the principle of religious freedom is tenuous: the document had little influence on the development of the First Amendment. Even Magna Carta's authority for the principle of church autonomy is overstated, as the Carta had nothing to do with the development of that principle in American law. Finally, judicial reliance on Magna Carta for the principle of religious freedom risks elevating protections for religious institutions over the interests of individuals. As a result, the legacy of Magna Carta for the principle of religious freedom is mixed, at best.
An integrated Structure-from-Motion and time-lapse technique for quantifying ice-margin dynamics
Authors: MALLALIEU JOSEPH , CARRIVICK JONATHAN L. , QUINCEY DUNCAN J. , SMITH MARK W. , JAMES WILLIAM H.M. 
Published: October 2017

ABSTRACTFine resolution topographic data derived from methods such as Structure from Motion (SfM) and Multi-View Stereo (MVS) have the potential to provide detailed observations of geomorphological change, but have thus far been limited by the logistical constraints of conducting repeat surveys in the field. Here, we present the results from an automated time-lapse camera array, deployed around an ice-marginal lake on the western margin of the Greenland ice sheet. Fifteen cameras acquired imagery three-times per day over a 426 day period, yielding a dataset of ~19 000 images. From these data we derived 18 point clouds of the ice-margin across a range of seasons and successfully identified calving events (ranging from 234 to 1475 m2in area and 815–8725 m3in volume) induced by ice cliff undercutting at the waterline and the collapse of spalling flakes. Low ambient light levels, locally reflective surfaces and the large survey range hindered analysis of smaller scale ice-margin dynamics. Nevertheless, this study demonstrates that an integrated SfM-MVS and time-lapse approach can be employed to generate long-term 3-D topographic datasets and thus quantify ice-margin dynamics at a fine spatio-temporal scale. This approach provides a template for future studies of geomorphological change.