bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine With Preexisting Coronary Artery Disease
Authors: Hartmann Clair , Loconte Maurizio , Antonucci Elena , Holzhauser Michael , Hölle Tobias , Katzsch David , Merz Tamara , McCook Oscar , Wachter Ulrich , Vogt Josef A. , Hoffmann Andrea , Wepler Martin , Gröger Michael , Matejovic Martin , Calzia Enrico , Georgieff Michael , Asfar Pierre , Radermacher Peter , Nussbaum Benedikt L.
Published: October 2017

Objectives:

Investigation of the effects of hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease.

Design:

Prospective, controlled, randomized trial.

Setting:

University animal research laboratory.

Subjects:

Nineteen hypercholesterolemic pigs with preexisting coronary artery disease.

Interventions:

Anesthetized, mechanically ventilated, and surgically instrumented pigs underwent 3 hours of hemorrhagic shock (removal of 30% of the calculated blood volume and subsequent titration of mean arterial blood pressure ≈40 mm Hg). Postshock resuscitation (48 hr) comprised retransfusion of shed blood, crystalloids (balanced electrolyte solution), and norepinephrine support. Pigs were randomly assigned to “control” (Fio
2 0.3, adjusted for arterial oxygen saturation ≥ 90%) and “hyperoxia” (Fio
2 1.0 for 24 hr) groups.

Measurements and Main Results:

Before, at the end of shock and every 12 hours of resuscitation, datasets comprising hemodynamics, calorimetry, blood gases, cytokines, and cardiac and renal function were recorded. Postmortem, organs were sampled for immunohistochemistry, western blotting, and mitochondrial high-resolution respirometry. Survival rates were 50% and 89% in the control and hyperoxia groups, respectively (p = 0.077). Apart from higher relaxation constant τ at 24 hours, hyperoxia did not affect cardiac function. However, troponin values were lower (2.2 [0.9–6.2] vs 6.9 [4.8–9.8] ng/mL; p < 0.05) at the end of the experiment. Furthermore, hyperoxia decreased cardiac 3-nitrotyrosine formation and increased inducible nitric oxide synthase expression. Plasma creatinine values were lower in the hyperoxia group during resuscitation coinciding with significantly improved renal mitochondrial respiratory capacity and lower 3-nitrotyrosine formation.

Conclusions:

Hyperoxia during resuscitation from hemorrhagic shock in swine with preexisting coronary artery disease reduced renal dysfunction and cardiac injury, potentially resulting in improved survival, most likely due to increased mitochondrial respiratory capacity and decreased oxidative and nitrosative stress. Compared with our previous study, the present results suggest a higher benefit of hyperoxia in comorbid swine due to an increased susceptibility to hemorrhagic shock.
An update on the status of molecular testing for the indeterminate thyroid nodule and risk stratification of differentiated thyroid cancer
Authors: Nicholson Kristina J. , Yip Linwah
Published: October 2017

Purpose of review

Correct identification of malignancy in cytologically indeterminate thyroid nodules is a diagnostic challenge, leading to potentially unnecessary surgery in patients for whom final histology is benign. Similarly, many patients with differentiated thyroid cancer (DTC) undergo aggressive surgical management of tumors, which may ultimately have low-risk histologic features. Use of molecular testing strategies can aid in both the diagnosis of indeterminate thyroid nodules and preoperative risk stratification of DTC.

Recent findings

Validation studies of both the Afirma Gene Expression Classifier and Thyroseq Next-Generation Sequencing panel are ongoing. Both tests can be used to help rule out malignancy in indeterminate thyroid nodules. Recent additions to available molecular testing for indeterminate thyroid nodules include the Rosetta microRNA classifier and the augmentation of the ThyGenX gene panel with a microRNA reflex test (ThyraMIR). Mutational analysis of DTC shows that mutation in TERT alone, and in combination with other mutations, portends advanced disease.

Currently available molecular testing modalities are useful for ruling out malignancy in indeterminate thyroid nodules; however, longer-term follow-up studies are needed to confirm that test-negative nodules are truly benign. Analysis of specific gene mutations helps identify aggressive disease to guide prognostication and management, but further study is needed.
Attenuation of compulsive-like behavior by fluvoxamine in a non-induced mouse model of obsessive–compulsive disorder
Authors: Mitra Swarup , Bult-Ito Abel
Published: October 2017

The current study evaluated the role of strain and compulsive trait differences in response to fluvoxamine, a common obsessive–compulsive disorder (OCD) drug, in two different mouse strains (BIG1 and BIG2) with a spontaneous compulsive-like phenotype. For compulsive-like nest-building behavior, dose-dependent attenuation of nesting by fluvoxamine was observed for the BIG1 compulsive-like strain during the first hour after administration. No significant differences were found for the BIG2 strain during the first hour, although a dose-dependent trend similar to that in the BIG1 strain was observed. Fluvoxamine dose dependently decreased the number of marbles buried in both strains 1 h after administration. For anxiety-like behaviors in the open field, no significant drug effects were found for the latency to leave the center and the number of line crossings. Significant strain differences were observed, with the BIG2 strain showing higher anxiety-like behaviors and reduced locomotor activity compared with the BIG1 strain. Consequently, this study adds predictive validity to our mouse model of OCD, whereas the anxiety-like differences between the strains add heterogeneity to our mouse model, similar to the heterogeneity observed in OCD.
The Future of Obstetrics and Gynecology: MACRA, Electronic Health Records, and More
Authors: WING DEBORAH A.
Published: October 2017

There is immense change affecting obstetrical and gynecologic medical practice at this moment in time-involving reimbursement with the shift from volume-based to value-based care, increasing regulation, and workforce sustainability. Aspects to be reviewed in this chapter include reimbursements and Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), electronic medical records, physician satisfaction surveys, maintenance of certification, and physician burnout.
The Effect of Progressive Relaxation Exercises on Fatigue and Sleep Quality in Individuals With COPD
Authors: Yilmaz Cemile Kutmec , Kapucu Sevgisun
Published: October 2017

This randomized controlled experimental study was conducted to investigate the effect of progressive muscle relaxation exercises on dyspnea, fatigue, and sleep quality in individuals with chronic obstructive pulmonary disease. A Descriptive Questionnaire and the Chronic Obstructive Pulmonary Disease and Asthma Fatigue Scale, Chronic Obstructive Pulmonary Disease and Asthma Sleep Scale and Medical Research Council Dyspnea Scale were used for data collection. The decrease in the mean dyspnea, fatigue, and sleep scores in the intervention group was statistically significantly more pronounced than the patients in the control group (P < .05). Progressive relaxation exercises can be implemented to decrease the dyspnea, fatigue, and sleep problems seen in patients with moderate and advanced chronic obstructive pulmonary disease by nurses working in the clinic.
Taboo in the Workplace
Authors: Tsai Shu-Ling , Tsai Chang-Hsiung , Hsu Yu-Chien , Hsieh Mei-Hui , Kao Hsia-Tzu , Hsu Min-Tao
Published: October 2017

There has been an increased emphasis on nurses' mental health and well-being in the workplace. Psychologists have established a correlative link between individual's beliefs on luck and mental health. The pineapple taboo has been observed among Taiwanese hospital nurses as a prevalent superstitious belief for bringing luck or warding off increased clinical workloads, but how and why the ritual persists in the hospital workplace remains unknown. This article aims to explore the latent meaning of observance of the taboo and how it is related to nurses' clinical practice and possibly affects their mental health at work. A qualitative research was designed in line with the hermeneutic phenomenological method. Through purposive sampling, 18 nurse participants were recruited for in-depth semistructured interviews. Resulting from the ensuing analysis, 3 modalities were identified as constituting the spectrum of observance of the taboo: (a) “strictly not eating pineapple”; (b) “not eating pineapple at work”; and (c) “eating pineapple without admitting to doing so.” Each reflects the position of nurses revealed in relation to the pineapple taboo in clinical settings. Based on the subjective narratives of nurses, it may be understood as an active moral attempt at “being right” rather than a passive avoidance of bad luck in the taboo observation. The findings facilitate an appropriate understanding of the embedded meaning of nurses' workplace-related belief and its seminal function of empowerment for nurses in holistic nursing practice.
Essential Oils and Gastroparesis
Authors: Macoskey Chalyce , Dunn Dorothy J.
Published: October 2017

This study explored how essential oils for persons with gastroparesis symptoms affect the quality of life. Gastroparesis is a chronic delayed gastric motility disorder characterized by postprandial fullness, early satiety, nausea, vomiting, abdominal discomfort, bloating, depression, and anxiety. The aim of this study was to determine how essential oils support digestion and eliminate inflammation in the body as evidenced by self-reporting a decrease in symptoms, thereby improving quality of life. A qualitative descriptive methodology using Barrette's Theory of Power as Knowing Participation in Change thematic framework was used. Three main themes were extracted from the data: awareness of quality of life possibilities, freedom to make choices, and transforming health and hope. The constitutive theme that was synthesized became essential oils transform health, hope, and increase quality-of-life possibilities.
Ab Interno Gel Implant for the Treatment of Glaucoma Patients With or Without Prior Glaucoma Surgery: 1-Year Results
Authors: Hengerer Fritz H. , Kohnen Thomas , Mueller Michael , Conrad-Hengerer Ina
Published: October 2017

Purpose:

The purpose of this study is to evaluate IOP lowering effects and complication management of an ab interno gel implant for the treatment of patients refractory to antiglaucoma medication or glaucoma surgery.

Methods:

Retrospective analysis of the medical records of 242 consecutive eyes of 146 patients with uncontrolled intraocular pressure (IOP) despite maximum tolerated medical therapy or prior surgical intervention that underwent XEN45 implantation (as sole procedure or in combination with cataract surgery) between March 2014 and June 2015. Data included IOP, number of glaucoma medications, the need for additional surgery, needling, and complications.

Results:

During the study period, mean IOP had decreased by 54.1% from 32.19 (±9.1) mm Hg to 14.24 (±4.0) mm Hg (P=0.00; Wilcoxon test). The number of antiglaucoma medications had decreased from a mean of 3.13±1.0 to 0.3±0.7 (P=0.00; Wilcoxon test). Needling was required between week 1 and months 3 in 27.7% of all eyes to enhance the outflow. Hypotony (IOP<6 mm Hg) was observed in 9 eyes (4.0%) at 1 month but normalized in all eyes at 12 months postoperatively. Two eyes experienced hypotony requiring the refill of the anterior chamber.

Conclusions:

Our data indicate that the XEN45 gel implant has a favorable safety profile and is an effective treatment option for controlling IOP in glaucoma patients with unregulated IOP despite IOP lowering medical therapy or prior surgical intervention. It offers an effective approach, both as sole procedure and in combination with cataract surgery.
Helmet Use and Risk-Taking Behavior Among Skiers and Snowboarders
Authors: Willick Stuart E. , Wagner Graham , Ericson Don , Josten George , Teramoto Masaru , Davis Jeremy
Published: October 2017

Objective:

To characterize factors associated with helmet use and risk-taking behavior among recreational skiers and snowboarders.

Design:

Observational study.

Setting:

Large, western United States mountain resort.

Participants:

1285 male and female recreational skiers and snowboarders were interviewed during a single winter ski season.

Independent Variables:

Helmet use, demographic, and sport-related characteristics.

Main Outcome Measures:

Brief sensation seeking scale (BSSS) as a measure of risk-taking behavior and self-reported risk compensation.

Results:

Of the respondents (N = 1285), 17.5%, 12.5%, and 70.0% reported that they never, sometimes, and always wore a helmet, respectively. Multiple linear regression analysis showed that individuals reporting sometimes wearing a helmet had significantly higher BSSS scores than those reporting never wearing a helmet (P = 0.031) or always wearing it (P = 0.018). Male gender, younger age, snowboarding, higher perceived sport ability, more days per year skiing or snowboarding, and more time spent in the terrain park were significantly associated with higher BSSS scores (P < 0.05). Logistic regression analysis focusing on subgroups of respondents who reported either sometimes or always wearing a helmet indicated that the odds of taking more risks when wearing a helmet for inconsistent helmet users was 75% higher than the odds for those who reported always wearing a helmet (P = 0.06).

Conclusions:

Inconsistent helmet users have characteristics of risk-taking behavior and risk compensation. Male gender, younger age, snowboarding, higher perceived sport ability, and more time spent on the mountain and in the terrain park are also important determinants of risk-taking behavior.
Risk of Cervical Intra-epithelial Neoplasia and Invasive Cancer of the Cervix in DES Daughters
Authors: Verloop J. , van Leeuwen F. E. , Helmerhorst Th. J. M. , de Kok I. M. C. M. , van Erp E. J. M. , van Boven H. H. , Rookus M. A.
Published: October 2017

(Abstracted from Gynecol Oncol 2017;144:305–311)

Several million pregnant women worldwide received diethylstilbestrol (DES) from the late 1940s to the early 1970s to prevent miscarriages and other pregnancy complications. Women exposed to DES in utero have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix; their risk of non–CCA-invasive cervical cancer remains unclear.
Non-opioid Pain Management in Benign Minimally Invasive Hysterectomy: A Systematic Review
Authors: Blanton Emily , Lamvu Georgine , Patanwala Insiyyah , Barron Kenneth I. , Witzeman Kathryn , Tu Frank F. , As-Sanie Sawsan
Published: October 2017

(Abstracted from Am J Obstet Gynecol 2017;216(6):557–567)

A national survey found that more than 70% of postsurgical patients experience moderate to extreme pain after discharge, and nearly 28% of these have severe to extreme pain. A minimally invasive hysterectomy is typically associated with less postoperative pain than a laparotomy approach.
Surgical Pain After Transobturator and Retropubic Midurethral Sling Placement
Authors: Thomas Tonya N. , Siff Lauren N. , Jelovsek J. Eric , Barber Matthew
Published: October 2017

(Abstracted from Obstet Gynecol 2017;130:118–125)

A safe and effective surgical treatment for stress urinary incontinence is the midurethral sling. There are 2 surgical approaches: retropubic and transobturator.
Total Pregnancy Loss After Chorionic Villus Sampling and Amniocentesis: A Cohort Study
Authors: Bakker M. , Birnie E. , Robles de Medina P. , Sollie K. M. , Pajkrt E. , Bilardo C. M.
Published: October 2017

(Abstracted from Ultrasound Obstet Gynecol 2017;49:599–606)

Invasive prenatal procedures such as chorionic villus sampling (CVS) and amniocentesis are often assessed based on their procedure-related fetal loss rate (FLR), which is defined as the total FLR minus the spontaneous FLR. Spontaneous FLR is determined based on the maternal risk profile, whereas procedure-related risk depends on operator experience, technical difficulties, and instruments utilized.
Molecular structure of human KATP in complex with ATP and ADP
Authors: Lee Kenneth Pak Kin , Chen Jue , MacKinnon Roderick
Published: October 2017

In many excitable cells KATP channels respond to intracellular adenosine nucleotides: ATP inhibits while ADP activates. We present two structures of the human pancreatic KATP channel, containing the ABC transporter SUR1 and the inward-rectifier K+channel Kir6.2, in the presence of Mg2+and nucleotides. These structures, referred to as quatrefoil and propeller forms, were determined by single-particle cryo-EM at 3.9 Å and 5.6 Å, respectively. In both forms ATP occupies the inhibitory site in Kir6.2. The nucleotide-binding domains of SUR1 are dimerized with Mg2+-ATP in the degenerate site and Mg2+-ADP in the consensus site. A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form, and is disrupted in the quatrefoil form. These structures support the role of SUR1 as an ADP sensor and highlight the lasso extension as a key regulatory element in ADP’s ability to override ATP inhibition.
Functional pathways for metabolic network-based data analysis: the MetPath algorithm
Authors: Mattei Gianluca , Zielinski Daniel C. , Gan Zhuohui , Ramazzotti Matteo , Palsson Bernhard O.
Published: October 2017

Analyzing biological data using pathways helps identify trends in data tied to the function of a network. A large number of pathway-based analysis tools have been developed toward this goal. These pathways are often manually curated and thus associations are subject to the biases of the curator. A potentially attractive alternative is to define pathways based on the inherent functionality and connectivity of the network itself. Within metabolism, functionality is defined by the production and consumption of metabolites, and connectivity by metabolites participating in reactions through common enzymes. In this work, we present an algorithm, termed MetPath, that calculates pathways for production and consumption of metabolites. We show how these pathways have attractive properties, such as the ability to integrate multiple data types and weight contribution of genes within the pathway by their functional contribution to metabolite production/consumption. Pathways calculated in this manner are condition-specific and thus are custom tailored to the system of interest, in contrast to curated pathways. We find that these pathways predict gene expression correlation better compared to manually-curated pathways. Additionally, we find that these pathways can be used to understand gene expression changes between growth conditions and between cell types. This work serves to better understand the functional pathway structure underlying cell metabolism and helps to enable systems analyses of high-throughput data.
Potential forMethanosarcinato contribute to uranium reduction during acetate-promoted groundwater bioremediation
Authors: Holmes Dawn E , Orelana Roberto , Giloteaux Ludovic , Wang Li-Ying , Shrestha Pravin , Williams Kenneth , Lovley Derek R , Rotaru Amelia-Elena
Published: October 2017

Previous studies ofin situbioremediation of uranium-contaminated groundwater with acetate injections have focused on the role ofGeobacterspecies in U(VI) reduction because of a lack of other abundant known U(VI)-reducing microorganisms. Monitoring the levels of methyl CoM reductase subunit A (mcrA) transcripts during an acetate-injection field experiment demonstrated that acetoclastic methanogens from the genusMethanosarcinawere enriched after 40 days of acetate amendment. The increased abundance ofMethanosarcinacorresponded with an accumulation of methane in the groundwater. An enrichment culture dominated by aMethanosarcinaspecies with the sameMethanosarcina mcrAsequence that predominated in the field experiment could effectively convert acetate to methane. In order to determine whetherMethanosarcinaspecies could be participating in U(VI) reduction in the subsurface, cell suspensions ofM. barkeriwere incubated in the presence of U(VI) with acetate provided as the electron donor. U(VI) was reduced by metabolically activeM. barkericells, however, no U(VI) reduction was observed in inactive controls. These results demonstrate thatMethanosarcinaspecies could play an important role in the long-term bioremediation of uranium-contaminated aquifers after depletion of Fe(III) oxides limits the growth ofGeobacterspecies. The results also suggest thatMethanosarcinahave the potential to influence uranium geochemistry in a diversity of anaerobic sedimentary environments.
The Effect of Targeted Vaccination Against Mycobacterium Avium ssp. Paratuberculosis (MAP) in a Multiple Sclerosis Mouse Model: Implications for Causation
Authors: Warmoth Michael R.
Published: October 2017

Epidemiologic evidence relating to the causation of Multiple Sclerosis, based upon twin concordance studies, implicates both genetic and environmental contributions. The HLA-DRB1/ HLA-A haplotype confers a 23 fold increase in MS prevalence above its baseline of 1 per 1,000 persons. Epigenetic factors, such as an aberrant response to Epstein Barr Virus (EBV) and Vitamin D deficiency can increase that risk 36 and 2 fold respectively. Evidence of an association between elevated MAP antibodies and Multiple Sclerosis has been reported.

A prospective randomized controlled trial was performed in SJL mice exposed to the myelin-related oligopeptide PLP139-151; a relapsing-remitting Experimental Autoimmune Encephalitis (EAE) model. 100 mice were randomized into five groups of 20. Group 1-Unimmunized prior to disease induction. Group 2-Immunized twice with a 74 kDa fusion protein vaccine against MAP; delivered 28 days and 7 days prior to disease induction. Group 3- 1 dose of 74 kDa vaccine 10 days post-disease induction. Group 4- Attenuated whole cell MAP vaccine (ΔSigH) 28 days prior to disease induction. Group 5- ΔSigH vaccine 10 days post disease induction.

Disability was quantified using a EAE disability scoring reference ranging from 0 to 5.

Significant decreases in peak disability were seen in the bimodal peaks of this relapsing-remitting model 38% (p<0.006) and 40% (p<0.001). ΔsigH immunized mice lost half as much weight as controls post disease induction. The results suggest that environmental MAP antigen exposure may play an etiologic role in the development of EAE.
Two SecA/SecY Systems with Distinct Roles in the Ecological Adaptations of Bacteria
Authors: Jiang Xiaowei , Fares Mario A.
Published: October 2017

Bacteria interact with their environment through the secretion of a specific set of proteins (known as secretome) through various secretion systems. Molecular modifications of these secretion systems may lead to the emergence of new bacterial-environment interactions, although this remains unexplored. In this study we investigate the possible link between molecular and functional changes in secretion proteins and the ecological diversity of bacteria. We studied functional modifications in secretion proteins by identifying events of functional evolutionary divergence—that is, changes at the molecular level that have driven changes of protein’s function. We present data supporting that these functional diversifications occurred in essential secretion proteins in bacteria. In particular, functional divergence of the two most important secretion proteins SecA and SecY in pathogenic bacteria suggests that molecular changes at these proteins are responsible for their adaptations to the host. Functional divergence has mainly occurred at protein domains involved in ATP hydrolysis in SecA and membrane pore formation in SecY. This divergence is stronger in pathogenic bacteria for protein copies resulting from the duplication of SecA/SecY, known as SecA2/SecY2. In concert with these results, we find that the secretome of bacteria with the strongest functional divergence is enriched for proteins specialized in the interaction with specific environments. We unravel evolutionary signatures that link mutations at secretion proteins to the ecological diversification of bacteria.
Enzyme Intermediates Captured “on-the-fly” by Mix-and-Inject Serial Crystallography
Authors: Olmos Jose , Pandey Suraj , Martin-Garcia Jose M. , Calvey George , Katz Andrea , Knoska Juraj , Kupitz Christopher , Hunter Mark S. , Liang Mengning , Oberthuer Dominik , Yefanov Oleksandr , Wiedorn Max , Heyman Michael , Holl Mark , Pande Kanupriya , Barty Anton , Miller Mitchell D. , Stern Stephan , Roy-Chowdhury Shatabdi , Coe Jesse , Nagaratnam Nirupa , Zook James , Verburgt Jacob , Norwood Tyler , Poudyal Ishwor , Xu David , Koglin Jason , Seaberg Matt , Zhao Yun , Bajt Saša , Grant Thomas , Mariani Valerio , Nelson Garrett , Subramanian Ganesh , Bae Euiyoung , Fromme Raimund , Fung Russel , Schwander Peter , Frank Matthias , White Thomas , Weierstall Uwe , Zatsepin Nadia , Spence John , Fromme Petra , Chapman Henry N. , Pollack Lois , Tremblay Lee , Ourmazd Abbas , Phillips George N. , Schmidt Marius
Published: October 2017

Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases. Here, we demonstrate a general method for capturing enzyme catalysis ‘in-action’ by ‘mix-and-inject serial crystallography’. Specifically, we follow the catalytic reaction of theMycobacterium tuberculosisα-lactamase with the 3rdgeneration antibiotic ceftriaxone by time-resolved serial femtosecond crystallography. The results reveal, in near atomic detail, antibiotic cleavage and inactivation on the millisecond to second time scales including the crossover from transition state kinetics to steady-state kinetics.

Synopsis

An enzymatically catalyzed reaction is initiated by diffusion based mixing of substrate and followed at runtime by time-resolved serial crystallography using a free electron laser.
Disease-specific biases in alternative splicing and tissue-specific dysregulation revealed by multitissue profiling of lymphocyte gene expression in type 1 diabetes
Authors: Newman Jeremy R.B. , Conesa Ana , Mika Matthew , New Felicia N. , Onengut-Gumuscu Suna , Atkinson Mark A. , Rich Stephen S. , McIntyre Lauren M. , Concannon Patrick
Published: October 2017

Genome-wide association studies (GWAS) have identified multiple, shared allelic associations with many autoimmune diseases. However, the pathogenic contributions of variants residing in risk loci remain unresolved. The location of the majority of shared disease-associated variants in noncoding regions suggests they contribute to risk of autoimmunity through effects on gene expression in the immune system. In the current study, we test this hypothesis by applying RNA sequencing to CD4+, CD8+, and CD19+lymphocyte populations isolated from 81 subjects with type 1 diabetes (T1D). We characterize and compare the expression patterns across these cell types for three gene sets: all genes, the set of genes implicated in autoimmune disease risk by GWAS, and the subset of these genes specifically implicated in T1D. We performed RNA sequencing and aligned the reads to both the human reference genome and a catalog of all possible splicing events developed from the genome, thereby providing a comprehensive evaluation of the roles of gene expression and alternative splicing (AS) in autoimmunity. Autoimmune candidate genes displayed greater expression specificity in the three lymphocyte populations relative to other genes, with significantly increased levels of splicing events, particularly those predicted to have substantial effects on protein isoform structure and function (e.g., intron retention, exon skipping). The majority of single-nucleotide polymorphisms within T1D-associated loci were also associated with one or morecis-expression quantitative trait loci (cis-eQTLs) and/or splicing eQTLs. Our findings highlight a substantial, and previously underrecognized, role for AS in the pathogenesis of autoimmune disorders and particularly for T1D.
Accounting for GC-content bias reduces systematic errors and batch effects in ChIP-seq data
Authors: Teng Mingxiang , Irizarry Rafael A.
Published: October 2017

The main application of ChIP-seq technology is the detection of genomic regions that bind to a protein of interest. A large part of functional genomics’ public catalogs is based on ChIP-seq data. These catalogs rely on peak calling algorithms that infer protein-binding sites by detecting genomic regions associated with more mapped reads (coverage) than expected by chance, as a result of the experimental protocol's lack of perfect specificity. We find that GC-content bias accounts for substantial variability in the observed coverage for ChIP-seq experiments and that this variability leads to false-positive peak calls. More concerning is that the GC effect varies across experiments, with the effect strong enough to result in a substantial number of peaks called differently when different laboratories perform experiments on the same cell line. However, accounting for GC content bias in ChIP-seq is challenging because the binding sites of interest tend to be more common in high GC-content regions, which confounds real biological signals with unwanted variability. To account for this challenge, we introduce a statistical approach that accounts for GC effects on both nonspecific noise and signal induced by the binding site. The method can be used to account for this bias in binding quantification as well to improve existing peak calling algorithms. We use this approach to show a reduction in false-positive peaks as well as improved consistency across laboratories.
High-throughput single-molecule telomere characterization
Authors: McCaffrey Jennifer , Young Eleanor , Lassahn Katy , Sibert Justin , Pastor Steven , Riethman Harold , Xiao Ming
Published: October 2017

We have developed a novel method that enables global subtelomere and haplotype-resolved analysis of telomere lengths at the single-molecule level. An in vitro CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human (TTAGGG)n DNA tracts in genomes that have also been barcoded using a separate nickase enzyme that recognizes a 7-bp motif genome-wide. High-throughput imaging and analysis of large DNA single molecules from genomes labeled in this fashion using a nanochannel array system permits mapping through subtelomere repeat element (SRE) regions to unique chromosomal DNA while simultaneously measuring the (TTAGGG)n tract length at the end of each large telomere-terminal DNA segment. The methodology also permits subtelomere and haplotype-resolved analyses of SRE organization and variation, providing a window into the population dynamics and potential functions of these complex and structurally variant telomere-adjacent DNA regions. At its current stage of development, the assay can be used to identify and characterize telomere length distributions of 30–35 discrete telomeres simultaneously and accurately. The assay's utility is demonstrated using early versus late passage and senescent human diploid fibroblasts, documenting the anticipated telomere attrition on a global telomere-by-telomere basis as well as identifying subtelomere-specific biases for critically short telomeres. Similarly, we present the first global single-telomere-resolved analyses of two cancer cell lines.
Nascent RNA sequencing reveals a dynamic global transcriptional response at genes and enhancers to the natural medicinal compound celastrol
Authors: Dukler Noah , Booth Gregory T. , Huang Yi-Fei , Tippens Nathaniel , Waters Colin T. , Danko Charles G. , Lis John T. , Siepel Adam
Published: October 2017

Most studies of responses to transcriptional stimuli measure changes in cellular mRNA concentrations. By sequencing nascent RNA instead, it is possible to detect changes in transcription in minutes rather than hours and thereby distinguish primary from secondary responses to regulatory signals. Here, we describe the use of PRO-seq to characterize the immediate transcriptional response in human cells to celastrol, a compound derived from traditional Chinese medicine that has potent anti-inflammatory, tumor-inhibitory, and obesity-controlling effects. Celastrol is known to elicit a cellular stress response resembling the response to heat shock, but the transcriptional basis of this response remains unclear. Our analysis of PRO-seq data for K562 cells reveals dramatic transcriptional effects soon after celastrol treatment at a broad collection of both coding and noncoding transcription units. This transcriptional response occurred in two major waves, one within 10 min, and a second 40–60 min after treatment. Transcriptional activity was generally repressed by celastrol, but one distinct group of genes, enriched for roles in the heat shock response, displayed strong activation. Using a regression approach, we identified key transcription factors that appear to drive these transcriptional responses, including members of the E2F and RFX families. We also found sequence-based evidence that particular transcription factors drive the activation of enhancers. We observed increased polymerase pausing at both genes and enhancers, suggesting that pause release may be widely inhibited during the celastrol response. Our study demonstrates that a careful analysis of PRO-seq time-course data can disentangle key aspects of a complex transcriptional response, and it provides new insights into the activity of a powerful pharmacological agent.
Synthesis and coordination chemistry of the PPN ligand 2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine
Authors: Han Delong , Andres Benjamin , Spannenberg Anke , Beweries Torsten
Published: October 2017

The synthesis and crystal structure of the multidentate PPN ligand 2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine (L), C19H35NP2, are described. In the isostructural tetrahedral Fe and Co complexes of type LMCl2 (M = Fe, Co), namely {2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine-κ2
P,N}dichloridoiron(II), [FeCl2(C19H35NP2)], and {2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine-κ2
P,N}dichloridocobalt(II), [CoCl2(C19H35NP2)], the ligand adopts a bidentate P,N-coordination, whereas in the case of the octahedral Mn complex {2-[bis(diisopropylphosphanyl)methyl]-6-methylpyridine-κ2
P,P′}bromidotricarbonylmanganese(I), [MnBr(C19H35NP2)(CO)3], the ligand coordinates via both P atoms to the metal centre.
Crystal structure of methyl (Z)-2-[(Z)-3-methyl-2-({(E)-1-[(R*)-4-methylcyclohex-3-en-1-yl]ethylidene}hydrazinylidene)-4-oxothiazolidin-5-ylidene]acetate
Authors: Fawzi Mourad , Auhmani Aziz , Ait Itto Moulay Youssef , Riahi Abdelkhalek , Chevreux Sylviane , Ketatni El Mostafa
Published: October 2017

The new title 4-thiazolidinone derivative, C16H21N3O3S, was obtained from the cyclization reaction of 4-methyl-3-thiosemicarbazone and dimethyl acetylenedicarboxylate (DMAD). The cyclohexylidene ring has an envelope conformation with the stereogenic centre C atom as the flap. Its mean plane makes a dihedral angle of 56.23 (9)° with the thiazolidine ring mean plane. In the crystal, molecules are linked by C—H...O hydrogen bonds forming chains propagating in the [001] direction. Within the chains there are offset π–π interactions between the thiazolidine rings of inversion-related molecules [centroid–centroid distance = 3.703 (1) Å]. The chains are linked by further C—H...O hydrogen bonds, forming slabs parallel to theacplane.
Geocentralization and Thainess
Authors: Carter Jason Lee
Published: October 2017

Purpose

Thailand desires to improve its economic competitiveness in the Southeast Asia-Pacific region and utilizes the World Economic Forum’s Global Competitiveness Report (GCR) on the 12 Pillars of Competitiveness to gauge this progress. The purpose of this paper is to study the outcomes for the fifth pillar on “Higher education and training” to identify the challenges to institutional management for the design and implementation of business administration programs.

Design/methodology/approach

The first hypothesis on causality and impact is a comparison of curricula design from published material between Thai and similar highly rated programs from the GCR using a statistical variance method. The second hypothesis is a proposed improvement model for implementation, geocentralization, analyzed using an inferential percentage differentiation.

Findings

The findings reveal a marked misalignment in relevant vs irrelevant curriculum design, with implementation performance results showing lower outcomes from traditional learning methods as compared to geocentralization.

Originality/value

Final remarks outline recommendations that Thai higher education administrators can utilize for improving curriculum design and implementation.
Rapid calculation method for estimating static and dynamic performances of closed hydrostatic guideways
Authors: Wang Zhiwei , Liu Yi , Wang Feng
Published: October 2017

Purpose

The purpose of this paper is to establish a simplified model of the closed hydrostatic guideway for the rapid analysis of static and dynamic characteristics. Further, the influence of compressibility and dynamic frequency are taken into consideration in the new dynamic model.

Design/methodology/approach

The new model is based on the second kind of Lagrange equation. In this model, the closed hydrostatic guideway is supported by 12 pads, and each oil pad is equivalent to a nonlinear spring-damper system. The equivalent spring coefficient and damper coefficient of the oil pad are extracted by the three different equivalent methods. Finally, the validation experiments of step load response and dynamic stiffness are conducted on a hydrostatic guideway.

Findings

For solving the step response, the linear spring-damper model and the nonlinear spring-damper Model 1 are better than the nonlinear spring-damper Model 2. The accuracy of the three methods are very high for static stiffness calculation. For the calculation of dynamic stiffness, the nonlinear spring-damper Model 2 is better than the nonlinear spring-damper Model 1. The linear spring-damper model has low precision for dynamic stiffness calculation, especially at high frequency. The accuracy of the new model is validated by experiments.

Originality/value

The equivalent method of nonlinear spring-damper system has higher accuracy. Different equivalent methods should be adopted for different load types. The computational speeds of the new dynamic model with the three methods are much better than finite element method (about ten times).
Squeeze film performance of parallel annular plates by ferrofluid couple stress lubricant considering effects of rotational inertia
Authors: Dolatsara Nioosha Ghasemi , Daliri Maghsood , Shameli Moharram
Published: October 2017

Purpose

The purpose of this paper is to investigate squeezing and rotating motions between two parallel annular discs lubricated by ferro-fluid couple stress lubricant in the presence of a uniform magnetic field.

Design/methodology/approach

Based upon the Stokes couple stress theory and ferro-hydrodynamic model of Shliomis, squeeze film characteristics between two parallel annular discs are obtained.

Findings

According to the results, it is found that the combined effects of couple stress and ferro-fluid lubricant increase squeeze film performance with respect to the classical Newtonian lubricant. However, an increase in the rotational inertia parameter reduces squeeze film characteristics.

Originality/value

This paper is relatively original and describes the squeeze film characteristics between two parallel annular discs with rotational inertia, couple stress and ferro-fluid lubricant effects.
Frictional wear stability mechanisms of an activated carbon composite derived from palm kernel by phase transformation study
Authors: Mahmud Dayang Nor Fatin , Abdollah Mohd Fadzli Bin , Masripan Nor Azmmi Bin , Tamaldin Noreffendy , Amiruddin Hilmi
Published: October 2017

Purpose

The purpose of this paper is to investigate the mechanisms of frictional wear stability of an activated carbon composite derived from palm kernel using phase transformation study.

Design/methodology/approach

The unlubricated sliding test was executed using a ball-on-disc tribometer at different loads with a constant speed, sliding distance and temperature.

Findings

Results of this paper suggest that stability of friction and wear of the test materials are primarily due to the phase transformation of the composite surface layer.

Research limitations/implications

However, the effectiveness of the transfer layer as a medium for low friction and wear is only limited at certain applied loads.

Originality/value

This is the first study, to the authors’ knowledge, to find out the mechanisms of low frictional wear properties of an activated carbon composite derived from palm kernel using phase transformation study.
Experimental study of starvation in grease-lubricated finite line contacts
Authors: Wang Zhijian , Shen Xuejin , Chen Xiaoyang , Han Qiang , Shi Lei
Published: October 2017

Purpose

The purpose of this paper is to study starvation in grease-lubricated finite line contacts and to understand film-forming mechanisms of grease-lubricated finite line contacts.

Design/methodology/approach

A multiple-contact optical elastohydrodynamic (EHL) test rig is constructed to investigate the influences of lubricant properties on film thickness and lubrication conditions at different working conditions. The film thickness is calculated according to the relative light intensity principle. The degree of starvation is evaluated by the air–oil meniscus distance and the corresponding film thickness.

Findings

The experimental results show that for greases with high-viscosity base oil, the high-frequency fluctuation of film thickness is observed in low-speed operating conditions. Reducing the viscosity of the base oil and improving running speed can weaken the fluctuation of film thickness. The degree of starvation increases with increasing base oil viscosity, rolling speed and the crown drop. In addition, reducing the replenishment time by reducing the gap between the rollers also can increase the degree of starvation.

Originality/value

Starvation is often to occur in finite line contacts, such as roller bearings and gears; there are still limited finite line contact EHL test rigs, much less multiple-contact optical test rigs. Therefore, the present work is undertaken to construct the multiple-contact test rig and to evaluate the mechanism of starvation in finite line contacts.
The effect of the arc on annular-thrust aerostatic porous bearings
Authors: Khan Polina V. , Segu Dawit Zenebe , Hwang Pyung
Published: October 2017

Purpose

Aerostatic porous bearings are important for guide rails and spindles. It is well-known that flow restrictors made of porous materials offer major advantages over conventional restrictors in such bearings, including design and manufacturing, load-carrying capacity, stiffness, damping and dynamic stability. Thus, this work numerically investigates the effect of the arc on a new combined annular-thrust aerostatic porous bearing.

Design/methodology/approach

The static characteristics of an annular-thrust aerostatic porous bearing were studied using a fast finite element scheme. The pressure distribution, radial load and thrust load were analyzed as functions of the arc, permeability and eccentricity.

Findings

The results reveal that the radial load achieves maximal values at an optimal arc value between 200 and 300, and the thrust load increases monotonically with increasing arc.

Originality/value

This work developed a new combined annular-thrust aerostatic porous bearing to investigate the effect of arc on the annular-thrust aerostatic porous bearings to increase the load-carrying capacity.
Curbing electronic shopper perceived opportunism and encouraging trust
Authors: San-Martín Sonia , Jimenez Nadia
Published: October 2017

Purpose

Consumers can face a situation of information asymmetry in electronic shopping (ES). The purpose of this paper to examine the relationships between: relational variables such as satisfaction, trust and perceived opportunism; and website cues (cognitive signals such as security and personalization, and experiential signals, such as design and entertainment).

Design/methodology/approach

The paper opted for the structural equation methodology to analyze data collected from 447 Spanish e-shoppers.

Findings

Results show different factors that relate to satisfaction, trust and perceived opportunism in ES. Satisfactory experience with ES and entertainment emerge as the most relevant factors to achieve trust and prevent perceived opportunism in e-commerce.

Originality/value

The five contributions of this study are: the introduction of variables from several theoretical approaches to the study of an agency problem in e-commerce; the study of different ways to gain buyer trust and reduce perceived opportunism in an electronic shopper-vendor relationship; the application of signaling theory as part of the process of helping the principal (e-shopper) to solve their shopping problem in a context of information asymmetry; the analysis of the impact of external cues from e-vendor/site, which allows for a comparison between internal experiences and external quality signals; and the study of entertainment as an important hedonic variable in order to have satisfied and confident e-shoppers.
Trustworthy data-driven networked production for customer-centric plants
Authors: Preuveneers Davy , Joosen Wouter , Ilie-Zudor Elisabeth
Published: October 2017

Purpose

Industry 4.0 envisions a future of networked production where interconnected machines and business processes running in the cloud will communicate with one another to optimize production and enable more efficient and sustainable individualized/mass manufacturing. However, the openness and process transparency of networked production in hyperconnected manufacturing enterprises pose severe cyber-security threats and information security challenges that need to be dealt with. The paper aims to discuss these issues.

Design/methodology/approach

This paper presents a distributed trust model and middleware for collaborative and decentralized access control to guarantee data transparency, integrity, authenticity and authorization of dataflow-oriented Industry 4.0 processes.

Findings

The results of a performance study indicate that private blockchains are capable of securing IoT-enabled dataflow-oriented networked production processes across the trust boundaries of the Industry 4.0 manufacturing enterprise.

Originality/value

This paper contributes a decentralized identity and relationship management for users, sensors, actuators, gateways and cloud services to support processes that cross the trust boundaries of the manufacturing enterprise, while offering protection against malicious adversaries gaining unauthorized access to systems, services and information.