bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Analysis of Mating Type Genes and Transcriptome Analysis during Fruiting Body Development ofBotrytis cinerea
Authors: Rodenburg Sander Y. A. , Terhem Razak B. , Veloso Javier , Stassen Joost H. M. , van Kan Jan A. L.
Published: February 2018

Botrytis cinereais a plant-pathogenic fungus producing apothecia as sexual fruiting bodies. To study the function of mating type (MAT) genes, single-gene deletion mutants were generated in both genes of theMAT1-1locus and both genes of theMAT1-2locus. Deletion mutants in twoMATgenes were entirely sterile, while mutants in the other twoMATgenes were able to develop stipes but never formed an apothecial disk. Little was known about the reprogramming of gene expression during apothecium development. We analyzed transcriptomes of sclerotia, three stages of apothecium development (primordia, stipes, and apothecial disks), and ascospores by RNA sequencing. Ten secondary metabolite gene clusters were upregulated at the onset of sexual development and downregulated in ascospores released from apothecia. Notably, more than 3,900 genes were differentially expressed in ascospores compared to mature apothecial disks. Among the genes that were upregulated in ascospores were numerous genes encoding virulence factors, which reveals that ascospores are transcriptionally primed for infection prior to their arrival on a host plant. Strikingly, the massive transcriptional changes at the initiation and completion of the sexual cycle often affected clusters of genes, rather than randomly dispersed genes. Thirty-five clusters of genes were jointly upregulated during the onset of sexual reproduction, while 99 clusters of genes (comprising >900 genes) were jointly downregulated in ascospores. These transcriptional changes coincided with changes in expression of genes encoding enzymes participating in chromatin organization, hinting at the occurrence of massive epigenetic regulation of gene expression during sexual reproduction.

IMPORTANCEFungal fruiting bodies are formed by sexual reproduction. We studied the development of fruiting bodies (“apothecia”) of the ubiquitous plant-pathogenic ascomyceteBotrytis cinerea. The role of mating type genes in apothecium development was investigated by targeted mutation. Two genes are essential for the initiation of sexual development; mutants in these genes are sterile. Two other genes were not essential for development of stipes; however, they were essential for stipes to develop a disk and produce sexual ascospores. We examined gene expression profiles during apothecium development, as well as in ascospores sampled from apothecia. We provide the first study ever of the transcriptome of pure ascospores in a filamentous fungus. The expression of numerous genes involved in plant infection was induced in the ascospores, implying that ascospores are developmentally primed for infection before their release from apothecia.
The ColM Family, Polymorphic Toxins Breaching the Bacterial Cell Wall
Authors: Ghequire Maarten G. K. , Buchanan Susan K. , De Mot René
Published: February 2018

Bacteria host an arsenal of antagonism-mediating molecules to combat for ecologic space. Bacteriocins represent a pivotal group of secreted antibacterial peptides and proteins assisting in this fight, mainly eliminating relatives. Colicin M, a model for peptidoglycan-interfering bacteriocins in Gram-negative bacteria, appears to be part of a set of polymorphic toxins equipped with such a catalytic domain (ColM) targeting lipid II. Diversifying recombination has enabled parasitism of different receptors and has also given rise to hybrid bacteriocins in which ColM is associated with another toxin module. Remarkably, ColM toxins have recruited a diverse array of immunity partners, comprising cytoplasmic membrane-associated proteins with different topologies. Together, these findings suggest that different immunity mechanisms have evolved for ColM, in contrast to bacteriocins with nuclease activities.
An Autocrine Proliferation Repressor Regulates
Dictyostelium discoideum
Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
Authors: Tang Yu , Wu Yuantai , Herlihy Sarah E. , Brito-Aleman Francisco J. , Ting Jose H. , Janetopoulos Chris , Gomer Richard H.
Published: February 2018

In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe
Dictyostelium discoideum
. AprA is a chemorepellent for and inhibits the proliferation of
D. discoideum
. We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH (
grlH¯
cells) show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in
grlH¯
cells (
grlH¯/grlH

OE

) rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in
D. discoideum
.

IMPORTANCE
Little is known about how eukaryotic cells can count themselves and thus regulate the size of a tissue or density of cells. In addition, little is known about how eukaryotic cells can sense a repellant signal and move away from the source of the repellant, for instance, to organize the movement of cells in a developing embryo or to move immune cells out of a tissue. In this study, we found that a eukaryotic microbe uses G protein-coupled receptors to mediate both cell density sensing and chemorepulsion.
Genomewide Transcriptional Responses of Iron-Starved Chlamydia trachomatis Reveal Prioritization of Metabolic Precursor Synthesis over Protein Translation
Authors: Brinkworth Amanda J. , Wildung Mark R. , Carabeo Rey A.
Published: February 2018

By utilizing an experimental approach that monitors the immediate global response of
Chlamydia trachomatis
to iron starvation, clues to long-standing issues in
Chlamydia
biology are revealed, including how
Chlamydia
adapts to this stress. We determined that this pathogen initiates a transcriptional program that prioritizes replenishment of nutrient stores over replication, possibly in preparation for rapid growth once optimal iron levels are restored. Transcription of genes for biosynthesis of metabolic precursors was generally upregulated, while those involved in multiple steps of translation were downregulated. We also observed an increase in transcription of genes involved in DNA repair and neutralizing oxidative stress, indicating that
Chlamydia
employs an “all-or-nothing” strategy. Its small genome limits its ability to tailor a specific response to a particular stress. Therefore, the “all-or-nothing” strategy may be the most efficient way of surviving within the host, where the pathogen likely encounters multiple simultaneous immunological and nutritional insults.
Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation?
Authors: Jefferis Barbara J , Parsons Tessa J , Sartini Claudio , Ash Sarah , Lennon Lucy T , Papacosta Olia , Morris Richard W , Wannamethee S Goya , Lee I-Min , Whincup Peter H
Published: February 2018

Objectives

To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour.

Methods

Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978–1980. In 2010–2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71–92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016.

Results

After median 5.0 years’ follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality.

Conclusions

In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults.
Do I need to have the MRCGP to work as a GP?
Authors: Charlton Rodger
Published: February 2018

Got a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Could you tell me what training I need to succeed in medical informatics and whether it helps to be a clinician?
Authors: Al-Ubaydli Mohammad
Published: February 2018

Got a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Ever been stalked?⇓
Authors: McIvor Ronan J
Published: February 2018

In today's world of easy access to information, it is becoming more common for doctors to be the stalker's target. Ronan McIvor gives some advice to help minimise your risk of being stalked by patients and also what to do if you are being stalked
Working in the media 2: getting a foot in the door
Authors: Easton Graham
Published: February 2018

Even when you're raring to go, the media world can seem like a closed shop. Graham Easton and others offer some tips on getting a foot in the door
Modernising Medical Careers—what's all the fuss about?
Authors: MacDonald Rhona
Published: February 2018

Rhona MacDonald finds out what doctors on the ground really think
What are the prospects of getting an SpR post in obstetrics and gynaecology in the United Kingdom for overseas doctors with experience and with MD MRCOG?
Authors: Hapangama Dharani
Published: February 2018

Have a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone (
www.bmjcareers.com/advicezone
) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
What to do if you are taken hostage
Authors: Palmer Ian P
Published: February 2018

You may think an article about how to survive if you are taken hostage is a bit far fetched for Career Focus, but doctors are increasingly interested in working in other countries either as part of their training or as voluntary workers with non-governmental organisations. So we asked
Ian Palmer
to give some advice
Exploring the lived experience and chronic low back pain beliefs of English-speaking Punjabi and white British people: a qualitative study within the NHS
Authors: Singh Gurpreet , Newton Christopher , O’Sullivan Kieran , Soundy Andrew , Heneghan Nicola R
Published: February 2018

Introduction

Disabling chronic low back pain (CLBP) is associated with negative beliefs and behaviours, which are influenced by culture, religion and interactions with healthcare practitioners (HCPs). In the UK, HCPs encounter people from different cultures and ethnic backgrounds, with South Asian Indians (including Punjabis) forming the largest ethnic minority group. Better understanding of the beliefs and experiences of ethnic minorities with CLBP might inform effective management.

Objectives

To explore the CLBP beliefs and experiences of English-speaking Punjabi and white British people living with CLBP, explore how beliefs may influence the lived experience of CLBP and conduct cross-cultural comparisons between the two groups.

Design

Qualitative study using semistructured interviews set within an interpretive description framework and thematic analysis.

Setting

A National Health Service hospital physiotherapy department, Leicester, UK.

Participants

10 CLBP participants (5 English-speaking Punjabi and 5 white British) purposively recruited from physiotherapy waiting lists.

Results

Participants from both groups held negative biomedical CLBP beliefs such as the ‘spine is weak’, experienced unfulfilling interactions with HCPs commonly due to a perceived lack of support and negative psychosocial dimensions of CLBP with most participants catastrophising about their CLBP. Specific findings to Punjabi participants included (1) disruption to cultural-religious well-being, as well as (2) a perceived lack of understanding and empathy regarding their CLBP from the Punjabi community. In contrast to their white British counterparts, Punjabi participants reported initially using passive coping strategies; however, all participants reported a transition towards active coping strategies.

Conclusion

CLBP beliefs and experiences, irrespective of ethnicity, were primarily biomedically orientated. However, cross-cultural differences included cultural-religious well-being, the community response to CLBP experienced by Punjabi participants and coping styles. These findings might help inform management of people with CLBP.
Pediatric dog bites: a population-based profile
Authors: Fein Jackson , Bogumil David , Upperman Jeffrey S , Burke Rita V
Published: February 2018

Background

Previous studies have identified risk factors for dog bites in children, but use data from individual trauma centers, with limited generalizability. This study identifies a population risk profile for pediatric dog bites using the National Trauma Data Bank. We hypothesized that the population at risk was younger boys, that such bites occur at home, are moderately severe, and are on the face or neck.

Methods

For this retrospective cross-sectional study, a sample of 7912 children 17 years old and younger with International Classification of Diseases (ICD)-9 event code E906.0, for dog bites, were identified. Datasets from 2007 to 2014 were used. Data included patient’s gender, age, ICD-9 primary and location E-codes, AIS body region and AIS severity.

Results

Most children were 6–12 years old and female, but a similar number fell into the narrower range of 0–2 years old. Injuries in the younger group frequently occurred at home, on the face and head, and with minor severity. Age of the child predicts the location of incident (P<0.001), the severity of injury (P<0.001) and the body region of the injury (P<0.001). Body region of the injury predicted its severity (P<0.001).

Discussion

Younger children are more likely to receive dog bites, and bites incurred are likely of greater severity. Children this young cannot yet be taught how to properly interact with a dog.

Conclusions

Dog bites are a significant source of morbidity for children. Based on the population risk factors profile generated, this study recommends targeting live dog education towards the parents of young children.
Using photography to enhance GP trainees’ reflective practice and professional development
Authors: Rutherford  , Forde Emer , Priego-Hernandez Jacqueline , Butcher Aurelia , Wedderburn Clare
Published: February 2018

The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most general practitioners (GP) training programmes. Teaching through the humanities is a growing area within medical education, but one which is often considered a voluntary ‘add-on’ for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees’ reflective capacity, self-awareness and professional development. Photography was used as a tool to develop GP trainees’ skills in recognising and articulating the attitudes, feelings and values that might impact on their clinical work and to enhance their confidence in their ability to deal with these concerns/issues. We submit that photography is uniquely well suited for facilitating insight and self-reflection because it provides the ability to record ‘at the touch of a button’ those scenes and images to which our attention is intuitively drawn without the need for—or the interference of—conscious decisions. This allows us the opportunity to reflect later on the reasons for our intuitive attraction to these scenes. These photography workshops were a compulsory part of the GP training programme and, despite the participants’ traditional scientific backgrounds, the results clearly demonstrate the willingness of participants to accept—even embrace—the use of art as a tool for learning. The GP trainees who took part in this project acknowledged it to be beneficial for both their personal and professional development.
Multiparametric MRI of intracranial aneurysms treated with the Woven EndoBridge (WEB): a case of Faraday’s cage?
Authors: Nawka Marie Teresa , Sedlacik Jan , Frölich Andreas , Bester Maxim , Fiehler Jens , Buhk Jan-Hendrik
Published: February 2018

Objective

To evaluate multiparametric MRI including non-contrast and contrast-enhanced morphological and angiographic techniques for intracranial aneurysms treated with the single-layer Woven EndoBridge (WEB) embolization system applying simultaneous digital subtraction angiography (DSA) as the reference of standard.

Materials and methods

We retrospectively identified all patients with incidental and acute ruptured intracranial aneurysms treated with a WEB device (WEB SL and WEB SLS) between March 2014 and June 2016 in our neurovascular center with early (within 7 days) postinterventional multiparametric MRI as well as mid-term (5–8 months) follow-up MRI and DSA available. Occlusion rates were recorded both in DSA and MR angiography (MRA). In MRI, signal intensities within the WEB as well as in the occluded dome distal to the WEB, if present, were measured by region-of-interest (ROI) analysis.

Results

Twenty-five patients fulfilled the inclusion criteria. Rates of complete/adequate occlusion at mid-term follow-up were 84% with both MRA and DSA. A strong signal loss within the WEB was observed in all MR sequences at initial and follow-up examinations. ROI analysis did not reveal significant differences in non-contrast (P=0.946) and contrast-enhanced imaging (P=0.377). A T1-hyperintense thrombus in the non-WEB-carrying dome was a frequent observation.

Conclusions

Signal intensity measurements in multiparametric MRI suggest that neither contrast-enhanced MRA nor morphological sequences are capable of revealing reliable information on the WEB lumen, presumably due to radio frequency shielding. MRI is therefore not suitable for confirming complete thrombus formation within the WEB.
Glial fibrillary acidic protein antibody-positive meningoencephalomyelitis
Authors: Zarkali Angeliki , Cousins Oliver , Athauda Dilan , Moses Samuel , Moran Nicholas , Harikrishnan Sreedharan
Published: February 2018

Glial fibrillary acidic protein antibody-positive meningoencephalomyelitis is a newly described, possibly under-recognised, severe inflammatory condition of the nervous system. The clinical presentation is variable but most commonly is a combination of meningitis, encephalitis and myelitis; other manifestations may include seizures, psychiatric symptoms and tremor. There is a significant association with malignancies, often occult, and with other autoimmune conditions. Although the disease responds well to corticosteroids acutely, it typically relapses when these are tapered, and so patients need long-term immunosuppression. We report a young man presenting with subacute meningoencephalitis and subsequent myelitis, and discuss the typical presentation and management of this severe but treatable condition.
Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study
Authors: Fleischmann Roy , Winkle Peter , Miner Jeffrey N , Yan Xiaohong , Hicks Liz , Valdez Shakti , Hall Jesse , Liu Sha , Shen Zancong , Gillen Michael , Hernandez-Illas Martha
Published: February 2018

Objectives

Verinurad (RDEA3170) is a high affinity, selective uric acid transporter (URAT1) inhibitor indevelopment for treating gout and asymptomatic hyperuricaemia. This phase IIa study evaluated the pharmacodynamics, pharmacokinetics and safety of verinurad combined with allopurinol versus allopurinol alone in adults with gout.

Methods

Forty-one subjects were randomised into two cohorts of verinurad (2.5–20 mg) plus allopurinol (300 mg once daily) versus allopurinol 300 mg once daily, 600 mg once daily or 300 mg twice daily alone. Each treatment period was 7 days. Serial plasma/serum and urine samples were assayed for verinurad, allopurinol, oxypurinol and uric acid.

Results

Serum pharmacodynamic data pooled across cohorts demonstrated maximum per cent decreases in serum urate (sUA) from baseline (Emax) at 7–12 hours after verinurad plus allopurinol treatment. Combination treatment decreased sUA in dose-dependent manner: least-squares means Emaxwas 47%, 59%, 60%, 67%, 68% and 74% for verinurad doses 2.5, 5, 7.5, 10, 15 and 20 mg plus allopurinol 300 mg once daily, versus 40%, 54% and 54% for allopurinol 300 mg once daily, 600 mg once daily and 300 mg twice daily. Verinurad had no effect on allopurinol plasma pharmacokinetics, but decreased oxypurinol Cmaxby 19.0%–32.4% and area under the plasma concentration–time curve from time zero to the last measurable time point by 20.8%–39.2%. Verinurad plus allopurinol was well tolerated with no serious adverse events (AEs), AE-related withdrawals or renal-related events. Laboratory values showed no clinically meaningful changes.

Conclusion

Verinurad coadministered with allopurinol produced dose-dependent decreases in sUA. All dose combinations of verinurad and allopurinol were generally well tolerated. These data support continued investigation of oral verinurad in patients with gout.

Trial registration number

NCT02498652.
Evidence for a second ankylosing spondylitis-associatedRUNX3regulatory polymorphism
Authors: Vecellio Matteo , Cortes Adrian , Roberts Amity R , Ellis Jonathan , Cohen Carla Jayne , Knight Julian C , Brown Matthew A , Bowness Paul , Wordsworth Bryan Paul
Published: February 2018

Objectives

To explore the functions ofRUNX3single nucleotide polymorphisms (SNPs) associated with ankylosing spondylitis (AS).

Methods

Individual SNP associations were evaluated in 4230 UK cases. Their effects on transcription factor (TF) binding, transcription regulation, chromatin modifications, gene expression and gene interactions were tested by database interrogation, luciferase reporter assays, electrophoretic mobility gel shifts, chromatin immunoprecipitation and real-time PCR.

Results

We confirmed the independent association of AS withrs4265380, which was robust (P=4.7×10−6) to conditioning on another nearby AS-associatedRUNX3SNP (rs4648889). ARUNX3haplotype incorporating both SNPs was strongly associated with AS (OR 6.2; 95% CI 3.1 to 13.2, P=1.4×10−8). In a large UK cohort,rs4265380is associated with leucocyte counts (including monocytes).RUNX3expression is lower in AS peripheral blood mononuclear cells than healthy controls (P<0.002), independent ofrs4265380genotype. Enhancer function for thisRUNX3region was suggested by increased luciferase activity (approximately tenfold; P=0.005) for reporter constructs containingrs4265380. In monocytes, there was differential allelic binding of nuclear protein extracts to a 50 bp DNA probe containingrs4265380that was strongly augmented by lipopolysaccharide activation. TF binding also included the histone modifier p300. There was enrichment for histone modifications associated with active enhancer elements (H3K27Ac and H3K79Me2) that may be allele dependent. Hi-C database interrogation showed chromosome interactions of RUNX3 bait with the nearby RP4-799D16.1 lincRNA.

Conclusions

The association of AS with thisRUNX3regulatory region involves at least two SNPs apparently operating in different cell types. Monocytes may be potential therapeutic targets in AS.
Cardiovascular complications during anaesthesia for surgical correction of an aberrant right subclavian artery in a dog
Authors: Ida Keila Kazue , Sandersen Charlotte , Noël Stéphanie , Marolf Vincent
Published: February 2018

A six‐month‐old neutered male German shepherd dog with aberrant right subclavian artery (ARSA) was premedicated with methadone, medetomidine and then fentanyl; anaesthesia was induced with propofol and maintained with infusions of medetomidine and fentanyl and isoflurane in oxygen. Hartmann’s solution and noradrenaline were administered for cardiovascular support. Arterial pressure was measured using Doppler technique in both metacarpal arteries and invasive technique in both dorsal pedal arteries. During ARSA occlusion test, severe hypotension (30 mmHg) in the right forelimb, bradycardia (45 bpm) and advanced atrioventricular blocks (AVB) were observed. The occlusion test was interrupted; atropine was administered; cardiovascular parameters, except AVB, were normalised; medetomidine and noradrenaline were interrupted. Other two attempts of ARSA occlusion generated similar cardiovascular side effects. The surgical correction was precluded and the animal was recovered from anaesthesia. This case indicates that ARSA occlusion can be followed by severe arrhythmias and focus on the management of these alterations.
Intraobserver and interobserver agreement on the radiographical diagnosis of canine cranial cruciate ligament rupture
Authors: Bogaerts Evelien , Van der Vekens Elke , Verhoeven Geert , de Rooster Hilde , Van Ryssen Bernadette , Samoy Yves , Putcuyps Ingrid , Van Tilburg Johan , Devriendt Nausikaa , Weekers Frederik , Bertal Mileva , Houdellier Blandine , Scheemaeker Stephanie , Versteken Jeroen , Lamerand Maryline , Feenstra Laurien , Peelman Luc , Van Nieuwerburgh Filip , Saunders Jimmy H , Broeckx Bart J G
Published: February 2018

Even though radiography is one of the most frequently used imaging techniques for orthopaedic disorders, it has been demonstrated that the interpretation can vary between assessors. As such, the purpose of this study was to examine the intraobserver and interobserver agreement and the influence of level of expertise on the interpretation of radiographs of the stifle in dogs with and without cranial cruciate ligament rupture (CCLR). Sixteen observers, divided in four groups according to their level of experience, evaluated 30 radiographs (15 cases with CCLR and 15 control stifles) twice. Each observer was asked to evaluate joint effusion, presence and location of degenerative joint disease, joint instability and whether CCLR was present or absent. Overall, intraobserver and interobserver agreement ranged from fair to almost perfect with a trend towards increased agreement for more experienced observers. Additionally, it was found that stifles that were classified with high agreement have either overt disease characteristics or no disease characteristics at all, in comparison to the ones that are classified with a low agreement. Overall, the agreement on radiographic interpretation of CCLR was high, which is important, as it is the basis of a correct diagnosis and treatment.
Investigation into the influence of excavation of twin-bored tunnels within weak rock masses adjacent to slopes
Authors: Vlachopoulos N. , Vazaios I. , Madjdabadi B.M.
Published: February 2018

The focus of this investigation is twin tunnelling projects designed and constructed adjacent to slopes. To this end, several state-of-the-art two-dimensional (2-D) and three-dimensional (3-D) numerical models for multiple scenarios were utilized. The novelty of this research (further highlighted by two case studies) explicitly demonstrates that for 2-D and 3-D elastic and plastic analyses for weak rock masses, the interaction between the two tunnel branches for various conditions show how the pillar width minimally influences such interaction past two diameter widths of separation. As well, the 3-D sequential longitudinal tunnel excavation of the twin tunnel does not significantly influence the crown displacements of the two tunnels prior to construction of the mid-span of the twin tunnel. Slope stability analysis was conducted by employing the novel shear strength reduction (SSR) method. These findings confirm that changes in the location of the twin tunnels with respect to the slope and one another in combination with the natural angle of the slope can improve the overall stability without any other special measures taken. As well, by having the twin tunnel pillar width constant, the vertical translation of the tunnels (i.e., increase in the overburden) is more beneficial than that of a horizontal translation, resulting in a higher factor of safety.
Synthesis and characteristics of organotin-based catalysts for acetylene hydrochlorination
Authors: Wu Yi-Bo , Li Bo-Wen , Li Fu-Xiang , Xue Jian-Wei , Lv Zhi-Ping
Published: February 2018

Organotin-based catalysts prepared by a facile and green synthesis route were used in the acetylene hydrochlorination reaction. In detail, organotin-based catalysts were directly synthesized by supporting both organotin and nitrogen compounds on a coal-based columnar activated carbon (AC) using both incipient wetness impregnation and calcination methods. Interestingly, upon addition of nitrogen compounds, the resultant (SnCl4 + C16H34Cl2Sn)/AC catalysts showed higher activity and stability when compared the its (SnCl4 + C16H34Cl2Sn + C2N4H4)/AC counterpart at 200 °C and a gas hourly space velocity (GHSV, C2H2 based) of 30 h−1. According to the results, organotin was demonstrated to be the active site, whereas the incorporation of nitrogen allowed partial mitigation of the loss of active components.
Eucalyptus globulus Inhibits Inflammasome-Activated Pro-Inflammatory Responses and Ameliorate Monosodium Urate-Induced Peritonitis in Murine Experimental Model
Authors: Ji Young-Eun , Sun Xiao , Kim Myong-Ki , Li Wan Yi , Lee Sang Woo , Koppula Sushruta , Yu Sang-Hyeun , Kim Han-Bi , Kang Tae-Bong , Lee Kwang-Ho
Published: February 2018

Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-[Formula: see text] secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1[Formula: see text], providing scientific support for its traditional use in the treatment of inflammation-related disorders.
A demonstration that electroweak theory can violate parity automatically (leptonic case)
Authors: Furey C.
Published: February 2018

We bring to light an electroweak model which has been reappearing in the literature under various guises.[Formula: see text] In this model, weak isospin is shown to act automatically on states of only a single chirality (left). This is achieved by building the model exclusively from the raising and lowering operators of the Clifford algebra [Formula: see text]. That is, states constructed from these ladder operators mimic the behaviour of left- and right-handed electrons and neutrinos under unitary ladder operator symmetry. This ladder operator symmetry is found to be generated uniquely by [Formula: see text] and [Formula: see text]. Crucially, the model demonstrates how parity can be maximally violated, without the usual step of introducing extra gauge and extra Higgs bosons, or ad hoc projectors.
Pressure effects on structural, electronic, elastic and lattice dynamical properties of XSi2(X = Cr, Mo, W) from first principles
Authors: Zhu Haiyan , Shi Liwei , Li Shuaiqi , Zhang Shaobo , Xia Wangsuo
Published: February 2018

First-principles calculations have been performed to study the structure, elastic and lattice dynamical properties of C40 XSi2(X=Cr, Mo, W) under hydrostatic pressure. The obtained structural parameters are in line with existing experimental and theoretical data. The evolutions of fundamental bandgap energies, elastic moduli, IR absorption spectra with pressure have been investigated in detail. Our results indicate that the energy gaps of XSi2(X=Cr, Mo, W) show different trends as the pressure increases. Larger BH/GHratio and Poisson’s ratio are achieved with pressure, suggesting an improved ductility for XSi2(X=Cr, Mo, W). Moreover, a large elastic anisotropy under pressure is exhibited in Young’s anisotropic factors. The infrared-active phonon frequencies exhibit substantial blueshifts under pressure.
ON SOME FUNCTIONALS OF THE FIRST PASSAGE TIMES IN MODELS WITH SWITCHING STOCHASTIC VOLATILITY
Authors: GAPEEV PAVEL V. , BROCKHAUS OLIVER , DUBOIS MATHIEU
Published: February 2018

We compute some functionals related to the joint generalized Laplace transforms of the first times at which two-dimensional diffusion-type Markov processes exit half strips. It is assumed that the state space components are driven by constantly correlated Brownian motions and the dynamics of the coefficients are described by a continuous-time Markov chain. The method of proof is based on the solutions of the equivalent boundary-value problems for systems of elliptic-type partial differential equations for the associated value functions. The results are illustrated on several two-dimensional continuous mean-reverting or diverting models of switching stochastic volatility.
Improving SIMD Parallelism via Dynamic Binary Translation
Authors: Hong Ding-Yong , Liu Yu-Ping , Fu Sheng-Yu , Wu Jan-Jan , Hsu Wei-Chung
Published: February 2018

Recent trends in SIMD architecture have tended toward longer vector lengths, and more enhanced SIMD features have been introduced in newer vector instruction sets. However, legacy or proprietary applications compiled with short-SIMD ISA cannot benefit from the long-SIMD architecture that supports improved parallelism and enhanced vector primitives, resulting in only a small fraction of potential peak performance. This article presents a dynamic binary translation technique that enables short-SIMD binaries to exploit benefits of new SIMD architectures by rewriting short-SIMD loop code. We propose a general approach that translates loops consisting of short-SIMD instructions to machine-independent IR, conducts SIMD loop transformation/optimization at this IR level, and finally translates to long-SIMD instructions. Two solutions are presented to enforce SIMD load/store alignment, one for the problem caused by the binary translator’s internal translation condition and one general approach using dynamic loop peeling optimization. Benchmark results show that average speedups of 1.51× and 2.48× are achieved for an ARM NEON to x86 AVX2 and x86 AVX-512 loop transformation, respectively.
Detecting the Behavior of Design Patterns through Model Checking and Dynamic Analysis
Authors: Lucia Andrea De , Deufemia Vincenzo , Gravino Carmine , Risi Michele
Published: February 2018

We present a method and tool (ePAD) for the detection of design pattern instances in source code. The approach combines static analysis, based on visual language parsing and model checking, and dynamic analysis, based on source code instrumentation. Visual language parsing and static source code analysis identify candidate instances satisfying the structural properties of design patterns. Successively, model checking statically verifies the behavioral aspects of the candidates recovered in the previous phase. We encode the sequence of messages characterizing the correct behaviour of a pattern as Linear Temporal Logic (LTL) formulae and the sequence diagram representing the possible interaction traces among the objects involved in the candidates as Promela specifications. The model checker SPIN verifies that candidates satisfy the LTL formulae. Dynamic analysis is then performed on the obtained candidates by instrumenting the source code and monitoring those instances at runtime through the execution of test cases automatically generated using a search-based approach. The effectiveness of ePAD has been evaluated by detecting instances of 12 creational and behavioral patterns from six publicly available systems. The results reveal that ePAD outperforms other approaches by recovering more actual instances. Furthermore, on average ePAD achieves better results in terms of correctness and completeness.
Choosing an Animal Model for the Study of Functional Dyspepsia
Authors: Ye Yang , Wang Xue-Rui , Zheng Yang , Yang Jing-Wen , Yang Na-Na , Shi Guang-Xia , Liu Cun-Zhi
Published: February 2018

Functional dyspepsia (FD) is a common functional gastrointestinal disorder with pain or discomfort in the upper abdomen as the main characteristic. The prevalence of FD worldwide varies between 5% and 11%. This condition adversely affects attendance and productivity in the workplace. Emerging evidence is beginning to unravel the pathophysiologies of FD, and new data on treatment are helping to guide evidence-based practice. In order to better understand the pathophysiologies of FD and explore better treatment options, various kinds of animal models of FD have been developed. However, it is unclear which of these models most closely mimic the human disease. This review provides a comprehensive overview of the currently available animal models of FD in relationship to the clinical features of the disease. The rationales, methods, merits, and disadvantages for modelling specific symptoms of FD are discussed in detail.
Real-Time Human Detection for Aerial Captured Video Sequences via Deep Models
Authors: AlDahoul Nouar , Md Sabri Aznul Qalid , Mansoor Ali Mohammed
Published: February 2018

Human detection in videos plays an important role in various real life applications. Most of traditional approaches depend on utilizing handcrafted features which are problem-dependent and optimal for specific tasks. Moreover, they are highly susceptible to dynamical events such as illumination changes, camera jitter, and variations in object sizes. On the other hand, the proposed feature learning approaches are cheaper and easier because highly abstract and discriminative features can be produced automatically without the need of expert knowledge. In this paper, we utilize automatic feature learning methods which combine optical flow and three different deep models (i.e., supervised convolutional neural network (S-CNN), pretrained CNN feature extractor, and hierarchical extreme learning machine) for human detection in videos captured using a nonstatic camera on an aerial platform with varying altitudes. The models are trained and tested on the publicly available and highly challenging UCF-ARG aerial dataset. The comparison between these models in terms of training, testing accuracy, and learning speed is analyzed. The performance evaluation considers five human actions (digging, waving, throwing, walking, and running). Experimental results demonstrated that the proposed methods are successful for human detection task. Pretrained CNN produces an average accuracy of 98.09%. S-CNN produces an average accuracy of 95.6% with soft-max and 91.7% with Support Vector Machines (SVM). H-ELM has an average accuracy of 95.9%. Using a normal Central Processing Unit (CPU), H-ELM’s training time takes 445 seconds. Learning in S-CNN takes 770 seconds with a high performance Graphical Processing Unit (GPU).
A Traditional Herbal Formula Xianlinggubao for Pain Control and Function Improvement in Patients with Knee and Hand Osteoarthritis: A Multicenter, Randomized, Open‐Label, Controlled Trial
Authors: Wang Fei , Shi Lei , Zhang Yaonan , Wang Kunzheng , Pei Fuxing , Zhu Hanmin , Shi Zhanjun , Tao Tianzun , Li Zhihua , Zeng Ping , Wang Xiaobing , Ji Quan , Qin Ling , Xue Qingxun
Published: February 2018

Evidence of efficacy of a traditional herbal formula Xianlinggubao (XLGB) for treatment of osteoarthritis (OA) is limited. The present study was designed to evaluate the efficacy of XLGB in the management of patients with knee and hand OA. This was a multicenter, stratified, open‐label, randomized controlled trial conducted at six centers in China. People aged 40 or above, diagnosed with OA of the knee or hand, were randomly assigned to the XLGB treatment group or watchful waiting control group. Main outcome measures were the changes in the numeric pain rating scales (NPRS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) or the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) scores, from baseline to 6 months. In total 534 patients (272 to XLGB and 262 to control group) received interventions. Participants in the XLGB group exhibited significant improvement in NPRS (P < 0.001) and WOMAC score (P < 0.001) or AUSCAN score (P < 0.001) compared to control group. Treatment with XLGB at current regime significantly reduced pain and improved function of the knee and hand in patients with OA over a 6‐month period, implying that XLGB could be suggested as an alternative treatment for patients with knee or hand OA.
Field Reaction Experiments of Carbonate Minerals in Spring Waters: Natural Analogue of Geologic CO2 Storage
Authors: Sorai Masao , Sasaki Munetake , Kuribayashi Takahiro
Published: February 2018

To diminish the uncertainty of the mineral trapping rate during geologic CO2 storage, the growth rate of carbonate minerals was measured in CO2-containing spring waters, which can be regarded as a natural analogue of geologic CO2 storage. The authors’ approach, using nanoscale analysis of seed crystal surfaces after immersion into spring waters, enables rapid and accurate measurement of mineral reaction rates. The results show that calcite growth rates in spring waters were lower by 1–3 orders than the values given in a database of laboratory experiment results. We verified the traditional paradigm that Mg2+ controls carbonate reaction kinetics. An increase of the Mg/Ca ratio to around 5 by adding Mg2+ to spring waters markedly reduced the calcite growth rate. However, even if effects of Mg2+ and flow rate are considered, we were unable to explain satisfactorily the difference of the calcite growth rates between those of spring waters and laboratory experiments. Therefore, other factors might also be related to the slow growth rate in nature. The present results, including the fact such that neither dolomite nor magnesite was formed even at the high Mg/Ca ratio, are expected to provide an important constraint to overestimation of the mineral trapping rate.
Role of Interleukin- (IL-) 17 in the Pathogenesis and Targeted Therapies in Spondyloarthropathies
Authors: Chyuan I-Tsu , Chen Ji-Yih
Published: February 2018

Spondyloarthropathy (SpA) is a unique type of joint inflammation characterized by coexisting erosive bone damage and pathological new bone formation. Previous genetic association studies have demonstrated that several cytokine pathways play a critical role in the pathogenesis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other types of SpA. In addition to several well-known proinflammatory cytokines, recent studies suggest that IL-17 plays a pivotal role in the pathogenesis of SpA. Further evidence from human and animal studies have defined that IL-17 and IL-17-producing cells contribute to tissue inflammation, autoimmunity, and host defense, leading to the following pathologic events associated with SpA. Recently, several clinical trials targeting IL-17 pathways demonstrated the positive response of IL-17 blockade in treating AS, indicating a great potential of IL-17-targeting therapy in SpA. In this review article, we have discussed the contributing role of IL-17 and different IL-17-producing cells in the pathogenesis of SpA and provided an outline of therapeutic application of the IL-17 blockade in the treatment of SpA. Other targeted cytokines associated with IL-17 axis in SpA will also be included.
Modulation of Pulse Train Using Leapfrogging Pulses Developed in Unbalanced Coupled Nonlinear Transmission Lines
Authors: Narahara Koichi
Published: February 2018

The leapfrogging pulses in two unbalanced electrical nonlinear transmission lines (NLTLs) with capacitive couplings are investigated for efficient modulation of a pulse train. Due to the resonant interactions, the nonlinear solitary waves in the NLTLs exhibit complementary behaviors of amplitudes and phases called leapfrogging. For maximizing resonance, both solitary waves should have a common average velocity. Sharing the common velocity, the characteristic impedance can still be freely designed for two coupled solitary waves. In this study, we characterize the leapfrogging pulses developed in unbalanced NLTLs having distinct characteristic impedance. Through the soliton perturbation theory and numerical time-domain calculations, it is found that both the leapfrogging frequency and the voltage variations of pulse amplitudes increase as the difference in the characteristic impedance becomes large. These properties can improve the on/off ratio of modulated pulse train.
Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder
Authors: Grootendorst-van Mil Nina H. , Huiskens Anna R. M. , Dieleman Sieds , Birkenhäger Tom K.
Published: February 2018

The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted.