bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of Passenger Rail Vehicles Under Blast Conditions: Testing and Modeling
Authors: Rakoczy Przemyslaw , Wilson Nicholas , Bruce Ian , Myers Stephanie
Published: July 2017

The mission of the U.S. Transportation Security Administration (TSA) is protection of the nation’s transportation systems to ensure freedom of movement for people and commerce. In furtherance of its mission, TSA’s Office of Security Capabilities has contracted with Transportation Technology Center, Inc. (TTCI) and Arup North America Ltd (Arup) to conduct research to quantify the vulnerability of railcars and infrastructure to damage caused by the use of explosives. The main objectives of the ongoing research program are to develop tools to evaluate the performance of existing railcar structures, develop potential mitigation measures for current railcars, and investigate future advanced designs under blast conditions. TTCI performed a series of full-scale tests on three major passenger railcar types: light rail, commuter and transit. Test scenarios were developed based on extensive risk assessment and historical data. Tested scenarios include single internal charges in various locations, simultaneous internal charges and external charges on a station platform. Well instrumented tests provide experimental assessments of existing railcars’ blast performance and data for validation and refinements of finite element blast models developed by Arup. The blast models incorporate sophisticated computational fluid dynamics (CFD) modeling of blast events to predict blast wave propagation and pressure applied on the structure. Hitherto research has focused on the railcar structure. However the test series has provided information on damage to infrastructure, including rail, ties, ballast, and both catenary and third-rail electrification systems. The finite-element blast models will provide railcar designers the means to investigate the effects of blast mitigation measures and reduce the need for physical tests. Several mitigation measures were installed and tested to evaluate their effectiveness. One car was equipped with typical interior components including seats and partition walls. One side of the car was equipped with standard components and the other side with remedial components that are intended to mitigate the effects of a blast. A similar approach was used for windows. This configuration allowed direct comparisons and performance assessments of the blast mitigation measures. Companion modeling and finite element analysis (FEA) of the blast response of the railcar and interior components provided a computational tool by which mitigation measures may be assessed and refined. This paper summarizes recent research sponsored by TSA and conducted by TTCI and Arup on blast vulnerability of railcars and infrastructure to damage caused by the use of explosives.
Evaluating the Effect of Breakdown Fouling and Water Content on the Ballast Degradation Characteristics
Authors: Faghihi Kashani Hamed , Ho Carlton L. , Hyslip James P.
Published: July 2017

Railroad ballast as a layer of track substructure performs important tasks such as increasing the bearing capacity of the sleepers, providing large voids for drainage and resisting the forces applied to the super-structure. Contamination of ballast as the result of ballast breakdown known as breakdown fouling can prevent ballast from performing its job and also affects the engineering properties of ballast. This paper discusses the drained static triaxial testing on granite ballast material with different amount of breakdown fouling and water content. Large-scale triaxial equipment was used for this testing program at the University of Massachusetts, Amherst. These tests were performed to study the effect of fouling and water content, on the strength properties and degradation characteristics of railroad ballasted track. Ballast with three different fouling percentages from clean to highly fouled ballast (<5%, 15% and 30%) and four water contents from dry to field capacity were tested under three different confining pressures. The results show that although an increase in moisture degrades the fouled ballast, increase in breakdown fouling at constant moisture conditions increases the strength of the ballast.
Brazilian Rail Network Statement: A Tool for Fostering Rail Interoperability
Authors: Barbosa Fábio C.
Published: July 2017

The Brazilian Rail Regulatory Framework was reviewed in 2011 by the National In Land Transport Agency (ANTT), with the edition of a package of Regulatory Resolutions (Resolution nº. 3,694 - Regulation of General Rules for Shippers and Rail Companies, Resolution nº. 3,695 - Regulation of Trackage and Haulage Rights, and Resolution nº. 3,696 - Regulation for Stretch Production Targets and Safety Targets Procedure Agreements) with the basic objectives of: i) create incentives for rail interoperability, ii) promote intra sector competition and, hence, enhance rail role in the national transport sector, and iii) establish new funding sources for the rail sector, in order to support investments needed for increasing rail system capacity. These, together with other structural measures already adopted by ANTT, such as the regulation of investments made by rail concessionaires and the revision of rail price cap rates, complemented the package of rail regulatory measures. For the effective implementation of the principles set out in the mentioned rail regulatory framework review, however, it was necessary to develop a sort of tools to allow regulatory control and reduce asymmetric information within the actors of this important industry. Among these tools, it is highlighted the Rail Network Statement, established by Resolution ANTT nº. 3,695/2011, basically composed of a compilation of the existing rail network main operational and technical data, such as rail gauges, load capacities, operational speeds, clearances, location of locomotives and wagons repair facilities as well as fuel stations, including an inventory of traffic capacity, with a survey of available capacity in all sections of the national rail network. This dataset was intended to reduce asymmetric information between rail industry players - Regulatory Authority, Rail Carriers and Shippers, and, so, enhance the negotiation processes for interoperability operations and investments agreements. Rail Network Statement must be filed annually by Concessionaires, and after a critical analysis and data review by the regulatory agency, it is released on its website for public access to support rail interoperability planning and negotiation process. This work is supposed to present an overview of Brazilian Rail Network Statement structure, with a Case Study Analysis of 2013 Edition, the first issued, with a strong focus on rail capacity analysis, an essential requirement for rail interoperability.
Fixed-Order Controller Design for a High Speed Railway Vehicle
Authors: Türkay Semiha , Leblebici Aslı S. , Akçay Hüseyin
Published: July 2017

Advanced active suspension systems has attracted considerable attention in modern railway vehicle designs in recent years. The purpose of the suspension is to attenuate the vehicle vibrations due to various rail excitations. With active suspensions it is aimed to improve the performance in some cases, while not making it worse in others. The performance-related objectives can be approximately translated in different norm bounds on certain transfer functions or impulse responses.

In this paper, a multi-objective problem is formulated as a non-convex and non-smooth optimization problem for a full-car railway vehicle modelled with seventeen-degrees-of-freedom (17 DOF) and excited by random rail inputs. The controller order restricted to be less than or equal to the passive system model order. For a range of orders, controllers are synthesized by using the HIFOO toolbox.
First record of Hexathrombium (Acari: Microtrombidiidae) on Tetracha (Tetracha) brasiliensis brasiliensis (Coleoptera: Cicindelidae) in Argentina
Authors: Almada Melina Soledad , Cédola Claudia Viviana
Published: July 2017

Mites of the genus Hexathrombium Cooreman were collected from Tetracha (Tetracha) brasiliensis brasiliensis (Cicindelidae) in Bt cotton crops. This is the first record of this mite in Argentina.
Corpus of deaf speech for acoustic and speech production research
Authors: Mendel Lisa Lucks , Lee Sungmin , Pousson Monique , Patro Chhayakanta , McSorley Skylar , Banerjee Bonny , Najnin Shamima , Kapourchali Masoumeh Heidari
Published: July 2017

A corpus of recordings of deaf speech is introduced. Adults who were pre- or post-lingually deafened as well as those with normal hearing read standardized speech passages totaling 11 h of .wav recordings. Preliminary acoustic analyses are included to provide a glimpse of the kinds of analyses that can be conducted with this corpus of recordings. Long term average speech spectra as well as spectral moment analyses provide considerable insight into differences observed in the speech of talkers judged to have low, medium, or high speech intelligibility.
A push for low-carbon fuels pays off in California
Authors: Service Robert F.
Published: July 2017

But new EPA rule would cut federal support for advanced biofuels like biodiesel
Guanine glycation repair by DJ-1/Park7 and its bacterial homologs
Authors: Richarme Gilbert , Liu Cailing , Mihoub Mouadh , Abdallah Jad , Leger Thibaut , Joly Nicolas , Liebart Jean-Claude , Jurkunas Ula V. , Nadal Marc , Bouloc Philippe , Dairou Julien , Lamouri Aazdine
Published: July 2017

Not-so-sweet DNA damage repaired

Glyoxal and methylglyoxal, by-products of sugar metabolism that are present in all cells, can react with, and thus damage, DNA. Indeed, glycation of guanine (G) is as prevalent as the major product of oxidative damage in DNA, 8-oxo-dG. Richarme
et al.
show that both prokaryotes and eukaryotes have dedicated systems that specifically repair glycation damage (see the Perspective by Dingler and Patel). The parkinsonism-associated protein DJ-1/Park7 and its bacterial homologs Hsp31, YhbO, and YajL direct the enzymatic repair of damaged glycated bases in DNA. The proteins also clean up the more vulnerable pool of free nucleotides in the cell, which are more susceptible to glycation than the nucleotides within DNA.

Science
, this issue p.
208
; see also p.
130
Control and local measurement of the spin chemical potential in a magnetic insulator
Authors: Du Chunhui , van der Sar Toeno , Zhou Tony X. , Upadhyaya Pramey , Casola Francesco , Zhang Huiliang , Onbasli Mehmet C. , Ross Caroline A. , Walsworth Ronald L. , Tserkovnyak Yaroslav , Yacoby Amir
Published: July 2017

Diamonds to the rescue

Keeping track of spin transport inside a spintronic device is challenging. Du
et al.
came up with a method involving diamond nitrogen-vacancy (NV) centers, which can act like tiny, very sensitive magnetometers. The authors placed diamond nanobeams containing the NV centers in close proximity to the sample. This allowed them to measure the spin chemical potential of spin waves—so-called magnons—with nanometer resolution in the material yttrium iron garnet. Because NV centers are also sensitive to temperature, the method may be of use in spin caloritronics.

Science
, this issue p.
195
All-oxide–based synthetic antiferromagnets exhibiting layer-resolved magnetization reversal
Authors: Chen Binbin , Xu Haoran , Ma Chao , Mattauch Stefan , Lan Da , Jin Feng , Guo Zhuang , Wan Siyuan , Chen Pingfan , Gao Guanyin , Chen Feng , Su Yixi , Wu Wenbin
Published: July 2017

Making an oxide-layered antiferromagnet

Antiferromagnetism, a state of matter where ordered neighboring spins point in opposite directions, can be engineered in layered heterostructures, which affords control over their properties. Doing so in oxide heterostructures is tricky because the necessary ferromagnetism of the constituent layers may not survive thinning to nanometer thicknesses. Chen
et al.
overcame this materials challenge by finding and growing the right combination of substrate, magnetic, and insulating layers to engineer antiferromagnetic coupling. The resulting superlattices, consisting of alternating layers of a ferromagnetic oxide and an insulating material, exhibit layer-by-layer switching of magnetization.

Science
, this issue p.
191
History of winning remodels thalamo-PFC circuit to reinforce social dominance
Authors: Zhou Tingting , Zhu Hong , Fan Zhengxiao , Wang Fei , Chen Yang , Liang Hexing , Yang Zhongfei , Zhang Lu , Lin Longnian , Zhan Yang , Wang Zheng , Hu Hailan
Published: July 2017

The brain circuits of a winner

Social dominance in mice depends on their history of winning in social contests. Zhou
et al.
found that this effect is mediated by neuronal projections from the thalamus to a brain region called the dorsomedial prefrontal cortex. Selective manipulation of synapses driven by this input revealed a causal relationship between circuit activity and mental effort–based dominance behavior. Thus, synapses in this pathway store the memory of previous winning or losing history.

Science
, this issue p.
162
Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition
Authors: Zenk Fides , Loeser Eva , Schiavo Rosaria , Kilpert Fabian , Bogdanović Ozren , Iovino Nicola
Published: July 2017

Intergenerational transcription taming

Parents provide genetic information that guides the development of the offspring. Zenk
et al.
show that epigenetic information, in the form of the repressive mark H3K27me3, is also propagated to the offspring and regulates proper gene expression in the embryo. Preventing the propagation of maternally inherited H3K27me3 led to precocious gene activation and, ultimately, embryo lethality.

Science
, this issue p.
212
Improving vaccine trials in infectious disease emergencies
Authors: Lipsitch Marc , Eyal Nir
Published: July 2017

Unprecedented global effort is under way to facilitate the testing of countermeasures in infectious disease emergencies. Better understanding of the various options for trial design is needed in advance of outbreaks, as is preliminary global agreement on the most suitable designs for the various scenarios. What would enhance the speed, validity, and ethics of clinical studies of such countermeasures? Focusing on studies of vaccine efficacy and effectiveness in emergencies, we highlight three needs: for formal randomized trials—even in most emergencies; for individually randomized trials—even in many emergencies; and for six areas of innovation in trial methodology. These needs should inform current updates of protocols and roadmaps.
Opportunities and challenges in modeling emerging infectious diseases
Authors: Metcalf C. Jessica E. , Lessler Justin
Published: July 2017

The term “pathogen emergence” encompasses everything from previously unidentified viruses entering the human population to established pathogens invading new populations and the evolution of drug resistance. Mathematical models of emergent pathogens allow forecasts of case numbers, investigation of transmission mechanisms, and evaluation of control options. Yet, there are numerous limitations and pitfalls to their use, often driven by data scarcity. Growing availability of data on pathogen genetics and human ecology, coupled with computational and methodological innovations, is amplifying the power of models to inform the public health response to emergence events. Tighter integration of infectious disease models with public health practice and development of resources at the ready has the potential to increase the timeliness and quality of responses.
Can we beat influenza?
Authors: Zhang Wenqing , Webster Robert G.
Published: July 2017

For the past 65 years, the Global Influenza Surveillance and Response System (GISRS), coordinated by the World Health Organization (WHO), has engaged in open and efficient sharing of information, viruses, and responsibilities. The GISRS's extraordinary longevity can be attributed to several generations of dedicated scientists and to the engagement of over 100 countries, often with limited resources. Currently, only two influenza A viruses and two influenza B clades are circulating and causing disease in humans, but 16 additional subtypes of influenza A viruses are circulating in nature (14 in birds and two in bats). Of the latter, six occasionally infect humans, providing an ever-looming pandemic threat. However, there is still a lack of fundamental knowledge to predict if and when a particular viral subtype will acquire pandemic ability. We therefore still fail to predict influenza pandemics, and this must change.
The importance of being modular
Authors: Sales-Pardo Marta
Published: July 2017

An experiment proves the value of modularity in complex systems under perturbation
The Sun spotters
American Eclipse
David Baron
Liveright, 2017. 349 pp.
Authors: Carson Jennifer
Published: July 2017

An 1878 eclipse offered American scientists the chance to prove their scientific chops. Did they deliver?
Tailor-made T cells for cancer therapy
Authors: Byrne Leah C.
Published: July 2017

Investigators from two teams have created personalized vaccines for the treatment of melanoma by identifying tumor-specific neoantigens.
Mitochondrial Cochaperone Mge1 Is Involved in Regulating Susceptibility to Fluconazole in
Saccharomyces cerevisiae
and
Candida
Species
Authors: Demuyser Liesbeth , Swinnen Erwin , Fiori Alessandro , Herrera-Malaver Beatriz , Verstrepen Kevin , Van Dijck Patrick
Published: July 2017

MGE1
encodes a yeast chaperone involved in Fe-S cluster metabolism and protein import into the mitochondria. In this study, we identified
MGE1
as a multicopy suppressor of susceptibility to the antifungal fluconazole in the model yeast
Saccharomyces cerevisiae
. We demonstrate that this phenomenon is not exclusively dependent on the integrity of the mitochondrial DNA or on the presence of the drug efflux pump Pdr5. Instead, we show that the increased dosage of Mge1 plays a protective role by retaining increased amounts of ergosterol upon fluconazole treatment. Iron metabolism and, more particularly, Fe-S cluster formation are involved in regulating this process, since the responsible Hsp70 chaperone, Ssq1, is required. Additionally, we show the necessity but, by itself, insufficiency of activating the iron regulon in establishing the Mge1-related effect on drug susceptibility. Finally, we confirm a similar role for Mge1 in fluconazole susceptibility in the pathogenic fungi
Candida glabrata
and
Candida albicans
.

IMPORTANCE
Although they are mostly neglected compared to bacterial infections, fungal infections pose a serious threat to the human population. While some of them remain relatively harmless, infections that reach the bloodstream often become lethal. Only a few therapies are available, and resistance of the pathogen to these drugs is a frequently encountered problem. It is thus essential that more research is performed on how these pathogens cope with the treatment and cause recurrent infections. Baker’s yeast is often used as a model to study pathogenic fungi. We show here, by using this model, that iron metabolism and the formation of the important iron-sulfur clusters are involved in regulating susceptibility to fluconazole, the most commonly used antifungal drug. We show that the same process likely also occurs in two of the most regularly isolated pathogenic fungi,
Candida glabrata
and
Candida albicans
.
Disguised as a Sulfate Reducer: Growth of the Deltaproteobacterium
Desulfurivibrio alkaliphilus
by Sulfide Oxidation with Nitrate
Authors: Thorup Casper , Schramm Andreas , Findlay Alyssa J. , Finster Kai W. , Schreiber Lars
Published: July 2017

This study demonstrates that the deltaproteobacterium
Desulfurivibrio alkaliphilus
can grow chemolithotrophically by coupling sulfide oxidation to the dissimilatory reduction of nitrate and nitrite to ammonium. Key genes of known sulfide oxidation pathways are absent from the genome of
D. alkaliphilus
. Instead, the genome contains all of the genes necessary for sulfate reduction, including a gene for a reductive-type dissimilatory bisulfite reductase (DSR). Despite this, growth by sulfate reduction was not observed. Transcriptomic analysis revealed a very high expression level of sulfate-reduction genes during growth by sulfide oxidation, while inhibition experiments with molybdate pointed to elemental sulfur/polysulfides as intermediates. Consequently, we propose that
D. alkaliphilus
initially oxidizes sulfide to elemental sulfur, which is then either disproportionated, or oxidized by a reversal of the sulfate reduction pathway. This is the first study providing evidence that a reductive-type DSR is involved in a sulfide oxidation pathway. Transcriptome sequencing further suggests that nitrate reduction to ammonium is performed by a novel type of periplasmic nitrate reductase and an unusual membrane-anchored nitrite reductase.

IMPORTANCE
Sulfide oxidation and sulfate reduction, the two major branches of the sulfur cycle, are usually ascribed to distinct sets of microbes with distinct diagnostic genes. Here we show a more complex picture, as
D. alkaliphilus
, with the genomic setup of a sulfate reducer, grows by sulfide oxidation. The high expression of genes typically involved in the sulfate reduction pathway suggests that these genes, including the reductive-type dissimilatory bisulfite reductases, are also involved in as-yet-unresolved sulfide oxidation pathways. Finally,
D. alkaliphilus
is closely related to cable bacteria, which grow by electrogenic sulfide oxidation. Since there are no pure cultures of cable bacteria,
D. alkaliphilus
may represent an exciting model organism in which to study the physiology of this process.
Drought Stress Results in a Compartment-Specific Restructuring of the Rice Root-Associated Microbiomes
Authors: Santos-Medellín Christian , Edwards Joseph , Liechty Zachary , Nguyen Bao , Sundaresan Venkatesan
Published: July 2017

Plant roots support complex microbial communities that can influence plant growth, nutrition, and health. While extensive characterizations of the composition and spatial compartmentalization of these communities have been performed in different plant species, there is relatively little known about the impact of abiotic stresses on the root microbiota. Here, we have used rice as a model to explore the responses of root microbiomes to drought stress. Using four distinct genotypes, grown in soils from three different fields, we tracked the drought-induced changes in microbial composition in the rhizosphere (the soil immediately surrounding the root), the endosphere (the root interior), and unplanted soils. Drought significantly altered the overall bacterial and fungal compositions of all three communities, with the endosphere and rhizosphere compartments showing the greatest divergence from well-watered controls. The overall response of the bacterial microbiota to drought stress was taxonomically consistent across soils and cultivars and was primarily driven by an enrichment of multiple
Actinobacteria
and
Chloroflexi
, as well as a depletion of several
Acidobacteria
and
Deltaproteobacteria
. While there was some overlap in the changes observed in the rhizosphere and endosphere communities, several drought-responsive taxa were compartment specific, a pattern likely arising from preexisting compositional differences, as well as plant-mediated processes affecting individual compartments. These results reveal that drought stress, in addition to its well-characterized effects on plant physiology, also results in restructuring of root microbial communities and suggest the possibility that constituents of the altered plant microbiota might contribute to plant survival under extreme environmental conditions.

IMPORTANCE
With the likelihood that changes in global climate will adversely affect crop yields, the potential role of microbial communities in enhancing plant performance makes it important to elucidate the responses of plant microbiomes to environmental variation. By detailed characterization of the effect of drought stress on the root-associated microbiota of the crop plant rice, we show that the rhizosphere and endosphere communities undergo major compositional changes that involve shifts in the relative abundances of a taxonomically diverse set of bacteria in response to drought. These drought-responsive microbes, in particular those enriched under water deficit conditions, could potentially benefit the plant as they could contribute to tolerance to drought and other abiotic stresses, as well as provide protection from opportunistic infection by pathogenic microbes. The identification and future isolation of microbes that promote plant tolerance to drought could potentially be used to mitigate crop losses arising from adverse shifts in climate.
Dengue Virus Hijacks a Noncanonical Oxidoreductase Function of a Cellular Oligosaccharyltransferase Complex
Authors: Lin David L. , Cherepanova Natalia A. , Bozzacco Leonia , MacDonald Margaret R. , Gilmore Reid , Tai Andrew W.
Published: July 2017

Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation. However, the OST subunit MAGT1, which associates with STT3B, is also required for DENV propagation. MAGT1 expression requires STT3B, and a catalytically inactive STT3B also rescues MAGT1 expression, supporting the hypothesis that STT3B serves to stabilize MAGT1 in the context of DENV infection. We found that the oxidoreductase CXXC active site motif of MAGT1 was necessary for DENV propagation, as cells expressing an AXXA MAGT1 mutant were unable to support DENV infection. Interestingly, cells expressing single-cysteine CXXA or AXXC mutants of MAGT1 were able to support DENV propagation. Utilizing the engineered peroxidase APEX2, we demonstrate the close proximity between MAGT1 and NS1 or NS4B during DENV infection. These results reveal that the oxidoreductase activity of the STT3B-containing OST is necessary for DENV infection, which may guide the development of antiviral agents targeting DENV.

IMPORTANCE
The host oligosaccharyltransferase (OST) complexes have been identified as essential host factors for dengue virus (DENV) replication; however, their functions during DENV infection are unclear. A previous study showed that the canonical OST activity was dispensable for DENV replication, suggesting that the OST complexes serve as scaffolds for DENV replication. However, our work demonstrates that one function of the OST complex during DENV infection is to provide oxidoreductase activity via the OST subunit MAGT1. We also show that MAGT1 associates with DENV NS1 and NS4B during viral infection, suggesting that these nonstructural proteins may be targets of MAGT1 oxidoreductase activity. These results provide insight into the cell biology of DENV infection, which may guide the development of antivirals against DENV.
Lack of AcrB Efflux Function Confers Loss of Virulence on
Salmonella enterica
Serovar Typhimurium
Authors: Wang-Kan Xuan , Blair Jessica M. A. , Chirullo Barbara , Betts Jonathan , La Ragione Roberto M. , Ivens Alasdair , Ricci Vito , Opperman Timothy J. , Piddock Laura J. V.
Published: July 2017

AcrAB-TolC is the paradigm resistance-nodulation-division (RND) multidrug resistance efflux system in Gram-negative bacteria, with AcrB being the pump protein in this complex. We constructed a nonfunctional AcrB mutant by replacing D408, a highly conserved residue essential for proton translocation. Western blotting confirmed that the AcrB D408A mutant had the same native level of expression of AcrB as the parental strain. The mutant had no growth deficiencies in rich or minimal medium. However, compared with wild-type SL1344, the mutant had increased accumulation of Hoechst 33342 dye and decreased efflux of ethidium bromide and was multidrug hypersusceptible. The D408A mutant was attenuated
in vivo
in mouse and
Galleria mellonella
models and showed significantly reduced invasion into intestinal epithelial cells and macrophages
in vitro
. A dose-dependent inhibition of invasion was also observed when two different efflux pump inhibitors were added to the wild-type strain during infection of epithelial cells. RNA sequencing (RNA-seq) revealed downregulation of bacterial factors necessary for infection, including those in the
Salmonella
pathogenicity islands 1, 2, and 4; quorum sensing genes; and
phoPQ
. Several general stress response genes were upregulated, probably due to retention of noxious molecules inside the bacterium. Unlike loss of AcrB protein, loss of efflux function did not induce overexpression of other RND efflux pumps. Our data suggest that gene deletion mutants are unsuitable for studying membrane transporters and, importantly, that inhibitors of AcrB efflux function will not induce expression of other RND pumps.

IMPORTANCE
Antibiotic resistance is a major public health concern. In Gram-negative bacteria, overexpression of the AcrAB-TolC multidrug efflux system confers resistance to clinically useful drugs. Here, we show that loss of AcrB efflux function causes loss of virulence in
Salmonella enterica
serovar Typhimurium. This is due to the reduction of bacterial factors necessary for infection, which is likely to be caused by the retention of noxious molecules inside the bacterium. We also show that, in contrast to loss of AcrB protein, loss of efflux does not induce overexpression of other efflux pumps from the same family. This indicates that there are differences between loss of efflux protein and loss of efflux that make gene deletion mutants unsuitable for studying the biological function of membrane transporters. Understanding the biological role of AcrB will help to assess the risks of targeting efflux pumps as a strategy to combat antibiotic resistance.
Parasite Microbiome Project: Systematic Investigation of Microbiome Dynamics within and across Parasite-Host Interactions
Authors: Dheilly Nolwenn M. , Bolnick Daniel , Bordenstein Seth , Brindley Paul J. , Figuères Cédric , Holmes Edward C. , Martínez Martínez Joaquín , Phillips Anna J. , Poulin Robert , Rosario Karyna
Published: July 2017

Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions.
Insights into Butyrate Production in a Controlled Fermentation System via Gene Predictions
Authors: Esquivel-Elizondo S. , Ilhan Z. E. , Garcia-Peña E. I. , Krajmalnik-Brown R.
Published: July 2017

This study demonstrates how bioinformatics tools, such as metagenome functional prediction from 16S rRNA genes, can help understand biological systems and reveal microbial interactions in controlled systems (e.g., bioreactors). Results obtained from controlled systems are easier to interpret than those from human/animal studies because observed changes may be specifically attributed to the design conditions imposed on the system. Bioinformatics analysis allowed us to identify potential butyrogenic phylotypes and associated butyrate metabolism pathways when we systematically varied the PH2in a carefully controlled fermentation system. Our insights may be adapted to butyrate production studies in biohydrogen systems and gut models, since butyrate is a main product and a crucial fatty acid in human/animal colon health.
Acute Achilles tendon rupture
Authors: Singh Dishan
Published: July 2017

This is one of a series of occasional articles highlighting conditions that may be more common than many doctors realise or may be missed at first presentation. The series advisers are Anthony Harnden, professor of primary care, Department of Primary Care Health Sciences, University of Oxford, and Richard Lehman, general practitioner, Banbury. To suggest a topic for this series, please email us at practice@bmj.com.
Prevalence and risk factors of latent tuberculosis infection in Africa: a systematic review and meta-analysis protocol
Authors: Basera Tariro J , Ncayiyana Jabulani , Engel Mark E
Published: July 2017

Introduction

Latent tuberculosis infection (LTBI) remains a major public health problem and one of the major contributors to the pool of active tuberculosis cases. The true burden of LTBI in Africa is not known. Early modelling studies estimate that over 33% of the world’s population is infected with latent tuberculosis. We propose conducting a systematic review and a meta-analysis to evaluate the burden and risk factors of LTBI in Africa reported in studies from 2000 to 2017.

Methods and analysis

We will include cross-sectional studies, cohort studies and case-control studies estimating either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) confirmed prevalence of LTBI and associated risk factors among people in African countries. A comprehensive search of relevant literature will be conducted on electronic databases using common and medical subject heading (MeSH) terms for LTBI, and an African search filter. Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a quality score assessment tool. Standardised data extraction will be carried out after which prevalence estimates will be pooled using random-effects models in Stata V.13. Where there is sufficient data , subgroup meta-analyses will be conducted by risk factors including participant’s age group, occupation, location and HIV status. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols 2015 Statement.

Ethics and dissemination

No ethical issues were foreseen given that this was a protocol for a systematic review of published studies. The results of this study will be published in a peer-reviewed journal and presented at conferences.

Trial registration number

Systematic review registration: PROSPERO CRD42016037997
Retrospective analysis of newly recorded certifications of visual impairment due to diabetic retinopathy in Wales during 2007–2015
Authors: Thomas Rebecca L , Luzio Stephen D , North Rachel V , Banerjee Sanjiv , Zekite Antra , Bunce Catey , Owens David R
Published: July 2017

Objective

The aim of this study was to analyse the changes in new certifications for both sight impairment (SI) and severe sight impairment (SSI, blindness) in Wales due to diabetic retinopathy (DR)/maculopathy between 2007 and 2015.

Research design and methods

This is a retrospective analysis of annual data of new certifications for visual impairment and blindness (Certificate of Vision Impairment) for England and Wales derived from the national database provided by the Certifications Office, Moorfields Eye Hospital, over a period of 8 years from 2007.

Results

In Wales there were 339 less new certifications for both SI and severe SSI from any cause combined from 2007–2008 to 2014–2015. The number SI and SSI combined specifically due to DR was reduced by 22 in people with known diabetes. This was a reduction in new certifications over the observation period from 82.4 to 46.9 per 100 000 (−43.1%) with a fall in SSI from 31.3 to 15.8 per 100 000 (−49.4%), respectively. During this observation period however, there was a parallel increase in 52 229 (39.8%) persons with diabetes in Wales.

Conclusions

While acknowledging the limitations of the certification process and the increasing numbers of persons with diabetes, the incidence of SI and SSI per 100 000 population of persons with diabetes in Wales has almost halved over an 8-year period up to 2015. This may reflect the earlier diagnosis of DR and sight-threatening DR since the introduction of screening and/or improved diabetes management with timely onward referral and newer treatments.
Concomitant preterm birth and severe small-for-gestational age birth weight among infants of immigrant mothers in Ontario originating from the Philippines and East Asia: a population-based study
Authors: Bartsch Emily , Park Alison L , Jairam Jennifer , Ray Joel G
Published: July 2017

Objectives

Women from the Philippines form one of the largest immigrant groups to North America. Their newborns experience higher rates of preterm birth (PTB), and separately, small-for-gestational age (SGA) birth weight, compared with other East Asians. It is not known if Filipino women are at elevated risk of concomitant PTB and severe SGA (PTB–SGA), a pathological state likely reflective of placental dysfunction and neonatal morbidity.

Methods

We conducted a population-based study of all singleton or twin live births in Ontario, from 2002 to 2011, among immigrant mothers from the Philippines (n=27 946), Vietnam (n=15 297), Hong Kong (n=5618), South Korea (n=5148) and China (n=42 517). We used modified Poisson regression to generate relative risks (RR) of PTB-SGA, defined as a birth <37 weeks’ gestation and a birth weight <5th percentile. RRs were adjusted for maternal age, parity, marital status, income quintile, infant sex and twin births.

Results

Relative to mothers from China (2.3 per 1000), the rate of PTB–SGA was significantly higher among infants of mothers from the Philippines (6.5 per 1000; RR 2.91, 95% CI 2.27 to 3.73), and those from Vietnam (3.7 per 1000; RR 1.68, 95% CI 1.21 to 2.34). The RR of PTB–SGA was not higher for infants of mothers from Hong Kong or South Korea.

Interpretation

Among infants born to immigrant women from five East Asian birthplaces, the risk of PTB–SGA was highest among those from the Philippines. These women and their fetuses may require additional monitoring and interventions.
BET 2: Poor evidence on whether teaching cognitive debiasing, or cognitive forcing strategies, lead to a reduction in errors attributable to cognition in emergency medicine students or doctors
Authors: Oliver Govind , Oliver Gopal , Body Rick
Published: July 2017

A short review was carried out to see if teaching cognitive forcing strategies reduces cognitive error in the practice of emergency medicine. Two relevant papers were found using the described search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. There is currently little evidence that teaching cognitive forcing strategies reduces cognitive error in the practice of emergency medicine.
MDHAQ/RAPID3 scores in patients with osteoarthritis are similar to or higher than in patients with rheumatoid arthritis: a cross-sectional study from current routine rheumatology care at four sites
Authors: El-Haddad Carlos , Castrejon Isabel , Gibson Kathryn A , Yazici Yusuf , Bergman Martin J , Pincus Theodore
Published: July 2017

Objective

To compare patients with a primary diagnosis of osteoarthritis (OA) versus rheumatoid arthritis (RA) for scores on a patient self-report MDHAQ/RAPID3 (Multidimensional Health Assessment Questionnaire/Routine Assessment of Patient Index Data 3), and for physician global assessment (DOCGL).

Methods

All patients with all diagnoses complete an MDHAQ/RAPID3 at all routine rheumatology visits in the waiting area before seeing a rheumatologist at four sites, one in Australia and three in the USA. The two-page MDHAQ includes 0–10 scores for physical function (in 10 activities), pain and patient global assessment [on 0–10 visual analogue scales (VAS)], compiled into a 0–30 RAPID3, as well as fatigue and self-report painful joint count scales. Rheumatologists estimate a 0–10 DOCGL VAS. Demographic, MDHAQ/RAPID3 and DOCGL data from a random visit were compared in patients with RA versus patients with OA using multivariate analysis of variance, adjusted for age, disease duration and formal education level.

Results

Median RAPID3 was higher in OA versus RA at all four sites (11.7–16.8 vs 6.2–11.8) (p<0.001 at three sites). Median DOCGL in OA versus RA was 5 vs 4, 4 vs 3.7, 2.2 vs 2.5 and 2 vs 1. Patterns were similar for individual RAPID3 items, fatigue and painful joint scales, and in stratified analyses of patients aged 55–70.

Conclusion

Patient MDHAQ/RAPID3 and physician DOCGL indicate similar or higher disease burden in OA versus RA. Routine MDHAQ/RAPID3 allows direct comparisons of the two diseases. The findings suggest possible revision of current clinical and public policy views concerning OA.
Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial
Authors: Mease Philip J , Kavanaugh Arthur , Coates Laura C , McInnes Iain B , Hojnik Maja , Zhang Ying , Anderson Jaclyn K , Dorr Alexander P , Gladman Dafna D
Published: July 2017

Objectives

To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs).

Methods

Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144.

Results

In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers.

Conclusions

Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs.
Up–down colorings of virtual-link diagrams and the necessity of Reidemeister moves of type II
Authors: Oshiro Kanako , Shimizu Ayaka , Yaguchi Yoshiro
Published: July 2017

We introduce an up–down coloring of a virtual-link (or classical-link) diagram. The colorabilities give a lower bound of the minimum number of Reidemeister moves of type II which are needed between two [Formula: see text]-component virtual-link (or classical-link) diagrams. By using the notion of a quandle cocycle invariant, we give a method to detect the necessity of Reidemeister moves of type II between two given virtual-knot (or classical-knot) diagrams. As an application, we show that for any virtual-knot diagram [Formula: see text], there exists a diagram [Formula: see text] representing the same virtual-knot such that any sequence of generalized Reidemeister moves between them includes at least one Reidemeister move of type II.
Incompressible SPH Modeling of Rotary Micropump Mixers
Authors: Shamsoddini Rahim
Published: July 2017

In the present study, for the first time, the flow and mass transfer in the rotary micropump-micromixers were investigated by the SPH method. In fact, the present work shows the ability of the SPH method to model the mixing process due to pumping action. The incompressible SPH method applied for modeling is improved by the kernel gradient corrective tensor, a particle shifting algorithm, and an improved periodic boundary condition. SPH is a proper method for modeling the mixing process because there is no modeling for the convective terms and so, the false diffusion is not observed in the SPH modeling. In the present study, first, a viscous micropump comprising a microchannel in which a circular cylinder rotates with special eccentricity is modeled and validated. Then, the geometry is manipulated in order to achieve a desirable micromixer.
N-ary hyperstructures associated to the genotypes of F2-offspring
Authors: Al-Tahan M. , Davvaz B.
Published: July 2017

In this paper, we consider an application of hyperstructure theory in biological inheritance in which we deal with [Formula: see text]-ary hyperstructures associated to the genotypes of the second generation [Formula: see text] for [Formula: see text]. First, we define a hyperoperation × (mating) on [Formula: see text] and prove that it is a cyclic [Formula: see text]-semigroup under the defined hyperoperation. Then we define a ternary hyperstructure [Formula: see text] associated to the genotypes of [Formula: see text] and prove that [Formula: see text] is a ternary [Formula: see text]-semigroup. Finally, we define a [Formula: see text]-ary hyperstructure [Formula: see text] associated to the genotypes of [Formula: see text] and prove that [Formula: see text] is a [Formula: see text]-ary [Formula: see text]-semigroup.
Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle
Authors: Ruby Maxwell A. , Riedl Isabelle , Massart Julie , Åhlin Marcus , Zierath Juleen R.
Published: July 2017

Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5′-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism.