bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative study between responses of isolated bovine and equine digital arteries to vasoactive mediators
Authors: Zizzadoro C. , Caruso M. , Punzi S. , Crescenzo G. , Zongoli F. , Belloli C.
Published: July 2017

Hemodynamic perturbations, partly resulting from abnormal vasoconstriction of digital vessels, have been implicated in the pathogenesis of bovine and equine laminitis. This study compared the responsiveness of isolated bovine (BDA) and equine (EDA) digital arteries to pharmacological agents that stimulate receptor systems involved in the regulation of normal vessel tone. The role of the endothelium and the short‐ and longer‐term effects of an experimentally induced endothelial damage were also evaluated. Species‐related differences were found in the vessel reactivity to all of the receptor agonists tested. In intactBDA, as compared to intactEDA, norepinephrine was a more effective vasoconstrictor, 5‐hydroxytryptamine a more effective but less potent vasoconstrictor, isoproterenol a less effective vasodilator and carbamylcholine a less potent vasodilator. InBDA, but not inEDA, the contractile responses to norepinephrine and 5‐hydroxytryptamine were enhanced immediately after endothelium removal. However, the contractile reactivity of denudedBDAreturned to basal values following overnight incubation. The differences suggest species specificity for the pathophysiology of digital vasomotor tone and function in horses and cattle.
Esophageal function testing: Billing and coding update
Authors: Khan A. , Massey B. , Rao S. , Pandolfino J.
Published: July 2017

Background and Purpose

Esophageal function testing is being increasingly utilized in diagnosis and management of esophageal disorders. There have been several recent technological advances in the field to allow practitioners the ability to more accurately assess and treat such conditions, but there has been a relative lack of education in the literature regarding the associated Common Procedural Terminology (CPT) codes and methods of reimbursement. This review, commissioned and supported by the American Neurogastroenterology and Motility Society Council, aims to summarize each of the CPT codes for esophageal function testing and show the trends of associated reimbursement, as well as recommend coding methods in a practical context. We also aim to encourage many of these codes to be reviewed on a gastrointestinal (GI) societal level, by providing evidence of both discrepancies in coding definitions and inadequate reimbursement in this new era of esophageal function testing.
The “sharing” economy: labor, inequality, and social connection on for‐profit platforms
Authors: Schor Juliet B. , Attwood‐Charles William
Published: July 2017

For social analysts, what has come to be called the “sharing economy” raises important questions. After a discussion of history and definitions, we focus on 3 areas of research in the for‐profit segment, also called the platform economy: social connection, conditions for laborers, and inequalities. Although we find that some parts of the platform economy, particularly Airbnb, do foster social connection, there are also ways in which even shared hospitality is becoming more like conventional exchange. With respect to labor conditions, we find they vary across platforms and the degree to which workers are dependent on the platform to meet their basic needs. On inequality, there is mounting evidence that platforms are facilitating person‐to‐person discrimination by race. In addition, platforms are advantaging those who already have human capital or physical assets, in contrast to claims that they provide widespread opportunity or even advantage less privileged individuals.
The Effects of Knowledge about Poverty, Exposure to Poverty and Trust on Policymakers’ Perceptions about Poverty
Authors: Lahat Lihi
Published: July 2017

This article explores two questions: (1) Does knowledge about poverty and exposure to poverty affect the perceptions of policymakers about how to deal with the problem? (2) Does policymakers’ trust in members of society affect their perceptions regarding ways of dealing with poverty? Based on interviewees with 103 policymakers in Israel, the findings reveal that knowledge about poverty and trust in the members of society have an effect on policy perceptions. The result may have a theoretical contribution to the policy theory at the individual level and practical implications for policy entrepreneurs.
D antibodies in pregnant women in multiethnic Suriname: the observational RheSuN study
Authors: Zonneveld Rens , Kanhai Humphrey H.H. , Lamers Margriet , Brand Anneke , Zijlmans Wilco C.W.R. , Schonewille Henk
Published: July 2017

BACKGROUND

Maternal antibodies against the D antigen are the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). In high‐income countries, the risk of D immunization has been reduced by routine antenatal and postpartum administration of RhIG from 13% to less than 0.5%. In less‐resourced countries, such as Suriname, red blood cell (RBC) antibody screening during pregnancy and prophylactic RhIG administration are not routine. Accurate data on D immunization risk is not available. In the RheSuN (Rhesus Surinamese Neonates) study, the prevalence and the hemolytic potential of maternal D antibodies were investigated.

STUDY DESIGN AND METHODS

A multicenter cross‐sectional study in four major hospitals in Paramaribo, Suriname, covering 90% of approximately 10,000 births yearly in Suriname. Included were D– pregnant women of various ethnicities seeking routine prenatal care and/or their newborns.

RESULTS

D antibodies were detected in 19 of 214 D– pregnancies (8.9%; 95% confidence interval, 5.1%‐12.7%), in 2.0% of primigravid and 11.7% of multigravid women. The direct antiglobulin test was positive in 11 of 13 tested D+ newborns. Determination of D antibody titers and antibody‐dependent cell mediated cytotoxicity (ADCC) assay revealed three newborns at high risk for HDFN (ADCC > 50%).

CONCLUSION

D immunization risk in Suriname women is comparable to the pre–anti‐D prophylaxis era in high‐income countries. Recommended is free‐of‐charge routine RBC antibody screening and prophylactic RhIG administration for women at risk for D antibody formation as part of standard of ante‐ and postnatal care.
New localities and awn morphology variation in Miscanthus ×ogiformis
Authors: Hayakawa Hiroshi , Nishiwaki Aya , Nishida Tomoko , Konuma Akihiro
Published: July 2017

Miscanthus ×ogiformis is a hybrid between Miscanthus sacchariflorus and Miscanthus sinensis and its several synonyms indicate the insufficient understanding of the morphological variation of its awn on the spikelet, which is a key characteristic for identifying Miscanthus species. In the present study, all the Miscanthus specimens in 19 herbaria were examined in order to find new localities for Miscanthus ×ogiformis. Thirty‐nine Miscanthus ×ogiformis specimens appeared to be naturally occurring hybrids, as their callus hair length, awn length, and callus‐to‐spikelet ratio differed from those found in the parental species. Therefore, new Miscanthus ×ogiformis individuals with morphological variations are likely to be discovered and these strains might be useful as new genetic resources for this biomass crop.
Multiplexed gene control reveals rapid mRNA turnover
Authors: Baudrimont Antoine , Voegeli Sylvia , Viloria Eduardo Calero , Stritt Fabian , Lenon Marine , Wada Takeo , Jaquet Vincent , Becskei Attila
Published: July 2017

Researchers develop a new method to show that messenger RNA molecules live much shorter lives in the cell than previously thought.
Disabling Cas9 by an anti-CRISPR DNA mimic
Authors: Shin Jiyung , Jiang Fuguo , Liu Jun-Jie , Bray Nicolas L. , Rauch Benjamin J. , Baik Seung Hyun , Nogales Eva , Bondy-Denomy Joseph , Corn Jacob E. , Doudna Jennifer A.
Published: July 2017

Natural inhibitors of Cas9 pretend to be DNA and block target binding, and using them in human cells can reduce off-target events.
The Cross-Species Mycobacterial Growth Inhibition Assay (MGIA) Project, 2010–2014
Authors: Brennan Michael J. , Tanner Rachel , Morris Sheldon , Scriba Thomas J. , Achkar Jacqueline M. , Zelmer Andrea , Hokey David A. , Izzo Angelo , Sharpe Sally , Williams Ann , Penn-Nicholson Adam , Erasmus Mzwandile , Stylianou Elena , Hoft Daniel F. , McShane Helen , Fletcher Helen A.
Published: July 2017

The development of a functional biomarker assay in the tuberculosis (TB) field would be widely recognized as a major advance in efforts to develop and to test novel TB vaccine candidates efficiently. We present preliminary studies using mycobacterial growth inhibition assays (MGIAs) to detect
Mycobacterium bovis
BCG vaccine responses across species, and we extend this work to determine whether a standardized MGIA can be applied in characterizing new TB vaccines. The comparative MGIA studies reviewed here aimed to evaluate robustness, reproducibility, and ability to reflect
in vivo
responses. In doing so, they have laid the foundation for the development of a MGIA that can be standardized and potentially qualified. A major challenge ahead lies in better understanding the relationships between
in vivo
protection,
in vitro
growth inhibition, and the immune mechanisms involved. The final outcome would be a MGIA that could be used with confidence in TB vaccine trials. We summarize data arising from this project, present a strategy to meet the goals of developing a functional assay for TB vaccine testing, and describe some of the challenges encountered in performing and transferring such assays.
Single-Particle Detection of Transcription following Rotavirus Entry
Authors: Salgado Eric N. , Upadhyayula Srigokul , Harrison Stephen C.
Published: July 2017

Infectious rotavirus particles are triple-layered, icosahedral assemblies. The outer layer proteins, VP4 (cleaved to VP8* and VP5*) and VP7, surround a transcriptionally competent, double-layer particle (DLP), which they deliver into the cytosol. During entry of rhesus rotavirus, VP8* interacts with cell surface gangliosides, allowing engulfment into a membrane vesicle by a clathrin-independent process. Escape into the cytosol and outer-layer shedding depend on interaction of a hydrophobic surface on VP5* with the membrane bilayer and on a large-scale conformational change. We report here experiments that detect the fate of released DLPs and their efficiency in initiating RNA synthesis. By replacing the outer layer with fluorescently tagged, recombinant proteins and also tagging the DLP, we distinguished particles that have lost their outer layer and entered the cytosol (uncoated) from those still within membrane vesicles. We used fluorescent
in situ
hybridization with probes for nascent transcripts to determine how soon after uncoating transcription began and what fraction of the uncoated particles were active in initiating RNA synthesis. We detected RNA synthesis by uncoated particles as early as 15 min after adding virus. The uncoating efficiency was 20 to 50%; of the uncoated particles, about 10 to 15% synthesized detectable RNA. In the format of our experiments, about 10% of the added particles attached to the cell surface, giving an overall ratio of added particles to RNA-synthesizing particles of between 250:1 and 500:1, in good agreement with the ratio of particles to focus-forming units determined by infectivity assays. Thus, RNA synthesis by even a single, uncoated particle can initiate infection in a cell.

IMPORTANCE
The pathways by which a virus enters a cell transform its packaged genome into an active one. Contemporary fluorescence microscopy can detect individual virus particles as they enter cells, allowing us to map their multistep entry pathways. Rotaviruses, like most viruses that lack membranes of their own, disrupt or perforate the intracellular, membrane-enclosed compartment into which they become engulfed following attachment to a cell surface, in order to gain access to the cell interior. The properties of rotavirus particles make it possible to determine molecular mechanisms for these entry steps. In the work described here, we have asked the following question: what fraction of the rotavirus particles that penetrate into the cell make new viral RNA? We find that of the cell-attached particles, between 20 and 50% ultimately penetrate, and of these, about 10% make RNA. RNA synthesis by even a single virus particle can initiate a productive infection.
Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the Presence and Absence of RNA Template
Authors: Hellström Kirsi , Kallio Katri , Utt Age , Quirin Tania , Jokitalo Eija , Merits Andres , Ahola Tero
Published: July 2017

Alphaviruses are positive-strand RNA viruses expressing their replicase as a polyprotein, P1234, which is cleaved to four final products, nonstructural proteins nsP1 to nsP4. The replicase proteins together with viral RNA and host factors form membrane invaginations termed spherules, which act as the replication complexes producing progeny RNAs. We have previously shown that the wild-type alphavirus replicase requires a functional RNA template and active polymerase to generate spherule structures. However, we now find that specific partially processed forms of the replicase proteins alone can give rise to membrane invaginations in the absence of RNA or replication. The minimal requirement for spherule formation was the expression of properly cleaved nsP4, together with either uncleaved P123 or with the combination of nsP1 and uncleaved P23. These inactive spherules were morphologically less regular than replication-induced spherules. In the presence of template, nsP1 plus uncleaved P23 plus nsP4 could efficiently assemble active replication spherules producing both negative-sense and positive-sense RNA strands. P23 alone did not have membrane affinity, but could be recruited to membrane sites in the presence of nsP1 and nsP4. These results define the set of viral components required for alphavirus replication complex assembly and suggest the possibility that it could be reconstituted from separately expressed nonstructural proteins.

IMPORTANCE
All positive-strand RNA viruses extensively modify host cell membranes to serve as efficient platforms for viral RNA replication. Alphaviruses and several other groups induce protective membrane invaginations (spherules) as their genome factories. Most positive-strand viruses produce their replicase as a polyprotein precursor, which is further processed through precise and regulated cleavages. We show here that specific cleavage intermediates of the alphavirus replicase can give rise to spherule structures in the absence of viral RNA. In the presence of template RNA, the same intermediates yield active replication complexes. Thus, partially cleaved replicase proteins play key roles that connect replication complex assembly, membrane deformation, and the different stages of RNA synthesis.
Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site
Authors: Bogers Willy M. J. M. , Barnett Susan W. , Oostermeijer Herman , Nieuwenhuis Ivonne G. , Beenhakker Niels , Mortier Daniella , Mooij Petra , Koopman Gerrit , Remarque Edmund , Martin Gregoire , Lai Rachel Pei-Jen , Dey Antu K. , Sun Yide , Burke Brian , Ferrari Guido , Montefiori David , Martin Loic , Davis David , Srivastava Indresh , Heeney Jonathan L.
Published: July 2017

Strategies are needed to improve the immunogenicity of HIV-1 envelope (Env) antigens (Ag) for more long-lived, efficacious HIV-1 vaccine-induced B-cell responses. HIV-1 Env gp140 (native or uncleaved molecules) or gp120 monomeric proteins elicit relatively poor B-cell responses which are short-lived. We hypothesized that Env engagement of the CD4 receptor on T-helper cells results in anergic effects on T-cell recruitment and consequently a lack of strong, robust, and durable B-memory responses. To test this hypothesis, we occluded the CD4 binding site (CD4bs) of gp140 by stable cross-linking with a 3-kDa CD4 miniprotein mimetic, serving to block ligation of gp140 on CD4+T cells while preserving CD4-inducible (CDi) neutralizing epitopes targeted by antibody-dependent cellular cytotoxicity (ADCC) effector responses. Importantly, immunization of rhesus macaques consistently gave superior B-cell (P< 0.001) response kinetics and superior ADCC (P< 0.014) in a group receiving the CD4bs-occluded vaccine compared to those of animals immunized with gp140. Of the cytokines examined, Ag-specific interleukin-4 (IL-4) T-helper enzyme-linked immunosorbent spot (ELISpot) assays of the CD4bs-occluded group increased earlier (P= 0.025) during the inductive phase. Importantly, CD4bs-occluded gp140 antigen induced superior B-cell and ADCC responses, and the elevated B-cell responses proved to be remarkably durable, lasting more than 60 weeks postimmunization.

IMPORTANCEAttempts to develop HIV vaccines capable of inducing potent and durable B-cell responses have been unsuccessful until now. Antigen-specific B-cell development and affinity maturation occurs in germinal centers in lymphoid follicles through a critical interaction between B cells and T follicular helper cells. The HIV envelope binds the CD4 receptor on T cells as soluble shed antigen or as antigen-antibody complexes, causing impairment in the activation of these specialized CD4-positive T cells. We proposed that CD4-binding impairment is partly responsible for the relatively poor B-cell responses to HIV envelope-based vaccines. To test this hypothesis, we blocked the CD4 binding site of the envelope antigen and compared it to currently used unblocked envelope protein. We found superior and durable B-cell responses in macaques vaccinated with an occluded CD4 binding site on the HIV envelope antigen, demonstrating a potentially important new direction in future design of new HIV vaccines.
Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in Trypanosoma brucei
Authors: Kruzel Emilia K. , Zimmett George P. , Bangs James D.
Published: July 2017

African trypanosomes are protozoan parasites that cause African sleeping sickness. Critical to the success of the parasite is the variant surface glycoprotein (VSG), which covers the parasite cell surface and which is essential for evasion of the host immune system. VSG is membrane bound by a glycolipid (GPI) anchor that is attached in the earliest compartment of the secretory pathway, the endoplasmic reticulum (ER). We have previously shown that the anchor acts as a positive forward trafficking signal for ER exit, implying a cognate receptor mechanism for GPI recognition and loading in coated cargo vesicles leaving the ER. Here, we characterize a family of small transmembrane proteins that act at adaptors for this process. This work adds to our understanding of general GPI function in eukaryotic cells and specifically in the synthesis and transport of the critical virulence factor of pathogenic African trypanosomes.
Facial palsy and atrial fibrillation: a special case of Ramsay Hunt syndrome
Authors: Ayoub Fares , Mahtta Dhruv , Federico Roland-Austin , Kaufmann Michael
Published: July 2017

Ramsay Hunt syndrome (herpes zoster oticus) is a rare complication of latent Varicella Zoster virus infection. It can be complicated by permanent hearing loss, loss of taste and postherpetic neuralgia. Although Ramsay Hunt syndrome most prominently involves the facial nerve, a number of other cranial nerves can be involved such as the vestibulocochlear, glossopharyngeal and the vagus nerve. We report on a case of Ramsay Hunt syndrome with cranial polyneuritis complicated by atrial fibrillation. Vagal involvement as evidenced by physical examination and MRI findings was present in our patient. We hypothesise that viral vagal neuritis likely contributed to the development of atrial fibrillation in our patient through involvement of the autonomic components of the vagus nerve.
Urodynamic findings in Susac syndrome: first reported filling cystometrogram
Authors: Nzenza Tatenda Calvin , Hoag Nathan , Hennessey Derek Barrry , Gani Johan
Published: July 2017

Susac syndrome is a rare neurological disease, with only 300 cases reported in the literature. Lower urinary symptoms are not an uncommon feature of the disease, yet there is no information on specific dysfunction typical urodynamic findings associated with the disease. We present what we believe to be the first reported filling cystometrogram study of Susac syndrome for the evaluation of voiding dysfunction.
Multicentre, randomised clinical trial of paediatric concussion assessment of rest and exertion (PedCARE): a study to determine when to resume physical activities following concussion in children
Authors: Ledoux Andrée-Anne , Barrowman Nicholas J , Boutis Kathy , Davis Adrienne , Reid Sarah , Sangha Gurinder , Farion Ken J , Belanger Kevin , Tremblay Mark S , Yeates Keith Owen , DeMatteo Carol , Reed Nick , Zemek Roger
Published: July 2017

Introduction

Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol.

Methods and analysis

This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total of 350 participants, aged 10–17.99 years, who present within 48 hours of an acute concussion, will be recruited and randomly assigned to either the study intervention protocol (resumption of physical activity 72 hours postconcussion even if experiencing symptoms) or physical rest until fully asymptomatic. Participants will document their daily physical and cognitive activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks postinjury. Compliance with the intervention will be measured using an accelerometer (24 hours/day for 14 days). Symptoms will be measured using the validated Health and Behaviour Inventory. A linear multivariable model, adjusting for site and prognostically important covariates, will be tested to determine differences between groups. The proposed protocol adheres to the RCT-CONSORT guidelines.

Discussion

This trial will determine if early resumption of non-contact physical activity following concussion reduces the burden of concussion and will provide healthcare professionals with the evidence by which to recommend the best timing of reintroducing physical activities.

Trial registration number

Trial identifier (Clinicaltrials.gov)NCT02893969.
Guidelines for reporting meta-epidemiological methodology research
Authors: Murad Mohammad Hassan , Wang Zhen
Published: July 2017

Published research should be reported to evidence users with clarity and transparency that facilitate optimal appraisal and use of evidence and allow replication by other researchers. Guidelines for such reporting are available for several types of studies but not for meta-epidemiological methodology studies. Meta-epidemiological studies adopt a systematic review or meta-analysis approach to examine the impact of certain characteristics of clinical studies on the observed effect and provide empirical evidence for hypothesised associations. The unit of analysis in meta-epidemiological studies is a study, not a patient. The outcomes of meta-epidemiological studies are usually not clinical outcomes. In this guideline, we adapt items from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) to fit the context of meta-epidemiological studies.
Comments on the dilemma in the June issue: Resisting the urge to prescribe vancomycin
Authors: McCulloch Steven
Published: July 2017

In the dilemma discussed in the May issue of In Practice, you are treating a dog with pyoderma, which has had poor clinical results follow a week of topical antibiotics. You test and find meticillin‐resistance Staphylococcus pseudintermedius. You prescribe oral doxycycline but the client asks why vancomycin has not been prescribed (IP, June 2017, vol 39, pp 294‐295). Manuel Magalhães‐Sant’Ana argues that relying on third tier antibiotics is strongly discouraged. While one can be tempted to appease the client, the vet has a moral duty not to. Depending on results from sensitivity tests, it may be that first or second tier antibiotics can resolve the pyoderma.
Towards establishing effective commercial driver training standards: analysis of industry opinions from Alberta
Authors: Gargoum Suliman A. , Kim Amy Miyoung , Zhang Hui , Qiu Tony Z.
Published: July 2017

Commercial driver licensing programs ensure that drivers have the appropriate skills to perform their duties in a safe and efficient manner. Establishing such standards with good compliance requires understanding industry professionals’ opinions on aspects of current training. In this paper achieving that objective is attempted through analyzing opinions of employees of Alberta Motor Transportation Association’s member companies. Participants included commercial drivers, managers, and training staff. Participants were questioned about the commercial driving and training experience, and attitudes towards standard training. Also, the survey questioned respondents on specific training courses when considering them from several different perspectives. Overall, the results show high acceptance and need for standard training. The results support establishment of a program that increases basic pre-licensing training, requires specific training classes to be taken by drivers, and specifies financial responsibility. The findings of this paper provide a foundation for forming unified policies on standard driver training in Canada.
Antioxidant compound (E)-2-benzylidene-4-phenyl-1,3-diselenole protects rats against thioacetamide-induced acute hepatotoxicity
Authors: Reis Angélica S. , Pinz Mikaela P. , Bortolatto Cristiani F. , Jesse Cristiano R. , Savegnago Lucielli , Roman Silvane , Luchese Cristiane , Wilhelm Ethel A.
Published: July 2017

The aim of this study was to investigate whether (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) protects against hepatotoxicity induced by thioacetamide (TAA). On the first day of treatment, male adult Wistar rats received BPD (10 or 50 mg·kg–1). On the second day, the rats received a single intraperitoneal injection of TAA (400 mg·kg–1). Twenty-four hours after TAA administration, biochemical determinations and liver histological analysis were carried out. BPD (50 mg·kg–1) reduced plasma aspartate and alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities increased by TAA exposure. Treatment with BPD was effective against increased lipid peroxidation levels and attenuated a decrease in hepatic reduced glutathione and ascorbic acid levels as well as an inhibition of glutathione peroxidase activity caused by TAA exposure. The higher dose of BPD protected against the inhibition of hepatic δ-aminolevulinic dehydratase activity induced by TAA. Finally, histopathological examination of the liver showed that BPD markedly ameliorated TAA-induced hepatic injury. In conclusion, BPD protected against hepatotoxicity and oxidative stress caused by TAA exposure in rats.
The effects of roads on habitat selection and movement patterns of the American badger subspecies Taxidea taxus jacksoni in Ontario, Canada
Authors: Sunga Julia , Sayers Josh , Cottenie Karl , Kyle Christopher J. , Ethier Danielle M.
Published: July 2017

Road mortality is identified as a threat to American badger (Taxidea taxus (Schreber, 1777)) populations across Canada. Understanding habitat selection and movement in relation to roads is therefore vital to their conservation. Using telemetry data and road-kill locations of badgers in southwestern Ontario, we examined the relationship between habitat selection, movement patterns, and roads at three spatial scales. At the study-area scale, we assessed the effects of habitat attributes on burrow site selection. Several individuals placed their burrows closer to primary highways than expected, suggesting that badgers are not sensitive to human disturbances at this scale. Using straight-line movement trajectories between burrows, we analyzed individual movement patterns within home ranges. All badgers showed some degree of road avoidance, either crossing fewer roads or roads that posed lower mortality risk. At the road-crossing scale, we compared landscape features surrounding road-kill locations to random locations along the same roadway. There was a positive relationship between road-kill locations and number of water-based linear features and higher density of hedgerow cover. Our results provide evidence that badger movement is influenced by roads at multiple scales, which has important implications for managers interested in developing road-mitigation strategies for this endangered population.
Bistable Helmholtz dark spatial optical solitons in materials with self-defocusing saturable nonlinearity
Authors: Christian J. M. , Lundie M. J.
Published: July 2017

We present, to the best of our knowledge, the first exact dark spatial solitons of a nonlinear Helmholtz equation with a self-defocusing saturable refractive-index model. These solutions capture oblique (arbitrary-angle) propagation in both the forward and backward directions, and they can also exhibit a bistability characteristic. A detailed derivation is presented, obtained by combining coordinate transformations and direct-integration methods, and the corresponding solutions of paraxial theory are recovered asymptotically as a subset. Simulations examine the robustness of the new Helmholtz solitons, with stationary states emerging from a range of perturbed input beams.
Parallel Algorithms for Generating Distinguishing Sequences for Observable Non-deterministic FSMs
Authors: Hierons Robert M. , Türker Uraz Cengiz
Published: July 2017

A distinguishing sequence (DS) for a finite-state machine (FSM) is an input sequence that distinguishes every pair of states of the FSM. There are techniques that generate a test sequence with guaranteed fault detection power, and it has been found that shorter test sequences can be produced if DSs are used. Despite these benefits, however, until recently the only published DS generation algorithms have been for deterministic FSMs. This article develops a massively parallel algorithm, which can be used in Graphics Processing Units (GPUs) Computing, to generate DSs from partial observable non-deterministic FSMs. We also present the results of experiments using randomly generated FSMs and some benchmark FSMs. The results are promising and indicate that the proposed algorithm can derive DSs from partial observable non-deterministic FSMs with 32,000 states in an acceptable amount of time.
Improved Approximation Algorithm for Steiner
k
-Forest with Nearly Uniform Weights
Authors: Dinitz Michael , Kortsarz Guy , Nutov Zeev
Published: July 2017

In the Steiner
k
-Forest problem, we are given an edge weighted graph, a collection
D
of node pairs, and an integer
k
⩽ |
D
|. The goal is to find a min-weight subgraph that connects at least
k
pairs. The best known ratio for this problem is min {
O
(√
n
),
O
(√
k
)} [Gupta et al. 2010]. In Gupta et al. [2010], it is also shown that ratio ρ for Steiner
k
-Forest implies ratio
O
(ρ · log
2
n
) for the related Dial-a-Ride problem. The only other algorithm known for Dial-a-Ride, besides the one resulting from Gupta et al. [2010], has ratio
O
(√
n
) [Charikar and Raghavachari 1998].

We obtain approximation ratio
n
0.448
for Steiner
k
-Forest and Dial-a-Ride with unit weights, breaking the
O
(√
n
) approximation barrier for this natural case. We also show that if the maximum edge-weight is
O
(
n
ϵ
), then one can achieve ratio
O
(
n
(1 + ϵ) · 0.448
), which is less than √
n
if ϵ is small enough. The improvement for Dial-a-Ride is the first progress for this problem in 15 years. To prove our main result, we consider the following generalization of the Minimum
k
-Edge Subgraph (M
k
-ES) problem, which we call Min-Cost ℓ-Edge-Profit Subgraph (MCℓ-EPS): Given a graph
G
= (
V
,
E
) with edge-profits
p
= {

p
e

:
e
∈
E
} and node-costs
c
= {

c
v

:
v
∈
V
}, and a lower profit bound ℓ, find a minimum node-cost subgraph of
G
of edge-profit at least ℓ. The M
k
-ES problem is a special case of MCℓ-EPS with unit node costs and unit edge profits. The currently best known ratio for M
k
-ES is
n
3-2√2 + ϵ
[Chlamtac et al. 2012]. We extend this ratio to MCℓ-EPS for general node costs and profits bounded by a polynomial in
n
, which may be of independent interest.
Exploiting Stable Data Dependency in Stream Processing Acceleration on FPGAs
Authors: Sun Yuliang , Wang Lanjun , Wang Chen , Wang Yu
Published: July 2017

With the unique feature of fine-grained parallelism,
field-programmable gate arrays
(FPGAs) show great potential for streaming algorithm acceleration. However, the lack of a design framework, restrictions on FPGAs, and ineffective tools impede the utilization of FPGAs in practice. In this study, we provide a design paradigm to support streaming algorithm acceleration on FPGAs. We first propose an abstract model to describe streaming algorithms with homogeneous sub-functions (HSF) and stable data dependency (SDD), which we call the HSF-SDD model. Using this model, we then develop an FPGA framework, PE-Ring, that has the advantages of (1) fully exploiting algorithm parallelism to achieve high performance, (2) leveraging block RAM to serve large scale parameters, and (3) enabling flexible parameter adjustments. Based on the proposed model and framework, we finally implement a specific converter to generate the register-transfer level representation of the PE-Ring. Experimental results show that our method outperforms ordinary FPGA design tools by one to two orders of magnitude. Experiments also demonstrate the scalability of the PE-Ring.
A CDT-Styled End-to-End Chinese Discourse Parser
Authors: Kong Fang , Zhou Guodong
Published: July 2017

Discourse parsing is a challenging task and plays a critical role in discourse analysis. Since the release of the Rhetorical Structure Theory Discourse Treebank and the Penn Discourse Treebank, the research on English discourse parsing has attracted increasing attention and achieved considerable success in recent years. At the same time, some preliminary research on certain subtasks about discourse parsing for other languages, such as Chinese, has been conducted. In this article, we present an end-to-end Chinese discourse parser with the Connective-Driven Dependency Tree scheme, which consists of multiple components in a pipeline architecture, such as the elementary discourse unit (EDU) detector, discourse relation recognizer, discourse parse tree generator, and attribution labeler. In particular, the attribution labeler determines two attributions (i.e., sense and centering) for every nonterminal node (i.e., discourse relation) in the discourse parse trees. Systematically, our parser detects all EDUs in a free text, generates the discourse parse tree in a bottom-up way, and determines the sense and centering attributions for all nonterminal nodes by traversing the discourse parse tree. Comprehensive evaluation on the Connective-Driven Dependency Treebank corpus from both component-wise and error-cascading perspectives is conducted to illustrate how each component performs in isolation, and how the pipeline performs with error propagation. Finally, it shows that our end-to-end Chinese discourse parser achieves an overall F1 score of 20% with full automation.
Cleansing indoor RFID tracking data
Authors: Baba Asif Iqbal , Lu Hua , Pedersen Torben Bach , Jaeger Manfred
Published: July 2017

The Radio-Frequency Identification (RFID) technology has been increasingly deployed in indoor environments for object tracking and monitoring. However, the uncertain characteristics of RFID data, including noise and incompleteness hinder RFID data querying and analysis at higher levels. Hence, it is of paramount importance to cleanse the RFID data for such applications. This paper introduces our comprehensive research on cleansing RFID data in indoor settings. We focus on two inherent errors in such RFID data: false positives (unexpected cross readings) and false negatives (missing readings). In our proposed
graph model based approach
, we design a probabilistic distance-aware graph to represent the indoor topology, the deployment of RFID readers and their sensing parameters. We also augment the graph with transition probabilities that capture how likely objects move from one RFID reader to another. Based on the proposed graph, we design cleansing algorithms to reduce false positives and recover false negatives. In the
learning-based approach
, we propose an Indoor RFID Multi-variate Hidden Markov Model (IR-MHMM) to capture the uncertainties of indoor RFID data as well as the correlation of moving object locations and object's RFID readings. We solely use raw RFID data for the learning of the IR-MHMM parameters. Using the resulting IR-MHMM, the learning-based approach is able to deliver cleansing performance comparable to and even better than that of the graph model based approach, although the former requires much less prior knowledge than the latter.
AccessCSforall
Authors: Ladner Richard E. , Stefik Andreas
Published: July 2017

For the past ten years there has been a concerted effort to bring computer science to K-12 students in the United States (US) and in other countries. There is a growing realization that computer science is a fundamental subject like mathematics and sciences. In order to make this effort include the approximately 7.4 million K-12 students with disabilities in the US we created AccessCSforAll, a National Science Foundation project that began in 2014. In this article we review the activities of AccessCSforAll in the professional development of teachers and in tool and curriculum development.
Mechanism of action of the anti-inflammatory connexin43 mimetic peptide JM2
Authors: Rhett J. Matthew , Calder Bennett W. , Fann Stephen A. , Bainbridge Heather , Gourdie Robert G. , Yost Michael J.
Published: July 2017

Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43) mimetic peptide juxtamembrane 2 (JM2) reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue-engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity. JM2 is based on the sequence of the Cx43 microtubule binding domain, and microtubules have a confirmed role in intracellular trafficking of Cx43 vesicles. Therefore, we tested the effect of JM2 on Cx43-microtubule interaction and microtubule polymerization. We found that JM2 enhanced Cx43-microtubule interaction and that microtubule polymerization was significantly enhanced. Taken together, these data suggest that JM2 inhibits trafficking of Cx43 to the cell surface by promoting irrelevant microtubule polymerization and thereby reduces the number of hemichannels in the plasma membrane available to participate in proinflammatory purinergic signaling. Importantly, this work indicates that JM2 may have therapeutic value in the treatment of proliferative diseases such as cancer. We conclude that the targeted action of JM2 on Cx43 channels may improve the tolerance of implanted tissue-engineered constructs against the innate inflammatory response.
Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges
Authors: Maertin Sandrina , Elperin Jason M. , Lotshaw Ethan , Sendler Matthias , Speakman Steven D. , Takakura Kazuki , Reicher Benjamin M. , Mareninova Olga A. , Grippo Paul J. , Mayerle Julia , Lerch Markus M. , Gukovskaya Anna S.
Published: July 2017

Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore, pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion, and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells, basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mechanistic target of rapamycin. Basal, but not stress-induced, autophagy is necessary for PaCa cell proliferation, and AA supply is even more critical to maintain PaCa cell growth. To gain insight into the underlying mechanisms, we analyzed the effects of autophagy inhibition and AA depletion on PaCa cell metabolism. PaCa cells display mixed oxidative/glycolytic metabolism, with oxidative phosphorylation (OXPHOS) predominant. Both autophagy inhibition and AA depletion dramatically decreased OXPHOS; furthermore, pharmacologic inhibitors of OXPHOS suppressed PaCa cell proliferation. The data indicate that the maintenance of OXPHOS is a key mechanism through which autophagy and AA supply support PaCa cell growth. We find that the expression of oncogenic activation mutation in GTPase Kras markedly promotes basal autophagy and stimulates OXPHOS through an autophagy-dependent mechanism. The results suggest that approaches aimed to suppress OXPHOS, particularly through limiting AA supply, could be beneficial in treating PDAC.

NEW & NOTEWORTHY Cancer cells in the highly desmoplastic pancreatic ductal adenocarcinoma confront nutrient [i.e., amino acids (AA)] deprivation and hypoxia, but how pancreatic cancer (PaCa) cells adapt to these conditions is poorly understood. This study provides evidence that the maintenance of mitochondrial function, in particular, oxidative phosphorylation (OXPHOS), is a key mechanism that supports PaCa cell growth, both in normal conditions and under the environmental stresses. OXPHOS in PaCa cells critically depends on autophagy and AA supply. Furthermore, the oncogenic activation mutation in GTPase Kras upregulates OXPHOS through an autophagy-dependent mechanism.
Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide
Authors: Nalli Ancy D. , Bhattacharya Sayak , Wang Hongxia , Kendig Derek M. , Grider John R. , Murthy Karnam S.
Published: July 2017

Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cyclic guanosine 5′-monophosphate (cGMP). The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse, and human, l-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser1756 (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor S-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S. The inhibitory effect of l-cysteine, but not NaHS, on PDE5 activity was blocked in cells transfected with CSE siRNA or treated with CSE inhibitor d,l-propargylglycine (dl-PPG), suggesting activation of CSE and generation of H2S in response to l-cysteine. H2S levels were increased in response to l-cysteine, and the effect of l-cysteine was augmented by GSNO in a cGMP-dependent protein kinase-sensitive manner, suggesting augmentation of CSE/H2S by cGMP/PKG pathway. As a result, GSNO-induced relaxation was inhibited by dl-PPG. In flat-sheet preparation of colon, l-cysteine augmented calcitonin gene-related peptide release in response to mucosal stimulation, and in intact segments, l-cysteine increased the velocity of pellet propulsion. These results demonstrate that in colonic smooth muscle, there is a novel interplay between NO and H2S. NO generates H2S via cGMP/PKG pathway, and H2S, in turn, inhibits PDE5 activity and augments NO-induced cGMP levels. In the intact colon, H2S promotes colonic transit.

NEW & NOTEWORTHY Hydrogen sulfide (H2S) and nitric oxide (NO) are important regulators of gastrointestinal motility. The studies herein provide the cross talk between NO and H2S signaling to mediate smooth muscle relaxation and colonic transit. H2S inhibits phosphodiesterase 5 activity to augment cGMP levels in response to NO, which, in turn, via cGMP/PKG pathway, generates H2S. These studies suggest that interventions targeted at restoring NO and H2S homeostasis within the smooth muscle may provide novel therapeutic approaches to mitigate motility disorders.
Dynamic regulation of lysine acetylation: the balance between acetyltransferase and deacetylase activities
Authors: Hyndman Kelly A. , Knepper Mark A.
Published: July 2017

Reversible posttranslational modification of proteins is a critically important process in physiological regulation in all tissues, including the kidney. Lysine acetylation occurs in all organisms, including prokaryotes, and is regulated by a balance between the lysine acetyltransferases (adding an acetyl group to the ε-amino group of a lysine) and deacetylases (removing it). The kidney is an organ rich with acetylated lysines, which map to >2,000 unique histone and nonhistone proteins. However, the functional significance of these modifications remains to be discovered. Here, we have compiled gene lists of the acetyltransferases and deacetylases in the mammalian genomes and mapped their mRNA expression along the renal tubule. These lists will be useful for generating targeted approaches to test the physiological or pathophysiological significance of lysine acetylation changes in the kidney.