bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional regulation of hormone‐synthesis and signaling pathways by overexpressing cytokinin‐synthesis contributes to improved drought tolerance in creeping bentgrass
Authors: Xu Yi , Burgess Patrick , Huang Bingru
Published: May 2017

The objective of this study was to investigate transcriptomic changes and molecular factors regulated by cytokinins that may contribute to improved drought tolerance in creeping bentgrass (Agrostis stolonifera) overexpressing adenine isopentenyltransferase (ipt). Wild‐type (WT) and ipt‐transgenic plants were maintained well irrigated or exposed to 21 days of drought stress in growth chambers. Transcriptomic analysis conducted by RNA‐seq revealed 661 and 648 upregulated and 764 and 862 downregulated drought‐responsive genes (DRGs) in the WT and ipt‐transgenic plants, respectively, under drought stress using adjusted P‐value of 0.001 and log2 fold change. Gene ontology (GO) term classification showed that a greater number of DRGs were found in ipt‐transgenic plants than in WT plants pertaining to biological functions including metabolic process, cellular process, cell structure and growth, macromolecular complex, and binding and catalytic activity, whereas fewer DRGs were found in ipt‐transgenic plants than in WT plants pertaining to response to stimulus and antioxidant activity. Furthermore, plant hormone signal transduction pathway analysis revealed three downregulated transcripts [type B – Arabidopsis response regulators (B‐ARR), ABA‐responsive element binding factor (ABF) and pyrabactin resistance/like (PYR/PYL)] and two upregulated transcripts (BIN2 and JAZ) that were significantly differentiated between ipt‐transgenic and WT plants under drought stress, which are particularly interesting for further investigation of molecular mechanisms of hormone‐regulation of drought tolerance.
A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy
Authors: Horner Richard L. , Grace Kevin P. , Wellman Andrew
Published: May 2017

ABSTRACT

There is currently no pharmacotherapy for obstructive sleep apnoea (OSA) but there is no principled a priori reason why there should not be one. This review identifies a rational decision‐making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for OSA. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their OSA pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any OSA pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for OSA pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for OSA treatment that are of the most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to OSA pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of ‘druggable’ targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure OSA per se, but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays.
Portable oxygen concentrators versus oxygen cylinder during walking in interstitial lung disease: A randomized crossover trial
Authors: Khor Yet H. , McDonald Christine F. , Hazard Anita , Symons Karen , Westall Glen , Glaspole Ian , Goh Nicole S.L. , Holland Anne E.
Published: May 2017

ABSTRACT

Background and objective

Ambulatory oxygen therapy is often provided to patients with interstitial lung disease (ILD). Lightweight portable oxygen concentrators (POCs) provide an alternative to traditional portable systems such as compressed oxygen cylinders; however, their efficacy in patients with ILD has not been assessed. This study aimed to evaluate the clinical performance of three ambulatory oxygen systems (two different POCs and a compressed oxygen cylinder) during 6‐min walk tests (6MWTs) in patients with ILD and exertional desaturation.

Methods

A total of 20 participants with ILD of varying aetiologies who demonstrated exertional desaturation to <90% on room air during 6MWT were recruited. Each participant performed two 6MWTs while breathing room air. On a subsequent day, two further 6MWTs were performed, in random order: one breathing oxygen via a POC (either the Inogen One G2 POC or the EverGo POC at the setting of 6) and one with a compressed oxygen cylinder (at 5 L/min).

Results

There were no significant differences in nadir oxygen saturation (SpO2
) during 6MWTs using different portable oxygen devices (Trial 1: mean SpO2
for Inogen One G2 POC: 82.3 ± 3.5% vs oxygen cylinder: 80.3 ± 2.2%, P = 0.14; Trial 2: mean SpO2
for EverGo POC: 85.7 ± 7.7% vs oxygen cylinder: 86.1 ± 6.1%, P = 0.79). The mean 6‐min walk distances were not significantly different among the three devices.

Conclusion

The performance of the Inogen One G2 POC and the EverGo POC had comparable performance with that of the compressed oxygen cylinder during walking in patients with ILD and exertional desaturation.
Cough is less common and less severe in systemic sclerosis‐associated interstitial lung disease compared to other fibrotic interstitial lung diseases
Authors: Cheng Jasmine Z. , Wilcox Pearce G. , Glaspole Ian , Corte Tamera J. , Murphy Darra , Hague Cameron J. , Ryerson Christopher J.
Published: May 2017

ABSTRACT

Background and objective

The objectives of this study were to determine the prevalence and characteristics of cough in idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP) and systemic sclerosis‐associated interstitial lung disease (SSc‐ILD).

Methods

Cough severity was measured in consecutive patients with IPF (n = 77), HP (n = 32) and SSc‐ILD (n = 67) using a 10‐cm visual analogue scale (VAS). Dyspnoea and quality of life were measured using established questionnaires. Cough severity was compared across ILD subtypes and predictors of cough severity were determined using multivariate analysis.

Results

Cough was more common in IPF and chronic HP compared to SSc‐ILD (87% and 83% vs 68%, P = 0.02). The median (interquartile range) VAS score was 39 (17–65) in the IPF cohort, 29 (11–48) in HP and 18 (0–33) in SSc‐ILD (P < 0.0001). Cough was more often productive in chronic HP and IPF (63% and 43% vs 21%, P < 0.001). Cough severity was independently predicted only by ILD diagnosis and higher dyspnoea score. Cough severity was not associated with other common causes of cough. Cough was a significant predictor of quality of life in IPF and SSc‐ILD with adjustment for age, sex, dyspnoea and ILD severity; however, cough was not associated with quality of life in chronic HP.

Conclusion

Cough is more frequent, more severe and more often productive in IPF and chronic HP compared to SSc‐ILD, despite similar ILD severity in these cohorts. Cough severity is strongly and independently associated with dyspnoea and pulmonary function, and is a significant contributor to reduced quality of life in both IPF and SSc‐ILD.
Elastography in endobronchial ultrasound: Stretching the boundary of minimally invasive staging further
Authors: Steinfort Daniel P.
Published: May 2017

See article, page 972
Partitioning strength exercises as an alternative training modality for patients with COPD
Authors: Vaes Anouk W.
Published: May 2017

See related Article
The Effectiveness of aid in Improving Regulations: An Empirical Assessment
Authors: Busse Matthias , Hoekstra Ruth , Osei Robert Darko
Published: May 2017

The paper empirically assesses the impact of foreign aid on the change in economic freedom, which is closely related to the quality of regulations. We build on a relatively large panel of 77 developing countries and examine the period 2002–2012 using different econometric methods. In addition to standard country fixed‐effects regressions as well as estimations in first differences, we apply the system Generalised Method of Moments estimator. We, therefore, control for the potential endogeneity of foreign aid. We find that highly targeted aid can be a driver of change: Sectorspecific Aid for Business has a significantly positive impact on regulations across developing countries, but we do not find any effects for overall aid or aid directed at broad governance areas. The result that Aid for Business drives improvements in regulatory quality is robust using different model specifications and country samples. The strongest results are found for low‐income countries and for subsamples that exclude outliers. This outcome could partly explain the inconclusive evidence from the previous literature and it confirms our hypothesis that targeted, sector‐specific aid matters.
Tax(i)ing the Poor? Commuting Costs in South African Cities
Authors: Kerr Andrew
Published: May 2017

In this paper, I describe the monetary and time costs of commuting to work in South African cities, and how these have changed in the post‐Apartheid era. I interpret these results in light of a paper by Brueckner, who used a simple urban model to suggest that location and commuting patterns by race could change as a result of the repeal of Apartheid era legislation such as the Group Areas Act that made it impossible for black South Africans to live near the centre of cities. A key finding is that monetary and time costs of commuting in South African cities are high and have increased in the post‐Apartheid period. Journey times are much higher than the OECD country average and a sample of developing country cities. Part of the explanation for increasing average commute times is population growth in South African cities, which has been substantial. Both the population and number of commuters doubled between 1993 and 2013 in the six metropolitan municipalities (metros) analysed in this paper. Since commuting costs a substantial amount and generates negative externalities through congestion I also explore the financing of public transport.
Remittance, Institutions and Investment Volatility Interactions: An Intercontinental Analysis
Authors: Ajide Kazeem B. , Adeniyi Oluwatosin , Raheem Ibrahim D.
Published: May 2017

Generating massive investment for growth and development has been one of the main policy goals of most economies around the globe. Countries, most especially developing ones, are highly susceptible to investment volatility owing largely to the fragile nature of their economies as well as weaknesses in terms of dysfunctional institutions. Therefore, sound economic management suggests the need to better understand possible sources for mitigating the adverse effects of investment volatility. Remittances have been identified as important capital flows which do a good job of dousing macroeconomic volatilities. It is on this basis that the study sought to uncover the causal relationship between remittances and investment volatility via the intermediating role of institutions. Using a panel of 70 countries and the system Generalized Method of Moments (GMM) estimator, three insightful outcomes come to the fore. First, remittances played countercyclical roles across the estimated regressions. Second, institutional quality had no significant role in mitigating investment volatility and lastly, the interactive terms of both remittances and institutions significantly mitigated the negative impacts of investment volatility with the exception of the political component of the institutional architecture. Policy suggestions are drawn based on our results.
Caring behaviours directly and indirectly affect nursing students' critical thinking
Authors: Chen Shu‐Yueh , Chang Hsing‐Chi , Pai Hsiang‐Chu
Published: May 2017

Objectives

The purpose of this study was to determine the effect of caring behaviours on critical thinking and to examine whether self‐reflection mediates the effect of caring on critical thinking. We also tested whether caring behaviours moderated the relationship between self‐reflection and critical thinking.

Methods

For this descriptive, correlational, cross‐sectional study, we recruited 293 fifth‐year nursing students from a junior college in southern Taiwan. Data were collected in 2014 on critical thinking, caring behaviours and self‐reflection with insight using the Taiwan Critical Thinking Disposition Inventory, a Chinese version of the Caring Assessment Report Evaluation Q‐sort, and a Chinese version of the Self‐Reflection and Insight Scale, respectively. Relationships among variables were analysed by structural equation modelling, with the partial least squares method and Sobel test.

Results

The results showed that caring behaviours significantly positively affected critical thinking (β = 0.56, t = 12.37, p < 0.001) and self‐reflection with insight (β = 0.54, t = 11.99, p < 0.001). Self‐reflection and insight significantly positively affected critical thinking (β = 0.34, t = 6.48, p < 0.001). Further, self‐reflection and insight mediated the relationship between caring behaviours and critical thinking. Caring behaviours did not, however, moderate the relationship between self‐reflection (β = 0.001, t = 0.021, p > 0.05) and critical thinking.

Conclusion

Caring behaviours directly affect self‐reflection with insight and critical thinking. In addition, caring behaviours also indirectly affect critical thinking through self‐reflection and insight.
(Can) Not talk about it – Urinary incontinence from the point of view of stroke survivors: a qualitative study
Authors: Kohler Myrta , Mayer Hanna , Kesselring Jürg , Saxer Susi
Published: May 2017

Purpose

The current study intends to gain an in‐depth understanding of stroke survivors' lived experience of urinary incontinence and its treatment in an inpatient rehabilitation clinic.

Methods

A qualitative approach was chosen. Semi‐structured individual interviews with ten stroke survivors suffering from urinary incontinence were conducted in an inpatient rehabilitation clinic and analysed using qualitative content analysis with an inductive approach.

Results

‘(Can) not talk about it’ was identified as the first main category. The affected persons do not talk about urinary incontinence because they are ashamed. At the same time, no one asks them about this issue. Psychological strain is so high that patients feel the need to talk about incontinence, but from their point of view, conversations with nurses – if they indeed occur – are superficial or nurses do not listen. Therefore, patients' needs and concerns are not properly considered. ‘Trying to command incontinence’ was also identified as a main category. Participants reported that they try to command incontinence and to develop their own strategies in order to hide urinary incontinence and prevent shameful situations. However, this proved mostly unsuccessful and resulted in resignation to their condition.

Conclusion

It is important to raise awareness within the treatment team of urinary incontinence in stroke survivors. Team members should be able to communicate about urinary incontinence in an open and empathic way. Obviously, there is great potential for supporting stroke survivors in dealing with incontinence.
Freeze artifact on full‐field optical coherence tomography skin imaging
Authors: Durkin J. R. , Ogrich L. , Morales‐Neira D. , Dundumalla S. , Abdelmalek M.
Published: May 2017

Background/Purpose

Full‐field optical coherence tomography (FFOCT) is an emerging imaging technique for rapid histological analysis. As FFOCT is introduced into the Mohs workflow, it is important to document the effect of tissue freezing on FFOCT images and any effect FFOCT has on frozen sections. Our study aimed to evaluate the changes on FFOCT images after tissue freezing as well as FFOCT imaging effects on frozen sectioning.

Methods

Six normal skin specimens were imaged using FFOCT and subsequently frozen using a cryostat. The specimens were then reimaged using FFOCT and compared for any differences. To evaluate the effect of FFOCT imaging on frozen sections, five normal skin specimens were bisected and one half was imaged using FFOCT. Both halves underwent frozen sectioning and analysis.

Results

Significant changes in the fat, sebaceous glands, eccrine glands, and dermal collage and minimal changes in the epidermis were seen after freezing. No effect on frozen sectioning was seen after FFOCT imaging.

Conclusion

As FFOCT is studied for use in Mohs, clinicians should be aware that freezing prior to imaging introduces significant artifact in the FFOCT image. If possible, specimens should undergo imaging prior to being frozen.
Changing seas in the Early–Middle Miocene of Central Europe: a Mediterranean approach to Paratethyan stratigraphy
Authors: Sant Karin , V. Palcu Dan , Mandic Oleg , Krijgsman Wout
Published: May 2017

The Miocene palaeogeographic evolution of the Paratethys Sea is still poorly constrained. Here, we use modern Mediterranean biochronology to provide an up‐to‐date overview of changing seas in Central Europe. Instead of a Paratethys that waxed and waned with fluctuating global sea levels, we show that the development of different seas was mainly controlled by tectonic phases. The Early Miocene “Ottnangian Sea” (~18 Ma) was connected to the Mediterranean via the Rhône valley, while the “Karpatian Sea” (~16.5 Ma) was initiated by a tectonically induced marine transgression through the Trans‐Tethyan gateway. In most Central European basins, the establishment of the “Badenian Sea” (<15.2 Ma), triggered by subduction‐related processes in the Pannonian and Carpathian domain, is significantly younger (by ~1 Myr) than usually estimated. The updated palaeogeographic reconstructions provide a better understanding of the concepts of basin dynamics, land–sea distribution and palaeoenvironmental change in the Miocene of Central Europe.
A multicenter, retrospective, case‐cohort study of the epidemiology and risk factors for Clostridium difficile infection among cord blood transplant recipients
Authors: Alonso Carolyn D. , Braun David A. , Patel Ishan , Akbari Mona , Oh Daniel Jungmyung , Jun Tomi , McMasters Malgorzata , Hammond Sarah P. , Glotzbecker Brett , Cutler Corey , Leffler Daniel A. , Ballen Karen K. , Kelly Ciarán P.
Published: May 2017

Background

Clostridium difficile infection (CDI) is the leading cause of health‐care associated infectious diarrhea. The aim of this study was to evaluate the epidemiology and risk factors for CDI in the 100 days following umbilical cord blood transplantation (UCBT) at three Boston hospitals.

Methods

We performed a multicenter, retrospective, case‐cohort study of 226 UCBT recipients at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, and Dana Farber/Brigham and Women's Cancer Center from 2003 to 2012. CDI was defined as diarrhea (≥3 unformed bowel movements for at least 2 days) plus a positive stool test for toxinogenic C. difficile and not attributed to any other cause.

Results

Among 226 UCBT recipients, 22 patients (9.7%) developed CDI within the first 100 days of transplant (corresponding to an infection rate of 10.8 cases per 10 000 person‐days). The 100‐day and 1‐year rates were stable across the time period and between institutions. UCBT recipients with CDI were more likely than non‐CDI patients to be older, with higher body mass indices, and to have received an antipseudomonal penicillin agent. In a time‐dependent case‐cohort analysis of the risk factors associated with CDI in the first 100 days after UCBT, bacterial infection after UCBT was the strongest risk factor for CDI (hazard ratio 2.8; 95% confidence interval 1.08‐7.24; P=.03), after adjustment for transplant variables including antibiotic exposure.

Conclusion

This study verifies the previously reported risk factors for CDI including older age and antibiotic exposure and identifies a novel association between bacterial infections and risk for CDI.
Salmonella Typhi genomics: envisaging the future of typhoid eradication
Authors: Yap Kien‐Pong , Thong Kwai Lin
Published: May 2017

Next‐generation whole‐genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development.
Islamic economics and a third fundamental theorem of welfare economics
Authors: Khan Hayat
Published: May 2017

The discipline of economics started as a moral science but became detached from moral concerns over time to emulate natural science and to adopt positivism. Consequently, mainstream economics assumes people to be sordidly selfish. The teachings of Islam, however, promote social preferences where individuals should be other‐regarding and have preferences over social outcomes. This paper replaces the selfish agent with a social agent and presents the results in a theorem referred to as the third fundamental theorem of welfare economics (TFTWE). The TFTWE states that “when the selfish agents are replaced with the social agents, market outcomes are Pareto optimal, equitable, and unique”. This is an important result which has widespread implications. We show that the TFTWE holds under conditions where the first two fundamental theorems of welfare economics fail and that a Walrasian equilibrium is more likely to exist when selfish preferences are non‐convex. Unlike the popular convention, there is no equity‐efficiency trade‐off. In fact we point to the possibility of reversal in equity‐efficiency trade‐off.
Biomechanical comparison between pins and polymethylmethacrylate and the SOP locking plate system to stabilize canine lumbosacral fracture‐luxation in flexion and extension
Authors: Nel Johannes J. , Kat Cor‐Jacques , Coetzee Gert L. , van Staden Paul J.
Published: May 2017

Objective

To determine the stability of a simulated complete L7‐S1 fracture‐luxation immobilized with SOP locking plate system, compared to pins and polymethylmethacrylate (PMMA).

Study design

In vitro biomechanical study.

Animals

Cadaver specimens of 18 skeletally mature large‐breed dogs.

Materials and Methods

Specimens were randomly stabilized with one of the two fixation techniques. Lumbosacral spine specimens (L5‐S3) were subjected to a bending moment applied to the caudal and cranial ends of the specimen. The biomechanical parameters (ie, range of motion [ROM], neutral zone [NZ], and elastic zone stiffness [EZS]) were compared between fixation techniques.

Results

No difference was found between the means of the NZ in flexion (P = .3458), extension (P = .1255), and total value (P = .3458) of L7‐S1 stabilized with the two fixation techniques. Mean ROM in flexion (P = .2386), extension (P = .1255), and mean of EZS in extension (P = .4094) did not differ between fixations. The only significant differences were in the means of total ROM and means of the EZS in flexion, with the means being smaller with SOP fixation.

Conclusion

The stability of the two fixation techniques in flexion and in extension was similar for the L7‐S1 and adjacent L5‐L6 junctions, while the mean of ROM of L6‐L7 in flexion was smaller with SOP fixation.

Clinical Relevance

Stability of the resulting construct should be considered when selecting an implant. Our results provide evidence that fixation via pin‐PMMA or SOP provide similar stability for L7‐S1 fracture‐luxation. In this context, other factors become more important in selecting the fixation method.
In vitro skin expansion: Wound healing assessment
Authors: Prim Peter M. , Kim Han Su , Shapiro Lindsey E. , Lee Jae Sung , Kaan James H. , Jackson John D. , Yoo James J. , Atala Anthony , Lee Sang Jin
Published: May 2017

For treatments requiring split‐thickness skin grafts, it is preferable to mesh the grafts. This reduces the amount of excised skin and covers more wound area. The mesh technique, however, destroys surface continuity, which results in scarring. Strain‐based bioreactors, on the other hand, have successfully expanded split‐thickness skin grafts in vitro within a 7‐day period, increasing graft coverage. After in vitro expansion, the expanded skin grafts were tested in a porcine full‐thickness excisional wound model. Expanded graft take rate was 100%. Volumetric, histologic, and mechanical assessments indicated that expanded grafts were comparable to unexpanded grafts (positive control). While there was considerable variation in expansion (31% to −3.1%), this technique has the potential to enhance the coverage area of skin grafts while reducing or eliminating scarring.
A randomized clinical trial of a human acellular dermal matrix demonstrated superior healing rates for chronic diabetic foot ulcers over conventional care and an active acellular dermal matrix comparator
Authors: Cazzell Shawn , Vayser Dean , Pham Hau , Walters Jodi , Reyzelman Alexander , Samsell Brian , Dorsch Kimberly , Moore Mark
Published: May 2017

This study compared the efficacy and safety of a human acellular dermal matrix (ADM), D‐ADM, with a conventional care arm and an active comparator human ADM arm, GJ‐ADM, for the treatment of chronic diabetic foot ulcers. The study design was a prospective, randomized controlled trial that enrolled 168 diabetic foot ulcer subjects in 13 centers across 9 states. Subjects in the ADM arms received one application but could receive one additional application of ADM if deemed necessary. Screen failures and early withdrawals left 53 subjects in the D‐ADM arm, 56 in the conventional care arm, and 23 in the GJ‐ADM arm (2:2:1 ratio). Subjects were followed through 24 weeks with major endpoints at Weeks 12, 16, and 24. Single application D‐ADM subjects showed significantly greater wound closure rates than conventional care at all three endpoints while all applications D‐ADM displayed a significantly higher healing rate than conventional care at Week 16 and Week 24. GJ‐ADM did not show a significantly greater healing rate over conventional care at any of these time points. A blinded, third party adjudicator analyzed healing at Week 12 and expressed “strong” agreement (κ = 0.837). Closed ulcers in the single application D‐ADM arm remained healed at a significantly greater rate than the conventional care arm at 4 weeks posttermination (100% vs. 86.7%; p = 0.0435). There was no significant difference between GJ‐ADM and conventional care for healed wounds remaining closed. Single application D‐ADM demonstrated significantly greater average percent wound area reduction than conventional care for Weeks 2–24 while single application GJ‐ADM showed significantly greater wound area reduction over conventional care for Weeks 4–6, 9, and 11–12. D‐ADM demonstrated significantly greater wound healing, larger wound area reduction, and a better capability of keeping healed wounds closed than conventional care in the treatment of chronic DFUs.
Barium strontium oxide functionalized carbon nanotubes thin film thermionic emitter with superior thermionic emission capability
Authors: Jin Feng , Beaver Allyn
Published: May 2017

Despite their potential, thin film thermionic emitters are yet to appear in real device applications. The main shortcoming for thin film thermionic emitters is their weak emission capability as compared to conventional thermionic cathodes. In this study, a high performance thin film thermionic emitter with emission capability on par with that of a conventional thermionic cathode is presented. This thin film emitter combines a large Schottky effect induced by the carbon nanotubes with a low work function oxide surface coating, resulting in a dramatic increase of thermionic emission. Emission current density as high as 4.5 A/cm2 was obtained at a typical thermionic emission temperature of 1380 K. The growth and fabrication techniques for this emitter are also compatible with the silicon process, making it possible to incorporate this thin film thermionic emitter into other semiconductor devices for potential new device applications.
Inertio-elastic instability in Taylor-Couette flow of a model wormlike micellar system
Authors: Mohammadigoushki Hadi , Muller Susan J.
Published: May 2017

In this work, we use flow visualization and rheometry techniques to study the dynamics and evolution of secondary flows in a model wormlike micellar solution sheared between concentric cylinders, i.e., in a Taylor-Couette cell. The wormlike micellar solution studied in this work contains cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal). This system can be shear banding and highly elastic, nonshear banding and moderately elastic, or nearly Newtonian as the temperature is varied over a narrow range. The effect of elasticity on transitions and instabilities is probed by changing the temperature over a wide range of elasticity (El ≪ 1, El ≈ 1, and El ≫ 1). Elasticity is defined as the ratio of the Weissenberg number to the Reynolds number. For shear banding wormlike micelle solutions where El ≫ 1, a primary transition from the base Couette flow to stationary vortices that are evenly spaced in the axial direction of the shear cell and are characterized by an asymptotic wave-length is observed. The dimensionless wave-length at the onset of this shear banding transition for CTAB/NaSal system turns out to be much larger than those reported for other shear banding wormlike micelle systems. For the same fluid at a temperature where it shear-thins but does not display shear banding, El ≈ 1, and for slow ramp speeds, the primary transition is to distinct structures that are not stationary but rather travel in the axial direction. At low elasticity (El ≪ 1), where the fluid behaves as a nearly Newtonian fluid, several transitions from purely azimuthal Couette flow to modified Taylor vortex flows and finally chaotic regimes are documented. The behavior in the shear-banding and nonshear-banding regimes are discussed and compared with results in related systems. The possibility of hysteresis in the flow transitions as well as the effects of co-rotation and counter-rotation of the cylinders on transitions and instabilities are also examined for a wide range of elasticity.
An environment-dependent transcriptional network specifies human microglia identity
Authors: Gosselin David , Skola Dylan , Coufal Nicole G. , Holtman Inge R. , Schlachetzki Johannes C. M. , Sajti Eniko , Jaeger Baptiste N. , O’Connor Carolyn , Fitzpatrick Conor , Pasillas Martina P. , Pena Monique , Adair Amy , Gonda David D. , Levy Michael L. , Ransohoff Richard M. , Gage Fred H. , Glass Christopher K.
Published: May 2017

Of mice and men's microglia

Microglia are immune system cells that function in protecting and maintaining the brain. Gosselin
et al.
examined the epigenetics and RNA transcripts from single microglial cells and observed consistent profiles among samples despite differences in age, sex, and diagnosis. Mouse and human microglia demonstrated similar microglia-specific gene expression profiles, as well as a shared environmental response among microglia collected either immediately after surgery (ex vivo) or after culturing (in vitro). Interestingly, those genes exhibiting differences in expression between humans and mice or after culturing were often implicated in neurodegenerative diseases.

Science
, this issue p.
eaal3222
Nuclear safety regulation in the post-Fukushima era
Authors: Lyman Edwin , Schoeppner Michael , von Hippel Frank
Published: May 2017

Flawed analyses underlie lax U.S. regulation of spent fuel
Whole cell maps chart a course for 21st-century cell biology
Authors: Horwitz Rick , Johnson Graham T.
Published: May 2017

Building a multiscale, dynamic human cell atlas will require a massive community effort
Mycoplasma pneumoniae from the Respiratory Tract and Beyond
Authors: Waites Ken B. , Xiao Li , Liu Yang , Balish Mitchell F. , Atkinson T. Prescott
Published: May 2017

Mycoplasma pneumoniaeis an important cause of respiratory tract infections in children as well as adults that can range in severity from mild to life-threatening. Over the past several years there has been much new information published concerning infections caused by this organism. New molecular-based tests forM. pneumoniaedetection are now commercially available in the United States, and advances in molecular typing systems have enhanced understanding of the epidemiology of infections. More strains have had their entire genome sequences published, providing additional insights into pathogenic mechanisms. Clinically significant acquired macrolide resistance has emerged worldwide and is now complicating treatment.In vitrosusceptibility testing methods have been standardized, and several new drugs that may be effective against this organism are undergoing development. This review focuses on the many new developments that have occurred over the past several years that enhance our understanding of this microbe, which is among the smallest bacterial pathogens but one of great clinical importance.
Reducing V3 Antigenicity and Immunogenicity on Soluble, Native-Like HIV-1 Env SOSIP Trimers
Authors: Ringe Rajesh P. , Ozorowski Gabriel , Rantalainen Kimmo , Struwe Weston B. , Matthews Katie , Torres Jonathan L. , Yasmeen Anila , Cottrell Christopher A. , Ketas Thomas J. , LaBranche Celia C. , Montefiori David C. , Cupo Albert , Crispin Max , Wilson Ian A. , Ward Andrew B. , Sanders Rogier W. , Klasse P. J. , Moore John P.
Published: May 2017

Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs) but can also expose binding sites for some types of nonneutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such “off-target” immune responses. Accordingly, we have assessed how to minimize the exposure of V3 non-NAb epitopes and thereby reduce their immunogenicity by introducingN-glycans within the V3 region of BG505 SOSIP trimers. We found that inserting glycans at positions 306 and 314 (termed M1 and M7) markedly reduced V3 antigenicity while improving the presentation of trimer apex bNAb epitopes. Both added glycans were shown to be predominantly of the Man6GlcNAc2form. The additional introduction of the E64K ground-state stabilizing substitution markedly reduced or ablated soluble CD4 (sCD4) induction of non-NAb epitopes in V3 and/or associated with the coreceptor binding site. When a V3 glycan- and E64K-modified trimer variant, BG505 SOSIP.664-E64K.M1M7, was tested in rabbits, V3 immunogenicity was eliminated while the autologous NAb response was unchanged.

IMPORTANCETrimeric proteins are being developed for future HIV-1 vaccine trials in humans, with the goal of eliciting broadly active neutralizing antibodies (NAbs) that are active against a wide variety of circulating strains. In animal models, the present generation of native-like trimer immunogens, exemplified by the BG505 SOSIP.664 construct, induces narrow-specificity antibodies against the neutralization-resistant (tier-2), sequence-matched virus and more broadly active antibodies against sequence-divergent atypically neutralization-sensitive (tier-1) viruses. A concern in the trimer immunogen design field has been whether the latter off-target antibodies might interfere with the induction of the more desired responses to tier-2 epitopes. Here, we have inserted two glycans into the dominant site for tier-1 NAbs, the gp120 V3 region, to block the induction of off-target antibodies. We characterized the new trimers, tested them as immunogens in rabbits, and found that the blocking glycans eliminated the induction of tier-1 NAbs to V3-epitopes.
A Map of the Arenavirus Nucleoprotein-Host Protein Interactome Reveals that Junín Virus Selectively Impairs the Antiviral Activity of Double-Stranded RNA-Activated Protein Kinase (PKR)
Authors: King Benjamin R. , Hershkowitz Dylan , Eisenhauer Philip L. , Weir Marion E. , Ziegler Christopher M. , Russo Joanne , Bruce Emily A. , Ballif Bryan A. , Botten Jason
Published: May 2017

Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. These viruses encode only four proteins to accomplish the viral life cycle, so each arenavirus protein likely plays unappreciated accessory roles during infection. Here we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoproteins (NPs) of the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) and the New World arenavirus Junín virus (JUNV) strain Candid #1. Bioinformatic analysis of the identified protein partners of NP revealed that host translation appears to be a key biological process engaged during infection. In particular, NP associates with the double-stranded RNA (dsRNA)-activated protein kinase (PKR), a well-characterized antiviral protein that inhibits cap-dependent protein translation initiation via phosphorylation of eIF2α. JUNV infection leads to increased expression of PKR as well as its redistribution to viral replication and transcription factories. Further, phosphorylation of PKR, which is a prerequisite for its ability to phosphorylate eIF2α, is readily induced by JUNV. However, JUNV prevents this pool of activated PKR from phosphorylating eIF2α, even following exposure to the synthetic dsRNA poly(I·C), a potent PKR agonist. This blockade of PKR function is highly specific, as LCMV is unable to similarly inhibit eIF2α phosphorylation. JUNV's ability to antagonize the antiviral activity of PKR appears to be complete, as silencing of PKR expression has no impact on viral propagation. In summary, we provide a detailed map of the host machinery engaged by arenavirus NPs and identify an antiviral pathway that is subverted by JUNV.

IMPORTANCE
Arenaviruses are important human pathogens for which FDA-approved vaccines do not exist and effective antiviral therapeutics are needed. Design of antiviral treatment options and elucidation of the mechanistic basis of disease pathogenesis will depend on an increased basic understanding of these viruses and, in particular, their interactions with the host cell machinery. Identifying host proteins critical for the viral life cycle and/or pathogenesis represents a useful strategy to uncover new drug targets. This study reveals, for the first time, the extensive human protein interactome of arenavirus nucleoproteins and uncovers a potent antiviral host protein that is neutralized during Junín virus infection. In so doing, it shows further insight into the interplay between the virus and the host innate immune response and provides an important data set for the field.
Unique Features of
Aeromonas
Plasmid pAC3 and Expression of the Plasmid-Mediated Quinolone Resistance Genes
Authors: Kim Dae-Wi , Thawng Cung Nawl , Lee Sang Hee , Cha Chang-Jun
Published: May 2017

In the present study, plasmid pAC3 isolated from a highly fluoroquinolone-resistant isolate of
Aeromonas
species was sequenced and found to contain two fluoroquinolone resistance genes,
aac
(
6′
)-
Ib-cr
and
qnrS2
. Comparative analyses of plasmid pAC3 and other
Aeromonas
sp. IncU-type plasmids revealed a mobile insertion cassette element with a unique structure containing a
qnrS2
gene and a typical miniature inverted-repeat transposable element (MITE) structure. This study also revealed that this MITE sequence appears in other
Aeromonas
species plasmids and chromosomes. Our results also demonstrate that the fluoroquinolone-dependent expression of
qnrS2
is associated with
rsd
in
E. coli
DH5α harboring plasmid pAC3. Our findings suggest that the mobile element may play an important role in
qnrS2
dissemination and that
Aeromonas
species constitute an important reservoir of fluoroquinolone resistance determinants in the environment.
A case of confusion: paraneoplastic encephalomyelitis in an elderly patient suspected of having urinary tract infection-associated delirium
Authors: McKinnon Chris , Manchanda Simmie
Published: May 2017

Acute confusion is a common symptom of physical illness in the older patient. In the majority, it is transient and resolves on treatment of precipitants. In a subset of patients, however, neurological decline is progressive, raising concern about a serious underlying cause. We describe the case of a 71-year-old woman who developed progressive cognitive impairment following insertion of a permanent pacemaker for sinoatrial arrests. An initial diagnosis of delirium secondary to a urinary tract infection was suspected; however, the patient became increasingly confused despite treatment. Laboratory tests revealed serum anti-Hu paraneoplastic antibodies, and CT chest identified an occult lung tumour. Cervical lymph node histopathology confirmed a diagnosis of small cell carcinoma of the lung. Although a rare cause of confusion, paraneoplastic encephalomyelitis should be recognised early to allow timely identification and treatment of the associated cancer.
Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis
Authors: Paulon Emma , Nastou Despoina , Jaboli Francesca , Marin Juana , Liebler Eric , Epstein Owen
Published: May 2017

Background

Gastric electric stimulation (GES) is a treatment approach to refractory gastroparesis, possibly acting centrally via afferent vagus nerve stimulation (VNS). Non-invasive VNS (nVNS) is a potential alternative to GES that could eliminate the safety risks of or identify likely responders to implantable neurostimulators.

Objective

This open-label proof-of-concept study assessed the effects of nVNS in patients with severe drug-refractory gastroparesis.

Methods

Patients used the Gastroparesis Cardinal Symptom Index (GCSI) to grade symptoms in diaries daily for 2 weeks before treatment (baseline) and during ≥3 weeks of nVNS therapy. Adverse events (AEs) were also diarised. Treatment was self-administered using an nVNS device (gammaCore, electroCore) and consisted of 120 s stimulations to the vagus nerve in the neck (two stimulations to each side three times daily during weeks 1 and 2; three stimulations to each side three times daily during week 3 and beyond).Responsewas defined as a ≥1 point decrease from baseline in GCSI score.

Results

Thirty-five patients enrolled; 23 were compliant with study procedures and were included in the analysis; 7 continued treatment beyond 3 weeks. Response rates were 35% (8/23) at 3 weeks and 43% (10/23) for the duration of therapy (3–6 weeks). For the entire cohort and the 10 responders, improvements from baseline were noted for mean total GCSI and GCSI subscale scores (nausea/vomiting, postprandial fullness/early satiety, bloating). No serious AEs were reported.

Conclusions

These preliminary results provide a signal that nVNS may be useful for treating refractory gastroparesis. Larger controlled studies are warranted.
Canada’s federal database is inadequate for the assessment of environmental consequences of oil and gas pipeline failures
Authors: Belvederesi Chiara , Thompson Megan S. , Komers Petr E.
Published: May 2017

In Canada, the National Energy Board (NEB) regulates inter-provincial oil and gas pipelines and maintains historical records that contain data on oil and gas pipeline accidents; these data include information about operators, the accidents’ cause, and the resulting consequences. New inter-provincial pipelines are being built in Canada to transport fuels, but no comprehensive statistical analysis of the risk to environmental receptors exists. This study assesses the quality and quantity of NEB pipeline failure data available in Canada with a focus on environmental consequences and investigates differences between Canada and a more thoroughly studied jurisdiction, the United States, in tracking accident data. The discrepancies in agencies’ jurisdiction and regulated mileage are analyzed, along with reporting criteria and initial recording year. The level of detail provided by the two agencies is compared, identifying deficiencies in data collection. The Pipeline and Hazardous Materials Safety Administration (PHMSA) regulates 76% of pipelines in the United States, whereas the NEB only monitors 9% of pipelines in Canada. PHMSA provides four databases that include accidents from the 1980s for most pipelines and from 2011 for liquefied natural gas facilities; the NEB database includes accident data starting from 2008, which derive primarily from transmission pipelines. Information about environmental consequences is quite detailed in the US database, which reports 21 descriptive fields, whereas in Canada only two NEB database fields describe environmental outcomes. Moreover, dissimilarities in accident reporting criteria prevent the combination of data from the two agencies. Consequently, the NEB database does not allow for statistically robust and system wide analysis of the environmental consequences of pipeline failures in Canada. Furthermore, to calculate failure rates (annual number of accidents per kilometre of pipeline) for regulated pipelines, annual total mileage estimates are required. Mileage per year is provided by PHMSA for gas gathering, transmission, and distribution pipelines starting from 1984, and for hazardous liquid pipelines from 2004; the NEB provides annual mileage from 2010, a shorter period of record. The Canadian federal agencies are encouraged to improve accuracy and consistency in recording past accidents and in collecting pipeline data, with the goal of preventing and minimizing future pipeline failures.
Entanglement between two scalar fields in an expanding spacetime
Authors: Alexander Helder , da Paz I. G. , Sampaio Marcos
Published: May 2017

We study the evolution of two scalar fields entangled via a mutual interaction in an expanding spacetime. We compute the logarithmic negativity to leading order in perturbation theory and show that for the lowest order in the coupling constants, the mutual interaction will give rise to the survival of the quantum correlations in the limit of the smooth expansion. The results suggest that interacting fields can codify more information about the underlying expansion spacetime and lead to interesting observable effects.