bluuebunny/crossref_metadata_2025 huggingface dataset:
Heteroscedastic Conditional Auto-Regression Models for Areally Referenced Temporal Processes for Analysing California Asthma Hospitalization Data
Authors: Quick Harrison , Carlin Bradley P. , Banerjee Sudipto
Published: April 2015

Often in regionally aggregated spatiotemporal models, a single variance parameter is used to capture variability in the spatial structure of the model, ignoring the effect that spatially varying factors may have on the variability in the underlying process. We extend existing methodologies to allow for region-specific variance components in our analysis of monthly asthma hospitalization rates in California counties, introducing a heteroscedastic conditional auto-regression model that can greatly improve the fit of our spatiotemporal process. After demonstrating the effectiveness of our new model via simulation, we reanalyse the asthma hospitalization data and note some important findings.
Experimental Investigation on Joining Dissimilar Aluminum Alloy 6061 to TRIP 780/800 Steel Through Friction Stir Welding
Authors: Liu Xun , Lan Shuhuai , Ni Jun
Published: April 2015

Friction stir welding (FSW) technique has been successfully applied to butt joining of aluminum alloy 6061-T6 to one type of advanced high strength steel (AHSS), transformation induced plasticity (TRIP) 780/800 with the highest weld strength reaching 85% of the base aluminum alloy. Mechanical welding forces and temperature were measured under various sets of process parameters and their relationships were investigated, which also helped explain the observed macrostructure of the weld cross section. Compared with FSW of similar aluminum alloys, only one peak of axial force occurred during the plunge stage. Three failure modes were identified during tensile tests of weld specimens, which were further analyzed based on the microstructure of joint cross sections. Intermetallic compound (IMC) layer with appropriate thickness and morphology was shown to be beneficial for enhancing the strength of Al–Fe interface.
Synergistic Effects of Fatigue and Marine Environments on Carbon Fiber Vinyl-Ester Composites
Authors: Afshar Arash , Alkhader Maen , Korach Chad S. , Chiang Fu-Pen
Published: April 2015

Fiber-reinforced polymer (FRP) composites used in the construction of composite-based civil and military marine crafts are often exposed to aggressive elements that include ultraviolet radiation, moisture, and cyclic loadings. With time, these elements can individually and more so cooperatively degrade the mechanical properties and structural integrity of FRP composites. To assist in increasing the long-term reliability of composite marine crafts, this work experimentally investigates the cooperative damaging effects of ultraviolet (UV), moisture, and cyclic loading on the structural integrity of carbon fiber reinforced vinyl-ester marine composite. Results demonstrate that UV and moisture can synergistically interact with fatigue damage mechanisms and accelerate fatigue damage accumulation. For the considered composite, damage and S–N curve models with minimal fitting constants are proposed. The new models are derived by adapting well-known cumulative fatigue damage models to account for the ability of UV and moisture to accelerate fatigue damaging effects.
Marine Applications of Gas Turbine Generating Sets
Authors: Higgins R. E. , Kay O. F.
Published: April 2015

Applications of gas turbine-generator sets in marine service are discussed with emphasis on service requirements and limitations of equipment. Characteristics of the gas turbine-generator set are compared to alternative equipment. Examples of installations which are in service are cited to illustrate the method in which gas turbine-generator sets are utilized to best advantage in marine applications. A summary of experience and suggestions for future improvements of such applications is presented.
Turbine Total Energy for Power Generation and Drying: Case History Reports
Authors: Dahline James W.
Published: April 2015

This paper discusses gas-turbine installations in the Burns Brick Company plant in Macon, Ga., and the Cattle Marketers, Inc., plant near St. Cloud, Fla. In the Burns plant the turbine is used for power generation with exhaust heat used for drying brick. In the Cattle Marketers plant the turbine is used for power generation with exhaust heat used for drying grass to make hay. Turbine fuel heat usage of 91.7 and 84.6 percent are obtained in the plants. Short-term pay-out periods and attractive profit on investment are promised by these installations.
Environmental Factors in Engine Design for Military Applications
Authors: Horton James H.
Published: April 2015

The paper describes the extreme conditions of environment to which military equipment is subjected, and the problems involved and techniques used to enable engines to operate in these environments. Among the effects considered are low and high temperature, high altitude, ingested dust, high humidity and salt spray. Data are also included on noise-level requirements and techniques for noise suppression in gas turbines. Most of the subject matter relates to gas turbines, but comparisons are made in some instances with reciprocating engines in order to clearly delineate basic differences in design and technical approaches for solving environmental problems. The paper indicates that partial solutions have been achieved and that research and development is being continued to achieve more complete solutions.
Thermal-Stress and Low-Cycle Fatigue Data on Typical Materials
Authors: Horton K. E. , Hallander J. M. , Foley D. D.
Published: April 2015

This paper presents the results of low-cycle-fatigue tests wherein either thermal strain or mechanical strain was the independent variable. The materials investigated were primarily ferrous alloys for use in nuclear reactors. The analysis of results was based on plastic-strain-range measurements which could be made reproducibly in the 2 × 10−5 range. Graphs of plastic strain range versus cycles to failure were often found to be independent of large variations in temperature and cycle time. The results from thermal-fatigue and constant-temperature-fatigue tests were usually indistinguishable on these graphs, suggesting that identical metallurgical phenomena occurred in each type of test.
Low-Leakage Dynamic Seal to Space
Authors: Lessley R. L. , Hodgson J. N.
Published: April 2015

A space power-system, turbine-shaft seal capable of restricting the leakage of mercury vapor and of oil to the space environment is described. This seal was designed to permit use of oil-lubricated bearings in the turbine-alternator assembly of a mercury Rankine cycle. In the intended application it is located between the turbine and the adjacent bearing. The seal uses slinger-pump, visco-pump, and molecular-pump elements. The role and limitations of each element are discussed. Test rigs were used to determine the adequacy of each seal element. The significance of the resulting data is discussed. Two additional test rigs were built for evaluation of the complete seal. Leakage rates of less than 1 lb per year were measured. This seal, a part of the SNAP-8 power-conversion system, is believed to be the first successful development of a functional dynamic seal to space.
Pinpointing Vibration in Rotating Machinery
Authors: Ness Hugh W.
Published: April 2015

Time and money currently are being saved in many companies by use of advanced techniques and instruments for the analysis of vibration in rotating machinery. Of equal or even greater importance, design and quality-control engineers are learning facts about their machines which allow them to design and produce superior products. The purpose of this paper is to review these advanced techniques and instruments which are applicable to research and development, design, overhaul and repair, maintenance, production, and quality-control facilities. In addition, these techniques and instruments can be applied to airborne, shipboard, flight-line, test-cell, and laboratory vibration testing.
Onset of Mechanical Separation in Bellows-Supported Rotary Face Seals
Authors: Hart Franklin D. , Zorowski Carl F.
Published: April 2015

The problem of incipient dynamic mechanical separation in bellows-supported rotary face seals is analyzed assuming the bellows to be represented by a series of distributed springs and dampers supporting a rigid seal carrier. An expression is developed for the distribution of contact forces between the seal and mating rings generated by the coupled effects of shaft pulsation and mating-ring wobble. This expression is used to determine the operating conditions which will produce the onset of separation by applying the criterion that the contact force distribution will go to zero at some point on the seal when separation is imminent. Results are presented in the form of equations and graphs which define the minimum initial compression necessary to maintain continuous contact in terms of system resilience and damping, amplitude of mating-ring wobble and shaft pulsation, and operating frequency.
Supercharging of Gas Turbines by Forced Draft Fans With Evaporative Intercooling
Authors: Foster-Pegg R. W.
Published: April 2015

The capability of gas turbines may be increased by supercharging with cooled air from a forced-draft fan. The paper reviews potential applications, economics and procedures for calculating gas-turbine capability when supercharged. Several committed installations of supercharged gas turbines are also reviewed.
Comparison of Some Analytical and Experimental Correlations of Axial-Flow Turbine Efficiency
Authors: Amann Charles A. , Sheridan David C.
Published: April 2015

The first phase of the axial-flow turbine design problem involves selection of a velocity diagram. This choice exerts an important influence on turbine efficiency. Design charts relating turbine efficiency to the velocity diagram, through a work coefficient and a flow coefficient, are therefore useful in preliminary design. In this study such design charts are constructed using two established analytical methods. The results are compared with a published correlation based on experimental data. Simple constructional methods are indicated whereby these charts can be used to obtain preliminary estimates of rotor blade stress and relative temperature, two factors influencing blade life.
Turbine Noise: Its Significance in the Civil Aircraft Noise Problem
Authors: Smith M. J. T. , Bushell K. W.
Published: April 2015

The authors show the presence of noise from the turbine of a turbojet or turbofan engine to be a significant contributor the overall engine noise. They review currently available information from both full-scale engines and model turbines and correlate it along lines following those previously developed for fans and compressors.
Proposed Gas Turbine Procurement Standard: Object, Scope, Definition and Description of Terms
Authors: Jenkins D. R. , Harmon R. A.
Published: April 2015

This paper gives definitions for the terms used in the series of ASME papers (see Appendix) constituting a proposed Gas Turbine Procurement Standard.
Filamentary bipolar electric pulse induced resistance switching in amorphous silicon resistive random access memory
Authors: Ebrahim Rabi , Mithun Kumar Ramasahayam , Badi Nacer , Wu Naijuan , Ignatiev Alex
Published: April 2015

Metal/amorphous silicon/metal resistive random access memory structures fabricated with sets of tungsten and copper electrodes have exhibited electric pulse induced resistance switching with unique dependence on electrode material. Electrical forming, which is required to initiate bipolar resistance switching, was found to depend on the electrode material and was found to be enough to produce Joule heating, which may result in diffusion of the metal electrode ions into the α-Si to form a metallic filament. The Joule heating and heat transfer during the electrical forming process have been simulated using comsol multiphysics 4.3b software. The results showed that the produced heat is enough to cause electrode diffusion into α-Si. Tungsten and copper electrode materials were use with the W/α-Si/W samples showing much better switching characteristics compared to the Cu/α-Si/Cu samples. A model for filament formation, and bipolar resistance switching based on electrode material diffusion into α-Si, has been suggested.
Coping Strategies Used by Athletic Training Majors to Manage Clinical and Academic Responsibilities
Authors: Mazerolle Stephanie M. , Bowman Thomas G. , Fister Carrie
Published: April 2015

Context:

Athletic training majors are at risk for experiencing elevated stress, frustrations, and eventual burnout. Evidence suggests that stressors can accumulate over time, but academic standing can plausibly influence experiences with stress.

Objective:

Gain information related to coping strategies used by athletic training majors to manage their stress and frustrations to prevent burnout.

Design:

Online qualitative study.

Setting:

Athletic training programs.

Patients or Other Participants:

10 sophomores, 9 juniors, and 4 seniors completed the online questionnaire. The athletic training majors were recruited from four institutions with accredited programs.

Data Collection and Analysis:

Data were collected in March 2013 via asynchronous online interviewing via QuestionPro. All participants responded to the same set of 25 questions and data were analyzed following a general inductive approach. The questionnaire was reviewed by a peer and piloted. Multiple analyst coding was completed.

Results:

We identified an overarching theme of personal coping strategies, which athletic training majors used to manage and cope with their stressors. These strategies were simply considered outside the confines of the athletic training program itself, and included outside support networks, physical outlets, and time management skills. We acknowledged athletic training majors also employed stress-relieving strategies that were facilitated within or by the athletic training program itself. Specifically, our participants noted that they received support from peer and programmatic personnel (preceptors, faculty).

Conclusions:

Athletic training majors must develop personal strategies that can help them best alleviate their stressors, but also must have strong support in place especially within their athletic training programs. We recommend that athletic training majors reflect upon what strategies work best for them and to find hobbies and personal interests that help them de-stress and rejuvenate from their demanding workloads.
Intrarater and Interrater Agreement of the Intrinsic Foot Muscle Test
Authors: Facchini Stephanie J. , Hoch Matthew C. , Smith Deanna H. , Hoch Johanna M.
Published: April 2015

Context:

The intrinsic foot muscle test (IFMT) is purported to identify intrinsic foot muscle (IFM) weakness during clinical examination. However, before this test can be used in clinical practice the clinometric properties must be determined. In addition, it is unclear if the IFMT provides information regarding the integrity of the foot arch beyond static foot posture assessments such as the navicular drop test (NDT).

Objective:

To determine the reliability of the IFMT as well as its correlation with the NDT.

Setting:

Laboratory.

Patients or other Participants:

Two novice ATs served as the raters. The NDT was assessed by a third investigator during the first session. Twenty-five participants (16 females, 9 males; age: 22.4 ± 1.7 years; height: 170.8 ± 10.2 cm; mass: 73.5 ± 12.8 kg) completed two data collection sessions separated by one week.

Interventions:

During each session the IFMT was assessed bilaterally in a counterbalanced order by the raters. Each test was rated simultaneously by both raters during each trial and the raters were blinded to each other’s results during and between test sessions.

Main Outcome Measures:

The independent variable was time (session one and session two) and the dependent variables included rating on the IFMT and navicular drop height.

Results:

Intrarater agreement was poor to fair (κ = .03−.41) and interrater agreement was fair to moderate (κ = .25−.60). Post hoc Wilcoxon rank tests demonstrated a significant number of participants improved between sessions for both raters. A weak correlation was observed between the NDT and IFMT for both right (r = −.14 to .04, p < .49) and left (r = −.19 to .07, p < .37) feet.

conclusion:

The IFMT demonstrated poor to fair intrarater and fair to moderate interrater agreement, suggesting future research is needed to modify this method of measuring IFM function. The improvement between sessions indicates a potential familiarization period within the test. The weak correlation between the IFMT and NDT indicates these tests evaluate different aspects of foot function.
Hand Motor Control: Maturing an Immature Science
Authors: Cole Kelly J.
Published: April 2015

In the target article Mark Latash has argued that there is but a single bona-fide theory for hand motor control (referent configuration theory). If this is true, and research is often phenomenological, then we must admit that the science of hand motor control is immature. While describing observations under varying conditions is a crucial (but early) stage of the science of any field, it is also true that the key to maturing any science is to vigorously subject extant theories and budding laws to critical experimentation. If competing theories are absent at the present time is it time for scientists to focus their efforts on maturing the science of hand motor control through critical testing of this long-standing theory (and related collections of knowledge such as the uncontrolled manifold)?
Neural Control of Hand Movements
Authors: Perez Monica A.
Published: April 2015

Most of our daily actions involve movements of the hand. The neuronal pathway contributing to the control of hand movements are complex and not yet completely understood. Recent studies highlight how task-dependent changes in cortical and subcortical pathways driven by contralateral and ipsilateral influences may open avenues to further understand the complexity of hand actions in healthy and disease. In the following section studies using transcranial magnetic and electrical stimulation in healthy subjects and in individuals with chronic incomplete spinal cord injury will be highlighted to further understand neuronal pathways involved in the control of voluntary activity by hand muscles.
Observation of isolated monopoles in a quantum field
Authors: Ray M. W. , Ruokokoski E. , Tiurev K. , Möttönen M. , Hall D. S.
Published: April 2015

Making a monopole in an atomic gas

Some “grand unified theories” of physics predict the existence of the so-called magnetic monopole. No such particles have been seen, but analogs of monopoles may be observable in quantum fluids. Ray
et al.
created such an analog in a gas of ultracold
87
Rb atoms with three spin states at their disposal. The authors used a protocol involving external magnetic fields with particular spatial distributions to create and observe a monopole-like spin texture in the gas.

Science, this issue p.
544
Mechanistic origins of bombardier beetle (Brachinini) explosion-induced defensive spray pulsation
Authors: Arndt Eric M. , Moore Wendy , Lee Wah-Keat , Ortiz Christine
Published: April 2015

A beetle's internal bomb

Bombardier beetles shoot a toxic pulse at potential predators and other harassers. The toxic spray is created by a chemical reaction that occurs inside the beetle's body. Although the details of the reaction are known, how the beetle is able to precisely combine the chemicals at appropriate times and release the pulse at regular intervals has remained a mystery. Arndt
et al.
used synchrotron x-ray imagery to observe the process as it occurs within live beetles. Expansion and contraction of an internal expansion membrane facilitate the precise cyclic injection of reactants and the subsequent ejection of toxic sprays that keep the beetle's predators at bay.

Science
, this issue p.
563
Beyond crystallography: Diffractive imaging using coherent x-ray light sources
Authors: Miao Jianwei , Ishikawa Tetsuya , Robinson Ian K. , Murnane Margaret M.
Published: April 2015

X-ray crystallography has been central to the development of many fields of science over the past century. It has now matured to a point that as long as good-quality crystals are available, their atomic structure can be routinely determined in three dimensions. However, many samples in physics, chemistry, materials science, nanoscience, geology, and biology are noncrystalline, and thus their three-dimensional structures are not accessible by traditional x-ray crystallography. Overcoming this hurdle has required the development of new coherent imaging methods to harness new coherent x-ray light sources. Here we review the revolutionary advances that are transforming x-ray sources and imaging in the 21st century.
Direct observation of hierarchical protein dynamics
Authors: Lewandowski Józef R. , Halse Meghan E. , Blackledge Martin , Emsley Lyndon
Published: April 2015

A hierarchy of protein motions

Functioning proteins are not static but explore complex conformational energy landscapes. Lewandowski
et al.
used multinuclear solid-state nuclear magnetic resonance experiments to measure protein motion over a broad range of temperatures and time scales. Above 160 K there was a strong coupling between solvent and protein motion. The hierarchy of motions as the temperature increased revealed the dynamic modes that relate solvent, sidechain, and backbone motion.

Science
, this issue p.
578
The quantum halo state of the helium trimer
Authors: Kornilov Oleg
Published: April 2015

Femtosecond laser pulses help to take a snapshot of the huge elusive Efimov state

[Also see Report by

Kunitski
et al.

]
Complete Genome Sequences for 35 Biothreat Assay-Relevant
Bacillus
Species
Authors: Johnson Shannon L. , Daligault Hajnalka E. , Davenport Karen W. , Jaissle James , Frey Kenneth G. , Ladner Jason T. , Broomall Stacey M. , Bishop-Lilly Kimberly A. , Bruce David C. , Gibbons Henry S. , Coyne Susan R. , Lo Chien-Chi , Meincke Linda , Munk A. Christine , Koroleva Galina I. , Rosenzweig C. Nicole , Palacios Gustavo F. , Redden Cassie L. , Minogue Timothy D. , Chain Patrick S.
Published: April 2015

In 2011, the Association of Analytical Communities (AOAC) International released a list of
Bacillus
strains relevant to biothreat molecular detection assays. We present the complete and annotated genome assemblies for the 15 strains listed on the inclusivity panel, as well as the 20 strains listed on the exclusivity panel.
Microbiological and Clinical Studies of Legionellosis in 33 Patients with Cancer
Authors: Han Xiang Y. , Ihegword Andrea , Evans Scott E. , Zhang Jiaqi , Li Li , Cao Hongjing , Tarrand Jeffrey J. , El-Kweifi Omar
Published: April 2015

Legionella, a large group of environmental Gram-negative bacteria, represents an occasional cause of pneumonia. We analyzed the microbiological and clinical features of 33 consecutive cases ofLegionellainfections that occurred at the University of Texas MD Anderson Cancer Center, Houston, TX, from 2002 to 2014. TheLegionellastrains were isolated from bronchoscopy specimens (32 strains) and a blood culture (1 strain) and were identified by sequencing analysis of the full-length 16S rRNA gene. The 33 strains involved 12Legionellaspecies or subspecies: 15 strains ofL. pneumophilasubsp.pneumophila, 3 strains ofL. pneumophilasubsp.fraseriorL. pneumophilasubsp.pascullei, 4 strains of “L. donaldsonii,” 3 strains ofL. micdadei, and one each ofL. bozemanae,L. feeleii,L. gormanii,L. longbeachae,L. maceachernii,L. parisiensis,L. sainthelensi, andLegionellasp. strain D5382. All patients except one asymptomatic carrier showed pneumonia, including one with concurrent bacteremia. Nine patients died, with this infection being the immediate cause of death in six. Twenty-seven patients had underlying hematologic malignancies. Twenty-three patients were leukopenic. Six patients were recipients of allogeneic hematopoietic stem cell transplant, with their infections caused by fiveLegionellaspecies. Together, these results suggest that diverseLegionellaspecies infect patients with cancer in the Houston area and its vicinity. The five cases of pneumonia due toL. donaldsoniiandLegionellasp. D5382 are likely the first reports of human infection with these organisms.
Sepsis Due to a Novel Urease-Positive Helicobacter Species in a Young Man
Authors: Mori Nobuaki , Kagawa Narito , Higuchi Akiko , Aoki Yasuko , Ohkusu Kiyofumi
Published: April 2015

We report the first case of sepsis with enterocolitis that was caused by a novel urease-positive
Helicobacter
species in a young man. The isolate was characterized via 16S rRNA gene sequencing and their biochemical properties, and the patient was successfully treated with short-term antimicrobial therapy; no recurrence was observed.
Direct Detection of Influenza A and B Viruses in Less Than 20 Minutes Using a Commercially Available Rapid PCR Assay
Authors: Binnicker Matthew J. , Espy Mark J. , Irish Cole L. , Vetter Emily A.
Published: April 2015

We compared an FDA-cleared rapid (<20 min) PCR assay (Cobas Liat; Roche Diagnostics) to our routine influenza A and B real-time PCR assay (Simplexa Flu A/B & RSV Direct; Focus Diagnostics) using respiratory swabs (
n
= 197). The Cobas Liat influenza A and B assays demonstrated sensitivities of 99.2% (123/124) and 100% (23/23), respectively, while showing a specificity of 100% for each target.
Genome-Based Characterization of Emergent Invasive Neisseria meningitidis Serogroup Y Isolates in Sweden from 1995 to 2012
Authors: Törös Bianca , Hedberg Sara T. , Unemo Magnus , Jacobsson Susanne , Hill Dorothea M. C. , Olcén Per , Fredlund Hans , Bratcher Holly B. , Jolley Keith A. , Maiden Martin C. J. , Mölling Paula
Published: April 2015

Invasive meningococcal disease (IMD) caused by
Neisseria meningitidis
serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is now the dominating serogroup, and in 2012, the serogroup Y disease incidence was 0.46/100,000 population. We previously showed that a strain type belonging to sequence type 23 was responsible for the increased prevalence of this serogroup in Sweden. The objective of this study was to investigate the serogroup Y emergence by whole-genome sequencing and compare the meningococcal population structure of Swedish invasive serogroup Y strains to those of other countries with different IMD incidence. Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (
n
= 186). These isolates were compared to a collection of serogroup Y isolates from England, Wales, and Northern Ireland from 2010 to 2012 (
n
= 143), which had relatively low serogroup Y incidence, and two isolates obtained in 1999 in the United States, where serogroup Y remains one of the major causes of IMD. The meningococcal population structures were similar in the investigated regions; however, different strain types were prevalent in each geographic region. A number of genes known or hypothesized to have an impact on meningococcal virulence were shown to be associated with different strain types and subtypes. The reasons for the IMD increase are multifactorial and are influenced by increased virulence, host adaptive immunity, and transmission. Future genome-wide association studies are needed to reveal additional genes associated with serogroup Y meningococcal disease, and this work would benefit from a complete serogroup Y meningococcal reference genome.
Enterovirus 71 Proteins 2A and 3D Antagonize the Antiviral Activity of Gamma Interferon via Signaling Attenuation
Authors: Wang Li-Chiu , Chen Su-O , Chang Shih-Ping , Lee Yi-Ping , Yu Chun-Keung , Chen Chia-Ling , Tseng Po-Chun , Hsieh Chia-Yuan , Chen Shun-Hua , Lin Chiou-Feng
Published: April 2015

Enterovirus 71 (EV71) infection causes severe mortality involving multiple possible mechanisms, including cytokine storm, brain stem encephalitis, and fulminant pulmonary edema. Gamma interferon (IFN-γ) may confer anti-EV71 activity; however, the claim that disease severity is highly correlated to an increase in IFN-γ is controversial and would indicate an immune escape initiated by EV71. This study, investigating the role of IFN-γ in EV71 infection using a murine model, showed that IFN-γ was elevated. Moreover, IFN-γ receptor-deficient mice showed higher mortality rates and more severe disease progression with slower viral clearance than wild-type mice.In vitroresults showed that IFN-γ pretreatment reduced EV71 yield, whereas EV71 infection caused IFN-γ resistance with attenuated IFN-γ signaling in IFN regulatory factor 1 (IRF1) gene transactivation. To study the immunoediting ability of EV71 proteins in IFN-γ signaling, 11 viral proteins were stably expressed in cells without cytotoxicity; however, viral proteins 2A and 3D blocked IFN-γ-inducedIRF1transactivation following a loss of signal transducer and activator of transcription 1 (STAT1) nuclear translocation. Viral 3D attenuated IFN-γ signaling accompanied by a STAT1 decrease without interfering with IFN-γ receptor expression. Restoration of STAT1 or blocking 3D activity was able to rescue IFN-γ signaling. Interestingly, viral 2A attenuated IFN-γ signaling using another mechanism by reducing the serine phosphorylation of STAT1 following the inactivation of extracellular signal-regulated kinase without affecting STAT1 expression. These results demonstrate the anti-EV71 ability of IFN-γ and the immunoediting ability by EV71 2A and 3D, which attenuate IFN-γ signaling through different mechanisms.

IMPORTANCEImmunosurveillance by gamma interferon (IFN-γ) may confer anti-enterovirus 71 (anti-EV71) activity; however, the claim that disease severity is highly correlated to an increase in IFN-γ is controversial and would indicate an immune escape initiated by EV71. IFN-γ receptor-deficient mice showed higher mortality and more severe disease progression, indicating the anti-EV71 property of IFN-γ. However, EV71 infection caused cellular insusceptibility in response to IFN-γ stimulation. We used anin vitrosystem with viral protein expression to explore the novel IFN-γ inhibitory properties of the EV71 2A and 3D proteins through the different mechanisms. According to this study, targeting either 2A or 3D pharmacologically and/or genetically may sustain a cellular susceptibility in response to IFN-γ, particularly for IFN-γ-mediated anti-EV71 activity.
New Noncoding Lytic Transcripts Derived from the Epstein-Barr Virus Latency Origin of Replication,
oriP
, Are Hyperedited, Bind the Paraspeckle Protein, NONO/p54nrb, and Support Viral Lytic Transcription
Authors: Cao Subing , Moss Walter , O'Grady Tina , Concha Monica , Strong Michael J. , Wang Xia , Yu Yi , Baddoo Melody , Zhang Kun , Fewell Claire , Lin Zhen , Dong Yan , Flemington Erik K.
Published: April 2015

We have previously shown that the Epstein-Barr virus (EBV) likely encodes hundreds of viral long noncoding RNAs (vlncRNAs) that are expressed during reactivation. Here we show that the EBV latency origin of replication (
oriP
) is transcribed bi-directionally during reactivation and that both leftward (oriPtLs) and rightward (oriPtRs) transcripts are largely localized in the nucleus. While the oriPtLs are most likely noncoding, at least some of the oriPtRs contain the BCRF1/vIL10 open reading frame. Nonetheless, oriPtR transcripts with long 5′ untranslated regions may partially serve noncoding functions. Both oriPtL and oriPtR transcripts are expressed with late kinetics, and their expression is inhibited by phosphonoacetic acid. RNA sequencing (RNA-seq) analysis showed that oriPtLs and oriPtRs exhibited extensive “hyperediting” at their Family of Repeat (FR) regions. RNA secondary structure prediction revealed that the FR region of both oriPtLs and oriPtRs may form large evolutionarily conserved and thermodynamically stable hairpins. The double-stranded RNA-binding protein and RNA-editing enzyme ADAR was found to bind to oriPtLs, likely facilitating editing of the FR hairpin. Further, the multifunctional paraspeckle protein, NONO, was found to bind to oriPt transcripts, suggesting that oriPts interact with the paraspeckle-based innate antiviral immune pathway. Knockdown and ectopic expression of oriPtLs showed that it contributes to global viral lytic gene expression and viral DNA replication. Together, these results show that these new vlncRNAs interact with cellular innate immune pathways and that they help facilitate progression of the viral lytic cascade.

IMPORTANCE
Recent studies have revealed that the complexity of lytic herpesviral transcriptomes is significantly greater than previously appreciated with hundreds of viral long noncoding RNAs (vlncRNAs) being recently discovered. Work on cellular lncRNAs over the past several years has just begun to give us an initial appreciation for the array of functions they play in complex formation and regulatory processes in the cell. The newly identified herpesvirus lncRNAs are similarly likely to play a variety of different functions, although these functions are likely tailored to specific needs of the viral infection cycles. Here we describe novel transcripts derived from the EBV latency origin of replication. We show that they are hyperedited, that they interact with a relatively newly appreciated antiviral pathway, and that they play a role in facilitating viral lytic gene expression. These investigations are a starting point to unraveling the complex arena of vlncRNA function in herpesvirus lytic replication.
Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer
Authors: Lee Peter S. , Zhu Xueyong , Yu Wenli , Wilson Ian A.
Published: April 2015

We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA
3
-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA
3
-SS has increased thermostability compared to wild-type HA, and binding of head- and stem-targeted antibodies (Abs) is preserved; only minor structural changes are found in the vicinity of the additional disulfide. This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens.
The Nectin-4/Afadin Protein Complex and Intercellular Membrane Pores Contribute to Rapid Spread of Measles Virus in Primary Human Airway Epithelia
Authors: Singh Brajesh K. , Hornick Andrew L. , Krishnamurthy Sateesh , Locke Anna C. , Mendoza Crystal A. , Mateo Mathieu , Miller-Hunt Catherine L. , Cattaneo Roberto , Sinn Patrick L.
Published: April 2015

The discovery that measles virus (MV) uses the adherens junction protein nectin-4 as its epithelial receptor provides a new vantage point from which to characterize its rapid spread in the airway epithelium. We show here that in well-differentiated primary cultures of airway epithelial cells from human donors (HAE), MV infectious centers form rapidly and become larger than those of other respiratory pathogens: human respiratory syncytial virus, parainfluenza virus 5, and Sendai virus. While visible syncytia do not form after MV infection of HAE, the cytoplasm of an infected cell suddenly flows into an adjacent cell, as visualized through wild-type MV-expressed cytoplasmic green fluorescent protein (GFP). High-resolution video microscopy documents that GFP flows through openings that form on the lateral surfaces between columnar epithelial cells. To assess the relevance of the protein afadin, which connects nectin-4 to the actin cytoskeleton, we knocked down its mRNA. This resulted in more-limited infectious-center formation. We also generated a nectin-4 mutant without the afadin-binding site in its cytoplasmic tail. This mutant was less effective than wild-type human nectin-4 at promoting MV infection in primary cultures of porcine airway epithelia. Thus, in airway epithelial cells, MV spread requires the nectin-4/afadin complex and is based on cytoplasm transfer between columnar cells. Since the viral membrane fusion apparatus may open the passages that allow cytoplasm transfer, we refer to them as intercellular membrane pores. Virus-induced intercellular pores may contribute to extremely efficient measles contagion by promoting the rapid spread of the virus through the upper respiratory epithelium.

IMPORTANCE
Measles virus (MV), while targeted for eradication, still causes about 120,000 deaths per year worldwide. The recent reemergence of measles in insufficiently vaccinated populations in Europe and North America reminds us that measles is extremely contagious, but the processes favoring its spread in the respiratory epithelium remain poorly defined. Here we characterize wild-type MV spread in well-differentiated primary cultures of human airway epithelial cells. We observed that viral infection promotes the flow of cytoplasmic contents from infected to proximal uninfected columnar epithelial cells. Cytoplasm flows through openings that form on the lateral surfaces. Infectious-center growth is facilitated by afadin, a protein connecting the adherens junction and the actin cytoskeleton. The viral fusion apparatus may open intercellular pores, and the cytoskeleton may stabilize them. Rapid homogenization of cytoplasmic contents in epithelial infectious centers may favor rapid spread and contribute to the extremely contagious nature of measles.
Risk behaviours and prevalence of sexually transmitted infections and HIV in a group of Dominican gay men, other men who have sex with men and transgender women
Authors: Brito Maximo O , Hodge David , Donastorg Yeycy , Khosla Shaveta , Lerebours Leonel , Pope Zachary
Published: April 2015

Objectives

The objectives of this study were to estimate the point prevalence of sexually transmitted infection (STI) and to investigate the sexual practices and behaviours associated with STIs in a group of gay men, other men who have sex with men and transgender women (GMT) in the province of La Romana, Dominican Republic.

Design

A cross-sectional study of a convenience sample of GMT persons.

Setting

The study was conducted in the province of La Romana, Dominican Republic, in June–July 2013.

Participants

Out of 117 GMT persons screened, a total of 100 completed the study. Participants had to be at least 18 years of age, reside in La Romana and have had sex with another man in the preceding 12 months. All participants were interviewed and tested for STI.

Primary outcome measure

The main outcome of interest was the detection of any STI (HIV, herpes simplex virus type 2 (HSV-2), syphilis, hepatitis B or C) by serology.

Results

Among 100 participants, the median age was 22 years (range 18–65). One-third had consumed illicit drugs the preceding year and only 43% consistently used condoms. Prevalence was 38% for HSV-2, 5% for HIV and 13% for syphilis. There were no cases of hepatitis B or C. Factors associated with the odds of a STI were age >22 years (OR=11.1, 95% CI 3.6 to 34.5), receptive anal intercourse (OR=4.2, 95% CI 1.3 to 13.6) and having ≥2 male sexual partners during the preceding month (OR=4, 95% CI 1.3 to 12.5).

Conclusions

In this group of GMT persons, seroprevalence of STI was high, and a number of risk behaviours were associated with STI. These preliminary data will help inform policy and programmes to prevent HIV/STI in GMT persons in the region.
Development, reliability, and validity testing of Toddler NutriSTEP: a nutrition risk screening questionnaire for children 18–35 months of age
Authors: Randall Simpson Janis , Gumbley Jillian , Whyte Kylie , Lac Jane , Morra Crystal , Rysdale Lee , Turfryer Mary , McGibbon Kim , Beyers Joanne , Keller Heather
Published: April 2015

Nutrition is vital for optimal growth and development of young children. Nutrition risk screening can facilitate early intervention when followed by nutritional assessment and treatment. NutriSTEP (Nutrition Screening Tool for Every Preschooler) is a valid and reliable nutrition risk screening questionnaire for preschoolers (aged 3–5 years). A need was identified for a similar questionnaire for toddlers (aged 18–35 months). The purpose was to develop a reliable and valid Toddler NutriSTEP. Toddler NutriSTEP was developed in 4 phases. Content and face validity were determined with a literature review, parent focus groups (n = 6; 48 participants), and experts (n = 13) (phase A). A draft questionnaire was refined with key intercept interviews of 107 parents/caregivers (phase B). Test–retest reliability (phase C), based on intra-class correlations (ICC), Kappa (κ) statistics, and Wilcoxon tests was assessed with 133 parents/caregivers. Criterion validity (phase D) was assessed using Receiver Operating Characteristic (ROC) curves by comparing scores on the Toddler NutriSTEP to a comprehensive nutritional assessment of 200 toddlers with a registered dietitian (RD). The Toddler NutriSTEP was reliable between 2 administrations (ICC = 0.951, F = 20.53, p < 0.001); most questions had moderate (κ ≥ 0.6) or excellent (κ ≥ 0.8) agreement. Scores on the RD nutrition risk rating and the Toddler NutriSTEP were correlated (r = 0.67, p < 0.000). The area under the ROC curve for moderate and high RD risk ratings were 84.6% and 82.7%, respectively. Cut-points of ≥21 (sensitivity 86%; specificity 61%) (moderate risk) and ≥26 (sensitivity 95%; specificity 63%) (high risk) were determined. The Toddler NutriSTEP questionnaire is both reliable and valid for screening for nutritional risk in toddlers.
Crystal growth and characterization of a semi-organic nonlinear optical (NLO) material: L-phenylalanine cadmium chloride
Authors: Jagadeesh M.R. , Suresh Kumar H.M. , Ananda Kumari R.
Published: April 2015

L-phenylalanine cadmium chloride (LPCC) single crystals were grown from aqueous solution using the slow evaporation solution technique. The grown crystals were analyzed through various characterization techniques. Structural study reveals that LPCC belongs to a monoclinic crystal system with the space group P1. The presences of various functional groups were identified by Fourier transform infrared analysis. Optical absorption study was carried out and complete transparency in the visible region was observed with a lower cutoff wavelength of 261 nm. The surface morphology was analyzed through scanning electron micrograph studies. LPCC is thermally stable up to 265 °C as determined by thermogravimetric – differential thermal analysis studies. Dielectric behavior as a function of frequency was examined. The mechanical behavior was studied by Vicker’s microhardness tester. To explore the nonlinear optical property, the Kurtz powder method was employed and second harmonic generation efficiency was determined.
Optical second-harmonic generation in a two-dimensional system
Authors: Gu Mingliang , Zhu Xun , Zhang Chaojin
Published: April 2015

Several parameters that affect the optical second-harmonic generation (SHG) coefficients in the two-dimensional Coulomb system have been discussed. Due to the changes of the Coulomb potential coefficients and geometric factor, it is shown that the optical SHG coefficients' changes are effectively controlled. Moreover, the SHG coefficients depend strongly on the system size and relaxation time.
A review on symmetries for certain Aedes aegypti models
Authors: Freire Igor Leite , Torrisi Mariano
Published: April 2015

We summarize our results related with mathematical modeling of Aedes aegypti and its Lie symmetries. Moreover, some explicit, group-invariant solutions are also shown. Weak equivalence transformations of more general reaction diffusion systems are also considered. New classes of solutions are obtained.
Induction of cardioprotection by small netrin-1-derived peptides
Authors: Li Qiang , Cai Hua
Published: April 2015

We have shown that netrin-1 induces potent cardioprotection via extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent endothelial nitric oxide synthase (eNOS)/NO activation. The present study investigated cardioprotective effects of small netrin-1-derived peptides. We synthesized three laminin (Lam) V peptides and found those time dependently increased phosphorylation of ERK1/2 and eNOSs1179 in endothelial cells at the same molar concentration used for netrin-1. Preperfusion with Lam V peptides induced a substantial reduction in infarct size (control 39.3 ± 0.2% vs. 14.6 ± 2.3%, 23.0 ± 2.8%, and 18.8 ± 0.8% for V1, V2, and V3, respectively). Furthermore, reperfusion with all three also induced potent cardioprotection (control 37.6 ± 1.3% vs. 17.6 ± 3.2%, 20.6 ± 1.7%, and 15.8 ± 2.0% for V1, V2, and V3, respectively), implicating that these peptides are consistently beneficial whenever they are delivered to the heart. Based on the sequence alignment, we found a region of high sequence homology and synthesized smaller peptides [V1-9 amino acid (aa), V2-10aa, and V3-11aa]. These smaller peptides markedly reduced infarct size during reperfusion (V1-9aa 16.8 ± 2.2%, V2-10aa 18.6 ± 1.7%, and V3-11aa 16.7 ± 3.0% vs. control 37.6 ± 1.3%). A negative control V3-16aa with no sequence homology failed to protect the heart. Of note, the core area has the characteristic sequence of: C x(1–2)C x(3–4)T x(0–1)G. Furthermore, all three smaller peptides induced NO production in endothelial cells that could in turn diffuse to cardiomyocytes to promote survival. Combined applications of V1-9aa and V2-10aa synergistically induced more NO production. Taken together, these data strongly suggest that small netrin-1-derived peptides are highly effective in protecting the heart against myocardial ischemia-reperfusion injury and has the potential to be developed into peptide drugs directly applicable to the treatment of myocardial infarction.
Exon 4-encoded sequence is a major determinant of cytotoxicity of apolipoprotein L1
Authors: Khatua Atanu K. , Cheatham Amber M. , Kruzel Etty D. , Singhal Pravin C. , Skorecki Karl , Popik Waldemar
Published: April 2015

The apolipoprotein L1 (APOL1) gene ( APOL1) product is toxic to kidney cells, and its G1 and G2 alleles are strongly associated with increased risk for kidney disease progression in African Americans. Variable penetrance of the G1 and G2 risk alleles highlights the significance of additional factors that trigger or modify the progression of disease. In this regard, the effect of alternative splicing in the absence or presence of G1 or G2 alleles is unknown. In this study we investigated whether alternative splicing of non-G1, non-G2 APOL1 ( APOL1 G0) affects its biological activity. Among seven APOL1 exons, exons 2 and 4 are differentially expressed in major transcripts. We found that, in contrast to APOL1 splice variants B3 or C, variants A and B1 demonstrate strong toxicity in human embryonic kidney (HEK293T) cells. Subsequently, we established that exon 4 is a major determinant of toxicity of variants A and B1 and that extracellular release of these variants is dispensable for their cytotoxicity. Although only variants A and B1 induced nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, exon 4-positive and -negative APOL1 variants stimulated perinuclear accumulation of unprocessed autophagosomes. Knockdown of endogenous TFEB did not attenuate APOL1 cytotoxicity, indicating that nuclear translocation of TFEB is dispensable for APOL1 toxicity. Our findings that a human podocyte cell line expresses exon 4-positive and -negative APOL1 transcripts suggest that these variants may play a differential role in podocyte pathology. In summary, we have identified exon 4 as a major determinant of APOL1 G0 cytotoxicity.