bluuebunny/crossref_metadata_2025 huggingface dataset:
A Brazilian Disk Test for the Evaluation of the Shear Strength of Epoxy‐Joined Ceramics
Authors: Martin Eric , Pavia Fabio , Ventrella Andrea , Avalle Massimiliano , Lara‐Curzio Edgar , Ferraris Monica
Published: May 2012

Brazilian disk test is here analyzed as a test method to determine the strength of joined ceramics. The test specimen consisted of two silicon carbide half‐disks diametrically bonded with a brittle adhesive (Araldite AV119™). Several tests were performed with different angles of the adhesive layer with respect to the diametral line of loading. An elastic finite element analysis is used to determine the maximum shear stress and the normal compressive stress within the joint. Assuming a failure criterion based on a shear stress condition, this procedure allows evaluating the shear strength of the epoxy adhesive.
First record of family Stephanidae (Hymenoptera: Stephanoidea) from South Korea with three recognized species
Authors: Kim Chang‐Jun , Lee Jong‐Wook
Published: May 2012

Foenatopus ruficollis (Enderlein, 1913), Parastephanellus matsumotoi van Achterberg, 2006 and Schlettererius determinatorius Madl, 1991 of the family Stephanidae, are reported for the first time in South Korea. The superfamily Stephanoidea is also new to South Korea. A key to the species, diagnosis and photographs of diagnostic characters are provided.
The Relation Between Breakfast Skipping and School Performance in Adolescents
Authors: Boschloo Annemarie , Ouwehand Carolijn , Dekker Sanne , Lee Nikki , de Groot Renate , Krabbendam Lydia , Jolles Jelle
Published: May 2012

Breakfast skipping is common in adolescents, but research on the effects of breakfast skipping on school performance is scarce. This current cross‐sectional survey study of 605 adolescents aged 11–18 years investigated whether adolescents who habitually skip breakfast have lower end‐of‐term grades than adolescents who eat breakfast daily. Additionally, the roles of sleep behavior, namely chronotype, and attention were explored. Results showed that breakfast skippers performed lower at school than breakfast eaters. The findings were similar for younger and older adolescents and for boys and girls. Adolescents with an evening chronotype were more likely to skip breakfast, but chronotype was unrelated to school performance. Furthermore, attention problems partially mediated the relation between breakfast skipping and school performance. This large‐scale study emphasizes the importance of breakfast as a determinant for school performance. The results give reason to investigate the mechanisms underlying the relation between skipping breakfast, attention, and school performance in more detail.
The Olympic Games in the Long Eighteenth Century
Authors: RADFORD PETER
Published: May 2012

‘Olimpick Games’ were held in the Cotswolds annually throughout the eighteenth century. They were never merely local festivities, and were well known by people who might not normally have paid attention to sport, partly because of their royal support and partly because they drew on a belief that sporting festivals were expressions of Englishness, as old as the nation itself and as important to it as was sport to the ancient Greeks. Other events were also given the name ‘Olympic’, which became the way to describe many well‐organised sporting events in England, and this had an influence on the modern Olympic movement.
Gilbert West's Dissertation on the Olympick Games (1749): ‘Established upon great Political Views’
Authors: ZEBROWSKI MARTHA K.
Published: May 2012

Gilbert West's Dissertation on the Olympick Games is the first modern history of the ancient games. The Dissertation incorporates a bibliographic essay, historical conjecture and narrative, and descriptions of the venue, athletes and events at Olympia. West considered the ancient games a political institution foremost, and demonstrated the importance of seeing the games as an elemental institution embedded in and revealing of the larger political culture of ancient Greece. With the Dissertation, West joined British Classical scholars, translators and literary figures who found in ancient Greek liberty, virtue and patriotic valour models for the British nation in the eighteenth century.
PPARγ Agonist Pioglitazone Reverses Memory Impairment and Biochemical Changes in a Mouse Model of Type 2 Diabetes Mellitus
Authors: Jiang Li‐Ying , Tang Su‐Su , Wang Xiao‐Yun , Liu Li‐Ping , Long Yan , Hu Mei , Liao Ming‐Xing , Ding Qi‐Long , Hu Wei , Li Jia‐Chang , Hong Hao
Published: May 2012

Aims: Pioglitazone, known as a peroxisome proliferator‐activated receptor γ (PPARγ) agonist, is used to treat type 2 diabetes mellitus (T2DM). T2DM has been associated with reduced performance on numerous domains of cognitive function. Here, we investigated the effects of pioglitazone on memory impairment in a mouse model with defects in insulin sensitivity and secretion, namely high‐fat diet (HFD) streptozotocin (STZ)‐induced diabetic mice. Methods: ICR mice were fed with HFD for 4 weeks and then injected with a single low dose of STZ followed by continued HFD feeding for an additional 4 weeks. Pioglitazone (18 mg/kg, 9 mg/kg body weight) was orally administered for 6 weeks once daily. Y‐maze test and Morris water maze test (MWM) were employed for testing learning and memory. Serum glucose, serum insulin, serum triglyceride, brain β‐amyloid peptide (Aβ), brain β‐site amyloid precursor protein cleaving enzyme (BACE1), brain nuclear factor κB (NF‐κB), and brain receptor for advanced glycation end products (RAGE) were also tested. Results: The STZ/HFD diabetic mice, characterized by hyperglycemia, hyperlipemia and hypoinsulinemia, performed poorly on Y‐maze and MWM hence reflecting impairment of learning and memory behavior with increases of Aβ40/Aβ42, BACE1, NF‐κB, and RAGE in brain. Treatment of PPARγ agonist, pioglitazone (18 or 9 mg/kg body weight), significantly reversed diabetes‐induced impairment of learning and memory behavior, which is involved in decreases of Aβ40/Aβ42 via inhibition of NF‐κB, BACE1 and RAGE in brain as well as attenuation of hyperglycemia, hyperlipemia, and hypoinsulinemia. Conclusions: It is concluded that PPARγ agonist pioglitazone may be considered as potential pharmacological agents for the management of cognitive dysfunction in T2DM.
Redeploy Illinois Program: The Impact on Juveniles, Families, and the Juvenile Justice System
Authors: Kethineni Sesha
Published: May 2012

The Redeploy Illinois (RI) pilot program was created to give Illinois counties financial support to provide community‐based services for nonviolent youths who would otherwise be committed to the Department of Juvenile Justice, which oversees juvenile correctional institutions. The current project assesses: 1) the RI data in McLean County; 2) the attitudes and perceptions of the youths in the program; 3) the views of family members of RI youths; and 4) the views of the probation officers, attorneys, and service providers. This research will provide a comprehensive understanding of the impact of the RI program on youths, families, victims, and the justice system.
Abundant and diverse endophytic actinobacteria associated with medicinal plant Maytenus austroyunnanensis in Xishuangbanna tropical rainforest revealed by culture‐dependent and culture‐independent methods
Authors: Qin Sheng , Chen Hua‐Hong , Zhao Guo‐Zhen , Li Jie , Zhu Wen‐Yong , Xu Li‐Hua , Jiang Ji‐Hong , Li Wen‐Jun
Published: May 2012

Endophytes are now considered as an important component of biodiversity. However, the diversity of endophytic actinobacteria associated with tropical rainforest native medicinal plants is essentially unknown. In this study, the diversity of endophytic actinobacteria residing in root, stem and leaf tissues of medicinal plant Maytenus austroyunnanensis collected from tropical rainforest in Xishuangbanna, China was investigated with a combination of cultivation and culture‐independent analysis on the basis of 16S rRNA gene sequencing. By using different selective isolation media and methods, a total of 312 actinobacteria were obtained, and they were affiliated with the order Actinomycetales (distributed into 21 genera). Based on a protocol for endophytes enrichment, three 16S rRNA gene clone libraries were constructed and 84 distinct operational taxonomic units were identified and they distributed among the orders Actinomycetales and Acidimicrobiales, including eight suborders and at least 38 genera with a number of rare actinobacteria genera. Phylogenetic analysis showed that 32% of the clones in the libraries had lower than 97% similarities with related type strains. Interestingly, six genera from the order Actinomycetales and uncultured clones from Acidimicrobiales have not, to our knowledge, been previously reported as endophytes. Our study confirms abundant endophytic actinobacterial consortium in tropical rainforest native plant and suggests that this special habitat represents an underexplored reservoir of diverse and novel actinobacteria of potential interest for bioactive compounds discovery.
Evaluation of the ADViSOR project: Cross‐situational behaviour monitoring of high‐risk offenders in prison and the community
Authors: McDougall Cynthia , Pearson Dominic A. S. , Willoughby Hazel , Bowles Roger A.
Published: May 2012

Purpose. The release on licence of prisoners who have committed serious violent and/or sexual offences requires rigorous risk assessment and risk management. This study evaluates the ADViSOR project, designed to examine the contribution of prison behaviour monitoring to community supervision of a sample of the highest risk offenders released in England and Wales under Multi‐Agency Public Protection Arrangements (MAPPA).

Method. The offence‐related behaviour of a total group (n= 25) of MAPPA prisoners in one prison, due for release in the following year to two adjacent probation trust areas, was monitored. Their behaviours in the community were followed up for 1 year. A comparison group (n= 36) was formed of the total number of MAPPA prisoners released from prisons nationally to the same two probation trusts.

Results. The frequencies of ADViSOR negative behaviours in prison and the community were strongly correlated, rs (25) = .55, p= .004, as were positive behaviours, rs (25) = .56, p= .004. No statistically significant correlations were found either under usual MAPPA processes in the ADViSOR prison or comparison group prisons. The frequency of ADViSOR negative behaviours statistically significantly predicted, with 92% accuracy, the offenders who would reoffend or be recalled to prison (n= 8). Statistically significant similarities in types of behaviour were also identified.

Conclusion. Results are discussed in terms of the contribution of behavioural monitoring to risk prediction with high‐risk offenders, consistency of cross‐situational behaviours, and implications for policy and practice.
Experimental Heat Transfer Investigation of an Aggressive Intermediate Turbine Duct
Authors: Arroyo Osso Carlos , Gunnar Johansson T. , Wallin Fredrik
Published: May 2012

In most designs of two-spool turbofan engines, intermediate turbine ducts (ITDs) are used to connect the high-pressure turbine (HPT) with the low-pressure turbine (LPT). Demands for more efficient engines with reduced emissions require more “aggressive ducts,” ducts which provide both a higher radial offset and a larger area ratio in the shortest possible length, while maintaining low pressure losses and avoiding nonuniformities in the outlet flow that might affect the performance of the downstream LPT. The work presented in this paper is part of a more comprehensive experimental and computational study of the flowfield and the heat transfer in an aggressive ITD. The main objectives of the study were to obtain an understanding of the mechanisms governing the heat transfer in ITDs and to obtain high quality experimental data for the improvement of the CFD-based design tools. This paper presents and discusses the results of the experimental study. The duct studied was a state-of-the-art “aggressive” design with nine thick nonturning structural struts. It was tested in a large-scale low-speed experimental facility with a single-stage HPT. In this paper measurements of the steady convective heat transfer coefficient (HTC) distribution on both endwalls and on the strut for the duct design inlet conditions are presented. The heat transfer measurement technique used is based on infrared thermography. Part of the results of the flow measurements is also included.
An Investigation of Reynolds Lapse Rate for Highly Loaded Low Pressure Turbine Airfoils With Forward and Aft Loading
Authors: Eric Lyall M. , King Paul I. , Sondergaard Rolf , Clark John P. , McQuilling Mark W.
Published: May 2012

This paper presents an experimental and computational study of the midspan low Reynolds number loss behavior for two highly loaded low pressure turbine airfoils, designated L2F and L2A, which are forward and aft loaded, respectively. Both airfoils were designed with incompressible Zweifel loading coefficients of 1.59. Computational predictions are provided using two codes, Fluent (with k-kl-ω model) and AFRL’s Turbine Design and Analysis System (TDAAS), each with a different eddy-viscosity RANS based turbulence model with transition capability. Experiments were conducted in a low speed wind tunnel to provide transition models for computational comparisons. The Reynolds number range based on axial chord and inlet velocity was 20,000 < Re < 100,000 with an inlet turbulence intensity of 3.1%. Predictions using TDAAS agreed well with the measured Reynolds lapse rate. Computations using Fluent however, predicted stall to occur at significantly higher Reynolds numbers as compared to experiment. Based on triple sensor hot-film measurements, Fluent’s premature stall behavior is likely the result of the eddy-viscosity hypothesis inadequately capturing anisotropic freestream turbulence effects. Furthermore, rapid distortion theory is considered as a possible analytical tool for studying freestream turbulence that influences transition near the suction surface of LPT airfoils. Comparisons with triple sensor hot-film measurements indicate that the technique is promising but more research is required to confirm its utility.
Investigation of Pool Boiling Critical Heat Flux Enhancement on a Modified Surface Through the Dynamic Wetting of Water Droplets
Authors: Ahn Ho Seon , Kim Joonwon , Kim Moo Hwan
Published: May 2012

Dynamic wetting behaviors of water droplet on the modified surface were investigated experimentally. Dynamic contact angles were measured as a characterization method to explain the extraordinary pool boiling critical heat flux (CHF) enhancement on the zirconium surface by anodic oxidation modification. The sample surface is rectangular zirconium alloy plates (20 × 25 × 0.7 mm), and 12 μl of deionized water droplets were fallen from 40 mm of height over the surface. Dynamic wetting movement of water on the surface showed different characteristics depending on static contact angle (49.3 deg–0 deg) and surface temperature (120 °C–280 °C). Compared with bare surface, wettable and spreading surface had no-receding contact angle jump and seemed stable evaporating meniscus of liquid droplet in dynamic wetting condition on hot surface. This phenomenon could be explained by the interaction between the evaporation recoil and the surface tension forces. The surface tension force increased by micro/nanostructure of the modified zirconium surface suppresses the vapor recoil force by evaporation which makes the water layer unstable on the heated surface. Thus, such increased surface force could sustain the water layer stable in pool boiling CHF condition so that the extraordinary CHF enhancement could be possible.
Selective chemical etch of gallium nitride by phosphoric acid
Authors: Lee Chongmin , Hite Jennifer K. , Mastro Michael A. , Freitas Jaime A. , Eddy Charles R. , Kim Hong-Yeol , Kim Jihyun
Published: May 2012

The authors report on the direct comparison of the chemical etch characteristics on both Ga- and N-face gallium nitride (GaN) by phosphoric acid. First, Ga-face GaN was grown next to N-face GaN by a polarity inversion method in a metal-organic chemical vapor deposition reactor. Micro-photoluminescence, atomic force microscopy, scanning electron microscopy, and micro-Raman spectroscopy were used to analyze the etch characteristics of Ga- and N-face GaN before and after a H3PO4-based chemical etch. Ga-face was chemically stable in a phosphoric acid solution. However, the chemical etch continued proceeding on the N-face GaN due to the weak repulsive force to OH− ions. Dodecagonal nano-pyramids which dramatically enhanced the photoluminescence intensity were observed on N-face GaN after a H3PO4-based chemical etch.
Effect of surface contamination on electron tunneling in the high bias range
Authors: Qin Hailang , Goh Kuan Eng Johnson , Bosman Michel , Li Xiang , Pey Kin Leong , Troadec Cedric
Published: May 2012

The effect of surface contamination on the electron tunneling in the high bias range is investigated from the perspective of ballistic electron emission microscopy (BEEM). A comparative BEEM study on the Au/SiO2/Si devices shows that there is a significant difference in the high bias range between the experiments performed with in situ and ex situ deposited Au. Detailed studies show that the difference arises from the contaminations during air exposure. These contaminations significantly accelerated the material transfer between the tip and the sample during tunneling and lead to the unreliability of BEEM studies in the high bias range on the ex situ prepared sample.
Estimation of organ and effective dose due to Compton backscatter security scans
Authors: Hoppe Michael E. , Schmidt Taly Gilat
Published: May 2012

Purpose:

To estimate organ and effective radiation doses due to backscatter security scanners using Monte Carlo simulations and a voxelized phantom set.

Methods:

Voxelized phantoms of male and female adults and children were used with theGEANT4 toolkit to simulate a backscatter security scan. The backscatter system was modeled based on specifications available in the literature. The simulations modeled a 50 kVp spectrum with 1.0 mm‐aluminum‐equivalent filtration and a previously measured exposure of approximately 4.6 μR at 30 cm from the source. Photons and secondary interactions were tracked from the source until they reached zero kinetic energy or exited from the simulation's boundaries. The energy deposited in the phantoms' respective organs was tallied and used to calculate total organ dose and total effective dose for frontal, rear, and full scans with subjects located 30 and 75 cm from the source.

Results:

For a full screen, all phantoms' total effective doses were below the established 0.25 μSv standard, with an estimated maximum total effective dose of 0.07 μSv for full screen of a male child. The estimated maximum organ dose due to a full screen was 1.03 μGy, deposited in the adipose tissue of the male child phantom when located 30 cm from the source. All organ dose estimates had a coefficient of variation of less than 3% for a frontal scan and less than 11% for a rear scan.

Conclusions:

Backscatter security scanners deposit dose in organs beyond the skin. The effective dose is below recommended standards set by the Health Physics Society (HPS) and the American National Standards Institute (ANSI) assuming the system provides a maximum exposure of approximately 4.6 μR at 30 cm.
Learning Biology by Recreating and Extending Mathematical Models
Authors: Chiel Hillel J. , Gill Jeffrey P. , McManus Jeffrey M. , Shaw Kendrick M.
Published: May 2012

Dynamics of Biological Systems, the IBI Prize–winning module, brings mathematics into the biology laboratory.
Temperature-Dependent Alterations in Host Use Drive Rapid Range Expansion in a Butterfly
Authors: Pateman Rachel M. , Hill Jane K. , Roy David B. , Fox Richard , Thomas Chris D.
Published: May 2012

New Digs

Many studies predict range alterations among species in response to climate change. Species, however, cannot be thought of as truly independent entities, because they all exist as a part of an interacting community. Most discussions of such interactions have focused on the potential restrictions they might place on range expansion; however,

Pateman
et al.

(p.
1028
) show that climate change has the potential to increase the number of species that can interact and thus facilitate expansion. British data collected by the general public on sightings of the Brown Argus butterfly and its host plants revealed an increased affiliation between the butterflies and a previously little-used group of plants. As summers warmed, populations associated with the new host were more productive than those associated with the more “traditional” host, which facilitated expansion of the butterflies into novel regions.
Predicting Pragmatic Reasoning in Language Games
Authors: Frank Michael C. , Goodman Noah D.
Published: May 2012

Who's Who

Different languages rely on distinct sets of terminology to classify relatives, such as maternal grandfather in English, and precision in language usage is a key component for successful communication (see the Perspective by

Levinson

).
Kemp and Regier
(p.
1049
) propose an organizing framework whereby kinship classification systems can all be seen to optimize or nearly optimize both simplicity and precision. The labels applied to kin are constructed from simple units and are precise enough to reduce confusion and ambiguity when used in communication.
Frank and Goodman
(p.
998
) show that simplicity and precision also explain how listeners correctly infer the meaning of speech in the context of referential communication.
Kinship Categories Across Languages Reflect General Communicative Principles
Authors: Kemp Charles , Regier Terry
Published: May 2012

Who's Who

Different languages rely on distinct sets of terminology to classify relatives, such as maternal grandfather in English, and precision in language usage is a key component for successful communication (see the Perspective byLevinson).Kemp and Regier(p.1049) propose an organizing framework whereby kinship classification systems can all be seen to optimize or nearly optimize both simplicity and precision. The labels applied to kin are constructed from simple units and are precise enough to reduce confusion and ambiguity when used in communication.Frank and Goodman(p.998) show that simplicity and precision also explain how listeners correctly infer the meaning of speech in the context of referential communication.
FKF1 Conveys Timing Information for CONSTANS Stabilization in Photoperiodic Flowering
Authors: Song Young Hun , Smith Robert W. , To Benjamin J. , Millar Andrew J. , Imaizumi Takato
Published: May 2012

Spring Into Flower

In spring, plants respond to increasing day length and shifts in the spectrum of solar irradiance by releasing the flowering induction pathway, which includes expression of the FLOWERING LOCUS T (FT) protein.

Song
et al.

(p.
1045
) have now identified a trio of controls brought to bear on FT gene expression by the FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) protein. FKF1 removes a repressor and also stabilizes the activating CONSTANS (CO) protein in the afternoons through a binding interaction enhanced by blue light—an increasing component of solar irradiation during spring. Then FKF1 itself helps to activate transcription of the CO gene. Thus, by removing the repressor and shoring up the activator, FKF1 sets flowering on its way.
On Ruts and Getting Out of Them
The Power of Habit
Why We Do What We Do in Life and Business

by Charles Duhigg

Random House, New York, 2012. 395 pp. $28. ISBN 9781400069286.
Authors: Wood Wendy
Published: May 2012

Duhigg recounts engaging stories that illuminate how habits function and offer hope to those trying to change their behavior.
Kinship and Human Thought
Authors: Levinson Stephen C.
Published: May 2012

Language and communication are central to shaping concepts such as kinship categories.
Transit Reflections
Measuring the Universe
From the Transit of Venus to the Edge of the Cosmos

Marek Kukula and Rebekah Higgitt, curators

Royal Observatory Greenwich, London. 1 March to 2 September 2012. www.rmg.co.uk/visit/events/measuring-the-universe
Authors: Dixon Deborah
Published: May 2012

The Royal Observatory marks the upcoming transit of Venus with a small exhibition on our efforts to grasp the vast distances of the universe.
Cultivating Global Science
Authors: Suresh Subra
Published: May 2012

In our rapidly expanding global scientific research enterprise, good science anywhere is good for science everywhere, provided that there exists an open flow of information with transparent processes to promote rigorous peer review and scientific integrity. Last year on this page, I emphasized that collaboration across national boundaries requires a global ecosystem that nurtures and accelerates the pace of scientific discoveries to address the many grand challenges facing humanity.
*
The heads of major science and engineering research funding agencies from nearly 50 countries—primarily representing the G-20 and the Organisation for Economic Co-operation and Development—took the first steps toward this goal by convening at the U.S. National Science Foundation (NSF) in Virginia, for the first Global Merit Review Summit. The outcomes and momentum from the meeting, held on 14 and 15 May 2012, reflect the serious commitment of nations to ensure that science functions in a coherent and well-coordinated manner among developed and developing nations, maintains the public trust, and addresses each nation's unique needs for economic growth, national security, and human capital development.
Senate Bills Would Make Room for More STEM Graduates
Authors: Mervis Jeffrey
Published: May 2012

The U.S. Senate has waded into the debate over whether to permit more foreign-born scientists trained at U.S. universities to stay in the country.
Homegrown Organic Matter Found on Mars, But No Life
Authors: Kerr Richard A.
Published: May 2012

Researchers have discovered organic matter encased in once-molten martian rocks, demonstrating that the planet has been producing its own organic matter for eons with no help from life.
Military's Plan to Buy Biofuels Hits Roadblock in U.S. House
Authors: Service Robert F.
Published: May 2012

The U.S. House of Representatives last week blocked the Department of Defense from buying more costly substitutes for petroleum-based fuels.
NSF Gives Clinical Students a Shot At Winning Graduate Fellowships
Authors: Carpenter Siri
Published: May 2012

The U.S. National Science Foundation has restored the funding eligibility of students in graduate psychology programs, allowing a doctoral student in psychology to win a prestigious Graduate Research Fellowship.
The Burdens of Being a Biped
Authors: Pennisi Elizabeth
Published: May 2012

A number of musculoskeletal issues are rooted in our evolutionary history, in particular to the switch to walking upright more than 7 million years ago.
HDL Itself Does Not Prevent Heart Attacks
Authors: Pennisi Elizabeth
Published: May 2012

A new genetic analysis presented at the meeting shows that while high HDL might correlate with a healthier heart, it's not itself responsible for lowering heart attack risks.
Rapid Detection of Streptococcus pyogenes in Pleural Fluid Samples from Pediatric Patients with Empyema
Authors: Zheng Xiaotian , O'Leary Amanda , Uhl James R. , Patel Robin , Shulman Stanford T.
Published: May 2012

A total of 120 pleural fluid specimens from 113 pediatric patients were tested using two rapid antigen detection assays for
Streptococcus pyogenes
. Results were compared to culture, Gram stain, and PCR results. Each rapid antigen assay detected 9 out of 10 (90%) PCR-positive samples, with 100% specificity. These antigen detection assays are useful to provide microbiological diagnosis of empyema caused by
S. pyogenes
.
Simian Genogroup I Picobirnaviruses: Prevalence, Genetic Diversity, and Zoonotic Potential
Authors: Wang Yuhuan , Bányai Krisztián , Tu Xinming , Jiang Baoming
Published: May 2012

We previously reported the first detection of simian picobirnaviruses (PBVs) by polyacrylamide gel electrophoresis in fecal specimens of two monkeys with diarrhea in China. We now report the detection of genogroup I PBVs in 48% (44/92) of the fecal specimens by reverse transcriptase PCR (RT-PCR) and amplicon sequencing using primers specific for the RNA-dependent RNA polymerase (RDRP) gene. Molecular characterization of these 44 strains demonstrated both sequence conservation and diversity among simian PBVs and among simian, porcine, and human PBVs. We further determined full-length sequences of segment 2 of the two simian PBV strains, monkey/CHN-14/2002 and monkey/CHN-49/2002, and demonstrated 52.5% to 54.2% nucleotide sequence similarity to the corresponding gene of the bovine strain RUBV and the prototype human strain 1-CHN-97 of genogroup I PBVs and an even lower similarity (38.4%) to segment 2 of the prototype human genogroup II strain 4-GA-91. Further studies are needed to investigate the epidemiology and pathogenesis of PBVs in animals and humans.
Activation of Innate Immune Responses in the Central Nervous System during Reovirus Myelitis
Authors: Schittone Stephanie A. , Dionne Kalen R. , Tyler Kenneth L. , Clarke Penny
Published: May 2012

Reovirus infection of the murine spinal cord (SC) was used as a model system to investigate innate immune responses during viral myelitis, including the activation of glia (microglia and astrocytes) and interferon (IFN) signaling and increased expression of inflammatory mediators. Reovirus myelitis was associated with the pronounced activation of SC glia, as evidenced by characteristic changes in cellular morphology and increased expression of astrocyte and microglia-specific proteins. Expression of inflammatory mediators known to be released by activated glia, including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), chemokine (C-C motif) ligand 5 (CCL 5), chemokine (C-X-C motif) ligand 10 (CXCL10), and gamma interferon (IFN-γ), was also significantly upregulated in the SC of reovirus-infected animals compared to mock-infected controls. Reovirus infection of the mouse SC was also associated with increased expression of genes involved in IFN signaling, including IFN-stimulated genes (ISG). Further, reovirus infection of mice deficient in the expression of the IFN-α/β receptor (IFNAR−/−) resulted in accelerated mortality, demonstrating that IFN signaling is protective during reovirus myelitis. Experiments performed inex vivoSC slice cultures (SCSC) confirmed that resident SC cells contribute to the production of at least some of these inflammatory mediators and ISG during reovirus infection. Microglia, but not astrocytes, were still activated, and glia-associated inflammatory mediators were still produced in reovirus-infected INFAR−/−mice, demonstrating that IFN signaling is not absolutely required for these neuroinflammatory responses. Our results suggest that activated glia and inflammatory mediators contribute to a local microenvironment that is deleterious to neuronal survival.
The A33-Dependent Incorporation of B5 into Extracellular Enveloped Vaccinia Virions Is Mediated through an Interaction between Their Lumenal Domains
Authors: Chan Winnie M. , Ward Brian M.
Published: May 2012

There are two mechanisms for the incorporation of B5 into the envelope of extracellular virions produced by orthopoxviruses, one that requires A33 and one that does not. We have hypothesized that the A33-dependent mechanism requires a direct interaction between A33 and B5. In this study, chimeric constructs of A33 and B5/B5-green fluorescent protein (GFP) were used to show that the two proteins interact through their lumenal domains and that the coiled-coil domain of B5 is sufficient for an interaction with A33. Furthermore, our experiments reveal that a transmembrane domain, not necessarily its own, is requisite for the lumenal domain of B5 to interact with A33. In contrast, the lumenal domain of A33 is sufficient for interaction with B5. Furthermore, the lumenal domain of A33 is sufficient to restore the proper localization of B5-GFP in infected cells. Taken together, our results demonstrate that the lumenal domains of A33 and B5 interact and that the interaction is required for the incorporation of B5-GFP into extracellular virions, whereas the incorporation of A33 is independent of B5. These results suggest that viral protein incorporation into extracellular virions is an active process requiring specific protein-protein interactions.
Increased Interaction between Vaccinia Virus Proteins A33 and B5 Is Detrimental to Infectious Extracellular Enveloped Virion Production
Authors: Chan Winnie M. , Ward Brian M.
Published: May 2012

Two mechanisms exist for the incorporation of B5 into extracellular virions, one of which is dependent on A33. In the companion to this paper (
W. M. Chan and B. M. Ward, J. Virol. 86:8210–8220, 2012
), we show that the lumenal domain of A33 is sufficient for interaction with the coiled-coil domain of B5 and capable of directing B5-green fluorescent protein (GFP) into extracellular virions. Here, we have created a panel of charge-to-alanine mutations in the lumenal domain of A33 to map the B5 interaction site. While none of these mutations abolished the interaction with B5, a subset displayed an increased interaction with both B5 and B5-GFP. Both B5 and B5-GFP recombinant viruses expressing these mutant proteins in place of normal A33 had a small-plaque phenotype. The increased interaction of the mutant proteins was detected during infection, suggesting that normally the interaction is either weak or transient. In addition, the increased A33-B5 interaction was detected on virions produced by recombinant viruses and correlated with reduced target cell binding. Taken together, these results show that both B5 and B5-GFP interact with A33 during infection and that the duration of this interaction needs to be regulated for the production of fully infectious extracellular virions.
Subunit-Selective Mutational Analysis and Tissue Culture Evaluations of the Interactions of the E138K and M184I Mutations in HIV-1 Reverse Transcriptase
Authors: Xu Hong-Tao , Oliveira Maureen , Quashie Peter K. , McCallum Matthew , Han Yingshan , Quan Yudong , Brenner Bluma G. , Wainberg Mark A.
Published: May 2012

The emergence of HIV-1 drug resistance remains a major obstacle in antiviral therapy. M184I/V and E138K are signature mutations of clinical relevance in HIV-1 reverse transcriptase (RT) for the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (3TC) and emtricitabine (FTC) and the second-generation (new) nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV), respectively, and the E138K mutation has also been shown to be selected by etravirine in cell culture. The E138K mutation was recently shown to compensate for the low enzyme processivity and viral fitness associated with the M184I/V mutations through enhanced deoxynucleoside triphosphate (dNTP) usage, while the M184I/V mutations compensated for defects in polymerization rates associated with the E138K mutations under conditions of high dNTP concentrations. The M184I mutation was also shown to enhance resistance to RPV and ETR when present together with the E138K mutation. These mutual compensatory effects might also enhance transmission rates of viruses containing these two mutations. Therefore, we performed tissue culture studies to investigate the evolutionary dynamics of these viruses. Through experiments in which E138K-containing viruses were selected with 3TC-FTC and in which M184I/V viruses were selected with ETR, we demonstrated that ETR was able to select for the E138K mutation in viruses containing the M184I/V mutations and that the M184I/V mutations consistently emerged when E138K viruses were selected with 3TC-FTC. We also performed biochemical subunit-selective mutational analyses to investigate the impact of the E138K mutation on RT function and interactions with the M184I mutation. We now show that the E138K mutation decreased rates of polymerization, impaired RNase H activity, and conferred ETR resistance through the p51 subunit of RT, while an enhancement of dNTP usage as a result of the simultaneous presence of both mutations E138K and M184I occurred via both subunits.
Herpes Simplex Virus 2 Infection Impacts Stress Granule Accumulation
Authors: Finnen Renée L. , Pangka Kyle R. , Banfield Bruce W.
Published: May 2012

Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2α. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2α phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle.
Role of Nuclear Factor-κB in Oxidative Stress Associated with Rabies Virus Infection of Adult Rat Dorsal Root Ganglion Neurons
Authors: Kammouni Wafa , Hasan Leena , Saleh Ali , Wood Heidi , Fernyhough Paul , Jackson Alan C.
Published: May 2012

Recent studies in an experimental model of rabies showed major structural changes in the brain involving neuronal processes that are associated with severe clinical disease. Cultured adult rat dorsal root ganglion (DRG) neurons infected with the challenge virus standard-11 strain of rabies virus (CVS) showed axonal swellings and immunostaining for 4-hydroxy-2-nonenal (4-HNE), indicating evidence of lipid peroxidation associated with oxidative stress and reduced axonal growth compared to that of mock-infected DRG neurons. We have evaluated whether nuclear factor (NF)-κB might act as a critical bridge linking CVS infection and oxidative stress. On Western immunoblotting, CVS infection induced expression of the NF-κB p50 subunit compared to that of mock infection. Ciliary neurotrophic factor, a potent activator of NF-κB, had no effect on mock-infected rat DRG neurons and reduced the number of 4-HNE-labeled puncta. SN50, a peptide inhibitor of NF-κB, and CVS infection had an additive effect in producing axonal swellings, indicating that NF-κB is neuroprotective. The fluorescent signal for subunit p50 was quantitatively evaluated in the nucleus and cytoplasm of mock- and CVS-infected rat DRG neurons. At 24 h postinfection (p.i.), there was a significant increase in the nucleus/cytoplasm ratio, indicating increased transcriptional activity of NF-κB, perhaps as a response to stress. At both 48 and 72 h p.i., there was significantly reduced nuclear localization of NF-κB. CVS infection may induce oxidative stress by inhibiting nuclear activation of NF-κB. A rabies virus protein may directly inhibit NF-κB activity. Further investigations are needed to gain a better understanding of the basic mechanisms involved in the oxidative damage associated with rabies virus infection.
Switching on RNA Silencing Suppressor Activity by Restoring Argonaute Binding to a Viral Protein
Authors: Szabó Edit Z. , Manczinger Máté , Göblös Anikó , Kemény Lajos , Lakatos Lóránt
Published: May 2012

We found that
Sweet potato feathery mottle virus
(SPFMV) P1, a close homologue of
Sweet potato mild mottle virus
P1, did not have any silencing suppressor activity. Remodeling the Argonaute (AGO) binding domain of SPFMV P1 by the introduction of two additional WG/GW motifs converted it to a silencing suppressor with AGO binding capacity. To our knowledge, this is the first instance of the transformation of a viral protein of unknown function to a functional silencing suppressor.
A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies
Authors: Doria-Rose Nicole A. , Georgiev Ivelin , O'Dell Sijy , Chuang Gwo-Yu , Staupe Ryan P. , McLellan Jason S. , Gorman Jason , Pancera Marie , Bonsignori Mattia , Haynes Barton F. , Burton Dennis R. , Koff Wayne C. , Kwong Peter D. , Mascola John R.
Published: May 2012

Antibody PG9 is a prototypical member of a class of V1/V2-directed antibodies that effectively neutralizes diverse strains of HIV-1. We analyzed strain-specific resistance to PG9 using sequence and structural information. For multiply resistant strains, mutations in a short segment of V1/V2 resulted in gain of sensitivity to PG9 and related V1/V2 neutralizing antibodies, suggesting both a common mechanism of HIV-1 resistance to and a common mode of recognition by this class of antibodies.
Genome Sequence of a Reassortant Strain of Bluetongue Virus Serotype 23 from Western India
Authors: Maan Sushila , Maan Narender S. , Guimera Marc , Nomikou Kyriaki , Singh Karam Pal , Pullinger Gillian , Belaganahalli Manjunatha N. , Mertens Peter P. C.
Published: May 2012

The full genome sequence (19,177 bp) of an Indian strain (IND1988/02) of bluetongue virus (BTV) serotype 23 was determined. This virus was isolated from a sheep that had been killed during a severe bluetongue outbreak that occurred in Rahuri, Maharashtra State, western India, in 1988. Phylogenetic analyses of these data demonstrate that most of the genome segments from IND1988/02 belong to the major “eastern” BTV topotype. However, genome segment 5 belongs to the major “western” BTV topotype, demonstrating that IND1988/02 is a reassortant. This may help to explain the increased virulence that was seen during this outbreak in 1988. Genome segment 5 of IND1988/02 shows >99% sequence identity with some other BTV isolates from India (e.g., BTV-3 IND2003/08), providing further evidence of the existence and circulation of reassortant strains on the subcontinent.
New PARP Gene with an Anti-Alphavirus Function
Authors: Atasheva Svetlana , Akhrymuk Maryna , Frolova Elena I. , Frolov Ilya
Published: May 2012

Alphaviruses represent a highly important group of human and animal pathogens, which are transmitted by mosquito vectors between vertebrate hosts. The hallmark of alphavirus infection in vertebrates is the induction of a high-titer viremia, which is strongly dependent on the ability of the virus to interfere with host antiviral responses on both cellular and organismal levels. The identification of cellular factors, which are critical in orchestrating virus clearance without the development of cytopathic effect, may prove crucial in the design of new and highly effective antiviral treatments. To address this issue, we have developed a noncytopathic Venezuelan equine encephalitis virus (VEEV) mutant that can persistently replicate in cells defective in type I interferon (IFN) production or signaling but is cleared from IFN signaling-competent cells. Using this mutant, we analyzed (i) the spectrum of cellular genes activated by virus replication in the persistently infected cells and (ii) the spectrum of genes activated during noncytopathic virus clearance. By applying microarray-based technology and bioinformatic analysis, we identified a number of IFN-stimulated genes (ISGs) specifically activated during VEEV clearance. One of these gene products, the long isoform of PARP12 (PARP12L), demonstrated an inhibitory effect on the replication of VEEV, as well as other alphaviruses and several different types of other RNA viruses. Additionally, overexpression of two other members of the PARP gene superfamily was also shown to be capable of inhibiting VEEV replication.
An Epstein-Barr Virus (EBV) Mutant with Enhanced BZLF1 Expression Causes Lymphomas with Abortive Lytic EBV Infection in a Humanized Mouse Model
Authors: Ma Shi-Dong , Yu Xianming , Mertz Janet E. , Gumperz Jenny E. , Reinheim Erik , Zhou Ying , Tang Weihua , Burlingham William J. , Gulley Margaret L. , Kenney Shannon C.
Published: May 2012

Immunosuppressed patients are at risk for developing Epstein-Barr Virus (EBV)-positive lymphomas that express the major EBV oncoprotein, LMP1. Although increasing evidence suggests that a small number of lytically infected cells may promote EBV-positive lymphomas, the impact of enhanced lytic gene expression on the ability of EBV to induce lymphomas is unclear. Here we have used immune-deficient mice, engrafted with human fetal hematopoietic stem cells and thymus and liver tissue, to compare lymphoma formation following infection with wild-type (WT) EBV versus infection with a “superlytic” (SL) mutant with enhanced BZLF1 (Z) expression. The same proportions (2/6) of the WT and SL virus-infected animals developed B-cell lymphomas by day 60 postinfection; the remainder of the animals had persistent tumor-free viral latency. In contrast, all WT and SL virus-infected animals treated with the OKT3 anti-CD3 antibody (which inhibits T-cell function) developed lymphomas by day 29. Lymphomas in OKT3-treated animals (in contrast to lymphomas in the untreated animals) contained many LMP1-expressing cells. The SL virus-infected lymphomas in both OKT3-treated and untreated animals contained many more Z-expressing cells (up to 30%) than the WT virus-infected lymphomas, but did not express late viral proteins and thus had an abortive lytic form of EBV infection. LMP1 and BMRF1 (an early lytic viral protein) were never coexpressed in the same cell, suggesting that LMP1 expression is incompatible with lytic viral reactivation. These results show that the SL mutant induces an “abortive” lytic infection in humanized mice that is compatible with continued cell growth and at least partially resistant to T-cell killing.
Progressive Loss of Memory T Cell Potential and Commitment to Exhaustion during Chronic Viral Infection
Authors: Angelosanto Jill M. , Blackburn Shawn D. , Crawford Alison , Wherry E. John
Published: May 2012

T cell exhaustion and loss of memory potential occur during many chronic viral infections and cancer. We investigated when during chronic viral infection virus-specific CD8 T cells lose the potential to form memory. Virus-specific CD8 T cells from established chronic infection were unable to become memory CD8 T cells if removed from infection. However, at earlier stages of chronic infection, these virus-specific CD8 T cells retained the potential to partially or fully revert to a memory differentiation program after transfer to infection-free mice. Conversely, effector CD8 T cells primed during acute infection were not protected from exhaustion if transferred to a chronic infection. We also tested whether memory and exhausted CD8 T cells arose from different subpopulations of effector CD8 T cells and found that only the KLRG1
lo
memory precursor subset gave rise to exhausted CD8 T cells. Together, these studies demonstrate that CD8 T cell exhaustion is a progressive developmental process. Early during chronic infection, the fate of virus-specific CD8 T cells remains plastic, while later, exhausted CD8 T cells become fixed in their differentiation state. Moreover, exhausted CD8 T cells arise from the memory precursor and not the terminally differentiated subset of effector CD8 T cells. These studies have implications for our understanding of senescence versus exhaustion and for therapeutic interventions during chronic infection.