bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of High Current Cycling on the Performance of SOFC Single Cells
Authors: Heneka Markus J. , Ivers-Tiffée Ellen
Published: December 2011

In this contribution, the performance of solid oxide fuel cells (SOFC) under high current density load cycles is studied by means of electrical measurements and material analyses. Our study is an important premise for the application of accelerated life testing (ALT) to SOFC single cells. In reliability engineering ALT is a well known method for rapid lifetime evaluation [Nelson, W., Accelerated Life Testing, 1990, John Wiley, New York]. Furthermore, our results are of particular interest for the (La,Sr)MnO3-zirconia system. We find that during current treatment, a nanoporous domain containing lanthanum zirconate is formed at the cathode-electrolyte interface. The nanoporosity leads to an enhanced cathode performance while the formation of lanthanum zirconate degrades the mechanical stability of the interface.
An Investigation On Deformation-Based Surface Texturing
Authors: Zhou Rui , Cao Jian , Ehmann Kornel , Xu Chun
Published: December 2011

Surface textures have various applications, such as friction/wear reduction and light absorbing enhancement. Deformation-based surface texturing has the potential of economically creating micro-scale surface textures over a large surface area. A novel desktop surface texturing system is proposed for efficiently and economically fabricating microchannels on the surface of thin sheet material for microfluid and friction/wear reduction applications. Both the experimental and numerical studies were employed to analyze the problems of the flatness of the textured sheet, the uniform of the channel depth and pile-ups built up during the surface texturing process. The results demonstrated a clear relationship between relative velocity of the upper and lower rolls and the flatness of the textured sheet and the final profile of the microchannels.
Role of surface intermediates in enhanced, uniform growth rates of TiO2 atomic layer deposition thin films using titanium tetraisopropoxide and ozone
Authors: Cleveland Erin R. , Henn-Lecordier Laurent , Rubloff Gary W.
Published: December 2011

Atomic layer deposition (ALD) growth of TiO2 thin films from titanium tetraisopropoxide (TTIP) and ozone has been studied as a function of dose and purge recipes. A novel dosing scheme was designed to introduce the TTIP precursor into the reaction chamber in multiple “μpulses” with orwithout delay times for desorption of surface product species, analogous to conventional ALDpurge cycles. Larger doses led to significantly higher growth rates while maintaining excellent uniformity across 100 mm wafers, effects which underscore the importance of surface residence times in rather complex surface reaction pathways. The production of H2O/OH surface species during the TTIP half-cycle is intrinsic to the reaction, leading to secondary reaction mechanisms and believed responsible for the enhanced growth rates and accompanying high uniformity.
Extraction of a low-current discharge from a microplasma for nanoscale patterning applications at atmospheric pressure
Authors: Lee Seung Whan , Zamani Hamidreza , Feng Philip X.-L. , Mohan Sankaran R.
Published: December 2011

The authors present a scheme to extract a low-current discharge from a microplasma at atmospheric pressure for nanopatterning applications. The extracted discharge is generated by applying a high positive voltage to an independent electrode and accelerating electrons from the microplasma. Current-voltage (I–V) characteristics of the extracted discharge show high stability at low currents and tunability over a wide range of currents. Exposure of metal precursor loaded films to the extracted discharge results in electrochemical reduction of metal ions to solid metal, as confirmed by X-ray photoelectron spectroscopy. Combining this approach with masking techniques allows the transfer of nanoscale patterns of metal at ambient conditions.
Detecting Novel Associations in Large Data Sets
Authors: Reshef David N. , Reshef Yakir A. , Finucane Hilary K. , Grossman Sharon R. , McVean Gilean , Turnbaugh Peter J. , Lander Eric S. , Mitzenmacher Michael , Sabeti Pardis C.
Published: December 2011

A statistical method reveals relationships among variables in complex data sets.
Uninformed Individuals Promote Democratic Consensus in Animal Groups
Authors: Couzin Iain D. , Ioannou Christos C. , Demirel Güven , Gross Thilo , Torney Colin J. , Hartnett Andrew , Conradt Larissa , Levin Simon A. , Leonard Naomi E.
Published: December 2011

Uninformed individuals inhibit extremism and enforce fair representation during collective decision-making.
The Tricarboxylic Acid Cycle in Cyanobacteria
Authors: Zhang Shuyi , Bryant Donald A.
Published: December 2011

Contrary to expectations, many photosynthetic cyanobacteria maintain a metabolic flexibility that works in the dark.
A Coherent Signature of Anthropogenic Nitrogen Deposition to Remote Watersheds of the Northern Hemisphere
Authors: Holtgrieve Gordon W. , Schindler Daniel E. , Hobbs William O. , Leavitt Peter R. , Ward Eric J. , Bunting Lynda , Chen Guangjie , Finney Bruce P. , Gregory-Eaves Irene , Holmgren Sofia , Lisac Mark J. , Lisi Peter J. , Nydick Koren , Rogers Lauren A. , Saros Jasmine E. , Selbie Daniel T. , Shapley Mark D. , Walsh Patrick B. , Wolfe Alexander P.
Published: December 2011

Deposition of reactive nitrogen from human activities occurred in the preindustrial era.
Recombinant Innovation
Genentech
The Beginnings of Biotech

by Sally Smith Hughes

University of Chicago Press, Chicago, 2011. 229 pp. $25, £16. ISBN 9780226359182. Synthesis.
Authors: Barnett Gerald
Published: December 2011

Drawing from oral histories, Hughes describes the origins, growth, and fall of the biotech pioneer Genentech.
A Correlation for the 21st Century
Authors: Speed Terry
Published: December 2011

A novel statistical approach has been developed that can uncover nonlinear associations in large data sets.
Search for Higgs Boson Yields a Definite Maybe
Authors: Cho Adrian
Published: December 2011

This week, two teams of physicists reported tantalizing signs that the Higgs boson has been spotted. But one team sees additional oddities, so the results haven't bowled everyone over.
U.K. to Open Health Records as E.U. Considers Restrictions
Authors: Vogel Gretchen
Published: December 2011

A new British proposal to make health data more available to scientists may run smack into the European Union, which is exploring revisions to its data-protection guidelines.
Suresh Expects Low-Cost Ideas Will Mean a Big Payoff for NSF
Authors: Mervis Jeffrey
Published: December 2011

The director of the National Science Foundation has hit the ground running with a flurry of new programs aimed at leveraging precious federal dollars.
Extended Safety and Efficacy Studies of the Attenuated Brucella Vaccine Candidates 16MΔvjbRand S19ΔvjbRin the Immunocompromised IRF-1−/−Mouse Model
Authors: Arenas-Gamboa A. M. , Rice-Ficht A. C. , Fan Y. , Kahl-McDonagh M. M. , Ficht T. A.
Published: December 2011

The global distribution of brucellosis and high incidence in certain areas of the world warrant the development of a safer and efficacious vaccine. For the past 10 years, we have focused our attention on the development of a safer, but still highly protective, live attenuated vaccine for human and animal use. We have demonstrated the safety and protective efficacy of the vaccine candidates 16MΔvjbRand S19ΔvjbRagainst homologous and heterologous challenge in multiple immunocompetent animal models, including mice and deer. In the present study, we conducted a series of experiments to determine the safety of the vaccine candidates in interferon regulatory factor-1-knockout (IRF-1−/−) mice. IRF-1−/−mice infected with either wild-typeBrucella melitensis16M or the vaccine strainBrucella abortusS19 succumb to the disease within the first 3 weeks of infection, which is characterized by a marked granulomatous and neutrophilic inflammatory response that principally targets the spleen and liver. In contrast, IRF-1−/−mice inoculated with either the 16MΔvjbRor S19ΔvjbRvaccine do not show any clinical or major pathological changes associated with vaccination. Additionally, when 16MΔvjbR- or S19ΔvjbR-vaccinated mice are challenged with wild-typeBrucella melitensis16M, the degree of colonization in multiple organs, along with associated pathological changes, is significantly reduced. These findings not only demonstrate the safety and protective efficacy of thevjbRmutant in an immunocompromised mouse model but also suggest the participation of lesser-known mechanisms in protective immunity against brucellosis.
Age-Dependent IgG Subclass Responses to Plasmodium falciparum EBA-175 Are Differentially Associated with Incidence of Malaria in Mozambican Children
Authors: Dobaño Carlota , Quelhas Diana , Quintó Llorenç , Puyol Laura , Serra-Casas Elisa , Mayor Alfredo , Nhampossa Tacilta , Macete Eusebio , Aide Pedro , Mandomando Inacio , Sanz Sergi , Puniya Sanjeev K. , Singh Bijender , Gupta Puneet , Bhattacharya Arindam , Chauhan Virander S. , Aponte John J. , Chitnis Chetan E. , Alonso Pedro L. , Menéndez Clara
Published: December 2011

Plasmodium falciparum
blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to
Plasmodium falciparum
blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age. We found that IgG subclass responses to EBA-175 were differentially associated with the incidence of malaria in the follow-up period. A double amount of cytophilic IgG1 or IgG3 was associated with a significant decrease in the incidence of malaria (incidence rate ratio [IRR] = 0.49, 95% confidence interval [CI] = 0.25 to 0.97, and
P
= 0.026 and IRR = 0.44, CI = 0.19 to 0.98, and
P
= 0.037, respectively), while a double amount of noncytophilic IgG4 was significantly correlated with an increased incidence of malaria (IRR = 3.07, CI = 1.08 to 8.78,
P
= 0.020). No significant associations between antibodies to the 19-kDa fragment of MSP-1 (MSP-1
19
) or AMA-1 and incidence of malaria were found. Age, previous episodes of malaria, present infection, and neighborhood of residence were the main factors influencing levels of antibodies to all merozoite antigens. Deeper understanding of the acquisition of antibodies against vaccine target antigens in early infancy is crucial for the rational development and deployment of malaria control tools in this vulnerable population.
Comparative Evaluation of Profiles of Antibodies to Mycobacterial Capsular Polysaccharides in Tuberculosis Patients and Controls Stratified by HIV Status
Authors: Yu Xian , Prados-Rosales Rafael , Jenny-Avital Elisabeth R. , Sosa Katherine , Casadevall Arturo , Achkar Jacqueline M.
Published: December 2011

Despite the complexity of tuberculosis (TB) serology, antibodies (Abs) remain attractive biomarkers for TB. Recent evidence of a mycobacterial capsule that consists mainly of the polysaccharides arabinomannan (AM) and glucan provides new options for serologic targets. For this study, Ab responses to AM and glucan for 47 U.S. TB patients (33 HIV negative [HIV
−
], 14 HIV positive [HIV
+
]), 42 healthy controls, and 38 asymptomatic HIV
+
controls were evaluated by enzyme-linked immunosorbent assays (ELISAs). The results were compared with Ab responses to the mycobacterial glycolipid cell wall antigen lipoarabinomannan (LAM) and to the proteins malate synthase (MS) and MPT51. We found that the main immunoglobulin (Ig) isotype response to polysaccharides was IgG, predominantly of subclass IgG2. IgG responses to AM were significantly higher for HIV
−
and HIV
+
TB cases than for controls (
P
, <0.0001 and <0.01, respectively); significantly higher for HIV
−
than for HIV
+
TB cases (
P
, <0.01); and significantly higher in sputum smear-positive than smear-negative patients in both HIV
−
and HIV
+
cases (
P
, 0.01 and 0.02, respectively). In both TB groups, titers of Ab to glucan were significantly lower than titers of Ab to AM (
P
, <0.0001). IgG responses to AM and MS or to AM and MPT51 did not correlate with each other in HIV
−
TB patients, while they correlated significantly in HIV
+
TB patients (
P
, 0.01 and 0.05, respectively). We conclude that Ab responses to AM could contribute to the serodiagnosis of TB, especially for HIV
−
TB patients. This study also provides new and important insights into the differences in the profiles of Abs to mycobacterial antigens between HIV
−
and HIV
+
TB patients.
First Worldwide Proficiency Study on Variable-Number Tandem-Repeat Typing of Mycobacterium tuberculosis Complex Strains
Authors: de Beer Jessica L. , Kremer Kristin , Ködmön Csaba , Supply Philip , van Soolingen Dick ,   the Global Network for the Molecular Surveillance of Tuberculosis 2009
Published: December 2011

Although variable-number tandem-repeat (VNTR) typing has gained recognition as the new standard for the DNA fingerprinting of
Mycobacterium tuberculosis
complex (MTBC) isolates, external quality control programs have not yet been developed. Therefore, we organized the first multicenter proficiency study on 24-locus VNTR typing. Sets of 30 DNAs of MTBC strains, including 10 duplicate DNA samples, were distributed among 37 participating laboratories in 30 different countries worldwide. Twenty-four laboratories used an in-house-adapted method with fragment sizing by gel electrophoresis or an automated DNA analyzer, nine laboratories used a commercially available kit, and four laboratories used other methods. The intra- and interlaboratory reproducibilities of VNTR typing varied from 0% to 100%, with averages of 72% and 60%, respectively. Twenty of the 37 laboratories failed to amplify particular VNTR loci; if these missing results were ignored, the number of laboratories with 100% interlaboratory reproducibility increased from 1 to 5. The average interlaboratory reproducibility of VNTR typing using a commercial kit was better (88%) than that of in-house-adapted methods using a DNA analyzer (70%) or gel electrophoresis (50%). Eleven laboratories using in-house-adapted manual typing or automated typing scored inter- and intralaboratory reproducibilities of 80% or higher, which suggests that these approaches can be used in a reliable way. In conclusion, this first multicenter study has documented the worldwide quality of VNTR typing of MTBC strains and highlights the importance of international quality control to improve genotyping in the future.
PCR Identification of Bacteria in Blood Culture Does Not Fit the Daily Workflow of a Routine Microbiology Laboratory
Authors: Karumaa Santra , Kärpänoja Pauliina , Sarkkinen Hannu
Published: December 2011

We have evaluated the GenoType blood culture assay (Hain Lifescience, Nehren, Germany) for the identification of bacteria in 233 positive blood cultures and assessed its suitability in the workflow of a routine microbiology laboratory. In 68/233 (29.2%) samples, the culture result could not be confirmed by the GenoType assay due to a lack of primers in the test, multiple organisms in the sample, or inconsistency with respect to the identification by culture. Although the GenoType blood culture assay gives satisfactory results for bacteria for which primers are available, there are difficulties in applying the test in the routine microbiology laboratory.
Metastatic Complications from Staphylococcus intermedius, a Zoonotic Pathogen
Authors: Hatch Steven , Sree Aruna , Tirrell Sandra , Torres Brenda , Rothman Alan L.
Published: December 2011

Metastatic infection is an infrequent complication of non-
Staphylococcus aureus
staphylococcal infection. Here we report a case of bloodstream infection due to
Staphylococcus intermedius
. To our knowledge, ours is the only known case of metastatic infection with
S. intermedius
.
Virological Diagnosis of Herpes Simplex Virus 1 Esophagitis by Quantitative Real-Time PCR Assay
Authors: Jazeron Jean-François , Barbe Coralie , Frobert Emilie , Renois Fanny , Talmud Déborah , Brixi-Benmansour Hedia , Brodard Véronique , Andréoletti Laurent , Diebold Marie-Danièle , Lévêque Nicolas
Published: December 2011

Herpes simplex virus 1 (HSV-1) esophagitis diagnosis is routinely based on the endoscopic findings confirmed by histopathological examination of the esophagitis lesions. Virological diagnosis is not systematically performed and restricted to viral culture or to qualitative PCR assay from esophagitis biopsy specimens. The aim of this study was to assess the interest of quantitative real-time PCR assay in HSV-1 esophagitis diagnosis by comparing the results obtained to those of histological examination associated with immunohistochemical staining, which is considered the “gold standard.” From 53 esophagitis biopsy specimens, the PCR assay detected HSV-1 in 18 of 19 histologically proven to have herpetic esophagitis and in 9 of 34 that had esophagitis related to other causes, demonstrating sensitivity, specificity, positive predictive value, and negative predictive value of 94.7%, 73%, 66.7%, and 96%, respectively. Interestingly, HSV-1 was not detected in 16 specimens without the histological aspect of esophagitis. The viral loads normalized per μg of total extracted DNA in each biopsy specimen detected positive by HSV PCR were then compared and appeared to be significantly higher in histopathologically positive herpetic esophagitis (median = 2.9 × 10
6
± 1.1 × 10
8
) than in histopathologically negative herpetic esophagitis (median = 3.1 × 10
3
± 6.2 × 10
3
) (
P
= 0.0009). Moreover, a receiver operating characteristics analysis revealed that a viral load threshold greater than 2.5 × 10
4
copies would allow an HSV-1 esophagitis diagnosis with a sensitivity and specificity of 83.3% and 100%, respectively. In conclusion, this work demonstrated that HSV quantitative PCR results for paraffin-embedded esophageal tissue was well correlated to histopathological findings for an HSV-1 esophagitis diagnosis and could be diagnostic through viral load assessment when histopathological results are missing or uncertain.
Population Structure of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis Strains in South Africa
Authors: Chihota Violet N. , Müller Borna , Mlambo Charmaine K. , Pillay Manormoney , Tait Marisa , Streicher Elizabeth M. , Marais Else , van der Spuy Gian D. , Hanekom Madeleine , Coetzee Gerrit , Trollip Andre , Hayes Cindy , Bosman Marlein E. , Gey van Pittius Nico C. , Victor Tommie C. , van Helden Paul D. , Warren Robin M.
Published: December 2011

Genotyping of multidrug-resistant (MDR)
Mycobacterium tuberculosis
strains isolated from tuberculosis (TB) patients in four South African provinces (Western Cape, Eastern Cape, KwaZulu-Natal, and Gauteng) revealed a distinct population structure of the MDR strains in all four regions, despite the evidence of substantial human migration between these settings. In all analyzed provinces, a negative correlation between strain diversity and an increasing level of drug resistance (from MDR-TB to extensively drug-resistant TB [XDR-TB]) was observed. Strains predominating in XDR-TB in the Western and Eastern Cape and KwaZulu-Natal Provinces were strongly associated with harboring an
inhA
promoter mutation, potentially suggesting a role of these mutations in XDR-TB development in South Africa. Approximately 50% of XDR-TB cases detected in the Western Cape were due to strains probably originating from the Eastern Cape. This situation may illustrate how failure of efficient health care delivery in one setting can burden health clinics in other areas.
Engineered Combined-Positive-Control Template for Real-Time Reverse Transcription-PCR in Multiple-Pathogen-Detection Assays
Authors: Kodani Maja , Winchell Jonas M.
Published: December 2011

Recently we evaluated a custom TaqMan array card (TAC) detection system, formerly known as a TaqMan low-density array (TLDA) card, for simultaneous real-time PCR identification of 21 pathogens and three control targets in duplicate from respiratory specimens (M. Kodani et al., J. Clin. Microbiol. 49:2175–2182, 2011). We engineered an adaptable and expandable system of
in vitro
RNA transcripts to serve as a combined positive control for both DNA and RNA targets in multiple-pathogen-detection technologies based on real-time reverse transcription-PCR.
HPV 9G DNA Chip: 100% Clinical Sensitivity and Specificity
Authors: An Heejung , Song Keum-Soo , Nimse Satish Balasaheb , Kim Junghoon , Nguyen Van-Thuan , Ta Van-Thao , Sayyed Danishmalik Rafiq , Kim Taisun
Published: December 2011

We describe a novel HPV 9G DNA chip test for the accurate and reliable genotyping of human papillomavirus (HPV). The HPV 9G DNA chip test established its efficiency in terms of a signal-to-background ratio (SBR) of 200, which is 50 times superior to commercial HPV DNA chips, and 100% target-specific hybridization at 25°C. We compared the genotyping results for the 439 clinical samples by the HPV 9G DNA chip test with the sequencing results for the MY11/GP6+ (M2) primer set-mediated PCR products. The discrimination of HPV genotypes in the 151 HPV-positive clinical samples by the HPV 9G DNA chip test were 100% identical with the sequencing analysis. The clinical sensitivities of HPV genotyping by the HPV 9G DNA chip test and a commercial HPV DNA chip test were 100% and 88%, respectively. However, the clinical specificities of HPV genotyping by the HPV 9G DNA chip test and the commercial HPV DNA chip test were 100% and 94%, respectively. The 100% clinical sensitivity and specificity of the HPV 9G DNA chip test make it a promising diagnostic tool for HPV genotyping.
Serum Galactomannan and (1→3)-β-d-Glucan Assays for Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia
Authors: Issa Nicolas C. , Koo Sophia , Lynch Robert C. , Gay Charline , Hammond Sarah P. , Baden Lindsey R. , Ghobrial Irene M. , Finkelman Malcolm A. , Marty Francisco M.
Published: December 2011

We assessed the performance of galactomannan and (1→3)-β-d-glucan in 29 serum samples from patients with multiple myeloma and Waldenstrom's macroglobulinemia without invasive fungal disease to address issues of false positivity and uninterpretable results previously reported among patients with these conditions. Galactomannan and (1→3)-β-d-glucan assays were not falsely elevated in any patient. (1→3)-β-d-glucan assay results were uninterpretable in 24% of patients. Patients with IgG levels of >2,000 mg/dl had higher odds of uninterpretable (1→3)-β-d-glucan results.
Role of Specific Innate Immune Responses in Herpes Simplex Virus Infection of the Central Nervous System
Authors: Wang Jennifer P. , Bowen Glennice N. , Zhou Shenghua , Cerny Anna , Zacharia An , Knipe David M. , Finberg Robert W. , Kurt-Jones Evelyn A.
Published: December 2011

Herpes simplex virus 1 (HSV-1) causes a spectrum of disease, including herpes labialis, herpes keratitis, and herpes encephalitis, which can be lethal. Viral recognition by pattern recognition receptors plays a central role in cytokine production and in the generation of antiviral immunity. The relative contributions of different Toll-like receptors (TLRs) in the innate immune response during central nervous system infection with HSV-1 have not been fully characterized. In this study, we investigate the roles of TLR2, TLR9, UNC93B1, and the type I interferon (IFN) receptor in a murine model of HSV-1 encephalitis. TLR2 is responsible for detrimental inflammatory cytokine production following intracranial infection with HSV-1, and the absence of TLR2 expression leads to increased survival in mice. We prove that inflammatory cytokine production by microglial cells, astrocytes, neutrophils, and monocytes is mediated predominantly by TLR2. We also demonstrate that type I IFNs are absolutely required for survival following intracranial HSV-1 infection, as mice lacking the type I IFN receptor succumb rapidly following infection and have high levels of HSV in the brain. However, the absence of TLR9 does not impact survival, type I IFN levels, or viral replication in the brain following infection. The absence of UNC93B1 leads to a survival disadvantage but does not impact viral replication or type I IFN levels in the brain in HSV-1-infected mice. These results illustrate the complex but important roles that innate immune receptors play in host responses to HSV-1 during infection of the central nervous system.
Identification of RNA Helicase A as a Cellular Factor That Interacts with Influenza A Virus NS1 Protein and Its Role in the Virus Life Cycle
Authors: Lin Li , Li Yang , Pyo Hyun-Mi , Lu Xinya , Raman Sathya N. Thulasi , Liu Qiang , Brown Earl G. , Zhou Yan
Published: December 2011

Influenza A virus NS1 protein has multiple functions in the infected cell during the virus life cycle. Identification of novel cellular factors that interact with NS1 and understanding their functions in virus infection are of great interest. Recombinant viruses carrying a tagged NS1 are valuable for investigation of interactions between NS1 and cellular factors in the context of virus infection. Here, we report the generation of replication-competent recombinant influenza A viruses bearing a Strep tag in the NS1 protein. Purification of a protein complex associated with Strep-tagged NS1 from virus-infected cells followed by mass spectrometry revealed a number of attractive host factors. Among them, we focused our study on RNA helicase A (RHA) in this report. Through biomedical and functional analyses, we demonstrated that RHA interacts with NS1 in an RNA-dependent manner. Knockdown of RHA resulted in a significant reduction on virus yield and polymerase activity in a minigenome assay. Our cell-free viral genome replication assay showed that viral RNA replication and transcription can be enhanced by addition of RHA, and the enhanced effect of RHA required its ATP-dependent helicase activity. In summary, we established a system to identify cellular factors that interact with NS1 protein during virus infection and furthermore demonstrated that RHA interacts with NS1 and enhances viral replication and transcription.
Naturally Occurring Antibodies That Recognize Linear Epitopes in the Amino Terminus of the Hepatitis C Virus E2 Protein Confer Noninterfering, Additive Neutralization
Authors: Tarr Alexander W. , Urbanowicz Richard A. , Jayaraj Dhanya , Brown Richard J. P. , McKeating Jane A. , Irving William L. , Ball Jonathan K.
Published: December 2011

Chronic hepatitis C virus (HCV) infection can persist even in the presence of a broadly neutralizing antibody response. Various mechanisms that underpin viral persistence have been proposed, and one of the most recently proposed mechanisms is the presence of interfering antibodies that negate neutralizing responses. Specifically, it has been proposed that antibodies targeting broadly neutralizing epitopes located within a region of E2 encompassing residues 412 to 423 can be inhibited by nonneutralizing antibodies binding to a less conserved region encompassing residues 434 to 446. To investigate this phenomenon, we characterized the neutralizing and inhibitory effects of human-derived affinity-purified immunoglobulin fractions and murine monoclonal antibodies and show that antibodies to both regions neutralize HCV pseudoparticle (HCVpp) and cell culture-infectious virus (HCVcc) infection albeit with different breadths and potencies. Epitope mapping revealed the presence of overlapping but distinct epitopes in both regions, which may explain the observed differences in neutralizing phenotypes. Crucially, we failed to demonstrate any inhibition between these two groups of antibodies, suggesting that interference by nonneutralizing antibodies, at least for the region encompassing residues 434 to 446, does not provide a mechanism for HCV persistence in chronically infected individuals.
The Paramyxovirus Fusion Protein C-Terminal Region: Mutagenesis Indicates an Indivisible Protein Unit
Authors: Zokarkar Aarohi , Lamb Robert A.
Published: December 2011

Paramyxoviruses enter host cells by fusing the viral envelope with a host cell membrane. Fusion is mediated by the viral fusion (F) protein, and it undergoes large irreversible conformational changes to cause membrane merger. The C terminus of PIV5 F contains a membrane-proximal 7-residue external region (MPER), followed by the transmembrane (TM) domain and a 20-residue cytoplasmic tail. To study the sequence requirements of the F protein C terminus for fusion, we constructed chimeras containing the ectodomain of parainfluenza virus 5 F (PIV5 F) and either the MPER, the TM domain, or the cytoplasmic tail of the F proteins of the paramyxoviruses measles virus, mumps virus, Newcastle disease virus, human parainfluenza virus 3, and Nipah virus. The chimeras were expressed, and their ability to cause cell fusion was analyzed. The chimeric proteins were variably expressed at the cell surface. We found that chimeras containing the ectodomain of PIV5 F with the C terminus of other paramyxoviruses were unable to cause cell fusion. Fusion could be restored by decreasing the activation energy of refolding through introduction of a destabilizing mutation (S443P). Replacing individual regions, singly or doubly, in the chimeras with native PIV5 F sequences restored fusion to various degrees, but it did not have an additive effect in restoring activity. Thus, the F protein C terminus may be a specific structure that only functions with its cognate ectodomain. Alanine scanning mutagenesis of MPER indicates that it has a regulatory role in fusion since both hyperfusogenic and hypofusogenic mutations were found.
Glycoproteins D of Equine Herpesvirus Type 1 (EHV-1) and EHV-4 Determine Cellular Tropism Independently of Integrins
Authors: Azab Walid , Osterrieder Nikolaus
Published: December 2011

Equine herpesvirus type 1 (EHV-1) and EHV-4 are genetically and antigenically very similar, but their pathogenic potentials are strikingly different. The differences in pathogenicity between both viruses seem to be reflected in cellular host range: EHV-1 can readily be propagated in many cell types of multiple species, while EHV-4 entry and replication appear to be restricted mainly to equine cells. The clear difference in cellular tropism may well be associated with differences in the gene products involved in virus entry and/or spread from cell to cell. Here we show that (i) most of the EHV-1 permissive cell lines became resistant to EHV-1 expressing EHV-4 glycoprotein D (gD4) and the opposite was observed for EHV-4 harboring EHV-1 gD (gD1). (ii) The absence of integrins did not inhibit entry into and replication of EHV-1 in CHO-K1 or peripheral blood mononuclear cells (PBMC). Furthermore, integrin-negative K562 cells did not acquire the ability to bind to gD1 when αVβ3 integrin was overexpressed. (iii) PBMC could be infected with similar efficiencies by both EHV-1 and EHV-4
in vitro
. (iv) In contrast to results for equine fibroblasts and cells of endothelial or epithelial origin, we were unable to block entry of EHV-1 or EHV-4 into PBMC with antibodies directed against major histocompatibility complex class I (MHC-I), a result that indicates that these viruses utilize a different receptor(s) to infect PBMC. Cumulatively, we provide evidence that efficient EHV-1 and EHV-4 entry is dependent mainly on gD, which can bind to multiple cell surface receptors, and that gD has a defining role with respect to cellular host range of EHV-1 and EHV-4.
Hepatitis C Virus Proteins Inhibit C3 Complement Production
Authors: Mazumdar Budhaditya , Kim Hangeun , Meyer Keith , Bose Sandip K. , Di Bisceglie Adrian M. , Ray Ratna B. , Ray Ranjit
Published: December 2011

The third component of human complement (C3) plays a central role in innate immune function as its activation is required to trigger classical as well as alternative complement pathways. In this study, we have observed that sera from patients chronically infected with hepatitis C virus (HCV) displayed significantly lower C3 levels than sera from healthy individuals. Liver biopsy specimens from the same patients also exhibited lower C3 mRNA expression than liver tissues from healthy donors. C3 mRNA level was reduced in hepatocytes upon infection with cell culture-grown HCV genotype 1a or 2a
in vitro
. Further analysis suggested that HCV core protein displayed a weak repression of C3 promoter activity by downregulating the transcription factor farnesoid X receptor (FXR). On the other hand, HCV NS5A protein strongly downregulated C3 promoter activity at the basal level or in the presence of interleukin-1β (IL-1β) as an inducer. In addition, the expression of the transcription factor CAAT/enhancer binding protein beta (C/EBP-β), which binds to the IL-1/IL-6 response element in the C3 promoter, was inhibited in liver biopsy specimens. Furthermore, expression of C/EBP-β was reduced in hepatocytes infected with cell culture-grown HCV, as well as in hepatocytes transfected with the NS5A genomic region of HCV. Together, these results underscore the role of HCV NS5A protein in impairing innate immune function.
Infectious Spleen and Kidney Necrosis Virus (a Fish Iridovirus) Enters Mandarin Fish Fry Cells via Caveola-Dependent Endocytosis
Authors: Guo Chang-Jun , Wu Yan-Yan , Yang Li-Shi , Yang Xiao-Bo , He Jian , Mi Shu , Jia Kun-Tong , Weng Shao-Ping , Yu Xiao-Qiang , He Jian-Guo
Published: December 2011

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus
Megalocytivirus
from the family
Iridoviridae
. Megalocytiviruses have been implicated in more than 50 fish species infections and currently threaten the aquaculture industry, causing great economic losses in China, Japan, and Southeast Asia. However, the cellular entry mechanisms of megalocytiviruses remain largely uncharacterized. In this study, the main internalization mechanism of ISKNV was investigated by using mandarin fish fry (MFF-1) cells. The progression of ISKNV infection is slow, and infection is not inhibited when the cells are treated with ammonium chloride (NH
4
Cl), chloroquine, sucrose, and chlorpromazine, which are inhibitors of clathrin-dependent endocytosis. The depletion of cellular cholesterol by methyl-β-cyclodextrin results in the significant inhibition of ISKNV infection; however, the infection is resumed with cholesterol replenishment. Inhibitors of caveolin-1-involved signaling events, including phorbol 12-myristate 13-acetate (PMA), genistein, and wortmannin, impair ISKNV entry into MFF-1 cells. Moreover, ISKNV entry is dependent on dynamin and the microtubule cytoskeleton. Cofraction analysis of ISKNV and caveolin-1 showed that ISKNV colocates with caveolin-1 during virus infection. These results indicate that ISKNV entry into MFF-1 cells proceeds via classical caveola-mediated endocytosis and is dependent on the microtubules that serve as tracks along which motile cavicles may move via a caveola-caveosome-endoplasmic reticulum (ER) pathway. As a fish iridovirus, ISKNV entry into MFF-1 cells is different from the clathrin-mediated endocytosis of frog virus 3 entry into mammalian cells (BHK-21) at 28°C, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection.
Sexual harassment and abuse in sport: the role of the team doctor: Table 1
Authors: Marks Saul , Mountjoy Margo , Marcus Madalyn
Published: December 2011

Sexual harassment and abuse occur in all sports and at all levels with an increased risk at the elite level. The physical and psychological consequences of sexual harassment and abuse are significant for the athlete, their team and for the health and integrity of sport in general. The sports medicine health professional has an integral role to play in the prevention of sexual harassment and abuse in sport. This paper provides sport healthcare professionals with a practical guide on prevention strategies and advice on the recognition and management of suspected abuse.
MONOPOLES OVER FUZZY TWO-SPHERE BY ONE SEQUENCE OF THE IRREPS OF SU(2)
Authors: DEHGHANI A. , FAKHRI H. , HASHEMI A. , LOTFIZADEH M. , MOJAVERI B.
Published: December 2011

The purpose of this paper is to use the idea in J. Geom. Phys.42, 54 (2002) to compute the topological charges for a (finite) sequence of noncommutative line bundles over the fuzzy sphere. Central to this task is to construct projective modules associated with sequence of the irreducible sub-representations of the tensor product of two different irreps of SU (2). The topological charges corresponding to such fuzzy line bundles are fractional and different from each other. However, in the commutative limit, those tend to Chern numbers of a sequence of the complex line bundles over two-sphere.
ICECUBE-DEEPCORE-PINGU: FUNDAMENTAL NEUTRINO AND DARK MATTER PHYSICS AT THE SOUTH POLE
Authors: KOSKINEN D. JASON
Published: December 2011

The IceCube neutrino observatory at the South Pole uses 1 km3 of instrumented ice to detect both astrophysical and atmospheric neutrinos. Expanding the capabilities of the original design, the DeepCore sub-array is a low-energy extension to IceCube which will collect [Formula: see text] atmospheric neutrinos a year. The high statistics sample will allow DeepCore to make neutrino oscillation measurements at higher energies and longer baselines than current experiments. The first successful observation of neutrino induced cascades in a neutrino telescope has recently been observed in DeepCore, which upon further cultivation should help refine atmospheric neutrino flux models. Besides the fundamental neutrino physics, the low-energy reach of DeepCore, down to as low as 10 GeV, and multi-megaton effective volume will enhance indirect searches for WIMP-like dark matter. A new proposal seeking to lower the energy reach down to [Formula: see text] GeV known as the Phased IceCube Next Generation Upgrade (or PINGU) will also be described.
FREED LEPTOGENESIS
Authors: ZHURIDOV DMITRY V.
Published: December 2011

Economical extensions of the Standard Model (SM), in which famous Davidson–Ibarra bound on the CP asymmetry relevant for leptogenesis may be significantly relaxed by the loop effects, comparing to predictions of the SM extended only by heavy right-handed neutrinos with hierarchical masses, are discussed. This leads to decreasing of the lower bound on the heavy neutrino masses and increasing of the upper bound on the light neutrino masses, which is testable. In addition, the considered theory may help to solve the dark matter problem.
COMPUTATIONAL FLUID DYNAMIC SIMULATION OF THE NANOELECTRICAL DISCHARGE MACHINING PROCESS
Authors: TAHMASEBIPOUR G. , TAHMASEBIPOUR Y. , GHOREISHI M.
Published: December 2011

Electrical discharge machining (EDM) process is one of the advanced machining processes that can machine the various complex shapes from all conductor and semiconductor materials. Wide and diverse applications of Micro-EDM process in microfabrication and micro- to nano-miniaturization tendency is promising application of Nano-EDM process in nanofabrication. The Nano-EDM is a precise, sensitive and costly process. Therefore, simulation of nanocrater produced by each spark in this process prevents spending extra time and cost to perform Nano-EDM process through trial and error method. In this paper nanocrater machined by the Nano-EDM process on a gold nanofilm is simulated under practically experimental conditions. Radius, depth and volume of the nanocrater are evaluated versus process conditions (average power and pulse duration) and workpiece thickness (50 nm, 100 nm and 300 nm). It is observed that radius of the nanocrater is increased exponentially with increasing spark pulse duration. Also, depth, volume of the removed material from the workpiece surface and material removal rate (MRR) are increased with increasing consumed energy by each spark. By increasing thickness of the nanofilm, volume of the removed material and dimensions of the nanocrater are decreased.
Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation
Authors: Mathes C. M. , Bueter M. , Smith K. R. , Lutz T. A. , le Roux C. W. , Spector A. C.
Published: December 2011

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9–39) (30 μg/kg), agonist exendin-4 (1 μg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01–1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5–3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9–39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.
Review:Lessons from in vitro studies and a related intracellular angiotensin II transgenic mouse model
Authors: Cook Julia L. , Re Richard N.
Published: December 2011

In the classical renin-angiotensin system, circulating ANG II mediates growth stimulatory and hemodynamic effects through the plasma membrane ANG II type I receptor, AT1. ANG II also exists in the intracellular space in some native cells, and tissues and can be upregulated in diseases, including hypertension and diabetes. Moreover, intracellular AT1receptors can be found associated with endosomes, nuclei, and mitochondria. Intracellular ANG II can function in a canonical fashion through the native receptor and also in a noncanonical fashion through interaction with alternative proteins. Likewise, the receptor and proteolytic fragments of the receptor can function independently of ANG II. Participation of the receptor and ligand in alternative intracellular pathways may serve to amplify events that are initiated at the plasma membrane. We review historical and current literature relevant to ANG II, compared with other intracrines, in tissue culture and transgenic models. In particular, we describe a new transgenic mouse model, which demonstrates that intracellular ANG II is linked to high blood pressure. Appreciation of the diverse, pleiotropic intracellular effects of components of the renin-angiotensin system should lead to alternative disease treatment targets and new therapies.
Beyond proteinuria: VDR activation reduces renal inflammation in experimental diabetic nephropathy
Authors: Sanchez-Niño Maria-Dolores , Bozic Milica , Córdoba-Lanús Elizabeth , Valcheva Petya , Gracia Olga , Ibarz Merce , Fernandez Elvira , Navarro-Gonzalez Juan F. , Ortiz Alberto , Valdivielso Jose Manuel
Published: December 2011

Local inflammation is thought to contribute to the progression of diabetic nephropathy. The vitamin D receptor (VDR) activator paricalcitol has an antiproteinuric effect in human diabetic nephropathy at high doses. We have explored potential anti-inflammatory effects of VDR activator doses that do not modulate proteinuria in an experimental model of diabetic nephropathy to gain insights into potential benefits of VDR activators in those patients whose proteinuria is not decreased by this therapy. The effect of calcitriol and paricalcitol on renal function, albuminuria, and renal inflammation was explored in a rat experimental model of diabetes induced by streptozotocin. Modulation of the expression of mediators of inflammation by these drugs was explored in cultured podocytes. At the doses used, neither calcitriol nor paricalcitol significantly modified renal function or reduced albuminuria in experimental diabetes. However, both drugs reduced the total kidney mRNA expression of IL-6, monocyte chemoattractant protein (MCP)-1, and IL-18. Immunohistochemistry showed that calcitriol and paricalcitol reduced MCP-1 and IL-6 in podocytes and tubular cells as well as glomerular infiltration by macrophages, glomerular cell NF-κB activation, apoptosis, and extracellular matrix deposition. In cultured podocytes, paricalcitol and calcitriol at concentrations in the physiological and clinically significant range prevented the increase in MCP-1, IL-6, renin, and fibronectin mRNA expression and the secretion of MCP-1 to the culture media induced by high glucose. In conclusion, in experimental diabetic nephropathy VDR activation has local renal anti-inflammatory effects that can be observed even when proteinuria is not decreased. This may be ascribed to decreased inflammatory responses of intrinsic renal cells, including podocytes, to high glucose.
Peroxisome proliferator-activated receptor-γ agonists repress epithelial sodium channel expression in the kidney
Authors: Borsting Emily , Cheng Vicki Pei-Chun , Glass Chris K. , Vallon Volker , Cunard Robyn
Published: December 2011

Thiazolidinediones (TZDs), known as peroxisome proliferator-activated receptor (PPAR) agonists, are used to treat type 2 diabetes. However, ∼5% of patients experience the treatment-limiting side effect of edema. Studies have implicated activation of the epithelial sodium channel (ENaC) as a cause of TZD-induced fluid retention, although there have been conflicting reports. The goal of this study was to resolve the role of PPARγ in control of ENaC isoforms in the kidney. Herein, we demonstrate in mice that rosiglitazone (RGZ), a PPARγ ligand, increases body weight and abdominal fat pad fluid content and reduces hematocrit. Seven days of RGZ decreases ENaCα and ENaCβ mRNA and ENaCγ protein expression in the kidney cortex, and acute treatment for 5 h with pioglitazone, another potent TZD, does not increase renal ENaC isoform mRNA or protein expression. Pioglitazone also decreases ENaCα and ENaCγ mRNA expression in a cortical collecting duct cell line. As no direct transcriptional studies had been conducted, we examined the PPARγ-dependent regulation of ENaC. Pioglitazone represses ENaCγ promoter activity, and this repression is partially relieved by inhibition of protein synthesis. Chromatin immunoprecipitation assays revealed that repression is associated with a decrease in histone H4K5 acetylation at the proximal ENaCγ promoter. In summary, TZDs do not increase ENaC mRNA expression in the kidney, and in fact repress the ENaCγ promoter via an indirect transcriptional mechanism.