bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the cross‐correlation component of the multiscale structural similarity metric (R* metric) for the evaluation of medical images
Authors: Prieto Gabriel , Guibelalde Eduardo , Chevalier Margarita , Turrero Agustín
Published: July 2011

Purpose:

The aim of the present work is to analyze the potential of the cross‐correlation component of the multiscale structural similarity metric (R*) to predict human performance in detail detection tasks closely related with diagnostic x‐ray images. To check the effectiveness of R*, the authors have initially applied this metric to a contrast detail detection task.

Methods:

Threshold contrast visibility using the R* metric was determined for two sets of images of a contrast‐detail phantom (CDMAM). Results from R* and human observers were compared as far as the contrast threshold was concerned. A comparison between the R* metric and two algorithms currently used to evaluate CDMAM images was also performed.

Results:

Similar trends for the CDMAM detection task of human observers and R* were found in this study. Threshold contrast visibility values using R* are statistically indistinguishable from those obtained by human observers (F‐test statistics:p > 0.05).

Conclusions:

These results using R* show that it could be used to mimic human observers for certain tasks, such as the determination of contrast detail curves in the presence of uniform random noise backgrounds. The R* metric could also outperform other metrics and algorithms currently used to evaluate CDMAM images and can automate this evaluation task.
On the Monte Carlo simulation of electron transport in the sub‐1 keV energy range
Authors: Thomson Rowan M. , Kawrakow Iwan
Published: July 2011

Purpose:

The validity of “classic” Monte Carlo (MC) simulations of electron and positron transport at sub‐1 keV energies is investigated in the context of quantum theory.

Methods:

Quantum theory dictates that uncertainties on the position and energy‐momentum four‐vectors of radiation quanta obey Heisenberg's uncertainty relation; however, these uncertainties are neglected in “classical” MC simulations of radiation transport in which position and momentum are known precisely. Using the quantum uncertainty relation and electron mean free path, the magnitudes of uncertainties on electron position and momentum are calculated for different kinetic energies; a validity bound on the classical simulation of electron transport is derived.

Results:

In order to satisfy the Heisenberg uncertainty principle, uncertainties of 5% must be assigned to position and momentum for 1 keV electrons in water; at 100 eV, these uncertainties are 17 to 20% and are even larger at lower energies. In gaseous media such as air, these uncertainties are much smaller (less than 1% for electrons with energy 20 eV or greater).

Conclusions:

The classical Monte Carlo transport treatment is questionable for sub‐1 keV electrons in condensed water as uncertainties on position and momentum must be large (relative to electron momentum and mean free path) to satisfy the quantum uncertainty principle. Simulations which do not account for these uncertainties are not faithful representations of the physical processes, calling into question the results of MC track structure codes simulating sub‐1 keV electron transport. Further, the large difference in the scale at which quantum effects are important in gaseous and condensed media suggests that track structure measurements in gases are not necessarily representative of track structure in condensed materials on a micrometer or a nanometer scale.
Production and dosimetric aspects of the potent Auger emitter 58mCo for targeted radionuclide therapy of small tumors
Authors: Thisgaard H. , Elema D.R. , Jensen M.
Published: July 2011

Purpose:

Based on theoretical calculations, the Auger emitter58mCo has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long‐lived ground state 58gCo is unfortunately unavoidable, as is ingrowth of the ground state following the isomeric decay of 58mCo. The impact of 58gCo as a β+‐ and γ‐emitting impurity should be included in the dosimetric analysis. The purpose of this study was to investigate this critical part of dosimetry based on experimentally determined production yields of 58mCo and 58gCo using a low‐energy cyclotron. Also, the cellular S‐values for 58mCo have been calculated and are presented here for the first time.

Methods:

58mCo was produced via the 58Fe(p,n)58mCo nuclear reaction on highly enriched 58Fe metal. In addition, radiochemical separations of produced radio‐cobalt from natFe target material were performed. The theoretical subcellular dosimetry calculations for 58mCo and 58gCo were performed using the MIRD formalism, and the impact of the increasing ground state impurity on the tumor‐to‐normal‐tissue dose ratios (TND) per disintegration as a function of time after end of bombardment (EOB) was calculated.

Results:

192 ± 8 MBq of58mCo was produced in the irradiation corresponding to a production yield of 10.7 MBq/μAh. The activity of 58gCo was measured to be 0.85% ± 0.04% of the produced 58mCo activity at EOB. The radio‐cobalt yields in the rapid separations were measured to be >97% with no detectable iron contaminations in the cobalt fractions. Due to the unavoidable coproduction and ingrowth of the long‐lived ground state 58gCo, the TND and the potency of the 58mCo decrease with time after EOB. If a future treatment with a 58mCo labeled compound is not initiated before, e.g., 21 h after EOB, the resulting TND will be approximately 50% of the TND of ‘pure’ 58mCo as a result of the increased normal tissue dose from the ground state.Conclusions: The Auger emitter 58mCo is a potent radioisotope for targeted radionuclide therapy, and the production of therapeutic quantities should be achievable using a small biomedical cyclotron. However, the unavoidable coproduction and ingrowth of the long‐lived ground state 58gCo requires fast radiochemical processing and use of future 58mCo‐labeled radiopharmaceuticals in order to exploit the high achievable TND of 58mCo.
Iterative reconstruction for differential phase contrast imaging using spherically symmetric basis functions
Authors: Köhler Thomas , Brendel Bernhard , Roessl Ewald
Published: July 2011

Purpose:

The purpose of this work is to combine two areas of active research in tomographic x‐ray imaging. The first one is the use of iterative reconstruction (IR) techniques. The second one is differential phase contrast imaging (DPCI).

Methods:

The authors derive a maximum likelihood (ML) reconstruction algorithm with regularization for DPCI. Forward and back‐projection are implemented using spherically symmetric basis functions (blobs) and differential footprints, thus completely avoiding the need for numerical differentiation throughout the reconstruction process. The method is applied to the problem of reconstruction of an object from sparsely sampled projections.

Results:

The results show that the proposed method can handle the sparsely sampled data efficiently. In particular no streak artifacts are visible which are present in images obtained by filtered back‐projection (FBP).

Conclusions:

IR algorithms have a wide spectrum of proven advantages in the area of conventional computed tomography. The present work describes for the first time, how a matched forward and back‐projection can be implemented for DPCI, which is furthermore free of any heuristics. The newly developed ML reconstruction algorithm for DPCI shows that for the case of sparsely sampled projection data, an improvement in image quality is obtained that is qualitatively comparable to a corresponding situation in conventional x‐ray imaging. Based on the proposed operators for forward and back‐projection, a large variety of IR algorithms is thus made available for DPCI.
Topological Defects Coupling Smectic Modulations to Intra–Unit-Cell Nematicity in Cuprates
Authors: Mesaros A. , Fujita K. , Eisaki H. , Uchida S. , Davis J. C. , Sachdev S. , Zaanen J. , Lawler M. J. , Kim Eun-Ah
Published: July 2011

A theoretical model explains how electronic states with different symmetries coexist and interact.
Cilia-Like Beating of Active Microtubule Bundles
Authors: Sanchez Timothy , Welch David , Nicastro Daniela , Dogic Zvonimir
Published: July 2011

In vitro–assembled microtubule bundles exhibit oscillatory beating patterns and organize into metachronal waves.
A Common Scaling Rule for Abundance, Energetics, and Production of Parasitic and Free-Living Species
Authors: Hechinger Ryan F. , Lafferty Kevin D. , Dobson Andy P. , Brown James H. , Kuris Armand M.
Published: July 2011

Incorporation of energy flow between trophic levels yields a common scaling component for abundance in relation to body size.
Projecting Coral Reef Futures Under Global Warming and Ocean Acidification
Authors: Pandolfi John M. , Connolly Sean R. , Marshall Dustin J. , Cohen Anne L.
Published: July 2011

Many physiological responses in present-day coral reefs to climate change are interpreted as consistent with the imminent disappearance of modern reefs globally because of annual mass bleaching events, carbonate dissolution, and insufficient time for substantial evolutionary responses. Emerging evidence for variability in the coral calcification response to acidification, geographical variation in bleaching susceptibility and recovery, responses to past climate change, and potential rates of adaptation to rapid warming supports an alternative scenario in which reef degradation occurs with greater temporal and spatial heterogeneity than current projections suggest. Reducing uncertainty in projecting coral reef futures requires improved understanding of past responses to rapid climate change; physiological responses to interacting factors, such as temperature, acidification, and nutrients; and the costs and constraints imposed by acclimation and adaptation.
Host Cell Invasion by Apicomplexan Parasites: Insights from the Co-Structure of AMA1 with a RON2 Peptide
Authors: Tonkin Michelle L. , Roques Magali , Lamarque Mauld H. , Pugnière Martine , Douguet Dominique , Crawford Joanna , Lebrun Maryse , Boulanger Martin J.
Published: July 2011

The structure of a eukaryotic pathogen adhesin bound to its receptor provides a basis for design of therapeutics.
Onset of Plate Tectonics
Authors: Van Kranendonk Martin J.
Published: July 2011

Analysis of diamonds from the subcontinental mantle reveals that plate tectonics started 3 billion years ago.
A Versatile Molecular Trap Built from Hydrogen-Bonded Tiles
Authors: Lauher Joseph W.
Published: July 2011

A molecular host structure accommodates a wide range of guests that are selected on size alone.
Future Prospects for Cereals That Fix Nitrogen
Authors: Beatty Perrin H. , Good Allen G.
Published: July 2011

What are the next steps in engineering crop plants that fix nitrogen and make their own fertilizer?
Bringing It Together with RNA
Authors: Thodey Kate , Smolke Christina D.
Published: July 2011

Synthetic RNA nanostructures can direct biochemical pathways in cells.
Searchers in a Desert

Nostalgia for the Light
Patricio Guzmán, Director

Atacama Productions, Blinker Filmproduktion, and Cronomedia, Chile/France/Spain/Germany, 2010. (U.S. distributor: Icarus Films, New York.) 90 minutes. http://icarusfilms.com/new2011/nost.html
Authors: Hameed Salman
Published: July 2011

Drawing on intersections among astronomy, anthropology, and human rights in Chile's Atacama desert, Guzmán's film reflects on the ways we create meaning from history.
Europe Unveils 'Radical' Plan to Reform Fishing Industry
Authors: Malakoff David
Published: July 2011

On 13 July, the European Commission launched what it called a "radical" effort to reform flawed fisheries policies that have led to decades of overfishing, plummeting catches, and extensive damage to marine ecosystems.
Why Do Parrots Talk? Venezuelan Site Offers Clues
Authors: Morell Virginia
Published: July 2011

The world's longest-running study of wild parrots shifts focus to a new question: What do parrots say to each other in the wild?
For Best Ticket to the Afterlife, Pay Up
Authors: Pringle Heather
Published: July 2011

Bioarchaeologists reported at the meeting that only elite members of ancient Egyptian society consistently benefited from all the tricks of the embalmers' trade, thereby boosting their chances of a pleasurable afterlife.
Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants
Authors: Abramczuk Beatriz Mariana , Mazzola Taís Nitsch , Moreno Yara Maria Franco , Zorzeto Tatiane Queiroz , Quintilio Wagner , Wolf Paulo Silva , Blotta Maria Heloisa , Morcillo André Moreno , da Silva Marcos Tadeu Nolasco , dos Santos Vilela Maria Marluce
Published: July 2011

Little is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, ≥1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders (χ2=10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.
Antibody Profiling of Borrelia burgdorferi Infection in Horses
Authors: Burbelo Peter D. , Bren Kathleen E. , Ching Kathryn H. , Coleman Adam , Yang Xiuli , Kariu Toru , Iadarola Michael J. , Pal Utpal
Published: July 2011

Infection withBorrelia burgdorferiis common in horses and ponies from the New England and mid-Atlantic regions of the United States. Here, we evaluated luciferase immunoprecipitation systems (LIPS) for profiling antibody responses against three different antigenic targets for the diagnosis of equineB. burgdorferiinfection. LIPS testing of horse serum samples suspected of Lyme infection revealed that approximately 75% of the horse samples (114/159) were seropositive against the synthetic VOVO antigen, comprising repeated immunodominant C6 epitopes as well as OspC immunodominant epitopes. A comparison of VOVO and immunofluorescence assays (IFA) showed that 51% of the samples were positive in both assays (VOVO+/IFA+), 13% were VOVO−/IFA+, 21% were VOVO+/IFA−, and 15% were negative in both. To further understand humoral responses toB. burgdorferiand reconcile the diagnostic differences between IFA and VOVO, two additionalB. burgdorferiLIPS tests were performed with DbpA and DbpB. Robust seropositive antibody responses against DbpA and/or DbpB were detected in 98% (79/81) of the VOVO+/IFA+and 93% (50/54) of the discrepant samples. Additionally, some of the samples negative by both VOVO and IFA showed immunoreactivity against DbpA and/or DbpB. Overall, 94% of the suspected horse samples were seropositive by LIPS, and heat map analysis revealed that seropositive samples often were immunoreactive with at least two of the three antigens. These results suggest that LIPS tests employing multiple recombinant antigens offer a promising approach for the evaluation of antibody responses in Lyme disease.
Epidemiology and Evolutionary Characteristics of the Porcine Reproductive and Respiratory Syndrome Virus in China between 2006 and 2010
Authors: Li Bin , Fang Liurong , Guo Xueliang , Gao Jianfeng , Song Tao , Bi Jing , He Kongwang , Chen Huanchun , Xiao Shaobo
Published: July 2011

In 2006, an emerging highly pathogenic strain of porcine reproductive and respiratory syndrome virus (PRRSV), which causes continuous high fever and a high proportion of deaths in vaccinated pigs of all ages, broke out in mainland China and spread rapidly to neighboring countries. To examine the epidemiology and evolutionary characteristics of Chinese PRRSV after the 2006 outbreak, we tested 2,981 clinical samples collected from 2006 to 2010 in China, determined 153 Nsp2 sequences and 249 ORF5 sequences, and analyzed the epidemiology and genetic diversity of Chinese PRRSV. Our results showed that the percentage of PRRSV-positive specimens collected from sick pigs averaged 60.85% in the past 5 years and that the highly pathogenic PRRSV has become the dominant strain in China. Furthermore, a reemerging strain which apparently evolved from the highly pathogenic PRRSV strain in 2006 appeared to be widely prevalent in China from 2009 onwards. Sequence analyses revealed that the hypervariable region of Nsp2 in most of the isolates contained a discontinuous deletion equivalent to 30 amino acids, along with other types of deletions. Extensive amino acid substitutions in the GP5 sequence translated from ORF5 were found, particularly in the potential neutralization epitope and the N-glycosylation sites. Our results suggest that Chinese PRRSV has undergone rapid evolution and can circumvent immune responses induced by currently used vaccines. Information from this study will help in understanding the evolutionary characteristics of Chinese PRRSV and assist ongoing efforts to develop and use PRRSV vaccines in the future.
Clostridium clostridioforme and Atopobium minutum Clinical Isolates with VanB-Type Resistance in France
Authors: Marvaud Jean-Christophe , Mory Francine , Lambert Thierry
Published: July 2011

Acquired vancomycin resistance in Gram-positive anaerobes has been reported only in Australia and Canada from rare
vanB
-positive stool samples in the absence of vancomycin-resistant enterococci (VRE). We report the emergence of VanB-type resistance in
Clostridium clostridioforme
and
Atopobium minutum
involved in human infections in France.
A Novel Eukaryote-Made Thermostable DNA Polymerase Which Is Free from Bacterial DNA Contamination
Authors: Niimi Hideki , Mori Masashi , Tabata Homare , Minami Hiroshi , Ueno Tomohiro , Hayashi Shirou , Kitajima Isao
Published: July 2011

To achieve the production of a thermostable DNA polymerase free from bacterial DNA contamination, we developed eukaryote-made thermostable DNA (
Taq
) polymerase. The novel eukaryote-made thermostable DNA polymerase resolves the problem of contaminating bacterial DNA in conventional bacterially made thermostable DNA polymerase as a result of its manufacture and incomplete purification. Using eukaryote-made thermostable DNA polymerase, the sensitive and reliable detection of bacteria becomes feasible for large fields, thereby making the development of a wide range of powerful applications possible.
Evaluation and Verification of the Seeplex Diarrhea-V ACE Assay for Simultaneous Detection of Adenovirus, Rotavirus, and Norovirus Genogroups I and II in Clinical Stool Specimens
Authors: Higgins Rachel R. , Beniprashad Melissa , Cardona Mark , Masney Steven , Low Donald E. , Gubbay Jonathan B.
Published: July 2011

Acute viral gastroenteritis is an intestinal infection that can be caused by several different viruses. Here we describe the evaluation and verification of Seeplex Diarrhea-V ACE (Seeplex DV), a novel commercial multiplex reverse transcription-PCR (RT-PCR) assay that detects 5 diarrheal pathogens, including adenovirus, rotavirus, norovirus genogroup I (GI) and GII, and astrovirus. We describe a retrospective study of 200 clinical specimens of which 177 were stool specimens previously tested for the presence of gastrointestinal viruses by electron microscopy (EM) and/or real-time RT-PCR (rRT-PCR). The remaining 23 specimens comprised other human pathogens of viral or bacterial origin. Discordant norovirus GI and GII results were resolved using a commercial kit; discordant adenovirus and rotavirus results were resolved using a home brew multiplex rRT-PCR assay. Diagnostic sensitivities and specificities were calculated before and after discordant analysis. After discordant analysis, estimated diagnostic sensitivities were 100% for adenovirus, rotavirus, and norovirus GI and 97% for norovirus GII. Diagnostic specificities after discordant analysis were 100% for adenovirus, rotavirus, and norovirus GI and 99.4% for norovirus GII. The 95% limits of detection were 31, 10, 2, and 1 genome equivalent per reaction for adenovirus, rotavirus, and norovirus GI and GII, respectively. The results demonstrate that the Seeplex DV assay is sensitive, specific, convenient, and reliable for the simultaneous detection of several viral pathogens directly in specimens from patients with gastroenteritis. Importantly, this novel multiplex PCR assay enabled the identification of viral coinfections in 12 (6.8%) stool specimens.
Increased Mortality in Young Candidemia Patients Associated with Presence of a Candida albicans General-Purpose Genotype
Authors: Schmid J. , Tortorano A. M. , Jones G. , Lazzarini C. , Zhang N. , Bendall M. J. , Cogliati M. , Wattimena S. , Klingspor L. ,   ECMM Survey,   French Mycoses Study Group
Published: July 2011

The yeast
Candida albicans
causes life-threatening candidemia. A general-purpose genotype (GPG; corresponds to clade 1) causes more infections than other
C. albicans
genotypes. To investigate if GPG strains also cause higher mortality, we developed a duplex PCR assay which was 98% accurate in identifying GPG strains in an international collection of strains typed with probe Ca3. We applied the assay to 635 European
C. albicans
candidemia isolates. Of these, 18% conformed to the GPG genotype, 4% were of a borderline genotype, and 78% were of a non-GPG genotype, broadly consistent with genotype distributions in earlier studies. The prevalence of GPG strains was increased in females and in younger patients, exceeding 40% in infants aged ≤1 year. Logistic regression confirmed sex and age as significant determinants of GPG prevalence. Across the entire patient cohort, there was no difference in mortality for patients infected with GPG strains or other strains (36% versus 37%). However, mortality in patients aged ≤48 years was 33% for infection with GPG strains but only 15% for infection with other strains (
z
test;
P
< 0.01). Mortality rates associated with GPG and non-GPG strains were comparable in older patients (39% versus 46%). A logistic regression analysis confirmed the age-dependent impact of genotype on mortality. Thus, GPG strains may be more virulent than other strains in younger patients. Because candidemia is usually caused by endogenous strains, our PCR assay could potentially be used as a risk assessment tool for identifying younger patients most at risk of death from candidemia.
Detection of Extended-Spectrum-β-Lactamase-Positive Escherichia coli in Bile Isolates from Two Dogs with Bacterial Cholangiohepatitis
Authors: Timofte Dorina , Dandrieux Julien , Wattret Andrew , Fick Jenny , Williams Nicola J.
Published: July 2011

This is the first report ofEscherichia coliisolates producing CTX-M-15, the predominant type of extended-spectrum β-lactamase (ESBL) associated with clinical disease in humans in the United Kingdom, in a United Kingdom pet dog. This report also describes the first isolation of CTX-M/Tem ESBL-positiveE. colifrom bile in dogs with hepatobiliary disease.
Retrospective and Prospective Verification of the Cepheid Xpert Influenza Virus Assay
Authors: Popowitch Elena B. , Rogers Elaine , Miller Melissa B.
Published: July 2011

We performed a retrospective (
n
= 121) and prospective (
n
= 305) verification of the Cepheid Xpert Flu assay to determine its performance characteristics. The overall sensitivity and specificity were 93% and 100%, respectively. Nasopharyngeal specimen sensitivities were 100% for seasonal influenza A/H1 virus and influenza A/H3 virus, 90% for influenza A/2009/H1N1 virus, and 95% for influenza B virus.
Pseudomonas aeruginosa Endophthalmitis after Penetrating Keratoplasty Transmitted from the Same Donor to Two Recipients Confirmed by Pulsed-Field Gel Electrophoresis
Authors: Oguido Ana Paula Miyagusko Taba , Casella Antonio Marcelo Barbante , Hofling-Lima Ana Luisa , Pacheco Sergio Arruda , Bispo Paulo José Martins , Marques Fernanda
Published: July 2011

Two devastating cases of multidrug-resistant
Pseudomonas aeruginosa
endophthalmitis after keratoplasty as the result of transmission from the same donor were confirmed by pulsed-field gel electrophoresis. Strategies for preventing donor-to-host transmission, such as the use of antimicrobial agents of greater efficacy and better methods for detecting microorganisms in preservation medium, could minimize this type of transmission.
Plasmid Vector-Linked Maturation of Natural Killer (NK) Cells Is Coupled to Antigen-Dependent NK Cell Activation during DNA-Based Immunization in Mice
Authors: Zhu Ren , Mancini-Bourgine Maryline , Zhang Xiao Ming , Bayard Florence , Deng Qiang , Michel Marie-Louise
Published: July 2011

Plasmid DNA vaccines serve in a wide array of applications ranging from prophylactic vaccines to potential therapeutic tools against infectious diseases and cancer. In this study, we analyzed the mechanisms underlying the activation of natural killer (NK) cells and their potential role in adaptive immunity during DNA-based immunization against hepatitis B virus surface antigen in mice. We observed that the mature Mac-1+CD27−NK cell subset increased in the liver of mice early after DNA injection, whereas the number of the less mature Mac-1+CD27+NK cells in the liver and spleen was significantly reduced. This effect was attributed to bacterial sequences present in the plasmid backbone rather than to the encoded antigen and was not observed in immunized MyD88-deficient mice. The activation of NK cells by plasmid-DNA injection was associated with an increase in their effector functions that depended on the expressed antigen. Maturation of NK cells was abrogated in the absence of T cells, suggesting that cross talk exists between NK cells and antigen-specific T cells. Taken together, our data unravel the mechanics of plasmid vector-induced maturation of NK cells and plasmid-encoded antigen-dependent activation of NK cells required for a crucial role of NK cells in DNA vaccine-induced immunogenicity.
Artificial Recombination May Influence the Evolutionary Analysis of Newcastle Disease Virus
Authors: Song Qingqing , Cao Yongzhong , Li Qun , Gu Min , Zhong Lei , Hu Shunlin , Wan Hongquan , Liu Xiufan
Published: July 2011

The recombination rate in Newcastle disease virus (NDV) was as high as 10% in RDP analysis with full-length NDV genome sequences available in GenBank. We found that two NDV strains, China/Guangxi09/2003 and NDV/03/018, previously reported as recombinants, failed to show any evidence of recombination upon complete genome resequencing. Furthermore, we were able to reproduce artificial recombination by amplification of the M gene in a mixed sample of strains LaSota and ZJ1. It appears that the recombination of NDV is not as common as has been reported. NDV sequences in GenBank should be analyzed with caution during bioinformatic analyses for natural recombination events.
Evasion and Subversion of Interferon-Mediated Antiviral Immunity by Kaposi's Sarcoma-Associated Herpesvirus: an Overview
Authors: Sathish Narayanan , Yuan Yan
Published: July 2011

Viral invasion of a host cell triggers immune responses with both innate and adaptive components. The innate immune response involving the induction of type I interferons (alpha and beta interferons [IFN-α and -β]) constitutes the first line of antiviral defenses. The type I IFNs signal the transcription of a group of antiviral effector proteins, the IFN-stimulated genes (ISGs), which target distinct viral components and distinct stages of the viral life cycle, aiming to eliminate invading viruses. In the case of Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma (KS), a sudden upsurge of type I IFN-mediated innate antiviral signals is seen immediately following both primary
de novo
infection and viral lytic reactivation from latency. Potent subversion of these responses thus becomes mandatory for the successful establishment of a primary infection following viral entry as well as for efficient viral assembly and egress. This review gives a concise overview of the induction of the type I IFN signaling pathways in response to viral infection and provides a comprehensive understanding of the antagonizing effects exerted by KSHV on type I IFN pathways wielded at various stages of the viral life cycle. Information garnered from this review should result in a better understanding of KSHV biology essential for the development of immunotherapeutic strategies targeted toward KSHV-associated malignancies.
Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication
Authors: Pudupakam R. S. , Kenney Scott P. , Córdoba Laura , Huang Yao-Wei , Dryman Barbara A. , LeRoith Tanya , Pierson F. William , Meng Xiang-Jin
Published: July 2011

The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity
in vitro
, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.
The
TRIM5
Gene Modulates Penile Mucosal Acquisition of Simian Immunodeficiency Virus in Rhesus Monkeys
Authors: Yeh Wendy W. , Rao Srinivas S. , Lim So-Yon , Zhang Jinrong , Hraber Peter T. , Brassard Laura M. , Luedemann Corinne , Todd John Paul , Dodson Alan , Shen Ling , Buzby Adam P. , Whitney James B. , Korber Bette T. , Nabel Gary J. , Mascola John R. , Letvin Norman L.
Published: July 2011

There is considerable variability in host susceptibility to human immunodeficiency virus type 1 (HIV-1) infection, but the host genetic determinants of that variability are not well understood. In addition to serving as a block for cross-species retroviral infection,
TRIM5
was recently shown to play a central role in limiting primate immunodeficiency virus replication. We hypothesized that
TRIM5
may also contribute to susceptibility to mucosal acquisition of simian immunodeficiency virus (SIV) in rhesus monkeys. We explored this hypothesis by establishing 3 cohorts of Indian-origin rhesus monkeys with different
TRIM5
genotypes: homozygous restrictive, heterozygous permissive, and homozygous permissive. We then evaluated the effect of
TRIM5
genotype on the penile transmission of SIVsmE660. We observed a significant effect of
TRIM5
genotype on mucosal SIVsmE660 acquisition in that no SIV transmission occurred in monkeys with only restrictive
TRIM5
alleles. In contrast, systemic SIV infections were initiated after preputial pocket exposures in monkeys that had at least one permissive
TRIM5
allele. These data demonstrate that host genetic factors can play a critical role in restricting mucosal transmission of a primate immunodeficiency virus. In addition, we used our understanding of
TRIM5
to establish a novel nonhuman primate penile transmission model for AIDS mucosal pathogenesis and vaccine research.
Interaction between Geminivirus Replication Protein and the SUMO-Conjugating Enzyme Is Required for Viral Infection
Authors: Sánchez-Durán Miguel A. , Dallas Mary B. , Ascencio-Ibañez José T. , Reyes Maria Ines , Arroyo-Mateos Manuel , Ruiz-Albert Javier , Hanley-Bowdoin Linda , Bejarano Eduardo R.
Published: July 2011

Geminiviruses are small DNA viruses that replicate in nuclei of infected plant cells by using plant DNA polymerases. These viruses encode a protein designated AL1, Rep, or AC1 that is essential for viral replication. AL1 is an oligomeric protein that binds to double-stranded DNA, catalyzes the cleavage and ligation of single-stranded DNA, and induces the accumulation of host replication machinery. It also interacts with several host proteins, including the cell cycle regulator retinoblastoma-related protein (RBR), the DNA replication protein PCNA (proliferating cellular nuclear antigen), and the sumoylation enzyme that conjugates SUMO to target proteins (SUMO-conjugating enzyme [SCE1]). The SCE1-binding motif was mapped by deletion to a region encompassing AL1 amino acids 85 to 114. Alanine mutagenesis of lysine residues in the binding region either reduced or eliminated the interaction with SCE1, but no defects were observed for other AL1 functions, such as oligomerization, DNA binding, DNA cleavage, and interaction with AL3 or RBR. The lysine mutations reduced or abolished virus infectivity in plants and viral DNA accumulation in transient-replication assays, suggesting that the AL1-SCE1 interaction is required for viral DNA replication. Ectopic AL1 expression did not result in broad changes in the sumoylation pattern of plant cells, but specific changes were detected, indicating that AL1 modifies the sumoylation state of selected host proteins. These results established the importance of AL1-SCE1 interactions during geminivirus infection of plants and suggested that AL1 alters the sumoylation of selected host factors to create an environment suitable for viral infection.
An Externalized Polypeptide Partitions between Two Distinct Sites on Genome-Released Poliovirus Particles
Authors: Lin Jun , Cheng Naiqian , Chow Marie , Filman David J. , Steven Alasdair C. , Hogle James M. , Belnap David M.
Published: July 2011

During cell entry, native poliovirus (160S) converts to a cell-entry intermediate (135S) particle, resulting in the externalization of capsid proteins VP4 and the amino terminus of VP1 (residues 1 to 53). Externalization of these entities is followed by release of the RNA genome (uncoating), leaving an empty (80S) particle. The antigen-binding fragment (Fab) of a monospecific peptide 1 (P1) antibody, which was raised against a peptide corresponding to amino-terminal residues 24 to 40 of VP1, was utilized to track the location of the amino terminus of VP1 in the 135S and 80S states of poliovirus particles via cryogenic electron microscopy (cryo-EM) and three-dimensional image reconstruction. On 135S, P1 Fabs bind to a prominent feature on the external surface known as the “propeller tip.” In contrast, our initial 80S-P1 reconstruction showed P1 Fabs also binding to a second site, at least 50 Å distant, at the icosahedral 2-fold axes. Further analysis showed that the overall population of 80S-P1 particles consisted of three kinds of capsids: those with P1 Fabs bound only at the propeller tips, P1 Fabs bound only at the 2-fold axes, or P1 Fabs simultaneously bound at both positions. Our results indicate that, in 80S particles, a significant fraction of VP1 can deviate from icosahedral symmetry. Hence, this portion of VP1 does not change conformation synchronously when switching from the 135S state. These conclusions are compatible with previous observations of multiple conformations of the 80S state and suggest that movement of the amino terminus of VP1 has a role in uncoating. Similar deviations from icosahedral symmetry may be biologically significant during other viral transitions.
A Functional Role for TorsinA in Herpes Simplex Virus 1 Nuclear Egress
Authors: Maric Martina , Shao Jianqiang , Ryan Randi J. , Wong Chun-Shu , Gonzalez-Alegre Pedro , Roller Richard J.
Published: July 2011

Herpes simplex virus 1 (HSV-1) capsids leave the nucleus by a process of envelopment and de-envelopment at the nuclear envelope (NE) that is accompanied by structural alterations of the NE. As capsids translocate across the NE, transient primary enveloped virions form in the perinuclear space. Here, we provide evidence that torsinA (TA), a ubiquitously expressed ATPase, has a role in HSV-1 nuclear egress. TA resides within the lumen of the endoplasmic reticulum (ER)/NE and functions in maintaining normal NE architecture. We show that perturbation of TA normal function by overexpressing torsinA wild type (TAwt) inhibits HSV-1 production. Ultrastructural analysis of infected cells overexpressing TAwt revealed reduced levels of surface virions in addition to accumulation of novel, double-membrane structures called virus-like vesicles (VLVs). Although mainly found in the cytoplasm, VLVs resemble primary virions in their size, by the appearance of the inner membrane, and by the presence of pUL34, a structural component of primary virions. Collectively, our data suggest a model in which interference of TA normal function by overexpression impairs de-envelopment of the primary virions leading to their accumulation in a cytoplasmic membrane compartment. This implies novel functions for TA at the NE.
T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary Syndrome
Authors: Hammerbeck Christopher D. , Hooper Jay W.
Published: July 2011

Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). In hamsters, ANDV causes a respiratory distress syndrome closely resembling human HPS. The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, T cell immunopathology has been implicated on the basis of circumstantial and corollary evidence. Here, we show that following ANDV challenge, hamster T cell activation corresponds with the onset of disease. However, treatment with cyclophosphamide or specific T cell depletion does not impact the course of disease or alter the number of surviving animals, despite significant reductions in T cell number. These data demonstrate, for the first time, that T cells are not required for hantavirus pathogenesis in the hamster model of human HPS. Depletion of T cells from Syrian hamsters did not significantly influence early events in disease progression. Moreover, these data argue for a mechanism of hantavirus-induced vascular permeability that does not involve T cell immunopathology.
High Prevalence of Simian Immunodeficiency Virus Infection in a Community of Savanna Chimpanzees
Authors: Rudicell Rebecca S. , Piel Alex K. , Stewart Fiona , Moore Deborah L. , Learn Gerald H. , Li Yingying , Takehisa Jun , Pintea Lilian , Shaw George M. , Moore Jim , Sharp Paul M. , Hahn Beatrice H.
Published: July 2011

Simian immunodeficiency virus of chimpanzees (SIVcpz) has a significant negative impact on the health, reproduction, and life span of chimpanzees, yet the prevalence and distribution of this virus in wild-living populations are still only poorly understood. Here, we show that savanna chimpanzees, who live in ecologically marginal habitats at 10- to 50-fold lower population densities than forest chimpanzees, can be infected with SIVcpz at high prevalence rates. Fecal samples were collected from nonhabituated eastern chimpanzees (
Pan troglodytes schweinfurthii
) in the Issa Valley (
n
= 375) and Shangwa River (
n
= 6) areas of the Masito-Ugalla region in western Tanzania, genotyped to determine the number of sampled individuals, and tested for SIVcpz-specific antibodies and nucleic acids. None of 5 Shangwa River apes tested positive for SIVcpz; however, 21 of 67 Issa Valley chimpanzees were SIVcpz infected, indicating a prevalence rate of 31% (95% confidence interval, 21% to 44%). Two individuals became infected during the 14-month observation period, documenting continuing virus spread in this community. To characterize the newly identified SIVcpz strains, partial and full-length viral sequences were amplified from fecal RNA of 10 infected chimpanzees. Phylogenetic analyses showed that the Ugalla viruses formed a monophyletic lineage most closely related to viruses endemic in Gombe National Park, also located in Tanzania, indicating a connection between these now separated communities at some time in the past. These findings document that SIVcpz is more widespread in Tanzania than previously thought and that even very low-density chimpanzee populations can be infected with SIVcpz at high prevalence rates. Determining whether savanna chimpanzees, who face much more extreme environmental conditions than forest chimpanzees, are more susceptible to SIVcpz-associated morbidity and mortality will have important scientific and conservation implications.
Mortality in carotid sinus hypersensitivity: a cohort study
Authors: Hampton Joanna L , Brayne Carol , Bradley Michelle , Kenny Rose Anne
Published: July 2011

Objective

Carotid sinus hypersensitivity (CSH) is common in older people. The authors hypothesise that patients with CSH have a higher mortality than a geographically, age-matched older cohort.

Design

A retrospective cohort study compared to geographical and age-matched data from the Office of National Statistics.

Setting

Specialist clinic in tertiary centre.

Patients

1504 patients with CSH were identified from a single syncope outpatient assessment service between 1990 and 2001.

Interventions

Vital status was confirmed, and death certificates were sought for all deceased patients up to 2003.

Main outcome measures

Kaplan–Meier survival curves were analysed within the cohort according to three different subtypes of CSH. Standardised mortality rates (SMRs) were determined using geographical and age-matched data from the Office of National Statistics.

Results

There was no difference between CSH patients and the general population in SMRs for all causes, or for cerebrovascular or cardiovascular deaths. There was no difference in survival between the three subtypes of CSH (p=0.2) within the study cohort.

Conclusion

CSH is not associated with a higher mortality than the general population, and there are no differences in mortality between the three subtypes of CSH. This confirms earlier findings and reinforces the neutral effect of CSH on mortality.
Clinical and epidemiological profile of patients with severe H1N1/09 pandemic influenza in Australia and New Zealand: an observational cohort study
Authors: Cheng Allen C , Kotsimbos Tom , Reynolds Anna , Bowler Simon D , Brown Simon G A , Hancox Robert J , Holmes Mark , Irving Louis , Jenkins Christine , Thompson Philip , Simpson Graham , Waterer Grant , Wood-Baker Richard , Kelly Paul M
Published: July 2011

Background

Pandemic influenza H1N1/09 emerged in April 2009 and spread widely in Australia and New Zealand. Although an unprecedented number of cases required intensive care, comparative community-based studies with seasonal influenza strains have not shown any significant differences in clinical symptoms or severity.

Methods

The authors performed active surveillance on confirmed influenza-related admissions and compared the clinical profile of patients with pandemic H1N1/09 influenza and patients with seasonal influenza at eight hospitals in Australia and one hospital in New Zealand.

Results

During the 1 July and 30 November 2009, 560 patients with confirmed influenza were admitted, of which 478 had H1N1/09, and 82 had other seasonal strains. Patients with H1N1/09 influenza were younger, were more likely to have fever and were more likely to be pregnant but less likely to have chronic obstructive pulmonary disease and ischaemic heart disease than patients with seasonal strains. Other clinical features and comorbidities were reported in similar proportions. Admission to intensive care was required in 22% of patients with H1N1/09 influenza and 12% in patients with other strains. Hospital mortality was 5% in patients with H1N1 influenza.

Conclusions

The clinical features of H1N1/09 influenza and seasonal strains were similar in hospitalised patients. A higher proportion of patients had comorbidities than had been reported in community-based studies. Although the overall mortality was similar, the authors found evidence that H1N1/09 caused severe disease in a higher proportion of hospitalised patients.
NEW CONSTRAINTS ON DARK MATTER FROM CMS AND ATLAS DATA
Authors: AKULA SUJEET , FELDMAN DANIEL , LIU ZUOWEI , NATH PRAN , PEIM GREGORY
Published: July 2011

Constraints on dark matter from the first CMS and ATLAS SUSY searches are investigated. It is shown that within the minimal supergravity model, the early search for supersymmetry at the LHC has depleted a large portion of the signature space in dark matter direct detection experiments. In particular, the prospects for detecting signals of dark matter in the XENON and CDMS experiments are significantly affected in the low neutralino mass region. Here the relic density of dark matter typically arises from slepton coannihilations in the early universe. In contrast, it is found that the CMS and ATLAS analyses leave untouched the Higgs pole and the Hyperbolic Branch/Focus Point regions, which are now being probed by the most recent XENON results. Analysis is also done for supergravity models with non-universal soft breaking where one finds that a part of the dark matter signature space depleted by the CMS and ATLAS cuts in the minimal SUGRA case is repopulated. Thus, observation of dark matter in the LHC depleted region of minimal supergravity may indicate non-universalities in soft breaking.
SOME CONSEQUENCES OF BORN'S RECIPROCAL RELATIVITY IN PHASE-SPACES
Authors: CASTRO CARLOS
Published: July 2011

We explore some novel consequences of Born's reciprocal relativity theory in flat phase-space and generalize the theory to the curved space–time scenario. We provide, in particular, six specific results resulting from Born's reciprocal relativity and which are not present in special relativity. These are: momentum-dependent time delay in the emission and detection of photons; energy-dependent notion of locality; superluminal behavior; relative rotation of photon trajectories due to the aberration of light; invariance of areas-cells in phase-space and modified dispersion relations. We finalize by constructing a Born reciprocal general relativity theory in curved space–time which requires the introduction of a complex Hermitian metric, torsion and nonmetricity. The latter procedure can be extended to the curved phase-space scenario.