bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons Learned From the Operation of Large-Scale Reprocessing-Recycling Facilities in France: What Is in It for China?
Authors: Gros Jean-Pierre 
Published: October 2017

AREVA has been running since decades nuclear reprocessing and recycling installations in France. Several industrial facilities have been built and used to this aim across the time.
Following those decades and with the more and more precise monitoring of the impact of those installations, precise data and lessons-learned have been collected that can be used for the stakeholders of potential new facilities.
China has expressed strong interest in building such facilities. As a matter of fact, the issue of accumulation of spent fuel is becoming serious in China and jeopardizes the operation of several nuclear power plants, through the running out of space of storage pools. Tomorrow, with the extremely high pace of nuclear development of China, accumulation of spent fuel will be unbearable.
Building reprocessing and recycling installations takes time. A decision has to be taken so as to enable the responsible development of nuclear in China. Without a solution for the back end of its nuclear fuel cycle, the development of nuclear energy will face a wall.
This is what the Chinese central government, through the action of its industrial CNNC, has well understood. Several years of negotiations have been held with AREVA. Everybody in the sector seems now convinced.
However, now that the negotiation is coming to an end, an effort should be done towards all the stakeholders, sharing actual information from France’s reference facilities on: safety, security, mitigation measures for health protection (of the workers, of the public), mitigation measures for the protection of the environment.
Most of this information is public, as France has since years promulgated a law on Nuclear transparency. China is also in need for more transparency, yet lacks means to access this public information, often in French language, so let’s open our books!
Recognising the Influence of Landslide Transition Zones in the Assessment of Pipeline Integrity
Authors: Laing Matthew , Young Andy 
Published: October 2017

Pipelines crossing mountainous areas are susceptible to ground movement loading from landslides. Structural analysis of pipeline performance from landslide loads is critical for making decisions on the requirement and timing of intervention activities. Current analytical assessment methodologies for pipelines affected by ground movement tend to assume the landslide as an abrupt boundary from the stable region to moving ground, causing an over conservative estimation of the condition of the pipeline. In-line inspection using inertial mapping tools provides invaluable information to assist in the determination of the current pipeline integrity but does not provide a complete picture because axial loads are not defined. Interpretation of in-line inspection data allows the estimation of a transition zone width between stable and unstable ground, where there is a progressive increase in ground movement. Due allowance for the transition zone can remove conservatisms in the assessment methodology and allow a pipeline integrity plan to be created.
This paper investigates the influence of landslide transition zone dimensions on the pipeline response and a methodology is developed for the prediction of the transition zone width. The interaction between the ground and the pipe movement is modelled using finite element analysis techniques.
The definition of the transition zone properties provides a more reliable prediction of the pipeline performance and enables the current and future pipe integrity to be established with greater confidence.
Rapid Detection and Differentiation of Clinically Relevant Candida Species Simultaneously from Blood Culture by Use of a Novel Signal Amplification Approach
Authors: Ao Wanyuan , Klonoski Joshua , Berlinghoff Eric , Jensen Jordan , Afroz Taliman , Munns Denton , Lindsey Wes , Denys Gerald , Jenison Robert 
Published: October 2017

ABSTRACT

Fungal bloodstream infections are a significant problem in the United States, with an attributable mortality rate of up to 40%. An early diagnosis to direct appropriate therapy has been shown to be critical to reduce mortality rates. Conventional phenotypic methods for fungal detection take several days, which is often too late to impact outcomes. Herein, we describe a cost-effective multiplex assay platform for the rapid detection and differentiation of major clinically relevant
Candida
species directly from blood culture. This approach utilizes a novel biotin-labeled polymer-mediated signal amplification process combined with targeting rRNA to exploit phylogenetic differences for sensitive and unambiguous species identification; this assay detects seven pathogenic
Candida
species (
C. albicans
,
C. glabrata
,
C. parapsilosis
,
C. tropicalis
,
C. krusei
,
C. lusitaniae
, and
C. guilliermondii
) simultaneously with very high specificity to the species level in less than 80 min with the limits of detection at 1 × 10
3
to 10 × 10
3
CFU/ml or as few as 50 CFU per assay. The performance of the described assay was verified with 67 clinical samples (including mixed multiple-species infections as well), with an overall 100% agreement with matrix-assisted laser desorption ionization (MALDI) mass spectrometry-based reference results. By providing a species identity rapidly, the clinician is aided with information that may direct appropriate therapy sooner and more accurately than current approaches, including PCR-based tests.
An Improved Extended-Spectrum-β-Lactamase Detection Test Utilizing Aztreonam plus Clavulanate
Authors: Thomson Gina K. , Ayaz Maaz , Lutes Kelli , Thomson Kenneth S. 
Published: October 2017

ABSTRACT

Clinical laboratories test for extended-spectrum β-lactamases (ESBLs) for epidemiological and infection control purposes and also for the potential of cephalosporins to cause therapeutic failures. Testing can be problematic, because the CLSI does not recommend the testing of all producers of ESBLs and also falsely negative results may occur with isolates that coproduce AmpC. Boronic acid-supplemented tests can enhance ESBL detection in AmpC producers. Because aztreonam inhibits AmpCs, a study was designed to compare ESBL detection by the CLSI disk test (CLSI), a boronic acid-supplemented CLSI disk test (CLSI plus BA), and an aztreonam plus clavulanate disk test (ATM plus CA). The study tested 100 well-characterized
Enterobacteriaceae
,
Acinetobacter baumannii
, and
Pseudomonas aeruginosa
isolates. Seventy produced TEM, SHV, or CTX-M ESBLs, with 15 coproducing an AmpC and 11 coproducing a metallo-β-lactamase. Thirty ESBL-negative isolates were also tested. Tests were inoculated by CLSI methodology and interpreted as positive if an inhibitor caused a zone diameter increase of ≥5 mm. The percentages of ESBL producers detected were as follows: ATM plus CA, 95.7%; CLSI plus BA, 88.6%; and CLSI, 78.6%. When AmpC was coproduced, the sensitivities of the tests were as follows: ATM plus CA, 100%; CLSI plus BA, 93.3%; and CLSI, 60%. ATM plus CA also detected an ESBL in 90.1% of isolates that coproduced a metallo-β-lactamase. Falsely positive tests occurred only with the CLSI and CLSI plus BA tests. Overall, the ATM plus CA test detected ESBLs more accurately than the CLSI and CLSI plus BA tests, especially with isolates coproducing an AmpC or metallo-β-lactamase.
Mutations in the Influenza A Virus M1 Protein Enhance Virus Budding To Complement Lethal Mutations in the M2 Cytoplasmic Tail
Authors: Liu Hsuan , Grantham Michael L. , Pekosz Andrew 
Published: October 2017

ABSTRACT
The influenza A virus M1 and M2 proteins play important roles in virus assembly and in the morphology of virus particles. Mutations in the distal cytoplasmic tail region of M2, and in particular a tyrosine-to-alanine mutation at residue 76 (Y76A), were essential for infectious virus production and filament formation while having limited effects on total virus particle budding. Using a novel selection method, mutations at seven different M1 amino acids (residue 73, 94, 135, 136, or 138 or a double mutation, 93/244) that are not found in circulating influenza virus strains or have not been previously identified to play a role in influenza A virus assembly were found to complement the lethal M2Y76A mutation. These M1 suppressor mutations restored infectious virus production in the presence of M2Y76A and mediated increased budding and filament formation even in the absence of M2. However, the efficiency of infectious virus replication was still dependent on the presence of the distal region of the M2 cytoplasmic tail. The data suggest that influenza A virus budding and genome incorporation can occur independently and provide further support for complementary roles of the M1 and M2 proteins in virus assembly.

IMPORTANCE
Influenza virus particle assembly involves the careful coordination of various viral and host factors to optimally produce infectious virus particles. We have previously identified a mutation at position 76 of the influenza A virus M2 protein that drastically reduces infectious virus production and filament formation with minimal effects on virus budding. In this work, we identified suppressor mutations in the M1 protein which complement this lethal M2 mutation by increasing the efficiency with which virus particles bud from infected cells and restoring filament formation at the infected-cell surface. M2 distal cytoplasmic domain sequences were still required for optimal infectivity. This indicates that M1 and M2 can functionally replace each other in some, but not all, aspects of virus particle assembly.
Deep Sequencing of Foot-and-Mouth Disease Virus Reveals RNA Sequences Involved in Genome Packaging
Authors: Logan Grace , Newman Joseph , Wright Caroline F. , Lasecka-Dykes Lidia , Haydon Daniel T. , Cottam Eleanor M. , Tuthill Tobias J. 
Published: October 2017

ABSTRACT
Nonenveloped viruses protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses can involve interactions between capsid proteins and secondary structures in the viral genome, as exemplified by the RNA bacteriophage MS2 and as proposed for other RNA viruses of plants, animals, and human. In the picornavirus family of nonenveloped RNA viruses, the requirements for genome packaging remain poorly understood. Here, we show a novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in the picornavirus foot-and-mouth disease virus (FMDV). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA, we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem-loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses.

IMPORTANCE
In order to transmit their genetic material to a new host, nonenveloped viruses must protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. For many nonenveloped RNA viruses the requirements for this critical part of the viral life cycle remains poorly understood. We have identified RNA sequences involved in genome packaging of the picornavirus foot-and-mouth disease virus. This virus causes an economically devastating disease of livestock affecting both the developed and developing world. The experimental methods developed to carry out this work are novel, simple, and transferable to the study of packaging signals in other RNA viruses. Improved understanding of RNA packaging may lead to novel vaccine approaches or targets for antiviral drugs with broad-spectrum activity.
Structure-Function Dissection of Pseudorabies Virus Glycoprotein B Fusion Loops
Authors: Vallbracht Melina , Brun Delphine , Tassinari Matteo , Vaney Marie-Christine , Pehau-Arnaudet Gérard , Guardado-Calvo Pablo , Haouz Ahmed , Klupp Barbara G. , Mettenleiter Thomas C. , Rey Felix A. , Backovic Marija 
Published: October 2017

ABSTRACT

Conserved across the family
Herpesviridae
, glycoprotein B (gB) is responsible for driving fusion of the viral envelope with the host cell membrane for entry upon receptor binding and activation by the viral gH/gL complex. Although crystal structures of the gB ectodomains of several herpesviruses have been reported, the membrane fusion mechanism has remained elusive. Here, we report the X-ray structure of the pseudorabies virus (PrV) gB ectodomain, revealing a typical class III postfusion trimer that binds membranes via its fusion loops (FLs) in a cholesterol-dependent manner. Mutagenesis of FL residues allowed us to dissect those interacting with distinct subregions of the lipid bilayer and their roles in membrane interactions. We tested 15 gB variants for the ability to bind to liposomes and further investigated a subset of them in functional assays. We found that PrV gB FL residues Trp187, Tyr192, Phe275, and Tyr276, which were essential for liposome binding and for fusion in cellular and viral contexts, form a continuous hydrophobic patch at the gB trimer surface. Together with results reported for other alphaherpesvirus gBs, our data suggest a model in which Phe275 from the tip of FL2 protrudes deeper into the hydrocarbon core of the lipid bilayer, while the side chains of Trp187, Tyr192, and Tyr276 form a rim that inserts into the more superficial interfacial region of the membrane to catalyze the fusion process. Comparative analysis with gBs from beta- and gamma-herpesviruses suggests that this membrane interaction model is valid for gBs from all herpesviruses.

IMPORTANCE
Herpesviruses are common human and animal pathogens that infect cells by entering via fusion of viral and cellular membranes. Central to the membrane fusion event is glycoprotein B (gB), which is the most conserved envelope protein across the herpesvirus family. Like other viral fusion proteins, gB anchors itself in the target membrane via two polypeptide segments called fusion loops (FLs). The molecular details of how gB FLs insert into the lipid bilayer have not been described. Here, we provide structural and functional data regarding key FL residues of gB from pseudorabies virus, a porcine herpesvirus of veterinary concern, which allows us to propose, for the first time, a molecular model to understand how the initial interactions by gBs from all herpesviruses with target membranes are established.
Distribution of Hepatitis B Virus Nuclear DNA
Authors: Li Mingming , Sohn Ji A. , Seeger Christoph 
Published: October 2017

ABSTRACT

Chronic hepatitis B affects over 300 million people who are at risk of developing liver cancer. The basis for the persistence of hepatitis B virus (HBV) in hepatocytes, even in the presence of available antiviral therapies, lies in the accumulation of covalently closed circular DNA (cccDNA) in nuclei of infected cells. While methods for cccDNA quantification from liver biopsy specimens and cell lines expressing the virus are known, information about cccDNA formation, stability, and turnover is lacking. In particular, little is known about the fate of cccDNA during cell division. To fill the gaps in knowledge concerning cccDNA biology, we have developed a fluorescence imaging
in situ
hybridization (FISH)-based assay for the detection of duck hepatitis B virus (DHBV) cccDNA and HBV nuclear DNA in established cell lines. Using FISH, we determined the distribution of cccDNA under conditions mimicking chronic infections with and without antiviral therapy, which prevents
de novo
viral replication. Our results showed that the copy numbers of viral nuclear DNA can vary by as much as 1.8 orders of magnitude among individual cells and that antiviral therapy leads to a reduction in nuclear DNA in a manner consistent with symmetrical distribution of viral DNA to daughter cells.

IMPORTANCE
A mechanistic understanding of the stability of HBV cccDNA in the presence of antiviral therapy and during cell division induced by immune-mediated lysis of infected hepatocytes will be critical for the future design of curative antiviral therapies against chronic hepatitis B. Current knowledge about cccDNA stability was largely derived from quantitative analyses of cccDNA levels present in liver samples, and little was known about the fate of cccDNA in individual cells. The development of a FISH-based assay for cccDNA tracking provided the first insights into the fate of DHBV cccDNA and nuclear HBV DNA under conditions mimicking antiviral therapy.
Resistance of Major Histocompatibility Complex Class B (MHC-B) to Nef-Mediated Downregulation Relative to that of MHC-A Is Conserved among Primate Lentiviruses and Influences Antiviral T Cell Responses in HIV-1-Infected Individuals
Authors: Mwimanzi Francis , Toyoda Mako , Mahiti Macdonald , Mann Jaclyn K. , Martin Jeffrey N. , Bangsberg David , Brockman Mark A. , Goulder Philip , Kirchhoff Frank , Brumme Zabrina L. , Ndung'u Thumbi , Ueno Takamasa 
Published: October 2017

ABSTRACTPatient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate major histocompatibility complex class A (MHC-A) and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A, on average, 11 to 32% more efficiently than MHC-B. Nef genotype/phenotype analyses in a cohort of HIV-1 subtype C-infected patients (n= 168), together with site-directed mutagenesis, revealed Nef position 9 as a subtype-specific determinant of differential HLA-A versus HLA-B downregulation activity. Nef clones harboring nonconsensus variants at codon 9 downregulated HLA-B (though not HLA-A) significantly better than those harboring the consensus sequence at this site, resulting in reduced recognition of infected target cells by HIV-1-specific CD8+effector cellsin vitro. Among persons expressing protective HLA class I alleles, carriage of Nef codon 9 variants was also associated with reducedex vivoHIV-specific T cell responses. Our results demonstrate that Nef's inferior ability to downregulate MHC-B compared to that of MHC-A is conserved across primate lentiviruses and suggest that this property influences antiviral cellular immune responses.IMPORTANCEPrimate lentiviruses encode the Nef protein that plays an essential role in establishing persistent infection in their respective host species. Nef interacts with the cytoplasmic region of MHC-A and MHC-B molecules and downregulates them from the infected cell surface to escape recognition by host cellular immunity. Using a panel of Nef alleles isolated from diverse primate lentiviruses including pandemic HIV-1 group M subtypes, we demonstrate that Nef proteins across all lentiviral lineages downregulate MHC-A approximately 20% more effectively than MHC-B. We further identify a naturally polymorphic site at Nef position 9 that contributes to the MHC-B downregulation function in HIV-1 subtype C and show that carriage of Nef variants with enhanced MHC-B downregulation ability is associated with reduced breadth and magnitude of MHC-B-restricted cellular immune responses in HIV-infected individuals. Our study underscores an evolutionarily conserved interaction between lentiviruses and primate immune systems that may contribute to pathogenesis.
In Vitro
Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice
Authors: Sutton Troy C. , Lamirande Elaine W. , Bock Kevin W. , Moore Ian N. , Koudstaal Wouter , Rehman Muniza , Weverling Gerrit Jan , Goudsmit Jaap , Subbarao Kanta 
Published: October 2017

ABSTRACT

Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous pandemics. H2 influenza viruses represent a pandemic threat due to continued circulation in wild birds and limited immunity in the human population. In the event of a pandemic, antiviral agents are the mainstay for treatment, but broadly neutralizing antibodies (bNAbs) may be a viable alternative for short-term prophylaxis or treatment. The hemagglutinin stem binding bNAbs CR6261 and CR9114 have been shown to protect mice from severe disease following challenge with H1N1 and H5N1 and with H1N1, H3N2, and influenza B viruses, respectively. Early studies with CR6261 and CR9114 showed weak
in vitro
activity against human H2 influenza viruses, but the
in vivo
efficacy against H2 viruses is unknown. Therefore, we evaluated these antibodies against human- and animal-origin H2 viruses A/Ann Arbor/6/1960 (H2N2) (AA60) and A/swine/MO/4296424/06 (H2N3) (Sw06).
In vitro
, CR6261 neutralized both H2 viruses, while CR9114 only neutralized Sw06. To evaluate prophylactic efficacy, mice were given CR6261 or CR9114 and intranasally challenged 24 h later with lethal doses of AA60 or Sw06. Both antibodies reduced mortality, weight loss, airway inflammation, and pulmonary viral load. Using engineered bNAb variants, antibody-mediated cell cytotoxicity reporter assays, and Fcγ receptor-deficient (
Fcer1g
−/−
) mice, we show that the
in vivo
efficacy of CR9114 against AA60 is mediated by Fcγ receptor-dependent mechanisms. Collectively, these findings demonstrate the
in vivo
efficacy of CR6261 and CR9114 against H2 viruses and emphasize the need for
in vivo
evaluation of bNAbs.

IMPORTANCE
bNAbs represent a strategy to prevent or treat infection by a wide range of influenza viruses. The evaluation of these antibodies against H2 viruses is important because H2 viruses caused a pandemic in 1957 and could cross into humans again. We demonstrate that CR6261 and CR9114 are effective against infection with H2 viruses of both human and animal origin in mice, despite the finding that CR9114 did not display
in vitro
neutralizing activity against the human H2 virus. These findings emphasize the importance of
in vivo
evaluation and testing of bNAbs.
MicroRNA gga-miR-130b Suppresses Infectious Bursal Disease Virus Replication via Targeting of the Viral Genome and Cellular Suppressors of Cytokine Signaling 5
Authors: Fu Mengjiao , Wang Bin , Chen Xiang , He Zhiyuan , Wang Yongqiang , Li Xiaoqi , Cao Hong , Zheng Shijun J. 
Published: October 2017

ABSTRACT
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression posttranscriptionally through silencing or degrading their targets, thus playing important roles in the immune response. However, the role of miRNAs in the host response against infectious bursal disease virus (IBDV) infection is not clear. In this study, we show that the expression of a series of miRNAs was significantly altered in DF-1 cells after IBDV infection. We found that the miRNA gga-miR-130b inhibited IBDV replication via targeting the specific sequence of IBDV segment A and enhanced the expression of beta interferon (IFN-β) by targeting suppressors of cytokine signaling 5 (SOCS5) in host cells. These findings indicate that gga-miR-130b-3p plays a crucial role in host defense against IBDV infection.

IMPORTANCE
This work shows that gga-miR-130b suppresses IBDV replication via directly targeting the viral genome and cellular SOCS5, the negative regulator for type I interferon expression, revealing the mechanism underlying gga-miR-130-induced inhibition of IBDV replication. This information will be helpful for the understanding of how host cells combat pathogenic infection by self-encoded small RNA and furthers our knowledge of the role of microRNAs in the cell response to viral infection.