bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Advanced Melting Process for HLW Vitrification, Joule-Heated Ceramic-Lined Melter (JHCM) and Cold-Crucible Induction Melter (CCIM)
Authors: Sakai Akira , Koikegami Hajime , Weisenburger Siegfried , Roth Guenther , Kanehira Norio , Komamine Satoshi
Published: October 2017

High level waste (HLW) originating from reprocessing of spent fuel commercial power reactors contains more than 40 different elements. Vitrification into borosilicate glass at 1100 ∼1200°C is the process of choice. It is routinely used to immobilize the radioactive waste constituents in a chemically stable matrix for a final geological disposal.

Melting process for commercial HLW glasses are variants of two basic designs. (1) The joule-heated ceramic-lined melter (JHCM) originally developed in the United States in 1973 and used in several nuclear sites in the world. (2) The hot-walled induction melter (HWIM), developed in France starting in 1962 and used in France and UK. These technologies, while effective, do pose limitations in waste form compositions and throughput rates. Particularly HLW originating from commercial spent fuel reprocessing usually contains noble metals elements such as ruthenium (Ru), rhodium (Rh), and palladium (Pd) which require special attention when this waste is vitrified.

Recent advances to both of these baseline technologies are beginning to be used with large gains to ensure waste form flexibility, throughputs, and noble metals compatibility. The next generation JHCMs use a steeply sloped bottom and a subsidiary-heating bottom drain to allow these noble metals particles to be effectively flushed from the melter with higher waste loadings. Similar melters are being installed near Guangyuan/Sichuan province, China by German consortium team and being developed for the second K-Facility melter at Rokkasho by Japan Nuclear Fuel Limited (JNFL). As another example the advanced JHCMs will be installed in the Hanford WTP project having large glass pool surface area with rapid bubbling. Significant improvements on induction melters have also been implemented. AREVA recently installed a cold-crucible induction melter (CCIM) in combination with a rotary calciner at La Hague in France. This melter uses radio frequency induction to power the glass melt itself and water cooling of the outer surface maintains a frozen glass shell (skull) as the glass contact material. Because no permanent refractories or embedded electrodes are used, this design allows for high-temperature operation and can tolerate more corrosive melts, and uses a water-cooled, motor-driven mechanical stirrer to comply with noble metals behavior.

This paper highlights some of these advances and suggests potential advantages and disadvantages of these next generation melter technologies comparing advanced JHCM with updated CCIM. In conclusion, these melters have made the technologies of choice for new HLW vitrification projects around the world.
Study on the Restrictive Factors and Countermeasures of Developing China’s Nuclear Safety Registered Qualification System
Authors: Chen Fangqiang , Zhang Bo , Zhang Zhenhua , Wang Qingsong , Wang Chengzhi
Published: October 2017

In order to improve the technical level of nuclear and radiation safety personnel, strengthen the nuclear safety culture, safeguard nuclear and radiation safety, China established Registered Nuclear Safety Engineer Qualification License System (hereinafter referred to as the registered qualification system). The registered qualification system has been implemented for more than ten years. The paper briefly discusses the background and situation of the construction of the registered qualification system, introduces the achievements and problems, and focuses on the analysis of the key factors restricting the development of the registered qualification system. Finally, some pertinent suggestions are given.
Thermal-Hydraulic Analysis of Fuel Assembly With Inner Duct Structure of an Advanced Loop-Type Sodium-Cooled Fast Reactor Using ASFRE Code
Authors: Kikuchi Norihiro , Imai Yasutomo , Yoshikawa Ryuji , Doda Norihiro , Tanaka Masaaki , Ohshima Hiroyuki
Published: October 2017

In the design study of an advanced loop-type sodium-cooled fast reactor in Japan Atomic Energy Agency, a specific fuel assembly (FA) named FAIDUS (Fuel Assembly with Inner DUct Structure) has been adopted as one of the measures to enhance safety of the reactor during the core disruptive accident. Thermal-hydraulics evaluations in FAIDUS under various operation conditions are required to confirm its design feasibility. In this study, thermal-hydraulics in FAIDUS are investigated by using a subchannel analysis code ASFRE, which is applicable to a wire-wrapped fuel pin bundle with a distributed resistance model and a simplified turbulence mixing model. At first, the distributed resistance model was validated by comparison of pressure drop coefficients with experimental data obtained in water experiments with simulated FAs under the condition of wide-range Reynolds number. And then, the turbulence mixing model was validated by comparison of temperature distribution in the pin bundle with experimental data obtained in sodium experiments with simulated FAs. After the applicability of ASFRE to FAs was confirmed through these validations, thermal-hydraulic analyses of a FA with 271 fuel pins without the inner duct and a FAIDUS with 255 fuel pins were conducted. The obtained results indicate that no significant asymmetric temperature distribution occurs in a FAIDUS as a FA without an inner duct. In addition, the temperature distribution of FAIDUS with 255 fuel pins under the low flow rate condition tended to be the same as that of a FA with 271 fuel pins due to the local flow acceleration and the flow redistribution caused by the buoyancy force.
FPGA-Based Technologies Improving the Efficiency of Point to Point Communications in Safety-Related DCSs
Authors: Li Le , Ma Zhaoyang , Zhou Fei
Published: October 2017

As a part of a reactor protection system in safety-related Distributed Control Systems (DCSs) applied in nuclear power plants, Point to Point Communications (PPC) mostly influence the response time of shutdown of a nuclear reactor. A new solution to improve efficiency for point to point communications is receiving increased attention. In this paper, a FPGA-based point to point communications system is proposed, which extremely enhances the communication efficiency for the network communication card with multi-ports. It also delivers a method to meet the requirement of high safety and reliability. In addition, the contribution of shortening the response time of shutdown of a nuclear reactor is presented, which is derived from analysing and calculating the response time based on FirmSys, the first DCS with safety class 1E produced by China with proprietary intellectual property. A validation scheme is also established for verifying the new proposed FPGA-based point to point communications system. The validated platform is built based on the current FirmSys system. The experimental data and calculated result are present in the article. In conclusion, it is proved that the FPGA-based point to point communications could be used to promote the efficiency of point to point communications and shorten the response time of shutdown of a nuclear reactor.
A Heat Dissipation Simulation Study in a CFD Way on Spent Nuclear Fuel Dry Stored in Underground Vertical Shaft
Authors: Hong-jian Zhang , Ren Yu , Xiao-fan Liu
Published: October 2017

In order to ensure the thermal safety of the spent fuel stored in an underground vertical shaft, an air current heat dissipation is simulated in CFD way using ANSYS FLUENT code. Forced convection heat dissipation is focused in the research. The air current in the shaft and the temperature distribution on the surface of the spent fuel canister are calculated. The result confirms the reliability and security of the spent fuel dry storage. Finally, based on the calculating result, a support structure is designed, and the storage position of the spent fuel canister in vertical shaft is discussed, to optimize the decay heat removal of the spent fuel, and to ensure the temperature measuring point is set in a reasonable position.
Mixed Oxide LWR Assembly Design Optimization Using Differential Evolution Algorithms
Authors: Charles Alan J. , Parks Geoffrey T.
Published: October 2017

Two new multi-objective differential evolution (DE) algorithms are used to optimize heterogeneous low-enriched uranium + mixed oxide fuel assemblies for use in a pressurized water reactor. The objectives were to maximize plutonium content and minimize the power peaking factor. A performance comparison to a genetic algorithm is used to evaluate the applicability of DE algorithms to nuclear fuel assembly design optimization problems. Results show that DE performs highly competitively against a more established algorithm and can arguably better represent the trade-off between both objectives through greater variety in the number of different pin arrangements explored and a higher reliability in finding the ‘true’ Pareto-front.
Probabilistic Assessment of Countermeasures for Loss of Ultimate Heat Sink to Spent Fuel Pool
Authors: Fujioka Bumpei , Hirokawa Naoki , Taniguchi Daisuke
Published: October 2017

In the Fukushima Dai-ichi nuclear power station, Loss of Ultimate Heat Sink (LUHS) was caused by the great east japan earthquake and the subsequent tsunami [1]. It resulted in severe accident in three units. In that time, fuel damage in Spent Fuel Pool (SFP) were prevented by the various countermeasures such as makeup by pump truck and recovery of injection systems /cooling water system.

In the past, Probabilistic Safety Assessment (PSA) has been developed with a focus on the reactor. After the accident, it has been acknowledged that SFP PSA is important to enhance the plant safety.

In this study, probabilistic assessment is performed to suggest countermeasures for LUHS to SFP.
Structural Integrity Management of Pipelines Based on Monitoring of Slope Movements With Slow Strain Rates
Authors: Aristizábal Ceballos Jaime Hernan , Cháves Agudelo Julián Fernando , Torres Castro Camilo E.
Published: October 2017

In slope movements with slow strain rates that affect rights of way (ROW) or its surrounding areas, an appropriate Inline Inspection (ILI) program with inertial modules may provide timely and quality information, with ease of matching with geotechnical events and lower costs than conventional monitoring methods. In virtue of above, for structural integrity management of pipeline, this information is necessary and its integration with the information obtained from other sources such as ROW patrol, terrain monitoring and pipeline monitoring. This document contains information related to the tracing, analysis and executed activities in the study case located in Colombian center-west, where neotectonic effects and a common ROW with a main highway converged.
Analysis and Mitigation Techniques for Axial Landslides to Pipeline: Case Study KM 35+690 Ocensa
Authors: Ocampo Andrés , Hernandez Jon , Pereira Ordoñez Mauricio , Corrales Julian
Published: October 2017

The present paper presents the analysis, carried out by the Ocensa pipeline, against a case of longitudinal or axial landslide to the pipeline in the KM 35 + 690, starting from the identification by inertial tool, the geotechnical characterization and the analysis of Soil-pipe interaction, excavation and stress relief and the techniques used to mitigate the effects of sliding on the pipe.
Comprehensive vaccine design for commensal disease progression
Authors: Jones Charles H. , Zhang Guojian , Nayerhoda Roozbeh , Beitelshees Marie , Hill Andrew , Rostami Pooya , Li Yi , Davidson Bruce A. , Knight Paul , Pfeifer Blaine A.
Published: October 2017

A comprehensive design offers global pneumococcal vaccine coverage.
Destruction and reformation of an iron-sulfur cluster during catalysis by lipoyl synthase
Authors: McCarthy Erin L. , Booker Squire J.
Published: October 2017

Refueling an enzyme

Lipoic acid is an eight-carbon fatty acid in which sulfur groups are appended on two carbon atoms by the enzyme lipoyl synthase (LipA). LipA provides the sulfurs from an auxiliary [4Fe-4S] cluster. McCarthy and Booker show that in
Escherichia coli
, the auxiliary LipA cluster is reconstituted by the iron-sulfur cluster carrier protein NfuA (see the Perspective by Rosenzweig). This occurs fast enough that LipA can act catalytically in the final step of lipoic acid biosynthesis.

Science
, this issue p.
373
; see also p.
307
Ultraslow waves on the nanoscale
Authors: Tsakmakidis Kosmas L. , Hess Ortwin , Boyd Robert W. , Zhang Xiang
Published: October 2017

Slow light on the nanoscale

When light passes through an optical material, its speed is reduced by the refractive index of that material. Under exceptional circumstances, light can be slowed to a walking pace or even stopped momentarily. Exploring approaches for practical applications, Tsakmakidis
et al.
review how the speed of light can be controlled using designed materials and fabricated structures. They show how the combination of slow light and nanotechnology gives rise to a number of effects of interest in signal processing and optoelectronic communication.

Science
, this issue p.
eaan5196
Single polymer growth dynamics
Authors: Liu Chunming , Kubo Kaori , Wang Endian , Han Kyu-Sung , Yang Feng , Chen Guanqun , Escobedo Fernando A. , Coates Geoffrey W. , Chen Peng
Published: October 2017

Watching growth, step by step

Polymers can grow through the stepwise addition of monomers to an active end site. One might think that this would happen in a continuous linear process. With a focus on ring-opening metathesis polymerization of norbornene catalyzed by a Grubbs' catalyst, Liu
et al.
describe the growth of a single polymer chain. By attaching one end of a growing polymer to a bead exerting a constant force on it, they measured the extension occurring during the growth of the polymer. Oddly, the extension of the growing polymer did not increase continuously. Instead, it exhibited consecutive wait-and-jump steps, owing to conformational entanglements formed by newly incorporated monomers.

Science
, this issue p.
352
Rotary and linear molecular motors driven by pulses of a chemical fuel
Authors: Erbas-Cakmak Sundus , Fielden Stephen D. P. , Karaca Ulvi , Leigh David A. , McTernan Charlie T. , Tetlow Daniel J. , Wilson Miriam R.
Published: October 2017

Acid fuels the motion of a threaded ring

A central goal in the construction of molecular-scale machines is the efficient achievement of one-way motion. Erbas-Cakmak
et al.
developed a class of machines that transmit pH changes into the two-stage guided motion of molecular rings threaded on a linear or cyclic axle. The design relies on temporary blocking groups and landing sites along the axle that toggle between active and passive states in response to acid or base. Trichloroacetic acid initiates the first stage of motion until it is decomposed by base in the solution, spurring the second phase.

Science
, this issue p.
340
Quantum control of molecular collisions at 1 kelvin
Authors: Perreault William E. , Mukherjee Nandini , Zare Richard N.
Published: October 2017

Tracking collisions in just one beam

Much of what we know about how quantum mechanics dictates chemical dynamics comes from half a century of studying controlled collisions between crossed pairs of molecular beams. Perreault
et al.
now show that even finer detail emerges in a study of hydrogen-deuterium (HD) collisions with D
2
in a single beam. The experimental setup lowers the collision temperature to ∼1 K, allowing precise control over the rotational energy and relative alignment of the colliding partners. Scattering events in which HD loses rotational energy occurred three times as readily if the HD was aligned perpendicular rather than parallel to the beam-propagation axis.

Science
, this issue p.
356
Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus Diversity and Evolution
Authors: Renner Daniel W. , Szpara Moriah L.
Published: October 2017

Until fairly recently, genome-wide evolutionary dynamics and within-host diversity were more commonly examined in the context of small viruses than in the context of large double-stranded DNA viruses such as herpesviruses. The high mutation rates and more compact genomes of RNA viruses have inspired the investigation of population dynamics for these species, and recent data now suggest that herpesviruses might also be considered candidates for population modeling. High-throughput sequencing (HTS) and bioinformatics have expanded our understanding of herpesviruses through genome-wide comparisons of sequence diversity, recombination, allele frequency, and selective pressures. Here we discuss recent data on the mechanisms that generate herpesvirus genomic diversity and underlie the evolution of these virus families. We focus on human herpesviruses, with key insights drawn from veterinary herpesviruses and other large DNA virus families. We consider the impacts of cell culture on herpesvirus genomes and how to accurately describe the viral populations under study. The need for a strong foundation of high-quality genomes is also discussed, since it underlies all secondary genomic analyses such as RNA sequencing (RNA-Seq), chromatin immunoprecipitation, and ribosome profiling. Areas where we foresee future progress, such as the linking of viral genetic differences to phenotypic or clinical outcomes, are highlighted as well.
Mechanisms of HERV-K (HML-2) Transcription during Human Mammary Epithelial Cell Transformation
Authors: Montesion Meagan , Bhardwaj Neeru , Williams Zachary H. , Kuperwasser Charlotte , Coffin John M.
Published: October 2017

Increasing evidence suggests that repetitive elements may play a role in host gene regulation, particularly through the donation of alternative promoters, enhancers, splice sites, and termination signals. Elevated transcript expression of the endogenous retrovirus group HERV-K (HML-2) is seen in many human cancers, although the identities of the individual proviral loci contributing to this expression as well as their mechanisms of activation have been unclear. Using high-throughput next-generation sequencing techniques optimized for the capture of HML-2 expression, we characterized the HML-2 transcriptome and means of activation in an
in vitro
model of human mammary epithelial cell transformation. Our analysis showed significant expression originating from 15 HML-2 full-length proviruses, through four modes of transcription. The majority of expression was in the antisense orientation and from proviruses integrated within introns. We found two instances of long terminal repeat (LTR)-driven provirus transcription but no evidence to suggest that these active 5′ LTRs were influencing nearby host gene expression. Importantly, LTR-driven transcription was restricted to tumorigenic cells, suggesting that LTR promoter activity is dependent upon the transcriptional environment of a malignant cell.

IMPORTANCE
Here, we use an
in vitro
model of human mammary epithelial cell transformation to assess how malignancy-associated shifts in the transcriptional milieu of a cell may impact HML-2 activity. We found 15 proviruses to be significantly expressed through four different mechanisms, with the majority of transcripts being antisense copies of proviruses located within introns. We saw active 5′ LTR use in tumorigenic cells only, suggesting that the cellular environment of a cancer cell is a critical component for induction of LTR promoter activity. These findings have implications for future studies investigating HML-2 as a target for immunotherapy or as a biomarker for disease.
Rice Stripe Tenuivirus Has a Greater Tendency To Use the Prime-and-Realign Mechanism in Transcription of Genomic than in Transcription of Antigenomic Template RNAs
Authors: Liu Xiaojuan , Jin Jing , Qiu Ping , Gao Fangluan , Lin Wenzhong , Xie Guohui , He Simiao , Liu Shunmin , Du Zhenguo , Wu Zujian
Published: October 2017

Most segmented negative-sense RNA viruses employ a process termed cap snatching, during which they snatch capped RNA leaders from host cellular mRNAs and use the snatched leaders as primers for transcription, leading to the synthesis of viral mRNAs with 5′ heterogeneous sequences (HSs). With traditional methods, only a few HSs can be determined, and identification of their donors is difficult. Here, the mRNA 5′ ends of
Rice stripe tenuivirus
(RSV) and
Rice grassy stunt tenuivirus
(RGSV) and those of their host rice were determined by high-throughput sequencing. Millions of tenuiviral HSs were obtained, and a large number of them mapped to the 5′ ends of corresponding host cellular mRNAs. Repeats of the dinucleotide AC, which are complementary to the U
1
G
2
of the tenuiviral template 3′-U
1
G
2
U
3
G
4
UUUCG, were found to be prevalent at the 3′ termini of tenuiviral HSs. Most of these ACs did not match host cellular mRNAs, supporting the idea that tenuiviruses use the prime-and-realign mechanism during cap snatching. We previously reported a greater tendency of RSV than RGSV to use the prime-and-realign mechanism in transcription with leaders cap snatched from a coinfecting reovirus. Besides confirming this observation in natural tenuiviral infections, the data here additionally reveal that RSV has a greater tendency to use this mechanism in transcribing genomic than in transcribing antigenomic templates. The data also suggest that tenuiviruses cap snatch host cellular mRNAs from translation- and photosynthesis-related genes, and capped RNA leaders snatched by tenuiviruses base pair with U
1
/U
3
or G
2
/G
4
of viral templates. These results provide unprecedented insights into the cap-snatching process of tenuiviruses.

IMPORTANCE
Many segmented negative-sense RNA viruses (segmented NSVs) are medically or agriculturally important pathogens. The cap-snatching process is a promising target for the development of antiviral strategies against this group of viruses. However, many details of this process remain poorly characterized. Tenuiviruses constitute a genus of agriculturally important segmented NSVs, several members of which are major viral pathogens of rice. Here, we for the first time adopted a high-throughput sequencing strategy to determine the 5′ heterogeneous sequences (HSs) of tenuiviruses and mapped them to host cellular mRNAs. Besides providing deep insights into the cap snatching of tenuiviruses, the data obtained provide clear evidence to support several previously proposed models regarding cap snatching. Curiously and importantly, the data here reveal that not only different tenuiviruses but also the same tenuivirus synthesizing different mRNAs use the prime-and-realign mechanism with different tendencies during their cap snatching.
Flow Cytometric Detection of PrPScin Neurons and Glial Cells from Prion-Infected Mouse Brains
Authors: Yamasaki Takeshi , Suzuki Akio , Hasebe Rie , Horiuchi Motohiro
Published: October 2017

In prion diseases, an abnormal isoform of prion protein (PrPSc) accumulates in neurons, astrocytes, and microglia in the brains of animals affected by prions. Detailed analyses of PrPSc-positive neurons and glial cells are required to clarify their pathophysiological roles in the disease. Here, we report a novel method for the detection of PrPScin neurons and glial cells from the brains of prion-infected mice by flow cytometry using PrPSc-specific staining with monoclonal antibody (MAb) 132. The combination of PrPScstaining and immunolabeling of neural cell markers clearly distinguished neurons, astrocytes, and microglia that were positive for PrPScfrom those that were PrPScnegative. The flow cytometric analysis of PrPScrevealed the appearance of PrPSc-positive neurons, astrocytes, and microglia at 60 days after intracerebral prion inoculation, suggesting the presence of PrPScin the glial cells, as well as in neurons, from an early stage of infection. Moreover, the kinetic analysis of PrPScrevealed a continuous increase in the proportion of PrPSc-positive cells for all cell types with disease progression. Finally, we applied this method to isolate neurons, astrocytes, and microglia positive for PrPScfrom a prion-infected mouse brain by florescence-activated cell sorting. The method described here enables comprehensive analyses specific to PrPSc-positive neurons, astrocytes, and microglia that will contribute to the understanding of the pathophysiological roles of neurons and glial cells in PrPSc-associated pathogenesis.

IMPORTANCEAlthough formation of PrPScin neurons is associated closely with neurodegeneration in prion diseases, the mechanism of neurodegeneration is not understood completely. On the other hand, recent studies proposed the important roles of glial cells in PrPSc-associated pathogenesis, such as the intracerebral spread of PrPScand clearance of PrPScfrom the brain. Despite the great need for detailed analyses of PrPSc-positive neurons and glial cells, methods available for cell type-specific analysis of PrPSchave been limited thus far to microscopic observations. Here, we have established a novel high-throughput method for flow cytometric detection of PrPScin cells with more accurate quantitative performance. By applying this method, we succeeded in isolating PrPSc-positive cells from the prion-infected mouse brains via fluorescence-activated cell sorting. This allows us to perform further detailed analysis specific to PrPSc-positive neurons and glial cells for the clarification of pathological changes in neurons and pathophysiological roles of glial cells.
Murine Hepatitis Virus nsp14 Exoribonuclease Activity Is Required for Resistance to Innate Immunity
Authors: Case James Brett , Li Yize , Elliott Ruth , Lu Xiaotao , Graepel Kevin W. , Sexton Nicole R. , Smith Everett Clinton , Weiss Susan R. , Denison Mark R.
Published: October 2017

Coronaviruses (CoVs) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that counteract the host innate immune response to facilitate efficient viral replication. CoV nonstructural protein 14 (nsp14) encodes 3′-to-5′ exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order
Nidovirales
, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade double-stranded RNA (dsRNA) replication intermediates. In this study, we tested the hypothesis that CoV ExoN also functions to antagonize the innate immune response. We demonstrate that viruses lacking ExoN activity [ExoN(−)] are sensitive to cellular pretreatment with interferon beta (IFN-β) in a dose-dependent manner. In addition, ExoN(−) virus replication was attenuated in wild-type bone marrow-derived macrophages (BMMs) and partially restored in interferon alpha/beta receptor-deficient (IFNAR
−/−
) BMMs. ExoN(−) virus replication did not result in IFN-β gene expression, and in the presence of an IFN-β-mediated antiviral state, ExoN(−) viral RNA levels were not substantially reduced relative to those of untreated samples. However, ExoN(−) virus generated from IFN-β-pretreated cells had reduced specific infectivity and decreased relative fitness, suggesting that ExoN(−) virus generated during an antiviral state is less viable to establish a subsequent infection. Overall, our data suggest murine hepatitis virus (MHV) ExoN activity is required for resistance to the innate immune response, and antiviral mechanisms affecting the viral RNA sequence and/or an RNA modification act on viruses lacking ExoN activity.

IMPORTANCE
CoVs encode multiple antagonists that prevent or disrupt an efficient innate immune response. Additionally, no specific antiviral therapies or vaccines currently exist for human CoV infections. Therefore, the study of CoV innate immune antagonists is essential for understanding how CoVs overcome host defenses and to maximize potential therapeutic interventions. Here, we sought to determine the contributions of nsp14 ExoN activity in the induction of and resistance to the innate immune response. We show that viruses lacking nsp14 ExoN activity are more sensitive than wild-type MHV to restriction by exogenous IFN-β and that viruses produced in the presence of an antiviral state are less capable of establishing a subsequent viral infection. Our results support the hypothesis that murine hepatitis virus ExoN activity is required for resistance to the innate immune response.
Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes
Authors: Choi Won-Suk , Jeong Ju Hwan , Kwon Jin Jung , Ahn Su Jeong , Lloren Khristine Kaith S. , Kwon Hyeok-Il , Chae Hee Bok , Hwang Jungwon , Kim Myung Hee , Kim Chul-Joong , Webby Richard J. , Govorkova Elena A. , Choi Young Ki , Baek Yun Hee , Song Min-Suk
Published: October 2017

Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited, and markers of resistance are poorly understood. Previously, we identified unique NAI resistance substitutions in AIVs of the N3, N7, and N9 NA subtypes. Here, we report profiles of NA substitutions that confer NAI resistance in AIVs of the N4, N5, N6, and N8 NA subtypes using gene-fragmented random mutagenesis. We generated libraries of mutant influenza viruses using reverse genetics (RG) and selected resistant variants in the presence of the NAIs oseltamivir carboxylate and zanamivir in MDCK cells. In addition, two substitutions, H274Y and R292K (N2 numbering), were introduced into each NA gene for comparison. We identified 37 amino acid substitutions within the NA gene, 16 of which (4 in N4, 4 in N5, 4 in N6, and 4 in N8) conferred resistance to NAIs (oseltamivir carboxylate, zanamivir, or peramivir) as determined using a fluorescence-based NA inhibition assay. Substitutions conferring NAI resistance were mainly categorized as either novel NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K). Our results demonstrate that each NA subtype possesses unique NAI resistance markers, and knowledge of these substitutions in AIVs is important in facilitating antiviral susceptibility monitoring of NAI resistance in AIVs.

IMPORTANCEThe frequency of human infections with avian influenza viruses (AIVs) has increased in recent years. Despite the availability of vaccines, neuraminidase inhibitors (NAIs), as the only available class of drugs for AIVs in humans, have been constantly used for treatment, leading to the inevitable emergence of drug-resistant variants. To screen for substitutions conferring NAI resistance in AIVs of N4, N5, N6, and N8 NA subtypes, random mutations within the target gene were generated, and resistant viruses were selected from mutant libraries in the presence of individual drugs. We identified 16 NA substitutions conferring NAI resistance in the tested AIV subtypes; some are novel and subtype specific, and others have been previously reported in other subtypes. Our findings will contribute to an increased and more comprehensive understanding of the mechanisms of NAI-induced inhibition of influenza virus and help lead to the development of drugs that bind to alternative interaction motifs.
Foamy Virus Vector Carries a Strong Insulator in Its Long Terminal Repeat Which Reduces Its Genotoxic Potential
Authors: Goodman Michael Aaron , Arumugam Paritha , Pillis Devin Marie , Loberg Anastacia , Nasimuzzaman Mohammed , Lynn Danielle , van der Loo Johannes Christiaan Maria , Dexheimer Phillip Joseph , Keddache Mehdi , Bauer Thomas Roy , Hickstein Dennis Durand , Russell David William , Malik Punam
Published: October 2017

Strong viral enhancers in gammaretrovirus vectors have caused cellular proto-oncogene activation and leukemia, necessitating the use of cellular promoters in “enhancerless” self-inactivating integrating vectors. However, cellular promoters result in relatively low transgene expression, often leading to inadequate disease phenotype correction. Vectors derived from foamy virus, a nonpathogenic retrovirus, show higher preference for nongenic integrations than gammaretroviruses/lentiviruses and preferential integration near transcriptional start sites, like gammaretroviruses. We found that strong viral enhancers/promoters placed in foamy viral vectors caused extremely low immortalization of primary mouse hematopoietic stem/progenitor cells compared to analogous gammaretrovirus/lentivirus vectors carrying the same enhancers/promoters, an effect not explained solely by foamy virus' modest insertional site preference for nongenic regions compared to gammaretrovirus/lentivirus vectors. Using CRISPR/Cas9-mediated targeted insertion of analogous proviral sequences into the
LMO2
gene and then measuring
LMO2
expression, we demonstrate a sequence-specific effect of foamy virus, independent of insertional bias, contributing to reduced genotoxicity. We show that this effect is mediated by a 36-bp insulator located in the foamy virus long terminal repeat (LTR) that has high-affinity binding to the CCCTC-binding factor. Using our LMO2 activation assay,
LMO2
expression was significantly increased when this insulator was removed from foamy virus and significantly reduced when the insulator was inserted into the lentiviral LTR. Our results elucidate a mechanism underlying the low genotoxicity of foamy virus, identify a novel insulator, and support the use of foamy virus as a vector for gene therapy, especially when strong enhancers/promoters are required.

IMPORTANCE
Understanding the genotoxic potential of viral vectors is important in designing safe and efficacious vectors for gene therapy. Self-inactivating vectors devoid of viral long-terminal-repeat enhancers have proven safe; however, transgene expression from cellular promoters is often insufficient for full phenotypic correction. Foamy virus is an attractive vector for gene therapy. We found foamy virus vectors to be remarkably less genotoxic, well below what was expected from their integration site preferences. We demonstrate that the foamy virus long terminal repeats contain an insulator element that binds CCCTC-binding factor and reduces its insertional genotoxicity. Our study elucidates a mechanism behind the low genotoxic potential of foamy virus, identifies a unique insulator, and supports the use of foamy virus as a vector for gene therapy.
Viperin Targets Flavivirus Virulence by Inducing Assembly of Noninfectious Capsid Particles
Authors: Vonderstein Kirstin , Nilsson Emma , Hubel Philipp , Nygård Skalman Larsård , Upadhyay Arunkumar , Pasto Jenny , Pichlmair Andreas , Lundmark Richard , Överby Anna K.
Published: October 2017

Efficient antiviral immunity requires interference with virus replication at multiple layers targeting diverse steps in the viral life cycle. We describe here a novel flavivirus inhibition mechanism that results in interferon-mediated obstruction of tick-borne encephalitis virus particle assembly and involves release of malfunctioning membrane-associated capsid (C) particles. This mechanism is controlled by the activity of the interferon-induced protein viperin, a broad-spectrum antiviral interferon-stimulated gene. Through analysis of the viperin-interactome, we identified the Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) as the cellular protein targeted by viperin. Viperin-induced antiviral activity, as well as C-particle release, was stimulated by GBF1 inhibition and knockdown and reduced by elevated levels of GBF1. Our results suggest that viperin targets flavivirus virulence by inducing the secretion of unproductive noninfectious virus particles via a GBF1-dependent mechanism. This as-yet-undescribed antiviral mechanism allows potential therapeutic intervention.

IMPORTANCE
The interferon response can target viral infection on almost every level; however, very little is known about the interference of flavivirus assembly. We show here that interferon, through the action of viperin, can disturb the assembly of tick-borne encephalitis virus. The viperin protein is highly induced after viral infection and exhibit broad-spectrum antiviral activity. However, the mechanism of action is still elusive and appears to vary between the different viruses, indicating that cellular targets utilized by several viruses might be involved. In this study, we show that viperin induces capsid particle release by interacting and inhibiting the function of the cellular protein Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1). GBF1 is a key protein in the cellular secretory pathway and is essential in the life cycle of many viruses, also targeted by viperin, implicating GBF1 as a novel putative drug target.
Asymmetrical accommodation in hyperopic anisometropic amblyopia
Authors: Toor Sonia , Horwood Anna M , Riddell Patricia
Published: October 2017

Background/aims

To investigate the presence of asymmetrical accommodation in hyperopic anisometropic amblyopia.

Methods

Accommodation in each eye and binocular vergence were measured simultaneously using a PlusoptiX SO4 photorefractor in 26 children aged 4–8 years with hyperopic anisometropic amblyopia and 13 controls (group age-matched) while they viewed a detailed target moving in depth.

Results

Without spectacles, only 5 (19%) anisometropes demonstrated symmetrical accommodation (within the 95% CI of the mean gain of the sound eye of the anisometropic group), whereas 21 (81%) demonstrated asymmetrical accommodation. Of those, 15 (58%) showed aniso-accommodation and 6 (23%) demonstrated ‘anti-accommodation’ (greater accommodation for distance than for near). In those with anti-accommodation, the response gain in the sound eye was (0.93±0.20) while that of the amblyopic eye showed a negative accommodation gain of (−0.44±0.23). Anti-accommodation resolved with spectacles. Vergence gains were typical in those with symmetrical and asymmetrical accommodation.

Conclusion

The majority of hyperopic anisometropic amblyopes demonstrated non-consensual asymmetrical accommodation. Approximately one in four demonstrated anti-accommodation.
How does sevoflurane induction, followed by a ketamine maintenance infusion, affect intraocular pressure? Establishment of an anaesthetic protocol for paediatric glaucoma examinations under anaesthesia
Authors: van der Walt Jessica Gwendoline , Roodt Francois , Tinley Christopher
Published: October 2017

Accurate measurement of intraocular pressure (IOP) is essential in paediatric glaucoma management. Children require serial measurements and examination under anaesthesia (EUA). Most anaesthetic agents reduce IOP, and the ideal time to measure IOP under anaesthesia is questionable.

Study purpose

To determine the effect of sevoflurane induction, followed by intravenous ketamine infusion on IOP, in children undergoing EUA for glaucoma or suspected glaucoma, and to establish the earliest time point at which reliable, repeatable IOP measurements can be obtained under anaesthesia.

Method

A prospective, descriptive study of IOP changes occurring in children requiring EUAs. A standardised anaesthetic protocol: sevoflurane induction, intravenous cannulation, 2 mg/kg intravenous ketamine bolus and 4 mg/kg/hour maintenance for 15 min. IOP measurements (taken supine with a Perkins applanation tonometer) and physiological variables were recorded.

Results

IOPs were measured in 25 children (50 eyes). Twenty-six eyes (52%) were glaucomatous. Mean patient age was 29 months (2–88 months). Physiological variables returned to baseline at 8 min, correlating with recorded sevoflurane elimination. Mean IOP after sevoflurane induction was 3.68 mm Hg lower than with ketamine maintenance at 15 min (95% CI 1.35 to 6.02 mm Hg) (p=0.002). Contrastingly, the difference in IOP between ketamine anaesthesia at 15 min and near wakefulness was 0.28 mm Hg (95% CI −2.23 to 2.79 mm Hg) (p=0.826).

Conclusion

Sevoflurane’s IOP-lowering effect is reversed 15 min after the discontinuation of the inhalational gas, if anaesthesia is maintained with an intravenous ketamine infusion. IOP measurements appear to stabilise at this time point until the point of near wakefulness and may reflect awake values.
Thermal properties of engineered barriers for a Canadian deep geological repository
Authors: Abootalebi Pedram , Siemens Greg
Published: October 2017

Global energy needs continue to rise along with society’s desire for carbon-reduced energy sources to limit climate change effects. One viable carbon-reduced energy source is nuclear power, which provides more than half the electricity requirements of the province of Ontario. Within Canada there are more than 2.5 million bundles of spent nuclear fuel, which will be stored in a deep geological repository. Efficiency of the repository system depends on dissipation of thermal energy. A comprehensive experimental study is presented on thermal properties of barrier materials. The influence of bentonite type, variability, moisture, and temperature on thermal properties is examined. Results show strong influence of moisture on thermal properties, some influence of temperature on low-density bentonite, minor influence of bentonite type, as well as low variability in the experimental measurements. The extensive database of physical measurements is compared with values from the literature and then used to statistically evaluate thermal property models selected from the literature. Using the base parameters from the literature, thermal property models performed adequately; however, soil-specific calibration of the model inputs improved the fit significantly. These results are now available to perform the numerical models for the proposed Canadian deep geological repository for used nuclear fuel.
Chow rings of Mp̃0,2(N,d) and M¯0,2(ℙN−1,d) and Gromov–Witten invariants of projective hypersurfaces of degree 1 and 2
Authors: Saito Hayato
Published: October 2017

In this paper, we prove formulas that represent two-pointed Gromov–Witten invariant [Formula: see text] of projective hypersurfaces with [Formula: see text] in terms of Chow ring of [Formula: see text], the moduli spaces of stable maps from genus [Formula: see text] stable curves to projective space [Formula: see text]. Our formulas are based on representation of the intersection number [Formula: see text], which was introduced by Jinzenji, in terms of Chow ring of [Formula: see text], the moduli space of quasi maps from [Formula: see text] to [Formula: see text] with two marked points. In order to prove our formulas, we use the results on Chow ring of [Formula: see text], that were derived by Mustaţǎ and Mustaţǎ. We also present explicit toric data of [Formula: see text] and prove relations of Chow ring of [Formula: see text].
The complete classification of a class of conformally flat Lorentzian hypersurfaces in ℝ14
Authors: Xie Zhenxiao , Wang Changping , Wang Xiaozhen
Published: October 2017

A three-dimensional Lorentzian hypersurface [Formula: see text] is called conformally flat if its induced metric is conformal to the flat Lorentzian metric, this property is preserved under the conformal transformation of [Formula: see text]. In this paper, using the projective light-cone model, we give a complete classification of those ones whose shape operators have two distinct real eigenvalues and cannot be diagonalizable. These hypersurfaces are conformal equivalent to cones, cylinders, or rotational hypersurfaces generated by B-scrolls (over null Frenet curves) in three-dimensional Lorentzian space forms.
The sigma meson from lattice QCD with two-pion interpolating operators
Authors: Howarth Dean , Giedt Joel
Published: October 2017

In this paper, we describe our studies of the sigma meson, [Formula: see text], using two-pion correlation functions. We use lattice quantum chromodynamics in the quenched approximation with so-called clover fermions. By working at unphysical pion masses we are able to identify a would-be resonance with mass less than [Formula: see text], and then extrapolate to the physical point. We include the most important annihilation diagram, which is “partially disconnected” or “single annihilation”. Because this diagram is quite expensive to compute, we introduce a somewhat novel technique for the computation of all-to-all diagrams, based on momentum sources and a truncation in momentum space. In practice, we use only [Formula: see text] modes, so the method reduces to wall sources. At the point where the mass of the pion takes its physical value, we find a resonance in the [Formula: see text] two-pion channel with a mass of approximately [Formula: see text] MeV, consistent with the expected properties of the sigma meson, given the approximations we are making.
Gravitational lensing by exotic objects
Authors: Asada Hideki
Published: October 2017

This paper reviews a phenomenological approach to the gravitational lensing by exotic objects such as the Ellis wormhole lens, where the exotic lens objects may follow a non-standard form of the equation of state or may obey a modified gravity theory. A gravitational lens model is proposed in the inverse powers of the distance, such that the Schwarzschild lens and exotic lenses can be described in a unified manner as a one parameter family. As observational implications, the magnification, shear, photo-centroid motion and time delay in this lens model are discussed.
Sign Language Fingerspelling Recognition Using Depth Information and Deep Belief Networks
Authors: Hu Yong , Zhao Hai-Feng , Wang Zhi-Gang
Published: October 2017

In the sign language fingerspelling scheme, letters in the alphabet are presented by a distinctive finger shape or movement. The presented work is conducted for autokinetic translating fingerspelling signs to text. A recognition framework by using intensity and depth information is proposed and compared with some distinguished works. Histogram of Oriented Gradients (HOG) and Zernike moments are used as discriminative features due to their simplicity and good performance. A Deep Belief Network (DBN) composed of three Restricted Boltzmann Machines (RBMs) is used as a classifier. Experiments are executed on a challenging database, which consists of 120,000 pictures representing 24 alphabet letters over five different users. The proposed approach obtained higher average accuracy, outperforming all other methods. This indicates the effectiveness and the abilities of the proposed framework.
An Improved Adaptive Level Set Method for Image Segmentation
Authors: Zhang Li , Wu Kai-Teng , Li Ping
Published: October 2017

In order to improve the accuracy of image segmentation, an improved adaptive level set method is proposed based on level set evolution without re-initialization method and adaptive distance preserving level set evolution method. A new definition of weight coefficient in evolution equations is the main innovation of this paper. The improved method can detect certain object boundaries, interior and exterior contours of an object, edges of multi-objects and weak boundaries of an object by synthetic and real images numerical experiments. Numerical results show that the improved adaptive level set method has faster segmentation speed and higher segmentation accuracy compared with the previous two methods, especially in weak boundaries and edges of multi-objects segmentation problems.