bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanical Behavior of a Balloon-Expandable Stent in a Stenotic Artery
Authors: Imani Misagh , Goudarzi A. M. , Ganji D. D. , Gerdroodbary M. Barzegar
Published: October 2014

The implantation of intravascular stent is a kind of coronary angioplasty to restore the blood flow perfusion to the downstream of the heart muscle tissue. Stent implantation is a mechanical procedure, the success of which depends to a good understanding of its mechanical behavior during the deployment. Computational studies may be used to investigate the mechanical behavior of stents and to determine the biomechanical interaction between the stent and the artery in a stenting procedure. The aim of this paper is to investigate the expansion characteristics of a certain stent as it is deployed and implanted in an artery containing a plaque, and try to reach to a model close to a real condition of stent implantation. Unlike most of the models proposed in the literature, all the steps of the deployment of a stent in the stenotic vessel (i.e. pressure increasing, constant load pressure and pressure decreasing) are simulated in this paper to show the behavior of stent in different stages of implantation. Results include stress distribution, radial gain, outer diameter changes, dogboning and foreshortening. According to the findings, the first step of deployment, i.e. pressure increasing, play a main role in the success of stent implantation.
Application of Recent Variance Expressions Associated With Binary Markov Processes for Detecting Changes in Bandwidth and Power With Application to Health Monitoring
Authors: Sherman Peter J.
Published: October 2014

Health condition monitoring often entails monitoring and detecting changes in the structure of associated random processes. A common trigger for an alarm is when the process amplitude exceeds a specified threshold for a certain period of time. A less common trigger for an alarm is when the process bandwidth changes significantly. This latter type of change occurs, for example, in EEG just prior to the onset of an epileptic seizure [Sherman (2008)]. One can monitor the process directly, or one can convert the process to a 0/1 process where 0 denotes ‘within’ and 1 denotes ‘outside of’ a specified tolerance. Such a process is given many names. One is a binary process, another is a Bernoulli process. If the underlying process is a Gauss-Markov process, then the associated 0/1 process becomes a Markov 0/1 process. The main parameters associated with such a process are the following probabilities: (i), (ii), and (iii). In this work we use the variance expressions for the estimators of these probabilities that were reported in Sherman (2011), in order to detect changes with specified false alarm probabilities. We demonstrate their value in detecting bandwidth change via zero-crossing estimates, and detecting amplitude change via threshold excursion estimates.
Android Hands: A State-of-the-Art Report
Authors: Vlachos Evgenios , Schärfe Henrik
Published: October 2014

Humans have adjusted their space, their actions, and their performed tasks according to their morphology, abilities, and limitations. Thus, the properties of a social robot should fit within these predetermined boundaries when, and if it is beneficial for the user, and the notion of the task. On such occasions, android and humanoid hand models should have similar structure, functions, and performance as the human hand. In this paper we present the anatomy, and the key functionalities of the human hand followed by a literature review on android/humanoid hands for grasping and manipulating objects, as well as prosthetic hands, in order to inform roboticists about the latest available technology, and assist their efforts to describe the state-of-the-art in this field.
Free Vibration of Micro Cantilever Beam With Electromagnetic Actuators
Authors: Askari Hassan , Esmailzadeh Ebrahim
Published: October 2014

Free vibration of cantilever beam with an electromagnetic actuator is studied. The governing equation of motion of the system is developed and the electromagnetic actuation part is added to the system. The system is modeled by 1DOF vibration mode. Three different analytical solution methods, namely, Krylov and Bogoliubov, Energy Balance and Modified Energy Balance are utilized to obtain the equations of motion and the frequency response of the system. Expression for the fundamental frequency is obtained using different types of analytical procedures. Frequency responses of the system are obtained using different numerical methods and the accuracy of the proposed approaches is studied. The influence of the initial conditions on the system performance is studied and the point where, the system starts to show an unstable behavior and quasi-periodic response is identified. Phase-plane trajectories are presented to elaborately analyze the dynamical behaviors of the system. Variations of the natural frequencies for different values of actuation parameter and the initial conditions are plotted to reveal the sensitivity of the objective system.
FORM Based Reliability Analysis With Accurate Sensitivity for Heat Conduction
Authors: Jin Weiya , Dennis Brian H. , He Xing , Wang Bo Ping , Gao Zengliang
Published: October 2014

The numerical analysis of heat transfer by finite element method (FEM) has been used widely. It is usually assumed that the parameters relevant to the heat transfer process are accurately known. However, many of these parameters may vary in a random way in reality. The reliability of the heat transfer performance is needed to be evaluated. The paper introduces an accurate, efficient sensitivity analysis method to compute the FEM response with respect to input parameters. Combining this sensitivity analysis, first order reliability method (FORM) algorithm based stochastic finite element method (SFEM) method is used to evaluate the reliability of the limit state for heat conduction of a benchmark plate with input uncertainties.
Using Parabolic Trough Concentrators With Tracking System for Heating Residential Water
Authors: Ramadan Mohamad , Khaled Mahmoud , Abdulhay Bakri , Hammoud Mohamad , Shaito Ali
Published: October 2014

The present work concerns a prototype implementation and an experimental study of a new design of water heating using parabolic troughs equipped with solar tracking system. Combining the two techniques of parabolic troughs and solar tracking permits to enhance the water heating by solar energy. A prototype is implemented to test the proposed approach. An experimental study is carried-out to test the performance of the system as well as the effect of the weather conditions on the system. The effect of each technique is evaluated separately by performing experiments with and without solar tracking and with/without parabolic mirrors. It is shown that with a parabolic trough of 0.6 m2 area, water can be heated from 23 to 57 °C. Moreover, the temperature can reach 69 °C when the tracking system is activated.
Using Iterative Code for Thermal Performance Prediction of Concentric Tube Heat Exchanger: Parametric Analysis
Authors: Ramadan Mohamad , Khaled Mahmoud , Al Shaer Ali , Hammoud Mohamad , El Hage Hicham
Published: October 2014

This paper handles numerical analyses that give attention to the relation between the thermal performance of concentric tube heat exchangers and its operational parameters. For this purpose, an iterative computational code is developed to compute thermal performance. The computations are based on supplying the code with the exchanger length, inner/outer diameters, inner/outer fluids, inner/outer flow rates and inner/outer inlet temperatures. A parametric analysis that examines the relation between the thermal performance of heat exchanger and inner/outer flow rates is presented. It is originated that the thermal performance and the overall heat transfer coefficient of a concentric tube heat exchanger increase through a rational function with the inner and outer flow rates.
Development of a Driving Cycle for Amman City With Performance Evaluation for ICE Vehicle
Authors: Abu Mallouh M. , Surgenor B. W. , Abdelhafez E. , Salah M. , Hamdan M.
Published: October 2014

A good driving cycle is needed for accurate evaluation of a vehicle’s performance in terms of emission and fuel consumption. Driving cycles obtained for certain cities or countries are not usually applicable to other cities or countries. Therefore, considerable research has been conducted on developing driving cycles for certain cities and regions. In this paper, a driving cycle for a taxi in Amman city, the capital of Jordan, is developed. Significant differences are noted when comparing the Amman driving cycle with other driving cycles. A model of a gasoline powered vehicle is used to conduct a performance comparison in terms of fuel economy and emissions utilizing the developed Amman driving cycle and six other worldwide driving cycles. The developed Amman driving cycle is very useful in obtaining accurate estimation of fuel economy and emissions for vehicles running on Amman roads and will be used in future work to study the performance of hybrid fuel cell/ battery vehicles.
Cracks Susceptibility Elimination in Fiber Laser Cladding of Ni-Based Alloy With Addition of Tungsten Carbides
Authors: Zarini Stefano , Previtali Barbara , Vedani Maurizio , Rovatti Ludovica
Published: October 2014

In plastic injection molding the most critical component in terms of wear and corrosion problem is represented by the barrel-screw system. This is due to the friction of plastic on the inner part of the barrel and to contact between the screw and the inner walls of the barrel. Fiber laser cladding is a promising technique that, through deposition of powder onto a substrate increases wearproprieties and consequently lifetime of the component. In particular, cladding Ni-Cr alloy with WC is an extremely promising combination of elements for this purpose. Specifically, WC is able to increase the hardness of the deposit so that it becomes more suitable for severe wear application. On the other hand, high Cr amount contained in the Ni-based alloy, guaranties high corrosion resistance for harsh environments. Nevertheless, this combination of materials is highly susceptible to cracks. Through the optimization of process parameters and preheating temperature (250-350-450-550°C) defect free coatingsare obtained. This work presentsan investigation on fiber laser cladding of Ni based alloy (Ni40, Ni60) with addition of spherical tungsten carbides (-53+20 μm) on C60 steel substrate. Optimal conditions are evaluated through macro and a micro analysis. In the first case penetrantliquids are used to evaluate crack presence. For the second field, micro hardness was measured and microstructure if cross-sectioned samples were investigated by optical microscopy.
Robot Assisted Modal Analysis on a Stationary Bladed Wheel
Authors: Bertini L. , Monelli B. , Neri P. , Santus C. , Guglielmo A.
Published: October 2014

This paper shows an automated procedure to experimentally find the eigenmodes of a bladed wheel with highly three-dimensional geometry. The stationary wheel is supported in free-free conditions, neglecting stress-stiffening effects. The single input / multiple output approach was followed. The vibration speed was measured by means of a laser-Doppler vibrometer, and an anthropomorphic robot was used for accurate orientation and positioning of the measuring laser beam, allowing multiple measurements during a limited testing time. The vibration at corresponding points on each blade was measured and the data elaborated in order to find the initial (lower frequency) modes. These modal shapes were then compared to finite element simulations and accurate frequency matching and exact number of nodal diameters obtained. Being the modes cyclically harmonic, the complex formulation could be attractive, being not affected by the angular phase of the mode representation. Nevertheless, stationary modes were experimentally detected, rather than rotating, and then the real representation was necessary. The discrete Fourier transform of the blade displacements easily allowed to find both the angular phase and the correct number of nodal diameters. Successful MAC experimental to analytical comparison was finally obtained with the real representation after introducing the proper angular phase for each mode.
When is a Drug Not a Drug? Troubling Silences and Unsettling Painkillers in the National Football League
Authors: King Samantha , Carey R. Scott , Jinnah Naila , Millington Rob , Phillipson Andrea , Prouse Carolyn , Ventresca Matt
Published: October 2014

This paper uses a genealogical approach to explore the conjuncture at which the longstanding but partial and uneasy silence surrounding painkiller use in the National Football League seems increasingly under threat. We historicize and problematize apparently self-evident narratives about painkiller use in contemporary football by interrogating the gendered, racialized and labor-related discourses surrounding Brett Favre’s 1996 admission of a dependency on Vicodin, as well as the latest rash of confessions of misuse by now retired athletes. We argue that these coconstructed and coconstructing moments of noise and silence are part of the same discursive system. This system serves to structure the emerging preoccupation with painkillers in the NFL, with Favre’s admission still working to placate anxieties surrounding the broader drug problems endemic to the league, and failing to disrupt our implicit knowingness about painkiller use, thus reinforcing ongoing cultures of silence and toughness in professional football.
Solo Sailing: An “Ordinary Girl”, Voluntary Risk-Taking and (Ir)Responsibility
Authors: Brown Mike , Penney Dawn
Published: October 2014

This article draws on material associated with a solo sailing circumnavigation, undertaken by 16 year old Jessica Watson in 2009–2010, to discuss how her voyage provided a focal point for debates relating to voluntary risk-taking conducted within the sport and leisure context. Specifically, we illustrate how public and media commentaries on her voyage reflect discourses of risk being infused and conflated with discourses of responsibility, youth and gender. Our analysis brings to the fore the contested, moral and political nature of risk discourses in contemporary western society. Public reaction to Watson’s voyage indicates that descriptions of western society as risk-averse fail to capture the situated and dynamic perceptions of risk.
Zooming in to see the bigger picture: Microfluidic and nanofabrication tools to study bacteria
Authors: Hol Felix J. H. , Dekker Cees
Published: October 2014

Experimental platforms for probing bacteria

Bacteria respond to a host of changing cues provided by their environment. Hol and Dekker review how microfluidic and nanofabricated devices can provide a platform to deliver different stimuli in a variety of environments. Bacterial quorum sensing and electron transport are among the problems that can be studied in this way.

Science
, this issue
10.1126/science.1251821
Polyubiquitylation drives replisome disassembly at the termination of DNA replication
Authors: Priego Moreno Sara , Bailey Rachael , Campion Nicholas , Herron Suzanne , Gambus Agnieszka
Published: October 2014

How to stop after copying the genome

Replication is highly regulated: Failure to copy any part of the genome or copying parts of it more than once can cause genome instability with potentially disastrous consequences. Maric
et al.
and Priego Moreno
et al.
show that the DNA replication machinery, which stably encircles DNA during the duplication process, is actively disassembled once replication is complete (see the Perspective by Bell). The protein ring encircling the DNA is covalently modified, which allows it to be opened and the whole replication complex to be removed from DNA by a special disassembly complex.

Science
, this issue
10.1126/science.1253596
, p.
477
; see also p.
418
Boundless no more
Authors: Vincent Amanda C. J. , Harris Jean M.
Published: October 2014

Ending illegal, unregulated, and unreported fishing would bring hope for ocean wildlife
High thermodynamic stability of parametrically designed helical bundles
Authors: Huang Po-Ssu , Oberdorfer Gustav , Xu Chunfu , Pei Xue Y. , Nannenga Brent L. , Rogers Joseph M. , DiMaio Frank , Gonen Tamir , Luisi Ben , Baker David
Published: October 2014

Building with alphahelical coiled coils

Understanding how proteins fold into well-defined three-dimensional structures has been a longstanding challenge. Increased understanding has led to increased success at designing proteins that mimic existing protein folds. This raises the possibility of custom design of proteins with structures not seen in nature. Thomson
et al.
describe the design of channelcontaining α-helical barrels, and Huang
et al.
designed hyperstable helical bundles. Both groups used rational and computational design to make new protein structures based on α-helical coiled coils but took different routes to reach different target structures.

Science
, this issue p.
485
, p.
481
Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution
Authors: Chen Bi-Chang , Legant Wesley R. , Wang Kai , Shao Lin , Milkie Daniel E. , Davidson Michael W. , Janetopoulos Chris , Wu Xufeng S. , Hammer John A. , Liu Zhe , English Brian P. , Mimori-Kiyosue Yuko , Romero Daniel P. , Ritter Alex T. , Lippincott-Schwartz Jennifer , Fritz-Laylin Lillian , Mullins R. Dyche , Mitchell Diana M. , Bembenek Joshua N. , Reymann Anne-Cecile , Böhme Ralph , Grill Stephan W. , Wang Jennifer T. , Seydoux Geraldine , Tulu U. Serdar , Kiehart Daniel P. , Betzig Eric
Published: October 2014

From single molecules to embryos in living color

Animation defines life, and the three-dimensional (3D) imaging of dynamic biological processes occurring within living specimens is essential to understand life. However, in vivo imaging, especially in 3D, involves inevitable tradeoffs of resolution, speed, and phototoxicity. Chen
et al.
describe a microscope that can address these concerns. They used a class of nondiffracting beams, known as 2D optical lattices, which spread the excitation energy across the entire field of view while simultaneously eliminating out-of-focus excitation. Lattice light sheets increase the speed of image acquisition and reduce phototoxicity, which expands the range of biological problems that can be investigated. The authors illustrate the power of their approach using 20 distinct biological systems ranging from single-molecule binding kinetics to cell migration and division, immunology, and embryonic development.

Science
, this issue
10.1126/science.1257998
Room-temperature enantioselective C–H iodination via kinetic resolution
Authors: Chu Ling , Xiao Kai-Jiong , Yu Jin-Quan
Published: October 2014

Ensuring handedness when breaking C-H bonds

Many organic compounds are chiral: They manifest two distinct mirror-image variants, or enantiomers. Kinetic resolution can transform one enantiomer to a desired product while leaving its mirror image unmodified. Chu
et al.
applied this strategy to a reaction that replaces aryl carbon–hydrogen bonds with carbon-iodine bonds. They used a chiral palladium catalyst that reacts selectively with just one of two enantiomers of various benzylamine derivatives. In medicinal chemistry, such selective synthesis of individual enantiomers is essential for screening interactions with chiral biomolecules such as proteins.

Science
, this issue p.
451
Beyond the rainbow
Authors: Koschowitz Marie-Claire , Fischer Christian , Sander Martin
Published: October 2014

Dinosaur color vision may have been key to the evolution of bird feathers
Antheridiogen determines sex in ferns via a spatiotemporally split gibberellin synthesis pathway
Authors: Tanaka Junmu , Yano Kenji , Aya Koichiro , Hirano Ko , Takehara Sayaka , Koketsu Eriko , Ordonio Reynante Lacsamana , Park Seung-Hyun , Nakajima Masatoshi , Ueguchi-Tanaka Miyako , Matsuoka Makoto
Published: October 2014

Sex determination driven by community cooperation

An optimized ratio of male and females in a sexually reproducing population helps to generate the genetic diversity useful to a species in a changing world. Tanaka
et al.
studied a fern in which the sex ratio is adjusted not by individual identity, but by signaling between individual plants (see the Perspective by Sun). Early-maturing individual ferns express some of the biosynthetic genes needed to make a precursor of the plant hormone gibberellin, which they secrete into the environment. Younger ferns, which express the enzymes needed to finalize synthesis of gibberellin, take up the signal and in response develop the organs that produce male gametes.

Science
, this issue p.
469
; see also p.
423
Sex and the single fern
Authors: Sun Tai-ping
Published: October 2014

Separation of the synthesis and sensing of a signaling molecule controls sex in ferns

[Also see Report by

Tanaka
et al.

]
China's private universities
Authors: Jin Huiqing
Published: October 2014

China's expansion of universities has not been on a level playing field. Earlier this year, Education Minister Guiren Yuan declared that the government must treat both public and private universities equally. As founder and president of one of China's largest private universities, I wholeheartedly agree. China's private universities can help usher in new opportunities for social and economic development, but they must be enabled to launch robust education programs and compete for research grants. Unless the government loosens restrictions on such endeavors, private universities could enter a tailspin, and such an erosion of higher education could threaten social stability.
How we tamed ourselves—and became modern
Authors: Gibbons Ann
Published: October 2014

“Self-domestication” turned humans into the cooperative species we are today.
Taiwan's ocean program reels from loss of ship, scientists
Authors: Normile Dennis
Published: October 2014

New vessel was sparking international collaborations.
Evaluation of the Efficacy of Outer Membrane Protein 31 Vaccine Formulations for Protection against Brucella canis in BALB/c Mice
Authors: Clausse Maria , Díaz Alejandra G. , Ibañez Andrés E. , Cassataro Juliana , Giambartolomei Guillermo H. , Estein Silvia M.
Published: October 2014

Canine brucellosis is an infectious disease caused by the Gram-negative bacteriumBrucella canis. Unlike conventional control programs for other species of the genusBrucella, currently there is no vaccine available against canine brucellosis, and preventive measures are simply diagnosis and isolation of infected dogs. New approaches are therefore needed to develop an effective and safe immunization strategy against this zoonotic pathogen. In this study, BALB/c mice were subcutaneously immunized with the following: (i) the recombinantBrucellaOmp31 antigen formulated in different adjuvants (incomplete Freund adjuvant, aluminum hydroxide, Quil A, and Montanide IMS 3012 VGPR), (ii) plasmid pCIOmp31, or (iii) pCIOmp31 plasmid followed by boosting with recombinant Omp31 (rOmp31). The immune response and the protective efficacy againstB. canisinfection were characterized. The different strategies induced a strong immunoglobulin G (IgG) response. Furthermore, spleen cells from rOmp31-immunized mice produced gamma interferon and interleukin-4 (IL-4) afterin vitrostimulation with rOmp31, indicating the induction of a mixed Th1-Th2 response. Recombinant Omp31 administered with different adjuvants as well as the prime-boost strategy conferred protection againstB. canis. In conclusion, our results suggest that Omp31 could be a useful candidate for the development of a subcellular vaccine againstB. canisinfection.
Multicentric Comparative Assessment of the Bio-Evolution Toxoplasma gondii Detection Kit with Eight Laboratory-Developed PCR Assays for Molecular Diagnosis of Congenital Toxoplasmosis
Authors: Filisetti Denis , Sterkers Yvon , Brenier-Pinchart Marie-Pierre , Cassaing Sophie , Dalle Frédéric , Delhaes Laurence , Pelloux Hervé , Touafek Fériel , Varlet-Marie Emmanuelle , Yera Hélène , Candolfi Ermano , Bastien Patrick
Published: October 2014

The detection of
Toxoplasma gondii
in amniotic fluid is an essential tool for the prenatal diagnosis of congenital toxoplasmosis and is currently essentially based on the use of PCR. Although some consensus is emerging, this molecular diagnosis suffers from a lack of standardization and an extreme diversity of laboratory-developed methods. Commercial kits for the detection of
T. gondii
by PCR were recently developed and offer certain advantages; however, they must be assessed in comparison with optimized reference PCR assays. The present multicentric study aimed to compare the performances of the Bio-Evolution
T. gondii
detection kit and laboratory-developed PCR assays set up in eight proficient centers in France. The study compared 157 amniotic fluid samples and found concordances of 99% and 100% using 76
T. gondii
-infected samples and 81 uninfected samples, respectively. Moreover, taking into account the classification of the European Research Network on Congenital Toxoplasmosis, the overall diagnostic sensitivity of all assays was identical and calculated to be 86% (54/63); specificity was 100% for all assays. Finally, the relative quantification results were in good agreement between the kit and the laboratory-developed assays. The good performances of this commercial kit are probably in part linked to the use of a number of good practices: detection in multiplicate, amplification of the repetitive DNA target rep529, and the use of an internal control for the detection of PCR inhibitors. The only drawbacks noted at the time of the study were the absence of uracil-
N
-glycosylase and small defects in the reliability of the production of different reagents.
Genotypic Susceptibility Testing of Mycobacterium tuberculosis Isolates for Amikacin and Kanamycin Resistance by Use of a Rapid Sloppy Molecular Beacon-Based Assay Identifies More Cases of Low-Level Drug Resistance than Phenotypic Lowenstein-Jensen Testing
Authors: Chakravorty Soumitesh , Lee Jong Seok , Cho Eun Jin , Roh Sandy S. , Smith Laura E. , Lee Jiim , Kim Cheon Tae , Via Laura E. , Cho Sang-Nae , Barry Clifton E. , Alland David
Published: October 2014

Resistance to amikacin (AMK) and kanamycin (KAN) in clinical
Mycobacterium tuberculosis
strains is largely determined by specific mutations in the
rrs
gene and
eis
gene promoter. We developed a rapid, multiplexed sloppy molecular beacon (SMB) assay to identify these mutations and then evaluated assay performance on 603 clinical
M. tuberculosis
DNA samples collected in South Korea. Assay performance was compared to gold-standard phenotypic drug susceptibility tests, including Lowenstein-Jensen (LJ) absolute concentration, mycobacterial growth indicator tubes (MGIT), and TREK Sensititre MycoTB MIC plate (MycoTB) methods. Target amplicons were also tested for mutations by Sanger sequencing. The SMB assay correctly detected 115/116 mutant and mixed sequences and 487/487 wild-type sequences (sensitivity and specificity of 99.1 and 100%, respectively). Using the LJ method as the reference, sensitivity and specificity for AMK resistance were 92.2% and 100%, respectively, and sensitivity and specificity for KAN resistance were 87.7% and 95.6%, respectively. Mutations in the
rrs
gene were unequivocally associated with high-level cross-resistance to AMK and KAN in all three conventional drug susceptibility testing methods. However,
eis
promoter mutations were associated with KAN resistance using the MGIT or MycoTB methods but not the LJ method. No testing method associated
eis
promoter mutations with AMK resistance. Among the discordant samples with AMK and/or KAN resistance but wild-type sequence at the target genes, we discovered four new mutations in the
whiB7
5′ untranslated region (UTR) in 6/22 samples. All six samples were resistant only to KAN, suggesting the possible role of these
whiB7
5′ UTR mutations in KAN resistance.
Nontoxigenic Vibrio cholerae Non-O1/O139 Isolate from a Case of Human Gastroenteritis in the U.S. Gulf Coast
Authors: Hasan Nur A. , Rezayat Talayeh , Blatz Peter J. , Choi Seon Young , Griffitt Kimberly J. , Rashed Shah M. , Huq Anwar , Conger Nicholas G. , Colwell Rita R. , Grimes D. Jay
Published: October 2014

An occurrence of
Vibrio cholerae
non-O1/O139 gastroenteritis in the U.S. Gulf Coast is reported here. Genomic analysis revealed that the isolate lacked known virulence factors associated with the clinical outcome of a
V. cholerae
infection but did contain putative genomic islands and other accessory virulence factors. Many of these factors are widespread among environmental strains of
V. cholerae
, suggesting that there might be additional virulence factors in non-O1/O139
V. cholerae
yet to be determined. Phylogenetic analysis revealed that the isolate belonged to a phyletic lineage of environmental
V. cholerae
isolates associated with sporadic cases of gastroenteritis in the Western Hemisphere, suggesting a need to monitor non-O1/O139
V. cholerae
in the interest of public health.
Family Clusters of Avian Influenza A H7N9 Virus Infection in Guangdong Province, China
Authors: Yi Lina , Guan Dawei , Kang Min , Wu Jie , Zeng Xianqiao , Lu Jing , Rutherford Shannon , Zou Lirong , Liang Lijun , Ni Hanzhong , Zhang Xin , Zhong Haojie , He Jianfeng , Lin Jinyan , Ke Changwen
Published: October 2014

Since its first identification, the epizootic avian influenza A H7N9 virus has continued to cause infections in China. Two waves were observed during this outbreak. No cases were reported from Guangdong Province during the first wave, but this province became one of the prime outbreak sites during the second wave. In order to identify the transmission potential of this continuously evolving infectious virus, our research group monitored all clusters of H7N9 infections during the second wave of the epidemic in Guangdong Province. Epidemiological, clinical, and virological data on these patients were collected and analyzed. Three family clusters including six cases of H7N9 infection were recorded. The virus caused severe disease in two adult patients but only mild symptoms for all four pediatric patients. All patients reported direct poultry or poultry market exposure history. Relevant environment samples collected according to their reported exposures tested H7N9 positive. Virus isolates from patients in the same cluster shared high sequence similarities. In conclusion, although continually evolving, the currently circulating H7N9 viruses in Guangdong Province have not yet demonstrated the capacity for efficient and sustained person-to-person transmission.
Semiquantitative Multiplexed Tandem PCR for Detection and Differentiation of Four Theileria orientalis Genotypes in Cattle
Authors: Perera Piyumali K. , Gasser Robin B. , Firestone Simon M. , Smith Lee , Roeber Florian , Jabbar Abdul
Published: October 2014

Oriental theileriosis is an emerging, tick-borne disease of bovines in the Asia-Pacific region and is caused by one or more genotypes of the
Theileria orientalis
complex. This study aimed to establish and validate a multiplexed tandem PCR (MT-PCR) assay using three distinct markers (major piroplasm surface protein, 23-kDa piroplasm membrane protein, and the first internal transcribed spacer of nuclear DNA), for the simultaneous detection and semiquantification of four genotypes (Buffeli, Chitose, Ikeda, and type 5) of the
T. orientalis
complex. Analytical specificity, analytical sensitivity, and repeatability of the established MT-PCR assay were assessed in a series of experiments. Subsequently, the assay was evaluated using 200 genomic DNA samples collected from cattle from farms on which oriental theileriosis outbreaks had occurred, and 110 samples from a region where no outbreaks had been reported. The results showed the MT-PCR assay specifically and reproducibly detected the expected genotypes (i.e., genotypes Buffeli, Chitose, Ikeda, and type 5) of the
T. orientalis
complex, reliably differentiated them, and was able to detect as little as 1 fg of genomic DNA from each genotype. The diagnostic specificity and sensitivity of the MT-PCR were estimated at 94.0% and 98.8%, respectively. The MT-PCR assay established here is a practical and effective diagnostic tool for the four main genotypes of
T. orientalis
complex in Australia and should assist studies of the epidemiology and pathophysiology of oriental theileriosis in the Asia-Pacific region.
A View of the E2-CD81 Interface at the Binding Site of a Neutralizing Antibody against Hepatitis C Virus
Authors: Harman Christine , Zhong Lilin , Ma Li , Liu Peter , Deng Lu , Zhao Zhong , Yan Hailing , Struble Evi , Virata-Theimer Maria Luisa , Zhang Pei
Published: October 2014

Hepatitis C virus (HCV) glycoprotein E2 is considered a major target for generating neutralizing antibodies against HCV, primarily due to its role of engaging host entry factors, such as CD81, a key cell surface protein associated with HCV entry. Based on a series of biochemical analyses in combination with molecular docking, we present a description of a potential binding interface formed between the E2 protein and CD81. The virus side of this interface includes a hydrophobic helix motif comprised of residues W
437
LAGLF
442
, which encompasses the binding site of a neutralizing monoclonal antibody, mAb41. The helical conformation of this motif provides a structural framework for the positioning of residues F442 and Y443, serving as contact points for the interaction with CD81. The cell side of this interface likewise involves a surface-exposed hydrophobic helix, namely, the D-helix of CD81, which coincides with the binding site of 1D6, a monoclonal anti-CD81 antibody known to block HCV entry. Our illustration of this virus-host interface suggests an important role played by the W
437
LAGLF
442
helix of the E2 protein in the hydrophobic interaction with the D-helix of CD81, thereby facilitating our understanding of the mechanism for antibody-mediated neutralization of HCV.

IMPORTANCE
Characterization of the interface established between a virus and host cells can provide important information that may be used for the control of virus infections. The interface that enables hepatitis C virus (HCV) to infect human liver cells has not been well understood because of the number of cell surface proteins, factors, and conditions found to be associated with the infection process. Based on a series of biochemical analyses in combination with molecular docking, we present such an interface, consisting of two hydrophobic helical structures, from the HCV E2 surface glycoprotein and the CD81 protein, a major host cell receptor recognized by all HCV strains. Our study reveals the critical role played by hydrophobic interactions in the formation of this virus-host interface, thereby contributing to our understanding of the mechanism for antibody-mediated neutralization of HCV.
Virulence Determinants in the PB2 Gene of a Mouse-Adapted H9N2 Virus
Authors: Liu Qingtao , Huang Junqing , Chen Yuxin , Chen Hongzhi , Li Qunhui , He Liang , Hao Xiaoli , Liu Jingjing , Gu Min , Hu Jiao , Wang Xiaoquan , Hu Shunlin , Liu Xiaowen , Liu Xiufan
Published: October 2014

The molecular bases of adaptation and pathogenicity of H9N2 influenza virus in mammals are largely unknown. Here, we show that a mouse-adapted PB2 gene with a phenylalanine-to-leucine mutation (F404L) mainly contributes to enhanced polymerase activity, replication, and pathogenicity of H9N2 in mice and also increases the virulence of the H5N1 and 2009 pandemic H1N1 influenza viruses. Therefore, we defined a novel pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals.
Activation of ATP Citrate Lyase by mTOR Signal Induces Disturbed Lipid Metabolism in Hepatitis B Virus Pre-S2 Mutant Tumorigenesis
Authors: Teng Chiao-Fang , Wu Han-Chieh , Hsieh Wen-Chuan , Tsai Hung-Wen , Su Ih-Jen
Published: October 2014

The development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has been found to be associated with disturbed lipid metabolism. To elucidate the role of lipid metabolism in HBV tumorigenesis, we investigated the dynamic pattern of lipid metabolism in HBV pre-S2 mutant-induced tumorigenesis. Lipid and gene expression profiles were analyzed in an
in vitro
culture system and in transgenic mouse livers harboring HBV pre-S2 mutant. The pre-S2 mutant transgenic livers showed a biphasic pattern of lipid accumulation, starting from mild fatty change in early (1 month) transgenic livers, which subsided and then, remarkably, increased in HCC tissues. This biphasic pattern was synchronized with ATP citrate lyase (ACLY) activation. Further analyses revealed that the pre-S2 mutant initiated an endoplasmic reticulum (ER) stress-dependent mammalian target of rapamycin (mTOR) signalling cascade. The pre-S2 mutant-induced mTOR signal activated the sterol regulatory element binding transcription factor 1 (SREBF1) to upregulate ACLY, which then activated the fatty acid desaturase 2 (FADS2), mediated through ACLY-dependent histone acetylation. Such an ER stress-dependent mTOR signal cascade also is important for the proliferation of hepatocytes
in vitro
and is further validated in HBV-related HCC tissues.

IMPORTANCE
Aberrations of lipid metabolism frequently occur in chronic HBV infection. Our results provide a potential mechanism of disturbed lipid metabolism in HBV pre-S2 mutant-induced tumorigenesis, which should be valuable for the design of HCC chemoprevention in high-risk HBV carriers.
Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to the Retrospective Identification of Taxonomically Unassigned Bunyaviruses and the Discovery of a Novel Member of the Genus Phlebovirus
Authors: Matsuno Keita , Weisend Carla , Kajihara Masahiro , Matysiak Colette , Williamson Brandi N. , Simuunza Martin , Mweene Aaron S. , Takada Ayato , Tesh Robert B. , Ebihara Hideki
Published: October 2014

Until the recent emergence of two human-pathogenic tick-borne phleboviruses (TBPVs) (severe fever with thrombocytopenia syndrome virus [SFTSV] and Heartland virus), TBPVs have been neglected as causative agents of human disease. In particular, no studies have addressed the global distribution of TBPVs, and consequently, our understanding of the mechanism(s) underlying their evolution and emergence remains poor. In order to provide a useful tool for the ecological and epidemiological study of TBPVs, we have established a simple system that can detect all known TBPVs, based on conventional reverse transcription-PCR (RT-PCR) with degenerate primer sets targeting conserved regions of the viral L genome segment. Using this system, we have determined that several viruses that had been isolated from ticks decades ago but had not been taxonomically identified are novel TBPVs. Full-genome sequencing of these viruses revealed a novel fourth TBPV cluster distinct from the three known TBPV clusters (i.e., the SFTS, Bhanja, and Uukuniemi groups) and from the mosquito/sandfly-borne phleboviruses. Furthermore, by using tick samples collected in Zambia, we confirmed that our system had enough sensitivity to detect a new TBPV in a single tick homogenate. This virus, tentatively designated Shibuyunji virus after the region of tick collection, grouped into a novel fourth TBPV cluster. These results indicate that our system can be used as a first-line screening approach for TBPVs and that this kind of work will undoubtedly lead to the discovery of additional novel tick viruses and will expand our knowledge of the evolution and epidemiology of TBPVs.

IMPORTANCE
Tick-borne phleboviruses (TBPVs) have been largely neglected until the recent emergence of two virulent viruses, severe fever with thrombocytopenia syndrome virus and Heartland virus. Little is known about the global distribution of TBPVs or how these viruses evolved and emerged. A major hurdle to study the distribution of TBPVs is the lack of tools to detect these genetically divergent phleboviruses. In order to address this issue, we have developed a simple, rapid, and cheap RT-PCR system that can detect all known TBPVs and which led to the identification of several novel phleboviruses from previously uncharacterized tick-associated virus isolates. Our system can detect virus in a single tick sample and novel TBPVs that are genetically distinct from any of the known TBPVs. These results indicate that our system will be a useful tool for the surveillance of TBPVs and will facilitate understanding of the ecology of TBPVs.
Functions of Antibodies
Authors: Forthal Donald N.
Published: October 2014

Antibodies can impact pathogens in the presence or in the absence of effector cells or effector molecules such as complement, and experiments can often sort out with precision the mechanisms by which an antibody inhibits a pathogenin vitro. In addition,in vivomodels, particularly those engineered to knock in or knock out effector cells or effector molecules, are excellent tools for understanding antibody functions. However, it is highly likely that multiple antibody functions occur simultaneously or sequentially in the presence of an infecting organismin vivo. The most critical incentive for measuring antibody functions is to provide a basis for vaccine development and for the development of therapeutic antibodies. In this respect, some functions, such as virus neutralization, serve to inhibit the acquisition of a pathogen or limit its pathogenesis. However, antibodies can also enhance replication or contribute to pathogenesis. This review emphasizes those antibody functions that are potentially beneficial to the host. In addition, this review will focus on the effects of antibodies on organisms themselves, rather than on the toxins the organisms may produce.
Human Metapneumovirus
Authors: Schuster Jennifer E. , Williams John V.
Published: October 2014

Human metapneumovirus (HMPV), a paramyxovirus identified in 2001, is a leading cause of respiratory tract infections in both children and adults. Seroprevalence studies demonstrate that the primary infection occurs before the age of 5 years, and humans are reinfected throughout life. The four subgroups of HMPV occur with year-to-year variability, and infection with one subgroup confers some serologic cross-protection. Experimental vaccines elicit a humoral response in both animal and human models and have been used to identify antigenic determinants. The main target of protective antibodies is the fusion (F) protein, although many of the remaining eight proteins are immunogenic. Monoclonal antibodies (mAbs) targeting the F protein are both protective and therapeutic in animal models. Most recently, the identification of broadly neutralizing antibodies against HMPV and respiratory syncytial virus demonstrates that common epitopes are present between the two viruses. Broadly neutralizing mAbs have significant clinical implications for prophylaxis and treatment of high-risk hosts as well as vaccine development.
Risk Factors for Shiga Toxin-ProducingEscherichia coli-Associated Human Diseases
Authors: Rivas Marta , Chinen Isabel , Miliwebsky Elizabeth , Masana Marcelo
Published: October 2014

We have reviewed the risk factors for the occurrence of Shiga toxin-producingEscherichia coli(STEC)-associated human diseases. The analysis of STEC surveillance data and trends shows differences in frequency and severity of the illnesses across countries, whereas the economic and social costs for the affected families, the community, and the health system are better estimated in developed countries. The occurrence of STEC infections is determined by the interaction of the pathogen, the reservoirs, and the biological, cultural, and behavioral aspects of the host. The main risk factors identified in earlier case-control and population-based studies were dietary behaviors and beef consumption. However, in recent years, other risky exposures have also emerged, like the consumption of raw vegetables and sprouts, working or camping in rural areas, visiting farms, and person-to-person transmission. Epidemiological changes have also been determined by the intensification of cattle production, the increase in centralized food production and distribution, and the growth in the volume of international trade of foods. The main lessons learned from recent large outbreaks are knowledge of virulence determinants of new pathogenic strains, recognition of new vehicles of infection, development of new methodologies for detecting STEC in foods and humans, improvement in food regulations and hygiene guidelines, new therapeutic approaches in the treatment of infected patients, establishment of continuous educational programs for food consumers, and enhanced cooperation and teamwork of regional and international networks.
Enterohemorrhagic
Escherichia coli
Virulence Gene Regulation
Authors: Mellies Jay L. , Lorenzen Emily
Published: October 2014

Coordinated expression of enterohemorrhagic
Escherichia coli
virulence genes enables the bacterium to cause hemorrhagic colitis and the complication known as hemolytic-uremic syndrome. Horizontally acquired genes and those common to
E. coli
contribute to the disease process, and increased virulence gene expression is correlated with more severe disease in humans. Researchers have gained considerable knowledge about how the type III secretion system, secreted effectors, adhesin molecules, and the Shiga toxins are regulated by environmental signals and multiple genetic pathways. Also emergent from the data is an understanding of how enterohemorrhagic
E. coli
regulates response to acid stress, the role of flagellar motility, and how passage through the human host and bovine intestinal tract causes disease and supports carriage in the cattle reservoir, respectively. Particularly exciting areas of discovery include data suggesting how expression of the myriad effectors is coordinately regulated with their cognate type III secretion system and how virulence is correlated with bacterial metabolism and gut physiology.
Role of Shiga/Vero Toxins in Pathogenesis
Authors: Obata Fumiko , Obrig Tom
Published: October 2014

Shiga toxin (Stx) is the primary cause of severe host responses including renal and central nervous system disease in Shiga toxin-producing
Escherichia coli
(STEC) infections. The interaction of Stx with different eukaryotic cell types is described. Host responses to Stx and bacterial lipopolysaccharide are compared as related to the features of the STEC-associated hemolytic-uremic syndrome (HUS). Data derived from animal models of HUS and central nervous system disease in vivo and eukaryotic cells in vitro are evaluated in relation to HUS disease of humans.
Enterohemorrhagic
Escherichia coli
Pathogenesis and the Host Response
Authors: Karpman Diana , Ståhl Anne-Lie
Published: October 2014

Enterohemorrhagic
Escherichia coli
(EHEC) is a highly pathogenic bacterial strain capable of causing watery or bloody diarrhea, the latter termed hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is defined as the simultaneous development of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The mechanism by which EHEC bacteria colonize and cause severe colitis, followed by renal failure with activated blood cells, as well as neurological symptoms, involves the interaction of bacterial virulence factors and specific pathogen-associated molecular patterns with host cells as well as the host response. The innate immune host response comprises the release of antimicrobial peptides as well as cytokines and chemokines in addition to activation and/or injury to leukocytes, platelets, and erythrocytes and activation of the complement system. Some of the bacterial interactions with the host may be protective in nature, but, when excessive, contribute to extensive tissue injury, inflammation, and thrombosis, effects that may worsen the clinical outcome of EHEC infection. This article describes aspects of the host response occurring during EHEC infection and their effects on specific organs.