bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlling Turbulence in Tight Rod Bundles
Authors: Merzari Elia , Fischer Paul
Published: December 2013

The flow in rod bundles is of key importance in a variety of engineering fields. It is representative, for instance, of the flow in a nuclear reactor core and the flow in a tube and shell heat exchanger. For particularly tight rod bundles (pitch to diameter ratio lower than 1.1 in hexagonal arrays) the flow is subject to a Kelvin-Helmholtz instability that is present in both laminar and turbulent flows and is likely to influence transition.

Such instability has been proven to exist in bare bundles and even in bundles containing spacing devices. In fact, rod bundles are typically separated by devices designed to keep the rods (or tubes) in place and avoid vibrations. Simple spacer designs, such as honeycomb arrays with dimples, do not remove the instability.

The present paper discusses a procedure to investigate the effect of spacing devices have on the most unstable mode of turbulence. A linear stability analysis of the laminar flow for several spacing device configurations has been performed by using adjoint methods. The results show the effect of the spacing on the formation of large scale coherent structures and help lay the ground for a theory of turbulence control in tight rod bundles.
Computational Fluid–Structure Interaction for Biological and Biomedical Flows
Authors: Tian F. B. , Dai H. , Luo H. , Doyle J. F. , Rousseau B.
Published: December 2013

In this paper, we describe a three-dimensional (3D) computational approach for computing the fluid–structure interaction (FSI) encountered in biological and biomedical flows. The approach combines a Cartesian grid based immerse-boundary method for the viscous incompressible flow and a finite-element method for the solid body mechanics. The separate subroutines of the finite-element method can handle general 3D bodies as well as thin-wall structures such as frames, membranes, and plates. Furthermore, both geometric nonlinearity due to large displacements and large rotations and material nonlinearity due to hyperelasticity have been incorporated. The flow and the solid body are meshed separately, and as the body deforms, no mesh regeneration is needed. The FSI solver has been validated against previous numerical and experimental studies. Applications in insect flight and vocal fold vibration have been demonstrated.
Analysis of Severe Erosion in Industrial Centrifugal Slurry Pumps
Authors: Madadnia Jafar , Amjad Mostafa , Kusnan Jeffry
Published: December 2013

Centrifugal pumps designed for homogenous slurries experience inefficiency, off-design operations, shorter service-life expectancy, and rapid geometry change due to localized and uneven erosion. Experimental and numerical research to design erosion-free pumps has been inconclusive due to complexity of heterogeneous, multiphase slurry flows and mechanism of the localized material losses.

This paper reports on erosion-effects of slurry flows on a number of industrial centrifugal pumps selected from an active copper mine field. The field samples include three metallic pumps operating in a serial-arrangement, and a number of worn pump-components with fully rubber-lined or metallic wetted-surfaces. Physical samples were also collected and photographed under an electronic microscope.

The analysis of the photographs shows directional groves, ripples-formations, pitting, cavities, spots, and abrasive-embedding on the pump surfaces. The effected regions included a) hub or tip of the vane leading edge of impellers, b) internal and external surfaces of shroud and downstream of expellers, c) front-liners/throat bush all at the proximity of the inlet throat/tube, and d) Volute surface close to the discharge throat/tube on the spiral tail. Analysis of eroded regions suggests a combination of mechanisms some similar with those found with a sustained flow acceleration and momentum change towards a surface. A wear model is therefore recommended for the severe erosion in pumps which resembles erosion by cavitation.

To further understand and verify the finding and to be able to predict and to avoid accelerated-erosion, an experimental modelling and a numerical modelling of slurry flows in two identical-centrifugal-pumps are conducted in series and preliminary results are presented. The project is in progress.
Study of Three-Dimensional Effects of Heaving Airfoils With an Immersed Boundary Method
Authors: Wei Z. , Zheng Z. C.
Published: December 2013

A three-dimensional numerical simulation is performed to study a heaving airfoil with an immersed boundary method. Flow around a heaving airfoil has been widely investigated by using two-dimensional simulation; while few previous works discussed the physical behavior of flow over heaving airfoils with three-dimensional effects. The purpose of this study is to identify characteristic features of flow over heaving airfoils in three-dimensional simulation in comparison with those in two-dimensional cases. In particular, the vortical wakes downstream of the heaving ellipsoid wing is characterized by a reversed-Karman-vortex-street-like structure, which is a reduced reversed-Karman vortex street. The implication of this characteristic is found to be the reduced leading-edge vortex on the 3D wing.

In order to fulfill the computational requirement, a parallel implementation of the immersed boundary method (Zhang & Zheng [1]) is presented. The pressure Poisson equation is solved with the assistance of a portable scientific parallel computational library (PETSc). This code is validated with a case of flow over a stationary sphere. The parallel performance is also demonstrated.
Experimental Investigation of Wicking Flow Through a Porous Medium as a Validation Approach for Numerical Simulations
Authors: Moeini Sedeh Mahmoud , Khodadadi J. M.
Published: December 2013

Wicking flow through a porous medium with nearly-spherical interconnected pores was investigated experimentally for validation of numerical simulations of multiphase flow through a porous structure. The experimental setup was designed to eliminate the effects of pressure gradient and gravity. The porous structure is a commercial graphite foam (PocoFoam® with an average pore size of 400 μm and porosity of 75%) and the penetrating liquid is cyclohexane. The penetration of the liquid into the foam sample is unidirectional. The liquid originates from a side reservoir toward an empty reservoir on the opposite side, with the porous sample between the reservoirs. The level of the liquid was kept constant on the fluid source side of the sample, i.e. in the reservoir full of liquid. Since the top side of the experimental setup is exposed to the ambient, there is no pressure gradient effect. Thus, penetration of the liquid occurs only as a result of interfacial effects (i.e. surface tension and contact angle) while pressure gradient and gravity play negligible roles. The instantaneous liquid penetration length (i.e. the average position of liquid interface) versus time was measured experimentally using video frame analysis of the tests recorded with a digital camera aligned with the experimental setup and observing from the top. The experiments were repeated several times to ensure their repeatability and the variations of the liquid interface position were obtained at different time instants. The results exhibit agreement with the theoretical Washburn equation for the liquid penetration length for horizontal wicking along cylindrical capillaries. Moreover, the possible causes of deviations from the Washburn equation were studied. Furthermore, the experimental results are in good agreement with numerical results of the liquid penetration through a series of pores. The numerical analysis was performed for a two-dimensional model that is based on the geometric features of the graphite foam sample and using the multiphase Volume-of-Fluid (VOF) method.
An Approximation Method for the Cavitation Eroded Surface
Authors: Nohmi Motohiko
Published: December 2013

Flow characteristics of hydraulic machineries could be highly influenced by cavitation erosion. In order to evaluate the effect of cavitation erosion on the flow characteristics, an approximation method of the cavitation eroded surface is proposed. The cavitation eroded surface shows very complicated geometry with some patterned structure. In this study the particular eroded surface of metallic material with the sponge like porous structure often referred as orange peel is numerically approximated considering computer generated image technology. A solid model that is hollowed out with a great number of spherical surfaces, shows similar structure with the cavitation eroded surface. This approximated geometry can be used as the boundary condition of following CFD process.
Experimental Investigation and Similarity Solution of the Axisymmetric Turbulent Wake With Rotation
Authors: Wosnik Martin , Dufresne Nathaniel
Published: December 2013

An experimental and analytical investigation of an axisymmetric turbulent wake with rotation was carried out. The axial and azimuthal (swirl) velocity fields were measured in the wake of a single 3-bladed model wind turbine with rotor diameter of 0.91m, up to 20 diameters downstream. The turbine was positioned in the free stream, near the entrance of the 6 m × 2.7 m cross section of the UNH Flow Physics Facility. Measurements were conducted at different rotor loading conditions with blade tip-speed ratios from 2.0 to 2.8. A pitot-static tube and constant temperature hot-wire anemometry with a multi-wire sensor were used to measure velocity fields. An equilibrium similarity theory for the turbulent axisymmetric wake with rotation was outlined, and first evidence for a new scaling function for the decay of the mean swirling velocity component, Wmax ∝ x−1 ∝ Uo3/2, was found.
Performance and Near-Wake Measurements for a Vertical Axis Turbine at Moderate Reynolds Number
Authors: Bachant Peter , Wosnik Martin
Published: December 2013

Experiments were performed with a 1 m diameter, 1 m tall three-bladed vertical axis turbine in a towing tank. Rotor power and drag (or thrust) were measured at a tow speed of 1 m/s, corresponding to a turbine diameter Reynolds number ReD = 106 and an approximate blade chord Reynolds number Rec = λU∞c/ν ∼ 105. Mechanical exergy efficiency estimates were computed from power and drag measurements using an actuator disk approach. Characteristics of the turbine’s near-wake were measured at one turbine diameter downstream. Variation of all three mean and fluctuating velocity components in the vertical and cross-stream directions were measured at peak turbine power output via acoustic Doppler velocimeter. The effect of tip speed ratio on near-wake mean velocity was observed at the turbine center line. Transverse profiles of mean velocity, fluctuating velocity, and Reynolds stresses were also measured at the turbine’s quarter height for two tip speed ratios of interest. Results are compared and contrasted with previous lower Reynolds number studies, and will provide a detailed data set for validation of numerical models.
A Hybrid Method for Flow-Induced Noise in Centrifugal Pumps Based on LES and FEM
Authors: Heng Yaguang , Yuan Shouqi , Hong Feng , Yuan Jianping , Si Qiaorui , Hu Bo
Published: December 2013

A hybrid method is adopted for predicting flow induced noise within a centrifugal pump. The whole calculating domains are meshed with structured grids, and the inner flow analyses are accomplished with LES (Large Eddy Simulation) method, Smagorinsky model is selected as the sub-grid scale model. Flow induced noise is predicted based on simulating results of inner flow, the noise which generated by inlet and impeller are equivalently transformed to Lighthill surface, and volute is calculated as a direct acoustic source. Furthermore, the flow induced noise test bench is built up for test verification. The simulated results show that the blade pass frequency fblade is predominant frequency of flow-induced noise, but the shaft rotation frequency frotating and 2fblade cannot be neglected. The noise becomes more serious as the flow deviates from the best efficiency point. The maximum difference between simulated results and experimental data is less than 3dB. Hence, the hybrid method which based on LES and FEM (Finite Element Method) is an effective method to predict the flow induced noise in centrifugal pumps.
Progressive Specification Rather than Intercalation of Segments During Limb Regeneration
Authors: Roensch Kathleen , Tazaki Akira , Chara Osvaldo , Tanaka Elly M.
Published: December 2013

Limb Regeneration Mirrors Development

Salamanders regenerate the right amount of limb after cutting anywhere along its length. A long-discussed explanation suggests that the regenerating tissue first sets the fingertips as a boundary and then regenerates everything in between. However,

Roensch
et al.

(p.
1375
) report that the limb regenerates in the opposite order. Similar to the processes followed during development, the regenerating salamander limb first establishes a field of cells with the identity of the cut site, and then cells progressively commit to alternate fates as they grow closer to the tip of the regenerated limb.
Direct and Reversible Hydrogenation of CO
2
to Formate by a Bacterial Carbon Dioxide Reductase
Authors: Schuchmann K. , Müller V.
Published: December 2013

Making CO
2
Work for You

Converting carbon dioxide (CO
2
) to formic acid (HCOOH) is an attractive substrate for the storage and recovery of hydrogen (H
2
) for use as fuel. Because CO
2
is relatively stable, however, its hydrogenation typically requires extreme conditions.
Schuchmann and Müller
(p.
1382
: see the Perspective by

Pereira

) isolated a hydrogen-dependent carbon dioxide reductase from
Acetobacterium woodii
that is nearly 2000-fold more effective than the fastest known chemical catalysts. The process, which relies on the formation of formate as a chemical intermediate, also works well in whole-cell systems of
A. woodii
when certain metabolic pathways are inhibited. The enzyme, whether isolated or present in host bacteria, may lead to the design of more efficient fuel cells capable of functioning under less harsh conditions than fuel cells based on chemical reactions alone.
The Hidden Geometry of Complex, Network-Driven Contagion Phenomena
Authors: Brockmann Dirk , Helbing Dirk
Published: December 2013

Predicting Disease Dissemination

In combating the global spread of an emerging infectious disease, answers must be obtained to three crucial questions: Where did the disease emerge? Where will it go next? When will it arrive?
Brockmann and Helbing
(p.
1337
; see the Perspective by

McLean

) analyzed disease spread via the “effective distance” rather than geographical distance, wherein two locations that are connected by a strong link are effectively close. The approach was successfully applied to predict disease arrival times or disease source using data from the the 2003 SARS viral epidemic, 2009 H1N1 influenza pandemic, and the 2011 foodborne enterohaemorrhagic
Escherichia coli
outbreak in Germany.
An Ode to Natural History
Tracks and Shadows
Field Biology As Art

by Harry W. Greene

University of California Press, Berkeley, 2013. 294 pp. $29.95, £19.95. ISBN 9780520232754.
Authors: Bonier Frances
Published: December 2013

Into this memoir, field biologist Greene weaves the natural history of snakes and the importance of sharing a love of nature with people.
My Oldest Sister Is a Sea Walnut?
Authors: Rokas Antonis
Published: December 2013

Decoding of the ctenophore genome prompts reevaluation of the complexity of the metazoan ancestor.

[Also see Research Article by

Ryan
et al.

]
The Hidden Codes That Shape Protein Evolution
Authors: Weatheritt Robert J. , Babu M. Madan
Published: December 2013

Constraints due to transcription factor binding within protein-coding regions of the genome result in biased codon usage and amino acid choice.

[Also see Report by

Stergachis
et al.

]
The Bioethics Commission on Incidental Findings
Authors: Gutmann Amy
Published: December 2013

Shared decision-making allows patients, participants, and consumers to decide what they do and do not want to know.
High-Resolution Typing of Leptospira interrogans Strains by Multispacer Sequence Typing
Authors: Zilber Anne-Laure , Picardeau Mathieu , Ayral Florence , Artois Marc , Demont Pierre , Kodjo Angeli , Djelouadji Zoheira
Published: December 2013

Leptospirosis is a worldwide zoonosis which is responsible for the typical form of Weil's disease. The epidemiological surveillance of the
Leptospira
species agent is important for host prevalence control. Although the genotyping methods have progressed, the identification of some serovars remains ambiguous. We investigated the multispacer sequence typing (MST) method for genotyping strains belonging to the species
Leptospira interrogans
, which is the main agent of leptospirosis worldwide. A total of 33 DNA samples isolated from the reference strains of
L. interrogans
serogroups Icterohaemorrhagiae, Australis, Canicola, and Grippotyphosa, which are the most prevalent serogroups in France, were analyzed by both the variable-number tandem-repeat (VNTR) and MST methods. An MST database has been constructed from the DNA of these reference strains to define the MST profiles. The MST profiles corroborated with the VNTR results. Moreover, the MST analysis allowed the identification at the serovar level or potentially to the isolate level for strains belonging to
L. interrogans
serovar Icterohaemorrhagiae, which then results in a higher resolution than VNTR (Hunter-Gaston index of 0.94 versus 0.68). Regarding
L. interrogans
serogroups Australis, Canicola, and Grippotyphosa, the MST and VNTR methods similarly identified the genotype. The MST method enabled the acquisition of simple and robust results that were based on the nucleotide sequences. The MST identified clinical isolates in correlation with the reference serovar profiles, thus permitting an epidemiological surveillance of circulating
L. interrogans
strains, especially for the Icterohaemorrhagiae serogroup, which includes the most prevalent strains of public health interest.
A Simplified Sequence-Based Identification Scheme for Bordetella Reveals Several Putative Novel Species
Authors: Spilker Theodore , Leber Amy L. , Marcon Mario J. , Newton Duane W. , Darrah Rebecca , Vandamme Peter , LiPuma John J.
Published: December 2013

The differentiation of
Bordetella
species, particularly those causing human infection, is problematic. We found that sequence analysis of an internal fragment of
nrdA
allowed differentiation of the currently named
Bordetella
species. Analysis of 107 “
Bordetella
” isolates recovered almost exclusively from human respiratory tract specimens identified several putative novel species.
Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving Antiretroviral Therapy in Africa and Asia
Authors: Monleau Marjorie , Aghokeng Avelin F. , Eymard-Duvernay Sabrina , Dagnra Anoumou , Kania Dramane , Ngo-Giang-Huong Nicole , Touré-Kane Coumba , Truong Lien X. T. , Chaix Marie-Laure , Delaporte Eric , Ayouba Ahidjo , Peeters Martine
Published: December 2013

Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at −20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance should be monitored.
Comparison of Conventional PCR, Multiplex PCR, and Loop-Mediated Isothermal Amplification Assays for Rapid Detection of Arcobacter Species
Authors: Wang Xiaoyu , Seo Dong Joo , Lee Min Hwa , Choi Changsun
Published: December 2013

This study aimed to develop a loop-mediated isothermal amplification (LAMP) method for the rapid detection of
Arcobacter
species. Specific primers targeting the 23S ribosomal RNA gene were used to detect
Arcobacter butzleri
,
Arcobacter cryaerophilus
, and
Arcobacter skirrowii
. The specificity of the LAMP primer set was assessed using DNA samples from a panel of
Arcobacter
and
Campylobacter
species, and the sensitivity was determined using serial dilutions of
Arcobacter
species cultures. LAMP showed a 10- to 1,000-fold-higher sensitivity than multiplex PCR, with a detection limit of 2 to 20 CFU per reaction
in vitro
. Whereas multiplex PCR showed cross-reactivity with
Campylobacter
species, the LAMP method developed in this study was more sensitive and reliable than conventional PCR or multiplex PCR for the detection of
Arcobacter
species.
Pork Meat as a Potential Source of Salmonella enterica subsp. arizonae Infection in Humans
Authors: Evangelopoulou Grammato , Kritas Spyridon , Govaris Alexander , Burriel Angeliki R.
Published: December 2013

Salmonella enterica
subsp.
arizonae
was isolated from 13 of 123 slaughtered pigs in central Greece. The samples cultured were feces, ileum tissue, mesenteric lymph nodes, and gallbladder swabs. A total of 74 isolates from 492 samples were identified as
Salmonella
spp. by use of standard laboratory culture media and two commercial micromethods and by use of a polyvalent slide agglutination test for the detection of O and H antigens. Among them were 19 (25.68%) suspected to be
S. enterica
subsp.
arizonae
according to analysis with standard laboratory culture media. Of those, 14 were identified as
S. enterica
subsp.
arizonae
by the API 20E (bioMérieux, France) and the Microgen GnA+B-ID (Microgen Bioproducts, Ltd., United Kingdom) identification systems. All the isolates were tested for resistance to 23 antimicrobials. Strains identified as
S. enterica
subsp.
arizonae
were resistant to 17 (70.8%) antibiotics. The highest proportions of resistance were observed for sulfamethoxazole-trimethoprim (71.4%), tetracycline (71.4%), ampicillin (64.3%), and amoxicillin (57.1%). Two isolates were resistant to aztreonam (7.1%) and tigecycline (7.1%), used only for the treatment of humans. Thus, pork meat may play a role in the transmission of antibiotic-resistant
S. enterica
subsp.
arizonae
to human consumers. This is the first report of
S. enterica
subsp.
arizonae
isolation from pigs.
Brain Abscess Caused by Ureaplasma urealyticum in an Adult Patient
Authors: Deetjen Philipp , Maurer Christoph , Rank Andreas , Berlis Ansgar , Schubert Sören , Hoffmann Reinhard
Published: December 2013

Ureaplasma urealyticum
is a fastidious bacterium usually residing in the female genitourinary tract. We present an exceedingly complicated case of a brain abscess secondary to mastoiditis by
U. urealyticum
in an adult hypogammaglobulinemic patient after rituximab treatment 3 years earlier.
Ablation of Nectin4 Binding Compromises CD46 Usage by a Hybrid Vesicular Stomatitis Virus/Measles Virus
Authors: Liu Yu-Ping , Russell Samuel P. , Ayala-Breton Camilo , Russell Stephen J. , Peng Kah-Whye
Published: December 2013

Measles virus (MV) immunosuppression is due to infection of SLAM-positive immune cells, whereas respiratory shedding and virus transmission are due to infection of nectin4-positive airway epithelial cells. The vaccine lineage MV strain Edmonston (MV-Edm) acquired an additional tropism for CD46 which is the basis of its oncolytic specificity. VSVFH is a vesicular stomatitis virus (VSV) encoding the MV-Edm F and H entry proteins in place of G. The virus spreads faster than MV-Edm and is highly fusogenic and a potent oncolytic. To determine whether ablating nectin4 tropism from VSVFH might prevent shedding, increasing its safety profile as an oncolytic, or might have any effect on CD46 binding, we generated VSVFH viruses with H mutations that disrupt attachment to SLAM and/or nectin4. Disruption of nectin4 binding reduced release of VSVFH from the basolateral side of differentiated airway epithelia composed of Calu-3 cells. However, because nectin4 and CD46 have substantially overlapping receptor binding surfaces on H, disruption of nectin4 binding compromised CD46 binding and greatly diminished the oncolytic potency of these viruses on human cancer cells. Thus, our results support continued preclinical development of VSVFH without ablation of nectin4 binding.
Infection of Myofibers Contributes to Increased Pathogenicity during Infection with an Epidemic Strain of Chikungunya Virus
Authors: Rohatgi Anjali , Corbo Joseph C. , Monte Kristen , Higgs Stephen , Vanlandingham Dana L. , Kardon Gabrielle , Lenschow Deborah J.
Published: December 2013

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that is known to cause severe arthritis and myositis in affected patients. The ongoing epidemic began in eastern Africa in 2004 and then spread to islands of the Indian Ocean, India, and Southeast Asia, ultimately afflicting millions. During this outbreak, more severe disease manifestations, including fatalities, have been documented. The reasons for this change in pathogenesis are multifactorial but likely include mutations that have arisen in the viral genome which could alter disease pathogenesis. To test this hypothesis, we used a murine model of CHIKV to compare the disease pathogeneses of two recombinant strains of CHIKV, the first derived from the La Reunion outbreak in 2006 (LR2006 OPY1) and the second isolated from Senegal in 1983 (37997). While the two strains exhibited similar growth in mammalian cells
in vitro
, we observed more severe clinical disease and pathology in mice infected with the LR2006 OPY1 strain of CHIKV, which included prolonged viremia and elevated viral titers and persistence in the muscle, resulting in devastating myonecrosis. Both CHIKV strains infected connective tissue fibroblasts of the muscle, but only the LR2006 OPY1 strain replicated within myofibers
in vivo
, despite similar growth of the two strains in these cell types
in vitro
. However, when the 37997 strain was administered directly into muscle, myofiber infection was comparable to that in LR2006 OPY1-infected mice. These results indicate that differences in the ability of the strain of CHIKV to establish infection in myofibers may contribute to the increased disease severity.

IMPORTANCE
CHIKV is an emerging pathogen that causes significant morbidity. Little is known about the pathogenesis of the disease, and this study suggests that the ability of a recent epidemic strain to infect myofibers results in increased disease severity. Better understanding of how CHIKV causes disease contributes to the ultimate goal of creating therapeutics to alleviate the impact of this debilitating virus.
STAT1 Interaction with E3-14.7K in Monocytes Affects the Efficacy of Oncolytic Adenovirus
Authors: Spurrell Emma , Gangeswaran Rathi , Wang Pengju , Cao Fengyu , Gao Dongling , Feng Baisui , Wold William , Tollefson Ann , Lemoine Nicholas R. , Wang Yaohe
Published: December 2013

Oncolytic viruses based on adenovirus type 5 (Ad5) have been developed as a new class of therapeutic agents for cancers that are resistant to conventional therapies. Clinical experience shows that these agents are safe, but virotherapy alone has not achieved long-term cure in cancer patients. The vast majority of oncolytic adenoviruses used in clinical trials to date have deletion of the E3B genes. It has been demonstrated that the antitumor potency of the E3B-deleted mutant (
dl
309) is inferior to adenovirus with E3B genes intact. Tumors treated with
dl
309 show markedly greater macrophage infiltration than E3B-intact adenovirus. However, the functional mechanisms for this were not previously known. Here, we demonstrate that deletion of E3B genes increases production of chemokines by monocytes after adenovirus infection and increases monocyte migration. The E3B 14,700-Da protein (E3B-14.7K) inhibits STAT1 function by preventing its phosphorylation and nuclear translocation. The STAT1 inhibitor, fludarabine, rescues the effect of E3B-14.7K deletion by downregulating target chemokine expression in human and murine monocytes and results in an enhanced antitumor efficacy with
dl
309
in vivo
. These findings have important implications for clinical use of E3B-deleted oncolytic adenovirus and other E3B-deleted adenovirus vector-based therapy.
Structural Basis for HIV-1 Neutralization by 2F5-Like Antibodies m66 and m66.6
Authors: Ofek Gilad , Zirkle Brett , Yang Yongping , Zhu Zhongyu , McKee Krisha , Zhang Baoshan , Chuang Gwo-Yu , Georgiev Ivelin S. , O'Dell Sijy , Doria-Rose Nicole , Mascola John R. , Dimitrov Dimiter S. , Kwong Peter D.
Published: December 2013

Antibodies m66.6 and 2F5 are the only effective human HIV-1-neutralizing antibodies reported thus far to recognize the N-terminal region of the membrane-proximal external region (MPER) of the gp41 subunit of the HIV-1 envelope glycoprotein. Although 2F5 has been extensively characterized, much less is known about antibody m66.6 or antibody m66, a closely related light-chain variant. Here, we report the crystal structure of m66 in complex with its gp41 epitope, along with unbound structures of m66 and m66.6. We used mutational and binding analyses to decipher antibody elements critical for their recognition of gp41 and determined the molecular basis that underlies their neutralization of HIV-1. When bound by m66, the N-terminal region of the gp41 MPER adopts a conformation comprising a helix, followed by an extended loop. Comparison of gp41-bound m66 to unbound m66.6 identified three light-chain residues of m66.6 that were confirmed through mutagenesis to underlie the greater breadth of m66.6-mediated virus neutralization. Recognition of gp41 by m66 also revealed similarities to antibody 2F5 both in the conformation of crucial epitope residues as well as in the angle of antibody approach. Aromatic residues at the tip of the m66.6 heavy-chain third complementarity-determining region, as in the case of 2F5, were determined to be critical for virus neutralization in a manner that correlated with antibody recognition of the MPER in a lipid context. Antibodies m66, m66.6, and 2F5 thus utilize similar mechanistic elements to recognize a common gp41-MPER epitope and to neutralize HIV-1.
Sirtuin 1 Regulates Hepatitis B Virus Transcription and Replication by Targeting Transcription Factor AP-1
Authors: Ren Ji-Hua , Tao Ying , Zhang Zhen-Zhen , Chen Wei-Xian , Cai Xue-Fei , Chen Ke , Ko Ben C. B. , Song Chun-Li , Ran Long-Kuan , Li Wan-Yu , Huang Ai-Long , Chen Juan
Published: December 2013

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Nevertheless, the molecular mechanism of HBV replication remains elusive. SIRT1 is a class III histone deacetylase that is a structure component of the HBV cccDNA minichromosome. In this study, we found by using microarray-based gene expression profiling analysis that SIRT1 was upregulated in HBV-expressing cells. Gene silencing of SIRT1 significantly inhibited HBV DNA replicative intermediates, 3.5-kb mRNA, and core protein levels. In contrast, the overexpression of SIRT1 augmented HBV replication. Furthermore, SIRT1 enhanced the activity of HBV core promoter by targeting transcription factor AP-1. The c-Jun subunit of AP-1 was bound to the HBV core promoter region, as demonstrated by using a chromatin immunoprecipitation assay. Mutation of AP-1 binding site or knockdown of AP-1 abolished the effect of SIRT1 on HBV replication. Finally, SIRT1 inhibitor sirtinol also suppressed the HBV DNA replicative intermediate, as well as 3.5-kb mRNA. Our study identified a novel host factor, SIRT1, which may facilitate HBV replication in hepatocytes. These data suggest a rationale for the use of SIRT1 inhibitor in the treatment of HBV infection.
Unification of the Globally Distributed Spindle-Shaped Viruses of the Archaea
Authors: Krupovic Mart , Quemin Emmanuelle R. J. , Bamford Dennis H. , Forterre Patrick , Prangishvili David
Published: December 2013

Viruses with spindle-shaped virions are abundant in diverse environments. Over the years, such viruses have been isolated from a wide range of archaeal hosts. Evolutionary relationships between them remained enigmatic, however. Here, using structural proteins as markers, we define familial ties among these “dark horses” of the virosphere and segregate all spindle-shaped viruses into two distinct evolutionary lineages, corresponding to
Bicaudaviridae
and
Fuselloviridae
. Our results illuminate the utility of structure-based virus classification and bring additional order to the virosphere.
Hantavirus Gn and Gc Glycoproteins Self-Assemble into Virus-Like Particles
Authors: Acuña Rodrigo , Cifuentes-Muñoz Nicolás , Márquez Chantal L. , Bulling Manuela , Klingström Jonas , Mancini Roberta , Lozach Pierre-Yves , Tischler Nicole D.
Published: December 2013

How hantaviruses assemble and exit infected cells remains largely unknown. Here, we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and Gc envelope glycoproteins lead to their self-assembly into virus-like particles (VLPs) which were released to cell supernatants. The viral nucleoprotein was not required for particle formation. Further, a Gc endodomain deletion mutant did not abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and reacted with patient sera.
Encephalomyocarditis Virus Leader Is Phosphorylated by CK2 and Syk as a Requirement for Subsequent Phosphorylation of Cellular Nucleoporins
Authors: Basta Holly A. , Bacot-Davis Valjean R. , Ciomperlik Jessica J. , Palmenberg Ann C.
Published: December 2013

Encephalomyocarditis virus
and
Theilovirus
are species in the
Cardiovirus
genus of the
Picornaviridae
family. For all cardioviruses, the viral polyprotein is initiated with a short Leader (L) protein unique to this genus. The nuclear magnetic resonance (NMR) structure of L
E
from encephalomyocarditis virus (EMCV) has been determined. The protein has an NH
2
-proximal CHCC zinc finger, a central linker, and a contiguous, highly acidic motif. The theiloviruses encode the same domains, with one or two additional, COOH-proximal domains, characteristic of the human Saffold viruses (SafV) and Theiler's murine encephalomyelitis viruses (TMEV), respectively. The expression of a cardiovirus L, in recombinant form, or during infection/transfection, triggers an extensive, cell-dependent, antihost phosphorylation cascade, targeting nucleoporins (Nups) that form the hydrophobic core of nuclear pore complexes (NPC). The consequent inhibition of active nucleocytoplasmic trafficking is potent and prevents the host from mounting an effective antiviral response. For this inhibition, the L proteins themselves must be phosphorylated. In cells (extracts or recombinant form), L
E
was shown to be phosphorylated at Thr
47
and Tyr
41
. The first reaction (Thr
47
), catalyzed by casein kinase 2 (CK2), is an obligatory precedent to the second event (Tyr
41
), catalyzed by spleen tyrosine kinase (Syk). Site mutations in L
E
, or kinase-specific inhibitors, prevented L
E
phosphorylation and subsequent Nup phosphorylation. Parallel experiments with L
S
(SafV-2) and L
T
(TMEV BeAn) proteins confirmed the general cardiovirus requirement for L phosphorylation, but CK2 was not the culpable kinase. It is likely that L
S
and L
T
are both activated by alternative kinases in different cell types, probably reactive within the Theilo-specific domains.

IMPORTANCE
An understanding of the diverse methods used by viruses to interfere with cellular processes is important because they can teach us how to control virus infections. This report shows how viruses in the same genus use different cellular enzymes to phosphorylate their proteins. If these processes are interfered with, the viruses are severely disabled.
Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotypes
Authors: Pope Welkin H. , Anders Kirk R. , Baird Madison , Bowman Charles A. , Boyle Michelle M. , Broussard Gregory W. , Chow Tiffany , Clase Kari L. , Cooper Shannon , Cornely Kathleen A. , DeJong Randall J. , Delesalle Veronique A. , Deng Lisa , Dunbar David , Edgington Nicholas P. , Ferreira Christina M. , Weston Hafer Kathleen , Hartzog Grant A. , Hatherill J. Robert , Hughes Lee E. , Ipapo Khristina , Krukonis Greg P. , Meier Christopher G. , Monti Denise L. , Olm Matthew R. , Page Shallee T. , Peebles Craig L. , Rinehart Claire A. , Rubin Michael R. , Russell Daniel A. , Sanders Erin R. , Schoer Morgan , Shaffer Christopher D. , Wherley James , Vazquez Edwin , Yuan Han , Zhang Daiyuan , Cresawn Steven G. , Jacobs-Sera Deborah , Hendrix Roger W. , Hatfull Graham F.
Published: December 2013

Genomic analysis of a large set of phages infecting the common host
Mycobacterium smegmatis
mc
2
155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode.

IMPORTANCE
The bacteriophage population is vast, dynamic, and old and plays a central role in bacterial pathogenicity. We know surprisingly little about the genetic diversity of the phage population, although metagenomic and phage genome sequencing indicates that it is great. Probing the depth of genetic diversity of phages of a common host,
Mycobacterium smegmatis
, provides a higher resolution of the phage population and how it has evolved. Three new phages constituting a new cluster M further expand the diversity of the mycobacteriophages and introduce novel features. As such, they provide insights into phage genome architecture, virion structure, and gene regulation at the transcriptional and translational levels.
Evasion of Antiviral Immunity through Sequestering of TBK1/IKKε/IRF3 into Viral Inclusion Bodies
Authors: Wu Xiaodong , Qi Xian , Qu Bingqian , Zhang Zerui , Liang Mifang , Li Chuan , Cardona Carol J. , Li Dexin , Xing Zheng
Published: December 2013

Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed during the replication of some viruses in infected cells, but their role in viral immune evasion has rarely been explored. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness caused by a novel phlebovirus in the
Bunyaviridae
. The SFTS viral nonstructural protein NSs can suppress host beta interferon (IFN-β) responses. NSs can form IBs in infected and transfected cells. Through interaction with tank-binding kinase 1 (TBK1), viral NSs was able to sequester the IKK complex, including IKKε and IRF3, into IBs, although NSs did not interact with IKKε or IRF3 directly. When cells were infected with influenza A virus, IRF3 was phosphorylated and active phosphorylated IRF3 (p-IRF3) was translocated into the nucleus. In the presence of NSs, IRF3 could still be phosphorylated, but p-IRF3 was trapped in cytoplasmic IBs, resulting in reduced IFN-β induction and enhanced viral replication. Sequestration of the IKK complex and active IRF3 into viral IBs through the interaction of NSs and TBK1 is a novel mechanism for viral evasion of innate immunity.
Vitamin D receptor gene polymorphisms and the risk of rickets among Asians: a meta-analysis
Authors: Mao Song , Huang Songming
Published: December 2013

This article has been retracted. Dr Songming Huang has advised that although he agreed to be listed as the correspondence author he should not have been named as a co-author of this publication because he made no contributions to it.

He and Song Mao have asked for the article to be retracted on the ground that data included in it and its conclusions are to a significant degree the same as those previously published in Chin J Evid Based Pediatr 2011;6:4.
Combined deficiency of proteins C and S: ischaemic stroke in young individuals
Authors: Patel Munna Lal , Sachan Rekha , Seth Ganesh
Published: December 2013

In adults of any age, the majority of strokes are ischaemic (caused by a blockage in the blood supply to the brain). Stroke in young individuals poses a major health problem. The WHO defines stroke as an event caused by the interruption of the blood supply to the brain, usually because of rupture of a blood vessel or blockage by a clot. This hampers the supply of oxygen and nutrients, causing damage to the brain tissue. Globally, stroke is the third commonest cause of mortality and the fourth leading cause of disease burden. Ischaemic stroke is the most common cerebrovascular disease, most often due to atherothrombotic diseases and uncommonly by disorders of hypercoagulation. Disorders of coagulation leading to thrombotic disorders are approximately 1% of all ischaemic strokes and 4–8% of strokes in young individuals. Similarly, combined deficiency of proteins C and S can lead to hypercoagulable state and rarely presents as a cerebrovascular accident. We describe here a case of a 25-year-old man who presented with right middle cerebral artery territory infarct due to protein C and S deficiency.
Tubercular duodenal, jejunal and ileocecal stricture in a patient
Authors: Sisodiya Rajesh , Ramachandra Lingadakai
Published: December 2013

Gastrointestinal tuberculosis is a major health problem in the developing countries. Duodenal involvement is uncommon and can mimic superior mesenteric artery syndrome. Our case presented as proximal intestinal obstruction had tubercular stricture in the third part of the duodenum, proximal jejunum and ileocecal region, an uncommon and difficult intraoperative situation.
Oral submucous fibrosis: a premalignant condition in a 14-year-old Indian girl
Authors: Deshpande Anshula , Kiran Shital , Dhillon Steffi , Mallikarjuna Rachappa
Published: December 2013

A 14-year-old Indian girl presented with difficulty in mouth opening and burning sensation while eating. On examination, blanching of the oral mucosa with diffuse white pigmented lesion of size 3.5 to 2 cm along with melanotic pigmentation was seen on the left buccal mucosa posteriorly. The patient was diagnosed with oral submucous fibrosis. A comprehensive treatment plan was made based on conservative management that included motivation and intense counselling of the patient and her parents so that she quits the habit of chewing areca nut and tobacco, along with systemic treatment of vitamin B complex supplements, antioxidants, multivitamins and oral physiotherapy. We present this case to highlight the difficulties faced by the clinical practitioners in providing treatment because of the taboos and myths associated with surgical treatment modality in rural population as well as to emphasise the menace of increasing consumption and availability of tobacco and areca nut to children.
Sarcoidosis: clinical mimicry of pulmonary embolism
Authors: Nasher Omar , Boldy David A
Published: December 2013

Sarcoidosis can manifest with clinical signs suggestive of pulmonary embolism (PE). A 36-year-old male patient presented with a 2-day history of left-sided pleuritic chest pain and dyspnoea. He was hypoxicand tachypnoeic, and initial blood tests showed a positive plasma D-dimer. Subsequent arterial blood gas showed respiratory alkalosis with type 1 respiratory failure. He was suspected to have a PE, and CT pulmonary angiogram (CTPA) was urgently arranged. This latter investigation did not show any impairment in pulmonary arterial blood flow but revealed bilateral hilar and mediastinal lymphadenopathy suggesting sarcoidosis. Serum calcium and ACE were also elevated. The patient was treated conservatively and discharged after 2 days with out-patient endobronchial ultrasound and clinic follow-up arranged.