bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Objective Optimization of Layered Elastic Metamaterials With Multiphase Microstructures
Authors: Xu Weikai , Wang Wei , Yang Tianzhi
Published: June 2013

Layered elastic metamaterials, which simultaneously exhibit negative effective mass density and bulk modulus, can be obtained with a unit cell of multiphase materials. In this paper, a systematic method for the design of multiphase layered elastic metamaterials is presented, and single objective along with multiobjective optimization models are proposed. Using the multiobjective genetic algorithm, the topologies of the layered periodic unit cell are designed for target frequency band structures characterizing negative wavenumbers. These obtained metamaterials with periodic unit cells can exhibit a negative refractive index in several frequency spectrums. This will be a reference for the design of 2/3-D elastic/acoustic negative refraction metamaterials.
Analysis of Phononic Bandgap Structures With Dissipation
Authors: Andreassen Erik , Jensen Jakob S.
Published: June 2013

We study wave propagation in periodic materials with dissipation using two different formulations. An ω(k)-formulation yields complex frequency solutions for nonvanishing dissipation whereas a k(ω)-formulation leads to complex wave numbers. For small (realistic) levels of material dissipation and longer wavelengths, we show that the two formulations produce nearly identical results in terms of propagation constant and wave decay. We use the k(ω)-formulation to compute loss factors with dissipative bandgap materials for steady-state wave propagation and create simplified diagrams that unify the spatial loss factor from dissipative and bandgap effects. Additionally, we demonstrate the applicability of the k(ω)-formulation for the computation of the band diagram for viscoelastic composites and compare the computed loss factors for low frequency wave propagation to existing results based on quasi-static homogenization theory.
Postbuckling Analysis of Snaked-Lay Pipelines Based on a New Deformation Shape
Authors: Liu Yuxiao , Li Xin , Zhou Jing , Song Hualing
Published: June 2013

Lateral buckling must be considered in exposed HP/HT pipeline design. The snaked-lay method is an effective lateral buckling control method, a new deformation shape of snaked-lay pipeline is presented, and a control criterion of offset angle is also presented. When the offset angle is small or offset angle is large while the pipeline length of snaked-lay is too short or long, the maximum moments of postbuckling pipeline are large. For these problems, a new controlling method combined with snaked-lay and sleeper is proposed, which is named the SS method. Using Ansys, a nonlinear finite element model considering the interaction of seabed-sleeper-pipeline is established. The SS method is proved to be feasible to control lateral buckling for submarine pipelines. Based on critical axial compressive force and maximum bending moment, a design criterion of sleeper height is suggested.
At Sea Experiment of a Hybrid Spar for Floating Offshore Wind Turbine Using 1/10-Scale Model
Authors: Utsunomiya Tomoaki , Matsukuma Hidekazu , Minoura Shintaro , Ko Kiyohiko , Hamamura Hideki , Kobayashi Osamu , Sato Iku , Nomoto Yoshihisa , Yasui Kentaro
Published: June 2013

This study aims at development of a cost-effective, floating offshore wind turbine. The prototype model considered herein is composed of (1) 2-MW horizontal-axis wind turbine (HAWT) of downwind type, (2) steel monotower with 55-m hub height above sea level, (3) steel-prestressed concrete (PC) hybrid SPAR-type foundation with 70-m draft, and (4) catenary mooring system using anchor chains. In order to demonstrate the feasibility of the concept, an at-sea experiment using a 1/10-scale model of the prototype has been made. The demonstrative experiment includes (1) construction of the hybrid SPAR foundation using PC and steel, the same as the prototype; (2) dry-towing and installation to the at-sea site at 30-m distance from the quay of the Sasebo shipbuilding yard; (3) generating electric power using a 1 kW HAWT; and (4) removal from the site. During the at-sea experiment, wind speed, wind direction, tidal height, wave height, motion of the SPAR, tension in a mooring chain, and strains in the tower and the SPAR foundation have been measured. Motion of the SPAR has been numerically simulated and compared with the measured values, where basically good agreement is observed.
Theoretical and Experimental Study of Locally Resonant and Bragg Band Gaps in Flexural Beams Carrying Periodic Arrays of Beam-Like Resonators
Authors: Xiao Yong , Wen Jihong , Wang Gang , Wen Xisen
Published: June 2013

In this paper, we present a design of locally resonant (LR) beams using periodic arrays of beam-like resonators (or beam-like vibration absorbers) attached to a thin homogeneous beam. The main purpose of this work is twofold: (i) providing a theoretical characterization of the proposed LR beams, including the band gap behavior of infinite systems and the vibration transmittance of finite structures, and (ii) providing experimental evidence of the associated band gap properties, especially the coexistence of LR and Bragg band gaps, and their evolution with tuned local resonance. For the first purpose, an analytical method based on the spectral element formulations is presented, and then an in-depth numerical study is performed to examine the band gap effects. In particular, explicit formulas are provided to enable an exact calculation of band gaps and an approximate prediction of band gap edges. For the second purpose, we fabricate several LR beam specimens by mounting 16 equally spaced resonators onto a free-free host beam. These specimens use the same host beam, but the resonance frequencies of the resonators on each beam are different. We further measure the vibration transmittances of these specimens, which give evidence of three interesting band gap phenomena: (i) transition between LR and Bragg band gaps; (ii) near-coupling effect of the local resonance and Bragg scattering; and (iii) resonance frequency of local resonators outside of the LR band gap.
Study of a Floating Foundation for Wind Turbines
Authors: Gueydon Sébastien , Weller Sam
Published: June 2013

Offshore wind farms are currently located predominantly in shallow water as it is possible to cost effectively install bottom fixed offshore turbines. Where shallow water sites are not available, floating offshore turbines could be a better solution than bottom fixed turbines. Currently three main concepts are promoted for the design of a floating wind turbine: a ballast stabilized floater (i.e., spar), a buoyancy stabilized floater (i.e., barge or semisubmersible), or a mooring stabilized floater (tension leg platform). In April 2011 the DeepCWind consortium visited MARIN to carry out model tests in the offshore wave basin with these three types of floating wind turbine platform. This paper reports a numerical study of a wind turbine supported by a semisubmersible floater. The response of the floating system to wind and wave conditions is compared to physical measurements at 1:50 model scale. The outcome of these comparisons is discussed in the conclusions of this paper.
Advances in silicon carbide science and technology at the micro- and nanoscales
Authors: Maboudian Roya , Carraro Carlo , Senesky Debbie G. , Roper Christopher S.
Published: June 2013

Advances in siliconcarbide microfabrication and growth process optimization for siliconcarbide nanostructures are ushering in new opportunities for microdevices capable of operation in a variety of demanding applications, involving high temperature, radiation, or corrosive environment. This review focuses on the materials science and processing technologies for siliconcarbidethin films and low dimensional structures, and details recent progress in manufacturing technology, including deposition, metallization, and fabrication of semiconductor microdevices, with emphasis on sensor technology. The challenges remaining in developing siliconcarbide as a mainstay materials platform are discussed throughout.
Imaging Morphogenesis: Technological Advances and Biological Insights
Authors: Keller Philipp J.
Published: June 2013

Morphogenesis, the development of the shape of an organism, is a dynamic process on a multitude of scales, from fast subcellular rearrangements and cell movements to slow structural changes at the whole-organism level. Live-imaging approaches based on light microscopy reveal the intricate dynamics of this process and are thus indispensable for investigating the underlying mechanisms. This Review discusses emerging imaging techniques that can record morphogenesis at temporal scales from seconds to days and at spatial scales from hundreds of nanometers to several millimeters. To unlock their full potential, these methods need to be matched with new computational approaches and physical models that help convert highly complex image data sets into biological insights.
Mechanics of Epithelial Tissue Homeostasis and Morphogenesis
Authors: Guillot Charlène , Lecuit Thomas
Published: June 2013

Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.
Structural Basis for Effector Control and Redox Partner Recognition in Cytochrome P450
Authors: Tripathi Sarvind , Li Huiying , Poulos Thomas L.
Published: June 2013

Getting Active

The P450 cytochromes are a family of enzymes that contain a heme cofactor and catalyze the oxidation of organic substrates, including drugs. Protein partners are required to deliver electrons to P450. Insight into this mechanism has come from studies of bacterial P450cam; however, a lack of structures of redox complexes has hindered understanding.

Tripathi
et al.

(p.
1227
) describe the high resolution crystal structures of oxidized and reduced P450cam complexed with its redox partner putidaredoxin (Pdx). Pdx favors binding to the more open form of P450cam, which enables establishment of the water-mediated H-bonded network required for proton-coupled electron transfer and O
2
activation.
Bayes' Theorem in the 21st Century
Authors: Efron Bradley
Published: June 2013

Bayes' theorem plays an increasingly prominent role in statistical applications but remains controversial among statisticians.
Europe Opens Door to Global Approach on Megaprojects
Authors: Cho Adrian
Published: June 2013

Updated European physics strategy sets the stage for global collaboration on megaprojects
Why Do So Many Neurons Commit Suicide During Brain Development?
Authors: Underwood Emily
Published: June 2013

Scientists have identified at least two, and possibly three, waves of neuronal cell death in the embryonic mammalian brain during development.
Comparison of Different Assays To Assess Human Papillomavirus (HPV) Type 16- and 18-Specific Antibodies after HPV Infection and Vaccination
Authors: Scherpenisse Mirte , Schepp Rutger M. , Mollers Madelief , Mooij Sofie H. , Meijer Chris J. L. M. , Berbers Guy A. M. , van der Klis Fiona R. M.
Published: June 2013

We compared the measurement of human papillomavirus (HPV)-specific serum antibody levels with the virus-like-particle multiplex immunoassay (VLP-MIA), competitive Luminex immunoassay (cLIA), and glutathione
S
-transferase (GST) L1-based MIA. Using a large panel of serum samples, these assays showed mutually good correlations for both naturally induced and vaccine-derived HPV-specific antibody levels. However, an adaptation of the GST L1-based MIA resulted in an improved correlation with both cLIA and VLP-MIA.
Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria
Authors: Ahmed Ismail Hodan , Ribacke Ulf , Reiling Linda , Normark Johan , Egwang Tom , Kironde Fred , Beeson James G. , Wahlgren Mats , Persson Kristina E. M.
Published: June 2013

Malaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 of
Plasmodium falciparum
3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27.Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinical
P. falciparum
isolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with the
P. falciparum
K1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates.
Oral Inoculation of Chickens with a Candidate Fowl Adenovirus 9 Vector
Authors: Deng Li , Sharif Shayan , Nagy Éva
Published: June 2013

Fowl adenoviruses (FAdVs) are a potential alternative to human adenovirus-based vaccine vectors. Our previous studies demonstrated that a 2.4-kb region at the left end of the FAdV-9 genome is nonessential for virus replication and is suitable for the insertion or replacement of transgenes. Ourin vivostudy showed that the virus FAdV-9Δ4, lacking six open reading frames (ORFs) at the left end of its genome, replicates less efficiently than wild-type FAdV-9 (wtFAdV-9) in chickens that were infected intramuscularly. However, the fecal-oral route is the natural route of FAdV infection, and the oral administration of a vaccine confers some advantages compared to administration through other routes, especially when developing an adenovirus as a vaccine vector. Therefore, we sought to investigate the effects of FAdV-9 in orally inoculated chickens. In the present study, we orally inoculated specific-pathogen-free (SPF) chickens with FAdV-9 and FAdV-9Δ4 and assessed virus shedding, antibody response, and viral genome copy number and cytokine gene expression in tissues. Our data showed that FAdV-9Δ4 replicated less efficiently than did wtFAdV-9, as evidenced by reduced virus shedding in feces, lower viral genome copy number in tissues, and lower antibody response, which are consistent with the results of the intramuscular route of immunization. Furthermore, we found that both wtFAdV-9 and FAdV-9Δ4 upregulated the mRNA expression of alpha interferon (IFN-α), IFN-γ, and interleukin-12 (IL-12). In addition, there was a trend toward downregulation of IL-10 gene expression caused by both viruses. These findings indicate that one or more of the six deleted ORFs contribute to modulating the host response against virus infection as well as virus replicationin vivo.
Rapid Wuchereria bancrofti-Specific Antigen Wb123-Based IgG4 Immunoassays as Tools for Surveillance following Mass Drug Administration Programs on Lymphatic Filariasis
Authors: Steel Cathy , Golden Allison , Kubofcik Joseph , LaRue Nicole , de los Santos Tala , Domingo Gonzalo J. , Nutman Thomas B.
Published: June 2013

The Global Programme to Eliminate Lymphatic Filariasis has an urgent need for rapid assays to detect ongoing transmission of lymphatic filariasis (LF) following multiple rounds of mass drug administration (MDA). Current WHO guidelines support using the antigen card immunochromatographic test (ICT), which detects active filarial infection but does not detect early exposure to LF. Recent studies found that antibody-based assays better serve this function. In the present study, two tests, a rapid IgG4 enzyme-linked immunosorbent assay (ELISA) and a lateral-flow strip immunoassay, were developed based on the highly sensitive and specific
Wuchereria bancrofti
antigen Wb123. A comparison of
W. bancrofti
-infected and -uninfected patients (with or without other helminth infections) demonstrated that both tests had high sensitivities and specificities (93 and 97% [ELISA] and 92 and 96% [strips], respectively). When the
W. bancrofti
-uninfected group was separated into those with other filarial/helminth infections (i.e., onchocerciasis, loiasis, and strongyloidiasis) and those who were parasite uninfected, the specificities of the assays varied between 91 and 100%. In addition, the geometric mean response by ELISA of
W. bancrofti
-infected patients was significantly higher than the response of those without
W. bancrofti
infection (
P
< 0.0001). Furthermore, the Wb123 ELISA and the lateral-flow strips had high positive and negative predictive values, giving valuable information on the size of survey population needed to be reasonably certain whether or not transmission is ongoing. These highly sensitive and specific IgG4 tests to the
W. bancrofti
Wb123 protein give every indication that they will serve as useful tools for post-MDA monitoring.
Serodiagnosis of Mycobacterium avium Complex and Mycobacterium abscessus Complex Pulmonary Disease by Use of IgA Antibodies to Glycopeptidolipid Core Antigen
Authors: Jeong Byeong-Ho , Kim Su-Young , Jeon Kyeongman , Lee Soo-Youn , Shin Sung Jae , Koh Won-Jung
Published: June 2013

An enzyme immunoassay kit that detects serum IgA antibody reacting to glycopeptidolipid core antigen derived from
Mycobacterium avium
complex (MAC) was not useful for differentiating MAC pulmonary disease (PD) from
Mycobacterium abscessus
complex PD (MAB-PD). However, this assay could be useful for differentiating MAC- and MAB-PD from pulmonary tuberculosis. (This study has been registered at ClinicalTrials.gov under registration no. NCT00970801.)
Cell Extract-Containing Medium for Culture of Intracellular Fastidious Bacteria
Authors: Singh Sudhir , Kowalczewska Malgorzata , Edouard Sophie , Eldin Carole , Perreal Céline , Weber Pascal , Azza Said , Raoult Didier
Published: June 2013

The culture of fastidious microorganisms is a critical step in infectious disease studies. As a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth ofCoxiella burnetii. Here, we demonstrate the exponential growth of several bacterial strains, including theC. burnetiiNine Mile phase I and phase II strains, andC. burnetiiisolates from humans and animals. Low-oxygen-tension conditions and the presence of small hydrophilic molecules and short peptides were critical for facilitating growth. Moreover, bacterial antigenicity was conserved, revealing the potential for this culture medium to be used in diagnostic tests and in the elaboration of vaccines againstC. burnetii. We were also able to grow the majority of previously tested intracellular and fastidious bacterial species, includingTropheryma whipplei,Mycobacterium bovis,Leptospiraspp.,Borreliaspp., and most putative bioterrorism agents. However, we were unable to cultureRickettsia africaeandLegionellaspp. in this medium. The versatility of this medium should encourage its use as a replacement for the cell-based culture systems currently used for growing several facultative and putative intracellular bacterial species.
The Kinase Activity of Ataxia-Telangiectasia Mutated Interferes with Adenovirus E4 Mutant DNA Replication
Authors: Gautam Dipendra , Bridge Eileen
Published: June 2013

Adenovirus (Ad) mutants that lack early region 4 (E4) are unable to produce the early regulatory proteins that normally inactivate the Mre11/Rad50/Nbs1 (MRN) sensor complex, which is a critical component for the ability of cells to respond to DNA damage. E4 mutant infection therefore activates a DNA damage response, which in turn interferes with a productive viral infection. MRN complex proteins localize to viral DNA replication centers in E4 mutant-infected cells, and this complex is critical for activating the kinases ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR), which phosphorylate numerous substrates important for DNA repair, cell cycle checkpoint activation, and apoptosis. E4 mutant growth defects are substantially rescued in cells lacking an intact MRN complex. We have assessed the role of the downstream ATM and ATR kinases in several MRN-dependent E4 mutant phenotypes. We did not identify a role for either ATM or ATR in “repair” of E4 mutant genomes to form concatemers. ATR was also not observed to contribute to E4 mutant defects in late protein production. In contrast, the kinase activity of ATM was important for preventing efficient E4 mutant DNA replication and late gene expression. Our results suggest that the MRN complex interferes with E4 mutant DNA replication at least in part through its ability to activate ATM.
Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody
Authors: Wang Zhiqing , Li Long , Pennington Janice G. , Sheng Ju , Yap Moh Lan , Plevka Pavel , Meng Geng , Sun Lei , Jiang Wen , Rossmann Michael G.
Published: June 2013

The 2H2 monoclonal antibody recognizes the precursor peptide on immature dengue virus and might therefore be a useful tool for investigating the conformational change that occurs when the immature virus enters an acidic environment. During dengue virus maturation, spiky, immature, noninfectious virions change their structure to form smooth-surfaced particles in the slightly acidic environment of the
trans
-Golgi network, thereby allowing cellular furin to cleave the precursor-membrane proteins. The dengue virions become fully infectious when they release the cleaved precursor peptide upon reaching the neutral-pH environment of the extracellular space. Here we report on the cryo-electron microscopy structures of the immature virus complexed with the 2H2 antigen binding fragments (Fab) at different concentrations and under various pH conditions. At neutral pH and a high concentration of Fab molecules, three Fab molecules bind to three precursor-membrane proteins on each spike of the immature virus. However, at a low concentration of Fab molecules and pH 7.0, only two Fab molecules bind to each spike. Changing to a slightly acidic pH caused no detectable change of structure for the sample with a high Fab concentration but caused severe structural damage to the low-concentration sample. Therefore, the 2H2 Fab inhibits the maturation process of immature dengue virus when Fab molecules are present at a high concentration, because the three Fab molecules on each spike hold the precursor-membrane molecules together, thereby inhibiting the normal conformational change that occurs during maturation.
Prion Replication Elicits Cytopathic Changes in Differentiated Neurosphere Cultures
Authors: Iwamaru Yoshifumi , Takenouchi Takato , Imamura Morikazu , Shimizu Yoshihisa , Miyazawa Kohtaro , Mohri Shirou , Yokoyama Takashi , Kitani Hiroshi
Published: June 2013

The molecular mechanisms of prion-induced cytotoxicity remain largely obscure. Currently, only a few cell culture models have exhibited the cytopathic changes associated with prion infection. In this study, we introduced a cell culture model based on differentiated neurosphere cultures isolated from the brains of neonatal prion protein (PrP)-null mice and transgenic mice expressing murine PrP (dNP0 and dNP20 cultures). Upon exposure to mouse Chandler prions, dNP20 cultures supported thede novoformation of abnormal PrP and the resulting infectivity, as assessed by bioassays. Furthermore, this culture was susceptible to various prion strains, including mouse-adapted scrapie, bovine spongiform encephalopathy, and Gerstmann-Sträussler-Scheinker syndrome prions. Importantly, a subset of the cells in the infected culture that was mainly composed of astrocyte lineage cells consistently displayed late-occurring, progressive signs of cytotoxicity as evidenced by morphological alterations, decreased cell viability, and increased lactate dehydrogenase release. These signs of cytotoxicity were not observed in infected dNP0 cultures, suggesting the requirement of endogenous PrP expression for prion-induced cytotoxicity. Degenerated cells positive for glial fibrillary acidic protein accumulated abnormal PrP and exhibited features of apoptotic death as assessed by active caspase-3 and terminal deoxynucleotidyltransferase nick-end staining. Furthermore, caspase inhibition provided partial protection from prion-mediated cell death. These results suggest that differentiated neurosphere cultures can provide anin vitrobioassay for mouse prions and permit the study of the molecular basis for prion-induced cytotoxicity at the cellular level.
A Novel Hepacivirus with an Unusually Long and Intrinsically Disordered NS5A Protein in a Wild Old World Primate
Authors: Lauck Michael , Sibley Samuel D. , Lara James , Purdy Michael A. , Khudyakov Yury , Hyeroba David , Tumukunde Alex , Weny Geoffrey , Switzer William M. , Chapman Colin A. , Hughes Austin L. , Friedrich Thomas C. , O'Connor David H. , Goldberg Tony L.
Published: June 2013

GB virus B (GBV-B; family
Flaviviridae
, genus
Hepacivirus
) has been studied in New World primates as a model for human hepatitis C virus infection, but the distribution of GBV-B and its relatives in nature has remained obscure. Here, we report the discovery of a novel and highly divergent GBV-B-like virus in an Old World monkey, the black-and-white colobus (
Colobus guereza
), in Uganda. The new virus,
guereza
hepacivirus (GHV), clusters phylogenetically with GBV-B and recently described hepaciviruses infecting African bats and North American rodents, and it shows evidence of ancient recombination with these other hepaciviruses. Direct sequencing of reverse-transcribed RNA from blood plasma from three of nine colobus monkeys yielded near-complete GHV genomes, comprising two distinct viral variants. The viruses contain an exceptionally long nonstructural 5A (NS5A) gene, approximately half of which codes for a protein with no discernible homology to known proteins. Computational structure-based analyses indicate that the amino terminus of the GHV NS5A protein may serve a zinc-binding function, similar to the NS5A of other viruses within the family
Flaviviridae
. However, the 521-amino-acid carboxy terminus is intrinsically disordered, reflecting an unusual degree of structural plasticity and polyfunctionality. These findings shed new light on the natural history and evolution of the hepaciviruses and on the extent of structural variation within the
Flaviviridae
.
Topological Analysis of HIV-1 Glycoproteins Expressed
In Situ
on Virus Surfaces Reveals Tighter Packing but Greater Conformational Flexibility than for Soluble gp120
Authors: Tong Tommy , Osawa Keiko , Robinson James E. , Crooks Ema T. , Binley James M.
Published: June 2013

In natural infection, antibodies interact with HIV-1 primarily through nonfunctional forms of envelope glycoproteins (Env), including uncleaved (UNC) gp160 and gp41 stumps. These antigens are important to fully characterize, as they may be decoys that promote nonneutralizing responses and may also be targets for nonneutralizing effector responses. In this study, we compared the antigenic properties of Env expressed
in situ
on pseudovirion virus-like particle (VLP) surfaces and soluble gp120 using harmonized enzyme-linked immunosorbent assays (ELISAs) and a panel of 51 monoclonal antibodies (MAbs). Only 32 of 46 soluble gp120-reactive MAbs recognized the primary UNC gp160 antigen of VLPs. Indeed, many epitopes were poorly exposed (C1, V2, C1-C4, C4, C4-V3, CD4 induced [CD4i], and PGT group 3) or obscured (C2, C5, and C1-C5) on VLPs. In further studies, VLP Env exhibited an increased degree of inter-MAb competition, the epicenter of which was the base of the V3 loop, where PGT, 2G12, V3, and CD4 binding site specificities competed. UNC gp160 also underwent more drastic soluble CD4 (sCD4)-induced conformational changes than soluble gp120, exposing CD4i, C1-C4, and V2 epitopes. A greater propensity of UNC gp160 to undergo conformational changes was also suggested by the induction of CD4i MAb binding to VLPs by a V3 MAb as well as by soluble CD4. The same effect was not observed for soluble gp120. Taken together, our data suggest that membrane-expressed UNC gp160 exists in a less “triggered” conformational state than soluble gp120 and that MAb binding to UNC gp160 tends to have greater conformational consequences.
Mutations in the Capsid Protein of Brome Mosaic Virus Affecting Encapsidation Eliminate Vesicle Induction
In Planta
: Implications for Virus Cell-to-Cell Spread
Authors: Bamunusinghe Devinka , Chaturvedi Sonali , Seo Jang-Kyun , Rao A. L. N.
Published: June 2013

Positive-strand RNA viruses are known to rearrange the endomembrane network to make it more conducive for replication, maturation, or egress. Our previous transmission electron microscopic (TEM) analysis showed that ectopic expression of wild-type (wt) capsid protein (CP) of
Brome mosaic virus
(BMV) has an intrinsic property of modifying the endoplasmic reticulum (ER) to induce vesicles similar to those present in wt BMV infection. In this study, we evaluated the functional significance of CP-mediated vesicle induction to the BMV infection cycle
in planta
. Consequently, the cytopathologic changes induced by wt CP or its mutants defective in virion assembly due to mutations engineered in either N- or C-proximal domains were comparatively analyzed by TEM in two susceptible (
Nicotiana benthamiana
and
Chenopodium quinoa
) and one nonhost (
N. clevelandii
) plant species. The results showed that in susceptible hosts, CP-mediated ER-derived vesicle induction is contingent on the expression of encapsidation-competent CP. In contrast, unlike in
N. benthamiana
and
C. quinoa
, transient expression of wt CP in nonhost
N. clevelandii
plants eliminated vesicle induction. Additionally, comparative source-to-sink analysis of virus spread in leaves of
N. benthamiana
and
N. clevelandii
coexpressing wt BMV and
Cucumber mosaic virus
(CMV) showed that despite
trans
-encapsidation, CMV failed to complement the defective cell-to-cell movement of BMV. The significance and relation of CP-mediated vesicle induction to virus cell-to-cell movement are discussed.
Role of RNA Interference (RNAi) in Dengue Virus Replication and Identification of NS4B as an RNAi Suppressor
Authors: Kakumani Pavan Kumar , Ponia Sanket Singh , S Rajgokul K. , Sood Vikas , Chinnappan Mahendran , Banerjea Akhil C. , Medigeshi Guruprasad R. , Malhotra Pawan , Mukherjee Sunil K. , Bhatnagar Raj K.
Published: June 2013

RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by
in vitro
dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication.
The Endosomal Pathway and the Golgi Complex Are Involved in the Infectious Bursal Disease Virus Life Cycle
Authors: Delgui Laura R. , Rodríguez José F. , Colombo María I.
Published: June 2013

Infectious bursal disease virus
(IBDV), a double-stranded RNA virus belonging to the
Birnaviridae
family, causes immunosuppression in chickens. In this study, we defined the localization of IBDV replication complexes based on colocalization analysis of VP3, the major protein component of IBDV ribonucleoproteins (RNPs). Our results indicate that VP3 localizes to vesicular structures bearing features of early and late endocytic compartments located in the juxtanuclear region. Interfering with the endocytic pathway with a dominant negative version of Rab5 after the internalization step leads to a reduction in virus titer. Triple-immunostaining studies between VP3, the viral RNA-dependent RNA polymerase VP1, and viral double-stranded RNA (dsRNA) showed a well-defined colocalization, indicating that the three critical components of the RNPs colocalize in the same structure, likely representing replication complexes. Interestingly, recombinant expressed VP3 also localizes to endosomes. Employing Golgi markers, we found that VP3-containing vesicles were closely associated with this organelle. Depolymerization of microtubules with nocodazole caused a profound change in VP3 localization, showing a punctate distribution scattered throughout the cytoplasm. However, these VP3-positive structures remained associated with Golgi ministacks. Similarly, brefeldin A (BFA) treatment led to a punctate distribution of VP3, scattered throughout the cytoplasm of infected cells. In addition, analysis of intra- and extracellular viral infective particles after BFA treatment of avian cells suggested a role for the Golgi complex in viral assembly. These results constitute the first study elucidating the localization of IBDV replication complexes (i.e., in endocytic compartments) and establishing a role for the Golgi apparatus in the assembly step of a birnavirus.
Echovirus 1 Entry into Polarized Caco-2 Cells Depends on Dynamin, Cholesterol, and Cellular Factors Associated with Macropinocytosis
Authors: Krieger Sophie E. , Kim Chonsaeng , Zhang Lili , Marjomaki Varpu , Bergelson Jeffrey M.
Published: June 2013

Enteroviruses invade their hosts by crossing the intestinal epithelium. We have examined the mechanism by which echovirus 1 (EV1) enters polarized intestinal epithelial cells (Caco-2). Virus binds to VLA-2 on the apical cell surface and moves rapidly to early endosomes. Using inhibitory drugs, dominant negative mutants, and small interfering RNAs (siRNAs) to block specific endocytic pathways, we found that virus entry requires dynamin GTPase and membrane cholesterol but is independent of both clathrin- and caveolin-mediated endocytosis. Instead, infection requires factors commonly associated with macropinocytosis, including amiloride-sensitive Na+/H+exchange, protein kinase C, and C-terminal-binding protein-1 (CtBP1); furthermore, EV1 accumulates rapidly in intracellular vesicles with dextran, a fluid-phase marker. These results suggest a role for macropinocytosis in the process by which EV1 enters polarized cells to initiate infection.
Thyroid neurofibroma in a female patient with neurofibromatosis type I: report of a case
Authors: Doulias T , Papaziogas B , Rosser J H , Koutelidakis I
Published: June 2013

Neurofibromas are benign tumours arising from the Schwann cells of peripheral nerves. They usually occur on the limbs and rarely present at other sites such as the thyroid gland. Lesions associated with the thyroid are usually benign but should be closely followed up. When the presence of a plexiform neurofibroma in the thyroid gland is confirmed by radiological investigations, total thyroidectomy is the treatment of choice because of the substantial risk of malignant transformation. This case report details a rare case of thyroid plexiform neurofibroma in a young female patient with known Von Recklinghausen disease.
High-grade GI lymphoma presenting with diarrhoea
Authors: Al-Rubaye Sinan , Henson Sophie , Mahdi Ali
Published: June 2013

A 63-year-old male carpenter presented with diarrhoea after returning from a holiday in Egypt with no other abdominal features. Physical examination showed generalised lymphadenopathy and splenomegaly. Blood tests including inflammatory markers were within normal limits. Microbiological stool sample analysis was unremarkable. Endoscopies of the large bowel showed patchy inflammation from the rectum to the hepatic flexure with multiple tiny polyps. Histology revealed a lymphocytic infiltrate suggestive of multiple lymphomatous polyposis. Some time later, he presented with small bowel obstruction requiring emergency laparotomy and ileostomy. After recovery from surgery he started definite treatment with chemotherapy resulting in complete remission.
Mortality differentials 1991−2005 by self-reported ethnicity: findings from the ONS Longitudinal Study
Authors: Scott Anne P , Timæus Ian M
Published: June 2013

Background

Research on ethnic differentials in mortality in England and Wales has focused on immigrants because, until now, studies collecting data on ethnicity have not covered sufficient deaths to investigate the subject. International migrants are selected for good health and tend to have low mortality.

Methods

We investigated all-cause mortality at ages 1−79 in 1991−2005 by self-reported ethnicity and country of birth. The data are from the Office for National Statistics Longitudinal Study of England and Wales for the cohort aged 0−64 in 1991 (n=436 195). Poisson regression was used to adjust the estimates for metropolitan residence and three indicators of socioeconomic status.

Results

White, Black Caribbean, Other Asian and Other immigrants all had lower mortality than Whites born in the UK. Indian, Pakistani, Bangladeshi and Chinese immigrants had lower mortality than the UK-born Whites living in similar circumstances to them. By contrast, the UK-born Black Caribbean group had higher mortality (RR=1.38, 95% CI 1.03 to 1.86) than the UK-born Whites. This excess mortality was accounted for by their low socioeconomic status. Within the Black Caribbean population, the UK-born individuals had significantly higher mortality than those born abroad whether or not the estimates were adjusted for socioeconomic status and metropolitan residence. Adjusting exposure time for undocumented emigration made little difference to the estimates.

Conclusions

Immigrants are selected for good health. This has offset the impact of socioeconomic disadvantage on the mortality of minority ethnic groups. As the immigrant population ages and the UK-born minority ethnic population grows, ethnic differentials in all-cause mortality are likely to change.
N-acetylcysteine alters substrate metabolism during high-intensity cycle exercise in well-trained humans
Authors: Trewin Adam J. , Petersen Aaron C. , Billaut Francois , McQuade Leon R. , McInerney Bernie V. , Stepto Nigel K.
Published: June 2013

We investigated the effects of N-acetylcysteine (NAC) on metabolism during fixed work rate high-intensity interval exercise (HIIE) and self-paced 10-min time-trial (TT10) performance. Nine well-trained male cyclists (V̇O2peak, 69.4 ± 5.8 mL·kg−1·min−1; peak power output (PPO), 385 ± 43 W; mean ± SD) participated in a double-blind, repeated-measures, randomised crossover trial. Two trials (NAC supplementation and placebo) were performed 7 days apart consisting of 6 × 5 min HIIE bouts at 82% PPO (316 ± 40 W) separated by 1 min at 100 W, and then after 2 min of recovery at 100 W, TT10was performed. Expired gases, venous blood, and electromyographic (EMG) data were collected. NAC did not influence blood glutathione but decreased lipid peroxidation compared with the placebo (P < 0.05). Fat oxidation was elevated with NAC compared with the placebo during HIIE bouts 5 and 6 (9.9 ± 8.9 vs. 3.9 ± 4.8 μmol·kg−1·min−1; P < 0.05), as was blood glucose throughout HIIE (4.3 ± 0.6 vs. 3.8 ± 0.6 mmol·L−1; P < 0.05). Blood lactate was lower with NAC after TT10(3.3 ± 1.3 vs. 4.2 ± 1.3 mmol·L−1; P < 0.05). Median EMG frequency of the vastus lateralis was lower with NAC during HIIE (79 ± 10 vs. 85 ± 10 Hz; P < 0.05), but not TT10(82 ± 11 Hz). Finally, NAC decreased mean power output 4.9% ± 6.6% (effect size = –0.3 ± 0.4, mean ± 90% CI) during TT10(305 ± 57 W vs. 319 ± 45 W). These data suggest that NAC alters substrate metabolism and muscle fibre type recruitment during HIIE, which is detrimental to time-trial performance.
Contributions of gopher mound and casting disturbances to plant community structure in a Cascade Range meadow complex
Authors: Case Madelon F. , Halpern Charles B. , Levin Simon A.
Published: June 2013

Pocket gophers (Geomyidae) are major agents of disturbance in North American grasslands. Gopher mounds bury existing plants and influence community structure through various mechanisms. However, in mountain meadows that experience winter snowpack, gophers also create winter castings, smaller tube-shaped deposits, previously ignored in studies of plant–gopher disturbance relationships. We studied the influences of the Mazama pocket gopher (Thomomys mazama Merriam, 1897) in montane meadows of the Oregon Cascades, quantifying community patterns at larger spatial scales than previously studied in this system and considering, for the first time, effects of both mounds and castings. We measured cover of disturbance and individual plant species along twenty 5 m transects in each of four plots with differing species composition. Total plant cover was negatively correlated with mounds and castings. However, only mounds influenced growth-form dominance, reducing graminoid cover and increasing the forb–graminoid ratio — effects attributable to the greater volume and longevity of mounds. Forb-disturbance relationships were variable among plots, likely due to differences in species’ tolerance of burial. Transect-scale richness and heterogeneity (variation in composition within transects) increased with disturbance. We conclude that frequent, small-scale disturbances create a shifting mosaic of vegetation states, reducing graminoid dominance and enhancing species richness and heterogeneity at larger spatial scales.
HODGE DUALITY OPERATORS ON LEFT-COVARIANT EXTERIOR ALGEBRAS OVER TWO- AND THREE-DIMENSIONAL QUANTUM SPHERES
Authors: ZAMPINI ALESSANDRO
Published: June 2013

Using non-canonical braidings, we first introduce a notion of symmetric tensors and corresponding Hodge operators on a class of left-covariant 3d differential calculi over SU q(2), then we induce Hodge operators on the left-covariant 2d exterior algebra over the Podles quantum sphere.
A CLASS OF RANDERS METRICS OF SCALAR FLAG CURVATURE
Authors: SHEN ZHONGMIN , XIA QIAOLING
Published: June 2013

We study homothetic vector fields on Randers manifolds of projectively isotropic flag curvature and use them to construct new Randers metrics of scalar flag curvature.
THE INFLUENCE OF THE COUPLING STRENGTH ON THE ELECTRON TRANSPORT THROUGH THE BENZENE-1,4-DITHIOLATE MOLECULAR JUNCTION
Authors: YU YUNJIN , LI YAOYU , WAN LANGHUI , WANG BIN , WEI YADONG
Published: June 2013

The electronic transport properties of one benzene-1,4-dithiolate molecule coupled by two aluminum metal leads were investigated by using first-principles method. The influence of the coupling distance between the molecule and the electrodes on I–V curve was studied thoroughly. Our calculations showed that when the system is in the most stable configuration, where the system total energy is the lowest, and the electron transport is in off-resonant state. Starting from the most stable configuration, when we gradually increase the distance between the molecule and electrodes and so decreasing the coupling strength of the molecule and electrodes, the conductance, as well as the I–V curve, does not decrease immediately but increase quickly at first. Only when we separate the molecule and electrodes far enough, the current begins to drop quickly. The total scattering charge density was presented in order to understand this phenomenon. A one-level quantum dot model is used to explain it. Finally, negative differential resistance was observed and analyzed.
ON THE BISPECTRUM OF COSMIC STRING SEEDED CMB FLUCTUATIONS
Authors: LANDRIAU M.
Published: June 2013

I compute the bispectrum of maps of cosmic microwave background (CMB) fluctuations seeded by cosmic strings from large to 30 arcminute scales. Examining the distribution of triangle configurations and comparing with Gaussian realizations with the same power spectrum, I conclude that the CMB bispectrum cannot pick up the mild non-Gaussianity present in the maps and thus that it cannot characterize cosmic string induced non-Gaussianity produced in the regimes probed by these maps.
MODIFIED HOLOGRAPHIC RICCI DARK ENERGY MODEL AND STATEFINDER DIAGNOSIS IN FLAT UNIVERSE
Authors: MATHEW TITUS K. , SURESH JISHNU , DIVAKARAN DIVYA
Published: June 2013

Evolution of the universe with modified holographic Ricci dark energy model is considered. Dependency of the equation of state parameter and deceleration parameter on the redshift and model parameters are obtained. It is shown that the density evolution of both the nonrelativistic matter and dark energy are same until recent times. The evolutionary trajectories of the model for different model parameters are obtained in the statefinder planes, r – s and r – q planes. The present statefinder parameters are obtained for different model parameter values, using that the model is differentiated from other standard models like the ΛCDM model. We have also shown that the evolutionary trajectories are depending on the model parameters, and at past times the dark energy is behaving like cold dark matter, with equation of state equal to zero.