bluuebunny/crossref_metadata_2025 huggingface dataset:
Where's France Córdova? In the Washington hot seat
Authors: Mervis Jeffrey
Published: May 2014

New NSF director jumps into the frying pan served up by Congress as it reviews agency programs.
Lost at sea
Authors: Normile Dennis
Published: May 2014

As the hunt for the missing Malaysian jet grows more challenging, authorities are pondering how to avert future aviation vanishing acts.
Macrophage Depletion Prior to Neospora caninum Infection Results in Severe Neosporosis in Mice
Authors: Abe Chisa , Tanaka Sachi , Ihara Fumiaki , Nishikawa Yoshifumi
Published: May 2014

We observed that murine macrophages showed greater activation and increased interleukin 6 (IL-6), IL-12p40, and interferon gamma (IFN-γ) production duringNeospora caninuminfection. Many macrophages migrated to the site of infection. Furthermore, macrophage-depleted mice exhibited increased sensitivity toN. caninuminfection. This study indicates that macrophages are required for achieving protective immunity againstN. caninum.
Successful Control of Winter Pyrexias Caused by Equine Herpesvirus Type 1 in Japanese Training Centers by Achieving High Vaccination Coverage
Authors: Bannai Hiroshi , Mae Naomi , Ode Hirotaka , Nemoto Manabu , Tsujimura Koji , Yamanaka Takashi , Kondo Takashi , Matsumura Tomio
Published: May 2014

Equine herpesvirus type 1 (EHV-1) is a major cause of winter pyrexia in racehorses in two training centers (Ritto and Miho) in Japan. Until the epizootic period of 2008-2009, a vaccination program using a killed EHV-1 vaccine targeted only susceptible 3-year-old horses with low antibody levels to EHV-1 antigens. However, because the protective effect was not satisfactory, in 2009-2010 the vaccination program was altered to target all 3-year-old horses. To evaluate the vaccine's efficacy, we investigated the number of horses with pyrexia due to EHV-1 or equine herpesvirus type 4 (EHV-4) infection or both and examined the vaccination coverage in the 3-year-old population and in the whole population before and after changes in the program. The mean (± standard deviation [SD]) estimated numbers of horses infected with EHV-1 or EHV-4 or both, among pyretic horses from 1999-2000 to 2008-2009 were 105 ± 47 at Ritto and 66 ± 44 at Miho. Although the estimated number of infected horses did not change greatly in the first period of the current program, it decreased from the second period, with means (±SD) of 21 ± 12 at Ritto and 14 ± 15 at Miho from 2010-2011 to 2012-2013. Vaccination coverage in the 3-year-old population was 99.4% at Ritto and 99.8% at Miho in the first period, and similar values were maintained thereafter. Coverage in the whole population increased more gradually than that in the 3-year-old population. The results suggest that EHV-1 epizootics can be suppressed by maintaining high vaccination coverage, not only in the 3-year-old population but also in the whole population.
Detection and Molecular Characterization of Mycobacterium microti Isolates in Wild Boar from Northern Italy
Authors: Boniotti M. Beatrice , Gaffuri Alessandra , Gelmetti Daniela , Tagliabue Silvia , Chiari Mario , Mangeli Anna , Spisani Matteo , Nassuato Claudia , Gibelli Lucia , Sacchi Cristina , Zanoni Mariagrazia , Pacciarini M. Lodovica
Published: May 2014

Approximately 23,000 hunter-harvested wild boars from the pre-Alpine area of northern Italy were examined for tuberculosis over a 9-year period (2003 to 2011). Retropharyngeal and mandibular lymph nodes from the wild boars were examined grossly, and 1,151 of the lymph nodes were analyzed in our laboratory by histology (728 samples) and culture isolation (819 samples).
Mycobacterium tuberculosis
complex (MTBC)-specific PCR (1,142 samples) was used for molecular-level detection in tissue samples, as was a
gyrB
restriction fragment length polymorphism (RFLP) assay (322 samples). Lesions compatible with tuberculosis and indistinguishable from those described in cases of
Mycobacterium bovis
infection had been observed since 2003.
Mycobacterium microti
was identified directly in 256 tissue samples by the adopted molecular approaches. However, only 26
M. microti
strains were obtained by culture isolation due to the well-known difficulties in isolating this slow-growing mycobacterium. During 2006, a prevalence study was performed in two provinces of the area, and the diffusion of
M. microti
was calculated to be 5.8% (95% confidence intervals surrounding the estimated prevalences [CI
P95%
], 3.94 to 7.68%). Over the following years (2007 to 2011), the presence of
M. microti
appeared to be stable. All isolates were genotyped by spoligotyping and exact tandem repeat analysis (ETR types A to F). In addition to the typical vole type (SB0118), a new spoligotype lacking the 43 spacers was found. Spoligotyping was also applied directly to tissue samples, and a geographical cluster distribution of the two spoligotypes was observed. This is the first report studying the diffusion and genetic variability of
M. microti
in wild boar.
The Molecular Bacterial Load Assay Replaces Solid Culture for Measuring Early Bactericidal Response to Antituberculosis Treatment
Authors: Honeyborne Isobella , Mtafya Bariki , Phillips Patrick P. J. , Hoelscher Michael , Ntinginya Elias N. , Kohlenberg Anke , Rachow Andrea , Rojas-Ponce Gabriel , McHugh Timothy D. , Heinrich Norbert
Published: May 2014

We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable
Mycobacterium tuberculosis
in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form.
Porcine Epidemic Diarrhea Virus Nucleocapsid Protein Antagonizes Beta Interferon Production by Sequestering the Interaction between IRF3 and TBK1
Authors: Ding Zhen , Fang Liurong , Jing Huiyuan , Zeng Songlin , Wang Dang , Liu Lianzeng , Zhang Huan , Luo Rui , Chen Huanchun , Xiao Shaobo
Published: May 2014

Porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea in piglets and results in large economic losses in many Asian and European countries. A large-scale outbreak of porcine epidemic diarrhea occurred in China in 2010, and the virus emerged in the United States in 2013 and spread rapidly, posing significant economic and public health concerns. Previous studies have shown that PEDV infection inhibits the synthesis of type I interferon (IFN), and viral papain-like protease 2 has been identified as an IFN antagonist. In this study, we found that the PEDV-encoded nucleocapsid (N) protein also inhibits Sendai virus-induced IFN-β production, IFN-stimulated gene expression, and activation of the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB. We also found that N protein significantly impedes the activation of the IFN-β promoter stimulated by TBK1 or its upstream molecules (RIG-I, MDA5, IPS-1, and TRAF3) but does not counteract its activation by IRF3. A detailed analysis revealed that the PEDV N protein targets TBK1 by direct interaction and that this binding sequesters the association between TBK1 and IRF3, which in turn inhibits both IRF3 activation and type I IFN production. Together, our findings demonstrate a new mechanism evolved by PEDV to circumvent the host's antiviral immunity.

IMPORTANCE
PEDV has received increasing attention since the emergence of a PEDV variant in China and the United States. Here, we identify nucleocapsid (N) protein as a novel PEDV-encoded interferon (IFN) antagonist and demonstrate that N protein antagonizes IFN production by sequestering the interaction between IRF3 and TBK1, a critical step in type I IFN signaling. This adds another layer of complexity to the immune evasion strategies evolved by this economically important viral pathogen. An understanding of its immune evasion mechanism may direct us to novel therapeutic targets and more effective vaccines against PEDV infection.
Uracil DNA Glycosylase BKRF3 Contributes to Epstein-Barr Virus DNA Replication through Physical Interactions with Proteins in Viral DNA Replication Complex
Authors: Su Mei-Tzu , Liu I-Hua , Wu Chia-Wei , Chang Shu-Ming , Tsai Ching-Hwa , Yang Pei-Wen , Chuang Yu-Chia , Lee Chung-Pei , Chen Mei-Ru
Published: May 2014

Epstein-Barr virus (EBV) BKRF3 shares sequence homology with members of the uracil-N-glycosylase (UNG) protein family and has DNA glycosylase activity. Here, we explored how BKRF3 participates in the DNA replication complex and contributes to viral DNA replication. Exogenously expressed Flag-BKRF3 was distributed mostly in the cytoplasm, whereas BKRF3 was translocated into the nucleus and colocalized with the EBV DNA polymerase BALF5 in the replication compartment during EBV lytic replication. The expression level of BKRF3 increased gradually during viral replication, coupled with a decrease of cellular UNG2, suggesting BKRF3 enzyme activity compensates for UNG2 and ensures the fidelity of viral DNA replication. In immunoprecipitation-Western blotting, BKRF3 was coimmunoprecipitated with BALF5, the polymerase processivity factor BMRF1, and the immediate-early transactivator Rta. Coexpression of BMRF1 appeared to facilitate the nuclear targeting of BKRF3 in immunofluorescence staining. Residues 164 to 255 of BKRF3 were required for interaction with Rta and BALF5, whereas residues 81 to 166 of BKRF3 were critical for BMRF1 interaction in glutathione
S
-transferase (GST) pulldown experiments. Viral DNA replication was defective in cells harboring BKRF3 knockout EBV bacmids. In complementation assays, the catalytic mutant BKRF3(Q90L,D91N) restored viral DNA replication, whereas the leucine loop mutant BKRF3(H213L) only partially rescued viral DNA replication, coupled with a reduced ability to interact with the viral DNA polymerase and Rta. Our data suggest that BKRF3 plays a critical role in viral DNA synthesis predominantly through its interactions with viral proteins in the DNA replication compartment, while its enzymatic activity may be supplementary for uracil DNA glycosylase (UDG) function during virus replication.

IMPORTANCE
Catalytic activities of both cellular UDG UNG2 and viral UDGs contribute to herpesviral DNA replication. To ensure that the enzyme activity executes at the right time and the right place in DNA replication forks, complex formation with other components in the DNA replication machinery provides an important regulation for UDG function. In this study, we provide the mechanism for EBV UDG BKRF3 nuclear targeting and the interacting domains of BKRF3 with viral DNA replication proteins. Through knockout and complementation approaches, we further demonstrate that in addition to UDG activity, the interaction of BKRF3 with viral proteins in the replication compartment is crucial for efficient viral DNA replication.
Particle Conformation Regulates Antibody Access to a Conserved GII.4 Norovirus Blockade Epitope
Authors: Lindesmith Lisa C. , Donaldson Eric F. , Beltramello Martina , Pintus Stefania , Corti Davide , Swanstrom Jesica , Debbink Kari , Jones Taylor A. , Lanzavecchia Antonio , Baric Ralph S.
Published: May 2014

GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute gastroenteritis. One primary obstacle to successful NoV vaccination is the extensive degree of antigenic diversity among strains. The major capsid protein of GII.4 strains is evolving rapidly, resulting in the emergence of new strains with altered blockade epitopes. In addition to characterizing these evolving blockade epitopes, we have identified monoclonal antibodies (MAbs) that recognize a blockade epitope conserved across time-ordered GII.4 strains. Uniquely, the blockade potencies of MAbs that recognize the conserved GII.4 blockade epitope were temperature sensitive, suggesting that particle conformation may regulate functional access to conserved blockade non-surface-exposed epitopes. To map conformation-regulating motifs, we used bioinformatics tools to predict conserved motifs within the protruding domain of the capsid and designed mutant VLPs to test the impacts of substitutions in these motifs on antibody cross-GII.4 blockade. Charge substitutions at residues 310, 316, 484, and 493 impacted the blockade potential of cross-GII.4 blockade MAbs with minimal impact on the blockade of MAbs targeting other, separately evolving blockade epitopes. Specifically, residue 310 modulated antibody blockade temperature sensitivity in the tested strains. These data suggest access to the conserved GII.4 blockade antibody epitope is regulated by particle conformation, temperature, and amino acid residues positioned outside the antibody binding site. The regulating motif is under limited selective pressure by the host immune response and may provide a robust target for broadly reactive NoV therapeutics and protective vaccines.

IMPORTANCE
In this study, we explored the factors that govern norovirus (NoV) cross-strain antibody blockade. We found that access to the conserved GII.4 blockade epitope is regulated by temperature and distal residues outside the antibody binding site. These data are most consistent with a model of NoV particle conformation plasticity that regulates antibody binding to a distally conserved blockade epitope. Further, antibody “locking” of the particle into an epitope-accessible conformation prevents ligand binding, providing a potential target for broadly effective drugs. These observations open lines of inquiry into the mechanisms of human NoV entry and uncoating, fundamental biological questions that are currently unanswerable for these noncultivatable pathogens.
Bilateral sclerosing orbital pseudotumour in an adult
Authors: Sripathi Smiti , Shenoy Poonam Mohan , Ayachit Anurag , Kadavigere Rajagopal
Published: May 2014

Sclerosing pseudotumour of the orbit is a rare idiopathic chronic inflammatory process, which greatly mimics neoplasms both clinically and on imaging studies. It is therefore important to differentiate this entity from true neoplasms and to rule out any systemic associations. We present a rare case of sclerosing orbital pseudotumour in an adult man with no systemic illnesses who presented with painless progressive proptosis of both eyes and showed a gradual initial response to steroid therapy but relapsed after a 2-year interval.
Cytological diagnosis of chondroblastoma: diagnostic challenge for the cytopathologist
Authors: Akhtar Kafil , Qadri Shagufta , Sen Ray Prasenjit , Sherwani Rana K
Published: May 2014

Chondroblastoma is an uncommon osseous neoplasm that accounts for less than 1% of all bone tumours. It characteristically arises in the epiphysis or epimetaphyseal region of long bones and has been reported to affect people of all ages with slight male predilection. WHO has defined chondroblastoma as ‘a benign, cartilage-producing neoplasm usually arising in the epiphyses of skeletally immature patients’. The authors document the cytological features on fine-needle aspiration cytology of a chondroblastoma which appeared as a lytic lesion in the upper end of the right fibula, an uncommon site, in an 18-year-old male patient. X-ray feature combined with fine-needle aspiration cytology favoured the diagnosis of chondroblastoma, which was further confirmed by histopathological examination.
Health inequalities in European cities: perceptions and beliefs among local policymakers
Authors: Morrison Joana , Pons-Vigués Mariona , Bécares Laia , Burström Bo , Gandarillas Ana , Domínguez-Berjón Felicitas , Diez Èlia , Costa Giuseppe , Ruiz Milagros , Pikhart Hynek , Marinacci Chiara , Hoffmann Rasmus , Santana Paula , Borrell Carme ,   and partners from the INEQ-Cities Project
Published: May 2014

Objective

To describe the knowledge and beliefs of public policymakers on social inequalities in health and policies to reduce them in cities from different parts of Europe during 2010 and 2011.

Design

Phenomenological qualitative study.

Setting

13 European cities.

Participants

19 elected politicians and officers with a directive status from 13 European cities.

Main outcome

Policymaker's knowledge and beliefs.

Results

Three emerging discourses were identified among the interviewees, depending on the city of the interviewee. Health inequalities were perceived by most policymakers as differences in life-expectancy between population with economic, social and geographical differences. Reducing health inequalities was a priority for the majority of cities which use surveys as sources of information to analyse these. Bureaucracy, funding and population beliefs were the main barriers.

Conclusions

The majority of the interviewed policymakers gave an account of interventions focusing on the immediate determinants and aimed at modifying lifestyles and behaviours in the more disadvantaged classes. More funding should be put towards academic research on effective universal policies, evaluation of their impact and training policymakers and officers on health inequalities in city governments.
Investigating the long-term consequences of adverse medical events among older adults
Authors: Carter Mary W , Zhu Motao , Xiang Jun , Porell Frank W
Published: May 2014

Objective

To investigate the long-term effect of medically serious adverse medical events (AMEs) among older adults.

Methods

We linked nationally representative survey and claims data from the Medicare Current Beneficiary Survey (1998–2004) with non-response files (1999–2005) and the Area Resource File, providing 12 541 beneficiaries with 428 373 person-months for analysis. Latent class analysis was used to assign severity status to episodes. Multinomial logistic regression was used to identify AME risk factors. The long-term consequences of AMEs on Medicare expenditures were examined by population average models. Survival analyses examined the long-term risk of death.

Results

Nearly 19% of participants experienced at least one AME, with 62% from outpatient claims. The risk of AMEs is greater among participants in poorer health, and increases with comorbidity and with impairment in performing activities of daily living or instrumental activities of daily living. Medicare expenditures during an AME episode increased sharply and remained higher than what would have otherwise been expected in quarters following an AME episode, and failed to return to pre-AME expenditure levels. Differences in survival rates were observable long after the AME episode concluded, with only 55% of the patients sustaining an AME surviving to the end of the study. In contrast, nearly 80% of those without an AME were estimated to have survived.

Conclusions

The impacts of AMEs are observable over extended periods of time and are associated with considerable excess mortality and costs. Efforts to monitor and prevent AMEs in both acute care and outpatient settings are warranted.
Populations of uncultivated American cranberry in sphagnum bog communities harbor novel assemblages of Actinobacteria with antifungal properties
Authors: Mason Charles J. , Zeldin Eric L. , Currie Cameron R. , Raffa Kenneth F. , McCown Brent H.
Published: May 2014

The American cranberry (Vaccinium macrocarpon Aiton) is a perennial plant in northern latitudes that co-occurs with sphagnum mosses in uncultivated populations, in habitats characterized by high acidity, low nitrogen, and fungal pathogens that thrive in wet environments. We investigated the association of Actinobacteria with cranberry and co-inhabiting sphagnum moss and their antifungal properties, across several natural populations. Based on 16S-rRNA gene phylogeny, the majority of these species were in the genus Streptomyces. Neither site nor plant source explained the phylogenetic relationships of these isolates. Most sequences did not group with known Streptomyces sequences, indicating a potentially high diversity of novel strains from this environment. We observed antibiosis by some Actinobacteria isolates against the phytopathogenic fungus Colletotrichum acutatum and a general antagonistic fungus, Trichoderma sp. Individual isolates varied in antifungal ability within and between fungi. Variation in bacterial antifungal properties was not explained by plant species or site, but was partially related to phylogenetic relationship. These results document novel associations between cranberry and sphagnum moss with Actinobacteria, including strains capable of inhibiting fungi. These results suggest candidates for development as biological control agents in agriculture.
Calculation of the μ → eγ muon decay in the small-neutrino-mass limit
Authors: Bu Jian-Ping , Liang Yu-Min , Gu Xue-Wen
Published: May 2014

The μ → eγ decay is strictly forbidden in the Standard Model, where the lepton flavour is conserved as an accidental symmetry, but in extensions of the Standard Model the lepton flavour is generally no longer conserved, so that decay can take place. In this paper we calculate the amplitude, in an Rξ gauge, of muon decay in the small-neutrino-mass limit. The result, in which ξ-dependence is cancelled, is different from the amplitude and the technical points obtained in previous work.
Solid-phase crystallization of high growth rate amorphous silicon films deposited by gas-jet electron beam plasma CVD method
Authors: Baranov E.A. , Khmel S.Ya. , Zamchiy A.O. , Cheskovskaya I.V. , Sharafutdinov M.R.
Published: May 2014

Solid phase crystallization of amorphous silicon films (a-Si:H) deposited by gas-jet electron beam plasma chemical vapor deposition method and annealed at 700 °C in vacuum has been investigated. This method provides high deposition rates (up to 2.3 nm/s) of a-Si:H thin films in a standard vacuum chamber. The effects of varying the substrate temperature from 190 to 415 °C on the structural and optical properties of the as-deposited amorphous films and postannealed nanocrystalline films have been investigated. The crystallite size was determined by X-ray diffraction (about 5–8 nm) and agrees with that obtained from Raman scattering. The estimated degree of crystallinity was 45%–59%. Optical transmission spectra were recorded to investigate the optical properties and thickness of the silicon thin films. The refractive index and optical band gap data was obtained for both as-deposited amorphous and post-annealed nanocrystalline silicon. The behavior of the refractive index of nanocrystalline silicon depending on the substrate temperature is correlated with the crystalline volume fraction. a-Si:H films obtained at low temperatures have larger crystallite size and better crystallinity after annealing.
Method to enhance traffic capacity for two-layer complex networks
Authors: Zhang Shuai , Liang Man-Gui , Li Hui-Jia
Published: May 2014

The study of traffic dynamics on multilayered networks is a hot issue, where the network topology is composed of two layers of subnetworks, such as wired–wireless networks and peer-to-peer networks. Virtual links on the logical layer can be changed or constructed easily, and therefore the topological structure of the upper logical layer can be efficiently constructed by a link removal strategy. In this paper, edges linking to nodes with large betweenness will be removed. The structure of the upper-layer network can be optimized freely based on our method. Simulation results show that for both shortest path routing strategy and efficient routing strategy, the traffic capacity of two-layer networks is significantly improved. In addition, the average transmission time of packets and the average path length are also investigated in this paper.
Clinical Efficacy of Acupuncture as an Adjunct to Methadone Treatment Services for Heroin Addicts: A Randomized Controlled Trial
Authors: Chan Yuan-Yu , Lo Wan-Yu , Li Tsai-Chung , Shen Lih-Jong , Yang Szu-Nian , Chen Yi-Hung , Lin Jaung-Geng
Published: May 2014

Scant scientific evidence supports the efficacy of acupuncture in the treatment of opiate dependence. The purpose of this study was to examine the effectiveness of acupuncture for heroin addicts on methadone maintenance by measuring the daily consumption of methadone, variations in the 36-item Short Form Health Survey-36 (SF-36) and Pittsburgh Sleep Quality Index (PSQI) scores, and heroin craving. Sixty heroin addicts were randomly assigned to true acupuncture (electroacupuncture at the Hegu [LI4] and Zusanli [ST36] acupoints, as well as acupuncture at the Ear Shenmen) or sham acupuncture (minimal acupuncture at the Hegu and Zusanli acupoints without electrical stimulation and superficial acupuncture at the Ear Shenmen), twice weekly for 4 weeks. From week 2 onwards, the daily dose of methadone was reduced by a significantly greater amount with true acupuncture compared with sham acupuncture. True acupuncture was also associated with a greater improvement in sleep latency at follow-up. All adverse events were mild in severity. Acupuncture appears to be a useful adjunct to methadone maintenance therapy (MMT) in heroin addiction.
Magnolol Reduced TNF-α-Induced Vascular Cell Adhesion Molecule-1 Expression in Endothelial Cells via JNK/p38 and NF-κB Signaling Pathways
Authors: Liang Chan-Jung , Lee Chiang-Wen , Sung Hsin-Ching , Chen Yung-Hsiang , Wang Shu-Huei , Wu Pei-Jhen , Chiang Yao-Chang , Tsai Jaw-Shiun , Wu Chau-Chung , Li Chi-Yuan , Chen Yuh-Lien
Published: May 2014

Expression of cell adhesion molecules by the endothelium and the attachment of leukocytes to these cells play major roles in inflammation and cardiovascular disorders. Magnolol, a major active component of Magnolia officinalis, has antioxidative and anti-inflammatory properties. In the present study, the effects of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells (HAECs) and the related mechanisms were investigated. TNF-α induced VCAM-1 protein expression and mRNA stability were significantly decreased in HAECs pre-treated with magnolol. Magnolol significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-α-treated HAECs. The decrease in VCAM-1 expression in response to TNF-α treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor. Magnolol also attenuates NF-κB activation and the translocation of HuR (an RNA binding protein) in TNF-α-stimulated HAECs. The VCAM-1 expression was weaker in the aortas of TNF-α-treated apo-E deficient mice with magnolol treatment. These data demonstrate that magnolol inhibits TNF-α-induced JNK/p38 phosphorylation, HuR translocation, NF-κB activation, and thereby suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken together, these results suggest that magnolol has an anti-inflammatory property and may play an important role in the prevention of atherosclerosis and inflammatory responses.
Ixeris dentataDecreases ER Stress and Hepatic Lipid Accumulation through Regulation of ApoB Secretion
Authors: Lee Mi-Rin , Lee Hwa-Young , Lee Geum-Hwa , Kim Hye-Kyung , Kim Nan-Young , Kim Seung Hyun , Kim Hyung-Ryong , Chae Han-Jung
Published: May 2014

Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid carrier proteins and their binding to hepatic TG and cholesterol are affected by ER stress. This study was designed to identify ER stress regulators with potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea, Japan, and China. To examine the regulatory effects of IXD against hepatic lipid accumulation and elucidate its suggested mechanism of ER stress, HepG2 hepatocytes were treated with IXD extract in the presence of palmitate. While palmitate induced an ER stress response in hepatocytes, as indicated by the upregulation of PERK, increased eukaryotic initiation factor 2α (eIF2α) phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP), and reduced secretion of apoB resulting in hepatic cellular accumulation of triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid accumulation and PERK/eIF2α/CHOP-axis of the ER stress response. The inhibition of the PERK/eIF2α/CHOP signaling pathway by IXD in palmitate-treated cells suggests that IXD regulates hepatic dyslipidemia through the regulation of ER stress.
Bufalin Induces Cell Death in Human Lung Cancer Cells through Disruption of DNA Damage Response Pathways
Authors: Wu Shin-Hwar , Wu Tzu-Yun , Hsiao Yung-Ting , Lin Ju-Hwa , Hsu Shu-Chun , Hsia Te-Chun , Yang Su-Tso , Hsu Wu-Huei , Chung Jing-Gung
Published: May 2014

Bufalin is a key component of a Chinese medicine (Chan Su) and has been proved effective in killing various cancer cells. Its role in inducing DNA damage and the inhibition of the DNA damage response (DDR) has been reported, but none have studied such action in lung cancer in detail. In this study, we demonstrated bufalin-induced DNA damage and condensation in NCI-H460 cells through a comet assay and DAPI staining, respectively. Western blotting indicated that bufalin suppressed the protein levels associated with DNA damage and repair, such as a DNA dependent serine/threonine protein kinase (DNA-PK), DNA repair proteins breast cancer 1, early onset (BRCA1), 14-3-3 σ (an important checkpoint keeper of DDR), mediator of DNA damage checkpoint 1 (MDC1), O6-methylguanine-DNA methyltransferase (MGMT) and p53 (tumor suppressor protein). Bufalin could activate phosphorylated p53 in NCI-H460 cells. DNA damage in NCI-H460 cells after treatment with bufalin up-regulated its ATM and ATR genes, which encode proteins functioning as sensors in DDR, and also up-regulated the gene expression (mRNA) of BRCA1 and DNA-PK. But bufalin suppressed the gene expression (mRNA) of p53 and 14-3-3 σ, however, bufalin did not significantly affect the mRNA of MGMT. In conclusion, bufalin induced DNA damage in NCI-H460 cells and also inhibited its DNA repair and checkpoint function.
Martingale solutions for stochastic active scalar equations perturbed by non-trace class noise
Authors: Zhu Rongchan , Zhu Xiangchan
Published: May 2014

In this paper we prove the existence of martingale solutions for the 2D stochastic fractional vorticity Navier–Stokes equation driven by space-time white noise for α ∈ (½, 1] and the 2D stochastic quasi-geostrophic equation on 𝕋2 for α ∈ (0, 1] driven by non-trace class noise. We also cover the case driven by non-trace class multiplicative noise for all α ∈ (0, 1].
Layout of Embedding Circulant Networks into Linear Hexagons and Phenylenes
Authors: RAJASINGH INDRA , AROCKIARAJ MICHEAL
Published: May 2014

Circulant network has been used for decades in the design of computer and telecommunication networks due to optimal fault-tolerance and routing capabilities. Further, it has been used in VLSI design and distributed computation.

Hexagonal chains are of great importance of theoretical chemistry because they are the natural graph representations of benzenoid hydrocarbons, a great deal of investigations in mathematical chemistry has been developed to hexagonal chains. Hexagonal chains are exclusively constructed by hexagons of length one. Phenylenes are a class of chemical compounds in which carbon atoms form 6 and 4 membered cycles.

Graph embedding has been known as a powerful tool for implementation of parallel algorithms or simulation of different interconnection networks. An embedding f of a guest graph G into a host graph H is a bijection on the vertices such that each edge of G is mapped into a path of H. The wirelength (layout) of this embedding is defined to be the sum of the length of the paths corresponding to the edges of G.

In this paper we obtain the minimum wirelength of embedding circulant networks into linear hexagonal chains and linear phenylenes. Further we discuss the embedding of faulty circulant networks into linear hexagonal chains and linear phenylenes.
Wireless Fair Intelligent Congestion Control — A QoS Performance Evaluation
Authors: FURQAN FATIMA , HOANG DOAN B.
Published: May 2014

In Broadband Wireless Access (BWA) networks, provisioning of Quality of Service (QoS) is absolutely essential for real time and non real time services. Congestion in these networks can lead to deterioration in QoS experienced by the network users. Congestion avoidance is rarely considered to ensure the QoS of wireless connections. Efforts are mainly aimed at reducing the overload once it has occurred. To avoid congestion at the base station in WiMAX networks, the WiMAX Fair Intelligent Congestion Control (WFICC) was proposed to ensure the traffic is scheduled in such a way that the base station output buffer operates around a target operating point without violating the QoS requirements of connections. The aim of this paper is to investigate WFICC thoroughly and evaluate its performance in terms of throughput, delay and jitter for different Classes of Services (CoSs) under various parameter settings of the algorithm.

A detailed and comprehensive simulation study on various settings of parameters is performed in ns-2. The results show that WFICC performs excellently in allocating resources fairly among Class of Services (CoSs) and also preserves their QoS requirements. Furthermore, WFICC is robust and easily adapted to various traffic conditions.
Differentiated Bandwidth Guarantees for Cloud Data Centers
Authors: LI YANGYANG , WANG HONGBO , DONG JIANKANG , LI JUNBO , CHENG SHIDUAN
Published: May 2014

By means of virtualization, computing and storage resources are effectively multiplexed by different applications in cloud data centers. However, there lacks useful approaches to share the internal network resource of cloud data centers. Invalid network sharing not only degrade the performance of applications, but also affect the efficiency of data center operation. To guarantee network performance of applications and provide fine-grained service differentiation, in this paper, we propose a differentiated bandwidth guarantee scheme for data center networks. Utility functions are constructed according to the throughput and delay sensitive characteristics of different applications. Aiming to maximize the utility of all applications, the problem is formulated as a multi-objective optimization problem. We solve this problem using a heuristic algorithm: the elitist Non-Dominated Sorted Genetic Algorithm-II(NSGA-II), and we make a multi-attribute decision to refine the solutions. Extensive simulations are conducted to show that our scheme provides minimum band-width guarantees and achieves more fine-grained service differentiation than existing approaches. The simulation also verifies that the proposed mechanism is suitable for arbitrary data center architectures.
Recent progress in adapting Poisson–Boltzmann methods to molecular simulations
Authors: Xiao Li , Wang Changhao , Luo Ray
Published: May 2014

Electrostatic solvation modeling based upon the Poisson–Boltzmann equation is widely used in studies of biomolecular structures and functions. This manuscript provides a thorough review of published efforts to adapt the numerical Poisson–Boltzmann methods to molecular simulations so that these methods can be extended to biomolecular studies involving conformational fluctuation and/or dynamics. We first review the fundamental works on how to define the electrostatic free energy and the Maxwell stress tensor. These topics are followed by three different strategies in developing algorithms to compute electrostatic forces and how to improve their numerical performance. Finally procedures are also presented in detail on how to discretize these algorithms for numerical calculations. Given the pioneer works reviewed here, further developmental efforts will be on how to balance efficiency and accuracy in these theoretical sound approaches — two important issues in applying any numerical algorithms for routine biomolecular applications. Even if not reviewed here, more advanced numerical solvers are certainly necessary to achieve higher accuracy than the widely used classical methods to improve the overall performance of the numerical Poisson–Boltzmann methods.
Study on the cooperativity of hydrogen bonds betweenH2YandHX(X=F,Cl,Br;Y=O,S,Se)
Authors: Liu Hexiu , Man Ruilin , Wang Zhaoxu , Liao Jianping , Li Xiaofang , Ma Songjiang , Yi Pinggui
Published: May 2014

The structure characteristics, interaction energies, cooperative energies of the complexes between chalcogen hydrides ( H2Y ) and halogen hydrides (HX) have been studied theoretically at the MP2 level with aug-cc-pVTZ basis set in this paper. The conclusions show that there are strong interactions between H2Y and HX. The stability of the complex is decided by the electronegativity of the negatively charged atom. The cooperativity is observed in the two or three hydrogen bonds of each trimer structures in title system. The values of the cooperative energies and the cooperative contributions all illustrate that the cooperativity is of great importance in these complexes. The "atoms in molecules" (AIM) analyses show that the complexes in title system are mainly electrostatic interactions (closed-shell interactions) in character. For H ⋯ O bonds in H2O ⋯ HF ⋯ H2O , H2O ⋯ HBr ⋯ H2O and HF ⋯ H2O ⋯ HF , the 1 < |Vc|/Gc< 2 and -Gc< Hc< 0 indicate the interactions in these compounds are between closed-shell interaction and opened-shell interaction.
Heuristics for Single Machine Scheduling Problem with Release Dates, Deteriorating Effect and Skilled Workforce with Learning Ability
Authors: Costa Antonio , Cappadonna Fulvio Antonio , Fichera Sergio
Published: May 2014

In this paper, the single machine total weighted completion time scheduling problem is studied. The jobs have nonzero release time and processing time increases during the production due to the effect of deterioration on the machine. An operator sets up the machine and manually loads the job in the machine and unloads it at the end of the working time. The setup time and the removal time are influenced by the ability of the worker due to his work experience and learning capacity. Heuristic algorithms are proposed to solve the scheduling problem, and their efficiency is evaluated on a wide benchmark.
Study and Analysis of GA-Based Heuristic Applied to Assembly Line Balancing Problem
Authors: Sivasankaran P. , Shahabudeen P.
Published: May 2014

Balancing assembly line in a mass production system plays a vital role to improve the productivity of a manufacturing system. In this paper, a single model assembly line balancing problem (SMALBP) is considered. The objective of this problem is to group the tasks in the assembly network into a minimum number of workstations for a given cycle time such that the balancing efficiency is maximized. This problem comes under combinatorial category. So, it is essential to develop efficient heuristic to find the near optimal solution of the problem in less time. In this paper, an attempt has been made to design four different genetic algorithm (GA)-based heuristics, and analyze them to select the best amongst them. The analysis has been carried out using a complete factorial experiment with three factors, viz. problem size, cycle time, and algorithm, and the results are reported.
Why was Asia Resilient? Lessons from the Past and for the Future
Authors: Jeasakul Phakawa , Lim Cheng Hoon , Lundback Erik
Published: May 2014

Asia proved to be remarkably resilient in the face of the global financial crisis, but why was its output performance stronger than that of other regions? The paper shows that better initial conditions — in the form of lower external and financial vulnerabilities — contributed significantly to Asia's resilience. Key pre-crisis factors included moderate credit expansion, reliance on deposit funding, enhanced bank asset quality, reduced external financing, and improved current accounts. These improvements reflected the lessons from the Asian financial crisis in the late 1990s, which helped to reshape both public policies and private sector behavior. Looking ahead, Asia is in the process of adjusting to more volatile external conditions and higher risk premiums. By drawing the right lessons from its pre-crisis experiences, Asia's economies will be better equipped to address new risks associated with increased cross-border capital flows and greater integration with the rest of the world.
Neoproterozoic ice sheets and olistoliths: multiple glacial cycles in the Kingston Peak Formation, California
Authors: Le Heron Daniel P. , Busfield Marie E. , Prave Anthony R.
Published: May 2014

The Kingston Peak Formation is a diamictite-bearing succession that crops out in the Death Valley region, California, USA. An exceptionally thick (>1.5 km) outcrop belt in its type area (the Kingston Range) provides clear insights into the dynamics of mid-Cryogenian (‘Sturtian’) ice sheets in Laurentia. Seven detailed logs allow the lateral and vertical distribution of facies associations to be assessed. We recognize (1) diamictite facies association (ice-proximal glacigenic debris flows), (2) lonestone-bearing facies association (ice-marginal hemipelagic deposits and low-density gravity flows with iceberg rafting), (3) pebble to boulder conglomerate facies association (ice-proximal cogenetic glacigenic debris flows and high-density turbidites), (4) megaclast facies association (olistostrome and hemipelagic sediments subject to ice-rafting), and (5) interbedded heterolithics facies association (low-density turbidites and hemipelagic deposits). The stratigraphic motif allows three glacial cycles to be inferred across the range. Ice-minimum conditions interrupting the Kingston Peak succession are associated with the development of an olistostrome complex, succeeded by a thick accumulation of boulder conglomerates deposited during ice readvance. The data testify to a strong glacial influence on sedimentation within this ancient subaqueous succession, and to highly dynamic ice sheet behaviour with clear glacial cycles during the Sturtian glaciation.
Using mechanical models to investigate the controls on fracture geometry and distribution in chalk
Authors: Welch Michael J. , Souque Christine , Davies Russell K. , Knipe Rob J.
Published: May 2014

Chalk is an important reservoir rock. However, owing to its low permeability, fractures are key to producing hydrocarbons from chalk reservoirs. Fractures in chalk usually form one of three geometric patterns: localized fractures (commonly concentric rings) developed around tips, bends and splays in larger faults; regularly spaced regional fracture sets; and fracture corridors comprising narrow zones of closely spaced parallel fractures. Localized fracture patterns are likely to give only local permeability enhancement; regional fracture sets and, especially, fracture corridors may provide long, high-permeability flow pathways through the chalk. Field mapping shows that both localized fracture patterns and fracture corridors often nucleate around larger faults; however, the fracture corridors rapidly propagate away from the faults following the regional stress orientation. It is therefore not necessary to know the detailed fault geometry to predict the geometry of the fracture corridors, although the fault density can help to predict the spacing of the fracture corridors. Mechanical modelling shows that while localized fracture patterns can form under normal fluid pressure conditions as a result of local stress anomalies around fault bends, tips and splays, fracture corridors can only form under conditions of fluid overpressure. Once they nucleate, they will continue to propagate until they either intersect another fault or the fluid pressure in them is dissipated.
High-salt diet blunts renal autoregulation by a reactive oxygen species-dependent mechanism
Authors: Fellner Robert C. , Cook Anthony K. , O'Connor Paul M. , Zhang Shali , Pollock David M. , Inscho Edward W.
Published: May 2014

High dietary salt is common in Western countries and is an important contributor to increased cardiovascular disease. Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is an essential function of the renal microcirculation that could be affected by excessive dietary salt. High salt (HS) increases renal ROS generation partly by the enzyme NADPH oxidase. We hypothesized that a HS diet would impair autoregulation via NADPH oxidase-dependent ROS generation. The role of NADPH-dependent ROS production on the blunted autoregulatory response with a HS diet was assessed in vitro and in vivo using the blood-perfused juxtamedullary nephron preparation and anesthetized rats, respectively. The increase in renal lipid peroxidation and p67 phox expression induced by HS was prevented by apocynin treatment. Control afferent arterioles exhibited normal autoregulatory behavior in response to acute increases in renal perfusion pressure, whereas arterioles from HS rats exhibited a blunted response. Autoregulatory behavior in HS rats was restored in vitro by acute exposure to the NADPH oxidase inhibitor apocynin. At the whole kidney level, in vivo experiments showed that both RBF and GFR declined in HS rats when left kidney renal perfusion pressure was reduced from ambient to 95 mmHg, whereas control rats maintained stable GFR and RBF consistent with efficient autoregulatory behavior. Apocynin treatment improved in vivo autoregulatory behavior in HS rats and had no detectable effect in normal salt diet-fed rats. These data support the hypothesis that impaired renal autoregulatory behavior in rats fed a HS diet is mediated by NADPH oxidase-derived ROS.
Relevant role of PKG in the progression of fibrosis induced by TNF-like weak inducer of apoptosis
Authors: Martín Paloma , Mora Inés , Cortes M. Alicia , Calleros Laura , García-Jerez Andrea , Ortiz Alberto , Rodríguez-Puyol Manuel , Rodríguez-Puyol Diego , Olmos Gemma
Published: May 2014

TNF-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that activates the FGF-inducible 14 receptor. Both TWEAK and the FGF-inducible 14 receptor are constitutively expressed in the kidney. TWEAK has been shown to modulate several biological responses, such as inflammation, proliferation, differentiation, and apoptosis, that contribute to kidney injury. However, the role of TWEAK in fibrosis and TWEAK-activated intracellular signaling pathways remain poorly understood. We tested the hypothesis that TWEAK can be a potent inducer of renal fibrosis by increasing transforming growth factor (TGF)-β1 expression (a well-known switch in the fibrosis process) through PKG-I downregulation. We showed that in human mesangial cells, TWEAK increased TGF-β1 expression and activity, leading to higher levels of the extracellular matrix protein fibronectin and decreased PKG-I expression and activity via the Ras pathway. PKG-I activation with 8-bromo-cGMP, Ras inactivation with dominant negative Ras, or Ras pathway inhibition with the ERK1/2 inhibitor PD-98059 resulted in the prevention of TWEAK-induced TGF-β1 upregulation. In vivo, exogenous administration of TWEAK to wild-type mice downregulated kidney PKG-I and increased kidney TGF-β1 expression. These effects were blunted in H-Ras knockout mice. Together, these data demonstrate, for the first time, the key role of PKG-I in TGF-β1 induction by TWEAK in kidney cells.