bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Structural Changes in the Organizational Form of Business Groups: Evidence from Korea*
Authors: Kim Hyungseok , Kim Woojin , Park Kyung Suh
Published: June 2012

This paper examines the effects of a series of regulatory changes that facilitated business groups in Korea to switch from a complex circular shareholding or “loop” structure to a more simplified and transparent pure holding company structure. Since these changes are likely to affect intra‐group dynamics of member firms in terms of their interdependence, we focus on changes in risk characteristics and how they are reflected in initial announcement returns. Using a business group‐level sample, we find that pure holding companies at the apex exhibit a significant decrease in beta subsequent to structural change, which is reflected in positive market reactions at the initial announcement. For other subsidiary member firms, however, we do not observe such patterns. On the other hand, idiosyncratic risk and volatility of operating performance significantly increase for both holding companies and subsidiaries following the switch. These results suggest that such structural changes alleviate business and financial interdependence among member firms, and that the benefits, if any, mostly accrue to (the shareholders of) the apex holding companies.
The impact of chewing gum resistance on immediate free recall
Authors: Rickman Sarah , Johnson Andrew , Miles Christopher
Published: June 2012

Although the facilitative effects of chewing gum on free recall have proved contentious (e.g., Tucha, Mecklinger, Maier, Hammerl, & Lange, 2004; Wilkinson, Scholey, & Wesnes, 2002), there are strong physiological grounds, for example, increased cerebral activity and blood flow following the act of mastication, to suppose facilitation. The present study manipulated resistance to mastication, that is, chewing four pellets versus one pellet of gum, with the assumption that increased resistance will accentuate cerebral activity and blood flow. Additionally, chewing rate was recorded for all participants. In a within‐participants design, participants performed a series of immediate free recall tasks while chewing gum at learning (one or four pellets) and recall (one or four pellets). Increased chewing resistance was not associated with increased memory performance, despite consistent chewing rates for both the one and four pellet conditions at both learning and recall. However, a pattern of recall consistent with context‐dependent memory was observed. Here, participants who chewed the equivalent number of gum pellets at both learning and recall experienced significantly superior word recall compared to those conditions where the number of gum pellets differed.
Design and Proof-of-Concept Validation of a Latched Arch Active Seal
Authors: Toma Monica , Luntz Jonathan , Brei Diann , Alexander Paul W. , Browne Alan L. , Johnson Nancy L.
Published: June 2012

Seals are integral to many industries such as aerospace, marine, oilfield, and automotive. A key performance metric for seal quality is quantified by the normal force between the seal and contact surface. Many applications have conflicting requirements on the normal force depending on the operational state. For example, in panel closures, to ease engagement of the seal the normal force (closing force) should be small; whereas, to maintain a high-quality seal the normal force (sealing force) should be large. While there is an abundance of seal technologies, there still exists a need for adaptable seals that can better accommodate the conflicting demands of multiple operational states and variations in application platforms. This paper introduces an active seal which controls normal force through modification of the structure of a rubber arch seal. While there are several options for actuation, this new technology is modeled, fabricated, and experimentally validated utilizing a shape memory alloy web actuation scheme. Finite element models provide a basis for a parametric study from which design guidelines are derived. The technology and supporting models/processes are demonstrated for an automotive panel closure successfully reducing the closing force by almost 50%, while simultaneously increasing the sealing force by over 30%.
Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets
Authors: Herfst Sander , Schrauwen Eefje J. A. , Linster Martin , Chutinimitkul Salin , de Wit Emmie , Munster Vincent J. , Sorrell Erin M. , Bestebroer Theo M. , Burke David F. , Smith Derek J. , Rimmelzwaan Guus F. , Osterhaus Albert D. M. E. , Fouchier Ron A. M.
Published: June 2012

Avian flu can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host.
Baseline Map of Carbon Emissions from Deforestation in Tropical Regions
Authors: Harris Nancy L. , Brown Sandra , Hagen Stephen C. , Saatchi Sassan S. , Petrova Silvia , Salas William , Hansen Matthew C. , Potapov Peter V. , Lotsch Alexander
Published: June 2012

Tropical Carbon Loss

Accurate and precise measures of tropical deforestation and the resulting carbon emissions are needed in order to formulate climate policy.

Harris
et al.

(p.
1573
; see the Perspective by

Zarin

) used satellite observations of deforestation within the tropics of three continents to estimate that gross annual carbon emissions were approximately 0.8 Pg Cyr
−2
(Pg = 10
15
g) for the years 2000 to 2005, from the loss of 43 million hectares of forest. This result, which is about one-third of some previous estimates, should serve as a baseline for future assessments of changes in the rate of loss of tropical forests.
Wnt/β-Catenin Signaling Regulates Telomerase in Stem Cells and Cancer Cells
Authors: Hoffmeyer Katrin , Raggioli Angelo , Rudloff Stefan , Anton Roman , Hierholzer Andreas , Del Valle Ignacio , Hein Kerstin , Vogt Riana , Kemler Rolf
Published: June 2012

From Wnt Signals to Telomerase Activity

Telomerase activity is associated with stem cell renewal and cancers, whereas a decrease in telomerase activity is seen during cell differentiation and senescence. Wnt/β-catenin signaling is also a critical regulator of stem cells, and deregulation of the pathway is associated with cancer. Now,

Hoffmeyer
et al.

(p.
1549
; see the Perspective by

Greider

) have found a link between these two pathways. In embryonic stem cells, β-catenin was able to regulate telomerase expression and activity directly. Similar observations were obtained in adult stem cells, a model of intestinal tumors, and human cancer cells.
FANCM Limits Meiotic Crossovers
Authors: Crismani Wayne , Girard Chloé , Froger Nicole , Pradillo Mónica , Santos Juan Luis , Chelysheva Liudmila , Copenhaver Gregory P. , Horlow Christine , Mercier Raphaël
Published: June 2012

No Crossing Over

To ensure the correct division of chromosome during the reduction division of meiosis, homologous chromosomes undergo double-strand breaks that—through crossing over and recombination—link the homologs together (and importantly introduce diversity into the genomes of gametes). But only a minority of these crossovers results in recombination—most are directed into non-crossover pathways.

Lorenz
et al.

(p.
1585
), working in the yeast
Schizosaccharomyces pombe
, and

Crismani
et al.

(p.
1588
), working in the higher plant
Arabidopsis thaliana
, looked for the factors that limit crossovers and promote non-crossover pathways. The homolog of the human
Fanconi anemia complementation group M (FANCM)
helicase protein was found to be a major meiotic anti-recombinase, which could drive meiotic recombination intermediates into the non-crossover pathway.
Comment on “Seroevidence for H5N1 Influenza Infections in Humans: Meta-Analysis”
Authors: Van Kerkhove Maria D. , Riley Steven , Lipsitch Marc , Guan Yi , Monto Arnold S. , Webster Robert G. , Zambon Maria , Nicoll Angus , Peiris J. S. Malik , Ferguson Neil M.
Published: June 2012

A better understanding of the severity of H5N1 in humans is needed. Wang
et al
. (Brevia, 23 March 2012, p. 1463; published online 23 February 2012) overinterpret the results of seroprevalence studies and take too little account of underlying uncertainties. Although the true risk of death from H5N1 infection will likely be lower than the 60% of reported laboratory-confirmed cases, there is little evidence of millions of missed infections.
Influenza: Options to Improve Pandemic Preparation
Authors: Rappuoli Rino , Dormitzer Philip R.
Published: June 2012

Science and society have been struggling to find a way to protect humankind from recurring epidemics and pandemics of influenza. Here, we review the options available in the short term and also briefly address the solutions that research may make available in the long term.
Breaking the Speed Limits of Phase-Change Memory
Authors: Loke D. , Lee T. H. , Wang W. J. , Shi L. P. , Zhao R. , Yeo Y. C. , Chong T. C. , Elliott S. R.
Published: June 2012

Exploiting Defects in a Jam

Phase-change materials that can readily switch between crystalline and amorphous states are increasingly finding use in nonvolatile memory devices (see the Perspective by

Hewak and Gholipour

). Using high-resolution transmission electron microscopy,

Nam
et al.

(p.
1561
) show that for Ge
2
Sb
2
Te
5
, the application of an electric field drives crystal dislocations in one direction, leading to their accumulation and eventual jamming, which causes the phase transition.

Loke
et al.

(p.
1566
) found that by applying a constant low voltage to Ge
2
Sb
2
Te
5
, they could accelerate its phase-switching speeds, without harming the long-term stability of the switched state.
The Eternal Silence of Neuronal Spaces
Consciousness
Confessions of a Romantic Reductionist

by Christof Koch

MIT Press, Cambridge, MA, 2012. 193 pp. $24.95, £17.95. ISBN 9780262017497.
Authors: Dehaene Stanislas
Published: June 2012

Writing for nonspecialists, Koch blends autobiography, philosophical reflections, and discussions of the neurobiology of consciousness.
Septin-Mediated Plant Cell Invasion by the Rice Blast Fungus,
Magnaporthe oryzae
Authors: Dagdas Yasin F. , Yoshino Kae , Dagdas Gulay , Ryder Lauren S. , Bielska Ewa , Steinberg Gero , Talbot Nicholas J.
Published: June 2012

Blasting Through

The fungus that causes rice blast disease,
Magnaporthe oryzae
, can lead to devastating reductions in rice yields.
M. oryzae
enters the plant by developing specialized infection structures called appressoria. Appressoria generate enormous internal turgor pressure that somehow creates invasive forces that physically break the plant cuticle.

Dagdas
et al.

(p.
1590
) found that a toroidal (doughnut-shaped) filamentous actin network forms at the base of the appressorium at the precise point where the penetration peg, which ruptures the rice leaf cuticle, will emerge. This network is scaffolded by means of four septin guanosine triphosphatases, which form a dynamic ring structure that colocalizes with F-actin. The findings reveal how fungi translate extreme pressure into localized physical force.
A Unifying Role for Prions in Neurodegenerative Diseases
Authors: Prusiner Stanley B.
Published: June 2012

A profound change in thinking about the etiologies of many neurodegenerative diseases has far-reaching implications for developing therapeutics.
Evolution, Safety, and Highly Pathogenic Influenza Viruses
Authors: Lipsitch Marc , Plotkin Joshua B. , Simonsen Lone , Bloom Barry
Published: June 2012

Experience with influenza has shown that predictions of virus phenotype or fitness from nucleotide sequence are imperfect and that predicting the timing and course of evolution is extremely difficult. Such uncertainty means that the risk of experiments with mammalian-transmissible, possibly highly virulent influenza viruses remains high even if some aspects of their laboratory biology are reassuring; it also implies limitations on the ability of laboratory observations to guide interpretation of surveillance of strains in the field. Thus, we propose that future experiments with virulent pathogens whose accidental or deliberate release could lead to extensive spread in human populations should be limited by explicit risk-benefit considerations.
Carbon from Tropical Deforestation
Authors: Zarin Daniel J.
Published: June 2012

Estimates of carbon emissions from tropical deforestation differ widely.
Genetic Events That Shape the Cancer Epigenome
Authors: Ryan Russell J. H. , Bernstein Bradley E.
Published: June 2012

Mutations in chromatin-related genes in human tumors support a role for epigenetic mechanisms in driving cancer.
Benefits and Risks of Influenza Research: Lessons Learned
Authors: Fauci Anthony S. , Collins Francis S.
Published: June 2012

Given the yearly challenge of seasonal influenza and the potential catastrophic consequences of future pandemics, the need for intensive basic and clinical influenza research is unquestionable. Although the fruits of decades of research have enabled dramatic improvements in our ability to prevent and treat influenza, many fundamental questions remain, including those related to the complex factors associated with host switching and transmission of influenza viruses. Recent public concern over two H5N1 influenza manuscripts that studied the transmissibility of influenza viruses has triggered intense discussion on dual-use research and the way forward.
NASA's New X-ray Satellite Packs Compact Power
Authors: Bhattacharjee Yudhijit
Published: June 2012

A new space telescope launched by NASA last week called NuSTAR could help astronomers determine what happens to matter swirling around a black hole and answer a host of other questions.
How Much Longer Will Moratorium Last?
Authors: Malakoff David
Published: June 2012

No one is sure when the landmark self-imposed moratorium on certain experiments on the H5N1 avian influenza virus agreed to by influenza researchers earlier this year will be lifted.
Steps Toward a Universal Flu Vaccine
Authors: Collier Joel H.
Published: June 2012

The pandemic flu vaccine elicits antibodies to conserved flu epitopes.
MicroRNAs, an Aquaporin Gene, and Asthma Pathogenesis
Authors: Reznik Marina
Published: June 2012

Aberrant microRNA expression identifies a novel asthma-associated gene.
Activity of Tedizolid Phosphate (TR-701) in Murine Models of Infection with Penicillin-Resistant and Penicillin-Sensitive Streptococcus pneumoniae
Authors: Choi Sunghak , Im Weonbin , Bartizal Ken
Published: June 2012

The
in vitro
activity of tedizolid (previously known as torezolid, TR-700) against penicillin-resistant
Streptococcus pneumoniae
(PRSP) clinical isolates and the
in vivo
efficacy of tedizolid phosphate (torezolid phosphate, TR-701) in murine models of PRSP systemic infection and penicillin-susceptible
S. pneumoniae
(PSSP) pneumonia were examined using linezolid as a comparator. The MIC
90
against 28 PRSP isolates was 0.25 μg/ml for tedizolid, whereas it was 1 μg/ml for linezolid. In mice infected systemically with a lethal inoculum of PRSP 1 h prior to a single administration of either antimicrobial, oral tedizolid phosphate was equipotent to linezolid (1 isolate) to 2-fold more potent than linezolid (3 isolates) for survival at day 7, with tedizolid phosphate 50% effective dose (ED
50
) values ranging from 3.19 to 11.53 mg/kg of body weight/day. In the PSSP pneumonia model, the ED
50
for survival at day 15 was 2.80 mg/kg/day for oral tedizolid phosphate, whereas it was 8.09 mg/kg/day for oral linezolid following 48 h of treatment with either agent. At equivalent doses (10 mg/kg once daily tedizolid phosphate or 5 mg/kg twice daily linezolid), pneumococcal titers in the lungs at 52 h postinfection were approximately 3 orders of magnitude lower with tedizolid phosphate treatment than with linezolid treatment or no treatment. Lung histopathology showed less inflammatory cell invasion into alveolar spaces in mice treated with tedizolid phosphate than in untreated or linezolid-treated mice. These results demonstrate that tedizolid phosphate is effective in murine models of PRSP systemic infection and PSSP pneumonia.
Decreased Specificity of an Assay for Recent Infection in HIV-1-Infected Patients on Highly Active Antiretroviral Treatment: Implications for Incidence Estimates
Authors: Chaillon Antoine , Le Vu Stéphane , Brunet Sylvie , Gras Guillaume , Bastides Frédéric , Bernard Louis , Meyer Laurence , Barin Francis
Published: June 2012

The aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4+T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%,P< 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations.
Molecular Characterization and Panton-Valentine Leucocidin Typing of Community-Acquired Methicillin-Sensitive Staphylococcus aureus Clinical Isolates
Authors: Otokunefor Kome , Sloan Tim , Kearns Angela M. , James Richard
Published: June 2012

Limited comprehensive molecular typing data exist currently for Panton-Valentine leucocidin (PVL)-positive, methicillin-sensitive
Staphylococcus aureus
(PVL-MSSA) clinical isolates. Characterization of PVL-MSSA isolates by multilocus sequence typing (MLST) and
spa
typing in this study showed a genetic similarity to PVL-positive, methicillin-resistant
S. aureus
(PVL-MRSA) strains, although three novel
spa
types and a novel MLST (ST1518) were detected. Furthermore, the detection of PVL phages and haplotypes in PVL-MSSA identical to those previously found in PVL-MRSA isolates highlights the role these strains may play as precursors of emerging lineages of clinical significance.
Epidural Abscess Caused by Streptobacillus moniliformis
Authors: Addidle Michael , Pynn Joanne , Grimwade Kate , Giola Massimo
Published: June 2012

We present an interesting case of a patient who developed an epidural abscess caused by
Streptobacillus moniliformis
. This is the first report in the medical literature of a spinal epidural abscess associated with this organism. Diagnosis of
S. moniliformis
infection requires a high degree of suspicion, and a delay may be inevitable when a relevant clinical history is lacking.
Detection of Extended-Spectrum β-Lactamase and Klebsiella pneumoniae Carbapenemase Genes Directly from Blood Cultures by Use of a Nucleic Acid Microarray
Authors: Fishbain Joel T. , Sinyavskiy Oleg , Riederer Kathleen , Hujer Andrea M. , Bonomo Robert A.
Published: June 2012

The growing crisis of multidrug-resistant (MDR) Gram-negative bacteria requires that current technologies permit the rapid detection of extended-spectrum β-lactamase (
bla
ESBL
) and
Klebsiella pneumoniae
carbapenemase (
bla
KPC
) genes. In the present study, we assessed the performance characteristics of a commercially available nucleic acid microarray system for the detection of
bla
ESBL
and
bla
KPC
genes directly from positive blood cultures. Using blood cultures (BCs) that contained Gram-negative bacilli identified by Gram staining, we isolated bacterial DNA using spin columns (BC-C) and rapid water lysis (BC-W). Twenty ESBL/KPC-positive and 20 ESBL/KPC-negative blood culture samples, as well as 20 non-lactose-fermenting organisms, were tested. The 20 isolates that were ESBL positive by phenotypic testing were also evaluated on solid medium (SM), and the DNA was extracted by use of a spin column (SM-C). The resulting 140 DNA extractions were assessed for DNA quantity and quality using 260/280-nm absorbance ratios, and DNA microarray analysis was performed in a blinded fashion. Microarray and phenotypic results were concordant for 98.3% of BC-W, 90% of BC-C, and 95% of SM-C samples. Compared to phenotypic testing, the sensitivity and specificity for BC-C samples were 88.9% and 100%, respectively, and for BC-W samples, the sensitivity and specificity were 94.4% and 100%, respectively. BC-W samples yielded the highest concordance with phenotypic results. Nucleic acid microarrays offer promise in the identification of
bla
ESBL
and
bla
KPC
genes directly from blood cultures, thereby reducing the time to identification of these important pathogens.
Effect of Manganese in Test Media on
In Vitro
Susceptibility of Enterobacteriaceae and Acinetobacter baumannii to Tigecycline
Authors: Veenemans J. , Mouton J. W. , Kluytmans J. A. J. W. , Donnely R. , Verhulst C. , van Keulen P. H. J.
Published: June 2012

We assessed the effect of increasing manganese concentrations in test media (0.001 to 1,024 mg/liter) on MICs of tigecycline. For both broth microdilution (BMD) and Etests, this effect was negligible for physiological concentrations, but MICs increased when concentrations exceeded 8 mg/liter. Susceptibility testing should be performed on media with standardized low manganese content.
Zoonotic Parasites of Bobcats around Human Landscapes
Authors: Carver Scott , Scorza Andrea V. , Bevins Sarah N. , Riley Seth P. D. , Crooks Kevin R. , VandeWoude Sue , Lappin Michael R.
Published: June 2012

We analyzed
Lynx rufus
fecal parasites from California and Colorado, hypothesizing that bobcats shed zoonotic parasites around human landscapes.
Giardia duodenalis
,
Cryptosporidium
,
Ancylostoma
,
Uncinaria
, and
Toxocara cati
were shed.
Toxoplasma gondii
serology demonstrated exposure.
Giardia
and
Cryptosporidium
shedding increased near large human populations. Genotyped
Giardia
may indicate indirect transmission with humans.
Roles of Cell Signaling Pathways in Cell-to-Cell Contact-Mediated Epstein-Barr Virus Transmission
Authors: Nanbo Asuka , Terada Haruna , Kachi Kunihiro , Takada Kenzo , Matsuda Tadashi
Published: June 2012

Epstein-Barr virus (EBV), a human gamma herpesvirus, establishes a life-long latent infection in B lymphocytes and epithelial cells following primary infection. Several lines of evidence indicate that the efficiency of EBV infection in epithelial cells is accelerated up to 10
4
-fold by coculturing with EBV-infected Burkitt's lymphoma (BL) cells compared to infection with cell-free virions, indicating that EBV infection into epithelial cells is mainly mediated via cell-to-cell contact. However, the molecular mechanisms involved in this pathway are poorly understood. Here, we establish a novel assay to assess cell-to-cell contact-mediated EBV transmission by coculturing an EBV-infected BL cell line with an EBV-negative epithelial cell line under stimulation for lytic cycle induction. By using this assay, we confirmed that EBV was transmitted from BL cells to epithelial cells via cell-to-cell contact but not via cell-to-cell fusion. The inhibitor treatments of extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-κB pathways blocked EBV transmission in addition to lytic induction. The blockage of the phosphoinositide 3-kinase (PI3K) pathway impaired EBV transmission coupled with the inhibition of lytic induction. Knockdown of the RelA/p65 subunit of NF-κB reduced viral transmission. Moreover, these signaling pathways were activated in cocultured BL cells and in epithelial cells. Finally, we observed that viral replication was induced in cocultured BL cells. Taken together, our data suggest that cell-to-cell contact induces multiple cell signaling pathways in BL cells and epithelial cells, contributing to the induction of the viral lytic cycle in BL cells and the enhancement of viral transmission to epithelial cells.
Characterization of the Early Steps of Human Parvovirus B19 Infection
Authors: Quattrocchi Silva , Ruprecht Nico , Bönsch Claudia , Bieli Sven , Zürcher Christoph , Boller Klaus , Kempf Christoph , Ros Carlos
Published: June 2012

The early steps of human parvovirus B19 (B19V) infection were investigated in UT7/Epo cells. B19V and its receptor globoside (Gb4Cer) associate with lipid rafts, predominantly of the noncaveolar type. Pharmacological disruption of the lipid rafts inhibited infection when the drug was added prior to virus attachment but not after virus uptake. B19V is internalized by clathrin-dependent endocytosis and spreads rapidly throughout the endocytic pathway, reaching the lysosomal compartment within minutes, where a substantial proportion is degraded. B19V did not permeabilize the endocytic vesicles, indicating a mechanism of endosomal escape without apparent membrane damage. Bafilomycin A
1
(BafA1) and NH
4
Cl, which raise endosomal pH, blocked the infection by preventing endosomal escape, resulting in a massive accumulation of capsids in the lysosomes. In contrast, in the presence of chloroquine (CQ), the transfer of incoming viruses from late endosomes to lysosomes was prevented; the viral DNA was not degraded; and the infection was boosted. In contrast to the findings for untreated or BafA1-treated cells, the viral DNA was progressively associated with the nucleus in CQ-treated cells, reaching a plateau by 3 h postinternalization, a time coinciding with the initiation of viral transcription. At this time, more than half of the total intracellular viral DNA was associated with the nucleus; however, the capsids remained extranuclear. Our studies provide the first insight into the early steps of B19V infection and reveal mechanisms involved in virus uptake, endocytic trafficking, and nuclear penetration.
Viral-Load-Dependent Effects of Liver Injury and Regeneration on Hepatitis B Virus Replication in Mice
Authors: Tian Yongjun , Chen Wen-ling , Kuo Cheng-fu , Ou Jing-hsiung James
Published: June 2012

Hepatitis B virus (HBV) is a hepatotropic virus that can cause severe liver diseases. By conducting studies using four different transgenic mouse lines that carry either the wild-type HBV genome or the HBV genome incapable of expressing the X gene, we found that liver injury and regeneration induced by a partial hepatectomy (PHx) could have different effects on HBV replication depending on the mouse lines. Further studies using hydrodynamic injection to introduce different amounts of the HBV genomic DNA into the mouse liver revealed that liver injury and regeneration induced by PHx enhanced HBV replication when viral load was low and suppressed HBV replication when viral load was high. These effects of liver injury and regeneration on HBV were independent of the HBV X protein and apparently due to alpha and beta interferons (IFN-α/β), as the effects could be abolished by the injection of anti-IFN-α/β antibodies. Further analysis indicated that PHx could induce the expression of hepatocyte nuclear factor 3 gamma (HNF3γ) when viral load was low and activate the signal transducer and activator of transcription 3 (Stat3) and suppress the expression of the suppressor of cytokine signaling 3 (SOCS3) irrespective of viral load. As both HNF3γ and Stat3 are required to activate the HBV enhancer I to stimulate HBV gene expression and replication, these results provided an explanation to the viral-load-dependent effect of liver injury and regeneration on HBV replication. Our studies thus revealed a novel interaction between HBV and its host and provided important information for understanding HBV replication and pathogenesis during liver injury.
Impact on the Endoplasmic Reticulum and Golgi Apparatus of Turnip Mosaic Virus Infection
Authors: Grangeon Romain , Agbeci Maxime , Chen Jun , Grondin Gilles , Zheng Huanquan , Laliberté Jean-François
Published: June 2012

The impact of turnip mosaic virus (TuMV) infection on the endomembranes of the host early secretory pathway was investigated using an infectious clone that has been engineered for tagging viral membrane structures with a fluorescent protein fused to the viral protein 6K
2
. TuMV infection led to the amalgamation of the endoplasmic reticulum (ER), Golgi apparatus, COPII coatamers, and chloroplasts into a perinuclear globular structure that also contained viral proteins. One consequence of TuMV infection was that protein secretion was blocked at the ER-Golgi interface. Fluorescence recovery after photobleaching (FRAP) experiments indicated that the perinuclear structure cannot be restocked in viral components but was dynamically connected to the bulk of the Golgi apparatus and the ER. Experiments with 6K
2
fused to photoactivable green fluorescent protein (GFP) showed that production of motile peripheral 6K
2
vesicles was functionally linked to the perinuclear structure. Disruption of the early secretory pathway did not prevent the formation of the perinuclear globular structure, enhanced the clustering of peripheral 6K
2
vesicles with COPII coatamers, and led to inhibition of cell-to-cell virus movement. This suggests that a functional secretory pathway is not required for the formation of the TuMV perinuclear globular structure and peripheral vesicles but is needed for successful viral intercellular propagation.
Characterization
In Vitro
and
In Vivo
of Pandemic (H1N1) 2009 Influenza Viruses Isolated from Patients
Authors: Watanabe Tokiko , Imai Masaki , Watanabe Shinji , Shinya Kyoko , Hatta Masato , Li Chengjun , Neumann Gabriele , Ozawa Makoto , Hanson Anthony , Zhong Gongxun , Fukuyama Satoshi , Kawakami Eiryo , Simmons Heather A. , Schenkman Daniel , Brunner Kevin , Capuano Saverio V. , Weinfurter Jason T. , Kilander Anette , Dudman Susanne G. , Suresh M. , Hungnes Olav , Friedrich Thomas C. , Kawaoka Yoshihiro
Published: June 2012

The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. Molecular evolutionary analyses of the 2009 pandemic influenza A H1N1 [A(H1N1)pdm09] virus revealed two major clusters, cluster I and cluster II. Although the pathogenicity of viruses belonging to cluster I, which became extinct by the end of 2009, has been examined in a nonhuman primate model, the pathogenic potential of viruses belonging to cluster II, which has spread more widely in the world, has not been studied in this animal model. Here, we characterized two Norwegian isolates belonging to cluster II, namely, A/Norway/3568/2009 (Norway3568) and A/Norway/3487-2/2009 (Norway3487), which caused distinct clinical symptoms, despite their genetic similarity. We observed more efficient replication in cultured cells and delayed virus clearance from ferret respiratory organs for Norway3487 virus, which was isolated from a severe case, compared with the efficiency of replication and time of clearance of Norway3568 virus, which was isolated from a mild case. Moreover, Norway3487 virus to some extent caused more severe lung damage in nonhuman primates than did Norway3568 virus. Our data suggest that the distinct replicative and pathogenic potentials of these two viruses may result from differences in their biological properties (e.g., the receptor-binding specificity of hemagglutinin and viral polymerase activity).
A Human CD4+T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus
Authors: Babon Jenny Aurielle B. , Cruz John , Ennis Francis A. , Yin Liusong , Terajima Masanori
Published: June 2012

The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4+T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of the HA protein of influenza A virus and the HA protein of influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4+T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain, and influenza B virus in cytotoxicity assays and intracellular-cytokine-staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMCs for T cell responses specific to this epitope and found individuals who hadex vivogamma interferon (IFN-γ) responses to the peptide epitope in enzyme-linked immunospot (ELISPOT) assays. Almost all donors who responded to the epitope had the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4+T cells, which are cross-reactive to both influenza A and B viruses.
Predictors of duodenal bulb biopsy performance in the evaluation of coeliac disease in children
Authors: Tanpowpong Pornthep , Broder-Fingert Sarabeth , Katz Aubrey J , Camargo Carlos A
Published: June 2012

Aims

Studies on the role of duodenal bulb biopsy (DBB) in coeliac disease (CD) evaluation have increased in recent years; growing evidence suggests that the disease can present solely in the duodenal bulb. Moreover, recent CD guidelines recommend obtaining a DBB. The study aim was to examine DBB performance in children undergoing CD evaluation and to identify independent predictors of DBB performance.

Methods

The authors performed a structured chart review of children aged <18 years who underwent CD evaluation between 2000 and 2010 at a large teaching hospital. The authors collected data including demographics, serology, endoscopy and histopathological findings. Predictors of DBB performance (obtained vs not obtained) were determined using multivariable logistic regression.

Results

Among 616 children who underwent endoscopy, DBB was performed in 103 children (17%, 95% CI 14% to 20%) with an increasing trend in the more recent years (2008–2010, 25%; 2004–2007, 16%; and 2000–2003, 5%, p<0.001). Three independent predictors of DBB performance were older age at endoscopy (OR 1.05 per year of age), gross gastric antral abnormalities (OR 2.81) and gross duodenal abnormalities (OR 5.55). Regarding the DBB histological findings, patchiness of CD was found in 15%. Positive Marsh III biopsy presented solely on the DBB in 6/103 (6%, 95% CI 2% to 12%) children.

Conclusions

The authors found a significant increase in DBB performance over time, but the overall performance remains suboptimal. Improving education on obtaining a DBB for CD evaluation is crucial, especially among those children in whom DBB is more likely to be omitted.
Reconstructive endovascular treatment of a ruptured vertebral artery dissecting aneurysm using the Pipeline embolization device
Authors: Ducruet Andrew F , Crowley R Webster , Albuquerque Felipe C , McDougall Cameron G
Published: June 2012

Background

The Pipeline embolization device has been used successfully to treat intracranial aneurysms with difficult morphologies. However, the need for dual antiplatelet therapy has limited its use after subarachnoid hemorrhage.

Case report

A 42-year-old woman with a ruptured dissecting aneurysm of her dominant vertebral artery (V4) was successfully treated by Pipeline embolization with preservation of flow through a covered posterior inferior cerebellar artery. This strategy preserved endovascular access for the treatment of severe posterior circulation vasospasm. She was a non-responder to thienopyridine agents and was thus maintained on aspirin and heparin, which was transitioned to warfarin following ventricular drain removal. The aneurysm remains angiographically obliterated at 6 months. Despite a moribund presentation and an extended hospitalization, she has made a remarkable neurological recovery.

Conclusions

Pipeline embolization may be used to treat a ruptured dissecting aneurysm in selected cases where parent vessel preservation is paramount.
Maximising the potential of voluntary counselling and testing for HIV: sexually transmitted infections and HIV epidemiology in a population testing for HIV and its implications for practice
Authors: Wu Hsiu , Wu Pei-Ying , Li Shu-Ying , Chang Sui-Yuan , Liu Wen-Chun , Wu Cheng-Hsin , Lo Yi-Cheng , Hsieh Chia-Yin , Sun Hsin-Yun , Hung Chien-Ching
Published: June 2012

Objectives

This study aimed to describe the epidemiology of HIV infection and sexually transmitted infections (STIs) among persons who attended voluntary counselling and testing (VCT) service for HIV and to assess whether the VCT programme reached the right population at risk in Taiwan.

Methods

From 2006 to 2010, questionnaire interview, integrated pretesting and post-testing counselling, followed by serological tests for HIV,Treponema pallidumandEntamoeba histolyticawere performed for all VCT clients; additional tests forChlamydia trachomatisandNeisseria gonorrhoeaeusing PCR assays of urine specimens were provided when the assays became available in two periods.

Results

During the study period, 10 198 VCT attendances occurred in 6863 clients, in whom 1685 (24.6%) had re-attendances. Male clients, men who have sex with men and clients with one-night stand and casual sexual partners were more likely to re-attend VCT service in the next 12 months. The overall STI prevalence was 3.5% for HIV infection, 2.2% syphilis, 1.0% amoebiasis, 4.7% chlamydia and 0.7% gonorrhoea. In logistic regression model, men who have sex with men were consistently independently associated with HIV infection, syphilis and amoebiasis. Among the repeaters, the incidence rate of HIV infection and syphilis was 3.4 and 1.6 per 100 person-years of follow-up, respectively. In Cox regression analysis, clients who used illicit non-injection recreational drugs and who practiced unprotected anal sex were at significantly higher risk of acquiring HIV infection and syphilis.

Conclusions

With higher rates of re-attendances and STIs, the VCT programme reached the population most at risk for HIV and STIs compared with other screening programmes in Taiwan. The potential of VCT programme can be maximised in the prevention and control of HIV infection and STIs by providing tests for more STIs and counselling to avoid use of recreational drugs and to promote safe sex.
The experiences of ethnic minority MSM using NHS sexual health clinics in Britain
Authors: McKeown Eamonn , Doerner Rita , Nelson Simon , Low Nicola , Robinson Angela , Anderson Jane , Elford Jonathan
Published: June 2012

Objective

To compare the experiences of ethnic minority and white British men who have sex with men (MSM) who attend NHS sexual health clinics in Britain.

Methods

In 2007–2008, a national sample of MSM living in Britain was recruited through websites, in sexual health clinics, bars, clubs and other venues. Men completed an online survey, which included questions about their experience of attending an NHS sexual health clinic.

Results

Analysis is restricted to 363 ethnic minority MSM and 4776 white British MSM who had attended an NHS sexual health clinic in the 12 months before the survey. Compared with white British men, men from an Indian, Pakistani or Bangladeshi background were more likely to be very anxious about attending the clinic (adjusted OR (aOR) 2.58, 95% CI 1.63 to 4.07), express concerns about being overheard at reception (aOR 1.68, 95% CI 1.10 to 2.58), be uncomfortable in the waiting area (aOR 2.08, 95% CI 1.35 to 3.22) or be afraid that people in their community would find out that they have sex with men (aOR 7.70, 95% CI 4.49 to 13.22). The adjusted ORs for being afraid that people in their community would find out that they have sex with men were also elevated for black Caribbean, black African, Chinese and other Asian men.

Conclusion

Sexual health clinics should be aware that some ethnic minority MSM, particularly those from an Indian, Pakistani or Bangladeshi background, have heightened concerns about clinic attendance and confidentiality compared with white British MSM.
Investigation of the vertical uplift capacity of deep water mudmats in clay
Authors: Chen R. , Gaudin C. , Cassidy M.J.
Published: June 2012

Subsea mudmats are used in deep water oil and gas fields to support seabed structures, such as pipelines, manifolds, and well heads. On soft soil, removing mudmats during maintenance or decommissioning may be difficult and costly due to the significant suction that develops at the mudmat–soil interface, considerably increasing the uplift resistance beyond the submerged self-weight of the mudmat. This paper describes a series of centrifuge tests performed to investigate the uplift resistance of plain mudmats resting on lightly overconsolidated clay. The model mudmat invert was instrumented with pore pressure transducers to monitor the suction developing at the mudmat invert at various uplift velocities, uplift eccentricities, and mudmat skirt lengths. The results show an increase in uplift resistance with pull-out velocity and the dominant role played by the uplift eccentricity in reducing suction at the mat invert. Simple predictive methods based on bearing capacity theory and combined loading interaction diagrams are provided.
Modeling contaminant transport through composite liner with a hole in the geomembrane
Authors: Rowe R. Kerry , Abdelatty Khaled
Published: June 2012

Contaminant transport through a single hole in a geomembrane (GM) that forms part of composite liner with a geosynthetic clay liner (GCL) for applied heads (0.3 and 1 m) and an applied pressure of about 100 kPa is modeled and compared with experimental results. The system was first permeated with distilled water until a steady state was reached. The permeant was then switched to an NaCl solution. The inferred interface transmissivity at steady state (after 280 days) is about 2.3 × 10−11 m2/s for both heads examined. After 800 days permeation with an 0.14 mol/L NaCl solution, the interface transmissivity between the geomembrane and GCL was inferred to have decreased from 2.3 × 10−11 to 1.1 × 10−11 m2/s for experiments with heads of both 0.3 and 1 m. Modeling of the flow and changes in the GCL hydraulic conductivity arising from interaction between the bentonite and the 0.14 mol/L NaCl permeant is shown to give excellent agreement with the observed leakage. The differences between modeling a uniform and nonuniform interface transmissivity is found to be small — with the leakage being dominated by the interface transmissivity 0.1 to 0.15 m from the hole in the GM. Typical published values for the diffusion coefficient for both the GCL and sandy soil are shown to give good predictions of effluent concentration with time and chloride distribution in the silty sand in contact with the composite liners at the end of the test.
Geotechnical characteristics of recycled crushed brick blends for pavement sub-base applications
Authors: Arulrajah A. , Piratheepan J. , Bo M.W. , Sivakugan N.
Published: June 2012

This paper presents the findings of a laboratory investigation on the characterization of recycled crushed brick when blended with recycled concrete aggregate and crushed rock for pavement sub-base applications. The engineering properties of the crushed brick blends were compared with typical state road authority specifications in Australia for pavement sub-base systems to ascertain the potential use of crushed brick blends in these applications. The experimental programme included particle-size distribution, modified Proctor compaction, particle density, water absorption, California bearing ratio (CBR), Los Angeles abrasion, pH, organic content, and repeated load triaxial tests. Laboratory tests were undertaken on mixtures of 10%, 15%, 20%, 25%, 30%, 40%, and 50% crushed brick blended with recycled concrete aggregate or crushed rock. The research indicates that up to 25% crushed brick could be safely added to recycled concrete aggregate and crushed rock blends in pavement sub-base applications. The repeated load triaxial test results on the blends indicate that the effects of crushed brick content on the mechanical properties in terms of permanent deformation and resilient modulus of both the recycled concrete aggregate and crushed rock blends were marginal compared to the effects on dry density and moisture content.
Failure analysis of the breached levee at the 17th Street Canal in New Orleans during Hurricane Katrina
Authors: Wang X. , Castay Mark
Published: June 2012

The breached levee system at the 17th Street Canal has been independently studied by conducting total and effective stress analyses. Performance of the levee system during the hurricane duration was investigated with special attention focused on the formation of a gap between the levee fills and the floodwall, and on the localized shear strain in the lacustrine clay layer. In contrast to the total stress analyses conducted by the Interagency Performance Evaluation Task Force (IPET) and the Independent Levee Investigation Team (ILIT), the effective stress analysis presented in this paper considered the soil – pore water interaction, and demonstrated evidences of initiation and mobilization of the localized shear strain.
NEAR AND FAR FIELD OPTICAL PATTERNS FORMATION BY ROTATIONAL SYMMETRY MASKS: APPLICATION TO OPTICAL SPATIAL SOLITON GENERATION
Authors: BADALYAN ANAHIT , MANTASHYAN PAYTSAR , MEKHITARYAN VAHRAM , NERSESYAN VARSENIK , DRAMPYAN RAFAEL
Published: June 2012

In this report we present the formation of necklace type optical beams from Gaussian beam by rotational symmetry masks. The detailed studies of space evolution of the optical beam formation from the near field to the far field by the use of 7-fold symmetry mask and a single mode laser beam were performed. Different types of necklace beams with different numbers of "pearls" periodically or quasi-periodically situated along the different radii rings were observed during the space evolution of the optical diffraction pattern.
HYPERICIN-MEDIATED DESTRUCTION OF COLLAGEN FIBERS REVEALED BY MULTIPHOTON MICROSCOPY
Authors: HOVHANNISYAN ARARAT ZH. , HOVHANNISYAN VLADIMIR A. , DONG CHEN-YUAN
Published: June 2012

Collagen is the major component of the extracellular matrix in skin, tendon, cartilage, cornea, bone, etc., and as a main structural protein is the key determinant of mechanical and functional properties of tissues and organs. Proper balance between synthesis and degradation of collagen fibers is critical for maintaining normal physiologic function; therefore, the modification of collagen fibers in a controlled manner is of high importance for biomedicine. In this work, using second harmonic generation (SHG) and two-photon excited auto-fluorescence (TPEF) microscopy, we revealed that hypericin, a natural pigment extracted from plant, induced structural modification of collagen based tissues. Dynamics of the process was monitored by time-lapse multiphoton imaging. It was demonstrated that hypericin–mediated process was considerably irreversible and has a potential to be used for destroying of abnormal tissues and treatment of some diseases.