bluuebunny/crossref_metadata_2025 huggingface dataset:
Envelope and pre-membrane protein structural amino acid mutations mediate diminished avian growth and virulence of a Mexican West Nile virus isolate
Authors: Langevin Stanley A. , Bowen Richard A. , Ramey Wanichaya N. , Sanders Todd A. , Maharaj Payal D. , Fang Ying , Cornelius Jennine , Barker Christopher M. , Reisen William K. , Beasley David W. C. , Barrett Alan D. T. , Kinney Richard M. , Huang Claire Y.-H. , Brault Aaron C.
Published: August 2011

The hallmark attribute of North American West Nile virus (WNV) strains has been high pathogenicity in certain bird species. Surprisingly, this avian virulent WNV phenotype has not been observed during its geographical expansion into the Caribbean, Central America and South America. One WNV variant (TM171-03-pp1) isolated in Mexico has demonstrated an attenuated phenotype in two widely distributed North American bird species, American crows (AMCRs) and house sparrows (HOSPs). In order to identify genetic determinants associated with attenuated avian replication of the TM171-03-pp1 variant, chimeric viruses between the NY99 and Mexican strains were generated, and their replicative capacity was assessed in cell culture and in AMCR, HOSP and house finch avian hosts. The results demonstrated that mutations in both the pre-membrane (prM-I141T) and envelope (E-S156P) genes mediated the attenuation phenotype of the WNV TM171-03-pp1 variant in a chicken macrophage cell line and in all three avian species assayed. Inclusion of the prM-I141T and E-S156P TM171-03-pp1 mutations in the NY99 backbone was necessary to achieve the avian attenuation level of the Mexican virus. Furthermore, reciprocal incorporation of both prM-T141I and E-P156S substitutions into the Mexican virus genome was necessary to generate a virus that exhibited avian virulence equivalent to the NY99 virus. These structural changes may indicate the presence of new evolutionary pressures exerted on WNV populations circulating in Latin America or may signify a genetic bottleneck that has constrained their epiornitic potential in alternative geographical locations.
Computational Phonology – Part I: Foundations
Authors: Heinz Jeffrey
Published: August 2011

Computational phonology approaches the study of sound patterns in the world's languages from a computational perspective. This article explains this perspective and its relevance to phonology. A restrictive, universal property of phonological patterns – they are regular – is established, and the hypothesis that they are subregular is presented. This article is intended primarily for phonologists who are curious about computational phonology, but do not have a rigorous background in mathematics or computation. However, it is also informative for readers with a background in computation and the basics of phonology, and who are curious about what computational analysis offers phonological theory.
Importance of temporal-envelope speech cues in different spectral regions
Authors: Ardoint Marine , Agus Trevor , Sheft Stanley , Lorenzi Christian
Published: August 2011

This study investigated the ability to use temporal-envelope (E) cues in a consonant identification task when presented within one or two frequency bands. Syllables were split into five bands spanning the range 70–7300 Hz with each band processed to preserve E cues and degrade temporal fine-structure cues. Identification scores were measured for normal-hearing listeners in quiet for individual processed bands and for pairs of bands. Consistent patterns of results were obtained in both the single- and dual-band conditions: identification scores increased systematically with band center frequency, showing that E cues in the higher bands (1.8–7.3 kHz) convey greater information.
Analysis and localization of blue whale vocalizations in the Solomon Sea using waveform amplitude data
Authors: Frank Scott D. , Ferris Aaron N.
Published: August 2011

During the Woodlark Basin seismic experiment in eastern Papua New Guinea (1999–2000), an ocean-bottom seismic array recorded marine mammal vocalizations along with target earthquake signals. The array consisted of 14 instruments, 7 of which were three-component seismometers with a fourth component hydrophone. They were deployed at 2.0–3.2 km water depth and operated from September 1999 through February 2000. While whale vocalizations were recorded throughout the deployment, this study focuses on 3 h from December 21, 1999 during which the signals are particularly clear. The recordings show a blue whale song composed of a three-unit phrase. That song does not match vocalization characteristics of other known Pacific subpopulations and may represent a previously undocumented blue whale song. Animal tracking and source level estimates are obtained with a Bayesian inversion method that generates probabilistic source locations. The Bayesian method is augmented to include travel time estimates from seismometers and hydrophones and acoustic signal amplitude. Tracking results show the whale traveled northeasterly over the course of 3 h, covering approximately 27 km. The path followed the edge of the Woodlark Basin along a shelf that separates the shallow waters of the Trobriand platform from the deep waters of the basin.
A numerical study on the propagation of Rayleigh and guided waves in cortical bone according to Mindlin’s Form II gradient elastic theory
Authors: Papacharalampopoulos Alexios , Vavva Maria G. , Protopappas Vasilios C. , Fotiadis Dimitrios I. , Polyzos Demosthenes
Published: August 2011

Cortical bone is a multiscale heterogeneous natural material characterized by microstructural effects. Thus guided waves propagating in cortical bone undergo dispersion due to both material microstructure and bone geometry. However, above 0.8 MHz, ultrasound propagates rather as a dispersive surface Rayleigh wave than a dispersive guided wave because at those frequencies, the corresponding wavelengths are smaller than the thickness of cortical bone. Classical elasticity, although it has been largely used for wave propagation modeling in bones, is not able to support dispersion in bulk and Rayleigh waves. This is possible with the use of Mindlin’s Form-II gradient elastic theory, which introduces in its equation of motion intrinsic parameters that correlate microstructure with the macrostructure. In this work, the boundary element method in conjunction with the reassigned smoothed pseudo Wigner–Ville transform are employed for the numerical determination of time-frequency diagrams corresponding to the dispersion curves of Rayleigh and guided waves propagating in a cortical bone. A composite material model for the determination of the internal length scale parameters imposed by Mindlin’s elastic theory is exploited. The obtained results demonstrate the dispersive nature of Rayleigh wave propagating along the complex structure of bone as well as how microstructure affects guided waves.
Ultrasonic anechoic chamber qualification: Accounting for atmospheric absorption and transducer directivity
Authors: Jenny Trevor , Anderson Brian E.
Published: August 2011

Qualifying an anechoic chamber for frequencies that extend into the ultrasonic range is necessary for research work involving airborne ultrasonic sound. The ANSI S12.55/ISO 3745 standard which covers anechoic chamber qualification does not extend into the ultrasonic frequency range, nor have issues pertinent to this frequency range been fully discussed in the literature. An increasing number of technologies employ ultrasound; hence the need for an ultrasonic anechoic chamber. This paper will specifically discuss the need to account for atmospheric absorption and issues pertaining to source transducer directivity by presenting some results for qualification of a chamber at Brigham Young University.
Striation-based beamforming for estimating the waveguide invariant with passive sonar
Authors: Rouseff Daniel , Zurk Lisa M.
Published: August 2011

The waveguide invariant summarizes the pattern of constructive and destructive interference between acoustic modes propagating in the ocean waveguide. For many sonar signal-processing schemes, it is essential to know the correct numerical value for the waveguide invariant. While conventional beamforming can estimate the ratio between the waveguide invariant and the range to the source, it cannot unambiguously separate the two terms. In the present work, striation-based beamforming is developed. It is shown that the striation-based beamformer can be used to produce an estimate for the waveguide invariant that is independent of the range. Simulation results are presented.
Concert hall acoustics assessment with individually elicited attributes
Authors: Lokki Tapio , Pätynen Jukka , Kuusinen Antti , Vertanen Heikki , Tervo Sakari
Published: August 2011

Concert hall acoustics was evaluated with a descriptive sensory analysis method by employing an individual vocabulary development technique. The goal was to obtain sensory profiles of three concert halls by eliciting perceptual attributes for evaluation and comparison of the halls. The stimuli were gathered by playing back anechoic symphony music from 34 loudspeakers on stage in each concert hall and recording the sound field with a microphone array. Four musical programs were processed for multichannel 3D sound reproduction in the actual listening test. Twenty screened assessors developed their individual set of attributes and performed a comparative evaluation of nine seats, three in each hall. The results contain the distinctive groups of elicited attributes and show good agreement within assessors, even though they applied individual attributes when rating the samples. It was also found that loudness and distance gave the strongest perceptual direction to the principal component basis. In addition, the study revealed that the perception of reverberance is related to the size of the space or to the enveloping reverberance, depending on the assessor.
Dolphin and sea lion auditory evoked potentials in response to single and multiple swept amplitude tones
Authors: Finneran James J. , Mulsow Jason , Schlundt Carolyn E. , Houser Dorian S.
Published: August 2011

Measurement of the auditory steady-state response (ASSR) is increasingly used to assess marine mammal hearing. These tests normally entail measuring the ASSR to a sequence of sinusoidally amplitude modulated tones, so that the ASSR amplitude function can be defined and the auditory threshold estimated. In this study, an alternative method was employed, where the ASSR was elicited by an amplitude modulated stimulus whose sound pressure level was slowly varied, or “swept,” over a range of levels believed to bracket the threshold. The ASSR amplitude function was obtained by analyzing the resulting grand average evoked potential using a short-time Fourier transform. The suitability of this technique for hearing assessment of bottlenose dolphins and California sea lions was evaluated by comparing ASSR amplitude functions and thresholds obtained with swept amplitude and discrete, constant amplitude stimuli. When factors such as the number of simultaneous tones, the number of averages, and the frequency analysis window length were taken into account, the performance and time required for the swept-amplitude and discrete stimulus techniques were similar. The decision to use one technique over another depends on the relative importance of obtaining suprathreshold information versus the lowest possible thresholds.
Evaluation of the echolocation model for range estimation of multiple closely spaced objects
Authors: Matsuo Ikuo
Published: August 2011

Experimental evidence indicates that bats can use frequency-modulated echolocation to identify objects with an accuracy of less than 1 μs. However, when modeling this process, it is difficult to estimate the delay times of multiple closely spaced objects by analyzing the echo spectrum, because the sequence of delay separations cannot be determined without information on the temporal changes in the interference patterns of the echoes. To extract the temporal changes, Gaussian chirplets with a carrier frequency compatible with bat emission sweep rates are introduced. The delay time for object 1 (T1) is estimated from the echo spectrum around the onset time. The T2 is obtained by adding the T1 to the delay separation between objects 1 and 2. Further objects are located in sequence by this procedure. Here echoes were measured from single and multiple objects at a low signal-to-noise ratio. It was confirmed that the delay time for a single object could be estimated with an accuracy of about 1.3 μs. The range accuracy was less than 6 μs when the frequency bandwidth was less than 10 kHz. The delay time for multiple closely spaced objects could be estimated with a high range resolution by extracting the interference pattern.
Acquisition of detailed laryngeal flow measurements in geometrically realistic models
Authors: Farley Jayrin , Thomson Scott L.
Published: August 2011

Characterization of laryngeal flow velocity fields is important to understanding vocal fold vibration and voice production. One common method for acquiring flow field data is particle image velocimetry (PIV). However, because using PIV with models that have curved surfaces is problematic due to optical distortion, experimental investigations of laryngeal airflow are typically performed using models with idealized geometries. In this paper a method for acquiring PIV data using models with realistic geometries is presented. Sample subglottal, intraglottal, and supraglottal PIV data are shown. Capabilities and limitations are discussed, and suggestions for future implementation are provided.
The use of the virtual source technique in computing scattering from periodic ocean surfaces
Authors: Abawi Ahmad T.
Published: August 2011

In this paper the virtual source technique is used to compute scattering of a plane wave from a periodic ocean surface. The virtual source technique is a method of imposing boundary conditions using virtual sources, with initially unknown complex amplitudes. These amplitudes are then determined by applying the boundary conditions. The fields due to these virtual sources are given by the environment Green’s function. In principle, satisfying boundary conditions on an infinite surface requires an infinite number of sources. In this paper, the periodic nature of the surface is employed to populate a single period of the surface with virtual sources and m surface periods are added to obtain scattering from the entire surface. The use of an accelerated sum formula makes it possible to obtain a convergent sum with relatively small number of terms (∼40). The accuracy of the technique is verified by comparing its results with those obtained using the integral equation technique.
MED23
Mutation Links Intellectual Disability to Dysregulation of Immediate Early Gene Expression
Authors: Hashimoto Satoru , Boissel Sarah , Zarhrate Mohammed , Rio Marlène , Munnich Arnold , Egly Jean-Marc , Colleaux Laurence
Published: August 2011

A single missense mutation is linked to intellectual impairment.
Expanding the Genetic Code of
Escherichia coli
with Phosphoserine
Authors: Park Hee-Sung , Hohn Michael J. , Umehara Takuya , Guo Li-Tao , Osborne Edith M. , Benner Jack , Noren Christopher J. , Rinehart Jesse , Söll Dieter
Published: August 2011

Engineered bacterial translation can be used to direct site-specific insertion of an amino acid into proteins.
Neutron Activation Analysis of a Particle Returned from Asteroid Itokawa
Authors: Ebihara M. , Sekimoto S. , Shirai N. , Hamajima Y. , Yamamoto M. , Kumagai K. , Oura Y. , Ireland T. R. , Kitajima F. , Nagao K. , Nakamura T. , Naraoka H. , Noguchi T. , Okazaki R. , Tsuchiyama A. , Uesugi M. , Yurimoto H. , Zolensky M. E. , Abe M. , Fujimura A. , Mukai T. , Yada Y.
Published: August 2011

Laboratory analysis of samples returned from an asteroid establishes a direct link between asteroids and meteorites and provides clues to the complex history of the asteroid and its surface.
Architecturally Complex Polymers with Controlled Heterogeneity
Authors: Matyjaszewski Krzysztof
Published: August 2011

New materials result by creating polymers that combine the many ways in which chains are connected and composition and functionality are varied.
Well-Being and Its Consequences
The Changing Body
Health, Nutrition, and Human Development in the Western World Since 1700

by Roderick Floud, Robert W. Fogel, Bernard Harris, and Sok Chul Hong

Cambridge University Press, Cambridge, 2011. 457 pp. $90, £55. ISBN 9780521879750. Paper, $32.99, £19.99. ISBN 9780521705615. New Approaches to Economic and Social History.
Authors: Haddad Lawrence
Published: August 2011

The authors survey causes and consequences of changes in health, mortality, diet, and "the disease environment" in Europe and the United States over the past four centuries.
Another NOTCH for Cancer
Authors: Brakenhoff Ruud H.
Published: August 2011

Next-generation sequencing reveals
NOTCH1
as an important tumor suppressor gene in head and neck cancer.
Arranging a Cellular Checkerboard
Authors: Choi Wangsun , Peifer Mark
Published: August 2011

Heterotypic cell adhesion mediated by nectins directs the complex cellular architecture of the inner ear.
A Rabbit Vaginal Cell-Derived Antimicrobial Peptide, RVFHbαP, Blocks Lipopolysaccharide-Mediated Inflammation in Human Vaginal CellsIn Vitro
Authors: Patgaonkar Mandar S. , Sathe Ameya , Selvaakumar C. , Reddy K. V. R.
Published: August 2011

Antimicrobial peptides (AMPs) constitute a phylogenetically ancient form of innate immunity that provides host defense at various mucosal surfaces, including the vagina. Recently, we have identified one such AMP, rabbit vaginal fluid hemoglobin alpha peptide (RVFHbαP), from the vaginal lavage of rabbits (Oryctolagus cuniculus). The recent demonstration of a protective role of this peptide in erythrocytes and vaginal cells led us to investigate (i) the lipopolysaccharide (LPS) interactive domain in RVFHbαP and (ii) whether RVFHbαP of rabbit origin modulates the cellular immune responses of another species (humans)in vitro. HeLa-S3, a human vaginal epithelial cell line (hVEC), was exposed to LPS alone (10 μg/ml for 6 h), or LPS-induced cells were treated with RVFHbαP (70.45 μM for 1 h) and cultured for 24 h, and the results obtained were compared with the medium control. We show here that RVFHbαP exerts an anti-inflammatory activity in hVECs, as suggested by the prevention of LPS-induced production of extracellular (supernatant) and intracellular (lysate) levels of cytokines (interleukin 6 [IL-6] and IL-1α) and chemokines (IL-8 and monocyte chemoattractant protein 1 [MCP-1]). The demonstration of Toll-like receptor 4 (TLR4) and NF-κB expression in hVECs and the observations of RVFHbαP suppression of human β-defensin-1 (hBD1) mRNA expression further support the hypothesis of a genomic activity of RVFHbαP. Confocal microscopy and flow cytometry results demonstrate that RVFHbαP inhibits LPS-induced phagocytosis ofEscherichia coliby macrophages. The chemotaxis studies performed using the Boyden chamber Transwell method showed the increased migration of U937 cells when supernatants of LPS-induced hVECs were used, and this effect was inhibited by RVFHbαP. In conclusion, our study proposes a novel explanation for the protective role of RVFHbαP in inflammation-associated infections, which not only may provide the new cellular targets for the screening of RVFHbαP ligands acting in the vaginal tissue but also has the potential to develop RVFHbαP as a therapeutic agent for reproductive tract infections.
Complete Genome Sequence of Streptomyces cattleya NRRL 8057, a Producer of Antibiotics and Fluorometabolites
Authors: Barbe Valérie , Bouzon Madeleine , Mangenot Sophie , Badet Bernard , Poulain Julie , Segurens Béatrice , Vallenet David , Marlière Philippe , Weissenbach Jean
Published: August 2011

Streptomyces cattleya
, a producer of the antibiotics thienamycin and cephamycin C, is one of the rare bacteria known to synthesize fluorinated metabolites. The genome consists of two linear replicons. The genes involved in fluorine metabolism and in the biosynthesis of the antibiotic thienamycin were mapped on both replicons.
External Quality Assessment for Enterovirus 71 and Coxsackievirus A16 Detection by Reverse Transcription-PCR Using Armored RNA as a Virus Surrogate
Authors: Song Liqiong , Sun Shipeng , Li Bo , Pan Yang , Li Wenli , Zhang Kuo , Li Jinming
Published: August 2011

Three armored RNAs (virus-like particles [VLPs]) containing target sequences from enterovirus 71 (EV71) and coxsackievirus A16 (CA16) and a pan-enterovirus (pan-EV) sequence were constructed and used in an external quality assessment (EQA) to determine the performance of laboratories in the detection of EV71 and CA16. The EQA panel, which consisted of 20 samples, including 14 positive samples with different concentrations of EV and either EV71 or CA16 armored RNAs, 2 samples with all 3 armored RNAs, and 4 negative-control samples (NaN
3
-preserved minimal essential medium [MEM] without VLPs), was distributed to 54 laboratories that perform molecular diagnosis of hand, foot, and mouth disease (HFMD) virus infections. A total of 41 data sets from 41 participants were returned; 5 (12.2%) were generated using conventional in-house reverse transcription-PCR (RT-PCR) assays, and 36 (87.8%) were generated using commercial real-time RT-PCR assays. Performance assessments of laboratories differed; 12 (29.3%) showed a need for improvement. Surprisingly, 4 laboratories were unable to detect EV71 RNA in any samples, even those containing the highest concentration of 10
7
IU/ml. Furthermore, the detection sensitivity for EV71 among all laboratories (82.1%) was substantially lower than that for EV (97.4%) or CA16 (95.1%). Overall, the results of the present study indicate that EQA should be performed periodically to help laboratories monitor their ability to detect HFMD viruses and to improve the comparability of results from different laboratories.
Diagnostic Strategy Used To Establish Etiologies of Encephalitis in a Prospective Cohort of Patients in England
Authors: Ambrose H. E. , Granerod J. , Clewley J. P. , Davies N. W. S. , Keir G. , Cunningham R. , Zuckerman M. , Mutton K. J. , Ward K. N. , Ijaz S. , Crowcroft N. S. , Brown D. W. G. ,   on behalf of the UK Aetiology of Encephalitis Study Group
Published: August 2011

The laboratory diagnostic strategy used to determine the etiology of encephalitis in 203 patients is reported. An etiological diagnosis was made by first-line laboratory testing for 111 (55%) patients. Subsequent testing, based on individual case reviews, resulted in 17 (8%) further diagnoses, of which 12 (71%) were immune-mediated and 5 (29%) were due to infection. Seventy-five cases were of unknown etiology. Sixteen (8%) of 203 samples were found to be associated with either
N
-methyl-
d
-aspartate receptor or voltage-gated potassium channel complex antibodies. The most common viral causes identified were herpes simplex virus (HSV) (19%) and varicella-zoster virus (5%), while the most important bacterial cause was
Mycobacterium tuberculosis
(5%). The diagnostic value of testing cerebrospinal fluid (CSF) for antibody was assessed using 139 samples from 99 patients, and antibody was detected in 46 samples from 37 patients. Samples collected at 14 to 28 days were more likely to be positive than samples taken 0 to 6 days postadmission. Three PCR-negative HSV cases were diagnosed by the presence of virus-specific antibody in the central nervous system (CNS). It was not possible to make an etiological diagnosis for one-third of the cases; these were therefore considered to be due to unknown causes. Delayed sampling did not contribute to these cases. Twenty percent of the patients with infections with an unknown etiology showed evidence of localized immune activation within the CNS, but no novel viral DNA or RNA sequences were found. We conclude that a good standard of clinical investigation and thorough first-line laboratory testing allows the diagnosis of most cases of infectious encephalitis; testing for CSF antibodies allows further cases to be diagnosed. It is important that testing for immune-mediated causes also be included in a diagnostic algorithm.
High-Resolution Melting Approach to Efficient Identification and Quantification of H275Y Mutant Influenza H1N1/2009 Virus in Mixed-Virus-Population Samples
Authors: Lee Hong Kai , Lee Chun Kiat , Loh Tze Ping , Tang Julian Wei-Tze , Tambyah Paul Anantharajah , Koay Evelyn Siew-Chuan
Published: August 2011

The single-nucleotide variation 823C to T (His275Tyr), responsible for oseltamivir drug resistance has been detected in some isolates of the influenza A/H1N1/2009 virus. Early detection of the presence of this oseltamivir-resistant strain allows prompt consideration of alternative treatment options. An isolated-probe–asymmetric amplification PCR (Roche LightCycler v2.0) and high-resolution melting (HRM) method using unlabeled probes and amplified products (Idaho LightScanner 32) was designed and optimized to detect and estimate the proportion of H275Y mutants in influenza A/H1N1/2009 virus samples. The lower limit of quantification within the linear range of PCR assay detection was 200 copies/reaction. The melting peaks of the H275Y-specific unlabeled probe for the wild-type A/H1N1/2009 and H275Y mutant viruses were clearly distinguishable at 65.5°C and 69.0°C, respectively, at various ratios of wild-type/mutant virus population standards. The 95% detection limit for the 10% mutant sample pool was 1,200 copies/reaction (95% confidence interval, 669.7 to 3,032.6 copies/reaction). This HRM assay was tested with 116 archived clinical specimens. The quantitative HRM results obtained with samples containing mixed mutant–wild-type virus populations, at threshold cycle (

C
T

) values of <29, compared well to those obtained with a pyrosequencing method performed by an independent laboratory. The quantitative feature of this assay allows the proportions of mutant and wild-type viral populations to be determined, which may assist in the conventional clinical management of infected patients and potentially more preemptive clinical management. This validated quantitative HRM method, with its low running cost, is well positioned as a rapid, high-throughput screening tool for oseltamivir resistance mutations in influenza A/H1N1/2009 virus-infected patients, with the potential to be adapted to other influenza virus species.
Emergence of a Novel Shiga Toxin-Producing Escherichia coli O Serogroup Cross-Reacting with Shigella boydii Type 10
Authors: Iguchi Atsushi , Iyoda Sunao , Seto Kazuko , Ohnishi Makoto ,   on behalf of the EHEC Study Group
Published: August 2011

This is the first report of the isolation of Shiga toxin-producing
Escherichia coli
(STEC) strains whose O antigens were genetically and serologically identical to those of
Shigella boydii
type 10, from human feces. The novel STEC O serogroup may be widespread in Japan and associated with diarrhea and hemorrhagic colitis.
Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes
Authors: Hyland Paula L. , McDade Simon S. , McCloskey Rachel , Dickson Glenda J. , Arthur Ken , McCance Dennis J. , Patel Daksha
Published: August 2011

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels
in vitro
, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.
Alphavirus-Induced Encephalomyelitis: Antibody-Secreting Cells and Viral Clearance from the Nervous System
Authors: Metcalf Talibah U. , Griffin Diane E.
Published: August 2011

Sindbis virus (SINV) infection of the central nervous system (CNS) provides a model for understanding the role of the immune response in recovery from alphavirus infection of neurons. Virus clearance occurred in three phases: clearance of infectious virus (days 3 to 7), clearance of viral RNA (days 8 to 60), and maintenance of low levels of viral RNA (>day 60). The antiviral immune response was initiated in the cervical lymph nodes with rapid extrafollicular production of plasmablasts secreting IgM, followed by germinal center production of IgG-secreting and memory B cells. The earliest inflammatory cells to enter the brain were CD8+T cells, followed by CD4+T cells and CD19+B cells. During the clearance of infectious virus, effector lymphocytes in the CNS were primarily CD8+T cells and IgM antibody-secreting cells (ASCs). During the clearance of viral RNA, there were more CD4+than CD8+T cells, and B cells included IgG and IgA ASCs. At late times after infection, ASCs in the CNS were primarily CD19+CD38+CD138−Blimp-1+plasmablasts, with few fully differentiated CD38−CD138+Blimp-1+plasma cells. CD19+CD38+surface Ig+memory B cells were also present. The level of antibody to SINV increased in the brain over time, and the proportion of SINV-specific ASCs increased from 15% of total ASCs at day 14 to 90% at 4 to 6 months, suggesting specific retention in the CNS during viral RNA persistence. B cells in the CNS continued to differentiate, as evidenced by accumulation of IgA ASCs not present in peripheral lymphoid tissue and downregulation of major histocompatibility complex (MHC) class II expression on plasmablasts. However, there was no evidence of germinal center activity or IgG avidity maturation within the CNS.
Systems Analysis of Immune Responses in Marek's Disease Virus-Infected Chickens Identifies a Gene Involved in Susceptibility and Highlights a Possible Novel Pathogenicity Mechanism
Authors: Smith Jacqueline , Sadeyen Jean-Remy , Paton Ian R. , Hocking Paul M. , Salmon Nigel , Fife Mark , Nair Venugopal , Burt David W. , Kaiser Pete
Published: August 2011

Marek's disease virus (MDV) is a highly contagious oncogenic alphaherpesvirus that causes disease that is both a cancer model and a continuing threat to the world's poultry industry. This comprehensive gene expression study analyzes the host response to infection in both resistant and susceptible lines of chickens and inherent expression differences between the two lines following the infection of the host. A novel pathogenicity mechanism, involving the downregulation of genes containing HIC1 transcription factor binding sites as early as 4 days postinfection, was suggested from this analysis. HIC1 drives antitumor mechanisms, suggesting that MDV infection switches off genes involved in antitumor regulation several days before the expression of the MDV oncogene
meq
. The comparison of the gene expression data to previous QTL data identified several genes as candidates for involvement in resistance to MD. One of these genes, IRG1, was confirmed by single nucleotide polymorphism analysis to be involved in susceptibility. Its precise mechanism remains to be elucidated, although the analysis of gene expression data suggests it has a role in apoptosis. Understanding which genes are involved in susceptibility/resistance to MD and defining the pathological mechanisms of the disease gives us a much greater ability to try to reduce the incidence of this virus, which is costly to the poultry industry in terms of both animal welfare and economics.
Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection
Authors: Liu Pinghuang , Overman R. Glenn , Yates Nicole L. , Alam S. Munir , Vandergrift Nathan , Chen Yue , Graw Frederik , Freel Stephanie A. , Kappes John C. , Ochsenbauer Christina , Montefiori David C. , Gao Feng , Perelson Alan S. , Cohen Myron S. , Haynes Barton F. , Tomaras Georgia D.
Published: August 2011

Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection.
Factors associated with use of slip-resistant shoes in US limited-service restaurant workers
Authors: Verma Santosh K , Courtney Theodore K , Corns Helen L , Huang Yueng-Hsiang , Lombardi David A , Chang Wen-Ruey , Brennan Melanye J , Perry Melissa J
Published: August 2011

Objectives

Slips and falls are a leading cause of injury at work. Several studies have indicated that slip-resistant shoes can reduce the risk of occupational slips and falls. Few studies, however, have examined the determinants of slip-resistant shoe use. This study examined the individual and workplace factors associated with slip-resistant shoe use.

Methods

475 workers from 36 limited-service restaurants in the USA participated in a study of workplace slipping. Demographic and job characteristic information about each participant was collected. Restaurant managers provided information on whether slip-resistant shoes were provided and paid for by the employer and whether any guidance was given regarding slip-resistant shoe use when they were not provided. Kitchen floor coefficient of friction was measured. Slip-resistant status of the shoes was determined by noting the presence of a ‘slip-resistant’ marking on the sole. Poisson regression with robust SE was used to calculate prevalence ratios.

Results

320 participants wore slip-resistant shoes (67%). In the multivariate analysis, the prevalence of slip-resistant shoe use was lowest in 15–19-year age group. Women were more likely to wear slip-resistant shoes (prevalence ratio 1.18, 95% CI 1.07 to 1.31). The prevalence of slip-resistant shoe use was lower when no guidance regarding slip-resistant shoes was given as compared to when they were provided by the employer (prevalence ratio 0.66, 95% CI 0.55 to 0.79). Education level, job tenure and the mean coefficient of friction had no significant effects on the use of slip-resistant shoes.

Conclusion

Provision of slip-resistant shoes was the strongest predictor of their use. Given their effectiveness and low cost, employers should consider providing slip-resistant shoes at work.
Long-term effect of nutritional counselling on desired gain in body mass and lean body mass in elite athletes
Authors: Garthe Ina , Raastad Truls , Sundgot-Borgen Jorunn
Published: August 2011

Lean body mass (LBM) is important in power-related sports. In athletes with heavy training loads and competitions, it may be difficult to increase and maintain LBM during the season. The purpose of this study was to evaluate the long-term effects on body composition after an 8–12 week weight-gain period with or without nutritional guidance. Twenty-one elite athletes where randomized to 1 of 2 groups: the nutritional counselling group (NCG; n = 12, 18.5 ± 1.7 y, 67.8 ± 7.4 kg) and the ad libitum group (ALG; n = 9, 19.6 ± 2.7 y, 74.2 ± 5.7 kg). The NCG followed a meal plan that provided a surplus of 506 ± 84 kcal·day–1, whereas the ALG had an ad libitum energy intake (EI) during the strength-training (4 sessions per week) intervention. Body mass (BM) and body composition were measured pre- and postintervention, and 6 and 12 months after the intervention. EI in the NCG was normalized after 12 months, whereas EI in the ALG was unchanged during or after the intervention. BM increased more in the NCG than in the ALG during the intervention (4.3% ± 0.9% vs. 1.0% ± 0.6%) and after 12 months (6.0% ± 0.9% vs. 1.8% ± 0.7%). LBM increased in the NCG during the intervention (2.8% ± 0.5%) and after 12 months (4.4% ± 1.0%), whereas LBM in the ALG was unchanged. The NCG managed to maintain and increase BM and LBM after the intervention period. Hence, the focus on nutritional guidance, in addition to strength training, seems to be preferable for obtaining the long-term effect of weight gain in athletes.
ELECTROWEAK THEORY WITH A MINIMAL LENGTH
Authors: KOBER MARTIN
Published: August 2011

According to the introduction of a minimal length to quantum field theory, which is directly related to a generalized uncertainty principle, the implementation of the gauge principle becomes much more intricated. It has been shown in another paper how gauge theories have to be extended in general, if there is assumed the existence of a minimal length. In this paper this generalization of the description of gauge theories is applied to the case of Yang–Mills theories with gauge group SU(N) to consider especially the application to the electroweak theory as it appears in the Standard Model. The modifications of the lepton-, Higgs- and gauge field sector of the extended Lagrangian of the electroweak theory maintaining local gauge invariance under SU(2)L ⊗ U(1)Y transformations are investigated. There appear additional interaction terms between the leptons or the Higgs particle respectively with the photon and the W- and Z-bosons as well as additional self-interaction terms of these gauge bosons themselves. It is remarkable that in the quark sector where the full gauge group of the Standard Model, SU(3)c ⊗ SU(2)L ⊗ U(1)Y, has to be considered there arise coupling terms between the gluons und the W- and Z-bosons which means that the electroweak theory is not separated from quantum chromodynamics anymore.
THE BOUNDED CONFIDENCE MODEL OF OPINION DYNAMICS
Authors: GÓMEZ-SERRANO JAVIER , GRAHAM CARL , LE BOUDEC JEAN-YVES
Published: August 2011

The bounded confidence model of opinion dynamics, introduced by Deffuant et al., is a stochastic model for the evolution of continuous-valued opinions within a finite group of peers. We prove that, as time goes to infinity, the opinions evolve globally into a random set of clusters too far apart to interact, and thereafter all opinions in every cluster converge to their barycenter. We then prove a mean-field limit result, propagation of chaos: as the number of peers goes to infinity in adequately started systems and time is rescaled accordingly, the opinion processes converge to i.i.d. nonlinear Markov (or McKean–Vlasov) processes; the limit opinion processes evolve as if under the influence of opinions drawn from its own instantaneous law, which are the unique solution of a nonlinear integro-differential equation of Kac type. This implies that the (random) empirical distribution processes converge to this (deterministic) solution. We then prove that, as time goes to infinity, this solution converges to a law concentrated on isolated opinions too far apart to interact, and identify sufficient conditions for the limit not to depend on the initial condition, and to be concentrated at a single opinion. Finally, we prove that if the equation has an initial condition with a density, then its solution has a density at all times, develop a numerical scheme for the corresponding functional equation, and show numerically that bifurcations may occur.
CRYPTANALYSIS AND IMPROVEMENT OF THE SECURE QUANTUM SEALED-BID AUCTION WITH POSTCONFIRMATION
Authors: XU GUO-AI , ZHAO ZHI-WEN , CHEN XIU-BO , YANG YI-XIAN
Published: August 2011

In this paper, the cryptanalysis about the quantum sealed-bid auction, whose feature is that by introducing a postconfirmation mechanism the malicious bidders cannot collude with auctioneers, is given. We found that a malicious bidder can obtain the other bidders' bids with a probability of 0.854. Moreover, there will be a higher probability if some bidders collude to attack the other bidders' bids. To prevent such attacks, we propose an effective improvement by means of the hash function.
A calcineurin homologous protein is required for sodium-proton exchange events in the C. elegans intestine
Authors: Wagner Jamie , Allman Erik , Taylor Ashley , Ulmschneider Kiri , Kovanda Timothy , Ulmschneider Bryne , Nehrke Keith , Peters Maureen A.
Published: August 2011

Caenorhabditis elegans defecation is a rhythmic behavior, composed of three sequential muscle contractions, with a 50-s periodicity. The motor program is driven by oscillatory calcium signaling in the intestine. Proton fluxes, which require sodium-proton exchangers at the apical and basolateral intestinal membranes, parallel the intestinal calcium flux. These proton shifts are critical for defecation-associated muscle contraction, nutrient uptake, and longevity. How sodium-proton exchangers are activated in time with intestinal calcium oscillation is not known. The posterior body defecation contraction mutant ( pbo-1) encodes a calcium-binding protein with homology to calcineurin homologous proteins, which are putative cofactors for mammalian sodium-proton exchangers. Loss of pbo-1 function results in a weakened defecation muscle contraction and a caloric restriction phenotype. Both of these phenotypes also arise from dysfunctions in pH regulation due to mutations in intestinal sodium-proton exchangers. Dynamic, in vivo imaging of intestinal proton flux in pbo-1 mutants using genetically encoded pH biosensors demonstrates that proton movements associated with these sodium-proton exchangers are significantly reduced. The basolateral acidification that signals the first defecation motor contraction is scant in the mutant compared with a normal animal. Luminal and cytoplasmic pH shifts are much reduced in the absence of PBO-1 compared with control animals. We conclude that pbo-1 is required for normal sodium-proton exchanger activity and may couple calcium and proton signaling events.
Thermal acclimation in Antarctic fish: transcriptomic profiling of metabolic pathways
Authors: Windisch Heidrun Sigrid , Kathöver Raphaela , Pörtner Hans-Otto , Frickenhaus Stephan , Lucassen Magnus
Published: August 2011

It is widely accepted that adaptation to the extreme cold has evolved at the expense of high thermal sensitivity. However, recent studies have demonstrated significant capacities for warm acclimation in Antarctic fishes. Here, we report on hepatic metabolic reorganization and its putative molecular background in the Antarctic eelpout ( Pachycara brachycephalum ) during warm acclimation to 5°C over 6 wk. Elevated capacities of cytochrome c oxidase suggest the use of warm acclimation pathways different from those in temperate fish. The capacity of this enzyme rose by 90%, while citrate synthase (CS) activity fell by 20% from the very beginning. The capacity of lipid oxidation by hydroxyacyl-CoA dehydrogenase remained constant, whereas phosphoenolpyruvate carboxykinase as a marker for gluconeogenesis displayed 40% higher activities. These capacities in relation to CS indicate a metabolic shift from lipid to carbohydrate metabolism. The finding was supported by large rearrangements of the related transcriptome, both functional genes and potential transcription factors. A multivariate analysis (canonical correspondence analyses) of various transcripts subdivided the incubated animals in three groups, one control group and two responding on short and long timescales, respectively. A strong dichotomy in the expression of peroxisome proliferator-activated receptors-1α and -β receptors was most striking and has not previously been reported. Altogether, we identified a molecular network, which responds sensitively to warming beyond the realized ecological niche. The shift from lipid to carbohydrate stores and usage may support warm hardiness, as the latter sustain anaerobic metabolism and may prepare for hypoxemic conditions that would develop upon warming beyond the present acclimation temperature.