bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quasi-Monte-Carlo Comparison of Parametric and Semiparametric Regression Methods for Heavy-tailed and Non-normal Data: an Application to Healthcare Costs
Authors: Jones Andrew M. , Lomas James , Moore Peter T. , Rice Nigel
Published: October 2015

We conduct a quasi-Monte-Carlo comparison of the recent developments in parametric and semiparametric regression methods for healthcare costs, both against each other and against standard practice. The population of English National Health Service hospital in-patient episodes for the financial year 2007–2008 (summed for each patient) is randomly divided into two equally sized subpopulations to form an estimation set and a validation set. Evaluating out-of-sample using the validation set, a conditional density approximation estimator shows considerable promise in forecasting conditional means, performing best for accuracy of forecasting and among the best four for bias and goodness of fit. The best performing model for bias is linear regression with square-root-transformed dependent variables, whereas a generalized linear model with square-root link function and Poisson distribution performs best in terms of goodness of fit. Commonly used models utilizing a log-link are shown to perform badly relative to other models considered in our comparison.
Collective versus Individual Effects in Survival Analysis of Multiple Failures
Authors: Li Jialiang , Huang Zhipeng , Ma Shuangge , Lee Mei‐Ling Ting
Published: October 2015

In survival analysis, we sometimes encounter data with multiple censored outcomes. Under certain scenarios, partial or even all covariates have ‘similar’ relative risks on the multiple outcomes in the Cox regression analysis. The similarity in covariate effects can be quantified using the proportionality of regression coefficients. Identifying the proportionality structure, or equivalently whether covariates have individual or collective effects, may have important scientific implications. In addition, it can lead to a smaller set of unknown parameters, which in turn results in more accurate estimation. In this article, we develop a novel approach for identifying the proportionality structure. Simulation shows the satisfactory performance of the proposed approach and its advantage over estimation under no assumed structure. We analyse three datasets to demonstrate the practical application of the proposed approach.
Genomic full‐length sequence of two HLA‐A alleles, A*02:48 and A*02:251, identified by cloning and sequencing
Authors: Lu L. , Xu Y. P.
Published: October 2015

Genomic sequences of HLA‐A*02:48 and A*02:251, identified by cloning and sequencing from two Chinese donors.
THREE TESLA MAGNETIC RESONANCE IMAGING FINDINGS IN 12 CASES OF CANINE CENTRAL EUROPEAN TICK‐BORNE MENINGOENCEPHALOMYELITIS
Authors: Beckmann Katrin , Steffen Frank , Ohlerth Stefanie , Kircher Patrick R. , Carrera Inés
Published: October 2015

Central European tick‐borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick‐borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick‐borne encephalomyelitis, history of a stay in endemic areas for tick‐borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick‐borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow‐up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2‐weighted sequences compared to white matter, iso‐ to hypointense in T1‐weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick‐borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics.
Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high‐fat diet
Authors: Shah Amin , Reyes Laura M. , Morton Jude S. , Fung David , Schneider Jillian , Davidge Sandra T.
Published: October 2015

Key points

Prenatal hypoxia, a common outcome of many pregnancy complications, predisposes offspring to chronic diseases in later life.

We investigated the effect of prenatal hypoxia, on a background of a high‐fat diet, on metabolic and cardiac function in adult male and female rat offspring. We also examined the therapeutic role of resveratrol supplementation in preventing metabolic and cardiac dysfunction.

Prenatal hypoxia impaired both metabolic and cardiac function in male and only cardiac function in female rat offspring. We also observed that male rat offspring were more susceptible to metabolic and cardiac dysfunction as compared with their female counterparts; this provides evidence of sexual dichotomy in the fetal programming of diseases due to prenatal hypoxia.

Resveratrol supplementation in the diet improved metabolic and cardiac function independent of sex; this provides evidence of a possible therapeutic role of resveratrol in susceptible male and female rat offspring exposed to prenatal hypoxia.

Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high‐fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia–reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex‐specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.
Degradation of proton depth dose distributions attributable to microstructures in lung‐equivalent material
Authors: Titt Uwe , Sell Martin , Unkelbach Jan , Bangert Mark , Mirkovic Dragan , Oelfke Uwe , Mohan Radhe
Published: October 2015

Purpose:

The purpose of the work reported here was to investigate the influence of sub‐millimeter size heterogeneities on the degradation of the distal edges of proton beams and to validate Monte Carlo (MC) methods’ ability to correctly predict such degradation.

Methods:

A custom‐designed high‐resolution plastic phantom approximating highly heterogeneous, lung‐like structures was employed in measurements and in Monte Carlo simulations to evaluate the degradation of proton Bragg curves penetrating heterogeneous media.

Results:

Significant differences in distal falloff widths and in peak dose values were observed in the measured and the Monte Carlo simulated curves compared to pristine proton Bragg curves. Furthermore, differences between simulations of beams penetrating CT images of the phantom did not agree well with the corresponding experimental differences. The distal falloff widths in CT image‐based geometries were underestimated by up to 0.2 cm in water (corresponding to 0.8–1.4 cm in lung tissue), and the peak dose values of pristine proton beams were overestimated by as much as ˜35% compared to measured curves or depth‐dose curves simulated on the basis of true geometry. The authors demonstrate that these discrepancies were caused by the limited spatial resolution of CT images that served as a basis for dose calculations and lead to underestimation of the impact of the fine structure of tissue heterogeneities. A convolution model was successfully applied to mitigate the underestimation.

Conclusions:

The results of this study justify further development of models to better represent heterogeneity effects in soft‐tissue geometries, such as lung, and to correct systematic underestimation of the degradation of the distal edge of proton doses.
Optimal design of modal beamformers for circular arrays
Authors: Yan Shefeng
Published: October 2015

An approach to optimal design of circular harmonics based modal beamformers for circular arrays is presented. Theoretical analysis shows the equivalence between the element-space and circular-harmonics-domain beamformers. By deriving the expression for the signal and noise covariance matrices, array manifold, and the array response in terms of the circular-harmonics-domain beamforming weights, the weights design problem is formulated as one of minimum variance distortionless response beamforming in the circular harmonics domain. It is found that the well-known phase-mode beamformer for circular arrays can be viewed as an ideal minimum variance distortionless response beamformer against the planarly isotropic noise in the circular harmonics domain. This interesting result is useful for analyzing and evaluating the performance of the phase-mode circular arrays. In this circular-harmonics-domain beamformer, additional constraints can be imposed to improve its robustness and control the sidelobes, which is important in practical applications. The developed approach can include both the delay-and-sum and phase-mode beamformers as special cases, which leads to very flexible designs. Simulation and experimental results show excellent performance of the proposed beamforming approach.
The relationship between speech segment duration and vowel centralization in a group of older speakers
Authors: Fletcher Annalise R. , McAuliffe Megan J. , Lansford Kaitlin L. , Liss Julie M.
Published: October 2015

This study examined the relationship between average vowel duration and spectral vowel quality across a group of 149 New Zealand English speakers aged 65 to 90 yr. The primary intent was to determine whether participants who had a natural tendency to speak slowly would also produce more spectrally distinct vowel segments. As a secondary aim, this study investigated whether advancing age exhibited a measurable effect on vowel quality and vowel durations within the group. In examining vowel quality, both flexible and static formant extraction points were compared. Two formant measurements, from selected [ɐ:], [i:], and [o:] vowels, were extracted from a standard passage and used to calculate two measurements of vowel space area (VSA) for each speaker. Average vowel duration was calculated from segments across the passage. The study found a statistically significant relationship between speakers' average vowel durations and VSA measurements indicating that, on average, speakers with slower speech rates produced more acoustically distinct speech segments. As expected, increases in average vowel duration were found with advancing age. However, speakers' formant values remained unchanged. It is suggested that the use of a habitually slower speaking rate may assist speakers in maintaining acoustically distinct vowels.
Eigenvector pruning method for high resolution beamforming
Authors: Quijano Jorge E. , Zurk Lisa M.
Published: October 2015

This paper introduces an eigenvector pruning algorithm for the estimation of the signal-plus-interference eigenspace, required as a preliminary step to subspace beamforming. The proposed method considers large-aperture passive array configurations operating in environments with multiple maneuvering targets in background noise, in which the available data for estimation of sample covariances and eigenvectors are limited. Based on statistical properties of scalar products between deterministic and complex random vectors, this work defines a statistically justified threshold to identify target-related features embedded in the sample eigenvectors, leading to an estimator for the signal-bearing eigenspace. It is shown that data projection into this signal subspace results in sharpening of beamforming outputs corresponding to closely spaced targets and provides better target separation compared to current subspace beamformers. In addition, the proposed threshold gives the user control over the worst-case scenario for the number of false detections by the beamformer. Simulated data are used to quantify the performance of the subspace estimator according to the distance between estimated and true signal subspaces. Beamforming resolution using the proposed method is analyzed with simulated data corresponding to a horizontal line array, as well as experimental data from the Shallow Water Array Performance experiment.
Nobel for antimalarial drug highlights East-West divide
Authors: Normile Dennis
Published: October 2015

Traditional Chinese medicine's vast cornucopia has produced many claims, few bona fide drugs.
Buzz food
Authors: Kupferschmidt Kai
Published: October 2015

Feeding insect meal to livestock could help the planet, but will it be good for people?
CO
2
capture from humid flue gases and humid atmosphere using a microporous coppersilicate
Authors: Datta Shuvo Jit , Khumnoon Chutharat , Lee Zhen Hao , Moon Won Kyung , Docao Son , Nguyen Thanh Huu , Hwang In Chul , Moon Dohyun , Oleynikov Peter , Terasaki Osamu , Yoon Kyung Byung
Published: October 2015

Grabbing CO
2
from wet gas streams

It is a challenge to extract CO
2
from typical gas streams, such as the flue gas from a power plant. This is because any water in the stream tends to prevent CO
2
absorption and may also degrade the absorbing material. Datta
et al.
developed a microporous copper silicate that avoids these problems. Most other materials have sites that absorb both water and CO
2
at the same sites, and in that fight, the water tends to win. Although their material still absorbs water, it has separate sites for the CO
2
absorption. It also shows good stability despite the absorbed water and can be reused.

Science
, this issue p.
302
The Atlantic Multidecadal Oscillation without a role for ocean circulation
Authors: Clement Amy , Bellomo Katinka , Murphy Lisa N. , Cane Mark A. , Mauritsen Thorsten , Rädel Gaby , Stevens Bjorn
Published: October 2015

Ocean circulation changes not needed

What causes the pattern of sea surface temperature change that is seen in the North Atlantic Ocean? This naturally occurring quasi-cyclical variation, known as the Atlantic Multidecadal Oscillation (AMO), affects weather and climate. Some have suggested that the AMO is a consequence of variable large-scale ocean circulation. Clement
et al.
suggest otherwise. They find that the pattern of AMO variability can be produced in a model that does not include ocean circulation changes, but only the effects of changes in air temperatures and winds.

Science
, this issue p.
320
Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2
Authors: Jiao Lianying , Liu Xin
Published: October 2015

A tripartite gene silencing complex

The formation of specialized cell types during development involves the silencing of genes not required in those cell types. An important player in this silencing process is the polycomb repressive complex 2 (PRC2), which methylates histone H3 on lysine residue 27 (H3K27me). Jiao and Liu determined the x-ray crystal structure of a functional PRC2 complex from a thermophilic yeast species (see the Perspective by Schapira). The intimate association of the three subunits confers stability to PRC2. The structure also reveals how the reaction product, H3K27me, stimulates PRC2 allosterically and how a cancer-associated histone mutation blocks the PRC2 active site.

Science
, this issue p.
10.1126/science.aac4383
; see also p.
278
Suboptimization of developmental enhancers
Authors: Farley Emma K. , Olson Katrina M. , Zhang Wei , Brandt Alexander J. , Rokhsar Daniel S. , Levine Michael S.
Published: October 2015

For gene enhancers, less is more

Weak enhancer sequences provide just the right amount of gene activity. Farley
et al.
systematically examined millions of synthetic variants of the Otx enhancer, a motif needed for gene expression in the nervous system of the sea squirt Ciona. Proper gene activity resulted when there were imperfect matches to the motif showing strongest enhancer binding and gene activation. When “optimal” motifs were incorporated, ectopic expression ensued, with aberrant gene activation outside the nervous system.

Science
, this issue p.
325
Concise total synthesis of glucosepane
Authors: Draghici Cristian , Wang Tina , Spiegel David A.
Published: October 2015

Getting a handle on a cross-linking motif

Although protein backbones consist exclusively of amino acids, various other molecules in the cell often get latched on afterward in a process termed posttranslational modification. In one such motif, called glucosepane, the side chains of lysine and arginine form a condensed cross-link through a reaction sequence with glucose. Formation of this cross-link is of interest in diabetes research. Draghici
et al.
now report a chemical synthesis of glucosepane outside the broader environment of a surrounding protein (see the Perspective by Boger). This synthesis should facilitate more precise characterization of the structure and function of the motif in vivo.

Science
, this issue p.
294
; see also p.
275
Pumping up the quantum
Authors: Cleland Andrew N.
Published: October 2015

A superconducting amplifier is used to boost quantum signals

[Also see Report by

Macklin
et al.

]
Restoring the sense of touch
Authors: Anikeeva Polina , Koppes Ryan A.
Published: October 2015

Flexible circuitry mimics the way skin transduces pressure signals

[Also see Report by

Tee
et al.

]
Personalization in practice
Authors: Iyengar Ravi , Altman Russ B. , Troyanskya Olga , FitzGerald Garret A.
Published: October 2015

Dynamic computational modeling integrated with experimentation can enable precision medicine
Violence and women's health
Authors: Adler Nancy E. , Johnson Paula A.
Published: October 2015

Last month, the Association of American Universities' Campus Climate Survey provided a disturbing picture of the extent of sexual assault on campuses in the United States. Almost a quarter of female graduates surveyed from 27 institutions indicated having experienced sexual assault during their undergraduate period. Distressingly, violence on campuses is part of a larger epidemic of sexual violence in the United States, making it a major women's issue. The widespread prevalence of exposure to violence and its immediate harm and long-term health consequences argue for greater efforts in both research and treatment.
Sequence Variation in Amplification Target Genes and Standards Influences Interlaboratory Comparison of BK Virus DNA Load Measurement
Authors: Solis Morgane , Meddeb Mariam , Sueur Charlotte , Domingo-Calap Pilar , Soulier Eric , Chabaud Angeline , Perrin Peggy , Moulin Bruno , Bahram Seiamak , Stoll-Keller Françoise , Caillard Sophie , Barth Heidi , Fafi-Kremer Samira
Published: October 2015

International guidelines define a BK virus (BKV) load of ≥4 log
10
copies/ml as presumptive of BKV-associated nephropathy (BKVN) and a cutoff for therapeutic intervention. To investigate whether BKV DNA loads (BKVL) are comparable between laboratories, 2 panels of 15 and 8 clinical specimens (urine, whole blood, and plasma) harboring different BKV genotypes were distributed to 20 and 27 French hospital centers in 2013 and 2014, respectively. Although 68% of the reported results fell within the acceptable range of the expected result ±0.5 log
10
, the interlaboratory variation ranged from 1.32 to 5.55 log
10
. Polymorphisms specific to BKV genotypes II and IV, namely, the number and position of mutations in amplification target genes and/or deletion in standards, arose as major sources of interlaboratory disagreements. The diversity of DNA purification methods also contributed to the interlaboratory variability, in particular for urine samples. Our data strongly suggest that (i) commercial external quality controls for BKVL assessment should include all major BKV genotypes to allow a correct evaluation of BKV assays, and (ii) the BKV sequence of commercial standards should be provided to users to verify the absence of mismatches with the primers and probes of their BKV assays. Finally, the optimization of primer and probe design and standardization of DNA extraction methods may substantially decrease interlaboratory variability and allow interinstitutional studies to define a universal cutoff for presumptive BKVN and, ultimately, ensure adequate patient care.
Standardization of Operator-Dependent Variables Affecting Precision and Accuracy of the Disk Diffusion Method for Antibiotic Susceptibility Testing
Authors: Hombach Michael , Maurer Florian P. , Pfiffner Tamara , Böttger Erik C. , Furrer Reinhard
Published: October 2015

Parameters like zone reading, inoculum density, and plate streaking influence the precision and accuracy of disk diffusion antibiotic susceptibility testing (AST). While improved reading precision has been demonstrated using automated imaging systems, standardization of the inoculum and of plate streaking have not been systematically investigated yet. This study analyzed whether photometrically controlled inoculum preparation and/or automated inoculation could further improve the standardization of disk diffusion. Suspensions of
Escherichia coli
ATCC 25922 and
Staphylococcus aureus
ATCC 29213 of 0.5 McFarland standard were prepared by 10 operators using both visual comparison to turbidity standards and a Densichek photometer (bioMérieux), and the resulting CFU counts were determined. Furthermore, eight experienced operators each inoculated 10 Mueller-Hinton agar plates using a single 0.5 McFarland standard bacterial suspension of
E. coli
ATCC 25922 using regular cotton swabs, dry flocked swabs (Copan, Brescia, Italy), or an automated streaking device (BD-Kiestra, Drachten, Netherlands). The mean CFU counts obtained from 0.5 McFarland standard
E. coli
ATCC 25922 suspensions were significantly different for suspensions prepared by eye and by Densichek (
P
< 0.001). Preparation by eye resulted in counts that were closer to the CLSI/EUCAST target of 10
8
CFU/ml than those resulting from Densichek preparation. No significant differences in the standard deviations of the CFU counts were observed. The interoperator differences in standard deviations when dry flocked swabs were used decreased significantly compared to the differences when regular cotton swabs were used, whereas the mean of the standard deviations of all operators together was not significantly altered. In contrast, automated streaking significantly reduced both interoperator differences, i.e., the individual standard deviations, compared to the standard deviations for the manual method, and the mean of the standard deviations of all operators together, i.e., total methodological variation.
Proton Channel Activity of Influenza A Virus Matrix Protein 2 Contributes to Autophagy Arrest
Authors: Ren Yizhong , Li Chufang , Feng Liqiang , Pan Weiqi , Li Liang , Wang Qian , Li Jiashun , Li Na , Han Ling , Zheng Xuehua , Niu Xuefeng , Sun Caijun , Chen Ling
Published: October 2015

Influenza A virus infection can arrest autophagy, as evidenced by autophagosome accumulation in infected cells. Here, we report that this autophagosome accumulation can be inhibited by amantadine, an antiviral proton channel inhibitor, in amantadine-sensitive virus infected cells or cells expressing influenza A virus matrix protein 2 (M2). Thus, M2 proton channel activity plays a role in blocking the fusion of autophagosomes with lysosomes, which might be a key mechanism for arresting autophagy.
The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus
Authors: Ng Wy Ching , Londrigan Sarah L. , Nasr Najla , Cunningham Anthony L. , Turville Stuart , Brooks Andrew G. , Reading Patrick C.
Published: October 2015

It is well established that influenza A virus (IAV) attachment to and infection of epithelial cells is dependent on sialic acid (SIA) at the cell surface, although the specific receptors that mediate IAV entry have not been defined and multiple receptors may exist. Lec2 Chinese hamster ovary (CHO) cells are SIA deficient and resistant to IAV infection. Here we demonstrate that the expression of the C-type lectin receptor langerin in Lec2 cells (Lec2-Lg) rendered them permissive to IAV infection, as measured by replication of the viral genome, transcription of viral mRNA, and synthesis of viral proteins. Unlike SIA-dependent infection of parental CHO cells, IAV attachment and infection of Lec2-Lg cells was mediated via lectin-mediated recognition of mannose-rich glycans expressed by the viral hemagglutinin glycoprotein. Lec2 cells expressing endocytosis-defective langerin bound IAV efficiently but remained resistant to IAV infection, confirming that internalization via langerin was essential for infectious entry. Langerin-mediated infection of Lec2-Lg cells was pH and dynamin dependent, occurred via clathrin- and caveolin-mediated endocytic pathways, and utilized early (Rab5
+
) but not late (Rab7
+
) endosomes. This study is the first to demonstrate that langerin represents an authentic receptor that binds and internalizes IAV to facilitate infection. Moreover, it describes a unique experimental system to probe specific pathways and compartments involved in infectious entry following recognition of IAV by a single cell surface receptor.

IMPORTANCE
On the surface of host cells, sialic acid (SIA) functions as the major attachment factor for influenza A viruses (IAV). However, few studies have identified specific transmembrane receptors that bind and internalize IAV to facilitate infection. Here we identify human langerin as a transmembrane glycoprotein that can act as an attachment factor and a
bone fide
endocytic receptor for IAV infection. Expression of langerin by an SIA-deficient cell line resistant to IAV rendered cells permissive to infection. As langerin represented the sole receptor for IAV infection in this system, we have defined the pathways and compartments involved in infectious entry of IAV into cells following recognition by langerin.
Identification of
MEF2B
,
EBF1
, and
IL6R
as Direct Gene Targets of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Critical for EBV-Infected B-Lymphocyte Survival
Authors: Tempera Italo , De Leo Alessandra , Kossenkov Andrew V. , Cesaroni Matteo , Song Hui , Dawany Noor , Showe Louise , Lu Fang , Wikramasinghe Priyankara , Lieberman Paul M.
Published: October 2015

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the EBV-encoded nuclear antigen and sequence-specific DNA binding protein required for viral origin binding and episome maintenance during latency. EBNA1 can also bind to numerous sites in the cellular genome and can provide a host cell survival function, but it is not yet known how EBNA1 sequence-specific binding is responsible for host cell survival. Here, we integrate EBNA1 chromatin immunoprecipitation sequencing (ChIP-Seq) with transcriptome sequencing (RNA-Seq) after EBNA1 depletion to identify cellular genes directly regulated by EBNA1 that are also essential for B-cell survival. We first compared EBNA1 ChIP-Seq patterns in four different EBV-positive cell types, including Burkitt lymphoma (BL) cells, nasopharyngeal carcinoma (NPC) cells, and lymphoblastoid cell lines (LCLs). EBNA1 binds to ∼1,000 sites that are mostly invariant among cell types and share a consensus recognition motif. We found that a large subset of EBNA1 binding sites are located proximal to transcription start sites and correlate genome-wide with transcription activity. EBNA1 bound to genes of high significance for B-cell growth and function, including
MEF2B
,
IL6R
, and
EBF1
. EBNA1 depletion from latently infected LCLs results in the loss of cell proliferation and the loss of gene expression for some EBNA1-bound genes, including
MEF2B
,
EBF1
, and
IL6R
. Depletion of MEF2B, EBF1, or IL6R partially phenocopies EBNA1 depletion by decreasing the cell growth and viability of cells latently infected with EBV. These findings suggest that EBNA1 binds to a large cohort of cellular genes important for cell viability and implicates EBNA1 as a critical regulator of transcription of host cell genes important for enhanced survival of latently infected cells.

IMPORTANCE
Epstein-Barr virus (EBV) latent infection is responsible for a variety of lymphoid and epithelial cell malignancies. EBNA1 is the EBV-encoded nuclear antigen that is consistently expressed in all EBV-associated cancers. EBNA1 is known to provide a host cell survival function, but the mechanism is not known. EBNA1 is a sequence-specific binding protein important for viral genome maintenance during latency. Here, by integrating ChIP-Seq and RNA-Seq, we demonstrate that EBNA1 binds directly to the promoter regulatory regions and upregulates the transcription of host genes that are important for the survival of EBV-infected cells. Identification of EBNA1 target genes provides potential new targets for therapeutic intervention in EBV-associated disease.
Comparative
In Vitro
and
In Vivo
Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8]
Authors: Shao Lulu , Fischer David D. , Kandasamy Sukumar , Rauf Abdul , Langel Stephanie N. , Wentworth David E. , Stucker Karla M. , Halpin Rebecca A. , Lam Ham Ching , Marthaler Douglas , Saif Linda J. , Vlasova Anastasia N.
Published: October 2015

The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes.

IMPORTANCE
The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will contribute to the development of new surveillance and prevention tools. Additionally, studies of cross-protection between the newly identified emerging G9 porcine RV strains and a human G1 RV vaccine strain in a susceptible host (swine) will allow evaluation of G9 strains as potential novel vaccine candidates to be included in porcine or human vaccines.
Benign pneumatosis intestinalis after bilateral lung transplantation
Authors: Ling Florence Y , Zafar Abdul Mueed , Angel Luis F , Mumbower Amy L
Published: October 2015

This series details two cases of benign pneumatosis intestinalis (PI) in patients post-lung transplant, which were discovered incidentally on routine surveillance chest radiographs during ambulatory clinic visits. Both patients had uneventful post-transplant recovery and were asymptomatic at presentation. The patients were admitted for observation. Contrast-enhanced abdominal CT scans confirmed the plain film findings. Both cases were managed conservatively with bowel rest, intravenous hydration and serial abdominal examinations. The patients had unremarkable hospital courses and were both discharged in good condition. Our current understanding of benign PI in patients post-transplant is limited to a few case series and case reports. Greater awareness of this entity may decrease unnecessary invasive procedures and improve management of these patients.
Recurrent spontaneous subcutaneous emphysema in a patient with rheumatoid arthritis
Authors: Adelowo Olufemi , Akintayo Richard Oluyinka , Olaosebikan Hakeem , Oba Rasheedat
Published: October 2015

Pulmonary air leak syndromes are extremely rare complications of systemic autoimmune connective tissue diseases and the occurrence of spontaneous subcutaneous emphysema (SSE) from pulmonary leak in the absence of pneumothorax or pneumomediastinum is even rarer. We report a case of recurrent SSE in a patient with rheumatoid arthritis and interstitial lung disease. The SSE was managed conservatively each time and it resorbed over several days. There has been no previous documented report of SSE in the absence of pneumomediastinum, pneumothorax or pulmonary nodules in a patient with RA.
Differing perceptions of safety culture across job roles in the ambulatory setting: analysis of the AHRQ Medical Office Survey on Patient Safety Culture
Authors: Hickner John , Smith Scott A , Yount Naomi , Sorra Joann
Published: October 2015

Background

Experts in patient safety stress the importance of a shared culture of safety. Lack of consensus may be detrimental to patient safety. This study examines differences in patient safety culture perceptions among providers, management and staff in a large national survey of safety culture in ambulatory practices in the USA.

Methods

The US Agency for Healthcare Research and Quality Medical Office Survey on Patient Safety Culture (SOPS) assesses perceptions about patient safety issues and event reporting in medical offices (ie, ambulatory practices). Using the 2014 data, we analysed responses from medical offices with at least five respondents. We calculated differences in perceptions of patient safety culture across six job positions (physicians, management, nurse practitioners (NPs)/physician assistants (PAs), nurses, clinical support staff and administrative/clerical staff) for 10 survey composites, the average of the 10 composites and an overall patient safety rating using multivariate hierarchical linear regressions.

Results

We analysed data from 828 medical offices with responses from 15 523 providers and staff, with an average 20 completed surveys per medical office (range: 5–367) and an average medical office response rate of 65% (range: 3%–100%). Management had significantly more positive patient safety culture perceptions on nine of 10 composite scores compared with all other job positions, including physicians. The composite that showed the largest difference was Communication Openness; Management (85% positive) was 22% points more positive than other clinical and support staff and administrative/clerical staff. Physicians were significantly more positive than PAs/NPs, nursing staff, other clinical and support staff and administrative/clerical staff on four composites: Communication About Error, Communication Openness, Staff Training and Teamwork, ranging from 3% to 20% points more positive.

Conclusions

These findings suggest that managers need to pay attention to the training needs of office staff, since this was an area with one of the greatest gaps in perceptions. In addition, both office managers and physicians need to encourage more open communication. As medical offices innovate to improve value, efficiency and patient-centred care, it is important that they continue to foster shared perceptions about what organisational members need, understanding that those perceptions may differ systematically by job position.
Traditional serrated adenomas of the upper digestive tract
Authors: Rubio CA
Published: October 2015

For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma–carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract.
Detection of Epstein–Barr virus in different sources of materials from patients with oral lichen planus: a case–control study
Authors: Vieira Rúbia da Rocha , Ferreira Lígia Lavezo , Biasoli Éder Ricardo , Bernabé Daniel Galera , Nunes Cáris Maroni , Miyahara Glauco Issamu
Published: October 2015

Aims

To detect the presence of Epstein–Barr virus (EBV) DNA in different sources of materials from a matched group of patients with oral lichen planus (OLP) and a group of people without OLP lesions, and to correlate the presence of virus with epidemiological variables of the groups studied.

Methods

Fresh tissue samples, saliva, exfoliated cells and plasma of 24 patients with OLP lesions (cases) and 17 patients without OLP lesions (controls) were collected. EBV was detected by nested PCR.

Results

Viral positivity was obtained in 62.5% of tissue samples; in 70.8% of exfoliated cell samples; in 33.3% of blood plasma samples and in 75% of saliva samples in the cases; and in 35.3% of tissue samples; 82.4% of exfoliated cell samples; in 47.1% of blood plasma samples and in 64.7% of saliva samples in the controls. There was a predominance of women in both groups. Variables not atrophic-erosive were most affected by EBV.

Conclusions

No relationship between EBV and OLP was found. However, all sources tested in this study were considered suitable for the detection of viruses.
Smoluchowski aggregation–fragmentation equations: Fast numerical method to find steady-state solutions
Authors: Stadnichuk Vladimir , Bodrova Anna , Brilliantov Nikolai
Published: October 2015

In this paper, we propose an efficient and fast numerical method of finding a stationary solution of large systems of aggregation–fragmentation equations of Smoluchowski type for concentrations of reacting particles. This method is applicable when the stationary concentrations steeply decrease with increasing aggregate size, which is fulfilled for the most important cases. We show that under rather mild restrictions, imposed on the kernel of the Smoluchowski equation, the following numerical procedure may be used: First, a complete solution for a relatively small number of equations (a “seed system”) is generated and then the result is exploited in a fast iterative scheme. In this way the new approach allows to obtain a steady-state solution for rather large systems of equations, by orders of magnitude faster than the standard schemes.
Influence of spin polarizability on liquid gas phase transition in the nuclear matter
Authors: Rezaei Z. , Bigdeli M. , Bordbar G. H.
Published: October 2015

In this paper, we investigate the liquid gas phase transition for the spin polarized nuclear matter. Applying the lowest order constrained variational (LOCV) method, and using two microscopic potentials, AV18 and UV14+TNI, we calculate the free energy, equation of state (EOS), order parameter, entropy, heat capacity and compressibility to derive the critical properties of spin polarized nuclear matter. Our results indicate that for the spin polarized nuclear matter, the second-order phase transition takes place at lower temperatures with respect to the unpolarized one. It is also shown that the critical temperature of our spin polarized nuclear matter with a specific value of spin polarization parameter is in good agreement with the experimental result.
A Stochastic Description on Adhesion of Molecular Bond Clusters Between Rigid Media with Curved Interfaces
Authors: Wang Jizeng , Huang Qiangzeng
Published: October 2015

Cellular adhesion is mediated by the formation and rupture of specific molecular bonds between ligands and receptors. As an idealized model, based on the Markov process assumption, we present a detailed theoretical analysis of the stochastic dynamics of a cluster of parallel bonds between two rigid bodies with curved interfaces under displacement- and force-controlled loadings, respectively. Regarding the equilibrium cluster size, strength, bond distribution and life time, exact solutions from the corresponding one-step master equations are obtained for the special cases of clusters with fixed separations or clusters with flat interfaces, while the general cases of those with curved interfaces are dealt with numerical techniques. Especially, Monte Carlo simulations are performed to verify the proposed analytical results and to demonstrate interesting differences between stochastic adhesion behaviors of the clusters under loading protocols of fixed separations and fixed forces, respectively.
The contribution of Sir Arthur Smith Woodward to the palaeoichthyology of Brazil – Smith Woodward's types from Brazil
Authors: Brito Paulo M. , Richter Martha
Published: October 2015

Sir Arthur Smith Woodward published many scientific works on fossil fishes from Brazil, among them the description of 14 new species and the redefinition of two lectotypes. This paper provides an illustrated, taxonomic update on the following taxa, together with comments on their repository and other relevant remarks:
Lissodus nitidus
(Woodward, 1888),
Rhinoptera prisca
Woodward, 1907, ‘
Lepidotes
’
mawsoni
Woodward, 1888, ‘
Lepidotes
’
souzai
Woodward, 1908
a
,
Calamopleurus mawsoni
(Woodward, 1902), ‘
Belonostomus
’
carinatus
Mawson & Woodward, 1907,
Paleopiquitinga brasiliensis
(Woodward, 1939),
Lignobrycon ligniticus
(Woodward, 1898),
Brycon avus
(Woodward, 1898),
Steindachneridion iheringi
(Woodward, 1898),
Scombroclupeoides scutata
(Woodward, 1908
a
),
Macracara prisca
Woodward, 1939,
Mawsonia gigas
Woodward, 1907,
Mawsonia minor
Woodward, 1908
a
;
Vinctifer comptoni
(Agassiz, 1841) and
Notelops brama
(Agassiz, 1841).
Aging augments renal vasoconstrictor response to orthostatic stress in humans
Authors: Clark Christine M. , Monahan Kevin D. , Drew Rachel C.
Published: October 2015

The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP. However, how healthy aging affects the renal vasoconstrictor response to LBNP is unknown. Therefore, 10 young (25 ± 1 yr; means ± SE) and 10 older (66 ± 2 yr) subjects underwent graded LBNP (−15 and −30 mmHg) while beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), arterial BP (Finometer), and heart rate (HR; electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as mean BP/RBFV. All baseline cardiovascular variables were similar between groups, except diastolic BP was higher in older subjects ( P < 0.05). Increases in RVR during LBNP were greater in the older group compared with the young group (older: −15 mmHg Δ10 ± 3%, −30 mmHg Δ20 ± 5%; young: −15 mmHg Δ2 ± 2%, −30 mmHg Δ6 ± 2%; P < 0.05). RBFV tended to decrease more ( P = 0.10) and mean BP tended to decrease less ( P = 0.09) during LBNP in the older group compared with the young group. Systolic and diastolic BP, pulse pressure, and HR responses to LBNP were similar between groups. These findings suggest that aging augments the renal vasoconstrictor response to orthostatic stress in humans.
Hypothalamic fatty acid sensing in Senegalese sole (Solea senegalensis): response to long-chain saturated, monounsaturated, and polyunsaturated (n-3) fatty acids
Authors: Conde-Sieira Marta , Bonacic Kruno , Velasco Cristina , Valente Luisa M. P. , Morais Sofia , Soengas José L.
Published: October 2015

We assessed the presence of fatty acid (FA)-sensing mechanisms in hypothalamus of Senegalese sole ( Solea senegalensis) and investigated their sensitivity to FA chain length and/or level of unsaturation. Stearate (SA, saturated FA), oleate (OA, monounsaturated FA of the same chain length), α-linolenate [ALA, a n-3 polyunsaturated fatty acid (PUFA) of the same chain length], and eicosapentanoate (EPA, a n-3 PUFA of a larger chain length) were injected intraperitoneally. Parameters related to FA sensing and neuropeptide expression in the hypothalamus were assessed after 3 h and changes in accumulated food intake after 4, 24, and 48 h. Three FA sensing systems characterized in rainbow trout were also found in Senegalese sole and were activated by OA in a way similar to that previously characterized in rainbow trout and mammals. These hypothalamic FA sensing systems were also activated by ALA, differing from mammals, where n-3 PUFAs do not seem to activate FA sensors. This might suggest additional roles and highlights the importance of n-3 PUFA in fish diets, especially in marine species. The activation of FA sensing seems to be partially dependent on acyl chain length and degree of saturation, as no major changes were observed after treating fish with SA or EPA. The activation of FA sensing systems by OA and ALA, but not SA or EPA, is further reflected in the expression of hypothalamic neuropeptides involved in the control of food intake. Both OA and ALA enhanced anorexigenic capacity compatible with the activation of FA sensing systems.