bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Shiga Toxin-Negative Escherichia coli O157:H7 Enteropathogenic or Enterohemorrhagic Escherichia coli? Comprehensive Molecular Analysis Using Whole-Genome Sequencing
Authors: Ferdous Mithila , Zhou Kai , Mellmann Alexander , Morabito Stefano , Croughs Peter D. , de Boer Richard F. , Kooistra-Smid Anna M. D. , Rossen John W. A. , Friedrich Alexander W.
Published: August 2015

The ability of
Escherichia coli
O157:H7 to induce cellular damage leading to disease in humans is related to numerous virulence factors, most notably the
stx
gene, encoding Shiga toxin (Stx) and carried by a bacteriophage. Loss of the Stx-encoding bacteriophage may occur during infection or culturing of the strain. Here, we collected
stx
-positive and
stx
-negative variants of
E. coli
O157:H7/NM (nonmotile) isolates from patients with gastrointestinal complaints. Isolates were characterized by whole-genome sequencing (WGS), and their virulence properties and phylogenetic relationship were determined. Because of the presence of the
eae
gene but lack of the
bfpA
gene, the
stx
-negative isolates were considered atypical enteropathogenic
E. coli
(aEPEC). However, they had phenotypic characteristics similar to those of the Shiga toxin-producing
E. coli
(STEC) isolates and belonged to the same sequence type, ST11. Furthermore, EPEC and STEC isolates shared similar virulence genes, the locus of enterocyte effacement region, and plasmids. Core genome phylogenetic analysis using a gene-by-gene typing approach showed that the sorbitol-fermenting (SF)
stx
-negative isolates clustered together with an SF STEC isolate and that one non-sorbitol-fermenting (NSF)
stx
-negative isolate clustered together with NSF STEC isolates. Therefore, these
stx
-negative isolates were thought either to have lost the Stx phage or to be a progenitor of STEC O157:H7/NM. As detection of STEC infections is often based solely on the identification of the presence of
stx
genes, these may be misdiagnosed in routine laboratories. Therefore, an improved diagnostic approach is required to manage identification, strategies for treatment, and prevention of transmission of these potentially pathogenic strains.
Inactivation of the Human Cytomegalovirus
US20
Gene Hampers Productive Viral Replication in Endothelial Cells
Authors: Cavaletto Noemi , Luganini Anna , Gribaudo Giorgio
Published: August 2015

The human cytomegalovirus (HCMV)
US12
gene family includes a group of 10 contiguous genes (
US12
to
US21
) encoding predicted seven-transmembrane-domain (7TMD) proteins that are nonessential for replication within cultured fibroblasts. Nevertheless, inactivation of some
US12
family members affects virus replication in other cell types; e.g., deletion of
US16
or
US18
abrogates virus growth in endothelial and epithelial cells or in human gingival tissue, respectively, suggesting a role for some US12 proteins in HCMV cell tropism. Here, we provide evidence that another member,
US20
, impacts the ability of a clinical strain of HCMV to replicate in endothelial cells. Through the use of recombinant HCMV encoding tagged versions of the US20 protein, we investigated the expression pattern, localization, and topology of the US20-encoded protein (pUS20). We show that pUS20 is expressed as a partially glycosylated 7TMD protein which accumulates late in infection in endoplasmic reticulum-derived peripheral structures localized outside the cytoplasmic virus assembly compartment (cVAC). US20-deficient mutants generated in the TR clinical strain of HCMV exhibited major growth defects in different types of endothelial cells, whereas they replicated normally in fibroblasts and epithelial cells. While the attachment and entry phases in endothelial cells were not significantly affected by the absence of US20 protein, US20-null viruses failed to replicate viral DNA and express representative E and L mRNAs and proteins. Taken together, these results indicate that US20 sustains the HCMV replication cycle at a stage subsequent to entry but prior to E gene expression and viral DNA synthesis in endothelial cells.

IMPORTANCE
Human cytomegalovirus (HCMV) is a major pathogen in newborns and immunocompromised individuals. A hallmark of HCMV pathogenesis is its ability to productively replicate in an exceptionally broad range of target cells, including endothelial cells, which represent a key target for viral dissemination and replication in the host, and to contribute to both viral persistence and associated inflammation and vascular diseases. Replication in endothelial cells depends on the activities of a set of viral proteins that regulate different stages of the HCMV replication cycle in an endothelial cell type-specific manner and thereby act as determinants of viral tropism. Here, we report the requirement of a HCMV protein as a postentry tropism factor in endothelial cells. The identification and characterization of HCMV endotheliotropism-regulating proteins will advance our understanding of the molecular mechanisms of HCMV-related pathogenesis and help lead to the design of new antiviral strategies able to exploit these functions.
Viral Polymerase-Helicase Complexes Regulate Replication Fidelity To Overcome Intracellular Nucleotide Depletion
Authors: Stapleford Kenneth A. , Rozen-Gagnon Kathryn , Das Pratyush Kumar , Saul Sirle , Poirier Enzo Z. , Blanc Hervé , Vidalain Pierre-Olivier , Merits Andres , Vignuzzi Marco
Published: August 2015

To date, the majority of work on RNA virus replication fidelity has focused on the viral RNA polymerase, while the potential role of other viral replicase proteins in this process is poorly understood. Previous studies used resistance to broad-spectrum RNA mutagens, such as ribavirin, to identify polymerases with increased fidelity that avoid misincorporation of such base analogues. We identified a novel variant in the alphavirus viral helicase/protease, nonstructural protein 2 (nsP2) that operates in concert with the viral polymerase nsP4 to further alter replication complex fidelity, a functional linkage that was conserved among the alphavirus genus. Purified chikungunya virus nsP2 presented delayed helicase activity of the high-fidelity enzyme, and yet purified replication complexes manifested stronger RNA polymerization kinetics. Because mutagenic nucleoside analogs such as ribavirin also affect intracellular nucleotide pools, we addressed the link between nucleotide depletion and replication fidelity by using purine and pyrimidine biosynthesis inhibitors. High-fidelity viruses were more resistant to these conditions, and viral growth could be rescued by the addition of exogenous nucleosides, suggesting that mutagenesis by base analogues requires nucleotide pool depletion. This study describes a novel function for nsP2, highlighting the role of other components of the replication complex in regulating viral replication fidelity, and suggests that viruses can alter their replication complex fidelity to overcome intracellular nucleotide-depleting conditions.

IMPORTANCE
Previous studies using the RNA mutagen ribavirin to select for drug-resistant variants have highlighted the essential role of the viral RNA-dependent RNA polymerase in regulating replication fidelity. However, the role of other viral replicase components in replication fidelity has not been studied in detail. We identified here an RNA mutagen-resistant variant of the nsP2 helicase/protease that conferred increased fidelity and yet could not operate in the same manner as high-fidelity polymerases. We show that the alphavirus helicase is a key component of the fidelity-regulating machinery. Our data show that the RNA mutagenic activity of compounds such as ribavirin is coupled to and potentiated by nucleotide depletion and that RNA viruses can fine-tune their replication fidelity when faced with an intracellular environment depleted of nucleotides.
Positive Selection in CD8+T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages
Authors: Machkovech Heather M. , Bedford Trevor , Suchard Marc A. , Bloom Jesse D.
Published: August 2015

Numerous experimental studies have demonstrated that CD8+T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+T cells. Here we use a novel computational approach to test for selection in CD8+T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.

IMPORTANCEThere is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the “trunk” of the phylogenetic tree. Overall, our results show that CD8+T cells targeting nucleoprotein play an important role in shaping influenza virus evolution.
Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States
Authors: Rajão Daniela S. , Gauger Phillip C. , Anderson Tavis K. , Lewis Nicola S. , Abente Eugenio J. , Killian Mary Lea , Perez Daniel R. , Sutton Troy C. , Zhang Jianqiang , Vincent Amy L.
Published: August 2015

Human-like swine H3 influenza A viruses (IAV) were detected by the USDA surveillance system. We characterized two novel swine human-like H3N2 and H3N1 viruses with hemagglutinin (HA) genes similar to those in human seasonal H3 strains and internal genes closely related to those of 2009 H1N1 pandemic viruses. The H3N2 neuraminidase (NA) was of the contemporary human N2 lineage, while the H3N1 NA was of the classical swine N1 lineage. Both viruses were antigenically distant from swine H3 viruses that circulate in the United States and from swine vaccine strains and also showed antigenic drift from human seasonal H3N2 viruses. Their pathogenicity and transmission in pigs were compared to those of a human H3N2 virus with a common HA ancestry. Both swine human-like H3 viruses efficiently infected pigs and were transmitted to indirect contacts, whereas the human H3N2 virus did so much less efficiently. To evaluate the role of genes from the swine isolates in their pathogenesis, reverse genetics-generated reassortants between the swine human-like H3N1 virus and the seasonal human H3N2 virus were tested in pigs. The contribution of the gene segments to virulence was complex, with the swine HA and internal genes showing effects
in vivo
. The experimental infections indicate that these novel H3 viruses are virulent and can sustain onward transmission in pigs, and the naturally occurring mutations in the HA were associated with antigenic divergence from H3 IAV from humans and swine. Consequently, these viruses could have a significant impact on the swine industry if they were to cause more widespread outbreaks, and the potential risk of these emerging swine IAV to humans should be considered.

IMPORTANCE
Pigs are important hosts in the evolution of influenza A viruses (IAV). Human-to-swine transmissions of IAV have resulted in the circulation of reassortant viruses containing human-origin genes in pigs, greatly contributing to the diversity of IAV in swine worldwide. New human-like H3N2 and H3N1 viruses that contain a mix of human and swine gene segments were recently detected by the USDA surveillance system. The human-like viruses efficiently infected pigs and resulted in onward airborne transmission, likely due to the multiple changes identified between human and swine H3 viruses. The human-like swine viruses are distinct from contemporary U.S. H3 swine viruses and from the strains used in swine vaccines, which could have a significant impact on the swine industry due to a lack of population immunity. Additionally, public health experts should consider an appropriate assessment of the risk of these emerging swine H3 viruses for the human population.
Knockout of cGAS and STING Rescues Virus Infection of Plasmid DNA-Transfected Cells
Authors: Langereis Martijn A. , Rabouw Huib H. , Holwerda Melle , Visser Linda J. , van Kuppeveld Frank J. M.
Published: August 2015

It is well known that plasmid DNA transfection, prior to virus infection, negatively affects infection efficiency. Here, we show that cytosolic plasmid DNA activates the cGAS/STING signaling pathway, which ultimately leads to the induction of an antiviral state of the cells. Using a transient one-plasmid clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, we generated cGAS/STING-knockout cells and show that these cells can be infected after plasmid DNA transfection as efficiently as nontransfected cells.
Conflict-of-interest disclosure at medical journals in Japan: a nationwide survey of the practices of journal secretariats
Authors: Kojima Takako , Green Joseph , Barron J Patrick
Published: August 2015

Objectives

Medical journals in Japan generally have appropriate policies regarding disclosure of conflicts of interest (COI). However, COI management depends on the staff members of each journal's editorial secretariat. This study's objectives were to find out (A) whether COI disclosure and the journal's role in it are clearly understood by the journal’s secretariat staff, (B) how much experience the editorial secretariat has in actually handling issues related to disclosure and (C) what kind of help or support they need.

Setting and design

In January 2014, questionnaires were sent to the editorial secretariats of journal-publishing societies belonging to the Japanese Association of Medical Sciences (JAMS).

Participants

The response rate was 100%, and the respondents represented 121 journals published by the 118 JAMS member societies (at the time of the survey).

Primary and secondary outcome measures

Information was collected on the history of COI policies and on how those policies were implemented. At the end of the questionnaire, there was an open-ended call for comments.

Results

Compulsory COI disclosure began between 2010 and 2013 for 60.3% of the journals (73/121). Handling of COI issues was not uniform: 17.4% (21/121) of respondents do not pursue cases of dubious disclosure, and 47.9% (58/121) do not require COI disclosures from editorial board members. Very few of the editorial secretariats had clearly-stated consequences for violations of COI-disclosure policy (33/121, 27.3%), and only 28.9% offered COI education (35/121). Respondents’ comments indicated that uniform, easily-searchable guidance regarding COI policies and implementation would be welcome.

Conclusions

Although commitment is widespread, policy implementation is inconsistent and COI experience is lacking. Clear, easy-to-use guidelines are desired by many societies. The JAMS is to be commended for supporting this country-wide investigation; other countries and regions are encouraged to perform similar investigations to respond to needs regarding COI management.
Evaluation of an evidence based quality improvement innovation for patients with musculoskeletal low back pain in an accident and emergency setting
Authors: Potier Tara , Tims Emily , Kilbride Cherry , Rantell Khadija
Published: August 2015

We conducted a five stage pilot study which initially consisted of a review of 75 case notes of people attending an emergency department (ED) in an inner London Teaching Hospital with musculoskeletal (MSK) low back pain (LBP). This review highlighted inconsistencies in how they were assessed and managed across and within different staff groups. We found patient documentation was often incomplete and that a biomedical model approach to the management of these patients was common.

As a result, four further stages in the project were conducted. Our primary aim was to evaluate the impact of implementing a locally developed quality improvement intervention for the assessment and treatment of MSK LBP in this ED. Secondary aims were to explore the user experience of the new pathway, measured by the patient experience questionnaire (PEQ), and any associated health economic costs of changes in practice. The quality improvement intervention consisted of an evidence based low back pain pathway (EBLBPP), a staff educational program, and a patient education booklet.

We undertook a retrospective baseline audit of 100 clinical records of patients was undertaken prior to the instigation of the quality improvement intervention, and four months post implementation. The pre-defined variables of interest were: documentation of the case history, examination, classification of back pain (and if correct), prescribed management and if the documentation was compliant with medico-legal standards. All patients in the study were sent a PEQ to complete and return in a self-addressed envelope. Estimated health costs associated with each patient episode of care were calculated including re-attendance episodes for any people presenting with MSK LBP within a four week period.

There was a significant improvement in all areas evaluated post implementation in all groups (simple, referred and simple, referred and serious spinal pathology combined). In particular; screening for red flags (22%) and biopsychosocial factors (29%), as well as noting the prevalence of previous symptoms (44%), observation of the painful area (57%), and analysis classification (59%) at a at 95% confidence interval (CI). In terms of management, an increase in adherence to the analgesic ladder, patients receiving reassurance and appropriate referral back to their GP’s increased 45%, 23% and 44% at 95% CI respectively. Unfortunately, there was insufficient data to draw any meaningful conclusions from the patient experience data due to a low response rate.

In conclusion, the introduction of the EBLBPP, patient education leaflet and teaching training for staff involved in the treatment of MSK LBP patients has improved the quality and consistency of the documented assessment and subsequent management of MSK LBP patients.
Ventricular arrhythmia storm in the era of implantable cardioverter-defibrillator
Authors: Looi Khang-Li , Tang Anthony , Agarwal Sharad
Published: August 2015

In the era of widespread use of implantable cardioverter-defibrillators (ICDs) for both primary and secondary prevention of sudden cardiac death, a significant proportion of patients experience episodes of multiple ventricular tachycardia/fibrillation over a short period of time requiring device interventions. The episodes are termed ventricular arrhythmia (VA) or electrical storms. VA storm is a tragic experience for patients, with many psychological consequences. Current management for VA storms remains complex. Acutely, administration of β-blockers, amiodarone and sedation or intubation is generally required to suppress sympathetic tone. Interventional treatment includes catheter ablation and sympathetic blockade by left cardiac sympathetic denervation. Strategies to modify autonomic tone to suppress VAs are the rationale of various novel interventions that have been published in recent studies. All patients with VA storm should be considered for transfer to an experienced high-volume tertiary centre for evaluation and treatment to prevent further recurrence of VA storm.
Drying-induced shrinkage of Boom clay: an experimental investigation
Authors: Prime Noémie , Levasseur Séverine , Miny Laurent , Charlier Robert , Léonard Angélique , Collin Frédéric
Published: August 2015

Drying-induced shrinkage of geomaterials may have a strong effect on geostructure stability and deformation. The settlement of foundations and fracture openings in slopes, roads, and tunnel walls may be due to drying shrinkage. However, there is still a lack of knowledge concerning shrinkage evolution with time and shrinkage propagation within the material. In this study, the shrinkage of a specific clayey rock — Boom clay — under drying conditions is investigated experimentally. This rock is a deep geological formation, which is under study for high-level and long-term radioactive waste storage in Belgium. Two experimental campaigns are presented. The first, based on the vapour equilibrium drying technique and coupled with sample size manual measurement, aims to characterize the material shrinkage in balanced states. The second, based on the convective drying technique and coupled with shape monitoring using X-ray tomography, aims to analyse how shrinkage develops before reaching a steady state. Both approaches put in evidence the shrinkage anisotropy of this structurally bedded rock, with a ratio around 2 between the direction of maximum strains and the direction of minimum strains. However, the two drying techniques also provide complementary results as the relation between the amount of shrinkage and the retention curve (for uniform drying imposed with saline solutions) and the kinetics of shrinkage propagation inside the material (for nonuniform drying imposed with air convection).
Theoretical investigations of the g factors of orthorhombic Cu2+ site in oxycarbonate phase YBa2Cu2.95(CO3)0.35O6.6
Authors: Xu Yong-Qiang , Wu Shao-Yi , Zhang Zhi-Hong , Dong Hui-Ning
Published: August 2015

The [Formula: see text] factors of orthorhombic [Formula: see text] site in oxycarbonate phase [Formula: see text] are theoretically investigated using the perturbation formulas of the [Formula: see text] factors for an orthorhombically elongated [Formula: see text] cluster. This pseudo-octahedral [Formula: see text] center is formed by two apical oxygen ligands and four coplanar oxygen ions belonging to the respective four neighboring carbonate groups. The [Formula: see text] cluster is found to suffer the relative axial elongation of about 0.04 Å and the perpendicular bond length variation of about 0.12 Å due to the Jahn–Teller effect. The theoretical [Formula: see text] factors based on the local structural parameters show good agreement with the experimental data.
The low-energy quadrupole mode of nuclei
Authors: Frauendorf S.
Published: August 2015

The phenomenological classification of collective quadrupole excitations by means of the Bohr–Hamiltonian (BH) is reviewed with focus on signatures for triaxility. The variants of the microscopic BH derived by means of the Adiabatic Time-Dependent Mean Field theory from the Pairing-plus-quadrupole–quadrupole interaction, the Shell Correction Method, the Skyrme Energy Density Functional, the Relativistic Mean Field Theory and the Gogny interaction are discussed and applications to concrete nuclides reviewed. The Generator Coordinate Method for the five-dimensional quadrupole deformation space and first applications to triaxial nuclei are presented. The phenomenological classification in the framework of the Interacting Boson Model is discussed with a critical view on the boson number counting rule. The recent success in calculating the model parameters by mapping the mean field deformation energy surface on the bosonic one is discussed and the applications listed. A critical assessment of the models is given with focus on the limitations due to the adiabatic approximation. The Tidal Wave approach and the Triaxial Projected Shell Model are presented as practical approaches to calculate spectral properties outside the adiabatic region.
AN EPIDEMIOLOGICAL MODEL WITH MULTIPLE ENDEMIC STATES
Authors: VILLAVICENCIO-PULIDO GEISER , BARRADAS IGNACIO , BEATRIZ LUNA
Published: August 2015

We present a model describing the dynamics of an infectious disease for which the force of infection is diminished through a reaction of the susceptible to the number of infected individuals. We show that, even though the structure of the model is a simple one, different kinds of backward bifurcation can appear for values of the basic reproductive number bigger than one. Under some conditions on the parameters, multiple endemic equilibria may appear for values of the basic reproductive number less or greater than one.
A SIMPLE MODEL FOR CONTROL OF TUMOR CELLS
Authors: MARGARIT D. H. , ROMANELLI L.
Published: August 2015

The Kirschner-Panetta model describes the poblational competition between effector cells and tumor cells. We analize external changes in the parameters and mechanisms to obtain the decreasing of tumor cells. These variations were performed by three different ways: Oscillations, spikes with the natural frequency of the system, and spikes with Normal Distribution. It was observed that the amount of tumor cells decreases to zero if we change simultaneously the parameters properly.
A MATHEMATICAL MODEL FOR HUMAN AND ANIMAL LEPTOSPIROSIS
Authors: BACA-CARRASCO DAVID , OLMOS DANIEL , BARRADAS IGNACIO
Published: August 2015

In this paper, we propose a SI model for the study of human and animal leptospirosis. Unlike other models for leptospirosis which consider only rodents as infection vectors, we consider that humans can be infected not only through contact with rodents, but also through any other animal that serves as a reservoir for the bacteria, and through contact with bacteria that are free in the environment. We calculate the basic reproductive number for this model, which is given in terms of the basic reproductive numbers of simpler subsystems of the original model, and propose some intervention techniques for controlling the disease based on our results.
CONSEQUENCES OF MULTIPLE ALLEE EFFECT IN AN OPEN ACCESS FISHERY MODEL
Authors: GONZÁLEZ-OLIVARES EDUARDO , FLORES JOSÉ D.
Published: August 2015

This work deals with the dynamics of a bioeconomic continuous time model, where the combined action of the fishing effort exerted by men (as a predator) and multiple Allee effect or depensation on the growth rate of a self-regenerating resource (the prey) are considered.

It has been recently established that a depensation phenomenon appears by diverse causes and new functions have been proposed to describe multiple Allee effects. One of these formalizations is here incorporated in the well-known Smith's model, one of the simplest models to open access fisheries.

We prove that this new and complex expression is topologically equivalent to a simpler form. Then, we postulate that the parsimony principle must be used to describe this phenomenon.

It is also shown that in the phase plane of biomass-effort on the proposed model, the origin is an attractor equilibrium for all parameters values as a consequence of the Allee effect. Moreover, there is a subset of the parameter values, for which two limit cycles exist surrounding the unique positive equilibrium point of the system, one of them being asymptotically stable (the non damped oscillatory tragedy of the commons); hence, multiestability exists, particularly three-stability.
SEX DIFFERENCES IN FEED INTAKE, BEHAVIOR AND WEIGHT GAINED BY GREATER RHEAS (RHEA AMERICANA) IN CAPTIVITY DURING THE PRE-REPRODUCTIVE SEASON
Authors: SIMOY MARIA VERONICA , MILANO FERNANDO A. , MARINELLI CLAUDIA B. , FERNANDEZ GUSTAVO J. , CANZIANI GRACIELA A.
Published: August 2015

The use of common rhea, Rhea americana, as breeding bird requires knowledge of nutritional physiology. It is important the analysis jointly of feed intake, behavior and weight gain. Our objective was to determine and analyze differences in the feed intake, weight gained and behavior of captive subadults and adults male and female rheas during autumn and winter in the Humid Pampas, Argentina. Neither males nor females showed significant seasonal differences in the weights with which they initiated the trials. Daily feed consumption didn't show significant differences neither between seasons nor between sexes. However, we observed differences in weight gain by males between seasons and during the autumn trial, the weight gain was higher for males. Rhea behavior also varied seasonally. Males and females spent more time preening and resting than walking and feeding during autumn, the opposite occurred in winter. The males had a higher tendency towards walking than to feeding, the females showed the opposite in autumn. Analyzing the feed intake, weight gained and the time spent on feeding we hypothesized that males are more efficient for feeding. This analysis allowed us to observe there are nutritional issues that can be explained from a behavioral point of view.
QUASI-DETERMINISTIC POPULATION DYNAMICS IN STOCHASTIC COUPLED MAPS
Authors: GUTIERREZ JAVIER ARMANDO , APARICIO JUAN PABLO
Published: August 2015

We studied the stochastic dynamics of coupled map lattices for small local populations. Quasi-deterministic dynamics is lost when considering one isolated population or two populations linked by dispersal. In a one-dimensional ring linked by closest neighbors some intermittent synchronization is observed. Finally we show that in two-dimensional lattices long-term synchronization take place above a critical value of the dispersal probability and the system displays a quasi-deterministic dynamics.
An Industrial Application of Thermal Convection Analysis
Authors: Kanayama H.
Published: August 2015

A coupling analysis of thermal convection problems is performed in this work. By approximating the material derivative along the trajectory of fluid particle, the characteristic curve (CC) method can be considered. The most attractive advantage of this method is the symmetry of the linear system, which enables some classic symmetric linear iterative solvers, like the conjugate gradient (CG) method or the minimal residual (MINRES) method, to be used to solve the interface problem of the domain decomposition system. An application to industrial problems is demonstrated to show the effectiveness of our approach.
Soliton Kernels for Solving PDEs
Authors: Uddin Marjan , Jan H. U. , Ali Amjad , Shah I. A.
Published: August 2015

There are many important applications in the fields of computer experiments, response surface modeling, finance and image processing, where some special types of nonstandard kernels performed better than standard kernels. These kernels are more appropriate than standard kernels when looking at special solutions of partial differential equations (PDEs). For example some nonlinear time-dependent PDEs have soliton like solutions, so soliton kernels would more suit to approximate the solution. In this work, we recover the solution of equal width equation using soliton kernels.
Convergence Analysis of Discontinuous Finite Volume Methods for Elliptic Optimal Control Problems
Authors: Sandilya Ruchi , Kumar Sarvesh
Published: August 2015

In this paper, we discuss the convergence analysis of discontinuous finite volume methods applied to distribute the optimal control problems governed by a class of second-order linear elliptic equations. In order to approximate the control, two different methodologies are adopted: one is the method of variational discretization and second is piecewise constant discretization technique. For variational discretization method, optimal order of convergence in the [Formula: see text]-norm for state, adjoint state and control variables is derived. Moreover, optimal order of convergence in discrete [Formula: see text]-norm is also derived for state and adjoint state variables. Whereas, for piecewise constant approximation of control, first order convergence is derived for control, state and adjoint state variables in the [Formula: see text]-norm. In addition to that, optimal order of convergence in discrete [Formula: see text]-norm is derived for state and adjoint state variables. Also, some numerical experiments are conducted to support the derived theoretical convergence rate.
On the kinematic interpretation of timelike ruled surfaces
Authors: Önder Mehmet , Ekinci Zehra
Published: August 2015

Timelike ruled surfaces are studied in dual Lorentzian space [Formula: see text] by considering E. Study Mapping and Blaschke frame. A reference timelike ruled surface is considered and associated surfaces are defined. First, it is shown that the surface generated by the instantaneous screw axis (ISA) is a Mannheim offset of reference surface. Later, the kinematic interpretations between these surfaces are introduced by means of Blaschke invariants.
Risk of Falling in Older Women II
Authors: Armas Laura , Lappe Joan , Boyce Maureen , Byrne Mark , Inagaki Asia A. , Cheng Shih-Chuan , Malik Davender S. , Mordeson John N.
Published: August 2015

We examine the five methods for determining the degree of the risk of falling in older women. These five methods are the Analytic Hierarchy Process (AHP), the Guiasu method, the Yen method, the set-valued statistical method, and the Dempster–Shafer method. We consider the weight of importance of the experts involved. We show that the coefficients of the factors for the risk of falling for the AHP equation may be different than those determined by the weighted AHP method, but that they remain exactly the same for the Guiasu, Yen, and set-valued statistical methods. We also determine conditions under which the coefficients of the factors are the same for the weighted AHP, Guiasu, Yen, and set-valued statistical methods.
Risk for Carotid Intima–Medial Thickness in Recently Menopausal Women Enrolled in the Kronos Early Estrogen Prevention Study (KEEPS): Determination Using Fuzzy Logic
Authors: Mordeson John N. , Malik D. S. , Miller Virginia M. , Hunter Larry W. , Jayachandran Muthuvel , Shepherd Alex , Budney Sarah
Published: August 2015

Previously, the biological factors were weighed by the expert opinions. In this paper, we evaluate the risk factors proposed by the expert opinions. We use fuzzy logic techniques for predicting risk for development of carotid intima–medial thickness (CIMT) using expert opinion and various factors associated with CIMT in recently menopausal women. Study participants were enrolled in the Kronos Early Estrogen Prevention Study (KEEPS), a four-year study where participants were assigned to either oral or transdermal hormone treatments or to placebo. We use preference modeling techniques to determine the consensus winner of the causal factors. We use a measure to determine the degree to which one factor is preferred to another. We also determine the extent to which a factor is preferred to another by "most" experts. We determine the degree to which the experts agree. We consider a model concerning social networks and the effects of these networks on persons' opinions.
Deep proteomic profiling of vasopressin-sensitive collecting duct cells. I. Virtual Western blots and molecular weight distributions
Authors: Yang Chin-Rang , Tongyoo Pumipat , Emamian Milad , Sandoval Pablo C. , Raghuram Viswanathan , Knepper Mark A.
Published: August 2015

The mouse mpkCCD cell line is a continuous cultured epithelial cell line with characteristics of renal collecting duct principal cells. This line is widely used to study epithelial transport and its regulation. To provide a data resource useful for experimental design and interpretation in studies using mpkCCD cells, we have carried out “deep” proteomic profiling of these cells using three levels of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by tandem mass spectrometry to identify and quantify proteins. The analysis of all resulting samples generated 34.6 gigabytes of spectral data. As a result, we identified 6,766 proteins in mpkCCD cells at a high level of stringency. These proteins are expressed over eight orders of magnitude of protein abundance. The data are provided to users as a public data base ( https://helixweb.nih.gov/ESBL/Database/mpkFractions/ ). The mass spectrometry data were mapped back to their gel slices to generate “virtual Western blots” for each protein. For most of the 6,766 proteins, the apparent molecular weight from SDS-PAGE agreed closely with the calculated molecular weight. However, a substantial fraction (>15%) of proteins was found to run aberrantly, with much higher or much lower mobilities than predicted. These proteins were analyzed to identify mechanisms responsible for altered mobility on SDS-PAGE, including high or low isoelectric point, high or low hydrophobicity, physiological cleavage, residence in the lysosome, posttranslational modifications, and expression of alternative isoforms due to alternative exon usage. Additionally, this analysis identified a previously unrecognized isoform of aquaporin-2 with apparent molecular mass <20 kDa.
Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1
Authors: Chang Hui-Hua , Young Steven H. , Sinnett-Smith James , Chou Caroline Ei Ne , Moro Aune , Hertzer Kathleen M. , Hines Oscar Joe , Rozengurt Enrique , Eibl Guido
Published: August 2015

Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca2+-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca2+ response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca2+ signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects.
Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells
Authors: Srinivasan Padmanabhan , Nabokina Svetlana , Said Hamid M.
Published: August 2015

Thiamin is essential for normal metabolic activity of all mammalian cells, including those of the pancreas. Cells obtain thiamin from their surroundings and enzymatically convert it into thiamin pyrophosphate (TPP) in the cytoplasm; TPP is then taken up by mitochondria via a specific carrier the mitochondrial TPP transporter (MTPPT; product of the SLC25A19 gene). Chronic alcohol exposure negatively impacts the health of pancreatic acinar cells (PAC), but its effect on physiological/molecular parameters of MTPPT is not known. We addressed this issue using mouse pancreatic acinar tumor cell line 266-6 and primary PAC of wild-type and transgenic mice carrying the SLC25A19 promoter that were fed alcohol chronically. Chronic alcohol exposure of 266-6 cells (but not to its nonoxidative metabolites ethyl palmitate and ethyl oleate) led to a significant inhibition in mitochondrial TPP uptake, which was associated with a decreased expression of MTPPT protein, mRNA, and activity of the SLC25A19 promoter. Similarly, chronic alcohol feeding of mice led to a significant inhibition in expression of MTPPT protein, mRNA, heterogeneous nuclear RNA, as well as in activity of SLC25A19 promoter in PAC. While chronic alcohol exposure did not affect DNA methylation of the Slc25a19 promoter, a significant decrease in histone H3 euchromatin markers and an increase in H3 heterochromatin marker were observed. These findings show, for the first time, that chronic alcohol exposure negatively impacts pancreatic MTPPT, and that this effect is exerted, at least in part, at the level of Slc25a19 transcription and appears to involve epigenetic mechanism(s).
Effect of an acute increase in central blood volume on cerebral hemodynamics
Authors: Ogoh Shigehiko , Hirasawa Ai , Raven Peter B. , Rebuffat Thomas , Denise Pierre , Lericollais Romain , Sugawara Jun , Normand Hervé
Published: August 2015

Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (−26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate ( r = −0.888, P < 0.0001) and an increase in total vascular conductance ( r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight ( P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced ( P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance ( r = −0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.
Molecular mechanisms of ischemic preconditioning in the kidney
Authors: Kapitsinou Pinelopi P. , Haase Volker H.
Published: August 2015

More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review.
Interactions between target location and reward size modulate the rate of microsaccades in monkeys
Authors: Joshua Mati , Tokiyama Stefanie , Lisberger Stephen G.
Published: August 2015

We have studied how rewards modulate the occurrence of microsaccades by manipulating the size of an expected reward and the location of the cue that sets the expectations for future reward. We found an interaction between the size of the reward and the location of the cue. When monkeys fixated on a cue that signaled the size of future reward, the frequency of microsaccades was higher if the monkey expected a large vs. a small reward. When the cue was presented at a site in the visual field that was remote from the position of fixation, reward size had the opposite effect: the frequency of microsaccades was lower when the monkey was expecting a large reward. The strength of pursuit initiation also was affected by reward size and by the presence of microsaccades just before the onset of target motion. The gain of pursuit initiation increased with reward size and decreased when microsaccades occurred just before or after the onset of target motion. The effect of the reward size on pursuit initiation was much larger than any indirect effects reward might cause through modulation of the rate of microsaccades. We found only a weak relationship between microsaccade direction and the location of the exogenous cue relative to fixation position, even in experiments where the location of the cue indicated the direction of target motion. Our results indicate that the expectation of reward is a powerful modulator of the occurrence of microsaccades, perhaps through attentional mechanisms.
A positive feedback at the cellular level promotes robustness and modulation at the circuit level
Authors: Dethier Julie , Drion Guillaume , Franci Alessio , Sepulchre Rodolphe
Published: August 2015

This article highlights the role of a positive feedback gating mechanism at the cellular level in the robustness and modulation properties of rhythmic activities at the circuit level. The results are presented in the context of half-center oscillators, which are simple rhythmic circuits composed of two reciprocally connected inhibitory neuronal populations. Specifically, we focus on rhythms that rely on a particular excitability property, the postinhibitory rebound, an intrinsic cellular property that elicits transient membrane depolarization when released from hyperpolarization. Two distinct ionic currents can evoke this transient depolarization: a hyperpolarization-activated cation current and a low-threshold T-type calcium current. The presence of a slow activation is specific to the T-type calcium current and provides a slow positive feedback at the cellular level that is absent in the cation current. We show that this slow positive feedback is required to endow the network rhythm with physiological modulation and robustness properties. This study thereby identifies an essential cellular property to be retained at the network level in modeling network robustness and modulation.