bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Conserved PapB Family Member, TosR, Regulates Expression of the Uropathogenic Escherichia coli RTX Nonfimbrial Adhesin TosA while Conserved LuxR Family Members TosE and TosF Suppress Motility
Authors: Engstrom Michael D. , Alteri Christopher J. , Mobley Harry L. T. 
Published: June 2014

ABSTRACT

A heterogeneous subset of extraintestinal pathogenic
Escherichia coli
(ExPEC) strains, referred to as uropathogenic
E. coli
(UPEC), causes most uncomplicated urinary tract infections. However, no core set of virulence factors exists among UPEC strains. Instead, the focus of the analysis of urovirulence has shifted to studying broad classes of virulence factors and the interactions between them. For example, the RTX nonfimbrial adhesin TosA mediates adherence to host cells derived from the upper urinary tract. The associated
tos
operon is well expressed
in vivo
but poorly expressed
in vitro
and encodes TosCBD, a predicted type 1 secretion system. TosR and TosEF are PapB and LuxR family transcription factors, respectively; however, no role has been assigned to these potential regulators. Thus, the focus of this study was to determine how TosR and TosEF regulate
tosA
and affect the reciprocal expression of adhesins and flagella. Among a collection of sequenced UPEC strains, 32% (101/317) were found to encode TosA, and nearly all strains (91% [92/101]) simultaneously carried the putative regulatory genes. Deletion of
tosR
alleviates
tosA
repression. The
tos
promoter was localized upstream of
tosR
using transcriptional fusions of putative promoter regions with
lacZ
. TosR binds to this region, affecting a gel shift. A 100-bp fragment 220 to 319 bp upstream of
tosR
inhibits binding, suggesting localization of the TosR binding site. TosEF, on the other hand, downmodulate motility when overexpressed by preventing the expression of
fliC
, encoding flagellin. Deletion of
tosEF
increased motility. Thus, we present an additional example of the reciprocal control of adherence and motility.
AraC/XylS Family Stress Response Regulators Rob, SoxS, PliA, and OpiA in the Fire Blight Pathogen Erwinia amylovora
Authors: Pletzer Daniel , Schweizer Gabriel , Weingart Helge 
Published: June 2014

ABSTRACT

Transcriptional regulators of the AraC/XylS family have been associated with multidrug resistance, organic solvent tolerance, oxidative stress, and virulence in clinically relevant enterobacteria. In the present study, we identified four homologous AraC/XylS regulators, Rob, SoxS, PliA, and OpiA, from the fire blight pathogen
Erwinia amylovora
Ea1189. Previous studies have shown that the regulators MarA, Rob, and SoxS from
Escherichia coli
mediate multiple-antibiotic resistance, primarily by upregulating the AcrAB-TolC efflux system. However, none of the four AraC/XylS regulators from
E. amylovora
was able to induce a multidrug resistance phenotype in the plant pathogen. Overexpression of
rob
led to a 2-fold increased expression of the
acrA
gene. However, the
rob
-overexpressing strain showed increased resistance to only a limited number of antibiotics. Furthermore, Rob was able to induce tolerance to organic solvents in
E. amylovora
by mechanisms other than efflux. We demonstrated that SoxS from
E. amylovora
is involved in superoxide resistance. A
soxS
-deficient mutant of Ea1189 was not able to grow on agar plates supplemented with the superoxide-generating agent paraquat. Furthermore, expression of
soxS
was induced by redox cycling agents. We identified two novel members of the AraC/XylS family in
E. amylovora
. PliA was highly upregulated during the early infection phase in apple rootstock and immature pear fruits. Multiple compounds were able to induce the expression of
pliA
, including apple leaf extracts, phenolic compounds, redox cycling agents, heavy metals, and decanoate. OpiA was shown to play a role in the regulation of osmotic and alkaline pH stress responses.
What keeps family physicians busy in Portugal? A multicentre observational study of work other than direct patient contacts
Authors: Granja Mónica , Ponte Carla , Cavadas Luís Filipe 
Published: June 2014

ObjectivesTo quantify the time spent by family physicians (FP) on tasks other than direct patient contact, to evaluate job satisfaction, to analyse the association between time spent on tasks and physician characteristics, the association between the number of tasks performed and physician characteristics and the association between time spent on tasks and job satisfaction.DesignCross-sectional, using time-and-motion techniques. Two workdays were documented by direct observation. A significance level of 0.05 was adopted.SettingMulticentric in 104 Portuguese family practices.ParticipantsA convenience sample of FP, with lists of over 1000 patients, teaching senior medical students and first-year family medicine residents in 2012, was obtained. Of the 217 FP invited to participate, 155 completed the study.Main outcomes measuredTime spent on tasks other than direct patient contact and on the performance of more than one task simultaneously, the number of direct patient contacts in the office, the number of indirect patient contacts, job satisfaction, demographic and professional characteristics associated with time spent on tasks and the number of different tasks performed, and the association between time spent on tasks and job satisfaction.ResultsFP (n=155) spent a mean of 143.6 min/day (95% CI 135.2 to 152.0) performing tasks such as prescription refills, teaching, meetings, management and communication with other professionals (33.4% of their workload). FP with larger patient lists spent less time on these tasks (p=0.002). Older FP (p=0.021) and those with larger lists (p=0.011) performed fewer tasks. The mean job satisfaction score was 3.5 (out of 5). No association was found between job satisfaction and time spent on tasks.ConclusionsFP spent one-third of their workday in coordinating care, teaching and managing. Time devoted to these tasks decreases with increasing list size and physician age.
Hydro-chemical modelling of
in situ
behaviour of bituminized radioactive waste in Boom Clay
Authors: Mokni N. , Olivella S. , Valcke E. , Bleyen N. , Smets S. , Li X. , Sillen X. 
Published: June 2014

Abstract

The hydro-chemical (CH) interaction between swelling Eurobitum bituminized radioactive waste (BW) and Boom Clay was investigated to assess the feasibility of geological disposal for the long-term management of this waste. First, the long-term behaviour of BW in contact with water was studied. A CH formulation of chemically and hydraulically coupled flow processes in porous materials containing salt crystals is discussed. The formulation incorporates the strong dependence of the osmotic efficiency of the bitumen membrane on porosity and assumes the existence of high salt concentration gradients that are maintained for a long time and that influence the density and motion of the fluid. The impacts of temporal and spatial variations of key transport parameters (i.e. osmotic efficiency (σ), intrinsic permeability (
k
), diffusion, etc.) were investigated. Porosity was considered the basic variable. For BW porosity varies in time because of the water uptake and subsequent processes (i.e. dissolution of salt crystals, swelling of hydrating layers, compression of highly leached layers). New expressions of σ and
k
describing the dependence of these parameters on porosity are proposed. Several cases were analysed. The numerical analysis was proven to be able to furnish a satisfactory representation of the main observed patterns of the behaviour in terms of osmotic-induced swelling, leached mass of NaNO
3
and progression of the hydration front when heterogeneous porosity and crystal distributions have been assumed. Second, the long-term behaviour of real Eurobitum drums in disposal conditions, and in particular its interaction with the surrounding clay, was investigated. Results of a CH analysis are presented.
Coupled hydromechanical modelling of the mine-by experiment at Meuse-Haute-Marne underground rock laboratory France
Authors: Yildizdag K. , Shao H. , Hesser J. , Noiret A. , Soennke J. 
Published: June 2014

Abstract
At the Meuse-Haute-Marne underground rock laboratory, France, a mine-by experiment was performed in the niche GCS by ANDRA. A 3D coupled hydraulic and mechanical (HM) continuum model was applied to understand the coupled HM mechanisms in the Callovo–Oxfordian claystone. Features such as transverse isotropy, shrinkage phenomena and permeability change induced by mechanical deformation were considered using the numerical code RockFlow. Intensive parameter studies in comparison with measured deformation and pore pressure data reduced model uncertainties. Fully saturated models showed very precise calculation results for the far-field zone sensors, but rapidly decreased pore pressure and continuously increased deformation in the near-field zone cannot be interpreted adequately even considering shrinkage and partially saturated flow models. A 2D isotropic damage model taking stiffness degradation into account was applied and acceptable calculation results were obtained for pore pressure evolution. However, the time-dependent deformation cannot be evaluated by the current model.
Selective and Potent Akt Inhibition Triggers Anti-Myeloma Activities and Enhances Fatal Endoplasmic Reticulum Stress Induced by Proteasome Inhibition
Authors: Mimura Naoya , Hideshima Teru , Shimomura Toshiyasu , Suzuki Rikio , Ohguchi Hiroto , Rizq Ola , Kikuchi Shohei , Yoshida Yasuhiro , Cottini Francesca , Jakubikova Jana , Cirstea Diana , Gorgun Gullu , Minami Jiro , Tai Yu-Tzu , Richardson Paul G. , Utsugi Teruhiro , Iwama Atsushi , Anderson Kenneth C. 
Published: June 2014

Abstract
The PI3K/Akt pathway plays a crucial role in the pathogenesis of multiple myeloma (MM) in the bone marrow (BM) milieu. However, efficacy of selective and potent Akt inhibition has not yet been fully elucidated. In this study, we, therefore, examined the biologic impact of selective and potent Akt inhibition by a novel allosteric inhibitor TAS-117. TAS-117 induced significant growth inhibition, associated with downregulation of phosphorylated Akt (p-Akt), selectively in MM cell lines with high baseline p-Akt. Cytotoxicity of TAS-117 was also observed in patient MM cells, but not in normal peripheral blood mononuclear cells. Importantly, TAS-117 induced significant cytotoxicity in MM cells even in the presence of BM stromal cells, associated with inhibition of IL6 secretion. Oral administration of TAS-117 significantly inhibited human MM cell growth in murine xenograft models. TAS-117 triggered apoptosis and autophagy, as well as induction of endoplasmic reticulum (ER) stress response with minimal expression of C/EBP homologous protein (CHOP), a fatal ER stress marker. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity, associated with increased CHOP and PARP cleavage and blockade of bortezomib-induced p-Akt, suggesting that TAS-117 augments bortezomib-induced ER stress and apoptotic signaling. Carfilzomib-induced cytotoxicity was similarly enhanced by TAS-117. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity in vivo, associated with prolonged host survival. Our results show that selective and potent Akt inhibition by TAS-117 triggers anti-MM activities in vitro and in vivo, as well as enhances cytotoxicity of proteasome inhibition, providing the preclinical framework for clinical evaluation of selective Akt inhibitors, alone and in combination with proteasome inhibitors in MM. Cancer Res; 74(16); 4458–69. ©2014 AACR.
Ernesto Nathan Rogers e a polêmica da arquiteta brasileira
Authors: Sanches Aline Coelho 
Published: June 2014

Entre 1954 e 1959 se desenvolvem duas polêmicas originadas da tentativa de se redefinir uma posição com relação à arquitetura moderna: aquela gerada pela crítica de Max Bull à arquitetura moderna brasileira e a crítia de Reyner Banham à arquitetura italiana. Nas duas, Ernesto Nathan Rogers e a revista <<Casabella-Continuità>>, dirigida por ele, tiveram parte importante. Esclarecer o papel de Rogers na primeira polêmica, a relação entre suas idéias e obras e a arquitetura brasileira e a rede de relações que estabeleceu no Brasil, é um dos objetivos deste artigo, assim como discutir temas e problemas levantados pelo episódio e repensar a sua atualidade.
Efeitos da prática da natação adaptada sobre o perfil bioquímico e o estado de condicionamento físico de indivíduos com lesão medular
Authors: Almeida Patricia A. de , Barbosa Valéria R.C. , Dias Matheus C. , Neiva Cassiano M. 
Published: June 2014

Introdução: A ausência de exercícios físicos gerada pela imobilização dos membros inferiores conduza mudanças na composição corporal que geralmente estão associadas com o desequilíbrio da taxametabólica que somados ao estado sedentário podem resultar em obesidade, diabetes mellitus edoenças cardiovasculares. Assim, a melhora do condicionamento físico pode contribuir para promoçãode saúde e qualidade de vida desses indivíduos. Como existe um número muito reduzido de pesquisasnesse sentido, nossa proposta foi investigar os efeitos de um programa de natação adaptada, emprotocolo intervalado, para pessoas com lesão medular, tendo como objetivo verificar a melhora do seucondicionamento físico e, conseqüentemente, de algumas variáveis bioquímicas importantes para asaúde. Metodologia: Participaram do estudo 17 indivíduos com lesão medular, sedentários, distribuí-dos em 2 grupos: 11 participantes do grupo treinamento (GT) e 6 do grupo controle (GC). No GT foiaplicado um protocolo de treinamento intervalado em natação, durante oito semanas consecutivas, 3vezes por semana. O protocolo empregou a braçada do nado peito, nos períodos de trabalho de intensidade moderada a intensa, e a braçada do nado costas, nos períodos de recuperação ativa. O GC nãoparticipou de nenhuma atividade física. Em ambos os grupos foi realizada a coleta de sangue para aanálise bioquímica, antes (avaliação) e após (reavaliação) o programa de natação. Resultados e Discussão: As concentrações de triglicerídeos, colesterol total e LDL-colesterol não apresentaram altera-ções significativas da avaliação para a reavaliação, em ambos os grupos. Entretanto no GT, na dosagem de HDL-colesterol foram observadas diferenças significativas (p=0,0110), evidenciando umamelhora na fase pós-treinamento, o que não ocorreu no GC. Com relação ao estado de condicionamento físico, os resultados revelaram uma diferença significativa em relação ao tempo e à distância percorrida na água quando comparados com a fase pré-treinamento (p<0,001), demonstrando uma grande melhora na capacidade de deslocamento com a braçada do nado peito e uma melhora significativa dafunção cardiorrespiratória. Conclusão: O programa de natação intervalado empregado, com intensidade de moderada à intensa, pode, mesmo em curto período de tempo, promover alterações positivasnos valores de HDL-colesterol dos indivíduos com lesão medular estudados, além de melhorar substancialmente seu condicionamento físico.
Alterações na expressão de genes para citocinas, fatores de crescimento e seus receptores estão associadas com as neoplasias epiteliais ovarianas
Authors: Souza Ana Élida Nogueira , Esmeraldo Maria Irisleide Diógenes Bezerra , Araújo Vinícius Ramalho Dantas , Silva José Roberto Viana 
Published: June 2014

O câncer de ovário é o câncer ginecológico de maior letalidade e mais difícil de ser diagnosticado. Cercade 3/4 dos tumores malignos de ovário apresentam-se em estágio avançado no momento do diagnóstico inicial. A etiologia do câncer de ovário parece ser multifatorial, incluindo fatores reprodutivos, familiares e pessoais. Diversos fatores envolvidos no desenvolvimento do câncer de ovário vêm sendo estudados, buscando melhor entender seu desenvolvimento. O tumor originado do epitélio superficial do ovário é o tipo mais frequente e tem sido associado com alterações na expressão de kit ligante (KL), do receptor de fator epidermal de crescimento (EGF-R), assim como a super expressão e ativação de genes como o HER, myc, ras e p53. O objetivo desta revisão é descrever as características dos tipos de tumores ovarianos e discutir a influência das gonadotrofinas e as alterações na expressão de genespara citocinas, fatores de crescimento e seus receptores nas neoplasias ovarianas.
Effects of Waves on Tabular Ice-Shelf Calving
Authors: Ren Diandong , Leslie Lance M. 
Published: June 2014

Abstract
As a conveyor belt transferring inland ice to ocean, ice shelves shed mass through large, systematic tabular calving, which also plays a major role in the fluctuation of the buttressing forces. Tabular iceberg calving involves two stages: first is systematic cracking, which develops after the forward-slanting front reaches a limiting extension length determined by gravity–buoyancy imbalance; second is fatigue separation. The latter has greater variability, producing calving irregularity. Whereas ice flow vertical shear determines the timing of the systematic cracking, wave actions are decisive for ensuing viscoplastic fatigue. Because the frontal section has its own resonance frequency, it reverberates only to waves of similar frequency. With a flow-dependent, nonlocal attrition scheme, the present ice model [Scalable Extensible Geoflow Model for Environmental Research-Ice flow submodel (SEGMENT-Ice)] describes an entire ice-shelf life cycle. It is found that most East Antarctic ice shelves have higher resonance frequencies, and the fatigue of viscoplastic ice is significantly enhanced by shoaling waves from both storm surges and infragravity waves (~5 × 10−3 Hz). The two largest embayed ice shelves have resonance frequencies within the range of tsunami waves. When approaching critical extension lengths, perturbations from about four consecutive tsunami events can cause complete separation of tabular icebergs from shelves. For shelves with resonance frequencies matching storm surge waves, future reduction of sea ice may impose much larger deflections from shoaling, storm-generated ocean waves. Although the Ross Ice Shelf (RIS) total mass varies little in the twenty-first century, the mass turnover quickens and the ice conveyor belt is ~40% more efficient by the late twenty-first century, reaching 70 km3 yr−1. The mass distribution shifts oceanward, favoring future tabular calving.
Falls in people with MS—an individual data meta-analysis from studies from Australia, Sweden, United Kingdom and the United States
Authors: Nilsagård Y , Gunn H , Freeman J , Hoang P , Lord S , Mazumder Rajarshi , Cameron Michelle 
Published: June 2014

Background: Falls are common in people with multiple sclerosis (PwMS). Previous studies have generally included small samples and had varied methods. Objectives: The objectives of this paper are to compile fall rates across a broad range of ages and disease severity and to definitively assess the extent to which MS-associated and demographic factors influence fall rates. Methods: Individual data from studies in four countries that prospectively measured falls for three months were analyzed. We determined fall rates, prevalence of fallers (≥1 falls) and frequent fallers (≥2 falls), location and timing of falls, and fall-related demographic factors. Results: A total of 537 participants reported 1721 falls: 56% were fallers and 37% frequent fallers. Most falls occurred indoors (65%) between 6 a.m. and 6 p.m. (75%). Primary progressive MS was associated with significantly increased odds of being a faller (odds ratio (OR) 2.02; CI 1.08–3.78). Fall risk peaked at EDSS levels of 4.0 and 6.0 with significant ORs between 5.30 (2.23–12.64) and 5.10 (2.08–12.47). The fall rate was lower in women than men (relative risk (RR) 0.80; CI 0.67–0.94) and decreased with increasing age (RR 0.97 for each year, CI 0.95–0.98). Conclusion: PwMS are at high risk of falls and there are important associations between falls and MS-associated disability, gender and age.
In-Country Migration and Risk Factors for HIV Acquisition among Pregnant Women in Tijuana, Mexico
Authors: Viani Rolando M. , Araneta Maria R. , Spector Stephen A. 
Published: June 2014

Objective: To compare HIV prevalence and HIV acquisition risk behaviors between pregnant women residents and migrants. Design: A cross-sectional study of pregnant women of unknown HIV status seeking care at Tijuana General Hospital, Mexico. Methods: Pregnant women attending the labor and delivery unit or the prenatal clinic had a rapid HIV test drawn, with positive results confirmed by Western blot. Migrants were defined as women who had resided in Tijuana for less than 5 years. Results: Between 2007 and 2008, a total of 3331 pregnant women consented to participate. The HIV seroprevalence did not differ between Tijuana residents (18 of 2502, 0.72%) and migrants (3 of 829, 0.36%, P = .32). In multivariate regression analyses, HIV acquisition risk behaviors included methamphetamine use (adjusted odds ratio [OR]: 6.03, 95% confidence interval [CI]: 2.3–15.8, P < .001) and first presentation at labor (adjusted OR: 5.0, 95% CI: 1.6–15.3, P = .005), adjusted for migrant status, age, and history of sexually transmitted infections. Conclusion: The overall HIV seroprevalence was 0.63% and did not differ between Tijuana residents and migrants.
Should health insurers target prevention of cardiovascular disease?: a cost-effectiveness analysis of an individualised programme in Germany based on routine data
Authors: Aljutaili Majed , Becker Christian , Witt Sabine , Holle Rolf , Leidl Reiner , Block Michael , Brachmann Johannes , Silber Sigmund , Bestehorn Kurt , Stollenwerk Björn 
Published: June 2014

AbstractBackgroundCardiovascular diseases are the main cause of death worldwide, making their prevention a major health care challenge. In 2006, a German statutory health insurance company presented a novel individualised prevention programme (KardioPro), which focused on coronary heart disease (CHD) screening, risk factor assessment, early detection and secondary prevention. This study evaluates KardioPro in CHD risk subgroups, and analyses the cost-effectiveness of different individualised prevention strategies.MethodsThe CHD risk subgroups were assembled based on routine data from the statutory health insurance company, making use of a quasi-beta regression model for risk prediction. The control group was selected via propensity score matching based on logistic regression and an approximate nearest neighbour approach. The main outcome was cost-effectiveness. Effectiveness was measured as event-free time, and events were defined as myocardial infarction, stroke and death. Incremental cost-effectiveness ratios comparing participants with non-participants were calculated for each subgroup. To assess the uncertainty of results, a bootstrapping approach was applied.ResultsThe cost-effectiveness of KardioPro in the group at high risk of CHD was €20,901 per event-free year; in the medium-risk group, €52,323 per event-free year; in the low-risk group, €186,074 per event-free year; and in the group with known CHD, €26,456 per event-free year. KardioPro was associated with a significant health gain but also a significant cost increase. However, statistical significance could not be shown for all subgroups.ConclusionThe cost-effectiveness of KardioPro differs substantially according to the group being targeted. Depending on the willingness-to-pay, it may be reasonable to only offer KardioPro to patients at high risk of further cardiovascular events. This high-risk group could be identified from routine statutory health insurance data. However, the long-term consequences of KardioPro still need to be evaluated.