bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of oxysterols in vascular ageing
Authors: Gargiulo Simona , Gamba Paola , Testa Gabriella , Leonarduzzi Gabriella , Poli Giuseppe 
Published: December 2015

AbstractThe ageing endothelium progressively loses its remarkable and crucial ability to maintain homeostasis of the vasculature, as it acquires a proinflammatory phenotype. Cellular and structural changes gradually accumulate in the blood vessels, and markedly in artery walls. Most changes in aged arteries are comparable to those occurring during the atherogenic process, the latter being more marked: pro‐oxidant and proinflammatory molecules, mainly deriving from or triggered by oxidized low density lipoproteins (oxLDLs), are undoubtedly a major driving force of this process. Oxysterols, quantitatively relevant components of oxLDLs, are likely candidate molecules in the pathogenesis of vascular ageing, because of their marked pro‐oxidant, proinflammatory and proapoptotic properties. An increasing bulk of experimental data point to the contribution of a variety of oxysterols of pathophysiological interest, also in the age‐related genesis of endothelium dysfunction, intimal thickening due to lipid accumulation, and smooth muscle cell migration and arterial stiffness due to increasing collagen deposition and calcification. This review provides an updated analysis of the molecular mechanisms whereby oxysterols accumulating in the wall of ageing blood vessels may ‘activate’ endothelial and monocytic cells, through expression of an inflammatory phenotype, and ‘convince’ smooth muscle cells to proliferate, migrate and, above all, to act as fibroblast‐like cells.
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Ideas infantiles sobre la producción de noticias en los medios
Authors: Perelman Flora , Nakache Débora , Rubinovich Gabriela , Rodríguez María Elena , Dib María Jimena 
Published: December 2015

<p class="p1">Los objetivos de la investigación cualitativa que enmarca este artículo son indagar las ideas infantiles a propósito de la producción de noticias y generar situaciones didácticas que promuevan la lectura crítica de los medios. El foco de este artículo de investigación está en los saberes discursivos y en las líneas de progresión de las conceptualizaciones sobre la producción y circulación de noticias de alumnos de sexto de primaria de la Ciudad de Buenos Aires. Los niños advierten requisitos para que un hecho sea noticia, pero no logran dilucidar que las noticias están sometidas a procesos de selección y elaboración mediáticos. </p>
Maquillar los cuerpos / Transmutar en movimiento: Reflexiones acerca de las reelaboraciones de la danza butoh y sus máscaras
Authors: Aschieri Patricia 
Published: December 2015

<p class="Default">La danza <em>butoh</em> suele identificarse con el uso de la pintura blanca sobre los cuerpos. Sin embargo, las reelaboraciones de esta expresión dancístico-teatral de la vanguardia japonesa en Argentina, presentan cierto desvanecimiento de esta característica. Casi sin maquillaje los cuerpos conservan cada vez más los rasgos que los individualizan y particularizan. Si en tanto como sostiene Lévi-Strauss (1997), la máscara niega tanto como afirma, si está hecha de aquello que dice pero también de lo que excluye, me propongo en este trabajo reflexionar acerca de los posibles significados de su ausencia o desvanecimiento. Para ello, desarrollaré desde una perspectiva fenomenológica, los conceptos <em>de transmutación somática</em> o <em>corporizada</em> e <em>imaginación sensorial</em>. Describiré a partir de los resultados de la etnografía realizada para mi tesis doctoral, aquellos rasgos de las trayectorias corporales previas de los performers que inciden poniéndose de manifiesto en las reelaboraciones.</p>
Parametric Design Study About Seismic Isolation System for Fast Reactor JSFR
Authors: Kawasaki Nobuchika , Yamamoto Tomohiko , Fukasawa Tsuyoshi , Okamura Shigeki 
Published: December 2015

Japanese seismic conditions are getting severer and natural frequencies of components are getting lower due to the enlargements of components’ size, therefore response accelerations and buckling margins of reactor vessels were parametrically surveyed with attention to thicknesses, diameters, and isolation frequencies for reviewing necessary isolation specification.
For the first, Japanese seismic condition and present specification of JSFR isolation system are introduced in this paper. RV installed floor responses were calculated based on this seismic condition and the relationship of natural frequencies, initiated stresses, and buckling margins against vessel thicknesses and diameters were shown with trend.
Expansion characteristic of isolation system was evaluated by parametric acceleration response analyses. Comparing the response of isolation system with 8Hz vertical natural frequency with other natural frequency’s isolation, response ratios against natural frequencies were calculated.
Japanese seismic design condition may become severer than present one, and a natural frequency of main component may decrease. However based on the buckling margin with present plant specifications and the expansion characteristic of isolation system, the advanced isolation system with 8Hz vertical natural frequency was selected as the isolation system of JSFR at still present occasion.
Analytical Study of 1D Periodic Foundations for Structural Vibration Isolation
Authors: Witarto W. , Yan Y. , Wang S. J. , Mo Y. L. , Chang K. C. , Tang Y. , Ruis M. 
Published: December 2015

The application of periodic foundations for structural vibration isolation has been intensively studied in the past decade. The ability of the periodic foundation to block the seismic wave on certain frequency ranges has put this kind of foundations as a prosperous next generation of seismic isolators. This paper first describes general idea of basic theory of one dimensional (1D) periodic foundation. The parametric studies based on the material and the geometric properties conducted in the past are discussed. The experimental tests on 1D periodic foundation are reported as well. Based on the promising results of the past research, 1D periodic foundations have been regarded as one of the simplest, yet effective foundation to block the seismic wave in all directions.
In addition to the review of the existing studies, enhanced analyses of 1D periodic foundations have been performed and are presented in this paper. Finite element analysis model of 1D periodic foundations with a three story steel frame as the superstructure was utilized for the parametric study. The study was conducted under both Shear Wave (S-Wave) and Primary Wave (P-Wave). The independent variables include the number of unit cells in the periodic foundation, the foundation and superstructure interaction, and the main frequency content of earthquake ground motion. It is found that the main frequency content of the earthquake and the natural frequency of the super structure-periodic foundation system play the major role in the superstructure response. While the number of unit cell affect the superstructure response, the effect is not as significant as the aforementioned.
Full Scale Simulation-Based Study on Dynamic Response of BWR Fuel Assemblies Under Seismic Loading
Authors: Yoshimura Shinobu , Yamada Tomonori , Koide Yuichi , Onitsuka Shohei , Iijima Tadashi 
Published: December 2015

The purpose of this study is to investigate dynamic response behaviors of fuel assemblies in a boiling water reactor (BWR) under seismic loading. The core of BWR consists of several hundreds of fuel assemblies. They are supported with both top guide and fuel support and are surrounded by coolant water. It is important to grasp their dynamic response behaviors under seismic loading for securing the structural integrity of the fuel assembly itself as well as for assessing control rod scrammability. In this study, we employ two different numerical simulation methods of acoustic fluid-structure interaction (AFSI) developed by the present authors independently. The one is a three-dimensional parallel finite element method for AFSI problems with solid elements based on a partitioned coupling approach, while the other is a finite element method of beam elements for fuel assemblies combining added mass matrix, which represents coupled inertia effects caused by coolant water.
Both methods are first applied to a problem of 36 fuel assemblies for numerical verification, and then applied to a problem of 368 fuel assemblies for validation. The latter problem was set up based on the demonstration test performed by the NUPEC (Nuclear Power Engineering Corporation) in 1986. Both simulation results agreed well with each other in all cases, and the simulated results also agreed well with the experimental ones. In addition, we have precisely discussed seismic response behaviors of the fuel assemblies, which were not shown in the demonstration test. Accordingly, we conclude that the both developed simulation methods are powerful tools to grasp the precise behavior of fuel assemblies of BWR under seismic loading and to improve the seismic safety design of BWR core.
Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration
Authors: Giffin Louise , West John A. , Damania Blossom 
Published: December 2015

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi's sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman's disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6's impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore, latent and
de novo
KSHV infections of endothelial cells also induce CEACAM1 expression. Collectively, our data suggest that vIL-6 modulates endothelial cell migration by upregulating the expression of cellular factors, including CEACAM1.

IMPORTANCE
Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with the development of three human malignancies, Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. KSHV expresses many factors that enable the virus to manipulate the host environment in order to persist and induce disease. The viral interleukin-6 (vIL-6) produced by KSHV is structurally and functionally homologous to the human cytokine interleukin-6, except that vIL-6 is secreted slowly and functions primarily from inside the host cell. To investigate the unique intracellular role of vIL-6, we analyzed the impact of vIL-6 on endothelial cell gene expression. We report that vIL-6 significantly alters the expression of genes associated with cell movement, including that for CEACAM1. The gene for CEACAM1 was upregulated by vIL-6 and by latent and primary KSHV infection and promotes vIL-6-mediated endothelial cell migration. This work advances the field's understanding of vIL-6 function and its contribution to KSHV pathogenesis.
Greater vertical impact loading in female runners with medically diagnosed injuries: a prospective investigation
Authors: Davis Irene S , Bowser Bradley J , Mullineaux David R 
Published: December 2015

BackgroundRunning has been critical to human survival. Therefore, the high rate of injuries experienced by modern day runners is puzzling. Landing on the heel, as most modern day shod runners do, results in a distinct vertical impact force that has been shown to be associated with running-related injuries. However, these injury studies were retrospective in nature and do not establish cause and effect.ObjectiveTo determine whether runners with high impacts are at greater risk for developing medically diagnosed injuries.Methods249 female runners underwent a gait analysis to measure vertical instantaneous loading rate, vertical average loading rate (VALR), vertical impact peak (VIP) and peak vertical force. Participants then recorded their mileage and any running-related injuries monthly in a web-based, database programme. Variables were first compared between the entire injured (INJ; n=144) and uninjured (n=105) groups. However, the focus of this study was on those injured runners seeking medical attention (n=103) and those who had never injured (n=21).ResultsThere were no differences between the entire group of injured and uninjured groups. However, all impact-related variables were higher in those with medically diagnosed injuries compared with those who had never been injured. (effect size (ES) 0.4–0.59). When VALR was >66.0 body weight (BW)/s, the odds of being DX_INJ were 2.72 (95% CI 1.0 to 7.4). Impact loading was associated with bony and soft-tissue injuries.ConclusionsVertical average loading rate was lower in female runners classified as ‘never injured’ compared with those who had been injured and sought medical attention.
Efficacy of metacognitive therapy for prolonged grief disorder: protocol for a randomised controlled trial
Authors: Wenn Jenine , O'Connor Moira , Breen Lauren J , Kane Robert T , Rees Clare S 
Published: December 2015

IntroductionStudies of effective psychotherapy for individuals suffering from the effects of prolonged grief disorder (PGD) are scarce. This paper describes the protocol for an evaluation of a metacognitive therapy programme designed specifically for PGD, to reduce the psychological distress and loss of functioning resulting from bereavement.Methods and analysisThe proposed trial comprises three phases. Phase 1 consists of a review of the literature and semistructured interviews with key members of the target population to inform the development of a metacognitive therapy programme for Prolonged Grief. Phase 2 involves a randomised controlled trial to implement and evaluate the programme. Male and female adults (N=34) will be randomly assigned to either a wait list or an intervention group. Measures of PGD, anxiety, depression, rumination, metacognitions and quality of life will be taken pretreatment and posttreatment and at the 3-month and 6-month follow-up. The generalised linear mixed model will be used to assess treatment efficacy. Phase 3 will test the social validity of the programme.DiscussionThis study is the first empirical investigation of the efficacy of a targeted metacognitive treatment programme for PGD. A focus on identifying and changing the metacognitive mechanisms underpinning the development and maintenance of prolonged grief is likely to be beneficial to theory and practice.EthicsEthics approval was obtained from Curtin University Human Research Ethics Committee (Approval number HR 41/2013.)Trial registration numberACTRN12613001270707.
Early childhood constraint therapy for sensory/motor impairment in cerebral palsy: a randomised clinical trial protocol
Authors: Chorna Olena , Heathcock Jill , Key Alexandra , Noritz Garey , Carey Helen , Hamm Ellyn , Nelin Mary Ann , Murray Micah , Needham Amy , Slaughter James C , Maitre Nathalie L 
Published: December 2015

IntroductionCerebral palsy (CP) is the most common physical disability in childhood. It is a disorder resulting from sensory and motor impairments due to perinatal brain injury, with lifetime consequences that range from poor adaptive and social function to communication and emotional disturbances. Infants with CP have a fundamental disadvantage in recovering motor function: they do not receive accurate sensory feedback from their movements, leading to developmental disregard. Constraint-induced movement therapy (CIMT) is one of the few effective neurorehabilitative strategies shown to improve upper extremity motor function in adults and older children with CP, potentially overcoming developmental disregard.Methods and analysisThis study is a randomised controlled trial of children 12–24 months corrected age studying the effectiveness of CIMT combined with motor and sensory-motor interventions. The study population will comprise 72 children with CP and 144 typically developing children for a total of N=216 children. All children with CP, regardless of group allocation will continue with their standard of care occupational and physical therapy throughout the study. The research material collected will be in the form of data from high-density array event-related potential scan, standardised assessment scores and motion analysis scores.Ethics and disseminationThe study protocol was approved by the Institutional Review Board. The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.Trial registration numberNCT02567630.
Peptide–Drug Conjugate GnRH–Sunitinib Targets Angiogenesis Selectively at the Site of Action to Inhibit Tumor Growth
Authors: Argyros Orestis , Karampelas Theodoros , Asvos Xenophon , Varela Aimilia , Sayyad Nisar , Papakyriakou Athanasios , Davos Constantinos H. , Tzakos Andreas G. , Fokas Demosthenes , Tamvakopoulos Constantin 
Published: December 2015

Abstract
The potential to heighten the efficacy of antiangiogenic agents was explored in this study based on active targeting of tumor cells overexpressing the gonadotropin-releasing hormone receptor (GnRH-R). The rational design pursued focused on five analogues of a clinically established antiangiogenic compound (sunitinib), from which a lead candidate (SAN1) was conjugated to the targeting peptide [d-Lys6]-GnRH, generating SAN1GSC. Conjugation of SAN1 did not disrupt any of its antiangiogenic or cytotoxic properties in GnRH-R–expressing prostate and breast tumor cells. Daily SAN1GSC treatments in mouse xenograft models of castration-resistant prostate cancer resulted in significant tumor growth delay compared with equimolar SAN1 or sunitinib alone. This efficacy correlated with inhibited phosphorylation of AKT and S6, together with reduced Ki-67 and CD31 expression. The superior efficacy of the peptide–drug conjugate was also attributed to the finding that higher amounts of SAN1 were delivered to the tumor site (∼4-fold) following dosing of SAN1GSC compared with equimolar amounts of nonconjugated SAN1. Importantly, treatment with SAN1GSC was associated with minimal hematotoxicity and cardiotoxicity based on measurements of the left ventricular systolic function in treated mice. Our results offer preclinical proof-of-concept for SAN1GSC as a novel molecule that selectively reaches the tumor site and downregulates angiogenesis with negligible cardiotoxicity, thus encouraging its further clinical development and evaluation. Cancer Res; 76(5); 1181–92. ©2015 AACR.
Trends in United States Prostate Cancer Incidence Rates by Age and Stage, 1995–2012
Authors: Hoffman Richard M. , Meisner Angela L.W. , Arap Wadih , Barry Marc , Shah Satyan K. , Zeliadt Steven B. , Wiggins Charles L. 
Published: December 2015

Abstract
Background: The advent of PSA testing in the late 1980s substantially increased prostate cancer incidence rates. Concerns about overscreening and overdiagnosis subsequently led professional guidelines (circa 2000 and later) to recommend against routine PSA testing. We evaluated trends in prostate cancer incidence, including late-stage diagnoses, from 1995 through 2012.
Methods: We used joinpoint regression analyses to evaluate all-, localized/regional-, and distant-stage prostate cancer incidence trends based on Surveillance, Epidemiology, and End Results (SEER) data. We stratified analyses by age (50–69, 70+). We reported incidence trends as annual percent change (APC).
Results: Overall age-adjusted incidence rates for localized/regional stage prostate cancer have been declining since 2001, sharply from 2010 to 2012 [APC, −13.1; 95% confidence intervals (CI), −23.5 to −1.3]. Distant-stage incidence rates have declined since 1995, with greater declines from 1995 to 1997 (APC, −8.4; 95% CI, −2.3 to −14.1) than from 2003 to 2012 (APC, −1.0; 95% CI, −1.7 to −0.4). Distant-stage incidence rates declined for men ages 70+ from 1995 to 2012, but increased in men ages 50 to 69 years from 2004 to 2012 (APC, 1.7; 95% CI, 0.2 to 3.2).
Conclusions: Guidelines discouraging routine prostate cancer screening were temporally associated with declining localized/regional prostate cancer incidence rates; however, incidence rates of distant-stage disease are now increasing in younger men.
Impact: This trend may adversely affect prostate cancer mortality rates. Cancer Epidemiol Biomarkers Prev; 25(2); 259–63. ©2015 AACR.
A Phase I Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Combination Therapy with Refametinib plus Sorafenib in Patients with Advanced Cancer
Authors: Adjei Alex A. , Richards Donald A. , El-Khoueiry Anthony , Braiteh Fadi , Becerra Carlos H.R. , Stephenson Joe J. , Hezel Aram F. , Sherman Morris , Garbo Lawrence , Leffingwell Diane P. , Iverson Cory , Miner Jeffrey N. , Shen Zancong , Yeh Li-Tain , Gunawan Sonny , Wilson David M. , Manhard Kimberly J. , Rajagopalan Prabhu , Krissel Heiko , Clendeninn Neil J. 
Published: December 2015

Abstract
Purpose: To assess the safety and tolerability of the small-molecule allosteric MEK inhibitor refametinib combined with sorafenib, in patients with advanced solid malignancies.
Experimental Design: This phase I dose-escalation study included an expansion phase at the maximum tolerated dose (MTD). Patients received refametinib/sorafenib twice daily for 28 days, from a dose of refametinib 5 mg plus sorafenib 200 mg to a dose of refametinib 50 mg plus sorafenib 400 mg. Plasma levels of refametinib, refametinib metabolite M17, and sorafenib were measured for pharmacokinetic assessments. Tumors were biopsied at the MTD for analysis of MEK pathway mutations and ERK phosphorylation.
Results: Thirty-two patients were enrolled in the dose-escalation cohort. The MTD was refametinib 50 mg twice daily plus sorafenib 400 mg twice daily. The most common treatment-related toxicities were diarrhea and fatigue. Refametinib was readily absorbed following oral administration (plasma half-life of ∼16 hours at the MTD), and pharmacokinetic parameters displayed near-dose proportionality, with less than 2-fold accumulation after multiple dosing. Another 30 patients were enrolled in the MTD cohort; 19 had hepatocellular carcinoma. The combination was associated with significantly reduced ERK phosphorylation in 5 out of 6 patients biopsied, with the greatest reductions in those with KRAS or BRAF mutations. Disease was stabilized in approximately half of patients, and 1 patient with colorectal cancer achieved a partial response at the MTD lasting approximately 1 year.
Conclusions: In this phase I study, refametinib plus sorafenib was well tolerated, with good oral absorption, near-dose proportionality, and target inhibition in a range of tumor types. Clin Cancer Res; 22(10); 2368–76. ©2015 AACR.