Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension.

Increased physical activity is recommended for the general population and to patients of many diseases because of its health benefits but can be contraindicated if it is thought a risk for serious cardiovascular events. One such condition is pulmonary artery hypertension (PAH). PAH and right ventricular failure was induced in rats by a single injection of monocrotaline (MCT). MCT rats with voluntary access to a running wheel ran on average 2km per day. The time for half the animals to develop heart failure signs (median survival time) was 28 days (exercise failure (EF) group), significantly longer than sedentary animals (sedentary failure (SF) group), 23 days). The contractility of single failing myocytes in response to increasing demand (stimulation frequency) was significantly impaired compared with both sedentary control (SC) and exercising control (EC) myocytes. However, myocytes from exercising MCT rats, tested at 23 days (EM group) showed responses intermediate to the control (SC, EC) and failing (SF, EF) groups. We conclude that voluntary exercise is beneficial to rats with heart failure induced by PAH and this is evidence to support the consideration of appropriate exercise regimes for potentially vulnerable groups

The Betic Ophiolites and the Mesozoic Evolution of the Western Tethys

The Betic Ophiolites consist of numerous tectonic slices, metric to kilometric in size, of eclogitized mafic and ultramafic rocks associated to oceanic metasediments, deriving from the Betic oceanic domain. The outcrop of these ophiolites is aligned along 250 km in the Mulhacen Complex of the Nevado-Filabride Domain, located at the center-eastern zone of the Betic Cordillera (SE Spain). According to petrological/geochemical inferences and SHRIMP (Sensitive High Resolution Ion Micro-Probe) dating of igneous zircons, the Betic oceanic lithosphere originated along an ultra-slow mid-ocean ridge, after rifting, thinning and breakup of the preexisting continental crust. The Betic oceanic sector, located at the westernmost end of the Tethys Ocean, developed from the Lower to Middle Jurassic (185-170 Ma), just at the beginning of the Pangaea break-up between the Iberia-European and the Africa-Adrian plates. Subsequently, the oceanic spreading migrated northeastward to form the Ligurian and Alpine Tethys oceans, from 165 to 140 Ma. Breakup and oceanization isolated continental remnants, known as the Mesomediterranean Terrane, which were deformed and affected by the Upper Cretaceous-Paleocene Eo-Alpine high-pressure metamorphic event, due to the intra-oceanic subduction of the Jurassic oceanic lithosphere and the related continental margins. This process was followed by the partial exhumation of the subducted oceanic rocks onto their continental margins, forming the Betic and Alpine Ophiolites. Subsequently, along the Upper Oligocene and Miocene, the deformed and metamorphosed Mesomediterranean Terrane was dismembered into different continental blocks collectively known as AlKaPeCa microplate (Alboran, Kabylian, Peloritan and Calabrian). In particular, the Alboran block was displaced toward the SW to occupy its current setting between the Iberian and African plates, due to the Neogene opening of the Algero-Provencal Basin. During this translation, the different domains of the Alboran microplate, forming the Internal Zones of the Betic and Rifean Cordilleras, collided with the External Zones representing the Iberian and African margins and, together with them, underwent the later alpine deformation and metamorphism, characterized by local differences of P-T (Pressure-Temperature) conditions. These Neogene metamorphic processes, known as Meso-Alpine and Neo-Alpine events, developed in the Nevado-Filabride Domain under Ab-Ep amphibolite and greenschists facies conditions, respectively, causing retrogradation and intensive deformation of the Eo-Alpine eclogites.This research was funded by Project CGL2009-12369 of the Spanish Ministry of Science and Innovation, co-financed with FEDER funds, and by Research Group RNM 333 of Junta de Andalucía (Spain)

L-NAME treatment enhances exercise-induced content of myocardial heat shock protein 72 (Hsp72) in rats

Background/Aim: Nitric oxide (NO) modulates the expression of the chaperone Hsp72 in the heart, and exercise stimulates both NO production and myocardial Hsp72 expression. The main purpose of the study was to investigate whether NO interferes with an exercise-induced myocardial Hsp72 expression. Methods: Male Wistar rats (70-100 days) were divided into control (C, n= 12), L-NAME-treated (L, n= 12), exercise (E, n= 13) and exercise plus L-NAME-treated (EL, n= 20) groups. L-NAME was given in drinking water (700 mg. L-1) and the exercise was performed on a treadmill (15-25 m.min(-1), 40-60 min. day(-1)) for seven days. Left ventricle (LV) protein Hsp content, NOS and phosphorylated-NOS (p-NOS) isoforms were measured using Western blotting. The activity of NOS was assayed in LV homogenates by the conversion of [H-3] L-arginine to [H-3] L-citrulline. Results: Hsp72 content was increased significantly (223%; p < 0.05) in the E group compared to the C group, but exercise alone did not alter the NOS content, p-NOS isoforms or NOS activity. Contrary to our expectation, L-NAME enhanced (p < 0.05) the exercise-induced Hsp72 content (EL vs. C, L and E groups = 1019%, 548% and 457%, respectively). Although the EL group had increased stimulatory p-eNOS(Ser1177) (over 200%) and decreased inhibitory p-nNOS(Ser852) (similar to 50%) compared to both the E and L groups (p < 0.05), NOS activity was similar in all groups. Conclusions: Our results suggest that exercise-induced cardiac Hsp72 expression does not depend on NO. Conversely, the in vivo L-NAME treatment enhances exercise-induced Hsp72 production. This effect may be due to an increase in cardiac stress. Copyright (C) 2011 S. Karger AG, Basel275479486CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA E INOVAÇÃO DO ESPÍRITO SANTO - FAPESsem informaçã

OBEDIS Core Variables Project : European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.Peer reviewe

The United States of America and Scientific Research

To gauge the current commitment to scientific research in the United States of America (US), we compared federal research funding (FRF) with the US gross domestic product (GDP) and industry research spending during the past six decades. In order to address the recent globalization of scientific research, we also focused on four key indicators of research activities: research and development (R&D) funding, total science and engineering doctoral degrees, patents, and scientific publications. We compared these indicators across three major population and economic regions: the US, the European Union (EU) and the People's Republic of China (China) over the past decade. We discovered a number of interesting trends with direct relevance for science policy. The level of US FRF has varied between 0.2% and 0.6% of the GDP during the last six decades. Since the 1960s, the US FRF contribution has fallen from twice that of industrial research funding to roughly equal. Also, in the last two decades, the portion of the US government R&D spending devoted to research has increased. Although well below the US and the EU in overall funding, the current growth rate for R&D funding in China greatly exceeds that of both. Finally, the EU currently produces more science and engineering doctoral graduates and scientific publications than the US in absolute terms, but not per capita. This study's aim is to facilitate a serious discussion of key questions by the research community and federal policy makers. In particular, our results raise two questions with respect to: a) the increasing globalization of science: “What role is the US playing now, and what role will it play in the future of international science?”; and b) the ability to produce beneficial innovations for society: “How will the US continue to foster its strengths?

Cell-to-Cell Signaling Influences the Fate of Prostate Cancer Stem Cells and Their Potential to Generate More Aggressive Tumors

An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issue, we isolated a rare tumor cell population on the basis of its CD44+CD24− phenotype from the human androgen-independent prostate carcinoma cell line DU145 and established its CSC properties. The behavior of selected CSC was investigated with respect to the bulk DU145 cells. The injection of CSC in nude mice generated highly vascularized tumors infiltrating the adjacent tissues, showing high density of neuroendocrine cells and expressing low levels of E-cadherin and β-catenin as well as high levels of vimentin. On the contrary, when a comparable number of unsorted DU145 cells were injected the resulting tumors were less aggressive. To investigate the different features of tumors in vivo, the influence of differentiated tumor cells on CSC was examined in vitro by growing CSC in the absence or presence of conditioned medium from DU145 cells. CSC grown in permissive conditions differentiated into cell populations with features similar to those of cells held in aggressive tumors generated from CSC injection. Differently, conditioned medium induced CSC to differentiate into a cell phenotype comparable to cells of scarcely aggressive tumors originated from bulk DU145 cell injection. These findings show for the first time that CSC are able to generate differentiated cells expressing either highly or scarcely aggressive phenotype, thus influencing prostate cancer progression. The fate of CSC was determined by signals released from tumor environment. Moreover, using microarray analysis we selected some molecules which could be involved in this cell-to-cell signaling, hypothesizing their potential value for prognostic or therapeutic applications

Influence of different types of solvent on the effectiveness of nanolime treatments on highly porous mortar substrates

Historic calcareous structures suffer from weathering processes that result in the loss of some of their original properties. Nanolime products represent an attractive choice for the consolidation of these substrates containing calcite due to their high chemical compatibility with the original structure. The effectiveness of nanolime products has been widely proven for superficial consolidation treatments (e.g. plasters and wall-paintings). However, its consolidation mechanism in highly porous substrates (e.g. limestones or lime mortars) still needs to be fully understood. The aim of this paper is to study the influence of different types of solvent on the effectiveness of nanolime treatments on highly porous lime-mortars. The consolidation effectiveness is investigated by evaluating changes on superficial cohesion, porosity, drilling resistance, water absorption by capillarity, drying rate and aesthetic properties. Results showed that nanolime dispersed in a mixture of isopropanol (50%) and water (50%) yielded slightly better consolidation properties in terms of reduction in porosity, increase in strength and penetration within coarse lime-mortars than nanolime dispersed in other solvents

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Alignment of the CMS silicon tracker during commissioning with cosmic rays

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS silicon tracker, consisting of 1440 silicon pixel and 15 148 silicon strip detector modules, has been aligned using more than three million cosmic ray charged particles, with additional information from optical surveys. The positions of the modules were determined with respect to cosmic ray trajectories to an average precision of 3–4 microns RMS in the barrel and 3–14 microns RMS in the endcap in the most sensitive coordinate. The results have been validated by several studies, including laser beam cross-checks, track fit self-consistency, track residuals in overlapping module regions, and track parameter resolution, and are compared with predictions obtained from simulation. Correlated systematic effects have been investigated. The track parameter resolutions obtained with this alignment are close to the design performance.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Commissioning and performance of the CMS pixel tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published verion of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe pixel detector of the Compact Muon Solenoid experiment consists of three barrel layers and two disks for each endcap. The detector was installed in summer 2008, commissioned with charge injections, and operated in the 3.8 T magnetic field during cosmic ray data taking. This paper reports on the first running experience and presents results on the pixel tracker performance, which are found to be in line with the design specifications of this detector. The transverse impact parameter resolution measured in a sample of high momentum muons is 18 microns.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)