Anti-proliferative effect of main dietary phytosterols and \u3b2-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 \u2013 and oxidative stress induced apoptosis

\u3b2-cryptoxanthin (\u3b2-Cx) and phytosterols (Ps) have potential against different cancer types,including colon cancer. However, their combined action has not been reported so far. Human colon cancer Caco-2 cells were treated 24 h with \u3b2-Cx and/or main dietary Ps (\u3b2-sitosterol, campesterol and stigmasterol), alone or in combination, at concentrations compatible with physiological human serum levels. A decrease in cell viability due to apoptosis (rise in sub-G1 population and exposure of membrane phosphatidylserine) was accompanied with dephosphorylation of BAD, mitochondrial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca2+ influx and increase of RONS levels as initial triggers. Ps and \u3b2-Cx, alone or in combination showed anti-proliferative activity against human colon adenocarcinoma Caco-2 cells through the mitochondrial pathway of apoptosis. No additive or synergistic effects were observed.The importance of bioactivity-guided assays with mixtures of dietary bioactive compounds to determine their eventual interactions in the functional food context is demonstrated

Trigger and Aperture of the Surface Detector Array of the Pierre Auger Observatory

The surface detector array of the Pierre Auger Observatory consists of 1600 water-Cherenkov detectors, for the study of extensive air showers (EAS) generated by ultra-high-energy cosmic rays. We describe the trigger hierarchy, from the identification of candidate showers at the level of a single detector, amongst a large background (mainly random single cosmic ray muons), up to the selection of real events and the rejection of random coincidences. Such trigger makes the surface detector array fully efficient for the detection of EAS with energy above $3\times 10^{18}$ eV, for all zenith angles between 0$^\circ$ and 60$^\circ$, independently of the position of the impact point and of the mass of the primary particle. In these range of energies and angles, the exposure of the surface array can be determined purely on the basis of the geometrical acceptance.Comment: 29 pages, 12 figure

Ultrahigh energy neutrinos at the Pierre Auger observatory

The observation of ultrahigh energy neutrinos (UHEνs) has become a priority in experimental astroparticle physics. UHEνs can be detected with a variety of techniques. In particular, neutrinos can interact in the atmosphere (downward-going ν) or in the Earth crust (Earth-skimming ν), producing air showers that can be observed with arrays of detectors at the ground. With the surface detector array of the Pierre Auger Observatory we can detect these types of cascades. The distinguishing signature for neutrino events is the presence of very inclined showers produced close to the ground (i.e., after having traversed a large amount of atmosphere). In this work we review the procedure and criteria established to search for UHEνs in the data collected with the ground array of the Pierre Auger Observatory. This includes Earth-skimming as well as downward-going neutrinos. No neutrino candidates have been found, which allows us to place competitive limits to the diffuse flux of UHEνs in the EeV range and above.P. Abreu ... K. B. Barber ... J. A. Bellido ... R. W. Clay ... M. J. Cooper ... B. R. Dawson ... T. A. Harrison ... A. E. Herve ... V. C. Holmes ... J. Sorokin ... P. Wahrlich ... B. J. Whelan ... et al

Bioaccesibility of plant sterols and their oxides in enriched fruit and/or milk-based beverages

Plant sterols (PS) have many beneficial functions, like LDL-cholesterol reduction upon other effects on lipid parameters. PS are prone to oxidation and can give rise to plant sterol oxidation products (POPs), which have been suggested to be cytotoxic. The aim was to evaluate the bioaccesibility of phytosterols and their oxides in fruit and/or milk based beverages enriched with PS after a simulated gastrointestinal digestion. Four PS-fortified beverages were analyzed (fruit beverages without milk (Fb), with milk (Fb\u2019M), with &#946;-cryptoxanthin (FbM) and only milk (M)) and their corresponding bioaccessible fractions (BF). PS source was the same (0.7 g/100 g) for all the samples. The applied in vitro digestion method was according to Granado et al. (2007) to obtain the BF (soluble fraction). The extraction and purification of PS and POPs was achieved by lipid extraction (for the beverages), followed by saponification, unsaponificable extraction and silica SPE purification (only for POPs). They were determined by GC-FID (PS) and GC-MS (POPs). Total contents of PS in the analyzed beverages ranged between 607.08 and 743.05 mg/100 g beverage. The concentration order of PS was \u3b2-sitosterol > sitostanol > campesterol > stigmasterol > campestanol. A statistically significative (p <0.05) decrease in the PS content among beverages and the BAF (22.23-44.98 mg/100 g beverage) was observed, even though the relative percentages of the different PS were similar before and after digestion process. Total POP contents in the beverages ranged between 47.64 and 68.97 \u3bcg/100 g sample and 31.05-44.31 \u3bcg/100 g sample in the beverages and the BF, respectively. In all cases, \u3b2-sitosterol oxides (\u3b1/\u3b2-hydroxy, triol and 7-keto) were the only POPs detected. In the beverages, the most abundant oxide was 7-keto, whereas in the BF triol was the main one. The profile of POPs depended on the beverage or BF considered. Bioaccessibility (%) of PS and POPs were 2.99\u20137.41 and 34.17\u201393.01, respectively. The effect of simulated gastrointestinal digestion applied to PS and POPs studied, resulted to be different, showing that POPs bioaccessibility is much more higher than that of PS

EU Pancreas: An Integrated European Platform for Pancreas Cancer Research - from Basic Science to Clinical and Public Health Interventions for a Rare Disease.

Background: Large-scale international collaboration is essential to decipher relevant information in the context of omics-scale interrogations in cancer research. This is even more important for rare and fatal diseases like pancreas cancer (PC). Methods: The COST Action BM1204 is a unique platform to facilitate the collaboration of a broad range of European and international PC multidisciplinary research groups in order to: (1) integrate knowledge and experience in a multidisciplinary way 'from cell to society', (2) promote the application of uniform study tools and protocols, (3) foster their optimal use by early-stage researchers, (4) enhance the mobility and training of researchers, and (5) disseminate the results produced to the broader society. Results: This Action will develop novel interdisciplinary tools for collaborative research to improve our understanding of PC and its prevention, diagnosis and treatment. It also aims to answer questions related to the etiology, early detection, evidence-based and personalized treatment, and health management for PC. Furthermore, the Action will contribute to new insights into PC personalized medicine and beyond as well as to the understanding of complex and rare diseases taking PC as a best practice example. The Action aims at attracting young scholars across a range of disciplines in collaboration with more experienced researchers and enhancing active European participation in the international scenario of PC research. Conclusion: The ultimate aim is to foster PC research in Europe and to coordinate this effort with other international initiatives to reduce disease mortality. (c) 2013 S. Karger AG, Basel

Impacto del proyecto PERSECC en la productividad de las MYPES de calzado de la ciudad de Trujillo, 2017

RESUMEN La presente investigación tiene como propósito determinar el impacto del proyecto creado por la Oficina de Proyectos de Investigación, Desarrollo e Innovación de CITEccal Trujillo, el “Proyecto de Reactivación del Sector Cuero y Calzado” en la productividad de las MYPES del sector calzado en relación con la incidencia que tenga este con el comportamiento de las ventas, producción y demás indicadores de las empresas que aplicaron a PERSECC durante el año 2017, con la finalidad de demostrar la labor del Estado al tomar medidas orientadas a elevar los niveles de competitividad de las empresas en estudio en relación a la reactivación de dicho sector. Para el desarrollo del presente trabajo de investigación, se utilizaron fuentes de información primaria debido a que serán documentos directos que se obtendrán de la oficina de Investigación, Desarrollo e Innovación de CITEccal Trujillo. Para esto, se tuvo en cuenta el análisis de la documentación de los datos recopilados del registro anual y evolución trimestral de ventas, producción, capacidad instalada, capacidad productiva, inversión en I+D+i, recurso humano, plan de acción del programa PERSECC, los cuales fueron facilitados directamente del área de la oficina de proyectos I+D+i para la realización del proyecto. Luego, se recopilaron los datos a través del análisis documental para ser procesados en tablas y gráficos, en seguida se determinaron las medias usando la Prueba T - Student para datos relacionados (muestras dependientes). Finalmente para medir la relación entre las variables en estudio se calculó el valor de probabilidad estadístico por el cual se rechaza la hipótesis nula y se acepta la hipótesis alternativa. De esta manera, la investigación llega a la conclusión que existen diferencias estadísticamente significativas entre los valores trimestrales de todos los indicadores analizados de las MYPES de calzado de la ciudad de Trujillo anteriores y posteriores de la aplicación del proyecto PERSECC, lo que significa que el proyecto PERSECC incide de manera significativa en la evolución de los indicadores de la productividad de cada una de las empresas del sector Calzado que aplicaron al proyecto. La principal recomendación que se hace al área de Proyectos I+D+i, es que el jefe de Proyectos autorice la continuación de la aplicación anual del Proyecto PERSECC con la finalidad de ampliar la participación de más MYPES, manteniendo un continuo control del registro de la data con respecto a la evaluación y seguimiento de indicadores en la mejora de su productividad y de esta manera, definir mejor el apoyo de la labor que viene realizando el CITEccal Trujillo para el aumento de la competitividad de las empresas del sector calzado. Palabras clave: Proyecto, Soporte Productivo, I+D, Productividad, Mypes (Micro y Pequeñas Empresas), Sector Calzado, Producción Calzado, Comercio Calzado.ABSTRACT The purpose of this research is to determine the impact of the project created by the Research, Development and Innovation Projects Office of CITEccal Trujillo, the "PERSECC" project in the productivity of the MSEs of the footwear sector in relation to the impact that this has with the behavior of sales, production and other indicators of the companies that applied to PERSECC during the year 2017, in order to demonstrate the work of the State to take measures aimed at raising the levels of competitiveness of companies under study in relation to the reactivation of this sector. For the development of this research work, primary information sources were used because they will be direct documents that will be obtained from the Research, Development and Innovation office of CITEccal Trujillo. For this, the analysis of the documentation of the annual record and quarterly evolution of sales, production, installed capacity, productive capacity, investment in R & D & I, human resources, action plan of the PERSECC program was taken account, which were provided directly from the area of the R + D + i project office for the realization of the project. Then, the data was collected through the documentary analysis to be processed in tables and graphs, consequently sample means were determined using the T - Student test for related data (dependent samples). Finally, to measure the relationship between the variables under study, it has been estimated the statistical probability value by which the null hypothesis is rejected and the alternative hypothesis is accepted. The main recommendation made to the area of R + D + i Projects, is that the Project Manager continues to authorize the application of the PERSECC Project in the coming years in order to expand the participation of more MYPES, maintaining a continuous control of the registry of the data with respect to the evaluation and monitoring of indicators to improve their productivity and, in this way, better define the support of the work that CITEccal Trujillo has been doing to increase the competitiveness of companies in the footwear sector

Health-related quality of life in multiple sclerosis: Effects of natalizumab

Objective: To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods: HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-la (IFN-\u3b2-1a) plus natalizumab 300mg (n = 589), or IFN-\u3b2-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results: Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation: HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. \ua9 2007 American Neurological Association. Published by Wiley-Liss, Inc

Curriculum corruption? : On the place of subjects in secondary school curriculum making

The production of a W boson in association with a single charm quark is studied using 4.6 fb-1 of pp collision data at 1as = 7TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+-00.30 at Q2 = 1.9 GeV, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally the cross-section ratio \u3c3(W+ + c)/\u3c3(W- +c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s\u2013s quark asymmetry