620 research outputs found

    Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

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    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA

    On the Core of Dynamic Cooperative Games

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    We consider dynamic cooperative games, where the worth of coalitions varies over time according to the history of allocations. When defining the core of a dynamic game, we allow the possibility for coalitions to deviate at any time and thereby to give rise to a new environment. A coalition that considers a deviation needs to take the consequences into account because from the deviation point on, the game is no longer played with the original set of players. The deviating coalition becomes the new grand coalition which, in turn, induces a new dynamic game. The stage games of the new dynamical game depend on all previous allocation including those that have materialized from the deviating time on. We define three types of core solutions: fair core, stable core and credible core. We characterize the first two in case where the instantaneous game depends on the last allocation (rather than on the whole history of allocations) and the third in the general case. The analysis and the results resembles to a great extent the theory of non-cooperative dynamic games.Comment: 25 page

    FLICK: developing and running application-specific network services

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    Data centre networks are increasingly programmable, with application-specific network services proliferating, from custom load-balancers to middleboxes providing caching and aggregation. Developers must currently implement these services using traditional low-level APIs, which neither support natural operations on application data nor provide efficient performance isolation. We describe FLICK, a framework for the programming and execution of application-specific network services on multi-core CPUs. Developers write network services in the FLICK language, which offers high-level processing constructs and application-relevant data types. FLICK programs are translated automatically to efficient, parallel task graphs, implemented in C++ on top of a user-space TCP stack. Task graphs have bounded resource usage at runtime, which means that the graphs of multiple services can execute concurrently without interference using cooperative scheduling. We evaluate FLICK with several services (an HTTP load-balancer, a Memcached router and a Hadoop data aggregator), showing that it achieves good performance while reducing development effort

    Matrix controlled channel diffusion of sodium in amorphous silica

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    To find the origin of the diffusion channels observed in sodium-silicate glasses, we have performed classical molecular dynamics simulations of Na2_2O--4SiO2_2 during which the mass of the Si and O atoms has been multiplied by a tuning coefficient. We observe that the channels disappear and that the diffusive motion of the sodium atoms vanishes if this coefficient is larger than a threshold value. Above this threshold the vibrational states of the matrix are not compatible with those of the sodium ions. We interpret hence the decrease of the diffusion by the absence of resonance conditions.Comment: 5 pages, 4 figure

    Metamorfosis del Contar. Semiosis/Memoria V. MassmediaciĂłn: formatos y dispositivos. 16H344

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    Se explora la prensa gråfica en soporte papel y digital como complejo mnemosemiótico y comunicativo, para dar cuenta de la conformación y las características de este tipo de dispositivo performativo. Se indaga y analiza, con un enfoque interdisciplinar (Semiótica, Anålisis del Discurso, Comunicación) y desde una perspectiva crítica y política, el diario en su totalidad y el trabajo de massmediación que lleva a cabo este tipo de textualidad compleja. Se pretende describir y caracterizar el formato, sus matrices semio-discursivas y comunicativas, y relevar y analizar los diversos géneros y discursos que lo conforman

    Efeitos de um Programa de Intervenção Baseado no Modelo Integral nas CompetĂȘncias TĂ©cnico-TĂĄcticas no Futebol

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    Resumen: El objetivo del presente estudio es comprobar los efectos de un programa de intervenciĂłn basado en el modelo comprensivo sobre las habilidades tĂ©cnico – tĂĄcticas en fĂștbol. La muestra estuvo conformada por 36 jugadores (11.1 ± 0.5 años) de dos equipos de fĂștbol formativo. El diseño del estudio ha sido cuasiexperimental pre – post con grupo control y el instrumento de recolecciĂłn de datos utilizado fue la Herramienta Observacional de EvaluaciĂłn TĂ©cnico – TĂĄctica (HOET-T). Para el anĂĄlisis de los datos se utilizĂł la prueba t student para muestras emparejadas y los principales resultados demuestran que el programa de intervenciĂłn basado en el modelo comprensivo mejoro significativamente las habilidades tĂ©cnico – tĂĄcticas de proteger el balĂłn, recuperar el balĂłn, avanzar hacia la meta, obstaculizar el avance hacia la meta y el juego colectivo en ofensiva con y sin balĂłn. En conclusiĂłn, el modelo comprensivo mejora el desarrollo de habilidades tĂ©cnico – tĂĄcticas individuales y colectivas en ofensiva y en defensiva contribuyendo a la adquisiciĂłn de aprendizajes significativos del fĂștbol en los procesos de formaciĂłn deportiva.Abstract: The aim of this study is to test the effects of an intervention program based on the comprehensive model on technical-tactical skills in soccer. The sample consisted of 36 players (11.1 ± 0.5 years) from two youth soccer teams. The study design was quasi-experimental pre-post with a control group and the data collection instrument used was the Observational Technical-Tactical Evaluation Tool (HOET-T). For data analysis, the t student test was used for paired samples and the main results show that the intervention program based on the comprehensive model significantly improved the technical-tactical skills of protecting the ball, recovering the ball, advancing towards the goal, hindering the advance towards the goal and collective offensive play with and without the ball. In conclusion, the comprehensive model improves the development of individual and collective technical-tactical skills in offense and defense, contributing to the acquisition of significant soccer learning in sports training processes.Resumo: O objetivo do presente estudo Ă© testar os efeitos de um programa de intervenção baseado no modelo compreensivo sobre as competĂȘncias tĂ©cnico-tĂĄcticas no futebol. A amostra foi constituĂ­da por 36 jogadores (11,1 ± 0,5 anos) de duas equipas de futebol juvenil. O desenho do estudo foi quasi-experimental prĂ©-pĂłs com um grupo de controlo e o instrumento de recolha de dados utilizado foi o Observational Technical-Tactical Evaluation Tool (HOET-T). Para a anĂĄlise dos dados utilizĂĄmos o teste t student para amostras emparelhadas e os principais resultados mostram que o programa de intervenção baseado no modelo integral melhorou significativamente as competĂȘncias tĂ©cnico-tĂĄcticas de proteção da bola, recuperação da bola, avanço para a baliza, impedimento do avanço para a baliza e jogo coletivo ofensivo com e sem bola. Em conclusĂŁo, o modelo compreensivo melhora o desenvolvimento das capacidades tĂ©cnico-tĂĄcticas individuais e colectivas no jogo ofensivo e defensivo, contribuindo para a aquisição de aprendizagens futebolĂ­sticas significativas no processo de treino desportivo

    Preferencias del tratamiento en pacientes con Espondiloartritis axial

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    IntroducciĂłn: una de las premisas del Treat to Target (T2T) es la decisiĂłn conjunta del tratamiento entre el reumatĂłlogo y el paciente. Por esta razĂłn las preferencias del paciente juegan un rol fundamental en el Ă©xito del tratamiento a corto y largo plazo. El objetivo de este estudio fue evaluar las preferencias de tratamiento de los pacientes con Espondiloartritis axial (EsPax) e identificar factores asociados a su elecciĂłn

    The new resilience of emerging and developing countries: systemic interlocking, currency swaps and geoeconomics

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    The vulnerability/resilience nexus that defined the interaction between advanced and developing economies in the post-WWII era is undergoing a fundamental transformation. Yet, most of the debate in the current literature is focusing on the structural constraints faced by the Emerging and Developing Countries (EDCs) and the lack of changes in the formal structures of global economic governance. This paper challenges this literature and its conclusions by focusing on the new conditions of systemic interlocking between advanced and emerging economies, and by analysing how large EDCs have built and are strengthening their economic resilience. We find that a significant redistribution of ‘policy space’ between advanced and emerging economies have taken place in the global economy. We also find that a number of seemingly technical currency swap agreements among EDCs have set in motion changes in the very structure of global trade and finance. These developments do not signify the end of EDCs’ vulnerability towards advanced economies. They signify however that the economic and geoeconomic implications of this vulnerability have changed in ways that constrain the options available to advanced economies and pose new challenges for the post-WWII economic order

    Climate drives fire synchrony but local factors control fire regime change in northern Mexico

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    The occurrence of wildfire is influenced by a suite of factors ranging from “top-down” influences (e.g., climate) to “bottom-up” localized influences (e.g., ignitions, fuels, and land use). We carried out the first broad-scale assessment of wildland fire patterns in northern Mexico to assess the relative influence of top-down and bottom-up drivers of fire in a region where frequent fire regimes continued well into the 20th century. Using a network of 67 sites, we assessed (1) fire synchrony and the scales at which synchrony is evident, (2) climate drivers of fire, and (3) asynchrony in fire regime changes. We found high fire synchrony across northern Mexico between 1750 and 2008, with synchrony highest at distances oscillations, especially El Niño-Southern Oscillation, were important drivers of fire synchrony. However, bottom-up factors modified fire occurrence at smaller spatial scales, with variable local influence on the timing of abrupt, unusually long fire-free periods starting between 1887 and 1979 CE. Thirty sites lacked these fire-free periods. In contrast to the neighboring southwestern United States, many ecosystems in northern Mexico maintain frequent fire regimes and intact fire–climate relationships that are useful in understanding climate influences on disturbance across scales of space and time

    Locomotor adaptability in persons with unilateral transtibial amputation

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    Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb
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