Diabetes Mellitus and Reprogrammed Glucose Metabolism in Pancreatic Cancer: Features for Clinical Translation

The reprogrammed metabolism of cancer cells underlies the shift of glucose energetics from the highly efficient oxidative phosphorylation to the less efficient aerobic glycolysis, the Warburg effect. This phenomenon, with the activation of the glutamine pathway, advantage survival and proliferation of pancreatic ductal adenocarcinoma (PDAC) cells, which live in an adverse hypoxic and nutrient restricted microenvironment. In PDAC, glucose metabolic alterations occur also at the whole organism, diabetes mellitus (DM) being diagnosed in approximately 60% to 80% of patients. The association beteen PDAC and DM is a dual face phenomenon, DM being both a risk factor for and a consequence of this tumor type. Data from epidemiology indicate that longstanding DM increases PDAC risk 1.5 to 2.0 fold, probably because of the pro-proliferative effects of hyperinsulinemia. By contrast early onset DM, i.e. diabetes diagnosed no more than two years prior to cancer diagnosis, is considered a consequence of PDAC. Secondary DM is due to complex interactions between tumor cells, tumor microenvironment and pancreatic endocrine cells. In this scenario the role of the inflammatory S100A8 calcium binding protein, matrix metalloproteinases, Vanin1 or amylin has been experimentally demonstrated. However, the efforts made to translate in the clinical practice any individual new poteantial biomarker failed, because none reached enough sensitivity and specificity to be considered a reliable biomarker to diagnose PDAC even in high risk subjects as those with new onset DM. Therefore the identification and clinical validation of new biomarkers remains a challenge for future studies

Is there such a thing as free government data?

The recently-amended European Public Sector Information (PSI) Directive rests on the assumption that government data is a valuable input for the knowledge economy. As a default principle, the directive sets marginal costs as an upper bound for charging PSI. This article discusses the terms under which the 2013 consultation on the implementation of the PSI Directive addresses the calculation criteria for marginal costs, which are complex to define, especially for internet-based services. What is found is that the allowed answers of the consultation indirectly lead the responder to reason in terms of the average incremental cost of allowing reuse, instead of the marginal cost of reproduction, provision and dissemination. Moreover, marginal-cost pricing (or zero pricing) is expected to lead to economically efficient results, while aiming at recouping the average incremental cost of allowing re-use may lead to excessive fees

micro and macro modelling approaches for the evaluation of the carbon impacts of transportation

Abstract To quantify CO2 emissions from road transport, literature suggests the adoption of several alternative methods, based on transport modelling and carbon modules. Some of these methods are labelled as a micro approach and others as a macro approach. Their distinction is made according to the temporal and spatial horizons, the aim of the study and the degree of accuracy required. This paper presents these methods and discusses their appropriateness, whereby special focus is laid on the potential of the micro approach on ICT, based on a literature review of several European projects. We conclude that the adoption of the micro approach, is quite promising – mostly at the urban level, despite the computational efforts required and the technical difficulties to model driver behaviors. Thus, further research is required to overcome the numerous sources of scientific uncertainties

Inflammatory bowel diseases: from pathogenesis to laboratory testing

Inflammatory bowel diseases (IBDs), which comprise the two major clinical subtypes, Crohn's disease and ulcerative colitis, incur high morbidity and potential mortality. The present study reviews data on the pathogenesis and diagnosis of IBDs. The pathogenesis depends on complex interactions between susceptibility genes, environmental factors, and innate and adaptive immunity, the understanding of which is crucial to discovering novel laboratory biomarkers. Traditional laboratory tests for the diagnosis, prognosis and assessment of disease activity of IBDs are reported on, and the biochemical properties, pre-analytical and analytical aspects and clinical utility of the fecal markers lactoferrin and calprotectin are described. DNA testing and established (ASCA and pANCA) and emerging (ACCA, ALCA, AMCA, OmpC) serum markers are described; a further aspect to be addressed is the clinical use of pharmacogenetics for the treatment of IBDs

Collaborative Open Data versioning: a pragmatic approach using Linked Data

Most Open Government Data initiatives are centralised and unidirectional (i.e., they release data dumps in CSV or PDF format). Hence for non trivial applications reusers make copies of the government datasets to curate their local data copy. This situation is not optimal as it leads to duplication of efforts and reduces the possibility of sharing improvements. To improve the usefulness of publishing open data, several authors recommeded to use standard formats and data versioning. Here we focus on publishing versioned open linked data (i.e., in RDF format) because they allow one party to annotate data released independently by another party thus reducing the need to duplicate entire datasets. After describing a pipeline to open up legacy-databases data in RDF format, we argue that RDF is suitable to implement a scalable feedback channel, and we investigate what steps are needed to implement a distributed RDFversioning system in production

Unidos y separados : La configuración de un peronismo progresista en la década del 80

Nuestro interés en este trabajo se centra en analizar de qué modo el grupo de intelectuales que conforma Unidos construye un espacio simbólico propio, y cómo, desde ese espacio, buscan intervenir en las discusiones de la política partidaria. En este sentido, pensamos a la publicación como un escenario de consensos y conflictos permanentes, no solo debido a los acuerdos o diferencias de sus propios integrantes, sino también debido a la constante redefinición del vínculo entre intelectuales y política que allí se gestiona. Si bien la revista nuclea a un grupo de intelectuales, su voluntad de intervenir en la política hará que una gran parte de ellos termine ocupando cargos políticos durante el período analizado, trasgrediendo el mero papel de intelectuales ajenos al compromiso partidario. Las preguntas que pretendemos responder en este trabajo buscan tanto reconstruir la identidad política que el grupo intenta forjar, como entender el lugar desde el cual lo hacen y el contexto en el que lo hacen. Al reivindicarse como peronistas, quienes escriben en Unidos ¿qué elementos del peronismo rescatan y cuales desechan? ¿De qué forma consiguen integrar esos elementos en un relato que logre coherencia y resulte útil para la nueva coyuntura política? ¿Qué relaciones establecen, en el plano discursivo, con otros sectores dentro del peronismo tales como la Renovación, la ortodoxia peronista o el menemismo? ¿Qué visión sostienen del alfonsinismo y de qué forma programan una alternativa al gobierno?Facultad de Humanidades y Ciencias de la Educació

The renewal peronism in question: an approach to the experience of peronism during the '80s

Este trabajo recorre la experiencia sufrida por el peronismo durante la década del ‘80, prestando especial atención a la fracción conocida con el nombre de Renovación Peronista. Los renovadores, que en un comienzo se definieron en contraposición a los dirigentes ortodoxos que controlaban el PJ, irán paulatinamente ganado espacios dentro del partido hasta lograr acceder a su control formal a comienzos de 1988. Una vez desplazados los ortodoxos de las posiciones de poder dentro del PJ, se desatará en el interior del grupo renovador un enfrentamiento entre sus dos máximos representantes, Antonio Cafiero y Carlos Menem, produciendo una severa modificación en la composición y el sentido de la Renovación. Comprender los procesos que desencadenaron el origen y el desarrollo posterior de la Renovación es el objetivo primario de este artículo, así como también explorar su identidad dentro del contexto político argentino.This article surveys the experience suffered by Peronism during the '80s, with special attention to the fraction known as the Renewal Peronism. The renewals, which at first were defined in opposition to the orthodox leaders who controlled the PJ, will gradually won spaces within the party to gain access to formal control in early 1988. Once displaced the orthodox from positions of power within the PJ, was unleashed a confrontation inside the renewal fraction between its two top representatives, Antonio Cafiero and Carlos Menem, causing a severe change in the composition and direction of the Renewal Peronism. To understand the processes that triggered the origin and subsequent growth of the Renewal Peronism is the primary objective of this article, as well as explore their identity within the political context of Argentina.Facultad de Humanidades y Ciencias de la Educació

SMAD4 loss enables EGF, TGF\u3b21 and S100A8/A9 induced activation of critical pathways to invasion in human pancreatic adenocarcinoma cells

Epidermal Growth Factor (EGF) receptor overexpression, KRAS, TP53, CDKN2A and SMAD4 mutations characterize pancreatic ductal adenocarcinoma. This mutational landscape might influence cancer cells response to EGF, Transforming Growth Factor \u3b21 (TGF\u3b21) and stromal inflammatory calcium binding proteins S100A8/A9. We investigated whether chronic exposure to EGF modifies in a SMAD4-dependent manner pancreatic cancer cell signalling, proliferation and invasion in response to EGF, TGF\u3b21 and S100A8/A9. BxPC3, homozigously deleted (HD) for SMAD4, and BxPC3-SMAD4+ cells were or not stimulated with EGF (100 ng/mL) for three days. EGF pre-treated and non pretreated cells were stimulated with a single dose of EGF (100 ng/mL), TGF\u3b21 (0,02 ng/mL), S100A8/A9 (10 nM). Signalling pathways (Reverse Phase Protein Array and western blot), cell migration (Matrigel) and cell proliferation (XTT) were evaluated. SMAD4 HD constitutively activated ERK and Wnt/\u3b2-catenin, while inhibiting PI3K/AKT pathways. These effects were antagonized by chronic EGF, which increased p-BAD (anti-apoptotic) in response to combined TGF\u3b21 and S100A8/A9 stimulation. SMAD4 HD underlied the inhibition of NF-\u3baB and PI3K/AKT in response to TGF\u3b21 and S100A8/A9, which also induced cell migration. Chronic EGF exposure enhanced cell migration of both BxPC3 and BxPC3-SMAD4+, rendering the cells less sensitive to the other inflammatory stimuli. In conclusion, SMAD4 HD is associated with the constitutive activation of the ERK and Wnt/\u3b2-catenin signalling pathways, and favors the EGF-induced activation of multiple signalling pathways critical to cancer proliferation and invasion. TGF\u3b21 and S100A8/A9 mainly inhibit NF-\u3baB and PI3K/AKT pathways and, when combined, sinergize with EGF in enhancing anti-apoptotic p-BAD in a SMAD4-dependent manner

Deserenata : Composición de una obra electroacústica para sitio específico

Deserenata es un obra electroacústica peripatética1 para sitio específico compuesta para participar de las Primeras Jornadas de Músicas Actuales NuJaS 2017, organizadas en el Conservatorio Provincial Gilardo Gilardi de la ciudad de La Plata (CPGG). El trabajo se dividió en cuatro etapas. I: prospección acústica de los posibles sitios de interés dentro del edificio del CPGG. II: configuración de la electroacústica, generación y selección del material sonoro. III: producción de la obra. IV: presentación y evaluación de la obra.Facultad de Arte