Los Indicadores de calidad de agua como una herramienta para la integración de contenidos de recursos hídricos, mediante la metodología de enseñaza por proyectos

La enseñanza de las ciencias tiene potencialidades muy significativas para desarrollar competencias que requieren los alumnos para su desempeño en la sociedad, esto se lograría a través de dos procesos largos y complejos que son la alfabetización científica y la educación ambiental. Ambos procesos actúan como herramientas para la toma de medidas. Actualmente los temas relacionados con el medio ambiente, se han posicionado en las agendas sociales, políticas y educativas con gran fuerza. La enseñanza de temas medioambientales, dado su complejidad y su abordaje sistémico, implica la reformulación de las estrategias didácticas a utilizar. En particular, el método de enseñanza por proyectos, puede considerarse como apropiado para tal fin. Es por ello que esta metodología de enseñanza permite vincular temáticas o problemas que sean de interés para los alumnos y que merezcan ser tratados por sí mismos, como lo es el Índice de Calidad de Agua (ICA) del Arroyo del Azul, situado en el centro de la Pcia. de Buenos Aires. Así mismo, en el desarrollo de la presente ponencia se incluye la aplicación del ICA en agua del Arroyo del Azul, con el fin de reconocer su Calidad de Agua. Este tipo de trabajos permite reformular prácticas que lleven a los alumnos a trabajar en forma conjunta con el docente, el trabajo en temas que sean de interés o que tengan un significado en la sociedad y que los alumnos realicen actividades y experiencias que los lleve a comprender y realizar un cambio conceptual.Trabajos del área Ciencias NaturalesDepartamento de Ciencias Exactas y Naturale

Los Indicadores de calidad de agua como una herramienta para la integración de contenidos de recursos hídricos, mediante la metodología de enseñaza por proyectos

La enseñanza de las ciencias tiene potencialidades muy significativas para desarrollar competencias que requieren los alumnos para su desempeño en la sociedad, esto se lograría a través de dos procesos largos y complejos que son la alfabetización científica y la educación ambiental. Ambos procesos actúan como herramientas para la toma de medidas. Actualmente los temas relacionados con el medio ambiente, se han posicionado en las agendas sociales, políticas y educativas con gran fuerza. La enseñanza de temas medioambientales, dado su complejidad y su abordaje sistémico, implica la reformulación de las estrategias didácticas a utilizar. En particular, el método de enseñanza por proyectos, puede considerarse como apropiado para tal fin. Es por ello que esta metodología de enseñanza permite vincular temáticas o problemas que sean de interés para los alumnos y que merezcan ser tratados por sí mismos, como lo es el Índice de Calidad de Agua (ICA) del Arroyo del Azul, situado en el centro de la Pcia. de Buenos Aires. Así mismo, en el desarrollo de la presente ponencia se incluye la aplicación del ICA en agua del Arroyo del Azul, con el fin de reconocer su Calidad de Agua. Este tipo de trabajos permite reformular prácticas que lleven a los alumnos a trabajar en forma conjunta con el docente, el trabajo en temas que sean de interés o que tengan un significado en la sociedad y que los alumnos realicen actividades y experiencias que los lleve a comprender y realizar un cambio conceptual.Trabajos del área Ciencias NaturalesDepartamento de Ciencias Exactas y Naturale

Recent Technological Developments on LGAD and iLGAD Detectors for Tracking and Timing Applications

This paper reports the last technological development on the Low Gain Avalanche Detector (LGAD) and introduces a new architecture of these detectors called inverse-LGAD (iLGAD). Both approaches are based on the standard Avalanche Photo Diodes (APD) concept, commonly used in optical and X-ray detection applications, including an internal multiplication of the charge generated by radiation. The multiplication is inherent to the basic n++-p+-p structure, where the doping profile of the p+ layer is optimized to achieve high field and high impact ionization at the junction. The LGAD structures are optimized for applications such as tracking or timing detectors for high energy physics experiments or medical applications where time resolution lower than 30 ps is required. Detailed TCAD device simulations together with the electrical and charge collection measurements are presented through this work.Comment: Keywords: silicon detectors, avalanche multiplication, timing detectors, tracking detectors. 8 pages. 8 Figure

Gain and time resolution of 45 μ\mum thin Low Gain Avalanche Detectors before and after irradiation up to a fluence of 101510^{15} neq_{eq}/cm2^2

Low Gain Avalanche Detectors (LGADs) are silicon sensors with a built-in charge multiplication layer providing a gain of typically 10 to 50. Due to the combination of high signal-to-noise ratio and short rise time, thin LGADs provide good time resolutions. LGADs with an active thickness of about 45 $\mu$m were produced at CNM Barcelona. Their gains and time resolutions were studied in beam tests for two different multiplication layer implantation doses, as well as before and after irradiation with neutrons up to $10^{15}$ n$_{eq}$/cm$^2$. The gain showed the expected decrease at a fixed voltage for a lower initial implantation dose, as well as for a higher fluence due to effective acceptor removal in the multiplication layer. Time resolutions below 30 ps were obtained at the highest applied voltages for both implantation doses before irradiation. Also after an intermediate fluence of $3\times10^{14}$ n$_{eq}$/cm$^2$, similar values were measured since a higher applicable reverse bias voltage could recover most of the pre-irradiation gain. At $10^{15}$ n$_{eq}$/cm$^2$, the time resolution at the maximum applicable voltage of 620 V during the beam test was measured to be 57 ps since the voltage stability was not good enough to compensate for the gain layer loss. The time resolutions were found to follow approximately a universal function of gain for all implantation doses and fluences.Comment: 17 page

Colon cancer subtypes: Concordance, effect on survival and selection of the most representative preclinical models

Multiple gene-expression-based subtypes have been proposed for the molecular subdivision of colon cancer in the last decade. We aimed to cross-validate these classifiers to explore their concordance and their power to predict survival. A gene-chip-based database comprising 2,166 samples from 12 independent datasets was set up. A total of 22 different molecular subtypes were re-trained including the CCHS, CIN25, CMS, ColoGuideEx, ColoGuidePro, CRCassigner, MDA114, Meta163, ODXcolon, Oncodefender, TCA19, and V7RHS classifiers as well as subtypes established by Budinska, Chang, DeSousa, Marisa, Merlos, Popovici, Schetter, Yuen, and Watanabe (first authors). Correlation with survival was assessed by Cox proportional hazards regression for each classifier using relapse-free survival data. The highest efficacy at predicting survival in stage 2-3 patients was achieved by Yuen (p = 3.9e-05, HR = 2.9), Marisa (p = 2.6e-05, HR = 2.6) and Chang (p = 9e-09, HR = 2.35). Finally, 61 colon cancer cell lines from four independent studies were assigned to the closest molecular subtype. © 2016 The Author(s)

Differential Scanning Fluorometry Signatures as Indicators of Enzyme Inhibitor Mode of Action: Case Study of Glutathione S-Transferase

Differential scanning fluorometry (DSF), also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST) as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH). Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization

Mutational Profiling of Kinases in Human Tumours of Pancreatic Origin Identifies Candidate Cancer Genes in Ductal and Ampulla of Vater Carcinomas

BACKGROUND: Protein kinases are key regulators of cellular processes (such as proliferation, apoptosis and invasion) that are often deregulated in human cancers. Accordingly, kinase genes have been the first to be systematically analyzed in human tumors leading to the discovery that many oncogenes correspond to mutated kinases. In most cases the genetic alterations translate in constitutively active kinase proteins, which are amenable of therapeutic targeting. Tumours of the pancreas are aggressive neoplasms for which no effective therapeutic strategy is currently available. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a DNA-sequence analysis of a selected set of 35 kinase genes in a panel of 52 pancreatic exocrine neoplasms, including 36 pancreatic ductal adenocarcinoma, and 16 ampulla of Vater cancer. Among other changes we found somatic mutations in ATM, EGFR, EPHA3, EPHB2, and KIT, none of which was previously described in cancers. CONCLUSIONS/SIGNIFICANCE: Although the alterations identified require further experimental evaluation, the localization within defined protein domains indicates functional relevance for most of them. Some of the mutated genes, including the tyrosine kinases EPHA3 and EPHB2, are clearly amenable to pharmacological intervention and could represent novel therapeutic targets for these incurable cancers

Beam test results of a 16 ps timing system based on ultra-fast silicon detectors

In this paper we report on the timing resolution of the first production of 50 micro-meter thick Ultra-Fast Silicon Detectors (UFSD) as obtained in a beam test with pions of 180 GeV/c momentum. UFSD are based on the Low-Gain Avalanche Detectors (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test belongs to the first production of thin (50 {\mu}m) sensors, with an pad area of 1.4 mm2. The gain was measured to vary between 5 and 70 depending on the bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution, determined comparing the time of arrival of the particle in one or more UFSD and the trigger counter, for single UFSD was measured to be 35 ps for a bias voltage of 200 V, and 26 ps for a bias voltage of 240 V, and for the combination of 3 UFSD to be 20 ps for a bias voltage of 200 V, and 15 ps for a bias voltage of 240 V.Comment: 7 pages, 8 figures, 1 table, Subm. to NIM

Völkisch und sozial? : Neonazistische Agitation gegen die neue EU-Freizügigkeit für Arbeitnehmerinnen

Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe

LGR6 Is a High Affinity Receptor of R-Spondins and Potentially Functions as a Tumor Suppressor

BACKGROUND: LGR6 (leucine-rich repeat containing, G protein-coupled receptor 6) is a member of the rhodopsin-like seven transmembrane domain receptor superfamily with the highest homology to LGR4 and LGR5. LGR6 was found as one of the novel genes mutated in colon cancer through total exon sequencing and its promoter region is hypermethylated in 20-50% of colon cancer cases. In the skin, LGR6 marks a population of stem cells that can give rise to all cell lineages. Recently, we and others demonstrated that LGR4 and LGR5 function as receptors of R-spondins to potentiate Wnt/β-catenin signaling. However, the binding affinity and functional response of LGR6 to R-spondins, and the activity of colon cancer mutants of LGR6 have not been determined. PRINCIPAL FINDINGS: We found that LGR6 also binds and responds to R-spondins 1-3 with high affinity to enhance Wnt/β-catenin signaling through increased LRP6 phosphorylation. Similar to LGR4 and LGR5, LGR6 is not coupled to heterotrimeric G proteins or to β-arrestin following R-spondin stimulation. Functional and expression analysis of three somatic mutations identified in colon cancer samples indicates that one mutant fails to bind and respond to R-spondin (loss-of-function), but the other two have no significant effect on receptor function. Overexpression of wild-type LGR6 in HeLa cells leads to increased cell migration following co-treatment with R-spondin1 and Wnt3a when compared to vector control cells or cells overexpressing the loss-of-function mutant. CONCLUSIONS: LGR6 is a high affinity receptor for R-spondins 1-3 and potentially functions as a tumor suppressor despite its positive effect on Wnt/β-catenin signaling