109 research outputs found

    Bringing Math teachers to ICT for teaching and learning

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    En este documento se presenta una primera fase de un proceso de introducción de tecnologías digitales de la información y comunicación (TICS) en formación de profesores de matemáticas en ejercicio del Departamento del Tolima en Colombia. Se han indagado los procesos cognitivos de representación en conexión con los tipos de procesos y pensamiento matemáticos definidos en los Lineamientos Curriculares para el área de Matemáticas en Colombia. Se han empleado 10 software libres en la red de Internet y se han encontrado índices de dificultad en la resolución de problemas y en el empleo de representaciones.This paper presents a first phase of a process of introducing digital technologies of information and communication (ICT) into mathematics teacher training in exercise of the Department of Tolima in Colombia. The inquiry explores the cognitive processes of representation in connection with the types of mathematical thinking and processes defined in the Curriculum Guidelines for Mathematics area in Colombia. Have been used 10 software free in the Internet and found rates of difficulty in problem solving and the use of representations

    Hallazgos Antropológicos y Arqueológicos en el Complejo Kárstico de El Sidron (Vallobal, Infesto, Concejo de Piloña, Asturias)

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    El Sidrón es conocido desde los años sesenta por sus manifestaciones artísticas paleolíticas y el yacimiento arqueológico que esta cavidad contiene. En 1994 fue descubierta una amplia colección de material óseo por parte de un grupo de espeleólogos que realizaba una travesía del sistema. Creyendo que se trataba de restos de cadáveres de la Guerra Civil española (1936-1939), informaron a la Guardia Civil de Infiesto quien, por orden del Juzgado de esta misma localidad, procedió a su remisión al Laboratorio de Antropología del Instituto Anatómico Forense de Madrid para su estudio. Este trabajo aporta los principales datos que recogía el informe inicial presentado a la Consejería de Cultura del Principado de Asturias a comienzos del mes de noviembre de 1998, destacando la presencia de restos óseos cuyos rasgos morfológicos y características biométricas mandibulares son compatibles con la presencia de, al menos tres individuos de la especie homo sapiens neanderthalensis, constituyendo un hallazgo antropológico y arqueológico de la máxima importancia

    Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.

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    CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC

    Reef state and performance as indicators of cumulative impacts on coral reefs

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    Coral bleaching, cyclones, outbreaks of crown-of-thorns seastar, and reduced water quality (WQ) threaten the health and resilience of coral reefs. The cumulative impacts from multiple acute and chronic stressors on “reef State” (i.e., total coral cover) and “reef Performance” (i.e., the deviation from expected rate of total coral cover increase) have rarely been assessed simultaneously, despite their management relevance. We evaluated the dynamics of coral cover (total and per morphological groups) in the Central and Southern Great Barrier Reef over 25 years, and identified and compared the main environmental drivers of State and Performance at the reef level (i.e. based on total coral cover) and per coral group. Using a combination of 25 environmental metrics that consider both the frequency and magnitude of impacts and their lagged effects, we find that the stressors that correlate with State differed from those correlating with Performance. Importantly, we demonstrate that WQ metrics better predict Performance than State. Further, inter-annual dynamics in WQ (here available for a subset of the data) improved the explanatory power of WQ metrics on Performance over long-term WQ averages. The lagged effects of cumulative acute stressors, and to a lesser extent poor water quality, correlated negatively with the Performance of some but not all coral groups. Tabular Acropora and branching non-Acropora were the most affected by water quality demonstrating that group-specific approaches aid in the interpretation of monitoring data and can be crucial for the detection of the impact of chronic pressures. We highlight the complexity of coral reef dynamics and the need of evaluating Performance metrics in order to prioritise local management interventions

    ¿Es la obesidad un factor de riesgo para el trastorno de déficit de atención con hiperactividad (TDAH)?

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    lteraciones en el desarrollo de la atencióny la organización conductual puedenconfigurar cuadros clínicos comoel trastorno déficit de atención (TDA) que puede estaracompañado o no de hiperactividad (TDAH), este últimoparece tener una relación directa con otros diagnósticosde tipo endocrino como la obesidad. El objetivo del estudioes analizar la relación que existe entre el TDAH y laobesidad. Es por ello que se realiza una revisión sistemáticade estudios científicos revelando relaciones y diferenciasentre ambos trastornos desde una mirada fisiológica,cognoscitiva y comportamental. Se concluye que la relaciónentre el TDAH y la obesidad se da por factores genéticos,por variaciones dopaminérgicas, cambios en patronesde sueño, desajustes emocionales y por alteraciones en laregulación de la conducta; igualmente influyen factoressociales relacionados con el cuidado en el embarazo y laalimentación de las mujeres antes y durante la gestación

    Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

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    <p>Abstract</p> <p>Background</p> <p>Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements.</p> <p>Results</p> <p>We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer-approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in <it>Saccharomyces cerevisiae</it>. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast <it>Saccharomyces cerevisiae </it>to heat shock</p> <p>Conclusion</p> <p>Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.</p

    Predicting Responses of Geo-ecological Carbonate Reef Systems to Climate Change: A Conceptual Model and Review

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    [Chapter Abstract] 230Coral reefs provide critical ecological and geomorphic (e.g. sediment production for reef-fronted shoreline maintenance) services, which interact in complex and dynamic ways. These services are under threat from climate change, requiring dynamic modelling approaches that predict how reef systems will respond to different future climate scenarios. Carbonate budgets, which estimate net reef calcium carbonate production, provide a comprehensive ‘snap-shot’ assessment of reef accretionary potential and reef stability. These budgets, however, were not intended to account for the full suite of processes that maintain coral reef services or to provide predictive capacity on longer timescales (decadal to centennial). To respond to the dual challenges of enhancing carbonate budget assessments and advancing their predictive capacity, we applied a novel model elicitation and review method to create a qualitative geo-ecological carbonate reef system model that links geomorphic, ecological and physical processes. Our approach conceptualizes relationships between net carbonate production, sediment transport and landform stability, and rates knowledge confidence to reveal major knowledge gaps and critical future research pathways. The model provides a blueprint for future coral reef research that aims to quantify net carbonate production and sediment dynamics, improving our capacity to predict responses of reefs and reef-fronted shorelines to future climate change.https://nsuworks.nova.edu/occ_facbooks/1116/thumbnail.jp

    Modelling and Analysis of Central Metabolism Operating Regulatory Interactions in Salt Stress Conditions in a L-Carnitine Overproducing E. coli Strain

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    Based on experimental data from E. coli cultures, we have devised a mathematical model in the GMA-power law formalism that describes the central and L-carnitine metabolism in and between two steady states, non-osmotic and hyperosmotic (0.3 M NaCl). A key feature of this model is the introduction of type of kinetic order, the osmotic stress kinetic orders (gOSn), derived from the power law general formalism, which represent the effect of osmotic stress in each metabolic process of the model

    PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

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    Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy

    RLIP76, a Glutathione-Conjugate Transporter, Plays a Major Role in the Pathogenesis of Metabolic Syndrome

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    PURPOSE: Characteristic hypoglycemia, hypotriglyceridemia, hypocholesterolemia, lower body mass, and fat as well as pronounced insulin-sensitivity of RLIP76⁻/⁻ mice suggested to us the possibility that elevation of RLIP76 in response to stress could itself elicit metabolic syndrome (MSy). Indeed, if it were required for MSy, drugs used to treat MSy should have no effect on RLIP76⁻/⁻ mice. RESEARCH DESIGN AND METHODS: Blood glucose (BG) and lipid measurements were performed in RLIP76⁺/⁺ and RLIP76⁻/⁻ mice, using Ascensia Elite Glucometer® for glucose and ID Labs kits for cholesterol and triglycerides assays. The ultimate effectors of gluconeogenesis are the three enzymes: PEPCK, F-1,6-BPase, and G6Pase, and their expression is regulated by PPARγ and AMPK. The activity of these enzymes was tested by protocols standardized by us. Expressions of RLIP76, PPARα, PPARγ, HMGCR, pJNK, pAkt, and AMPK were performed by Western-blot and tissue staining. RESULTS: The concomitant activation of AMPK and PPARγ by inhibiting transport activity of RLIP76, despite inhibited activity of key glucocorticoid-regulated hepatic gluconeogenic enzymes like PEPCK, G6Pase and F-1,6-BP in RLIP76⁻/⁻ mice, is a salient finding of our studies. The decrease in RLIP76 protein expression by rosiglitazone and metformin is associated with an up-regulation of PPARγ and AMPK. CONCLUSIONS/SIGNIFICANCE: All four drugs, rosiglitazone, metformin, gemfibrozil and atorvastatin failed to affect glucose and lipid metabolism in RLIP76⁻/⁻ mice. Studies confirmed a model in which RLIP76 plays a central role in the pathogenesis of MSy and RLIP76 loss causes profound and global alterations of MSy signaling functions. RLIP76 is a novel target for single-molecule therapeutics for metabolic syndrome
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