Ubiquitylation in immune disorders and cancer: from molecular mechanisms to therapeutic implications

Conjugation of ubiquitin to proteins (ubiquitylation) has emerged to be one of the most crucial post-translational modifications controlling virtually all cellular processes. What was once regarded as a mere signal for protein degradation has turned out to be a major regulator of molecular signalling networks. Deregulation of ubiquitin signalling is closely associated with various human pathologies. Here, we summarize the current knowledge of ubiquitin signalling in immune deficiencies and cancer as well as the available therapeutic strategies targeting the ubiquitin system in combating these pathogenic conditions

Ubiquitylation in immune disorders and cancer: from molecular mechanisms to therapeutic implications

Conjugation of ubiquitin to proteins (ubiquitylation) has emerged to be one of the most crucial post-translational modifications controlling virtually all cellular processes. What was once regarded as a mere signal for protein degradation has turned out to be a major regulator of molecular signalling networks. Deregulation of ubiquitin signalling is closely associated with various human pathologies. Here, we summarize the current knowledge of ubiquitin signalling in immune deficiencies and cancer as well as the available therapeutic strategies targeting the ubiquitin system in combating these pathogenic conditions

Dynamic Pricing, Advanced Metering, and Demand Response in Electricity Markets

Presents an overview and analysis of the possible approaches to bringing an active demand side into electricity markets. Part of a series of research reports that examines energy issues facing California

Addressing Genetic Tumor Heterogeneity through Computationally Predictive Combination Therapy

Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. We use RNA interference to model heterogeneous tumors, and demonstrate successful validation of computational predictions for how optimized drug combinations can yield superior effects on these tumors both in vitro and in vivo. Importantly, we discover here that for many such tumors knowledge of the predominant subpopulation is insufficient for determining the best drug combination. Surprisingly, in some cases, the optimal drug combination does not include drugs that would treat any particular subpopulation most effectively, challenging straightforward intuition. We confirm examples of such a case with survival studies in a murine preclinical lymphoma model. Altogether, our approach provides new insights about design principles for combination therapy in the context of intratumoral diversity, data that should inform the development of drug regimens superior for complex tumors.National Cancer Institute (U.S.) (NCI Integrative Cancer Biology Program (ICBP), Grant U54-CA112967-06)National Institutes of Health (U.S.) (NIH/National Institute of General Medical Sciences (NIGMS) Interdepartmental Biotechnology Training Program, 5T32GM008334)National Cancer Institute (U.S.) (Koch Institute Support (core) Grant P30-CA14051

Encouraging learners to speak fluently using in-context photography through community based learning activities

1 archivo de lectura en pdf.​El propósito de este proyecto es determinar los efectos del uso de fotografías en contexto para mejorar la fluidez oral a través del enfoque de aprendizaje basado en la comunidad. Esta investigación de acción colaborativa fue realizada con 60 estudiantes de octavo grado con nivel pre A1, de dos instituciones en Colombia. Las instituciones CEDID Ciudad Bolívar y Marco Antonio Carreño Silva, de carácter público en la capital de Colombia. En estudios anteriores sobre el aprendizaje basado en la comunidad, los investigadores aplicaron estrategias interesantes para desarrollar las habilidades de producción oral y escrita, mediante el uso de ayudas visuales como las herramientas primarias. Investigaciones locales anteriores han demostrado un desarrollo curricular de parte de los profesores, la investigación del alumnado y la de alfabetización en inglés. Sin embargo, estas se han centrado principalmente en habilidades de pensamiento crítico y no se han concentrado en la mejora de una habilidad particular de la lengua, específicamente de producción oral. Estos estudios no se centraron en el uso de fotografías orientadas a la comunidad para fomentar la fluidez oral, que es el foco de esta investigación. A lo largo de la intervención pedagógica, las docentes (quienes también actuaron como investigadoras) compilaron información a través de fotografías, artefactos, rúbricas, y vídeos. También, se implementó una encuesta al final de cada una de las tres etapas de la implementación pedagógica para recoger información sobre los estudiantes y su desempeño

Teaching Material Development with Challenge Based Learning (CBL) Basis to Improve Critical Thinking Ability on Human Reproduction System Material of Class XI IPA 4 Students at MAN Pinrang

The study aims at (1) developing teaching material based on Challenge Based Learning (CBL) basis in Human Reproduction System material, (2) Obtaining data of validity and effectiveness of teaching material with CBL basis on Reproduction System material, and (3) describing students critical thinking ability improvement after teaching by using teaching material based on CBL. The study is research and development. The study was conducted at MAN Pinrang in March 2016 to June 2016. The subject of the study was the students of class XII IPA 4 at MAN Pinrang of academic year 2015/2016 which consisted of 38 students. The development design referred to 4D development model by Thiagarajan consist of 4 stages, namely defining, design, development, dissemination with the teaching product in forms of student`s book with CBL basis and student`s work sheet with CBL basis. The result of the study reveal that (1) the teaching material with CBL basis developed has met valid criteria with the total mean score for all assessment indicators V=100%. The validity of teaching material is stated at the level of strong relevancy with content validity coefficient more than 0.75 or V>75% from the ideal score 100%, (2) the teaching material with CBL basis has met effective criteria based on the result of students` response on students` book with the mean of positive response is  97.37% and the response on the student`s work sheet with the mean of positive response is 91.58%; (3) the critical thinking ability of grade XI IPA 4 students at MAN Pinrang after being taught by employing teaching material with CBL basis has improved by 18.34 with the mean score 61.06 in cycle I and 75.39 in cycle II.Keywords: Challenge Based Learning, Critical Thinking Ability

Assessment in the Use of Excel Competency for Problem Solving Using the Approach of Expert and Novice Theory

The assessment of Competency-Based Learning (CBL) generally lacks a foundation to guide the construction of instruments that accords the nature and goals of this educational model. The measurement instruments normally used in CBL only provide a numerical score with limited information about the levels of competencies reached. This research aims to outline an assessment model that gives room to infer the individual's level of achieved competencies. The study is grounded in the theory of experts and novices and employed a mixed methodology in order not only to discover the measurement of the levels of competency from a numerical perspective but also to qualitatively understand how the students achieve a certain level of expertise in a concrete disciplinary area. The focus of this research study was on problem solving using Excel. Five professors participated in criteria selection, problem design, and the assessment process. We concluded that CBL assessment can be implemented in a more integral way when supported by theoretical frameworks that permit instructors to assess students' achievements and give more effective feedback related to their strengths and weaknesses.L’évaluation de l’apprentissage basé sur la compétence n’a pas, de façon générale, de fondement pour guider la construction d’instruments qui cadrent avec la nature et les objectifs de ce modèle éducatif. Les instruments de mesure normalement utilisés en apprentissage basé sur la compétence fournissent uniquement une note numérique et des données limitées quant aux niveaux de compétences acquises. Cette recherche veut fournir un aperçu d’un modèle d’évaluation qui comporte une marge permettant de déduire le niveau de compétences acquises par les élèves. L’étude s’appuie sur la théorie des experts et des débutants. Elle repose sur une méthodologie mixte de sorte à découvrir comment mesurer les niveaux de compétence à partir de valeurs numériques, ainsi que comment comprendre, de façon qualitative, comment les élèves atteignent un certain niveau d’expertise dans un domaine concret. La recherche misait la résolution de problèmes en utilisant Excel. Cinq professeurs ont participé à la sélection des critères, à la conception des problèmes et au processus d’évaluation. Nous avons conclu que l’évaluation de l’apprentissage basé sur la compétence peut être mise en œuvre de manière plus intégrée quand elle est appuyée par des cadres théoriques permettant aux enseignants d’évaluer les performances des élèves et fournir de la rétroaction plus efficace sur leurs forces et leurs faiblesses

Simulation of a Clustering Scheme for Vehicular Ad Hoc Networks Using a DEVS-based Virtual Laboratory Environment

ANT 2018, The 9th International Conference on Ambient Systems, Networks and Technologies, Porto, PORTUGAL, 08-/05/2018 - 11/05/2018Protocol design is usually based on the functional models developed according to the needs of the system. In Intelligent Transport Systems (ITS), the features studied regarding Vehicular Ad hoc Networks (VANET) include self-organizing, routing, reliability, quality of service, and security. Simulation studies on ITS-dedicated routing protocols usually focus on their performance in specific scenarios. However, the evolution of transportation systems towards autonomous vehicles requires robust protocols with proven or at least guaranteed properties. Though formal approaches provide powerful tools for system design, they cannot be used for every types of ITS components. Our goal is to develop new tools combining formal tools such as Event-B with DEVS-based (Discrete Event System Specification) virtual laboratories in order to design the models of ITS components which simulation would allow proving and verifying their properties in large-scale scenarios. This paper presents the models of the different components of a VANET realized with the Virtual Laboratory Environment (VLE). We point out the component models fitting to formal modeling, and proceed to the validation of all designed models through a simulation scenario based on real-world road traffic data