Identificación of ERBB4 and SOX1 role in central nervous system tumors. Implication in medulloblastoma and glioblastoma.

223 p.Los tumores cerebrales, como el glioblastoma (GBM) en adultos y el meduloblastoma (MB) en niños, representan uno de los retos más importantes de la medicina actual, ya que resisten a las terapias disponibles, recurren y se diseminan. Dichos tumores presentan una alta heterogeneidad, ya que albergan una subpoblación de células madre tumorales (CSCs), responsables de la metástasis, resistencia a tratamientos y recurrencia tumoral. Además, la desregulación de aquellos genes relacionados con el desarrollo embrionario y el mantenimiento de las células madre, como ERBB4 y SOX1, parece ser crítica para el desarrollo y la progresión del fenotipo canceroso. La presente tesis doctoral tiene como objetivo principal determinar la función de ambos genes en el GBM y el MB, así como establecer su relación con las CSCs específicas de cada tumor (GSCs y MBSCs, respectivamente). En primer lugar, observamos que ERBB4 tiene una función esencial en el desarrollo del cerebelo, controlando la población de las células progenitoras y su proceso de migración. Además, determinamos que ERBB4 se encuentra altamente expresado en los MBs del Grupo 4 y SOX1 en los del Grupo SHH, asociándose en ambos casos a una peor supervivencia. Al inhibir la expresión de ERBB4 y SOX1, observamos una reducción de la viabilidad celular, capacidad de autorrenovación, y de iniciación y progresión tumoral. Asimismo, identificamos un enriquecimiento de la expresión de SOX1 y ERBB4 en las MBSCs. También establecimos una relación entre la elevada expresión de SOX1 y una peor supervivencia en GBM, además del enriquecimiento de su expresión en las GSCs. Por último, al inhibir la expresión de SOX1 en GBM, observamos una disminución de la capacidad de proliferación, iniciación y progresión tumoral. En conjunto, nuestros resultados sugieren un papel oncogénico hasta ahora no descrito de ERBB4 y SOX1 en MB y GBM. Además, este trabajo propone la inhibición de ERBB4 y SOX1 como una estrategia terapéutica prometedora para atacar las CSCs y así combatir la resistencia a las terapias

Assertion-based Analysis via Slicing with ABETS

[EN] We present ABETS, an assertion-based, dynamic analyzer that helps diagnose errors in Maude programs. ABETS uses slicing to automatically create reduced versions of both a run's execution trace and executed program, reduced versions in which any information that is not relevant to the bug currently being diagnosed is removed. In addition, ABETS employs runtime assertion checking to automate the identification of bugs so that whenever an assertion is violated, the system automatically infers accurate slicing criteria from the failure. We summarize the main services provided by ABETS, which also include a novel assertionbased facility for program repair that generates suitable program fixes when a state invariant is violated. Finally, we provide an experimental evaluation that shows the performance and effectiveness of the system.This work has been partially supported by the EU (FEDER) and Spanish MINECO grant TIN2015-69175-C4-1-R, and by Generalitat Valenciana PROMETEOII/2015/013. J. Sapina was supported by FPI-UPV grant SP2013-0083.Alpuente Frasnedo, M.; Frechina, F.; Sapiña Sanchis, J.; Ballis, D. (2016). Assertion-based Analysis via Slicing with ABETS. Theory and Practice of Logic Programming. 16(5):515-532. https://doi.org/10.1017/S1471068416000375S51553216

Estrategias de reparación para sitios web incompletos

El desarrollo y mantenimiento de sitios Web no es un tarea fácil. Garantizar que la información de un sitio Web es consistente resulta cada vez más difícil, por ello los administradores Web necesitan de mecanismos que ayuden a reparar estas inconsistencias. En este trabajo, completamos la metodología de reparación semiautomática de sitios Web erróneos presentada en un trabajo anterior con el tratamiento de los errores de completitud. Comenzamos con la categorización de dichos errores mediante dos nuevos órdenes que definimos sobre el conjunto de errores de completitud obtenidos en el proceso de verificación. Utilizando estos ordenes, definimos sendas estrategias capaces de minimizar la cantidad de acciones de reparación a realizarse para generar un sitio Web completo con respecto a su especificación.IV Workshop de Ingeniería de Software y Base de DatosRed de Universidades con Carreras en Informática (RedUNCI

Estrategias de reparación para sitios web incompletos

El desarrollo y mantenimiento de sitios Web no es un tarea fácil. Garantizar que la información de un sitio Web es consistente resulta cada vez más difícil, por ello los administradores Web necesitan de mecanismos que ayuden a reparar estas inconsistencias. En este trabajo, completamos la metodología de reparación semiautomática de sitios Web erróneos presentada en un trabajo anterior con el tratamiento de los errores de completitud. Comenzamos con la categorización de dichos errores mediante dos nuevos órdenes que definimos sobre el conjunto de errores de completitud obtenidos en el proceso de verificación. Utilizando estos ordenes, definimos sendas estrategias capaces de minimizar la cantidad de acciones de reparación a realizarse para generar un sitio Web completo con respecto a su especificación.IV Workshop de Ingeniería de Software y Base de DatosRed de Universidades con Carreras en Informática (RedUNCI

Exploring Conditional Rewriting Logic Computations

[EN] Trace exploration is concerned with techniques that allow computation traces to be dynamically searched for specific contents. Depending on whether the exploration is carried backward or forward, trace exploration techniques allow provenance tracking or impact tracking to be done. The aim of provenance tracking is to show how (parts of) a program output depends on (parts of) its input and to help estimate which input data need to be modified to accomplish a change in the outcome. The aim of impact tracking is to identify the scope and potential consequences of changing the program input. Rewriting Logic (RWL) is a logic of change that supplements (an extension of) the equational logic by adding rewrite rules that are used to describe (nondeterministic) transitions between states. In this paper, we present a rich and highly dynamic, parameterized technique for the forward inspection of RWL computations that allows the nondeterministic execution of a given conditional rewrite theory to be followed up in different ways. With this technique, an analyst can browse, slice, filter, or search the traces as they come to life during the program execution. The navigation of the trace is driven by a user-defined, inspection criterion that specifies the required exploration mode. By selecting different inspection criteria, one can automatically derive a family of practical algorithms such as program steppers and more sophisticatedThis work has been partially supported by the EU (FEDER) and the Spanish MEC project Ref. TIN2010-21062-C02-02, the Spanish MICINN complementary action Ref. TIN2009-07495-E, and by Generalitat Valenciana Ref. PROMETEO2011/052. This work was carried out during the tenure of D. Ballis' ERCIM "Alain Bensoussan" Postdoctoral Fellowship. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement N. 246016. F. Frechina was supported by FPU-ME grant AP2010-5681, and J. Sapina was supported by FPI-UPV grant SP2013-0083.Alpuente Frasnedo, M.; Ballis, D.; Frechina Navarro, F.; Sapiña Sanchis, J. (2015). Exploring Conditional Rewriting Logic Computations. Journal of Symbolic Computation. 69:3-39. https://doi.org/10.1016/j.jsc.2014.09.028S3396

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed

Fixing Web Sites Using Correction Strategies 1

Abstract — The development and the maintenance of Web sites are difficult tasks. To maintain the consistency of everlarger, complex Web sites, Web administrators need effective mechanisms that aid them in fixing every possible inconsistency. In this paper, we present an extension of a methodology for semiautomatically repairing faulty Web site which we developed in a previous work. As a novel contribution, we define two correction strategies with the aim of increasing the level of automation of our repair method. Specifically, the proposed strategies minimize both the amount of information to be changed and the number of repair actions to be executed in a faulty Web site to make it correct. I

Filtering of XML Documents 1

Abstract — In this paper, we present a simple, easy-to-use, rewriting-like methodology for filtering information in an XML document. Essentially, we define a specification language which allows one to extract relevant data (positive filtering) as well as to exclude useless and misleading contents (negative filtering) from a set of XML documents according to some given criteria. We believe that our methodology achieves the right tradeoff between expressive power and simplicity of use, and thus it may be also fruitfully employed by those users who typically prefer to avoid formal languages. I