Caracterización de la pérdida del gen NOMO1 en cáncer colorrectal

[ES] A nivel global, el cáncer colorrectal es el tercer tumor más frecuente y la segunda causa de muerte por cáncer, generando más de 900.000 fallecimientos cada año. El CCR se considera una enfermedad del adulto mayor donde la edad es el factor más influyente para su aparición, en consonancia con la mayoría de las enfermedades neoplásicas. Sin embargo, aunque la incidencia del CCR está en aumento debido al envejecimiento poblacional, la mortalidad por este tipo de tumor ha ido disminuyendo. Esto se debe a la implementación y mejora de los programas de cribado para el diagnóstico precoz a los que se someten las personas mayores de 50 años, así como a la aparición de estrategias terapéuticas más eficaces. En cambio, la incidencia del cáncer colorrectal en pacientes menores de 50 años (EOCRC) ha aumentado considerablemente en las últimas décadas, representando en el momento actual el 10% del total de casos de CCR. Así, el EOCRC esporádico (75-80% de todos los casos de EOCRC) presenta importantes limitaciones, tanto para su diagnóstico precoz como para la identificación de biomarcadores específicos que permitan diagnosticar, pronosticar y diseñar planes de tratamiento eficientes. Este subgrupo de pacientes se caracteriza por un diagnóstico de la enfermedad en estadio avanzado, peor pronóstico y por presentar fenotipos más agresivos del tumor. Sin embargo, a diferencia del CCR de aparición tardía, las bases genéticas y los mecanismos de carcinogénesis implicados en el EOCRC son, hoy en día, una incógnita por resolver. Un estudio preliminar de nuestro grupo, con el objetivo de identificar diferencias moleculares entre el CCR de aparición temprana y tardía, identificó una deleción recurrente en la región cromosómica 16p13.12-p13.11 en pacientes con EOCRC esporádico. Dentro de esta región se localiza el gen NOMO1, delecionado en homocigosis de forma somática en más del 80% de los casos de EOCRC, independientemente del estado de la región 16p156. Además, la pérdida en heterocigosis del gen NOMO1 también fue identificada en lesiones benignas precursoras de la enfermedad (pólipos). Con todo esto, la deleción del gen NOMO1 se posiciona como una alteración recurrente en EOCRC, aunque se desconocen los mecanismos moleculares alterados en tumores con este perfil genómico. Por ello, en este trabajo de tesis doctoral se hipotetiza que la pérdida del gen NOMO1 podría ser un evento precoz en el desarrollo del EOCRC, por lo que podría utilizarse como un biomarcador de malignización. Vistos estos antecedentes, se propusieron los siguientes objetivos con el fin de identificar los mecanismos moleculares que podrían estar alterados en aquellos tumores con inactivación de NOMO1: 1. Caracterizar funcionalmente la pérdida de NOMO1 en cáncer colorrectal de aparición temprana (EOCRC). 1.1 Generar distintas líneas celulares knockout (KO) para NOMO1 mediante el sistema de edición génica CRISPR/cas9. 1.2 Caracterizar el fenotipo de las líneas celulares NOMO1-KO. 1.3 Identificar posibles rutas de señalización alteradas tras la inactivación de NOMO1 mediante el análisis del perfil transcriptómico y proteómico de las líneas celulares carentes de este gen. 2. Determinar si la pérdida de Nomo1 es una mutación driver o passenger en EOCRC. 2.1 Generar un modelo murino condicional para Nomo1 mediante la herramienta de edición génica CRISPR/cas9. 2.2 Realizar un análisis anatomopatológico de los modelos murinos con inactivación de Nomo1. 3. Analizar la sensibilidad al tratamiento con 5-fluorouracilo, irinotecán, oxaliplatino y cisplatino de las líneas celulares carentes de NOMO1. 4. Estudiar la longitud telomérica y analizar su implicación en EOCRC

A suitable integral equation for the quasi-TEM analysis of hybrid strip/slot-like structures

This paper reports on a suitable formulation of the spectraldomain/integral-equation method for the quasi-TEM analysis of hybrid strip/slot-like planar lines. The free surface charge distribution is used as an unknown on the strip-like interface, whereas the electric field is used on the slot-like region. This formulation allows us to reduce the number of basis functions and makes possible a unified treatment of the problem. A single type of basis functions is used, leading to a quasi-analytical evaluation of the Galerkin matrix entries. The performance of the method is illustrated with a practical example structure useful for coupler design

The Beauty of Symmetry: Common-mode rejection filters for high-speed interconnects and balanced microwave circuits

Common-mode rejection filters operating at microwave frequencies have been the subject of intensive research activity in the last decade. These filters are of interest for the suppression of common-mode noise in high-speed digital circuits, where differential signals are widely employed due to the high immunity to noise, electromagnetic interference (EMI) and crosstalk of differential-mode interconnects. These filters can also be used to improve common-mode rejection in microwave filters and circuits dealing with differential signals. Ideally, common-mode stopband filters should be transparent for the differential mode from DC up to very high frequencies (all-pass), should preserve the signal integrity for such mode, and should exhibit the widest and deepest possible rejection band for the common mode in the region of interest. Moreover, these characteristics should be achieved by means of structures with the smallest possible size. In this article, several techniques for the implementation of common-mode suppression filters in planar technology are reviewed. In all the cases, the strategy to simultaneously achieve common-mode suppression and all-pass behavior for the differential mode is based on selective mode-suppression. This selective mode suppression (either the common or the differential mode) in balanced lines is typically (although not exclusively) achieved by symmetrically loading the lines with symmetric resonant elements, opaque for the common-mode and transparent for the differential mode (common-mode suppression), or vice versa (differential-mode suppression).MINECO, Spain-TEC2013-40600-R, TEC2013-41913-PGeneralitat de Catalunya-2014SGR-15

Aplicación de nuevos materiales en productos náuticos de recreo

Estudio de viabilidad de la aplicación de fibra de basalto en la fabricación de tablas de kitesurf, la cual se construye con un laminado tipo sándwich, constituida de varias capas de fibra de basalto como refuerzo, resina epoxi como matriz y un núcleo de PVC espumado. También se realizan simulaciones por medio de software de cálculo de elementos finitos, para analizar las características mecánicas y los parámetros del proceso de infusión de resina.Hijano Martel, AJ. (2011). Aplicación de nuevos materiales en productos náuticos de recreo. Universitat Politècnica de València. http://hdl.handle.net/10251/60006Archivo delegad

Artificial magnetic metamaterial design by using spiral resonators

A metallic planar particle, that will be called spiral resonator (SR), is introduced as a useful artificial atom for artificial magnetic media design and fabrication. A simple theoretical model which provides the most relevant properties and parameters of the SR is presented. The model is validated by both electromagnetic simulation and experiments. The applications of SR's include artificial negative magnetic permeability media (NMPM) and left-handed-media (LHM) design. The main advantages of SR's for such purpose are small electrical size at resonance, absence of magnetoelectric coupling (thus avoiding bianisotropic effects in the continuous medium made of these particles), and easy fabrication. Experimental confirmation of NMPM and LHM behavior using SR's is also reported.Ministerio de Ciencia y Tecnología TIC2001-316

Design of compact low-pass elliptic filters using double-sided MIC technology

A novel implementation of stepped-impedance low-pass elliptic filters is presented in this paper. The filters are based on the well-known technique of cascading high- and low-impedance sections to simulate the ladder LC lumped-circuit prototype. We propose in this study a new approach to build up the constitutive circuit elements by taking advantage of the use of both sides of the substrate. The use of double-sided technology yields both design flexibility and good circuit performance. High-impedance sections are achieved by using slots in the backside of the substrate, whereas low-impedance sections are obtained with parallel-plate capacitors. In order to achieve the transmission poles corresponding to the elliptic design, these capacitors are series connected to the ground plane by means of high-impedance coplanar-waveguide lines, which mainly act as inductors. As a final step, meandering techniques have been applied to the high-impedance sections of the filter to reduce the overall circuit size. The measurement of several fabricated filters shows fairly good agreement between theory and experiment.Ministerio de Educación y Ciencia TEC2004-03214Junta de Andalucía TIC-25

Parallel coupled microstrip filters with ground-plane aperture for spurious band suppression and enhanced coupling

Parallel coupled microstrip sections with a slotted ground plane are proposed as building blocks of coupled-line microstrip filters with enhanced performance. It is shown that, by proper adjustment of the ground-plane slot dimensions, the double frequency spurious band associated with unequal even/odd electrical lengths can be suppressed or meaningfully reduced. As an additional feature, this simple design relaxes tolerances of strip width and spacing in those cases where tightly coupled high-impedance sections are required. A rough preliminary design can be obtained within a few seconds using a fast optimization algorithm based on a quasi-TEM analysis of the coupled sections. Fine tuning is based on the use of a commercial electromagnetic simulator. Finally, experimental check of filter performance is provided.Ministerio de Ciencia y Tecnología TIC2001-316

European Union legislation overview about used vegetable oils recycling: the spanish and italian case studies

The employment of used vegetable oils (UVOs) as raw materials in key sectors as energy production or bio-lubricant synthesis represents one of the most relevant priorities in the European Union (EU) normative context. In many countries, the development of new production processes based on the circular economy model, as well as the definition of future energy and production targets, involve the utilization of wastes as raw material. In this context, the main currently applied EU regulations are presented and discussed. As in the EU, the general legislative process consists of the definition in each State Member of specific legislation, which transposes the EU indications. Two relevant countries are herein considered: Italy and Spain. Through the analysis of the conditions required in both countries for UVOs’ collection, disposal, storage, and recycling, a wide panorama of the current situation is provided

Design of wide-band semi-lumped bandpass filters using open split ring resonators

Open split ring resonators (OSRRs) are used in this letter to design wide-band semi-lumped bandpass filters. OSRRs work as lumped LC series elements due to their small electrical size and can be then used as building blocks of reduced size band pass filters. The values of the capacitance, C, and inductance, L, of the OSRR are controlled by adjusting the geometrical parameters of the coupled open rings. In our design, the OSRRs are connected through quarter-wave lines which act as inverters. The impedance of these inverters have been conveniently calculated to achieve the filter specifications. Finally bending and/or meandering techniques have been applied so as to obtain highly compact designs. Experimental verification is provided and good agreement has been found between electromagnetic simulations and measurements.Ministerio de Educación y Ciencia TEC2004-04249-C02-01, TEC2004-04249-C02-02, TEC2004-0321