In Silico Design and Selection of CD44 Antagonists:implementation of computational methodologies in drug discovery and design

Drug discovery (DD) is a process that aims to identify drug candidates through a thorough evaluation of the biological activity of small molecules or biomolecules. Computational strategies (CS) are now necessary tools for speeding up DD. Chapter 1 describes the use of CS throughout the DD process, from the early stages of drug design to the use of artificial intelligence for the de novo design of therapeutic molecules. Chapter 2 describes an in-silico workflow for identifying potential high-affinity CD44 antagonists, ranging from structural analysis of the target to the analysis of ligand-protein interactions and molecular dynamics (MD). In Chapter 3, we tested the shape-guided algorithm on a dataset of macrocycles, identifying the characteristics that need to be improved for the development of new tools for macrocycle sampling and design. In Chapter 4, we describe a detailed reverse docking protocol for identifying potential 4-hydroxycoumarin (4-HC) targets. The strategy described in this chapter is easily transferable to other compounds and protein datasets for overcoming bottlenecks in molecular docking protocols, particularly reverse docking approaches. Finally, Chapter 5 shows how computational methods and experimental results can be used to repurpose compounds as potential COVID-19 treatments. According to our findings, the HCV drug boceprevir could be clinically tested or used as a lead molecule to develop compounds that target COVID-19 or other coronaviral infections. These chapters, in summary, demonstrate the importance, application, limitations, and future of computational methods in the state-of-the-art drug design process

Applying A Methodology For Educating Students With Special Needs: A Case Study

The introduction of innovative educational technologies opens up new ways of interacting with students. We propose to exploit this potential to help in the education of children with special needs. We analyze the state of the art of tools supporting the teaching process, focusing on the omissions of existing research. We propose a new framework to help throughout the whole teaching process and describe its application to Proyecto Aprender (Learn Project), an educational resource targeting children with learning difficulties. Finally, we outline some conclusions and current/future research lines

Improvement of the sensory and autonomous capability of robots through olfaction: the IRO Project

Proyecto de Excelencia Junta de Andalucía TEP2012-530Olfaction is a valuable source of information about the environment that has not been su ciently exploited in mobile robotics yet. Certainly, odor information can contribute to other sensing modalities, e.g. vision, to successfully accomplish high-level robot activities, such as task planning or execution in human environments. This paper describes the developments carried out in the scope of the IRO project, which aims at making progress in this direction by investigating mechanisms that exploit odor information (usually coming in the form of the type of volatile and its concentration) in problems like object recognition and scene-activity understanding. A distinctive aspect of this research is the special attention paid to the role of semantics within the robot perception and decisionmaking processes. The results of the IRO project have improved the robot capabilities in terms of efciency, autonomy and usefulness.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Analyzing interference between RGB-D cameras for human motion tracking

Multi-camera RGB-D systems are becoming popular as sensor setups in Computer Vision applications but they are prone to cause interference between them, compromising their accuracy. This paper extends previous works on the analysis of the noise introduced by interference with new and more realistic camera configurations and different brands of devices. As expected, the detected noise increases as distance and angle grows, becoming worse when interference is present. Finally, we evaluate the effectiveness of the proposed solutions of using DC vibration motors to mitigate them. The results of this study are being used to assess the effect of interference when applying these setups to human motion tracking.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Plan Propio de Investigación de la UMA. Junta de Andalucía, proyecto TEP2012-53

Building Accessible Flash Applications: an XML-Based Toolkit

The use of Flash as a web-based multimedia development tool has spread lately. Although a big effort has gone into improving its accessibility, there are still accessibility gaps requiring programming or purchase from another supplier. This makes building an accessible Flash application an ad hoc, complex and time-consuming task. With the aim of lightening the accessibility-related workload, we have implemented a toolkit that helps to create accessible multimedia Flash resources. This toolkit specifies the accessibility features as XML configuration files. It includes a library that works like a wrapper abstracting the logic layer of the different events and iterations from the physical layer. This way, new functionalities can easily be added. Additionally, it has been successfully used to build teaching and teaching support systems

In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates

CD44 promotes metastasis, chemoresistance, and stemness in different types of cancer and is a target for the development of new anti-cancer therapies. All CD44 isoforms share a common N-terminal domain that binds to hyaluronic acid (HA). Herein, we used a computational approach to design new potential CD44 antagonists and evaluate their target-binding ability. By analyzing 30 crystal structures of the HA-binding domain (CD44HAbd), we characterized a subdomain that binds to 1,2,3,4-tetrahydroisoquinoline (THQ)-containing compounds and is adjacent to residues essential for HA interaction. By computational combinatorial chemistry (CCC), we designed 168,190 molecules and compared their conformers to a pharmacophore containing the key features of the crystallographic THQ binding mode. Approximately 0.01% of the compounds matched the pharmacophore and were analyzed by computational docking and molecular dynamics (MD). We identified two compounds, Can125 and Can159, that bound to human CD44HAbd (hCD44HAbd) in explicit-solvent MD simulations and therefore may elicit CD44 blockage. These compounds can be easily synthesized by multicomponent reactions for activity testing and their binding mode, reported here, could be helpful in the design of more potent CD44 antagonists

A Framework to Support Development of Learning Applications for Disabled Children

Multimedia resources are an important tool that can be used by teachers in the classroom as a learning aid for learners with disabilities or by parents and children at home. However, disabled children are not always able to use existing assistive technologies because they are not experienced enough, suffer from medium/profound disability, or simply do not have the financial resources to buy commercial tools. Additionally, today’s adapted tools are not always valid for a broad spectrum of disabled users and often focus on a user group. We claim that potential applications and resources for people with special needs must self-adapt to user capabilities and skills, reducing the use of external assistive technologies. In this paper, we present a guide for developers to create accessible applications and resources that reduce workload

La posible adhesión de Serbia a la Unión Europea: Balance del discurso mediático en España

Serbia's possible accession to the European Union and the progressive Europeanisation of ex-Yugoslav countries has depended on certain historical, economic and political circumstances. Serbia and the EU's relations have been marked by complex issues such as the Kosovo conflict, relations with Russia or the surrender of war criminals sought by the International Criminal Tribunal for the former Yugoslavia. Spain, for its part, has maintained good relations with the Balkan country and is one of the European states that does not recognize Kosovo's independence. This text aims to know what framing the Spanish press uses when dealing with Serbia's possible accession to the EU and what role various variables play, such as the Catalan conflict or the Kosovar case. Through a quantitative methodology, specifically factor analysis, this research provides original and novel data on a little-studied subject.La posible adhesión de Serbia a la Unión Europea y la progresiva europeización de los países exyugoslavos ha dependido de ciertas circunstancias históricas, económicas y políticas. La relaciones de Serbia y la UE han estado marcadas por complejas cuestiones como el conflicto de Kosovo, las relaciones con Rusia o la entrega de los criminales de guerra buscados por el Tribunal Penal Internacional para la ex Yugoslavia. España por su parte ha mantenido buenas relaciones con el país balcánico y es uno de los Estados europeos que no reconoce la independencia de Kosovo. El presente texto pretende conocer qué encuadres utiliza la prensa española a la hora de tratar la posible adhesión de Serbia a la UE y qué papel desempeñan diversas variables, como el conflicto catalán o el caso kosovar. A través de una metodología de carácter cuantitativo, concretamente el análisis factorial, esta investigación aporta datos originales y novedosos sobre un tema escasamente estudiado

Sistema de Biorremediación on-line para la Eliminación de Radionúclidos en Aguas Radiactivas

En estudios previos desarrollados en la Central Nuclear de Cofrentes (Valencia), se ha observado que los microorganismos presentes en las aguas radiactivas de las piscinas de almacenamiento de combustible nuclear gastado son capaces de colonizar las superficies metálicas de las paredes y conducciones y formar biopelículas sobre éstas. Estas biopelículas retienen los radionúclidos de las aguas contribuyendo a su descontaminación. En este proyecto, se ha diseñado una planta piloto para la biodescontaminación de las aguas radiactivas. Actualmente el agua radiactiva procedente de las piscinas de combustible se hace pasar por resinas de intercambio iónico que posteriormente tienen que ser gestionadas como residuos radiactivos. En este proyecto, al agua se hace pasar a través de un biorreactor que contiene ovillos de acero inoxidable susceptibles de ser colonizados por los microorganismos existentes en dichas aguas. A su paso por el biorreactor, el agua entra en contacto con el material del ovillo, formándose una biopelícula que retiene los radionúclidos presentes en el agua. La biopelícula es fácilmente eliminada por cualquier procedimiento convencional de descontaminación radioquímica de materiales y los radionúclidos se pueden concentrar en un volumen pequeño de eluyente para su recuperación, disposición final o contención. A continuación, el material del biorreactor puede ser gestionado como material no radiactivo

Heterogeneous networks do not promote cooperation when humans play a Prisoner's dilemma

It is not fully understood why we cooperate with strangers on a daily basis. In an increasingly global world, where interaction networks and relationships between individuals are becoming more complex, different hypotheses have been put forward to explain the foundations of human cooperation on a large scale and to account for the true motivations that are behind this phenomenon. In this context, population structure has been suggested to foster cooperation in social dilemmas, but theoretical studies of this mechanism have yielded contradictory results so far; additionally, the issue lacks a proper experimental test in large systems. We have performed the largest experiments to date with humans playing a spatial Prisoner's Dilemma on a lattice and a scale-free network (1,229 subjects). We observed that the level of cooperation reached in both networks is the same, comparable with the level of cooperation of smaller networks or unstructured populations. We have also found that subjects respond to the cooperation that they observe in a reciprocal manner, being more likely to cooperate if, in the previous round, many of their neighbors and themselves did so, which implies that humans do not consider neighbors' payoffs when making their decisions in this dilemma but only their actions. Our results, which are in agreement with recent theoretical predictions based on this behavioral rule, suggest that population structure has little relevance as a cooperation promoter or inhibitor among humans.Work supported by Fundación Ibercivis and projects MOSAICO, PRODIEVO, FIS2008-01240, FIS2009-13364-C02-01, FIS2009-12648-C03-02, and Complexity-NET RESINEE, from Ministerio de Ciencia e Innovación (Spain); by project MODELICO-CM from Comunidad de Madrid (Spain); and by a project to FENOL from Comunidad de Aragón (Spain)