Network analysis and machine learning assist drug repurposing and safety assessment in neurological diseases

In recent decades, two prominent trends have influenced the data modeling field, namely network analysis and machine learning. This thesis explores the practical applications of these techniques within the domain of drug research, unveiling their multifaceted potential for advancing our comprehension of complex biological systems. The research undertaken during this PhD program is situated at the intersection of network theory, computational methods, and drug research. Across six projects presented herein, there is a gradual increase in model complexity. These projects traverse a diverse range of topics, with a specific emphasis on drug repurposing and safety in the context of neurological diseases. The aim of these projects is to leverage existing biomedical knowledge to develop innovative approaches that bolster drug research. The investigations have produced practical solutions, not only providing insights into the intricacies of biological systems, but also allowing the creation of valuable tools for their analysis. In short, the achievements are: • A novel computational algorithm to identify adverse events specific to fixed-dose drug combinations. • A web application that tracks the clinical drug research response to SARS-CoV-2. • A Python package for differential gene expression analysis and the identification of key regulatory "switch genes". • The identification of pivotal events causing drug-induced impulse control disorders linked to specific medications. • An automated pipeline for discovering potential drug repurposing opportunities. • The creation of a comprehensive knowledge graph and development of a graph machine learning model for predictions. Collectively, these projects illustrate diverse applications of data science and network-based methodologies, highlighting the profound impact they can have in supporting drug research activities.

Modelling the infrastructure of the “Śivadharma Database”

A Digital Scholarly Edition is a conceptually and structurally sophisticated entity. Throughout the centuries, diverse methodologies have been employed to reconstruct a text transmitted through one or multiple sources, resulting in various edition types. With the advent of digital technology in philology, these practices have undergone a significant transformation, compelling scholars to reconsider their approach in light of the web. In the digital age, philologists are expected to possess (too) advanced technical skills to prepare interactive and enriched editions, even though, in most cases, only mechanical or documentary editions are published online. The Śivadharma Database is a web Content Management System (CMS) designed to facilitate the preparation, publication, and updating of Digital Scholarly Editions. By providing scholars with a user-friendly CRUD web application to reconstruct and annotate a text, they can prepare their textus with additional components such as apparatus, notes, translations, citations, and parallels. It is possible by leveraging an annotation system based on HTML and graph data structure. This choice is made because the text entity is multidimensional and multifaceted, even if its sequential presentation constrains it. In particular, editions of South Asian texts of the Śivadharma corpus, the case study of this research, contain a series of phenomena that are difficult to manage formally, such as overlapping hierarchies. Hence, it becomes necessary to establish the data structure best suited to represent this complexity. In Śivadharma Database, the textus is an HTML file readily displayable. Textual fragments, annotated via an interface without requiring philologists to write code and saved in the backend, form the atomic unit of multiple relationships organised in a graph database. This approach enables the formal representation of complex and overlapping textual phenomena, allowing for good annotation expressiveness with minimal effort to learn the relevant technologies during the editing workflow.

Self-supervised Information Retrieval basato su deep metric learning

La tesi ha lo scopo di ricercare, esaminare ed implementare un sistema di Machine Learning, un Recommendation Systems per precisione, che permetta la racommandazione di documenti di natura giuridica, i quali sono già stati analizzati e categorizzati appropriatamente, in maniera ottimale, il cui scopo sarebbe quello di accompagnare un sistema già implementato di Information Retrieval, istanziato sopra una web application, che permette di ricercare i documenti giuridici appena menzionati.

Un ponte tra Crowdsourcing e Crowdsensing: L'implementazione di SmartCrowd

L’elaborato presenta lo sviluppo di un’applicazione web che unisce il con- cetto di crowdsourcing, ovvero un paradigma in cui una colletività esegue una mansione per il raggiungimento di un obiettivo; e il concetto di crowd- sensing, paradigma nel quale un gruppo di persone, utilizzando il proprio dispositivo mobile, condivide dati, che possono essere successivamente stu- diati. SmartCrowd si pone come intermediario tra questi due modelli, e la sua implementazione permette di raccogliere dati da una “folla” che faccia uso dei dispositivi mobili, usufruendo di una piattaforma di crowdsourcing. Con SmartCrowd vengono create le campagne, ovvero insieme di attività svol- te dagli utenti finali; esiste un sistema di interazione con la piattaforma di crowdsourcing di Microworkers, volta al reclutamento delle persone; la con- divisione dei dati tramite smartphone, usando il sensore GPS, eseguita dagli utenti ed infine, tramite SmartCrowd è possibile analizzare i dati ricevuti e fare una valutazione positiva o negativa.

Smart Mirror: remote verification of an identity document holder

Nowadays, some activities, such as subscribing an insurance policy or opening a bank account, are possible by navigating through a web page or a downloadable application. Since the user is often “hidden” behind a monitor or a smartphone, it is necessary a solution able to guarantee about their identity. Companies are often requiring the submission of a “proof-of-identity”, which usually consists in a picture of an identity document of the user, together with a picture or a brief video of themselves. This work describes a system whose purpose is the automation of these kinds of verifications.

Towards a Smart Campus Digital Twin: Promoting Awareness and Sustainability Through Wayfinding and Real-Time Environmental Data

The newly inaugurated Navile District of the University of Bologna is a complex created along the Navile canal, that now houses various teaching and research activities for the disciplines of Chemistry, Industrial Chemistry, Pharmacy, Biotechnology and Astronomy. A Building Information Modeling system (BIM) gives staff of the Navile campus several ways to monitor buildings in the complex throughout their life cycle, one of which is the ability to access real-time environmental data such as room temperature, humidity, air composition, and more, thereby simplifying operations like finding faults and optimizing environmental resource usage. But smart features at Navile are not only available to the staff: AlmaMap Navile is a web application, whose development is documented in this thesis, that powers the public touch kiosks available throughout the campus, offering maps of the district and indications on how to reach buildings and spaces. Even if these two systems, BIM and AlmaMap, don't seem to have many similarities, they share the common intent of promoting awareness for informed decision making in the campus, and they do it while relying on web standards for communication. This opens up interesting possibilities, and is the idea behind AlmaMap Navile 2.0, an app that interfaces with the BIM system and combines real-time sensor data with a comfort calculation algorithm, giving users the ability not just to ask for directions to a space, but also to see its comfort level in advance and, should they want to, check environmental measurements coming from each sensor in a granular manner. The end result is a first step towards building a smart campus Digital Twin, that can support all the people who are part of the campus life in their daily activities, improving their efficiency and satisfaction, giving them the ability to make informed decisions, and promoting awareness and sustainability.

Proyecto de implementación de una webapp para una agencia de viajes

Elaboración de un proyecto en el que se ha creado la documentación completa de una aplicación web para una agencia de viajes ficticia para la consulta y reserva de los productos que desea ofrecer a sus clientes.

Web Classroom Application. Digital technologies to study theory, history and criticism of architecture at Escuela Superior de Arquitectura UPMadrid. The search for some guides to direct the inquiry learning

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Aplicación de administración con Angular, Node y Express para una aplicación Django

En este trabajo de fin de grado se ha desarrollado una aplicación de administración que sustituye a las que ofrecen por defecto las aplicaciones creadas con el framework de desarrollo web Django. La aplicación está compuesta por dos partes: un servidor, desarrollado con Node y Express, que ataca a la base de datos MySQL de la aplicación Django (es el nexo de unión entre ambas), y expone una API que es utilizada por la otra parte que compone la aplicación, la parte del cliente. La API es totalmente privada, siendo necesario un token de autenticación válido para poder obtener una respuesta satisfactoria de la misma. La generación del token también es tarea del servidor. El cliente, que es la parte que ve el usuario final, está desarrollada usando el framework Angular. La interfaz de usuario utiliza Bootstrap, por lo que su visualización es correcta en cualquier tipo de dispositivo, tanto de escritorio como móvil. En definitiva, se ha desarrollado una aplicación JavaScript End-to-End, empleando las últimas tecnologías web, mejorando ostensiblemente, las prestaciones que ofrece un panel de administración generado automáticamente por una aplicación Django.

Epidermal iontophoresis: II. Application of the ionic mobility-pore model to the transport of local anesthetics

Purpose, An in vitro study was carried out to determine the iontophoretic permeability of local anesthetics through human epidermis. The relationship between physicochemical structure and the permeability of these solutes was then examined using an ionic mobility-pore model developed to define quantitative relationships. Methods. The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetracaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine, bupivacaine, etidocaine, cinchocaine) were determined through excised human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivity measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the ionic mobility-pore model and to determine the best predictor of iontophoretic permeability of the local anesthetics. Results. The logarithm of the iontophoretic permeability coefficient (log PCj,iont) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held constant. Multiple linear regressions confirmed that log PCj,iont was best defined by ionic mobility (and its determinants: conductivity, pK(a) and MW) and MW. Conclusions. Our results suggest that of the properties studied, the best predictors of iontophoretic transport of local anesthetics are ionic mobility (or pK(a)) and molecular size. These predictions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epidermal permselectivity and other factors as defined by the model.

Web-based application programming interface to solve nonlinear optimization problems

Nonlinear Optimization Problems are usual in many engineering fields. Due to its characteristics the objective function of some problems might not be differentiable or its derivatives have complex expressions. There are even cases where an analytical expression of the objective function might not be possible to determine either due to its complexity or its cost (monetary, computational, time, ...). In these cases Nonlinear Optimization methods must be used. An API, including several methods and algorithms to solve constrained and unconstrained optimization problems was implemented. This API can be accessed not only as traditionally, by installing it on the developer and/or user computer, but it can also be accessed remotely using Web Services. As long as there is a network connection to the server where the API is installed, applications always access to the latest API version. Also an Web-based application, using the proposed API, was developed. This application is to be used by users that do not want to integrate methods in applications, and simply want to have a tool to solve Nonlinear Optimization Problems.

Sigla WEBGIS portal: an open source Web-based GIS application for the portuguese bluetongue Entomologiacal surveillance program.

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Ciência e Sistemas de Informação Geográfica

Gellan gum-Ionic liquid membranes for electrochromic device application

Biopolymer-based materials have been of particular interest and they are alternatives to synthetic polymers based on the decreasing oil resources. The polymer electrolytes were doped with choline-based IL N,N,Ntrimethyl- N-(2-hydroxyethyl)ammonium bis(trifluoromethylsulfonyl)imide ([N1 1 1 2(OH)][NTf2]), or Er (CF3SO3)3 or both. The polymer electrolytes were employed in the production of glass/ITO/WO3/electrolyte/ CeO2–TiO2/ITO/glass electrochromic devices (ECDs). The lowest onset temperature for the degradation of all the SPEs is at ~130 °C for the Gellan Er (CF3SO3)3 (10:1) this temperature range of stability is wide enough for a material to be applied as an electrolyte/separator component in electrochemical devices. The three ECDs displayed fast switching speed (ca. 15 s). Gellan [N1 1 1 2(OH)][NTf2] Er (CF3SO3)3 (5:1:10) exhibited an electrochromic contrast of 4.2% in the visible region, the coloration efficiency attained at 555 nm was 3.5 and 0.90 cm-2 C-1 in the “colored” and “bleached” states, respectively, and the open circuit memorywas 48 h. Preliminary tests performed with a prototype electrochromic device (ECD) incorporating WO3 as cathodic electrochromic layer, are extremely encouraging.

Portal web inmobiliario

Aquest projecte neix d'una demanda real d'una empresa del sector immobiliari, amb la finalitat d'actualitzar i augmentar les funcionalitats que presenta la web d'aquesta, s'ha implementat un aplicatiu que satisfà tant a l'empresa com als seus clients potencials. S'ha elaborat una completa documentació que inclou una memòria on es descriuen detalladament totes les etapes seguides en el desenvolupament del projecte, un manual d'usuari documentat gràficament, una valoració econòmica del projecte i una descripció de cadascun dels scripts utilitzats per facilitar el manteniment de l'aplicació.