49 research outputs found

    Antitumoral effects of attenuated Listeria monocytogenes in a genetically engineered mouse model of melanoma

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    Attenuated Listeria monocytogenes (Lmat-LLO) represents a valuable anticancer vaccine and drug delivery platform. Here we show that in vitro Lmat-LLO causes ROS production and, in turn, apoptotic killing of a wide variety of melanoma cells, irrespectively of their stage, mutational status, sensitivity to BRAF inhibitors or degree of stemness. We also show that, when administered in the therapeutic setting to Braf/Pten genetically engineered mice, Lmat-LLO causes a strong decrease in the size and volume of primary melanoma tumors, as well as a reduction of the metastatic burden. At the molecular level, we confirm that the anti-melanoma activity exerted in vivo by Lmat-LLO depends also on its ability to potentiate the immune response of the organism against the infected tumor. Our data pave the way to the preclinical testing of listeria-based immunotherapeutic strategies against metastatic melanoma, using a genetically engineered mouse rather than xenograft models

    Interazioni proteiche mediate da PKD1 (Protein Kinase D1)

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    La famiglia delle Protein chinasi D (PKD) è composta da 3 isoforme: PKD1, PKD2, PKD3. Sono tutte serina/treonina chinasi regolate dalla via di trasduzione del segnale del diacilglicerolo e coinvolte in meccanismi di sopravvivenza cellulare, proliferazione e invasione cellulare. Inoltre sono implicate nel trasporto delle proteine dal Golgi alla membrana plasmatica (trans Golgi network). Tale trasporto prevede la formazione di vescicole ed è regolato in maniera isoforma specifica, in quanto ogni isoforma determina il traffico di un gruppo specifico di proteine. In particolare, PKD1 oltre a regolare il trasporto proteico dal Golgi, è importante per altre funzioni cellulari, tra cui: vie di segnale da recettori di membrana, protezione dallo stress ossidativo nei mitocondri, regolazione della forma cellulare, motilità e adesione. Una delle principali differenze tra le tre isofome di PKD è localizzata al C-terminale delle proteine: PKD1 e PKD2 presentano un potenziale motivo di riconoscimento per domini di legame di tipo “PDZ”, mentre PKD3 non presenta tale motivo. Kidins220 (kinase D-interacting substrate of 220 kDa) è uno dei substrati di PKD1, identificato per la prima volta in cellule di feocromocitoma di ratto (PC12). PKD1 non solo è implicata nella sua fosforilazione, ma anche nella sua corretta localizzazione a livello della membrana citoplasmatica. Dati in letteratura suggeriscono che l’interazione tra Kidins220 e PKD1 possa essere mediata da un’altra proteina contenente un dominio PDZ. Obiettivo del mio lavoro di tesi è stato verificare che il mediatore dell’interazione tra queste due proteine sia una proteina con due domini PDZ, che in un precedente studio del nostro laboratorio è stata identificata come interattore diretto di Kidins220: PDZRN3 (Ring PDZ containing protein 3). Lo studio si è basato prevalentemente sull’analisi di proteine ricombinanti attraverso esperimenti di Pull-Down e Co-Immunoprecipitazione utilizzando come modello cellule umane in coltura

    Human Machine Interface Issues for Drone Fleet Management

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    The use of Unmanned Aerial Systems, commonly called drones, today is massively growing. Drones can be remotely piloted (RPAS - Remotely Piloted Aircraft System) or they can automatically fly. Recently applications are emerging which require the use of fleet of drones and a related human machine interface to ensure better performance and reliability. Safety in those system is a priority aspect. A major cause for accidents involving drones is ground operators’ error, due to poorly designed user interfaces. Therefore, the interest in human factors arises with the aim of contributing to the maintenance of high safety standards of flight missions through the systematic application of usability principles during the development of the inter-faces. The present work reports on an ongoing study meant to design Ground Control Station interfaces for multiple RPAS control, with the goal to enhance operators’ performance and increase the probability of mission success

    Dyslexeasy-App to Improve Readability through the Extracted Summary for Dyslexic Users

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    The evaluation of Dyslexeasy, a reading program for mobile Android devices that is specifically built for people with dyslexia, is presented in this research. Dyslexeasy combines the most effective approach to show text to persons with dyslexia with a unique feature: progressive text reproduction. Our first prototype is for Italian, despite the fact that the novel algorithm employed for this unique feature is language agnostic. We conducted a pilot study with possible stakeholders to evaluate Dyslexeasy. Working with five dyslexic participants, we assessed the effectiveness of the algorithm on the basis of dyslexia, as well as the user experience. Our findings reveal that the participants were satisfied with the quality of the text generated by the algorithm and the overall user experience. As a result, we argue in this paper that a mobile app like Dyslexeasy could have a significant influence on persons with dyslexia

    The Making of Accessible Android Applications: An Empirical Study on the State of the Practice

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    Context. Nowadays, mobile applications represent the principal means to enable human interaction. Being so pervasive, these applications should be made usable for all users: accessibility collects the guidelines that developers should follow to include features allowing users with disabilities (e.g., visual impairments) to better interact with an application.Problem. While research in this field is gaining interest, there is still a notable lack of knowledge on how developers practically deal with the problem: (i) whether they are aware and take accessibility guidelines into account when developing apps, (ii) which guidelines are harder for them to implement, and (iii) which tools they use to be supported in this task.Objective. To bridge the gap of knowledge on the state of the practice concerning the accessibility of mobile applications. Method. Adopting a mixed-method research approach, we aim to (i) verify how accessibility guidelines are implemented in mobile applications through a coding strategy and (ii) survey mobile developers on the issues and challenges of dealing with accessibility in practice.Limitations. Threats are represented by the size of the app sample and the number of answers to our survey study
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