APP controls the formation of PI(3,5)P2 vesicles through its binding of the PIKfyve complex

Phosphoinositides are signalling lipids that are crucial for major signalling events as well as established regulators of membrane trafficking. Control of endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the latter a lipid of low abundance but significant physiological relevance. PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve function results in dramatic neurodegeneration. Despite the significance of PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid Precursor Protein (APP), a central molecule in Alzheimer’s disease, associates with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP intracellular domain directly binds purified Vac14. We also show that the closely related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether APP family proteins can additionally form direct protein–protein interaction with PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family members are required for supporting PIKfyve function. Interestingly, the PIKfyve complex is required for APP trafficking, suggesting a feedback loop in which APP, by binding to and stimulating PI(3,5)P2 vesicle formation may control its own trafficking. These data suggest that altered APP processing, as observed in Alzheimer’s disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and homeostasis with important implications for our understanding of the mechanism of neurodegeneration in Alzheimer’s disease.

Emerging perspectives on the design, use, and evaluation of mobile and handheld devices

Human-computer interaction is a growing field of study in which researchers and professionals aim to understand and evaluate the impact of new technologies on human behavior. With the integration of smart phones, tablets, and other portable devices into everyday life, there is a greater need to understand the influence of such technology on the human experience. Emerging Perspectives on the Design, Use, and Evaluation of Mobile and Handheld Devices is an authoritative reference source consisting of the latest scholarly research and theories from international experts and professionals on the topic of human-computer interaction with mobile devices. Featuring a comprehensive collection of chapters on critical topics in this dynamic field, this publication is an essential reference source for researchers, educators, students, and practitioners interested in the use of mobile and handheld devices and their impact on individuals and society as a whole. This publication features timely, research-based chapters pertaining to topics in the design and evaluation of smart devices including, but not limited to, app stores, category-based interfaces, gamified mobility applications, mobile interaction, mobile learning, pervasive multimodal applications, smartphone interaction, and social media use.

The amyloid precursor protein (APP) binds the PIKfyve complex and modulates its function

Phosphoinositides are important components of eukaryotic membranes that are required for multiple forms of membrane dynamics. Phosphoinositides are involved in defining membrane identity, mediate cell signalling and control membrane trafficking events. Due to their pivotal role in membrane dynamics, phosphoinositide de-regulation contributes to various human diseases. In this review, we will focus on the newly emerging regulation of the PIKfyve complex, a phosphoinositide kinase that converts the endosomal phosphatidylinositol-3-phosphate [PI(3)P] to phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2)], a low abundance phosphoinositide of outstanding importance for neuronal integrity and function. Loss of PIKfyve function is well known to result in neurodegeneration in both mousemodels and human patients. Our recent work has surprisingly identified the amyloid precursor protein (APP), the central molecule in Alzheimer s disease aetiology, as a novel interaction partner of a subunit of the PIKfyve complex, Vac14. Furthermore, it has been shown that APP modulates PIKfyve function and PI(3,5)P2 dynamics, suggesting that the APP gene family functions as regulator of PI(3,5)P2 metabolism. The recent advances discussed in this review suggest a novel, unexpected, â-amyloid-independent mechanism for neurodegeneration in Alzheimer s disease.

A cell-permeable tool for analysing APP intracellular domain function and manipulation of PIKfyve activity

The mechanisms for regulating PIKfyve complex activity are currently emerging. The PIKfyve complex, consisting of the phosphoinositide kinase PIKfyve (also known as FAB1), VAC14 and FIG4, is required for the production of phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2). PIKfyve function is required for homeostasis of the endo/lysosomal system and is crucially implicated in neuronal function and integrity, as loss of function mutations in the PIKfyve complex lead to neurodegeneration in mouse models and human patients. Our recent work has shown that the intracellular domain of the Amyloid Precursor Protein (APP), a molecule central to the aetiology of Alzheimer's disease binds to VAC14 and enhances PIKfyve function. Here we utilise this recent advance to create an easy-to-use tool for increasing PIKfyve activity in cells. We fused APP's intracellular domain (AICD) to the HIV TAT domain, a cell permeable peptide allowing proteins to penetrate cells. The resultant TAT-AICD fusion protein is cell permeable and triggers an increase of PI(3,5)P2. Using the PI(3,5)P2 specific GFP-ML1Nx2 probe we show that cell-permeable AICD alters PI(3,5)P2 dynamics. TAT-AICD also provides partial protection from pharmacological inhibition of PIKfyve. All three lines of evidence show that the APP intracellular domain activates the PIKfyve complex in cells, a finding that is important for our understanding of the mechanism of neurodegeneration in Alzheimer's disease.

A longitudinal evaluation of the acceptability and impact of a diet diary app for older adults with age-related macular degeneration

Ongoing advances in technology are increasing the scope for enhancing and supporting older adults’ daily living. The digital divide between older and younger adults raises concerns, however, about the suitability of technological solutions for older adults, especially for those with impairments. Taking older adults with Age-Related Macular Degeneration (AMD) as a case study, we used user-centred and participatory design approaches to develop an assistive mobile app for self-monitoring their intake of food [12,13]. In this paper we report on findings of a longitudinal field evaluation of our app that was conducted to investigate how it was received and adopted by older adults with AMD and its impact on their lives. Demonstrating the benefit of applying inclusive design methods for technology for older adults, our findings reveal how the use of the app raises participants’ awareness and facilitates self-monitoring of diet, encourages positive (diet) behaviour change, and encourages learning.

Un webservice per collegare il cittadino con la propria situazione debitoria

La tesi tratta di un web service capace di estrapolare i dati da un database Oracle utilizzato da un gestionale già esistente, per darli come output ad un portale da cui il cittadino si potrà collegare, visionandoli. Il gestionale si occupa della fase coattiva, ovvero quando un contribuente non paga una multa o una qualsiasi tassa; fino ad oggi non era possibile far vedere in via telematica i dati della situazione coattiva di un contribuente. Grazie al web service da me creato un portale potrà fare vedere i dati al contribuente tramite esso. Inoltre grazie a questo web service in futuro si potranno collegare anche con altri portali o app smartphone per dare ulteriori servizi al cittadino.

Desarrollo de una app para la generación preventiva de alertas sanitarias

Desde hace unos años, parece que la informática ha ido invadiendo numerosos campos de la ciencia, se ha ido consolidando como parte fundamental en el desarrollo y la tecnología y ya se puede ver como motor de la economía, las comunicaciones, el comercio e incluso, la medicina. Este trabajo se centra en la aplicación de la informática en el área de las enfermedades infecciosas, intentando contribuir con una nueva idea que revolucione el mundo de las mismas dentro de la medicina, en una situación en la que el término “Smart City” cada vez es más importante. Se trata de un sistema formado por una app para Android y una web controlada y gestionada por un médico, la cual permite identificar posibles usuarios contagiados, localizar focos de contagios y gestionar de una manera óptima, el estado y los avisos de cada usuario. En esta memoria se describe el trabajo realizado, la arquitectura del sistema, las tecnologías utilizadas, el diseño de la aplicación móvil y de la página web, su implementación, las pruebas realizadas, las conclusiones a las que se ha llegado y las posibles mejoras que se podrían incluir en el proyecto en un futuro.

Investigation of PHY, MAC and APP layers for adaptive and cross-layer optimization in IEEE802.11 WLAN

Due to huge popularity of portable terminals based on Wireless LANs and increasing demand for multimedia services from these terminals, the earlier structures and protocols are insufficient to cover the requirements of emerging networks and communications. Most research in this field is tailored to find more efficient ways to optimize the quality of wireless LAN regarding the requirements of multimedia services. Our work is to investigate the effects of modulation modes at the physical layer, retry limits at the MAC layer and packet sizes at the application layer over the quality of media packet transmission. Interrelation among these parameters to extract a cross-layer idea will be discussed as well. We will show how these parameters from different layers jointly contribute to the performance of service delivery by the network. The results obtained could form a basis to suggest independent optimization in each layer (an adaptive approach) or optimization of a set of parameters from different layers (a cross-layer approach). Our simulation model is implemented in the NS-2 simulator. Throughput and delay (latency) of packet transmission are the quantities of our assessments. © 2010 IEEE.

Chronic smartphone gaming consumption and positive coping practice

Purpose - Chronic consumption practice has been greatly accelerated by mobile, interactive and smartphone gaming technology devices. This study explores how chronic consumption of smartphone gaming produces positive coping practice. Design/methodology/approach - Underpinned by cognitive framing theory, empirical insights from eleven focus groups (n=62) reveal how smartphone gaming enhances positive coping amongst gamers and non-gamers. Findings - The findings reveal how the chronic consumption of games allows technology to act with privileged agency that resolves tensions between individuals and collectives. Consumption narratives of smartphone games, even when play is limited, lead to the identification of three cognitive frames through which positive coping processes operate: (a) the market generated frame, (b) the social being frame, and (c) the citizen frame. Research limitations/implications – This paper adds to previous research by providing an understanding of positive coping practice in the smartphone chronic gaming consumption. Originality/value - In smartphone chronic gaming consumption, cognitive frames enable positive coping by fostering appraisal capacities in which individuals confront, hegemony, culture and alterity-morality concerns. 

Towards automated Android app collusion detection

Android OS supports multiple communication methods between apps. This opens the possibility to carry out threats in a collaborative fashion, c.f. the Soundcomber example from 2011. In this paper we provide a concise definition of collusion and report on a number of automated detection approaches, developed in co-operation with Intel Security.

Konceptet mobilitet som tjänst : Viktiga kompetenser och möjliga utmaningar vid vidareutvecklingen av MaaS i Sverige.

Transport and travel is necessary for our society to function. Today, the privately owned car stands for more than half of all personal trips in Sweden. In the last couple of years researchers have highlighted the idea that personal transport is facing a paradigm shift, which means a reduction in the use and dependent of the privately owned car and an increased focus on individuals buying their Mobility as a Service (MaaS). MaaS is described as an integrated mix of different mobility services which are arranged in the form of customized mobility packages to the customer. These mobility packages can be compared to a mobile phone subscription, which includes various mobility services, such as train, bus, subway, taxi, carpool, etc. in various amounts depending on the individual's changing needs. The individual can take care of their own travel planning, booking and payment via an app in their smartphone. What distinguish MaaS from other mobility services is that the customer can travel from door-to-door instead of a predefine station to another. There have been various Maas projects around the world in order to increase understanding of the concept of MaaS, there is still a lot of unanswered questions and researchers would like to see more studies in the field, in order to find factors that are important and vital to the concept MaaS. The aim of the thesis is to: Discuss some competences that may be significant for the further development of the concept Maas in Sweden and discuss potential challenges that may arise at further development of the concept MaaS in Sweden. This study is based on previous research and experiences and thoughts on the concept MaaS from various stakeholders with knowledge and experience of the concept. This study has an abductive approach. Primary data were obtained through qualitative semistructured interviews with eight people who have knowledge and experience of the Maas. The main conclusions in this study is that the competences that are most important in the development of MaaS is collaborative skills and competences required to create an attractive mobility package based on customer needs. One challenge identified in this study is the challenge of creating individualized mobility package in which different types of mobility services are integrated. Another challenge can arise when public and private organizations collaborate and when new organizations enter the transport network and try to cooperate with the established organizations

Sistema de información para el seguimiento de la actividad y evolución de personas residentes en centros de atención personalizada

[ES] CronCare es una plataforma que establece una nueva vía bidireccional de comunicación entre los Centros de Atención Especializada y los familiares de sus residentes a través del uso de la tecnología. Conscientes de la importancia de la implicación de la familia en la realidad de los centros, esta herramienta se ha diseñado para ser un canal seguro, ágil y eficiente. La familia de cada residente recibe en su smartphone notificaciones en tiempo real de los eventos y las anotaciones que tienen lugar en el centro. El equipo de cuidadores dispondrá de una app para tabletas Android (también compatible con teléfonos) con la que podrá tomar los registros que alimentan al sistema y notificar a los familiares.

Analisi dei percorsi ciclabili registrati tramite smartphone sulla rete stradale di Bologna nell'ultimo triennio

La diffusione di smartphone con GPS si è rilevata utile per lo studio di modelli di scelta del percorso da parte di utenti che si muovono in bicicletta. Nel 2012 è stata ideata la ‘European Cyclinq Challenge’ (ECC), che consiste in una “gara” europea tra città: vince quella nella quale i rispettivi abitanti registrano il maggior numero di chilometri effettuati in bicicletta. In questo modo è possibile conoscere in forma anonima i percorsi realmente seguiti dai partecipanti alla gara: nel caso in esame, sono state fornite le tracce GPS registrate a Bologna sotto forma di punti catalogati ogni 10-15 secondi, a cui sono associate informazioni di coordinate, codice identificativo e istante di registrazione. Una fase di map-matching associa tali punti alla rete stradale di Bologna, descritta nel caso in esame dalla rete di Open Street Maps (OSM). Un elemento che garantisce al meglio la comprensione relativa alle scelte dei ciclisti, è quello di confrontarle con l’alternativa più breve, per capire quanto un utente sia disposto a discostarsi da essa per privilegiare ad esempio la sicurezza personale, il fatto di evitare pendenze elevate o incroci pericolosi. A partire dai punti GPS, che rappresentano l’origine e la destinazione di ogni viaggio, è possibile individuare sulla rete il percorso più corto che li congiunge, eseguendo sulla stessa rete tramite l’algoritmo di Dijkstra, considerando come unico attributo di costo la lunghezza. È stato possibile, mediante questi dati, effettuare un confronto nei tre anni di studio, relativamente alla distribuzione statistica delle lunghezze dei viaggi percorsi dagli utenti, a quanto questi si discostino dal percorso più breve ed infine come varia la percentuale dei viaggi effettuati nelle diverse tipologie stradali. Un’ultima analisi evidenzia la possibile tendenza degli utenti che si spostano in bicicletta nella città di Bologna, a utilizzare percorsi caratterizzati dalla presenza di numerosi incroci semaforizzati.

Quantification of upper limb motor symptoms of Parkinson’s disease using a smartphone

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Sviluppo di una app di ausilio per persone non vedenti per Android

La tesi prevede lo sviluppo di una app di ausilio per persone non vedenti per ambiente Android. L'applicazione ha due scopi principali: rilevazione degli ostacoli che l'utente incontra nel proprio cammino, tramite un apposito visore, con successivo invio di informazioni sugli ostacoli rilevati tramite output audio e tattili e realizzazione di una versione personalizzata di Google Maps che l'utente può utilizzare nella maniera più comoda e sicura possibile.