O sistema dois-hidrido de levedura para confirmação da sinalização de APP Tipo-Noth

Inúmeras potenciais funções foram sugeridas para a APP (Proteína Precursora de Amilóide de Alzheimer), contudo, fisiologicamente, a função precisa da APP não foi ainda desvendada. A APP tem características consistentes com a função de molécula-receptora, capaz de reconhecer sinais extracelulares. Também relevante para este trabalho, é o facto de que a sinalização através de RIP (Proteólise Intramembranar Regulada) tem consequências na expressão génica, como no caso da sinalização tipo-Notch. Tal como a proteína Notch, a APP é processada resultando num fragmento C-terminal designado por AICD (Domínio Intracelular da APP). Neste trabalho é focado o papel importante na sinalização nuclear desempenhado pelo fragmento AICD, especificamente através da interacção com proteínas adaptadoras, promovendo a transcrição. Com o objectivo de contribuir para uma melhor compreensão da base molecular da DA (Doença de Alzheimer), torna-se importante investigar as vias de localização nuclear do AICD e o seu envolvimento na transcrição génica, possivelmente afectando proteínas até agora não associadas à DA. Por estes motivos é fundamental a identificação de novas proteínas que interajam com a APP. Um rastreio foi efectuado, utilizando o sistema Dois-Híbrido em Levedura, para identificar interacções específicas do AICD no cérebro humano e, assim, caracterizar o interactoma do AICD. Foi feito o rastreio de aproximadamente 1.1x108 clones de uma biblioteca de cDNA de cérebro humano com o domínio C-terminal da APP com a mutação Y687E, que mimetiza o estado fosforilado. De experiências anteriores deste laboratório sabemos que a tirosina-687 afecta a localização subcelular da APP e é também consensual que a fosforilação é importante nos mecanismos de transdução de sinais, daí a utilização deste mutante parecer apropriada. O rastreio originou 55 clones positivos que foram analisados para identificar proteínas que interagem com a APP. Dois clones são particularmente importantes, a RanBPM e a Transportin-SR2, visto que estão associadas ao transporte de proteínas para o núcleo e confirmam a sinalização nuclear da APP. ABSTRACT: Many putative functions for APP (Alzheimer’s amyloid precursor protein) have been suggested, although the precise physiological function of APP remains to be elucidated. APP has characteristics consistent with it having a role as a receptor, capable of mediating extracellular signals. Also of relevance to the work described here is that RIP (Regulated Intramembrane Proteolysis) signalling can have consequences in gene expression, similar to Notch signalling. Like the latter, APP is processed by RIP resulting in a C-terminal fragment known as AICD. Here we test the hypothesis that the AICD fragment may play an important role in nuclear signalling, specifically by interacting with adaptor proteins potentiating transcription. Therefore, in order to contribute to our understanding of the molecular basis of AD (Alzheimer’s disease) it is important to investigate the pathways of AICD nuclear targeting and its involvement in gene transcription, possibly affecting other proteins hitherto not associated with AD. Thus, it is important to identify AICD binding proteins. A Yeast Two-Hybrid (YTH) screen was performed to identify human brainspecific AICD binding proteins, and thus characterize the AICD interactome. The screen of approximately 1.1 x108 clones from a human brain cDNA library was carried out using the AICD fragment with an Y687E mutation, which mimics phosphorylation on that residue. From previous work carried out in the laboratory we know that tyrosine-687 phosphorylation affects subcellular localization of APP, and it is also recognized that phosphorylation events are important in signal transduction mechanisms, hence the use of this mutant is appropriate. The YTH screen yielded 55 positive clones that were analysed and several novel brain-specific APP binding proteins were identified. Two clones were particularly important, RanBPM and Transportin-SR2, being that they are associated with the nuclear transport of proteins, and support the nuclear signalling for APP.

Expérimentation de l'apprentissage par problèmes (APP) en formation initiale pour développer les compétences professionnelles des enseignants au primaire

Ce mémoire fait état d'un changement de pratique dans la manière de former les futurs enseignants au primaire. Il permet de se familiariser avec l'apprentissage par problèmes (APP) et de comprendre l'intérêt d'utiliser cette méthode d'apprentissage dans une visée de professionnalisation des enseignants (Béchard, 2001, Iglesias, 2002, Lessard, 2005, Galand et Frenay, 2005). S'appuyant sur une méthodologie de recherche-intervention, notre démarche s'est inscrite dans une approche descriptive et compréhensive. Ainsi, cette étude nous a permis d'expérimenter l'APP dans un cours de didactique du français du programme de BEPP de l'Université de Sherbrooke, pour ensuite exposer les difficultés rencontrées et les bénéfices perçus par les étudiants en lien avec l'utilisation de l'APP, particulièrement en ce qui a trait au développement des compétences professionnelles. Les résultats obtenus semblent très prometteurs quant à l'atteinte des objectifs visés.

App mobile “My Corine de Farme”

Trabalho de projeto apresentado à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Publicidade e Marketing.

Projeto de desenvolvimento de App de apoio ao cliente para operador de telecomunicações

Trabalho de projeto apresentado à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Publicidade e Marketing.

How to design and develop There App: A mobile app focused on live video streaming, promoting new social interactions

This work project aims to demonstrate how to design and develop an innovative concept of video streaming app. The project combines technology push and market pull theories into developing a product that is more suitable for the customer needs, with the particularity that there is no other way of seeing any place in the world, live and ondemand. An analysis on the bigger influencers in terms of design-thinking and new product development, as Tim Brown or Paul Trott, lead to a better understanding on how There App should evolve, keeping in mind the customer desires and technical features.

Opportunities and threats for the launch of a smartphone app

Field lab: Entrepreneurial and innovative ventures

Impact of mobile app user acquisition on managerial decisions: Evidence from empirical experiment

In this research we conducted a mixed research, using qualitative and quantitative analysis to study the relationship and impact between mobile advertisement and mobile app user acquisition and the conclusions companies can derive from it. Data was gathered from management of mobile advertisement campaigns of a portfolio of three different mobile apps. We found that a number of implications can be extracted from this intersection, namely to product development, internationalisation and management of marketing budget. We propose further research on alternative app users sources, impact of revenue on apps and exploitation of product segments: wearable technology and Internet of Things.

Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.

La Implantació de l’aprenentatge basat en problemes (APB-APP) en l’educació universitària: anàlisi d’una experiència

En aquest document es detalla l’experiència que s’ha portat a terme en l’Escola Politècnica Superior de la UdG. Concretament en l’assignatura de Fonaments Físics per l’enginyeria en l’àmbit de les titulacions de Disseny Industrial i d’Enginyeria Tècnica Industrial especialitat en Mecànica. L’objectiu general de l’activitat és aportar als alumnes els coneixements bàsics sobre camps elèctrics i teoria de circuits, des dels fonaments conceptuals, passant per l’aplicació dels conceptes en problemes fins a realitzar un esquema del procés, així com la utilització de les noves tecnologies tot aplicant com a tècnica d’aprenentatge basat en problemes: Project Based Learning (APB)

L'Avaluació en l'APP: l'experiència de l'INSA de Tolosa (França)

Presentació de l'experiència d'avaluació en APP a l'Institut Nacional de Ciències Aplicades de Tolosa

Mobile App Development Platforms

Tutorial Resources

Mobile Design Principles and JQuery Mobile App Customisation

Slide to go with Panopto recording for MA Communication Design on best practice for mobile ui design and some basic JQuery Mobile Customisation. Big thanks to Jonathan Stark Luke Wroblewski Jared Spool Without whom this would not have been made