ABCA7 is the closest homologue of ABCA1, which is established to play a key role in reverse cholesterol transport. ABCA1 deficiency causes Tangier disease and several ABCA1 modulations have been recently associated with Alzheimer’s disease. Prior research on ABCA7 focused on its role in macrophage lipid efflux and phagocytosis, however, tissue expression studies in mice revealed that ABCA7 is highly expressed in the brain. The function of ABCA7 in the brain is unknown and the purpose of this thesis was therefore to investigate the potential function of ABCA7 in the brain and the possible implications for Alzheimer’s disease. This was achieved by using in vitro models that transiently express ABCA7 and in vivo models including ABCA7 knockout (ABCA7 KO) mice and human APP transgenic (APPSwInd Tg) mice. ABCA7 was shown to potently stimulate cholesterol efflux from cells to extracellular apoE acceptors. Additionally, apoE expression was decreased by 20% in the brains of ABCA7 KO mice compared to wild type littermate controls and by 46% in ABCA7-deficient macrophages. In vitro models that stably express human APP protein demonstrated that the transient expression of ABCA7 increased intracellular APP targeting, which led to the inhibition of APP processing and a resultant decrease in the production of Aβ. In addition, ABCA7-deficient macrophages displayed impaired capacity to endocytose and degrade Aβ oligomers. Finally, in aged APPSwInd Tg mice where abundant amyloid plaques were present, ABCA7 expression was significantly decreased by 48%. Since cholesterol homeostasis modulates APP processing, the findings of this thesis suggest that ABCA7 may have a role in maintaining cellular cholesterol homeostasis via cholesterol efflux to apoE acceptors and possibly by regulating intracellular trafficking of specific membrane proteins. In summary, ABCA7 was clearly shown in this thesis to have an effect on Aβ generation, clearance and degradation. Furthermore, ABCA7 expression was also affected by Aβ deposition in the brain. Even though more work is required to further elucidate the exact function of ABCA7, the findings presented in this thesis provide the first clues to the function of ABCA7 in the brain.

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Sócio-Econômico, Programa de Pós-Graduação em Administração, Florianópolis, 2017 / Made available in DSpace on 2017-12-12T03:28:25Z (GMT). No. of bitstreams: 1 349185.pdf: 2988664 bytes, checksum: 48187560df5586205b125bc23d98c9cf (MD5) Previous issue date: 2017 / O objetivo central desta tese é o de compreender a gestão de uma Unidade de Conservação (UC) federal gerida pelo ICMBio. Para atingi-lo, realizei um estudo etnográfico entre os anos de 2014 e 2015 em uma área protegida situada na cidade de Florianópolis, Santa Catarina. O referencial teórico-analítico que utilizei se inicia com uma discussão sobre o posicionamento epistemológico assumido, baseie-me, fundamentalmente, nos autores pragmatistas clássicos. Posteriormente, apresento o surgimento de estudiosos preocupados com o tratamento da ação social, em especial, os estudos baseados em práticas e a sociologia pragmática francesa. Com isso, exponho as ferramentas analíticas que foram utilizadas, em especial, questões da sociologia da expertise e noções do pensamento de Gilbert Simondon. Ao finalizar as exposições teórica e metodológica, introduzi um capítulo destinado aos elementos para a ação, composto por um conjunto de documentos que esboçam o campo de atuação das UCs. Em seguida, identifiquei e analisei as práticas dessa organização, como resultado me deparei com dois fenômenos que garantem certos modos de existência à organização, personalização e personificação. No primeiro, a organização ganha aspectos peculiares que a individualiza das demais, no segundo é influenciada pelas características pessoais e grupais dos servidores. Após a exposição das práticas da UC estudada, busquei um salto analítico, com análises dos referenciais dinâmicos para as ações dessas organizações, que puderam ser identificados a partir de seis operadores, a saber: individuações, materialidade, formas de organização, situações de prova, redes inter-organizacionais e noções de responsabilidade. No último capítulo, realizei comparações entre a literatura representativa e difundida sobre gestão e os gestores, que é utilizada para embasar as metodologias aplicadas no ICMBio com os elementos evidenciados por esta tese, com base na pesquisa etnográfica realizada. Nesse sentido, compreendi que a gestão é um fenômeno de coordenação de ações que garante espaços para negociações sobre o engendramento de ações coletivas que resultarão em performances organizacionais, que poderão ser alvos de julgamentos. / Abstract : The central objective of this thesis is to understand the management of a Federal Conservation Unit (UC) managed by ICMBio. To achieve this, I conducted an ethnographic study between 2014 and 2015 in a protected area located in the city of Florianópolis, Santa Catarina. The theoretical-analytical framework that I have used begins with a discussion of the assumed epistemological positioning, based fundamentally on the classical pragmatist authors. Subsequently, I present the emergence of scholars concerned with the treatment of social action, in particular, practice-based studies and French pragmatic sociology. With this, I present the analytical tools that were used, in particular, questions of the sociology of expertise and notions of the Gilbert Simondon thought. At the end of the theoretical and methodological expositions, I introduced a chapter devoted to the elements for action, composed of a set of documents that outline the field of action of UCs. Then, I identified and analyzed the practices of this organization, as a result I came across two phenomena that guarantee certain modes of existence to the organization, personalization and personification. In the first, the organization gains peculiar aspects that individualize it from the others, in the second it is influenced by the personal and group characteristics of the servers. After analyzing the practices of the UC studied, I looked for an analytical leap, with analyzes of the dynamic references for the actions of these organizations, that could be identified from six operators, namely: individuations, materiality, forms of organization, proof situation, Inter-organizational networks and notions of responsibility. In the last chapter, I made comparisons between the representative and diffused literature on management and managers, which is used to support the methodologies applied in the ICMBio with the elements evidenced by this thesis, based on the ethnographic research carried out. In this sense, I understood that management is a phenomenon of coordination of actions that guarantees spaces for negotiations on the generation of collective actions that will result in organizational performances that may be the targets of judgments.

Målet med det här arbetet har varit att ta fram en Androidapplikation som kan spåra användaren och ge information om hur användaren rört sig med tid, distans altitud och hastighet. Applikationen ska vara individuellt fungerande men det stora syftet är att den ska fungera som en av tre delar i en större applikation med fler funktioner för de som är ute i skogen och rör på sig. Då inte alla telefoner har en inbyggd stegräknare kommer en undersökning göras för att se vilken sensor som lämpar sig bäst för att räkna steg och sedan använda den i applikationen. Resultatet blev en fungerande applikation som spårar användaren med hjälp av GPS, räknar antalet steg med antingen den inbyggda stegräknaren eller med hjälp av gyroskopet som visade sig vara den mest lämpade sensorn att räkna steg med. Utöver det så presenteras information om tid, distans och vilken altitud användaren rört sig på. All information kan sparas och användaren kan scrolla i en lista med sparade rutter.

Syftet med studien är att undersöka hur lärplattan används i olika lärmiljöer på ett flertalförskolor i en kommun. Lärplattan är idag ett verktyg som både förskollärare och barnskötareanvänder i verksamheten bland barnen på förskolan. Digitala verktyg är för barnen idag ettcentralt och vanligt arbetsverktyg som inte längre är en fråga om det ska användas i förskolaneller inte, utan hur det ska arbetas med i förskolan.Metoden som används i studien är intervjuer med sex respondenter, både förskollärare ochbarnskötare. Det insamlade materialet utifrån intervjufrågorna har tolkats och sammanställts istudiens resultatdel.Resultatet visar att lärplattan som används av pedagogerna ses som ett komplement med bådefördelar och nackdelar. Fördelarna är att lärplattan kan göra arbetet lättare för pedagogerna i denpedagogiska verksamheten, ta bort administrativt arbete och att flera barn kan interagera medverktyget samtidigt oberoende av om de har språket eller inte. Nackdelar kring lärplattan är attden medför mycket oro över hur den påverkar barnens inlärning. Många pedagoger saknarkunskap för verktyget och väljer att låta den ligga vilket då resulterar i att lärplattan blir enbarnvakt istället för ett verktyg för lärande.

Alzheimer's disease (AD) is a neurodegenerative disease associated with progressive dementia. This mini-review focuses on how the amyloid precursor protein (APP) plays a central role in AD and Down syndrome as the regulator of the APP-BP1/hUba3 activated neddylation pathway. It is argued that the physiological function of APP is to downregulate the level of β-catenin. However, this APP function is abnormally amplified in patients with familial AD (FAD) mutations in APP and presenilins, resulting in the hyperactivation of neddylation and the decrease of β-catenin below a threshold level. Evidence in the literature is summarized to show that dysfunction of APP in downregulating β-catenin may underlie the mechanism of neuronal death in AD and Down syndrome.

Nuestro proyecto consiste es crear una aplicación que sea intermediaria entre los estudiantes actuando como clientes, que necesiten llegar a su destino a través de carros particulares de manera segura, cómoda y rápida, con conductores, los cuales serán otros estudiantes que dispongan de vehículos y vayan por rutas similares o iguales. Nuestro mercado objetivo son jóvenes universitarios de la ciudad de Lima de 18 a 24 años de un nivel socioeconómico A, B y C. Además, nuestro servicio se diferencia de la competencia, ya que tenemos como política desarrollar actividades de RSE para preservar el cuidado del medio ambiente. Asimismo, cabe resaltar que el mercado limeño es altamente atractivo por la creciente demanda en donde dice que este año y el próximo año la demanda de carros aumentará en 250 mil carros cada año. Para el desarrollo del proyecto, se han realizado análisis cualitativo y cuantitativo, utilizando herramientas como entrevistas y aplicación de encuestas, teniendo como fin determinar el comportamiento de los usuarios y medir el nivel de aceptación de nuestro proyecto. Finalmente, se explicará y se desarrollará el plan financiero y los principales KPI´s de rentabilidad de negocio, la cual permitirá demostrar la sostenibilidad, rentabilidad y escalabilidad del negocio. / Our Business Entrepreneurship Assignment is about creating an app that is an intermediary between students acting as customers, who need to reach their destination through private cars safely, comfortably and quickly and students with cars playing as drivers that go by similar routes. We set as target market is young university students in the city of Lima from 18 to 24 years of socioeconomic level A, B and C. In addition, our service differs from the competition, since we have as policy to develop CSR activities to preserve the care of the environment. Also, it should be noted that the limeño market is highly attractive due to the growing demand where it says that this year and next year the demand for cars will increase by 250 thousand cars each year. For the development of the project, qualitative and quantitative analysis has been carried out, using tools such as interviews and survey application, with the purpose of determining the behavior of users and measuring the level of acceptance of our project. Finally, the financial plan and the main KPIs of business profitability will be explained and developed, which will allow demonstrating the sustainability, profitability and scalability of the business. / Trabajo de investigación

Indiana University-Purdue University Indianapolis (IUPUI) / Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the post-mortem deposition of amyloid-beta (Aβ) containing neuritic plaques and tau-loaded tangles. According to the amyloid hypothesis, the generation of Aβ via the cleavage of Aβ precursor protein (APP) by β-APP site-cleaving enzyme 1 (BACE1) is a causative step in the development of AD. Therefore, targeting the production and/or clearance of Aβ peptide (by Aβ-degrading enzymes such as Neprilysin) would help understand the disorder as well as serves as therapeutic potential to treat the disorder. MicroRNA are small, noncoding RNA capable of modulating protein expression by primarily targeting their 3’UTR. Therefore, identifying miRNA which target APP, BACE1 and Neprilysin (NEP) would elucidate the complicated regulatory mechanisms involved in protein turnover and provide novel drug targets. We identified miR-20b as a modulator of APP and soluble Aβ. We also identified the target site for miR-20b’s binding on the APP 3’UTR. Further, miR-20b exerts influence on neuronal morphology, likely due to its APP reduction. We also identified miR-298 as a dual regulator of APP and BACE1 and confirmed miR-298’s targeting of both 3’UTRs. We also showed that miR-298 overexpression reduced levels of both soluble Aβ40 and Aβ42 peptides. Additionally, we identified two SNPs in proximity to the MIR298 gene, which are associated with AD-related biomarkers. Based on these results, we showed miR-298 targets a specific isoform of tau by putatively binding a non-canonical target site on the MAPT 3’UTR. Finally, the insertion of the NEP 3’UTR into a reporter vector increases reporter expression; suggesting regulatory elements targeting the 3’UTR. We subsequently identified miR-216 as reducing NEP 3’UTR-mediated luciferase activity. We also measured levels of NEP protein in various mammalian tissue – such as rodent and human fetal tissue, and subsequently showed measurable Aβ levels in correlation with NEP expression. Therefore, herein, we have identified miRNA involved in the regulation of proteins implicated in the pathogenesis of AD.

No description available.

No description available.

Android malware collusion is a new threat model that occurs when multiple Android apps communicate in order to execute an attack. This threat model threatens all Android users' private information and system resource security. Although recent research has made advances in collusion detection and classification, security analysts still do not have robust tools which allow them to definitively identify colluding Android applications. Specifically, in order to determine whether an alert produced by a tool scanning for Android collusion is a true-positive or a false-positive, the analyst must perform manual analysis of the suspected apps, which is both time consuming and prone to human errors. In this thesis, we present a new approach to definitive Android collusion detection and confirmation by rendering inter-component communications between a set of potentially collusive Android applications. Inter-component communications (abbreviated to ICCs), are a feature of the Android framework that allows components from different applications to communicate with one another. Our approach allows Android security analysts to inspect all ICCs within a set of suspicious Android applications and subsequently identify collusive attacks which utilize ICCs. Furthermore, our approach also visualizes all potentially collusive data-flows within each component within a set of apps. This allows analysts to inspect, step-by-step, the the data-flows that are currently used by collusive attacks, or the data-flows that could be used for future collusive attacks. Our tool effectively visualizes the malicious and benign ICCs in sets of proof-of-concept and real-world colluding applications. We conducted a user study which revealed that our approach allows for accurate and efficient identification of true- and false-positive collusive ICCs while still maintaining usability. / Master of Science