For many years, community colleges that chose to offer community college baccalaureate (CCB) programs were looked upon in a negative light (Rice, 2015). However, as the need for specialized baccalaureates within specific fields and job markets have continued to grow (McKee, 2005), CCB programs are becoming more widely accepted throughout the United States. In spite of this paradigm shift, Mississippi is one of the remaining states that have not embraced the idea of CCB programs, in spite of its statistical deficiency in regards to baccalaureate degree holding citizens (Williams, 2010). The focus of this study was to explore the perceptions of community college administrators in Mississippi with regards to the influence of CCB programs to the community college mission of institutions in their state. This study indicates that administrators in Mississippi recognize the benefits of offering CCB programs, but do not want CCB programs to take away from the well-established statewide higher education system through mission creep. Many of the strong position statements received overwhelmingly neutral responses. In contrast, Administrators who chose to give their opinion indicated that they are not familiar with how CCB programs are implemented, and do not believe that Mississippi is ready for CCB programs across the state. However, respondents felt that the community college mission is always evolving, should meet students’ needs, and varies from location to location. The findings also show that administrators are favorable to the piloting of CCB programs at a few (1-2) institutions, even though they believe the programs will take funding away from current programs and do not want community colleges evolving into 4-year institutions. The study also concludes that there is a significant difference between institution size and survey questions #18 and #20. There is also a significant difference between length of time in the community college sector and survey questions #15, #17, and #18.

Hypertension is a global disease that many effected people in developing countries is not aware of. Hypertension is linked with cardiovascular disease. Prehypertension is not a disease but if not correctly treated, it could develop into hypertension. The aim of the study was to investigate if there are any differences in circadian blood pressure between two study groups, one group with normal blood pressure and one group with prehypertension. This study was a explorative study and its design is based on measurements of blood pressure values and a questionnaire was used to help get the data collection. 51 students volunteered to have their blood pressure taken from them and out of these 51, 24 where selected into two groups of 12 each for the Ambulatory blood pressure monitoring. hese 24 students would be a part of our study and an ambulatory (Schiller-102 plus) blood pressure monitor was used to collect the data. The prevalence of prehypertension findings in the clinical testing phase was 37% of the population. There was a variation between the groups during the day (systolic) but there was not a significant difference during the night.

Planning, optimalization, production management, process management, production, ERP

Multi functional health monitoring wearable devices are quite prominent these days. Usually these devices are battery-operated and consequently are limited by their battery life (from few hours to a few weeks depending on the application). Of late, it was realized that these devices, which are currently being operated at fixed voltage and frequency, are capable of operating at multiple voltages and frequencies. By switching these voltages and frequencies to lower values based upon power requirements, these devices can achieve tremendous benefits in the form of energy savings. Dynamic Voltage and Frequency Scaling (DVFS) techniques have proven to be handy in this situation for an efficient trade-off between energy and timely behavior. Within imec, wearable devices make use of the indigenously developed MUSEIC v2 (Multi Sensor Integrated circuit version 2.0). This system is optimized for efficient and accurate collection, processing, and transfer of data from multiple (health) sensors. MUSEIC v2 has limited means in controlling the voltage and frequency dynamically. In this thesis we explore how traditional DVFS techniques can be applied to the MUSEIC v2. Experiments were conducted to find out the optimum power modes to efficiently operate and also to scale up-down the supply voltage and frequency. Considering the overhead caused when switching voltage and frequency, transition analysis was also done. Real-time and non real-time benchmarks were implemented based on these techniques and their performance results were obtained and analyzed. In this process, several state of the art scheduling algorithms and scaling techniques were reviewed in identifying a suitable technique. Using our proposed scaling technique implementation, we have achieved 86.95% power reduction in average, in contrast to the conventional way of the MUSEIC v2 chip’s processor operating at a fixed voltage and frequency. Techniques that include light sleep and deep sleep mode were also studied and implemented, which tested the system’s capability in accommodating Dynamic Power Management (DPM) techniques that can achieve greater benefits. A novel approach for implementing the deep sleep mechanism was also proposed and found that it can obtain up to 71.54% power savings, when compared to a traditional way of executing deep sleep mode. / Nuförtiden så har multifunktionella bärbara hälsoenheter fått en betydande roll. Dessa enheter drivs vanligtvis av batterier och är därför begränsade av batteritiden (från ett par timmar till ett par veckor beroende på tillämpningen). På senaste tiden har det framkommit att dessa enheter som används vid en fast spänning och frekvens kan användas vid flera spänningar och frekvenser. Genom att byta till lägre spänning och frekvens på grund av effektbehov så kan enheterna få enorma fördelar när det kommer till energibesparing. Dynamisk skalning av spänning och frekvens-tekniker (såkallad Dynamic Voltage and Frequency Scaling, DVFS) har visat sig vara användbara i detta sammanhang för en effektiv avvägning mellan energi och beteende. Hos Imec så använder sig bärbara enheter av den internt utvecklade MUSEIC v2 (Multi Sensor Integrated circuit version 2.0). Systemet är optimerat för effektiv och korrekt insamling, bearbetning och överföring av data från flera (hälso) sensorer. MUSEIC v2 har begränsad möjlighet att styra spänningen och frekvensen dynamiskt. I detta examensarbete undersöker vi hur traditionella DVFS-tekniker kan appliceras på MUSEIC v2. Experiment utfördes för att ta reda på de optimala effektlägena och för att effektivt kunna styra och även skala upp matningsspänningen och frekvensen. Eftersom att ”overhead” skapades vid växling av spänning och frekvens gjordes också en övergångsanalys. Realtidsoch icke-realtidskalkyler genomfördes baserat på dessa tekniker och resultaten sammanställdes och analyserades. I denna process granskades flera toppmoderna schemaläggningsalgoritmer och skalningstekniker för att hitta en lämplig teknik. Genom att använda vår föreslagna skalningsteknikimplementering har vi uppnått 86,95% effektreduktion i jämförelse med det konventionella sättet att MUSEIC v2-chipets processor arbetar med en fast spänning och frekvens. Tekniker som inkluderar lätt sömn och djupt sömnläge studerades och implementerades, vilket testade systemets förmåga att tillgodose DPM-tekniker (Dynamic Power Management) som kan uppnå ännu större fördelar. En ny metod för att genomföra den djupa sömnmekanismen föreslogs också och enligt erhållna resultat så kan den ge upp till 71,54% lägre energiförbrukning jämfört med det traditionella sättet att implementera djupt sömnläge.

Made available in DSpace on 2011-05-04T12:36:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2009 / O objetivo desta dissertação consiste em investigar o processo de construção da identidade profissional de médicos que se dedicam à assistência a pacientes que apresentam doenças progressivas e ameaçadoras da continuidade existencial e que têm contribuído para o desenvolvimento dos Cuidados Paliativos no Brasil. Buscamos conhecer a trajetória profissional destes médicos desde a escolha da medicina como profissão até o encontro com a filosofia e a prática dos Cuidados Paliativos. Com este intuito, realizamos entrevistas semiestruturadas,colhidas segundo a metodologia de História Oral de Vida. Foram entrevistados seis médicos de diferentes especialidades que ocupam cargos diretivos em uma das associações profissionais voltadas para a disseminação e legitimação política e social dos Cuidados Paliativos no Brasil. Os depoentes se destacam no cenário nacional no que diz respeito às discussões sobre esta temática e mantêm contato com importantes instituições internacionais. Por esta razão, chamamos o conjunto de entrevistados de elite médica paliativista. Percebemos uma pobre interlocução entre os médicos paliativistas, o que se reflete na ausência de uma identidade integrada desse grupo profissional. Os entrevistados acentuaram as competências humanitárias necessárias ao bom exercício da Medicina Paliativa, mas, no entanto, não foram explicitadas as competências específicas a este campo profissional, que justificariam seu reconhecimento pelas entidades médicas competentes comouma nova área de atuação ou especialidade.

Hydrogel, semi-interpenetrating polymer network, poly(2-hydroxyethyl methacrylate), diffusion

This Master Thesis is the research done in the country of Rwanda. The project leads to study the climate of this country in order to establish whether this climate could be used to produce energy from air and to implement the first wind turbine for serving the nation.   After an introduction about the historical background of wind power, the thesis work deals with assessment of wind energy potential of Rwanda in focusing of the most suitable place for wind power plants. The best location with annual mean wind speed, the rate of use of turbine with hub height for an annual production per year, the mean wind speeds for 6 sites of Rwanda based on ECMWF for climatic data for one year at relief of altitude of 100m and coordinates are reported too.   The result of energy produced and calculations were done based on power hitting wind turbine generator in order to calculate Kinetic energy and power available at the best location to the measurement over the period of 12 months, that could be hoped for long term.   With help of logarithmic law, where wind speed usually increases with increasing in elevation and the desired wind speeds at all 6 sites were used. The annual energy production was taken into account at the best site with desired wind speed at the initial cost of turbine as well as the cost of energy (COE).However, with comparison of the tariff of EWSA, the price of Wind designed in this Research per kWh is cheaper and suitable for people of Rwanda. / <p><em>Rwanda has considerable opportunities development energy from hydro sources, methane gas, solar and peat deposits. Most of these energy sources have not been fully exploited, such as solar, wind and geothermal. As such wood is still being the major source of energy for 94 per cent of the population and imported petroleum products consume more than 40 per cent of foreign exchange. Energy is a key component of the Rwandan economy. It is thus recognized that the current inadequate and expensive energy supply constitutes a limiting factor to sustainable development. Rwanda’s Vision 2020 emphasizes the need for economic growth, private investment and economic transformation supported by a reliable and affordable energy supply as a key factor for the development process. To achieve this transformation, the country will need to increase energy production and diversify into alternative energy sources. Rwandan nations don’t have small-scale solar, wind, and geothermal devices in operation providing energy to urban and rural areas. These types of energy production are especially useful in remote locations because of the excessive cost of transporting electricity from large-scale power plants. The application of renewable energy technology has the potential to alleviate many of the problems that face the people of Rwanda every day, especially if done so in a sustainable manner that prioritizes human rights.</em></p>

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal. / The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal. / The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.

No description available.