Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our previous reports suggest that HIV-1 transactivator of transcription (Tat) can directly cause pathology in neural progenitors and oligodendroglia (OLs) (Hauser et al. 2009). Thus, we have hypothesized that NPCs and/or glial progenitors may be targets of HIV proteins ± opiates drugs of abuse. To determine whether progenitors are targets of HIV-1, a multi-plex assay was performed to assess chemokine/cytokine expression after treatment with viral proteins Tat or glycoprotein 120 (gp120) with/without morphine. Murine striatal progenitors released increased amount of the beta-chemokines CCL5/regulated upon activation, normal T cell expressed and secreted (RANTES), CCL3/macrophage inflammatory protein-1α (MIP-1α), and CCL4/macrophage inflammatory protein-1β (MIP-1β) after 12 h exposure to HIV-1 Tat, but no to gp120. Secreted factors from Tat-treated progenitors were chemoattractive towards microglia, an effect blocked by 2D7 anti- C-C chemokine receptor type 5 (CCR5) antibody pre-treatment. Tat and opiates have interactive effects on astroglial chemokine secretion, but this interaction did not occur in progenitors. We also examined effects of Tat and morphine on proliferation and lineage progression of NPCs in vitro and in vivo. In vitro, Tat and morphine independently reduced the proliferation and population of Sox2+ and Olig2+ cells in the absence of cell death. The interactive effects of morphine and either Tat or supernatant from HIV-1SF162 infected monocytes varied depending on outcome measure and time of exposure, but interactive effects occurred primarily on proliferation. In rare instances, viable human progenitors were associated with p24 immunolabeling suggesting that progenitors may be infected, a concept that is still controversial. To investigate effects of Tat and morphine on NPCs in vivo, we used a mouse model in which HIV-1 Tat1-86 is conditionally expressed in astroglia. In vivo results in neonatal striata were similar to those in cell cultures. We extended the experiments into adult mice with inducing Tat expression for 3 month and the effect of sexes was examined in these animals. Intriguingly, males showed more Tat-induced impairment in behavioral tests (rotarod, grip strength, light-dark box) than females. Tat+ males also showed a greater reduction in the proportion of NeuN+ cells and NeuN immunoreactivity in the striatum, accompanied by greater microglial activation (3-nitrotyrosine+/Iba-1+). Unbiased stereological estimation in Nissl staining revealed that the depletion of NeuN immunoreactivity in these mice was not due to neuron cell death or loss, because the total neuron number in striatum and total striatal volume were not affected by long-term Tat induction. Tat exposure appears to selectively reduce levels of NeuN in living neurons, although the reason is not known. Therefore, both the enhanced microglial reactivity and depletion of NeuN levels in males may help to explain sex-specific behavioral outcomes. Sox2+ and Olig2+ cells showed equivalent reduction in their population in both sexes. Overall, our findings show that CNS progenitors, including both undifferentiated NPCs and glial progenitors, are vulnerable to individual or combined effects of HIV-1 or Tat and opiates. Changes in progenitor dynamics may alter the balance of cell populations in both the developing and adult CNS. We speculate that such changes may contribute to the behavioral abnormalities that we observed in Tat+ mice and which appear to model aspects of motor, cognitive and anxiety deficits in HIV-infected patients.

Este trabalho apresenta o estudo de um inversor NPC de 6 kW e 380 V, trifÃsico, para interconexÃo de sistemas de geraÃÃo distribuÃda à rede elÃtrica. O inversor à estudado nas frequÃncias de chaveamento de 3, 4 e 6 kHz, sendo interligado à rede elÃtrica atravÃs dos filtros L e LCL. Para identificar qual filtro passivo, L ou LCL, se adequa melhor ao inversor em estudo foram realizadas simulaÃÃes numÃricas para diferentes situaÃÃes, validando o projeto do inversor e a modelagem vetorial desenvolvida. A resposta do controle à satisfatÃria, pois o inversor à capaz de controlar o fluxo de potÃncia ativa e reativa entregues à rede elÃtrica. Diante dos resultados obtidos percebeu-se que o filtro LCL apresentou um menor conteÃdo harmÃnico para as trÃs frequÃncias estudadas em relaÃÃo ao filtro L. Ambos os filtros atenderam aos requisitos da norma Std IEEE 1543, no entanto o filtro L à o mais indicado para o inversor em estudo, pois alÃm de atender a norma, o mesmo apresenta um menor custo quando comparado ao filtro LCL. / This paper presents the study of a 6 kW, 380 V, three phase NPC inverter for interconnecting distributed generation unit to the grid. The inverter is studied with switching frequency of 3, 4 and 6 kHz, and it is interconnected to the grid through L and LCL filters. To identify which passive filter, L or LCL, is best suited to the inverter under study, a mathematical model has been proposed and several numerical simulations have been carried out to validate the design of the inverter and vector model developed. The control response is satisfactory, since the inverter is able to control the flow of active and reactive power delivered to the grid. Based on these results it was noticed that the LCL filter showed a lower harmonic content for the three frequencies studied in relation to the filter L. Both filters met the requirements of the standard IEEE Std 1543, however the filter L is the most suitable for the inverter under study, because the filter L not only meet the standard but also it presents a lower cost when compared to the LCL filter.

Niemann-Pick Type C (NPC) disease is an autosomal recessive disorder that results in accumulation of unesterified cholesterol in late endosomes/lysosomes (LE/Ls), leading to progressive neurodegeneration and premature death. Microglia are resident immune cells of the central nervous system, which upon activation can secrete potentially neurotoxic molecules such as tumor necrosis factor-alpha (TNFα). Inappropriate activation of microglia has been implicated in NPC disease. Primary microglia cultures from the cerebral cortex of Npc1-/- mice have an altered cholesterol distribution characteristic of NPC-deficient cells. Immunocytochemical analysis revealed increased TNFα staining in Npc1-/- microglia. However, Npc1-/- and Npc1+/+ microglia showed similar mRNA levels of pro-inflammatory cytokines and similar levels of TNFα secretion. To determine whether Npc1-/- microglia contribute to neuron death in NPC disease, microglia were co-cultured with cerebellar granule cells. Surprisingly, the extent of neuronal death was the same in neurons cultured with Npc1+/+ or Npc1-/- microglia. Thus, Npc1-/- microglia have an altered phenotype compared to Npc1+/+ microglia, but this does not lead to neuron death in an in vitro co-culture system. Treatment options for NPC disease remain limited. A consequence of cholesterol sequestration in the LE/Ls, is that cholesterol movement to the endoplasmic reticulum, where cholesterol metabolism is regulated, is impaired. Cyclodextrin (CD), a compound that binds cholesterol, has recently been found to delay the onset of neurological symptoms and prolong life of Npc1-/- mice. Since the brain consists of both neurons and glia, it remains unclear if CD acts directly on neurons and/or other cells in the brain. Neurons cultured from the cerebellum and astrocytes cultured from the cortex of Npc1-/- mice were treated with a low dose (0.1mM) of CD. This treatment decreased cholesterol sequestration and decreased the rate of cholesterol synthesis in Npc1-/- neurons and astrocytes. CD also decreased mRNAs encoding proteins involved in cholesterol synthesis in Npc1-/- neurons and increased genes involved in cholesterol efflux in Npc1-/- astrocytes. Moreover, CD increased cholesterol esterification in Npc1-/- astrocytes. These results suggest that cholesterol trapped in LE/Ls in Npc1-/- neurons and astrocytes was released by CD treatment and reached the ER, thereby regulating cholesterol homeostasis. / Experimental Medicine

<p>Detta är ett projekt som diskuterar och framställer en arkitektur för dynamisk dialog i dataspel. Den är skapad för att kunna ge mer spelarinteraktion i datarollspel i form av större frihet när det gäller hur en spelare vill spela sin karaktär samtidigt som den även ska ge bättre respons från NPC:er, just i ämnet dialoger. Beroende på vad och, framför allt, hur du som spelare säger något ska du få olika känslomässiga respons från dem. De ska kunna bli irriterade, hata, gilla och älska dig, med mera, samtidigt som de även ska kunna bli rädda för dig. Utöver detta har de även försetts med individuella minnen som tillåter dem att komma ihåg vad du har sagt och hur många gånger du har sagt det, vilket i sin tur tillåter att du får olika respons ju fler gånger du säger samma sak.</p>

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No description available.

Neste tabalho à realizado o estudo de um conversor de trÃs nÃveis com ponto neutro grampeado (NPC), proposto para a interligaÃÃo de sistemas de conversÃo de energia à rede elÃtrica. Para tanto à utilizado um filtro indutivo L, tÃcnicas de controle vetorial, e a tÃcnica PLLcomo mÃtodo de sincronismo. SÃo desenvolvidas equaÃÃes para a determinaÃÃo das perdas do conversor, as quais podem ser aplicadas a diversas tÃcnicas de modulaÃÃo PWM. TrÃs tÃcnicas sÃo apresentadas: modulaÃÃo PD; modulaÃÃo com injeÃÃo de terceiro harmÃnico (THIPWM); e modulaÃÃo vetorial baseada em portadora (CB-SVPWM). Toda a modelagem do sistema à apresentada, bem como um exemplo de projeto para um sistema de 6 kW.SÃo realizadas simulaÃÃes computacionaispara diferentes estudos de caso, validando o projeto do conversor e a modelagem desenvolvida. A resposta Ãs dinÃmicas do sistema à satisfatÃria, sendo o conversor capaz de controlar o fluxo de potÃncia ativa (com fator de potÃncia uniÃrio) e reativa entregues à rede. / This work deals with the study of a three-level inverter with Neutral Point Clamped (NPC), proposed for the interconnection of energy conversion systems to the grid. In order to accomplish a complete study, an inductive filter L is proposed, as well as vector control techniques and a PLL synchronization method. Equations are developed for the determination of the losses of the converter, which can be applied to various PWM techniques. Three Modulation techniques are presented: Phase Disposition modulation(PD), modulation with injection of the third harmonic (THIPWM) and carrier-based space vector modulation (SVPWM-CB). The complete modeling system is presented, as well as an example for designing a system of 6 kW. Numerical simulations are performed for different study cases, validating the converter design and modeling developed. The simulation results show that the proposed NPC converter is fully satisfactory, the converter being able to control the active (unity power factor) and reactive power flow delivered to the grid.

Detta är ett projekt som diskuterar och framställer en arkitektur för dynamisk dialog i dataspel. Den är skapad för att kunna ge mer spelarinteraktion i datarollspel i form av större frihet när det gäller hur en spelare vill spela sin karaktär samtidigt som den även ska ge bättre respons från NPC:er, just i ämnet dialoger. Beroende på vad och, framför allt, hur du som spelare säger något ska du få olika känslomässiga respons från dem. De ska kunna bli irriterade, hata, gilla och älska dig, med mera, samtidigt som de även ska kunna bli rädda för dig. Utöver detta har de även försetts med individuella minnen som tillåter dem att komma ihåg vad du har sagt och hur många gånger du har sagt det, vilket i sin tur tillåter att du får olika respons ju fler gånger du säger samma sak.

Massively Multiplayer Online Role Playing Games (MMORPGs) are a prominent genre in today's video game industry with the most popular MMORPGs generating billions of dollars in revenue and attracting millions of players. As they have grown, they have become a major target for both technological research and sociological research. In such research, it is nearly impossible to reach the same player scale from any self-made technology or sociological experiments. This greatly limits the amount of control and topics that can be explored. In an effort to make up a lacking or non-existent player-base for custom-made MMORPG research scenarios A.I. agents, impersonating human players, can be used to "bootstrap" the research scenario to reach the necessary massive number of players that define the game genre. This thesis presents a system that makes its human players and A.I. players indistinguishable while preserving the basic characteristics of a typical MMORPG. To better achieve identical perception of human and A.I. players, our system centers around the collection, sharing, and exchange of information while limiting the means of expression and actions of players. A gameplay scenario built on the Panoptyk engine was constructed to imitate gameplay experienced in major MMORPGs. We conducted a user-study where subjects play through the scenario with a varying number of A.I. players unknown to them. Three versions of the scenario were created to assess how indistinguishable human and A.I. players were and vice versa. We found, across 24 participants, there were 32% correct identifications, 30% incorrect identifications, and 38% answers of "I don't know". This was broken down into 20% correct identifications, 42% incorrect identifications, and 38% answers of "I don't know" for bot characters and 46% correct identifications, 16% incorrect identifications, and 38% answers of ``I don't know'' for human characters.

This study shows the importance of leading toward missional change within BUSA in post-1994 contexts incorporating global, afro-centric missional perspectives as South African Baptists. As my research will indicate, BUSA is at a crucial junction, and I contend that BUSA’s main problem is primarily a missiological problem, with ecclesiastical challenges that urgently need to be addressed by BUSA’s leaders. The importance of BUSA’s critical self- reflection and analysis is paramount. Does BUSA and her mission have a future, or will it fade into obscurity? Utilizing the South African Baptist faith heritage as an important interlocutor with a view to retrospective and prospective Baptist ecclesiology in post- 1994 South African society. Special recognition is given to the contribution of emerging Afro-centric missional voices within the current South African/African context. In doing so, this study seeks to be leadership-oriented, biblically-based and Afro-centric in its approach to missional change with South African Baptist Union churches. Toward missional leadership within BUSA churches this study: <ul> <li>1. Uncovers the importance of an Afro-centric missional ecclesiology, taking into consideration both local and global trends and conversations.</li> <li>2. Uncover a retrospective view of Baptist Ecclesiology within the Southern African context, with its relevance to the history and present-day context of ministry within BUSA.</li> <li>3. Analyses existing statistical data found within the Baptist Annual Handbook, to establish denominational trends since 1994, with a view to identifying significant ministry trends operable within BUSA.</li> 4. Collects, analyses and interprets data from a number of churches from within the Baptist Union of Southern Africa that stand out as significant in three or more ‘missional indicators’ in the first tier of research and analysis. In reading through the pages to follow, you will journey alongside the researcher in:</li> </ul> <ul> <li> Analysing and interpreting the history of Baptists in South Africa with reference to BUSA, BCSA, SABMS and the ABK through a ‘missional lens’</li>. <li> Critically examining current trends visible within BUSA churches since 1994 to the present-day.</li> <li> Undertaking qualitative research to identify phenomenology of people’s shared experience in BUSA</li> <li> Interpreting and objectifying statistical results drawn from qualitative research at local church level; making further recommendations towards an Afro-centric missional ecclesiology relevant to BUSA churches in post-1994 contexts.</li> </ul> / Thesis (PhD)--University of Pretoria, 2012. / Science of Religion and Missiology / unrestricted