Human Immunodeficiency Virus Type 1 (HIV-1), the virus that causes Acquired Immunodeficiency Syndrome (AIDS), attacks the immune system leaving patients susceptible to opportunistic infections that eventually cause death. Highly Active Antiretroviral Therapy, HAART, is the current drug strategy used to combat HIV. It is a combination therapy that includes HIV-1 Reverse Transcriptase and HIV-1 Protease inhibitors. Drug resistant strains arise that evade current HAART treatments; therefore novel drugs are needed. HIV-1 regulatory proteins such as Tat, Rev, Nef, Vpr, Vpu, and Vif are attractive new drug targets. Of particular interest is the HIV-1 Vif protein and its cellular binding partner APOBEC3G. In the absence of HIV-1 Vif, APOBEC3G, a cytidine deaminase, is able to mutate the viral cDNA and render the virus noninfectious. HIV-1 Vif binds to APOBEC3G and targets it for proteosomal degradation through an interaction with a Cullin-RING ligase complex. Blocking the HIV-1 Vif APOBEC3G interaction would allow APOBEC3G to perform its antiviral function. An attractive strategy to target the HIV-1 Vif APOBEC3G interaction would be a structure-based one. To apply structure-based drug design approaches to HIV-1 Vif and APOBEC3G, I attempted to collect high resolution structural data on HIV-1 Vif and APOBEC3G. My attempts were unsuccessful because the milligram quantities of soluble protein required were not obtained. Therefore, in Chapter III I used chemical cross-linking and mass spectrometry to probe the structural topology of HIV-1 Vif obtaining low resolution structural data. Chemical cross-linking formed HIV-1 Vif multimers including dimers, trimers, and tetramers. Analysis of the cross-linked monomer revealed that HIV-1 Vif’s N-terminal domain is a well-folded, compact, globular domain, where as the C-teriminal domain is predicted to be disordered. In addition, disorder prediction programs predicted the C-terminal domain of HIV-1 Vif to be disordered. Upon oligomerization the C-terminal domain undergoes a disorder-to-order transition that not only facilitates oligomerization but may facilitate other protein-protein interactions. In addition, HIV-1 Vif oligomerization bring Lys34 and Glu134 in close proximity to each other likely creating one molecular surface forming a “hot spot” of biological activity. In Chapter IV I confirmed my low resolution structural data via peptide competition experiments where I identified peptides that can be used as scaffolds for future drug design. HIV-1 Vif oligomerization is concentration dependent. The HIV-1 Vif peptides Vif(29-43) and Vif(125-139) were able to disrupt HIV-1 Vif oligomerization, which confirms the low resolution structural data. HIV-1 Vif peptides Vif(25-39) and Vif(29-43) reduced the amount of APOBEC3G immobilized on the Protein A beads, reduced the amount of HIV-1 Vif interacting with APOBEC3G, or degraded APOBEC3G itself. These peptides could be used as scaffolds to design novel drugs that disrupt the function of HIV-1 Vif and or APOBEC3G. Therefore, low resolution structural data and peptide competition experiments were successful in identifying structurally important domains in HIV-1 Vif. They also provided insight into a possible mechanism for HIV-1 Vif function where a disorder-to-order transition facilitates HIV-1 Vif’s ability to interact with a diverse set of macromolecules. These data advance our structural understanding of HIV-1 Vif and they will facilitate future highresolution studies and novel drug designs.

The empirical paper studies the relationship between property value and hedonic attributes. To indentify the determinant characteristics the influent the private real estate price, their degrees of significance and help with the valuation procedure, 8870 private residential property transactions with caveats lodged across country are selected from Urban Redevelopment Authority of Singapore. 40 models are tested and RMSE, R-Square, Adjusted R-Square, F-Value tests are performed to discover the overall fitness of the models. Breusch-Pagan F-Test is performed to test the existence of heteroskedasticity and VIF test to check multicolinearity. Z score is performed to check the spatial autocorrelation. Three founding are discovered. Firstly, size, age, floor level, population density level, latitude and construction status are core attributes resulting from the regression. Secondly, new district zones classified by functions are detected instead of 28 administrative districts. Thirdly, government policies and local customs (Feng Shui) are proven to be determinant variables as well. Two suggestions are given to regulate the market in the end of this article.

Ce travail repose sur l'étude hydrodynamique et hydrochimique des hauts plateaux du massif calcaire de la Chartreuse (massifs subalpins). Les phénomènes d'infiltration et d'évapotranspiration ainsi que les phénomènes karstiques sont aussi étudiés

Submitted by Cássio da Cruz Nogueira (cassionogueirakk@gmail.com) on 2017-01-26T14:08:26Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_RelacaoNiveisCelulas.pdf: 1497302 bytes, checksum: 78ac1c0249801de7e4874f91cccef7f3 (MD5) / Approved for entry into archive by Edisangela Bastos (edisangela@ufpa.br) on 2017-01-27T13:37:52Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_RelacaoNiveisCelulas.pdf: 1497302 bytes, checksum: 78ac1c0249801de7e4874f91cccef7f3 (MD5) / Made available in DSpace on 2017-01-27T13:37:52Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_RelacaoNiveisCelulas.pdf: 1497302 bytes, checksum: 78ac1c0249801de7e4874f91cccef7f3 (MD5) Previous issue date: 2015-08-31 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Estudos anteriores mostraram haver uma relação direta entre níveis de linfócitos T CD4+ e taxas evolutivas do HIV-1 (DIAZ et al., 2008; LEMEY et al., 2007; NOSTROM et al., 2014). Além disso, outros fatores também afetam a variabilidade do no gene env: por exemplo ação de anticorpos neutralizantes - Nabs (FROST et al., 2005), a variação nos sítios de glicosilação (LEAL et al., 2012; LEAL et al., 2008), a ligação nos receptores da célula alvo (i.e., CD4, CXCR4, CCR5), e ainda, a escolha dos receptores CCR5 para CXCR4 (MILD et al., 2013). Com isso a relação entre diversificação viral e níveis células T CD4+ no gene env pode ser circunstancial. O gene vif, por outro lado, é mais conservado e não sujeito ao viés presente no gene env (i.e., sítios de glicosilação, etc.). Assim, para estudar a influência dos níveis de células T CD4+ na variabilidade do HIV, foi usado a estimativa do regime seletivo (dN e dS) através do modelo de códons e análise filogenética de indivíduos não relacionados (inter-hospedeiro). Foram utilizadas sequências do HIV-1 de indivíduos não correlacionados, obtidas a partir do banco de dados de Los Alamos. As sequências foram separadas em categorias de níveis de linfócitos T CD4, e posteriormente analisadas. A análise mostrou não haver relação direta entre os níveis de células T CD4+ e as taxas evolutivas em gp120 e no gene vif do HIV-1 dos subtipos B e C em uma abordagem populacional. / Previous studies have shown a direct relationship between levels of CD4+ Tlymphocytes and evolutionary rates of HIV-1 (DIAZ et al, 2008; LEMEY et al, 2007; NOSTROM et al, 2014.). Other factors also affect the variability of the env gene: for example function of neutralizing antibodies - Nabs (FROST et al., 2005), the variation in glycosylation sites; (LEAL et al, 2012 LEAL et al., 2008), binding to target cell receptors (i.e, CD4, CXCR4, CCR5), and also the switch from CCR5 to CXCR4 receptor (MILD et al., 2013). Thus, the relationship between viral levels diversification and CD4 + T cells in the env gene can be circumstantial. The vif gene, on the other hand, it is retained and not subject to bias present in the env gene (i.e, glycosylation sites, etc.). Thus, to study the influence of CD4 + T cells levels in HIV variability, the estimate of the selective regimes was used (Nonsynonymous Substitutions - dN and Synonymous Substitutions - dS) by a codon-based model and phylogenetic analysis of unrelated individuals (inter-host). HIV-1 sequences were used of the not-correlated individuals, obtained from the Los Alamos Database. The sequences were separated into CD4+ levels of categories and then analyzed. The analysis revealed no direct correlation between CD4+ T cell levels and evolutionary rates in gp120 and vif gene from HIV-1, subtypes B and C in a population approach.

The binding of HIV-1 Vif to the cellular cytidine deaminase Apobec3G and subsequent prevention of Apobec3G virion incorporation have recently been identified as critical steps for the successful completion of the HIV-1 viral life cycle. This interaction occurs in the cytoplasm where Vif complexes with Apobec3G and directs its degradation via the proteasome pathway or sequesters it away from the assembling virion, thereby preventing viral packaging of Apobec3G. While many recent studies have focused on several aspects of Vif interaction with Apobec3G, the subcellular localization of Vif and Apobec3G during the viral life cycle have not been fully considered. Inhibition of Apobec3G requires direct interaction of Vif with Apobec3G, which can only be achieved when both proteins are present in the same subcellular compartment. In this thesis, a unique approach was utilized to study the impact of Vif subcellular localization on Vif function. The question of whether localization could influence function was brought about during the course of studying a severely attenuated viral isolate from a long-term non-progressor who displayed a remarkable disease course. Initial observations indicated that this highly attenuated virus contained a mutant Vif protein that inhibited growth and replication. Upon further investigation, it was found that the Vif defect was atypical in that the mutant was fully functional in in vitro assays, but that it was aberrantly localized to the nucleus in the cell. This provided the basis for the study of Vif localization and its contribution to Vif function. In addition to the unique Vif mutant that was employed, while determining the localization and replication phenotypes of the differentially localized Vif proteins, a novel pathway for Vif function was defined. Copious publications have recently defined the mechanism for Vif inhibition of Apobec3G. Vif is able to recruit Apobec3G into a complex that is targeted for degradation by the proteasome. However, this directed degradation model did not fully explain the complete neutralization of Apobec3G observed in cell culture. Other recent works have proposed the existence of a second, complementary pathway for Vif function. This pathway is defined here as formation of an aggresome that prevents Apobec3G packaging by binding and sequestering Apobec3G in a perinuclear aggregate. This second mechanism is believed to work in parallel with the already defined directed degradation pathway to promote complete exclusion of Apobec3G from the virion. The data presented here provide insight into two areas of HIV research. First, the work on the naturally occurring Vif mutant isolated from a long-term non-progress or confirms the importance of Vif in in vivo pathogenesis and points to Vif as a potentially useful gene for manipulation in vaccine or therapy design due to its critical contributions to in vivo virus replication. Additionally, the work done to address the subcellular localization of Vif led to the proposal of a second pathway for Vif function. This could have implications in the field of basic Vif research in terms of completely understanding and defining the functions of Vif. Again, a more complete knowledge about Vif can help in the development of novel therapies aimed at disrupting Vif function and abrogating HIV-1 replication.

Master's thesis deals with the assessment of quality of Ultra HDTV video sequences applying objective metrics. Thesis theoretically describes coding of selected codecs H.265/HEVC and VP9, objective video quality metrics and also subjective methods for assessment of the video sequences quality. Next chapter deals with the implementation of the H.265/HEVC and the VP9 codecs at selected video sequences in the raw format from which arises the test sequences database. Quality of these videos is measured afterwards by objective metrics and selected subjective method. These results are compared for the purpose of finding the most consistent correlations among objective metrics and subjective assessment.

This undergraduate thesis is an examination of the works of Odorannus (c. 985-c. 1046), a monk of the abbey of Saint Pierre-le-Vif in Sens, France. A prominent monk in his community, Odorannus was involved in constructing and celebrating his monastery's prosperity and identity. At times, however, he was at variance with his brethren, even experiencing a brief period in exile. This essay explores aspects of Odorannus' compilation, a collection which the monk himself gathered together in his old age, in terms of the dynamic relationship between self and community in a Benedictine monastery of the central Middle Ages.

Methyl bromide (MBr) was widely used as a soil fumigant to manage soilborne pests in plasticulture vegetable production; however, it has been banned by the United Nations Environment Programme. Alternatives to MBr must be implemented to sustain fresh market tomato productivity. Possible MBr alternatives include new fumigant compounds, improved plastic mulch, and grafting. Methyl iodide (MeI) and dimethyl disulfide (DMDS) were tested as fumigant alternatives to MBr for the control of yellow nutsedge and soilborne pathogens of tomato. Virtually impermeable film (VIF) and totally impermeable film (TIF) were tested for fumigant retention and yellow nutsedge control in tomato. Grafting onto resistant rootstocks was tested for bacterial wilt and nematode management in tomato. In the absence of a soil fumigant, TIF suppressed yellow nutsedge better than VIF. TIF increased fumigant retention compared to VIF at similar application rates. Reduced fumigant application rates could be used in combination with TIF while maintaining fumigant concentrations, weed control, and crop yields comparable to greater use rates with VIF. Shank applied DMDS rates could be lowered to 281 L/ha under TIF from 468 L/ha under VIF; shank applied MeI application rates could be reduced to 56 L/ha under TIF compared to 93 L/ha under VIF and drip applied DMDS could be reduced from 561 L/ha under VIF film to 374 L/ha under TIF. Grafting susceptible commercial tomato cultivars onto resistant tomato hybrid rootstocks increased yields and plant survival in bacterial wilt infested fields. "Cheong Gang", "BHN 998", and "BHN 1054" were the best performing rootstocks for bacterial wilt resistance and tomato fruit yield in severely infested fields. Grafting increased tomato yield and decreased root galling from root-knot nematodes in an infested field. Hybrid rootstock "RST 106" resulted in the lowest root-knot nematode galling. In conclusion, TIF with reduced rates of DMDS or MeI is a viable MBr alternative for fresh market tomato production to retain effective doses of fumigant, manage yellow nutsedge and maintain yields. Grafting is an effective MBr alternative to manage bacterial wilt and root-knot nematode and maintain tomato yields. / Ph. D.

本研究主要目的在探討公司宣告海外直接投資，是否會對股東財富有正面的影響，主要透過資本市場上，公司股票價格的漲跌來判斷其影響的方向及程度。研究期間為民國81年到84年，篩選出175筆對外投資宣告的樣本資料，採用事件研究法和市場模式來進行殘差分析，以估算及檢定事件期的平均異常報酬和累積平均異常報酬。此外，由於一些金融性資產如股票、債券、期貨等具有高度變異性的特質，造成殘差項之變異數不再為固定常數，而受上一期異質變異數之影響，且隨時間變動而變動，因此本研究也採用異質條件變異數法(GARCH)來分析。 　　一、總樣本而言 　　公司宣告進行對外直接投資，在宣告日當天股價有顯著為正的顯著異常報酬，股東認為公司進行投資是以公司價值極大化為目標，並能增加股東財富。 　　而本研究也根據不同的統計方法和檢定來比較結果差異，發現T檢定組、Z檢定組、OLS整體樣本組和OLS+GARCH整體樣本組四組所得的實證結果相當一致－異常報酬的變化方向皆相同且宣告日當天的異常報酬都顯著為正。 　　二、一般最小平方法(OLS)和異質條件變異數法之比較 　　本研究接著將72個具有異質變異數特性的樣本，分別以OLS法和GARCH法進行異常報酬的比較，實證結果發現，以OLS法估計具異質變異數的樣本，其平均異常報酬在事件日當天為正，達5%之顯著水準(t=2.459)，而以GARCH法估計的具異質變異數的樣本，其正向異常酬在事件日當天顯著水準為15%(t=1.569)，並不顯著異於零。 　　三、橫斷面複迴歸分析 　　就橫斷面分析結果來看，營業規模和投資東南亞地區達10%的顯著水準能解釋與異常報酬的關係，但呈現負向反應，表營業規模愈大則愈不利於股東財富和投資東南亞並無法增加股東財富。而其他解釋變數則未達顯著水準，其中經營績效、中國大陸地區之迴歸係數符號為正；相對投資金額、獨資之迴歸係數則為負。 　　整體而言，公司從事海外直接投資的宣告，股東都視之為利多消息，顯示海外直接投資對台灣企業的發展和延續有著重要的意義，然而在企業宣告投資後的跨國經營與管理才是台灣企業能否在全球競爭下，成功挑戰廿一世紀的關鍵因素。