<p>&nbsp / </p> <p align="left">One of the most common HIV-associated opportunistic infections is candidiasis, caused by <i><font face="TimesNewRoman,Italic">Candida albicans </font></i><font lang="KO" face="TimesNewRoman">or other </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species. In immune suppressed subjects, this commensal organism can cause an increase in patient morbidity and mortality due to oropharyngeal or systemic dissemination. Limited information exists on the prevalence and antifungal susceptibility of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species in the African continent, the most HIV-affected region globally and home to new and emerging drug resistant </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species. The mechanisms of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">drug resistance in the African continent have also not been described. In this study, 255 </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species isolated from the oral mucosa of HIV-positive South African and Cameroonian patients were identified using differential and chromogenic media and their drug susceptibility profiles tested using the disk diffusion method and the TREK Sensititre system, an automated broth microdilution method. </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">cell wall fractions were run on SDSPAGE and HPLC-MS with the aim of identifying peptides specifically expressed by antifungal drug resistant isolates. Comparisons between the two groups of isolates revealed differences in </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species prevalence and drug susceptibility with interesting associations observed between specific drug resistance and duration of ARV therapy. This study showed that fluconazole, the drug of choice for the treatment of candidiasis in the African continent, is not an effective therapy for most cases of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">infection, and suggests that regional surveillance be implemented in the continent. A multiple-drug resistant </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">strain was identified in this study, a finding that has not previously been documented. The use of proteomics tools allowed for the identification of peptides involved in drug resistance and the elucidation of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">colonization mechanisms in HIV-infected African patients.</font></i></i></i></i></i></i></i></i></i></i></p>

<p>&nbsp / </p> <p align="left">One of the most common HIV-associated opportunistic infections is candidiasis, caused by <i><font face="TimesNewRoman,Italic">Candida albicans </font></i><font lang="KO" face="TimesNewRoman">or other </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species. In immune suppressed subjects, this commensal organism can cause an increase in patient morbidity and mortality due to oropharyngeal or systemic dissemination. Limited information exists on the prevalence and antifungal susceptibility of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species in the African continent, the most HIV-affected region globally and home to new and emerging drug resistant </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species. The mechanisms of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">drug resistance in the African continent have also not been described. In this study, 255 </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species isolated from the oral mucosa of HIV-positive South African and Cameroonian patients were identified using differential and chromogenic media and their drug susceptibility profiles tested using the disk diffusion method and the TREK Sensititre system, an automated broth microdilution method. </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">cell wall fractions were run on SDSPAGE and HPLC-MS with the aim of identifying peptides specifically expressed by antifungal drug resistant isolates. Comparisons between the two groups of isolates revealed differences in </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">species prevalence and drug susceptibility with interesting associations observed between specific drug resistance and duration of ARV therapy. This study showed that fluconazole, the drug of choice for the treatment of candidiasis in the African continent, is not an effective therapy for most cases of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">infection, and suggests that regional surveillance be implemented in the continent. A multiple-drug resistant </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">strain was identified in this study, a finding that has not previously been documented. The use of proteomics tools allowed for the identification of peptides involved in drug resistance and the elucidation of </font><i><font face="TimesNewRoman,Italic">Candida </font><font lang="KO" face="TimesNewRoman">colonization mechanisms in HIV-infected African patients.</font></i></i></i></i></i></i></i></i></i></i></p>

Thesis (doctoral)--Uppsala universitet, 1994. / Summary in English. Includes bibliographical references (p. [246]-253).

Thesis (doctoral)--Uppsala universitet, 1994. / Summary in English. Includes bibliographical references (p. [246]-253).

Philosophiae Doctor - PhD / One of the most common HIV-associated opportunistic infections is candidiasis, caused by Candida albicans or other Candida species. In immune suppressed subjects, this commensal organism can cause an increase in patient morbidity and mortality due to oropharyngeal or systemic dissemination. Limited information exists on the prevalence and antifungal susceptibility of Candida species in the African continent, the most HIV-affected region globally and home to new and emerging drug resistant Candida species. The mechanisms of Candida drug resistance in the African continent have also not been described. In this study, 255 Candida species isolated from the oral mucosa of HIV-positive South African and Cameroonian patients were identified using differential and chromogenic media and their drug susceptibility profiles tested using the disk diffusion method and the TREK Sensititre system, an automated broth microdilution method. Candida cell wall fractions were run on SDSPAGE and HPLC-MS with the aim of identifying peptides specifically expressed by antifungal drug resistant isolates. Comparisons between the two groups of isolates revealed differences in Candida species prevalence and drug susceptibility with interesting associations observed between specific drug resistance and duration of ARV therapy. This study showed that fluconazole, the drug of choice for the treatment of candidiasis in the African continent, is not an effective therapy for most cases of Candida infection, and suggests that regional surveillance be implemented in the continent. A multiple-drug resistant Candida strain was identified in this study, a finding that has not previously been documented. The use of proteomics tools allowed for the identification of peptides involved in drug resistance and the elucidation of Candida colonization mechanisms in HIV-infected African patients.

This thesis aims a critical reading of two American series also aired in Brazil: Star Trek and Heroes. The survey proposes to observe dissensus from the multitude present on both TV series. The multitude (HARDT; NEGRI, 2000) is a social force capable of challenging the sovereign power and to establish new forms of social organization, their presence may present dissensus (RANCIÈRE, 2010), new elements to what is conventionally considered and sense, the sensitive system already established. This movement is associated with materialistic conception of history that suggests seeking tensions against the dominant social order (BENJAMIN, 1987). The Star Trek series debuted in 1966 and its last episode was broadcast in 1969. The series was produced by Desilu Productions and broadcast by NBC, and your transmission took place at a time when American foreign policy has to tend less to an imperialist activity than to a policing action to a supranational order service. The hypothesis is that his narrative shows the will of the multitude to prevent the exercise of the former European sovereignty and to overcome the nationalist struggles. The Heroes series was produced in partnership by Tailwind Productions, NBC, Universal Television and Universal Media Studios. Four seasons were exhibited from 2006 to 2009. The series covers the history of characters who, because of genetic mutations, discover powers that make them special. Although they appear in different parts of the world, there is some force that, in many ways, remains interconnection between the characters. The hypothesis is that the special abilities of Heroes characters may be attached to faculties of the multitude able to oppose the order of global capitalism. The overall objective of this research is, as stated initially, to look for dissensus from multitude inside the series. It is possible to see that these cultural objects do not carry a single system of presentation attached to commercial logic, but let see, within their respective contexts of production, transformative capacities against the established order. It can be said that the tensions in the series denote trouble for tradition defended by the dominator, presenting challenging ways to read the story doing justice to the dominated. / Submitted by Carolini da Rocha (carolini.rocha@unisul.br) on 2017-05-09T12:50:52Z No. of bitstreams: 2 jeanrzhoullou.pdf: 2355014 bytes, checksum: 53c7c03bc132c6a3dc6fa6c11cf22807 (MD5) Jean Raphael Zimmermann Houllou.pdf: 770947 bytes, checksum: 818c2879f4b96ee04555885d98022d3e (MD5) / Approved for entry into archive by Carolini da Rocha (carolini.rocha@unisul.br) on 2017-05-09T12:52:32Z (GMT) No. of bitstreams: 2 jeanrzhoullou.pdf: 2355014 bytes, checksum: 53c7c03bc132c6a3dc6fa6c11cf22807 (MD5) Jean Raphael Zimmermann Houllou.pdf: 770947 bytes, checksum: 818c2879f4b96ee04555885d98022d3e (MD5) / Made available in DSpace on 2017-05-09T12:52:32Z (GMT). No. of bitstreams: 2 jeanrzhoullou.pdf: 2355014 bytes, checksum: 53c7c03bc132c6a3dc6fa6c11cf22807 (MD5) Jean Raphael Zimmermann Houllou.pdf: 770947 bytes, checksum: 818c2879f4b96ee04555885d98022d3e (MD5) Previous issue date: 2016 / A presente tese pretende uma leitura crítica de dois seriados norte-americanos, também veiculados no Brasil: Star Trek e Heroes. O exame propõe observar dissensos da multidão presentes em ambos os seriados de TV. A multidão (HARDT; NEGRI, 2000) é como uma força social capaz de desafiar o poder soberano e instituir novas formas de organização social; sua presença pode apresentar dissensos (RANCIÈRE, 2010), ou seja, novos elementos para aquilo que convencionalmente é considerado e sentido, o regime do sensível já estabelecido. Esse movimento se associa a concepção de história materialista que sugere a procura de tensões contra a ordem social dominante (BENJAMIN, 1987). O seriado Star Trek estreou em 1966 e seu último episódio foi transmitido em 1969. A série foi produzida pela Desilu Productions e exibida pela NBC, e sua transmissão se deu num momento em que a política externa americana passou a tender menos para uma atividade imperialista do que para uma ação de policiamento a serviço de uma ordem supranacional. A hipótese é a de que sua narrativa apresenta a vontade da multidão em impedir o exercício da antiga soberania europeia e em superar as lutas nacionalistas. O seriado Heroes foi produzido em parceria pela Tailwind Productions, NBC,Universal Television e Universal Media Studios. Foram exibidas quatro temporadas de 2006 a 2009. A série aborda a história de personagens que, em razão de mutações genéticas, se descobrem portadores de poderes que os tornam especiais. Embora apareçam em diferentes partes do mundo, existe alguma força que, de variadas formas, mantém os personagens interconectados. A hipótese em Heroes é a de que as habilidades especiais dos personagens podem ser associadas às faculdades da multidão capazes de se opor à ordem do capitalismo global. O objetivo geral desta pesquisa consiste, como afirmado inicialmente, em averiguar dissensos da multidão dentro dos seriados. É possível observar que estes objetos da cultura não carregam um regime único de apresentação ligado à lógica mercantil, mas permitem constatar, dentro de seus respectivos contextos de produção, capacidades transformadoras contra a ordem constituída. Pode-se afirmar que as tensões observadas nos seriados denotam problemas para a tradição defendida pelo dominador apresentando formas desafiadoras à leitura da história e fazendo justiça aos dominados.

No description available.

From the late 1830s Boer settlers conquered and settled vast new lands outside the Cape Colony. Although they more than doubled the area of European domination, historians have categorised Boer society outside the British colonies as primitive and dismissed the Boer conquests as an abberation from the broader process of European expansion. Such a distinction is no longer tenable. This study, which focuses on the Obrigstad/Lydenburg area, shows that the Boers were an integral part of European expansion in southern Africa. Settler expansion did not occur in a vacuum. Booming demand for commodities sparked economic growth across the sub-continent; the Boers were part of this process and consistently strove to produce for the region's expanding markets. In tandem with the expanding regional system, the Boer economy grew constantly. This was reflected in the centralisation of power in the Z.A.R. as Boer producers created formal political and administrative structures to further their economic interests. (A parallel process culminated in the Cape with colonists receiving representative government in March 1853.) This correlation between political and economic development was evident in the creation of a coercive labour system by the Boer state. Through their control of state structures, the Boers employed measures ranging from brute force to punitive taxation, legally enforceable contracts and pass laws to procure and control workers. It is important to note that the creation of a coercive labour system by the Boers paralleled similar developments in the Cape Colony. The speed with which the Boer economy expanded in comparison to the Cape, however, meant that stages in the development of an unfree labour force which had been chronologically distinct in the Cape coexisted within the Boer coercive system. Boer dependence on coerced labour made conflict with African groups inevitable. African groups in the eastern Transvaal had already been partly moulded by predatory economic forces emanating from the Portuguese settlements on the east coast since at least the 1750s. The arrival of the Boers in the 1840s greatly accelerated this process. Some groups were crushed, but others were able to obtain the means to resist Boer rule by interfacing with the settler economy. The economic forces which drove Boer settlement were thus not confined to the white settlers: Boer expansion was paralleled by the rise of African survivor states. The Dlamini, for example, built the powerful Swazi state by exchanging captives, ivory and cattle for guns and horses. Similarly, the Pedi, through the large scale expon of migrant labour, were able to acquire the means to challenge Boer authority in the late 1870s. Oearly then, the Boers 'Were not only representative of the wider settler social and economic order, but were acting in response to the same circumstances as the British settlers, Portuguese traders and African survivor states. It is thus impossible to continue to classify them as retrogressive and distinct from other groups in the region.

Philosophiae Doctor - PhD / One of the most common HIV-associated opportunistic infections is candidiasis, caused by Candida albicans or other Candida species. In immune suppressed subjects, this commensal organism can cause an increase in patient morbidity and mortality due to oropharyngeal or systemic dissemination. Limited information exists on the prevalence and antifungal susceptibility of Candida species in the African continent, the most HIV-affected region globally and home to new and emerging drug resistant Candida species. The mechanisms of Candida drug resistance in the African continent have also not been described. In this study, 255 Candida species isolated from the oral mucosa of HIV-positive South African and Cameroonian patients were identified using differential and chromogenic media and their drug susceptibility profiles tested using the disk diffusion method and the TREK Sensititre system, an automated broth microdilution method. Candida cell wall fractions were run on SDSPAGE and HPLC-MS with the aim of identifying peptides specifically expressed by antifungal drug resistant isolates. Comparisons between the two groups of isolates revealed differences in Candida species prevalence and drug susceptibility with interesting associations observed between specific drug resistance and duration of ARV therapy. This study showed that fluconazole, the drug of choice for the treatment of candidiasis in the African continent, is not an effective therapy for most cases of Candida infection, and suggests that regional surveillance be implemented in the continent. A multiple-drug resistant Candida strain was identified in this study, a finding that has not previously been documented. The use of proteomics tools allowed for the identification of peptides involved in drug resistance and the elucidation of Candida colonization mechanisms in HIV-infected African patients.

La morphine demeure l'antalgique de référence pour le traitement de la douleur (nociception), mais elle est également responsable d‘effets secondaires importants. Des études ont montré que les animaux privés de canaux potassiques TREK-1 (TWIK-related K+channels) étaient plus sensibles à la douleur. Plus récemment, il a été démontré que le canal potassique TREK-1 joue un rôle crucial dans l'analgésie induite par la morphine chez les souris, alors qu'il n'est pas impliqué dans les effets secondaires (constipation, dépression respiratoire et dépendance). Ces résultats suggèrent que les canaux TREK-1 constituent des cibles d‘intérêt pour la conception de nouveaux antalgiques sans effets indésirables liés aux opioïdes. Des études antérieures au sein de notre laboratoire ont permis l'identification de quatre structures chefs de file, activatrices des canaux TREK-1, présentant une activité antalgique in vivo. La structure 3D du canal TREK-1 n‘étant pas élucidée au moment de nos travaux, nous avons décidé d'effectuer une optimisation basée sur une étude de relation structure-activité (RSA). Trente-six analogues ont été synthétisés par condensation de Knoevenagel et évalués pour leur effet antalgique (test de l‘acide acétique, test de la plaque chaude) et leur capacité à activer le canal TREK-1 (électrophysiologie). La capacité des substituants du noyau aromatique à établir des interactions de type liaison hydrogène ainsi que le volume de ces substituants ont une influence déterminante sur l'activité. Des résultats prometteurs ont émergé de cette étude RSA: 5 molécules présentent une très bonne activité antalgique (> 50% d'inhibition de la douleur, test de la plaque chaude) ainsi que d'une bonne activation de TREK-1 canaux (R ≥ 2 à 10 μM ou R ≥ 4 au-dessus de 20 μM). / Morphine remains the analgesic of reference for the treatment of pain (nociception), but it is also responsible for serious adverse effects. Research studies have shown that animals deprived of potassium channels TREK-1 (TWIK-related K+ channels) were over-sensitive to pain. More recently, it has been demonstrated that the TREK-1 potassium channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence. These results suggest that the TREK-1 channels constitute targets of interest for the design of novel analgesics without opioid-like adverse effects. Previous studies within our consortium led to the identification of four lead structures as TREK-1 activators exhibiting analgesic activity in vivo.Since the 3D structure of TREK-1 was not available at the time, we decided to perform hit optimization by conventional structure-activity relationship (SAR) studies. Thirty six analogs were synthesized via Knoevenagel condensation and evaluated for their analgesic effect (writhing test, hot plate assay) and their ability to activate TREK-1 channel (electrophysiology). It turned out that the possibility to form hydrogen bonding interaction (aryl moiety) and the volume of substituents of the amide or ester has a crucial influence on activity. Promising results emerged from this SAR study: 5 molecules display a very good analgesic activity (> 50% inhibition of pain, hot plate assay) as well as a good activation of TREK-1 channels (R ≥ 2 at 10μM or R ≥ 4 above 20μM).