No description available.

Les Alphavirus sont des virus à ARN enveloppés, d’un diamètre de 70 nm, à structure icosaédrique à symétrie de type T=4 (Choi et al. 1991; Cheng et al. 1995; Garoff et al. 2004). Ces virus, dont la répartition est mondiale, sont capables d’infecter une grande variétés d’animaux vertébrés (mammifères, oiseaux, poissons). Ces virus sont des arbovirus, c’est-à_dire des virus transmis par des arthropodes. Dans le cas des Alphavirus, la vectorisation est faite par des moustiques appartenant à plusieurs espèces. A ce jour, 29 espèces d’Alphavirus ont été identifiés, dont au moins 6 sont pathogènes pour l’Homme. Chez l’Homme, certains Alphavirus sont responsables d'encéphalites, d'arthrites, de fièvres, d'éruptions cutanées et peuvent être fatals (Thiruvengadam et al. 1965; Pialoux et al. 2006).Le premier Alphavirus isolé fut l'Encephalite Equine de l'Ouest (WEEV), en 1930 (Meyer et al. 1931). Les virus de l'encéphalite de l'Est (VEEV) et le virus de l'Encephalite Equine du Vénézuéla (VEEV) furent isolés respectivement en 1933 et 1938 (Gibbs EP. 1976 ; Beck et al. 1938 ; Kubes et al. 1939). Le Virus Sindbis isolé en Egypte en 1952 (Taylor et al. 1955), fut le premier Alphavirus responsables d’arthrites à être isolé. La mise en évidence de l'existence du CHIKV se fera 1952 en Tanzanie (Robinson 1955) (Lumsden 1955). Suivent alors les découvertes de l'ensemble des autres Alphavirus. Le South Elephent Seal virus (SESV), identifié en 2000 sur l'île australienne de Macquarie, est à l’heure actuelle le dernier Alphavirus découvert. La phylogénétique des souches de Chikungunya permet d’identifier des clades différents pour les souches d’Afrique de l’Est, de l’Ouest ou d’Asie, et l’analyse phylogénétique est très proche du O’Nyong-Nyong (Powers et al. 2000), Le séquençage de différents isolats de l’épidémie de 2005, a permis de mettre en évidence chez certains d’entre eux une mutation dans la glycoprotéine de l'enveloppe plus précisément dans E1, (Schuffenecker et al. 2006). Cette mutation entraine la substitution d'une arginine en position 226 au lieu de la valine (A226V), est un élément clé pour déterminer le choix d'un nouveau vecteur pour la transmission ou Aedes albopictus (qui le transmet sur l'île de La Réunion) par rapport au vecteur Aedes aegypti (Tsetsarkin et al. 2007). Cette mutation a ensuite été également trouvée en Inde en 2007. (Arankalle et al. 2007; Kumar et al. 2008; Santhosh et al. 2008).Le tableau clinique classique débute souvent par l’apparition brutale d’une forte fièvre (40°C) pendant 3 / 10 jours accompagnée de frissons intermittents (Deller et al.1967). La fièvre est, dans certains cas, bi-phasique, c’est-à-dire qu’elle diminue durant un ou deux jours, avant de remonter brutalement. Elle est généralement suivie d’érythèmes, de courbatures douloureuses ou myalgies et douleurs musculaires (Ozden et al. 2007) en particulier celles impliquant la douleur au niveau des extrémités (poignés, phalanges et chevilles) (Robinson 1955; Jadhav et al. 1965; Thiruvengadam et al. 1965). Egalement migraine, éruptions cutanées maculo-papuleuses parfois prurigineuses. L'éruption touchant le thorax et le visage les mains et les pieds, chez les enfants ont été observées des éruptions de type bulleux accompagné par un détachement cutané (Talarmin et al. 2007). L'évolution de la maladie régresse progressivement. Il n’y a aucun traitement antiviral efficace contre le CHIKV. Le traitement est donc essentiellement symptomatique et composé d'antalgiques non salicylés, de paracétamol et d'anti-inflammatoires non stéroïdiens. Ce travail se compose de deux parties : 1 partie sur l’étude phylogénétique du CHIKV et 1 partie sur l'étude des molécules antivirales. [...] / The Alphavirus RNA viruses are enveloped with a diameter of 70 nm, icosahedral structure with symmetry of type T = 4 (Choi et al. 1991; Cheng et al. 1995; Garoff et al. 2004). These viruses, whose distribution is worldwide, can infect a wide variety of vertebrates (mammals, birds, fish). These viruses are arboviruses, is à_dire viruses transmitted by arthropods. In the case of Alphavirus, the vectorization is done by mosquitoes from several species.To date, 29 species of Alphavirus have been identified, including at least six are pathogenic for humans. In humans, some are responsible for Alphavirus encephalitis, arthritis, fever, rash and can be fatal (Thiruvengadam et al. 1965; Pialoux et al. 2006).The first was isolated Alphavirus Equine Encephalitis West (Weeve) in 1930 (Meyer et al. 1931). The encephalitis virus Eastern (VEEV) and virus Venezuelan equine encephalitis (VEEV) were isolated respectively in 1933 and 1938 (Gibbs EP. 1976; Beck et al. 1938; Kubes et al. 1939 ). Sindbis virus isolated in Egypt in 1952 (Taylor et al. 1955), was the first Alphavirus responsible for arthritis to be isolated. The demonstration of the existence of CHIKV in Tanzania will be 1952 (Robinson 1955) (Lumsden 1955). Then follow the discoveries of all other Alphavirus. The South Elephent Seal virus (SESV), identified in 2000 on the Australian island of Macquarie is now the last Alphavirus discovered. The phylogenetic strains of Chikungunya can identify different clades for strains of East African, Western or Asian, and phylogenetic analysis is very close O'Nyong-Nyong (Powers and al. 2000), The sequencing of different isolates of the epidemic of 2005, helped to highlight some of them a mutation in the envelope glycoprotein more specifically in E1 (Schuffenecker et al. 2006). This mutation causes the substitution of an arginine at position 226 instead of valine (A226V), is a key element in determining the choice of a new vector for the transmission or Aedes albopictus (which transmits on the island of La meeting) with respect to the vector Aedes aegypti (Tsetsarkin et al. 2007). This mutation was later also found in India in 2007. (Arankalle et al. 2007; Kumar et al. 2008; Santhosh et al. 2008).The classic presentation often begins with sudden onset of high fever (40°C) for 3 / 10 days intermittent chills (Deller and al.1967). Fever is, in some cases, bi-phasic, that is to say, it decreases during a day or two before rising sharply. It is usually followed by erythema, pain or stiffness of muscle pain and muscle aches (Ozden et al. 2007) especially those involving pain in the extremities (wrists, ankles and knuckles) (Robinson 1955; Jadhav et al. 1965; Thiruvengadam et al. 1965). Also headache, rash maculopapular itchy sometimes. The rash affecting the chest and face hands and feet, children were seen eruptions like bullous skin accompanied by a detachment (Talarmin et al. 2007). The evolution of the disease regresses gradually. There is no antiviral therapy effective against CHIKV. Treatment is essentially symptomatic and consists of non-analgesic salicylates, paracetamol and anti-inflammatory drugs. This work consists of two parts: one part on the phylogenetic study of CHIKV and one part of the study of antiviral molecules. [...]

Nuclear transfer (NT), or cloning, which is the transfer of a donor nucleus to a recipient enucleated oocyte, has been successfully achieved to produce viable offspring in many species. The process is very inefficient, as reprogramming of the donor nucleus is required, and losses are high throughout development. Placentation abnormalities are a common feature amongst cloned animals. Incomplete nuclear reprogramming and erroneous epigenetic imprinting may contribute to aberrant protein transcription and DNA mutations, affecting mitochondrial metabolism and inducing cellular stress. In vitro produced embryos under high oxygen culture conditions may also suffer oxidative stress, with the resulting reactive oxygen species causing mitochondrial DNA mutations and cellular stress similar to clones. In this study, expression of oxidative stress protein markers (Hsp60, SOD2, Hsp70) in NT cotyledons were compared to artificial insemination (AI) at different time points of gestation (days 50, 100, and 150). As a continuum of the oxidative stress investigation in cloned cotyledons, in vitro produced embryos were cultured under 20% oxygen compared to the control 7% oxygen laboratory standard culture, with oxidative stress protein markers examined between the groups at blastocyst stage (day 7) and day 15. Embryo morphology was also observed to determine apparent physiological differences between the treatment and control embryos. No previous studies to date have investigated the developmental effects of oxidative stress in day 15 bovine embryos. The significant differences in oxidative stress proteins observed at several time points in the NT and AI groups were not repeatable, possibly due to sample freeze/thaw degradation. Morphological differences observed between embryos cultured in 20% oxygen and control groups were visually apparent, although not quantified. At day 15 manganese superoxide dismutase expression was significantly lower in the 20% group compared to control. The 20% oxygen group did not show higher heat shock protein 60 expression than control, however the same results have been observed in another study at blastocyst stage. The results of this study suggest that the effect of oxidative stress on embryonic development is evident yet inconclusive in bovine NT cotyledons, however does not appear apparent in day 15 embryos following culture in 20% oxygen.

Cytogenetic analysis of the malignant clone is clinically important in haematological malignancy. Analysis by metaphase cytogenetics is restricted to the small proportion of malignant cells which are actively dividing. This thesis explores the dynamics of malignant clones using the technique of fluorescence in situ hybridization (FISH) to visualize chromosomal abnormalities in interphase (non-dividing) cells. Hyperdiploid (>46 chromosomes) clones have been investigated by interphase FISH in acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) using appropriate chromosome-specific probes. A hyperdiploid clone was detected in interphase cells in 9/65 patients with ALL in whom metaphase cytogenetics had failed or was normal. A single hyperdiploid cell was identified as clonal in one patient with MDS but not in six others with AML, MDS or ALL. The involvement of different cell lineages in the malignant clone was investigated by simultaneous FISH and identification of the cell type by morphology or monoclonal antibodies. In ALL, hyperdiploid clones were restricted to the lymphoid blasts in 9/9 cases, while Philadelphia (Ph) positive clones, (identified by probes to the genes m- BCR or M-BCR and ABL which fuse as a result of the translocation) were found either in lymphoid blasts alone (1/3 cases) or in both lymphoid and myeloid cells (2/3 cases). In AML trisomy 8 (using a chromosome 8-specific probe) and an 11q23 abnormality (which split YAC 13HH4) were both found only in the myeloid blasts, in 3/3 and 2/2 cases respectively. A sensitive method for the detection of hyperdiploid \geq 50 clones in ALL was developed for minimal residual disease detection. Simultaneous probing of three chromosomes enabled detection of one hyperdiploid cell in 10,000. Heterogeneity in the speed with which the clone was eliminated in remission was seen in 16 patients and early relapse was detected in one patient.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 33-36). Also available via the Internet.

Code cloning is a common practice in software development. However, code cloning has both positive aspects such as accelerating the development process and negative aspects such as causing code bloat. After a decade of active research, it is clear that removing all of the clones from a software system is not desirable. Therefore, it is better to manage clones than to remove them. A software system can have thousands of clones in it, which may serve multiple purposes. However, some of the clones may cause unwanted management difficulties and clones like these should be refactored. Failure to manage clones may cause inconsistencies in the code, which is prone to error. Managing thousands of clones manually would be a difficult task. A clone management system can help manage clones and find patterns of how clones evolve during the evolution of a software system. In this research, we propose a framework for constructing and visualizing clone genealogies with change patterns (e.g., inconsistent changes), bug information, developer information and several other important metrics in a software system. Based on the framework we design and build an interactive prototype for a multi-touch surface (e.g., an iPad). The prototype uses a variety of techniques to support understanding clone genealogies, including: identifying and providing a compact overview of the clone genealogies along with their key characteristics; providing interactive navigation of genealogies, cloned source code and the differences between clone fragments; providing the ability to filter and organize genealogies based on their properties; providing a feature for annotating clone fragments with comments to aid future review; and providing the ability to contact developers from within the system to find out more information about specific clones. To investigate the suitability of the framework and prototype for investigating and managing cloned code, we elicit feedback from practicing researchers and developers, and we conduct two empirical studies: a detailed investigation into the evolution of function clones and a detailed investigation into how clones contribute to bugs. In both empirical studies we are able to use the prototype to quickly investigate the cloned source code to gain insights into clone use. We believe that the clone management system and the findings will play an important role in future studies and in managing code clones in software systems.

Made available in DSpace on 2014-06-12T16:31:41Z (GMT). No. of bitstreams: 2 arquivo6185_1.pdf: 1986687 bytes, checksum: 8a72beab280fcdc564c73079c55a4aee (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2007 / O aumento da resistência bacteriana aos antibióticos é uma ameaça à saúde da população mundial, aumentando as recorrências por doenças infecciosas, devido ao surgimento de bactérias multirresistentes que dificulta e onera o tratamento antimicrobiano. Um exemplo importante destes germes, é o S. aureus MRSA que no Brasil, como em outras partes do mundo, são os microorganismos frequentemente isolados, tendo sua maior prevalência a nível hospitalar, sendo também uma importante causa de infecções na comunidade. A ocorrência de S. aureus MRSA multirresistentes susceptíveis só a vancomicina, constitui um grave problema a resolver, ainda mais, com o surgimento recente de cepas de S. aureus com susceptibilidade intermediária e resistentes a vancomicina. Deste fato, é de fundamental importância, a pesquisa de compostos alternativos, principalmente a partir de plantas medicinais que constitui uma fonte inesgotável de novas moléculas. No presente trabalho, foram escolhidas duas plantas para estudar o perfil fitoquímico e antimicrobiano: Caesalpinia pyramidalis Tull. (Catingueira), das leguminosas e Schinopsis brasiliensis Engl. (Baraúna ou braúna), das anacardiáceas, ambas as famílias com representantes de reconhecida atividade biológica, incluída a antimicrobiana. Neste sentido foi estudada a atividade dos extratos secos (por extração hexanólica, em acetato de etila ou metanol) da folha, casca do caule, casca da raiz, flor, vagem e semente da Braúna e Catingueira inicialmente frente a padrões ATCC de bactérias Gram negativas e Gram positivas, confirmando-se uma melhor ação para Staphylococcus aureus. Na segunda etapa os ensaios foram realizados com 22 cepas de Staphylococcus aureus, 18 isolados clínicos MRSA multirresistentes identificados como Clones Epidêmicos, 2 isolados S. aureus MSSA e 2 cepas padrões ATCC. Dos resultados obtidos para as plantas em estudo, a Schinopsis brasiliensis apresentou melhor atividade sobre as cepas de S. aureus, inclusive os clones epidêmicos mais resistentes. Os extratos secos de extração metanólica foram mais ativos com dados de CMI para a flor e raiz de Braúna de 125 μg.mL-1 quanto que pela técnica de poços foram obtidos para uma das cepas de Staphylococcus aureus MRSA multirresistente (CEB) halos da ordem de 20 mm. Os extratos secos de extração por acetato de etila mostraram-se menor ação, o que pode ser atribuído à uma difusão diminuída no agar. Nos testes, os antibióticos usados como padrão foram tetraciclina e oxacilina na determinação das CMI e tetraciclina na técnica de poços, confirmando a oxacilina o caráter MRSA ou MSSA das cepas e a tetraciclina seu perfil de resistência. Os dois diluentes utilizados DMSO à 50% e Tween 80 à 4% não apresentaram nenhuma inibição. Concluindo, considera-se que as plantas em estudo e particularmente a Schinopsis brasiliensis apresentou uma atividade promissora sobre as cepas de S. aureus MRSA inclusive os clones multirresistentes, considerando-se que em parte esta atividade é justificada pela presença de flavonóides e, especialmente, ácidos fenólicos que foram detectados experimentalmente por bioautografia confirmando dados da literatura e por screening fitoquímico

No description available.

No description available.

No description available.