Dissertations / Theses on the topic 'Hit identification'
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Nordqvist, Anneli. "Hit Identification and Hit Expansion in Antituberculosis Drug Discovery : Design and Synthesis of Glutamine Synthetase and 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase Inhibitors." Doctoral thesis, Uppsala universitet, Avdelningen för organisk farmaceutisk kemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-155428.
Full textLi, Hui. "Algorithms for the selection of optimal spaced seed sets for transposable element identification." Miami University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=miami1283178156.
Full textNobili, Alberto [Verfasser]. "Improving biocatalysts via semi-rational protein design : use of a multiple sequence alignment platform to reduce screening efforts and facilitate hit identification / Alberto Nobili." Greifswald : Universitätsbibliothek Greifswald, 2016. http://d-nb.info/1113294191/34.
Full textEhrt, Christiane [Verfasser], Daniel [Akademischer Betreuer] Rauh, and Stefan M. [Gutachter] Kast. "Protein binding site comparison : The impact of binding site similarity on hit identification in early drug discovery / Christiane Ehrt ; Gutachter: Stefan M. Kast ; Betreuer: Daniel Rauh." Dortmund : Universitätsbibliothek Dortmund, 2019. http://d-nb.info/1197903011/34.
Full textSpadaro, Alessandro [Verfasser], and Rolf W. [Akademischer Betreuer] Hartmann. "Pharmacophore aided hit identification, structural optimization and biological evaluation of benzothiazole derivatives as new potent and selective non-steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 / Alessandro Spadaro. Betreuer: Rolf W. Hartmann." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2012. http://d-nb.info/1052338666/34.
Full textChen, Zhiqiang. "Identification of HIF-1 inhibitors." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503047.
Full textSeddon, Deborah Ann. "Impossible identifications : Shakespeare and his readers (1830-1930)." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616135.
Full textBenson, Claire Elizabeth. "Genetics of familial hip osteoarthritis :identification of genetic susceptibility factors." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491996.
Full textCrozier, J. R. "Enjoying Jesus Christ and the riches of his grace do you know how rich you are in Christ? a seven-week adventure /." Online full text .pdf document, available to Fuller patrons only, 2003. http://www.tren.com.
Full textLedwaba, Neria Hunadi. "Identification of employees needs to be addressed in the HIV/AIDS programme at Aventis Pharmaceutical Company." Diss., Pretoria : [s.n.], 2003. http://upetd.up.ac.za/thesis/available/etd-11182003-132232.
Full textSiri, Åhman. "Wait, I'm him now? : Identification and choice in games with more than one protagonist." Thesis, Högskolan i Skövde, Institutionen för informationsteknologi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-15418.
Full textArtefakten som användes i arbetet utvecklades i samarbete med Amanda Thim
Embretsén, Hanna, and Maria Palmberg. "En enfärgad regnbåge : Hur den homosexuella normen formas i HBT-magasinet QX." Thesis, Linnéuniversitetet, Institutionen för samhällsvetenskaper, SV, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-24076.
Full textAbner, Erik 1986. "Identification of HIV-1 reactivating quinoline compounds as bromodomain inhibitors." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/565528.
Full textUpon HIV-1 infection, a reservoir of HIV latently infected resting T cells prevents the eradication of the virus from patients. To achieve eradication, the existing virus suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. Our group previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol), which is capable of reactivating viral transcription through an unknown mechanism. The objective of this project was to identify the molecular binding partners of MMQO and elaborate their role in the reactivation of HIV-1. We established that MMQO is capable of inducing HIV-1 independently of viral proteins by inducing transcription from proviral minigenomes lacking genes for viral components, allowing us to hypothesize that the compound primarily functions through host factors. Characterizing MMQO’s transcriptional profiles with total mRNA expression microarrays, we were able to identify numerous traits provoked by the drug. MMQO displayed a robust immunosuppressive nature, it affected cell proliferation by diminishing cMyc and Bcl-2 protein levels and increased the dysregulation of acetylation sensitive genes. These hallmarks indicated that MMQO mimics acetylated lysines of core histones and functions as a bromodomain and extraterminal domain (BET) protein family inhibitor. Further gene expression and proteomic analysis confirmed this supposition and we demonstrated that MMQO deposes of the BET family member Brd4 from global chromatin and antagonizes the pro-latent role of Brd4 near the transcription start site of HIV-1. Computational docking models also confirmed MMQO’s specificity towards the BET family bromodomains and an in vitro screening against the family members by FRET identified MMQO to have the highest affinity towards the Brd9 protein. Finally, we established that the inhibition of Brd9 had minimal effect on the proviral expression, suggesting that the primary function of MMQO on HIV-1 can be attributed to the displacement of Brd4. Due to the broad range of properties characteristic to BET family inhibitors, these molecules are currently being evaluated in clinical trials against various types of cancers and immune conditions. The dual functioning scaffold compound MMQO is a new member of this class of drugs. The minimalistic structure of MMQO shows promise for it to be further optimized for higher affinities towards Brd9 / 4 and could potentially be of use in research against a variety of diseases, including HIV.
Grace, Christopher. "Diagnostically significant antigens of Treponema pallidum subsp. pallidum : identification, serological efficacy, and characterisation of the major antigenic determinants." Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311861.
Full textMarcus, Benjamin J. "Predictors of Engagement in the Community Affected by HIV and AIDS." Scholarship @ Claremont, 2009. http://scholarship.claremont.edu/cgu_etd/6.
Full textWu, Hao, and 吴昊. "Identification of drug resistant mutations in HIV-1 latently infected patients under successful HAART and in CRF_BC variants selected invitro." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47149826.
Full textBallalai, Rodrigo Clemente. "O jovem no movimento hip hop : espaço potencial de criatividade e identificação? /." Assis : [s.n.], 2009. http://hdl.handle.net/11449/97560.
Full textBanca: Diana Pancini de Sá Antunes Ribeiro
Banca: Leila Rute Oliveira Gurgel do Amaral
Resumo: A partir de experiência de estágios da graduação em Psicologia, particularmente no trabalho desenvolvido junto ao "Programa de Liberdade Assistida" da FEBEM, unidade Bauru, quando oferecemos um pronto atendimento psicológico a seus participantes, iniciamos o contato com o movimento hip hop. Entrevistamos jovens que se identificam com o movimento hip hop, analisando sua trajetória ao ingressarem nos grupos organizados de hip hop do município de Bauru. Analisamos suas biografias e percepções que estes jovens têm de si e de sua realidade social. O instrumento utilizado foi a entrevista semi dirigida, cuja aplicação ocorreu individualmente O procedimento para a análise das informações se apoiou no método psicanalítico. Analisamos o que leva os jovens a participarem do referido movimento, por meio do conceito psicanalítico de identificação. Verificamos que a significação que os jovens atribuem ao hip hop pode ser entendido como um espaço potencial de criatividade, de acordo com a teoria do psicanalista inglês Donald Winnicott. Encontramos diferentes usos desse movimento cultural, de acordo com a singularidade de cada participante, inclusive manifestado pelos diversos meios de participação artística e ideológica de seus componentes. No campo identificatório consideramos o movimento hip hop como modelo identificatório contemporâneo e significativo para grande parcela da população jovem. Como apresenta Maria Rita Kehl, o tratamento de irmãos ("manos") indica um campo de identificação horizontal com um grupo de pessoas iguais, oriundas de uma mesma realidade dolorosa; distinto de uma identificação vertical, tal como ocorre na grande massa em relação ao líder ou ídolo.
Abstract: During the course of training in psychology, especially in a work with the Program of Freedom Febem Assisted in the unit of Bauru, offering psychological care ready to participants, initiated the contact with the hip hop movement. In this study, we analyzed the motivation of some young people to join this movement, to perform such analysis, we used the psychoanalytic concept of identification. We want to check the meaning given by these young people to the hip hop movement, and if this can be seen as a potential space for creativity. Young people interviewed are identified with the hip hop movement, and why we are looking at their life stories the moment they began to join the hip hop movement organized in the city of Bauru. I reviewed their biographies and their perceptions about themselves and about social reality in which they live. We conducted semi-directed interviews with each couple in particular. We use the psychoanalytic method to analyze the content of the interviews, especially the theory developed by psychoanalyst Donald Winnicot.
Mestre
LORAIN, STEPHANIE. "La famille des genes hir : etude chez les eucaryotes et elements d'analyse fonctionnelle par identification de partenaires moleculaires." Paris 6, 1998. http://www.theses.fr/1998PA066556.
Full textJacobs, Michael A. "Identification and characterization of a chloroplast-encoded His-Asp signal transduction protein in the toxic stramenopile Heterosigma akashiwo /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/5250.
Full textGálvez, Celada Cristina. "Identification of immunovirological factors that determine an extremely low viral reservoir: approaching the cure of HIV-1 infection." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/671118.
Full textCasi 40 millones de personas viven actualmente con el virus de la inmunodeficiencia humana tipo 1 (VIH-1) en el mundo, y más de 30 millones de muertes se atribuyen al VIH-1 desde el comienzo de la epidemia. El desarrollo de la terapia antirretroviral combinada (TARc) es uno de los principales éxitos médicos del siglo XX, ya que suprime eficazmente la viremia plasmática, mejora la función del sistema inmunológico, reduce la mortalidad y morbilidad, y el riesgo de transmisión viral. Sin embargo, la TARc no puede curar la infección debido a la presencia de células infectadas de forma latente, lo que se conoce como reservorio viral. El número de células latentemente infectadas presentes en el cuerpo varía notablemente entre diferentes individuos infectados por VIH-1. Bajos niveles de reservorios se han relacionado tradicionalmente con un control del VIH-1 o buen pronóstico de la enfermedad, pero los factores específicos que provocan esta reducción del reservorio aún se desconocen. En este contexto, el objetivo de esta tesis es caracterizar los factores clínicos, virales e inmunogenéticos asociados con la reducción del reservorio del VIH-1 en tres modelos diferentes: [1]controladores naturales de la infección con un largo seguimiento (Controladores de Elite Excepcionales o EEC), [2]individuos con un reservorio de VIH-1 espontáneamente bajo a pesar de una progresión normal de la infección (LoViReT), y [3]personas VIH-1+ en las que se observa una caída del reservorio después de un trasplante alogénico de células madre hematopoyéticas (allo-HSCT). Nuestros resultados mostraron que los bajos niveles de reservorio observados en los EEC se debieron a la combinación de virus defectivos que no evolucionan con factores genéticos protectores del huésped junto con respuestas inmunitarias potentes específicas del VIH-1. La combinación de estos factores parece importante para controlar la replicación del VIH-1 y alcanzar una cura funcional espontánea. Por otro lado, los individuos LoViReT parecen tener un establecimiento defectivo del reservorio de VIH-1 ya que se observaron bajos niveles de reservorio en sangre (incluso antes del inicio del tratamiento) y santuarios anatómicos. Esto estaba acompañado por una distribución sesgada de la latencia en las diferentes subpoblaciones de células T CD4+ hacia subpoblaciones de vida más corta. Sin embargo, aunque los individuos LoViReT mostraron un sistema inmunológico preservado, no se observaron respuestas inmunitarias específicas del VIH-1 y, por lo tanto, no se esperaría que controlaran la replicación del VIH-1 en ausencia de TARc. Finalmente, el estudio de individuos infectados por VIH-1 que recibieron un trasplante alogénico de células madre hematopoyéticas mostró una notable disminución del reservorio de VIH-1 en sangre periférica y compartimentos anatómicos, incluso en el contexto de células con un CCR5 salvaje. Esto probablemente fue debido a un potente efecto de injerto contra VIH-1 causado por factores específicos del trasplante como un rápido quimerismo, células procedentes de un donante adulto y la presencia de enfermedad del injerto contra huésped. Desafortunadamente, la falta de respuestas potentes específicas de VIH-1 sostenidas en el tiempo resultaría en un rebote viral, como se observó en uno de los individuos estudiados que fue trasplantado con células con un CCR5 salvaje. En conjunto, demostramos que los factores relacionados con una función viral alterada son importantes para la reducción del reservorio de VIH-1. Aun así, para controlar la replicación del VIH-1 en ausencia de TARc será necesaria la combinación con respuestas inmunes potentes específicas de VIH-1, como sucede en los EEC. Futuros ensayos clínicos en personas con un reservorio bajo de VIH-1, como individuos LoViReT o que hayan recibido un trasplante alogénico de células madre, serían de gran interés en estrategias destinadas a estimular las respuestas inmunes específicas del VIH-1 con el objetivo de curar
Nearly 40 million individuals are currently living with the human immunodeficiency virus type 1 (HIV-1) worldwide and more than 30 million deaths can be attributed to HIV-1 since the start of the epidemic. The development of combination antiretroviral therapy (cART) was one of the major medical success of the 20th century as it effectively suppresses plasma viremia, improves the immune system function, reduces mortality and morbidity, and the risk of viral transmission. However, cART cannot cure the infection due to the presence of latently infected cells. The number of latently infected cells present in the body, known as the reservoir, varies notably among different HIV-1-infected individuals. Low levels of reservoirs are traditionally related to HIV-1 control or good disease prognosis, but the specific factors provoking a reduction of this reservoir are still unknown. In this context, the aim of this thesis is to characterize the clinical, viral and immunogenetic factors associated with the reduction of the HIV-1 reservoir in three different models: [1] a natural long-term control of the infection (Exceptional Elite controllers or EEC), [2] a natural low HIV-1 reservoir despite regular HIV-1 progression (Low Viral Reservoir Treated individuals or LoViReT), and [3] an induced low reservoir after allogeneic hematopoietic stem cell transplant (allo-HSCT) in persons living with HIV-1. Our results showed that the low-level reservoirs observed in EEC were due to a combination of defective non-evolving virus with protective host genetic factors together with potent HIV-1 specific immune responses. Altogether, the combination of those factors seems important to control HIV-1 replication and reach a spontaneous functional cure. On the other hand, LoViReT individuals seem to have an impaired HIV-1 reservoir establishment since the low levels of reservoir were observed in blood (even before the initiation of treatment) and anatomical sanctuaries. This was supported by a skewed distribution of the provirus among the different CD4+ T cells subpopulations towards short-live subpopulations. However, although LoViReT individuals have a preserved general immune system, they do not have HIV-1 specific immune responses and therefore are not able to control HIV-1 replication in the absence of cART. Finally, the study of HIV-1-infected individuals that received an allo-HSCT showed a remarkably decline of the HIV-1 reservoir in peripheral blood and anatomical compartments, even in the setting of CCR5 wild-type cells. This was most likely due to a potent graft versus HIV-1 effect caused by specific factors of the transplant as a rapid engraftment, an adult donor, or a graft versus host disease. Unfortunately, the lack of a potent HIV-1 specific immune responses sustained in time would result in viral rebound, as observed in one of the studied individuals transplanted with CCR5 wild-type cells. Altogether, we showed that factors related to an impaired viral function will be important to the reduction of HIV-1 reservoir. A combination with a potent HIV-1 specific immune response will be necessary to control the HIV-1 replication in the absence of cART as happened in EEC. Future clinical trials in individuals with a low HIV-1 reservoir, like LoViReT or allo-HSCT individuals, would be of great interest in strategies aimed at boosting HIV-1 immune specific responses with the ultimate goal of curing HIV-1.
Universitat Autònoma de Barcelona. Programa de Doctorat en Bioquímica, Biologia Molecular i Biomedicina
Tartour, Kevin. "Identification et caractérisation d’une nouvelle famille de facteur de restriction - les IFITMs." Thesis, Lyon, École normale supérieure, 2014. http://www.theses.fr/2014ENSL0972.
Full textHIV, as all viruses, hijacks the cellular machinery to its benefits. Nevertheless, a range of proteins protects cells by an autonomous way, they are called restriction factor and belong to a system called “the intrinsic immunity”. Up to now, a certain number of cellular proteins, most of which belong to this defense system, have been described to be more or less detrimental for HIV replication, as for example, APOBEC3G, Tetherin, TRIM5α and SamHD1. Given that a large number of cellular restriction factors are likely to be discovered, we started to screen to look for new ones. Among a lot of candidates, we have identified a family of proteins interfering with HIV: the IFITMs. Previously, studies described IFITMs as proteins protecting cell against viral entry and fighting a lot of viruses, including HIV. In this thesis, we described a new antiviral mechanism mediated by IFITMs against retroviruses. When IFITMs are expressed in cells producing new virions, there is a high defect of infectious particle release due to a defect of particle release and a defect of the infectivity of particles. We focus on the intrinsic defect of infectivity and we show that particles cannot anymore enter into target cells and this observation is correlated with the incorporation of IFITMs in viral membranes. The defect is located at the fusion step and is not explained by a defect of envelope incorporation.To conclude, IFITMs have a double restrictive effect, protecting cells from incoming viruses and decreasing the production of infectious particles
Ballalai, Rodrigo Clemente [UNESP]. "O jovem no movimento hip hop: espaço potencial de criatividade e identificação?" Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/97560.
Full textA partir de experiência de estágios da graduação em Psicologia, particularmente no trabalho desenvolvido junto ao “Programa de Liberdade Assistida” da FEBEM, unidade Bauru, quando oferecemos um pronto atendimento psicológico a seus participantes, iniciamos o contato com o movimento hip hop. Entrevistamos jovens que se identificam com o movimento hip hop, analisando sua trajetória ao ingressarem nos grupos organizados de hip hop do município de Bauru. Analisamos suas biografias e percepções que estes jovens têm de si e de sua realidade social. O instrumento utilizado foi a entrevista semi dirigida, cuja aplicação ocorreu individualmente O procedimento para a análise das informações se apoiou no método psicanalítico. Analisamos o que leva os jovens a participarem do referido movimento, por meio do conceito psicanalítico de identificação. Verificamos que a significação que os jovens atribuem ao hip hop pode ser entendido como um espaço potencial de criatividade, de acordo com a teoria do psicanalista inglês Donald Winnicott. Encontramos diferentes usos desse movimento cultural, de acordo com a singularidade de cada participante, inclusive manifestado pelos diversos meios de participação artística e ideológica de seus componentes. No campo identificatório consideramos o movimento hip hop como modelo identificatório contemporâneo e significativo para grande parcela da população jovem. Como apresenta Maria Rita Kehl, o tratamento de irmãos (“manos”) indica um campo de identificação horizontal com um grupo de pessoas iguais, oriundas de uma mesma realidade dolorosa; distinto de uma identificação vertical, tal como ocorre na grande massa em relação ao líder ou ídolo.
During the course of training in psychology, especially in a work with the Program of Freedom Febem Assisted in the unit of Bauru, offering psychological care ready to participants, initiated the contact with the hip hop movement. In this study, we analyzed the motivation of some young people to join this movement, to perform such analysis, we used the psychoanalytic concept of identification. We want to check the meaning given by these young people to the hip hop movement, and if this can be seen as a potential space for creativity. Young people interviewed are identified with the hip hop movement, and why we are looking at their life stories the moment they began to join the hip hop movement organized in the city of Bauru. I reviewed their biographies and their perceptions about themselves and about social reality in which they live. We conducted semi-directed interviews with each couple in particular. We use the psychoanalytic method to analyze the content of the interviews, especially the theory developed by psychoanalyst Donald Winnicot.
Yuan, Tingting, and 袁婷婷. "Identification of intermediate antibodies of broadly neutralizing HIV-1 human monoclonal antibody b12 and characterization of variable loops of HIV-1 envelop glycoprotein." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196445.
Full textOtieno, Fredrick Odhiambo. "Use of modified respondent driven sampling methodology to enhance identification and recruitment of most at risk persons into an HIV prevention trial in Kisumu, Western Kenya." University of the Western Cape, 2016. http://hdl.handle.net/11394/4975.
Full textThis thesis presents research on the use of modified respondent driven sampling (mRDS) methodology to enhance identification and recruitment of key populations (KP) into an HIV prevention trial in Kisumu, western Kenya through a three phase mixed method study. The study was carried out in Kisumu, western Kenya within the Kenya Medical Research Institute (KEMRI) and the US Centers for Disease Control and Prevention (CDC) Research and Public Health Collaboration platform. The three phases included: 1. PHASE I: Identification and determination of categories of KPs and techniques of locating and motivating them to participate in HIV prevention trials.2. PHASE II: Design and Implementation of a mRDS methodology in recruiting Ks into HIV prevention trials.3. PHASE III: Evaluation of the mRDS in recruitment of KPs into an HIV incidence cohort study. Methods Phase I of the study included the conduct of in depth interviews which were used to identify different categories of persons considered to be KPs within Kisumu, identify strategies of locating the KPs and determine motivators and inhibitors of KPs participation in HIV prevention trials. Phase II on the other hand included the administration of a survey that had been refined in Phase I. The survey was used to design a mRDS methodology which was then implemented to recruit KPs into the survey. Phase III evaluated the success of the mRDS in recruiting KPs into an HIV prevention study by assessing the risk profiles for participants screened and enrolled into the Phase III study. Ethical approval for the study was sought from the ethics committee of the Kenya Medical Research Institute, the US CDC and the University of the Western Cape.The study recruited 53 individuals into phase I and was able to 8 identify different categories of people considered to be KPs and the 4 salient strategies that could be used to recruit them into HIV prevention studies. The phase also identified 8 potential motivators and 9 potential inhibitors to participation in HIV prevention research. These categories and salient strategies were used in phase II to develop and pilot a mRDS methodology in recruiting 203 individuals into a survey. The survey was used as a validation tool for the risk levels of persons recruited by the mRDS using the variables of inconsistent condom use and having multiple partners. The validated mRDS was then applied in the recruitment of 1,292 participants in phase III of thestudy. These study participants had characteristics similar to those seen in similar studies and elucidated from phases I and II of the study. HIV seropositivity was used as the variable for validating risk levels of participants in this study and this was found to be higher that that seen in general population and comparable to that seen in other KPs groups in the region. Results: Overall the study was able to identify different categories of people considered to be at high riskof HIV acquisition. The groups identified included people who frequent bars (e.g. bar workers, drunkards, sex workers, businessmen), people who work in transportation (e.g. truck drivers, matatu drivers, motorcycle drivers, taxi drivers, bicycle taxi drivers), fishermen/fishmongers, MSM and hair salon workers. The study also identified using personal contact, link persons, peer mobilisers and leaders as strategies of identifying and locating KPs. The study used the mRDS successfully in recruiting participants with evaluation of inconsistent condom use and multiple sexual partnerships showing the participants to be of high risk behaviour. Of all the females in the study, only 3.3% were pregnant. The prevalence of Chlamydia was 2.9%, gonorrhoea was 5.0%, syphilis was 0.4% and HSV-2 was 46.0%. Those who tested positive for HIV were 26.2% with 42.3% of the HIV positive participants having CD4 counts of between 250 – 500 cells/ml. Recommendations and Conclusion:The mRDS was successful in recruiting KPs in an HIV prevention trial. Majority of the participants reported inconsistent condom use and having multiple sex partners. In addition to MSM, SW and transport industry workers, fisherfolk, discordant couples, widowers, street youth, car washers and police also form part of KPs groups. The HIV prevalence was higher amongst these groups compared to general population with discordant couples having the highest HIV prevalence. The study recommends that mRDS should be used to identify and recruit KPs as it not only allows for faster recruitment of KPs, it also reduces the expense and complexity associated with coupon management in the standard RDS.
Heyman, Heino Martin. "Identification of anti-HIV compounds in Helichrysum species (Asteraceae) by means of NMR-based metabolomic guided fractionation." Thesis, University of Pretoria, 2013. http://hdl.handle.net/2263/40273.
Full textThesis (PhD)--University of Pretoria, 2013.
gm2014
Plant Science
unrestricted
Jegede, Oyebisi. "Identification and Characterization of Novel Antiretroviral Compounds: from Small Molecule Library Screening to Rationally Designed Compounds." [Kent, Ohio] : Kent State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1185563176.
Full textTitle from PDF t.p. (viewed Mar. 11, 2009). Advisor: Miguel Quiñones-Mateu. Keywords: HIV/AIDS, drug discovery, small molecule library screening, characterization of new antiretroviral drugs, highly active antiretroviral therapy. Includes bibliographical references (p. 180-200).
Fleta, Soriano Eric 1983. "Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/402212.
Full textCientos de factores del huésped relacionados con infecciones virales por VIH, hepatitis C, dengue o virus del Nilo occidental han sido identificados. Como muchos de esos factores del huésped son compartidos por diferentes virus, el bloqueo químico de un componente celular clave asociado al virus podría actuar de forma efectiva como un tratamiento antiviral de amplio espectro. Antivirales de amplio espectro contra factores del huésped podrían reducir la complejidad y el coste del tratamiento, incrementar el cumplimiento de la terapia y pueden suponer una barrera mayor al desarrollo de resistencia. En esta tesis un cribado de alta capacidad anti-VIH fue aplicado a una librería de metabolitos secundarios de myxobacteria. Compuestos con alta actividad anti-VIH y baja toxicidad fueron clasificados como hits y dos de ellos (ratjadone A y soraphen A) fueron seleccionados para posteriores estudios. El mecanismo de inhibition de VIH de ambos compuestos es descrito aquí. Los resultados presentados en esta tesis muestran que usar antivirales de amplio espectro contra factores del huésped es un opción viable para tratamientos antivirales y que los compuestos identificados pueden ser estudiados para el desarrollo de fármacos.
Dadgar, Majid. "Pattern Language: Identification of design opportunities for the child with Autism Spectrum Disorder (ASD) to develop his/her social skills." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313619497.
Full textÁlvarez, Marimón Mª Elena. "Structural studies of Heteromeric Amino acid Transporters (HATs): Validation of the first 3D structural model of a HAT (human 4F2hc/LAT2) and identification of new HAT targets for 3D‐crystallization." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/284082.
Full textLos transportadores heteroméricos de aminoácidos (HAT) median el transporte de aminoácidos a través de la membrana plasmática. Representan el único ejemplo de transportadores de solutos formado por dos subunidades distintas unidas por un puente disulfuro. Debido a su gran relevancia en fisiología (asociados a aminoacidurias, infección por virus, cáncer,…) el estudio de su estructura-función resulta clave. Debido a su naturaleza, son proteínas difíciles de cristalizar, de las que sólo se conoce la estructura atómica del ectodominio de 4F2hc humano. En este escenario la tesis se centró en la validación del primer modelo 3D a baja resolución de un HAT humano (4F2hc/LAT2), mediante experimentos de crosslinking entre subunidades, e identificación de nuevos candidatos para cristalización 3D. Para ello se seleccionaron 24 subunidades ligeras de distintas especies eucariotas y se testaron en un proceso de selección para determinar el/los mejores candidatos. El primer objetivo de la tesis concluyó con la determinación de residuos concretos en 4F2hc y LAT2 cercanos a una distancia de 3-14 Å mediante la utilización de crosslinkings de cisteínas. Finalmente, tres líneas distintas: el modelo 3D obtenido por microscopía electrónica de transmisión y tinción negativa de partículas individuales (en colaboración con Dr. Fotiadis), los experimentos de crosslinking, y el docking generado en colaboración con Dr. Fdz-Recio, demostraron que 4F2hc-ED cubre, casi completamente, la superficie extracelular de LAT2. Además, se demostró que el ectodominio de 4F2hc es suficiente para estabilizar LAT2. Como resultados del segundo objetivo, tres subunidades ligeras fueron seleccionadas, tras adaptar el protocolo desarrollado por Drew et al.,2008, como mejores candidatas para estudios de cristalización 3D. Posteriormente, distintas estrategias se siguieron para mejorar la estabilidad de la mejor candidata: eliminación de la cisteína reactiva, adición de lípidos a la muestra, cambio de sistema de expresión para aumentar su expresión a células de insecto Sf9. Además, se generaron mutantes delecionados en N y C terminal para reducir su flexibilidad y aumentar la probabilidad de cristalización. Se concluyó en encontrar un buen candidato para estudios de cristalización.
Janvier-Chemy, Blandine. "Identification d'épitopes B des protéines de core des virus HIV-1 et HIV-2 : application au développement de tests pronostiques." Compiègne, 1990. http://www.theses.fr/1990COMPD326.
Full textGramatica, Andrea. "HIV-1: identification of a pathway for virus release and development of a new nanotechnological strategy to counteract the infection." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2014. http://dx.doi.org/10.18452/17013.
Full textHuman immunodeficiency virus 1 (HIV-1) hijacks proteins and signaling pathways of the host cell for its own life cycle, thereby impairing many functions of immune cells, including pathogen-phagocytosis by macrophages. The overall weakening of immune functions eventually results in the development of acquired immunodeficiency syndrome (AIDS). HIV-1 assembly takes place at the plasma membrane as well as in endosomal compartments and is governed by the structural polyprotein Gag, which is also sufficient for the release of virus-like particles (VLPs) from the host cell. It was shown that an induced high cytoplasmic calcium concentration increases the amount of VLPs in endo-lysosomal compartments and results in a dramatic enhancement of VLP release [1,2]. However, the mechanism by which calcium can promote the release of VLPs remains to be determined. The first part of this work shows that release of calcium from lysosomes causes fusion between endosomes and lysosomes as well as exocytosis of lysosomeentrapped VLPs. This mechanism is regulated by Synaptotagmin VII and prevents degradation of a part of the late endosome- and lysosome-entrapped VLPs. The second part focuses on the development of a nanobiotechnological system for the clearance of Env/Gag-VLPs (HIV-VLPs) by macrophages. This system is based on immunoliposomes that (1) bind HIV-VLPs via anti-Env antibodies and (2) are phagocytosed by macrophages due to the presence of phosphatidylserine (PS), an apoptotic signal. Essentially, the PS-liposomes mimic apoptotic cells thereby inducing internalization and lysosomal delivery of bound HIV-VLPs. These immunoliposomes exploit an efficient internalization pathway not impaired upon HIV-1 infection. The results of this thesis provide new insights into the intracellular pathways controlling HIV-1 release and demonstrate that PS-immunoliposomes can represent a novel nanomedical approach for viral clearance and HIV antigen presentation.
Long, Kimberly Renee. "Identification and Characterization of Agv1, a Pre-Metazoan Arf GAP: A Dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/339.
Full textVazquez, Ana Carolina. "Identification and characterization of compounds with antiviral activity against influenza viruses." [Kent, Ohio] : Kent State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1227644336.
Full textTitle from PDF t.p. (viewed Dec. 14, 2009) Advisor: Miguel E. Quinones-Mateu. Keywords: biomedical research, cellular biology, molecular biology, virology. Includes bibliographical references (p. 201-228)
Shehadeh, Nancy. "Ethnic Identification: Its Impact on HIV/AIDS Risk among Migrant and Seasonal Workers in South Florida." FIU Digital Commons, 2012. http://digitalcommons.fiu.edu/etd/722.
Full textBirckhead, Traci M. "For the Sake of His House| The Role of Leadership Development of Lay Leaders of an African American Protestant Church in Enhancing Organizational Identification." Thesis, The George Washington University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10931942.
Full textThis research study examined the organizational identification process of lay church leaders. The organizational identification process is important to all organizations, as it increases an individual’s connection to the organization and thus has the potential to increase attendance, commitment, group behaviors, and the enactment of organizational policies. Lay leaders are key to the success of churches, as the weight of leadership lies within these structured leadership positions of small, established ministries.
One research question guided this study: What is the role of leadership development of lay leaders in enhancing their organizational identification? The research site for this single descriptive case study was First Baptist Church of Highland Park, a large, African American Protestant church located near Washington, DC. Data were collected through interviews with lay leaders of three ministries of this church—deacons, ministers, and trustees—as well as observation and document analysis. Lay leaders were selected as the participants for this study since most roles and positions of leadership within the church involve this volunteer, lay leader base, and these individuals are trained for the ministry through an extensive leadership development process developed and provided by the church.
This study found that (1) the early life of lay leaders made a difference in how the leadership development program affected their organizational identification; (2) the associated ministry roles and responsibilities, as refined in the leadership development process, enhanced their process of organizational identification; (3) the self-esteem of the lay leaders developed through their leader training process and was an important factor in further enhancing their process of organizational identification; and (4) the church’s identity and specific aspects of its mission and values were central in the organizational identification process.
Gentili, Matteo. "Identification of viral and host mechanisms that determine innate immune activation by the DNA sensor cGAS." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB023.
Full textNucleic acids are potent activators of innate immune responses. To control infections, multicellular organisms have developed multiple ways to detect pathogens. One of these is the recognition of DNA in the cytoplasm. Presence of DNA in the cytoplasm is usually linked to infections by bacteria or viruses, such as HIV. Cyclic GMP-AMP synthase (cGAS) is an essential cytosolic sensor for DNA in mammals. Upon DNA recognition, cGAS synthetizes the small second messenger cyclic GMP-AMP (cGAMP), which activates innate immune signaling pathways. cGAS plays a pivotal role in response to microbes and in the development of autoimmune diseases such as interferonopathies. This thesis investigate the role of cGAS in response to viruses and to self DNA. By exploring the cGAS-mediated response to HIV, we found that in cells producing virus, cGAS-synthesized cGAMP is packaged in viral particles and extracellular vesicles. Viral particles efficiently deliver cGAMP to target cells and activate a potent antiviral response. The transfer of cGAMP requires cGAS catalytic activity and fusion of the viral particles with the target cells. We also showed that in the context of an infection, DNA viruses such as MVA and mCMV can package cGAMP. Therefore viral mediated cGAMP transfer is a generalized defense mechanism of the innate immune system. We further investigated cGAS activation by DNA focusing our attention on nuclear chromatin DNA. In eukaryotic cells, DNA is compartmentalized in two organelles: the nucleus and the mitochondrion. Nuclear compartmentalization of DNA can be transiently lost upon nuclear envelope breakdown during cell division and upon nuclear envelope ruptures in migrating dendritic cells (DCs). We found that nuclear envelope breakdown or loss of nuclear envelope integrity leads to cGAS recruitment on the nuclear DNA. We also showed that DCs present with a nuclear pool of cGAS at steady state. Nuclear envelope breakdown during cell cycle leads to cGAS recruitment to the nuclear DNA. By manipulating cGAS localization, we showed that cGAS is poorly active when in the nucleus, and that providing exogenous DNA unmasked its full enzymatic activity. Expression of nuclear localized-cGAS in DCs leads to DCs maturation and Type I interferon (IFN) production. The N-terminal region of cGAS regulates cGAS nuclear/cytoplasmic distribution in interphase cells and we established Lamin A/C as required for cGAS accessibility to nuclear DNA in migrating DCs. Unexpectedly, we show that cGAS is not activated upon nuclear envelope rupture. Finally, we identify the pericentromeric heterochromatin as the preferential binding DNA for expressed nuclear cGAS in DCs. Altogether, our study shows the nucleus to act as an intracellular immune-privileged site for the activation of cGAS. Collectively, we have shown relevance of cGAS activation upon viral infection and uncovered a Trojan horse mechanism of cGAMP incorporation in the viral progeny. We have also described yet to be defined regulatory mechanisms that limit responses towards chromatin DNA in the nucleus. As evidence grows for cGAS involvement in response to pathogens, in autoimmune diseases, in response to DNA damage and in the development of cell senescence, fully understanding the mechanisms of distinction between self and pathogen related DNA by the sensor will be important to develop effective means to regulate the pathway
Bonaventure, Boris. "Cribles CRISPR/Cas9 à l'échelle du génome : identification de l'hélicase à ARN DDX42 comme nouvel inhibiteur viral." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTT035.
Full textGenome-wide CRISPR/Cas9 knock-out genetic screens are powerful approaches to unravel new regulators of various cellular processes, including viral replication cycles. With the aim of identifying new cellular inhibitors of HIV-1, we have developed a whole-genome CRISPR/Cas9 knock-out screen using the ability of type I interferon to potently inhibit HIV-1 infection in order to create a cellular environment hostile to HIV-1 replication. This screen led to the identification of the DEAD-box RNA helicase, DDX42, as an intrinsic inhibitor of HIV-1. Cells depleted for DDX42 became more susceptible to HIV-1 infection both in the presence and in the absence of interferon. The ability of endogenous DDX42 to potently inhibit HIV-1 infection was observed in cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages. Similarly, DDX42 overexpression potently inhibited HIV-1 infection. The positive impact of DDX42 depletion on HIV-1 infection was directly correlated to a substantial increase in viral DNA accumulation, pinpointing an inhibitory role of DDX42 on reverse transcription. Within cells, DDX42 was found primarily in the nucleus but was also present in the cytoplasm. Interestingly, proximity ligation assays showed that DDX42 was in the close vicinity of HIV-1 Capsid during infection of primary monocyte-derived macrophages. Investigation on DDX42 specificity showed that different lentiviruses, the retrovirus MLV and the retrotransposition of LINE-1 were inhibited by DDX42. Finally, we reveal that DDX42 was able to decrease infection with a variety of viruses including alphaviruses, flaviviruses and coronaviruses
Younan, Patrick. "Identification and Characterization of SNAPIN as a Novel Antagonist of HIV-1 Egress: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/460.
Full textEloraby, Ghada. "Identification of protein targets of nevirapine reactive metabolites using click chemistry and mass spectrometry-based differential proteomics." Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/8995.
Full textRésumé : Les effets indésirables (EI) sont les effets indésirables causés après l'administration d'une dose unique ou une administration prolongée du médicament ou le résultat de la combinaison de deux médicaments ou plus. La Réaction idiosyncratique (IDR) est une réaction indésirable qui ne se produit pas dans la plupart des patients traités avec un médicament et qui ne comporte pas l'effet thérapeutique du médicament. IDR sont imprévisibles et peuvent mettre la vie du malade en danger. Cette réaction dépend des caractéristiques chimiques du médicaments et/ou de la réponse immunitaire individuelle du patient. IDR est un problème majeur pour le développement de médicaments car ils ne sont généralement pas détectés au cours des essais cliniques. Dans cette étude, nous nous sommes concentrés sur la Réaction idiosyncratique de névirapine (NVP) qui est un inhibiteur de transcriptase inverse non nucléosidique utilisé pour le traitement du virus d'immunodéficience humaine (VIH). L'utilisation de NVP est limitée par une incidence relativement élevée d'éruption cutanée. NVP provoque également une éruption cutanée chez les rats femelles de souche Brown Norway. Notre étude vise à mieux comprendre les IDRs induites par l'administration de NVP chez l'animal. La présente étude vise à vérifier l'hypothèse que les problèmes cutanés associés à la prise de NVP soient attribuables à la modification post-traductionnelle de protéines détactable par spectrométrie de masse. Les principaux objectifs de ce projet étaient : 1) Déterminer si la Nevirapine alcynes (NVP-ALK), un analogue de la NVP peut développer la même éruption cutanée que la NVP. La NVP-ALK a été couplé avec de la biotine en utilisant la réaction chimique (click chemistry). 2) Détecter les modifications post-traductionelles des proteines par Western blot et des techniques de spectrométrie de masse, pour comprendre le mécanisme de la toxicité induite par la NVP. 3) Identifier les protéines modifiées en utilisant le moteur de recherche MASCOT pour l'identification des protéines, en comparant le les spectres de masse obtenus avec les spectres théoriques pour trouver une séquence correspondante de peptide. 4) Tester si la NVP et ses métabolites peuvent provoquer des effets nocifs, comme l'induction d'un stress oxydatif dans les cellules (par la mesure de la glutathionylation des protéines). Les résultats ont montré que la névirapine est métabolisé en métabolite réactif ce qui provoque une modification de la kératine. Ainsi nos résultats suggèrent que la kératine est la cible des métabolites de la NVP-ALK.
Paoletti, Audrey. "Étude des étapes précoces de l’infection par le VIH-1 : identification d’un nouveau point de contrôle immunitaire immunitaire impliquant le récepteur P2Y2 et la protéine NLRP3." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS240.
Full textIn 3 decades infection with the virus of the human immunodeficiency of type 1 (HIV-1) caused over than 34 million deaths and the surge of new multiresistant virus strains require the development of novel antiretroviral strategies.Our laboratories revealed a new signaling pathway involving in the early step of HIV-1 infection, involving a hemichannel (Pannexin-1), a common danger signal (extracellular ATP) and a purinergic receptor (P2Y2). These three cellular events are also players in the immune response; we decided to continue the study of proteins involved in the innate immune response during the early stages of infection by HIV -1.Here we demonstrated during this work a new interaction between the purinergic receptor P2Y2 and protein of the inflammasome NLRP3. We demonstrate that P2Y2-stimulated migration of macrophages is inhibited by NLRP3 inflammasome activation. Conversely, NLRP3-dependent macrophage polarization, interleukin-1 β secretion and pyroptosis are under the control of P2Y2-induced autophagy.Finally, the results suggest that the interaction between NLRP3 and P2Y2 is a new immunological checkpoint that regulates macrophage functions. Following this work, we analyzed the role of this immunological control during infection by HIV -1 and have demonstrated that activation of the inflammasome NLRP3 prevents the activation of the purinergic signaling channel involving ATP, pannexin -1 and the P2Y2 receptor, and which allows the entry of HIV -1 in its target cells. Our research and bring to light the capacity of the NLRP3 inflammasome to represent a new inducible restriction factor of HIV-1.All of this research work highlights the existence in macrophages of a new immune system checkpoint involving NLRP3 protein and P2Y2 receptor and can be modulated in order to develop new therapeutic approaches to fight against the emergence of viruses resistant to conventional retroviral treatments
Dupont, Maeva. "Identification of novel factors involved in the exacerbation of HIV-1 infection and spread among macrophages in the tuberculosis context." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30211.
Full textMycobacterium tuberculosis (Mtb), the bacteria causing tuberculosis (TB), and the human immunodeficiency virus type 1 (HIV-1), the etiological agent of acquired immunodeficiency syndrome (AIDS), act in synergy to exacerbate the progression of each other in co-infected patients. While clinical evidence reveals a frequent increase of the viral load at co-infected anatomical sites, the mechanisms explaining how Mtb favours HIV-1 progression remain insufficiently understood. Macrophages are the main target for Mtb. Their infection by the bacilli likely shapes the microenvironment that favours HIV-1 infection and replication at sites of co-infection. To address this issue, I took advantage of an in vitro model mimicking the TB-associated microenvironment (cmMTB, "conditioned media of Mtb-infected macrophages") previously established in the laboratory; a model that renders macrophages susceptible to intracellular pathogens like Mtb. Upon joining the team, I participated in the study on how Mtb exacerbates HIV-1 replication in macrophages, using this model. We found that cmMTB-treated macrophages (M(cmMTB)) have an enhanced ability to form intercellular membrane bridges called tunneling nanotubes (TNT), which increase the capacity of the virus to transfer from one macrophage to another, leading to the exacerbation of HIV-1 production and spread. The principal objective of my PhD thesis was to identify novel factors that are involved in the exacerbation of HIV-1 replication in macrophages in the context of tuberculosis. To this end, a transcriptomic analysis of M(cmMTB) was conducted, and revealed two key factors: the Siglec-1 receptor and type I interferon (IFN-I)/STAT1 signaling. The first part of my PhD thesis dealt with the characterization of Siglec-1 as a novel factor involved in the synergy between Mtb and HIV-1 in macrophages. First, I demonstrated that its increased expression in M(cmMTB) was dependent on IFN-I. Second, in Mtb and simian immunodeficiency virus co-infected non-human primates, I established a positive correlation between the abundance of Siglec-1+ alveolar macrophages and the pathology, associated with the activation of the IFN-I/STAT-1 pathway. [...]
Ahuka, Mundeke Steve. "Identification et caractérisation moléculaires des rétrovirus simiens et évaluation du risque de transmission à l'homme en Afrique Centrale." Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON1T002.
Full textSIVs and SLTVs infecting apes and monkeys in Africa are the progenitors of HIV and HTLV. Numerous African non-human primates are infected with SIV and STLV and humans continue to be exposed to these viruses by hunting and handling of primate bushmeat. Therefore the risk of cross-species transmissions from primates to humans is still persistent. We showed that SIVagi infecting captive agile mangabey is most closely related to SIVrcm from a wild-caught red capped mangabey from Cameroon. We observed also phylogeographic clustering among SIVdeb strains from Cameroon, DRC and Uganda, but also among distinct areas in Cameroon. We adapted and evaluated a novel high troughput immune assay that included 34 different HIV and SIV antigens in a single well. Using this tool and others, we found a high SIV and STLV prevalence especially among the most hunted monkeys in DRC. We identified also new SIV and STLV lineages. On the other hand, we did not find any evidence of SIV infection in bonobos. However, we showed, for the first time, that fecal samples could be used to detect STLV infection in bonobos that are naturally infected with STLV-2 and 3. The results obtained during this thesis contribute to the improvement of our knowledge on retroviral infections in nonhuman primates from Central Africa, complete information on HIV and HTLV reservoirs and provide background information on human transmission risk of these infections in central Africa especially in DRC
Ligot, Damien. "Trans-musicalité « taike » : Distinction d’une nouvelle « taiwanité » au sein d'un underground local (1990-2010)." Thesis, Lyon 3, 2012. http://www.theses.fr/2012LYO30022/document.
Full textIn the 1990's and 2000's, the underground music scene in Taiwan successively gave birth to the Taik – also called Taike Rock 台客搖滾 taike yaogun – then to Taiwan Traditional Rap 台灣味唸歌 Taiwan wei niange. These "trans-musical" currents are similar in many issues such as the claim to local folk traditions, accompanied however by accomodating a strong cultural mix and by a need to define – to identify – themselves outside the alienating good taste, so dictated since the late 1940's by the hegemonic "dominant" culture focused along the lines of the Republic of China. This thesis proposes a ''sensitive'' approach to a particular subculture, furthermore tempered by a critique of theories developed by Pierre Bourdieu in Distinction: A Social Critique of the Judgment of Taste. It has been backed up by field studies conducted between 2005 and 2010 according to the principles of the participant-observer and trends of thought enlightened by cultural studies and works of authors such as Dick Hebdige and Stuart Hall. It attempts also – through the prism of trans-musicality – to define the place of the local "Taike" subculture in the global history of other comparable subcultures, as an essentiel link between Taiwan and the rest of the world
Morphet, Marilynn Norma. "Method for identification of effective first-line treatment for HAART naïve HIV/AIDS patients." Thesis, Queensland University of Technology, 2002.
Find full textPicard, Léa. "Identification of Novel Viral Interacting Proteins through the Detection of Genetic INNovations (DGINN) combined with functional assays." Thesis, Lyon, 2020. http://www.theses.fr/2020LYSEN031.
Full textThe identification of cellular proteins that interfere with virus replication is a key challenge in virology. Amongst them, finding those engaged in long-term virus-host interaction and co-evolution is of particular interest. In the host, such selective pressures induce diverse genetic innovations, such as site-specific positive selection, gene copy number variation, recombination, etc. Under the hypothesis that genetic innovations in innate immunity may particularly occur in viral interacting proteins, we developed a pipeline for retrieving orthologous sequences, aligning them and reconstructing their phylogeny, followed by the detection of genetic innovations. This streamlined procedure uniquely allows for the detection of paralogous genes, recombination breakpoints, and signatures of positive selection with several widely-used methods. We validated this evolutionary and predictive pipeline on genes with known selection profiles. Furthermore, we screened two datasets of candidate genes. The first one was composed of 56 genes which knock-downs impact the interferon response to viral infection. The second one was composed of 60 genes upregulated in macrophages resistant to HIV infection. We found numerous genes presenting important marks of genetic conflict, thus potentially encoding for novel Viral Interacting Proteins. Two of these candidates are undergoing functional characterization for their role in the HIV replicative cycle, and others are pending further investigation. Overall, we designed a complete and highly-flexible pipeline, available to the public, that can screen large datasets and allow researchers to rank candidate genes in order to prioritize their wet-lab experiments
Truter, Jan Hendrik Lodewyk. "'n Teologies-empiriese ondersoek na die rol wat gemeentebou in die beplanning en oprigting van kerkkomplekse binne die Nederduitsch Hervormde Kerk van Afrika die afgelope tien jaar gespeel het." Diss., Pretoria : [s.n.], 2005. http://upetd.up.ac.za/thesis/available/etd-05232006-162503/.
Full textGray, Laura. "Stéréotypes liés à l’activité physique et la fatigue chez les personnes vivant avec le VIH : une identification des mécanismes psychologiques et physiologiques impliqués." Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4217/document.
Full textPhysical activity (PA) has been reported to have many beneficial effects among people living with HIV (PLHIV), especially on fatigue, which is one of the main prevalent symptom and possible side effects of treatments in this population. Nevertheless, PLHIV remain insufficiently active according to PA recommendations. Based on contemporary theories of stereotypes applied to health behaviours (e.g., Stereotype Embodiment Theory, Levy, 2009; Stereotype Threat Theory, Steele & Aronson, 1995) and an integrative approach of fatigue (Kluger et al., 2013), this doctoral work postulated that exercise stereotypes endorsement or activation would play a role in the PA level of PLHIV and in their performance in fatiguing tasks. The first part of this dissertation identified the content of stereotypes related to PA and HIV through a qualitative approach (Study 1) and conducted the development and validation of a specific scale (Study 2). The second part aimed at identifying the mechanisms at play in the relationship between exercise stereotypes, fatigue and PA. Results showed that exercise stereotypes might influence PA through ego depletion mechanisms, as indexed by perceived fatigue and, be tempered by exercise self-efficacy (Study 3). Perceived fatigue and performance fatigability might also depend on the PA level of PLHIV, the more physically active PLHIV being characterised by lower perceived fatigue and performance fatigability (Study 4). Finally, based on stereotype threat theory, the last part of this doctoral work indicated that the nonexerciser stereotype threat could affect performance fatigability in less active PLHIV (Study 5) but not in healthy adults (Study 6). Furthermore, self-efficacy tempered the effect of the nonexerciser stereotype in less active PLHIV (Study 5). These results enrich the literature on stereotypes in the PA domain while raising interesting questions for contemporary models of fatigue in chronic diseases
Davis, Robert M. "Asymmetrical Information Market Failure Triggered by the Chicago School's Profit Motive Paradigm: A Case Study of Virginia's Public Higher Education Market and Media Identification of Public Value Failure." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/23281.
Full textMaster of Public Administration
Zheng, Yue. "Identification d'une plante médicinale africaine par le DNA barcoding et étude de composés à activité anti-HIV de cette plante." Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ095/document.
Full textMy thesis project deals with the identification, by DNA barcoding, of an African medicinal plant and the study of anti-HIV compounds from this plant. A first analysis of the ITS2 marker sequence determined from DNA extracted from the wood suggested that the plant could belong to the Cassia or the related Senna genus. A further analysis of ITS2 as well as of trnH-psbA spacer sequences from about 50 species of the two genera allowed me to identify the plant as Cassia abbreviata. The sequence alignments, which reveal unique features present in the Cassia but not the Senna sequences, were used to construct phylogenetic trees showing the clear separation of the species of the Cassia and the Senna genus. The two markers therefore allow a quick discrimination between the species of the Cassia and the Senna genus and appear to be excellent barcode markers for identification of these species. Following the identification of the plant I have tested the crude ethanol extract as well as 57 purified compounds from the plant for an anti-HIV activity. The extract, as well as one of the compounds, namely piceatannol, showed a broad spectrum of antiviral activities for HIV and HSV. They inhibited HIV-1 infection at the early stage against various reference strains and resistant clinical isolates independent of the co-receptor usage (IC50: 10.47-40.77 μg/ml, CC50>1000 μg/ml; IC50: 8.04-47.46 μM,CC50>300 μM, respectively). Neither the crude extract nor piceatannol had an effect on CD4 and CCR5/CXCR4. The crude extract blocked CD4-gp120 interaction while piceatannol did not, indicating that CE may target gp120 and piceatannol may act as a non-specific viral attachment inhibitor. Moreover, piceatannol inhibited HIV infection of TZM-Bl target cells in an in vitro female genital tract model and did not activate PBMCs, suggesting that it may represent a good candidate as microbicide. Other anti-HIV compounds found in Cassia abbreviata include oleanolic acid, palmitic acid, taxifolin and three other compounds the structure of which is presently being elucidated
Fouche, Jean-Paul. "A diffusion tensor imaging study in HIV patients with and without apathy." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/5146.
Full textENGLISH ABSTRACT: HIV/AIDS is a global epidemic that accounts for a large percentage of the mortality in South Africa every year. Since the implementation of anti-retroviral treatment, HIV positive individuals have been living longer, and the cognitive impairment associated with the disease is becoming increasingly apparent. During the initial systemic infection of HIV, the virus migrates through the blood-brain barrier and inflicts axonal injury by causing upregulation of cytokines and neurotoxic proteins. HIV-associated dementia is a neuropsychological classification of cognitive impairment in HIV and a variety of symptoms have been classified as a part of the dementia complex. One of these is apathy, which is thought to be a precursor for dementia in HIV patients. Three groups of individuals have been recruited and scanned using magnetic resonance imaging (MRI) to examine changes in the brain. These are an HIV non-apathetic cohort, an HIV apathetic cohort and a healthy control cohort. Diffusion tensor imaging (DTI) is an MRI technique used to quantitatively assess white matter (WM) integrity using metrics such as fractional anisotropy (FA). Voxel-based analysis, tract-based spatial statistics (TBSS) and tractography are three established DTI analysis methods that have been applied in numerous studies. However, there are certain methodological strengths and limitations associated with each technique and therefore all three of these techniques were used to compare WM differences across groups. The frontal-subcortical pathways are known to be abnormal in apathy, and this has been demonstrated in a number of imaging studies. Most of these studies have examined apathy in the context of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s. However, to our knowledge this is the first DTI study in HIV apathetic patients. With the tractography method, the anterior thalamic radiation and the corpus callosum were reconstructed for each individual to determine whether there were any global changes in these tracts. No significant changes were found. However, a variety of regions in the WM were significantly abnormal in the HIV cohorts when comparing the data at a voxel-based level and using TBSS. This included areas such as the genu and splenium of the corpus callosum, the internal capsule and corona radiata. Changes in frontal WM for the HIV apathy group are an indication of dysfunction in the frontal-striatal circuits, and previous literature has implicated these circuits in the neuropathology of apathy in a variety of central nervous system (CNS) disorders.
AFRIKAANSE OPSOMMING: MIV/VIGS is `n wêreldwye epidemie wat verantwoordelik is vir `n hoë sterftesyfer in Suid- Afrika elke jaar. Sedert die inleiding van anti-retrovirale behandeling, het die MIV-positiewe populasie se lewensduur verleng. Tesame met langer lewensduur, het die kognitiewe verswakking wat geassosieer word met die siekte ook meer prominent na vore gekom. Gedurende die beginstadium van sistemiese infeksie in MIV is daar `n migrasie van die virus deur die bloed-breinskans. MIV kan indirek verantwoordelik wees vir aksonale beskadiging deur verhoging van neurotoksiese proteine en sitokinien te induseer. MIV-geassosieerde demensie is `n neurosielkundige klassifikasie van kognitiewe verswakking in MIV en verskeie simptome is al geïdentifiseer as deel van die demensie kompleks. Een van die simptome is apatie en daar word gespekuleer dat dit `n voorloper is vir demensie in MIV pasiënte. Drie groepe individue was gewerf vir die studie en geskandeer deur magnetiese resonansie beeldvorming (MRB) om sodoende veranderinge in die brein te ondersoek. Die groepe was onderskeidelik `n HIV nie-apatiese kohort, `n HIV apatiese kohort en `n gesonde kontrole kohort. Diffusie tensor beelding (DTB) is `n MRB tegniek wat toegepas word om witstof integriteit te meet deur gebruik te maak van maatstawwe soos fraksionele anisotropie (FA). “Voxel-based analysis”, “tract-based spatial statistics (TBSS)” en “tractography” is drie gevestigde DTB analitiese metodes wat al in talle studies toegepas was. Daar is egter sekere metodologiese voordele en beperkings verbonde aan elke tegniek en daarom is al drie tegnieke gebruik om witstof verskille tussen groepe te vergelyk. Die frontale-subkortikale roetes in die brein is bekend vir abnormaliteite in apatie en dit was ook al gedemonstreer in verskeie studies. Die meeste van die studies het apatie ondersoek in die konteks van neurodegeneratiewe siektes soos Alzheimer se siekte en Parkinson se siekte. Maar sover ons weet is hierdie die eerste DTB studie in MIV pasiënte met apatie. Met die “tractography” metode was die anterior thalamic radiation en corpus callosum herbou vir elke individu. Dit was om te bepaal of daar enige globale veranderinge is in hierdie gebiede, maar geen beduidende veranderinge is gevind nie.`n Verskeidenheid van gebiede in die witstof was beduidend abnormaal in die MIV kohorte wanneer die data vergelyk was met “TBSS” en “voxel-based analysis.” Dit het gebiede ingesluit soos die genu en splenium van die corpus callosum, die internal capsule en die corona radiata. Veranderinge in die frontale witstof vir die MIVapatie groep is `n aanduiding van disfunksie in die frontale-striatale bane. Vorige literatuur impliseer dat hierdie bane betrokke is in die neuro-patologie van apatie in verskeie sentrale senuweestelsel (SS) steurings.