Dissertations / Theses on the topic 'Susceptibilite alternative'
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Frison, Jean-Claude. "Cristallogenèse et caractérisations d'oxydes supraconducteurs du système Tl-Ba-Ca-Cu-O." Phd thesis, Université Sciences et Technologies - Bordeaux I, 1990. http://tel.archives-ouvertes.fr/tel-00170306.
Full textNganga, Léon. "Contribution à l'étude du matériau supraconducteur à température critique élevée YBa2Cu3O7: cristallogénèse et caractérisations physico-chimiques." Phd thesis, Université Sciences et Technologies - Bordeaux I, 1990. http://tel.archives-ouvertes.fr/tel-00173106.
Full textZaharieva, Emanuela. "Susceptibility of alternative splicing to interference by xenobiotics : implications for the use of Drosophila in toxicological studies." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4648/.
Full textBrinis, Drifa. "Dynamique d'aimantation dans les assemblées d'agrégats ferromagnétiques : effets des interactions." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR049/document.
Full textIn our work, we used Monte Carlo technique to simulate the effect of dipolar interactions on the magnetization reversal of a ferromagnetic nanoparticles assembly. In our model, we considered nanoparticles with uniaxial anisotropy and specifically the Cobalt. With the condition KV/kBT >> 1, the magnetic moment of each nanoparticle is fixed in its equilibrium positions and it can not fluctuate around. We chose to our investigation the ac susceptibility because it provides the advantage of making the study with a wide frequency range without changing measurement technique, because the measurement time is equal to the inverse of the frequency of the alternating magnetic field applied. We studied twelve types of assemblies each one differs from the other by some properties : The shape of the assembly, the spatial distribution of the nanoparticles or the distribution of the anisotropy axes. And we discerned the influence of each of theses parameters on the effect of dipolar interactions on the magnetization reversal
Ito, Dai. "Evaluation of susceptibility to wheat streak mosaic virus among small grains and alternative hosts in the Great Plains." Thesis, Montana State University, 2011. http://etd.lib.montana.edu/etd/2011/ito/ItoD0511.pdf.
Full textMontesinos, Herrero Clara Isabel. "Evaluation of alternatives to synthetic fungicides to control citrus postharvest diseases." Doctoral thesis, Universitat Politècnica de València, 2016. http://hdl.handle.net/10251/63662.
Full text[ES] Los cítricos (Citrus spp. fam. Rutaceae) son la fruta más consumida a nivel mundial y se cultivan en más de un centenar de países. Durante el manejo en poscosecha, la mayor parte de las pérdidas se deben a enfermedades fúngicas, que durante décadas se han controlado mediante tratamientos con fungicidas de síntesis. Sin embargo, su uso está continuamente más restringido por parte de los distribuidores y cadenas de supermercados, que reducen el Límite Máximo de Residuos (LMR) a un tercio del establecido o incluso prohíben el uso de ciertos fungicidas. Esto ha provocado la pérdida de eficacia de los tratamientos y el desarrollo de cepas de patógenos resistentes a los fungicidas. Se necesitan pues alternativas para sustituir o combinar con el uso de fungicidas de síntesis. El objetivo de este trabajo fue evaluar tratamientos alternativos contra las podredumbres verde y azul, causadas por Penicillium digitatum (Pers.: Fr.) Sacc. y Penicillium italicum Wehmer, respectivamente. Aditivos alimentarios y sustancias GRAS se probaron en test in vivo preliminaries contra los mohos verde y azul. El benzoato sódico (BS; Capítulo 1) y el sorbato potásico (SP; Capítulo 2) fueron los más eficaces. Baños de 60 s en 3% (p/v) BS sobre 50°C redujeron en un 90% la incidencia de las podredumbres verde y azul en naranjas 'Valencia Late' tras 7 días a 20°C. Estos tratamientos fueron también efectivos en naranjas 'Lanelate', limones 'Fino' y mandarinas híbridas 'Ortanique', pero no en mandarinas 'Clemenules'. La combinación de baños calientes de BS con dosis bajas de imazalil (IMZ) fueron sinérgicas. Un nuevo método colorimétrico que empleó la extracción del SP de la fruta macerada, seguido de una reacción con ácido 2-tiobabitúrico (Capítulo 3) mostró que en naranjas tratadas con SP almacenadas a 15°C, los residuos descendieron rápidamente al inicio y lentamente más tarde, hasta que dejaron de descender tras 6 días. Un doble aclarado rápido con agua corriente inmediatamente después de la inmersión de limones en SP al 2% (p/v), eliminó más del 90% del residuo de SP. Los choques gaseosos a 33ºC y 15kPa CO2 durante 24 h o 30 kPa O2 durante 48 h controlaron de manera eficaz las podredumbres verde y azul tras 7 días de incubación a 20ºC, pero el control de las dos podredumbres descendió tras 15 días (Capítulo 4). En almacenamiento en frío, tras 14, 28 y 42 días, la incidencia de moho verde en mandarinas 'Clemenules' y 'Ortanique' tratadas con baños con SP y 30kPa O2 durante 48h se redujo en un 100, 96 y 68%, y 100, 97 y 79%, respectivamente. De nuevo, una fuerte sinergia se observó entre los tratamientos (Capítulo 5). Las podredumbres verde y azul se controlaron eficazmente mediante la fumigación de limones y naranjas durante 6 h a 22ºC con dos dosis de 3000 ¿L L-1 amoniaco, inyectadas al inicio del tratamiento y 2 h después (Capítulo 6). El tratamiento con amoniaco controló una cepa de P. digitatum resistente a IMZ. Cuando la fruta se bañó en 10 o 30 mg L-1 IMZ (un 10% de la dosis comercial) antes de la fumigación con amoniaco, una sola aplicación con 1500 ¿L L-1 amoniaco fue suficiente para controlar las dos podredumbres, y el incremento en la eficacia fue aditivo o sinérgico. Todos estos tratamientos, a diferentes niveles, podrían sustituir a los fungicidas de síntesis o aumentar la eficacia de los tratamientos con IMZ en el manejo poscosecha de los cítricos. El desarrollo de las podredumbres verde y azul en las especies y variedades de cítricos más importantes comercialmente se evaluó durante cuatro campañas consecutivas y se relacionó con los parámetros de calidad de la fruta (Capítulo 7). La susceptibilidad de los cultivares en orden creciente fue Nova, Sanguinelli, Ortanique, Lanelate, Navelate, Fortune, Clemenules, Valencia, W. Navel, Oronules, Clemenpons, Marisol, Salustiana, Hernandina, y Nadorcott. Las características de la corteza fueron los parámetros de calidad
[CAT] Els cítrics (Citrus spp. fam. Rutaceae) son la fruita més consumida a nivell mundial i es cultiven en un centenar de països. Durant la poscollita, la major part de les pèrdues es deuen a malalties fúngiques, que durant dècades s'han controlat mitjançant tractaments amb fungicides de síntesi. No obstant, l'ús d'aquestes pràctiques està contínuament més restringit per part dels distribuïdors y cadenes de supermercats, que redueixen el Límit Màxim de Residus (LMR) a un terç del permès per la legislació o inclús prohibeixen l'ús d'alguns fungicides. Açò ha provocat la minora de l'eficàcia dels tractaments poscollita i el desenvolupament de soques dels patògens resistents als fungicides. Es necessari per lo tant trobar i implementar alternatives per a substituir o combinar l'ús de fungicides de síntesi. L'objectiu d'aquest treball ha sigut avaluar tractaments alternatius contra les podridures verda i blava, causades per Penicillium digitatum (Pers.: Fr.) Sacc. i Penicillium italicum Wehmer, respectivament. Additius alimentaris i substàncies GRAS es provaren en test in vivo preliminars contra les podridures verda i blava. El benzoat sòdic (BS; Capítol 1) i el sorbat potàsic (SP; Capítol 2) foren els més eficaços. Solucions calentes de BS combinades amb baixes dosis d'imazalil (IMZ) foren sinèrgiques. Esta combinació va reduir l'incidència de les podridures verda i blava en quasi el 100% en taronges 'Valencia Late' després de 8 setmanes a 5°C i 7 dies a 20°C. En assajos semicomercials mandarines 'Marisol', la combinació SP+IMZ a 20°C va permetre una baixada significativa de la dosis de IMZ sense perdre eficàcia contra la podridura verda. Un nou mètode colorimètric que inclou l'extracció del SP de la fruita macerada, seguit d'una reacció amb àcid 2-tiobabitúric (Capítol 3) mostrà que en taronges tractades amb SP conservades a 15°C, els residus descendiren ràpidament al inici i lentament mes tard, fins que deixaren de descendir després de 6 dies. Un doble rentat ràpid amb aigua corrent immediatament després de d'immersió de llimones en SP al 2% (p/v), eliminà més del 90% del residu de SP. Els xocs gasosos a 33ºC i 15kPa CO2 durant 24 h o 30 kPa O2 durant 48 h controlaren de manera eficaç les podridures verda i blava després de 7 dies d'incubació a 20ºC, però el control de les dos podridures descendí després de 15 dies (Capítol 4). La combinació de banys amb SP i xocs gasosos mostrà un efecte sinèrgic, que mantingué l'eficàcia dels tractaments combinats durant 15 dies. En conservacions en fred, després de 14, 28 i 42 dies, d'incidència de podridura verda en mandarines 'Clemenules' i 'Ortanique' tractades en banys amb SP i 30kPa O2 durant 48h es reduí en un 100, 96 i 68%, i 100, 97 i 79%, respectivament. De nou, una forta sinergia s'observà entre els tractaments (Capítol 5). Les podridures verda i blava es controlaren eficaçment mitjançant la fumigació de llimones i taronges durant 6 h a 22ºC amb dos dosis de 3000 ¿L L-1 amoníac, injectades al inici del tractament i 2 h després (Capítol 6). El tractament amb amoníac controlà una soca de P. digitatum amb un alt nivell de resistència a IMZ. Tots estos tractaments, a diferents nivells, podrien substituir als fungicides de síntesis o augmentar l'eficàcia dels tractaments amb IMZ en el maneig poscollita dels cítrics. El desenvolupament de les podridures verda i blava en les especies y varietats de cítrics més importants comercialment s'avaluà durant quatre campanyes consecutives i es relacionà amb els paràmetres de qualitat de la fruita (Capítol 7). La susceptibilitat dels distints cultivars en ordre creixent fon Nova, Sanguinelli, Ortanique, Lanelate, Navelate, Fortune, Clemenules, Valencia, W. Navel, Oronules, Clemenpons, Marisol, Salustiana, Hernandina, i Nadorcott. Les característiques de la pell foren els paràmetres de qualitat més influents en la susceptibilitat dels cítrics a les pod
Montesinos Herrero, CI. (2016). Evaluation of alternatives to synthetic fungicides to control citrus postharvest diseases [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/63662
TESIS
Moran, Andrew J. "An Assessment of the Susceptibility to Corrosion from Alternating Current of Cathodically Protected Steel Pipelines in Soils." University of Akron / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=akron1590695228893218.
Full textSagne, Charlotte. "Polymorphisms in G-quadruplex regions of the TP53 tumour suppressor gene : Impact on cancer susceptibility and expression of p53 N-terminal isoforms." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T072/document.
Full textThe TP53 gene is a highly polymorphic gene with 85 polymorphisms described. Some of these have been associated with an increase of cancer susceptibility, for example rs10425222 that can modulate certain p53 activities. However for others such as rs17878362, the most studied intronic polymorphism, the association with cancer risk is more controversial. To investigate the influence of rs17878362 on cancer susceptibility, we analysed its role in sporadic and familial contexts. The results are paradoxical with an increase of sporadic cancer associated with the rs17878362 A2A2 genotype whereas the rs17878362 A2 allele is associated with a “protective” effect in the context of Li-Fraumeni patients carrying a TP53 germline mutation on an A1 haplotype. These observations suggest that specific TP53 haplotypes could modulate p53’s tumour suppression capacities. A possible hypothesis to explain this could be that somatic mutations are carried on different haplotypes of TP53 present at different allele frequencies in the population. In addition, TP53 is expressed as several protein isoforms, such as D40p53, which inhibits p53’s suppressive activity. D40p53 can be produced from an alternative spliced transcript that retains intron 2. We have shown that G-quadruplexes, tri-dimensional structures formed in G-rich sequences, are formed in intron 3 and regulate the retention of intron 2 and the formation of the p53I2 transcript. We also observed that rs1642785 (located in intron 2) could regulate p53I2’s stability. These results suggest that the TP53 polymorphisms located in a 412 bp region located between exon 2 and exon 4 regulate the expression of p53 isoforms in a temporal sequence of events by modulating the pre-mRNA formation (rs17878362), mRNA stability (rs1642785) and protein functions (rs1042522).p53 isoforms’ expression is thus finely regulated by mechanisms involving TP53 polymorphisms, which are also associated with altered cancer susceptibility
Trigui, Mounir. "Etude des susceptibilites magnetiques en champ alternatif et continu de carottes de la croute oceanique en vue de l'interpretation des diagraphies electromagnetiques et magnetiques." Paris 6, 1987. http://www.theses.fr/1987PA066652.
Full textSena, Júlio Nascimento [UNESP]. "O uso de sistema de informação geográfica na avaliação de diferentes alternativas de geração de cartas de suscetibilidade à erosão." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/98103.
Full textA erosão do solo é um fenômeno que tem preocupado o homem nas últimas décadas, despertando grande interesse de muitos pesquisadores no que se refere às causas que levam a sua origem, evolução e controle, em razão desta atingir e inutilizar extensas áreas de terras, levando assim à ter a sua previsão uma elevada importância. Com a elaboração das cartas de suscetibilidade a erosão levando em conta os atributos como solo, rocha, declividade e etc. Juntamente com o SIG serão realizados o cruzamento dos atributos mais rapidamente e eficientemente, para que se possa representar melhor a realidade do local, demonstrando assim o potencial desenvolvimento de processos erosivos. Neste trabalho será considerada a importância relativa dos atributos do meio físico com diferentes escalas de peso dadas por diferentes técnicas de avaliação, pesos iguais, pesos diferentes de acordo com a visão de Mauro (2001), pesos diferentes definidos a partir de outros trabalhos da literatura, e pesos diferentes definidos com base em AHP. Com a elaboração de cartas de suscetibilidade à erosão, usando quatro diferentes técnicas, pretende-se desenvolver uma sistemática de atribuição de pesos, que possa ser aplicada a outras bacias hidrográficas. A área a ser estudada será a micro bacia do Prosa localizada a cidade de Campo Grande – Mato Grosso do Sul. Com o produto desta pesquisa pretende-se fornecer subsídios para a realização de outras pesquisas que possam melhorar as condições ambientais de uma determinada micro bacia, para um melhor estudo sobre a elaboração de cartas de suscetibilidades a erosão, bem como, demonstrar que através da utilização de um sistema da informação geográfica é possível realizar estudos ambientais, desenvolver novas técnicas de avaliação ambiental.
The soil erosion is a phenomenon that has worried man in recent decades, arousing great interest to many researchers regarding the causes leading to their origin, evolution and control, because of that achieve and become unusable large areas of land, taking thus to have its forecast high importance.With the preparation of susceptibility charts to the erosion taking into account the attributes as soil, rock, slope, etc. Along with the GIS will be made the crossing of the attributes more quickly and efficiently so that it can better represent the reality of the place, thus demonstrating the potential development of erosive processes.This work will be considered the relative importance of the attributes in the physical scales with different weight given by different techniques for evaluation, equal weights, different weights according to the vision of Mauro (2001), defined different weights from other works of literature, and defined different weights based on AHP. With the establishment of susceptibility charts to the erosion, using four different techniques, it is intended to develop a systematic allocation of weights, which can be applied to other river basins. The area to be studied will be the basin of the micro Prosa located in the city of Campo Grande - Mato Grosso do Sul With the product of this research aims to provide subsidies for the implementation of other searches that might improve the environmental conditions of a particular micro basin for a better study on the establishment of suscetibilidades charts erosion, as well as to demonstrate that through the use of the information geographical system it’s possible to realize environmental studies, developing new techniques for environmental estimation.
Sena, Júlio Nascimento. "O uso de sistema de informação geográfica na avaliação de diferentes alternativas de geração de cartas de suscetibilidade à erosão /." Ilha Solteira : [s.n.], 2008. http://hdl.handle.net/11449/98103.
Full textBanca: Maurício Augusto Leite
Banca: Reinaldo Lorandi
Resumo: A erosão do solo é um fenômeno que tem preocupado o homem nas últimas décadas, despertando grande interesse de muitos pesquisadores no que se refere às causas que levam a sua origem, evolução e controle, em razão desta atingir e inutilizar extensas áreas de terras, levando assim à ter a sua previsão uma elevada importância. Com a elaboração das cartas de suscetibilidade a erosão levando em conta os atributos como solo, rocha, declividade e etc. Juntamente com o SIG serão realizados o cruzamento dos atributos mais rapidamente e eficientemente, para que se possa representar melhor a realidade do local, demonstrando assim o potencial desenvolvimento de processos erosivos. Neste trabalho será considerada a importância relativa dos atributos do meio físico com diferentes escalas de peso dadas por diferentes técnicas de avaliação, pesos iguais, pesos diferentes de acordo com a visão de Mauro (2001), pesos diferentes definidos a partir de outros trabalhos da literatura, e pesos diferentes definidos com base em AHP. Com a elaboração de cartas de suscetibilidade à erosão, usando quatro diferentes técnicas, pretende-se desenvolver uma sistemática de atribuição de pesos, que possa ser aplicada a outras bacias hidrográficas. A área a ser estudada será a micro bacia do Prosa localizada a cidade de Campo Grande - Mato Grosso do Sul. Com o produto desta pesquisa pretende-se fornecer subsídios para a realização de outras pesquisas que possam melhorar as condições ambientais de uma determinada micro bacia, para um melhor estudo sobre a elaboração de cartas de suscetibilidades a erosão, bem como, demonstrar que através da utilização de um sistema da informação geográfica é possível realizar estudos ambientais, desenvolver novas técnicas de avaliação ambiental.
Abstract: The soil erosion is a phenomenon that has worried man in recent decades, arousing great interest to many researchers regarding the causes leading to their origin, evolution and control, because of that achieve and become unusable large areas of land, taking thus to have its forecast high importance.With the preparation of susceptibility charts to the erosion taking into account the attributes as soil, rock, slope, etc. Along with the GIS will be made the crossing of the attributes more quickly and efficiently so that it can better represent the reality of the place, thus demonstrating the potential development of erosive processes.This work will be considered the relative importance of the attributes in the physical scales with different weight given by different techniques for evaluation, equal weights, different weights according to the vision of Mauro (2001), defined different weights from other works of literature, and defined different weights based on AHP. With the establishment of susceptibility charts to the erosion, using four different techniques, it is intended to develop a systematic allocation of weights, which can be applied to other river basins. The area to be studied will be the basin of the micro Prosa located in the city of Campo Grande - Mato Grosso do Sul With the product of this research aims to provide subsidies for the implementation of other searches that might improve the environmental conditions of a particular micro basin for a better study on the establishment of suscetibilidades charts erosion, as well as to demonstrate that through the use of the information geographical system it's possible to realize environmental studies, developing new techniques for environmental estimation.
Mestre
Abdelaoui, Moustapha. "Etude de structures à jonction P+N au silicium préamorphisé au germanium à haute énergie : modélisation et caractérisation sous l'effet d'un champ magnétique continu et alternatif basse fréquence." Rouen, 2004. http://www.theses.fr/2004ROUES010.
Full textIn the context of the electromagnetic compatibility of electronic components, this thesis dealt with studying silicon high-energy germanium preamorphised P+N junctions under a pure magnetic field : either DC or low frequency. The study has been carried out using a magnetic susceptibility workbench has been set up within the laboratory. A first approach has allowed the characterisation of the studied samples without applying a magnetic field, and the implementing of a reliable Spice model for all the samples. Under a DC magnetic field, the magnetic susceptibility depends on the considered bias voltage, and then on the transport mechanisms that govern the operation of the component. In the two types of polarisation, the variation of the current increases with the magnetic field intensity. In the diffusion zone, it varies like B2. The low frequency magnetic field, in contrast with the DC magnetic field, acts primarily in the generation-recombination zone. The apparent activation energy that characterises the reverse current is strongly dependent on the frequency of the magnetic field and the technology of the samples. The presence of electrically active defects contributes to an increase of the magnetic susceptibility around detection temperatures associated to the DLTS spectra
Thompson, Cole S. "New strategies for managing dollar spot and silvery-thread moss in creeping bentgrass putting greens." Thesis, Kansas State University, 2011. http://hdl.handle.net/2097/7980.
Full textDepartment of Horticulture, Forestry, and Recreation Resources
Jack D. Fry
Dollar spot, caused by Sclerotinia homoeocarpa F.T. Bennett, and silvery-thread moss (Bryum argenteum Hedw.) are pests affecting creeping bentgrass (Agrostis stolonifera L.) that typically require pesticide inputs. New strategies for pest management may reduce chemical inputs. The objectives of these 2009-2010 field studies were to evaluate: 1) creeping bentgrass cultivars for dollar spot susceptibility; 2) alternative chemical controls for silvery-thread moss; and 3) the response of silvery-thread moss to nitrogen (N) sources. During peak dollar spot development, ‘Declaration’, ‘A-4’, and ‘Crenshaw’ had 7.5, 139.4, and 288.9 infection centers m[superscript]-2 under fairway and 2.1, 27.2, and 106.9 infection centers m[superscript]-2 under putting green conditions, respectively. Two spring and two fall spot applications of sodium or potassium bicarbonate (45 g a.i. L[superscript]-1), premixed essential oil, and broadcast applications of carfentrazone-ethyl at 0.09 kg a.i. ha[superscript]-1 suppressed moss 39% to 55% compared to untreated in 2009. Spot sprays of sodium or potassium bicarbonate, and essential oil, were phytotoxic to creeping bentgrass and required up to 8 or 18 days, respectively, to return to acceptable quality. Fertilization with liquid urea (N at 16.3 kg ha[superscript]-1 biweekly, 210 kg ha[superscript]-1 annually) resulted in 147%, 150%, and 155% more moss than fertilization with IBDU, organic N, and granular urea, respectively, and 156% more moss compared to untreated. Fertilization with urea (liquid or granular) resulted in the best creeping bentgrass color. Averaged across the entire season, plots treated with organic N had unacceptable color in 2009. Nitrogen concentrations in moss tissue ranged from 0.4% to 1.0% and were always significantly lower than N concentrations observed in creeping bentgrass (1.1% to 2.1%), regardless of treatment. In 2010, moss treated with liquid urea had higher tissue N concentrations (1.0%) than untreated moss (0.5%) or that fertilized with IBDU (0.4%). In summary, use of dollar spot-resistant creeping bentgrass cultivars could reduce fungicide requirements. Bicarbonate and essential oil products can reduce moss severity at a similar level to carfentrazone-ethyl, but rates and/or application methods need to be optimized to avoid injury to creeping bentgrass. Applications of liquid urea enhanced moss coverage in creeping bentgrass compared to other N sources.
Trigui, Mounir. "Etude des susceptibilités magnétiques en champ alternatif et continu de carottes de la croûte océanique en vue de l'interprétation des diagraphies électromagnétiques et magnétiques." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37610371x.
Full textBozec, Xavier. "Etude par traces de cycles d'hysteresis sous champ alternatif de la dynamique de vortex dans les supraconducteurs YBaCuO et BiSrCaCuO monocristallins et dans la céramique YSmBaCuO." Toulouse, INSA, 1992. http://www.theses.fr/1992ISAT0013.
Full textPatterson, Steve. "ALTERNATING SSFP PERMITS RAPID, BANDING-ARTIFACT-FREE BALANCED SSFP FMRI." 2013. http://hdl.handle.net/10222/40672.
Full textKao, Chao-Hsiung, and 高照雄. "Single frequency Alternating Current magnetic susceptibility Reduction for assaying biomolecule C-reactive protein." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/81466136965045666347.
Full text陳俊言. "Single Frequency Alternating Current Magnetic Susceptibility Reduction for Assaying Biomolecule C-Reactive Protein." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/12322603211776504310.
Full textNaicker, Dshanta Dyanedi. "Effects and mechanisms of interleukin-10 promoter polymorphisms on HIV-1 susceptibility and pathogenesis." Thesis, 2012. http://hdl.handle.net/10413/9957.
Full textThesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.
Healy, Jasmine. "Alternative strategies for deciphering the genetic architecture of childhood Pre-B acute lymphoblastic leukemia." Thèse, 2010. http://hdl.handle.net/1866/4665.
Full textChildhood acute lymphoblastic leukemia (ALL) is a complex and heterogeneous genetic disease. Although it is the most common pediatric cancer, its etiology remains poorly understood. Previous studies provided evidence that childhood ALL might originate through the collective contribution of different genes controlling the efficiency of carcinogen metabolism, the capacity of maintaining DNA integrity and the response to oxidative stress, as well as environmental factors. In my doctoral research project I attempted to further dissect the genetic intricacies underlying childhood ALL. I postulated that a child’s susceptibility to ALL may be influenced, in part, by functional sequence variation in genes encoding components of two core biologic pathways: G1/S cell cycle control and DNA double-strand break repair. Using a unique two-tiered study design consisting of both unrelated ALL cases and healthy controls, as well as case-parent trios, I performed a pathway-based candidate-gene association study to investigate the role of sequence variants in the promoter regions of 12 candidate cell cycle genes and 7 DNA repair genes, in modulating ALL risk among children. Polymorphisms in promoter regions (pSNPs) could perturb transcription factor binding and lead to differences in gene expression levels that in turn could modify the risk of disease. To better depict the complex genetic architecture of childhood ALL, I used multiple analytical approaches. First, individual genes/variants were tested for association with disease, while functional in vitro validation was performed to evaluate the impact of the pSNPs on differential transcription factor binding and allele-specific promoter activity. These analyses led to four published articles. Given that these genes are not likely to act alone to confer disease risk I used an integrative approach to explore the possibility that combinations of functionally relevant pSNPs among several components of the same or of interconnected pathways, could contribute to modified childhood ALL risk either through pathway-specific or epistatic effects; this work was recently submitted for publication. Finally, childhood ALL is thought to arise in utero suggesting that the parents, and in particular the mother, may play an important role in shaping disease susceptibility in their offspring. Using simulations, I investigated the performance of existing methods to test for maternal genotype associations using a case-parent trio/case-control hybrid design, and then assessed the impact of maternally-mediated genetic effects on ALL susceptibility among children. This published work was the first to show that the mother’s genotype can indeed influence the risk of leukemia in children, further corroborating the importance of considering parentally-mediated effects in the study of early-onset diseases. In conclusion, my doctoral work lead to the identification of novel genetic susceptibility loci for childhood ALL and provided evidence for the implication of the cell cycle control and DNA repair pathways in leukemogenesis. Better elucidation of the genetic mechanisms underlying the pathogenesis of ALL in children could be of great diagnostic value and provide data to help guide risk-directed therapy and improve disease management and outcome. Ultimately, this study brings us one step closer to unraveling the genetic architecture of childhood ALL and provides a stepping-stone towards disease prevention.