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1

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.

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Les cristaux de phases supraconductrices de formulation générale, TlmBa2Can-1CunO2n+m+2 (avec m=1, 2 et n=1, 2, 3) ont été préparés par une technique de croissance en flux. Chaque phase a été caractérisée par diffraction X (Weissenberg, Buerger, cristal tournant) et par micro-spectroscopie Raman. L'analyse par microsonde électronique a révélé des déficits cationiques par rapport a la formulation idéale. Une étude par HREM a montré dans la plupart des cristaux l'absence d'intercroissance à l'échelle atomique. La température critique a été mise en évidence par mesures électriques, mesures sous champ magnétique continu et susceptibilite alternative. Le comportement magnétique révèle une très forte anisotropie entre les propriétés supraconductrices dans la direction de l'axe c et dans le plan (a, b) (Hc1(c)/Hc1(a,b)=1000 pour la phase 2212). Les courbes d'effet Meissner et d'effet d'écran révèle que l'aimantation est réversible près de Tc et irréversible a plus basse température. La ligne d'irréversibilite (H*, T*) a été caractérisée pour la phase 2212.
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2

Nganga, 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.

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Des monocristaux de YBa2Cu3O7 ont été préparés par une méhode de flux en creuset d'or. Une analyse des spirales de croissance et des domaines ferroélastiques révélés par une étude en microscopie optique en lumière polarisée et en microscopie électronique a balayage sur la face principale (001) à été effectuée. Un ensemble de caractérisations physico-chimiques (diffraction X, EPMA, détermination de la température critique par mesures électriques, spectroscopie micro-Raman, mesures des susceptibilités alternatives en champ faible) réalisé sur des cristaux bruts de croissance et recuits sous oxygène à permis de relier l'évolution des propriétés supraconductrices à la non stoechiométrie en oxygène. Enfin le phénomène de dégradation atmosphérique de YBa2Cu3O7 à été confirmé par une étude sur monocristal, à l'aide des techniques spectroscopiques (micro-Raman, Auger, XPS)
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3

Zaharieva, 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/.

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Alternative splicing occurs in more than 90% of human genes and is particularly abundant in the nervous system. It has been recognized that toxicity can be caused at the level of pre-mRNA processing and potentially lead to age-dependent neurodegeneration upon low-dose chronic exposure. ELAV (Embryonic Lethal Abnormal Visual system)/Hu family proteins are prototype RNA binding protein and gene specific regulators of alternative mRNA splicing in the nervous system. Analysis of mutants in ELAV family proteins shows overlapping and distinct functions during development and age-dependent neurodegeneration. Overexpression of ELAV family proteins further revealed that cytoplasmic localization of ELAV family proteins in associated with enhanced neurotoxicity. Intriguingly all Drosophila ELAV family proteins and mammalian Hu proteins can regulate neuron-specific alternative splicing of Drosophila neuroglian gene- a known ELAV target. The blood brain barrier (BBB) and efficient excretion are protective mechanisms making delivery of many drugs to the brain difficult in vivo. Therefore, I analyzed the roles of a number of key Organic Anion Transporter Protein (OATP) and Multi- Drug Resistance (MDR) proteins and established a sensitized genetic background for CNS drug delivery. To assess if xenobiotics can interfere with ELAV function leading to neurodevelopmental/neurodegenerative defects, I assessed ELAV regulation of its major target erect wing (ewg) using an ewg fluorescent reporter, which recapitulates endogenous ELAV-mediated splicing and allows rapid visualization of potential modulators. From a compound screen in a sensitized genetic background, I identified a number of xenobiotics that cause changes in ewg splicing, indicating interference with ELAV function. Importantly, these compounds also phenocopy specific characteristics of ELAV mutants. My approach demonstrates the potential for using Drosophila in drug screening and neurotoxicity assessments.
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4

Brinis, Drifa. "Dynamique d'aimantation dans les assemblées d'agrégats ferromagnétiques : effets des interactions." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR049/document.

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Dans notre travail, nous avons utilisé la technique Monte Carlo afin de simuler l'effet des interactions dipolaires sur le retournement de l'aimantation d'une assemblée de nanoparticules ferromagnétiques. Dans notre modèle, nous avons considéré des nanoparticules à anisotropie uniaxiale, plus précisément le Cobalt. Avec la condition KV/kBT >> 1, le moment magnétique de chaque nanoparticule est figé dans ses positions d'équilibre et il ne peut pas fluctuer autour. Nous avons choisi de faire notre étude par le biais de la susceptibilité alternative car elle apporte l'avantage de pouvoir faire l'étude sur une large gamme de fréquences sans avoir à changer de technique de mesure puisque le temps de mesure est égale à l'inverse de la fréquence du champ appliqué. Nous avons étudié douze types d'assemblées chacune diffère de l'autre soit par sa forme, la distribution spatiale des nanoparticules ou la distribution des axes d'anisotropie. Et nous avons discerné l'influence de chaque paramètre sur l'effet des interactions dipolaires sur le retournement de l'aimantation
In 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
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5

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.

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Wheat streak mosaic virus (WSMV), endemic in small grains production areas of the Great Plains, causes yield losses of wheat 2 to 5% annually. Yield loss in individual fields can reach 100%. Control relies on cultural practices to control the vector, the wheat curl mite (Aceria tosichella Keifer, WCM), and the use of resistant or tolerant varieties. WSMV and WCM depend on living tissue for survival and reproduction, including common grassy weeds. Little is known about the relative importance of these weeds as alternative hosts of WSMV. The purpose of these studies was to evaluate the risk of infection with WSMV in commonly grown wheat varieties and various grassy weed species, information useful to understanding WSMV epidemiology and control. Winter wheat, spring wheat and barley varieties in Montana were evaluated in the field by measuring the effect of fall vs. spring inoculation and variety on incidence, symptom severity, and yield components. Winter wheat varieties from five states, and spring wheat and barley varieties from Montana were tested for incidence and absorbance in greenhouse. Fall-inoculated winter wheat had less effect of WSMV inoculation compared to spring-inoculated winter wheat. Yields of spring wheat varieties were largely reduced by WSMV inoculation. There was no correlation between yield and incidence or symptom severity. In greenhouse studies, the highest incidence was observed in varieties from Idaho and Nebraska, whereas the highest relative absorbance was observed in varieties from Montana. In 2008 and 2009, surveys of common grassy weeds were conducted. Grass species from croplands in six states were selected and mechanically inoculated to determine the susceptibility to WSMV. Grassy weeds were also evaluated as a source of WSMV by measuring transmission efficiency with virulifeous WCM. Bromus tectorum was the most prevalent grassy weed and the most frequent viral host. Aegilops cylindrica, and Avena fatua had the highest incidence and relative absorbance. There were no differences in the susceptibility of grass species to WSMV by their state of origin. WCM transmission study indicated infected grass species had lower transmission efficiency than from infected wheat. These studies will benefit producers in Montana to assess their risk of WSMV based on variety selection and the presence of grassy weeds.
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6

Montesinos, 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.

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[EN] Citrus spp. (Rutaceae) are the most widely produced fruits and they are grown in over a hundred countries. During postharvest, major losses are caused by fungal diseases, that for decades have been controlled by treatments with synthetic fungicides. However, their use is continuously more restricted by distributors and supermarket chains, which lower the Maximum Residue Level (MRL) to one third of the authorized or even ban the use of certain fungicides. This has loss of efficacy of treatments and development of resistant strains of pathogens. Alternatives are necessary to substitute or combine the use of synthetic fungicides. The objective of the present work was to evaluate alternative treatments against green and blue molds, caused by Penicillium digitatum (Pers.: Fr.) Sacc. and Penicillium italicum Wehmer, respectively. Food additives and GRAS substances were tested in in vivo preliminary tests against green and blue molds. Potassium sorbate (PS) (Chapter 2) and sodium benzoate (SB) (Chapter 1) were the most effective. 60-s dips in 3% (w/v) SB above 50°C reduced by 90% green and blue mold incidence on 'Valencia' oranges after 7 days at 20°C. This treatment was also effective on 'Lanelate' oranges, 'Fino' lemons and 'Ortanique' mandarins, but not on 'Clemenules' mandarins. Heated solutions combining SB with low doses of imazalil (IMZ) were synergistic. In semi-commercial trials with 'Marisol' Clementine mandarins, the combination PS+IMZ at 20°C allowed a significant reduction of the IMZ doses still controlling green mold. A new colorimetric method that employed extraction of PS from macerated fruit, followed by reaction with 2-thiobarbituric acid (Chapter 3) showed that in oranges treated with PS and stored at 15°C, residues declined initially rapidly and later more slowly, until residues stopped declining after 6 d. A brief double-dip rinse in tap water, immediately after immersion of lemons in a 2% (w/v) PS, removed more than 90% of PS residue. Exposure at 33ºC with 15 kPa CO2 for 24 h or 30 kPa O2 for 48 h effectively controlled both green and blue molds after 7 days of incubation at 20ºC, but control of both diseases lowered after 15 days (Chapter 4). Combining PS dip treatments with gas exposure showed a synergistic effect, that maintained the efficacy of combined treatments during 15 days. In cold storage, after 14, 28, and 42 days, green mold incidence on 'Clemenules' and 'Ortanique' mandarins treated with PS dips and 30kPa O2 for 48h was reduced by 100, 96 and 68%, and 100, 97 and 79%, respectively. Again, a synergistic effect between treatments was observed (Chapter 5). Postharvest green mold and blue molds were effectively controlled by fumigation of lemons and oranges for 6 h at 22ºC with two applied dosages of 3000 ¿L L-1 of ammonia that was injected initially and again 2 h later (Chapter 6). Ammonia fumigation controlled an IMZ-resistant isolate of P. digitatum. When fruit were first immersed in 10 or 30 mg L-1 IMZ (about 10% of typical commercial rates) before ammonia fumigation, a single fumigation with 1500 ¿L L-1 of ammonia was adequate to control both diseases and the increase in effectiveness was additive or synergistic. All these treatments, at different degrees, could replace synthetic fungicides or augment IMZ performance in citrus postharvest decay management. The development of green and blue molds on the most commercially important citrus species and cultivars was assessed for four consecutive harvest seasons and associated with fruit quality parameters (Chapter 7). Fruit susceptibility of the cultivars to green mold in increasing order was Nova, Sanguinelli, Ortanique, Lanelate, Navelate, Fortune, Clemenules, Valencia, W. Navel, Oronules, Clemenpons, Marisol, Salustiana, Hernandina, and Nadorcott. Peel characteristics were the most influencing quality parameters on the susceptibility of citrus fruit to green and blue molds.
[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
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7

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.

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8

Sagne, 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.

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Le gène TP53 est extrêmement polymorphique avec 85 polymorphismes décrits. Certains de ces polymorphismes sont associés à une augmentation du risque de cancer, par exemple rs10425222 peut moduler les fonctions de p53. Cependant, pour d’autres, comme le rs17878362 qui est le polymorphisme intronique le plus étudié, leur association avec une augmentation du riques au cancer est controversée.Pour analyser l’association entre le polymorphisme rs17878362 et la susceptibilité au cancer, nous avons analysé son rôle dans des contextes de cancers sporadiques et familiaux. Les résultats obtenus pour le polymorphisme rs17878362 sont paradoxaux avec une augmentation des cancers sporadiques associée avec le génotype A2A2 alors que l’allèle A2 est associé avec un effet « protectif » chez les patients atteints du syndrome de Li-Fraumeni porteurs d’une mutation germinale de TP53 situé sur l’haplotype A1. Ces observations suggèrent que des haplotypes spécifiques de TP53 pourraient moduler les capacités suppressives de p53. Une hypothèse possible est que les différents haplotypes de TP53 présenteraienrt des mutations somatiques à des fréquences différentes dans la population.De plus, le gène TP53 exprime différentes isoformes, comme le D40p53, inhibant l’activité suppressive de p53. Le D40p53 peut être produite par le maintien de l’intron 2 par épissage alternatif. Nous avons montré que les G-quadruplexes, des structures tridimensionnelles formées dans des régions riches en G, sont formés dans l’intron 3 et régulent la rétention de l’intron 2 et la formation du transcrit p53I2. Nous avons aussi observé que le polymorphisme rs1652785 (localisé dans l’intron 2) semble réguler la stabilité du p53I2. Ces résultats suggèrent que les polymorphismes de TP53 localisés dans une région de 412 pb située entre l’exon 2 et l’exon 4 régulent l’expression des isoformes de p53 dans une séquence temporelle d’évènements en modulant la formation des pré-ARNm (rs17878362), la stabilité des ARNm (rs1642785) et les fonctions protéiques (rs10425222).L’expression des isoformes de p53 est donc finement régulée par des mécanismes impliquant les polymorphismes de TP53 qui sont aussi associés avec une altération dans la susceptibilité au cancer
The 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
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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.

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10

Sena, 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.

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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.
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.
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11

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.

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Orientador: José Augusto de Lollo
Banca: 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
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12

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.

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Dans le contexte des préoccupations actuelles concernant les problèmes de compatibilité électromagnétique des composants électroniques, cette thèse a été consacrée à l'étude de jonctions P+N au silicium préamorphisées au germanium à haute énergie soumises à l'influence d'un champ magnétique pur continu ou alternatif basse fréquence grâce à un banc de mesure de susceptibilité magnétique mis au point au laboratoire. Une première approche expérimentale a permis la caractérisation des jonctions étudiées en absence de champ magnétique et le développement à l'aide du logiciel Spice d'un modèle électrique fiable pour tous les échantillons. Sous champ magnétique continu, la susceptibilité magnétique dépend de la polarisation considérée et donc des mécanismes de transport régissant le fonctionnement du composant. Dans les deux cas de polarisation, la variation du courant augmente avec l'intensité du champ magnétique. Dans la région de diffusion, elle varie comme B2. Le champ magnétique alternatif, à la différence du champ magnétique continu, agit essentiellement dans la zone de génération-recombinaison. L'énergie d'activation apparente caractérisant le courant inverse est fortement dépendante de la fréquence du champ magnétique ainsi que de la technologie de fabrication des échantillons. La présence de défauts électriquement actifs contribue à une augmentation de la susceptibilité magnétique autour des températures de détection associées aux spectres DLTS des échantillons
In 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
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13

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.

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Master of Science
Department 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.
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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.

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15

Bozec, 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.

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Les phenomenes lies a l'ancrage des lignes de flux (vortex), constituent des problemes de grande importance pour les applications futures des supraconducteurs a haute temperature critique; un fort piegeage etant associe a des densites de courant critique elevees. Le travail que nous presentons sur la dynamique de vortex est en etroite relation avec ces mecanismes de piegeage. Nous etudierons dans ce memoire, les differents modeles regissant la dynamique de vortex qui peuvent intervenir dans des monocristaux d'ybacuo et de bisrcacuo ainsi que dans une ceramique ysmbacuo. Le trace de cycles d'hysteresis sous champ alternatif en fonction de la frequence et l'amplitude du champ va constituer le support experimental de notre etude. L'analyse de ces cycles etablira que les modeles de relaxation d'aimantation thermiquement activee expliquent correctement les resultats obtenus sur les cristaux d'ybacuo, permettant de mesurer des energies d'ancrage. Par contre, du fait d'une anisotropie plus prononcee et d'une chute de la densite de courant critique a haute temperature, nous mettrons en evidence dans les composes bisrcacuo, une dynamique de vortex gouvernee principalement par des forces de viscosite
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16

Patterson, Steve. "ALTERNATING SSFP PERMITS RAPID, BANDING-ARTIFACT-FREE BALANCED SSFP FMRI." 2013. http://hdl.handle.net/10222/40672.

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Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is the dominant tool used for mapping human brain function because it is non-invasive, does not use ionizing radiation, and offers relatively high spatial and temporal resolution compared to other neuroimaging techniques. Unfortunately, conventional fMRI techniques cannot map brain function in the inferior temporal cortex (ITC) and orbitofrontal cortex (OFC). These brain regions experience severe magnetic field distortions due to magnetic susceptibility mismatch with the neighboring air-filled ear-canals (ITC) or sinus cavities (OFC), causing loss of the fMRI signal. Functional imaging capability is important for gaining a better understanding of these brain regions and the diseases that commonly affect them (Alzheimer’s disease and epilepsy (ITC), Parkinson’s disease and schizophrenia (OFC)). Balanced steady state free precession (balanced SSFP) is a relatively new fMRI technique that can measure function in all brain regions. Rather than diffuse signal loss, balanced SSFP images exhibit signal loss in spatially periodic, narrow bands. Banding artifacts cannot be eliminated in a single scan, but the phase of the banding artifacts can be controlled by the experimenter, permitting the combination of two antiphase balanced SSFP images to produce a single image free of banding artifacts. Unfortunately, image-corrupting transient signal oscillations limit the rate at which the banding artifact phase can be modified, such that the banding-artifact-free image acquisition rate is prohibitively slow for most clinical and neuroscience applications. This work describes the development of a modified balanced SSFP fMRI technique, alternating SSFP, which permits rapid, banding-artifact-free balanced SSFP fMRI. Theoretical modeling was used to find a rapid transition between antiphase balanced SSFP images with minimal transient signal oscillations. Monte Carlo simulations were used to optimize alternating SSFP acquisition parameters for BOLD sensitivity, with comparison to established balanced SSFP acquisitions. Rat fMRI was used to confirm these predictions. Finally, the ability of alternating SSFP to provide rapid, banding-artifact-free balanced SSFP fMRI in humans at 4 T was demonstrated.
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17

Kao, 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.

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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.

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19

Naicker, Dshanta Dyanedi. "Effects and mechanisms of interleukin-10 promoter polymorphisms on HIV-1 susceptibility and pathogenesis." Thesis, 2012. http://hdl.handle.net/10413/9957.

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HIV infection has risen to pandemic proportions. Interleukin-10 (IL-10), a potent antiinflammatory cytokine has been shown to enhance the establishment and persistence of chronic viral infections through inactivation of effector antiviral immune responses and it may also directly influence HIV-1 replication in cells of diverse lineages. IL-10 promoter polymorphisms have been shown to affect HIV-1 susceptibility and pathogenesis. However, the underlying mechanisms are poorly understood. We investigated the relationship between IL-10 promoter variants, plasma IL-10 levels, and markers of disease outcome in chronically HIV-1-infected individuals. To investigate the mechanistic role of IL-10 and its genetic variants on HIV pathogenesis, we studied markers of activation on B cells, CD4+ and CD8+ T cells, and assessed effects on CD4+ T cell proliferation with and without blockade of the IL- 10 pathway. We used Taqman genotyping assays to genotype three IL-10 promoter single nucleotide polymorphisms (SNPs) in our study cohort. Baseline plasma IL-10 levels were measured using Luminex technology for 112 individuals. Viral load, CD4+ T cell counts and cytotoxic T lymphocyte (CTL) immune responses were measured at baseline. The rate of CD4+ T cell decrease was calculated in 300 individuals with a median follow-up of 25 months. CD38, CD95, Ki67, IgG and PD-1, markers of activation or exhaustion were measured on B cells, and CD38, CD95, Ki67, HLA-DR and PD-1 were measured on CD4+ and CD8+ T cells in a subset of 63 individuals. CD4+ T cell proliferation was measured using Carboxyfluorescein succinimidyl ester (CFSE) assays, following IL-10 receptor blockade in a subset of 31 individuals. The IL-10 -1082G, -592A and -3575 variants were observed at frequencies of 0.3, 0.34 and 0.23 respectively, in our study cohort. Plasma IL-10 levels were significantly higher in the - 1082GG group than in the combined AA/AG group (p=0.0006). There was a significant association between the 592AA genotype and a greater breadth of CTL responses compared to the CC and CA (p= 0.002 and 0.004 respectively). The -592AA genotype associated significantly with an attenuated loss of CD4 cells (p= 0.0496), with -592AA having the least change in CD4 cells per year. The median expression of HLA-DR, a marker of T cell activation was significantly higher in the-1082AA group for CD8 cells (p= 0.047), and the - 592AA group for CD4 T cells (p= 0.01). The median expression of IgG on the surface of B cells was significantly higher in the -1082GG genotype and the -592CC genotype (p=0.0183 and 0.0659 respectively). Overall, IL-10 variants correlated with IL-10 expression and CD4 decline during chronic HIV-1 infection. IL-10 promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels, which in-turn, may affect the breadth of CTL responses. Furthermore, the increased expression of HLA-DR and PD-1 on CD8+ and CD4+ T cells, indicates that lower IL-10 levels are associated with increased immune activation and immune exhaustion. The increased expression of IgG on B cells, suggests that in a setting of lower IL-10, there is possibly a bias towards a Th2 immune response. These data suggest a significant role for IL-10 genetic variants and IL-10 in HIV pathogenesis. Further studies to determine whether and how the IL-10 pathway may be manipulated for therapeutic or vaccine strategies for HIV are warranted.
Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.
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20

Healy, Jasmine. "Alternative strategies for deciphering the genetic architecture of childhood Pre-B acute lymphoblastic leukemia." Thèse, 2010. http://hdl.handle.net/1866/4665.

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La leucémie lymphoblastique aigüe (LLA) est une maladie génétique complexe. Malgré que cette maladie hématologique soit le cancer pédiatrique le plus fréquent, ses causes demeurent inconnues. Des études antérieures ont démontrées que le risque à la LLA chez l’enfant pourrait être influencé par des gènes agissant dans le métabolisme des xénobiotiques, dans le maintient de l’intégrité génomique et dans la réponse au stress oxydatif, ainsi que par des facteurs environnementaux. Au cours de mes études doctorales, j’ai tenté de disséquer davantage les bases génétiques de la LLA de l’enfant en postulant que la susceptibilité à cette maladie serait modulée, au moins en partie, par des variants génétiques agissant dans deux voies biologiques fondamentales : le point de contrôle G1/S du cycle cellulaire et la réparation des cassures double-brin de l’ADN. En utilisant une approche unique reposant sur l’analyse d’une cohorte cas-contrôles jumelée à une cohorte de trios enfants-parents, j’ai effectué une étude d’association de type gènes/voies biologiques candidats. Ainsi, j’ai évaluer le rôle de variants provenant de la séquence promotrice de 12 gènes du cycle cellulaire et de 7 gènes de la voie de réparation de l’ADN, dans la susceptibilité à la LLA. De tels polymorphismes dans la région promotrice (pSNPs) pourraient perturber la liaison de facteurs de transcription et mener à des différences dans les niveaux d’expression des gènes pouvant influencer le risque à la maladie. En combinant différentes méthodes analytiques, j’ai évalué le rôle de différents mécanismes génétiques dans le développement de la LLA chez l’enfant. J’ai tout d’abord étudié les associations avec gènes/variants indépendants, et des essaies fonctionnels ont été effectués afin d’évaluer l’impact des pSNPs sur la liaison de facteurs de transcription et l’activité promotrice allèle-spécifique. Ces analyses ont mené à quatre publications. Il est peu probable que ces gènes de susceptibilité agissent seuls; j’ai donc utilisé une approche intégrative afin d’explorer la possibilité que plusieurs variants d’une même voie biologique ou de voies connexes puissent moduler le risque de la maladie; ces travaux ont été soumis pour publication. En outre, le développement précoce de la LLA, voir même in utero, suggère que les parents, et plus particulièrement la mère, pourraient jouer un rôle important dans le développement de cette maladie chez l’enfant. Dans une étude par simulations, j’ai évalué la performance des méthodes d’analyse existantes de détecter des effets fœto-maternels sous un design hybride trios/cas-contrôles. J’ai également investigué l’impact des effets génétiques agissant via la mère sur la susceptibilité à la LLA. Cette étude, récemment publiée, fût la première à démontrer que le risque de la leucémie chez l’enfant peut être modulé par le génotype de sa mère. En conclusions, mes études doctorales ont permis d’identifier des nouveaux gènes de susceptibilité pour la LLA pédiatrique et de mettre en évidence le rôle du cycle cellulaire et de la voie de la réparation de l’ADN dans la leucémogenèse. À terme, ces travaux permettront de mieux comprendre les bases génétiques de la LLA, et conduiront au développement d’outils cliniques qui amélioreront la détection, le diagnostique et le traitement de la leucémie chez l’enfant.
Childhood 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.
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