O câncer de mama é a neoplasia mais comum entre as mulheres. Sua etiologia é complexa, onde tanto fatores ambientais como genéticos podem contribuir para o desenvolvimento tumoral. Estima-se que 5 a 10% dos casos de carcinomas de mama sejam representados pelos carcinomas de mama familial e 90 a 95% sejam representados pelos carcinomas de mama esporádicos. Independente da etiologia, um dos principais agravantes é consequência da habilidade das células tumorais metastizar. Mutações podem levar a mudança ou perda de expressão de diferentes genes e isto possibilita que as células adquiram particularidades genéticas e fenotípicas que contribuem para a progressão do tumor através da aquisição de vantagens que medeiam a sua sobrevivência. Dentre estas vantagens adquiridas está a capacidade das células tumorais de escaparem da destruição pelas células imunológicas ou, até mesmo, utilizarem estas células a seu favor, na promoção de um microambiente tumoral inflamatório que pode auxiliar o desenvolvimento da angiogênese que posteriormente facilitará a metástase. As características dos carcinomas de mama são as principais ferramentas para avaliação do diagnóstico e prognóstico da doença. Portanto, o objetivo de nosso trabalho foi a análise de quatro variantes polimórficas de genes que codificam importantes moléculas do sistema imunológico, duas relacionadas aos genes que codificam os receptores de quimiocinas, CCR2 e CCR5, e duas relacionadas ao gene HLA-G em 188 mulheres com carcinoma de mama (105 com câncer de mama familial e 83 com câncer de mama esporádico) e em 151 mulheres sem carcinoma e sem história familiar de câncer (grupo controle), como possíveis marcadores de diagnóstico e prognóstico do carcinoma de mama. Para a análise da variante do CCR2, denominada CCR264I, e para a análise de uma das variantes que codifica a molécula de HLA-G, denominada +3142, utilizou-se a técnica PCR-RFLP. Para a análise da variante do gene CCR5, denominada CCR5delta32 e para a análise da outra variante do HLA-G, caracterizada pela inserção de 14pb na região 3’UTR do gene, utilizou-se a técnica PCR. As frequências alélicas, genotípicas e haplotípicas foram estimadas e comparadas entre os grupos de mulheres, usando o Teste Qui-Quadrado ou o Teste Exato de Fisher e, posteriormente, foram relacionadas a fatores de diagnóstico e prognóstico. Observou-se maiores frequências dos alelos selvagens do CCR2, Val (p=0,040, OR 0,61, IC 95% = 0,38 – 0,98) e do CCR5, Wt (p=0,032, OR 0,46, IC 95% = 0,23 – 0,94) e maior frequência do haplótipo duplo selvagem Wt/Val destas mesmas variantes gênicas dos genes CCR2 e CCR5, nas mulheres do grupo controle (p=0,030) em relação às mulheres com câncer de mama familial. Quando as variantes foram avaliadas em conjunto com os parâmetros clínicos, observou-se que as mulheres com carcinoma de mama esporádico apresentavam a doença em idade mais elevada (57,29 ± 8,457 anos e 44,23 ± 12,092 anos para mulheres com câncer de mama esporádico e familial, respectivamente, p < 0.001) e de forma mais agressiva, com maior frequência dos carcinomas invasores (p = 0,001) que as mulheres com carcinoma de mama familial. Além disso, as variantes de inserção/deleção de 14 pb do HLA-G e CCR264I, mostraram relação positiva com a agressividade tumoral nestas mulheres (p = 0,039 e p = 0,005). Nossos dados sugerem que os carcinomas invasores possam estar relacionados a uma maior infiltração de células imunológicas e com o aumento da inflamação no microambiente tumoral, mediados pelo receptor CCR2 e pela molécula HLA-G, respectivamente. / Breast cancer is the most common cancer among women. Its etiology is complex, where genetic, environmental and endocrine factors contribute to tumor development. It is estimated that 5 to 10% of the breast cancers are represented by familial breast cancers and 90 to 95% are represented by sporadic breast cancers. Independent of the etiology, the major aggravating consequence is the ability of tumor cells to metastasize. Mutations can lead to a change or loss of expression a different genes and this allows the appearance of genetic and phenotypic features which contribute to tumor progression. Among these features is the ability of tumor cells to evade from the immune cells or even use immune cells in the promotion of a inflammatory microenvironment promotion which may help angiogenesis and, later, metastasis. The aim of our study was to evaluate four important polymorphic variants of genes which encode important immune system molecules, two related genes encoding chemokine receptors, CCR2 and CCR5, and two related to HLA-G gene in 188 women with breast cancer (105 women with familial breast cancer and 83 with sporadic breast cancer) and 151 women without cancer and family history of cancer (control group), such as potential markers for diagnosis and prognosis of breast cancer. CCR2 polymorphism, CCR264I, and one HLA-G polymorphism, +3142, were genotyped by PCR-RFLP. CCR5delta32 and 14pb HLA-G polymorphism were genotyped by PCR. Allelic, genotypic and haplotypic frequencies were estimated and compared between the groups using the Chi-square test or Fisher's exact test and subsequently were associated to diagnostic and prognostic factors. We observed a higher allelic frequency of the CCR2 wild type allele, Val (p = 0.040, OR 0.61, 95% CI = 0.38 - 0.98) e CCR5 wild type allele, Wt (p = 0.032, OR 0.46, CI 95% = 0.23 - 0.94) and higher haplotype frequency of the double wild type variants (Wt/Val) of these same genes (CCR2 and CCR5) in women in the control group (p = 0.030) compared to women with familial breast cancer. All polymorphisms were evaluated together with the clinical parameters and it was observed that women with breast cancer showed sporadic cancer latter (57.29 ± 8.457 years and 44.23 ± 12.092 years for women with sporadic breast cancer and familial breast cancer, respectively, p < 0.001) and more invasiveness (p = 0.001) as compared to women with familial breast cancer. Moreover, the HLA-G 14pb and CCR264I polymorphism, showed a positive association with tumor aggressiveness in women with sporadic breast cancer (p = 0.039 and p = 0.005, respectively). Our data suggest that invasive cancers may be associated with increased immune cells infiltration and inflammation in the tumor microenvironment mediated by both CCR2 receptor and HLA-G molecule.

Our aim is to calculate some graphs associated with two of the larger sporadicsimple groups, Fi₂₄ and the Baby Monster. Firstly we calculate the point line collinearity graph for a maximal 2-local geometry of Fi₂₄. If T is such a geometry, then the point line collinearity graph G will be the graph whose vertices are the points in T, with any two vertices joined by an edge if and only if they are incident with a common line. We found that the graph has diameter 5 and we give its collapsed adjacency matrix. We also calculate part of the commuting involution graph, C, for the class 2C of the Baby Monster, whose vertex set is the conjugacy class 2C, with any two elements joined by an edge if and only if they commute. We have managed to place all vertices inside C whose product with a fixed vertex t does not have 2 power order, with all evidence pointing towards C having diameter 3.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13063号 / 論医博第2121号 / 新制||医||1018(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 髙橋 良輔, 教授 福原 俊一, 教授 中山 健夫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(理学) / 甲第24422号 / 理博第4921号 / 新制||理||1703(附属図書館) / 京都大学大学院理学研究科地球惑星科学専攻 / (主査)准教授 齊藤 昭則, 教授 石岡 圭一, 教授 田口 聡 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Safe and efficient traffic control remains a challenging task with the continued increase in the number of vehicles, especially in urban areas. This manuscript focuses on traffic control at intersections, since urban roads with closely spaced intersections are often prone to queue spillbacks, which disrupt traffic flows across the entire network and increase congestion. While various intelligent traffic control solutions exist for autonomous systems, they are not applicable to or ineffective against human-operated vehicles or mixed traffic. On the other hand, existing approaches to manage intersections with human-operated vehicles, cannot adequately adjust to dynamic traffic conditions. This manuscript presents a technology-agnostic adaptive real-time server based approach to dynamically determine signal timings at an intersection based on changing traffic conditions and queue lengths (i.e., wait times) to minimize, if not eliminate, spillbacks without unnecessarily increasing delays associated with intersection crossings. We also provide timeliness guarantee bounds by analyzing the travel time delays, hence making our approach more dependable and predictable. The proposed approach was validated in simulations and on a realistic hardware testbed with robots mimicking human driving behaviors. Compared to the pre-timed traffic control and an adaptive scheduling based traffic control, our algorithm is able to avoid spillbacks under highly dynamic traffic conditions and improve the average crossing delay in most cases by 10--50 %. / Master of Science / Safe and efficient traffic control remains a challenging task with the continued increase in the number of vehicles, especially in urban areas. This manuscript focuses on traffic control at intersections, since urban roads with closely spaced intersections are often prone to congestion that blocks other intersection upstream, which disrupt traffic flows across the entire network. While various intelligent traffic control solutions exist for autonomous systems, they are not applicable to or ineffective against human-operated vehicles or mixed traffic. On the other hand, existing approaches to manage intersections with human-operated vehicles, cannot adequately adjust to dynamic traffic conditions. This work presents a technologyagnostic adaptive approach to dynamically determine signal timings at an intersection based on changing traffic conditions and queue lengths (i.e., wait times) to minimize, if not eliminate, spillbacks without unnecessarily increasing delays associated with intersection crossings. We also provide theoretical bounds to guarantee the performance of our approach in terms of the travel delays that may incur on the vehicles in the system, hence making our approach more dependable and predictable. The proposed approach was validated in simulations and on a realistic hardware testbed which uses robots to mimic human driving behaviour in an urban environment. Comparisons with widely deployed and state-of-the-art traffic control techniques show that our approach is able to minimize spillbacks as well as improve on the average crossing delay in most cases.

La maladie sporadique de Creutzfeldt-Jakob (sCJD) est une encéphalopathie spongiforme transmissible mortelle caractérisée par une large gamme de manifestations cliniques et pathologiques. Les caractéristiques pathologiques de la SDMC dépendent en grande partie de la présence d'une forme mal repliée de protéine prion cellulaire (PrPC); Connu sous le nom de PrPSC et polymorphisme (méthionine et valine) au codon 129 du gène PRNP qui code pour PrPC. Les facteurs étiologiques exacts de la MCSJ sont encore inconnus. Le génotype Codon 129 du gène PRNP et le type de PrPSC (type 1 ou type 2) influent sur l'hétérogénéité de la maladie telle que définie par des caractéristiques pathologiques spécifiques de la région qui peuvent réguler les voies moléculaires qui conduisent au développement de phénotypes pathogènes dépendants des sous-types. Dans cette étude, nous avons étudié l'ensemble de la réglementation protéomique dans la région cerebrale du cerveau des deux sous-types les plus répandus (MM1 et VV2) des patients atteints de SDMC utilisant une électrophorèse sur gel bidimensionnelle (2DE) et une spectrométrie de masse. L'analyse de toutes les taches de protéines sur les gels 2DE avec le logiciel DECODON Delta2D a révélé vingt-cinq taches de protéines différenciées et l'identification de ces taches avec MALDI-TOF MS / MS a révélé quatre-vingts trois protéines différentiellement réglementées dans les deux sous-types dans la région du cervebelle du cerveau par les patients atteints de sCJD. Quarante protéines dans le sous-type MM1 et quarante-trois protéines dans le sous-type VV2 ont été classées. Douze protéines étaient communément réglementées dans les deux sous-types, dont cinq d'entre elles présentaient une régulation expresnelle inverse et le repos sept avait une régulation expresnelle similaire dans les deux sous-types. Les trois principaux mécanismes moléculaires cellulaires réglementés dans les deux sous-types comprennent: i) le cycle cellulaire; L'expression des gènes et la mort cellulaire, ii) - la réponse au stress cellulaire / le stress oxydatif et iii) - la transduction du signal et les fonctions synaptiques La plupart des protéines sous la classification des réponses au stress cellulaire étaient associées aux fonctions moléculaires cellulaires liées au stress oxydatif. DJ-1 qui est un capteur bien connu de stress oxydatif, a également été jugé réglementé dans la catégorie des réponses au stress cellulaire. Le DJ-1 protège les cellules contre le stress oxydatif directement en translocant au noyau pour l'activation de gènes antioxydants et indirectement en activant la voie Nrf2 / ARE. Nos résultats expérimentaux ont démontré l'activation de la voie Nrf2 / ARE dans les sous-types MM1 et VV2 de sCJD. Le DJ-1 a également montré une régulation positive significative dans son expression de l'ARNm dans les sous-types MM1 et VV2 mais l'expression des protéines uniquement dans le sous-type VV2 dans le cervelet du cerveau des patients atteints de sCJD. En outre, l'expression de la protéine DJ-1 a également été augmentée au cours des stades pré-symptomatiques et symptomatiques dans le cervelet du cerveau des modèles de souris de sCJD (MM1 et VV2) et pendant le stade clinique dans les échantillons de CSF des patients atteints de SDMC. Ces résultats suggèrent l'implication du stress oxydatif lors de la pathophysiologie de la SDMC et l'utilisation de DJ-1 comme capteur potentiel de stress oxydatif pendant la phase clinique de la sCJD.

[pt] Os cinco grupos de Mathieu, M24;M23;M22;M12 e M11, compõem a primeira família de grupos esporádicos do Teorema de classificacão dos grupos simples finitos. Neste trabalho apresentaremos os grupos de Mathieu e alguns objetos relacionados a construcão deles como o Código de Golay e o Sistema de Steiner. Também, no decorrer do texto, surgiram espontaneamente alguns subgrupos dos grupos de Mathieu. / [en] The five Mathieu groups, M24;M23;M22;M12 and M11, form the first family of sporadic groups of Theorem classification of finite simple groups. In this paper we present the Mathieu groups and some objects related to building them as the Golay code and the Steiner system. Also, throughout the text, arose spontaneously some subgroups of groups of Mathieu.

I will be going over writing representations of both permutation and monomial progenitors, which include 2^{*4} : D_4, 2^(*7) :L_2 (7) as permutation progenitors, and monomial progenitors 7^(*2) :_m S_3 \times 2, 11^{*2} :_m (5:2)^{*}5, 11^{*3} :_m (25:3), 11^{*4} :_m (4 : 5)^{*}5. Also, the images of these different progenitors at both lower and higher fields and orders. \\ We will also do the double coset enumeration of S5 over D6, S6 over 5 : 4, A_5 x A_5 over (5:2)^{*}5, and go on to also do the double coset enumeration over maximal subgroups for larger constructions. We will also do the construction of sporadic group M22 over maximal subgroup A7, and also J1 with the monomial representation 7^(*2) :_m S_3 \times 2 over maximal subgroup PSL(2,11). We will also look at different extension problems of composition factors of different groups, and determine the isomorphism types of each extension.

No description available.

Approximately 85% of Canadians are physically inactive. This project seeks to support physical activity (PA) as a health intervention within primary care using innovative approaches to help people access community-based PA opportunities. We hypothesize that participants will increase and maintain their moderate to vigorous PA in 10-minute bouts (MVPA10Mins) over 10-months. One-hundred-nineteen patients recruited from two primary care facilities did not change their primary outcome of MVPA10Mins from baseline to 10-months. However, secondary outcomes light and total sporadic PA increased by the 4th month and were maintained until 10-months. Furthermore, self-report data including self-efficacy, mood, and quality of life all improved by the end of the 4-month intervention. Sedentary time increased from baseline to 4-months and was sustained until 10-months. The ENCOURAGE intervention did not increase MVPA10Mins over time. However, improvements in other secondary outcomes indicate that a multilevel intervention delivered within primary care may contribute to health behavior changes.