Orientador: Dagmar Ruth Stach Machado / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-21T15:02:48Z (GMT). No. of bitstreams: 1 Bianchi_HenriquedeOliveira_M.pdf: 6836642 bytes, checksum: aae9f7b606a807a8c74a13a7677091c7 (MD5) Previous issue date: 2012 / Resumo: A doença periodontal (DP) é uma doença inflamatória crônica que acomete os tecidos que suportam o dente, podendo resultar na perda dentária. O agente etiológico da DP é a placa bacteriana que se forma junto ao dente, no entanto, é a resposta imune do hospedeiro que vai determinar a suscetibilidade ao desenvolvimento e a progressão da DP. Uma resposta imune com perfil pró inflamatório, representado por linfócitos T helper (Th) 1 e Th17, leva à progressão da DP, enquanto que com perfil antiinflamatório, representado por linfócitos Th2 e T regulatórios, não há desenvolvimento da doença. Citocinas pró-inflamatórias induzem a expressão de metaloproteinases de matriz (MMP) e inibem a expressão de seus inibidores, os inibidores teciduais de metaloproteinases de matriz (TIMP). O desequilíbrio dos níveis de MMPs/TIMPs é responsável pela degradação da matriz extracelular, presente na DP. Essa resposta pró-inflamatória também leva os desbalanço da expressão do ligante do receptor ativador do fator nuclear kappa B (RANKL) e seu inibidor, a osteoprotegerina (OPG), resultando na reabsorção do osso alveolar, o ponto chave da lesão tecidual na DP. Indivíduos obesos apresentam maior predisposição ao desenvolvimento da DP e apresentam uma maior severidade da doença. Desse modo, o presente trabalho teve como objetivo analisar a influência da obesidade nas alterações gênicas e protéicas associadas à resposta inflamatória e à destruição tecidual durante o desenvolvimento e progressão da DP induzida por ligadura em ratos. A obesidade induzida por dieta hiperlipídica (DHL) foi caracterizada por intolerância à glicose, glicemia elevada, elevado índice de Lee, alterações hepáticas, aumento do peso das gorduras viscerais, hiperinsulinemia e alterações nos níveis plasmáticos de colesterol. Animais do grupo DHL apresentaram uma maior expressão gênica e protéica de citocinas pró-inflamatórias no tecido gengival acometido pela DP. Em especial, a expressão da interleucina (IL) 17, da IL6 e do interferon gama (IFNG) foi significativamente maior em relação ao grupo alimentado com ração normolipídica. Não foram observadas diferenças muito significativas entre os dois grupos na expressão das citocinas antiinflamatórias IL4, IL10 e fator de transformação do crescimento beta (Tgfb). O grupo DHL apresentou um aumento da expressão gênica de MMPs, em especial da Mmp13, e uma diminuição na expressão de Timp1, Timp2 e Reversion Inducing Cysteine-rich Protein with Kazal Motifs (Reck). Ademais, foi observado um aumento significativo da razão Rankl/Opg no grupo DHL, acompanhado de maior reabsorção do osso alveolar. A alimentação com a dieta hiperlipídica induziu alterações metabólicas características da obesidade, que resultaram na exacerbação da resposta inflamatória no tecido gengival com DP. Essa resposta pró-inflamatória, polarizada para os perfis Th1 e Th17, levou ao desbalanço da expressão gênica das razões MMPs/TIMPs e Rankl/Opg. Por fim, a desregulação dos mediadores da destruição tecidual e de seus inibidores resultou no agravamento da DP, com aumento da reabsorção do osso alveolar. Desse modo, esse trabalho possibilitou relacionar o estado obeso à progressão da DP / Abstract: Periodontal disease (PD) is a chronic inflammatory disease that affects the tissues that support the teeth and can result in tooth loss. The etiological agent of PD is the dental plaque, which can be formed on the surface of the tooth. However, the host immune response is determinant for the susceptibility to development and progression of PD. Immune responses with a pro-inflammatory profile, represented by T helper (Th) 1 and Th17 cells, leads to PD progression, whereas an anti-inflammatory profile, represented by Th2 and T regulatory cells, is associated with no disease development. Proinflammatory cytokines induce expression of matrix metalloproteinases (MMP) and inhibit expression of their inhibitors, called tissue inhibitors of metalloproteinases (TIMP). The imbalance of MMPs/TIMPs levels is responsible for the characteristic degradation of the extracellular matrix in PD. The proinflammatory response also leads to expression imbalance of the receptor activator of nuclear factor kappa B ligand (RANKL) and its inhibitor, osteoprotegerin (OPG), resulting in alveolar bone resorption, which is the key event in tissue damage in PD. It is known that obese individuals have a higher predisposition to PD development and present a greater disease severity. Thus, the present study aimed to evaluate the influence of obesity on gene and protein changes associated with the inflammatory response and tissue destruction during the development and progression ligature-induced PD in rats. The high fat diet-induced obesity (HFD) was characterized by impaired glucose tolerance, increased blood glucose level, increased Lee index, liver alterations, increased weight of visceral fat, hyperinsulinemia and changes in plasma levels of cholesterol. Animals from HFD group showed a higher protein and gene expression of pro-inflammatory cytokines in gingival tissue affected by PD. In particular, the expression of interleukin (IL) 17, of IL6 and interferon gamma (IFNG) was significantly higher compared to the group fed a normolipidic diet. There were not much significant differences between both groups in the expression of anti-inflammatory cytokines IL4, IL10 and transforming growth factor beta (Tgfb). HFD group showed an increased MMPs gene expression, especially Mmp13, and a decrease in the expression of Timp1, Timp2 and Reversion Inducing Cysteine-rich Protein with Kazal Motifs (Reck). Moreover, we observed a significant increase in Rankl/Opg ratio in group HFD, followed by greater alveolar bone resorption. HFD induced metabolic changes that are characteristic of obesity, which resulted in exacerbation of inflammatory response in gingival tissue with PD. This pro-inflammatory response, which was polarized to Th1 and Th17 profiles, led to an imbalance in MMPs/TIMPs and Rankl/Opg gene expression ratios. Finally, the deregulation of the mediators of tissue destruction and their inhibitors resulted in worsening of PD with increased alveolar bone resorption. Therefore, this study allowed a correlation between obesity and PD progression / Mestrado / Imunologia / Mestre em Genética e Biologia Molecular

RANKL et RANK sont membres de la superfamille des TNF et de la superfamille des TNF-récepteurs, respectivement. Ils sont connus pour jouer un rôle important dans la régulation de la masse osseuse et dans le développement et la fonction du système immunitaire. Cependant des questions restent. Nous avons utilisé des souris génétiquement modifiées pour répondre à certaines de ces questions, en particulier en utilisant une souris dont les cellules stromales réticulaires marginales manquent RANKL dans les ganglions lymphatiques. Les résultats obtenus lors de cette thèse fournissent de nouvelles informations importantes sur l'impact positif de RANKL stromal sur les macrophages des ganglions lymphatiques concomitantes avec une fonction des cellules B amélioré et une pathogénicité virale réduit. Nous avons constaté que RANKL stromal régule l'expression de lymphotoxine et CXCL13, deux molécules clés de l'homéostasie des cellules B et de l'intégrité cellulaire des organes lymphoïdes secondaires. L’activité du RANKL semble suivre une hiérarchie temporelle sur lymphotoxine/TNFα, vu que le phénotype causé par le déficit en RANKL a une pénétrance augmenté avec l'âge. De plus, nous démontrons que RANKL active les cellules endotheliales lymphatiques des ganglions lymphatiques et on a trouvé que l'intégrine ITGA2b est un nouvel indicateur pour les cellules endotheliales lymphatiques activés. Ainsi, avec MAdCAM-1, ITGA2b sert comme un nouveau marqueur pour les cellules endothéliales lymphatiques qui sont constitutivement activés par le RANKL stromal. Au total, les données confirment l'importance de RANKL pour l'homéostasie des ganglions lymphatiques et dévoile les mécanismes ci-inconnus des fonctions de RANKL. À la lumière de cela et le fait que RANKL est sensible aux hormones féminines, nous avons étudié le rôle de RANKL dans le syndrome de Sjögren, une maladie inflammatoire chronique des glandes salivaires et lacrymales avec une forte polarisation de sexe féminin. Nous apportons la preuve que la neutralisation du RANKL réduit la taille des organes lymphoïdes tertiaire. En perspective, une éventuelle diaphonie entre les cellules endothéliales lymphatiques et les macrophages ou les cellules réticulaires marginales reste à clarifier. En outre, d'autres travaux sont nécessaires pour élucider le mécanisme par lequel RANKL stimule les maladies inflammatoires chroniques présentant des structures lymphoïdes tertiaires, afin de faire RANKL une nouvelle cible pour la thérapie. / RANKL and RANK are members of the TNF-superfamily and TNF-receptor superfamily, respectively. They are known to play an important role in the regulation of bone mass and in the development and the function of the immune system. However questions still remain. We have used genetically modified mice to address some of these questions, in particular by using a mouse whose lymph node marginal reticular stromal cells lack RANKL. The results obtained during this PhD provide important new insights into the positive impact of stromal RANKL on lymph node macrophages concomitant with enhanced B cell function and reduced viral pathogenicity. We found that stromal RANKL regulates lymphotoxin and CXCL13 expression, two key molecules for B cell homeostasis and secondarylymphoid organ cellular integrity. RANKL activity seems to follow a temporal hierarchy over lymphotoxin/TNFα, as the phenotype caused by stromal RANKL-deficiency has increased penetrance with age. Furthermore, we demonstrate that RANKL activates lymph node lymphatic endothelial cells and found that the integrin ITGA2b is a new indicator for activated lymphatic endothelial cells. Thus, together with MAdCAM-1, ITGA2b serves as a novel marker for those lymphatic endothelial cells that are constitutively activated by stromal RANKL. Altogether, the data reinforce the importance of RANKL for the lymph node homeostasis and uncover here to unknown mechanisms of RANKL functions.In light of this and the fact that RANKL is responsive to female hormones, we studied the role of RANKL in the Sjögrens syndrome, a chronic inflammatory disease of salivary and lacrimal glands with a strong female sex bias. We provide evidence that RANKL neutralization reduces tertiary lymphoid organ size. On the perspective side, a possible cross talk between lymph node lymphatic endothelial cells and macrophages or marginal reticular cells remains to be clarified.Furthermore, further work is required to elucidate the mechanism by which RANKL stimulates chronic inflammatory diseases presenting tertiary lymphoid structures, in order to make RANKL a new target for therapy.

Let Q(√(-d)) be an imaginary quadratic field with discriminant Δ. We use the isomorphism between the ideal class groups of the field and the equivalence classes of binary quadratic forms to find the structure of the class group. We determine the structure by combining two of Shanks' algorithms [7, 8]. We utilize this method to find fields with cyclic factors that have order a large power of 2, or fields with class groups of high 5-ranks or high 7-ranks. / Master of Science

<p>The question about how to determine the rank of a tensor has been widely studied in the literature. However the analytical methods to compute the decomposition of tensors have not been so much developed even for low-rank tensors.</p><p>In this report we present analytical methods for finding real and complex PARAFAC decompositions of 2 x 2 x 2 tensors before computing the actual rank of the tensor.</p><p>These methods are also implemented in MATLAB.</p><p>We also consider the question of how best lower-rank approximation gives rise to problems of degeneracy, and give some analytical explanations for these issues.</p>

The question about how to determine the rank of a tensor has been widely studied in the literature. However the analytical methods to compute the decomposition of tensors have not been so much developed even for low-rank tensors. In this report we present analytical methods for finding real and complex PARAFAC decompositions of 2 x 2 x 2 tensors before computing the actual rank of the tensor. These methods are also implemented in MATLAB. We also consider the question of how best lower-rank approximation gives rise to problems of degeneracy, and give some analytical explanations for these issues.

This master's thesis addresses numerical methods of computing the typical ranks of tensors over the real numbers and explores some properties of tensors over finite fields. We present three numerical methods to compute typical tensor rank. Two of these have already been published and can be used to calculate the lowest typical ranks of tensors and an approximate percentage of how many tensors have the lowest typical ranks (for some tensor formats), respectively. The third method was developed by the authors with the intent to be able to discern if there is more than one typical rank. Some results from the method are presented but are inconclusive. In the area of tensors over nite filds some new results are shown, namely that there are eight GLq(2) GLq(2) GLq(2)-orbits of 2 2 2 tensors over any finite field and that some tensors over Fq have lower rank when considered as tensors over Fq2 . Furthermore, it is shown that some symmetric tensors over F2 do not have a symmetric rank and that there are tensors over some other finite fields which have a larger symmetric rank than rank.

Low rank approximation is the problem of finding two low rank factors W and H such that the rank(WH) << rank(A) and A ≈ WH. These low rank factors W and H can be constrained for meaningful physical interpretation and referred as Constrained Low Rank Approximation (CLRA). Like most of the constrained optimization problem, performing CLRA can be computationally expensive than its unconstrained counterpart. A widely used CLRA is the Non-negative Matrix Factorization (NMF) which enforces non-negativity constraints in each of its low rank factors W and H. In this thesis, I focus on scalable/distributed CLRA algorithms for constraints such as boundedness and non-negativity for large real world matrices that includes text, High Definition (HD) video, social networks and recommender systems. First, I begin with the Bounded Matrix Low Rank Approximation (BMA) which imposes a lower and an upper bound on every element of the lower rank matrix. BMA is more challenging than NMF as it imposes bounds on the product WH rather than on each of the low rank factors W and H. For very large input matrices, we extend our BMA algorithm to Block BMA that can scale to a large number of processors. In applications, such as HD video, where the input matrix to be factored is extremely large, distributed computation is inevitable and the network communication becomes a major performance bottleneck. Towards this end, we propose a novel distributed Communication Avoiding NMF (CANMF) algorithm that communicates only the right low rank factor to its neighboring machine. Finally, a general distributed HPC- NMF framework that uses HPC techniques in communication intensive NMF operations and suitable for broader class of NMF algorithms.

Today more and more people buy second-hand products on internet. As the typical durable goods, second-hand cars are very popular among consumers. In recent years, the sale of second-hand cars increases quickly in China. In addition, there is still potential in the second-hand market. On the other hand, consumers are the subject in the second-hand market. So what consumers take into consideration is important when buying second-hand cars. We have chosen some social factors that influence consumers’ decision when they purchase second-hand cars. Furthermore, we have analyzed the importance of these social factors and the relationship between factors.The purpose of this study is to give vehicle dealers a guide how consumers with different characteristics will pay attention to different factors of the cars but also to guide consumers to make a rational decision when they buy second-hand cars.We have chosen the EKB model as our basic theory. A quantitative research approach and cross sectional research design were used in this study. The link of our questionnaire was published in Baidu Tieba after being designed by SOJUMP and we collected 151 responses. Then, respondent demographics, cross tabulations analysis, one-way ANOVA analysis, Cronbach’s alpha, and sorting analysis were analyzed.The results show that information about the real condition of the car is the most important factor influencing customers when purchasing second-hand cars, price is the second most influencing factor, vehicle model and brand are the third and the fourth respectively, after-sales service ranks the least as most influencing factor.

Existing scholarship on Thomas Middleton and Thomas Dekker’s The Roaring Girl, or Moll Cutpurse primarily focuses on the title character and her unconventional gender presentation. This highlighting of Moll deemphasizes the other intriguing aspects of the play, including its thematic concerns involving issues of prejudice, reputation, gender, class, marriage, and sexuality. This thesis takes the spotlight off of Moll and shines it instead on a selection of other significant characters—including Sir Alexander Wengrave, Sebastian Wengrave, Mary Fitzallard, and a grouping of minor characters who have earned this play its designation as a city comedy: Laxton, Goshawk, the Openworks, and the Gallipots.

Data-mining has become a hot topic in recent years. It consists of extracting relevant information or structures from data such as: pictures, textual material, networks, etc. Such information or structures are usually not trivial to obtain and many techniques have been proposed to address this problem, including Independent Component Analysis, Latent Sematic Analysis, etc. Nonnegative Matrix Factorization is yet another technique that relies on the nonnegativity of the data and the nonnegativity assumption of the underlying model. The main advantage of this technique is that nonnegative objects are modeled by a combination of some basic nonnegative parts, which provides a physical interpretation of the construction of the objects. This is an exclusive feature that is known to be useful in many areas such as Computer Vision, Information Retrieval, etc. In this thesis, we look at several aspects of Nonnegative Matrix Factorization, focusing on numerical algorithms and their applications to different kinds of data and constraints. This includes Tensor Nonnegative Factorization, Weighted Nonnegative Matrix Factorization, Symmetric Nonnegative Matrix Factorization, Stochastic Matrix Approximation, etc. The recently proposed Rank-one Residue Iteration (RRI) is the common thread in all of these factorizations. It is shown to be a fast method with good convergence properties which adapts well to many situations.