Introdução: O aumento da sobrevida dos pacientes com lúpus eritematoso sistêmico (LES) foi acompanhado por um aumento da frequência de comorbidades, tais como osteoporose e fraturas. Há descrições de associação de polimorfismos dos genes receptor ativador do fator nuclear kappa B (RANK), seu ligante (RANKL) e da osteoprotegerina (OPG) com alterações de densidade e fragilidade óssea, entretanto, não há estudos que avaliam estes polimorfismos em pacientes com LES. Objetivos: Avaliar polimorfismos de nucleotídeo único (SNP) dos genes RANKL, OPG e RANK em pacientes pré-menopausadas com LES e sua associação com densidade mineral óssea (DMO), fraturas vertebrais e concentrações séricas de sRANKL e OPG. Métodos: 211 mulheres com LES na pré-menopausa e 154 controles saudáveis foram avaliadas. Os seguintes SNPs foram avaliados por PCR em tempo real: RANKL [290 A > G (rs2277438)], OPG [1181 G > C (rs2073618), 245 T > G (rs3134069), 163 A>G (rs3102735)] e RANK [A > G (rs3018362)]. Concentrações séricas de OPG e sRANKL foram determinadas por ELISA, DMO e fraturas vertebrais por DXA (densitometria de dupla emissão com fonte de raios-X). Resultados: Pacientes e controles apresentaram frequência semelhante do alelo G do gene RANKL 290 A > G (41,2 vs. 40,3%, p=0,91), do alelo C do gene OPG 1181 G >C (62,6 vs. 61,0%, p=0,83), do alelo G da OPG 245 T>G (21,3 vs. 22,7%, p=0,80) do alelo G da OPG 163 A > G (96,2 vs. 87,0%, p=1,00) e do alelo G do RANK A > G (88,2 vs. 96,8%, p=0,75). Quando analisados os pacientes com LES, a frequência dos genótipos associados AG/GG do gene RANKL 290 A>G foi menos frequente em pacientes com fraturas vertebrais que em pacientes sem fraturas (28,1 vs. 46,9%, p=0,01). Com relação à densidade mineral óssea, a frequência dos genótipos associados TG/GG do polimorfismo 245 T > G da OPG foi maior em pacientes com baixa densidade mineral óssea do que em pacientes com densidade mineral óssea normal (31,4 vs. 18,1%, p=0,04). Não houve associação da DMO/fraturas com polimorfismos da OPG 1181 G > C, OPG 163 A > G e RANK A > G. Também não houve associação dos polimorfismos com as concentrações séricas de sRANKL e OPG. Conclusões: O presente trabalho demonstra pela primeira vez que variações genéticas no sistema OPG/RANKL podem desempenhar um papel importante na remodelação óssea e fratura em paciente pré-menopausadas com LES / Introduction: Survival rate improvement in systemic lupus erythematosus was accompanied by an increase in the incidence of long-term bone disorders such as osteoporosis, fractures and osteonecrosis. Polymorphisms of receptor activator of nuclear factor (NF)-kB ligand (RANKL) and osteoprotegerin (OPG) genes are known to influence bone mineral density and structure. However, there are no studies assessing these polymorphisms in SLE patients. Objective: To evaluate receptor activator of nuclear factor-kB (RANK) it ligand (RANKL) and osteoprotegerin (OPG) genes single nucleotide polymorphisms (SNP) in premenopausal SLE patients and their association with sRANKL and OPG serum levels, vertebral fractures and bone mineral density (BMD). Methods: 211 premenopausal SLE patients (ACR criteria) and 154 healthy controls were enrolled. SNPs of RANKL [290 A > G (rs2277438)], OPG [1181G > C (rs2073618), 245T>G (rs3134069), 163 A>G (rs3102735)] and RANK [A > G (rs3018362)] were obtained by real-time PCR. sRANKL/OPG serum levels were determined by ELISA. BMD and vertebral fractures were evaluated by dual energy X-ray absorptiometry. Results: SLE patients and controls had similar frequency of RANKL 290 G allele (41.2 vs. 40.3%, p=0.91), OPG 1181 C allele (62.6 vs. 61.0%, p=0.83), OPG 245 G allele (21.3 vs. 22.7%, p=0.80), OPG 163 G allele (96.2 vs. 87.0%, p=1.00) and RANK G allele (88.2 vs. 96.8%, p=0.75). Further analysis of SLE patients revealed that the frequency of RANKL 290 G allele was lower in patients with fractures than in patients without fractures (28.1 vs. 46.9%, p=0.01). In addition, the frequency of OPG 245 G allele was higher in patients with low BMD than in patients with normal BMD (31.4 vs. 18.1%, p=0.04). No association of OPG 1181 G > C, OPG 163 A > G and RANK A > G SNPs with BMD/fractures were found. Also, no association was observed between RANKL/OPG/RANK SNPs and sRANKL/OPG serum levels. Conclusions. Our study provides novel data demonstrating that RANKL/OPG genetic variations seem to play a role in bone remodeling and particularly in its main complication, fracture, in premenopausal patients with SLE

O conhecimento dos eventos biológicos que ocorrem no periápice dos dentes com necrose pulpar se torna importante para compreender o desenvolvimento das lesões periapicais. Muitas são as moléculas e mediadores que participam na instalação da lesão periapical, a partir da infecção bacteriana que ocorre no interior dos canais radiculares. Assim, o objetivo do presente trabalho foi avaliar moléculas do sistema imune inato, da osteoclastogênese e metaloproteinases em lesões periapicais (LP) induzidas experimentalmente em camundongos knockout e wild type. Para esse objetivo, o presente estudo foi dividido em dois trabalhos distintos. O primeiro teve como objetivo avaliar a expressão de metaloproteinase 2 (MMP2) e metaloproteinase 9 (MMP9) durante a progressão da LP em camundongos knockout para TLR2 (TLR2 KO) e MyD88 (MyD88 KO), em comparação com camundongos wild type (WT). O segundo estudo avaliou a correlação da expressão gênica e imunomarcação de RANK, RANKL, OPG, TLR2 e MyD88 durante a progressão da LP em camundongos WT. No primeiro estudo lesões periapicais foram induzidas em molares inferiores de 54 camundongos TLR2 KO, MyD88 KO e WT (n=18/grupo). Após 7, 21 e 42 dias, os animais foram eutanaziados e as mandíbulas foram dissecadas e submetidas a processamento histotécnico. Os cortes histológicos foram submetidos a imunohistoquímica e posteriormente foi avaliada presença ou ausência de MMP2 e MMP9 nos diferentes grupos. No segundo estudo, 35 camundongos WT foram utilizados. As lesões periapicais foram induzidas nos primeiros molares inferiores de ambos os lados. Após 0 (G0), 7 (G7), 21 (G21) e 42 (G42) dias, os animais foram anestesiados e eutanasiados para que as mandíbulas fossem dissecadas e divididas ao meio.O lado direito das mandíbulas foi para o processamento histotécnico, para posterior marcação de RANK, RANKL, OPG, TLR2 e MyD88, por meio da imuno-histoquímica do lado esquerdo da mandíbula foi utilizado para a extração de RNA, para a determinação da expressão gênica de RANK (Tnfrsf11a), RANKL (Tnfrsf11), OPG (Tnfrsf11b), TLR2 (Tlr2) e MyD88 (Myd88) utilizando quantificação em Tempo Real da Reação da Polimerase em Cadeia (qRT-PCR). Para ambos os estudos, testes paramétricos e não paramétricos foram realizados com nível de significância de 5%. Foi possível observar, no primeiro estudo, que nos períodos iniciais da progressão da lesão periapical, houve um aumento na imunomarcação de MMP9 nos camundongos TLR2 KO e MyD88 KO, quando comparados aos WT, diferente da MMP2 que não se observou nenhum aumento na imunomarcação. No entanto, aos 42 dias observou-se uma redução da imunomarcação de MMP2 e um aumento da MMP9 nos camundongos TLR2 KO. Adicionalmente, no segundo estudo, foi possível observar um aumento da imunomarcação para RANK, RANKL, OPG, TLR2 e MyD88 durante a progressão da lesão periapical (p<0,05). O aumento da expressão de Tnfrsf11 foi diferente entre os grupos G0 e G42, e G21 e G42 (p=0,006). No entanto, a expressão de Tnfrsf11b foi diferente entre os grupos G0 e G7, G7, G21 e G42, sendo possível observar uma diminuição dessa expressão ao longo do tempo (p<0,001). Tlr2 foi mais expresso entre os grupos G0 e G42 (p=0,03). E a expressão da molécula Myd88 foi estatisticamente significante entre os grupos G0 e G7, G21 e G42 (p=0,01). A razão Tnfrsf11/Tnfrsf11b aumentou durante a progressão da lesão periapical (p=0,002). Também foi possível observar uma correlação moderada entre Myd88 e Rankl (r=0,42; p=0,03) e entre Myd88 e Tlr2 (r=0,48; p<0,0001). Após as metodologias empregadas e os dados analisados, concluímos que a produção de MMP2 e MMP9 foi modulada por TLR2 e Myd88 durante a progressão da lesão periapical. Alem disso, podemos sugerir que existe uma correlação positiva entre o sistema RANK/RANKL/OPG e as proteínas do sistema imune inato, TLR2 e MyD88, durante a perda óssea decorrente da infecção bacteriana dos canais radiculares e posterior progressão da lesão periapical. / Knowledge of the biological events occurring inteeth apex with pulp necrosis becomes important to understand the development of periapical lesions. There are manymolecules and mediators that participate in the installation of the periapical lesion, from the bacterial infection that occurs inside the root canals. Thus, the aim of the present study was to evaluate molecules of the innate immune system, osteoclastogenesis and metalloproteinases in experimentally apical periodontitis (AP) induced in knockout and wild type mice. For this purpose, the present study was divided into two distinct studies. The first one aimed to evaluate the expression of metalloproteinases 2 (MMP2) and metalloproteinases 9 (MMP9) during the progression of AP in TLR2 knockout mice (TLR2 KO) and MyD88 knockout mice (MyD88 KO), compared to wild type mice (WT). The second study evaluated the correlation of gene expression and immunostaining of RANK, RANKL, OPG, TLR2 and MyD88 during LP progression in WT mice. In the first study AP were induced in lower molars of 54 TLR2 KO, MyD88 KO and WT mice (n = 18 / group). After 7, 21 and 42 days, the animals were euthanized and the jaws were dissected and submitted to histotechnical processing. The histological sections were submitted to immunohistochemistry and subsequently the presence or absence of MMP2 and MMP9 in the different groups was evaluated. In the second study, 35 WT mice were used. Periapical lesions were induced in the lower first molars on both sides. After 0 (G0) to 7 (G7), 21 (G21) and 42 (G42) days, the animals were anesthetized and euthanized so that the jaws were dissected and divided in half. The right side of the jaws was for the histotechnic processing, for subsequent imunostaining of RANK, RANKL, OPG, TLR2 and MyD88, through immunohistochemistry and the left side of the jaws was used for the extraction of RNA, for the determination of expression of RANK (Tnfrsf11a), RANKL (Tnfrsf11), OPG (Tnfrsf11b), TLR2 (Tlr2) and MyD88 (Myd88) using Quantification Real Time of Polymerase Chain Reaction (qRT-PCR). For both studies, parametric and non-parametric tests were performed with significance level of 5%. It was possible to observe in the first study that in the initial periods of AP progression there was an increase in MMP9 immunostaining in TLR2 KO and MyD88 KO mice when compared to WT, different from MMP2 that no increase in immunostaining was observed. However, at 42 days there was a reduction in MMP2 immunostaining and an increase of MMP9 in TLR2 KO mice was observed. Additionally, in the second study, it was possible to observe an increase in the immunostaining for RANK, RANKL, OPG, TLR2 and MyD88 during periapical lesion progression (p <0.05). The increase in Tnfrsf11 expression was different between groups G0 and G42, and G21 and G42 (p = 0.006). However, the expression of Tnfrsf11b was different between the G0 and G7, G7, G21 and G42 groups, and a decrease in expression over time (p <0.001) was observed. Tlr2 was more expressed between the G0 and G42 groups (p = 0.03). And the expression of the Myd88 molecule was statistically significant between the G0 and G7, G21 and G42 groups (p = 0.01). The Tnfrsf11 / Tnfrsf11b ratio increased during the AP progression (p = 0.002). It was also possible to observe a moderate correlation between Myd88 and Rankl (r = 0.42, p = 0.03) and between Myd88 and Tlr2 (r = 0.48, p <0.0001). After the methodologies used and the data analyzed, we conclude that the production of MMP2 and MMP9 was modulated by TLR2 and Myd88 during the AP progression. In addition, we can suggest that there is a positive correlation between the RANK / RANKL / OPG system and the proteins of the innate immune system, TLR2 and MyD88, during bone loss due to bacterial infection of the root canals and subsequent progression of the apical periodontitis.

Made available in DSpace on 2014-07-29T15:21:58Z (GMT). No. of bitstreams: 1 Dissertacao parte1 Larissa Santana Arantes Elias.pdf: 1237563 bytes, checksum: 572e0535bd8ddf8a3d9cd5c693a6aa5f (MD5) Previous issue date: 2010-03-19 / The RANK (receptor activator of nuclear factor Kappa-Beta)-RANKL (receptor activator of nuclear factor-kappa beta ligand)-OPG (osteoprotegerin) system is the principal means of differentiating and activating osteoclasts. Changes along this path have been associated with various bone related lesions (BRL), whether benign or malignant, such as osteosarcoma (OS). This system induces resorption when it is deregulated, and in the case of LROs, by replacing the bone tissue for fibrous tissue with the presence of various forms of ossification. And in this same context another protein, osteocalcin (OC), a marker of late ossification, plays a key role in the diagnosis of these lesions. This being so, the objective of this study was to identify, quantify and compare cell RANK+, RANKL+, OPG+ and OC+ in lesions of the jaw with bone involvement: ossifying fibroma (OF), fibrous dysplasia (FD), simple bone cysts (SBC), central giant cell lesions (CGCL) and osteosarcoma (OS) so as to contribute to understanding the pathogenesis and establishing the diagnosis of these lesions. RANK+, RANKL+, OPG+ and OC+ cells were identified by the technique of immunohistochemistry, a method of immunoperoxidase and polymer, in 10 samples of OF, FD, SBC, CGCL and 5 samples of OS. Our results showed that all samples were positive for RANK, RANKL, OPG and OC. In the stromal fibroblast-like cells, the OF (P<0.001), CGCL (P=0.007) and OS (P=0,058) presented a greater expression of RANKL than OPG, in contrast with both the SBC (P=0.003) and the FD (P<0.001). As for bone-matrix (cells around bone/osteoid-osteoblast and osteoclast), the OS (P=0.24) and OF (P=0.001) samples demonstrated a higher RANKL immunoreactivity and and a lower in FD (P=0.001) and SBC (P=0.4) samples. In terms of OC, a higher expression was shown in FD, SBC, and OS (P=0.008). Our results suggest that OF, CGCL and OS express bone metabolism regulators, which may be related to increased bone resorption in these lesions. In addition, osteoblastic involvement was seen in FD and OS. Note: The superscript + is where it appears. Programs to copy some formatting errors. / O sistema RANK (receptor activator of nuclear factor Kappa-Beta)-RANKL (receptor activator of nuclear factor-kappa beta ligand)-OPG (osteoprotegerin) constitui uma das principais vias de diferenciação e ativação dos osteoclastos e alterações nessa via tem sido associadas a diversas lesões relacionadas ao osso (LRO), benignas e maligna como no osteossarcoma (OS). Esse sistema quando desregulado induz reabsorção, e no caso das LROs, através da substituição do tecido ósseo por um tecido fibroso com a presença de várias formas de ossificação. E nesse contexto outra proteína, a osteocalcina (OC), que é um marcador tardio de ossificação, desempenha um papel fundamental no diagnóstico destas lesões. Portanto, o objetivo do presente estudo foi identificar, quantificar e comparar células RANK+, RANKL+, OPG+ e OC+ em lesões dos maxilares com envolvimento ósseo: fibroma ossificante (FO), displasia fibrosa (DF), cisto ósseo simples (COS), lesão central de células gigantes (LCCG) e osteossarcoma (OS). As células RANK+, RANKL+, OPG+ e OC+ foram identificadas pela técnica da imunoistoquímica, método da imunoperoxidase e do polímero, em 10 amostras de FO, DF, COS, LCCG e 5 amostras de OS. Quando comparado as lesões entre si, tanto nas células fibroblásticas estromais quanto da matriz óssea, nossos resultados demonstraram que os ativadores da reabsorção óssea (RANK/RANKL) apresentam uma maior expressão no FO e LCCG e, o inibidor da reabsorção (OPG) e a OC apresentaram maior na DF e COS. Em adição, nossos achados revelam que o OS apresenta alta expressão de todas as proteínas avaliadas, quando comparadas àquelas das LROs. Todavia, uma maior expressão de RANKL em relação à OPG e OC foi evidenciada nesta neoplasia. Nossos resultados sugerem que o FO, a LCCG e o OS expressam reguladores do metabolismo ósseo que podem estar relacionados com a reabsorção óssea aumentada nessas lesões, sendo que na DF e no OS foi observado envolvimento osteoblástico. OBS: A + está sobrescrita onde aparece. Programas copiam com erros certas formatações.

O diabete melito é uma doença metabólica com alta prevalência na população e quando no estado descompensado pode causar diversas complicações metabólicas e clínicas, entre elas a osteoporose. Entretanto, ainda não foram completamente esclarecidos os mecanismos pelos quais o diabete diminui a densidade mineral óssea e aumenta o risco a fraturas. Recentemente foram descritos alguns genes que estão envolvidos no turnover ósseo: OPG, RANK e RANKL. Além disso, o uso de hipoglicemiantes orais como as tiazolidinedionas (TZD), pode influenciar negativamente o metabolismo ósseo. Com a finalidade de identificar marcadores sensíveis de alteração do metabolismo ósseo foram investigadas as relações entre a expressão dos genes OPG, RANK e RANKL em células do sangue periférico e a resposta a TZDs em pacientes com DM2. Foram selecionados 52 indivíduos (36 diabéticos e 16 normoglicêmicos), no Instituto Dante Pazzanese de Cardiologia. Os indivíduos diabéticos foram tratados com pioglitazona (15, 30 e 45 mg/ dia/ via oral) por 16 semanas. Foram colhidas amostras de sangue, antes e após o tratamento para determinação de exames laboratoriais e extração de RNA total. A expressão de mRNA dos genes OPG, RANK e RANKL foi quantificada e avaliada por RT-PCR em tempo real, empregando-se o GAPD como controle endógeno. Observou-se que nos pacientes DM2 após o tratamento com pioglitazona, houve diminuição da glicemia de jejum, glicemia pós-prandial, insulina, Hb1Ac, índices HOMA-IR e HOMA-&#946; e aumento nas concentrações séricas de HDL, demonstrando a eficácia do tratamento. Ao comparar a expressão dos genes entre o grupo DM2 (sem tratamento) e o grupo normoglicêmico (NG), foi evidenciado um aumento da expressão de OPG no grupo NG em relação ao grupo DM2, e ao analisar a expressão entre as mulheres, constatou-se aumento da expressão de RANK no grupo DM2 em relação ao grupo NG. Além disso, ao correlacionar a expressão dos genes com as dosagens dos parâmetros bioquímicos, constatou-se que o aumento da expressão de RANK e RANKL está relacionado com o aumento das concentrações de cálcio ionizado e diminuição da expressão de OPG. Esses dados sugerem que a atividade osteoclástica está aumentada nos pacientes DM2 e com o tratamento o quadro osteoporótico pode ser agravado. / The diabetes mellitus is a metabolic disease with high prevalence in the population and can cause various metabolic and clinic complications, including osteoporosis, when it is decompensated. However, the mechanisms by which diabetes decreases bone mineral density and increases the risk of fractures are not completely clarified. Recently some genes which are involved in bone turnover were described: OPG, RANK and RANKL. Moreover, the treatment using oral hypoglycemic drugs such as thiazolidinediones (TZD), may negatively affect the bone metabolism. In order to identify sensitive markers related to the bone metabolism, were investigated the relationship between the expression of genes OPG, RANK and RANKL in peripheral blood leukocytes and the response to TZDs treatment in patients with DM2. Fifty-two individuals were selected (36 diabetics and 16 normoglycemics) at Dante Pazzanese Institute of Cardiology. Diabetic patients were treated with pioglitazone (15, 30 and 45 mg I day I oral) during 16 weeks. Blood samples were collected for biochemical analyses and total RNA extraction, before and after treatment. Gene expression of the genes OPG, RANK and RANKL in peripheral blood mononuclear cells was evaluated by Real Time PCR, using the GAPD housekeeping gene as the endogenous reference. In DM2 patients after treatment with pioglitazone there was reduction in their fasting glycemia, postprandial glycemia, insulin, Hb1Ac, HOMA-IR and HOMA-&#946; indices, and their serum concentrations of HDL increased, which demonstrates the effectiveness of the treatment. The bone profile markers have not altered after treatment, suggesting an anabolic action of the insulin in bone metabolism of these patients. Normoglycemics (NG) group gene expression, when compared with DM2 group (with no treatment), had increased OPG expression. Besides, RANK expression in group DM2 was higher than NG group when it was analyzed among women. Furthermore, having correlated the expression of the genes with the biochemical parameters data, the increase on RANK and RANKL gene expression is related to increased concentrations of ionized calcium and to decreased expression of OPG gene. These results are suggestive that osteoclastic activity is higher in DM2 patients, the treatment can exacerbate osteoporosis severity and the bone markers does not have enough sensibility to differentiate changes in individuals with type 2 diabetes mellitus.

The thesis deals with image classifiers and their implementation using FPGA technology. There are discussed weak and strong classifiers in the work. As an example of strong classifiers, the AdaBoost algorithm is described. In the case of weak classifiers, basic types of feature classifiers are shown, including Haar and Gabor wavelets. The rest of work is primarily focused on LBP, LRP and LR classifiers, which are well suitable for efficient implementation in FPGAs. With these classifiers is designed pseudo-parallel architecture. Process of classifications is divided on software and hardware parts. The thesis deals with hardware part of classifications. The designed classifier is very fast and produces results of classification every clock cycle.

This diploma thesis deals with ant colony optimization for shortest path problems. In the theoretical part it describes Ant Colony Optimization. In the practical part ant colony optimization algorithms are selected for the design and implementation of shortest path problems in the Java.

Multivariate linear regression methods are widely used statistical tools in data analysis, and were developed when some response variables are studied simultaneously, in which our aim is to study the relationship between predictor variables and response variables through the regression coefficient matrix. The rapid improvements of information technology have brought us a large number of large-scale data, but also brought us great challenges in data processing. When dealing with high dimensional data, the classical least squares estimation is not applicable in multivariate linear regression analysis. In recent years, some approaches have been developed to deal with high-dimensional data problems, among which dimension reduction is one of the main approaches. In some literature, random projection methods were used to reduce dimension in large datasets. In Chapter 2, a new random projection method, with low-rank matrix approximation, is proposed to reduce the dimension of the parameter space in high-dimensional multivariate linear regression model. Some statistical properties of the proposed method are studied and explicit expressions are then derived for the accuracy loss of the method with Gaussian random projection and orthogonal random projection. These expressions are precise rather than being bounds up to constants. In multivariate regression analysis, reduced rank regression is also a dimension reduction method, which has become an important tool for achieving dimension reduction goals due to its simplicity, computational efficiency and good predictive performance. In practical situations, however, the performance of the reduced rank estimator is not satisfactory when the predictor variables are highly correlated or the ratio of signal to noise is small. To overcome this problem, in Chapter 3, we incorporate matrix projections into reduced rank regression method, and then develop reduced rank regression estimators based on random projection and orthogonal projection in high-dimensional multivariate linear regression models. We also propose a consistent estimator of the rank of the coefficient matrix and achieve prediction performance bounds for the proposed estimators based on mean squared errors. Envelope technology is also a popular method in recent years to reduce estimative and predictive variations in multivariate regression, including a class of methods to improve the efficiency without changing the traditional objectives. Variable selection is the process of selecting a subset of relevant features variables for use in model construction. The purpose of using this technology is to avoid the curse of dimensionality, simplify models to make them easier to interpret, shorten training time and reduce overfitting. In Chapter 4, we combine envelope models and a group variable selection method to propose an envelope-based sparse reduced rank regression estimator in high-dimensional multivariate linear regression models, and then establish its consistency, asymptotic normality and oracle property. Tensor data are in frequent use today in a variety of fields in science and engineering. Processing tensor data is a practical but challenging problem. Recently, the prevalence of tensor data has resulted in several envelope tensor versions. In Chapter 5, we incorporate envelope technique into tensor regression analysis and propose a partial tensor envelope model, which leads to a parsimonious version for tensor response regression when some predictors are of special interest, and then consistency and asymptotic normality of the coefficient estimators are proved. The proposed method achieves significant gains in efficiency compared to the standard tensor response regression model in terms of the estimation of the coefficients for the selected predictors. Finally, in Chapter 6, we summarize the work carried out in the thesis, and then suggest some problems of further research interest. / Dissertation / Doctor of Philosophy (PhD)

During the last decades, the power grid is getting rapidly digitalised in order to contribute to theestablishment of Smart Grids and evaluate efficiently the extracted bidirectional data from the powersystem infrastructure. This thesis focuses on the MV grid, since its design and operation have changedmainly because of distributed generation installations and the increased demand of information fromstakeholders. Thus, asset management constitutes a significant tool that can increase the reliability ofthe MV network’s operation and its level of control. Studies have shown that a maintenance planbased on condition monitoring of power system apparatuses would be more effective compared to theimplemented time-based scheduled maintenance.This project focuses on MV remotely controlled disconnectors since studies have shown that theirnumber of failures is double compared to manually operated ones. Since maneuverability andsecondary function are the causes of a major failure with the highest occurrence rate, motor currentmonitoring is studied in this thesis. Some devices that have the capability to monitor disconnectors’motor current, are presented. Additionally, the obtained max motor current measurements areevaluated through a parametric and a non-parametric statistical test. The main challenge of this thesisis to show whether the behaviour of motor current can be an indicator regarding to the disconnector’scondition status.Hence, the impact of different factors on the behaviour of motor current is investigated. It is concludedthat disconnectors without a failure during the studied period are more likely to have max motorcurrent measurements higher than 8A and especially in the interval [10-12]A. The difference in motorcurrent of disconnectors with a work order and without failure is more significant in 2015/2016. Itseems that under the aforementioned values of max motor current, a disconnector is more probable tohave the capability to operate properly. It is also concluded that in case of malfunction “Mellanläge”,the value of max motor current is lower than 8A with higher probability and it maybe indicates aproblem of the studied disconnector.Through the comparison in pairs, it could be concluded that the effect of the external environmentalconditions is not so high on the behaviour of disconnectors’ max motor current measurements. Incontrast, it seems that the implementation of a work order, the number of operations and if adisconnector is installed more northerly in Zone 3 play a more significant role on the behaviour of thisdisconnector’s max motor current measurements. Consequently, based on the aforementioned results itis shown that some of the investigated factors could constitute an indicator whether a disconnector ismore or less probable to have the capability to operate properly.Finally, it is calculated the reduction in the interruption cost that could be achieved in case ofimplementation of motor current monitoring on Vattenfall’s remotely controlled distributeddisconnectors. / Under de senaste årtiondena har kraftnät blivit snabbt digitaliserad För att bidra till upprättandet hosSmart Grids och effektivt utvärdera de extraherade dubbelriktade data från kraftsystemetsinfrastruktur. Denna exjobbsrapport fokuserar på MV-nätet, eftersom dess design och drift harförändrats främst på grund av distribuerade produktionsanläggningar och ökad efterfrågan påinformation från intressenter. Därför utgör ”asset management’’ ett viktigt verktyg som kan öka elnätstillförlitligheten och styrning. Studier har visat att elnäts underhåll baserad på tillståndsövervakningpå kraftsystemkomponenter skulle kunna vara effektivare jämfört med tidsbaserade schemalagdaunderhåll.Detta exjobb fokuserar på MV-fjärrstyrda frånskiljare eftersom studier har visat att deras felfrekvensär dubbelt högre jämfört med manuella. Eftersom problem i manövrerbarhet och sekundär funktionkan orsaka allvarliga fel med hög frekvens, har studien fokuserats på motorströmövervakningen idetta exjobb. Vissa produkter som har förmåga att övervaka frånskiljares motorström, presenteras.Dessutom utvärderas de maximala motorströmsmätningarna genom både parametriskt och ickeparametrisktstatistiskt test. Huvudutmaningen i denna avhandling är att utreda om motors strömmarkan vara en indikator för frånskiljares tillstånd.Olika faktorer hos motorströmmar har också undersökts. Det dras slutsatsen att frånskiljare utanmisslyckande manövern under den studerade perioden är mer benägna att ha maximalamotorströmmar högre än 8A och speciellt i intervallet [10-12] A. Skillnaden i motors strömmar hosfrånskiljare med arbetsorder och utan fel är mer signifikant under åren 2015/2016. Det verkar som attenligt ovan nämnda värden på max motorström, är en frånskiljare mer sannolikt att fungera korrekt.Det kommer också fram till att i händelse av "Mellanläge" är värdet av max motorströmmar lägre än8A med högre sannolikhet, detta kan kanske indikera ett problem hos frånskiljaren.Genom jämförelsen kan man dra slutsatsen att effekten av de yttre miljöförhållandena inte är så högpå maximala motorströmmar hos frånskiljare. Däremot verkar det som om genomförandet av enarbetsorder, antalet operationer och om en frånskiljare är installerad i zon 3 spelar en viktig roll föruppförandet av denna frånskiljares maximala motors strömmen. På grundval av det ovan nämndaresultatet framgår det att några av de undersökta faktorerna kan utgöra en indikator på att om enfrånskiljare är mer eller mindre sannolikt att ha förmågan att fungera korrekt.Slutligen visar beräkningar att minskningen av avbrottskostnaden kan uppnås vid genomförande avmotorströmövervakning på Vattenfalls fjärrstyrda distribuerade frånskiljare.

In this paper we study local rigidity of actions of simply connected Lie groups. In particular, we apply the Nash-Moser inverse function theorem to give sufficient conditions for the action of a simply connected Lie group to be locally rigid. Let $G$ be a Lie group, $H &lt; G$ a simply connected subgroup and $\Gamma &lt; G$ a cocompact lattice. We apply the result for general actions of simply connected groups to obtain sufficient conditions for the action of $H$ on $\Gamma\backslash G$ by right translations to be locally rigid. We also discuss some possible applications of this sufficient condition / I den här texten så studerar vi lokal rigiditet av gruppverkan av enkelt sammanhängande Liegrupper. Mer specifikt, vi applicerar Nash-Mosers inversa funktionssats för att ge tillräckliga villkor för att en gruppverkan av en enkelt sammanhängande grupp ska vara lokalt rigid. Låt $G$ vara en Lie grupp, $H &lt; G$ en enkelt sammanhängande delgrupp och $\Gamma &lt; G$ ett kokompakt gitter. Vi applicerar resultatet för generella gruppverkan av enkelt sammanhängande grupper för att få tillräckliga villkor för att verkan av $H$ på $\Gamma\backslash G$ med translationer ska vara lokalt rigid. Vi diskuterar också några möjliga tillämpningar av det tillräckliga villkoret.

Online shopping offers numerous benefits, but large product catalogs make it difficult for shoppers to understand the existence and characteristics of every item for sale. To simplify the decision-making process, online retailers use ranking models to recommend products relevant to each individual user. Contextual user data, such as location, time, or local weather conditions, can serve as valuable features for ranking models, enabling personalized real-time recommendations. Little research has been published on the usefulness of weather-based features for ranking models in online clothing retailing, which makes additional research into this topic worthwhile. Using Swedish sales and customer data from Babyshop, an online retailer of children’s fashion, this study examined possible correlations between local weather data and sales. This was done by comparing differences in daily weather and differences in daily shares of sold items per clothing category for two cities: Stockholm and Göteborg. With Malmö as an additional city, historical observational weather data from one location each in the three cities Stockholm, Göteborg, and Malmö was then featurized and used along with the customers’ postal towns, sales features, and sales trend features to train and evaluate the ranking relevancy of a gradient boosted decision trees learning to rank LightGBM ranking model with weather features. The ranking relevancy was compared against a LightGBM baseline that omitted the weather features and a naive baseline: a popularity-based ranker. Several possible correlations between a clothing category such as shorts, rainwear, shell jackets, winter wear, and a weather variable such as feels-like temperature, solar energy, wind speed, precipitation, snow, and snow depth were found. Evaluation of the ranking relevancy was done using the mean reciprocal rank and the mean average precision @ 10 on a small dataset consisting only of customer data from the postal towns Stockholm, Göteborg, and Malmö and also on a larger dataset where customers in postal towns from larger geographical areas had their home locations approximated as Stockholm, Göteborg or Malmö. The LightGBM rankers beat the naive baseline in three out of four configurations, and the ranker with weather features outperformed the LightGBM baseline by 1.1 to 2.2 percent across all configurations. The findings can potentially help online clothing retailers create more relevant product recommendations. / Internethandel erbjuder flera fördelar, men stora produktsortiment gör det svårt för konsumenter att känna till existensen av och egenskaperna hos alla produkter som saluförs. För att förenkla beslutsprocessen så använder internethandlare rankningsmodeller för att rekommendera relevanta produkter till varje enskild användare. Kontextuell användardata såsom tid på dygnet, användarens plats eller lokalt väder kan vara värdefulla variabler för rankningsmodeller då det möjliggör personaliserade realtidsrekommendationer. Det finns inte mycket publicerad forskning inom nyttan av väderbaserade variabler för produktrekommendationssystem inom internethandel av kläder, vilket gör ytterligare studier inom detta område intressant. Med hjälp av svensk försäljnings- och kunddata från Babyshop, en internethandel för barnkläder så undersökte denna studie möjliga korrelationer mellan lokal väderdata och försäljning. Detta gjordes genom att jämföra skillnaderna i dagligt väder och skillnaderna i dagliga andelar av sålda artiklar per klädeskategori för två städer: Stockholm och Göteborg. Med Malmö som ytterligare en stad så gjordes historiska metereologiska observationer från en plats var i Stockholm, Göteborg och Malmö till variabler och användes tillsammans med kundernas postorter, försäljningsvariabler och variabler för försäljningstrender för att träna och utvärdera rankningsrelevansen hos en gradient-boosted decision trees learning to rank LightGBM rankningsmodell med vädervariabler. Rankningsrelevansen jämfördes mot en LightGBM baslinjesmodel som saknade vädervariabler samt en naiv baslinje: en popularitetsbaserad rankningsmodell. Flera möjliga korrelationer mellan en klädeskategori som shorts, regnkläder, skaljackor, vinterkläder och och en daglig vädervariabel som känns-som-temperatur, solenergi, vindhastighet, nederbörd, snö och snödjup upptäcktes. Utvärderingen av rankingsrelevansen utfördes med mean reciprocal rank och mean average precision @ 10 på ett mindre dataset som bestod endast av kunddata från postorterna Stockholm, Göteborg och Malmö och även på ett större dataset där kunder med postorter från större geografiska områden fick sina hemorter approximerade som Stockholm, Göteborg eller Malmö. LigthGBM-rankningsmodellerna slog den naiva baslinjen i tre av fyra konfigurationer och rankningsmodellen med vädervariabler slog LightGBM baslinjen med 1.1 till 2.2 procent i alla konfigurationer. Resultaten kan potentiellt hjälpa internethandlare inom mode att skapa bättre produktrekommendationssystem.