This thesis deals with the no-depot minmax Multiple Traveling Salesmen Problem (MTSP), which can be formulated as follows. Given a set of n cities and k salesmen,find k disjoint tours (one for each salesmen) such that each city belongs to exactly one tour and the length of the longest of k tours is minimized. The no-depot assumption means that the salesmen do not start from and return to one fixed depot. The no-depot model can be applied in designing patrolling routes, as well as in business situations, especially where salesmen work from home or the company has no central office. This model can be also applied to the job scheduling problem with n jobs and k identical machines. Despite its potential applicability to a number of important situations, the research literature on the no-depot minmax k-TSP has been limited, with no reports on computational experiments. The previously published results included the proof of NP-hardness of the problem of interest, which motivates using heuristics for its solution. This thesis proposes several construction heuristic algorithms, including greedy algorithms, cluster first and route second algorithms, and route first and cluster second algorithms. As a local search method for a single tour, 2-opt search and Lin-Kernighan were used, and for a local search method between multiple tours, relocation and exchange (edge heuristics) were used. Furthermore, to prevent the drawback of trapping in the local minima, the simulated annealing method is used. Extensive computational experiments were carried out using TSPLIB instances. Among construction algorithms, route first and cluster second algorithms including removing two edges method performed best. In terms of running time, clustering first and routing second algorithms took shorter time on large-scale instances. The simulated annealing could produce better solutions than the descent method, but did not always perform well in terms of average solution. To evaluate the performance of the proposed heuristic methods, their solutions were compared with the optimal solutions obtained using a mixed-integer programming formulation of the problem. For small-scale problems, heuristic solutions were equal to the optimal solution output by CPLEX.

Unmanned Vehicles (UVs) are developed for several civil and military applications. For these applications, there is a need for multiple vehicles with different capabilities to visit and monitor a set of given targets. In such scenarios, routing problems arise naturally where there is a need to plan paths in order to optimally use resources and time. The focus of this thesis is to address a basic optimization problem that arises in this setting. We consider a routing problem where some targets have to be visited by specific vehicles. We approach this problem by dividing the routing into two sub problems: partitioning the targets while satisfying vehicle target constraints and sequencing. We solve the partitioning problem with the help of a minimum spanning tree algorithm. We use 3 different approaches to solve the sequencing problem; namely, the 2 approximation algorithm, Christofide's algorithm and the Lin - Kernighan Heuristic (LKH). The approximation algorithms were implemented in MATLAB. We also developed an integer programming (IP) model and a relaxed linear programming (LP) model in C with the help of Concert Technology for CPLEX, to obtain lower bounds. We compare the performance of the developed approximation algorithms with both the IP and the LP model and found that the heuristic performed very well and provided the better quality solutions as compared to the approximation algorithms. It was also found that the approximation algorithms gave better solutions than the apriori guarantees.

O HTLV-1 (Human T-Lymphotropic Virus) foi o primeiro retrovírus descoberto. Sua patogenia é relacionada à infecção das células T CD4+ e T CD8+ e sua disseminação depende da expansão clonal destas células. A imortalização celular e a resposta imune inflamatória direta contra o vírus levam os pacientes a desenvolverem a leucemia/ linfoma de células T do adulto (ATL) e paraparesia espástica tropical/mielopatia (TSP/HAM) respectivamente. Ainda que o vírus seja conhecido desde 1980, não existem trabalhos na literatura que evidenciem possíveis manifestações bucais associadas. Alguns estudos clínico-epidemiológicos, realizados em regiões altamente endêmicas para o vírus, apontam a possibilidade de associação entre o HTLV e a síndrome de Sjögren (SS). Este estudo objetivou conhecer melhor uma população HTLV+ identificando possíveis alterações estomatológicas. Foram avaliados 139 pacientes do Instituto de Infectologia Emilio Ribas, sendo que 112 (80,5%) eram HTLV-1+, 26 eram (18,7%) HTLV-2 + e 1 paciente era soropositivo para ambos os tipos virais. Entre os pacientes HTLV-1+, 88 (64,7%) eram assintomáticos e 48 (35,3%) apresentavam TSP/HAM. As alterações bucais mais freqüentes foram: xerostomia (26,5%), candidíase (25,4%), língua fissurada (22,1%) e língua depapilada (12,4%). Modelos de regressão logística multivariada confirmaram a TSP/HAM como um fator de risco independente para xerostomia (p=0,02), apresentando, pacientes TSP/HAM+, 3 vezes mais chances de desenvolver xerostomia quando comparados com pacientes sem TSP/HAM (OR=2,69; 95%IC=1,17-6,17). / HTLV-1 (human T-lymphotropic virus), the first retrovirus discovered, is associated with adult T cell leukemia/lymphoma (ATL) and tropical spastic paraparesis / HTLV associated myelopathy (TSP / HAM). Clinical studies and case reports in endemic areas showed the development of oral ALT and Sjögren`s syndrome in this patients. The aim of this study was to investigate the oral cavity of HTLV seropositive patients in São Paulo city. The present study was approved by the Institute of Infectious Diseases Emílio Ribas ethics committee. All patients answered a questionnaire designed for the study. Demographic and clinical data were recorded and then analyzed using Epi info (3.3.4 version) and SPSS Statistical Package for Social Sciences (v16.0). One hundred and thirty nine oral examinations were performed, 112 (80,5%) were HTLV-1 +, 26 were (18,7%) HTLV-2 + and one patient presented both types of HTLV. Sixty four (56,7%) were asymptomatic HTLV-1 seropositive patients, fourty nine (43,3%) patients were positive for HTLV-1 and TSP/HAM. HIV and HCV co-infection and comorbities were observed in 110 (79,1%) cases. Xerostomia (26,5%), candidosis (25,4%), oral fissured tongue (22,1%) and papillary atrophy of the tongue (12,4%) were the most prevalent oral manifestations found in these patients. Models of multivariate logistic regression confirmed the TSP / HAM as an independent risk factor for xerostomia (p = 0.02). Patients with TSP / HAM + were 3 times more likely to develop xerostomia when compared with patients without TSP / HAM (OR = 2.69, 95% CI = 1.17-6.17).

O HTLV-1 (Human T-Lymphotropic Virus) foi o primeiro retrovírus descoberto. Sua patogenia é relacionada à infecção das células T CD4+ e T CD8+ e sua disseminação depende da expansão clonal destas células. A imortalização celular e a resposta imune inflamatória direta contra o vírus levam os pacientes a desenvolverem a leucemia/ linfoma de células T do adulto (ATL) e paraparesia espástica tropical/mielopatia (TSP/HAM) respectivamente. Ainda que o vírus seja conhecido desde 1980, não existem trabalhos na literatura que evidenciem possíveis manifestações bucais associadas. Alguns estudos clínico-epidemiológicos, realizados em regiões altamente endêmicas para o vírus, apontam a possibilidade de associação entre o HTLV e a síndrome de Sjögren (SS). Este estudo objetivou conhecer melhor uma população HTLV+ identificando possíveis alterações estomatológicas. Foram avaliados 139 pacientes do Instituto de Infectologia Emilio Ribas, sendo que 112 (80,5%) eram HTLV-1+, 26 eram (18,7%) HTLV-2 + e 1 paciente era soropositivo para ambos os tipos virais. Entre os pacientes HTLV-1+, 88 (64,7%) eram assintomáticos e 48 (35,3%) apresentavam TSP/HAM. As alterações bucais mais freqüentes foram: xerostomia (26,5%), candidíase (25,4%), língua fissurada (22,1%) e língua depapilada (12,4%). Modelos de regressão logística multivariada confirmaram a TSP/HAM como um fator de risco independente para xerostomia (p=0,02), apresentando, pacientes TSP/HAM+, 3 vezes mais chances de desenvolver xerostomia quando comparados com pacientes sem TSP/HAM (OR=2,69; 95%IC=1,17-6,17). / HTLV-1 (human T-lymphotropic virus), the first retrovirus discovered, is associated with adult T cell leukemia/lymphoma (ATL) and tropical spastic paraparesis / HTLV associated myelopathy (TSP / HAM). Clinical studies and case reports in endemic areas showed the development of oral ALT and Sjögren`s syndrome in this patients. The aim of this study was to investigate the oral cavity of HTLV seropositive patients in São Paulo city. The present study was approved by the Institute of Infectious Diseases Emílio Ribas ethics committee. All patients answered a questionnaire designed for the study. Demographic and clinical data were recorded and then analyzed using Epi info (3.3.4 version) and SPSS Statistical Package for Social Sciences (v16.0). One hundred and thirty nine oral examinations were performed, 112 (80,5%) were HTLV-1 +, 26 were (18,7%) HTLV-2 + and one patient presented both types of HTLV. Sixty four (56,7%) were asymptomatic HTLV-1 seropositive patients, fourty nine (43,3%) patients were positive for HTLV-1 and TSP/HAM. HIV and HCV co-infection and comorbities were observed in 110 (79,1%) cases. Xerostomia (26,5%), candidosis (25,4%), oral fissured tongue (22,1%) and papillary atrophy of the tongue (12,4%) were the most prevalent oral manifestations found in these patients. Models of multivariate logistic regression confirmed the TSP / HAM as an independent risk factor for xerostomia (p = 0.02). Patients with TSP / HAM + were 3 times more likely to develop xerostomia when compared with patients without TSP / HAM (OR = 2.69, 95% CI = 1.17-6.17).

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-10-29T14:14:27Z No. of bitstreams: 1 Marcus Vinícius Alves Lima. Avaliação... 2014.pdf: 2528971 bytes, checksum: 51729fd9ac67351143ca0f2de5f23517 (MD5) / Made available in DSpace on 2014-10-29T14:14:27Z (GMT). No. of bitstreams: 1 Marcus Vinícius Alves Lima. Avaliação... 2014.pdf: 2528971 bytes, checksum: 51729fd9ac67351143ca0f2de5f23517 (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / O Brasil representa uma das áreas endêmicas para o vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) e a cidade de Salvador, Bahia, possui a maior prevalência nacional da infecção por este retrovírus (1,8%), com cerca de 50.000 pessoas infectadas. O HTLV-1 foi o primeiro retrovírus humano descrito e está classicamente associado à leucemia/linfoma de células T do adulto (ATLL) e à mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). A HAM/TSP é uma doença inflamatória do sistema nervoso central, cujos mecanismos imunopatogênicos não estão completamente elucidados. O papel dos linfócitos T citotóxicos na patogênese desta doença ainda não está bem definido. Neste estudo, foram avaliados o fenótipo e a função de linfócitos T citotóxicos de pacientes infectados pelo HTLV-1 com HAM/TSP. Ensaios de imunofenotipagem por citometria de fluxo foram conduzidos para avaliar a proporção das subpopulações de memória dos linfócitos T citotóxicos e mensurar potencial citotóxico destas células. Foram analisados 13 indivíduos não infectados e 49 infectados pelo HTLV-1 (18 sem mielopatia - ASS, 6 diagnosticados como HAM/TSP provável - HAM-PB - e 25 como HAM/TSP definido - HAM-D). Os indivíduos infectados apresentaram aumento da proporção de linfócitos T citotóxicos e de suas subpopulações de memória efetora em detrimento das células naive e de memória central. Não foi observada diferença na distribuição das subpopulações de memória dos CTLs entre os indivíduos infectados pelo HTLV-1. A quantidade de CTLs com atividade de degranulação foi significativamente menor nos pacientes HAM-D em comparação aos indivíduos ASS. O grupo HAM-D também apresentou redução (50%) da produção de IFN-γ pelos CTLs em relação ao grupo ASS. O grupo HAM-PB apresentou resultados similares ao grupo ASS quanto à atividade de degranulação e produção de IFN-γ. Aumento da expressão de IL-15 em células mononucleares do sangue periférico e em células CD14+ foi observado em todos os grupos de pacientes infectados em comparação com os indivíduos soronegativos para o HTLV-1. Estes resultados sugerem que os pacientes infectados pelo HTLV-1 com HAM/TSP apresentam prejuízo da resposta imune celular, caracterizado pela diminuição da quantidade de linfócitos T CD8+ com atividade de degranulação. / Brazil represents one of the largest endemic areas for human T-lymphotropic virus cells type 1 (HTLV-1) infection and associated diseases. Salvador, Bahia, is considered as the Brazilian city with the highest national HTLV-1prevalence (around 1.8% in the general population). HTLV -1 was the first human retrovirus described and is classically associated with adult Tcell leukemia/lymphoma (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic and progressive inflammatory disease of the central nervous system and your immunopathogenic mechanisms are not completely understood. The role of cytotoxic T-lymphocytes (CTLs) in the pathogenesis of this disease is still undefined. In this study we evaluated the phenotype and function of cytotoxic Tlymphocytes from HTLV-1-infected patients with HAM/TSP. Assays immunophenotyping by flow cytometry were conducted to assess the proportion of cytotoxic T-lymphocytes memory subsets and the cytotoxic potential of such cells. We analyzed 13 uninfected subjects (controls) and 49 HTLV-1-infected patients (18 without myelopathy (asymptomatic-ASS), 6 diagnosed as probable-HAM/TSP (HAM-PB) and 25 as defined-HAM/TSP (HAMD). Infected patients showed an increased proportion of cytotoxic T-lymphocytes and their subpopulations of effector memory cells at the expense of naive and central memory cells. The distribution of CTLs memory subsets resembled between HTLV-1-infected patients. The amount of CTLs with recent degranulation activity was significantly lower in HAM-D patients when compared to ASS group. The HAM-D group also showed IFN-γ production decrease (50%) by CTLs relative to the ASS group. The degranulation activity and IFN-γ production by cytotoxic T-lymphocytes were similar between the HAM-PB patients and ASS patients. Increased expression of IL-15 on peripheral blood mononuclear cells and CD14+cells was observed in all groups of infected patients when compared to not infected subjects. These results suggest that HTLV-1-infected individuals with HAM/TSP have cellular immune response impaired, characterized by decrease of CD8+ T-lymphocytes with degranulation activity.

No description available.

Diabetic nephropathy (DN) is a complication associated with diabetes and is characterized by proteinuria and a progressive loss of kidney function. The disease morphologically manifests as an increase in the extracellular matrix (ECM) produced by kidney cells including specialized mesangial cells found in the kidney glomeruli. The mesangial cells undergo increased proliferation and hypertrophy, produce ECM components at an elevated rate and in turn the ECM itself is broken down at a reduced rate. This leads to fibrosis, or the scarring of the glomeruli. The process of fibrosis is known to be promoted by pro-fibrotic factors such as transforming growth factor beta-1 (TGF-β1), which is activated by various proteins including thrombospondin-1 (TSP-1). Both of these proteins are known to have an increased rate of expression and activation in a high glucose environment and in the kidneys of diabetic patients. Glucose-regulate protein 78 (GRP78) is another protein altered by high glucose, as it is translocated to cell surface in DN (cell surface GRP78, csGRP78). In this study, we investigate the role csGRP78 has in the regulation of TSP-1 and downstream signaling by high glucose, using primary rat mesangial cell cultures. Our results confirm that TSP-1 protein levels are increased in the cell lysate and in the ECM of cells treated with high glucose. We further show that inhibitors of csGRP78 and downstream PI3K/Akt reduce the high glucose-induced increase in TSP1 at both protein and transcript levels, and attenuate TGF-β1 signaling. / Thesis / Master of Science (MSc) / Diabetic nephropathy is a condition that is associated with a gradual loss of kidney function as well as the presence of protein in the urine. As the name implies, diabetic nephropathy occurs as a result of diabetes mellitus. The disease causes the mesangial cells in the kidney to produce excess extracellular matrix leading to scarring in the kidney, a process called fibrosis. One of the key fibrotic proteins is called transforming growth factor beta-1 (TGF-β1), stored in a latent form. A major activator of TGF-β1 is thrombospondin-1 (TSP-1). Our results demonstrate that the cell surface localization of glucose regulated protein 78 (GRP78) is required for the upregulation of TSP-1 in a high glucose environment, leading to activation of profibrotic pathways that are well known to perpetuate the fibrotic phenotype seen in diabetic nephropathy.

Siekiant pagerinti kuriamų programinių produktų kokybę, IT įmonės taiko skirtingus proceso modelius. Populiariausi iš jų gebėjimo brandos modelis (CMMI) ir ISO 15504. Šie modeliai nusako, kas (kokie procesai) turi būti vykdoma brandžioje organizacijoje, tačiau neatsako į klausimą: kaip tai turi būti daroma. Komandinis programų kūrimo procesas (TSP) pateikia strategiją, kartu su procedūrų rinkiniu, skirtą disciplinuotų programų kūrimo metodų naudojimui komandos lygyje. Pagrindinė su TSP susijusi problema – oficialios dokumentacijos trūkumas. Pirmas darbo tikslas yra rekonstruoti TSP metodiką. Antras tikslas yra sukurti TSP diegimo metodiką. Pirmoje darbo dalyje yra aprašyta bendra TSP struktūra, TSP ryšys su asmeniniu programų kūrimo procesu (PSP) ir brandos modeliu CMMI. Antroje dalyje yra pateiktas rekonstruotas TSP modelis ir TSP diegimo metodika apibrėžtam projekto komandos tipui. / IT organizations use different models to guide their software process improvement efforts. The most popular are the Capability Maturity Model Integration for Software (CMMI-SW) and ISO 15504. Still these organizations often struggle with implementation details. Both the CMMI-SW and ISO 15504 describe what an organization at a high level of process maturity should be doing, but do not says how it should be implemented. The Team Software Process (TSP) provides a framework as well as a set of processes, procedures, guidelines, and tools for project teams to use in the mature software development process. The main problem of the Team Software Process is the lack of official documentation. So the first goal of this master thesis is to reconstruct TSP methodology. The second goal is to produce TSP implementation guide. This master thesis contains the main structure of the TSP, it’s relation with the Personal Software Process (PSP) ant the Capability Maturity Model (CMMI), reconstructed TSP model and TSP implementation guide for defined project team type.

Microaggregation is a method of statistical disclosure control that attempts to reconcile the need to release information to researchers with the need to protect privacy of individual records in a dataset. Under microaggregation, records are divided into groups containing at least k members. Actual data values of the members are replaced by the mean value of the group, such that each record in the group is indistinguishable from at least k-1 other records. The goal of microaggregation is to create groups of similar records such that information loss is minimized, where information loss is the sum squared deviation between the actual data values and the group means. Optimal multivariate microaggregation is an NP-hard problem, and heuristics have been proposed to generate solutions in reasonable running time. New heuristics are desirable for either producing groups with lower information loss, or for producing groups with similar information loss but lower computational complexity. Some of the best performing existing microaggregation heuristics are based on record ordering, since it has been proven that for a given ordering of records, the optimal set of groups for that particular ordering can be efficiently computed. This dissertation improves on previous heuristics that order records in a dataset and subsequently use this record ordering to generate high quality microaggregated k- partitions. This was accomplished by using heuristics from the traveling salesman problem (TSP) literature in order to more effectively order the records. In particular, two tour construction heuristics - the Greedy heuristic and the Quick Boruvka heuristic - that are comparable in complexity to extant microaggregation methods were investigated. Next, three tour improvement heuristics - 2-opt, 3-opt, and Lin-Kernighan - were used on the tours constructed to investigate whether further reduction in information loss could be achieved. The tour improvement heuristics - particularly the 3-opt and Lin-Kernighan heuristics - provided microaggregation solutions better than the best previous known solutions across several datasets and values of k.

The aim of this work is to investigate Ant Colony Algorithm for the traveling salesman problem (TSP). Ants of the artificial colony are able to generate successively shorter feasible tours by using information accumulated in the form of a pheromone trail deposited on the edges of the TSP graph. This paper is based on the ideas of ant colony algorithm and analysis the main parameters of the ant colony algorithm. Experimental results for solving TSP problems with ant colony algorithm show great effectiveness.