Dissertations / Theses: 'TSP'

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Desjardins, Nicholas. "On Applying Methods for Graph-TSP to Metric TSP." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35613.

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The Metric Travelling Salesman Problem, henceforth metric TSP, is a fundamental problem in combinatorial optimization which consists of finding a minimum cost Hamiltonian cycle (also called a TSP tour) in a weighted complete graph in which the costs are metric. Metric TSP is known to belong to a class of problems called NP-hard even in the special case of graph-TSP, where the metric costs are based on a given graph. Thus, it is highly unlikely that efficient methods exist for solving large instances of these problems exactly. In this thesis, we develop a new heuristic for metric TSP based on extending ideas successfully used by Mömke and Svensson for the special case of graph-TSP to the more general case of metric TSP. We demonstrate the efficiency and usefulness of our heuristic through empirical testing. Additionally, we turn our attention to graph-TSP. For this special case of metric TSP, there has been much recent progress with regards to improvements on the cost of the solutions. We find the exact value of the ratio between the cost of the optimal TSP tour and the cost of the optimal subtour linear programming relaxation for small instances of graph-TSP, which was previously unknown. We also provide a simplified algorithm for special graph-TSP instances based on the subtour linear programming relaxation.

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Feng, Yinda. "Ant colony for TSP." Thesis, Högskolan Dalarna, Datateknik, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:du-4824.

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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.

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Maris, Frederic. "Planification SAT et Planification Temporellement Expressive. Les Systèmes TSP et TLP-GP." Phd thesis, Université Paul Sabatier - Toulouse III, 2009. http://tel.archives-ouvertes.fr/tel-00442014.

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Cette thèse s'inscrit dans le cadre de la planification de tâches en intelligence artificielle. Après avoir introduit le domaine et les principaux algorithmes de planification dans le cadre classique, nous présentons un état de l'art de la planification SAT. Nous analysons en détail cette approche qui permet de bénéficier directement des améliorations apportées régulièrement aux solveurs SAT. Nous proposons de nouveaux codages qui intègrent une stratégie de moindre engagement en retardant le plus possible l'ordonnancement des actions. Nous présentons ensuite le système TSP que nous avons implémenté pour comparer équitablement les différents codages puis nous détaillons les résultats de nombreux tests expérimentaux qui démontrent la supériorité de nos codages par rapport aux codages existants. Nous présentons ensuite un état de l'art de la planification temporelle en analysant les algorithmes et l'expressivité de leurs langages de représentation. La très grande majorité de ces planificateurs ne permet pas de résoudre des problèmes réels pour lesquels la concurrence des actions est nécessaire. Nous détaillons alors les deux approches originales de notre système TLP-GP permettant de résoudre ce type de problèmes. Ces approches sont comparables à la planification SAT, une grande partie du travail de recherche étant déléguée à un solveur SMT. Nous proposons ensuite des extensions du langage de planification PDDL qui permettent une certaine prise en compte de l'incertitude, du choix, ou des transitions continues. Nous montrons enfin, grâce à une étude expérimentale, que nos algorithmes permettent de résoudre des problèmes réels nécessitant de nombreuses actions concurrentes.

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Maris, Frédéric. "Planification SAT et planification temporellement expressive : les systèmes TSP et TLP-GP." Toulouse 3, 2009. http://thesesups.ups-tlse.fr/688/.

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Cette thèse s'inscrit dans le cadre de la planification de tâches en intelligence artificielle. Après avoir introduit le domaine et les principaux algorithmes de planification dans le cadre classique, nous présentons un état de l'art de la planification SAT. Nous analysons en détail cette approche qui permet de bénéficier directement des améliorations apportées régulièrement aux solveurs SAT. Nous proposons de nouveaux codages qui intègrent une stratégie de moindre engagement en retardant le plus possible l'ordonnancement des actions. Nous présentons ensuite le système TSP que nous avons implémenté pour comparer équitablement les différents codages puis nous détaillons les résultats de nombreux tests expérimentaux qui démontrent la supériorité de nos codages par rapport aux codages existants. Nous présentons ensuite un état de l'art de la planification temporelle en analysant les algorithmes et l'expressivité de leurs langages de représentation. La très grande majorité de ces planificateurs ne permet pas de résoudre des problèmes réels pour lesquels la concurrence des actions est nécessaire. Nous détaillons alors les deux approches originales de notre système TLP-GP permettant de résoudre ce type de problèmes. Ces approches sont comparables à la planification SAT, une grande partie du travail de recherche étant déléguée à un solveur SMT. Nous proposons ensuite des extensions du langage de planification PDDL qui permettent une certaine prise en compte de l'incertitude, du choix, ou des transitions continues. Nous montrons enfin, grâce à une étude expérimentale, que nos algorithmes permettent de résoudre des problèmes réels nécessitant de nombreuses actions concurrentes
This thesis deals with Artificial Intelligence planning. After introducing the domain and the main algorithms in the classical framework of planning, we present a state of the art of SAT planning. We analyse in detail this approach which allows us to benefit directly from improvements brought regularly to SAT solvers. We propose new encodings integrating a least-commitment strategy postponing as much as possible the scheduling of actions. We then introduce the TSP system which we have implemented to equitably compare the different encodings and we detail the results of numerous experimental tests which show the superiority of our encodings in comparison with the existing ones. We introduce then a state of the art of temporal planning by analysing algorithms and expressiveness of their representation languages. The great majority of these planners do not allow us to solve real problems for which the concurrency of actions is required. We then detail the two original approaches of our TLP-GP system which allow us to solve this type of problem. As with SAT planning, a large part of search work is delegated to a SMT solver. We then propose extensions of the PDDL planning language which allows us to a certain extent to take into account uncertainty, choice, or continuous transitions. We show finally, thanks to an experimental study, that our algorithms allow us to solve real problems requiring numerous concurrent actions

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Na, Byungsoo. "Heurisic approaches for no-depot k-traveling salesmen problem with a minmax objective." Texas A&M University, 2003. http://hdl.handle.net/1969.1/5825.

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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.

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Gavrilov, Andrej. "Komandinio programų kūrimo proceso tyrimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2009. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2008~D_20090908_201812-38601.

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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.

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Palbom, Anna. "On Approximating Asymmetric TSP and Related Problems." Licentiate thesis, Stockholm : School of Computer Science and Communication, Kungl Tekniska högskolan, (KTH), 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3932.

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Hahsler, Michael, and Kurt Hornik. "TSP - Infrastructure for the Traveling Salesperson Problem." Department of Statistics and Mathematics, WU Vienna University of Economics and Business, 2006. http://epub.wu.ac.at/1230/1/document.pdf.

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The traveling salesperson or salesman problem (TSP) is a well known and important combinatorial optimization problem. The goal is to find the shortest tour that visits each city in a given list exactly once and then returns to the starting city. Despite this simple problem statement, solving the TSP is difficult since it belongs to the class of NP-complete problems. The importance of the TSP arises besides from its theoretical appeal from the variety of its applications. In addition to vehicle routing, many other applications, e.g., computer wiring, cutting wallpaper, job sequencing or several data visualization techniques, require the solution of a TSP. In this paper we introduce the R package TSP which provides a basic infrastructure for handling and solving the traveling salesperson problem. The package features S3 classes for specifying a TSP and its (possibly optimal) solution as well as several heuristics to find good solutions. In addition, it provides an interface to Concorde, one of the best exact TSP solvers currently available. (author's abstract)
Series: Research Report Series / Department of Statistics and Mathematics

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Hahsler, Michael, and Kurt Hornik. "TSP - Infrastructure for the Traveling Salesperson Problem." American Statistical Association, 2007. http://epub.wu.ac.at/3990/1/TSP.pdf.

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The traveling salesperson (or, salesman) problem (TSP) is a well known and important combinatorial optimization problem. The goal is to find the shortest tour that visits each city in a given list exactly once and then returns to the starting city. Despite this simple problem statement, solving the TSP is difficult since it belongs to the class of NP-complete problems. The importance of the TSP arises besides from its theoretical appeal from the variety of its applications. Typical applications in operations research include vehicle routing, computer wiring, cutting wallpaper and job sequencing. The main application in statistics is combinatorial data analysis, e.g., reordering rows and columns of data matrices or identifying clusters. In this paper, we introduce the R package TSP which provides a basic infrastructure for handling and solving the traveling salesperson problem. The package features S3 classes for specifying a TSP and its (possibly optimal) solution as well as several heuristics to find good solutions. In addition, it provides an interface to Concorde, one of the best exact TSP solvers currently available. (authors' abstract)

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Zhang, Jun. "Conception et réalisation de l'interface Moduleco-TSP." Paris 9, 1990. https://portail.bu.dauphine.fr/fileviewer/index.php?doc=1990PA090035.

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Cette thèse a pour objectif de concevoir et de réaliser l'interface entre le logiciel Moduleco et le logiciel TSP. Les principaux sujets abordés sont les suivants: 1) études approfondies de Moduleco-logiciel de modélisation macro-économique, et de TSP-logiciel de statistique et de calcul économétrique; 2) génération automatique de programmes TSP; 3) traduction des équations de syntaxe Moduleco en équations de syntaxe TSP; 4) récupération des résultats TSP dans Moduleco. Ce travail a été réalisé au sein du projet Moduleco de l'Inria-Rocquencourt

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Vella, Danielle. "Using DP-constraints to obtain improved TSP solutions." Thesis, University of Ottawa (Canada), 2001. http://hdl.handle.net/10393/6395.

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The Travelling Salesman Problem (TSP) is a well-known NP-hard problem. Although it is unlikely that an efficient algorithm will ever be found for the TSP, some success has been achieved for large real-world instances by using the branch and cut technique. This technique requires knowledge of classes of useful valid inequalities for the polytope associated with the TSP, as well as efficient separation routines for these classes of inequalities. The DP-constraints are a recently discovered class of valid inequalities for the TSP which contain the famous comb inequalities. An efficient separation routine is known for these constraints if certain conditions are satisfied by the point to be separated. This separation routine has never been implemented or tested. We present several performance enhancements that we made to the existing separation routine for these constraints and discuss our implementation of this improved algorithm. Our implementation runs in O(n3 lg n), where n is the number of vertices in the graph. We also show how the outcome of the separation routine can be translated into a DP-constraint that is in a suitable form for testing. We test our implementation and provide results that we believe show the usefulness of these inequalities and the separation routine within a branch and cut framework for the TSP.

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Kollin, Felix, and Adel Bavey. "Ant Colony Optimization Algorithms : Pheromone Techniques for TSP." Thesis, KTH, Skolan för datavetenskap och kommunikation (CSC), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-208374.

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Ant Colony Optimization (ACO) uses behaviour observed in real-life ant colonies in order to solve shortest path problems. Short paths are found with the use of pheromones, which allow ants to communicate indirectly. There are numerous pheromone distribution techniques for virtual ant systems and this thesis studies two of the most well known, Elitist and Max-Min. Implementations of Elitist and Max-Min ACO algorithms were tested using instances of the Traveling Salesman Problem (TSP). The performance of the different techniques are compared with respect to runtime, iterations and approximation quality when the optimal solution could not be found. It was found that the Elitist strategy performs better on small TSP instances where the number of possible paths are reduced. However, Max-Min proved to be more reliable and better performing when more paths could be chosen or size of the instances increased. When approximating solutions for large instances, Elitist was able to achieve high quality approximations faster than Max-Min. On the other hand, the overall quality of the approximations were better when Max-Min was studied after a slightly longer runtime, compared to Elitist.
Ant Colony Optimization (ACO) drar lärdom av beteende observerat hos riktiga myror för att lösa kortaste vägen problem. Korta vägar hittas med hjälp av feromoner, som tillåter myror att kommunicera indirekt. Det finns flera tekniker för att distribuera feromoner i virtuella myr-system och denna rapport kommer studera två av de mest kända, Elitist och Max-Min. Implementationer av Elitist och Max-Min ACO algoritmer testades med instanser av Handelsresandeproblemet (TSP). Prestandan hos de olika teknikerna jämförs med avseende på körtid, iterationer och approximeringskvalité när den optimala lösningen inte kunde hittas. Det konstaterades att Elitist strategin fungerar bättre på små TSP instanser där antalet möjliga stigar är begränsade. Däremot visade det sig Max-Min vara bättre och mer pålitlig när instansernas storlek ökades eller när fler stigar kunde väljas. När lösningar approximerades för stora instanser kunde Elitist uppnå approximationer med god kvalité snabbare än Max-Min. Däremot var den generella kvalitén hos approximationerna bättre när Max-Min studerades efter en lite längre körtid, jämfört med Elitist.

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Rohleder, Andreas. "Kandidatenmengen für das TSP : ein neuer heuristischer Ansatz /." Lohmar [u.a.] : Eul, 2006. http://deposit.d-nb.de/cgi-bin/dokserv?id=2837955&prov=M&dok_var=1&dok_ext=htm.

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Universiẗat, Diss., 2005 u.d.T.: Rohleder, Andreas: Ein Vorschlag zur Erzeugung von Kandidatenmengen zur Unterstützung der heuristischen Lösung des geometrischen zweidimensionalen Traveling Salesman Problems--Münster (Westfalen).

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Rohleder, Andreas. "Kandidatenmengen für das TSP ein neuer heuristischer Ansatz." Lohmar Köln Eul, 2005. http://deposit.d-nb.de/cgi-bin/dokserv?id=2837955&prov=M&dok_var=1&dok_ext=htm.

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Zugl.: Münster (Westfalen), Univ., Diss., 2005 u.d.T.: Rohleder, Andreas: Ein Vorschlag zur Erzeugung von Kandidatenmengen zur Unterstützung der heuristischen Lösung des geometrischen zweidimensionalen Traveling Salesman Problems

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Martins, Fabiana Martins e. "Avaliação clínica de alterações bucais em pacientes soropositivos para o HTLV." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-09042009-113747/.

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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).

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Lima, Marcus Vinícius Alves. "Avaliação fenotípica e funcional dos linfócitos T citotóxicos de indivíduos infectados pelo HTLV-1 com diagnóstico de HAM/TSP." Centro de Pesquisas Gonçalo Moniz, 2014. https://www.arca.fiocruz.br/handle/icict/8689.

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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.

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Nicolete, Larissa Deadame de Figueiredo. "Papel dos microRNAs humanos na infecção pelo HTLV-1." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-02032009-112507/.

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MicroRNAs (miRNAs) são RNA de fita simples (22 nucleotídeos) que atuam como reguladores da expressão gênica celular. Estudos recentes têm demonstrado o papel dos miRNAs como moduladores da resposta celular frente às infecções virais. O vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) é um retrovírus que apresenta genes estruturais comuns aos demais, além dos genes tax e rex, os quais dão origem às proteínas regulatórias. Entre elas, destaca-se a oncoproteína Tax, que é capaz de modular a expressão de genes celulares e virais, além de estar associada ao desencadeamento de patologias. Destacam-se duas manifestações clínicas associadas: a leucemia/linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV/paraparesia espástica tropical (HAM/TSP). Fatores relacionados ao hospedeiro também estão correlacionados ao aparecimento das patologias. No intuito de estabelecer se miRNAs humanos podem influenciar em processos celulares que se encontram desregulados pela Tax (diferenciação, transdução de sinais, apoptose, proliferação celular e tumorigênese), o objetivo deste projeto foi analisar a expressão de miRNAs em células mononucleares de sangue periférico (PBMC) de indivíduos infectados HTLV-1. Para tanto, realizamos análises in silico para mapear alvos de miRNAs humanos no gene tax do HTLV-1. Foram utilizados dois algoritmos (miRanda e RNAhybrid), com os seguintes parâmetros: score de 120 na região da semente; energia livre de até -15 kcal/mol. Assim, selecionou-se os hsa-miRNAs:149a, 648, 221, 222, 142-5p, 26a, 29a, 374 e 125b. Adicionalmente, foi observado que as regiões do gene tax, onde se ligam os miRNAs selecionados, são extremamente conservadas entre os diferentes subtipos de HTLV-1. Após estas análises in silico, realizou-se a validação dos miRNAs eleitos. Para tanto, foram isolados PBMC de 21 amostras de indivíduos-controle (CT), 10 portadores assintomáticos do HTLV-1 (HAC) e 12 com HAM/TSP (HAM). Do total de células, 1x106 tiveram seu DNA genômico extraído para quantificação da carga proviral (CPV) pela metodologia de PCR quantitativo em tempo real (qRT-PCR); 1x106 foram criopreservadas para quantificação de Tax por citometria de fluxo; 1x 107células foram utilizadas na extração de RNA para validação dos miRNAs por qRT-PCR. A fase orgânica do Trizol® foi utilizada para extração de proteínas totais e posterior análise da expressão de Tax por Western blot. A CPV apresentou-se significativamente aumentada (p= 0,0046) no grupo HAM, quando utilizado teste de Mann-Whitney. A expressão de Tax apresentou correlação significativa (p=0,0128) com a CPV, pelo teste de Spearmann e auxiliou na caracterização dos pacientes. O nível de expressão dos miRNAs foi avaliado nos grupos: CT vs Pacientes e CT vs HAC vs HAM por testes não-paramétricos de Mann-Whitney e Kruskal-wallis, respectivamente. Os miRNAs se mostraram desregulados no grupo de pacientes quando comparado ao grupo CT. Dentre estes, o hsa-miR-125b encontra-se aumentado significativamente no grupo de pacientes em relação ao controle (p=0,0285). Utilizou-se o teste de correlação de Spearmann, para associar a expressão de Tax com os miRNAs, porém os resultados encontrados não foram significativos. Apesar de não estar correlacionado com expressão de Tax, o hsa-miR-125b é responsável pela regulação de diversas proteínas, como TNF-, uma proteína inflamatória hiper-expressa em portadores do HTLV-1. Deste modo, acreditamos que este miRNA estaria aumentado proporcionalmente na tentativa de inibir a tradução desta proteína. Os resultados deste projeto sugerem a importância de esclarecer como os miRNAs humanos podem regular a infecção pelo HTLV-1 e gerar informações para o desenvolvimento de estratégias que possam interferir com a replicação e patogênese viral.
MicroRNAs (miRNAs) are simple strand RNA (22 nucleotides), which are regulators of cellular gene expression. Recent studies have been showed miRNAs role as modulators of cellular responses, when viral infection occurs. The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that presents the same regular structural genes compared to the other retrovirus, besides tax and rex genes, which encode regulatory proteins. In regard to this, Tax oncoprotein is a major determinant of viral persistence and pathogenesis. Two major diseases are related to this virus adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Host-related factors are also correlated with HAM/TSP development. To establish if human miRNAs could influence in the unregulated cellular process caused by Tax (differentiation, signal transduction, apoptosis, cellular proliferation and tumorigenesis), this study analyzed miRNA expression in peripheral blood mononuclear cells (PBMCs) from HTLV-1 infected patients. For this purpose, we performed in silico analyses to find human miRNAs that could targeted HTLV-1 tax region. We performed two algorithms (miRanda e RNAhybrid) and we set up two distinct parameters: score more than 120 in the seed region and minimum free energy until -15 kcal/mol. So, we have selected these hsa-miRNAs:149a, 648, 221, 222, 142-5p, 26a, 29a, 374 e 125b. Besides this, we compared several HTLV-1 sub-types and we observed that regions, where miRNAs are regulating, are extremely conserved. After the in silico analysis, we validated miRNAs that we have been chosen. We isolated PBMC samples from 21 control-individuals (CT), 10 from asymptomatic carriers and 12 from HAM/TSP (HAM). After the procedure, genomic DNA were extracted from 1x106 cells, in order to quantify the proviral load (PL) performing quantitative Real-Time PCR (qRT-PCR). Tax was measured by flow cytometry and for this procedure, we used 1x106 criopreserved cells. Amount 1x 107cells were used to total RNA extraction that was used to miRNAs validation by qRT-PCR. The organic phase from Trizol® was employed to extract total proteins, which were used to analyze Tax expression by Western blot. The PL was significantly higher in HAM group than HAC (p= 0,0046), when Mann-Whitney statistical test was employed. The Tax expression was significantly correlated to PL (p=0,0128) by Spearmann test and this finding provided us a better characterization of the patients. The miRNAs expression was detected in the following groups: CT vs Patients and CT vs HAC vs HAM by non-parametrical tests Mann-Whitney and Kruskal-wallis, respectively. The miRNAs presented unregulated themselves in the patient group, when we compared to CT group. We observed that hsa-miR-125b expression are significantly higher in patients group than controls (p=0,0285). We have tried to associate miRNAs with Tax expression, employing Spearmann test, but this analysis did not show significant values. Despite this, hsa-miR-125b is responsible for regulating several proteins, such as TNF-, which is an inflammatory protein overexpressed in HTLV-1 carriers. In conclusion, we propose that this miRNA could be increased as a way to inhibit TNF- translation. These results suggest the importance in understanding how human miRNAs could regulated the HTLV-1 infection. In addition to this, they could generate data to be used as therapeutic strategies for the control of viral replication and pathogenic processes.

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18

Costa, Giselle Calasans de Souza. "Investigação de polimorfismos no gene humano da glut1: correlação com a infecção pelo HTLV-1." reponame:Repositório Institucional da FIOCRUZ, 2008. https://www.arca.fiocruz.br/handle/icict/4216.

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Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-19T20:54:41Z No. of bitstreams: 1 Giselle Calasans de Souza Costa. Investigação de Polimorfismos no gene humano da Glut1 - CPqGM - Dissertação de Mestrado - 2008.pdf: 901999 bytes, checksum: f8d18c6846f38a411006c2e451309767 (MD5)
Made available in DSpace on 2012-07-19T20:54:41Z (GMT). No. of bitstreams: 1 Giselle Calasans de Souza Costa. Investigação de Polimorfismos no gene humano da Glut1 - CPqGM - Dissertação de Mestrado - 2008.pdf: 901999 bytes, checksum: f8d18c6846f38a411006c2e451309767 (MD5) Previous issue date: 2008
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil
O HTLV-1 é o agente etiológico da Paraparesia Espástica Tropical/Mielopatia Associada ao HTLV-1 (TSP/HAM) e da Leucemia/Linfoma das Células T do Adulto (ATLL). No entanto, o desenvolvimento de manifestações clínicas associadas ao HTLV-1 ocorre em 2-4% da população infectada e ainda não se sabe por que esta infecção permanece assintomática na maioria dos portadores. Tem sido sugerido que o desfecho da infecção pode ocorrer devido a variações (mutações) em genes do hospedeiro e/ou do vírus. Recentemente, foi demonstrado que o HTLV é capaz de utilizar a glicoproteína transportadora de glicose do tipo 1 (GLUT1) para infectar linfócitos T CD4+. Diversos estudos têm demonstrado uma associação entre mutações em regiões regulatórias de genes humanos e manifestação de doença. Polimorfismos no gene da GLUT1 foram associados à susceptibilidade a nefropatia diabética, em pacientes com diabetes mellitus dos tipos 1 e 2 em diferentes populações. Com o objetivo de verificar possíveis correlações entre polimorfismos nas regiões regulatórias e codificante do gene humano da GLUT1 com o desenvolvimento de TSP/HAM, analisamos os polimorfismos -2841A>T, XbaIG>T e HaeIIIT>C em indivíduos infectados pelo HTLV-1 e em indivíduos não-infectados de Salvador. Os SNPs XbaIG>T e HaeIIIT>C foram verificados por PCR/RFLP e o SNP -2841A>T, por seqüenciamento. Além disso, a carga proviral do HTLV-1 foi quantificada por PCR quantitativo em tempo real. Com o intuito de verificar a freqüência dos polimorfismos em GLUT1 na população brasileira com diferentes etnias, foi realizada a análise dos polimorfismos XbaIG>T e HaeIIIT>C em Ameríndios da tribo Tiriyó; descendentes de europeus da região Sul do Brasil; descendentes de japoneses, descendentes de europeus e afro-descendentes da região Sudeste. As freqüências genotípicas para os polimorfismos analisados estavam de acordo com o esperado pelo Equilíbrio de Hardy- Weinberg. O polimorfismo HaeIIIT>C estava em desequilíbrio de ligação com os polimorfismos XbaIG>T (χ2=37,555, p=0,003, 4 d.f.) e -2841A>T (χ2=∞, p=0,000, 4 d.f.). A freqüência do genótipo T/T do polimorfismo XbaIG>T foi mais elevada nos indivíduos assintomáticos e com TSP/HAM do que nos indivíduos oligosintomáticos. Em relação ao polimorfismo HaeIIIT>C, nós observamos uma maior freqüência do genótipo T/C nos pacientes com TSP/HAM. Quanto ao polimorfismo -2841A>T, foi verificada uma distribuição similar dos genótipos analisados em todos os grupos estudados. Não foram observadas diferenças estatisticamente significantes nas distribuições genotípicas e alélicas entre os indivíduos infectados e não-infectados pelo HTLV-1, assim como em relação ao status clínico dos pacientes infectados pelo HTLV- 1 nos polimorfismos XbaIG>T, HaeIIIT>C e -2841A>T. Em relação ao seqüenciamento de 339pb da região promotora de GLUT1, foi observada uma nova mutação G>T na posição -2807 em 6 indivíduos (1 assintomático, 2 com TSP/HAM e 3 não-infectados), caracterizando esta mutação como um polimorfismo. Nossos resultados indicam que os polimorfismos XbaIG>T, HaeIIIT>C e -2841A>T, apesar de, possivelmente, estarem relacionados com a entrada de glicose na célula (XbaIG>T e -2841A>T) não estão relacionados com a infecção pelo HTLV-1 nem com o desenvolvimento de TSP/HAM, sugerindo que as diferentes atividades realizadas pela proteína GLUT1 (transporte de glicose e recepção do HTLV-1) são mediadas por diferentes domínios da mesma. Quanto ao estudo de base populacional, nós confirmamos que as freqüências alélicas dos polimorfismos XbaIG>T e HaeIIIT>C variaram de acordo com a etnia.
The HTLV-1 is the etiological agent of Tropical spastic paraparesis/HTLV-1 associated mielopathy (TSP/HAM) and Adult T cell leukemia/lymphoma (ATLL). However, the development of HTLV-1 associated clinic manifestations occurs in 2-4% of the infected population and it is still an answered question why this infection remains asymptomatic at the most of the infected carriers. It has been suggested that the outcome of HTLV-1 associated disease manifestations may occur by individual and/or viral genetic variations (mutations). Recently, it was demonstrated that HTLV is able to use the Glucose transporter type 1 (GLUT1) to infect T CD4+ lymphocytes. Many studies have demonstrating an association between mutations in regulatory regions of human genes and disease manifestations. Polymorphisms in the GLUT1 gene were associated with susceptibility to diabetic nephropathy in patients with types 1 and 2 diabetes mellitus in different populations. To evaluate the role of GLUT1 gene polymorphisms in the development of TSP/HAM in HTLV-1 infected individuals, we had analyzed the -2841A>T, XbaIG>T and HaeIIIT>C polymorphisms in HTLV-1 infected and non-infected individuals from Salvador. The XbaIG>T and HaeIIIT>C SNP were analyzed by PCR/RFLP and the -2841A>T polymorphism, by sequencing. The proviral load of the HTLV-1 infected patients was analyzed by Real Time Quantitative PCR. We also analyzed the XbaIG>T and HaeIIIT>C polymorphisms in distinct Brazilian populations with different ethnic backgrounds: Amerindians from Tiriyó tribe, European descendants from Brazil South region; Japanese descendants, Europeans descendants and African descendants from Southeast region. Genotypic frequencies of the polymorphisms analyzed were in agreement with the expected by the Hardy-Weinberg Equilibrium. The HaeIIIT>C polymorphism was in linkage disequilibrium with the XbaIG>T (χ2=37.555, p=0.003, 4d.f.) and -2841A>T polymorphisms (χ2=∞, p=0.000, 4d.f.). T/T genotypic frequency of the XbaIG>T polymorphism was higher in asymptomatic and TSP/HAM individuals than in oligosymptomatics. Concerned to the HaeIIIT>C polymorphism, we observed a higher frequency of the T/C genotype in TSP/HAM patients. In relation to the -2841A>T polymorphism, it was verified a similar distribution of the analyzed genotypes in all studied groups. Genotypic and allelic frequencies of the three sites analyzed did not differ significantly for controls and HTLV-1 infected individuals. There were no differences in genotypic and allelic distribution among patients for either the presence or absence of HTLV-1 associated clinic manifestations. In relation to the sequencing of 339 bp of GLUT1 promoter region, it was observed a new mutation G>T at -2807 position in 6 individuals (1 asymptomatic, 2 with TSP/HAM and 3 non-infected). Regarding the quantification of the provirus load according to GLUT1 genotypes, we did not observe any differences. These results suggest that the XbaIG>T, HaeIIIT>C and -2841A>T polymorphisms, although possibly related with cell glucose entry (XbaIG>T and -2841A>T), do not contribute to HTLV-1 infection and to the genetic susceptibility of TSP/HAM in Brazilian HTLV-1 infected individuals, suggesting that different activities performed by GLUT1 protein (glucose transport and HTLV-1 entry) are mediated by its different domains. Concerned to the population study, we confirmed that the allelic frequencies from the XbaIG>T and HaeIIIT>C are influenced by ethnicity among the six Brazilian ethnic groups studied.

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Jeanne, Albin. "Interactions moléculaires TSP1 : CD47 : identification de nouveaux antagonistes à visée thérapeutique." Thesis, Reims, 2013. http://www.theses.fr/2013REIMS043.

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La thrombospondine-1 (TSP-1) est une glycoprotéine multi-modulaire exprimée de façon ubiquitaire qui régule de nombreux processus pathophysiologiques tels que l'adhérence cellulaire, la prolifération, l'apoptose, l'inflammation et les réponses cardiovasculaires. La TSP-1 est reconnue comme un acteur moléculaire majeur au sein du microenvironnement tumoral et constitue une cible de choix pour le développement d'agents thérapeutiques anti- cancéreux. L'interaction de la TSP-1 avec le récepteur membranaire CD47 est largement rapportée comme étant impliquée dans la progression tumorale et la mise en place d'une résistance aux traitements chiomiothérapeutiques. De ce fait, nous avons cherché à identifier et à caractériser un agent moléculaire novateur se comportant comme antagoniste sélectif de l'interaction TSP-1:CD47. Des expériences de docking protéine-protéine et de simulation moléculaire ont été réalisées afin de concevoir un nouveau peptide dérivé du CD47, nommé TAX2. Le peptide TAX2 empêche l'interaction de la TSP-1 avec le CD47, comme cela a été confirmé par co-immunoprécipitation et test ELISA. De manière intéressante, le peptide TAX2 inhibe la migration des cellules endothéliales, la formation de structures multi- cellulaires de type capillaire ainsi que le développement de micro-vaisseaux à partir d'explants aortiques. De façon cohérente avec ces observations, nos résultats mettent en évidence que le peptide TAX2 promeut la liaison de la TSP-1 au sein de complexes moléculaires comprenant le récepteur CD36, et inhibe en conséquence la voie de signalisation associée au VEGF et au VEGFR2. Enfin, une approche d'imagerie multi-modale et multi-échelles combinant des marquages histologiques, l'analyse de la densité micro-vasculaire, des analyses d'imagerie de résonance magnétique et d'imagerie infra-rouge à transformée de Fourier, ainsi qu'un suivi longitudinal par micro-tomographie à rayons X a été conduite afin de quantifier l'angiographie tumorale in vivo. Les résultats obtenus chez la souris C57Bl/6 révèlent que des administrations intra-péritonéales du peptide TAX2 perturbent fortement le réseau vasculaire associé à la tumeur de mélanome et induisent une importante nécrose tumorale entrainant l'effondrement de la tumeur. De plus, nous avons démontré que le peptide TAX2 inhibe considérablement la dissémination métastatique sans affecter les organes sains. Nous avons donc identifié le premier antagoniste sélectif de l'interaction TSP-1:CD47 qui, en contournant le problème des molécules existantes ciblant aveuglément le CD47, présente des activités anti-angiogéniques, anti-tumorales et anti-métastatiques in vivo qui pourraient à terme fournir de nouvelles approches thérapeutiques en pathologie tumorale
Thrombospondin-1 (TSP-1) is a ubiquitously expressed multi-modular glycoprotein involved in many pathophysiological processes including regulation of cell adhesion, proliferation, apoptosis, inflammation and cardiovascular response. TSP-1 is recognized as a major molecular actor within tumor microenvironment and constitutes an exciting target for the development of useful therapeutic agents against tumorigenesis. TSP-1 binding to CD47 membrane receptors is widely reported to support tumor progression and may drive chemotherapeutic drug resistance. Thus, we sought to identify and characterize an innovative molecular agent acting as selective antagonist for TSP-1:CD47 interaction. Protein-protein docking and molecular dynamics simulations were conducted to design a novel CD47-derived peptide, called TAX2. TAX2 prevents TSP-1 binding to CD47, as revealed by ELISA binding assays and co-immunoprecipitation experiments. Interestingly, TAX2 inhibits endothelial cell migration, formation of multi-cellular capillary-like structures and sprouting of microvessels from aortic explants. Consistently, our data highlighted that TAX2 peptide promotes TSP-1 binding to CD36-containing complexes, leading to disruption of VEGF/VEGFR2 signaling. Furthermore, a multi-modal and multi-scale imaging approach was conducted combining histopathological staining, tumor-associated microvessel density, magnetic resonance imaging analysis, Fourier transform infrared imaging and micro-computed tomography monitoring for 3D quantification and longitudinal follow-up of tumor angiography in vivo. The results obtained from C57Bl/6 mice revealed that intraperitoneal administration of TAX2 highly disturbs melanoma tumor vascularization network, inducing an extensive tumor necrosis and subsequent tumor collapse. Furthermore, we demonstrated that TAX2 drastically inhibits the melanoma lung metastases dissemination without affecting healthy organs. Overall, we designed the first selective antagonist for TSP-1:CD47 interaction. By bypassing the problem of existing molecules blindly targeting CD47, we revealed that TAX2 exhibits anti- angiogenic, anti-tumor and anti-metastatic activities in vivo that could supply new innovative therapeutic approaches against malignant diseases

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Fu, Yao. "Applications of Circulations and Removable Pairings to TSP and 2ECSS." Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31078.

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In this thesis we focus on two NP-hard and intensively studied problems: The travelling salesman problem (TSP), which aims to find a minimum cost tour that visits every node exactly once in a complete weighted graph, and the 2-edge-connected spanning subgraph problem (2ECSS), which aims to find a minimum size 2-edge-connected spanning subgraph in a given graph. TSP and 2ECSS have many real world applications. However, both problems are NP-hard which means it is unlikely that polynomial time algorithms exist to solve them, so methods that return close to optimal solutions are sought. In this thesis we mainly focus on k-approximation algorithms for the two problems, which efficiently return a solution within k times of the optimal solution. For a special case of TSP called graph TSP, using ideas from Momke and Svensson, we present a 25/18-approximation algorithm for a special class of graphs using circulations and T-joins, which improves the previous known best bound of 7/5 for such graphs. Moreover, if the graph does not contain special nodes, our algorithm ensures the ratio of 4/3. For 2ECSS, given any k-edge-connected graph G=(V,E), |V|=n, |E|=m, we present an approximation algorithm that gives a 2-edge-connected spanning subgraph with the number of edges at most n+(m-n)/(k-1)-(k-2)/(k-1) with a novel use of circulations, which improves both the approximation ratio and the simplicity of the proof compared to a result by Huh in 2004.

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21

Fraga, Igor Ives Santos. "F811aAssociação dos genes KIR2DL2/KIR2DL3 e alelos HLA-C do grupo 1 com a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP)." reponame:Repositório Institucional da FIOCRUZ, 2014. https://www.arca.fiocruz.br/handle/icict/11405.

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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
O controle da carga proviral do HTLV-1 depende em parte da lise de células infectadas por células citotóxicas mediada pelos linfócitos T CD8⁺ e pelas células NK (Natural killer). A família de receptores KIR (killer-cell immunoglobulin-like receptor) interage com as moléculas de HLA de classe I, principalmente os alelos do HLA C do grupo 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 e C*16), ativando ou inibindo a função destas células.O objetivo do presente estudo foi avaliar se os genes KIR2DL2/KIR2DL3 e os alelos de HLA-C do grupo 1 estão associados ao controle da carga proviral do HTLV-1 e ao diagnóstico de HAM/TSP. O estudo foi realizado no Centro de HTLV da Escola Bahiana de Medicina e Saúde Púbica, em Salvador-Bahia. A presença dos genes KIR2DL2 e KIR2DL3 foi determinada por PCR em tempo real (Syber Green). Foram incluídos 248 indivíduos infectados pelo HTLV-1 (161 assintomáticos e 87 com HAM/TSP) cujos alelos de HLA de classe I haviam sido previamente determinados. A carga proviral (quantificada por PCR em tempo real) e as frequências de indivíduos assintomáticos e com diagnóstico de HAM/TSP (Possível, Provável e Definido) foram comparadas de acordo com a presença ou ausência dos genes KIR avaliados. As frequências dos genes KIR2DL2 e KIR2DL3 foi 84,3% e 96,8%, respectivamente. Não foram observadas diferenças estatisticamente significantes na frequência de indivíduos que possuíam os genes (KIR2DL2 ou KIR2DL3) nos grupos clínicos, assim como na frequência de indivíduos que tinham simultaneamente os genes KIR e os alelos de HLA-C do grupo 1. Os indivíduos do grupo HAM/TSP possível que apresentavam o gene KIR2DL2 tinham menor carga proviral (2,9% de células infectadas) que os indivíduos sem este gene (19,2% de células infectadas) (p<0,001). Quando avaliamos a combinação da presença do gene KIR2DL2 com os alelos de HLA-C do grupo 1, menor carga proviral (2,1%) foi observada nos indivíduos que apresentavam algum dos alelos de HLA-C do grupo 1,comparados aqueles que portavam apenas KIR2DL2 (5,0%) (p=0,013). Menor carga proviral também foi observada nos indivíduos assintomáticos que portavam simultaneamente o gene KIR2DL2 e o alelo HLA-C*07, comparados aos indivíduos com apenas o gene KIR2DL2 (p=0,03), enquanto que os indivíduos com HAM/TSP-PB que tinham essa combinação (KIR2DL2/HLA-C*07) apresentaram tendência de menor carga proviral (p=0,051). Em conclusão, a presença da combinação do gene KIR2DL2 e de algum alelo de HLA-C do grupo 1 está associada ao controle da carga proviral. Este estudo quantificou pela primeira vez as frequências de genes KIR em uma coorte de indivíduos infectados pelo HTLV-1 do estado da Bahia. Estudos futuros são necessários para confirmar estes achados em outras populações e avaliar o valor prognóstico da associação de KIR2DL2 e HLA-C do grupo 1.
The control of proviral load of HTLV-1 depends in part of the lysis of infected cells mediated by cytotoxic CD8⁺T lymphocytes and NK (Natural killer) cells. The family of KIR (killer-cell immunoglobulin-like receptor) interacts with HLA class I molecules, especially those HLA-C alleles in-group 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 and C*16) by activating or inhibiting the function of these cells. The aim of this study was to evaluate if the KIR2DL2, KIR2DL3 genes and group 1 HLA-C alleles are associated with the control of proviral load of HTLV-1 and the diagnosis of HAM/TSP. The study was performed at Bahiana School HTLV Center of Medicine and Health Public, in Salvador, Bahia. The presence of KIR2DL2 and KIR2DL3 genes was determined by real-time PCR (Syber Green). The study included 248 subjects infected with HTLV-1(161 and 87 asymptomatic with HAM/TSP) whose HLA class I alleles were previously determined. The proviral load (quantified by real-time PCR) and the frequency asymptomatic individuals diagnosed with HAM/TSP (possibly, probably and definitive) were compared according to the presence or absence of KIR genes evaluated. The frequencies of KIR2DL2 and KIR2DL3 genes were 84.3% and 96.8%, respectively. No statistically significant differences were observed in the frequency of individuals who possessed the genes (KIR2DL2 or KIR2DL3) in clinical groups, as well as the frequency of individuals who had both the KIR genes and HLA-C alleles group 1. Individuals in the group HAM/TSP possible to KIR2DL2 showed that the gene had lower proviral load (2.9%of cells infected) individuals without this gene (19.2% infected cells) (p<0.001). When we evaluated the combination of the presence of KIR2DL2 and 2DL3 genes with HLA-C genes in group 1, lower proviral load (2.1%) was observed in individuals with any of the alleles of HLA-C group 1, compared who those which harbored only KIR2DL2 (5.0%) (p=0.013) .Minor proviral load was also observed in asymptomatic individuals which carried both the KIR2DL2 gene and HLA-C*07 allele when compared to individuals with only KIR2DL2 gene (p=0.03), whereas patients with HAM/TSP-PB that had this combination (KIR2DL2/HLA-C*07) tended to lower proviral load(p=0.051). In conclusion, the presence of the combination of KIR2DL2 gene and a HLA-C group1allele is associated with proviral load control. This study quantified for the first time the frequencies of KIR genes in a cohort of individuals infected with HTLV-1 in Bahia. Future studies are needed to confirm these findings in other populations and to evaluate the prognostic value of KIR2DL2 association and HLA-C group 1.

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Pinto, Mariana Tomazini. "Perfil de expressão gênica de linfócitos T CD4+ na infecção pelo HTLV-1." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-08082011-135045/.

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O vírus linfotrópico de células T humanas tipo 1 (HTLV-1) está associado etiologicamente à duas principais manifestações clínicas: a leucemia/linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV-1 ou paraparesia espástica tropical (HAM/TSP). Apenas 2 a 5% dos indivíduos infectados desenvolvem doenças associadas ao vírus, enquanto a maioria permanece assintomática. A HAM/TSP é uma manifestação inflamatória do sistema nervoso central e o mecanismo pelo qual o HTLV-1 induz o surgimento de HAM/TSP ainda não está totalmente esclarecido. Os linfócitos T CD4+ são os principais reservatórios do HTLV-1 in vivo e possuem uma participação importante na resposta imunológica dirigida a este retrovírus. Essas células são ativadas precocemente durante a infecção pelo HTLV-1 e auxiliam na resposta dos linfócitos T CD8 citotóxicos (CTLs), bem como na produção de anticorpos. No presente estudo, foi avaliado o perfil de expressão gênica global dos linfócitos T CD4+ isolados de portadores assintomáticos (HAC), pacientes com HAM/TSP e de indivíduos sadios (CT) por meio da metodologia de microarray. Os linfócitos T CD4+ utilizados foram isolados por separação imunomagnética e foram realizados microarrays de doze amostras individuais: quatro amostras do grupo CT, quatro amostras do grupo HAC e quatro do grupo HAM/TSP. Os dois últimos grupos continham duas amostras com alta e duas com baixa expressão da proteína Tax. As análises de agrupamento hierárquico revelaram que o perfil de expressão gênica dos indivíduos infectados pelo HTLV-1 difere dos indivíduos do grupo CT pela formação de dois agrupamentos distintos. Ademais, os indivíduos infectados pelo HTLV-1 se agruparam de acordo com o estado clínico e independente da expressão de Tax. Foram realizadas as comparações entre os grupos CT vs. HAC, CT vs. HAM/TSP e HAM/TSP vs. HAC e os dados demonstraram que 221, 254 e 70 genes estavam diferencialmente expressos, respectivamente. Além disso, foram observados 86 genes presentes nas intersecções entre CT vs. HAC x CT vs. HAM/TSP, 25 genes entre CT vs. HAM/TSP x HAM/TSP vs. HAC e apenas um gene entre CT vs. HAC x CT vs. HAM/TSP. Estes genes diferencialmente expressos estavam associados à citocinas, lise e migração celular. Os achados foram validados por PCR quantitativo em um total de 23 indivíduos assintomáticos, 17 com HAM/TSP e 25 indivíduos sadios. A validação evidenciou o aumento da expressão dos genes PXN, CXCR4, PRF1 e Foxp3 no grupo HAM/TSP em relação ao grupo HAC, além do aumento de IL-27 nos indivíduos do grupo HAC comparados com os indivíduos do grupo HAM/TSP. Adicionalmente, foi realizada a quantificação dos níveis protéicos de PRF1, GZMB, CXCR4 por citometria de fluxo. Entretanto, nenhuma diferença foi observada entre os diferentes grupos analisados. Ainda, por meio de citometria de fluxo, a população de células CD3+CD4+CD25hiFoxp3+, bem como CD4+Foxp3+ foram analisadas e observou-se maiores níveis de expressão de CD4+Foxp3+ nos indivíduos infectados pelo HTLV-1. A porcentagem de células CD3+CD4+CD25hiFoxp3+ não mostrou diferença significativa entre os três grupos comparados. Os resultados evidenciados neste projeto ressaltam a importância das células CD4+ no controle da resposta imune contra a infecção pelo HTLV-1. O aumento na expressão gênica de PXN e CXCR4, que fazem parte da via de sinalização de CXCR4, sugere a ocorrência de migração celular nos indivíduos com HAM/TSP, provavelmente para o SNC. Além disso, o aumento das células Treg parecem suprimir a atividade das células T CD8+ pela via perforina/granzima, que por sua vez aumentaria a carga proviral, aumentando assim o risco de desenvolvimento de HAM/TSP.
Human T-cell lymphotropic vírus type 1 (HTLV-1) is etiologically associated with two major diseases: the adult T cell lymphoma/leukaemia (ATLL) and the HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). About 2 to 5% of infected individuals will develop HTLV-1-related diseases, while the majority remains life-long asymptomatic carriers of the virus. HAM/TSP is an inflammatory manifestation of central nervous system and the mechanism involved in HAM/TSP development is not well elucidated. CD4+ T cells are the predominant subset of cells infected with HTLV-1 in vivo and they are also important as effector cells against the infection. These cells are early activated during infection with HTLV-1 and assist the response of CD8 cytotoxic T lymphocytes (CTLs) and antibody production. To identify genes differentially expressed among non-infected individuals (CT), asymptomatic (HAC) and HAM/TSP patients we applied the microarray using CD4+ T cells isolated from these individuals. The CD4+ T lymphocytes were isolated by magnetic cell separation system and twelve samples underwent microarray analysis, as follows: 4 CT, 4 HAC and 4 HAM/TSP samples. Two samples had high tax expression and two samples had low tax expression for both infected groups. The hierarchical clustering analysis showed that the gene expression profile of infected individuals is distinct from healthy individuals because two separate clusters were observed. HTLV-1-infected individuals clustering meets with patients clinical status. However, HTLV-1 CD4+ T cells clustering did not correlate with Tax protein expression. We found 221 genes differently expressed between CT and HAC groups, 254 genes between CT and HAM/TSP and 70 genes between HAC and HAM/TSP. Moreover, we observed 86 genes differently expressed in the intersections between CT vs. HAC x CT vs. HAM/TSP, 25 genes between CT vs. HAM/TSP x HAM/TSP vs. HAC and only one gene between CT vs. HAC x CT vs. HAM/TSP. These genes were associated with cytokines, cell lysis and cell migration. These results were validated by quantitative PCR in 23 HTLV-1 asymptomatic carriers, 17 patients with HAM/TSP and 25 healthy individuals. The validation revealed increased levels of expression of the genes PXN, CXCR4, PRF1, and Foxp3 in the HAM/TSP group compared with HAC group. IL-27 gene expression was increased in HAC group when compared with HAM/TSP group. Additionally, we performed the protein quantification of PRF1, GZMB, and CXCR4 by flow cytometry. However, no difference was observed among the three groups. We also analyzed CD3+CD4+CD25hiFoxp3+ and CD4+Foxp3+ populations by flow cytometry. There was an increase of CD4+Foxp3+ expression in HTLV-1-infected individual. No differences were observed in CD3+CD4+CD25hiFoxp3+ population among the three groups. The results shown in this project highlight the importance of CD4+ cells in controlling the immune response against HTLV-1. The gene expression profile of PXN and CXCR4 was increased. These genes are related to CXCR4 signaling pathway that can result in CD4+ T cells migration, probably to the central nervous system. It is also suggested that Treg cells can suppress the T CD8+ activity through perforin/granzyme pathway. This pathway enhances the proviral load increasing the risk of HAM/TSP development.

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Pereira, Tathiane Maistro Malta. "Análise do perfil de expressão gênica em linfócitos T CD8+ isolados de pacientes infectados pelo HTLV-1." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-21082009-092402/.

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MALTA, T.M. Análise do perfil de expressão gênica em linfócitos T CD8+ isolados de pacientes infectados pelo HTLV-1. 2009. 137f. Dissertação de Mestrado. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, 2009. O vírus linfotrópico de células T humanas tipo 1 (HTLV-1) foi o primeiro retrovírus humano descrito e está etiologicamente associado a duas principais manifestações clínicas: a leucemia ou linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV-1 ou paraparesia espástica tropical (HAM/TSP). É estimado que 3 a 5% das pessoas infectadas pelo HTLV-1 desenvolvem as doenças associadas, enquanto a maioria permanece assintomática. A HAM/TSP é uma manifestação inflamatória do sistema nervoso central e o mecanismo pelo qual o HTLV-1 induz o surgimento de HAM/TSP ainda é questão de debate. Os linfócitos T CD8+ citotóxicos (CTL) têm uma participação importante na resposta imunológica dirigida contra o HTLV-1 e a eficiência com que as CTLs eliminam as células infectadas pelo vírus está relacionada com a carga proviral (CPV) do indivíduo e consequentemente com o risco de desenvolvimento de HAM/TSP. No presente trabalho, foram avaliados os perfis de expressão gênica de linfócitos T CD8+ isolados de portadores assintomáticos (HAC), pacientes com HAM/TSP (HAM/TSP) e de indivíduos sadios (CT) por meio da metodologia de Serial Analysis of Gene Expression (SAGE). Os linfócitos T CD8+ utilizados foram isolados por meio de separação imunomagnética e um pool composto de quatro indivíduos infectados para cada grupo, HAC e HAM/TSP foi utilizado para a construção das bibliotecas. A análise do SAGE resultou num total de 51.017, 62.432 e 60.620 tags sequenciadas para as bibliotecas CT, HAC e HAM/TSP, respectivamente, o que permitiu a identificação de aproximadamente 12.000 transcritos diferentes em cada biblioteca. Foram identificados cerca de 900 genes diferencialmente expressos entre as bibliotecas CT e HAC ou HAM/TSP. A comparação dos grupos HAC e HAM/TSP revelou 290 genes. Um grande número destes genes diferencialmente expressos está envolvido com os processos de apoptose, adesão e migração celular. Os achados foram validados pela metodologia de PCR em tempo real em um total de 17 indivíduos assintomáticos, 14 com HAM/TSP e 24 indivíduos sadios. A validação evidenciou o aumento da expressão dos genes envolvidos na lise mediada por células PRF1, GZMB e GZMH, além do aumento de CCL5, ZAP70 e PXN nos indivíduos infectados pelo HTLV-1. Além disso, os resultados mostraram redução nos níveis de expressão de CXCR4 nesses pacientes. Adicionalmente, foi realizada a quantificação dos níveis protéicos de PRF1 e GZMB por citometria de fluxo e os resultados corroboraram com a PCR em tempo real. O perfil gênico dos linfócitos T CD8+ demonstrou a ocorrência de intensa ativação e migração celular durante a infecção pelo HTLV-1. Essas evidências indicam que as células CD8+ dos indivíduos infectados pelo HTLV-1 parecem contribuir mais para a proteção e controle da infecção pelo vírus, e menos para o desenvolvimento de HAM/TSP. Este foi o primeiro trabalho a analisar a expressão global de linfócitos T CD8+ nesta infecção por meio de SAGE e permitiu a geração de dados que serão empregados em diferentes abordagens na pesquisa com HTLV-1.
MALTA, T.M. Serial Analysis of Gene Expression in CD8+ T-cells isolated from HTLV-1 infected individuals. 2009. 137f. Dissertação de Mestrado. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, 2009. Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus discovered and is related with two major diseases: adult T cell lymphoma/leukaemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). About 3 to 5% of infected individuals will develop HTLV-1 related diseases, while the majority remains life-long asymptomatic carriers of the virus. HAM/TSP is an inflammatory manifestation of central nervous system and the mechanism involved in HAM/TSP development are not well elucidated. CD8+ cytotoxic T lymphocytes (CTL) have an important function in the immune response against the HTLV-1 and is related with the individual proviral load and so in the risk of HAM/TSP. To identify genes differentially expressed among non-infected individuals, asymptomatic (HAC) and HAM/TSP (HAM/TSP) patients we performed a serial analysis of gene expression (SAGE) using CD8+ T cells isolated from these individuals. The CD8+ T lymphocytes were isolated by magnetic cell separation system and HAC and HAM/TSP SAGE libraries were composed by pooled of four samples. SAGE analysis of 51,017, 62,432 and 60,620 tags from control, HAC and HAM/TSP groups respectively, allowed identification of approximately 12,000 different transcripts in each library. The expression profile revealed around 900 genes differentially expressed between control group and HAC or HAM/TSP, and 290 genes were identified between HAC and HAM/TSP groups. The expression profile revealed the presence of highly frequent transcripts related to apoptosis, cell adhesion and cell migration. These results were validated by real time PCR in 17 HTLV-1 asymptomatic carriers, 14 patients with HAM/TSP and 24 healthy individuals. The validation revealed the increased levels of expression of the cytolysis genes PRF1, GZMB and GZMH, and the increases of CCL5, ZAP70 and PXN in the HTLV-1 infected individuals. Besides, the CXCR4 was suppressed in these patients. Additionally, we performed the protein quantification of PRF1 and GZMB by flow cytometry and the real time PCR results were confirmed. The CD8+ T cells profiles showed strong cell activation and cell migration in HTLV-1 infection. These data suggests that CD8+ T cells from HTLV-1 individuals seem to contribute more to the protection and virus infection control than to the HAM/TSP development. This study represents the first extensive serial analysis of gene expression of CD8+T cells in HTLV-1 infection and allowed to generate data that will be used in different approaches in HTLV-1 research.

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24

Berndt, Stephanie. "Manufacturing Analysis and Process Optimization of Welded Parts." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378195880.

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25

Zangi, Shadi. "Cloning of the functional domains of TSP-1 for protein expression." Thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-107207.

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Thrombospondin-1 (TSP-1) is a multifunctional extracellular matrix glycoprotein that is released from platelets α-granule to regulate angiogenesis process. TSP-1 is well-known as an inhibitory factor of angiogenesis that binds to angiogenesis stimulating factors, for example fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor/scatter factor (HGF/SF), to inhibit angiogenesis. We have cloned TSP-1 domains separately to allow studying of their function and effect on proliferation of human umbilical vein endothelial cells (HUVECs). We used an Escherichia coli expressionsvektor including poly histidin-tags and lac-promoter for induction of the seven successfully cloned domains by IPTG and arabinose. Our result shows that we have very low expression and induction of our protein in the E.coli by IPTG and arabinose, which is most likely due to complications associated with expressing a human protein in a prokaryotic system.

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26

Onder, Ilter. "A Genetic Algorithm For Tsp With Backhauls Based On Conventional Heuristics." Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/12608726/index.pdf.

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A genetic algorithm using conventional heuristics as operators is considered in this study for the traveling salesman problem with backhauls (TSPB). Properties of a crossover operator (Nearest Neighbor Crossover, NNX) based on the nearest neighbor heuristic and the idea of using more than two parents are investigated in a series of experiments. Different parent selection and replacement strategies and generation of multiple children are tried as well. Conventional improvement heuristics are also used as mutation operators. It has been observed that 2-edge exchange and node insertion heuristics work well with NNX using only two parents. The best settings among different alternatives experimented are applied on traveling salesman problem with backhauls (TSPB). TSPB is a problem in which there are two groups of customers. The aim is to minimize the distance traveled visiting all the cities, where the second group can be visited only after all cities in the first group are already visited. The approach we propose shows very good performance on randomly generated TSPB instances.

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Eriksson, Olle, and Emil Erlandsson. "Experiences from Simulating TSP Clusters in the Simics Full System Simulator." Thesis, Blekinge Tekniska Högskola, Avdelningen för programvarusystem, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-5588.

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TSP (or Telecommunication Server Platform) is a scalable, high availability cluster operating system developed by Ericsson for use in the telecommunications industry. This thesis describes an attempt to simulate a TSP cluster in the full system simulator Simics, and talks about some of the possibilities offered by such a setup and full system simulation in general. This attempt to simulate TSP was unsuccessful in completely booting the cluster in Simics, but some of the experiences and problems encountered are described. A proposed development environment for working with TSP in Simics is also presented, along with scripts that were created during this thesis to alleviate the working process.
TSP (eller Telecommunication Server Platform) är en skalbar, högt tillgängligt kluster-operativsystem utvecklat av Ericsson för användning inom telekommunikationsindustrin. Den här rapporten beskriver ett försök att simulera TSP-kluster i full-system simulatorn Simics, och beskriver en del av de möjligheter med detta och full-system simulering i allmänhet. Det här försöket att simulera TSP lyckades inte att fullständigt boota klustret i Simics, men några av de erfarenheter och problem som stöttes på är beskrivna. En föreslagen utvecklingsmiljö presenteras också, tillsammans med script som skapades under det här arbetet för att underlätta arbetet.
Olle Eriksson, Contact info at www.olle-eriksson.com Emil Erlandsson, Contact info at www.buglix.org

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28

Valenzuela, Christine Lesley. "Evolutionary divide and conquer : a novel genetic approach to the TSP." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309534.

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Keiler, Kenneth Charles. "Substrate specificity, active-site residues, and function of the Tsp protease." Thesis, Massachusetts Institute of Technology, 1995. http://hdl.handle.net/1721.1/39746.

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Freitas, Daniel Melecchi de Oliveira. "Avaliação de PCA3, TSP-1, AMARC e AR no câncer de próstata." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/48998.

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Arnaut, Victor Almeida Cardoso de Oliveira. "Uso do Nintendo Wii em pacientes com HAM/TSP: Ensaio Clínico Randomizado." Escola de Medicina e Saúde Pública, 2014. http://www7.bahiana.edu.br//jspui/handle/bahiana/107.

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A mielopatia associada ao HTLV-1 ou paraparesia espástica tropical (HAM/TSP) é uma doença desmielinizante crônica e progressiva e que afeta predominantemente a medula espinal. O equilíbrio e a locomoção nos indivíduos acometidos ficam comprometidos e exige alternativas terapêuticas para a reabilitação. Objetivo: Verificar o efeito da Wii Terapia como recurso terapêutico adicional no tratamento de pacientes com HAM/TSP, verificando impactos no equilíbrio, dor e qualidade de vida. Metodologia: Ensaio clínico randomizado duplo cego realizado com 9 indivíduos com diagnóstico confirmado pelos critérios da OMS, divididos em dois grupos – G1 que realizou exercícios terapêuticos associado ao uso de jogos do Nintendo Wii e G2 que realizou somente exercícios terapêuticos. Todos os participantes foram submetidos a uma avaliação da dor pela escala visual analógica (EVA) e do equilíbrio pela escala de Berg, responderam a um questionário sobre qualidade de vida (SF-36), antes e depois das 10 sessões. Os dados foram analisados através dos testes T pareado (intra grupo) e não pareado (inter grupo), com alfa de 5% , poder de 80% e IC 95%. Resultados: Na análise intra grupo foi encontrada diferença apenas no escore da Escala de Berg e dos domínios capacidade funcional e aspectos emocionais do grupo teste (p<0,05). Na comparação do delta dos escores entre os grupos, os domínios aspectos emocionais (p=0,027) e capacidade funcional (p=0,054) foram diferentes entre os grupos. Conclusão: A terapia com realidade virtual usando o Nintendo Wii demonstrou impacto positivo superior em relação ao protocolo de exercícios funcionais sobre o equilíbrio e sobre os domínios de capacidade funcional e aspectos emocionais na qualidade de vida dos participantes.

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Sarkis, Sarkis. "Les lymphocytes TH17, nouveaux acteurs dans la paraparésie spastique tropicale ou myélopathie associée à HTLV-1 (TSP/HAM)." Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20015/document.

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La paraparésie spastique tropicale ou la myélopathie associée à HTLV-1 (TSP/HAM) est une maladie neurologique chronique caractérisée par le développement de paralysies spastiques des membres inférieurs et de déficits sensoriels divers. Une infiltration périvasculaire souvent observée dans le système nerveux central des patients atteints de TSP/HAM correspondant essentiellement à des lymphocytes T CD4+, cibles préférentielles du HTLV-1 in vivo. Cependant, le facteur déclencheur du processus inflammatoire de la TSP/HAM est toujours méconnu. De ce fait, nous nous sommes intéressés à l'étude de l'implication d'une nouvelle population inflammatoire des T CD4+, les TH17, dans cette pathologie. Une quantification de l'expression de l'ARNm d'IL-17, la cytokine inflammatoire sécrétée par les TH17, a été menée sur les cellules du sang périphérique issues de patients infectés ainsi que sur des lignées cellulaires chroniquement infectées par HTLV-1. L'expression élevée de l'IL-17 détectée dans les lignées cellulaires est corrélée avec celle de la protéine transactivatrice du HTLV-1, Tax. Par ailleurs, Tax induit l'expression du régulateur transcriptionnel clé des TH17, RORγ, par l'intermédiaire de la cytokine pro-inflammatoire Ostéopontine. Finalement, nous avons pu montrer l'existence d'une relation dynamique entre l'expression de l'ARNm de Tax, OPN, RORγ, IL-17 et IL-22 chez les patients asymptomatiques et TSP/HAM avec une expression d'IL-17 et d'IL-22 plus élevée chez le groupe des TSP/HAM. Nos résultats suggèrent que l'infection par HTLV-1 in vivo induirait une réponse TH17 qui pourrait avoir un rôle majeur dans la pathogenèse de la TSP/HAM
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological inflammatory disease of the central nervous system characterized by a chronic, progressive inflammatory demyelinating myelopathy. It is thought that the pathogenesis of this disease involves a predominant infiltration of CD4+ T cells which are the main subset of in vivo infected cells with HTLV-1. However, until now, the identity of the triggering factor which promotes the inflammatory process in HAM/TSP remains unclear. Therefore, we investigated the implication of the new CD4+ T cells inflammatory lineage TH17 in this disease. We quantified the mRNA expression levels of IL-17, a cytokine associated with the TH17 response, in peripheral blood from 10 HAM/TSP patients, 6 healthy asymotomatic carriers (HCs) and 4 normal uninfected controls as well as in HTLV-1-infected T-cell lines. Elevated production of IL-17 observed in HTLV-1-infected T-cell lines was correlated with the expression of Tax, the major HTLV-1 regulatory protein. Thus, we established that Tax increases the expression of RORγ, the TH17-lineage specific transactivator, by inducing Osteopontin expression, an inflammatory cytokine known to promote TH17 response. Finally, we demonstrated a dynamic relationship between the expression of Tax, Osteopontin, RORγ, IL-17 and IL-22 mRNAs in HCs and HAM/TSP patients, where higher expression of IL-17 and IL-22 were observed in HAM/TSP cases. These findings suggest that in vivo infection by HTLV-1 may lead to a deleterious deviation of CD4+ T Helper response to TH17, that could play a major role in HAM/TSP pathogenesis

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Otaguiri, Katia Kaori. "Estudo funcional de microRNAs na infecção pelo HTLV-1." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-21062013-140307/.

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O vírus linfotrópico de células T humanas (HTLV-1) foi o primeiro retrovírus descrito e está etiologicamente ligado a duas principais doenças: a leucemia/linfoma de célula T do adulto (ATLL) e a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). Apenas 0,3 a 5% dos indivíduos infectados desenvolvem essas doenças associadas, enquanto a maioria permanece assintomática. A HAM/TSP é uma manifestação inflamatória do sistema nervoso central e o mecanismo pelo qual o HTLV-1 induz o surgimento de HAM/TSP ainda não está totalmente esclarecido. Atualmente, uma abordagem promissora no entendimento de mecanismos, bem como na fisiopatogênese das infecções virais tem sido a avaliação da função de microRNAs (miRNAs). Há poucos dados na literatura envolvendo estas moléculas na infecção pelo HTLV-1 em linfócitos T CD4+ bem como no estabelecimento da doença HAM/TSP. No presente estudo, foi avaliada a expressão de miRNAs dos linfócitos T CD4+ isolados de portadores sem HAM/TSP (HAC), pacientes HAM/TSP e indivíduos sadios (CT) por meio de PCR em tempo real. A análise do perfil de expressão dos miRNAs nessas células revelou que 56 e 10 miRNAs apresentavamse mais 1,5 vezes aumentados no grupo HAM/TSP e HAC, respectivamente. O miR- 125b-1-1 apresentou expressão significamente maior no grupo HAC e o miR-146a, no grupo HAM/TSP. A análise in silico de predição de alvo demonstrou que o gene IFNG era potencialmente alvo do miR-125b-1-1 e os genes IRAK1 e TRAF6 do miR- 146a. Foi demonstrado que a expressão do IFNG no grupo HAC era 1,3 vezes mais elevado que o grupo CT e 1,8 vezes mais elevado no grupo HAM que no grupo CT. Houve um aumento na expressão de TRAF6 de 15,7 e 1,5 vezes nos grupos HAM/TSP e HAC, respectivamente. Não foi observada diferença na expressão de IRAK1 entre os três grupos. O ensaios de superexpressão do miR-125b-1-1 alterou a expressão do IFNG e do miR-146a alterou a expressão do gene IRAK1 e sua proteína. Os resultados evidenciados neste trabalho ressaltam a importância dos miRNAs na modulação de genes e proteínas importantes durante a infeção pelo HTLV-1. A correlação entre o miR-125b-1-1 e gene IFNG sugere que este miRNA esteja envolvido nos mecanismos de desenvolvimento de HAM/TSP. Além disso, a interação entre o miR-146a e os genes IRAK1 e TRAF6 sugerem que este miRNA esteja relacionado a mecanismos de persistência viral da infecção pelo HTLV-1 em linfócitos T CD4+.
Human T-cell lymphotropic vírus type 1 (HTLV-1) was the first human retrovirus discovered and it is related with two major diseases: adult T cell lymphoma/leukaemia (ATLL) and HTLV-1 -associated myelopathy/tropical spastic paraparesis (HAM/TS). About 0.3 to 5% of infected individuals will develop HTLV-1 related diseases, while the majority will remain life-long asymptomatic carriers of the virus. HAM/TSP is an inflammatory manifestation of central nervous system and the mechanism involved in HAM/TSP development is noy well elucidated. Currently, a promising approach on understanding the mechanisms as well as physiopathogenesis of viral infections has been the evaluation of the role of microRNAs (miRNAs) roles. There are few data involving CD4+ T cells miRNA expression in HTLV-1 infection as well as HAM/TSP establishment. To identify miRNAs differentially expressed in CD4+ T cells among non-infected individuals (CT), asymptomatic (HAC) and HAM/TSP patients we applied quantitative real time PCR. The analysis of miRNA expression profile in these cells showed 56 and 10 miRNAs upregulated 1.5 times in HAM/TSP and HAC groups, respectively. miR- 125b-1-1 was upregulated in HAC group and miR-146a in HAM/TSP. In silico analysis of target prediction showed that IFNG was a potentially miR-125b-1-1 target and IRAK1 and TRAF6 were miR-146a targets. IFNG expression was 1.3 higher in HAC than CT group and 1.8 higher in HAM/TSP than CT group. It was observed that TRAF6 expression was 15.7 and 1.5 times higher in HAM/TSP and HAC groups, respectively. There was no difference of IRAK1 expression among the three groups. Overexpression assays of miR-125b-1-1 altered IFNG expression and overexpression of miR-146a altered IRAK1 gene and protein expression. The results revealed that miRNAs modulate genes and proteins during HTLV-1 infection. miR- 125b-1-1 and IFNG gene correlation suggests that miR-125b-1-1 seems to contribute to HAM/TSP development. Besides, miR-146a and IRAK1 and TRAF6 interaction suggests that miT-146a seems to contribute to HTLV-1 establishment in CD4+ T cells.

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Cedraz, Leandro de Oliveira. "Concentrações plasmáticas de citocinas e quimiocinas na infecção pelo HTLV-1." reponame:Repositório Institucional da FIOCRUZ, 2015. https://www.arca.fiocruz.br/handle/icict/12753.

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Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
INTRODUÇÃO: O vírus linfotrópico das células T humano tipo 1 (HTLV-1) é endêmico na Bahia e está associado com doenças graves, como a Paraparesia Espástica Tropical/Mielopatia associada ao HTLV-1 (HAM/TSP) e a Dermatite Infecciosa associada ao HTLV-1 (DIH). Escassos trabalhos tem sido reportados com a avaliação de citocinas e quimiocinas em indivíduos jovens infectados pelo HTLV-1 e não existem dados sobre a manifestação simultânea DIH e HAM/TSP na faixa infanto-juvenil. OBJETIVO: Avaliar as concentrações plasmáticas de citocinas e quimiocinas na infecção pelo HTLV-1 em indivíduos infanto-juvenis. MÉTODO: Foram incluídos 61 indivíduos portadores do HTLV-1 distribuídos nos grupos Portadores assintomáticos, pacientes com a DIH, pacientes com DIH/HAM/TSP, pacientes com a HAM/TSP e 20 indivíduos saudáveis sem a infecção pelo HTLV-1, todos na faixa infanto-juvenil. As concentrações plasmáticas foram comparadas através do método de Elisa e de Cytometric Bead Array (CBA). As análises estatísticas foram realizadas com o GraphPad Prism 6.1 através do teste Mann Whitney para comparação das medianas e pelo teste Wilcoxon para comparação das amostras pareadas, e a avaliação das correlações pelo coeficiente de Spearman. RESULTADOS: As citocinas IL-2, IL-6 estiveram em maiores concentrações em todos os grupos de portadores do HTLV-1. Os indivíduos saudáveis apresentaram menores concentrações de IFN-γ que o grupo de indivíduos portadores assintomáticos e o grupo de pacientes com a DIH, além de menores concentrações de IL-4 e IL-10 quando comparado com os indivíduos infectados, contudo apenas a IL-10 esteve em concentrações diferentes nos indivíduos com o vírus. Os indivíduos saudáveis apresentaram maiores concentrações da quimiocina CCL-22. Portadores assintomáticos e pacientes com a DIH apresentaram menores concentrações de IL-1β quando comparados com indivíduos saudáveis. Os portadores assintomáticos apresentaram menores concentrações da IL-17 que os indivíduos não infectados. Os pacientes com a DIH/HAM/TSP apresentaram maiores concentrações para a IL-1β, quando comparado com o grupo de pacientes com a DIH e com o grupo de pacientes com a HAM/TSP, além de menores concentrações da quimiocina CCL-27. O grupo HAM/TSP apresentou menores concentrações de IL-8 que os grupos DIH e DIH/HAM/TSP. A carga proviral foi menor no grupo dos portadores assintomáticos, seguidos do grupo de pacientes com DIH, e do grupo de pacientes de DIH que também manifestaram HAM/TSP, já o grupo de pacientes com a HAM/TSP apresentaram cargas provirais menores que o grupo DIH e o grupo DIH/HAM/TSP. Apenas a IL-8 e IL-10 apresentaram correlações fracas com a carga proviral. Na remissão da DIH, houve maiores concentrações da CCL-27, enquanto o TNF-α esteve em maiores concentrações no momento em que o paciente apresentou a DIH/HAM/TSP. CONSIDERAÇÕES FINAIS: Na infecção pelo HTLV-1 na faixa infanto-juvenil ocorre uma desregulação imunológica acompanhada de um mecanismo imunomodulador. Nos portadores assintomáticos, parece existir um maior equilíbrio entre a resposta pro e anti-inflamatória. A manifestação de DIH e da HAM/TSP, parece estar relacionada com um maior desequilíbrio entre a resposta imunológica, e nos pacientes com a DIH/HAM/TSP esta resposta parece sofrer influência de mecanismos da comanifestação.
INTRODUCTION: The lymphotropic virus of cells T human type 1 (HTLV ) is endemic in Bahia and it is associated with serious diseases such as Tropical Spastic Paraparesis/associated myelopathy with HTLV-1 and Infectious Dermatitis associated with HTLV -1 (IDH). Very little work has been reported with the evaluation of cytokines and chemokines in the IDH and there has been no data on the manifestation simultaneous IDH and HAM\TSP in children and youth range. OBJECTIVE: To evaluate the plasma concentrations of cytokines and chemokines in HTLV-1 infection in children and young individuals. METHOD: We included 61 individuals HTLV-1 spread in groups Asymptomatic Carriers, patients with IDH, patients with IDH/HAM/TSP, patients with HAM/TSP and 20 healthy individuals without HTLV-1, all in children's range. Plasma concentrations were compared using the ELISA method and Cytometric Bead Array (CBA). Statistical analyzes were performed using GraphPad Prism 6.1 using the Mann Whitney test to compare the medians and the Wilcoxon test for comparison of paired samples, and evaluation of correlations by Spearman coefficient. RESULTS: The cytokines IL-2 and IL-6 concentrations were higher in all groups of patients with HTLV-1. Healthy individuals showed lower concentrations of IFN-γ to the group of asymptomatic individuals and the group of patients with IDH, in addition to lower concentrations of IL-4 and IL-10 when compared to infected individuals, but only IL-10 was in different concentrations in subjects with the virus. Healthy individuals showed higher concentrations of the chemokine CCL-22. Asymptomatic carriers and patients with IDH had lower IL-1β levels in comparison with healthy subjects. Asymptomatic carriers had lower IL-17 concentrations that Healthy individuals. Patients with IDH/HAM/TSP had higher concentrations of IL-1β compared with the group of patients with the IDH and the group of patients with HAM/TSP, and lower concentrations of CCL-27 chemokine. The HAM/TSP group had lower IL-8 concentrations of the IDH and IDH/HAM/TSP groups. The proviral load was lower in asymptomatic patients, followed by the group of patients with IDH, and the group of IDH patients also expressed HAM/TSP, the group of patients with HAM/TSP had lower proviral loads that the IDH group and IDH/HAM/TSP group. As IL-8 and IL-10 exhibit weak correlation with proviral load. In Remission IDH, there were higher concentrations of CCL-27, while TNF-α was higher concentrations at the time the patient showed IDH/HAM/TSP. CONCLUSIONS: In the HTLV-1 infection in children and young occurs an immune dysregulation accompanied of an immunomodulatory mechanism. In asymptomatic patients, there seems to be a greater balance between the response pro and anti-inflammatory. The manifestation of IDH and HAM/TSP seems to be related to a greater imbalance between the immune response, and in patients with IDH/HAM/TSP this answer seems to be influenced by mechanisms of co-expression mechanisms.

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DI, PLACIDO Andrea. "The close enough Traveling Salesman Problem: enhanced heuristics, applications and variants." Doctoral thesis, Università degli studi del Molise, 2022. https://hdl.handle.net/11695/115287.

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Il traveling salesman problem (TSP) è ampiamente studiato per la sua abilità di modellare un'ampia gamma di problemi. L'obiettivo è identificare il percorso minimo che visiti ogni città di un dato set e tornare alla città di partenza ("deposito"). Il TSP ha diverse applicazioni pratiche riguardanti il planning, la logistica, etc. Negli ultimi anni, generalizzazioni del TSP sono state ampiamente trattate per scopi logistici, come il close enough traveling salesman problem (CETSP) e il close enough arc routing problem (CEARP). Nel CETSP, ogni target ha un raggio d'azione entro il quale è considerato visitato. Da ciò, non siamo più vincolati alla posizione esatta, ma basta andare abbastanza vicino. In questo problema non siamo vincolati ad una rete stradale, quindi consideriamo le distanze euclidee. Invece, nel caso del CEARP, abbiamo sempre un raggio d'azione attorno ai target, ma siamo vincolati ad una rete stradale (archi) per definire la rotta. Il CETSP e CEARP hanno applicazioni pratiche in diversi scenari reali, come ad esempio per la lettura di contatori in un quartiere mediante sistemi a radio frequenza (RFID). In questa tesi, presentiamo uno studio approfondito del CETSP. Abbiamo prodotto un algoritmo genetico (GA) per la sua risoluzione, che fornisce soluzioni migliori nella maggior parte dei casi di benchmark considerati. Inoltre, presentiamo due metriche, TSPDegree (TSPD) e OverlappingCenter (OC), per la valutazione delle istanze del problema. Abbiamo comparato le nostre metriche con quelle già presenti in letteratura, nello specifico overlap ratio (OR), ottenendo che TSPD e OC forniscono maggiori informazioni sulle caratteristiche di un'istanza rispetto a OR. Riguardo OR, abbiamo identificato valori errati presenti in letteratura, e ne presentiamo i valori corretti. Presentiamo un caso di studio relativo alla diagnostica di pannelli solari. Nello specifico, abbiamo utilizzato un drone per controllare il corretto funzionamento di un campo fotovoltaico. Il suddetto caso è stato modellato come un CETSP e risolto mediante il nostro algoritmo, ottenendo ottimi risultati. In questo lavoro, introduciamo due varianti del CETSP, rispettivamente il mixed constrained generalized routing problem (MCGRP) e il generalized close enough traveling salesman problem (GCETSP). Il primo è una generalizzazione di CETSP e CEARP in cui introduciamo il concetto di zone di volo. Ne differenziamo due: una in cui il drone può volare liberamente (FFZ), e una in cui il volo è vincolato o proibito (CFZ). Il MCGRP si pone lo stesso obiettivo del CETSP ma nel rispetto dei vincoli delle zone di volo. Abbiamo formalmente definito il problema e lo abbiamo esaminato nei suoi casi limiti, ossia CETSP e CEARP. Il secondo è una variante del CETSP, in cui ogni target ha diverse aree associate ad esso, modellate come dischi concentrici, ognuna con un premio che decresce all'allontanarsi dal target. Lo scopo del GCETSP è quello di identificare la rotta di costo minimo che massimizza la differenza tra il premio totale e la lunghezza della rotta, visitando un disco per ogni target. Col GCETSP possiamo modellare diversi scenari applicativi in cui otteniamo maggiori benefici avvicinandoci al target. Abbiamo definito formalmente il problema e delle istanze per esso, e abbiamo adattato l'algoritmo risolutivo a questo problema. I risultati mostrano che il nostro approccio è in grado di risolvere il problema correttamente, fornendo eccellenti soluzioni.
The traveling salesman problem (TSP) is widely studied to model a wide range of problems. The objective is to identify the minimum path to visit each city in a given set and return to the city of departure ("depot"). TSP has several practical applications in planning, logistics, etc. In recent years, generalizations of TSP have been widely treated for logistical purposes, such as the close enough traveling salesman problem (CETSP) and the close enough arc routing problem (CEARP). In CETSP, each target has a range within which it is considered visited. Hence, we are no longer constrained to the exact location but just close enough. We are not bound to a road network in this problem, so we consider Euclidean distances. In contrast, in the case of CEARP, we always have a range around the targets, but we are constrained to a road network (arcs) to define the route. CETSP and CEARP have practical applications in several real-world scenarios, such as reading meters in a neighborhood using radio frequency identification (RFID) systems. In this thesis, we present an in-depth study of CETSP. We have produced a genetic algorithm (GA) for its resolution, which provides better solutions in most considered benchmark cases. In addition, we present two metrics, TSPDegree (TSPD) and OverlappingCenter (OC), for evaluating instances of the problem. We compared our metrics with those already present in the literature, precisely overlap ratio (OR), obtaining that TSPD and OC provide more information about the characteristics of an instance than OR. We identified incorrect values present in the literature and presented the corrected values regarding OR. We present a case study related to solar panel diagnostics. Specifically, we used a drone to check the correct operation of a solar array. The above case was modeled as a CETSP and solved using our algorithm, obtaining excellent results. This work introduces two variants of CETSP, respectively, the mixed constrained generalized routing problem (MCGRP) and the generalized close enough traveling salesman problem (GCETSP). The former is a generalization of CETSP and CEARP in which we introduce the concept of flight zones. We differentiate two of them: one in which the drone can fly freely (FFZ) and one in which the flight is constrained or prohibited (CFZ). The MCGRP has the same goal as CETSP but within the constraints of the flight zones. We have formally defined the problem and examined it in its limiting cases, namely CETSP and CEARP. The latter is a variant of CETSP. Each target has several areas, modeled as concentric disks, each with a premium that decreases as one moves away from the target. The purpose of GCETSP is to identify the minimum cost route that maximizes the difference between the total premium and the route length by visiting one disk per target. With GCETSP, we can model different application scenarios in which we get more benefits by getting closer to the target. We formally defined the problem and its instances and adapted the solving algorithm to this problem. The results show that our approach can solve the problem correctly, providing excellent solutions.

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Pedro, Carvalho de Oliveira Joaquim. "RUP-pe : uma metodologia ágil, baseada no RUP e no TSP, para pequenas equipes." Universidade Federal de Pernambuco, 2003. https://repositorio.ufpe.br/handle/123456789/2494.

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Pesquisas recentes têm mostrado que projetos de software de curta duração e que utilizam equipes pequenas possuem maiores chances de sucesso. Entretanto, a escolha da metodologia a ser utilizada neste tipo de projeto deve levar em consideração suas características, como a comunicação facilitada e o menor grau de formalismo nos artefatos. Para se utilizar metodologias de desenvolvimento pesadas, como o RUP e o OPEN, deve-se fazer uma adaptação da metodologia escolhida, pois elas se propõem servir a uma grande diversidade de projetos, possuindo um grande número de atividades, muitas vezes desnecessárias. Apesar do detalhamento de suas atividades ser útil para sua adoção, isto torna a adaptação da metodologia uma atividade complexa e custosa. Por outro lado, a adoção de metodologias ágeis, como XP e Scrum, muitas vezes não é suficiente. Por adotarem uma abordagem mais informal para o desenvolvimento de software, estas metodologias muitas vezes carecem de descrições mais detalhadas e deixam atividades importantes em segundo plano, como por exemplo, gerenciamento de riscos e planejamento de recursos. Caso se deseje estar alinhado ou de acordo com um modelo de qualidade como o Capability Maturity Model for Software (SW-CMM), esta informalidade é um obstáculo ainda maior. Todavia, várias práticas propostas por estas metodologias têm se mostrado eficazes em projetos pequenos. Como exemplos, temos a integração contínua e o uso de iterações de curta duração. Neste trabalho, apresentamos o RUP-pe, uma metodologia ágil, voltada para equipes de até 15 desenvolvedores. Ele foi elaborado com base no RUP e incorpora práticas de diversas metodologias ágeis. Além disto, também foi definido com base no TSP, um processo de software completamente alinhado com o SW-CMM. O objetivo do RUP-pe é ser uma metodologia adequada às pequenas equipes, sem ser excessivamente informal, e alinhada, desde sua definição, com um modelo de qualidade reconhecido mundialmente. São apresentadas as disciplinas Implementação e Gerenciamento de Projeto, e um website que possui todo o detalhamento das atividades propostas, servindo de guia para as equipes que desejem utilizá-lo

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Vale, Daniela Assis do. "Detecção de proteínas e partículas virais do HTLV-1 em glândulas salivares de pacientes com Síndrome de Sjögren e de infectados pelo HTLV-1." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/23/23154/tde-24012018-113520/.

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O HTLV-1 (human T-cell lymphotropic virus type 1) foi o primeiro retrovírus humano a ser identificado. O HTLV-1 tem a capacidade de ativar e gerar uma intensa resposta inflamatória, podendo levar a alterações em diversos tecidos que mimetizam uma doença autoimune. Do complexo de doenças associadas ao HTLV-1, a Síndrome de Sjögren (SS) figura entre as mais estudadas. No entanto, nenhuma relação definitiva foi ainda estabelecida. Este trabalho propõe-se a investigar indícios da presença do HTLV-1 em glândulas salivares menores de pacientes infectados por esse retrovírus e comparar as alterações morfológicas em glândulas salivares menores de pacientes com HTLV-1 e de pacientes com SS não infectados. Amostras de glândula salivar menor foram coletadas de 14 pacientes HTLV+ que apresentavam síndrome seca (grupo de estudo) e 5 pacientes diagnosticados com SS e negativos para o HTLV (grupo controle). No grupo de estudo, o infiltrado inflamatório visto era composto principalmente por linfócitos T CD4+, no grupo controle a população majoritária foi de linfócitos B CD20+. Alterações morfológicas como fibrose e infiltração gordurosa foram mais comumente vistas nas amostras do grupo de estudo, sendo a diferença estatisticamente significativa (p=0,038 e 0,033 respectivamente). Na análise por PCR 11 (78,57%) dos casos do grupo de estudo foi detectado o gene tax e/ou rex do HTLV-1, no entanto 4 (80%) das amostras do grupo controle também foram positivas. O HTLV-1 mostra indícios de estar presente nas glândulas salivares de indivíduos com síndrome seca, no entanto pacientes HTLV-1+ apresentam alterações morfológicas em padrões diferentes dos vistos em pacientes com SS, denotando uma provável diferença no processo de ativação imunológica.
Human T-cell lymphotropic virus type I (HTLV-1) was the first human retrovirus to be discovered. HTLV-1 has the ability to activate and generate an intense inflammatory response, which can lead to changes in several tissues that mimic an autoimmune disease Of the complex of diseases associated with HTLV-1, Sjögren\'s Syndrome (SS) is among the most studied. The aim of this study is to investigate the presence of HTLV-1 in the minor salivary glands of patients infected with this retrovirus and to compare the morphological alterations in the salivary glands of patients with HTLV-1 and patients with SS uninfected. Minor salivary gland samples were obtained from 14 HTLV + patients with dry syndrome (study group) and 5 patients diagnosed with SS and HTLV negative (control group). In the study group, the inflammatory infiltrate was mainly composed of CD4+ T lymphocytes, in the control group the majority population was of CD20+ B lymphocytes. Morphological changes such as fibrosis and adipose tissue infiltration were more common in the study group, the difference was statistically significant (p = 0.038 and 0.033, respectively). The HTLV-1 tax and/or rex genes were detected by PCR in 11 (78.57%) patients of the study group, but 4 (80%) samples from the control group were also positive. HTLV-1 shows signs of being present in the salivary glands of individuals with dry syndrome however, HTLV-1+ patients present morphological alterations in different patterns from those observed in SS patients, denoting a probable difference in the immunological activation process.

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38

Mu, Zongxu. "Analysing the empirical time complexity of high-performance algorithms for SAT and TSP." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55351.

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The time complexity of problems and algorithms, i.e., the scaling of the time required for solving a problem instance as a function of instance size, is of key interest in theoretical computer science and practical applications. In this context, the propositional satisfiability (SAT) and the travelling salesperson (TSP) are two of the most intensely studied problems, and it is generally believed that solving SAT or TSP requires exponential time in the worst case. In this work, we refine and extend a recent empirical scaling analysis approach and study the empirical scaling of the running times of several prominent, high-performance SAT and TSP algorithms. For SAT, we focus on random 3-SAT instances from the phase transition region, arguably the most prominent model for difficult SAT instances, and obtain interesting and surprising scaling results for both SLS- and DPLL-based solvers. Particularly, we find solid support for polynomial scaling for SLS-based solvers on phase-transition random 3-SAT instances. We also show that DPLL-based solvers scale exponentially and are faster by only a constant factor in solving satisfiable instances compared to unsatisfiable instances. We further report empirical scaling results for two classes of random 4-SAT instances to gain additional insights into the performance of state-of-the-art SAT solvers. For TSP, we concentrate on two-dimensional random uniform Euclidean (RUE) instances, and characterise the scaling of running time for complete and incomplete algorithms for finding optimal solutions. Our results indicate that the scaling of all these algorithms is consistent with or bounded from above by root-exponential models of the form a·b^(√n). We also explored the impact of automated algorithm configuration on the scaling of these algorithms. Since our approach is applicable beyond SAT and TSP, to enable its broad use, we designed Empirical Scaling Analyser (ESA), an automated tool that can be conveniently used to study empirical scaling of many types of algorithms. In particular, ESA presents scaling analysis results in the form of automatically generated, detailed technical reports. Many results reported in this thesis, including most tables and figures, were automatically generated by ESA and are only slightly modified to fit here.
Science, Faculty of
Computer Science, Department of
Graduate

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39

Barbato, Michele. "A Polyhedral Approach for the Double TSP with Multiple Stacks and Lexicographical Orders." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCD049/document.

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Dans cette thèse nous considérons deux problèmes d'optimisation combinatoire.Le premier s'appelle problème du double voyageur de commerce avec contraintes de piles. Dans ce problème, un véhicule doit ramasser un certain nombre d'objets dans une région pour les livrer à des clients situés dans une autre région. Lors du ramassage, les objets sont stockés dans les différentes piles du véhicule et la livraison des objets se fait selon une politique de type last-in-first-out. Le ramassage et la livraison consistent chacune en une tournée Hamiltonienne effectuée par le véhicule dans la région correspondante.Nous donnons une formulation linéaire en nombres entiers pour ce problème. Elle est basée sur des variables de précédence et sur des contraintes de chemins infaisables. Nous donnons par la suite des résultats polyédraux sur l'enveloppe convexe des solutions de notre formulation. En particulier, nous montrons des liens forts avec un polytope associé au problème du voyageur de commerce et des liens avec un polytope de type set covering. Cette étude polyédrale nous permet de renforcer la formulation initiale et de développer un algorithme de coupes et branchements efficace. Le deuxième problème que nous considérons consiste à trouver la description des polytopes lexicographiques. Ces derniers sont les enveloppes convexes des points entiers lexicographiquement compris entre deux points entiers fixés. Nous donnons une description complète de ces polytopes en termes d'inégalités linéaires. Nous démontrons que la famille des polytopes lexicographiques est fermée par intersection
In this thesis we consider two problems arising in combinatorial optimization.The first one is the double traveling salesman problem with multiple stacks. In this problem a vehicle picks up a given set of items in a region and subsequently delivers them to demanding customers in another region. When an item is picked up, it is put in a stack of the vehicle. The items are delivered observing a last-in-first-out policy. The pickup phase and the delivery phase consist in two Hamiltonian circuits, each performed by the vehicle in the corresponding region. We give a new integer linear programming formulation for this problem. Its main features are the presence of precedence variables and new infeasible path constraints. We provide polyhedral results on the convex hull of the solutions to our formulation. In particular, we show strong links with a specific TSPpolytope and a specific set covering polytope. We deduce strengthening inequalities for the initial formulation, subsequently embedded in an efficient branch-and-cut algorithm. The second problem we consider consists in finding the description of the lexicographical polytopes. These are convex hulls of the integer points lexicographically between two given integer points. We give a complete description of these polytopes by means of linear inequalities. We show that the lexicographical polytope family is closed under intersection

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40

Demir, Erdem. "Analysis Of Evolutionary Algorithms For Constrained Routing Problems." Master's thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/12605083/index.pdf.

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This study focuses on two types of routing problems based on standard Traveling Salesman Problem, which are TSP with pickup and delivery (TSPPD) and TSP with backhauls (TSPB). In both of these problems, there are two types of customers, i.e. &ldquo
delivery customers&rdquo
demanding goods from depot and &ldquo
pickup customers&rdquo
sending goods to depot. The objective is to minimize the cost of the tour that visits every customer once without violating the side constraints. In TSPB, delivery customers should precede the pickup customers, whereas the vehicle capacity should not be exceeded in TSPPD. The aim of the study is to propose good Evolutionary Algorithms (EA) for these two problems and also analyze the adaptability of an EA, originally designed for the standard TSP, to the problems with side constraints. This effort includes commenting on the importance of feasibility of the solutions in the population with respect to these side constraints. Having this in mind, different EA strategies involving feasible or infeasible solutions are designed. These strategies are compared by quantitative experiments realized over a set of problem instances and the results are given.

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41

Vale, Daniela Assis do. "Prevalência da Síndrome de Sjögren em infectados pelo HTLV em São Paulo." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-04072013-160007/.

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O HTLV-1 (human T-cell lymphotropic virus type 1) foi o primeiro retrovírus humano a ser identificado. É comprovadamente o agente etiológico da leucemia/linfoma de células T no adulto (ATLL) e da paraparesia espástica tropical ou mielopatia associada ao HTLV (HAM/TSP). Porém se evidencia que o vírus possa estar relacionado a várias outras manifestações sistêmicas. A Síndrome de Sjögren (SS) é uma das desordens que têm sido associada ao HTLV-1. Embora a infecção pelo HTLV seja reconhecidamente endêmica no Brasil, não há informações sobre essa associação na população brasileira. Este trabalho propõe-se a investigar a prevalência de SS em pacientes infectados pelo HTLV e a prevalência de HTLV em pacientes diagnosticados com SS. Exames sorológicos para investigação do HTLV foram realizados em 50 pacientes da Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP) que apresentavam queixas compatíveis com a SS (grupo 1). No Instituto de Infectologia Emílio Ribas foram avaliados 129 pacientes HTLV+ que passaram pelo processo diagnóstico para a SS (grupo 2). Nenhum dos pacientes do grupo 1 apresentou soropositividade para o HTLV. No grupo 2, 46 (35,7%) apresentaram algum grau de xerostomia, 18 (13,95%) apresentaram xeroftalmia, 8 (6,2%) apresentaram hipossalivação, 2 (1,55%) apresentaram fluxo lacrimal alterado e 1 paciente (0,77%) apresentou autoanticorpos reagentes (anti-SSB). Foram executadas biópsias incisionais de glândulas salivares menores em 5 pacientes do grupo 2. Apenas 2 pacientes (1,55%) HTLV+ completaram os critérios para o diagnóstico de SS. A SS mostrou ser três vezes mais prevalente em pacientes HTLV+ do IIER do que nos pacientes que buscaram atendimento no serviço de Otorrinolaringologia da ISCMSP.
HTLV-1 (human T-cell lymphotropic virus type 1) was the first human retrovirus identified. It is proven to be the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and of a neurological disease known as HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). However, there is the evidence that the virus could be related to several other systemic manifestations. Sjögren\'s Syndrome (SS) is one of the disorders that have been associated with HTLV-1. Although HTLV infection is known to be endemic in Brazil, there is no information about this association in Brazilian population. This study proposes to investigate the prevalence of SS among patients infected with HTLV and the prevalence of HTLV among patients diagnosed with SS. Serological tests for HTLV were performed in 50 patients from Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP) with complaints compatible with the SS (group 1). At Institute of Infectious Diseases Emilio Ribas (IIER), 129 HTLV+ patients were evaluated and the diagnostic process for SS was performed (group 2). None of the patients in group 1 was positive for HTLV. In group 2, 46 (35.7%) reported any degree of xerostomia, 18 (13.95%) had xerophtalmia, hyposalivation was present in 8 (6.2%) patients and decrease in tear secretion, in only one patient (0.77%) the auto-antibodies was positive ( Anti-SSB). Incisional biopsies of labial minor salivary glands were executed in 5 patients in group 2. Only 2 HTLV+ patients (1.55%) have fulfilled the classification criteria for SS. SS proved to be three times more prevalent in HTLV patients from IIER than in patients who sought care in the service of Otorhinolaryngology at ISCMSP.

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42

Coutinho, Junior Raimundo. "Perfil de ativação dos linfócitos T de pacientes com mielopatia associada ao vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) / paraparesia tropical espástica (HAM/TSP) possível, provável e definido." Centro de Pesquisas Gonçalo Moniz, 2013. https://www.arca.fiocruz.br/handle/icict/7637.

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Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-05-22T14:08:18Z No. of bitstreams: 1 Raimundo Coutinho Junior. Perfil de ativação... 2014 .pdf: 1722380 bytes, checksum: 909bc68a97d8e0a06206d205cd3557f7 (MD5)
Made available in DSpace on 2014-05-22T14:08:18Z (GMT). No. of bitstreams: 1 Raimundo Coutinho Junior. Perfil de ativação... 2014 .pdf: 1722380 bytes, checksum: 909bc68a97d8e0a06206d205cd3557f7 (MD5) Previous issue date: 2013
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
O vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) é o agente etiológico da mielopatia associada ao HTLV / paraparesia espástica tropical (HAM / TSP ), que ocorre em menos de 5 % dos indivíduos infectados. A resposta imune controla parcialmente a infecção, porém pode estar ligada a patogênese da doença. O objetivo deste estudo foi caracterizar fenotipicamente as subpopulações de linfócitos T, em pacientes assintomáticos e com diagnóstico de HAM/TSP. Foram avaliados 103 pacientes acompanhados no Centro de HTLV da Escola Bahiana de Medicina e Saúde Pública (EBMSP) e 19 controles não infectados. Os pacientes foram categorizados de acordo com o grau de certeza do diagnóstico de HAM/TSP: possível (Ps), provável (Pb) e definido (D), além de pacientes assintomáticos (ASS). O perfil fenotípico (CD25, CD45RA, CD45RO, HLA-DR, CD25, CCR-7, CD62L) das subpopulações de linfócitos T CD4+ e T CD8+ e a expressão da proteína Tax de FoxP3 na subpopulação T CD4+ foram avaliados por citometria de fluxo. A carga proviral do HTLV foi quantificada por reação em cadeia da polimerase (PCR) em tempo real. As proporções dos linfócitos TCD4+HLA-DR+ e TCD8+HLA-DR foram significativamente maiores nos pacientes com HAM/TSP Ps, Pb e D comparados aos controles não infectados (p=0,003). Comparando-se o grupo de infectados, as proporções de linfócitos TCD4+ e TCD8+ expressando HLA-DR foram significantemente maiores em pacientes com HAM/TSP-Ps e D comparados a pacientes assintomáticos (p<0,0001). Além disso, houve uma correlação positiva entre porcentagem de linfócitos T CD4+ HLA-DR+ e a carga proviral (r=0,5, p=0,0003). As proporções de linfócitos T CD4+CD25+ foram maiores nos pacientes com HAM/TSP D comparados aos controles não infectados. Observou-se um aumento na proporção de células reguladoras (T CD4+FOXP3+) nos indivíduos assintomáticos e nos pacientes com HAM/TSP-D comparados a indivíduos não infectados (p=0,04). A carga proviral HTLV-1 foi maior no grupo de pacientes HAM/TSP-D do que em pacientes assintomáticos (p=0,0001). Observa-se uma diferença estatística entre a proporção de células CD4+TAX+ dos indivíduos assintomáticos (0,26%) e os pacientes HAM/TSP-Ps (5,26%) (p=0,04). Em conclusão, os pacientes com HAM/TSP Ps, Pb e D apresentam um perfil fenotípico de ativação celular, comparados aos controles não infectados. Além disso, os pacientes com HAM/TSP Pb e D apresentam maior expressão de HLA-DR nas subpopulações de linfócitos T CD4+ e T CD8+, comparados aos assintomáticos, indicando um perfil imunológico semelhante nestes dois subgrupos de pacientes.
The human T-cell lymphotropic vírus type 1(HTLV-1) is the etiological agent of HTLV- associated myelopathy/ Tropical spastic paraparesis(HAM/TSP), wich occurs in less then 5% of the infected individuals. The immune response partially controls the infection, but may be linked to the pathogenesis of disease. The aim of this study was to characterize phenotipically T lymphocyte subpopulations in asymptomatic and in patients diagnosed with HAM/TSP. We evaluated 103 patients treated at the center for HTLV of Bahia School of Medicine and Public Health (EBMSP) and 19 uninfected controls. Patients were categorized as asymptomatic and according to the degree of certainty of the diagnosis of HAM/TSP: Possible(Ps), Probable(Pb) and Definite(D). The phenotypic profile (CD25, CD45RA, CD45RO, HLA-DR, CCR-7, CD62L) subpopulation of CD4+ and CD8+ T Cells and expression of the protein Tax and Foxp3 in the subpopulation CD4+ T cells were evaluated by flow cytometry. The HTLV proviral load was quantified by polymerase chain reaction (PCR) in real time. The proportions of CD4+ and CD8+ expressing HLA-DR+ were significantly higher in patients (p<0.0001). In addition there were a correlation between CD4+ HLA-DR+ or CD8+ HLA-DR+ and the proviral load(R=0,5;p<0,0001). The proportions of CD4+CD25+ were higher in patients with HAM/TSP D compared to infected controls. There was an increased proportion of regulatory cells (CD4+Foxp3+) of asymptomatic individuals and patients HAM/TSP D, compared to the uninfected individuals (p=0.04). . There is a statistical difference between the proportion of CD4+TAX+ asymptomatic individuals (0.26%) patients and HAM/TSP-Ps (5.26%) (p = 0.04 ) . In conclusion, patients with HAM/TSP Ps, Pb and D exhibit a phenotypic profile of cell activation, compared to uninfected controls. In addition, patients with HAM/TSP Pb and D show higher expression of HLA -DR in subpopulations of T lymphocytes CD4+ and CD8+ T cells, compared to asymptomatic, indicating an immunological profile similar in both groups of patients

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43

Liu, Quan. "STUDY OF HEAT TRANSFER CHARACTERISTICS OF IMPINGING AIR JET USING PRESSURE ANDN TEMPERATURE SENSITIVE LUMINESCENT PAINT." Doctoral diss., University of Central Florida, 2006. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/2261.

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Luminescent coating measurement system is a relatively new technology for quantitative pressure and temperature measurement. Usually referred to as Pressure Sensitive Paint (PSP) and Temperature Sensitive Paint (TSP), luminescent coatings contain sensor molecules, which undergoes a luminescent transition when excited with light of proper wavelength. The reaction is pressure and/or temperature sensitive. The image of TSP or PSP coated model surface can be captured with a scientific grade camera and then processed to obtain full field temperature and pressure distribution with very high fidelity. The preparation time of the technique is short. The measurement system offers an economic alternative to conventional testing methods using large number of pressure taps and thermocouples. The purpose of the experiment in this thesis is to take the benefits of the TSP and PSP technique, develop a well-controlled process and then apply the technique for a fundamental study on jet impingement heat transfer. First, Uni-Coat TSP and Binary-FIB PSP purchased from ISSI Inc. are calibrated to high accuracy. The calibration uncertainty of TSP and PSP are found to be ±0.93 °C and ±0.12 psi over temperature and pressure ranges of 22 to 90 ° C and 5 to 14.7 psia, respectively. The photodegradation of TSP is then investigated with the same calibration system. The photodegradation refers to the phenomenon of decreasing emission intensity as the luminescent paint is exposed to the illumination light during testing. It was found that photodegradation rate is a strong function of temperature and the optical power of illumination lighting. The correlation developed in this work is expected to compensate the degradation of TSP to achieve high measurement accuracy. Both TSP and PSP were then applied in the flow and heat transfer measurement of single round impinging air jet. Various separation distance (Z/D) and jet Reynolds number are tested. Pressure measurement on the jet impinged target surface using PSP clearly shows the boundary of jet impingement zone, which broadens with separation distance. In heat transfer experiment using TSP, the "second peak" in local heat transfer occurring at radial distance r/D around 2 is clearly observed when the separation distance Z/D is shorter than the length of jet potential core. The slight variation in radial location and the amplitude of the "second peak" are captured as Z/D and jet Reynolds number change. The optimum Z/D of stagnation point heat transfer is found to be around 5. The effect of jet nozzle configuration is investigated. It is found that the heat transfer rate associated with "tube jet" is generally higher than that of "plate jet". The difference in heat transfer between the two jet configurations is related to the weaker entrainment effect associated with "plate jet", where the entrainment of surrounding air is confined by the injection plate, especially under small Z/D circumstances. When compared with the benchmark data in the literature, the averaged heat transfer data of "tube jet" matches the empirical data better than those of "plate jet". The maximum difference is 3.3% for tube jet versus 15.4% for plate jet at Reynolds number of 60000 and Z/D of 5. The effect of surface roughness on jet impingement heat transfer is also studied. Heat transfer can be significantly increased by the enhanced roughness of the target surface. The largest roughness effect is achieved near stagnation point at high jet Reynolds number. Compared to the heat transfer to a smooth plate, as high as 30.9% increase in area-averaged Nusselt number is observed over a rough surface at r/D=1.5 and jet Reynolds number of 60000. The most significant advance of the present work is that both temperature and pressure measurement be obtained with the same measurement system and with accuracy comparable to traditional testing methods. The procedures that were employed in this work should be easy to apply in any university or industrial testing facility. It provides a rapid testing tool that can help solve complex problems in aerodynamics and heat transfer
Ph.D.
Department of Mechanical, Materials and Aerospace Engineering;
Engineering and Computer Science
Mechanical Engineering

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44

Heaton, William. "New Record Ordering Heuristics for Multivariate Microaggregation." NSUWorks, 2011. http://nsuworks.nova.edu/gscis_etd/175.

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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.

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45

Rath, Géraldine El Btaouri Hassan Morjani Hamid. "Rôle anti-apoptotique de la TSP-1 dans les cellules thyroïdiennes normales et cancéreuses." S.n. : S.l, 2006. http://scdurca.univ-reims.fr/exl-doc/GED00000371.pdf.

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46

Simaitis, Rokas. "Iteratyviosios tabu paieškos algoritmo komivojažieriaus uždaviniui tyrimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2006. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2006~D_20060602_173228-37727.

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In this work, the iterated tabu search (ITS) algorithm for the traveling salesman problem (TSP) is discussed. The TSP is a well-known combinatorial optimization problem. Thus, solving the TSP means searching for the shortest closed tour in which every city is visited exactly once. Various heuristic algorithms can be used for solving the TSP, among them, tour construction heuristics, simulated annealing, genetic algorithms, etc. One of the promising heuristic techniques is the iterated tabu search approach. ITS consists of two main parts: standard tabu search (TS) and mutation of solutions. The goal of TS is finding a locally optimal solution in the neighbourhood of the current solution, while the mutation operators are responsible for escaping from the current local optimum and moving towards new regions in the solution space. Several mutation procedures have been analyzed in this work, in particular, exchange mutation, insert mutation, inversion mutation, and others. In order to investigated the performance of the mutation operators, computational experiments with the test instances from the TSP instances library TSPLIB were carried out. The results obtained from these experiments show that the mutation operators play the important role and influence the solution quality significantly.

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47

Beebe, Kirk. "Substrate recognition through modular domains : protein tyrosine phosphatase SHP-1 and tail-specific protease (TSP) /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488203158827833.

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Anastasi, Cyril. "De la maturation des collagènes à la régulation de la signalisation TGF-ß : nouveaux rôles moléculaires et cellulaires de la métalloprotéase BMP-1." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1097.

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Abstract:

La Bone Morphogenetic Protein-1 (BMP-1) est une métalloprotéase impliquée dans la maturation et l'activation de nombreuses molécules extracellulaires. Parmi celles-ci, on trouve notamment les collagènes fibrillaires, les protéines les plus abondante chez l'Homme, ainsi que les facteurs de croissance de la superfamille du TGF-ß, des protéines pléiotropes. Au travers de ses fonctions, BMP-1 joue un rôle crucial au cours du développement embryonnaire mais également durant les processus physiologiques et pathologiques de remodelage tissulaire (cicatrisation, fibroses, croissance osseuse, cancers...).Le projet présenté dans ce manuscrit a consisté à étudier plusieurs fonctions importantes de BMP-1 au niveau moléculaire et à caractériser les conséquences de ces activités au niveau de plusieurs types cellulaires.Dans un premier temps, un test quantitatif a été mis au point afin de pouvoir étudier en temps réel l'effet de BMP-1 sur les collagènes fibrillaires ainsi que les mécanismes de sa régulation. Par la suite, de nouveaux substrats de BMP-1 ont été mis en évidence, parmi lesquels des co-récepteurs du TGF-ß (Bétaglycan, CD109) ainsi qu'une protéine matricellulaire (TSP-1). L'étude de ces activités a permis de caractériser les multiples voies par lesquelles BMP-1 est capable de réguler l'activité du facteur de croissance TGF-ß.De plus, nous avons mis en évidence que le clivage de ces différents substrats entraine une modulation importante du phénotype de plusieurs lignées cellulaires (HT1080, HEK-293T) avec des effets au niveau de l'adhésion, la prolifération et la migration cellulaire. En conclusion, ce travail révèle que les activités de BMP-1 s'étendent bien au-delà de ce qui est actuellement décrit
Bone Morphogenetic Protein (BMP-1) is a metalloprotease known to be involved in the maturation and activation of several important extracellular proteins, including fibrillar collagens and growth factors of the TGF-beta superfamily. As a consequence, it is essential for embryonic development and tissue remodeling and has been clearly involved in lethal diseases such as fibrosis and cancer.This thesis project focused on the major molecular functions of BMP-1 and their implications for the phenotype of several cell types. First, a quantitative and real-time assay was developed to study the effect of BMP-1 and associated regulatory proteins on fibrillar collagens. Then, new BMP-1 substrates, such as TGF-ß co-receptors (Betaglycan and CD109) and matricellular proteins (TSP-1) were characterized in detail. Especially, we evidenced that these activities played a major role in the regulation of the TGF-ß pathway.Furthermore, we shown that these BMP-1 activities induce major phenotype changes (adhesion, proliferation, migration) in several cell lines including HT1080 and HEK-293T. Altogether, this work reveals that BMP-1 substrates extend far beyond what is presently described and open several perspectives for future studies

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Spiers, Alison. "Investigation into the interaction between the SsrA-tagging system and the periplasmic proteases Tsp and HtrA." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247921.

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50

Sánchez, de Ribera de Castro Olga. "Neuropsychological functions in sex offenders : empirical relations and an evaluation of the thinking skills programme (TSP)." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708857.

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Dissertations / Theses on the topic 'TSP'

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