Orientador: Vinicius Amaral Armentano / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação / Made available in DSpace on 2018-08-09T05:53:35Z (GMT). No. of bitstreams: 1 Prado_DanielFernandoMechlin_M.pdf: 451492 bytes, checksum: 0350938f30a018718f3b59654e155a93 (MD5) Previous issue date: 2007 / Resumo: Localização de facilidades é uma das atividades da área de logística que envolve decisões do número, localização e tamanho das facilidades a serem usadas. A localização de facilidades é uma questão central no planejamento estratégico de empresas públicas e privadas e está associada à variação da população em uma região, capital de investimento e estimativa de clientes que podem ser servidos. Este trabalho aborda o problema de localização de facilidades com restrições de capacidade e fonte única para atender a demanda de clientes. A fonte única impõe que um cliente seja atendido por uma única facilidade, e o objetivo é minimizar os custos de instalação e atendimento dos clientes. Este problema tem diversas aplicações, incluindo a localização de concentradores em redes de telecomunicações. Trata-se de um problema complexo de otimização combinatória, em que métodos exatos não produzem uma solução ótima em tempo viável, e portanto o uso de métodos heurísticos é pertinente. O objetivo deste trabalho é o desenvolvimento e implementação de um algoritmo de busca tabu para o problema, e comparação de seu desempenho com outros métodos apresentados na literatura. Palavras-chave: Localização de Facilidades, Otimização Combinatória, Heurística, Busca Tabu / Abstract: Facility location is a logistic problem that involves the decision on the number, location and capacity of facilities to be opened. Facility location is an important area in the strategic planning of public and private companies and is associated with population changes, money availability for investment and the estimation of the number of customers to be served. This work addresses on single source capacitated facility location problem. Single source imposes that each customer must be assigned to only one facility, and the objective is to minimize the installation and transportation costs. This problem has several applications, including the network concentrator location problem. It is a complex combinatorial optimization problem, which cannot be solved by exact methods in small computational times; therefore, heuristics methods are indicated. The objective of this thesis is the development and implementation of a tabu search algorithm for the problem and a comparative analysis with other methods available in the literature. Keywords: Facility location, Combinatorial Optimization, Heuristic, Tabu Search / Mestrado / Automação / Mestre em Engenharia Elétrica

The naturally occurring mineral of Cu2ZnSnS4 (CZTS) is a promising alternative absorber layer for thin film based photovoltaic devices. It has the remarkable advantage that it consists of abundant, inexpensive and non-toxic elements compared to its crystallographically related and highly successful counterparts: the Cu(In,Ga)(S,Se)2 (CIGSSe) and CuIn(S, Se)2 (CISSe) material systems. Therefore, there is real commercial potential for reduced material costs and improved device efficiencies. A two-stage high throughput combinatorial process for the fabrication of Cu-Zn-Sn-S thin film libraries is presented, which consists of either sequentially stacking or co-depositing Cu,Sn and Zn precursor layers by DC magnetron sputtering followed by a sulphurisation process. Sputtering conditions and target-substrate geometry are developed to give compositionally graded Cu-Zn-Sn precursor layers spanning a wide spatial region around the point of stoichiometry. Conversion into Cu-Zn-Sn-S libraries is achieved by thermally evaporating a uniform layer of sulphur directly onto the metal alloy and annealing the sample at 500 °C in a furnace. Effects of the precursor composition on the structural properties of the films prior to the incorporation of sulphur are investigated. The sulphurised libraries are then studied by Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Raman spectroscopy as a function of composition, to assess the effects on morphology and phase formation. Observations of changes in lattice parameters and crystallinity are clear. The opto-electronic and electrical properties of the CZTS film libraries are measured using photoconductivity and hot point probe techniques, respectively. Changes in the band gap and conductivity type are studied as a function of atomic ratios. Based on high performing compositions, devices have been fabricated with the highest achieving cell at 1.26 %. The observations are discussed in the context of the particular compositions and synthesis conditions, and recommendations are made for further work.

No description available.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder caused by mutations or deletions in the dystrophin gene. Utrophin up-regulation therapy is among the various therapeutic strategies that are being investigated to treat DMD. In this strategy utrophin, a dystrophin homologue, is up-regulated along the entire length of the sarcolemma to replace the absent dystrophin protein. Previous studies have revealed that utrophin A expression can be controlled by various transcriptional, post-transcriptional and translational mechanisms and pharmacological modulation of these pathways can stimulate its expression in muscle. In the present study we screened several FDA approved and natural pharmacological compounds that can potentially activate utrophin A expression in muscle. We found that AICAR (AMPK activator) and heparin (p38 activator) were most effective in stimulating utrophin A expression in our C2C12 muscle cell system. Next, we analyzed the effect of combining these activators on utrophin A expression in muscle cells and preclinical mdx mouse model of DMD. Our findings revealed that combinatorial treatment of AICAR and heparin instigated an additive effect on utrophin A expression both in C2C12 muscle cells and mdx mice. Further characterization of treated mdx mice revealed that combinatorial treatment of AICAR and heparin caused improvements in the dystrophic phenotype as indicated by decreased central nucleation, decreased fiber size variability and improved sarcolemmal integrity in dystrophic muscle. Together these findings established that combinatorial treatment of AICAR and heparin ameliorates the dystrophic phenotype in mdx mice and may serve as an effective therapeutic strategy for DMD.

Orientador: Orlando Lee / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Computação / Made available in DSpace on 2018-08-27T12:18:11Z (GMT). No. of bitstreams: 1 SanFelice_MarioCesar_D.pdf: 1457706 bytes, checksum: 4813f4ed44c52462656d56537d73d5dc (MD5) Previous issue date: 2015 / Resumo: Nesta tese estudamos problemas online das famílias de localização de instalações e de Steiner, através da abordagem de análise competitiva. O objetivo nestes problemas é construir uma rede de custo mínimo para atender a uma determinada demanda. Nós apresentamos resultados conhecidos para o problema Online da Localização de Instalações (OFL), o problema Online da Árvore de Steiner (OST) e o problema Online Single-Source Rent-or-Buy (OSRoB). O OFL consiste em atender a um conjunto de clientes, através da abertura de algumas instalações e da conexão de cada cliente com uma instalação aberta. O OST tem por objetivo conectar um conjunto de terminais utilizando uma árvore, que pode conter vértices não terminais, chamados vértices de Steiner. O OSRoB é uma versão rent-or-buy do OST, onde todos os terminais devem ser conectados a um nó especial chamado raíz. Os algoritmos e técnicas que apresentamos para estes problemas são importantes no desenvolvimento dos nossos algoritmos para os problemas que consideramos. Apresentamos novos resultados para o problema Online da Localização de Instalações com Coleta de Prêmios (OPFL), o problema Online da Árvore Estrela de Steiner (OSTS), e o problema Online da Localização de Instalações Conectadas (OCFL). O OPFL é uma generalização do OFL, em que alguns clientes podem ficar desconectados mediante o pagamento de penalidades. O OSTS é uma variante do OST, em que os vértices possuem custos não negativos. O OCFL é uma combinação do OFL e do OST, em que um conjunto de clientes precisa ser atendido através da abertura de algumas instalações, da conexão de cada cliente com uma instalação aberta, e da construção de uma árvore, mais custosa, que conecta as instalações abertas / Abstract: In this thesis we study online problems from the facility location and Steiner families, through the point of view of competitive analysis. The goal in these problems is to build a minimum cost network to attend a certain demand. We present known results for the Online Facility Location problem (OFL), the Online Steiner Tree problem (OST) and the Online Single-Source Rent-or-Buy problem (OSRoB). The OFL consists of serving a set of clients by opening some facilities and by connecting each client to a facility. The OST aims to connect a set of terminals in order to create a tree network, that may contain nonterminals, called Steiner nodes. The OSRoB is a rent-or-buy version of the OST, in which all terminals must be connected to a special node called root. The algorithms and techniques that we present for these problems play an important role in the design of our algorithms for the problems we consider. We present new results for the Online Prize-Collecting Facility Location problem (OPFL), the Online Steiner Tree Star problem (OSTS), and the Online Connected Facility Location problem (OCFL). The OPFL is a generalization of the OFL, in which some clients may be left unconnected by paying a penalty. The OSTS is a variant of the OST, in which the nodes have non-negative costs. The OCFL is a combination of the OFL and the OST, in which a set of clients needs to be served by opening some facilities, by connecting each client to a facility, and by creating a more expensive tree network that connects the open facilities / Doutorado / Ciência da Computação / Doutor em Ciência da Computação

O Problema de Minimização do Número Máximo de Pilhas Abertas (MOSP, do inglês minimization of open stacks problem) é um problema de otimização combinatória da família NP-Difícil que vem recebendo grande atenção na literatura especializada. Este trabalho apresenta novas contribuições em termos de modelos e técnicas de resolução para o problema. A primeira parte deste trabalho lidou com modelos matemáticos, sendo analisados os modelos existentes que se baseiam em programação inteira mista. Variações de um modelo da literatura foram propostas, com o objetivo de tentar diminuir o tempo de execução necessário para se obter uma solução exata com a utilização de pacotes comerciais. Os resultados mostraram que as propostas são capazes de acelerar a solução de algumas classes de instâncias mas, que de maneira geral, métodos baseados em relaxação linear encontram dificuldade em provar a otimalidade devido à baixa qualidade dos limitantes inferiores. Uma outra contribuição deste trabalho foi o desenvolvimento de um modelo conjunto para o problema MOSP e para o problema de minimização da duração de pedidos (MORP, do inglês minimization of order spread problem). Este modelo propõe um framework unificado em que os dois problemas podem ser resolvidos ao mesmo tempo, tendo suas funções objetivo individuais ponderadas através de pesos definidos pelo usuário. A segunda parte do trabalho voltou-se para o desenvolvimento de métodos heurísticos para o MOSP. Duas estratégias de solução foram desenvolvidas. O primeiro método propõe uma transformação heurística entre o problema MOSP e o clássico problema do caixeiro viajente (TSP, do inglês traveling salesman problem). A partir de uma representação em grafo do MOSP, o TSP é definido por meio de uma regra de atribuição de distâncias baseadas nos graus dos nós. Nos testes computacionais, a estratégia proposta mostrou-se eficiente em relação às heurísticas específicas para o MOSP, obtendo a solução ótima do MOSP em 80,42% das instâncias testadas e sendo competitiva em termos de tempo computacional com algumas das melhores heurísticas da literatura. O segundo método heurístico proposto utilizou a ideia de decomposição. De fato, neste método, um corte no grafo associado ao problema original divide-o em problemas menores, que são resolvidos. A solução global é obtida através da junção das soluções dos subproblemas e, em alguns casos, é possível demonstrar a otimalidade da solução obtida. Testes computacionais indicam a validade da proposta e apontam caminhos para pesquisas futuras / The minimization of open stacks problem (MOSP) is a well known NP-hard combinatorial optimization problem that has been extensively discussed in the specialized literature. This study presents some new contributions in terms of models and solution methods for this problem. The first part of this thesis dealt with mathematical models. The existing mixedinteger models have been analyzed and variants of a well known model have been proposed, with the goal of reducing the time needed by commercial packages to obtain proved-optimal solutions. The results of computational tests on a widely used set of instances have indicated that the modifications proposed are able to reduce the time needed to obtain optimal solutions for some classes of instances. Nevertheless, a conclusion has been the fact that mixed-integer programming models have difficulty in obtaining convergence due to the low quality linear relaxation bounds. Another contribution of this thesis is the proposal of a single model that is able to deal with both the MOSP and with the Minimization of Order Spread Problem (MORP). This unified framework allows both problems to be jointly solved, by using a weighted objective function that included both original objectives. The second part of this thesis dealt with the development of heuristic strategies. Two solution strategies have been proposed. The first method proposes a heuristic conversion between MOSP and Traveling Salesman Problem (TSP) instances. This conversion relies the assignment distances to the TSP instance based on the degree of the vertices of the associated MOSP graph. Computational tests have shown that the proposed methodology is efficient, both in terms of solution quality (optimal solutions were obtained for 80.42% of the tested instances) and computational effort. The second method uses a decomposition idea. A cut is made in the graph associated with the original MOSP problem, yielding two smaller problems, which are solved. In some cases, the obtained combined solution can be prover optimal. Computational tests have shown the validity of the proposal and indicate new research opportunities

In this doctoral thesis, four questions related to computational geometry are considered. The first is an extremal combinatorics question regarding triangles with vertices taken from a set of n points in convex position. More precisely, two such triangles can exhibit eight distinct configurations and, for each subset of these configurations, we are interested in the asymptotics of how many triangles one can have while avoiding configurations in the subset (as a function of n). For most of these subsets, we answer this question optimally up to a logarithmic factor in the form of several Turán-type theorems. The answers for the remaining few were in turn tied to that of a long-standing open problem which appeared in the literature in the contexts of monotone matrices, tripod packing and 2-comparable sets. The second problem, called Line Segment Covering (LSC), is about covering the cells of an arrangement of line segments with these line segments, where a segment covers the cells it is incident to. Recently, a PTAS, an APX -hardness proof and a FPT algorithm for variants of this problem have been shown. This paper and a new slight generalization of one of its results is included as a chapter. The third problem has been posed in the Sixth Annual Workshop on Geometry and Graphs and concerns the design of road networks to minimize the maximum travel time between two point sets in the plane. Traveling outside the roads costs more time per unit of distance than traveling on the roads and the total length of the roads can not exceed a budget. When the point sets are the opposing sides of a unit square and the budget is at most √2, we were able to come up with a few network designs that cover all possible cases and are provably optimal. Furthermore, when both point sets are the boundary of a unit circle, we managed to disprove the natural conjecture that a concentric circle is an optimal design. Finally, we consider collision-avoiding schedules of unit-velocity axis-aligned trains departing and arriving from points in the integer lattice. We prove a few surprising results on the existence of constant upper bounds on the maximum delay that are independent of the train network. In particular, these upper bounds are shown to always exist in two dimensions and to exist in three dimensions for unit-length trains. We also showed computationally that, for several scenarios, these upper bounds are tight.

Rank one subshifts are dynamical systems generated by a regular combinatorial process based on sequences of positive integers called the cut and spacer parameters. Despite the simple process that generates them, rank one subshifts comprise a generic set and are the source of many counterexamples. As a result, measure theoretic rank one subshifts, called rank one transformations, have been extensively studied and investigations into rank one subshifts been the basis of much recent work. We will answer several open problems about rank one subshifts. We completely classify the maximal equicontinuous factor for rank one subshifts, so that this factor can be computed from the parameters. We use these methods to classify when large classes of rank one subshifts have mixing properties. Also, we completely classify the situation when a rank one subshift can be a factor of another rank one subshift.

In affinity protein biotechnology the selective bindingbetween a chosen protein and an interacting biomolecule isutilized for a variety of applications including bioseparation,detection and therapy. Traditionally, affinity proteinsrecruited for such applications have been derived from naturalproteins or immunoglobulins generated via immunization routes.More recently, advances in the construction and handling oflarge collections of proteins(denoted libraries) generated invitro have opened up for new routes for the development ofaffinity proteins with desired properties. In this study, phage display selection technology was usedfor the isolation of novel human CD28 (hCD28)-specific affinityproteins from a protein library constructed by combinatorialprotein engineering of a 58 aa protein domain (Z) derived fromstaphylococcal protein A (SPA). From selections using hCD28 asa target molecule, several hCD28-specific affinity proteins(denoted affibodies) could be identified and analysis of theisolated affibody variants revealed a high degree of sequencehomology between the different clones. The biosensor analysisshowed that all variants bound to hCD28 with micromolardissociation constants (KD) and no significant cross-reactivitytowards the structurally related T-cell receptor hCTLA-4 couldbe observed. The apparent binding affinity for hCD28 of one ofthe isolated affibodies was further improved through fusion toa human Fc fragment fusion partner, resulting in a homodimericversion of the affibody ligand showing avidity effects uponhCD28 binding. Further, a co-culture experiment involvingJurkat T-cells and CHO cell lines tranfected to express eitherhuman CD80 or LFA-3 on the cell surface showed that apreincubation of Jurkat cells with one of the affibody variantsresulted in a specific concentration-dependent inhibition ofthe CD80 induced IL-2 production. This indicates that thisaffibody binds to hCD28 and specifically interferes with theco-stimulation signal mediated via hCD28 and hCD80. ACD28-specific binding protein could have potential as an agentfor various immunotherapy applications. In a second study, anaffinity protein-based strategy was investigated forsite-specific anchoring of proteins onto cellulose for woodfiber engineering purposes. Here, affinity proteins derivedfrom different sources were used for the assembly of acellulosome-like complex for specific and reversible anchoringof affinity domain-tagged reporter proteins to acellulose-anchored fusion protein. A fusion protein between acellulose binding module (Cel6A CBM1) derived from the fungalTrichoderma reesei and a five-domain staphylococcal protein A(SPA) moiety was constructed to serve as a platform for thedocking of reporter proteins produced as fusion to two copiesof a SPA-binding affibody affinity protein (denoted ZSPA-1),selected by phage display technology from a Z domain basedprotein library. In a series of experiments, involving repeatedwashing and low pH elutions, affinity tagged Enhanced GreenFluorescent Protein (EGFP) and Fusarium solani pisi lipasecutinase reporter proteins were both found to be specificallydirected from solution to a region of a cellulose-based filterpaper where the SPA-CBM fusion protein previously had beenpositioned. This showed that the cellulose-anchored SPA-Cel6ACBM1 fusion protein had been stably anchored to the surfacewith retained binding activity and that the interaction betweenSPA and the ZSPA-1 affibody domain was selective. phage display, combinatorial, selection, CD28, cellulosome,cellulose, affibody / NR 20140805

A connected digraph in which the in-degree of any vertex equals its out-degree is Eulerian; this baseline result is used as the basis of existence proofs for universal cycles (also known as ucycles or generalized deBruijn cycles or U-cycles) of several combinatorial objects. The existence of ucycles is often dependent on the specific representation that we use for the combinatorial objects. For example, should we represent the subset {2,5} of {1,2,3,4,5} as “25” in a linear string? Is the representation “52” acceptable? Or is it tactically advantageous (and acceptable) to go with {0,1,0,0,1}? In this paper, we represent combinatorial objects as graphs, as in [3], and exhibit the flexibility and power of this representation to produce graph universal cycles, or Gucycles, for k-subsets of an n-set; permutations (and classes of permutations) of [n]={1,2,…,n}, and partitions of an n-set, thus revisiting the classes first studied in [5]. Under this graphical scheme, we will represent {2,5} as the subgraph A of C5 with edge set consisting of {2,3} and {5,1}, namely the “second” and “fifth” edges in C5. Permutations are represented via their permutation graphs, and set partitions through disjoint unions of complete graphs.