Un des buts principaux de la biologie évolutive et de la médecine moléculaire consiste à reconstruire les relations phylogénétiques entre organismes à partir de leurs séquences moléculaires. En littérature, cette question est connue sous le nom d’inférence phylogénétique et a d'importantes applications dans la recherche médicale et pharmaceutique, ainsi que dans l’immunologie, l’épidémiologie, et la dynamique des populations. L’accumulation récente de données de séquences d’ADN dans les bases de données publiques, ainsi que la facilité relative avec laquelle des données nouvelles peuvent être obtenues, rend l’inférence phylogénétique particulièrement difficile (l'inférence phylogénétique est un problème NP-Hard sous tous les critères d’optimalité connus), de telle manière que des nouveaux critères et des algorithmes efficaces doivent être développés. Cette thèse a pour but: (i) d’analyser les limites mathématiques et biologiques des critères utilisés en inférence phylogénétique, (ii) de développer de nouveaux algorithmes efficaces permettant d’analyser de plus grands jeux de données.

La construction de modèles qui protègent contre les incertitudes dans les données, telles que la variabilité de l'information et l'imprécision est une des principales préoccupations en optimisation sous incertitude. L'incertitude peut affecter différentes domaines, comme le transport, les télécommunications, la finance, etc., ainsi que les différentes parts d'un problème d'optimisation, comme les coefficients de la fonction objectif et /ou les contraintes. De plus, l'ensemble des données incertaines peut être modélisé de différentes façons, comme sous ensembles compactes et convexes de l´espace réel de dimension n, polytopes, produits Cartésiens des intervalles, ellipsoïdes, etc. Une des approches possibles pour résoudre des tels problèmes est de considérer les versions minimax regret, pour lesquelles résoudre un problème sous incertitude revient à trouver une solution qui s'écarte le moins possible de la valeur solution optimale dans tout les cas. Dans le cas des incertitudes définies par intervalles, les versions minimax regret de nombreux problèmes combinatoires polynomiaux sont NP-difficiles, d'ou l'importance d'essayer de réduire l'espace des solutions. Dans ce contexte, savoir quand un élément du problème, représenté par une variable, fait toujours ou jamais partie d'une solution optimal pour toute réalisation des données (variables 1-persistentes et 0-persistentes respectivement), constitue une manière de réduire la taille du problème. Un des principaux objectifs de cette thèse est d'étudier ces questions pour quelques problèmes d'optimisation combinatoire sous incertitude. Nous étudions les versions minimax regret du problème du choix de p éléments parmi m, de l'arbre couvrant minimum et des deux problèmes de plus court chemin. Pour de tels problèmes, dans le cas des incertitudes définis par intervalles, nous étudions le problème de trouver les variables 1- et 0-persistentes. Nous présentons une procédure de pre-traitement du problème, lequel réduit grandement la taille des formulations des versions de minimax regret. Nous nous intéressons aussi à la version minimax regret du problème de programmation linéaire dans le cas où les coefficients de la fonction objectif sont incertains et l'ensemble des données incertaines est polyédral. Dans le cas où l'ensemble des incertitudes est défini par des intervalles, le problème de trouver le regret maximum est NP-difficile. Nous présentons des cas spéciaux ou les problèmes de maximum regret et de minimax regret sont polynomiaux. Dans le cas où l´ensemble des incertitudes est défini par un polytope, nous présentons un algorithme pour trouver une solution exacte au problème de minimax regret et nous discutons les résultats numériques obtenus dans un grand nombre d´instances générées aléatoirement. Nous étudions les relations entre le problème de 1-centre continu et la version minimax regret du problème de programmation linéaire dans le cas où les coefficients de la fonction objectif sont évalués à l´aide des intervalles. En particulier, nous décrivons la géométrie de ce dernier problème, nous généralisons quelques résultats en théorie de localisation et nous donnons des conditions sous lesquelles certaines variables peuvet être éliminées du problème. Finalement, nous testons ces conditions dans un nombre d´instances générées aléatoirement et nous donnons les conclusions.

This thesis describes the development and use ofnon-immunoglobulin affinity proteins denoted affibodies asalternatives to antibodies in different immunotechnologyapplications. A 58 aa IgG Fc binding three-helix bundle domainZ, derived from staphylococcal protein A has been used asframework for library constructions, in which the face of themolecule involved in the native binding activity has beenengineered by combinatorial protein engineering. Recruting 13surface-located positions for simultanenous substitutionmutagenesis, using degenerated oligonucleotides for libraryassembly at the genetic level, two libraries differing in thechoice of codons were constructed to serve as general sourcesof novel affinity proteins. The libraries were adapted fordisplay onE. colifilamentous phage particles allowingin vitroselection of desired variants capable ofbinding a given target molecule. In selections using human IgAas target, several new IgA specific affibodies could beidentified. One variant ZIgA1, was further investigated and showed binding toboth IgA1 and IgA2 human subclasses as well as to secretoryIgA. This variant was further demonstrated uesful as ligand inaffinity chromatography purification for recovery of IgA fromdifferent samples including unconditioned human plasma.Affibodies of different specificities were also fused to otherprotein domains to construct fusion proteins of relevance forimmunotechnology applications. Using Fc of human IgG as genefusion partner, "artificial antbodies" could be produced inE. colias homodimeic proteins, where the antigenbinding was confered by N-terminally positioned affibodymoieties of different valencies. One area of application forthis type of constructs was demonstrated through specificdetection of the target protein by Western blotting. Exploitingthe uncomplicated structure of affibody affinity proteins, genefusions between affibodies and the homotetrameric reporterenzyme β-galactosidase were constructed, which could beproduced as soluble proteins intracellularly inE. coli. The potential use of such recombinantimmunoconjugates in immunotechnology was demonstrated in ELISAdot-blot and immunohistochemistry, where in the latter case IgAdepositions in the glomeruli of a human kidney biopsy could bespecfically detected with low background staining ofsurrounding tissues. In a novel format for sandwich ELISA, thepossible advantage of the bacterial origin of the affibodyclass of affinity proteins was investigated. As a means tocircumvent problems associated with the presence of humanheterophilic antibodies in serum, causing bakground signals dueto analyte-independent crosslinking of standard capture anddetection antibody reagents, assay formats based oncombinations of antibody and affibody reagents for capture anddetection were investigated and found to be of potentialuse. <b>Keywords:</b>phage display, combinatorial, affinity, IgAligand, immunohistochemistry, affibody-fusions

The thesis consists of four papers on combinatorial auctions and a summary. The first part is more of a practical nature and contains two papers. In the first paper, we study the performance of a caching technique in an optimal algorithm for a multi-unit combinatorial auction. In the second paper, we compare the revenues from a second-price combinatorial auction against a second-price one-shot simultaneous auction. In particular, we show that when the synergy parameter is small, the combinatorial auction gives a higher expected revenue than the one-shot. This is in contrast to an earliear result by Krishna and Rosenthal. We also compare the two mechanisms under the assumption that bidders are risk-averse. Such bidders are more sensitive to financial loss (winner's curse) that they tend to bid less aggressively, which leads to lower revenues. Since a direct analytical approach turns out to be difficult, we present numerical results that show which auction mechanism maximizes the seller's revenue depending on the values of synergy and aversion parameter. The second part is more theoretical. Here, we analyze the asymptotic performance of a greedy algorithm for a problem inspired by combinatorial auctions. In particular, we consider a special case in which every bid contains exactly 3 items, and use a Poisson process to model an auction with a random (Poisson) No. of bids. For this restricted case, winner determination problem is equivalent to a maximal 3-set packing on a weighted hypergraph, and hence NP-complete. However, the greedy algorithm approximates this special case within a factor of 3. In the third paper, we compute the asymptotic expected size of the partial allocation and its corresponding expected total revenue from the greedy algorithm, for some distribution of bid prices. In the final paper, we study the case of a deterministic number of bids, which is proportional to the number of distinguishable items in the auction, say M. Then, we prove that the number of bids allocated, suitably normalized, converges to a Normal random variable as M goes to infinity. As a prelude, we also prove that, both the number of bids allocated and those submitted, again suitably normalized, jointly converge in distribution to a continuous 2-dimensional Gaussian process as M goes to infinity.

We study the complexity of finding so called spanner paths between arbitrary nodes in Euclidean graphs. We study both general Euclidean graphs and a special type of graphs called Integer Graphs. The problem is proven NP-complete for general Euclidean graphs with non-constant stretches (e.g. (2n)^(3/2) where n denotes the number of nodes in the graph). An algorithm solving the problem in O(2^(0.822n)) is presented. Integer graphs are simpler and for these special cases a better algorithm is presented. By using a partial order of so called Images the algorithm solves the spanner path problem using O(2^(c(\log n)^2)) time, where c is a constant depending only on the stretch.

In this thesis we present a novel algorithm, <I>HyperCleaning*</I>, for effectively inferring phylogenetic trees. The method is based on the quartet method paradigm and is guaranteed to recover the best supported edges of the underlying phylogeny based on the witness quartet set. This is performed efficiently using a collapsing mechanism that employs memory/time tradeoff to ensure no loss of information. This enables <I>HyperCleaning*</I> to solve the relaxed version of the Maximum-Quartet-Consistency problem feasibly, thus providing a valuable tool for inferring phylogenies using quartet based analysis.

Combinatorial auctions (CAs) are an important mechanism for allocating multiple items while allowing agents to specify preferences over bundles of items. In order to communicate these preferences, agents submit bids, which consist of one or more items and a value indicating the agent’s preference for these items. The process of determining the allocation of items is known as the winner determination problem (WDP). WDP for CAs is known to be NP-complete in the general case. We consider two distinct graph representations of a CA; the bid graph and the item graph. In a bid graph, vertices represent bids, and two vertices are adjacent if and only if the bids share items in common. In an item graph, each vertex represents a unique item, there is a vertex for each item, and any bid submitted by any agent must induce a connected subgraph of the item graph. We introduce a new definition of combinatorial auction equivalence by declaring two CAs equivalent if and only if their bid graphs are isomorphic. Parameterized complexity theory can be used to further distinguish between NP-hard problems. In order to make use of parameterized complexity theory in the investigation of a problem, we aim to find one or more parameters that describe some aspect of the problem such that if we fix these parameters, then either the problem is still hard (fixed-parameter intractable), or the problem can be solved in polynomial time (fixed-parameter tractable). We analyze WDP using bid graphs from within the formal scope of parameterized complexity theory. This approach has not previously been used to analyze WDP for CAs, although it has been used to solve set packing, which is related to WDP for CAs and is discussed in detail. We investigate a few parameterizations of WDP; some of the parameterizations are shown to be fixed-parameter intractable, while others are fixed-parameter tractable. We also analyze WDP when the graph class of a bid graph is restricted. We also discuss relationships between item graphs and bid graphs. Although both graphs can represent the same problem, there is little previous work analyzing direct relationships between them. Our discussion on these relationships begins with a result by Conitzer et al. [7], which focuses on the item graph representation and its treewidth, a property of a graph that measures how close the graph is to a tree. From a result by Gavril, if an item graph has treewidth one, then the bid graph must be chordal [16]. To apply the other direction of Gavril’s theorem, we use our new definition of CA equivalence. With this new definition, Gavril’s result shows that if a bid graph of a CA is chordal, then we can construct an item graph that has treewidth one for some equivalent CA.

One of the simplest, but still NP-hard, routing problems is the Traveling Salesman Problem (TSP). In the TSP, one is given a set of cities and a way of measuring the distance between cities. One has to find the shortest tour that visits all cities exactly once and returns back to the starting city. In state-of-the-art algorithms, they all assume that a complete graph is given as an input. However, for very large graphs, generating all edges in a complete graph, which corresponds to finding shortest paths for all city pairs, could be time-consuming. This is definitely a major obstacle for some real-life applications, especially when the tour needs to be generated in real-time. The objective, in this thesis, is to find a near-optimal TSP tour with a reduced set of edges in the complete graph. In particular, the following problems are investigated: which subset of edges can be produced in a shorter time comparing to the time for generating the complete graph? Is there a subset of edges in the complete graph that results in a better near-optimal tour than other sets? With a non-complete graph, which improvement algorithms work better? In this thesis, we study six algorithms to generate subsets of edges in a complete graph. To evaluate the proposed algorithms, extensive experiments are conducted with the well-known TSP data in a TSP library. In these experiments, we evaluate these algorithms in terms of tour quality, time and scalability.

A balanced tournament design of order <I>n</I>, BTD(<I>n</I>), defined on a 2<I>n</I>-set<I> V</i>, is an arrangement of the all of the (2<I>n</i>2) distinct unordered pairs of elements of <I>V</I> into an <I>n</I> X (2<I>n</i> - 1) array such that (1) every element of <I>V</i> occurs exactly once in each column and (2) every element of <I>V</I> occurs at most twice in each row. We will show that there exists a BTD(<i>n</i>) for <i>n</i> a positive integer, <i>n</i> not equal to 2. For <I>n</i> = 2, a BTD (<i>n</i>) does not exist. If the BTD(<i>n</i>) has the additional property that it is possible to permute the columns of the array such that for every row, all the elements of<I> V</I> appear exactly once in the first <i>n</i> pairs of that row and exactly once in the last <i>n</i> pairs of that row then we call the design a partitioned balanced tournament design, PBTD(<I>n</I>). We will show that there exists a PBTD (<I>n</I>) for <I>n</I> a positive integer, <I>n</I> is greater than and equal to 5, except possibly for <I>n</I> an element of the set {9,11,15}. For <I>n</I> less than and equal to 4 a PBTD(<I>n</I>) does not exist.

The <i>mixed postman problem</i> consists of finding a minimum cost tour of a mixed graph <i>M</i> = (<i>V</i>,<i>E</i>,<i>A</i>) traversing all its edges and arcs at least once. We prove that two well-known linear programming relaxations of this problem are equivalent. The <i>extra cost</i> of a mixed postman tour <i>T</i> is the cost of <i>T</i> minus the cost of the edges and arcs of <i>M</i>. We prove that it is <i>NP</i>-hard to approximate the minimum extra cost of a mixed postman tour. A related problem, known as the <i>windy postman problem</i>, consists of finding a minimum cost tour of an undirected graph <i>G</i>=(<i>V</i>,<i>E</i>) traversing all its edges at least once, where the cost of an edge depends on the direction of traversal. We say that <i>G</i> is <i>windy postman perfect</i> if a certain <i>windy postman polyhedron O</i> (<i>G</i>) is integral. We prove that series-parallel undirected graphs are windy postman perfect, therefore solving a conjecture of Win. Given a mixed graph <i>M</i> = (<i>V</i>,<i>E</i>,<i>A</i>) and a subset <i>R</i> &#8838; <i>E</i> &#8746; <i>A</i>, we say that a mixed postman tour of <i>M</i> is <i>restricted</i> if it traverses the elements of <i>R</i> exactly once. The <i>restricted mixed postman problem</i> consists of finding a minimum cost restricted tour. We prove that this problem is <i>NP</i>-hard even if <i>R</i>=<i>A</i> and we restrict <i>M</i> to be planar, hence solving a conjecture of Veerasamy. We also prove that it is <i>NP</i>-complete to decide whether there exists a restricted tour even if <i>R</i>=<i>E</i> and we restrict <i>M</i> to be planar. The <i>edges postman problem</i> is the special case of the restricted mixed postman problem when <i>R</i>=<i>A</i>. We give a new class of valid inequalities for this problem. We introduce a relaxation of this problem, called the <i>b-join problem</i>, that can be solved in polynomial time. We give an algorithm which is simultaneously a 4/3-approximation algorithm for the edges postman problem, and a 2-approximation algorithm for the extra cost of a tour. The <i>arcs postman problem</i> is the special case of the restricted mixed postman problem when <i>R</i>=<i>E</i>. We introduce a class of necessary conditions for <i>M</i> to have an arcs postman tour, and we give a polynomial-time algorithm to decide whether one of these conditions holds. We give linear programming formulations of this problem for mixed graphs arising from windy postman perfect graphs, and mixed graphs whose arcs form a forest.