Regular homomorphisms of minimal sets

The classification of minimal sets is a central theme in abstract topological dynamics. Recently this work has been strengthened and extended by consideration of homomorphisms. Background material is presented in Chapter I. Given a flow on a compact Hausdorff space, the action extends naturally to the space of closed subsets, taken with the Hausdorff topology. These hyperspaces are discussed and used to give a new characterization of almost periodic homomorphisms. Regular minimal sets may be described as minimal subsets of enveloping semigroups. Regular homomorphisms are defined in Chapter II by extending this notion to homomorphisms with minimal range. Several characterizations are obtained. In Chapter III, some additional results on homomorphisms are obtained by relativizing enveloping semigroup notions. In Veech's paper on point distal flows, hyperspaces are used to associate an almost one-to-one homomorphism with a given homomorphism of metric minimal sets. In Chapter IV, a non-metric generalization of this construction is studied in detail using the new notion of a highly proximal homomorphism. An abstract characterization is obtained, involving only the abstract properties of homomorphisms. A strengthened version of the Veech Structure Theorem for point distal flows is proved. In Chapter V, the work in the earlier chapters is applied to the study of homomorphisms for which the almost periodic elements of the associated hyperspace are all finite. In the metric case, this is equivalent to having at least one fiber finite. Strong results are obtained by first assuming regularity, and then assuming that the relative proximal relation is closed as well.

Polymer microspheres: synthesis, characterisation and post-functionalisation by olefin metathesis

Porous polymer particles are used in an extraordinarily wide range of advanced and everyday applications, from combinatorial chemistry, solid-phase organic synthesis and polymer-supported reagents, to environmental analyses and the purification of drinking water. The installation and exploitation of functional chemical handles on the particles is often a prerequisite for their successful exploitation, irrespective of the application and the porous nature of the particles. New methodology for the chemical modification of macroreticular polymers is the primary focus of the work presented in this thesis. Porous polymer microspheres decorated with a diverse range of functional groups were synthesised by the post-polymerisation chemical modification of beaded polymers via olefin cross metathesis. The polymer microspheres were prepared by the precipitation polymerisation of divinylbenzene in porogenic (pore-forming) solvents; the olefin cross-metathesis (CM) functionalisation reactions exploited the pendent (polymer-bound) vinyl groups that were not consumed by polymerisation. Olefin CM reactions involving the pendent vinyl groups were performed in dichloromethane using second-generation Grubbs catalyst (Grubbs II), and a wide range of coupling partners used. The results obtained indicate that high quality, porous polymer microspheres synthesised by precipitation polymerisation in near-θ solvents can be functionalised by olefin CM under very mild conditions to install a diverse range of chemical functionalities into a common polydivinylbenzene precursor. Gel-type polymer microspheres were prepared by the precipitation copolymerisation reaction of divinylbenzene and allyl methacrylate in neat acetonitrile. The unreacted pendent vinyl groups that were not consumed by polymerisation were subjected to internal and external olefin metathesis-based hypercrosslinking reactions. Internal hypercrosslinking was carried out by using ring-closing metathesis (RCM) reactions in toluene using Grubbs II catalyst. Under these conditions, hypercrosslinked (HXL) polymers with specific surface areas around 500 m2g-1 were synthesised. External hypercrosslinking was attempted by using CM/RCM in the presence of a multivinyl coupling partner in toluene using second-generation Hoveyda-Grubbs catalyst. The results obtained indicate that no HXL polymers were obtained. However, during the development of this methodology, a new type of polymerisation was discovered with tetraallylorthosilicate as monomer.

Exact solutions to the short sea shipping distribution problem

Short sea shipping has several advantages over other means of transportation, recognized by EU members. The maritime transportation could be dealt like a combination of two well-known problems: the container stowage problem and routing planning problem. The integration of these two well-known problems results in a new problem CSSRP (Container stowage and ship routing problem) that is also an hard combinatorial optimization problem. The aim of this work is to solve the CSSRP using a mixed integer programming model. It is proved that regardless the complexity of this problem, optimal solutions could be achieved in a reduced computational time. For testing the mathematical model some problems based on real data were generated and a sensibility analysis was performed.

Trabalhar com a matemática em educação de infância

Este estudo tem como principal objetivo compreender e analisar o modo como crianças de creche e jardim-de-infância resolvem problemas matemáticos e o que pode constranger a resolução. Em particular, procurei analisar a atividade matemática que as crianças desenvolvem quando se confrontam com problemas matemáticos e os desafios com que se deparam. Do ponto de vista metodológico, o estudo enquadra-se numa abordagem qualitativa de investigação e num paradigma interpretativo. Além disso, trata-se de uma investigação-ação orientada pela questão “como otimizar a atividade de resolver problemas matemáticos em contextos de educação de infância?”. Neste âmbito, propus a quatro crianças de creche e a 21 de jardim-de-infância um conjunto de tarefas selecionadas para, potencialmente, terem, para si, algum grau de desafio. Os principais métodos de recolha de dados foram a observação participante, a análise documental e um inquérito por questionário realizado às educadoras cooperantes. O estudo ilustra que é possível envolver crianças de creche e de jardim-de-infância numa atividade de resolução de problemas matemáticos e que esta atividade é favorecida se o contexto dos problemas estiver próximo do que fazem no dia-a-dia da sala. Durante o processo de resolução das tarefas propostas, foram mobilizadas e trabalhadas diversas noções matemáticas. Na creche, todas as crianças evidenciaram possuir conhecimentos acerca da noção topológica “dentro de” e “fora de” e algumas foram bem-sucedidas no uso do processo de classificação, tendo em conta um critério. Neste âmbito, recorreram a representações ativas. No jardim-de-infância, todas as crianças conseguiram fazer a contagem sincronizada das letras do seu nome, de indicar a quantidade de letras, o que indicia o conhecimento da noção de cardinal, e de representar esta quantidade recorrendo tanto a numerais como a representações icónicas. Além disso, foram capazes de interpretar uma tabela de modo a construir um gráfico com barras e de elaborar um pictograma, o que revela possuírem conhecimentos ao nível da literacia estatística. Por último, algumas crianças foram bem-sucedidas na descoberta de estratégias de resolução de problemas que lhes permitiram inventariar exaustivamente todas as possibilidades de resolução e contar, organizadamente, estas possibilidades. No decurso desta atividade surgiram tentativas de generalização, embora nem sempre corretas, sobressaindo o recurso a representações ativas nomeadamente à dramatização de situações. Quanto aos desafios com que se depararam destacam-se, no caso da creche, o uso correto do processo de classificação. No caso do jardim-de-infância, as crianças demonstraram dificuldades em distinguir a legenda do pictograma dos dados, em resolver um problema em que estava em jogo o sentido combinatório da multiplicação e em encontrar estratégias de generalização. O estudo indicia, ainda, que é essencial que o educador proponha tarefas diversificadas e desafiantes que, partindo sempre da curiosidade e interesse das crianças, lhes permitam trabalhar com ideias matemáticas importantes e representar adequadamente o conhecimento com que lidam.

An experimental study of adaptive control for evolutionary algorithms

International audience

Tabu search for the cyclic bandwidth problem

International audience

Boosting the performance of metaheuristics for the MinLA problem using a more discriminating evaluation function

International audience

Iterated responsive threshold search for the quadratic multiple knapsack problem

International audience

Effective Learning-Based Hybrid Search for Bandwidth Coloring

International audience

Mathematical Programming Models for Influence Maximization on Social Networks

In this dissertation, we apply mathematical programming techniques (i.e., integer programming and polyhedral combinatorics) to develop exact approaches for influence maximization on social networks. We study four combinatorial optimization problems that deal with maximizing influence at minimum cost over a social network. To our knowl- edge, all previous work to date involving influence maximization problems has focused on heuristics and approximation. We start with the following viral marketing problem that has attracted a significant amount of interest from the computer science literature. Given a social network, find a target set of customers to seed with a product. Then, a cascade will be caused by these initial adopters and other people start to adopt this product due to the influence they re- ceive from earlier adopters. The idea is to find the minimum cost that results in the entire network adopting the product. We first study a problem called the Weighted Target Set Selection (WTSS) Prob- lem. In the WTSS problem, the diffusion can take place over as many time periods as needed and a free product is given out to the individuals in the target set. Restricting the number of time periods that the diffusion takes place over to be one, we obtain a problem called the Positive Influence Dominating Set (PIDS) problem. Next, incorporating partial incentives, we consider a problem called the Least Cost Influence Problem (LCIP). The fourth problem studied is the One Time Period Least Cost Influence Problem (1TPLCIP) which is identical to the LCIP except that we restrict the number of time periods that the diffusion takes place over to be one. We apply a common research paradigm to each of these four problems. First, we work on special graphs: trees and cycles. Based on the insights we obtain from special graphs, we develop efficient methods for general graphs. On trees, first, we propose a polynomial time algorithm. More importantly, we present a tight and compact extended formulation. We also project the extended formulation onto the space of the natural vari- ables that gives the polytope on trees. Next, building upon the result for trees---we derive the polytope on cycles for the WTSS problem; as well as a polynomial time algorithm on cycles. This leads to our contribution on general graphs. For the WTSS problem and the LCIP, using the observation that the influence propagation network must be a directed acyclic graph (DAG), the strong formulation for trees can be embedded into a formulation on general graphs. We use this to design and implement a branch-and-cut approach for the WTSS problem and the LCIP. In our computational study, we are able to obtain high quality solutions for random graph instances with up to 10,000 nodes and 20,000 edges (40,000 arcs) within a reasonable amount of time.

Development of docetaxel and alendronate-loaded chitosan-conjugated polylactide-co-glycolide nanoparticles: In vitro characterization in osteosarcoma cells

Purpose: To develop docetaxel (DTX)- and alendronate (ALN)-loaded, chitosan (CS)-conjugated polylactide- co-glycolide (PLGA) nanoparticles (NPs) to increase therapeutic efficacy in osteosarcoma cells. Methods: Drug-loaded PLGA NPs were prepared by nanoprecipitation and chemically conjugated by the carboxylic group of PLGA to the amine-bearing CS polymer. The nanocarrier was characterized by dynamic light scattering, transmission electron microscopy, scanning electron microscopy, and differential scanning calorimetry as well as by in vitro drug release and cell culture studies. Results: NP size was within the tumour targeting range (~200 nm) with an effective positive charge (20 mV), thus increasing cellular uptake efficiency. Morphological analysis revealed clear spherical particles with uniform dispersion. The NPs exhibited identical sustained release kinetics for both DTX and ALN. CS-conjugated PLGA with dual-drug-loaded (DTX and AL) NPs showed typical time-dependent cellular uptake and also displayed superior cytotoxicity in MG-63 cells compared with blank NPs, which were safe and biocompatible. Conclusion: Combined loading of DTX and ALN in NPs increased the therapeutic efficacy of the formulation for osteosarcoma treatment, thus indicating the potential benefit of a combinatorial drug regimen using nanocarriers for effective treatment of osteosarcoma.

Tools For Spatiotemporally Specific Proteomic Analysis In Multicellular Organisms

The emergence of mass spectrometry-based proteomics has revolutionized the study of proteins and their abundances, functions, interactions, and modifications. However, in a multicellular organism, it is difficult to monitor dynamic changes in protein synthesis in a specific cell type within its native environment. In this thesis, we describe methods that enable the metabolic labeling, purification, and analysis of proteins in specific cell types and during defined periods in live animals. We first engineered a eukaryotic phenylalanyl-tRNA synthetase (PheRS) to selectively recognize the unnatural L-phenylalanine analog p-azido-L-phenylalanine (Azf). Using Caenorhabditis elegans, we expressed the engineered PheRS in a cell type of choice (i.e. body wall muscles, intestinal epithelial cells, neurons, pharyngeal muscles), permitting proteins in those cells -- and only those cells -- to be labeled with azides. Labeled proteins are therefore subject to "click" conjugation to cyclooctyne-functionalized affnity probes, separation from the rest of the protein pool and identification by mass spectrometry. By coupling our methodology with heavy isotopic labeling, we successfully identified proteins -- including proteins with previously unknown expression patterns -- expressed in targeted subsets of cells. While cell types like body wall or pharyngeal muscles can be targeted with a single promoter, many cells cannot; spatiotemporal selectivity typically results from the combinatorial action of multiple regulators. To enhance spatiotemporal selectivity, we next developed a two-component system to drive overlapping -- but not identical -- patterns of expression of engineered PheRS, restricting labeling to cells that express both elements. Specifically, we developed a split-intein-based split-PheRS system for highly efficient PheRS-reconstitution through protein splicing. Together, these tools represent a powerful approach for unbiased discovery of proteins uniquely expressed in a subset of cells at specific developmental stages.

Étude de la médiane de permutations sous la distance de Kendall-Tau

La distance de Kendall-τ compte le nombre de paires en désaccord entre deux permuta- tions. La distance d’une permutation à un ensemble est simplement la somme des dis- tances entre cette permutation et les permutations de l’ensemble. À partir d’un ensemble donné de permutations, notre but est de trouver la permutation, appelée médiane, qui minimise cette distance à l’ensemble. Le problème de la médiane de permutations sous la distance de Kendall-τ, trouve son application en bio-informatique, en science politique, en télécommunication et en optimisation. Ce problème d’apparence simple est prouvé difficile à résoudre. Dans ce mémoire, nous présentons plusieurs approches pour résoudre le problème, pour trouver une bonne solution approximative, pour le séparer en classes caractéristiques, pour mieux com- prendre sa compléxité, pour réduire l’espace de recheche et pour accélérer les calculs. Nous présentons aussi, vers la fin du mémoire, une généralisation de ce problème et nous l’étudions avec ces mêmes approches. La majorité du travail de ce mémoire se situe dans les trois articles qui le composent et est complémenté par deux chapitres servant à les lier.

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.

Interrelated product design activities sequencing with efficient tabu search algorithms

This paper proposes and investigates a metaheuristic tabu search algorithm (TSA) that generates optimal or near optimal solutions sequences for the feedback length minimization problem (FLMP) associated to a design structure matrix (DSM). The FLMP is a non-linear combinatorial optimization problem, belonging to the NP-hard class, and therefore finding an exact optimal solution is very hard and time consuming, especially on medium and large problem instances. First, we introduce the subject and provide a review of the related literature and problem definitions. Using the tabu search method (TSM) paradigm, this paper presents a new tabu search algorithm that generates optimal or sub-optimal solutions for the feedback length minimization problem, using two different neighborhoods based on swaps of two activities and shifting an activity to a different position. Furthermore, this paper includes numerical results for analyzing the performance of the proposed TSA and for fixing the proper values of its parameters. Then we compare our results on benchmarked problems with those already published in the literature. We conclude that the proposed tabu search algorithm is very promising because it outperforms the existing methods, and because no other tabu search method for the FLMP is reported in the literature. The proposed tabu search algorithm applied to the process layer of the multidimensional design structure matrices proves to be a key optimization method for an optimal product development.