Multi-armed bandit (MAB) algorithms could be used to select a subset of the k most informative summary statistics, from a pool of m possible summary statistics, by reformulating the subset selection problem as a MAB problem. This is suggested by experiments that tested five MAB algorithms (Direct, Halving, SAR, OCBA-m, and Racing) on the reformulated problem and comparing the results to two established subset selection algorithms (Minimizing Entropy and Approximate Sufficiency). The MAB algorithms yielded errors at par with the established methods, but in only a fraction of the time. Establishing MAB algorithms as a new standard for summary statistics subset selection could therefore save numerous scientists substantial amounts of time when selecting summary statistics for approximate bayesian computation.

L’allogreffe de cellules souches hématopoïétiques (CSH) est un traitement standard pour hémopathies bénigne ou malignes et immunodéficience primaire. Cependant, sauf le GvHD et la rechute de la maladie, l’infection microbiologique notamment l’infection virale est la complication fréquente des allogreffes qui est souvent responsable de la morbidité et la mortalité. Ces infections surviennent souvent en l’absence de reconstitution immunitaire. Les traitements médicamenteux anti-viraux qui ne sont pas toujours efficace et avec une toxicité non inégligeable. Donc le traitement prometteux est l’immunothérapie cellulaire notamment celui-ci avec l’injection de lymphocytes T spécifiques anti-viraux (VSTs). A UTCT, la production de VSTs-ADV a été mis au point depuis 2010 et une protocole clinique avec VSTs-ADV est en cours. Donc mon travail est s’inscrit dans ce thème pour produire les VSTs-EBV afin de proposer une protocole clinique. Comme les lymphocytes T ont plusieurs sous-populations, chaque sous-population présente des caractères différentes et leur efficacité en immunothérapie est limité par leur caractère. Notamment avec la découverte de Lymphocytes T mémoire à cellules souches (TSCM) qui joue un rôle très important en immunothérapie anti-cancéreux ou anti-viraux, nous nous intéréssons à étudier la compostion de sous-populations de VSTs. A la fin, c’est toujours avantageux de produire le VSTs contre deux ou plusieurs virus simutanément avec une économie financielle et personnelle. Nous voulons produire le VSTs bispécifique. Dans ce travail, premièrement, nous montrons le résulat de la mise au point de la production de VSTs-EBV de grade clinique qui est confromé à la réglémentation européenne. 6 productions ont été réalisées avec un antigène synthétique préablement défini qui est compatible avec utilisation clinique. In vitro, ces VSTs-EBV montre une spécificité, efficacité et non toxicité. Deuxième, nous illustrons nos résulats sur l’étude déscriptive de sous-populations de VSTs-ADV et CMV. D’abord nous montrons la distribution de sous-populations de VSTs chez les donneurs saints (avant la séléction), puis nous analysons la distribution après séléction immunomagnétique et aussi après expansion in vitro avec cytokine IL-2. A la fin, nous montrons nos résultats préliminaires sur les 3 productions de VSTs bispécifique anti-ADV et anti-EBV. Et nous les comprarer avec les VSTs monospécifique au niveau de qualité de production et spécificité, efficacité et toxicité in vitro / Allogeneic hematopoietic stem cell transplantation (HSCT) is the standard treatment for malignant or non-malignant hematological disorders or primary immunodeficiencies. However, microbiological infections especially viral infections are the major cause for morbidity and mortality for the patients after HSCT except the GvHD and disease relapse. It comes often in the period of absence of cellular immunity when the antiviral treatment is not always efficiency with an important toxicity. So the alternative treatment is adoptive cellular immunotherapy by infusion of virus specific T cells (VSTs) which has been shown efficacy in virus infections control after HSCT. In UTCT, they have produced the VSTs-ADV with a good procedure conforming to the European laws for clinical use and a clinic trial is in processing. So my work was to produce the VSTs-EBV with the same model aiming to promote a clinic trial in future. Furthermore, there are several subsets of T lymphocytes. Each subset has their own unique feature which decides their efficacy in viral infection control. Especially the discovery of stem cell like memory T cells (TSCM) with an important self-renewed ability which is critical in successful immunotherapy in viral infection or tumor control inspire us to study the distribution of subsets for VSTs. Finally, it’s advantageous to produce the VSTs targeted two or more virus in the same time with one production which is more economical. So we are interested in producing the VSTs bi-specific to ADV and EBV. Here, we present firstly our results of six production of VSTs-EBV with a synthesized antigen which is compatible with clinic use and is defined in advance. Also the specificity, efficiency in eliminating the virus and the non toxicity with a weak alloreactivity are confirmed in vitro after a short-term cell culture with IL-2. Then we showed the results obtained with the T cell subset study in producing the VSTs-ADV for clinical trial and VSTs-CMV for validation of clinical grade medium TEXMACS for cell culture in producing the VSTs. We describe the distribution of T cell subsets in healthy donors (Before selection), also after selection and after expansion in vitro with IL-2. Finally, we present the preliminary results of producing the VSTs bi-specific with three donors, in total 3 VSTs-ADV, 3 VSTs-EBV and 3VSTs-ADV/EBV are generated. The comparison between the bi-specific VSTs and mono-specific VSTs in aspect of specificity, efficiency to eliminate the viral infection and toxicity of presenting the alloreactivity in vitro showed advantage to produce the bi-specific VSTs with one selection in keeping the same specific, efficiency and weak toxicity as mono-specific VSTs

<p>Neka je A neprazan skup&nbsp; i ℒ&nbsp;= (L, &le;) proizvoljna mreža sa nulom i jedinicom. Svako preslikavanje &micro;: A &rarr; L zovemo rasplinuti podskup od A. U ovoj tezi proučavali smo rasplinute posete i relacije rasplinutog poretka. Uveli smo neke nove pojmove: rasplinuta uređena grupa, rasplinuti pozitivan konus, rasplinuti negativan konus, rasplinuta mrežno uređena grupa. Posmatrajući strukturu svih relacija slabog rasplinutog poretka koje su podskup klasične relacije poretka &le; , do&scaron;li smo do zaključka da ova struktura predstavlja kompletnu mrežu. Takođe, važan zadatak je bio da ispitamo egzistenciju rasplinute mrežno uređene podgrupe <i>l</i>&nbsp;&ndash;uređene grupe koja nije linearno uređena. Bitan rezultat je rasplinuta mrežno uređena podgrupa date mrežno uređene grupe G, koja je konstruisana pomoću mreže svih kompleksnih <em>l</em> &ndash;podgrupa od G.</p> / <p>Let A be a nonempty set, and let <em>ℒ</em> = (L, &le;) be a lattice with 0 and 1. The mapping: &micro;: A &rarr; L is called a fuzzy subset of A. In this work we investigated fuzzy posets and fuzzy ordering relations. We introduced some new notions: fuzzy ordered groups, fuzzy positive cone, fuzzy negative cone, fuzzy lattice ordered group. Considering a structure of all weak fuzzy orderings contained in the crisp order &le;, we concluded that this structure represents a complete lattice. Also, an important task was to investigate the existence of a fuzzy lattice ordered subgroup of an <em>l</em>&ndash;ordered group which is not linearly ordered. A main result is a fuzzy lattice ordered subgroup of a given lattice ordered group G, which is constructed by the lattice of all convex <em>l</em>-subgroups of G.</p>

A síndrome de Rubinstein-Taybi (RTS, OMIM 180849) é uma doença autossômica dominante caracterizada por dismorfismos craniofaciais típicos, polegares e háluces alargados, infecções respiratórias recidivantes, retardo mental e de crescimento. RTS está associada com mutação no gene CREBBP. Na avaliação da imunocompetência de 17 portadores de RTS, observaram-se algumas alterações na resposta imune inata e adaptativa: leucocitose persistente, neutrófilos com desgranulopoiese, elevada concentração sérica de IgM e IgG1, produção normal de anticorpos contra antígenos protéicos e anti-polissacarídeos, elevados valores absolutos de células B totais, B \"naive\", B de memória, subpopulação B1 e de linfócitos B com IgM de membrana, e elevado percentual de apoptose de linfócitos B. DTH negativo para três antígenos e baixa resposta linfoproliferativa para antígenos protéicos. Diante do exposto, concluímos que os pacientes RTS apresentam alterações em vários mecanismos da resposta imune e principalmente, na imunidade humoral. Portanto, com este trabalho foi possível identificar as principais alterações imunológicas destes pacientes, e com isso, caracterizar quais os defeitos da resposta imune que pode estar associada com gene CREBBP. / Rubinstein-Taybi syndrome (RTS, OMIM 180849) is a dominant Mendelian disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental retardation and growth and recurrent respiratory infections. RTS is classically associated with CREBBP gene mutations, but recently, p300 gene mutations were reported in three individuals. In imunonocompetence investigation of a group of 17 patient of the RTS, we found that the patients really show alterations in more than one arm of the immune response. The main alterations were found in: a) innate immunity, patients have defects in the distribution of the granules citoplasmatic and partial absence of F-actin filament part of its polymorphonuclear cells. In addition, some patients had decreased phagocytic activity, b) humoral immunity: elevated serum IgM antibodies and IgG1 subclass, normal production of antibodies for protein antigens and antipolysaccharide, high absolute values of B cell total, B \"naive\", B memory, subpopulation B1 and B lymphocytes with the membrane IgM, and high percentage of apoptosis of B lymphocytes; c) cellular immunity: delayed hypersensitivity skin tests negative for three antigens and low lymphoproliferative response to protein antigens. Values reduced percentage of CD45RA+ , CD45RO+ T cells and high doublepositive CD45RA+/CD45RO +) T cell. Ahead of the severe recurrent respiratory infections that affect the patients with RTS, and of the evaluation of immunocompetence of these patients, we find that they have several alterations in mechanisms of immune response and mainly in humoral immunity. Therefore, with this study was to identify the major immunological alterations of these patients, and with this, which characterize the main defects of the immune response of the patients RTS that can is associated with gene CREBBP.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

A síndrome de Rubinstein-Taybi (RTS, OMIM 180849) é uma doença autossômica dominante caracterizada por dismorfismos craniofaciais típicos, polegares e háluces alargados, infecções respiratórias recidivantes, retardo mental e de crescimento. RTS está associada com mutação no gene CREBBP. Na avaliação da imunocompetência de 17 portadores de RTS, observaram-se algumas alterações na resposta imune inata e adaptativa: leucocitose persistente, neutrófilos com desgranulopoiese, elevada concentração sérica de IgM e IgG1, produção normal de anticorpos contra antígenos protéicos e anti-polissacarídeos, elevados valores absolutos de células B totais, B \"naive\", B de memória, subpopulação B1 e de linfócitos B com IgM de membrana, e elevado percentual de apoptose de linfócitos B. DTH negativo para três antígenos e baixa resposta linfoproliferativa para antígenos protéicos. Diante do exposto, concluímos que os pacientes RTS apresentam alterações em vários mecanismos da resposta imune e principalmente, na imunidade humoral. Portanto, com este trabalho foi possível identificar as principais alterações imunológicas destes pacientes, e com isso, caracterizar quais os defeitos da resposta imune que pode estar associada com gene CREBBP. / Rubinstein-Taybi syndrome (RTS, OMIM 180849) is a dominant Mendelian disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental retardation and growth and recurrent respiratory infections. RTS is classically associated with CREBBP gene mutations, but recently, p300 gene mutations were reported in three individuals. In imunonocompetence investigation of a group of 17 patient of the RTS, we found that the patients really show alterations in more than one arm of the immune response. The main alterations were found in: a) innate immunity, patients have defects in the distribution of the granules citoplasmatic and partial absence of F-actin filament part of its polymorphonuclear cells. In addition, some patients had decreased phagocytic activity, b) humoral immunity: elevated serum IgM antibodies and IgG1 subclass, normal production of antibodies for protein antigens and antipolysaccharide, high absolute values of B cell total, B \"naive\", B memory, subpopulation B1 and B lymphocytes with the membrane IgM, and high percentage of apoptosis of B lymphocytes; c) cellular immunity: delayed hypersensitivity skin tests negative for three antigens and low lymphoproliferative response to protein antigens. Values reduced percentage of CD45RA+ , CD45RO+ T cells and high doublepositive CD45RA+/CD45RO +) T cell. Ahead of the severe recurrent respiratory infections that affect the patients with RTS, and of the evaluation of immunocompetence of these patients, we find that they have several alterations in mechanisms of immune response and mainly in humoral immunity. Therefore, with this study was to identify the major immunological alterations of these patients, and with this, which characterize the main defects of the immune response of the patients RTS that can is associated with gene CREBBP.

<p>Neka je A neprazan skup i L = (L;&middot;) proizvoljna mreža sa nulom i jedinicom. Svako preslikavanje A&macr; : A &iexcl;! L zovemo rasplinuti podskup od A. Uobičajeno je da se rasplinute podgrupe defini&scaron;u na grupi. U radu su fazi podgrupe definisane na polugrupi kao i na rasplinutoj podpolugrupi. Jedan od glavnih rezultata je teorema o particiji rasplinutih kompletno regularnih polugrupa. Takođe su definisane rasplinute kongruencije i rasplinute&nbsp;jednakosti na rasplinutim podalgebrama neke algebre i ispitane njihove osobine. Uvedeni su pojmovi: podalgebre rasplinute podalgebre, rasplinutog homomorfizma rasplinute podalgebre na rasplinutu podalgebru i direktnog proizvoda rasplinutih podalgebri. Jedan od važnijih rezultata je teorema koja je uop&scaron;tenje teoreme Birkhoff-a na rasplinutim strukturama.</p> / <p>Let A be nonemptu set, and let L = (L; 6) be a lattice with 0 and 1. The mapping A&macr; : A ! L is called fuzzy subset of A. It is usual to define fuzzy subgroup on the group. In this work fuzzy semigroups are defined on the semigroup and on the fuzzy subsemigroup, too. As a main result is theorem about partition fuzzy completlu regular semigroup. Also, fuzzy congruences are defined, and fuzzy equolites on fuzzy subalgebras of an algebra and their propertes are investigated. We introduced some new notions: subalgebras of fuzzy subalgebras, fuzzy homomorphism of fuzzy subalgebra, and direct product of fuzzy subalgebras. One of the most important result is extension of Birkhoff&rsquo;s theorem on fuzzy structures.</p>

Ce mémoire porte sur l’étude des modèles autorégressifs avec variables exogènes et sélection d’indices. La littérature classique regorge de textes concernant la sélection d’indices dans les modèles autorégressifs. Ces modèles sont particulièrement utiles pour des données macroéconomiques mesurées sur des périodes de temps modérées à longues. Effectivement, la lourde paramétrisation des modèles complets peut souvent être allégée en utilisant la sélection d’indices aboutissant ainsi à des modèles plus parcimonieux. Les modèles à variables exogènes sont très intéressants dans le contexte où il est connu que les variables à l’étude sont affectées par d’autres variables, jouant le rôle de variables explicatives, que l’analyste ne veut pas forcément modéliser. Ce mémoire se propose donc d’étudier les modèles autorégressifs vectoriels avec variables exogènes et sélection d’indices. Ces modèles ont été explorés, entre autres, par Lütkepohl (2005), qui se contente cependant d’esquisser les développements mathématiques. Nous concentrons notre étude sur l’inférence statistique sous des conditions précises, la modélisation ainsi que les prévisions. Notre objectif est de comparer les modèles avec sélection d’indices aux modèles autorégressifs avec variables exogènes complets classiques. Nous désirons déterminer si l’utilisation des modèles avec sélection d’indices est marquée par une différence favorable au niveau du biais et de l’écart-type des estimateurs ainsi qu’au niveau des prévisions de valeurs futures. Nous souhaitons également comparer l’efficacité de la sélection d’indices dans les modèles autorégressifs ayant des variables exogènes à celle dans les modèles autorégressifs. Il est à noter qu’une motivation première dans ce mémoire est l’estimation dans les modèles autorégressifs avec variables exogènes à sous-ensemble d’indices. Dans le premier chapitre, nous présentons les séries temporelles ainsi que les diverses notions qui y sont rattachées. De plus, nous présentons les modèles linéaires classiques multivariés, les modèles à variables exogènes puis des modèles avec sélection d’indices. Dans le deuxième chapitre, nous exposons le cadre théorique de l’estimation des moindres carrés dans les modèles autorégressifs à sous-ensemble d’indices ainsi que le comportement asymptotique de l’estimateur. Ensuite, nous développons la théorie pour l’estimation des moindres carrés (LS) ainsi que la loi asymptotique des estimateurs pour les modèles autorégressifs avec sélection d’indices (SVAR) puis nous faisons de même pour les modèles autorégressifs avec variables exogènes et tenant compte de la sélection des indices (SVARX). Spécifiquement, nous établissons la convergence ainsi que la distribution asymptotique pour l’estimateur des moindres carrés d’un processus autorégressif vectoriel à sous-ensemble d’indices et avec variables exogènes. Dans le troisième chapitre, nous appliquons la théorie spécifiée précédemment lors de simulations de Monte Carlo. Nous évaluons de manière empirique les biais et les écarts-types des coefficients trouvés lors de l’estimation ainsi que la proportion de fois que le modèle ajusté correspond au vrai modèle pour différents critères de sélection, tailles échantillonnales et processus générateurs des données. Dans le quatrième chapitre, nous appliquons la théorie élaborée aux chapitres 1 et 2 à un vrai jeu de données provenant du système canadien d’information socioéconomique (CANSIM), constitué de la production mensuelle de fromage mozzarella, cheddar et ricotta au Canada, expliquée par les prix mensuels du lait de bovin non transformé dans les provinces de Québec, d’Ontario et de la Colombie-Britannique pour la période allant de janvier 2003 à juillet 2021. Nous ajustons ces données à un modèle autorégressif avec variables exogènes complet puis à un modèle autorégressif avec variables exogènes et sélection d’indices. Nous comparons ensuite les résultats obtenus avec le modèle complet à ceux obtenus avec le modèle restreint. Mots-clés : Processus autorégressif à sous-ensemble d’indices, variables exogènes, esti mation des moindres carrés, sélection de modèle, séries chronologiques multivariées, processus stochastiques, séries chronologiques. / This Master’s Thesis focuses on the study of subset autoregressive models with exoge nous variables. Many texts from the classical literature deal with the selection of indexes in autoregressive models. These models are particularly useful for macroeconomic data measured over moderate to long periods of time. Indeed, the heavy parameterization of full models can often be simplified by using the selection of indexes, thus resulting in more parsimonious models. Models with exogenous variables are very interesting in the context where it is known that the variables under study are affected by other variables, playing the role of explanatory variables, not necessarily modeled by the analyst. This Master’s Thesis therefore proposes to study vector subset autoregressive models with exogenous variables. These models have been explored, among others, by Lütkepohl (2005), who merely sketches proofs of the statistical properties. We focus our study on statistical inference under precise conditions, modeling and forecasting for these models. Our goal is to compare restricted models to full classical autoregressive models with exogenous variables. We want to determine whether the use of restricted models is marked by a favorable difference in the bias and standard deviation properties of the estimators as well as in forecasting future values. We also compare the efficiency of index selection in autoregressive models with exogenous variables to that in autoregressive models. It should be noted that a primary motivation in this Master’s Thesis is the estimation in subset autoregressive models with exogenous variables. In the first chapter, we present time series as well as the various concepts which are attached to them. In addition, we present the classical multivariate linear models, models with exogenous variables and then we present subset models. In the second chapter, we present the theoretical framework for least squares estimation in subset autoregressive models as well as the asymptotic behavior of the estimator. Then, we develop the theory for the estimation of least squares (LS) as well as the asymptotic distribution of the estimators for the subset autoregressive models (SVAR), and we do the same for the subset autoregressive models with exogenous variables (SVARX). Specifically, we establish the convergence as well as the asymptotic distribution for the least squares estimator of a subset autoregressive process with exogenous variables. In the third chapter, we apply the theory specified above in Monte Carlo simulations. We evaluate empirically the biases and the standard deviations of the coefficients found during the estimation as well as the proportion of times that the adjusted model matches the true model for different selection criteria, sample size and data generating processes. In the fourth chapter, we apply the theory developed in chapters 1 and 2 to a real dataset from the Canadian Socio-Economic Information System (CANSIM) consisting of the monthly production of mozzarella, cheddar and ricotta cheese in Canada, explained by the monthly prices of unprocessed bovine milk in the provinces of Quebec, Ontario and British Columbia from January 2003 to July 2021. We fit these data with a full autoregressive model with exogenous variables and then to a subset autoregressive model with exogenous variables. Afterwards, we compare the results obtained with the complete model to those obtained with the subset model. Keywords : Subset autoregressive process, exogenous variables, least squares estimation, model selection, multivariate time series, stochastic process, time series.

No description available.

We study games where a team of agents needs to collaborate against an adversary to achieve a common goal. The agents make their moves simultaneously, and they have different perceptions about the system state after each move, due to different sensing capabilities. Each agent can only act based on its own experiences, since no communication is assumed during the game. However, before the game begins, the agents can agree on some strategy. A strategy is winning if it guarantees that the agents achieve their goal regardless of how the opponent acts. Identifying a winning strategy, or determining that none exists, is known as the strategy synthesis problem. In this thesis, we only consider a simple objective where the agents must force the game into a given state. Much of the literature is focused on strategies that either rely on that the agents (a) can remember everything that they have perceived or (b) can only remember the last thing that they have perceived. The strategy synthesis problem is (in the general case) undecidable in (a) and has exponential running time in (b). We are interested in the middle, where agents can have finite memory. Specifically, they should be able to keep a finite-state machine, which they update when they make new observations. In our case, the internal state of each agent represents its knowledge about the state of affairs. In other words, an agent is able to update its knowledge, and act based on it. We propose an algorithm for constructing the finite-state machine for each agent, and assigning actions to the internal states before the game begins. Not every winning strategy can be found by the algorithm, but we are convinced that the ones found are valid ones. An important building block for the algorithm is the knowledge-based subset construction (KBSC) used in the literature, which we generalise to games with multiple agents. With our construction, the game can be reduced to another game, still with uncertain state information, but with less or equal uncertainty. The construction can be applied arbitrarily many times, but it appears as if it stabilises (so that no new knowledge is gained) after only a few steps. We discuss this and other interesting properties of our algorithm in the final chapters of this thesis. / Vi studerar spel där ett lag agenter behöver samarbeta mot en motståndare för att uppnå ett mål. Agenterna agerar samtidigt, och vid varje steg av spelet så har de olika uppfattning om spelets tillstånd. De antas inte kunna kommunicera under spelets gång, så agenterna kan bara agera utifrån sina egna erfarenheter. Innan spelet börjar kan agenterna dock komma överrens om en strategi. En sådan strategi är vinnande om den garanterar att agenterna når sitt mål oavsett hur motståndaren beter sig. Att hitta en vinnande strategi är känt som syntesproblemet. I den här avhandlingen behandlar vi endast ett enkelt mål där agenterna måste tvinga in spelet i ett givet tillstånd. Mycket av litteraturen handlar om strategier där agenterna antingen antas (a) kunna minnas allt som de upplevt eller (b) bara kunna minnas det senaste de upplevt. Syntesproblemet är (i det generella fallet) oavgörbart i (a) och tar exponentiell tid i (b). Vi är intressede av fallet där agenter kan ha ändligt minne. De ska kunna ha en ändlig automat, som de kan uppdatera när de får nya observationer. I vårt fall så representerar det interna tillståndet agentens kunskap om spelets tillstånd. En agent kan då uppdatera sin kunskap och agera utifrån den. Vi föreslår en algoritm som konstruerar en ändlig automat åt varje agent, samt instruktioner för vad agenten ska göra i varje internt tillstånd. Varje vinnande strategi kan inte hittas av algoritmen, men vi är övertygade om att de som hittas är giltiga. En viktig byggsten är den kunskapsbaserade delmängskonstruktionen (KBSC), som vi generaliserar till spel med flera agenter. Med vår konstruktion kan spelet reduceras till ett annat spel som har mindre eller lika mycket osäkerhet. Detta kan göras godtyckligt många gånger, men det verkar som om att ingen ny kunskap tillkommer efter bara några gånger. Vi diskuterar detta vidare tillsammans med andra intressanta egenskaper hos algoritmen i de sista kapitlen i avhandlingen.