The Trypanosoma cruzi Genome Project: Nuclear Karyotype and Gene Mapping of Clone CL Brener

By using improved pulsed field gel electrophoresis conditions, the molecular karyotype of the reference clone CL Brener selected for Trypanosoma cruzi genome project was established. A total of 20 uniform chromosomal bands ranging in size from 0.45 to 3.5 Megabase pairs (Mbp) were resolved in a single run. The weighted sum of the chromosomal bands was approximately 87 Mbp. Chromoblots were hybridized with 39 different homologous probes, 13 of which identified single chromosomes. Several markers showed linkage and four different linkage groups were identified, each comprising two markers. Densitometric analysis suggests that most of the chromosomal bands contain two or more chromosomes representing either homologous chromosomes and/or heterologous chromosomes with similar sizes

“Unmixing” Tissue Gene Expression Signatures from Tumor Biopsies

Emergent molecular measurement methods, such as DNA microarray, qRTPCR, andmany others, offer tremendous promise for the personalized treatment of cancer. Thesetechnologies measure the amount of specific proteins, RNA, DNA or other moleculartargets from tumor specimens with the goal of “fingerprinting” individual cancers. Tumorspecimens are heterogeneous; an individual specimen typically contains unknownamounts of multiple tissues types. Thus, the measured molecular concentrations resultfrom an unknown mixture of tissue types, and must be normalized to account for thecomposition of the mixture.For example, a breast tumor biopsy may contain normal, dysplastic and cancerousepithelial cells, as well as stromal components (fatty and connective tissue) and bloodand lymphatic vessels. Our diagnostic interest focuses solely on the dysplastic andcancerous epithelial cells. The remaining tissue components serve to “contaminate”the signal of interest. The proportion of each of the tissue components changes asa function of patient characteristics (e.g., age), and varies spatially across the tumorregion. Because each of the tissue components produces a different molecular signature,and the amount of each tissue type is specimen dependent, we must estimate the tissuecomposition of the specimen, and adjust the molecular signal for this composition.Using the idea of a chemical mass balance, we consider the total measured concentrationsto be a weighted sum of the individual tissue signatures, where weightsare determined by the relative amounts of the different tissue types. We develop acompositional source apportionment model to estimate the relative amounts of tissuecomponents in a tumor specimen. We then use these estimates to infer the tissuespecificconcentrations of key molecular targets for sub-typing individual tumors. Weanticipate these specific measurements will greatly improve our ability to discriminatebetween different classes of tumors, and allow more precise matching of each patient tothe appropriate treatment

AWSum-Combining Classification with Knowledge Aquisition

Many classifiers achieve high levels of accuracy but have limited applicability in real world situations because they do not lead to a greater understanding or insight into the^way features influence the classification. In areas such as health informatics a classifier that clearly identifies the influences on classification can be used to direct research and formulate interventions. This research investigates the practical applications of Automated Weighted Sum, (AWSum), a classifier that provides accuracy comparable to other techniques whilst providing insight into the data. This is achieved by calculating a weight for each feature value that represents its influence on the class value. The merits of this approach in classification and insight are evaluated on a Cystic Fibrosis and Diabetes datasets with positive results.

Maximum likelihood Linear Programming Data Fusion for Speaker Recognition

Biometric system performance can be improved by means of data fusion. Several kinds of information can be fused in order to obtain a more accurate classification (identification or verification) of an input sample. In this paper we present a method for computing the weights in a weighted sum fusion for score combinations, by means of a likelihood model. The maximum likelihood estimation is set as a linear programming problem. The scores are derived from a GMM classifier working on a different feature extractor. Our experimental results assesed the robustness of the system in front a changes on time (different sessions) and robustness in front a change of microphone. The improvements obtained were significantly better (error bars of two standard deviations) than a uniform weighted sum or a uniform weighted product or the best single classifier. The proposed method scales computationaly with the number of scores to be fussioned as the simplex method for linear programming.

Tietoverkon varmistusten simulointi ja optimointi

Tässä diplomityössä määritellään varmistusjärjestelmän simulointimalli eli varmistusmalli. Varmistusjärjestelmän toiminta optimoidaan kyseisen varmistusmallin avulla. Optimoinnin tavoitteena on parantaa varmistusjärjestelmän tehokkuutta. Parannusta etsitään olemassa olevien varmistusjärjestelmän resurssien maksimaalisella hyödyntämisellä. Varmistusmalli optimoidaan evoluutioalgoritmin avulla. Optimoinnissa on useita tavoitteita, jotka ovat ristiriidassa keskenään. Monitavoiteoptimointiongelma muunnetaan yhden tavoitteen optimointiongelmaksi muodostamalla tavoitefunktio painotetun summan menetelmän avulla. Rinnakkain edellisen menetelmän kanssa käytetään myös Pareto-optimointia. Pareto-optimaalisen rintaman pisteiden etsintä ohjataan lähelle painotetun summan menetelmän optimipistettä. Evoluutioalgoritmin toteutuksessa käytetään hyväksi varmistusjärjestelmiin liittyvää ongelmakohtaista tietoa. Työn tuloksena saadaan varmistusjärjestelmän simulointi- sekä optimointityökalu. Simulointityökalua käytetään kartoittamaan nykyisen varmistusjärjestelmän toimivuutta. Optimoinnin avulla tehostetaan varmistusjärjestelmän toimintaa. Työkalua voidaan käyttää myös uusien varmistusjärjestelmien suunnittelussa sekä nykyisten varmistusjärjestelmien laajentamisessa.

Offset-print mottling measurement using machine vision

Mottling is one of the key defects in offset-printing. Mottling can be defined as unwanted unevenness of print. In this work, diameter of a mottle spot is defined between 0.5-10.0 mm. There are several types of mottling, but the reason behind the problem is still not fully understood. Several commercial machine vision products for the evaluation of print unevenness have been presented. Two of these methods used in these products have been implemented in this thesis. The one is the cluster method and the other is the band-pass method. The properties of human vision system have been taken into account in the implementation of these two methods. An index produced by the cluster method is a weighted sum of the number of found spots, and an index produced by band-pass method is a weighted sum of coefficients of variations of gray-levels for each spatial band. Both methods produce larger indices for visually poor samples, so they can discern good samples from the poor ones. The difference between the indices for good and poor samples is slightly larger produced by the cluster method. 11 However, without the samples evaluated by human experts, the goodness of these results is still questionable. This comparison will be left to the next phase of the project.

Does evolution lead to maximizing behavior?

A long-standing question in biology and economics is whether individual organisms evolve to behave as if they were striving to maximize some goal function. We here formalize this "as if" question in a patch-structured population in which individuals obtain material payoffs from (perhaps very complex multimove) social interactions. These material payoffs determine personal fitness and, ultimately, invasion fitness. We ask whether individuals in uninvadable population states will appear to be maximizing conventional goal functions (with population-structure coefficients exogenous to the individual's behavior), when what is really being maximized is invasion fitness at the genetic level. We reach two broad conclusions. First, no simple and general individual-centered goal function emerges from the analysis. This stems from the fact that invasion fitness is a gene-centered multigenerational measure of evolutionary success. Second, when selection is weak, all multigenerational effects of selection can be summarized in a neutral type-distribution quantifying identity-by-descent between individuals within patches. Individuals then behave as if they were striving to maximize a weighted sum of material payoffs (own and others). At an uninvadable state it is as if individuals would freely choose their actions and play a Nash equilibrium of a game with a goal function that combines self-interest (own material payoff), group interest (group material payoff if everyone does the same), and local rivalry (material payoff differences).

Multi-Objective Genetic Algorithms for the Single Allocation Hub Location Problem

Hub Location Problems play vital economic roles in transportation and telecommunication networks where goods or people must be efficiently transferred from an origin to a destination point whilst direct origin-destination links are impractical. This work investigates the single allocation hub location problem, and proposes a genetic algorithm (GA) approach for it. The effectiveness of using a single-objective criterion measure for the problem is first explored. Next, a multi-objective GA employing various fitness evaluation strategies such as Pareto ranking, sum of ranks, and weighted sum strategies is presented. The effectiveness of the multi-objective GA is shown by comparison with an Integer Programming strategy, the only other multi-objective approach found in the literature for this problem. Lastly, two new crossover operators are proposed and an empirical study is done using small to large problem instances of the Civil Aeronautics Board (CAB) and Australian Post (AP) data sets.

L’utilisation de la polarimétrie radar et de la décomposition de Touzi pour la caractérisation et la classification des physionomies végétales des milieux humides : le cas du Lac Saint-Pierre.

Les milieux humides remplissent plusieurs fonctions écologiques d’importance et contribuent à la biodiversité de la faune et de la flore. Même s’il existe une reconnaissance croissante sur l’importante de protéger ces milieux, il n’en demeure pas moins que leur intégrité est encore menacée par la pression des activités humaines. L’inventaire et le suivi systématique des milieux humides constituent une nécessité et la télédétection est le seul moyen réaliste d’atteindre ce but. L’objectif de cette thèse consiste à contribuer et à améliorer la caractérisation des milieux humides en utilisant des données satellites acquises par des radars polarimétriques en bande L (ALOS-PALSAR) et C (RADARSAT-2). Cette thèse se fonde sur deux hypothèses (chap. 1). La première hypothèse stipule que les classes de physionomies végétales, basées sur la structure des végétaux, sont plus appropriées que les classes d’espèces végétales car mieux adaptées au contenu informationnel des images radar polarimétriques. La seconde hypothèse stipule que les algorithmes de décompositions polarimétriques permettent une extraction optimale de l’information polarimétrique comparativement à une approche multipolarisée basée sur les canaux de polarisation HH, HV et VV (chap. 3). En particulier, l’apport de la décomposition incohérente de Touzi pour l’inventaire et le suivi de milieux humides est examiné en détail. Cette décomposition permet de caractériser le type de diffusion, la phase, l’orientation, la symétrie, le degré de polarisation et la puissance rétrodiffusée d’une cible à l’aide d’une série de paramètres extraits d’une analyse des vecteurs et des valeurs propres de la matrice de cohérence. La région du lac Saint-Pierre a été sélectionnée comme site d’étude étant donné la grande diversité de ses milieux humides qui y couvrent plus de 20 000 ha. L’un des défis posés par cette thèse consiste au fait qu’il n’existe pas de système standard énumérant l’ensemble possible des classes physionomiques ni d’indications précises quant à leurs caractéristiques et dimensions. Une grande attention a donc été portée à la création de ces classes par recoupement de sources de données diverses et plus de 50 espèces végétales ont été regroupées en 9 classes physionomiques (chap. 7, 8 et 9). Plusieurs analyses sont proposées pour valider les hypothèses de cette thèse (chap. 9). Des analyses de sensibilité par diffusiogramme sont utilisées pour étudier les caractéristiques et la dispersion des physionomies végétales dans différents espaces constitués de paramètres polarimétriques ou canaux de polarisation (chap. 10 et 12). Des séries temporelles d’images RADARSAT-2 sont utilisées pour approfondir la compréhension de l’évolution saisonnière des physionomies végétales (chap. 12). L’algorithme de la divergence transformée est utilisé pour quantifier la séparabilité entre les classes physionomiques et pour identifier le ou les paramètres ayant le plus contribué(s) à leur séparabilité (chap. 11 et 13). Des classifications sont aussi proposées et les résultats comparés à une carte existante des milieux humide du lac Saint-Pierre (14). Finalement, une analyse du potentiel des paramètres polarimétrique en bande C et L est proposé pour le suivi de l’hydrologie des tourbières (chap. 15 et 16). Les analyses de sensibilité montrent que les paramètres de la 1re composante, relatifs à la portion dominante (polarisée) du signal, sont suffisants pour une caractérisation générale des physionomies végétales. Les paramètres des 2e et 3e composantes sont cependant nécessaires pour obtenir de meilleures séparabilités entre les classes (chap. 11 et 13) et une meilleure discrimination entre milieux humides et milieux secs (chap. 14). Cette thèse montre qu’il est préférable de considérer individuellement les paramètres des 1re, 2e et 3e composantes plutôt que leur somme pondérée par leurs valeurs propres respectives (chap. 10 et 12). Cette thèse examine également la complémentarité entre les paramètres de structure et ceux relatifs à la puissance rétrodiffusée, souvent ignorée et normalisée par la plupart des décompositions polarimétriques. La dimension temporelle (saisonnière) est essentielle pour la caractérisation et la classification des physionomies végétales (chap. 12, 13 et 14). Des images acquises au printemps (avril et mai) sont nécessaires pour discriminer les milieux secs des milieux humides alors que des images acquises en été (juillet et août) sont nécessaires pour raffiner la classification des physionomies végétales. Un arbre hiérarchique de classification développé dans cette thèse constitue une synthèse des connaissances acquises (chap. 14). À l’aide d’un nombre relativement réduit de paramètres polarimétriques et de règles de décisions simples, il est possible d’identifier, entre autres, trois classes de bas marais et de discriminer avec succès les hauts marais herbacés des autres classes physionomiques sans avoir recours à des sources de données auxiliaires. Les résultats obtenus sont comparables à ceux provenant d’une classification supervisée utilisant deux images Landsat-5 avec une exactitude globale de 77.3% et 79.0% respectivement. Diverses classifications utilisant la machine à vecteurs de support (SVM) permettent de reproduire les résultats obtenus avec l’arbre hiérarchique de classification. L’exploitation d’une plus forte dimensionalitée par le SVM, avec une précision globale maximale de 79.1%, ne permet cependant pas d’obtenir des résultats significativement meilleurs. Finalement, la phase de la décomposition de Touzi apparaît être le seul paramètre (en bande L) sensible aux variations du niveau d’eau sous la surface des tourbières ouvertes (chap. 16). Ce paramètre offre donc un grand potentiel pour le suivi de l’hydrologie des tourbières comparativement à la différence de phase entre les canaux HH et VV. Cette thèse démontre que les paramètres de la décomposition de Touzi permettent une meilleure caractérisation, de meilleures séparabilités et de meilleures classifications des physionomies végétales des milieux humides que les canaux de polarisation HH, HV et VV. Le regroupement des espèces végétales en classes physionomiques est un concept valable. Mais certaines espèces végétales partageant une physionomie similaire, mais occupant un milieu différent (haut vs bas marais), ont cependant présenté des différences significatives quant aux propriétés de leur rétrodiffusion.

Relativistic Thomas-Fermi description of collective modes in droplets of nuclear matter

Isoscalar collective modes in a relativistic meson-nucleon system are investigated in the framework of the time-dependent Thomas-Fermi method. The energies of the collective modes are determined by solving consistently the dispersion relations and the boundary conditions. The energy weighted sum rule satisfied by the models considered allows the identification of the giant resonances. The percentage of the energy weighted sum rule exhausted by the collective modes is in agreement with experimental data, but the agreement with the energy of the modes depends on the model considered.

“Unmixing” Tissue Gene Expression Signatures from Tumor Biopsies

Emergent molecular measurement methods, such as DNA microarray, qRTPCR, and many others, offer tremendous promise for the personalized treatment of cancer. These technologies measure the amount of specific proteins, RNA, DNA or other molecular targets from tumor specimens with the goal of “fingerprinting” individual cancers. Tumor specimens are heterogeneous; an individual specimen typically contains unknown amounts of multiple tissues types. Thus, the measured molecular concentrations result from an unknown mixture of tissue types, and must be normalized to account for the composition of the mixture. For example, a breast tumor biopsy may contain normal, dysplastic and cancerous epithelial cells, as well as stromal components (fatty and connective tissue) and blood and lymphatic vessels. Our diagnostic interest focuses solely on the dysplastic and cancerous epithelial cells. The remaining tissue components serve to “contaminate” the signal of interest. The proportion of each of the tissue components changes as a function of patient characteristics (e.g., age), and varies spatially across the tumor region. Because each of the tissue components produces a different molecular signature, and the amount of each tissue type is specimen dependent, we must estimate the tissue composition of the specimen, and adjust the molecular signal for this composition. Using the idea of a chemical mass balance, we consider the total measured concentrations to be a weighted sum of the individual tissue signatures, where weights are determined by the relative amounts of the different tissue types. We develop a compositional source apportionment model to estimate the relative amounts of tissue components in a tumor specimen. We then use these estimates to infer the tissuespecific concentrations of key molecular targets for sub-typing individual tumors. We anticipate these specific measurements will greatly improve our ability to discriminate between different classes of tumors, and allow more precise matching of each patient to the appropriate treatment

Multi-objective optimization scheme for static and dynamic multicast flows

Muchas de las nuevas aplicaciones emergentes de Internet tales como TV sobre Internet, Radio sobre Internet,Video Streamming multi-punto, entre otras, necesitan los siguientes requerimientos de recursos: ancho de banda consumido, retardo extremo-a-extremo, tasa de paquetes perdidos, etc. Por lo anterior, es necesario formular una propuesta que especifique y provea para este tipo de aplicaciones los recursos necesarios para su buen funcionamiento. En esta tesis, proponemos un esquema de ingeniería de tráfico multi-objetivo a través del uso de diferentes árboles de distribución para muchos flujos multicast. En este caso, estamos usando la aproximación de múltiples caminos para cada nodo egreso y de esta forma obtener la aproximación de múltiples árboles y a través de esta forma crear diferentes árboles multicast. Sin embargo, nuestra propuesta resuelve la fracción de la división del tráfico a través de múltiples árboles. La propuesta puede ser aplicada en redes MPLS estableciendo rutas explícitas en eventos multicast. En primera instancia, el objetivo es combinar los siguientes objetivos ponderados dentro de una métrica agregada: máxima utilización de los enlaces, cantidad de saltos, el ancho de banda total consumido y el retardo total extremo-a-extremo. Nosotros hemos formulado esta función multi-objetivo (modelo MHDB-S) y los resultados obtenidos muestran que varios objetivos ponderados son reducidos y la máxima utilización de los enlaces es minimizada. El problema es NP-duro, por lo tanto, un algoritmo es propuesto para optimizar los diferentes objetivos. El comportamiento que obtuvimos usando este algoritmo es similar al que obtuvimos con el modelo. Normalmente, durante la transmisión multicast los nodos egresos pueden salir o entrar del árbol y por esta razón en esta tesis proponemos un esquema de ingeniería de tráfico multi-objetivo usando diferentes árboles para grupos multicast dinámicos. (en el cual los nodos egresos pueden cambiar durante el tiempo de vida de la conexión). Si un árbol multicast es recomputado desde el principio, esto podría consumir un tiempo considerable de CPU y además todas las comuicaciones que están usando el árbol multicast serán temporalmente interrumpida. Para aliviar estos inconvenientes, proponemos un modelo de optimización (modelo dinámico MHDB-D) que utilice los árboles multicast previamente computados (modelo estático MHDB-S) adicionando nuevos nodos egreso. Usando el método de la suma ponderada para resolver el modelo analítico, no necesariamente es correcto, porque es posible tener un espacio de solución no convexo y por esta razón algunas soluciones pueden no ser encontradas. Adicionalmente, otros tipos de objetivos fueron encontrados en diferentes trabajos de investigación. Por las razones mencionadas anteriormente, un nuevo modelo llamado GMM es propuesto y para dar solución a este problema un nuevo algoritmo usando Algoritmos Evolutivos Multi-Objetivos es propuesto. Este algoritmo esta inspirado por el algoritmo Strength Pareto Evolutionary Algorithm (SPEA). Para dar una solución al caso dinámico con este modelo generalizado, nosotros hemos propuesto un nuevo modelo dinámico y una solución computacional usando Breadth First Search (BFS) probabilístico. Finalmente, para evaluar nuestro esquema de optimización propuesto, ejecutamos diferentes pruebas y simulaciones. Las principales contribuciones de esta tesis son la taxonomía, los modelos de optimización multi-objetivo para los casos estático y dinámico en transmisiones multicast (MHDB-S y MHDB-D), los algoritmos para dar solución computacional a los modelos. Finalmente, los modelos generalizados también para los casos estático y dinámico (GMM y GMM Dinámico) y las propuestas computacionales para dar slución usando MOEA y BFS probabilístico.

A simple variance formula for population size estimators by conditioning

This note considers the variance estimation for population size estimators based on capture–recapture experiments. Whereas a diversity of estimators of the population size has been suggested, the question of estimating the associated variances is less frequently addressed. This note points out that the technique of conditioning can be applied here successfully which also allows us to identify sources of variation: the variance due to estimation of the model parameters and the binomial variance due to sampling n units from a population of size N. It is applied to estimators typically used in capture–recapture experiments in continuous time including the estimators of Zelterman and Chao and improves upon previously used variance estimators. In addition, knowledge of the variances associated with the estimators by Zelterman and Chao allows the suggestion of a new estimator as the weighted sum of the two. The decomposition of the variance into the two sources allows also a new understanding of how resampling techniques like the Bootstrap could be used appropriately. Finally, the sample size question for capture–recapture experiments is addressed. Since the variance of population size estimators increases with the sample size, it is suggested to use relative measures such as the observed-to-hidden ratio or the completeness of identification proportion for approaching the question of sample size choice.

A simple variance formula for population size estimators by conditioning

This note considers the variance estimation for population size estimators based on capture–recapture experiments. Whereas a diversity of estimators of the population size has been suggested, the question of estimating the associated variances is less frequently addressed. This note points out that the technique of conditioning can be applied here successfully which also allows us to identify sources of variation: the variance due to estimation of the model parameters and the binomial variance due to sampling n units from a population of size N. It is applied to estimators typically used in capture–recapture experiments in continuous time including the estimators of Zelterman and Chao and improves upon previously used variance estimators. In addition, knowledge of the variances associated with the estimators by Zelterman and Chao allows the suggestion of a new estimator as the weighted sum of the two. The decomposition of the variance into the two sources allows also a new understanding of how resampling techniques like the Bootstrap could be used appropriately. Finally, the sample size question for capture–recapture experiments is addressed. Since the variance of population size estimators increases with the sample size, it is suggested to use relative measures such as the observed-to-hidden ratio or the completeness of identification proportion for approaching the question of sample size choice.

Equitability revisited: why the “equitable threat score” is not equitable

In the forecasting of binary events, verification measures that are “equitable” were defined by Gandin and Murphy to satisfy two requirements: 1) they award all random forecasting systems, including those that always issue the same forecast, the same expected score (typically zero), and 2) they are expressible as the linear weighted sum of the elements of the contingency table, where the weights are independent of the entries in the table, apart from the base rate. The authors demonstrate that the widely used “equitable threat score” (ETS), as well as numerous others, satisfies neither of these requirements and only satisfies the first requirement in the limit of an infinite sample size. Such measures are referred to as “asymptotically equitable.” In the case of ETS, the expected score of a random forecasting system is always positive and only falls below 0.01 when the number of samples is greater than around 30. Two other asymptotically equitable measures are the odds ratio skill score and the symmetric extreme dependency score, which are more strongly inequitable than ETS, particularly for rare events; for example, when the base rate is 2% and the sample size is 1000, random but unbiased forecasting systems yield an expected score of around −0.5, reducing in magnitude to −0.01 or smaller only for sample sizes exceeding 25 000. This presents a problem since these nonlinear measures have other desirable properties, in particular being reliable indicators of skill for rare events (provided that the sample size is large enough). A potential way to reconcile these properties with equitability is to recognize that Gandin and Murphy’s two requirements are independent, and the second can be safely discarded without losing the key advantages of equitability that are embodied in the first. This enables inequitable and asymptotically equitable measures to be scaled to make them equitable, while retaining their nonlinearity and other properties such as being reliable indicators of skill for rare events. It also opens up the possibility of designing new equitable verification measures.