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Thesis: B.S., Massachusetts Institute of Technology, Department of Mechanical Engineering, 1976 / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Includes bibliographical references. / B.S. / B.S. Massachusetts Institute of Technology, Department of Mechanical Engineering

Consumer's opinions and sentiments on products can reflect the performance of products in general or in various aspects. Analyzing these data is becoming feasible, considering the availability of immense data and the power of natural language processing. However, retailers have not taken full advantage of online comments. This work is dedicated to a solution for automatically analyzing and summarizing these valuable data at both product and category levels. In this research, a system was developed to retrieve and analyze extensive data from public online resources. A parallel framework was created to make this system extensible and efficient. In this framework, a star topological network was adopted in which each computing unit was assigned to retrieve a fraction of data and to assess sentiment. Finally, the preprocessed data were collected and summarized by the central machine which generates the final result that can be rendered through a web interface. The system was designed to have sound performance, robustness, manageability, extensibility, and accuracy.

In a historical frame of reference, this is a study of rural-urban migration to demonstrate the process of urbanization in Utah between 1900 and 1960. This study estimates the amount of internal migration for the state of Utah. Selected demographic variables such as size, age, and sex of the migrating population are studied. Changes in the population composition of the sending and receiving areas as a complement of rural-urban migration constitute the crux of this study. The indirect methods of estimating the net intercensal migration, census survival and life table survival ratio met hods, are used in tabulations. Limitations were imposed, as for availability of the data , in usage of any direct methods of migration measurement. The survival ratio met hods used, however, are the most reliable in this context. The results, indicating the intercensal amount of internal migration for Utah, shed some light on the urbanization process of the state. The findings, for the first time, demonstrate the volume and direction of the internal migration for Utah during the first six decades of the twentieth century. The results may substantially contribute to the state's future socio-economic plannings. Beyond a purely demographic analysis of the significance of migration lies the broad realm of manpower economics, institutional plannings, city plannings, rural problems, transportation, pollution, and a score of others. The population factor, naturally, cannot be separated from these social phenomena. The trends and directions of migration can, therefore, be used when and where future plans are formulated and past trends are studied.

Aspect oriented programming has over the last decade become the subject of intense research within the domain of software engineering. Aspect mining, which is concerned with identification of cross cutting concerns in legacy software, is an important part of this domain. Aspect refactoring takes the identified cross cutting concerns and converts these into new software constructs called aspects. Software that have been transformed using this process becomes more modularized and easier to comprehend and maintain. The first attempts at mining for aspects were dominated by manual searching and parsing through source code using simple tools. More sophisticated techniques have since emerged including evaluation of execution traces, code clone detection, program slicing, dynamic analysis, and use of various clustering techniques. The focus of most studies has been to maximize aspect mining performance measured by various metrics including those of aspect mining precision and recall. Other metrics have been developed and used to compare the various aspect mining techniques with each other. Aspect mining automation and presentation of aspect mining results has received less attention. Automation of aspect mining and presentation of results conducive to aspect refactoring is important if this research is going to be helpful to software developers. This research showed that aspect mining can be automated. A tool was developed which performed automated aspect mining and visualization of identified cross cutting concerns. This research took a different approach to aspect mining than most aspect mining research by recognizing that many different categories of cross cutting concerns exist and by taking this into account in the mining process. Many different aspect mining techniques have been developed over time, some of which are complementary. This study was different than most aspect mining research in that multiple complementary aspect mining algorithms was used in the aspect mining and visualization process.

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La maladie osseuse de Paget (MOP) est la deuxième maladie osseuse la plus fréquente après l'ostéoporose. Elle touche environ 3% de la population caucasienne après l'âge de 55 ans. La mutation p.Pro392Leu dans le gène appelé SQSTM1, liée à la MOP a été identifiée chez la moitié des formes familiales dans la population canadienne-française avec une transmission selon un mode autosomique dominant. Toutefois cette mutation n'explique pas complètement la maladie, notamment le phénotype cellulaire des ostéoclastes. Les objectifs de cette thèse étaient de mieux comprendre l'hétérogénéité clinique et moléculaire de la MOP, en étudiant les facteurs précoces contribuant au développement des phénotypes clinique et cellulaire de la MOP chez les apparentés porteurs de la mutation p.Pro392Leu, en recherchant un second gène modificateur de la mutation p.Pro392Leu dans certaines familles de notre cohorte et en étudiant l'effet modulateur de miR-16 sur l'expression du gène SQSTM1. Nous avons examiné les données des descendants adultes porteurs de la mutation p.Pro392Leu âgés de <90 ans et leurs parents atteints. Les caractéristiques cliniques des parents comprenaient le sexe, l'âge au diagnostic, le nombre d'os affectés, les taux de phosphatase alcaline totale sérique (tALPs). L'évaluation du phénotype pagétique chez les descendants à l'inclusion entre 1996 et 2009 comprenait le dosage des tALPs, la scintigraphie osseuse et les radiographies du crâne et du bassin. Une réévaluation approfondie du phénotype de ces descendants par imagerie osseuse et dosage des marqueurs biochimiques a été effectuée entre 2016 et 2018. Le séquençage de l'exome entier a été effectué en utilisant un HiSeq 2500 chez quatre patients de deux familles différentes avec la MOP non porteurs d'aucune mutation dans le gène SQSTM1. Le phénotype clinique a été défini par l'âge au diagnostic, le taux de tALPs, le nombre d'os atteints chez les patients porteurs de la mutation p. Pro392Leu et / ou du variant p.Val45Ile dans deux familles (n = 14 participants). Les quantifications de miR-16 et de SQSTM1 ont été effectuées respectivement dans le plasma (97 participants) et dans le sang total (83 participants) par RT-PCR quantitative chez des patients pagétiques avec ou sans la mutation p.Pro392Leu, des porteurs sains de cette mutation et des témoins sains non mutés. L'expression de miR-16 a été corrélée avec l'expression de SQSTM1 et des associations avec l'âge au diagnostic, le sexe, le taux de tALPs ainsi que le nombre d'os atteints ont été recherchées. L'impact du variant p.Val45Ile sur le phénotype ostéoclastique (ostéoclastogenèse, nombre de noyaux par ostéoclaste et résorption osseuse) a été évalué par différenciation in vitro des monocytes du sang périphérique en ostéoclastes matures avec du RANKL et hMCSF pendant 21 jours, chez des patients atteints de MOP porteurs d'un et/ou l'autre variant génétique, des porteurs sains de ces variants, des patients pagétiques non mutés et des témoins sains non mutés. Le phénotypage clinique complet pour rechercher une MOP asymptomatique chez 36 descendants sains porteurs de la mutation p.Pro392Leu a montré que parmi les 36 descendants avec un phénotype mis à jour, quatre d'entre eux ont développé un phénotype clinique de la MOP caractérisé par une hyperfixation monostotique ou polyostotique associée à des lésions radiographiques typiques dans les sites affectés, représentant une incidence de 1,83 par 1000 personnes-année. De plus, l'âge au diagnostic de la MOP a été retardé de 10 ans en moyenne chez les descendants adultes porteurs de la mutation p.Pro392Leu par rapport à leurs parents affectés. Nos résultats soutiennent l'utilité d'une surveillance régulière des adultes porteurs de cette mutation. L'effet modulateur de miR-16 sur l'expression du gène SQSTM1 par quantification de l'expression génique a conduit à une une corrélation négative non significative de l'expression du gène SQSTM1 par miR-16 chez les participants porteurs de la mutation p.Pro392Leu, chez les patients mutés et non mutés mais pas chez les contrôles sains (-0.17103, -0.11583 vs 0.05624, NS). Ce résultat suggère un rôle possible de miR-16 comme modificateur épigénétique dans la MOP. Une analyse de l'exome entier chez deux de nos grandes familles avec hérédité digénique a permis d'identifier un nouveau variant p.Val45Ile dans le gène DOCK6 qui pourrait être un gène modificateur de la mutation p.Pro392Leu. Ce variant rare p.Val45Ile pourrait atténuer la sévérité du phénotype clinique de la MOP causée par la mutation du gène SQSTM1 lorsque les deux variants sont portés parle même patient. Par contre, ce nouveau variant seul est suffisant pour donner lieu à un phénotype ostéoclastique pagétique mais ce dernier est moins sévère que celui observé avec la mutation p.Pro392Leu seule. Ce projet de thèse contribue ainsi à une meilleure compréhension des mécanismes physiopathologiques de la MOP qui pourraient conduire à une meilleure prise en charge clinique des patients avec la MOP et à l'identification de nouvelles possibilités diagnostiques ou thérapeutiques, notamment pour réguler le remodelage osseux. / Paget's disease of bone (PDB) is the second most common bone disease after osteoporosis. It affects approximately 3% of the Caucasian population after the age of 55 years old. The p.Pro392Leu mutation in the gene called SQSTM1, linked to PDB has been identified in half of the familial forms in the French-Canadian population with an autosomal dominant mode of inheritance. However, this mutation does not fully explain the disease, in particular the cellular phenotype of osteoclasts. The objectives of this study were to better understand the clinical and molecular heterogeneity of PDB, by studying the early factors contributing to the development of the clinical phenotype of PDB in relative carriers of the p.Pro392Leu mutation, by looking for a second modifier gene of p.Pro392Leu mutation in some families in our cohort and by studying the modulating effect of miR-16 on the expression of the SQSTM1 gene. We reviewed research records from adult offspring carriers of the p.Pro392Leu mutation aged <90 years and their affected parent. In parents, we collected data on sex, age at diagnosis, number of affected bones, total serum alkaline phosphatase levels (tALPs). PDB extended phenotype assessment relying on tALPs, total body bone scan and skull and pelvis radiographs, was performed in offspring at inclusion in 1996 to 2009. An extended phenotype reassessment of these offspring by bone imaging and biochemical markers assay was carried out between 2016 and 2018. The quantification of miR-16 and SQSTM1 was carried out respectively in plasma (97 participants) and in whole blood (83 participants) by quantitative RT-PCR in carriers of the p.Pro392Leu mutation (patients with PDB or healthy carriers), in not mutated patients with PDB and healthy controls not mutated. MiR-16 expression was correlated with SQSTM1 gene expression and associations with age at diagnosis, sex, tALPs and the number of affected bones were searched. Whole exome sequencing was performed using a HiSeq 2500 with the Agilent XT protocol on four patients from two different families with PDB not carriers of any SQSTM1 mutation in which at least one other sibling with PDB was carrier of the p.Pro392Leu mutation. The clinical phenotype was defined by the age at diagnosis, tALPs level, number of affected bones in patients carrying the p.Pro392Leu and/or p.Val45Ile variant in two families (n=14 participants). The impact of the p.Val45Ile variant on the osteoclastic phenotype (osteoclastogenesis, number of nuclei per osteoclast and bone resorption) was evaluated by in vitro differentiation of monocytes from peripheral blood into mature osteoclasts with RANKL and hMCSF for 21 days, in pagetic patient carriers of one and/or two variants, healthy carriers of these variants, pagetic patients not mutated and healthy controls not mutated. The complete clinical phenotyping to search for asymptomatic PDB in 36 healthy offspring carriers of the p.Pro392Leu mutation showed that among the 36 offspring with an updated phenotype, four of them developed a clinical phenotype of PDB characterized by monostotic or polyostotic increased bone uptake associated with typical radiographic lesions in the affected sites, representing an incidence of 1.83 per 1000 person-years. Moreover, the age at PDB diagnosis was delayed by 10 years in average in the adult offspring carriers the p.Pro392Leu mutation versus their affected parents. Our findings support the utility of a regular monitoring of the adult healthy offspring carriers of this mutation. The modulating effect of miR-16 on the expression of the SQSTM1 gene by gene expression quantification led a non significant negative correlation of the expression of the SQSTM1 gene by miR-16 in participant carriers of the p.Pro392Leu mutation, in patients mutated and not mutated but not in healthy controls (-0.17103, -0.11583 vs 0.05624, NS). This result suggests a possible role for miR-16 as an epigenetic modifier in PDB. An analysis of the whole exome in two of our large families with digenic inheritance allowed us to identify a new variant p.Val45Ile in the DOCK6 gene which could be a modifier gene for the p.Pro392Leu mutation. This rare variant p.Val45Ile could reduce the severity of the clinical phenotype of PDB caused by the mutation in the SQSTM1 gene when the two variants are carried by the same patient. On the other hand, this new variant alone gives rise to a pagetic osteoclastic phenotype but less severe than the one observed with the p.Pro392Leu mutation alone. This thesis project thus provided a better understanding of the pathophysiological mechanisms of PDB which could lead to better clinical management of patients with PDB and to the identification of new diagnostic or therapeutic possibilities, to regulate bone remodeling.

No description available.

<p> In this thesis new joint target tracking and classification techniques for aspect-dependent measurements are developed. Joint target tracking and classification methods can result in better tracking and classification performance than those treating these as two separate problems. Significant improvement in state estimation and classification performance can be achieved by exchanging useful information between the tracker and the classifier. Target classification in many target tracking algorithms is not typically done by taking into consideration the target-to-sensor orientation. However, the feature information extracted from the signal that originated from the target is generally a strong function of the target-to-sensor orientation. Since sensor returns are sensitive to this orientation, classification from a single sensor may not give exact target classes. Better classification results can be obtained by fusing feature measurements from multiple views of a target. In multitarget scenarios, handling the classification becomes more challenging due to the identifying the feature information corresponding to a target. That is, it is difficult to identify the origin of measurements. In this case, feature measurement origin ambiguities can be eliminated by integrating the classifier into multiframe data association. This technique reduces the ambiguity in feature measurements while improving track purity. </p> <p> A closed form expression for multiaspect target classification is not feasible. Then, training based statistical modeling can be used to model the unknown feature measurements of a target. In this thesis, the Observable Operator Model (OOM), a better alternative to the Hidden Markov Model (HMM), is used to capture unknown feature distribution of each target and thus can be used as a classifier. The proposed OOM based classification technique incorporates target-to-sensor orientation with a sequence of feature information from multiple sensors. Further, the multi-aspect classifier can be modeled using the OOM to handle unknown target orientation. The target orientation estimation using OOM can also be used to find improved estimates of the states of highly maneuverable targets with noisy kinematic measurements. One limiting factor in obtaining accurate estimates of highly maneuvering target states is the high level of uncertainty in velocity and acceleration components. The target orientation information is helpful in alleviating this problem to accurately determine the velocity and acceleration components. </p> <p> Various simulation studies based on two-dimensional scenarios are presented in this thesis to demonstrate the merits of the proposed joint target tracking and classification algorithms that use aspect-dependent feature measurements.</p> / Thesis / Doctor of Philosophy (PhD)

Depuis la publication des résultats de l'étude de la Women's Health Initiative (WHI) en juillet 2002, l'utilisation d'hormonothérapie de remplacement (HTR) a diminué substantiellement au sein de la population générale. Cependant, l'impact que les résultats de cette étude ont eu sur l'utilisation d'HTR par les femmes à haut risque de cancer du sein héréditaire demeure inconnu. Cette étude vise à comparer l'utilisation d'HTR, avant et après la publication des résultats de l'étude de la WHI, par les femmes testées pour une prédisposition génétique au cancer du sein. L'utilisation d'HTR a été évaluée à l'aide d'un questionnaire postal auto-administré un an suivant la divulgation du résultat du test génétique BRCA1/2. Les résultats obtenus indiquent que, globalement, l'utilisation d'HTR chez ces femmes demeure faible et ne semble pas avoir été influencée par la publication des résultats de l'étude de la WHI. Cependant, chez les non-porteuses de la mutation familiale, l'utilisation d'HTR a diminué significativement suivant la publication des résultats de l'étude de la WHI, une réduction similaire à celle observée chez les femmes de la population générale. Cette diminution concorde avec les recommandations émises par la Société canadienne du cancer suite à la publication de l'étude de la WHI à propos de l'utilisation d'HTR.