Industrial chemicals in European Union produced or imported in volumes above 1 tonne annually, necessitate a registration within REACH. A common problem, concerning these chemicals, is deficient information and lack of data for assessing the hazards posed to human health and the environment. Animal studies for the type of toxicological information needed are both expensive and time consuming, and to that an ethical aspect is added. Alternative methods to animal testing are thereby requested. REACH have called for an increased use of in silico tools for non-testing data as structure-activity relationships (SARs), quantitative structure-activity relationships (QSARs), and read-across. The main objective of the studies underlying this thesis is related to explore and refine the use of in silico tools in a risk assessment context of industrial chemicals. In particular, try to relate properties of the molecular structure to the toxic effect of the chemical substance, by using principles and methods of computational chemistry. The initial study was a survey of all industrial chemicals; the Industrial chemical map was created. A part of this map was identified including chemicals of potential concern. Secondly, the environmental pollutants, polychlorinated biphenyls (PCBs) were examined and in particular the non-dioxin-like PCBs (NDL-PCBs). A set of 20 NDL-PCBs was selected to represent the 178 PCB congeners with three to seven chlorine substituents. The selection procedure was a combined process including statistical molecular design for a representative selection and expert judgements to be able to include congeners of specific interest. The 20 selected congeners were tested in vitro in as much as 17 different assays. The data from the screening process was turned into interpretable toxicity profiles with multivariate methods, used for investigation of potential classes of NDL-PCBs. It was shown that NDL-PCBs cannot be treated as one group of substances with similar mechanisms of action. Two groups of congeners were identified. A group including in general lower chlorinated congeners with a higher degree of ortho substitution showed a higher potency in more assays (including all neurotoxic assays). A second group included abundant congeners with a similar toxic profile that might contribute to a common toxic burden. To investigate the structure-activity pattern of PCBs effect on DAT in rat striatal synaptosomes, ten additional congeners were selected and tested in vitro. NDL-PCBs were shown to be potent inhibitors of DAT binding. The congeners with highest DAT inhibiting potency were tetra- and penta-chlorinated with 2-3 chlorine atoms in ortho-position. The model was not able to distinguish the congeners with activities in the lower μM range, which could be explained by a relatively unspecific response for the lower ortho chlorinated PCBs. / Den europeiska kemikalielagstiftningen REACH har fastställt att kemikalier som produceras eller importeras i en mängd över 1 ton per år, måste registreras och riskbedömmas. En uppskattad siffra är att detta gäller för 30 000 kemikalier. Problemet är dock att data och information ofta är otillräcklig för en riskbedömning. Till stor del har djurförsök använts för effektdata, men djurförsök är både kostsamt och tidskrävande, dessutom kommer den etiska aspekten in. REACH har därför efterfrågat en undersökning av möjligheten att använda in silico verktyg för att bidra med efterfrågad data och information. In silico har en ungefärlig betydelse av i datorn, och innebär beräkningsmodeller och metoder som används för att få information om kemikaliers egenskaper och toxicitet. Avhandlingens syfte är att utforska möjligheten och förfina användningen av in silico verktyg för att skapa information för riskbedömning av industrikemikalier. Avhandlingen beskriver kvantitativa modeller framtagna med kemometriska metoder för att prediktera, dvs förutsäga specifika kemikaliers toxiska effekt. I den första studien (I) undersöktes 56 072 organiska industrikemikalier. Med multivariata metoder skapades en karta över industrikemikalierna som beskrev dess kemiska och fysikaliska egenskaper. Kartan användes för jämförelser med kända och potentiella miljöfarliga kemikalier. De mest kända miljöföroreningarna visade sig ha liknande principal egenskaper och grupperade i kartan. Genom att specialstudera den delen av kartan skulle man kunna identifiera fler potentiellt farliga kemiska substanser. I studie två till fyra (II-IV) specialstuderades miljögiftet PCB. Tjugo PCBs valdes ut så att de strukturellt och fysiokemiskt representerade de 178 PCB kongenerna med tre till sju klorsubstituenter. Den toxikologiska effekten hos dessa 20 PCBs undersöktes i 17 olika in vitro assays. De toxikologiska profilerna för de 20 testade kongenerna fastställdes, dvs vilka som har liknande skadliga effekter och vilka som skiljer sig åt. De toxicologiska profilerna användes för klassificering av PCBs. Kvantitativa modeller utvecklades för prediktioner, dvs att förutbestämma effekter hos ännu icke testade PCBs, och för att få ytterligare kunskap om strukturella egenskaper som ger icke önskvärda effekter i människa och natur. Information som kan användas vid en framtida riskbedömning av icke-dioxinlika PCBs. Den sista studien (IV) är en struktur-aktivitets studie som undersöker de icke-dioxinlika PCBernas hämmande effekt av signalsubstansen dopamin i hjärnan.

It's search metasynthesis type, in order to know, describe and analyze the academic literature in the Mental health and work area in the context of Brazilian postgraduate. Developed in five phases: Exploration, Refining, Crossing, Description and Analysis. With the first takes place cataloging of all the documents present in the files of theses and dissertations of the Coordination of Improvement of Higher Education Personnel - CAPES and the Virtual Health Library - Psychology - BVS-PSI from 10 search descriptors considered representative area in the literature. In the second phase, it is found among the documents found in the previous phase, which are related to the area, by reading the title, abstract and keywords of these. In the third phase is carried out a comparative analysis in order to eliminate duplicate documents. The fourth phase describes all documents according to type: thesis or dissertation; the historical ranking; area of knowledge; geographical disposition and institutional origin. In the last phase analyzes the contents of the descriptor located 16 theses Mental health and work, the most representative among those used in the previous phases. This phase identifies the following categories: history, social demands, public policy, epistemology, method and theory. The results indicate that mental health and work has its largest production, 84% under the master; in 1989 was located first thesis; between the years 2000 to 2012 88% of the documents were produced; predominance of studies related to psychology, 56% occurs; the southeast region has 46% of production; São Paulo accounts for 30%; production is 46 IES, being USP, UFRJ, UFRGS, UNB and the UFMG that most produce. There is even those produced studies respond to historically situated social demands; the relationship with the public policies is a challenge in view of the finding that the state should protect the work also has become precarious; the field of Occupational Health underlies the area; distinct methodological strategies and theoretical frameworks are used in studies. It is concluded that the adoption of an ethnographic approach as a method and an integrative approach as theoretical framework, the results achieved can convert into practical action in favor of labor, the fundamental premise of the area, given its epistemological assumptions. In this context, the researcher is involved turning their efforts to politically coherent performance with the field of Occupational Health. / Trata-se de pesquisa do tipo metassíntese, com vistas a conhecer, descrever e analisar a produção acadêmica da área da Saúde mental e trabalho no contexto da Pós-graduação brasileira. Desenvolve-se em cinco fases: Exploração, Refinamento, Cruzamento, Descrição e Análise. Com a primeira realiza-se a catalogação de todos os documentos presentes no banco de teses e dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e da Biblioteca Virtual em Saúde – Psicologia (BVS-PSI) a partir de 10 descritores de busca considerados representativos da área na literatura especializada. Na segunda fase, verifica-se, dentre os documentos localizados na fase anterior, quais guardam relação com a área, por meio da leitura do título, resumo e palavras-chave destes. Na terceira fase realiza-se uma análise comparativa a fim de eliminar duplicidade de documentos. A quarta fase descreve todos os documentos quanto ao tipo: tese ou dissertação; a seriação histórica; a área do conhecimento; a disposição geográfica e a procedência institucional. Na última fase analisa-se o conteúdo de 16 teses localizadas pelo descritor Saúde mental e trabalho, o mais representativo dentre os utilizados nas fases anteriores. Essa fase identifica as seguintes categorias: história, demandas sociais, políticas públicas, epistemologia, método e teoria. Os resultados indicam que a Saúde mental e trabalho tem sua maior produção, 84%, no âmbito do mestrado; no ano de 1989 foi localizada a primeira tese; entre os anos de 2000 a 2012 foram produzidos 88% dos documentos; ocorre predominância de estudos ligados à Psicologia, 56%; a região sudeste concentra 46% da produção; São Paulo, responde por 30%; encontra-se produção em 46 IES, sendo USP, UFRJ, UFRGS, UNB e UFMG as que mais produzem.Verifica-se ainda que os estudos produzidos respondem a demandas sociais historicamente situadas; a relação com as políticas públicas constitui um desafio tendo em vista a constatação de que o Estado, que deveria proteger o trabalho, também o tem tornado precário; o campo da Saúde do Trabalhador fundamenta a área; são utilizadas distintas estratégias metodológicas e referenciais teóricos nas pesquisas realizadas. Conclui-se que, a adoção de uma abordagem etnográfica enquanto método e de uma abordagem integradora enquanto referencial teórico, pode converter os resultados alcançados em ações práticas em favor do trabalho, premissa fundamental da área, tendo em vista seus pressupostos epistemológicos. Nesse contexto, o pesquisador é implicado politicamente voltando seus esforços para uma atuação coerente com o campo da Saúde do Trabalhador.

The purpose of this study was to investigate recommendations regarding professional standards for training and registration in pastoral work. The aim is to obtain professional recognition for Pastoral Counsellors/Therapists by accreditation and recognition from a relevant professional council. The goal is also to formulate these standards in line with the processes of the South African Qualification Authority (SAQA). The following four forms of pastoral work were distinguished and discussed: Mutual care, Pastoral care, Pastoral counselling, and Pastoral therapy. The Accreditation Committee proposed the following sub-fields: Human and Social Studies (Field 07): Religious and ethical foundation of society (sub-field). Health Sciences and Social Services (Field 09): Promotive health and developmental services, Preventative health, Curative health, Rehabilitative services (sub-fields). Proposals was adopted for the following Pastoral Counselling/Therapy The purpose of this study was to investigate recommendations regarding professional standards for training and registration in pastoral work. The aim is to obtain professional recognition for Pastoral Counsellors/Therapists by accreditation and recognition from a relevant professional council. The goal is also to formulate these standards in line with the processes of the South African Qualification Authority (SAQA). The following four forms of pastoral work were distinguished and discussed: Mutual care, Pastoral care, Pastoral counselling, and Pastoral therapy. The Accreditation Committee proposed the following sub-fields: Human and Social Studies (Field 07): Religious and ethical foundation of society (sub-field). Health Sciences and Social Services (Field 09): Promotive health and developmental services, Preventative health, Curative health, Rehabilitative services (sub-fields). Proposals was adopted for the following Pastoral Counselling!Therapy qualifications: Certificate in Pastoral Counselling (Basic) Certificate in Pastoral Counselling (Post Basic), Certificate in Pastoral Counselling (Intermediate), Diploma and post graduate degrees in Pastoral Counselling (Advanced), Masters and Doctorate Degrees in Pastoral Counselling (Specialist). After narrow consultation the level descriptors were discussed and accepted. As all proposals this will still be open for changes. The following roles were described using the format of a Qualification based on Unit Standards. Unit Standards are linked to the proposed six "roles" which are seen as generic to all Pastoral Counselling practices: Maintain effective relational and communication competence, Apply and maintain professional work ethics, Plan and facilitate pastoral counselling process, Engage in an effective personal development process, Design and conduct course of treatment, Conduct research, The roles and applied competencies for the pastoral counselling/therapy specialised field were defined. These roles may be used to re-shape current qualifications, as well as to research and design new qualifications. They are intended as initial guidelines for providers. The following registered categories for pastoral counsellors/therapists were proposed by the accreditation committee and accepted by SAAP: Category 1: Basic level pastoral counsellor (NQF Level 2) Category 2: Post basic level pastoral counsellor (NQF level 3) Category 3: Intermediate level pastoral counsellor (NQF Level 4) Category 4: Advanced level pastoral therapist (NQF Level 5/6) Category 5: Specialist level pastoral therapist (NQF Level 7 /8) The following outcomes (unit standards) for Pastoral Counsellors/Therapists were identified: UNIT 1: Applying work ethics UNIT 2: Understanding pastoral counselling theory UNIT 3: Facilitating pastoral counselling skills UNIT 4: Conducting research UNIT 5: Developing self-knowledge Some of the recommendations were: It became necessary to have some form of regulation and/or even "control" to prevent the abuse of people who ostensibly suffer from mental illness. To establish professional standards for training in pastoral counselling and to obtain professional recognition for pastoral counsellors/therapists through accreditation and recognition from a relevant professional council. In doing this we should also come to an agreement on a proper set of work ethics. It was recommend that the level descriptors should be further elaborated through a careful analysis of the standards proposed, but that the process of moving from general to specific descriptors should be adopted in the absence of meaningful generic level descriptors. It was recommend that the proposed standards and qualifications should only be adopted once processes is established where an SGB has been established and registered with SAQA, and these standards and qualifications have been accepted by providers, professional Pastoral Counsellors/Therapists, professional associations, etc. / Philosophy, Practical and Systematic Theology / M. Th. (Practical Theology (Pastoral Therapy))

Cette thèse est une collaboration entre le LAboratoire des Sciences et Matériaux pour l’Électronique et d’Automatique (LASMEA) de Clermont-Ferrand et le Laboratoire Vision et Ingénierie des Contenus (LVIC) du CEA LIST à Saclay. La première moitié de la thèse a été accomplie au sein de l’équipe ComSee (1) du LASMEA et la deuxième au LVIC. L’objectif de ces travaux est de concevoir un système de vidéo-assistance temps réel pour la détection d’évènements dans des scènes possiblement denses.La vidéosurveillance intelligente de scènes denses telles que des foules est particulièrement difficile, principalement à cause de leur complexité et de la grande quantité de données à traiter simultanément. Le but de cette thèse consiste à élaborer une méthode de détection d’évènements rares dans de telles scènes, observées depuis une caméra fixe. La méthode en question s’appuie sur l’analyse automatique de mouvement et ne nécessite aucune information à priori. Les mouvements nominaux sont déterminés grâce à un apprentissage statistique non supervisé. Les plus fréquemment observés sont considérés comme des évènements normaux. Une phase de classification permet ensuite de détecter les mouvements déviant trop du modèle statistique, pour les considérer comme anormaux. Cette approche est particulièrement adaptée aux lieux de déplacements structurés, tels que des scènes de couloirs ou de carrefours routiers. Aucune étape de calibration, de segmentation de l’image, de détection d’objets ou de suivi n’est nécessaire. Contrairement aux analyses de trajectoires d’objets suivis, le coût calculatoire de notre méthode est invariante au nombre de cibles présentes en même temps et fonctionne en temps réel. Notre système s’appuie sur une classification locale du mouvement de la scène, sans calibration préalable. Dans un premier temps, une caractérisation du mouvement est réalisée, soit par des méthodes classiques de flot optique, soit par des descripteurs spatio-temporels. Ainsi, nous proposons un nouveau descripteur spatio-temporel fondé sur la recherche d’une relation linéaire entre les gradients spatiaux et les gradients temporels en des zones où le mouvement est supposé uniforme. Tout comme les algorithmes de flot optique, ce descripteur s’appuie sur la contrainte d’illumination constante.Cependant en prenant en compte un voisinage temporel plus important, il permet une caractérisation du mouvement plus lisse et plus robuste au bruit. De plus, sa faible complexité calculatoire est bien adaptée aux applications temps réel. Nous proposons ensuite d’étudier différentes méthodes de classification : La première, statique, dans un traitement image par image, s’appuie sur une estimation bayésienne de la caractérisation du mouvement au travers d’une approche basée sur les fenêtres de Parzen. Cette nouvelle méthode est une variante parcimonieuse des fenêtres de Parzen. Nous montrons que cette approche est algorithmiquement efficace pour approximer de manière compacte et précise les densités de probabilité. La seconde méthode, basée sur les réseaux bayésiens, permet de modéliser la dynamique du mouvement. Au lieu de considérer ce dernier image par image, des séquences de mouvements sont analysées au travers de chaînes de Markov Cachées. Ajouté à cela, une autre contribution de ce manuscrit est de prendre en compte la modélisation du voisinage d’un bloc afin d’ajouter une cohérence spatiale à la propagation du mouvement. Ceci est réalisé par le biais de couplages de chaînes de Markov cachées.Ces différentes approches statistiques ont été évaluées sur des données synthétiques ainsi qu’en situations réelles, aussi bien pour la surveillance du trafic routier que pour la surveillance de foule.Cette phase d’évaluation permet de donner des premières conclusions encourageantes quant à la faisabilité de la vidéosurveillance intelligente d’espaces possiblement denses. / The automatic analysis of crowded areas in video sequences is particularly difficult because ofthe large amount of information to be processed simultaneously and the complexity of the scenes. We propose in this thesis a method for detecting abnormal events in possibly dense scenes observed from a static camera. The approach is based on the automatic classification of motion requiring no prior information. Motion patterns are encoded in an unsupervised learning framework in order to generate a statistical model of frequently observed (aka. normal) events. Then at the detection stage, motion patterns that deviate from the model are classified as unexpected events. The method is particularly adapted to scenes with structured movement with directional flow of objects or people such as corridors, roads, intersections. No camera calibration is needed, nor image segmentation, object detection and tracking. In contrast to approaches that rely on trajectory analysis of tracked objects, our method is independent of the number of targets and runs in real-time. Our system relies on a local classification of global scene movement. The local analysis is done on each blocks of a regular grid. We first introduce a new spatio-temporal local descriptor to characterize the movement efficiently. Assuming a locally uniform motion of space-time blocks of the image, our approach consists in determining whether there is a linear relationship between spatial gradients and temporal gradients. This spatio-temporal descriptor holds the Illumination constancy constraint like optical flow techniques, but it allows taking into account the spatial neighborhood and a temporal window by giving a smooth characterization of the motion, which makes it more robust to noise. In addition, its low computational complexity is suitable for real-time applications. Secondly, we present two different classification frameworks : The first approach is a static (frame by frame) classification approach based on a Bayesian characterization of the motion by using an approximation of the Parzen windowing method or Kernel Density Estimation (KDE) to model the probability density function of motion patterns.This new method is the sparse variant of the KDE (SKDE). We show that the SKDE is a very efficient algorithm giving compact representations and good approximations of the density functions. The second approach, based on Bayesian Networks, models the dynamics of the movement. Instead of considering motion patterns in each block independently, temporal sequences of motion patterns are learned by using Hidden Markov Models (HMM). The second proposed improvement consists in modeling the movement in one block by taking into account the observed motion in adjacent blocks. This is performed by the coupled HMM method. Evaluations were conducted to highlight the classification performance of the proposed methods,on both synthetic data and very challenging real video sequences captured by video surveillance cameras.These evaluations allow us to give first conclusions concerning automatic analyses of possibly crowded area.

Cette thèse CIFRE est effectuée dans un contexte industriel et présente un framework complet pour la détection, le suivi mono-caméra et de la ré-identification de personnes dans le contexte multi-caméras. Les performances élevés et le traitement en temps réel sont les deux contraintes critiques ayant guidé ce travail. La détection de personnes vise à localiser/délimiter les gens dans les séquences vidéo. Le détecteur proposé est basé sur une cascade de classifieurs de type LogitBoost appliqué sur des descripteurs de covariances. Une approche existante a fortement été optimisée, la rendant applicable en temps réel et fournissant de meilleures performances. La méthode d'optimisation est généralisable à d'autres types de détecteurs d'objets. Le suivi mono-caméra vise à fournir un ensemble d'images de chaque personne observée par chaque caméra afin d'extraire sa signature visuelle, ainsi qu'à fournir certaines informations du monde réel pour l'amélioration de la ré-identification. Ceci est réalisé par le suivi de points SIFT à l'aide d'une filtre à particules, ainsi qu'une méthode d'association de données qui infère le suivi des objets et qui gère la majorité des cas de figures possible, notamment les occultations. Enfin, la ré-identification de personnes est réalisée avec une approche basée sur l'apparence globale en améliorant grandement une approche existante, obtenant de meilleures performances tout en étabt applicable en temps réel. Une partie "conscience du contexte" est introduite afin de gérer le changement d'orientation des personnes, améliorant les performances dans le cas d'applications réelles. / This thesis is performed in industrial context and presents a whole framework for people detection and tracking in a camera network. It addresses the main process steps: people detection, people tracking in mono-camera context, and people re-identification in multi-camera context. High performances and real-time processing are considered as strong constraints. People detection aims to localise and delimits people in video sequences. The proposed people detection is performed using a cascade of classifiers trained using LogitBoost algorithm on region covariance descriptors. A state of the art approach is strongly optimized to process in real time and to provide better detection performances. The optimization scheme is generalizable to many other kind of detectors where all possible weak classifiers cannot be reasonably tested. People tracking in mono-camera context aims to provide a set of reliable images of every observed person by each camera, to extract his visual signature, and it provides some useful real world information for re-identification purpose. It is achieved by tracking SIFT features using a specific particle filter in addition to a data association framework which infer object tracking from SIFT points one, and which deals with most of possible cases, especially occlusions. Finally, people re-identification is performed using an appearance based approach by improving a state of the art approach, providing better performances while keeping the real-time processing advantage. A context-aware part is introduced to robustify the visual signature against people orientations, ensuring better re-identification performances in real application case.

Submitted by Maike Costa (maiksebas@gmail.com) on 2017-09-13T11:59:49Z No. of bitstreams: 1 arquivototal.pdf: 7758959 bytes, checksum: db745d41b196978192ebc789e25f442b (MD5) / Made available in DSpace on 2017-09-13T11:59:49Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 7758959 bytes, checksum: db745d41b196978192ebc789e25f442b (MD5) Previous issue date: 2016-02-26 / The use of plants for medicinal purposes is one of the oldest forms of medical practice of mankind, emphasizing the alkaloids because they present rich structural and pharmacological properties extensive variety. The drug design is aided by computer based strategies based on linkers or target. When developing new compounds, the structure-based techniques, such as docking, can be applied to study of certain receptor and its corresponding ligand, evaluating bindingprotein interactions. Whereas in the ligand-based methods, a database of known ligands is used, looking for ways to evaluate parameters (molecular descriptors) that can assist in the development of compounds with higher power. This study aimed to perform in silico studies to investigate drug-target interactions with alkaloids derived from natural products and their analogues with relevant pharmacological activity. Different molecular descriptors and methodologies were used in the studies developed. In chapter 2, the interaction of alkaloid bisindolic caulerpine (CLP) was evaluated with the enzyme involved in Alzheimer's disease (AD) monoamine oxidase B (MAO-B), and a database with 109 analogs. It was possible to observe a chemical parameter of inhibition of PLC analogues where the replacement of the radicals must be asymmetric with different polarity. The studies based on the linker and the structure associated with the classification drug-like chemical skeleton suggest that the PLC has potential use in the treatment of AD. In chapter 3, 8 alkaloids isolated Cissampelos sympodialis and 101 derivatives, had their inhibitory potential against enzyme (BACE, GSK-3β and MAO-A) involved in degenerative diseases assessed by in silico methods. consensual analysis showed affinity alkaloids bisbenzilisoquinolinics by BACE, incluindos the roraimine natural alkaloids and simpodialine-β-N-oxide, supporting interest in investigating this skeleton as an antagonist of this enzyme. In Chapter 4 we evaluated the multi-target potential of 148 aphorphinics alkaloids Annonaceae against Leishmania donovani. Six were selected enzymes of this neglected disease for theoretical study, which was associated with experimental four alkaloids available data and integrating the bank, which had pIC50 value inferior to 5.26. The xyloguyelline alkaloid was named as a potential multi-agent target, demonstrating activity against 5 of 6 enzymes evaluated, likely to activity of over 60%. fragment descriptors were used to create model-based binder in a parallel approach with molecular docking to predict the cytotoxic and against topoisomerase II activity azaphenantrene alkaloids in chapter 5. The cytotoxic activity of this skeleton alkaloids are well described in the literature, molecules having activity against several tumor cell lines. The IMB 6 analog and 23 IMB showed interesting activity and selectivity, with MolDock energy similar to liriodenine composed characterized by potent anti-tumor action, but with high toxicity. Important structural information is provided by spectroscopy nuclear magnetic resonance (NMR), and Chapter 6 aimed to discuss the importance of this technique for generating molecular descriptors. Studies that applied successfully in drug design NMR descriptors assisted by computer are described and several QSAR and QSPR having as support data chemical shifts. / A utilização de plantas com fins medicinais é uma das mais antigas formas de prática medicinal da humanidade, enfatizando os alcaloides, por apresentarem rica variedade estrutural e extensa propriedade farmacológica. O desenho de drogas auxiliado pelo computador é fundamentado em estratégias baseadas nos ligantes ou no alvo. No desenvolvimento de novos compostos, técnicas baseadas na estrutura, como o docking, podem ser aplicadas no estudo de um determinado receptor e seu respectivo ligante, avaliando as interações ligante-proteína. Ao passo que nos métodos baseados no ligante, um banco de ligantes conhecidos é utilizado, buscando modos de avaliar parâmetros (descritores moleculares) que possam auxiliar no desenvolvimento de compostos com maior potência. Este estudo teve como objetivo realizar estudos in silico para investigar interações fármaco-alvo com alcaloides oriundos de produtos naturais, e respectivos análogos, com relevante atividade farmacológica. Diferentes descritores moleculares e metodologias foram utilizadas nos estudos desenvolvidos. No capítulo 2, foi avaliado a interação do alcaloide bisindolico caulerpina (CLP) com a enzima envolvida na doença de Alzheimer (DA) monoamina oxidase B (MAO-B), além de um banco com 109 análogos. Foi possível observar um parâmetro químico de inibição dos análogos da CLP, onde a substituição dos radicais deve ser assimétrica com polaridade distinta. Os estudos dos baseados no ligante e na estrutura, associado à classificação drug-like, sugerem que o esqueleto químico da CLP tem potencial uso no tratamento da DA. No capítulo 3, 8 alcaloides isolados de Cissampelos sympodialis e 101 derivados, tiveram seu potencial inibitório contra enzimas (BACE, GSK-3β e MAO-A) envolvidas em doenças degenerativas avaliado por metodologias in silico. Análise consensual demonstrou afinidade de alcaloides bisbenzilisoquinolínicos pela BACE, incluindos os alcaloides naturais roraimina e simpodialina- β-N-oxide, suportando interesse em investigar este esqueleto como antagonista desta enzima. No capítulo 4 foi avaliado o potencial multi-target de 148 alcaloides aporfinicos de Annonaceae contra Leishmania donovani. Foram utilizadas seis enzimas desta doença negligenciada para o estudo teórico, que foi associado com dados experimentais de quatro alcaloides disponíveis e que integram o banco, que apresentaram valor pIC50 inferior a 5.26. O alcaloide xyloguyellina foi apontado como potencial agente multitarget, demonstrando atividade contra 5 das 6 enzimas avaliadas, com probabilidade de atividade superior a 60%. Descritores de fragmento foram utilizados para criar modelo baseado no ligante em uma abordagem paralela com docking molecular, para predizer a atividade citotóxica e contra topoisomerase II de azafenantreno alcaloides, no capítulo 5. A atividade citotóxica deste esqueleto de alcaloides está bem descrita na literatura, com diversas moléculas apresentando atividade contra linhagens de células tumorais. Os análogos IMB 6 e IMB 23 apresentaram interessante atividade e com seletividade, apresentando energia MolDock similar à liriodenina, composto caracterizado por potente ação antitumoral, porém com elevada toxicidade. Importantes informações estruturais são fornecidas pela espectroscopia de ressonância magnética nuclear (RMN), sendo o capítulo 6 destinado a discorrer sobre a importância desta técnica para geração de descritores moleculares. Estudos que aplicaram com sucesso descritores RMN em design de drogas assistida pelo computador encontram-se descritos, além de diversos estudos de QSAR e QSPR tendo como amparo dados de deslocamentos químicos.

The aim of this dissertation thesis was to study the factors affecting drug distribution and elimination and to use these factors to individualize dosing. The work consists of three thematic areas: estimation of the volume of distribution and subsequent dosing of selected drugs (vancomycin, amikacin, phenobarbital) using body size descriptors; estimation of clearance and subsequent dosing of selected drugs (vancomycin, amikacin, phenobarbital, perindopril) using renal function status markers; and the impact of drug interactions on the distribution and elimination of phenobarbital. The thesis summarizes original papers on these topics. Individual pharmacokinetic parameters were calculated for each patient based on their demographic and clinical characteristics, dosing records and measured serum drug levels. The relationships between distribution volume/drug clearance and body size descriptors/renal functional status markers were examined by regression analysis. Vancomycin volume of distribution was best predicted by the total body weight. Loading dose of 10.7 mg/kg of total body weight was optimal in patients taking continuous vancomycin and would lead to reducing of median time to reach target concentrations from 17 to 1 hour. On the contrary, amikacin volume of distribution was most associated...

Made available in DSpace on 2016-12-23T14:37:43Z (GMT). No. of bitstreams: 1 Sara Coser Morra.pdf: 1157047 bytes, checksum: ca26cc99cfaca69da596f91375dc0dcb (MD5) Previous issue date: 2012-07-12 / A goiabeira (Psidium guajava L.) é uma das fruteiras de maior importância econômica da família Myrtaceae. O Brasil é um dos maiores produtores de goiaba do mundo, sendo esta uma cultura potencial em expansão e rentabilidade. A polinização cruzada da espécie e a existência de pomares heterogêneos de propagação seminal resultam em variabilidade, permitindo a seleção de genótipos para o melhoramento da cultura. O objetivo deste trabalho foi estudar a diversidade genética em genótipos de P. guajava selecionados em pomar de origem seminal e cultivares por características morfológicas e químicas de qualidade de fruto, também associar dados de conteúdo de DNA nuclear (2C), cariótipo, morfológicos e de marcadores moleculares microssatélites. Verificou-se a existência de divergência entre as Cortibel com relação às características de fruto, com genótipos apresentando performance superior e genótipos com desempenho semelhante à cultivares, potenciais para uso em hibridações ou como cultivares. As análises cariotípica e de conteúdo de DNA nuclear (2C) mostraram que os genótipos possuem um genoma estável, pequeno e diplóide e características cariotípicas relacionadas a grupos ancestrais de angiospermas. O dendrograma UPGMA baseado em dados morfológicos e SSR evidenciaram diversidade entre os genótipos, com melhor discriminação pelos dados de SSR. Como a maioria dos genótipos mostraram similaridade morfológica para as características de frutos, aliada a dissimilaridade molecular, estes se mostraram interessantes para o uso em hibridações em programas de melhoramento. O conjunto de dados gerados contribuiu para expandir o conhecimento sobre o genoma e a diversidade genética em P. guajava. Também é importante na estruturação de programas de melhoramento para a cultura, além de contribuir para estudos evolutivos / Guava (Psidium guajava L.) is one of the most economically important fruit crop from Myrtaceae family. Brazil is one of the largest producers of guava in the world, which is a potential crop in growth and profitability. Cross-pollination of the species and the existence of heterogeneous seminal propagation orchards result in variability, allowing the selection of genotypes for crop improvement. The aim of this study was to evaluate genetic diversity between P. guajava L genotypes selected from seminal origin orchard and cultivars, by morphological and fruit quality chemical characteristics, also associate data from nuclear 2C-value, karyotypic, morphological and simple sequence repeat (SSR) marker. There were divergences between Cortibel selections by fruit characteristics, with genotypes showing superior and similar performance when compared with cultivated genotypes, potential for use in hibridation and as cultivars. Karyotype and nuclear 2C-value analyses showed that all genotypes have a stable and very small diploid genome (2n = 2X = 22; 2C = 0.95 pg), and karyotypic characteristics related to ancestral angiosperm groups. UPGMA dendrogram based on morphological and SSR data evidenced diversity among the genotypes, with better discrimination by SSR data. Since most genotypes showed morphological similarity for fruit characteristics, combined with molecular dissimilarity, the use of these genotypes in hybridation breeding programs could be of interest. The obtained data set contributed to expand the knowledge about genome and genetic diversity of P. guajava. Also are important to structure crop improvement programs and contribute to evolutionary approaches

Orientador: Ricardo da Silva Torres / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Computação / Made available in DSpace on 2018-08-13T11:00:01Z (GMT). No. of bitstreams: 1 Penatti_OtavioAugustoBizetto_M.pdf: 2250748 bytes, checksum: 57d5b2f9120a8eae69ee9881d363e9ce (MD5) Previous issue date: 2009 / Resumo: A crescente quantidade de imagens geradas e disponibilizadas atualmente tem eito aumentar a necessidade de criação de sistemas de busca para este tipo de informação. Um método promissor para a realização da busca de imagens e a busca por conteúdo. Este tipo de abordagem considera o conteúdo visual das imagens, como cor, textura e forma de objetos, para indexação e recuperação. A busca de imagens por conteúdo tem como componente principal o descritor de imagens. O descritor de imagens é responsável por extrair propriedades visuais das imagens e armazená-las em vetores de características. Dados dois vetores de características, o descritor compara-os e retorna um valor de distancia. Este valor quantifica a diferença entre as imagens representadas pelos vetores. Em um sistema de busca de imagens por conteúdo, a distancia calculada pelo descritor de imagens é usada para ordenar as imagens da base em relação a uma determinada imagem de consulta. Esta dissertação realiza um estudo comparativo de descritores de imagens considerando a Web como cenário de uso. Este cenário apresenta uma quantidade muito grande de imagens e de conteúdo bastante heterogêneo. O estudo comparativo realizado nesta dissertação é feito em duas abordagens. A primeira delas considera a complexidade assinto tica dos algoritmos de extração de vetores de características e das funções de distancia dos descritores, os tamanhos dos vetores de características gerados pelos descritores e o ambiente no qual cada descritor foi validado originalmente. A segunda abordagem compara os descritores em experimentos práticos em quatro bases de imagens diferentes. Os descritores são avaliados segundo tempo de extração, tempo para cálculos de distancia, requisitos de armazenamento e eficácia. São comparados descritores de cor, textura e forma. Os experimentos são realizados com cada tipo de descritor independentemente e, baseado nestes resultados, um conjunto de descritores é avaliado em uma base com mais de 230 mil imagens heterogêneas, que reflete o conteúdo encontrado na Web. A avaliação de eficácia dos descritores na base de imagens heterogêneas é realizada por meio de experimentos com usuários reais. Esta dissertação também apresenta uma ferramenta para a realização automatizada de testes comparativos entre descritores de imagens. / Abstract: The growth in size of image collections and the worldwide availability of these collections has increased the demand for image retrieval systems. A promising approach to address this demand is to retrieve images based on image content (Content-Based Image Retrieval). This approach considers the image visual properties, like color, texture and shape of objects, for indexing and retrieval. The main component of a content-based image retrieval system is the image descriptor. The image descriptor is responsible for encoding image properties into feature vectors. Given two feature vectors, the descriptor compares them and computes a distance value. This value quantifies the difference between the images represented by their vectors. In a content-based image retrieval system, these distance values are used to rank database images with respect to their distance to a given query image. This dissertation presents a comparative study of image descriptors considering the Web as the environment of use. This environment presents a huge amount of images with heterogeneous content. The comparative study was conducted by taking into account two approaches. The first approach considers the asymptotic complexity of feature vectors extraction algorithms and distance functions, the size of the feature vectors generated by the descriptors and the environment where each descriptor was validated. The second approach compares the descriptors in practical experiments using four different image databases. The evaluation considers the time required for features extraction, the time for computing distance values, the storage requirements and the effectiveness of each descriptor. Color, texture, and shape descriptors were compared. The experiments were performed with each kind of descriptor independently and, based on these results, a set of descriptors was evaluated in an image database containing more than 230 thousand heterogeneous images, reflecting the content existent in the Web. The evaluation of descriptors effectiveness in the heterogeneous database was made by experiments using real users. This dissertation also presents a tool for executing experiments aiming to evaluate image descriptors. / Mestrado / Sistemas de Informação / Mestre em Ciência da Computação

Dans cette thèse, nous nous intéressons à la reconnaissance d’images couleur à l’aide d’une nouvelle approche géométrique du domaine fréquentiel. La plupart des méthodes existantes ne traitent que les images en niveaux de gris au travers de descripteurs issus de la transformée de Fourier usuelle. L’extension de telles méthodes aux images multicanaux, comme par exemple les images couleur, consiste généralement à reproduire un traitement identique sur chacun des canaux. Afin d’éviter ce traitement marginal, nous étudions et mettons en perspective les différentes généralisations de la transformée de Fourier pour les images couleur. Ce travail nous oriente vers la transformée de Fourier Clifford pour les images couleur définie dans le cadre des algèbres géométriques. Une étude approfondie de celle-ci nous conduit à définir un algorithme de calcul rapide et à proposer une méthode de corrélation de phase pour les images couleur. Dans un deuxième temps, nous cherchons à généraliser à travers cette transformée de Fourier les définitions des descripteurs de Fourier de la littérature. Nous étudions ainsi les propriétés, notamment l’invariance à la translation, rotation et échelle, des descripteurs existants. Ce travail nous mène à proposer trois nouveaux descripteurs appelés “descripteurs de Fourier couleur généralisés”(GCFD) invariants en translation et en rotation.Les méthodes proposées sont évaluées sur des bases d’images usuelles afin d’estimer l’apport du contenu fréquentiel couleur par rapport aux méthodes niveaux de gris et marginales. Les résultats obtenus à l’aide d’un classifieur SVM montrent le potentiel des méthodes proposées ; les descripteurs GCFD se révèlent être plus compacts, de complexité algorithmique moindre pour des performances de classification au minimum équivalentes. Nous proposons également des heuristiques pour le choix du paramètre de la transformée de Fourier Clifford.Cette thèse constitue un premier pas vers une généralisation des méthodes fréquentielles aux images multicanaux. / In this thesis, we focus on color image recognition using a new geometric approach in the frequency domain. Most existing methods only process grayscale images through descriptors defined from the usual Fourier transform. The extension of these methods to multichannel images such as color images usually consists in reproducing the same processing for each channel. To avoid this marginal processing,we study and compare the different generalizations of color Fourier transforms. This work leads us to use the Clifford Fourier transform for color images defined in the framework of geometric algebra. A detailed study of it leads us to define a fast algorithm and to propose a phase correlation for colorimages. In a second step, with the aim of generalizing Fourier descriptors of the literature with thisFourier transform, we study their properties, including invariance to translation, rotation and scale.This work leads us to propose three new descriptors called “generalized color Fourier descriptors”(GCFD) invariant in translation and in rotation.The proposed methods are evaluated on usual image databases to estimate the contribution of color frequency content compared with grayscale and marginal methods. The results obtained usingan SVM classifier show the potential of the proposed methods ; the GCFD are more compact, have less computational complexity and give better recognition rates. We also propose heuristics for choosing the parameter of the color Clifford Fourier transform.This thesis is a first step towards a generalization of frequency methods to multichannel images.