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La classification OMS des tumeurs cérébrales de l'enfant distingue les tumeurs gliales des tumeurs glioneuronales, les gliomes circonscrits des infiltrants. Elle représente le meilleur indicateur pronostic mais se heurte pourtant à des limites de reproductibilité. Pour mieux préciser le diagnostic, mieux définir des sous-groupes de pronostic différent, et mieux orienter le thérapeutique, nous avons recherché les profils moléculaires de 108 tumeurs cérébrales circonscrites de l'enfant : astrocytome pilocytique (PA), tumeurs neuroépithéliales dysembryoplasiques (DNT), xanthoastrocytomes pléïomorphes (PXA) et gangliogliomes (GG). Aucune différence n'est retrouvée entre les gliomes corticaux de grade II (GC) et les DNT concernant IDH1 et 2, TP53 et la délétion1p19q. Les DNT non spécifiques et les GC partagent le même profil incluant CD34 et la mutation V600E de BRAF dans 50% des cas. Le PXA exprime la mutation V600E de BRAF dans plus de 50 % des cas et se rapproche du groupe des tumeurs glioneuronales. Concernant le PA, nous confirmons le caractère péjoratif de la topographie hypothalamo-chiasmatique, de l'histologie pilomyxoide, de l'âge inférieur à 36 mois et de l'exérèse partielle. A l'opposé des tumeurs infiltrantes qui appartiendraient au groupe " histones dépendantes", les tumeurs circonscrites pourraient être regroupées sous le terme "MAPKinases dépendantes". On y distinguerait alors les tumeurs avec fusion KIAA1543-BRAF de celles avec mutation V600E de BRAF. Ce travail a permis de mieux caractériser les tumeurs gliales et glioneuronales de l'enfant, reposant sur le transfert en routine de marqueurs moléculaires simples. / The OMS classification for pediatric brain tumors includes glial tumors and mixed glial and glioneuronal tumors, diffuse and no diffuse glioma. All strategic decision making are based on this current classification but it drives to some limits of diagnosis reproductibility.The goal of our study was to define molecular profils for low grade no diffuse pediatric brain tumors including pilocytic astrocytoma (PA), dysembryoplasic neuroepithelial tumor (DNT), pleiomorphic xanthoastrocytoma (PXA) and benign gangliogliome (GG), to improve the quality of diagnosis, define different subgroups with different prognosis and then to improve treatment strategy decision making.No molecular difference was found between cortical grade II glioma (GC) and DNT regarding IDH1 and 2 TP53 alterations and 1p19q deletion. Similarly 50 % of no specific form of DNT share the same molecular profil with GC with CD34 expression and V600E mutation of BRAF. PXA demonstrated BRAFV600E mutation in 60 % of cases. PXA could then be very close glioneuronal tumors. Finally in PA we confirmed the negative impact of hypothalochiasmatic location, pilomyxoid diagnosis and age lower than 36 months and partial resection. We could work on the elaboration of a new classification and define the group named “Histone dependant” for tumors with histone aberrations and the group named “MAPKinases dependant” for tumors with either KIAA 1543-BRAF fusion or V600E BRAF mutation.In conclusion, this work has led to improve the molecular profil characteristics of glioneuronal tumors of childhood with different easy diagnostic markers that can be used in routine practice, and could potentially replace DNA sequencing.

Submitted by Mariana Dornelles Vargas (marianadv) on 2015-05-05T14:04:12Z No. of bitstreams: 1 departamento_nacional.pdf: 13763326 bytes, checksum: 652b1f83fbc7c0039fef4e8fdba8b304 (MD5) / Made available in DSpace on 2015-05-05T14:04:12Z (GMT). No. of bitstreams: 1 departamento_nacional.pdf: 13763326 bytes, checksum: 652b1f83fbc7c0039fef4e8fdba8b304 (MD5) Previous issue date: 2008-04-14 / Nenhuma / O presente estudo focalizou a atuação do DNT no processo de sindicalização dos trabalhadores durante a Era Vargas. Órgão atrelado ao Ministério do Trabalho, o DNT foi responsável, a partir de 1931, por efetivar e reconhecer a organização dos operários brasileiros em sindicatos. Esse processo de organização sindical foi levado a cabo por uma série de decretos e leis sindicais que permitiram ao Estado, durante os quinze anos em que esteve no poder Getúlio Vargas, manter sob sua tutela os trabalhadores brasileiros, uma vez que, embora a sindicalização fosse livre até 1939, somente os sindicatos devidamente reconhecidos poderiam defender os seus operários frente aos organismos governamentais. O estudo aqui realizado apresenta três capítulos. O primeiro é um resgate da legislação social e sindical da Primeira República, para que se possa entender como se deu esse movimento operário e como o Estado articulou, através dessa legislação sindical, a relação entre Capital e Trabalho. Embora seja um capítulo independente, torna-se extremamente importante entender essa questão no período pré-30, para interpretar melhor os acontecimentos a partir de 1930. O segundo capítulo analisa a atuação do DNT durante a Era Vargas, como agiu e quais as questões que se fizeram presentes em relação à questão sindical no período, buscando uma compreensão de como se deu a relação entre Estado/operários sob a tutela do Poder Central. O terceiro capítulo visa entender, através dos jornais operários, como receberam e de que forma reagiram os operários ao controle dos sindicatos pelo DNT. Através dos jornais operários, foi possível identificar a evolução do pensamento dessa classe, que não ficou a revelia do Estado, participando ativamente desse processo. Desse modo, pode-se perceber que esses operários buscaram e queriam construir-se sob a organização sindical oficial, pois acreditavam que somente assim poderiam construir-se enquanto classe social consciente de seus direitos e deveres. / This study had its focus about the DNT – Nacional Work Department actuation in the process of unionize during the President Vargas age. DNT is an organ which bonds to Work Ministry and is responsable, after 1931, to recognize and organize the brazilian workers in trade union. This process of trade union organization could be made through several decrees and trade union laws which allowed to the Public Power, during fifteen years that Getulio Vargas was president to keep the guardian ship of brazilian workers because the trade union was free only to institution which were recognized by government and only these could defend the workers who were unionize when must fight with government institutions. This study has three chapters. The first chapter make a redeem of social and trade union legislation at First Republic to show how happened the workers moviment and the government about Work and Capital. Although is an independent chapter, it is very important to understand this question at the age before 1930 to think better about the events which happen after this time. The second chapter make analysis of the actuation of DNT and its relationship between institution and trade union. The third chapter wants to understand through workers newspapers, how were the reaction of workers about the control of trade union by DNT. It was possible identify the evolution of thinking between the workers, which were not whithout the knowledge. They fighted to construct a official trade union organization because they believe that only so they could be strong in this occuppation, conscious of their rights and owes.

AN ANALYSIS OF GLOBAL GENE EXPRESSION RESULTING FROM EXPOSURE TO ENERGETIC MATERIALS A Dissertation Presented for the Doctor of Philosophy Degree University of Tennessee, Knoxville VERNON LASHAWN MCINTOSH JR. August 2010 Dedication This dissertation is dedicated to my family. My mother and father Debra and Vernon McIntosh instilled in me the respect for academic excellence and the drive maximize my potential. Early on, my younger brother Kyle started showing signs of a shared interest in biology thus my desire to be a positive role model for him kept me motivated. Last but certainly not least, my loving wife and best friend Nichole has been there to offer love and support throughout my entire undergraduate and graduate degrees. It’s difficult to imagine making it this far without her (and that’s not just because she paid the bills). Abstract Characteristic transcriptional biomarkers have been identified for microbial cultures exposed to 2, 4, 6-trinitrotoluene (TNT), 2, 6-dinitrotoluene (DNT), or triacetone-triperoxide (TATP). This study describes the generation of expression profiles for exposure to each compound, the functional significance of each response, and the identification of the characteristic alterations in gene expression associated with exposure to each compound. Expression profiles were generated from a total of three different candidate organisms: Escherichia coli, Saccharomyces cerevisiae, and Pseudomonas putida. Common to all three organisms, TNT exposure resulted in increased expression of genes involved in toxin resistance and drug efflux systems. The S.cerevisiae and E.coli expression profiles were both characterized by increased expression of genes involved in iron-sulfur cluster assembly, sulfur containing amino acids, sulfate transport and assimilation and the metabolism of nitrogen compounds. Only E.coli and Saccharomyces were used to generate DNT induced expression profiles; both profiles exhibited high degrees of similarity with each organism’s respective TNT profiles. This was especially true of the E.coli profile where 25 of the 30 alterations were also observed after exposure to TNT. A computational discriminant functional analysis was performed to identify characteristic biomarkers for each exposure. For each compound a set of transcriptional biomarkers (10 or less) was developed. An additional set of biomarkers was developed encompassing both TNT and DNT exposure. These sets of genes serve as a transcriptional fingerprint for exposure to each respective compound. The sensitivity and specificity of each transcriptional fingerprint is sufficient to correctly identify exposure to energetic materials against a background of non-energetic compound exposures. This study makes several novel contributions to the greater body of scientific knowledge: • This is the first documented study of the interactions of TATP in any biological system. • This is the first comprehensive gene expression study of the TNT response by P. putida, E.coli or E.coli. • This is the first application of computational class prediction in the development of biomarkers for exposure to energetic materials

Duomenų perdavimas elektros tinklais. Magistro baigiamasis darbas elektronikos inžinerijos laipsniui. Vilniaus Gedimino technikos universitetas. Vilnius, 2012, 67 p., 38 iliustr., 15 lent., 27 bibl., 3 priedai. Darbo tikslas – sukurti ir ištirti duomenų perdavimo elektros tinklais sistemos modelį. Darbe išnagrinėti šiuolaikiniai duomenų perdavimo elektros tinklais standartai, ištirti šiuolaikiniai duomenų perdavimo elektros tinklais metodai, atskleisti pagrindiniai šiuolaikinių duomenų perdavimo elektros tinklais metodų trūkumai. Siekiant sumažinti šiuolaikinių sistemų trūkumus sudarytas duomenų perdavimo elektros tinklais sistemos modelis su dirbtiniu neuronų tinklu. Gautieji darbo rezultatai atitiko užduotyje iškeltus reikalavimus. / The goal of this work was to create and analize a power line comunication model. This work analizes up to date power line comunication standards, methods and the main disadvantages of these methods are discussed. To compensate these disadvantages a power line communication system model with an artificial neural network was proposed. The results of this work suits the task. The systems with the artificial neural network model gave positive results.

The primary aim of the work presented in this thesis was to change the inducer specificity of the DntR protein in order to improve the response to DNT. The long-term goal is to use this protein in a biosensor for DNT, a signature compound for detection of the explosive TNT. Another aspect of this work was to understand the mechanisms of inducer binding and how the binding of an inducer molecule changes the DntR structure into a state that triggers transcriptional activation. In the papers included in this thesis the inducer specificity of wt DntR has been investigated under different conditions. The functional effects of specific mutations have also been investigated, in some cases in combination with structure determination using X-ray crystallography. In addition, structural data offering insights into the details of inducer binding and conformational changes upon inducer binding are presented and discussed in terms of mechanisms for transcriptional activation by DntR. Furthermore, a directed evolution strategy was employed in order to find variants of DntR with improved response to DNT. A variant with a large improvement in the DNT response was isolated and characterized. In optimized growth conditions, this DntR variant had a nearly 10-fold increase in fluorescence in response to DNT compared to wt DntR. Specific substitutions found in this DntR variant are suggested to be important for changing the inducer response. / Syftet med denna avhandling har varit att förbättra förmågan hos proteinet DntR att upptäcka DNT. Det långsiktiga målet har varit att använda DntR i en biosensor för att upptäcka sprängämnet TNT, som avger DNT som en ”signaturmolekyl”. En annan aspekt har varit att bättre förstå den detaljerade mekanismen för hur DntR fungerar. DntR är ett protein som binder till en viss DNA sekvens (promotor) och reglerar hur gener intill denna promotorsekvens läses av. När en inducerande molekyl som t.ex. DNT binder till DntR förändras proteinets struktur på ett sådant sätt att DntR kan aktivera transkription av de gener som finns intill promotor-sekvensen. För att mäta hur DntR reagerar på olika inducerande molekyler har DntR uttryckts i bakterien Escherichia coli, som också innehållit promotorn som DntR binder till. Intill promotorn sitter en gen som kodar för proteinet GFP. När en inducerande molekyl binder till DntR, slås avläses gfp-genen, och det fluorescerande proteinet GFP produceras. Ju mer GFP som produceras i cellerna, desto högre fluorescens kan uppmätas när cellerna analyseras.   I de artiklar som presenteras i avhandlingen har vi undersökt hur olika substitutioner i DntR proteinet påverkar specificiten och sensitiviteten och hur dessa egenskaper kan påverkas av olika experimentella faktorer. Effekten av substitutioner har relaterats till strukturdata, där bilder av hur proteinet ser ut på molekylär nivå har tagits fram. Dessutom presenteras även en bild av hur DntR förändras beroende på om inducerande molekyler är bundna eller inte. En sådan strukturbild ökar förståelsen för de mekanismer som gör att bindning av en inducerande molekyl orsakar en förändring av formen hos DntR på så sätt att avläsning av gener kan aktiveras. Vi har också använt en metod där evolutionära processer härmats för att få fram varianter av DntR med förbättrad respons till DNT. En variant med en drastisk ökning av DNT-responsen har isolerats, och dess egenskaper har karaktäriserats. / At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript

Endocrine-disrupting chemicals (EDCs) are known to cause endocrine disruption (ED), developmental neurotoxicity (DNT), infertility and impaired embryo development. EDCs do therefore impose a threat to humans, wildlife and the environment. The present study investigated the effects of the reference compounds dihydrotestosterone, estradiol, benzo(a)pyrene, rosiglitazone, as well as the EDCs bisphenol F and perfluorooctanesulfonic acid at various concentrations on zebrafish embryos. The scientific questions of the study were to investigate how these environmental pollutants impact the development of zebrafish, what their molecular mechanisms are and what the link between ED and DNT is. Zebrafish embryos were exposed for 5 days to the compounds and various parameters on development were collected at different time points. The expression of 41 genes (qPCR) related to ED and DNT, and the levels of 23 steroids (LC-MS/MS) were determined. Gene correlations were determined with Pearson’s correlation test and paired t-tests were used to determine significantly altered gene activities. The significant gene expression changes were further related to the pathways of steroids in order to connect how gene activity impacted steroid levels. Exposure to estradiol, dihydrotestosterone and bisphenol F induced cyp19a1b expression which can affect personality traits. Perfluorooctanesulfonic acid interferes with thyroid hormone transport by binding to TTR causing profound effects on neurodevelopmental processes and cognitive functions. The compounds influenced genes that can disrupt endocrine systems which can cause neurodevelopmental impairments.

In the age of the General Data Protection Regulation (GDPR) and the California Consumer Privacy Act (CCPA), privacy and consent control have become even more apparent for every-day users of the internet. Privacy banners in all shapes and sizes asks for your permission through more or less challenging designs and makes privacy control more of a struggle than actually helping the users’ privacy. This thesis presents a novel solution expanding on the Advanced Data Protection Control (ADPC) mechanism in order to bridge current gaps in user data and privacy control. It moves the consent control to the browser interface to give a seamless and hassle-free experience for users, while at the same time offering content providers a way to be legally compliant with legislation including the GDPR. Motivated by an extensive academic review to evaluate previous work and identify current gaps in user data control, the aim of this thesis is to present a blueprint for future implementation of suggested features to support privacy control online for users globally.

Modern methods of speech synthesis are not suitable for restoration of song signals due to lack of vitality and intonation in the resulted sounds. The aim of presented work is to synthesize melismas met in Lithuanian folk songs, by applying Artificial Neural Networks. An analytical survey of rather a widespread literature is presented. First classification and comprehensive discussion of melismas are given. The theory of dynamic systems which will make the basis for studying melismas is presented and finally the relationship for modeling a melisma with nonlinear and dynamic systems is outlined. Investigation of the most widely used Linear Prediction Coding method and possibilities of its improvement. The modification of original Linear Prediction method based on dynamic LPC frame positioning is proposed. On its basis, the new melisma synthesis technique is presented. Developed flexible generalized melisma model, based on two Artificial Neural Networks – a Multilayer Perceptron and Adaline – as well as on two network training algorithms – Levenberg- Marquardt and the Least Squares error minimization – is presented. Moreover, original mathematical models of Fortis, Gruppett, Mordent and Trill are created, fit for synthesizing melismas, and their minimal sizes are proposed. The last chapter concerns experimental investigation, using over 500 melisma records, and corroborates application of the new mathematical models to melisma synthesis of one performer.

Modern methods of speech synthesis are not suitable for restoration of song signals due to lack of vitality and intonation in the resulted sounds. The aim of presented work is to synthesize melismas met in Lithuanian folk songs, by applying Artificial Neural Networks. An analytical survey of rather a widespread literature is presented. First classification and comprehensive discussion of melismas are given. The theory of dynamic systems which will make the basis for studying melismas is presented and finally the relationship for modeling a melisma with nonlinear and dynamic systems is outlined. Investigation of the most widely used Linear Prediction Coding method and possibilities of its improvement. The modification of original Linear Prediction method based on dynamic LPC frame positioning is proposed. On its basis, the new melisma synthesis technique is presented. Developed flexible generalized melisma model, based on two Artificial Neural Networks – a Multilayer Perceptron and Adaline – as well as on two network training algorithms – Levenberg- Marquardt and the Least Squares error minimization – is presented. Moreover, original mathematical models of Fortis, Gruppett, Mordent and Trill are created, fit for synthesizing melismas, and their minimal sizes are proposed. The last chapter concerns experimental investigation, using over 500 melisma records, and corroborates application of the new mathematical models to melisma synthesis of one performer.