Cyber attacks can target any nodes of the space infrastructure, and while these attacks are called non-violent, there is a credible capability to use cyber attacks to cause direct or indirect physical damage, injury or death. However, the vulnerability of satellites and other space assets to cyber attack is often overlooked, which is a significant failing given society's substantial and ever increasing reliance on satellite technologies. Through a policy analysis, this dissertation assess the set of political provisions provided by the European Union to address the cyber security issue of the space infrastructure. Such study aims at exploring the geopolitical consequences linked to space cyber security risks, and at assessing the political preparedness of the European Union to address these challenges. The perspective of transatlantic cooperation to further support both American and European effort to tackle this security risk is also addressed. The overarching value of the study is to contribute to future European cyber security for space and transatlantic debates by providing useful perspectives and key takeaways on these two domains. Ultimately, he existing set of policies are not sufficient to address the cyber security issue in Outer Space, a unified approach by the European Union and the United...

Critical infrastructures are vital services, and attacks on such systems affect people's social and economic well-being. Therefore, operators of such services must have appropriate measures in place to handle IT-related incidents. However, reports show that organisations classified as Operators of Essential Services (OES) do not have appropriate measures to handle IT-related incidents. A case study approach is used in this study to test the usability and the applicability of Wahlgren's Escalation Maturity Model level within various public sector organisations in Sweden regarding their escalation and communication of IT-related incidents. A follow-up semi-structured interview is also conducted with employees at the technical level to determine if the current organisation's maturity level shortcomings are known across different organisational levels. The tool's maturity level scaling attributes are difficult to understand because all organisations in this study achieve the same level of maturity, even though there is a wide range of performance regarding the number of questions answered in the affirmative. The data output generated from the testing of the model can assist organisations in improving their incident escalation activities. However, the lack of precision of the model makes it challenging to apply in the public sector. The results reveal that all the five organisations obtained an escalation maturity level of zero (0), non-existent, regarding escalation of IT-related incidents. As a result, with the current model, the participating organisations will have a difficult task complying with the NIS Directive's security and notification requirements.

No description available.

Cybersecurity threats have grown to become a global threat to private actors and states. While work processes are becoming more efficient, rapid technological developments are exposing network and information systems to vulnerabilities. The private sector plays a significant role in keeping the EU and Sweden safe in cyberspace since technological development is essentially controlled by private actors. When it comes to socially important activities, private actors both own and operate large parts of the market, which in turn means that attacks on private actors affecting trade secrets can pose a threat to market competition and economic prosperity. This thesis maps out how the EU has chosen to combat this with the NIS and NIS2 Directives. Specifically, this thesis maps out changes in cybersecurity requirements for private actors providing digital solutions in the light of NIS2. The previous NIS has shown to be inherently flawed with regards to the EU goal of achieving a high common level of security for network and information systems. The need for renewed legislation is therefore great and, as the investigation shows, NIS2 entails a change in the content, structure, and scope of important and essential entities. In short, the NIS2 Directive requires entities to perform their due diligence and document appropriate and proportionate measures based on an all-risk analysis. The increased and broadened requirements in NIS2, which are certainly justified by the increased cybersecurity threats, must also be weighed against an overly burdensome bureaucracy for authorities and private actors. In addition, this thesis analyzes the format of NIS2 and its potential impact on the internal market of the EU. Given the fact that it is a market regulation, a proportionality assessment is required in relation to the competitive disadvantages that an overly burdensome legislation may result in for private actors. At the same time, sanctions and enforcement measures must be sufficiently dissuasive. In conclusion, this thesis argues NIS2 to bring important changes, albeit still posing risks of further fragmenting the cybersecurity levels in the union due to the flexibility given to member states. However, NIS2 is a key step in the right direction towards achieving a high common level of cybersecurity across member states.

Endokrin aktive Substanzen (EACs) sind exogene Substanzen natürlichen oder synthetischen Ursprungs, die mit der Feedbackregulation hormoneller Netzwerke interferieren können und somit deren Homöostase beeinflussen. Störungen der Hypothalamus-Hypophysen-Schilddrüsenachse (HPT-Achse) haben weitreichende Konsequenzen, da Schilddrüsenhormone essentiell für die Regulation von Entwicklung, Wachstum und Stoffwechsel sind. In der vorliegenden Arbeit wurde das Wirkprofil potenter Inhibitoren der thyreotropen Achse am Beispiel von 4-Methylbenzyliden-campher (4-MBC) und Genistein (GEN) untersucht. Der UV-Filter 4-MBC wurde in der ovariektomierten Ratte als goitrogene Substanz identifiziert. 4-MBC interferiert auf Ebene von Hypothalamus und Hypophyse mit der Expression Feedback-assoziierter Gene und beeinflusst daher die Feedbackregulation der thyreotropen Achse. Darüber hinaus wird die Biosynthese von Schilddrüsenhormonen durch Inhibition des Iodidtransports bei gleichzeitig erhöhter messenger RNA (mRNA)-Konzentration des Natrium-Iodid-Symporters (NIS) durch 4-MBC beeinträchtigt. Parallel dazu lässt die verstärkte Expression des Angiogenesemarkers vascular endothelial growth factor (VEGF) nach subakuter Exposition auf die Entstehung einer Hypothyreose schließen. Die damit einhergehenden Veränderungen sind auch in peripheren Organen durch die Analyse 3,3‘,5-Triiod-L-thyronin (T3)-regulierter Zielgene dokumentiert. Zudem wurden diese Effekte maßgeblich durch die Expositionszeit beeinflusst, da nach chronischer Exposition vermutlich auch kompensatorische Prozesse eine wichtige Rolle spielen. Die gezeigten speziesspezifischen Effekte lassen sich möglicherweise auf Unterschiede in der Pharmakokinetik zurückführen, z.B. in Folge differentieller Expression von Cytochrom P450-Genen. / Endocrine active compounds (EACs) can be of natural or synthetic origin and show hormone-like effects that interfere with feedback regulation of hormonal networks. Interferences with the hypothalamic-pituitary-thyroid axis (HPT-axis) result in extensive consequences as thyroid hormones are essential for regulation of development, growth, and metabolism. In the work presented here, the active profile of potent inhibitors of the HPT-axis namely 4-methylbenzylidene-camphor (4-MBC) and genistein (GEN) was investigated. 4-MBC, a UV filter used in sunscreens and various cosmetics, was identified as a goiter causing agent using ovariectomized rats. 4-MBC acts at the level of hypothalamus and pituitary gland by modulating the expression of thyrotropin-releasing hormone (TRH) as well as thyroid-stimulating hormone (TSH) that regulate feedback on the HPT-axis. Furthermore, biosynthesis of thyroid hormones was impaired by 4-MBC secondary to the inhibition of iodide transport with concomitantly increased messenger RNA (mRNA)-levels of the sodium-iodide symporter (NIS). In parallel expression of the angiogenesis marker vascular endothelial growth factor (VEGF) was increased, indicating hypothyroidism. After the application of 4-MBC the expression of L-3,3’,5-triiodothyronine (T3)-regulated target genes was reduced in the periphery both on the mRNA and protein level. The documented species-specific effects indicate a difference in pharmacokinetics, possibly secondary to differential expression of cytochrome P450 genes. GEN is contained in soy and red clover and its mechanistic analysis was carried out in thyroid hormone receptor (TR) deficient mice (TRα0/0). The gender-dependent effects of GEN on tissue specificity did not follow an obvious pattern and warrant continuative analysis. The work presented here supports the assumption that EACs can interfere with function and regulation of the HPT-axis at levels that were previously considered safe.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-29T23:04:54Z No. of bitstreams: 1 IsabelleRibeiroBarbosa_TESE.pdf: 2469240 bytes, checksum: 9250242c7a43a110081c54313058a7b6 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-02T20:25:43Z (GMT) No. of bitstreams: 1 IsabelleRibeiroBarbosa_TESE.pdf: 2469240 bytes, checksum: 9250242c7a43a110081c54313058a7b6 (MD5) / Made available in DSpace on 2016-03-02T20:25:43Z (GMT). No. of bitstreams: 1 IsabelleRibeiroBarbosa_TESE.pdf: 2469240 bytes, checksum: 9250242c7a43a110081c54313058a7b6 (MD5) Previous issue date: 2015-03-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Os c?nceres que acometem os ?rg?os genitais masculinos e femininos, em conjunto com o c?ncer de mama, s?o respons?veis por cerca de 20% dos ?bitos por c?ncer no mundo. Conhecer os padr?es de mortalidade por esses c?nceres no Brasil, as mudan?as que se produziram ao longo do tempo, os grupos mais vulner?veis e a carga de mortalidade que se apresentar? no futuro s?o elementos b?sicos para a estrutura??o das a??es assistenciais e de vigil?ncia do c?ncer. O objetivo desse estudo foi analisar as tend?ncias de mortalidade pelos c?nceres que acometem ?rg?os que s?o espec?ficos a cada g?nero e projetar a mortalidade por esses c?nceres at? o ano de 2030, para o Brasil, regi?es e estados da federa??o. Trata-se de um estudo ecol?gico de base populacional que analisou os ?bitos, ocorridos no per?odo 1996 a 2010, decorrentes dos c?nceres de colo do ?tero, corpo do ?tero, mama feminina, ov?rios, vulva, vagina, pr?stata, p?nis e test?culos, registrados no Sistema de Informa??o sobre Mortalidade; as informa??es sobre popula??o foram obtidas do Instituto Brasileiro de Geografia e Estat?stica. Foi aplicada a Regress?o loglineal (Joinpoint regression) com taxas padronizadas (popula??o mundial: ASR-W) para estimar o Annual Percentage Change (APC), o Average Annual Percentage Change (AAPC), o intervalo de confian?a 95% e os pontos de inflex?o da curva; as proje??es foram calculadas atrav?s do programa Nordpred, inscrito no programa R, utilizando o modelo idade-per?odo-coorte, analisando posteriormente se as mudan?as que se produzir?o no futuro ser?o decorrentes da exposi??o aos fatores de risco e/ou da estrutura da popula??o exposta ao risco. Todas as an?lises tamb?m foram aplicadas para o conjunto de todos os ?bitos por c?ncer (com exce??o dos c?nceres de pele n?o-melanoma). Para o Brasil, a mortalidade pelos c?nceres de p?nis (APC=1,5% IC95% 0,7;2,3 p<0,05), test?culos (APC=1,6% IC95% 0,5;2,8 p<0,05) e ov?rios (APC=0,8% IC95% 0,1; 1,5 p<0,05), mostraram tend?ncia de aumento, enquanto os c?nceres de vulva e vagina (APC=-0,1% IC95% -0,9; 0,7 p=0,8), corpo de ?tero (APC= -0,3 IC95% -1,0; 0,5 p=0,4), mama (APC=0,4% IC95% -0,2;1,0 p=0,2) e de pr?stata (AAPC= 1,1% IC95% -0,2; 2,4 p=0,1) apresentaram tend?ncia de estabilidade. A mortalidade por c?ncer de colo de ?tero apresentou tend?ncia de redu??o (APC=-1,7% IC95%-2,2; -1,1 p<0,05). A an?lise do agrupamento de todos os ?bitos por c?ncer observou tend?ncia de aumento na mortalidade para o sexo masculino at? o ano de 2006 (APC= 1,2% IC95% 0,6;1,8 p<0,01), seguido de um per?odo de estabilidade. Para o sexo feminino, a tend?ncia ? de estabilidade (APC=0,4% IC95% -0,2;-1,8 p=0,2). As taxas de mortalidade para todos os c?nceres analisados mostraram, de maneira geral, tend?ncia de redu??o nas regi?es sul e sudeste, tend?ncia de aumento nas regi?es norte e nordeste, e estabilidade para a regi?o centro oeste. Na proje??o da mortalidade para o ano 2030, as regi?es norte e nordeste responder?o pelas maiores taxas de mortalidade para os c?nceres analisados; todavia, para as demais regi?es, ser? observada redu??o nas taxas em compara??o com o ?ltimo per?odo observado. Destacase o c?ncer de test?culo, para o qual ser? observado aumento de 33% na carga da mortalidade at? o ano 2030. Para os demais c?nceres, n?o ser?o observadas varia??es consider?veis nas taxas de mortalidade para o Brasil entre o ?ltimo per?odo observado e o ?ltimo per?odo projetado. A estrutura e o tamanho da popula??o brasileira ser?o os fatores que explicar?o os padr?es de mortalidade por esses c?nceres no futuro, embora para a regi?o nordeste, as varia??es ser?o explicadas, em maior medida, pelo aumento do risco para esses c?nceres. Conclui-se, portanto, que existe uma marcante desigualdade na distribui??o da mortalidade pelos c?nceres espec?ficos ao g?nero no Brasil, onde as regi?es mais pobres apresentam um quadro de aumento significativo do n?mero de ?bitos ao longo de uma s?rie hist?rica, e que em 2030, essas regi?es responder?o pelas maiores taxas de mortalidade no pa?s, com ?nfase para os c?nceres de p?nis, test?culos e ov?rios.

The diploma thesis "Data Standard of the Health Information Systems" deals with the structure of data standard including XML language. Further the thesis is focusing on hospital information system CLINICOM with the inclusion of the access to data records from its database Caché company InterSystems. Description of the National registers of health is also included.The concept of web application is also one part of the thesis which enables to generate reports in the data standard of the Ministry of Healt of the Czech Republic for mandatory reporting by NHIS registers in the time interval from the Caché database. Found records from the database can be printed for archiving. The work also deals with security access to the HIS server and data communication between health organizations.

The thesis entitled “Design and Development of Synthetic Methods using Metal-mediated and Metal-free Redox Reactions: Novel C-H Activations, Reductions and Oxidative Transformations” is presented in 4 chapters Chapter 1; Iodine catalyzed amination of benzoxazoles: efficient metal free route to 2-aminobenzoxazoles under mild conditions. The Chapter 1 of this thesis describes iodine catalyzed C-H activation of benzoxazole with primary and secondary amines to form oxidative aminated products. Selective C-H oxidation is a frontline area of modern chemical research as it offers the opportunities to new avenues and more direct synthetic strategies for the synthesis of complex organic molecules.1 In this context, transition metals such as palladium copper, nickel etc, are used extensively for the functional group directed C-H activation, and thus provides new, rapid, low-cost, and environmentally benign protocols for the construction of new chemical bonds.2 During the past two decades iodine and hypervalent iodine have been focus of great attention as they provide mild, chemoselective and environmentally benign strategies in contrast to toxic metal oxidants.3 In this chapter, a facile metal-free route of oxidative amination of benzoxazole with secondary or primary amines in the presence of catalytic amount of iodine (5 mol%) in aq tert-butyl hydroperoxide (1equiv) and AcOH (1.1 equiv) at ambient temperature, under the solvent-free reaction condition is presented. This user-friendly method to form C-N bonds produces tert-butanol and water as the by-products, which are environmentally benign. A wide range of benzoxazole derivatives containing electron-donating and electron-withdrawing groups were coupled with both primary and secondary amines (Scheme 1). Application of this methodology is demonstrated by synthesizing therapeutically active benzoxazoles by reacting 5-chloro-7-methylbenzoxazole with N-methylpiperazine and N-ethylhomopiperazine to obtain corresponding N-aminatedbenzaxozoles, which exhibit antidiarrhetic activity (Scheme 2).4 Scheme 2 Chapter 2: NIS catalyzed reactions. amidation of acetophenones and oxidative amination of propiophenones Chapter 2 is divided in to 2 parts. Part 1 describes the synthesis of α-ketoamides by using acetophenone and secondary amine in the presence of N-iodosuccinamide and TBHP in acetonitrile at room temperature, whereas Part 2 reveals the synthesis of 2-aminoketones by reacting aryl alkyl ketones and suitable secondary amine in the presence of NIS and TBHP. Part 1: Oxidative amidation, synthesis of α-ketoamide: Alpha α-ketoamides are important intermediates in organic synthesis that are present in a variety of natural products, and pharmaceutically active compounds. Herein, a mild and efficient conversion of acetophenones to α-ketoamide is documented by using aq.TBHP and N-iodosuccinamide (NIS) as a catalyst, at ambient temperature. This amidation reaction was found to be versatile as several aetophenone derivitives containing electron-withdrawing and electron-donating substituents underwent a facile amidation. It was also found that acetyl derivatives of heterocylic compounds could be easily converted to their corresponding ketoamides (few examples are shown in Scheme 3).5 Scheme3 Part 2 of Chapter 2 narrates a novel amination of propiophenone and its derivatives catalysed by NIS in the presence of TBHP to furnish their corresponding 2-aminoketone derivatives (Scheme 4). These derivatives are ubiquitous scaffolds that are present in a wide variety of therapeutic agents. Some of these compounds are used in the treatment of depression, smoking cessation, as monoamine uptake inhibitors, rugs for cancer. They are photoinitiators, precursors to β-aminoalcohols, such as pseudoephedrine analogues. 2-Aminoacetophenone analogues are also important intermediates for the formation of several heterocyclic compounds and are active moieties in several important drugs such as ifenprodil, Scheme 4. Chapter 3: Efficient oxidation of primary azides to nitriles This Chapter is divided in to 2 parts, which presents the oxidation of primary azides to their corresponding nitriles. Part 1: An Efficient oxidation of primary azides catalyzed by copper iodide: a convenient method for the synthesis of nitriles In Part 1, an efficient oxidation of primary azides catalyzed by copper iodide to their corresponding nitriles is reported. Herein, the oxidation of primary azide to nitrile is performed using catalytic amount of copper iodide, and aq TBHP in water at 100 ° C. This methodology is compatible with a wide range of primary benzylic azides that contain electron-donating and electron-withdrawing functional groups. The oxidation was found to be selective and a number of oxidizable functional groups were well-tolerated during the reaction conditions (few examples are shown in Scheme 5).6 Scheme 6 Furthermore, oxidation of secondary azides furnished the corresponding ketones in excellent yields (Scheme 6).6 In the Part 2 of Chapter 3, a non-metal catalysed oxidation of primary azides to nitriles at ambient temperature is reported. This part reveals the oxidation of primary azides to nitriles by employing catalytic amounts of KI (25 mol%), DABCO (25 mol%) and aq. TBHP (3 equiv., 70% solution in water). This reaction provides a good selectivity, as double and triple bonds were not oxidized under the reaction conditions. Additionally, chemoselective oxidation of benzylicazides against aliphatic azides increases the potential application of the present method (Scheme 7).7 Chapter 4: Chemoeselective reduction of olefins Part 1: Iron chloride catalysed aerobic reduction of olefins using aqueous hydrazine at ambient temperature Chapter 4 describes the reduction olefins and acetylenes, which is presented in two Parts. Part 1 documents utility of hydrazine (1.5 equiv) for the chemoselective reduction of nonpolarised carbon-carbon bond using iron catalysts. In this part, a chemoselective reduction of alkenes and alkynes in the presence of a variety of reducible functional groups is demonstrated (Scheme 8). The highlight of the present method is that the reduction proceeds well at room temperature and requires only 1.5 equiv of hydrazine hydrate. The olefin reduction by hydrazine depends upon the controlled release of diimide during the reduction. Generally, metal catalyzed reduction of olefins employ a large excess of hydrazine (10-20 equiv), which might be attributed to uncontrolled release of diimide during the reduction.8 Scheme 8 Part 2: Guanidine catalyzed aerobic reduction: a selective aerobic hydrogenation of olefins using aqueous hydrazine In Chapter 4, part 2, organocatalytic generation of diimide and its utility to reduce the double bonds is presented. Generation of diimide in situ by using organo catalysts and its use for the reduction of carbon-carbon double bond is one of the interesting topics in organic chemistry. It has been shown in this part of the thesis that the reduction of olefin at room temperature can be efficiently performed by using 10 mol% of guanidine nitrate, 2 equiv of aqueous hydrazine in oxygen atmosphere. This method tolerates a variety of reducible functional groups such as nitro, azido, and bromo and protective groups such as methyl ethers, benzyl ethers, and Cbz groups. It is also shown that terminal olefin can be selectively reduced in the presence of internal olefin (Scheme 9). Unlike other methods that employ diimide strategy, the present method is shown to be efficient in reducing substrates those contain internal double bonds such as cinnamyl alcohol and its derivatives

Dans la première partie du travail, nous avons étudié l’expression génique dans les cancers thyroïdiens survenus après l’explosion de la centrale nucléaire de Tchernobyl. L’incidence des cancers thyroïdiens papillaires a fortement augmenté après l’accident de Tchernobyl chez les enfants, offrant l’opportunité exceptionnelle d’étudier les caractéristiques moléculaires des cancers thyroïdiens radioinduits. Contrairement aux études précédentes qui comportaient toutes des facteurs confondants, nous avons pu investiguer l’expression des ARN messagers des tumeurs et de leurs tissus contra-latéraux normaux de patients exposés et de patients non exposés aux retombées radioactives, en utilisant une cohorte de patients appariés pour l’âge et l’ethnicité. L’irradiation d’une population conduit au développement de cancers dans une fraction de cette population. Les individus atteints peuvent l’avoir été de manière stochastique, ou à cause d’une prédisposition ou sensibilité particulière à l’irradiation. La comparaison des tumeurs exposées et non exposées permet d’étudier l’effet de l’irradiation, et celle des tissus normaux contralatéraux offre la possibilité d’étudier la susceptibilité aux radiations dont les implications sont nombreuses en médecine (radio-diagnostic, cancers secondaires) et en radioprotection. L’expression génomique complète a été analysée sur puces Affymetrix pour les tissus de 45 patients. Vingt-deux de ces patients ont été exposés aux retombées de Tchernobyl, vingt-trois autres, appariés selon l'âge et résidant dans les mêmes régions de l'Ukraine, n'ont pas été exposés à l’irradiation. Notre travail a mis en évidence l’existence d’une signature transcriptionnelle permettant de différencier les tissus normaux exposés des non exposés, les gènes qui composent cette signature ayant trait à la prolifération ;nos résultats suggèrent qu’un niveau plus élevé de prolifération dans les tissus normaux pourrait être associé aux cancers radioinduits, soit en tant que facteur prédisposant au cancer, soit en tant que conséquence de la radiation.<p><p>La deuxième partie du travail a été consacrée à la caractérisation in vitro de différentes lignées cellulaires humaines de cancers thyroïdiens. Ces lignées sont souvent employées comme modèles pour l’étude et le développement d’approches thérapeutiques pour ces cancers mais notre laboratoire a démontré que ces lignées s’étaient dédifférenciées au cours de leur propagation in vitro et que leurs profils transcriptionnels se rapprochaient essentiellement des tumeurs les plus dédifférenciées, les cancers anaplasiques. Nous avons tenté de ré-induire dans ces lignées l’expression des marqueurs de différenciation de la thyroïde au moyen d’agents épigénétiques, l’idée étant que ces gènes dont l’expression est caractéristique de la thyroïde ne s’expriment plus suite à l’action de mécanismes épigénétiques comme la méthylation au niveau de leurs promoteurs. Les cancers thyroïdiens dédifférenciés étant les plus agressifs et ayant perdu l’expression des facteurs de différenciation dont le transporteur sodium/iodure (NIS), ils sont inaccessibles au traitement par l’iode radioactif I131. La réexpression des marqueurs de différenciation thyroïdienne permettrait d’une part d’employer plus adéquatement les lignées comme modèle d’étude des cancers différenciés, et d’autre part d’envisager l’emploi de(s) substances(s) qui ont permis cette réexpression en tant que médicaments pour les cancers dédifférenciés. Nos travaux montrent que les traitements épigénétiques des lignées cancéreuses ne permettent pas une réinduction significative de la différenciation mais tendent à démontrer que l’inactivation épigénétique provoque dans ces lignées la perte de l’expression de gènes n’ayant aucun rôle utile pour la cellule au cours des milliers de réplications in vitro / In the first part of the work, we studied gene expression in thyroid cancers following the explosion of the Chernobyl nuclear power plant. The incidence of thyroid papillary cancers rose sharply after the Chernobyl accident in children, providing an exceptional opportunity to study the molecular characteristics of radiation-induced thyroid cancers. Unlike previous studies that included confounding factors, we were able to investigate the expression of messenger RNA from tumors and their normal contra-lateral tissue of patients exposed and not exposed to the fallout using a cohort of patients matched for age and ethnicity. The irradiation of a population leads to the development of cancer in a fraction of the population. Affected individuals may have been stochastically, or because of a particular predisposition or susceptibility to irradiation. Comparison of tumors exposed and unexposed allows to study the effect of irradiation, and the contra-lateral normal tissue offers the possibility to study the susceptibility to radiation whose implications are numerous: medical (radio - diagnosis, secondary cancers ) and radiation protection. The complete gene expression was analyzed on Affymetrix for tissues of 45 patients. Twenty- two of these patients were exposed to fallout from Chernobyl, twenty-three, matched for age and residing in the same regions of Ukraine have not been exposed to radiation. Our work has demonstrated the existence of a transcriptional signature allowing to differentiate exposed and unexposed normal tissues, and the genes that compose the signature are related to proliferation; our results suggest that a higher level of proliferation in normal tissues may be associated with radiation-induced cancers, either as a predisposing factor for cancer,or as a result of the radiation.<p><p>The second part was devoted to the in vitro characterization of different human cell lines of thyroid cancer. These lines are often used as models for the study and development of therapeutic approaches for these cancers, but our laboratory has demonstrated that these cell lines dedifferentiated during their in vitro propagation and their transcriptional profiles are essentially closer to the most dedifferentiated tumors, the anaplastic cancers. We tried to re- induce in these lines the expression of differentiation markers of thyroid using epigenetic agents, the idea being that these genes whose expression is characteristic of thyroid are no longer expressed due to epigenetic mechanisms such as methylation of their promoters. Dedifferentiated thyroid cancers are more aggressive and have lost the expression of differentiation factors including sodium/iodide transporter(NIS), they are inaccessible to treatment with radioactive iodine I131. Re-expression of thyroid differentiation markers could allow in one hand to use more adequately cell lines as models to study differentiated cancers, and secondly to consider the used substances that helped this re-expression as drugs for the dedifferentiated cancers. Our work shows that epigenetic treatments for cancer cell lines do not allow a significant re-induction of differentiation but tend to demonstrate that the epigenetic inactivation in these cell lines causes the loss of expression of genes that have no useful role in the cells over thousands of replication in vitro .<p><p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Geographic Information Systems and Network Information Systems are important tools for our society, used for handling geographic spatial data and large information networks. It is therefore important to make sure such tools are of high quality. GIS/NIS applications typically deal with a lot of data, possibly resulting in heavy loads of network traffic. This work aims to evaluate two different communications protocols and serialization formats for client-server communications efficiency in GIS/NIS applications. Specifically, these are HTTP/1.1, HTTP/2, Java Object Serialization and Google's Protocol Buffers. They were each implemented directly into a commercial GIS/NIS environment and evaluated by measuring two signature server calls in the system. Metrics that were examined are call duration, HTTP overhead size and HTTP payload size. The results suggest that HTTP/2 and Google's Protocol Buffers outperform HTTP/1.1 and Java Object Serialization respectively. An 87% decrease in HTTP overhead size was achieved when switching from HTTP/1.1 to HTTP/2. The HTTP payload size is also shown to decrease with the use of Protocol Buffers rather than Java Object Serialization, especially for communications where data consist of many different object types. Concerning call duration, the results suggest that the choice of communications protocol is more significant than the choice of serialization format for communications containing little data, while the opposite is true for communications containing much data. / Geografiska informationssystem och nätverksinformationssystem är viktiga redskap för vårt samhälle, vilka används för hantering av geografisk data och stora informationsnätverk. Det är därför viktigt att se till att sådana system är av hög kvalitet. GIS/NIS-applikationer behandlar vanligtvis stora mängder data, vilket kan resultera i mycket nätverkstrafik. I det här arbetet utvärderas två olika kommunikationsprotokoll och serialiseringsformat för kommunikationseffektivitet mellan klient och server i GIS/NIS-applikationer. Specifikt är dessa HTTP/1.1, HTTP/2, Java Objektserialisering och Googles Protocol Buffers. De implementerades var och en i en kommersiell GIS/NIS-miljö och utvärderades genom mätningar av två signaturanrop i systemet. De aspekter som observerades är kommunikationstiden, mängden HTTP-overhead och mängden HTTP-payload. Resultaten tyder på att HTTP/2 och Googles Protocol Buffers presterar bättre än HTTP/1.1 respektive Java Objektserialisering. En 87% minskning av mängden HTTP overhead uppnåddes då HTTP/1.1 ersattes med HTTP/2. En minskning av mängden HTTP payload observeras också med användning av Protocol Buffers snarare än Java Objektserialisering, särskilt för kommunikationer där data innehåller många olika objekttyper. Gällande kommunikationstiden tyder resultaten på att valet av kommunikationsprotokoll påverkar mer än valet av serialiseringsformat för kommunikationer med små mängder data, medan motsatsen gäller för kommunikationer med mycket data.