This thesis introduces the design and implementation of the extension of the system for lawful interception. The system is developed as a part of the Sec6Net project at FIT BUT and provides a platform for research activities in determining identities in computer networks. Parts which has the task of monitoring changes in a user's identity will be extended, so that the system is able to determine the identity even in the tunneled and translated networks. It describes the problems encountered during implementation and their solutions. There are described mechanisms for tunneling networks, mainly virtual private networks and transition mechanisms for IPv6, IP addresses and NAT variants. In the end the tests of the individual modules are described.

In this thesis, we explore the use of a centrally-coordinated peer-to-peer overlay as a possible solution to the live streaming problem. Our contribution lies in showing that such approach is indeed feasible given that a number of key challenges are met. The motivation behind exploring an alternative design is that, although a number of approaches have been investigated in the past, e.g. mesh-pull and tree-push, hybrids and best-of-both-worlds mesh-push, no consensus has been reached on the best solution for the problem of peer-to-peer live streaming, despite current deployments and reported successes. In the proposed system, we model sender/receiver peer assignments as an optimization problem. Optimized peer selection based on multiple utility factors, such as bandwidth availability, delays and connectivity compatibility, make it possible to achieve large source bandwidth savings and provide high quality of user experience. Clear benefits of our approach are observed when Network Address Translation constraints are present on the network. We have addressed key scalability issues of our platform by parallelizing the heuristic which is the core of our optimization engine and by implementing the resulting algorithm on commodity Graphic Processing Units (GPUs). The outcome is a Linear Sum Assignment Problem (LSAP) solver for time-constrained systems which produces near-optimal results and can be used for any instance of LSAP, i.e. not only in our system.   As part of this work, we also present our experience in working with Network Address Translators (NATs) traversal in peer-to-peer systems. Our contribution in this context is threefold. First, we provide a semi-formal model of state of the art NAT behaviors. Second, we use our model to show which NAT combinations can be theoretically traversed and which not. Last, for each of the combinations, we state which traversal technique should be used. Our findings are confirmed by experimental results on a real network. Finally, we address the problem of reproducibility in testing, debugging and evaluation of our peer-to-peer application. We achieve this by providing a software framework which can be transparently integrated with any already-existing software and which is able to handle concurrency, system time and network events in a reproducible manner. / QC 20110426

BACKGROUND: The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood and exerts anti-inflammatory and neuroprotective effects. Its projections reach hypothalamic nuclei which regulate the neuroendocrine stress response. Changes in noradrenergic signalling were reported in multiple sclerosis (MS) and psychiatric illness and may account for the high prevalence of comorbid depression and fatigue in MS patients. Associated studies of our study group—investigating stress response in obese and non-obese subjects—have shown increased activity of the stress axes including an association between hypothalamic-pituitary-adrenal (HPA) axis responsiveness and central noradrenaline transporter. OBJECTIVES: (i) To evaluate central NA transporter (NAT) availability in vivo in immunotherapy-naïve relapsing-remitting multiple sclerosis (RRMS) patients compared to healthy controls (HC), (ii) to measure hypothalamic-pituitary-adrenal (HPA) axis responsiveness and the arginine-vasopressin surrogate (AVP) copeptin in patients with RRMS and clinically isolated syndrome (CIS) compared to HC, (iii) to test whether HPA axis responsiveness is differentially associated to NAT availability in RRMS patients and HC. METHODS: 22 patients (11 RRMS, 11 CIS) were enrolled and compared to 22 sex- and age-matched HC. (i) Positron emission tomography (PET) was performed in 11 RRMS and 12 HC applying the NAT-selective radiotracer S,S-[11C]O-methylreboxetine ([11C]MRB) for intergroup comparison. (ii) All patients underwent the combined dexamethasone/corticotropin releasing hormone (dex/CRH) test. Plasma ACTH and cortisol curve parameters, and copeptin after dexamethasone intake were derived. (iii) MRB-PET imaging data were correlated to curve indicators and copeptin obtained from the dex/CRH test in RRMS patients. RESULTS: (i) RRMS patients show increased NAT availability in almost all subcortical regions, reaching statistical significance in the thalamus, amygdala, putamen and pons/midbrain. No association with clinical or psychometric variables was found. (ii) Immunotherapy-naïve RRMS patients show no significant changes in cortisol, ACTH or copeptin indices. (iii) There is no correlation between HPA axis indicators and NAT availability in RRMS patients. In HC, NAT availability correlated positively with cortisol curve indicators. CONCLUSION: This study supports the evidence for increased NAT availability in immunotherapy-naïve RRMS patients compared to HC. The increased NAT availability was shown in the subcortical brain regions (relevant to attention and emotional regulation) of the RRMS patients. In this cohort, no correlation with physical or psychometric scores was found. It will be further of interest, if these NAT changes longitudinally predispose to the psychiatric comorbidities which are frequently seen in MS patients or if they do in larger, more heterogenous sample sizes. Our cohort of early RRMS and CIS did not display a statistically significant alteration in the HPA axis responsiveness compared to HC. No association between NAT availability and HPA axis responsiveness could be detected in RRMS patients.:TABLE OF CONTENTS LIST OF ABBREVIATIONS…………………….………………………………………......4 LIST OF FIGURES…..….………………………….….……..…………………………..…5 I BIBLIOGRAPHIC DESCRIPTION…………………………..……………………………6 II INTRODUCTION…..…..………………………………………………………….............7 2.1 Multiple sclerosis — Background and scope……………....…………………..........7 2.1.1 Diagnostic criteria, subtypes and clinical features……….............….…………....7 2.1.2 Multiple sclerosis and its impact on daily life: fatigue.…...…...….............………9 2.2. Noradrenaline — neurotransmitter and immunomodulator…...…………….........10 2.2.1 Noradrenaline in the context of multiple sclerosis…………………….................11 2.2.2 Noradrenaline in the context of neuroinflammation and neurogenesis.............12 2.3 Noradrenaline transporter as regulator of noradrenergic transmission….…........13 2.3.1 Noradrenaline transporter imaging……………………………............................14 2.4 Neuroendocrine stress response……...…..……………………..……..……….......14 2.4.1 Noradrenaline in the context of stress response regulation…...........................15 2.4.2 Stress axis regulation in multiple sclerosis……….............……….....................16 III METHODS……………......……………………………………………………..……....19 3.1 Objectives and hypotheses.....……..…………………………………………….......19 3.2 Study design………………..….....………………………………….…..…………….20 3.3 Hypothalamic-pituitary-adrenal axis assessment using the combined dexamethasone/CRH test…….……...........……….....................................................21 3.4 Questionnaires……...…………………….....…………………………………………22 3.4.1 Beck-Depression-Inventory……………….............……….………………………22 3.4.2 Würzburger Erschöpfungsinventar bei MS….…………..….............……………22 3.5 PET imaging, imaging data processing and analysis………………….....………..23 3.6 Statistical analysis………………….………………………………………….....……23 IV RESULTS………….......……………………………………………….........................24 4.1 Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients – Publication….....……...…………24 4.2 HPA axis responsiveness does not differ between HC and RRMS or CIS patients…...………………………………...……………………………………….25 4.3 In RRMS patients, noradrenaline transporter availability of selected brain regions does not correlate with neuroendocrine indicators of stress responsiveness, but do positively correlate in healthy controls………………..….…..25 V SUMMARY………………….…………………………………………………………….31 5.1 Significantly changed noradrenaline transporter availability in RRMS patients in brain regions relevant to attention, vigilance and mood………….............31 5.2 Noradrenaline transporter availability is not significantly associated with psychometric and physical scores……..…………………...........................................32 5.3 HPA responsiveness does not significantly differ between early-stage RRMS patients, CIS patients and healthy controls………..…………………..............32 5.4 NAT DVR of selected brain regions do not reveal a significant association to HPA response in RRMS patients, but in healthy controls………...……..................33 5.5 Limitations..………………………………………………………………………….....35 5.6 Future directions…………………………………………………………………….....35 VI PUBLICATION BIBLIOGRAPHY…….……………………....…………….................36 VII ANHANG…….………..…...…..………..………………………………………………49 7.1 Publikationen…………..……….....…..……………………………………................49 7.1.1 Publikationen als Ko-Autorin…...…………..………..............…………………….50 7.1.1.1 Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls……..50 7.1.1.2 Post-dexamethasone serum copeptin corresponds to HPA axis responsiveness in human obesity...............................................................................51 7.2 Erklärung zum wissenschaftlichen Beitrag der Promovendin zur Publikationspromotion…………...........………………………………………………52 7.3 Erklärung über die eigenständige Abfassung der Arbeit...…....…………...…......53

Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy in the Department of African Languages at the University of Zululand, 2005. / The commoditization of Zulu culture has become commonplace in the tourism industry in South Africa. Zulu culture and cultural products like music; dance, crafts, landscapes and others are often packaged and consumed in the tourism attractions in Zululand and elsewhere. This thesis examines culture and gender issues related to the commoditization process of Zulu culture and cultural products. Focusing on specific case studies in selected tourist attractions in Zululand, the thesis concludes that rural Zulu women play minor roles as dancers, crafters, cooks, and waiters in the tourist attractions in Zululand. Their junior roles make them to play no role in decision making, neither do they own any assets in their work places, and may not, therefore, influence the commoditization and product authentication process of their own culture.

Cette thèse a été motivée par le nouveau contexte ubiquitaire des réseaux ambiants sans-fil. Les protocoles Internet ont été conçus il y a 30 ans sans prendre en considération l'usage nomade des réseaux et ne répondent pas aux nouvelles contraintes de la mobilité. Notre but a été de concevoir des mécanismes pour rendre la mobilité transparente aux applications et utilisateurs. Une partie de notre travail a été axé sur l'amélioration du délai du handoff au niveau physique 802.11 à quelques dizaines de millisecondes. Le déplacement des hôtes et le changement de réseau demandent souvent une reconfiguration des plusieurs paramètres au niveau IP. Dans le cas d'une mobilité locale, l'approche que nous avons choisi est de permettre aux hôtes de garder inchangées leurs adresses et de mettre en place des routes d'hôte dans le domaine local. Au contraire, pour la mobilité globale, le routage optimal à travers l'Internet nous oblige de concevoir une solution dans laquelle les hôtes mobiles changent leurs adresses IP, en conformité avec le réseau ou ils s'y trouvent. Notre solution est basée sur le principe général « de bout en bout » dans laquelle les deux hôtes impliquées dans une connexion sont les seuls à assurer le transfert de cette connexion aux nouveaux points d'attachement. Elle utilise l'interception des appels de la bibliothèque socket et des requêtes DNS ainsi que la translation locale d'adresses pour virtualiser les adresses IP réelles dans des identificateurs d'hôte stables présentés aux niveaux supérieurs.

Les systèmes pair-à-pair (P2P) sont aujourd'hui très populaires. Leur utilisation va de la messagerie instantanée au partage de fichiers, en passant par la sauvegarde et le stockage distribué ou encore le streaming video. Parmi les protocoles P2P, les protocoles basés sur le "gossip" sont une famille de protocoles qui a fait l'objet de nombreux travaux de recherche durant la dernière décennie. Les raisons de l'engouement pour les protocoles basés sur le "gossip" sont qu'ils sont considérés robustes, faciles à mettre en oeuvre et qu'ils ont des propriétés de passage à l'échelle intéressantes. Ce sont donc des candidats intéressants dès lors qu'il s'agit de réaliser des systèmes distribués dynamiques à large échelle. Cette thèse considère deux problématiques rencontrées lorsque l'on déploie des protocoles basé sur le "gossip" dans un environnement réel comme l'Internet. La première problématique est la prise en compte des pare-feux (NAT) dans le cadre des protocoles d'échantillonnage basés sur le "gossip". Ces protocoles font l'hypothèse que, a tout moment, chaque noeud est capable de communiquer avec n'importe quel noeud du réseau. Cette hypothèse est fausse dès lors que certains noeuds utilisent des NAT. Nous présentons Nylon, un protocole d'échantillonnage qui fonctionne malgré la présence de NAT. Nylon introduit un faible surcoût pour gérer les NAT et partage équitablement ce surcoût entre les noeuds possédant un NAT et les autres noeuds. La deuxième problématique que nous étudions est la possibilité de limiter la dissémination de messages de type "spam" dans les protocoles de dissémination basés sur le "gossip". Ces protocoles sont en effet des vecteurs idéaux pour diffuser les messages de type "spam" du fait qu'il n'y a pas d'autorité de contrôle permettant de filtrer les messages basés sur leur contenu. Nous proposons FireSpam, un protocole de dissémination basé sur le "gossip" qui permet de limiter la diffusion des messages de type "spam". FireSpam fonctionne par filtrage décentralisé (chaque noeud participe au filtrage). Par ailleurs, il fonctionne malgré la présence d'une fraction de noeuds malicieux (aussi appelés "Byzantins") et malgré la présence de noeuds dits "rationnels" (aussi appelés "égoïstes"). Ces derniers sont prêts à dévier du protocole s'ils ont un intérêt à le faire.

<p>The company Västra Mälardalens Kommunalförbund, VMKF, wishes to revise and optimize their present data and IP-telephony network as of today consists of the three municipalities Köping, Arboga and Kungsör. As a municipal corporation, they seek consultation regarding internal as well as external review and investigation of the main structure of the network, its functionality and safety. By today’s increasing demands of Internet accessibility, availability of services and security far more extends the requirement of a complete network design. The foundation of networking rests on the balance between each of these necessities. Therefore, it is of grave importance to optimize a network design, use of hardware and to minimize the administrative overhead. In particular, when the municipality is short of resources and time means money. By letting an impartial investigation of the network act as a starting point it was established that several improvement could be applied. Among these a reconstructed and improved network topology that includes subjects as routing, switching, safety and security, quality of service and technical administrative overhead and the implementation of a real time monitoring of network bandwidth consumption.</p> / <p>Företaget Västra Mälardalens Kommunalförbund, VMKF, har önskemål om att granska och optimera deras befintliga data- och IP-telefoninätverk som i dagsläget spänner över de tre kommunerna Köping, Arboga och Kungsör. Som ett kommunalägt företag önskar de konsultation rörande intern såväl som extern granskning och optimering av huvuddelen av nätverkets funktionalitet samt säkerhet. I och med dagens ökade Internetanvändning och funktionalitetsbehov ställs allt högre krav på tillgänglighet, säkerhet och användarvänlighet. Nätverksteknik bygger mycket på balansen mellan dessa tre punkter. Därför gäller det att optimera nätverkets design, hårdvaruanvändning och att minimera administrativa laster. Detta i synnerhet då kommunens resurser är knappa och då tid i dagens samhälle innebär pengar. Genom att låta en granskning över nätverket som det ser ut i dag ligga till grund konstaterades att flertalet förbättringsmöjligheter kunde genomföras. Bland dessa återfinns en omstrukturerad nätverksdesign som innefattar routing, switching, säkerhet, QoS och teknisk administration samt implementeringen av en realtidsövervakning av bandbreddsanvändning.</p>

The company Västra Mälardalens Kommunalförbund, VMKF, wishes to revise and optimize their present data and IP-telephony network as of today consists of the three municipalities Köping, Arboga and Kungsör. As a municipal corporation, they seek consultation regarding internal as well as external review and investigation of the main structure of the network, its functionality and safety. By today’s increasing demands of Internet accessibility, availability of services and security far more extends the requirement of a complete network design. The foundation of networking rests on the balance between each of these necessities. Therefore, it is of grave importance to optimize a network design, use of hardware and to minimize the administrative overhead. In particular, when the municipality is short of resources and time means money. By letting an impartial investigation of the network act as a starting point it was established that several improvement could be applied. Among these a reconstructed and improved network topology that includes subjects as routing, switching, safety and security, quality of service and technical administrative overhead and the implementation of a real time monitoring of network bandwidth consumption. / Företaget Västra Mälardalens Kommunalförbund, VMKF, har önskemål om att granska och optimera deras befintliga data- och IP-telefoninätverk som i dagsläget spänner över de tre kommunerna Köping, Arboga och Kungsör. Som ett kommunalägt företag önskar de konsultation rörande intern såväl som extern granskning och optimering av huvuddelen av nätverkets funktionalitet samt säkerhet. I och med dagens ökade Internetanvändning och funktionalitetsbehov ställs allt högre krav på tillgänglighet, säkerhet och användarvänlighet. Nätverksteknik bygger mycket på balansen mellan dessa tre punkter. Därför gäller det att optimera nätverkets design, hårdvaruanvändning och att minimera administrativa laster. Detta i synnerhet då kommunens resurser är knappa och då tid i dagens samhälle innebär pengar. Genom att låta en granskning över nätverket som det ser ut i dag ligga till grund konstaterades att flertalet förbättringsmöjligheter kunde genomföras. Bland dessa återfinns en omstrukturerad nätverksdesign som innefattar routing, switching, säkerhet, QoS och teknisk administration samt implementeringen av en realtidsövervakning av bandbreddsanvändning.

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

Submitted by Marcia Bacha (marcia.bacha@fgv.br) on 2012-05-09T14:46:01Z No. of bitstreams: 1 Kátia Regina Tinoco Ribeiro de Castro.pdf: 1485209 bytes, checksum: 780fa69cb5b6ce98bf6d976895b72c3a (MD5) / Approved for entry into archive by Marcia Bacha (marcia.bacha@fgv.br) on 2012-05-09T14:49:35Z (GMT) No. of bitstreams: 1 Kátia Regina Tinoco Ribeiro de Castro.pdf: 1485209 bytes, checksum: 780fa69cb5b6ce98bf6d976895b72c3a (MD5) / Made available in DSpace on 2012-05-09T14:49:44Z (GMT). No. of bitstreams: 1 Kátia Regina Tinoco Ribeiro de Castro.pdf: 1485209 bytes, checksum: 780fa69cb5b6ce98bf6d976895b72c3a (MD5) Previous issue date: 2012-03 / Com o crescente número de pedidos de medicamentos por meio de ações judiciais, o Poder Judiciário se viu na difícil função de decidir questões tão relevantes e urgentes para as quais não possuía, necessariamente, conhecimento técnico. O fenômeno intitulado 'judicialização da saúde' tem sido causa de preocupação, pois o alto gasto com a compra de medicamentos solicitados como resultado dessas ações podem interferir, diretamente, em verbas destinadas a outras políticas públicas e provoca uma discussão sobre o direito constitucional a saúde; que nesse aspecto é garantido a quem teve acesso a justiça. Na busca de dar auxilio aos magistrados na hora de decidirem sobre essas ações o Tribunal de Justiça do Estado do Rio de Janeiro em cooperação com a Secretaria de Justiça do Estado do Rio de Janeiro implementaram o Núcleo de Assessoria Técnica (NAT) em ações judiciais da saúde. Núcleo esse formado por profissionais ligados a saúde, que analisam detalhadamente os pedidos, confeccionam um parecer. Esse trabalho visa explanar sobre o funcionamento desse Núcleo e demonstrar se o auxilio técnico serve como instrumento de aperfeiçoamento das decisões judiciais na área da saúde. A abordagem para alcançar o nosso objetivo que é passa pelo conceito, doutrinas e características da Judicialização da saúde. Num segundo momento trabalharemos informações sobre o NAT, tratando da criação, objetivo, atribuição, dinâmica, com enfoque maior na atuação e expansão do Núcleo. Por fim, nosso objetivo é descrever, de forma mais detalhada, a ação do NAT com relação a quantos medicamentos são pedidos por via judicial, que tipo de medicamentos, os gastos com os mesmos e na opinião dos operadores de direito envolvidos nessa seara, como juízes e defensores, sobre o funcionamento do NAT. / With the growing number of requests for medical treatments through lawsuits, the judiciary found itself in the difficult function of deciding relevant and urgent issues for which it hadn't the technical knowledge necessary. The phenomenon called 'judicialization of health' has been a cause for concern because the high spending on these requested medication, as a result of these actions, interfere directly in funds for other public policies and brings up a discussion of the constitutional right to health; that in this respect is guaranteed to those who had access to the legal system. In seeking to provide assistance to judges when deciding on these actions, the Court of the State of Rio de Janeiro in cooperation with the Department of Justice of the State of Rio de Janeiro implemented the Technical Assistance Center (NAT, Portuguese acronym) in health related lawsuits . This center consists of health care professionals, that analize in detail the requests, bringing then an opinion. This paper aims to explain about the operation of the Center and to demonstrate if this technical support really works as a tool for improving judicial decisions in health care. The approach to achieve our goal which is through concept, doctrine and characteristics of Judicialization of health.In a second plan we work information about the NAT, dealing with its creation, purpose, allocation, dynamic, and with greater focus of its actions and expansion. Finally, our goal is to describe in more detail, the action of NAT related to how much medication is requested through court, what kind, how much is their spending on them and the opinion of attorneys, judges and district attorney involved in this area about the operation of the NAT.