<p>This thesis is an experimental study to evaluate the performance of different routing protocols in commonly deployed scenarios. This study mainly focuses on how much time each protocol consumes while recovering from a link-loss. It provides a guide line for the best routing solutions for ISPs, individual organizations or other types of providers which are engaged in providing reliable real-time communications to their subscribers. Such communications may include vehicle trafficking data, online TV programs (IPTV), voice over IP telephony (VoIP), weather forecasts, tracking systems and many other services which totally depend upon the reliability of real-time data streams, where any major loss in received data may bring significant negative results in the integrity of the entire application.</p><p>This work experimentally observes and tracks the loss of UDP packets when changes in the network topology occur. In order to make this observation in real network topologies, a custom-designed software tool has been developed. The tool is capable of delivering enough resources to a tester in evaluating the performance of routing protocols. All the test results derived from the software tool are statistically evaluated and on the basis of the outcome a better proposition can be provided to network administrators which face inconsistent topological issues.</p>

<p>Gilbert’s syndrome (GS) occurs in approximately 10% of the European population. The most common cause is homozygosity for UGT1A1*28, which is a TA repeat expansion in the promoter of UGT1A1. It is characterised by intermittent hyperbilirubinemia due to reduced hepatic activity of the  enzyme UDP-glucuronosyl-transferase 1A1(UGT1A1). GS also  alteres the pharmacokinetics of some drugs and increases the risk of drug toxicity. Irinotecan (Camptosar®, Campto®) is used in metastatic colorectal cancer and the active metabolite is inactivated by UGT1A1. Studies have shown that GS can be a risk factor for toxicity during irinotecan therapy.</p><p>Three different methods for genotyping of UGT1A1*28 have been tested.</p><p>PCR with electrophoresis used for size separation, melting temperature analysis and fluorescent PCR followed by fragment analysis on a capillary sequencer.</p><p>The last method was found to be superior. This method was used for genotyping of patients with colorectal cancer treated with irinotecan and 5-fluorouracil in the Nordic VI study. A significant association between UGT1A1 genotype and plasma bilirubin level before the start of irinotecan treatment was seen (ANOVA p<0.0001). Patients with GS had an overall increased risk of adverse drug reactions (Fishers Exact test p=0.02).</p><p>Gilbert’s syndrome can be diagnosed by genotyping UGT1A1*28 with a fragment analysis method. Genotyping of UGT1A1*28 can be used to identify patients with an increased risk of adverse reactions to irinotecan.<strong> </strong></p><p><strong> </strong></p> / <p>Gilberts syndrom (GS) drabbar upp till 10% av befolkningen i Västeuropa. GS beror på nedsatt aktivitet av enzymet UDP-glukuronosyltransferas 1A1 (UGT1A1) i levern. Den vanligaste orsaken är att individen är homozygot för en insertion av två baser i promotorn för genen UGT1A1. Denna genvariant kallas (TA)7TAA  eller UGT1A1*28. GS leder till intermittent stegring av bilirubin vid infektioner, men bilirubinstegring kan förekomma även utan utlösande agens. GS kan också leda till bilirubinstegring vid viss läkemedelsbehandling. Irinotekan (Campto®) används vid metastaserande colorektal cancer och dess aktiva metabolit inaktiveras av UGT1A1. Det finns rapporter om att GS ger ökad risk för toxiska biverkningar av irinotekan.</p><p>Tre metoder för att bestämma UGT1A1 har jämförts: PCR med elfores, PCR med smältpunktsanalys och PCR med fragmentanalys på sekvensator. Den sista metoden var bäst och användes för att genotypa UGT1A1 hos patienter med colorektal cancer från Nordic VI-studien. De behandlades med irinotekan i kombination med bolusinjektion eller infusion av 5-fluorouracil. Vi fann att  patienter med GS hade signifikant högre S-bilirubin före behandling jämfört med övriga patienter. De hade även ökad frekvens biverkningar av irinotekan (Fishers exakta test p=0,02).</p><p>Genotypning av UGT1A1 kan således användas för att diagnostisera Gilberts syndrom hos patienter med oförklarad bilirubinstegring. Det kan även användas för att identifiera patienter med ökad risk för biverkningar av irinotekan.</p>

UDP-glucose pyrophosphorylase (UGPase) is an important enzyme of carbohydrate metabolism in all living organisms. The main aim of this thesis was to investigate the function and regulation of plant UGP genes as well as the UGPase proteins. Both in vivo and in vitro approaches were used, including the use of transgenic plants deficient in UGPase activity, and using purified proteins and their mutants to elucidate the structure/ function properties of UGPase. In both Arabidopsis and aspen, there are two highly similar UGP genes being actively transcribed, but not to the same extent. For both species, the UGP genes could be classified into two categories: a “house-keeping” gene and a subsidiary gene, with the former functioning universally in all the tissues to support the normal growth, whereas the latter usually expressed at a lower level in most of the organs/tissues tested. Besides, the two UGP genes were also found being differentially regulated under abiotic stress conditions, e.g. low temperature. By investigating the Arabidopsis T-DNA insertion mutants, which respectively have one or both of the UGP genes knocked out, we noticed that as little as 10% of the remaining UGPase activity could still support normal growth and development under controlled conditions, with little or no changes in carbohydrate contents, including soluble sugars (e.g. sucrose), starch and cell wall polysaccharides. Those plants, however, had a significantly decreased fitness under field conditions, i.e. the plants most deficient in UGPase activity produced up to 50% less seeds than in wt. Therefore, we concluded that UGPase is not a rate-limiting enzyme in carbohydrate synthesis pathways, but still is essential in viability of Arabidopsis plants. In order to characterize two Arabidopsis UGPase isozymes, both proteins were heterologously overexpressed in prokaryotic cells and purified by affinity chromatography. The two isozymes showed little differences in physical and biochemical properties, including substrate specificity, Km values with substrates in both directions of the reaction, molecular masses, isoelectric point (pI), and equilibrium constant. On the other hand, possibilities of distinct post-translational regulatory mechanisms were indicated, based on amino acid (aa) motif analyses, and on 3D analyses of derived crystal structures of the two proteins. We used the heterologous bacterial system also to overexpress barley UGPase and several of its mutants, both single mutants and those with whole domains/ exons deleted. As a result, we have identified several aa residues/ protein domains that may be essential for structural integrity and catalytic/ substrate-binding properties of the protein. For instance, we found that the last exon of UGPase (8 aa at the end of C-terminus) was important for the protein ability to oligomerize and that Lys-260 and the second-to-last exon were essential for pyrophosphate (but not UDP-glucose) binding. The data emphasized the critical role of central part of the active site (so called NB-loop) in catalysis, but also pointed out to the role of N-terminus in catalysis and oligomerization, but not substrate binding, and that of C-terminus in both catalysis/substrate binding and oligomerization.

This thesis is an experimental study to evaluate the performance of different routing protocols in commonly deployed scenarios. This study mainly focuses on how much time each protocol consumes while recovering from a link-loss. It provides a guide line for the best routing solutions for ISPs, individual organizations or other types of providers which are engaged in providing reliable real-time communications to their subscribers. Such communications may include vehicle trafficking data, online TV programs (IPTV), voice over IP telephony (VoIP), weather forecasts, tracking systems and many other services which totally depend upon the reliability of real-time data streams, where any major loss in received data may bring significant negative results in the integrity of the entire application. This work experimentally observes and tracks the loss of UDP packets when changes in the network topology occur. In order to make this observation in real network topologies, a custom-designed software tool has been developed. The tool is capable of delivering enough resources to a tester in evaluating the performance of routing protocols. All the test results derived from the software tool are statistically evaluated and on the basis of the outcome a better proposition can be provided to network administrators which face inconsistent topological issues.

At Saab Aerosystems, situated in Linköping Sweden, there is a presentation and manoeuvre simulator simulating the fighter jet JAS-39 Gripen. This flight simulator is called PMSIM. In this thesis we study how to transfer sensor images generated by PMSIM to other simulators or desktop computers. The transmission is band-limited so some kind of image coding must be used. Because of this the greater part of this thesis is concerned with image coding. To fulfill the real time requirement the image coding has to be quite simple and the transmission has to be fast. To achieve fast transmission the network protocol has to use as little overhead information as possible. Such a protocol has therefore been designed and implemented. This report also includes a survey about real radio links. This survey investigates how the quality of the video stream can be affected by noise and other disturbing elements. The work in this report revolves around the implementation of a video link. The purpose of this link is to transmit and display sensor images. The link consists mainly of the three following parts: image coder, network link and image player. The image coding has been focused on MPEG and wavelets. The wavelet technique is not a well known coding principle for video applications. Although as a coding technique for still images the technique is well known. For instance it is used in the JPEG2000-standard. Experiments conducted and published in this report suggest that for some applications the wavelet technique can be a viable candidate, with respect to the MPEG technique, for a video coder.

Traditionally, communication systems have been dominated by voice applications. Today with the emergence of smartphones, focus has shifted towards packet switched networks. The Internet provides a wide variety of services such as video streaming, web browsing, e-mail etc, and IP trac models are needed in all stages of product development, from early research to system tests. In this thesis, we propose a multi-level model of IP traffic where the user behavior and the actual IP traffic generated from different services are considered as being two independent random processes. The model is based on observations of IP packet header logs from live networks. In this way models can be updated to reflect the ever changing service and end user equipment usage. Thus, the work can be divided into two parts. The first part is concerned with modeling the traffic from different services. A subscriber is interested in enjoying the services provided on the Internet and traffic modeling should reflect the characteristics of these services. An underlying assumption is that different services generate their own characteristic pattern of data. The FFT is used to analyze the packet traces. We show that the traces contains strong periodicities and that some services are more or less deterministic. For some services this strong frequency content is due to the characteristics of cellular network and for other it is actually a programmed behavior of the service. The periodicities indicate that there are strong correlations between individual packets or bursts of packets. The second part is concerned with the user behavior, i.e. how the users access the different services in time. We propose a model based on a Markov renewal process and estimate the model parameters. In order to evaluate the model we compare it to two simpler models. We use model selection, using the model's ability to predict future observations as selection criterion. We show that the proposed Markov renewal model is the best of the three models in this sense. The model selection framework can be used to evaluate future models.

Les maladies inflammatoires intestinales (MII) sont caractérisées par des périodes d’inflammation chronique entrecoupées de périodes de rémission. Les cellules épithéliales intestinales (CÉI) participent activement à l’élaboration de la réponse immune innée. Les nucléotides extracellulaires sont reconnus comme des molécules immunoactives. Cette thèse s’intéresse aux rôles de l’UDP et de son récepteur PDY[indice inférieur 6] dans l’expression et la sécrétion de CXCL8 par les CÉI et à leurs implications dans le recrutement des neutrophiles lors des maladies inflammatoires intestinales. Premièrement, la stimulation du récepteur PDY[indice inférieur 6] sur les CÉI, active une cascade de signalisation intracellulaire impliquant la phospholipase C (PLC), la protéine kinase Cð (PKCð) et la MAP kinase ERK1/2. La phosphorylation de c-fos par ERK1/2 induit la formation d’un dimère c-fos/c-jun. Le complexe AP-1 ainsi formé lie le promoteur de la chimiokine CXCL8 et stimule la transcription de celle-ci. La chimiokine est par la suite sécrétée dans le milieu extracellulaire. Deuxièmement, la présence d'UDP chez la souris, lors de l'induction d’une colite aigüe par le DSS aggrave les signes d'inflammation. L'UDP aggrave l'index de la sévérité de la maladie (DAI), le score histologique, la perméabilité de la muqueuse et le recrutement des intervenants cellulaire tel que les cellules T, les cellules dendritiques, les macrophages et les neutrophiles. Troisièmement, l'administration d'UDP aux souris en rémission dans un modèle de colite chronique est suffisante pour déclencher les symptômes d'inflammation. L'UDP aggrave le DAI, le score histologique et la perméabilité de la muqueuse. L'activation du récepteur P2Yð durant la colite chronique est responsable du recrutement différentiel des neutrophiles au détriment des cellules dendritiques tolérogéniques et des macrophages, ce qui somme toute aggrave la colite. Finalement, in cellulo, l'antagoniste du récepteur P2Y[indice inférieur 6], le MRS2578 réduit la relâche de la CXCL8 par les CÉI. In vivo, l'administration de MRS2578 dans le modèle aigu et chronique de colite réduit les signes d'inflammation. Cette thèse démontre l’importance du récepteur P2Y[indice inférieur 6] dans la réponse inflammatoire des cellules épithéliales intestinales, notamment dans la stimulation de la relâche de CXCL8 et dans le recrutement des cellules immunes tel que les neutrophiles. De plus, elle met en évidence le potentiel thérapeutique de l'administration d'antagoniste du récepteur P2Y[indice inférieur 6] lors des maladies inflammatoires intestinales.

Zugl.: Darmstadt, Techn. University, Diss., 2008.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-08-17T14:49:52Z No. of bitstreams: 1 IVO AUGUSTO ANDRADE ROCHA CALADO - DISSERTAÇÃO PPGCC 2010..pdf: 1680910 bytes, checksum: 4450f567f3a50b0c351dd900f342ea2f (MD5) / Made available in DSpace on 2018-08-17T14:49:52Z (GMT). No. of bitstreams: 1 IVO AUGUSTO ANDRADE ROCHA CALADO - DISSERTAÇÃO PPGCC 2010..pdf: 1680910 bytes, checksum: 4450f567f3a50b0c351dd900f342ea2f (MD5) Previous issue date: 2010-03-11 / A disseminação dos diferentes tipos de aplicações multimídia tem possibilitado uma maior interatividade entre usuários nas mais diversas localizações. Contudo, a falta de mecanismos que garantam níveis de qualidade de serviço, no núcleo da Internet, obriga tais aplicações a realizarem um contínuo processo de adaptação dos fluxos multimídia, de forma a atender aos níveis de transmissão disponíveis, tornando esta uma tarefa adicional no desenvolvimento de tais aplicações. Por outro lado, diante da grande heterogeneidade existente tanto em termos de recursos de transmissão disponíveis quanto de requisitos dos terminais envolvidos, a implementação de uma única abordagem de adaptação que dê um suporte satisfatório a todos os cenários mostra-se muitas vezes inviável, fazendo-se necessário a utilização de diferentes abordagens, de acordo com o contexto de utilização. Como consequência tem-se um aumento na complexidade do desenvolvimento. Neste trabalho apresenta-se uma infraestrutura para o desenvolvimento de aplicações multimídia com suporte à adaptação de fluxos. A partir desta infraestrutura, é possível obter uma flexibilização em como o processo de adaptação de fluxos multimídia será realizado, atendendo aos requisitos dos diferentes tipos de aplicações. Neste sentido, de forma a validar a infraestrutura proposta, foi realizado o desenvolvimento de dois estudos de caso visando demonstrar tanto o suporte oferecido ao desenvolvimento de aplicações multimídia quanto à extensibilidade da infraestrutura a partir da inclusão de novos mecanismos de adaptação. / The spread of different kinds of multimedia applications has enabled a powerful interaction between users in diverse locations. However, the best effort service nature of the Internet requires a continuous process of stream adaptation, in order to fetch such differents scenarios of transmission. As a consequence, this additional task should be met in the multimedia application development. On the other hand, according to the great heterogeneity of both transmission resources and terminal requirements, it is impracticable to define a unique adaptation method which be optimal for all scenarios. Therefore, we have an increasing complexity of multimedia application development. This work presents an infrastructure to multimedia application development to support stream adaptation. It provides a flexible way to implement and to use adaptation methods, meeting the requirements of different applications. Within this context, in order to validate the developed work, it was implemented two case studies: how to develop multimedia applications with support of stream adaptation and present the extensibility provided by proposed infrastructure through the dynamic addition of new adaptation methods.

Gilbert’s syndrome (GS) occurs in approximately 10% of the European population. The most common cause is homozygosity for UGT1A1*28, which is a TA repeat expansion in the promoter of UGT1A1. It is characterised by intermittent hyperbilirubinemia due to reduced hepatic activity of the  enzyme UDP-glucuronosyl-transferase 1A1(UGT1A1). GS also  alteres the pharmacokinetics of some drugs and increases the risk of drug toxicity. Irinotecan (Camptosar®, Campto®) is used in metastatic colorectal cancer and the active metabolite is inactivated by UGT1A1. Studies have shown that GS can be a risk factor for toxicity during irinotecan therapy. Three different methods for genotyping of UGT1A1*28 have been tested. PCR with electrophoresis used for size separation, melting temperature analysis and fluorescent PCR followed by fragment analysis on a capillary sequencer. The last method was found to be superior. This method was used for genotyping of patients with colorectal cancer treated with irinotecan and 5-fluorouracil in the Nordic VI study. A significant association between UGT1A1 genotype and plasma bilirubin level before the start of irinotecan treatment was seen (ANOVA p&lt;0.0001). Patients with GS had an overall increased risk of adverse drug reactions (Fishers Exact test p=0.02). Gilbert’s syndrome can be diagnosed by genotyping UGT1A1*28 with a fragment analysis method. Genotyping of UGT1A1*28 can be used to identify patients with an increased risk of adverse reactions to irinotecan. / Gilberts syndrom (GS) drabbar upp till 10% av befolkningen i Västeuropa. GS beror på nedsatt aktivitet av enzymet UDP-glukuronosyltransferas 1A1 (UGT1A1) i levern. Den vanligaste orsaken är att individen är homozygot för en insertion av två baser i promotorn för genen UGT1A1. Denna genvariant kallas (TA)7TAA  eller UGT1A1*28. GS leder till intermittent stegring av bilirubin vid infektioner, men bilirubinstegring kan förekomma även utan utlösande agens. GS kan också leda till bilirubinstegring vid viss läkemedelsbehandling. Irinotekan (Campto®) används vid metastaserande colorektal cancer och dess aktiva metabolit inaktiveras av UGT1A1. Det finns rapporter om att GS ger ökad risk för toxiska biverkningar av irinotekan. Tre metoder för att bestämma UGT1A1 har jämförts: PCR med elfores, PCR med smältpunktsanalys och PCR med fragmentanalys på sekvensator. Den sista metoden var bäst och användes för att genotypa UGT1A1 hos patienter med colorektal cancer från Nordic VI-studien. De behandlades med irinotekan i kombination med bolusinjektion eller infusion av 5-fluorouracil. Vi fann att  patienter med GS hade signifikant högre S-bilirubin före behandling jämfört med övriga patienter. De hade även ökad frekvens biverkningar av irinotekan (Fishers exakta test p=0,02). Genotypning av UGT1A1 kan således användas för att diagnostisera Gilberts syndrom hos patienter med oförklarad bilirubinstegring. Det kan även användas för att identifiera patienter med ökad risk för biverkningar av irinotekan.