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<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.

This thesis uses Jack Gilbert's Refusing Heaven to look critically at the evolution of American poetry.

O desenvolvimento de tecnologias de integração para circuitos integrados junto com a demanda de cada vez mais processamento digital de sinais, como em sistemas de telecomunicações e aplicações SOC, resultaram na crescente necessidade de circuitos mistos em tecnologia CMOS integrados em um único chip. Em um trabalho anterior, a arquitetura de uma interface analógica para ser usada em aplicações SOC mistas foi desenvolvida e implementada. Basicamente esta interface é composta por uma célula analógica fixa (fixed analog cell – FAC), que translada o sinal de entrada para uma freqüência de processamento fixa, e por um bloco digital que processa este sinal. Primeiramente, as especificações de sistema foram determinadas considerando o processamento de sinais de três bandas de freqüência diferentes: FM, vídeo e celular, seguido por simulações de alto-nível do sistema da FAC. Então, uma arquitetura heteródina integrada CMOS para o front-end que integrará a FAC, composto por 2 mixers ativos e um amplificador de ganho variável, foi apresentada, enumerando-se e propondo-se soluções para os desafios de projeto e metodologia. Os blocos analógicos/RF, juntamente com o front-end, foram projetados e implementados em tecnologia CMOS IBM 0.18μm, apresentando-se simulações e medidas de um protótipo físico. / The development of IC technologies coupled with the demand for more digital signal processing integrated in a single chip has created an increasing need for design of mixed-signal systems in CMOS technology. Previously, a general analog interface architecture targeted to mixed-signal systems on-chip applications was developed and implemented, which is composed by a fixed analog cell (FAC), that translates the input signal to a processing frequency, and a digital block, that processes the signal. The focus of this thesis is to analyze, design and implement analog/RF building blocks suitable for this system. First, a set of system specifications is developed and verified through system level simulations for the FAC system, aiming the signal processing of three target applications: FM, video and digital cellular frequency bands. Then, a fully CMOS integrated dual-conversion heterodyne front-end architecture with 2 active mixers and a variable-gain amplifier is presented, enumerating and proposing solutions for the design challenges and methodology. The stand-alone building blocks and the front-end system are designed and implemented in IBM 0.18μm CMOS process, presenting simulations and experimental data from an actual physical prototype.

Using a number of structurally innovative novels from the 1970s, 1980s and 1990s as a basis for study, this dissertation examines the representation of communities in postmodernist American fiction. While novels have often been critically studied from the standpoint of the individual and society, here the often neglected category of community is put under scrutiny. Yet rather than considering it from a sociological point of view, which can potentially favour historical, economic or political grounds for community, this study focuses on the ontological binds formed between individual and community. On one level this study connects formal qualities of postmodernist novels to a representation of community – especially literary conventions from the past that are foregrounded in the present texts. On another level it interrogates the limits of the individual in relation to others – how we emerge from others, how we are discrete from others, how much we can actually share with others, at what cost we stay or break with the others who have most influenced us. The primary novels studied here, each of which is deeply invested in the community as a locus for ontological interrogation, are Robert Coover’s "Gerald’s Party" (1985) and "John’s Wife" (1996), Gilbert Sorrentino’s "Crystal Vision" (1981) and "Odd Number" (1985), Harry Mathews’s "Cigarettes" (1987), Joseph McElroy’s "Women and Men" (1987), and Toni Morrison’s "Paradise" (1997). Despite their varied representations of and attitudes toward the individual in community, these texts share a common spectre of American Romanticism that inflects how we read the possibility of community in the postmodernist period.

This diploma thesis is specialized on a design of a high accuracy voltage reference Bandgap. A very low temperature coefficient and output voltage approx. 1,205V are the main features of this circuit. The paper contains a derivation of the Bandgap principle, examples of realizations of the circuits and methods of compensation temperature dependence and manufacture process, design of Brokaw and Gilbert reference, design of a testchip and measurement results.

Keywords Gilbert Simondon, Bernard Stiegler, Mark B. N. Hansen, philosophy, media, technology, humanism, individuation, information Abstract This text has two parallel objectives. First, to introduce the original work of french philosopher Gilbert Simondon. Second, to show its potential of his philosophy in relation to our thinking about the current media-techno- logically conditioned environment in which we live and through which we understand the world. I have two motivations for the first objective. First, the work of Gilbert Simondon is still completely unknown in Czech Repub- lic, therefore I find it necessary to offer to the reader the introduction of his work. Second, without such introduction it would be very difficult to ope- rate with his crucial concepts in the work of his contemporary interpreters whose contributions I will discuss in the second part of the text. The se- cond objective is motivated with my interest in delimitation of speculative and materialistic line of thinking based on the work of Gilbert Simondon. Such thought with its description of the world is in clear opposition with anthropocentrism. Nevertheless, it cannot be considered as a part of object oriented ontology neither. I'm not going to show the importance of Gilbert Simondon for media theory in this text. Rather, I will...

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The aim of this thesis is to report on a transdisciplinary approach, regarding the complexity of thinking about human embodiment in relation to machine embodiment. A practical dimension of this thesis is to elicit some principles for the design and evaluation of virtual embodiment. The transdisciplinary approach suggests, firstly, that a single discipline or reality is, on its own, not sufficient to explain the complexity and dynamism of the embodied interaction between the human and machine. Secondly, the thesis argues for thinking of transdisciplinary research as a process of individuation, becoming or transduction, that is, as a process of mediation between heterogeneous approaches rather than perceiving research as a stabilized cognitive schema designed to accumulate new outcomes to the already-there reality. Arguing for going beyond the individualized approaches to embodiment, this thesis analyzes three cases where the problems that appear in one case are resolved through the analysis of the following one. Consisting of three phases, this research moves from objective scientific 'reality' to more phenomenological, subjective and complex realities. The first study employs a critical review of embodied conversational agents in human-computer interaction (HCI) in a learning context using a comparative meta-analysis. Meta-analysis was applied because most of the studies for evaluating embodiment are experimental. A learning context was selected because the number of studies is suitable for meta-analysis and the findings could be generalized to other contexts. The analysis reveals that there is no 'persona effect', that is, the expected positive effect of virtual embodiment on the participant's affective, perceptive and cognitive measures. On the contrary, it shows the reduction of virtual embodiment to image and a lack of consideration for the participant's embodiment and interaction, in addition to theoretical and methodological shortcomings. The second phase solves these problems by focusing on Mark Hansen's phenomenological account of embodiment in new media. The investigation shows that Hansen improves on the HCI account by focusing on the participant's dynamic interaction with new media. Nevertheless, his views of embodied perception and affection are underpinned by a subjective patriarchal account leading to object/subject and body/work polarizations. The final phase resolves this polarization by analyzing the controversial work of Alan Turing on intelligent machinery. The research provides a different reading of the Turing Machine based on Simondon's concept of individuation, repositioning its materiality from the abstract non-existent to the actual-virtual realm and investigating the reasons for its abstraction. It relates the emergence of multiple human-machine encounters in Turing's work to the complex counter-becoming of what it describes as 'the Turing Machine compound'.

In the process of carving a new England out of the southern end of Vancouver Island in the later nineteenth century, the population of Victoria, BC sought to forge a British identity for themselves through music and its associated rituals. They did this through the pursuit of purposeful acts of cultural meaning. In the social sphere, concerts, parades, religious services, and theatrical productions heightened and inspired loyalty to Mother England. Victoria’s upper classes could then dominate by excluding those people—including Jewish, Chinese, Indigenous, African-American, and Hawaiian residents—who did not conform to that identity. In late-nineteenth-century Victoria, music became more than just a way to celebrate, worship, and recreate; it defined social life for British and non-British peoples alike and shaped the physical space in which they lived. This dissertation explores late nineteenth-century Victoria’s creation of a British identity through music. Ensuring that their churches had a powerful organ and talented organists, Victoria’s religious community proved that they could undertake Britain’s highest social point of sacred musical performance: the choral festival. Positioning George Frideric Handel’s Messiah—with its strong connotations of Britain and her Empire—as their showstopper, these choral festivals served to cement relationships between those citizens who considered themselves British, while also proclaiming this identity as a mark of superiority to the community at large. Itinerant opera troupes further strengthened these imperial bonds by importing European and British opera to Victoria. Through the performances of these professional travelling musicians, Victorian Victorians were able to experience high art and popular operatic music of the Western world, joining the particularly British Pinafore and Mikado crazes of the 1870s and 1880s. These itinerant singers thoroughly impressed local musicians, who avidly tried to reproduce what they had heard, first in instrumental overtures and medleys in the 1860s and 1870s, then with vocal and instrumental operatic numbers in miscellany concerts in the 1870s and 1880s, and finally with full operatic productions in the 1880s and beyond. As with choral festivals in the religious sphere, taking part in opera productions also helped to create a shared sense of British identity among Victoria’s upper classes, during a time when other defining factors of social placement were not yet secure. Settlers in Victoria removed the Indigenous and natural impediments to the construction of their new metropolis, in effect silencing their cultural “voice.” Besides the Indigenous peoples of Vancouver Island, other recent settlers posed challenges to British hegemony, especially Chinese immigrants and “coloured” people of African origin, many of whom came from the United States. Even the gender demographics in the male-dominated frontier society posed challenges to the civilizing process. The Jews of Victoria, the majority of whom were of German or English origin, present an ambiguous case of a cultural and religious community at the crossroads in mid-nineteenth-century Victoria. The butt of rising anti-Semitism in continental Europe, Victoria’s Jewish minority used music and ritual to establish themselves as members of the dominant class. / Graduate / 0413 / 0334 / 0357 / libby.concord@gmail.com