Causal discovery is the problem of learning causal relationships between variables from a set of data. One interesting area of use for causal discovery is the health care domain, where application could help facilitate a better understanding of disease and treatment mechanisms. The health care domain has recently undergone a major digitization, making available a large amount of data for use in learning algorithms, available in formats such as medical images or electronic health records. This thesis aims to explore the application of causal discovery on electronic health record data. We provide an overview of the field of causal discovery and identify 3 contemporary methods for causal discovery on time-series data which we apply on a preprocessed version of the MIMIC-IV data set. Each causal discovery method is run on time-series comprising of electronic health record data related to hospital stays for patients with sepsis. We provide an empiric report of the overlap between the learned graphs from different hospital stays as a heuristic evaluation measure. We find that it is possible to identify common themes in the learned graphs between different causal discovery methods, indicating potential practical value of causal discovery on electronic health record data. We also identify important considerations for future application and evaluation, such as incorporating extensive domain knowledge, and provide suggestions for future work. / Kausal upptäckt är problemet med att lära sig orsakssamband mellan variabler från en uppsättning data. Ett intressant användningsområde för kausal upptäckt är hälso- och sjukvårdsdomänen, där tillämpning kan bidra till en bättre förståelse av sjukdomar och behandlingsmekanismer. Sjukvårdsdomänen har nyligen genomgått en stor digitalisering vilket gör en stor mängd data tillgänglig för användning i inlärningsalgoritmer, tillgänglig i format som medicinska bilder eller elektroniska patientjournaler. Denna avhandling syftar till att utforska tillämpningen av kausal upptäckt på elektroniska patientjournaler. Vi ger en översikt över området för kausal upptäckt och identifierar 3 samtida metoder för kausal upptäckt på tidsseriedata som vi tillämpar på en förbearbetad version av MIMIC-IV-datauppsättningen. Varje identifierad metod för kausal upptäckt körs på tidsserier som består av elektroniska patientjournaler relaterade till sjukhusvistelser för patienter med sepsis. Vi tillhandahåller en empirisk rapport över överlappningen mellan de inlärda graferna från olika sjukhusvistelser som ett heuristiskt utvärderingsmått. Vi finner att det är möjligt att identifiera gemensamma teman i de inlärda graferna mellan olika kausala upptäcktsmetoder, vilket indikerar potentiellt praktiskt värde av kausal upptäckt på elektroniska patientjournaler. Vi identifierar också viktiga överväganden för framtida tillämpning och utvärdering, såsom att integrera omfattande domänkunskap, och ger förslag för framtida arbete.

Dados recentes do nosso laboratório sugerem que a enzima dipeptidil peptidase IV (DPPIV), uma serino-protease que pode ser encontrada ancorada na membrana celular de diversos tipos celulares ou na forma solúvel no plasma, possui um papel importante na fisiopatologia da insuficiência cardíaca (IC). Mais especificamente, demonstramos que a atividade da DPPIV circulante está associada com piores desfechos cardiovasculares em modelo experimental e pacientes com IC. Ademais, observamos que a inibição crônica da DPPIV atenua o desenvolvimento e/ou a progressão da IC em ratos submetidos à injúria do miocárdio. Entretanto, não é sabido se a inibição desta peptidase é capaz de reverter a disfunção cardiorrenal em ratos com IC estabelecida. Assim, este trabalho teve como objetivo testar a hipótese que a inibição da DPPIV exerce efeitos terapêuticos em ratos com IC. Para tal, ratos com IC foram tratados diariamente com o inibidor da DPPIV Vildagliptina (80 ou 120 mg/kg/dia) ou veículo (HF) durante quatro semanas. Ratos Sham não-tratados foram utilizados como controle. Análises ecocardiográficas demonstraram que ratos HF exibiram área fracional (FAC) menor e tempo de relaxamento isovolumétrico (TRIV) maior que ratos Sham. Por sua vez, o tratamento com a dose maior de Vildagliptina foi capaz de aumentar a FAC e diminuir o TRIV. Esta melhora funcional foi acompanhada por melhoras estruturais, visto que a inibição da DPPIV foi capaz de reduzir a hipertrofia cardíaca e a deposição de colágeno intersticial no miocárdio remanescente de ratos tratados com Vildagliptina em comparação aos ratos HF. Adicionalmente, ratos com IC exibiram maior teor de água nos pulmões, menor excreção urinária de sódio, menor fluxo urinário e menor ritmo de filtração glomerular em comparação ao grupo Sham. Por sua vez, o manuseio renal de sal e água foi completamente restaurado pelo tratamento crônico com 120 mg/kg/dia Vildagliptina. A normalização da função renal induzida pela inibição crônica da DPPIV foi associada com um aumento da expressão do receptor do peptídeo-1 semelhante ao glucagon (GLP-1) e maior ativação da proteína cinase A em córtex renal, isto é, da via de sinalização deflagrada pela ligação GLP-1/GLP-1R. Além disso, os níveis pós-prandiais do GLP-1, principal substrato da DPPIV que exerce ações insulinotrópicas, cardio e renoprotetoras, estavam mais baixos em ratos HF que em ratos Sham. Esta diminuição dos níveis circulantes de GLP-1 (ativo e total) em ratos HF foi acompanhada de intolerância à glicose bem como de maiores níveis plasmáticos de insulina. A inibição da DPPIV com Vildagliptina melhorou a biodisponibilidade e a secreção de GLP-1 após carga oral de glicose. Em conjunto, estes resultados sugerem que a inibição da DPPIV melhora a função cardiorrenal e metabólica de ratos com IC. Além disso, a secreção e a biodisponibilidade do GLP-1 encontram-se prejudicadas em ratos com IC e o tratamento com Vildagliptina é capaz de restaurar a sinalização mediada por este peptídeo. Assim, os inibidores da DPPIV podem ser eficazes não apenas para a prevenção, mas também para o tratamento da insuficiência cardíaca em ratos / Recent data from our laboratory suggest that the enzyme dipeptidyl peptidase IV (DPPIV), a serine protease that can be found anchored in the cell membrane of different cell types or in the soluble form in plasma, plays an important role in the pathophysiology of heart failure (HF). More specifically, we have demonstrated that the activity of circulating DPPIV is associated with poorer cardiovascular outcomes in an experimental model and patients with HF. In addition, we have found that chronic inhibition of DPPIV attenuates the development and/or progression of HF in rats with myocardial injury. However, it is unknown whether the inhibition of this peptidase is able to reverse the cardiorenal dysfunction in rats with established HF. Therefore, this study aimed to test the hypothesis that inhibition of DPPIV exerts therapeutic effects in rats with HF. To this end, HF rats were treated daily with the DPPIV inhibitor vildagliptin (80 or 120 mg/kg/day) or vehicle (HF) for four weeks. Untreated Sham rats were used as controls. Echocardiographic analysis demonstrated that HF rats exhibit lower fractional area change (FAC) and higher isovolumetric relaxation time (IVRT) than Sham rats. On the other hand, treatment with the highest dose of vildagliptin was able to increase FAC and decrease IVRT. These functional improvements were accompanied by structural improvements, since inhibition of DPPIV was also able to reduce cardiac hypertrophy and interstitial collagen deposition in the remaining myocardium of rats treated with vildagliptin rats compared to HF. In addition, HF rats exhibited higher water content in the lungs, lower urinary sodium excretion, lower urinary flow and lower glomerular filtration rate compared to the Sham group. In turn, the renal handling of salt and water was completely restored by chronic treatment with vildagliptin 120 mg/kg/day. Normalization of the renal function induced by chronic inhibition of DPPIV was associated with an increase in the expression of the glucagon like peptide-1 receptor (GLP-1R) and enhanced protein kinase A activation in the renal cortex, the signaling pathway triggered by bind between GLP-1/GLP-1R. In addition, the postprandial levels of GLP-1, the main substrate of DPPIV that exerts insulinotropic, cardio and renoprotective actions, were lower in HF rats than in Sham. This decrease in circulating levels of GLP-1 (active and total) in HF rats was accompanied by impaired glucose tolerance and higher plasma insulin levels. The inhibition of the DPPIV with vildagliptin improved the bioavailability and secretion after an oral glucose load. Taken together, these results suggest that the inhibition of DPPIV ameliorates the cardiorenal and metabolic function of rats with HF. Furthermore, bioavailability and secretion of GLP-1 are impaired in HF rats and vildagliptin is able to restore the signaling mediated by this peptide. Therefore, DPPIV inhibitors can be effective not only in preventing but also for the treatment of HF in rats

Dados recentes do nosso laboratório sugerem que a enzima dipeptidil peptidase IV (DPPIV), uma serino-protease que pode ser encontrada ancorada na membrana celular de diversos tipos celulares ou na forma solúvel no plasma, possui um papel importante na fisiopatologia da insuficiência cardíaca (IC). Mais especificamente, demonstramos que a atividade da DPPIV circulante está associada com piores desfechos cardiovasculares em modelo experimental e pacientes com IC. Ademais, observamos que a inibição crônica da DPPIV atenua o desenvolvimento e/ou a progressão da IC em ratos submetidos à injúria do miocárdio. Entretanto, não é sabido se a inibição desta peptidase é capaz de reverter a disfunção cardiorrenal em ratos com IC estabelecida. Assim, este trabalho teve como objetivo testar a hipótese que a inibição da DPPIV exerce efeitos terapêuticos em ratos com IC. Para tal, ratos com IC foram tratados diariamente com o inibidor da DPPIV Vildagliptina (80 ou 120 mg/kg/dia) ou veículo (HF) durante quatro semanas. Ratos Sham não-tratados foram utilizados como controle. Análises ecocardiográficas demonstraram que ratos HF exibiram área fracional (FAC) menor e tempo de relaxamento isovolumétrico (TRIV) maior que ratos Sham. Por sua vez, o tratamento com a dose maior de Vildagliptina foi capaz de aumentar a FAC e diminuir o TRIV. Esta melhora funcional foi acompanhada por melhoras estruturais, visto que a inibição da DPPIV foi capaz de reduzir a hipertrofia cardíaca e a deposição de colágeno intersticial no miocárdio remanescente de ratos tratados com Vildagliptina em comparação aos ratos HF. Adicionalmente, ratos com IC exibiram maior teor de água nos pulmões, menor excreção urinária de sódio, menor fluxo urinário e menor ritmo de filtração glomerular em comparação ao grupo Sham. Por sua vez, o manuseio renal de sal e água foi completamente restaurado pelo tratamento crônico com 120 mg/kg/dia Vildagliptina. A normalização da função renal induzida pela inibição crônica da DPPIV foi associada com um aumento da expressão do receptor do peptídeo-1 semelhante ao glucagon (GLP-1) e maior ativação da proteína cinase A em córtex renal, isto é, da via de sinalização deflagrada pela ligação GLP-1/GLP-1R. Além disso, os níveis pós-prandiais do GLP-1, principal substrato da DPPIV que exerce ações insulinotrópicas, cardio e renoprotetoras, estavam mais baixos em ratos HF que em ratos Sham. Esta diminuição dos níveis circulantes de GLP-1 (ativo e total) em ratos HF foi acompanhada de intolerância à glicose bem como de maiores níveis plasmáticos de insulina. A inibição da DPPIV com Vildagliptina melhorou a biodisponibilidade e a secreção de GLP-1 após carga oral de glicose. Em conjunto, estes resultados sugerem que a inibição da DPPIV melhora a função cardiorrenal e metabólica de ratos com IC. Além disso, a secreção e a biodisponibilidade do GLP-1 encontram-se prejudicadas em ratos com IC e o tratamento com Vildagliptina é capaz de restaurar a sinalização mediada por este peptídeo. Assim, os inibidores da DPPIV podem ser eficazes não apenas para a prevenção, mas também para o tratamento da insuficiência cardíaca em ratos / Recent data from our laboratory suggest that the enzyme dipeptidyl peptidase IV (DPPIV), a serine protease that can be found anchored in the cell membrane of different cell types or in the soluble form in plasma, plays an important role in the pathophysiology of heart failure (HF). More specifically, we have demonstrated that the activity of circulating DPPIV is associated with poorer cardiovascular outcomes in an experimental model and patients with HF. In addition, we have found that chronic inhibition of DPPIV attenuates the development and/or progression of HF in rats with myocardial injury. However, it is unknown whether the inhibition of this peptidase is able to reverse the cardiorenal dysfunction in rats with established HF. Therefore, this study aimed to test the hypothesis that inhibition of DPPIV exerts therapeutic effects in rats with HF. To this end, HF rats were treated daily with the DPPIV inhibitor vildagliptin (80 or 120 mg/kg/day) or vehicle (HF) for four weeks. Untreated Sham rats were used as controls. Echocardiographic analysis demonstrated that HF rats exhibit lower fractional area change (FAC) and higher isovolumetric relaxation time (IVRT) than Sham rats. On the other hand, treatment with the highest dose of vildagliptin was able to increase FAC and decrease IVRT. These functional improvements were accompanied by structural improvements, since inhibition of DPPIV was also able to reduce cardiac hypertrophy and interstitial collagen deposition in the remaining myocardium of rats treated with vildagliptin rats compared to HF. In addition, HF rats exhibited higher water content in the lungs, lower urinary sodium excretion, lower urinary flow and lower glomerular filtration rate compared to the Sham group. In turn, the renal handling of salt and water was completely restored by chronic treatment with vildagliptin 120 mg/kg/day. Normalization of the renal function induced by chronic inhibition of DPPIV was associated with an increase in the expression of the glucagon like peptide-1 receptor (GLP-1R) and enhanced protein kinase A activation in the renal cortex, the signaling pathway triggered by bind between GLP-1/GLP-1R. In addition, the postprandial levels of GLP-1, the main substrate of DPPIV that exerts insulinotropic, cardio and renoprotective actions, were lower in HF rats than in Sham. This decrease in circulating levels of GLP-1 (active and total) in HF rats was accompanied by impaired glucose tolerance and higher plasma insulin levels. The inhibition of the DPPIV with vildagliptin improved the bioavailability and secretion after an oral glucose load. Taken together, these results suggest that the inhibition of DPPIV ameliorates the cardiorenal and metabolic function of rats with HF. Furthermore, bioavailability and secretion of GLP-1 are impaired in HF rats and vildagliptin is able to restore the signaling mediated by this peptide. Therefore, DPPIV inhibitors can be effective not only in preventing but also for the treatment of HF in rats

Made available in DSpace on 2016-03-15T19:22:04Z (GMT). No. of bitstreams: 1 Rodrigo Marcondes Rocha1.pdf: 8501462 bytes, checksum: ed5ba05f6c5d0d1512b79237c9a8d232 (MD5) Previous issue date: 2013-02-22 / The theme of the present master s dissertation stems from the interest in the character and in the work of the German architect Walter Gropius (1883-1969) and it focuses on his coming to Brazil in January of 1954, when he participated in the Exposição Internacional de Arquitetura (event which was part of the II Bienal Internacional de Artes de São Paulo which coincided with the celebrations of the IV Centennial of the city s foundation), he got São Paulo s architecture award, in his first and unique edition he delivered an inaugural speech in the IV Congresso Brasileiro de Arquitetos and visited Rio de Janeiro and Petrópolis. In order to do so, archives of Fundação Bienal and publications and period periodicals were consulted, besides the relevant bibliography. Additional and fundamental information about the IV Congresso Brasileiro de Arquitetos were also recovered directly from the archives kept by the Paulista section of Instituto de Arquitetos do Brasil (IAB-SP). Hence, some valuable information were also recovered about the presence of Gropius in Brazil, aiming at complementing the barely spread content about this constant happening in the existing historiography, discussing frictions and proximities within the period in which Walter Gropius was in Brazil. / O tema desta dissertação de mestrado nasce do interesse pela obra e pela figura do arquiteto alemão Walter Gropius (1883-1969) e enfoca sua passagem pelo Brasil em janeiro de 1954, quando participou como destaque da Exposição Internacional de Arquitetura (evento integrante da II Bienal Internacional de Artes de São Paulo, que por sua vez coincidia com as comemorações do IV Centenário da fundação da cidade), recebeu o Prêmio São Paulo de Arquitetura, em sua primeira e única edição, proferiu a conferência inaugural do IV Congresso Brasileiro de Arquitetos, e ainda visitou o Rio de Janeiro e Petrópolis. Para tanto, consultamos os arquivos da Fundação Bienal e publicações e periódicos de época, além da bibliografia relevante. Informações adicionais e fundamentais sobre o IV Congresso Brasileiro de Arquitetos também foram recuperadas diretamente dos arquivos mantidos pela seção paulista do Instituto de Arquitetos do Brasil (IAB-SP). Assim foram recuperadas informações valiosas sobre a presença de Gropius no Brasil, com a finalidade de complementar o escasso conteúdo sobre este episódio constante da historiografia existente, discutindo atritos e aproximações gerados no período em que Walter Gropius esteve no Brasil.

Ce travail de recherche aborde les stratégies épistolaires et communicationnelles de Bettina von Arnim (1785-1859), femme de lettres allemande, pour prendre part aux débats politiques et sociaux pendant la période du Vormärz. Transgressant les frontières sociales, idéologiques, rhétoriques et celles des genres littéraires, Bettina von Arnim a tenté d’influer sur le roi de Prusse, Frédéric Guillaume IV, au moyen de ses correspondances, de ses ouvrages et de son réseau. Bettina von Arnim a élaboré des stratégies de communication et de persuasion pour secouer un système ministériel rigide et réactionnaire, obtenir des réformes politiques et sociales et modeler le souverain selon son idéal du Volkskönig. Cette étude va s’attacher à montrer les mécanismes employés par Bettina von Arnim pour s’immiscer dans un domaine exclusivement masculin, la politique. / This research project explores the activities and works of Bettina von Arnim (1785-1859), a German literary scholar, taking part in the political and social debates of the period ‘Vormarz’. Covering all social boundaries, ideologies, rhetoric and literary styles, Bettina attempted to influence the King of Prussia, Frederick William IV, with her letters, writings and network. Bettina von Arnim fabricated a persuasive communication strategy to disrupt a rigid ministerial system, get political and social reforms, and influence the Sovereign according to her model of the ‘Volkskönig’. This study attempts to show the tactics employed by Bettina von Arnim to infiltrate an exclusively male political structure. / Diese Dissertation beschäftigt sich mit den Brief- und Kommunikationsstrategien von Bettina von Arnim (1785-1859), die vor allem durch ihre Korrespondenz an den politischen und sozialen Debatten im Vormärz teilgenommen hatte. Unter häufiger Missachtung der sozialen, ideologischen und rhetorischen Gewohnheiten sowie der traditionellen Literaturgattungen war Bettina von Arnim bestrebt, dem preußischen König Friedrich Wilhelm IV. Ratschläge zu erteilen. Bettina von Arnim hat Überzeugungsstrategien entworfen, um einen starren und reaktionären Beamtenapparat zu umgehen und wachzurütteln, politische und soziale Reformen zu erzielen sowie das Staatsoberhaupt in Richtung auf ihr Ideal eines Volkskönigs zu beeinflussen. In dieser Arbeit sollen die von Bettina von Arnim verwendeten Mechanismen untersucht werden, wodurch sie sich in die Politik, eine den Männern vorbehaltene Domäne, einzumischen versuchte.

BAKGRUND: Fysisk aktivitet har påvisats ha en positiv effekt på de områden i hjärnan som är kopplade till inlärning och minne. Dock är det oklart hur stor påverkan en individs fysiska kapacitetsnivå har på dessa områden. SYFTE: Syftet med studien var att undersöka ifall en intervention i form av fysisk aktivitet kan påverka arbetsminnet, och ifall en grupp individer presterar annorlunda på ett arbetsminnestest efter interventionen beroende på deras syreupptagningsförmåga. METOD: Studien hade en kvantitativ och kvasiexperimentell design utan kontrollgrupp. En grupp om 33 kvinnor, åldern 20-30 år utförde testet som bestod utav minnestestet Letter-number sequencing task före och efter 10 minuters intervention i form av submaximal ergometercykling. Samtidigt som interventionen beräknades individernas maximala syreupptagningsförmåga med hjälp av Åstrands cykelergometertest. Beroende av resultatet på cykelergometertestet delades testpersonerna in i två grupper som representerade hög/mycket hög (grupp 1) syreupptagningsförmåga respektive låg/genomsnittlig (grupp 2) syreupptagningsförmåga. RESULTAT: Medianvärdet på LNS innan interventionen var 20,5 för grupp 1 (n=20) respektive 21 för grupp 2 (n=13). Detta medianvärde förbättrades med en enhet för båda grupperna vid LNS efter interventionen. Skillnaden inom gruppresultaten före och efter interventionen var icke-signifikant med ett P-värde på 0,614 för grupp 1 och 0,891 för grupp 2. Skillnaden i förändring mellan grupperna var heller ej signifikant med ett P-värde på 0,854. KONKLUSION: Arbetsminnet påverkades inte av 10 minuters fysisk aktivitet i någon av gruppjämförelserna. En individs syreupptagningsförmåga verkar heller inte påverka arbetsminnet. / BACKGROUND: Physical activity has been shown to have a positive effect on the areas of the brain connected to learning and memory. Even so, it is uncertain how much a person’s level of physical capacity influences these areas. OBJECTIVES: The purpose of the study was to examine if an intervention of physical activity could affect working memory, and whether a group of people perform differently during a working memory test after the intervention depending on their oxygen uptake. METHODS: The study had a quantitive and quasiexperimental design without control group. A group of 33 women, 20-30 years of age, conducted the test which consisted of the memory test Letter-number sequencing task before and after 10 minutes of submaximal ergometer cycling. During the intervention the individual’s maximal oxygen uptake was calculated with the Åstrand cycle ergometer test. Depending on the results from the cycle ergometer test, the testsubjects was split into two groups which represented high/very high (group 1) oxygen uptake and low/average (group 2) oxygen uptake. RESULTS: The median of LNS before the intervention was 20,5 for group 1 (n=20) and 21 for group 2 (n=13). This median improved with one unit for both groups at LNS after the intervention. The difference between the results within the groups before and after the intervention proved to be non-significant with a P-value of 0,614 for group 1 and 0,891 for group 2. The difference in change between the groups was neither significant with a P-value of 0,854. CONCLUSION: Working memory was not affected of 10 minutes of physical activity in neither of the comparison between the groups. It also seems that an individual’s oxygen uptake doesn’t affect working memory.

BAKGRUND: Fysisk aktivitet har påvisats ha en positiv effekt på de områden i hjärnan som är kopplade till inlärning och minne. Dock är det oklart hur stor påverkan en individs fysiska kapacitetsnivå har på dessa områden. SYFTE: Syftet med studien var att undersöka ifall en intervention i form av fysisk aktivitet kan påverka arbetsminnet, och ifall en grupp individer presterar annorlunda på ett arbetsminnestest efter interventionen beroende på deras syreupptagningsförmåga. METOD: Studien hade en kvantitativ och kvasiexperimentell design utan kontrollgrupp. En grupp om 33 kvinnor, åldern 20-30 år utförde testet som bestod utav minnestestet Letter-number sequencing task före och efter 10 minuters intervention i form av submaximal ergometercykling. Samtidigt som interventionen beräknades individernas maximala syreupptagningsförmåga med hjälp av Åstrands cykelergometertest. Beroende av resultatet på cykelergometertestet delades testpersonerna in i två grupper som representerade hög/mycket hög (grupp 1) syreupptagningsförmåga respektive låg/genomsnittlig (grupp 2) syreupptagningsförmåga. RESULTAT: Medianvärdet på LNS innan interventionen var 20,5 för grupp 1 (n=20) respektive 21 för grupp 2 (n=13). Detta medianvärde förbättrades med en enhet för båda grupperna vid LNS efter interventionen. Skillnaden inom gruppresultaten före och efter interventionen var icke-signifikant med ett P-värde på 0,614 för grupp 1 och 0,891 för grupp 2. Skillnaden i förändring mellan grupperna var heller ej signifikant med ett P-värde på 0,854. KONKLUSION: Arbetsminnet påverkades inte av 10 minuters fysisk aktivitet i någon av gruppjämförelserna. En individs syreupptagningsförmåga verkar heller inte påverka arbetsminnet. / BACKGROUND: Physical activity has been shown to have a positive effect on the areas of the brain connected to learning and memory. Even so, it is uncertain how much a person’s level of physical capacity influences these areas. OBJECTIVES: The purpose of the study was to examine if an intervention of physical activity could affect working memory, and whether a group of people perform differently during a working memory test after the intervention depending on their oxygen uptake. METHODS: The study had a quantitive and quasiexperimental design without control group. A group of 33 women, 20-30 years of age, conducted the test which consisted of the memory test Letter-number sequencing task before and after 10 minutes of submaximal ergometer cycling. During the intervention the individual’s maximal oxygen uptake was calculated with the Åstrand cycle ergometer test. Depending on the results from the cycle ergometer test, the testsubjects was split into two groups which represented high/very high (group 1) oxygen uptake and low/average (group 2) oxygen uptake. RESULTS: The median of LNS before the intervention was 20,5 for group 1 (n=20) and 21 for group 2 (n=13). This median improved with one unit for both groups at LNS after the intervention. The difference between the results within the groups before and after the intervention proved to be non-significant with a P-value of 0,614 for group 1 and 0,891 for group 2. The difference in change between the groups was neither significant with a P-value of 0,854. CONCLUSION: Working memory was not affected of 10 minutes of physical activity in neither of the comparison between the groups. It also seems that an individual’s oxygen uptake doesn’t affect working memory.

Kollagen IV assoziierte Nephropathien sind hereditäre Erkrankungen, die die glomeruläre Basalmembran betreffen. Homozygote Aberrationen des COL4A3- oder des COL4A4-Gens zeigen wie X-chromosomal dominant vererbte Mutationen des COL4A5-Gens das klinische Bild des Alport-Syndroms mit frühzeitigem terminalem Nierenversagen. Heterozygote COL4A3-Mutationen sind ursächlich für die benigne familiäre Hämaturie. Ein zusätzlicher Polymorphismus in Nphs2, welches das Schlitzmembranprotein Podocin kodiert, könnte hierbei zu einem aggravierten Krankheitsverlauf führen. Um diese These zu überprüfen, ist eine Analyse des glomerulären Filters, bestehend aus glomerulärer Basalmembran, der zwischen den Podozytenfüßen liegenden Schlitzmembran und Kapillarendothel notwendig. Nidogen-2 ist als Verbindungsprotein essenzieller Bestandteil der glomerulären Basalmembran. Die Ergebnisse der Untersuchungen des Proteins in der Basalmembran COL4A3 heterozygoter Mäuse mit zusätzlichem Podocin-Polymorphismus wichen stark von denen bei einfach COL4A3 heterozygoten Tieren ab. Es ergeben sich daher anhand von Nidogen-2 Hinweise, dass eine Mutation in Nphs2 den Krankheitsverlauf Kollagen IV assoziierter Erkrankungen modifizieren könnte.

My dissertation deals with personality of Jan Sádlo of Smilkov, who was a noble man in king's sevices and who lived at he turned of 13th and 14th century. Dissertation tries to express elemental aspects of his life, which determined his life and this dissertation also tries to complete missing information about his family, property and also tries to find in which community he could be found and with whom he kept in touch with and how can these persons influence his personality. Dissertation also deals with his career, mainly his activity in king's Václav IV. court, where he became a influential person, who became involved in political situation in country during the beginning of hussite revolution. In dissertation is also covered his political downfall and his death. Life of Jan Sádlo of Smilkov was in my dissertation shown as an exapmle of low nobleman who could due to political situation become influential person and who could become involved in political development. . Keywords gentry, court of Václav IV., holding, followers of Jan Hus, administrator of ro

Cette thèse porte sur la prérogative la plus importante du pape durant la première modernité, c’est-à-dire le pouvoir que lui donnaient les clefs du royaume des cieux. Cette faculté de lier et de délier tous les hommes dans l’économie du salut fut contestée au XVIe siècle par la Réforme protestante et par les monarchies européennes. L’enjeu est de comprendre comment la papauté affirma la nature spirituelle de sa suprématie tout en prétendant donner à celle-ci des effets politiques. Une première partie est consacrée aux controverses sur le pouvoir ecclésiastique du concile de Pise à la Réforme luthérienne. Une seconde partie examine les relations entre la papauté et les États à travers l’exercice du pouvoir de déposition. En raison de la richesse de la documentation conservée à l’Archivio Segreto Vaticano, une enquête approfondie est menée sur le cas de l’excommunication et de l’absolution d’Henri IV. Ce travail explique ainsi comment la politique romaine permit à la papauté de rester un acteur politique majeur dans l’Europe du XVIe siècle. / This PhD thesis deals with the most important prerogative of the pope during the early modern period, i. e. the power that the keys of the kingdom of heaven gave to him. This power to bind and to loose all men in the economy of Salvation was contested during the Sixteenth Century by the Protestant Reformation and by the european monarchies. What is at stake is to understand how the papacy asserted the spiritual value of the papal supremacy while asserting its political effects. A first part turns on the controversies about ecclesiastical power from the council of Pisa to the Lutheran Reformation. A second part deals with the relationship between the papacy and the states through the use of the deposing power. Owing to the richness of the documentation conserved in the Archivio Segreto Vaticano, a thorough inquiry is conducted on the case of the excommunication and of the absolution of Henry IV. This work explains thus how the roman policy enabled the papacy to remain a political actor of first importance in the Europe of the Sixteenth Century.