In this report the influence of the growth conditions on the surface morphology of AlGaN/GaN heterostructures grown on sapphire-based and bulk GaN substrates is nondestructively investigated with focus on the decoration of defects and the surface roughness. Under Ga-rich conditions specific types of dislocations are unintentionally decorated with shallow hillocks. In contrast, under Ga-lean conditions deep pits are inherently formed at these defect sites. The structural data show that the dislocation density of the substrate sets the limit for the density of dislocation-mediated surface structures after MBE overgrowth and no noticeable amount of surface defects is introduced during the MBE procedure. Moreover, the transfer of crystallographic information, e.g. the miscut of the substrate to the overgrown structure, is confirmed. The combination of our MBE overgrowth with the employed surface morphology analysis by atomic force microscopy (AFM) provides a unique possibility for a nondestructive, retrospective analysis of the original substrate defect density prior to device processing.

Le facteur VIII (FVIII) est une glycoprotéine de la coagulation plasmatique, co-facteur du facteur IX activé (FIXa). Son métabolisme dépend de multiples facteurs limitant ou favorisant sa survie ou sa fonction. L’objectif de ce travail était d’analyser les différents paramètres pouvant influencer le taux de FVIII circulant et sa fonction pro-coagulante. Il a compris 4 volets : 1) Nous avons montré que la rétention intra-cellulaire connue du FVIII était en grande partie liée à son agrégation et sa dégradation par les 2 voies protéasomale et lysosomale. 2) Nous avons analysé les mutations du gène F8 responsables de l’hémophilie A dans une large cohorte de patients. Leur analyse bio-informatique a permis de démontrer leur caractère délétère pour le FVIII. L’influence de ces mutations sur la survenue d’allo-anticorps anti-FVIII a été étudiée et stratifiée, en association avec l’origine ethnique et la recherche d’antécédents familiaux d’nticorps. 3) La recherche des facteurs influençant les taux de FVIII chez les conductrices d’hémophilie A a mis en évidence des déterminants majeurs : l’existence d’une maladie génétique additionnelle responsable d’un déficit en FVIII, le taux de facteur Willebrand et l’inactivation non aléatoire du chromosome X ; et des déterminants secondaires : l’âge, la sévérité de l’hémophilie, le polymorphisme D1241E du gène F8 et 5 nouveaux polymorphismes de la LRP1 localisés dans ses sites de liaison pour le FVIII. 4) Nous avons analysé 8 FVIII recombinant mutés in vitro en alanine dans la région 1808-1818 du FVIII. Les études antérieures n’analysant que la chaîne légère, ont montré que cette région était la plus affine pour le FIXa. Nous démontrons ici que la région 1808-1818 ne paraît pas si essentielle à la fonction du FVIIIcar au sein de la molécule entière, son affinité diminue et ses mutations n’altèrent que très modérément l’activité du FVIII. / The factor VIII (FVIII) is a glucoprotein of the coagulation, being the cofactor of the activated factor IX (FIXa). Its metabolism depends on various limiting factors or enhancing its survey or function. The objective of this research’s work was to analyse different parameters that could influence the plasma FVIII level and its pro-coagulant function. It included 4 parts : 1) We showed that the known intra-cellular retention of FVIII was mainly due to its aggregation and degradation following both proteasomal and lysosomal pathways. 2) We analysed FVIII gene mutations responsible for hemophilia A in a large patients cohort. The bio-informatic analysis demonstrated its deleterious consequence. The influence of these mutations on the anti-FVIII antibodies occurrence was stratified, in association with ethnicity and familial antecedent of inhibitor. 3) The research of factors influencing FVIII levels in hemophilia A carriers showed : i) major determinants such as the presence of an additional genetic disease characterised by a FVIII deficiency, the factor Willebrad’s level and the non-random inactivation of the X chromosome; and ii) minor determinants : age, severity of hemophilia, the polymorphism D1241E of FVIII gene, and 5 new polymorphisms of LRP1 located in its binding site for FVIII.4) We analysed 8 recombinant FVIII with in vitro created mutations in its 1808-1818 region. Previous studies that analysed only the FVIII light chain, have shown that this region constituted the more affine binding site of FVIII for FIXa. We demonstrated here that the 1808-1818 region is not as essential as it was reported because within the entire molecule, its affinity decreases and mutations affecting it do alter mildly the FVIII activity.

A solução de problemas é parte fundamental da manutenção da qualidade e da melhoria contínua. Ao longo dos anos diversos métodos foram desenvolvidos para solucionar problemas, todavia nem todos os métodos são aplicáveis em todos os problemas ou adequados para todos os setores. Caracterizado pelo ambiente em constante mudança, o setor hospitalar possui problemas complexos, cuja solução necessita de uma abordagem adequada e robusta. Dessa forma, o presente trabalho objetiva avaliar o desempenho de três métodos normalmente utilizados para solução de problemas: A3, RCA e FRAM, quando aplicados em ambiente hospitalar. Para esse fim, os três métodos foram aplicados no mesmo processo, de prescrição e medicação, de um hospital universitário. Os resultados das aplicações foram analisados de acordo com os critérios: número total de ações de melhoria propostas, dificuldade de implementação, a possibilidade de replicação das ações entre as unidades do hospital, o tempo necessário para aplicação dos métodos, o número de envolvidos, a necessidade de capacitação da equipe e um indicador de prioridade das ações propostas. Além disso, a percepção dos profissionais da saúde em relação aos métodos foi analisada. Os resultados demonstram que, no contexto avaliado, os métodos apresentaram um bom desempenho, por terem apresentado melhorias que, em média, foram consideradas adequadas pela instituição. / Problem solving is a fundamental part for quality maintenance and continuous improvement. Through the years many methods were developed to solve problems, though these methods do not apply to every problem, or are suitable to every type of activity. Kwon for its constant changing nature, hospitals have complex problems, which need a suitable and robust approach to solve. Thus, the present study has the objective of evaluating the performance of three methods usually used for problem solving: A3, RCA and FRAM, when applied on a hospital. For this, the three methods were applied in the same process, of prescription and medication, in an academic hospital. The results were analyzed accordingly to the following criteria: the total number of improvement actions proposed, implementation difficult, replication possibility along the departments of the hospital, the time needed to apply the methods, the number of people involved, the need of training for the team and an indicator for prioritization. Besides that, the health sector workers’ perception regards the methods was analyzed. The results evidence that, in the studied context, the methods had good performance, because introduced improvements that, on average, were considered suitable for the institution.

A solução de problemas é parte fundamental da manutenção da qualidade e da melhoria contínua. Ao longo dos anos diversos métodos foram desenvolvidos para solucionar problemas, todavia nem todos os métodos são aplicáveis em todos os problemas ou adequados para todos os setores. Caracterizado pelo ambiente em constante mudança, o setor hospitalar possui problemas complexos, cuja solução necessita de uma abordagem adequada e robusta. Dessa forma, o presente trabalho objetiva avaliar o desempenho de três métodos normalmente utilizados para solução de problemas: A3, RCA e FRAM, quando aplicados em ambiente hospitalar. Para esse fim, os três métodos foram aplicados no mesmo processo, de prescrição e medicação, de um hospital universitário. Os resultados das aplicações foram analisados de acordo com os critérios: número total de ações de melhoria propostas, dificuldade de implementação, a possibilidade de replicação das ações entre as unidades do hospital, o tempo necessário para aplicação dos métodos, o número de envolvidos, a necessidade de capacitação da equipe e um indicador de prioridade das ações propostas. Além disso, a percepção dos profissionais da saúde em relação aos métodos foi analisada. Os resultados demonstram que, no contexto avaliado, os métodos apresentaram um bom desempenho, por terem apresentado melhorias que, em média, foram consideradas adequadas pela instituição. / Problem solving is a fundamental part for quality maintenance and continuous improvement. Through the years many methods were developed to solve problems, though these methods do not apply to every problem, or are suitable to every type of activity. Kwon for its constant changing nature, hospitals have complex problems, which need a suitable and robust approach to solve. Thus, the present study has the objective of evaluating the performance of three methods usually used for problem solving: A3, RCA and FRAM, when applied on a hospital. For this, the three methods were applied in the same process, of prescription and medication, in an academic hospital. The results were analyzed accordingly to the following criteria: the total number of improvement actions proposed, implementation difficult, replication possibility along the departments of the hospital, the time needed to apply the methods, the number of people involved, the need of training for the team and an indicator for prioritization. Besides that, the health sector workers’ perception regards the methods was analyzed. The results evidence that, in the studied context, the methods had good performance, because introduced improvements that, on average, were considered suitable for the institution.

A solução de problemas é parte fundamental da manutenção da qualidade e da melhoria contínua. Ao longo dos anos diversos métodos foram desenvolvidos para solucionar problemas, todavia nem todos os métodos são aplicáveis em todos os problemas ou adequados para todos os setores. Caracterizado pelo ambiente em constante mudança, o setor hospitalar possui problemas complexos, cuja solução necessita de uma abordagem adequada e robusta. Dessa forma, o presente trabalho objetiva avaliar o desempenho de três métodos normalmente utilizados para solução de problemas: A3, RCA e FRAM, quando aplicados em ambiente hospitalar. Para esse fim, os três métodos foram aplicados no mesmo processo, de prescrição e medicação, de um hospital universitário. Os resultados das aplicações foram analisados de acordo com os critérios: número total de ações de melhoria propostas, dificuldade de implementação, a possibilidade de replicação das ações entre as unidades do hospital, o tempo necessário para aplicação dos métodos, o número de envolvidos, a necessidade de capacitação da equipe e um indicador de prioridade das ações propostas. Além disso, a percepção dos profissionais da saúde em relação aos métodos foi analisada. Os resultados demonstram que, no contexto avaliado, os métodos apresentaram um bom desempenho, por terem apresentado melhorias que, em média, foram consideradas adequadas pela instituição. / Problem solving is a fundamental part for quality maintenance and continuous improvement. Through the years many methods were developed to solve problems, though these methods do not apply to every problem, or are suitable to every type of activity. Kwon for its constant changing nature, hospitals have complex problems, which need a suitable and robust approach to solve. Thus, the present study has the objective of evaluating the performance of three methods usually used for problem solving: A3, RCA and FRAM, when applied on a hospital. For this, the three methods were applied in the same process, of prescription and medication, in an academic hospital. The results were analyzed accordingly to the following criteria: the total number of improvement actions proposed, implementation difficult, replication possibility along the departments of the hospital, the time needed to apply the methods, the number of people involved, the need of training for the team and an indicator for prioritization. Besides that, the health sector workers’ perception regards the methods was analyzed. The results evidence that, in the studied context, the methods had good performance, because introduced improvements that, on average, were considered suitable for the institution.

Detta examensarbete utfördes inom högskoleingenjörsprogrammet i maskinteknik påKarlstads universitet. Projektet var i samarbete med PLS Produkter AB i Skövde där omställningen på en maskin med namnet Tretapparen analyserades. Maskinen klassas somen multitasking maskin där syftet är tappning av olika typer av flaskor. Problemet är att detsker omställningar ofta då maskinen är flexibel och kan producera många olika typer avprodukter. Omställningarna sker då en ny produkttyp ska tillverkas och är väldigttidskrävande då nya inställningar på maskinen behöver göras. Maskinen och verktygenbehöver dessutom rengöras noga för att inte kontaminera nästa batch. Examensarbetets syfteär att effektivisera omställningen genom att tydliggöra omställningstiderna för maskinensolika moment och bidra med kultur- och kunskapsbyggande till företaget. Målet är att hittamöjliga lösningar som minskar ställtiden på de moment som tar längst tid att ställa om ochdär det kan antas finnas förbättringsmöjligheter. Därmed kan flödet på maskinen förbättras iden mån att antalet tillverkade produkter ökar. Förbättringsarbetet började med förstudier, intervjuer, datainsamlingar och att analyseravideos. All viktig information sammanställdes i en A3-modell där SMED var grunden förstrategierna som gjordes för att ställtidsreducera. Resultatet innebär en konvertering från intern till extern ställtid för varje moment var för sigefter respektive färdig omställning, 26 förbättringsförslag och en ny ordning föromställningsarbetet som tillsammans effektiviserar, standardiserar och planerar upp omställningsprocessen. Efter förändringen minskade omställningstiden med totalt 30%, vilket leder till att flödet påmaskinen förbättras då maskinen kan producera ungefär 217 produkter mer än i dagsläget. Islutet av arbetet gjordes en avrapportering till företaget där samtliga produktionsteam varnärvarande. / This degree project was carried out within the university engineering program in mechanicalengineering at Karlstad University. The project was in collaboration with PLS Produkter AB in Skövde, where the conversion on a machine called Tretapparen was analyzed. The machineis classified as a multitasking machine where the purpose is bottling different types of bottles.The problem is that there are changes often as the machine is flexible and can produce manydifferent types of products. The adjustments take place when a new product type is to bemanufactured and are very time-consuming as new settings on the machine need to be made.The machine and tools also need to be cleaned thoroughly so they do not contaminate thenext batch. The purpose of the degree project is to streamline the adjustment by clarifying theadjustment times for the machine's various steps and contributing cultural and knowledgebuilding to the company. The goal is to find possible solutions that reduce the set-up time onthe steps that take the longest time to adjust and where it can be assumed that there areopportunities for improvement. Thus, the flow on the machine can be improved to the extentthat the number of manufactured products increases. The improvement work began with feasibility studies, interviews, data collection andanalyzing videos. All important information was compiled in an A3-model where SMED wasthe basis for the strategies made to reduce downtime. The result implies conversion from internal to external set-up time for each step separatelyafter each completed conversion, 26 improvement proposals and a new arrangement for theconversion work that together streamlines, standardizes and plans the conversion process. After these changes, the adjustment time decreased by a total of 30%, which leads to animprovement in the flow on the machine as the machine can produce approximately 217products more than at present. At the end of the work, a report was made to the companywhere all production teams were present.

Streptococcus pneumoniae (S. pneumoniae) is a Gram-positive, encapsulated bacterium capable of causing significant morbidity and mortality throughout the world. A hallmark of S. pneumoniae infection is infiltration of neutrophils (PMNs) that assist in controlling the spread infection but may also contribute to pathology. Paradoxically, studies have shown that limiting PMN infiltration into the lumen of the lung during infection actually betters clinical outcome in experimental S. pneumoniae infection. The final step in PMN luminal trafficking is a Hepoxilin A3 (HXA3)-dependent migration across the pulmonary epithelium. HXA3 is a PMN chemoattractant that forms gradients along the polarized epithelial face, drawing PMNs from the basolateral to the apical surface during proinflammatory responses. HXA3 requires assistance of an integral- membrane protein transporter to escape the cell and form the gradient. The pulmonary HXA3 transporter is currently unidentified. In this work, we identify the pulmonary HXA3 transporter as the ATP-Binding Cassette Transporter (ABC transporter) Multi-drug Resistance Associated Protein 2 (ABCC2, MRP2). We demonstrate that MRP1 and MRP2 are divergent ABC- transporters that control transepithelial PMN migration through efflux of a distinct anti-inflammatory substance and the pro-inflammatory HXA3 in the context of Streptococcus pneumoniae infection. Enrichment of MRP2 on the plasma membrane requires detection of the bacterial virulence factors pneumolysin (PLY) and hydrogen peroxide. PLY and hydrogen peroxide not only coordinate MRP2 apical membrane enrichment but also influence HXA3-dependent PMN transepithelial migration. They influence migration through stimulation of epithelial intracellular calcium increases that are crucial for HXA3 production as well as MRP2 translocation to the plasma membrane. PLY and hydrogen peroxide are not sufficient in their signaling alone, however, and require at least one additional bacterial signal to induce HXA3/MRP2 proinflammatory activities.

This study examines the characteristics of the collapse of the stock market and the foreign exchange market in some Asian countries during the 1997 Asian Financial Crisis. The interaction of these two markets during the crisis period is also studied. The method used to detect and date-stamp the timeline of the collapse is the recursive regression approach proposed in Phillips, Shi, and Yu(2015a,b). Tests are conducted on a time series of logged real stock indices and real exchange rate against the US dollar. The dataset includes information about Hong Kong, South Korea, Thailand, Malaysia, Singapore, and Taiwan. Great depreciation periods were detected in the foreign exchange markets of all these countries. And the negative bubbles in the stock markets are only detected in Thailand, South Korea, Malaysia, and Singapore due to different reasons. Moreover, the order of the collapse in these two markets is different for different countries. For example, bubbles appear earlier in the stock markets than the start of the great depreciation period in the foreign exchange markets in Thailand, South Korea, and Malaysia, whereas crashes emerge in the two markets at the same time in Singapore. The order of the collapses occurring in the two markets suggests the transmission direction. Therefore, we find that the transmission mechanism between these two markets is different for different countries and is also different from that during the non-crisis period, as suggested by previous works using the traditional Granger causality test. / 本文研究主要著眼於1997亞洲金融危機中部分亞洲國家股票市場和外匯市場在暴跌中所表現出的泡沫化特點，同時對這兩個市場變化的聯動關系進行了討論。本文采用Phillips, Shi和Yu提出的循環回歸方法對市場中是否存在泡沫以及泡沫形成和破裂的時間進行了判斷和分析。本文的研究對象為經過通貨膨脹調整的香港、韓國、泰國、馬來西亞、新加坡和臺灣的股票指數（取對數）以及這些地區的貨幣對美元的實際匯率。在所有上述經濟體中，對美元匯率都呈現正泡沫，這意味著短期內貨幣呈現較大程度貶值。然而代表股市暴跌的負泡沫只出現在了韓國、泰國、馬來西亞和新加坡，這些負泡沫亦產生於不同的原因。同時，不同國家股市和匯市的泡沫產生順序也不盡相同：在韓國、泰國和馬來西亞，股市先於匯市產生負泡沫；而在新加坡，股市和匯市的泡沫同步產生。由於泡沫產生的時間先後順序可以為兩個市場的變動提供因果關系的證據，所以我們認為在上述亞洲經濟體中，股市和匯市變動的因果關系也不相同。我們也針對上述經濟體中股市與匯市變動的因果關系提出了與之前已有研究的不同意見。 / Zhu, Jinhui. / Thesis M.Phil. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 28-29). / Abstracts also in Chinese. / Title from PDF title page (viewed on 14, September, 2016). / Detailed summary in vernacular field only.

This thesis compares criminal defences of insanity and idiocy between 1660 and 1830 in northern England and southern Scotland, regions which have been neglected by the historiographies of British crime and "insanity defences". It is explained how and why English and Scottish theoretical principles differed or converged. In practice, however, courtroom participants could obtain to alternative conceptions of accountability and mental distraction. Quantitative and qualitative analyses are employed to reveal contemporary conceptions of mental afflictions and criminal responsibility, which provide inverse reflections of "normal" behaviour, speech and appearance. It is argued that the judiciary did not dictate the evaluation of prisoners' mental capacities at the circuit courts, as some historians have contended. Legal processes were determined by subtle, yet complex, interactions between "decision-makers". Jurors could reach conclusions independent from judicial coercion. Before 1830, verdicts of insanity could represent discord between bench and jury, rather than the concord emphasised by some scholars. The activities of counsel, testifiers and prisoners also impinged upon the assessment of a prisoner's mental condition and restricted the bench's dominance. Despite important evidentiary evolutions, the courtroom authentication of insanity and idiocy was not dominated by Britain's evolving medical professions (including "psychiatrists") before 1830. Lay, communal understandings of mental afflictions and criminal responsibility continued to inform and underpin the assessment of a prisoner's mental condition. Such decisions were affected by social dynamics, such as the social and economic status, gender, age and legal experience of key courtroom participants. Verdicts of insanity and the development of Britain's legal practices could both be shaped by micro- and macro-political considerations. This thesis opens new avenues of research for British "insanity defences", whilst offering comparisons to contemporary Continental legal procedures.

Producing desirable firmness is important in manufacturing tofu from soybeans. This study’s objective was to explore the environmental impact (location and year) on soybean chemical components and identify the correlations between chemical composition and the firmness of tofu made from soybeans planted in three locations over two years. Seventeen soybean Plant Introductions (PI) from the USDA Soybean Germplasm Collection and eight check varieties were planted in Mississippi, Virginia and Missouri in 2017 and 2018. Protein subunit composition, protein secondary structure, phytic acid content, Ca2+ and Mg2+ content were determined. The result showed that A3 subunit content was strongly correlated with tofu firmness. Environmental factors had a significant influence on some chemical components in soybean seeds as well as tofu texture. The current study confirmed the validity of using A3 peptide as a criterion for estimating tofu firmness in both tofu manufacturing and food-grade soybean trade.