O objetivo desta pesquisa foi avaliar a influência dos fatores culturais e institucionais do país de origem nas práticas contábeis utilizadas pelas empresas e, na sequência, analisar os impactos da existência de escolhas contábeis nas IFRS no nível de comparabilidade das informações contábeis de empresas localizadas em países com ambientes culturais e institucionais diferentes. A literatura sugere que a contabilidade é fortemente influenciada pelo ambiente no qual está inserida e que a comparabilidade é baseada no reflexo da substância econômica dos eventos, não na forma. Para tanto, foram analisadas três escolhas contábeis que existem ou existiam nas IFRS: (i) mensuração dos investimentos em joint ventures (consolidação proporcional ou MEP), (ii) reconhecimento e apresentação dos ganhos e perdas atuariais decorrentes dos planos de benefício definido (método do corredor, DRE ou DRA) e (iii) mensuração de PPI (custo ou valor justo). Os dados sobre as práticas contábeis foram coletados manualmente das demonstrações contábeis de 6.298 empresas de 27 países diferentes de 2005 até 2016. Portanto, foram coletadas e analisadas 53.908 demonstrações contábeis. Por meio da análise de cluster e utilizando um conjunto de variáveis culturais e institucionais, os 27 países foram classificados em 7 agrupamentos diferentes. Na sequência, foram avaliadas quais práticas contábeis predominavam em cada um desses países e como elas se relacionam com os agrupamentos formados e com as variáveis culturais e institucionais, através da estimação de modelos logísticos (hierárquicos na versão nula e não hierárquicos). Os resultados evidenciaram que uma parcela estatisticamente significante da variância das práticas contábeis é explicada pelo agrupamento de nível país e que todas as 12 variáveis culturais e institucionais são relevantes para explicar as práticas contábeis utilizadas pelas empresas em pelo menos uma das três escolhas contábeis analisadas. Por fim, utilizando a métrica de Comparabilidade dos Sistemas Contábeis desenvolvida por Barth et al. (2012), a presente pesquisa mensurou o nível de comparabilidade das informações contábeis entre as diversas combinações de clusters, com a finalidade de avaliar se as empresas eram mais comparáveis quando usavam exatamente a mesma prática contábil ou quando utilizavam práticas contábeis diferentes. Os resultados corroboram a tese proposta de que a existência de escolhas contábeis nas IFRS pode ser necessária para que as empresas utilizem as práticas contábeis que melhor refletem a substância econômica dos eventos, considerando a influência do ambiente cultural e institucional em que estão inseridas. Foram encontrados indícios de que a eliminação de escolhas contábeis, como a dos investimentos em joint ventures e de benefícios a empregados, pode reduzir a comparabilidade das informações contábeis, já que as empresas eram mais comparáveis quando utilizavam práticas contábeis diferentes. Assim, há evidências de que a adoção de padrões contábeis mais flexíveis contribui para a obtenção da comparabilidade em países com ambientes diferentes, reiterando que a substância econômica é mais importante que a forma. A principal contribuição desta pesquisa é fornecer evidências de que a obrigatoriedade de utilização da mesma prática contábil por empresas localizadas em ambientes culturais e institucionais diferentes pode resultar em uniformidade, mas não em comparabilidade das informações contábeis. / The purpose of this research was to evaluate the influence of cultural and institutional environment of each country in the accounting practices used by firms and, subsequently, to analyze the impacts of the existence of accounting choices in the IFRS Standards on the comparability of accounting information between firms from countries with different cultural and institutional environments. The literature suggests that accounting is strongly influenced by the environment and that comparability is based on the reflection of the economic substance of events, not on the form. Therefore, three accounting choices that exist or existed in IFRS Standards were analyzed: (i) measurement of joint venture investments (proportionate consolidation or equity method); (ii) recognition and presentation of actuarial gains and losses arising from defined benefit plans (corridor method, income statements or other comprehensive income) and (iii) measurement of investment properties (cost or fair value). The accounting practices\' data were manually collected from the financial statements of 6,298 firms from 27 different countries, from 2005 to 2016. Thus, we collected and analyzed 53,908 financial statements. Using cluster analysis and a set of cultural and institutional variables, the 27 countries were classified into 7 different clusters. Further, we analyzed the accounting practices that prevailed in each country and in each cluster; and how these accounting practices are influenced by the cultural and institutional variables, through the estimation of logistic models (hierarchical in the null version and non-hierarchical). The results indicate that the variance in accounting practices explained by the country level grouping is statistically significant and that all the 12 cultural and institutional variables are relevant to explain the accounting practices used by firms in at least one of the three accounting choices that were analyzed. Finally, using the Accounting System Comparability metric proposed by Barth et al. (2012), we measured the degree of comparability of accounting information among various combinations of clusters, in order to evaluate whether firms were more comparable when they used exactly the same accounting practice or when they used different accounting practices. The results corroborate the proposed thesis that the existence of accounting choices in the IFRS Standards may be necessary to allow firms to use those accounting practices that better reflect the economic substance of events, given the influence of the cultural and institutional environment in which they operate. We found evidence that the elimination of accounting choices, such as the choices about joint venture investments and employee benefits, may reduce the comparability of accounting information, given that firms were more comparable when they used different accounting practices. Thus, there is evidence that the adoption of more flexible accounting standards contributes to improve comparability in countries with different environments, reiterating that the economic substance is more important than the form. The main contribution of this research is to provide evidence that the mandatory requirement of the same accounting practices by firms from different cultural and institutional environments may result in uniformity, but not in comparability of accounting information.

<p>Pancreatic β-cells sense the concentration of glucose in the systemic circulation through metabolism of the sugar molecule. Failure to correlate the blood sugar concentration to an appropriate metabolic signal disrupts the function of the β-cell as a controller of glucose homeostasis and may contribute to the development of type 2 diabetes mellitus. Release of insulin is pulsatile and this thesis presents data that support that metabolism drives such pulsatile release. It is also found that increase in insulin release in response to elevation of the glucose concentration is only seen when the rise in glucose induces a prompt and sustained increase in mitochondrial metabolism. Such activation of mitochondrial metabolism depended on the metabolic state of the β-cell prior to the glucose challenge. In this context, prolonged periods of elevated levels of fatty acids are harmful to the pancreatic β-cell. To study the protein expression changes induced by fatty acids a protocol for islet protein profiling and identification of differently expressed proteins were developed. By using this protocol it was discovered that oleate decreased the cellular level of the chaperone peptidyl-prolyl isomerase B. The protocol was also used to study protein expression in islets obtained from mice fed a high-fat and/or a high-sucrose diet. Excess of glucocorticoids in the systemic circulation also cause a diabetic phenotype. Tissue response to glucocorticoids is regulated by the intracellular concentration of the active form of glucocorticoids, which is formed from the inactive form by the enzyme 11β-hydroxysteroid dehydrogenase type 1. It was found that pancreatic islets produce 11β-HSD1 protein in relation to substrate availability and that the amount of islet 11β-HSD1 protein was negatively correlated with insulin secretion.</p>

Pancreatic β-cells sense the concentration of glucose in the systemic circulation through metabolism of the sugar molecule. Failure to correlate the blood sugar concentration to an appropriate metabolic signal disrupts the function of the β-cell as a controller of glucose homeostasis and may contribute to the development of type 2 diabetes mellitus. Release of insulin is pulsatile and this thesis presents data that support that metabolism drives such pulsatile release. It is also found that increase in insulin release in response to elevation of the glucose concentration is only seen when the rise in glucose induces a prompt and sustained increase in mitochondrial metabolism. Such activation of mitochondrial metabolism depended on the metabolic state of the β-cell prior to the glucose challenge. In this context, prolonged periods of elevated levels of fatty acids are harmful to the pancreatic β-cell. To study the protein expression changes induced by fatty acids a protocol for islet protein profiling and identification of differently expressed proteins were developed. By using this protocol it was discovered that oleate decreased the cellular level of the chaperone peptidyl-prolyl isomerase B. The protocol was also used to study protein expression in islets obtained from mice fed a high-fat and/or a high-sucrose diet. Excess of glucocorticoids in the systemic circulation also cause a diabetic phenotype. Tissue response to glucocorticoids is regulated by the intracellular concentration of the active form of glucocorticoids, which is formed from the inactive form by the enzyme 11β-hydroxysteroid dehydrogenase type 1. It was found that pancreatic islets produce 11β-HSD1 protein in relation to substrate availability and that the amount of islet 11β-HSD1 protein was negatively correlated with insulin secretion.

Throughout the scientific world the topic of cannabis usage and its link with psychosis seems to be discussed intensively. Considering the fact that the Czech Republic is a country with one of the highest prevalence of cannabis usage in the world it becomes a sensitive issue even in our circumstances. In the theoretical part of the work we attempted to review current knowledge of a link between cannabinoid system, canabis usage and psychosis and to point out possible future therapeutic potential of cannabinoids in the treatment of psychotic diseases. In the practical part of the work we focused on verification of propsychotic features of THC in animal model with particular attention to validation of acute subcutaneous admonistration of this drug as a novel cannabinoid model of psychosis. At the same time we tried to elucidate antipsychotic effect of CBD in this model. We tested these hypotheses in two behavioral tests (open field test, PPI ASR) and electrophysiologically (quantitative EEG). The whole analysis is enriched with pharmacokinetic data from subcutanneous and oral administration of cannabinoids. Powered by TCPDF (www.tcpdf.org)

The delivery of small interfering RNAs (siRNA) is an efficient method for gene silencing through the induction of RNA interference (RNAi). It critically relies, however, on efficient vehicles for siRNA formulation, for transfection in vitro as well as for their potential use in vivo. While polyethylenimines (PEIs) are among the most studied cationic polymers for nucleic acid delivery including small RNA molecules, polypropylenimines (PPIs) have been explored to a lesser extent. Previous studies have shown the benefit of the modification of small PEIs by tyrosine grafting which are featured in this paper. Additionally, we have now extended this approach towards PPIs, presenting tyrosine-modified PPIs (named PPI-Y) for the first time. In this study, we describe the marked improvement of PPI upon its tyrosine modification, leading to enhanced siRNA complexation, complex stability, siRNA delivery, knockdown efficacy and biocompatibility. Results of PPI-Y/siRNA complexes are also compared with data based on tyrosine-modified linear or branched PEIs (LPxY or PxY). Taken together, this establishes tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery.

The purpose of this study is to examine whether the implementation of quantitative easing (QE) and quantitative tightening (QT) in the United States has detracted from the integrity of the country’s macroeconomic environment. In other words, does QE impact macroeconomic stability? Then, evaluate implications and externalities of stability as they relate to sustainability efforts. QE and QT are relatively new phenomena, understanding their effects and implications for the greater economy is a worthwhile endeavor, not least because QE is a current practice of so many central banks internationally. This study has two parallel investigations; first, a time series analysis conducted with a VAR model investigating the relationship of QE/QT usage by the Federal Reserve (Fed) on the macroeconomic stability of the United States. The data used in this study includes 242 monthly observations spanning January 2003 - February 2023. The second, is an OLS regression analysis evaluating whether macroeconomic stability is potentially correlated with sustainability efforts. For this study, 23 annual observations spanning 1995 – 2017 were used. Due in part to the general unavailability of genuine progress indicator (GPI) data. Based on the analysis conducted using a VAR model at lag t-4, QE has a positive relationship with Producer Price Index (PPI) and Federal Funds Rate (FFR). This is in accord with previous empirical literature on the subject. However, the second path of discovery failed to yield significant results with regard to the link between macroeconomic stability and sustainability efforts. Mention of this study’s limitations as well as avenues for future research can be found in the conclusion of this study.

Veränderungen in phosphorylierungsabhängigen Signalwegen, Akkumulation von Proteinaggregaten im Gehirn und neuronaler Zelltod sind Neurodegenerationskennzeichen und Indikatoren für überlappende molekulare Mechanismen. Um Einblicke in die involvierten Signalwege zu erhalten, wurde mit Hilfe eines modifizierten Hefe-Zwei-Hybrid (Y2H)-Systems für 71 Proteine, die mit neurologischen Erkrankungen assoziiert sind, proteomweit nach Protein-Protein Interaktionen (PPIs) gesucht. Für 21 dieser Proteine wurden PPIs identifiziert. Das Gesamtnetzwerk besteht aus 79 Proteinen und 90 PPIs von denen 5 phosphorylierungsabhängig sind. Ein Teil dieser PPIs wurde in unabhängigen Interaktionsassays mit einer Validierungsrate von 66 % getestet. Der netzwerkbasierte Versuch verbindet erfolgreich neurologische Erkrankungen untereinander aber auch mit zellulären Prozessen. Ser/Thr-Kinase abhängige PPIs verknüpfen zum Beispiel das Parkinson Protein 7 (PARK7, DJ1) mit den E3 Ligase Komponenten ASB3 und RNF31 (HOIP). Die Funktion dieser Proteine bekräftigt den Zusammenhang zwischen dem Ubiquitin-Proteasom-System und der Parkinson Krankheit (PD). Neurofibromin 2 (NF2, merlin) Isoformen und PARK7 interagieren mit der regulatorischen PI3K Untereinheit p55-gamma (PIK3R3). Diese PPIs basieren auf Tyr-Kinase Aktivität im modifizierten Y2H System und funktionellen PIK3R3 pTyr-Erkennungsmodulen (SH2 Domänen) in co-IP und Venus PCA Versuchen. Dies verknüpft den PI3K/AKT Überlebenssignalweg mit zwei unterschiedlichen neurologischen Erkrankungsphenotypen: dem PD assoziierten neuronalen Zelltod und der Neurofibromatose Typ 2-assoziierten Tumorentstehung. Die vergleichende Beobachtung von PIK3R3, AOF2 (KDM1A, LSD1) Interaktionen auf NF2 Isoformlevel offenbart eine Bevorzugung von Isoform 7 bei zytoplasmatischer Lokalisation, wohingegen Isoform 1 PPIs an der Membran lokalisiert sind. Das modifizierungsabhängige und isoformspezifische PPI Netzwerk ermöglichte neue Hypothesen zu molekularen Pathomechanismen. / Alterations in phosphorylation-dependent signalling pathways, accumulation of aggregated proteins in the brain and neuronal apoptosis are common to neurodegeneration and implicate overlapping molecular mechanism. To gain insight into involved pathways, a modified yeast-two hybrid (Y2H) system was applied to screen 71 proteins associated with neurological disorders in a proteome-wide manner. For 21 of these proteins interactions were identified including 5 phosphorylation-dependent ones. In total, the network connected 79 proteins through 90 protein-protein interactions (PPIs). A fraction of these Y2H PPIs was tested in secondary interaction assays with a validation rate of 66 %. The described network-based approach successfully identified proteins associated with more than one disorder and cellular functions connected to specific disorders. In particular, the network revealed Ser/Thr kinase-dependent PPIs between the Parkinson protein 7 (PARK7, DJ1) and the E3 ligase components ASB3 and RNF31 (HOIP). The function of these proteins further substantiates the established connection between Parkinson’s disease (PD) and ubiquitination-mediated proteasome (dis)functions. Neurofibromin 2 (NF2, merlin) isoforms and PARK7 were identified as PI3K regulatory subunit p55-gamma (PIK3R3) interactors. These PPIs required Tyr kinase coexpression in the modified Y2H system and functional PIK3R3 pTyr-recognition modules (SH2 domains) in co-IP and Venus PCA experiments. This finding implicates the PI3K/AKT survival pathway in PD-associated neuronal apoptosis and Neurofibromatosis type 2-associated tumour formation. Investigation of PIK3R3, AOF2 (KDM1A, LSD1) and EMILIN1 PPIs on NF2 isoform level revealed preferential isoform 7 binding and cytoplasmic or membrane localisation of these PPIs for isoform 7 or 1, respectively. The generated modification-dependent and isoform-specific PPI network triggered many hypotheses on the molecular mechanisms implicated in neurological disorders.

Mental toughness is accepted to be an important component of sporting performance, especially so in the domain of cricket. It has been called many names, such as Big Match Temperament, bottle, and mettle and it is widely believed that it plays a role in how successful a cricketer may be, although very difficult to define and explain. James Loehr described it as one’s ability to consistently perform to the upper limit of your talent and skill and numerous researchers have since tried to define the construct based on more empirical research. This research project consists of three articles on mental toughness. The first focuses on the consideration of extra-personal influences on the development and implementation of mental toughness programmes. The second focuses on examining the psychometric properties of the paper-and-pencil versions of the Sports Mental Toughness Questionnaire (SMTQ) and the Psychological Performance Inventory-Alternative (PPI-A). The third examines the differences in the demographic characteristics of a sample of cricketers on the online versions of the SMTQ and the PPI-A. The results suggest that extra-personal influences are exceptionally important in the development and implementation of mental toughness programmes for school level cricketers, especially motivational climate and social support. While the PPI-A and the SMTQ displayed some promising psychometric properties in the current study, researchers should apply these mental toughness inventories with circumspection, taking into account questions regarding dimensionality, item formulation and variation in sample characteristics (e.g., age and sporting code), until more research can be conducted using these inventories with larger and more varied samples and the understanding of the mental toughness construct improves. The examination of the demographic differences on scores of the SMTQ and PPI-A revealed inconclusive results on age, sex, and ethnicity, while competitive level was the only distinguishing characteristic in which respondents at high levels produced higher mental toughness scores. The three studies comprising this “by articles” format PHD dissertation will be referred to as Article 1, Article 2, and Article 3 and can be found in Chapters, 2, 3, and 4 respectively. / Psychology / D.Phil. (Psychology)

There has been a rapid growth of private participation in infrastructure projects throughout the world in the last three decades. China as the largest developing country in the world has a huge amount of demands for high quality infrastructure projects and public services. The government has actively developed and used the Build-Operation-Transfer (BOT) model to deliver public facilities and services, particularly after 2002. Certain benefits have been brought by the adoption of the BOT model in China's motorway and water sectors. However, issues were also found in the processes behind BOT applications. International organisations as well as scholars suggested that China should learn experiences and lessons from the UK and its PFI scheme. The UK has been the leading country to use private finance in developing public buildings and services. However, very little has been written addressing how lessons from British PFIs can be learnt by China to improve its BOT practice. This study is an attempt to address this vacuum in the existed literature. It was designed to explore the current problems of using BOTs in Chinese motorway and water sectors and looks at what needs to be improved, based upon the PFI lessons in the UK. A mixture of qualitative and quantitative methods has been employed and various methods of data collection used in this study. These included: 21 interviews, 2 observations and one focus group and the analysis on 14 government reports about BOTs in China. The governments' decision-makers, directors, project managers and contractors were involved in the research to explore the results and emerging issues involving the implementation of BOT models in 87 Chinese motorway and water projects in 10 cities covering six provinces. As a result of its findings, the research is able to discuss and identify the relevant experiences and lessons from PFIs in the UK to improve further application of China's BOTs. This study fills the gap in knowledge regarding comparisons between PFIs and BOTs. It also gives recommendations for good practice in relation to Chinese BOT policy decision making, development and evaluation. Finally, the study hopes to give recommendations that enable the implementation of BOT model in Chinese motorway and water sectors to be more successful in the future.

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