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The role of cortisol and cortisol dynamics in patients after aneurysmal subarachnoid hemorrhage
(2011)
Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a form of stroke which constitutes a severe trauma to the brain and often leads to serious long-term medical and psychosocial sequels which persist for years after the acute event. Recently, adrenocorticotrophic hormone deficiency has been identified as one possible consequence of the bleeding and is assumed to occur in around 20% of all survivors. Additionally, a number of studies report a high prevalence of post-SAH symptoms such as lack of initiative, fatigue, loss of concentration, impaired quality of life and psychiatric symptoms such as depression. The overlap of these symptoms and those of patients with untreated partial or complete hypopituitarism lead to the suggestion that neuroendocrine dysregulations may contribute to the psychosocial sequels of SAH. Therefore, one of the aims of this work is to gain insights into the role of neuroendocrine dysfunction on quality of life and the prevalence of psychiatric sequels in SAH-patients. Additionally, as data on cortisol dynamics after SAH are scarce, diurnal cortisol profiles are investigated in patients in the acute and chronic phase, as well as the cortisol awakening response and feedback sensitivity in the chronic phase after SAH. As a result, it can be shown that some SAH patients exhibit lower serum cortisol levels but at the same time a higher cortisol awakening response in saliva than healthy controls. Also, patients in the chronic phase after SAH do have a stable diurnal cortisol rhythm while there are disturbances in around 50% of all patients in the acute phase, leading to the conclusion that a single baseline measurement of cortisol is of no substantial use for diagnosing cortisol dysregulations in the acute phase after SAH. It is assumed that in SAH patients endocrine changes occur over time and that a combination of adrenal exhaustion and a subsequent downregulation of corticosteroid binding globulin may be the most probable causes for the dissociation of serum cortisol concentrations and salivary cortisol profiles in the investigated SAH patients. These changes may be an emergency response after SAH and, as elevated free cortisol levels are connected to a better psychosocial outcome in patients in the chronic phase after SAH, this reaction may even be adaptive.
The demand for reliable statistics has been growing over the past decades, because more and more political and economic decisions are based on statistics, e.g. regional planning, allocation of funds or business decisions. Therefore, it has become increasingly important to develop and to obtain precise regional indicators as well as disaggregated values in order to compare regions or specific groups. In general, surveys provide the information for these indicators only for larger areas like countries or administrative divisions. However, in practice, it is more interesting to obtain indicators for specific subdivisions like on NUTS 2 or NUTS 3 levels. The Nomenclature of Units for Territorial Statistics (NUTS) is a hierarchical system of the European Union used in statistics to refer to subdivisions of countries. In many cases, the sample information on such detailed levels is not available. Thus, there are projects such as the European Census, which have the goal to provide precise numbers on NUTS 3 or even community level. The European Census is conducted amongst others in Germany and Switzerland in 2011. Most of the participating countries use sample and register information in a combined form for the estimation process. The classical estimation methods of small areas or subgroups, such as the Horvitz-Thompson (HT) estimator or the generalized regression (GREG) estimator, suffer from small area-specific sample sizes which cause high variances of the estimates. The application of small area methods, for instance the empirical best linear unbiased predictor (EBLUP), reduces the variance of the estimates by including auxiliary information to increase the effective sample size. These estimation methods lead to higher accuracy of the variables of interest. Small area estimation is also used in the context of business data. For example during the estimation of the revenues of specific subgroups like on NACE 3 or NACE 4 levels, small sample sizes can occur. The Nomenclature statistique des activités économiques dans la Communauté européenne (NACE) is a system of the European Union which defines an industry standard classification. Besides small sample sizes, business data have further special characteristics. The main challenge is that business data have skewed distributions with a few large companies and many small businesses. For instance, in the automotive industry in Germany, there are many small suppliers but only few large original equipment manufacturers (OEM). Altogether, highly influential units and outliers can be observed in business statistics. These extreme values in connection with small sample sizes cause severe problems when standard small area models are applied. These models are generally based on the normality assumption, which does not hold in the case of outliers. One way to solve these peculiarities is to apply outlier robust small area methods. The availability of adequate covariates is important for the accuracy of the above described small area methods. However, in business data, the auxiliary variables are hardly available on population level. One of several reasons for that is the fact that in Germany a lot of enterprises are not reflected in business registers due to truncation limits. Furthermore, only listed enterprises or companies which trespass specific thresholds are obligated to publish their results. This limits the number of potential auxiliary variables for the estimation. Even though there are issues with available covariates, business data often include spatial dependencies which can be used to enhance small area methods. Next to spatial information based on geographic characteristics, group-specific similarities like related industries based on NACE codes can be used. For instance, enterprises from the same NACE 2 level, e.g. sector 47 retail trade, behave more similar than two companies from different NACE 2 levels, e.g. sector 05 mining of coal and sector 64 financial services. This spatial correlation can be incorporated by extending the general linear mixed model trough the integration of spatially correlated random effects. In business data, outliers as well as geographic or content-wise spatial dependencies between areas or domains are closely linked. The coincidence of these two factors and the resulting consequences have not been fully covered in the relevant literature. The only approach that combines robust small area methods with spatial dependencies is the M-quantile geographically weighted regression model. In the context of EBLUP-based small area models, the combination of robust and spatial methods has not been considered yet. Therefore, this thesis provides a theoretical approach to this scientific and practical problem and shows its relevance in an empirical study.
The complicated human alternative GR promoter region plays a pivotal role in the regulation of GR levels. In this thesis, both genomic and environmental factors linked with GR expression are covered. This research showed that GR promoters were susceptible to silencing by methylation and the activity of the individual promoters was also modulated by SNPs. E2F1 is a major element to drive the expression of GR 1F transcripts and single CpG dinucleotide methylation cannot mediate the inhibition of transcription in vitro. Also, the distribution of GR first exons and 3" splice variants (GRα and GR-P) is expressed throughout the human brain with no region-specific alternative first exon usage. These data mirrored the consistently low levels of methylation in the brain, and the observed homogeneity throughout the studied regions. Taken together, the research presented in this thesis explored several layers of complexity in GR transcriptional regulation.
There is a lot of evidence for the impact of acute glucocorticoid treatment on hippocampus-dependent explicit learning and memory (memory for facts and events). But there have been few studies, investigating the effect of glucocorticoids on implicit learning and memory. We conducted three studies with different methodology to investigate the effect of glucocorticoids on different forms of implicit learning. In Study 1, we investigated the effect of cortisol depletion on short-term habituation in 49 healthy subjects. 25 participants received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. Eye blink electromyogram (EMG) responses to 105 dB acoustic startle stimuli were assessed. Effective endogenous cortisol suppression had no effect on short-term habituation of the startle reflex, but startle eye blink responses were significantly increased in the metyrapone group. The latter findings are in line with previous human studies, which have shown that excess cortisol, sufficient to fully occupy central nervous system (CNS) corticosteroid receptors, may reduce startle eye blink. This effect may be mediated by CNS mechanisms controlling cortisol feedback. In Study 2, we investigated delay or trace eyeblink conditioning in a patient group with a relative hypocortisolism (30 patients with fibromyaligia syndrome/FMS) compared to 20 healthy control subjects. Conditioned eyeblink response probability was assessed by EMG. Morning cortisol levels, ratings of depression, anxiety and psychosomatic complaints as well as general symptomatology and psychological distress were assessed. As compared to healthy controls FMS patients showed lower morning cortisol levels, and trace eyeblink conditioning was facilitated whereas delay eyeblink conditioning was reduced. Cortisol measures correlate significantly only with trace eyeblink conditioning. Our results are in line with studies of pharmacologically induced hyper- and hypocortisolism, which affected trace eyeblink conditioning. We suggest that endocrine mechanisms affecting hippocampus-mediated forms of associative learning may play a role in the generation of symptoms in these patients.rnIn Study 3, we investigated the effect of excess cortisol on implicit sequence learning in healthy subjects. Oral cortisol (30 mg) was given to 29 participants, whereas 31 control subjects received placebo. All volunteers performed a 5-choice serial reaction time task (SRTT). The reaction speed of every button-press was determined and difference-scores were calculated as a proof of learning. Compared to the control group, we found a delayed learning in the cortisol group at the very beginning of the task. This study is the first human investigation, indicating impaired implicit memory function after exogenous administration of the stress hormone cortisol. Our findings support a previous neuroimaging study, which suggested that the medial temporal lobe (including the hippocampus) is also active in implicit sequence learning, but our results may also depend on the engagement of other brain structures.
This work is concerned with two kinds of objects: regular expressions and finite automata. These formalisms describe regular languages, i.e., sets of strings that share a comparatively simple structure. Such languages - and, in turn, expressions and automata - are used in the description of textual patterns, workflow and dependence modeling, or formal verification. Testing words for membership in any given such language can be implemented using a fixed - i.e., finite - amount of memory, which is conveyed by the phrasing finite-automaton. In this aspect they differ from more general classes, which require potentially unbound memory, but have the potential to model less regular, i.e., more involved, objects. Other than expressions and automata, there are several further formalisms to describe regular languages. These formalisms are all equivalent and conversions among them are well-known.However, expressions and automata are arguably the notions which are used most frequently: regular expressions come natural to humans in order to express patterns, while finite automata translate immediately to efficient data structures. This raises the interest in methods to translate among the two notions efficiently. In particular,the direction from expressions to automata, or from human input to machine representation, is of great practical relevance. Probably the most frequent application that involves regular expressions and finite automata is pattern matching in static text and streaming data. Common tools to locate instances of a pattern in a text are the grep application or its (many) derivatives, as well as awk, sed and lex. Notice that these programs accept slightly more general patterns, namely ''POSIX expressions''. Concerning streaming data, regular expressions are nowadays used to specify filter rules in routing hardware.These applications have in common that an input pattern is specified in form a regular expression while the execution applies a regular automaton. As it turns out, the effort that is necessary to describe a regular language, i.e., the size of the descriptor,varies with the chosen representation. For example, in the case of regular expressions and finite automata, it is rather easy to see that any regular expression can be converted to a finite automaton whose size is linear in that of the expression. For the converse direction, however, it is known that there are regular languages for which the size of the smallest describing expression is exponential in the size of the smallest describing automaton.This brings us to the subject at the core of the present work: we investigate conversions between expressions and automata and take a closer look at the properties that exert an influence on the relative sizes of these objects.We refer to the aspects involved with these consideration under the titular term of Relative Descriptional Complexity.
By rodent studies it has been shown that the mineralocorticoid receptor (MR) is a candidate gene for the investigation of cognitive functions comparable to human executive function. The present work addresses the question if polymorphisms in the MR gene can act as a "probe" to explain a part of the interindividual variance of human executive functions. For this purpose, 72 healthy young participants were assigned to four equally sized groups, concerning their particular MR genotype for two common MR polymorphisms. They were investigated in an electroencephalogram (EEG) test session, accomplishing two cognitive tests while delivering saliva samples for subsequent cortisol measures. The two tests chosen for the assessment of executive functions were the Attention Network Task (ANT) and a modified version of the Wisconsin Card Sorting Test (WCST).Chapter 1 of the present work reports of the rational bases for the empirical approach, which were built up on a broad theoretical background presented in Chapter 2. In the third chapter, the investigation and results of the statistical analysis for behavioral data (i.e. reaction times, accuracy/error rates) are presented. No association with MR polymorphisms was found for the reaction times of both tests. For the accuracy rate, differences between genotype groups were found for ANT and WCST, indicating an association of MR polymorphisms and accuracy in the Alertness and Executive Control network of the ANT and during the detection of an intradimensional shift in the WCST. Data acquisition and the results for EEG data analyses are presented in Chapter 4. The results show that groups differing for MR genotype show different activity over prefrontal motor areas during the process of answering to the ANT. Those group differences again were prominent for the Alertness and Executive Control network. A tendency for further significant group differences was found for activity on frontopolar positions in extradimensional rule switching. Chapter 5 summarizes the findings for the analysis of salivary free cortisol, showing a tendency for an association between MR polymorphisms and a mildly stimulated Hypothalamus-pituitary-adrenal (HPA) axis during the test situation. The results of the different measures are integrated and discussed in Chapter 6 within the scope of novel findings in investigating the functionality of the chosen MR polymorphisms. Finally, Chapter 7 gives an outlook on the methodology and constraints of future research strategies to further describe the role of the MR in human cognitive function.
The article deals with the untenable overloading of German criminal trial court judges presenting the overloading in detail and analyzing its reasons and consequences. In this context, serious failures by the German federal and state executive and legislative organs as well as undesirable developments of the Federal Constitutional Court's (BVerfG and the Federal Supreme Court of Justice's BGH) case law.
The 22nd annual conference of the European Consortium for Church and State Research took place from 11 to 14 November 2010 in Trier, Germany. Founded in 1989, the Consortium unites experts of law and religion of all Member States of the European Union. In annual meetings, various topics of the relations between religions and states within the European Union are discussed. This year- conference was dedicated to the topic "Religion in Public Education". Scholars from 27 European countries discussed inter alia the role of religion in the European member states" educational systems, opting out of school obligations for religious reasons, home schooling as well as religious dress and symbols in public schools. The present proceedings contain the opening lectures, all country reports and a report on the European Union law.
Stress represents a significant problem for Western societies inducing costs as high as 3-4 % of the European gross national products, a burden that is continually increasing (WHO Briefing, EUR/04/5047810/B6). The classical stress response system is the hypothalamic-pituitary-adrenal (HPA) axis which acts to restore homeostasis after disturbances. Two major components within the HPA axis system are the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Cortisol, released from the adrenal glands at the end of the HPA axis, binds to MRs and with a 10 fold lower affinity to GRs. Both, impairment of the HPA axis and an imbalance in the MR/GR ratio enhances the risk for infection, inflammation and stress related psychiatric disorders. Major depressive disorder (MDD) is characterised by a variety of symptoms, however, one of the most consistent findings is the hyperactivity of the HPA axis. This may be the result of lower numbers or reduced activity of GRs and MRs. The GR gene consists of multiple alternative first exons resulting in different GR mRNA transcripts whereas for the MR only two first exons are known to date. Both, the human GR promoter 1F and the homologue rat Gr promoter 1.7 seem to be susceptible to methylation during stressful early life events resulting in lower 1F/1.7 transcript levels. It was proposed that this is due to methylation of a NGFI-A binding site in both, the rat promoter 1.7 and the human promoter 1F. The research presented in this thesis was undertaken to determine the differential expression and methylation patterns of GR and MR variants in multiple areas of the limbic brain system in the healthy and depressed human brain. Furthermore, the transcriptional control of the GR transcript 1F was investigated as expression changes of this transcript were associated with MDD, childhood abuse and early life stress. The role of NGFI-A and several other transcription factors on 1F regulation was studied in vitro and the effect of Ngfi-a overexpression on the rat Gr promoter 1.7 in vivo. The susceptibility to epigenetic programming of several GR promoters was investigated in MDD. In addition, changes in methylation levels have been determined in response to a single acute stressor in rodents. Our results showed that GR and MR first exon transcripts are differentially expressed in the human brain, but this is not due to epigenetic programming. We showed that NGFI-A has no effect on endogenous 1F/1.7 expression in vitro and in vivo. We provide evidence that the transcription factor E2F1 is a major element in the transcriptional complex necessary to drive the expression of GR 1F transcripts. In rats, highly individual methylation patterns in the paraventricular nucleus of the hypothalamus (PVN) suggest that this is not related to the stressor but can rather be interpreted as pre-existing differences. In contrast, the hippocampus showed a much more uniform epigenetic status, but still is susceptible to epigenetic modification even after a single acute stress suggesting a differential "state‟ versus "trait‟ regulation of the GR gene in different brain regions. The results of this thesis have given further insight in the complex transcriptional regulation of GR and MR first exons in health and disease. Epigenetic programming of GR promoters seems to be involved in early life stress and acute stress in adult rats; however, the susceptibility to methylation in response to stress seems to vary between brain regions.
Contents: I. History of the Korean Civil Code II. Background for Initiation of the Amendment of the Civil Code (Property Law) and their Progress III. Fundamental Direction of the Amendment of the Civil Code (Property Law) IV. Major Foreign Statutes Used as Reference for the Amendment of the Civil Code (Property Law) V. Major Details of the Amendment of the Civil Code (Property Law) VI. Concluding Remarks: Evaluation
"Culture", in addition to its ethnic signification, can also express various groups' and communities' political and economic situation in society. As well as signifying the accommodation of ethnic diversity, the integration of dissimilar cultures in South Africa has to do with both the former oppressors and the formerly oppressed coming to terms with the oppression of the past, and with the equitable distribution of material means. Constitutional and other legal means have been designed to facilitate a process of integration dealing with the abovementioned issues. Some of these measures will be looked at. The speaker will argue that the integration of different cultures in South Africa cannot and will not be achieved if the law is invoked, in a strong arm fashion, trying to concoct a melting pot. The law can do no more than aiding the facilitation of a process of consolidation as precondition to nation building. Deep-seated, cultural differences among various sections of the population cannot and should not be denied or simply thought away.
The Constitution of Latvia
(2004)
The article offers a concise view on the constitution of the Baltic state of Latvia. After an introduction focusing on constitutional history, the author explores basic principles and human rights in the text of the constitution and explains the main constitutional bodies and their functions in legislative, executive and judiciary. Chapters on citizenship and religious rights round up this introduction to the Latvian Constitution.
Germany as law-exporting nation is a worldwide role model especially for its criminal law and criminal procedure law which has influenced several East Asian countries. The author offers a short historical overview on the establishment of the rule of law in Germany. He describes the role of the German Federal Constitution as source of criminal procedure law by referring to fundamental constitutional principles as well as giving specific case examples. The second part of the essay focuses on the relevance and application of the European Convention on Human Rights. The author points out basic principles of the European Convention on Human Rights and illustrates its influence on German legal practice.
The article deals with the responsibility of the financial sector under criminal law in Germany. This question has been of special interest since the beginning of the financial crisis. The author argues that the transactions of asset-backed securities based on American subprime mortgages fulfill all legal elements of the criminal offence "breach of trust" (Untreue). From the author's point of view, the people's legal loyalty would be severely affected if there were no criminal proceedings against such bankers who purchased those toxic asset-backed securities without sufficient information on their structure and value. Refraining from criminal prosecution even in cases causing high loss would send a dangerous signal towards the investment banking industry.
In recent years, Islamic banking has been one of the fastest growing markets in the financial world. Even to German banks, Islamic finance is not as 'foreign' as one might think. Indeed, several banks are already operating so-called "Islamic windows" in various Arab countries. However, German banks are still reluctant to offer 'Islamic' products in Germany, despite the fact that approximately 3.5 million Muslims currently live there. Potential reasons for this reluctance include widespread misunderstanding of Islamic banking in Germany and prevailing cultural prejudice towards Islam generally. The author seeks to address these concerns and to take an objective approach towards understanding the potential for Islamic banking in Germany. Legally, Islamic law cannot be the governing law of any contract in Germany. Therefore, the aim must be to draft contracts that are both enforceable under German law and consistent with the principles of Shari'a " the Islamic law. In this paper, the author gives a detailed legal analysis of the most common Islamic banking products and how they could be given effect under German law, while attempting to address widespread concerns about arbitration or parallel Shari'a courts. This publication is one of the first legal analysis of Islamic banking products in Germany. As such, its goal is not to be the final word, but rather to begin the conversation about potential problems and conflicts of Islamic banking in Germany that require further investigation.
Recent non-comparative studies diverge in their assessments of the extent to which German and Japanese post-Cold War foreign policies are characterized by continuity or change. While the majority of analyses on Germany find overall continuity in policies and guiding principles, prominent works on Japan see the country undergoing drastic and fundamental change. Using an explicitly comparative framework for analysis based on a role theoretical approach, this study reevaluates the question of change and continuity in the two countries" regional foreign policies, focusing on the time period from 1990 to 2010. Through a qualitative content analysis of key foreign policy speeches, this dissertation traces and compares German and Japanese national role conceptions (NRCs) by identifying policymakers" perceived duties and responsibilities of their country in international politics. Furthermore, it investigates actual foreign policy behavior in two case studies about German and Japanese policies on missile defense and on textbook disputes. The dissertation examines whether the NRCs identified in the content analysis are useful to understand and explain each country- particular conduct. Both qualitative content analysis and case studies demonstrate the influence of normative and ideational variables in foreign policymaking. Incremental adaptations in foreign policy preferences can be found in Germany as well as Japan, but they are anchored in established normative guidelines and represent attempts to harmonize existing preferences with the conditions of the post-Cold War era. The dissertation argues that scholars have overstated and misconstrued the changes underway by asserting that Japan is undergoing a sweeping transformation in its foreign policy.
Cortisol is a stress hormone that acts on the central nervous system in order to support adaptation and time-adjusted coping processes. Whereas previous research has focused on slow emerging, genomic effects of cortisol likely mediated by protein synthesis, there is only limited knowledge about rapid, non-genomic cortisol effects on in vivo neuronal cell activity in humans. Three independent placebo-controlled studies in healthy men were conducted to test effects of 4 mg cortisol on central nervous system activity, occurring within 15 minutes after intravenous administration. Two of the studies (N = 26; N = 9) used continuous arterial spin labeling as a magnetic resonance imaging sequence, and found rapid bilateral thalamic perfusion decrements. The third study (N = 14) revealed rapid cortisol-induced changes in global signal strength and map complexity of the electroencephalogram. The observed changes in neuronal functioning suggest that cortisol may act on the thalamic relay of non-relevant background as well as on task specific sensory information in order to facilitate the adaptation to stress challenges. In conclusion, these results are the first to coherently suggest that a physiologically plausible amount of cortisol profoundly affects functioning and perfusion of the human CNS in vivo by a rapid, non-genomic mechanism.
The overall objective of this thesis was to gain a deeper understanding of the antecedents, processes, and manifestations of uniqueness-driven consumer behavior. To achieve this goal, five studies have been conducted in Germany and Switzerland with a total of 1048 participants across different demographic and socio-economic backgrounds. Two concepts were employed in all studies: Consumer need for uniqueness (CNFU) and general uniqueness perception (GUP). CNFU (Tian, Bearden, & Hunter, 2001), a mainly US"based consumer research concept, measures the individual need, and thus the motivation to acquire, use, and dispose consumer goods in order to develop a unique image. GUP, adapted from the two-component theory of individuality (Kampmeier, 2001), represents a global and direct measure of self-ascribed uniqueness. Study #1 looked at the interrelation of the uniqueness-driven concepts. Therefore, GUP and CNFU were employed in the study as potential psychological factors that influence and predict uniqueness-driven consumer behavior. Different behavioral measures were used: The newly developed possession of individualized products (POIP), the newly developed products for uniqueness display (PFUD), and the already established uniqueness-enhancing behaviors (UEB). Analyses showed that CNFU mediates the relationship between GUP and the behavioral measures in a German speaking setting. Thus, GUP (representing self-perception) was identified as the driver behind CNFU (representing motivation) and the actual consumer behavior. Study #2 examined further manifestations of uniqueness-driven consumer behavior. For this purpose, an extreme form of uniqueness-increasing behavior was researched: Tattooing. The influence of GUP and CNFU on tattooing behavior was investigated using a sample derived from a tattoo exhibition. To do so, a newly developed measure to determine the percentage of the body covered by tattoos was employed. It was revealed that individuals with higher GUP and CNFU levels indeed have a higher tattooing degree. Study #3 further explored the predictive possibilities and limitations of the GUP and CNFU concepts. On the one hand, study #3 specifically looked at the consumption of customized apparel products as mass customization is said to become the standard of the century (Piller & Müller, 2004). It was shown that individuals with higher CNFU levels not only purchased more customized apparel products in the last six months, but also spend more money on them. On the other hand, uniqueness-enhancing activities (UEA), such as travel to exotic places or extreme sports, were investigated by using a newly developed 30-item scale. It was revealed that CNFU partly mediates the GUP and UEA relationship, proving that CNFU indeed predicts a broad range of consumer behaviors and that GUP is the driver behind the need and the behavior. Study #4, entered a new terrain. In contrast to the previous three studies, it explored the so termed "passive" side of uniqueness-seeking in the consumer context. Individuals might feel unique because business companies treat them in a special way. Such a unique customer treatment (UCT) involves activities like customer service or customer relationship management. Study #4 investigated if individuals differ in their need for such a treatment. Hence, with the need for unique customer treatment (NFUCT) a new uniqueness-driven consumer need was introduced and its impact on customer loyalty examined. Analyses, for example, revealed that individuals with high NFUCT levels receiving a high unique customer treatment (UCT) showed the highest customer loyalty, whereas the lowest customer loyalty was found among those individuals with high NFUCT levels receiving a low unique customer treatment (UCT). Study #5 mainly examined the processes behind uniqueness-driven consumer behavior. Here, not only the psychological influences, but also situational influences were examined. This study investigated the impact of a non-personal "indirect" uniqueness manipulation on the consumption of customized apparel products by simultaneously controlling for the influence of GUP and CNFU. Therefore, two equal experimental groups were created. Afterwards, these groups either received an e-mail with a "pro-individualism" campaign or a "pro-collectivism" campaign especially developed for study #5. The conducted experiment revealed that, individuals receiving a "pro-individualism" poster campaign telling the participants that uniqueness is socially appropriate and desired were willing to spend more money on customization options compared to individuals receiving a "pro-collectivism" poster campaign. Hence, not only psychological antecedents such as GUP and CNFU influence uniqueness-driven consumer behavior, but also situational factors.
Recently, optimization has become an integral part of the aerodynamic design process chain. However, because of uncertainties with respect to the flight conditions and geometrical uncertainties, a design optimized by a traditional design optimization method seeking only optimality may not achieve its expected performance. Robust optimization deals with optimal designs, which are robust with respect to small (or even large) perturbations of the optimization setpoint conditions. The resulting optimization tasks become much more complex than the usual single setpoint case, so that efficient and fast algorithms need to be developed in order to identify, quantize and include the uncertainties in the overall optimization procedure. In this thesis, a novel approach towards stochastic distributed aleatory uncertainties for the specific application of optimal aerodynamic design under uncertainties is presented. In order to include the uncertainties in the optimization, robust formulations of the general aerodynamic design optimization problem based on probabilistic models of the uncertainties are discussed. Three classes of formulations, the worst-case, the chance-constrained and the semi-infinite formulation, of the aerodynamic shape optimization problem are identified. Since the worst-case formulation may lead to overly conservative designs, the focus of this thesis is on the chance-constrained and semi-infinite formulation. A key issue is then to propagate the input uncertainties through the systems to obtain statistics of quantities of interest, which are used as a measure of robustness in both robust counterparts of the deterministic optimization problem. Due to the highly nonlinear underlying design problem, uncertainty quantification methods are used in order to approximate and consequently simplify the problem to a solvable optimization task. Computationally demanding evaluations of high dimensional integrals resulting from the direct approximation of statistics as well as from uncertainty quantification approximations arise. To overcome the curse of dimensionality, sparse grid methods in combination with adaptive refinement strategies are applied. The reduction of the number of discretization points is an important issue in the context of robust design, since the computational effort of the numerical quadrature comes up in every iteration of the optimization algorithm. In order to efficiently solve the resulting optimization problems, algorithmic approaches based on multiple-setpoint ideas in combination with one-shot methods are presented. A parallelization approach is provided to overcome the amount of additional computational effort involved by multiple-setpoint optimization problems. Finally, the developed methods are applied to 2D and 3D Euler and Navier-Stokes test cases verifying their industrial usability and reliability. Numerical results of robust aerodynamic shape optimization under uncertain flight conditions as well as geometrical uncertainties are presented. Further, uncertainty quantification methods are used to investigate the influence of geometrical uncertainties on quantities of interest in a 3D test case. The results demonstrate the significant effect of uncertainties in the context of aerodynamic design and thus the need for robust design to ensure a good performance in real life conditions. The thesis proposes a general framework for robust aerodynamic design attacking the additional computational complexity of the treatment of uncertainties, thus making robust design in this sense possible.
In a case of robbery, some people actually use violence to steal - but others may supply information or weapons, make the plans, act as lookouts, provide transport. Certainly the actual robbers are guilty - but what of the others? How does Hong Kong's version of the common law answer this question now? How should the question be answered in the future?
The main research question of this thesis was to set up a framework to allow for the identification of land use changes in drylands and reveal their underlying drivers. The concept of describing land cover change processes in a framework of global change syndrome was introduced by Schellnhuber et al. (1997). In a first step the syndrome approach was implemented for semi-natural areas of the Iberian Peninsula based on time series analysis of the MEDOKADS archive. In the subsequent study the approach was expanded and adapted to other land cover strata. Furthermore, results of an analysis of the relationship of annual NDVI and rainfall data were incorporated to designate areas that show a significant relationship indicating that at least a part of the variability found in NDVI time series was caused by precipitation. Additionally, a first step was taken towards the integration of socio-economic data into the analysis; population density changes between 1961 and 2008 were utilized to support the identification of processes related to land abandonment accompanied by cessation of agricultural practices on the one hand and urbanization on the other. The main findings of the studies comprise three major land cover change processes caused by human interaction: (i) shrub and woody vegetation encroachment in the wake of land abandonment of marginal areas, (ii) intensification of non-irrigated and irrigated, intensively used fertile regions and (iii) urbanization trends along the coastline caused by migration and the increase of mass tourism. Land abandonment of cultivated fields and the give-up of grazing areas in marginal mountainous areas often lead to the encroachment of shrubs and woody vegetation in the course of succession or reforestation. Whereas this cover change has positive effects concerning soil stabilization and carbon sequestration the increase of biomass involves also negative consequences for ecosystem goods and services; these include decreased water yield as a result of increased evapotranspiration, increasing fire risk, decreasing biodiversity due to landscape homogenization and loss of aesthetic value. Arable land in intensively used fertile zones of Spain was further intensified including the expansion of irrigated arable land. The intensification of agriculture has also generated land abandonment in these areas because less people are needed in the agricultural labour sector due to mechanization. Urbanization effects due to migration and the growth of the tourism sector were mapped along the eastern Mediterranean coast. Urban sprawl was only partly detectable by means of the MEDOKADS archive as the changes of urbanization are often too subtle to be detected by data with a spatial resolution of 1 km-². This is in line with a comparison of a Landsat TM time series and the NOAA AVHRR archive for a study area in the Greece that showed that small scale changes cannot be detected based on this approach, even though they might be of high relevance for local management of resources. This underlines the fact that land degradation processes are multi-scale problems and that data of several spatial and temporal scales are mandatory to build a comprehensive dryland observation system. Further land cover processes related to a decrease of greenness did not play an important role in the observation period. Thus, only few patches were identified, suggesting that no large-scale land degradation processes are taking place in the sense of decline of primary productivity after disturbances. Nevertheless, the land cover processes detected impact ecosystem functioning and using the example of shrub encroachment, bear risks for the provision of goods and services which can be valued as land degradation in the sense of a decline of important ecosystem goods and services. This risk is not only confined to the affected ecosystem itself but can also impact adjacent ecosystems due to inter-linkages. In drylands water availability is of major importance and the management of water resources is an important political issue. In view of climate change this topic will become even more important because aridity in Spain did increase within the last decades and is likely to further do so. In addition, the land cover changes detected by the syndrome approach could even augment water scarcity problems. Whereas the water yield of marginal areas, which often serve as headwaters of rivers, decreases with increasing biomass, water demand of agriculture and tourism is not expected to decline. In this context it will be of major importance to evaluate the trade-offs between different land uses and to take decisions that maintain the future functioning of the ecosystems for human well-being.
Extension of inexact Kleinman-Newton methods to a general monotonicity preserving convergence theory
(2011)
The thesis at hand considers inexact Newton methods in combination with algebraic Riccati equation. A monotone convergence behaviour is proven, which enables a non-local convergence. Above relation is transferred to a general convergence theory for inexact Newton methods securing the monotonicity of the iterates for convex or concave mappings. Several application prove the pratical benefits of the new developed theory.
During pregnancy every eighth woman is treated with glucocorticoids. Glucocorticoids inhibit cell division but are assumed to accelerate the differentiation of cells. In this review animal models for the development of the human fetal and neonatal hypothalamic-pituitary-adrenal (HPA) axis are investigated. It is possible to show that during pregnancy in humans, as in most of the here-investigated animal models, a stress hyporesponsive period (SHRP) is present. In this period, the fetus is facing reduced glucocorticoid concentrations, by low or absent fetal glucocorticoid synthesis and by reduced exposure to maternal glucocorticoids. During that phase, sensitive maturational processes in the brain are assumed, which could be inhibited by high glucocorticoid concentrations. In the SHRP, species-specific maximal brain growth spurt and neurogenesis of the somatosensory cortex take place. The latter is critical for the development of social and communication skills and the secure attachment of mother and child. Glucocorticoid treatment during pregnancy needs to be further investigated especially during this vulnerable SHRP. The hypothalamus and the pituitary stimulate the adrenal glucocorticoid production. On the other hand, glucocorticoids can inhibit the synthesis of corticotropin-releasing hormone (CRH) in the hypothalamus and of adrenocorticotropic hormone (ACTH) in the pituitary. Alterations in this negative feedback are assumed among others in the development of fibromyalgia, diabetes and factors of the metabolic syndrome. In this work it is shown that the fetal cortisol surge at the end of gestation is at least partially due to reduced glucocorticoid negative feedback. It is also assumed that androgens are involved in the control of fetal glucocorticoid synthesis. Glucocorticoids seem to prevent masculinization of the female fetus by androgens during the sexual gonadal development. In this work a negative interaction of glucocorticoids and androgens is detectable.
Mechanical and Biological Treatment (MBT) generally aims to reduce the amount of solid waste and emissions in landfills and enhance the recoveries. MBT technology has been studied in various countries in Europe and Asia. Techniques of solid waste treatment are distinctly different in the study areas. A better understanding of MBT waste characteristics can lead to an optimization of the MBT technology. For a sustainable waste management, it is essential to determine the characteristics of the final MBT waste, the effectiveness of the treatment system as well as the potential application of the final material regarding future utilization. This study aims to define and compare the characteristics of the final MBT materials in the following countries: Luxembourg (using a high degree technology), Fridhaff in Diekirch/Erpeldange, Germany (using a well regulated technology), Singhofen in Rhein-Lahn district, Thailand (using a low cost technology): Phitsanulok in Phitsanulok province. The three countries were chosen for this comparative study due to their unique performance in the MBT implementation. The samples were taken from the composting heaps of the final treatment process prior to sending them to landfills, using a random sampling standard strategy from August 2008 onwards. The size of the sample was reduced to manageable sizes before characterization. The size reduction was achieved by the quartering method. The samples were first analyzed for the size fraction on the day of collection. They were screened into three fractions by the method of dry sieving: small size with a diameter of <10 mm, medium size with a diameter of 10-40 mm and large size with a diameter of >40 mm. These fractions were further analyzed for their physical and chemical parameters such as particle size distribution (total into 12 size fractions), particle shape, porosity, composition, water content, water retention capacity and respiratory activity. The extracted eluate was analyzed for pH-value, heavy metals (lead, cadmium and arsenic), chemical oxygen demand, ammonium, sulfate and chloride. In order to describe and evaluate the potential application of the small size material as a final cover of landfills, the fraction of small size samples were tested for the geotechnical properties as well. The geotechnical parameters were the compaction test, permeability test and shear strength test. The detailed description of the treatment facilities and methods of the study areas were included in the results. The samples from the three countries are visibly smaller than waste without pretreatment. Maximum particle size is found to be less than 100 mm. The samples are found to consist of dust to coarse fractions. The small size with a diameter of <10 mm was highest in the sample from Germany (average 60% by weight), secondly in the sample from Luxembourg (average 43% by weight) and lowest in the sample from Thailand (average 15% by weight). The content of biodegradable material generally increased with decreasing particle sizes. Primary components are organic, plastics, fibrous materials and inert materials (glass and ceramics). The percentage of each components greatly depends on the MBT process of each country. Other important characteristics are significantly reduced water content, reduced total organic carbon and reduced potential heavy metals. The geotechnical results show that the small fraction is highly compact, has a low permeability and lot of water adsorbed material. The utilization of MBT material in this study shows a good trend as it proved to be a safe material which contained very low amounts of loadings and concentrations of chemical oxygen demand, ammonium, and heavy metals. The organic part can be developed to be a soil conditioner. It is also suitably utilized as a bio-filter layer in the final cover of landfill or as a temporary cover during the MBT process. This study showed how to identify the most appropriate technology for municipal solid waste disposal through the study of waste characterization.
The brain is the central coordinator of the human stress reaction. At the same time, peripheral endocrine and neural stress signals act on the brain modulating brain function. Here, three experimental studies are presented demonstrating this dual role of the brain in stress. Study I shows that centrally acting insulin, an important regulator of energy homeostasis, attenuates the stress related cortisol secretion. Studies II and III show that specific components of the stress reaction modulate learning and memory retrieval, two important aspects of higher-order brain function.
Legalisation cannot be fully explained by interest politics. If that were the case, the attitudes towards legalisation would be expected to be based on objective interests and actual policies in France and Germany would be expected to be more similar. Nor can it be explained by institutional agency, because there are no hints that states struggle with different normative traditions. Rather, political actors seek to make use of the structures that already exist to guar-antee legitimacy for their actions. If the main concern of governmental actors really is to accumulate legitimacy, as stated in the introduction, then politicians have a good starting position in the case of legalisation of illegal foreigners. Citizens" negative attitudes towards legalisation cannot be explained by imagined labour market competition; income effects play only a secondary role. The most important explanatory factor is the educational level of each individual. Objective interests do not trigger attitudes towards legalisation, but rather a basic men-tal predisposition for or against illegal immigrants who are eligible for legalisation. Politics concerning amnesties are thus not tied to an objectively given structure like the socio-economic composition of the electorate, but are open for political discretion. Attitudes on legalising illegal immigrants can be regarded as being mediated by beliefs and perceptions, which can be used by political agents or altered by political developments. However, politicians must adhere to a national frame of legitimating strategies that cannot be neglected without consequences. It was evident in the cross-country comparison of political debates that there are national systems of reference that provide patterns of interpretation. Legalisation is seen and incorporated into immigration policy in a very specific way that differs from one country to the next. In both countries investigated in this study, there are fundamental debates about which basic principles apply to legalisation and which of these should be held in higher esteem: a legal system able to work, humanitarian rights, practical considerations, etc. The results suggest that legalisation is "technicized" in France by describing it as an unusual but possible pragmatic instrument for the adjustment of the inefficient rule of law. In Germany, however, legalisation is discussed at a more normative level. Proponents of conservative immigration policies regard it as a substantial infringement on the rule of law, so that even defenders of a humanitarian solution for illegal immigrants are not able to challenge this view without significant political harm. But the arguments brought to bear in the debate on legalisation are not necessarily sound because they are not irrefutable facts, but instruments to generate legitimacy, and there are enough possibilities for arguing and persuading because socio-economic factors play a minor role. One of the most important arguments, the alleged pull effect of legalisation, has been subjected to an empirical investigation. In the political debate, it does not make any dif-ference whether this is true or not, insofar as it is not contested by incontrovertible findings. In reality, the results suggest that amnesties indeed exert a small attracting influence on illegal immigration, which has been contested by immigration friendly politicians in the French par-liament. The effect, however, is not large; therefore, some conservative politicians may put too much stress on this argument. Moreover, one can see legalisation as an instrument to restore legitimacy that has slipped away from immigration politics because of a high number of illegally residing foreigners. This aspect explains some of the peculiarities in the French debate on legalisation, e.g. the idea that the coherence of the law is secured by creating exceptional rules for legalising illegal immigrants. It has become clear that the politics of legalisation are susceptible to manipulation by introducing certain interpretations into the political debate, which become predominant and supersede other views. In this study, there are no signs of a systematic misuse of this constellation by any certain actor. However, the history of immigration policy is full of examples of symbolic politics in which a certain measure has been initiated while the actors are totally aware of its lack of effect. Legalisation has escaped this fate so far because it is a specific instrument that is the result of neglecting populist mechanisms rather than an ex-ample of a superficial measure. This result does not apply to policies concerning illegal immi-gration in general, both with regard to concealing a lack of control and flexing the state- muscles.
Stress and pain are common experiences in human lives. Both, the stress and the pain system have adaptive functions and try to protect the organism in case of harm and danger. However, stress and pain are two of the most challenging problems for the society and the health system. Chronic stress, as often seen in modern societies, has much impact on health and can lead to chronic stress disorders. These disorders also include a number of chronic pain syndromes. However, pain can also be regarded as a stressor itself, especially when we consider how much patients suffer from long-lasting pain and the impact of pain on life quality. In this way, the effects of stress on pain can be fostered. For the generation and manifestation of chronic pain symptoms also learning processes such as classical conditioning play an important role. Processes of classical conditioning can also be influenced by stress. These facts illustrate the complex and various interactions between the pain and the stress systems. Both systems communicate permanently with each other and help to protect the organism and to keep a homeostatic state. They have various ways of communication, for example mechanisms related to endogenous opioids, immune parameters, glucocorticoids and baroreflexes. But an overactivation of the systems, for example caused by ongoing stress, can lead to severe health problems. Therefore, it is of great importance to understand these interactions and their underlying mechanisms. The present work deals with the relationship of stress and pain. A special focus is put on stress related hypocortisolism and pain processing, stress induced hypoalgesia via baroreceptor related mechanisms and stress related cortisol effects on aversive conditioning (as a model of pain learning). This work is a contribution to the wide field of research that tries to understand the complex interactions of stress and pain. To demonstrate the variety, the selected studies highlight different aspects of these interactions. In the first chapter I will give a short introduction on the pain and the stress systems and their ways of interaction. Furthermore, I will give a short summary of the studies presented in Chapter II to V and their background. The results and their meaning for future research will be discussed in the last part of the first chapter. Chronic pain syndromes have been associated with chronic stress and alterations of the HPA axis resulting in chronic hypocortisolism. But if these alterations may play a causal role in the pathophysiology of chronic pain remains unclear. Thus, the study described in Chapter II investigated the effects of pharmacological induced hypocortisolism on pain perception. Both, the stress and the pain system are related to the cardiovascular system. Increase of blood pressure is part of the stress reaction and leads to reduced pain perception. Therefore, it is important for the usage of pain tests to keep in mind potential interferences from activation of the cardiovascular system, especially when pain inhibitory processes are investigated. For this reason we compared two commonly and interchangeably used pain tests with regard to the triggered autonomic reactions. This study is described in chapter III. Chapter IV and V deal with the role of learning processes in pain and related influences of stress. Processes of classical conditioning play an important role for symptom generation and manifestation. In both studies aversive eyeblink conditioning was used as a model for pain learning. In the study described in Chapter IV we compared classical eyeblink conditioning in healthy volunteers to patients suffering from fibromyalgia, a chronic pain disorder. Also, differences of the HPA axis, as part of the stress system, were taken in account. The study of Chapter V investigated effects of the very first stress reaction, particularly rapid non-genomic cortisol effects. Healthy volunteers received an intravenous cortisol administration immediately before the eyeblink conditioning. Rapid effects have only been demonstrated on a cellular level and on animal behavior so far. In general, the studies presented in this work may give an impression of the broad variety of possible interactions between the pain and the stress system. Furthermore, they contribute to our knowledge about theses interactions. However, more research is needed to complete the picture.
In this thesis, three studies investigating the impact of stress on the protective startle eye blink reflex are reported. In the first study a decrease in prepulse inhibition of the startle reflex was observed after intravenous low dose cortisol application. In the second study a decrease in reflex magnitude of the startle reflex was observed after pharmacological suppression of endogenous cortisol production. In the third study, a higher reflex magnitude of the startle reflex was observed at reduced arterial and central venous blood pressure. These results can be interpreted in terms of an adaption to hostile environments.
The visualization of relational data is at the heart of information visualization. The prevalence of visual representations for this kind of data is based on many real world examples spread over many application domains: protein-protein interaction networks in the field of bioinformatics, hyperlinked documents in the World Wide Web, call graphs in software systems, or co-author networks are just four instances of a rich source of relational datasets. The most common visual metaphor for this kind of data is definitely the node-link approach, which typically suffers from visual clutter caused by many edge crossings. Many sophisticated algorithms have been developed to layout a graph efficiently and with respect to a list of aesthetic graph drawing criteria. Relations between objects normally change over time. Visualizing the dynamics means an additional challenge for graph visualization researchers. Applying the same layout algorithms for static graphs to intermediate states of dynamic graphs may also be a strategy to compute layouts for an animated graph sequence that shows the dynamics. The major drawback of this approach is the high cognitive effort for a viewer of the animation to preserve his mental map. To tackle this problem, a sophisticated layout algorithm has to inspect the whole graph sequence and compute a layout with as little changes as possible between subsequent graphs. The main contribution and ultimate goal of this thesis is the visualization of dynamic compound weighted multi directed graphs as a static image that targets at visual clutter reduction and at mental map preservation. To achieve this goal, we use a radial space-filling visual metaphor to represent the dynamics in relational data. As a side effect the obtained pictures are very aesthetically appealing. In this thesis we firstly describe static graph visualizations for rule sets obtained by extracting knowledge from software archives under version control. In a different work we apply animated node-link diagrams to code-developer relationships to show the dynamics in software systems. An underestimated visualization paradigm is the radial representation of data. Though this kind of data has a long history back to centuries-old statistical graphics, only little efforts have been done to fully explore the benefits of this paradigm. We evaluated a Cartesian and a radial counterpart of a visualization technique for visually encoding transaction sequences and dynamic compound digraphs with both an eyetracking and an online study. We found some interesting phenomena apart from the fact that also laymen in graph theory can understand the novel approach in a short time and apply it to datasets. The thesis is concluded by an aesthetic dimensions framework for dynamic graph drawing, future work, and currently open issues.
Abstracts book of oral presentations and poster contributions for the mid-term conference of the Interreg IVB NWE project ForeStClim. The international conference took place in Nancy (France) from 20. to 22. September 2010. The topics of the conference sessions were as follows:rnSession 1: Projecting forest sites and stand shiftsrnSession 2: Climate change and water: modelling across spatial and temporal scalesrnSession 3: Addressing climate change in practical silvicultural decision support
Aggression is one of the most researched topics in psychology. This is understandable, since aggression behavior does a lot of harm to individuals and groups. A lot is known already about the biology of aggression, but one system that seems to be of vital importance in animals has largely been overlooked: the hypothalamic-pituitary-adrenal (HPA) axis. Menno Kruk and Jószef Haller and their research teams developed rodent models of adaptive, normal, and abnormal aggressive behavior. They found the acute HPA axis (re)activity, but also chronic basal levels to be causally relevant in the elicitation and escalation of aggressive behavior. As a mediating variable, changes in the processing of relevant social information is proposed, although this could not be tested in animals. In humans, not a lot of research has been done, but there is evidence for both the association between acute and basal cortisol levels in (abnormal) aggression. However, not many of these studies have been experimental of nature. rnrnOur aim was to add to the understanding of both basal chronic levels of HPA axis activity, as well as acute levels in the formation of aggressive behavior. Therefore, we did two experiments, both with healthy student samples. In both studies we induced aggression with a well validated paradigm from social psychology: the Taylor Aggression Paradigm. Half of the subjects, however, only went through a non-provoking control condition. We measured trait basal levels of HPA axis activity on three days prior. We took several cortisol samples before, during, and after the task. After the induction of aggression, we measured the behavioral and electrophysiological brain response to relevant social stimuli, i.e., emotional facial expressions embedded in an emotional Stroop task. In the second study, we pharmacologically manipulated cortisol levels 60min before the beginning of the experiment. To do that, half of the subjects were administered 20mg of hydrocortisone, which elevates circulating cortisol levels (cortisol group), the other half was administered a placebo (placebo group). Results showed that acute HPA axis activity is indeed relevant for aggressive behavior. We found in Study 1 a difference in cortisol levels after the aggression induction in the provoked group compared to the non-provoked group (i.e., a heightened reactivity of the HPA axis). However, this could not be replicated in Study 2. Furthermore, the pharmacological elevation of cortisol levels led to an increase in aggressive behavior in women compared to the placebo group. There were no effects in men, so that while men were significantly more aggressive than women in the placebo group, they were equally aggressive in the cortisol group. Furthermore, there was an interaction of cortisol treatment with block of the Taylor Aggression Paradigm, in that the cortisol group was significantly more aggressive in the third block of the task. Concerning basal HPA axis activity, we found an effect on aggressive behavior in both studies, albeit more consistently in women and in the provoked and non-provoked groups. However, the effect was not apparent in the cortisol group. After the aggressive encounter, information processing patterns were changed in the provoked compared to the non-provoked group for all facial expressions, especially anger. These results indicate that the HPA axis plays an important role in the formation of aggressive behavior in humans, as well. Importantly, different changes within the system, be it basal or acute, are associated with the same outcome in this task. More studies are needed, however, to better understand the role that each plays in different kinds of aggressive behavior, and the role information processing plays as a possible mediating variable. This extensive knowledge is necessary for better behavioral interventions.
This work addresses the algorithmic tractability of hard combinatorial problems. Basically, we are considering \NP-hard problems. For those problems we can not find a polynomial time algorithm. Several algorithmic approaches already exist which deal with this dilemma. Among them we find (randomized) approximation algorithms and heuristics. Even though in practice they often work in reasonable time they usually do not return an optimal solution. If we constrain optimality then there are only two methods which suffice for this purpose: exponential time algorithms and parameterized algorithms. In the first approach we seek to design algorithms consuming exponentially many steps who are more clever than some trivial algorithm (who simply enumerates all solution candidates). Typically, the naive enumerative approach yields an algorithm with run time $\Oh^*(2^n)$. So, the general task is to construct algorithms obeying a run time of the form $\Oh^*(c^n)$ where $c<2$. The second approach considers an additional parameter $k$ besides the input size $n$. This parameter should provide more information about the problem and cover a typical characteristic. The standard parameterization is to see $k$ as an upper (lower, resp.) bound on the solution size in case of a minimization (maximization, resp.) problem. Then a parameterized algorithm should solve the problem in time $f(k)\cdot n^\beta$ where $\beta$ is a constant and $f$ is independent of $n$. In principle this method aims to restrict the combinatorial difficulty of the problem to the parameter $k$ (if possible). The basic hypothesis is that $k$ is small with respect to the overall input size. In both fields a frequent standard technique is the design of branching algorithms. These algorithms solve the problem by traversing the solution space in a clever way. They frequently select an entity of the input and create two new subproblems, one where this entity is considered as part of the future solution and another one where it is excluded from it. Then in both cases by fixing this entity possibly other entities will be fixed. If so then the traversed number of possible solution is smaller than the whole solution space. The visited solutions can be arranged like a search tree. To estimate the run time of such algorithms there is need for a method to obtain tight upper bounds on the size of the search trees. In the field of exponential time algorithms a powerful technique called Measure&Conquer has been developed for this purpose. It has been applied successfully to many problems, especially to problems where other algorithmic attacks could not break the trivial run time upper bound. On the other hand in the field of parameterized algorithms Measure&Conquer is almost not known. This piece of work will present examples where this technique can be used in this field. It also will point out what differences have to be made in order to successfully apply the technique. Further, exponential time algorithms for hard problems where Measure&Conquer is applied are presented. Another aspect is that a formalization (and generalization) of the notion of a search tree is given. It is shown that for certain problems such a formalization is extremely useful.
N-acetylation by N-acetyltransferase 1 (NAT1) is an important biotransformation pathway of the human skin and it is involved in the deactivation of the arylamine and well-known contact allergen para-phenylenediamine (PPD). Here, NAT1 expression and activity were analyzed in antigen presenting cells (monocyte-derived dendritic cells, MoDCs, a model for epidermal Langerhans cells) and human keratinocytes. The latter were used to study exogenous and endogenous NAT1 activity modulations. Within this thesis, MoDCs were found to express metabolically active NAT1. Activities were between 23.4 and 26.6 nmol/mg/min and thus comparable to peripheral blood mononuclear cells. These data suggest that epidermal Langerhans cells contribute to the cutaneous N-acetylation capacity. Keratinocytes, which are known for their efficient N-acetylation, were analyzed in a comparative study using primary keratinocytes (NHEK) and different shipments of the immortalized keratinocyte cell line HaCaT, in order to investigate the ability of the cell line to model epidermal biotransformation. N-acetylation of the substrate para-aminobenzoic acid (PABA) was 3.4-fold higher in HaCaT compared to NHEK and varied between the HaCaT shipments (range 12.0"44.5 nmol/mg/min). Since B[a]P induced cytochrome p450 1 (CYP1) activities were also higher in HaCaT compared to NHEK, the cell line can be considered as an in vitro tool to qualitatively model epidermal metabolism, regarding NAT1 and CYP1. The HaCaT shipment with the highest NAT1 activity showed only minimal reduction of cell viability after treatment with PPD and was subsequently used to study interactions between NAT1 and PPD in keratinocytes. Treatment with PPD induced expression of cyclooxygenases (COX) in HaCaT, but in parallel, PPD N-acetylation was found to saturate with increasing PPD concentration. This saturation explains the presence of the PPD induced COX induction despite the high N-acetylation capacities. A detailed analysis of the effect of PPD on NAT1 revealed that the saturation of PPD N-acetylation was caused by a PPD-induced decrease of NAT1 activity. This inhibition was found in HaCaT as well as in primary keratinocytes after treatment with PPD and PABA. Regarding the mechanism, reduced NAT1 protein level and unaffected NAT1 mRNA expression after PPD treatment adduced clear evidences for substrate-dependent NAT1 downregulation. These results expand the existing knowledge about substrate-dependent NAT1 downregulation to human epithelial skin cells and demonstrate that NAT1 activity in keratinocytes can be modulated by exogenous factors. Further analysis of HaCaT cells from different shipments revealed an accelerated progression through the cell cycle in HaCaT cells with high NAT1 activities. These findings suggest an association between NAT1 and proliferation in keratinocytes as it has been proposed earlier for tumor cells. In conclusion, N-acetylation capacity of MoDCs as well as keratinocytes contribute to the overall N-acetylation capacity of human skin. NAT1 activity of keratinocytes and consequently the detoxification capacities of human skin can be modulated by the presence of exogenous NAT1 substrates and endogenous by the cell proliferation status of keratinocytes.
Stress is a common phenomenon for animals living in the wild, but also for humans in modern societies. Originally, the body's stress response is an adaptive reaction to a possibly life-threatening situation, and it has been shown to impact on energy distribution and metabolism, thereby increasing the chance of survival. However, stress has also been shown to impact on mating behaviour and reproductive strategies in animals and humans. This work deals with the effect of stress on reproductive behavior. Up to now, research has only focused on the effects of stress on reproduction in general. The effects of stress on reproduction may be looked at from two points of view. First, stress affects reproductive functioning by endocrine (e.g. glucocorticoid) actions on the reproductive system. However, stress can also influence reproductive behavior, i.e. mate choice and mating preferences. Animals and humans do not mate randomly, but exhibit preferences towards mating partners. One factor by which animals and humans choose their mating partners is similarity vs. dissimilarity: Similar mates usually carry more of one's own genes and the cooperation between similar mates is, at least theoretically, less hampered by expressing diverse behaviors. By mating with dissimilar mates on the other hand one may acquire new qualities for oneself, but also for one's offspring, useful to cope with environmental challenge. In humans we usually find a preference for similar mates. Due to the high costs of breeding, variables like cooperation and life-long partnerships may play a greater role than the acquaintance of new qualities.The present work focuses on stress effects on mating preferences of humans and will give a first answer to the question whether stress may affect our preference for similar mates. Stress and mating preferences are at the centre of this work. Thus, in the first Chapter I will give an introduction on stress and mating preferences and link these topics to each other. Furthermore, I will give a short summary of the studies described in Chapter II - Chapter IV and close the chapter with a general discussion of the findings and directions for further research on stress and mating preferences. Human mating behavior is complex, and many aspects of it may not relate to biology but social conventions and education. This work will not focus on those aspects but rather on cognitive and affective processing of erotic and sexually-relevant stimuli, since we assume that these aspects of mating behaviour are likely related to psychobiological stress mechanisms. Therefore, a paradigm is needed that measures such aspects of mating preferences in humans. The studies presented in Chapter II and Chapter III were performed in order to develop such a paradigm. In these studies we show that affective startle modulation may be used to indicate differences in sexual approach motivation to potential mating partners with different similarity levels to the participant. In Chapter IV, I will describe a study that aimed to investigate the effects of stress on human mating preferences. We showed that stress reverses human mating preferences: While unstressed individuals show a preference for similar mates, stressed individuals seem to prefer dissimilar mates. Overall, the studies presented in this work showed that affective startle modulation can be employed to measure mating preferences in humans and that these mating preferences are influenced by stress.
During and after application, pesticides enter the atmosphere by volatilisation and by wind erosion of particles on which the pesticide is sorbed. Measurements at application sites revealed that sometimes more than half of the amount applied is lost into the atmosphere within a few days. The atmosphere is an important part of the hydrologic cycle that can transport pesticides from their point of application and deposit them into aquatic and terrestrial ecosystems far from their point of use. In the region of Trier pesticides are widely used. In order to protect crops from pests and increase crop yields in the viniculture, six to eight pesticide applications take place between May and August. The impact that these applications have on the environmental pollution of the region is not yet well understood. The present study was developed to characterize the atmospheric presence, temporal patterns, transport and deposition of a variety of pesticides in the atmosphere of the area of Trier. To this purpose, rain samples were weekly collected at eight sites during the growing seasons 2000, 2001 and 2002, and air samples (gas and particle phases) were collected during the growing season 2002. Multiresidue analysis methods were developed to determine multiple classes of pesticides in rain water, particle- and gas-phase samples. Altogether 24 active ingredients and 3 metabolites were chosen as representative substances, focussing mainly on fungicides. Twenty-four of the 27 measured pesticides were detected in the rain samples; seventeen pesticides were detected in the air samples. The most frequently detected pesticides and at the highest concentrations, both in rain and air, were compounds belonging to the class of fungicides. The insecticide methyl parathion was also detected in several rain samples as well as two substances that are banned in Germany, such as the herbicides atrazine and simazine. Concentration levels varied during the growing season with the highest concentrations being measured in the late spring and summer months, coinciding with application times and warmer months. Concentration levels measured in the rain samples were, generally, in the order of rnng l-1. Though average concentrations for single substances were less than 100 ng l-1, total concentrations were considerable and in some instances well above the EU drinking water quality standard of 500 ng l-1 for total pesticides. Compared to the amounts applied for pest control, the amounts deposited by rain resulted between 0,004% and 0,10% of the maximum application rates. These low pesticide inputs from precipitation to surface-water bodies is not of concern in vinicultural areas where the impact of other sources, such as superficial runoff inputs from the treated areas and cleaning of field crop sprayers, is more important. However, the potential impacts of these aerial pesticide inputs to non-target sites, such as organic crops, and sensitive ecosystems are as yet not known. Concentration levels in the air samples were in the order of ng m-3 at sites close to the fields were pesticides were applied, while lower values, in the order of pg m-3, were detected at the site located further away from fields where applications were performed. The measured air concentration levels found in this study do not represent a concern for human health in terms of acute risk. Inhalation toxicity studies have shown that an acute potential risk only arises at air concentrations in the range of g m-3. Finally, it must be kept in mind that only a small number of chemicals that were applied in the area were analysed for in this study. In order to gain a better evaluation of the local atmospheric load of pesticides, a wider spectrum of applied substances (including metabolites) needs to be investigated.
Tropospheric ozone (O3) is known to have various detrimental effects on plants, such as visible leaf injury, reduced growth and premature senescence. Flux models offer the determination of the harmful ozone dose entering the plant through the stomata. This dose can then be related to phytotoxic effects mentioned above to obtain dose-response relationships, which are a helpful tool for the formulation of abatement strategies of ozone precursors. rnOzone flux models are dependant on the correct estimation of stomatal conductance (gs). Based on measurements of gs, an ozone flux model for two white clover clones (Trifolium repens L. cv Regal; NC-S (ozone-sensitive) and NC-R (ozone-resistant)) differing in their sensitivity to ozone was developed with the help of artificial neural networks (ANNs). White clover is an important species of various European grassland communities. The clover plants were exposed to ambient air at three sites in the Trier region (West Germany) during five consecutive growing seasons (1997 to 2001). The response parameters visible leaf injury and biomass ratio of NC-S/NC-R clone were regularly assessed. gs-measurements of both clones functioned as output of the ANN-based gs model, while corresponding climate parameters (i.e. temperature, vapour pressure deficit (VPD) and photosynthetic active radiation (PAR)) and various ozone concentration indices were inputs. The development of the model was documented in detail and various model evaluation techniques (e.g. sensitivity analysis) were applied. The resulting gs model was used as a basis for ozone flux calculations, which were related to above mentioned response parameters. rnThe results showed that the ANNs were capable of revealing and learning the complex relationship between gs and key meteorological parameters and ozone concentration indices. The dose-response relationships between ozone fluxes and visible leaf injury were reasonably strong, while those between ozone fluxes and NC-S/NC-R biomass ratio were fairly weak. The results were discussed in detail with respect to the suitability of the chosen experimental methods and model type.
For the first time, the German Census 2011 will be conducted via a new method the register based census. In contrast to a traditional census, where all inhabitants are surveyed, the German government will mainly attempt to count individuals using population registers of administrative authorities, such as the municipalities and the Federal Employment Agency. Census data that cannot be collected from the registers, such as information on education, training, and occupation, will be collected by an interview-based sample survey. Moreover, the new method reduces citizens' obligations to provide information and helps reduce costs significantly. The use of sample surveys is limited if results with a detailed regional or subject-matter breakdown have to be prepared. Classical estimation methods are sometimes criticized, since estimation is often problematic for small samples. Fortunately, model based small area estimators serve as an alternative. These methods help to increase the information, and hence the effective sample size. In the German Census 2011 it is possible to embed areas on a map in a geographical context. This may offer additional information, such as neighborhood relations or spatial interactions. Standard small area models, like Fay-Herriot or Battese-Harter-Fuller, do not account for such interactions explicitly. The aim of our work is to extend the classical models by integrating the spatial information explicitly into the model. In addition, the possible gain in efficiency will be analyzed.
This thesis introduces a calibration problem for financial market models based on a Monte Carlo approximation of the option payoff and a discretization of the underlying stochastic differential equation. It is desirable to benefit from fast deterministic optimization methods to solve this problem. To be able to achieve this goal, possible non-differentiabilities are smoothed out with an appropriately chosen twice continuously differentiable polynomial. On the basis of this so derived calibration problem, this work is essentially concerned about two issues. First, the question occurs, if a computed solution of the approximating problem, derived by applying Monte Carlo, discretizing the SDE and preserving differentiability is an approximation of a solution of the true problem. Unfortunately, this does not hold in general but is linked to certain assumptions. It will turn out, that a uniform convergence of the approximated objective function and its gradient to the true objective and gradient can be shown under typical assumptions, for instance the Lipschitz continuity of the SDE coefficients. This uniform convergence then allows to show convergence of the solutions in the sense of a first order critical point. Furthermore, an order of this convergence in relation to the number of simulations, the step size for the SDE discretization and the parameter controlling the smooth approximation of non-differentiabilites will be shown. Additionally the uniqueness of a solution of the stochastic differential equation will be analyzed in detail. Secondly, the Monte Carlo method provides only a very slow convergence. The numerical results in this thesis will show, that the Monte Carlo based calibration indeed is feasible if one is concerned about the calculated solution, but the required calculation time is too long for practical applications. Thus, techniques to speed up the calibration are strongly desired. As already mentioned above, the gradient of the objective is a starting point to improve efficiency. Due to its simplicity, finite differences is a frequently chosen method to calculate the required derivatives. However, finite differences is well known to be very slow and furthermore, it will turn out, that there may also occur severe instabilities during optimization which may lead to the break down of the algorithm before convergence has been reached. In this manner a sensitivity equation is certainly an improvement but suffers unfortunately from the same computational effort as the finite difference method. Thus, an adjoint based gradient calculation will be the method of choice as it combines the exactness of the derivative with a reduced computational effort. Furthermore, several other techniques will be introduced throughout this thesis, that enhance the efficiency of the calibration algorithm. A multi-layer method will be very effective in the case, that the chosen initial value is not already close to the solution. Variance reduction techniques are helpful to increase accuracy of the Monte Carlo estimator and thus allow for fewer simulations. Storing instead of regenerating the random numbers required for the Brownian increments in the SDE will be efficient, as deterministic optimization methods anyway require to employ the identical random sequence in each function evaluation. Finally, Monte Carlo is very well suited for a parallelization, which will be done on several central processing units (CPUs).
The subject of this thesis is a homological approach to the splitting theory of PLS-spaces, i.e. to the question for which topologically exact short sequences 0->X->Y->Z->0 of PLS-spaces X,Y,Z the right-hand map admits a right inverse. We show that the category (PLS) of PLS-spaces and continuous linear maps is an additive category in which every morphism admits a kernel and a cokernel, i.e. it is pre-abelian. However, we also show that it is neither quasi-abelian nor semi-abelian. As a foundation for our homological constructions we show the more general result that every pre-abelian category admits a largest exact structure in the sense of Quillen. In the pre-abelian category (PLS) this exact structure consists precisely of the topologically exact short sequences of PLS-spaces. Using a construction of Ext-functors due to Yoneda, we show that one can define for each PLS-space A and every natural number k the k-th abelian-group valued covariant and contravariant Ext-functors acting on the category (PLS) of PLS-spaces, which induce for every topologically exact short sequence of PLS-spaces a long exact sequence of abelian groups and group morphisms. These functors are studied in detail and we establish a connection between the Ext-functors of PLS-spaces and the Ext-functors for LS-spaces. Through this connection we arrive at an analogue of a result for Fréchet spaces which connects the first derived functor of the projective limit with the first Ext-functor and also gives sufficient conditions for the vanishing of the higher Ext-functors. Finally, we show that Ext^k(E,F) = 0 for a k greater or equal than 1, whenever E is a closed subspace and F is a Hausdorff-quotient of the space of distributions, which generalizes a result of Wengenroth that is itself a generalization of results due to Domanski and Vogt.
Large scale non-parametric applied shape optimization for computational fluid dynamics is considered. Treating a shape optimization problem as a standard optimal control problem by means of a parameterization, the Lagrangian usually requires knowledge of the partial derivative of the shape parameterization and deformation chain with respect to input parameters. For a variety of reasons, this mesh sensitivity Jacobian is usually quite problematic. For a sufficiently smooth boundary, the Hadamard theorem provides a gradient expression that exists on the surface alone, completely bypassing the mesh sensitivity Jacobian. Building upon this, the gradient computation becomes independent of the number of design parameters and all surface mesh nodes are used as design unknown in this work, effectively allowing a free morphing of shapes during optimization. Contrary to a parameterized shape optimization problem, where a smooth surface is usually created independently of the input parameters by construction, regularity is not preserved automatically in the non-parametric case. As part of this work, the shape Hessian is used in an approximative Newton method, also known as Sobolev method or gradient smoothing, to ensure a certain regularity of the updates, and thus a smooth shape is preserved while at the same time the one-shot optimization method is also accelerated considerably. For PDE constrained shape optimization, the Hessian usually is a pseudo-differential operator. Fourier analysis is used to identify the operator symbol both analytically and discretely. Preconditioning the one-shot optimization by an appropriate Hessian symbol is shown to greatly accelerate the optimization. As the correct discretization of the Hadamard form usually requires evaluating certain surface quantities such as tangential divergence and curvature, special attention is also given to discrete differential geometry on triangulated surfaces for evaluating shape gradients and Hessians. The Hadamard formula and Hessian approximations are applied to a variety of flow situations. In addition to shape optimization of internal and external flows, major focus lies on aerodynamic design such as optimizing two dimensional airfoils and three dimensional wings. Shock waves form when the local speed of sound is reached, and the gradient must be evaluated correctly at discontinuous states. To ensure proper shock resolution, an adaptive multi-level optimization of the Onera M6 wing is conducted using more than 36, 000 shape unknowns on a standard office workstation, demonstrating the applicability of the shape-one-shot method to industry size problems.
The catechol-O-methyltransferase gene (COMT) plays a crucial role in the metabolism of catecholamines in the frontal cortex. A single nucleotide polymorphism (Val158Met SNP, rs4680) leads to either methionine (Met) or valine (Val) at codon 158, resulting in a three- to fourfold reduction in COMT activity. The aim of the present study was to assess the COMT Val158Met SNP as a risk factor for attention-deficit/hyperactivity disorder (ADHD), ADHD symptom severity and co-morbid conduct disorder (CD) in 166 children with ADHD. The main finding of the present study is that the Met allele of the COMT Val158Met SNP was associated with ADHD and increased ADHD symptom severity. No association with co-morbid CD was observed. In addition, ADHD symptom severity and early adverse familial environment were positive predictors of lifetime CD. These findings support previous results implicating COMT in ADHD symptom severity and early adverse familial environment as risk factors for co-morbid CD, emphasizing the need for early intervention to prevent aggressive and maladaptive behavior progressing into CD, reducing the overall severity of the disease burden in children with ADHD.
Although it has been demonstrated that nociceptive processing can be modulated by heterotopically and concurrently applied noxious stimuli, the nature of brain processes involved in this percept modulation in healthy subjects remains elusive. Using functional magnetic resonance imaging (fMRI) we investigated the effect of noxious counter-stimulation on pain processing. FMRI scans (1.5 T; block-design) were performed in 34 healthy subjects (median age: 23.5 years; range: 20-31 yrs.) during combined and single application (duration: 15 s; ISI=36 s incl. 6 s rating time) of noxious interdigital-web pinching (intensity range: 6-15 N) and contact-heat (45-49 -°C) presented in pseudo-randomized order during two runs separated by approx. 15 min with individually adjusted equi-intense stimuli. In order to control for attention artifacts, subjects were instructed to maintain their focus either on the mechanical or on the thermal pain stimulus. Changes in subjective pain intensity were computed as percent differences (∆%) in pain ratings between single and heterotopic stimulation for both fMRI runs, resulting in two subgroups showing a relative pain increase (subgroup P-IN, N=10) vs. decrease (subgroup P-DE, N=12). Second level and Region of Interest analysis conducted for both subgroups separately revealed that during heterotopic noxious counter-stimulation, subjects with relative pain decrease showed stronger and more widespread brain activations compared to subjects with relative pain increase in pain processing regions as well as a fronto-parietal network. Median-split regression analyses revealed a modulatory effect of prefrontal activation on connectivity between the thalamus and midbrain/pons, supporting the proposed involvement of prefrontal cortex regions in pain modulation. Furthermore, the mid-sagittal size of the total corpus callosum and five of its subareas were measured from the in vivo magnetic resonance imaging (MRI) recordings. A significantly larger relative truncus size (P=.04) was identified in participants reporting a relative decrease of subjective pain intensity during counter-stimulation, when compared to subjects experiencing a relative pain increase. The above subgroup differences observed in functional and structural imaging data are discussed with consideration of potential differences in cognitive and emotional aspects of pain modulation.
Interoception - the perception of bodily processes - plays a crucial role in the subjective experience of emotion, consciousness and symptom genesis. As an alternative to interoceptive paradigms that depend on the participants" active cooperation, five studies are presented to show that startle methodology may be employed to study visceral afferent processing. Study 1 (38 volunteers) showed that startle responses to acoustic stimuli of 105 dB(A) intensity were smaller when elicited during the cardiac systole (R-wave +230 ms) as compared to the diastole (R +530 ms). In Study 2, 31 diabetic patients were divided into two groups with normal or diminished (< 6 ms/mmHg) baroreflex sensitivity (BRS) of heart rate control. Patients with normal BRS showed a startle inhibition during the cardiac systole as was found for healthy volunteers. Diabetic patients with diminished BRS did not show this pattern. Because diminished BRS is an indicator of impaired baro-afferent signal transmission, we concluded that cardiac modulation of startle is associated with intact arterial baro-afferent feedback. Thus, pre-attentive startle methodology is feasible to study visceral afferent processing. rnVisceral- and baro-afferent information has been found to be mainly processed in the right hemisphere. To explore whether cardiac modulation of startle eye blink is lateralized as well, in Study 3, 37 healthy volunteers received 160 unilateral acoustic startle stimuli presented to both ears, one at a time (R +0, 100, 230, 530 ms). Startle response magnitude was only diminished at R +230 ms and for left-ear presentation. This lateralization effect in the cardiac modulation of startle eye blink may reflect the previously described advantages of right-hemispheric brain structures in relaying viscero- and baro-afferent signal transmission. rnThis lateralization effect implies that higher cognitive processes may also play a role in the cardiac modulation of startle. To address this question, in Study 4, 25 volunteers responded first by 'fast as possible' button pushes (reaction time, RT), and second, rated perceived intensity of 60 acoustic startle stimuli (85, 95, or 105 dB; R +230, 530 ms). RT was divided into evaluation and motor response time. Increasing stimulus intensity enhanced startle eye blink, intensity ratings, and RT components. Eye blinks and intensity judgments were lower when startle was elicited at a latency of R +230 ms, but RT components were differentially affected. It is concluded that the cardiac cycle affects the attentive processing of acoustic startle stimuli. rnBeside the arterial baroreceptors, the cardiopulmonary baroreceptors represent another important system of cardiovascular perception that may have similar effects on startle responsiveness. To clarify this issue, in Study 5, Lower Body Negative Pressure at gradients of 0, -10, -20, and -30 mmHg was applied to unload cardiopulmonary baroreceptors in 12 healthy males, while acoustic startle stimuli were presented (R +230, 530 ms). Unloading of cardiopulmonary baroreceptors increased startle eye blink responsiveness. Furthermore, the effect of relative loading/unloading of arterial baroreceptors on startle eye blink responsiveness was replicated. These results demonstrate that the loading status of cardiopulmonary baroreceptors also has an impact on brainstem-based CNS processes. rnThus, the cardiac modulation of acoustic startle is feasible to reflect baro-afferent signal transmission of multiple neural sources, it represents a pre-attentive method that is independent of active cooperation, but its modulatory effects also reach higher cognitive, attentive processes.rn
International private equity development is highly volatile with increasing global diversification. This thesis examines the transaction patterns of cross-border private equity investment with a particular focus on the affinity of country pairs. Analysis is based on a comprehensive dataset of 99 countries over 25 years. A three-dimensional gravity model analysis covering source and host country over time exposes the effects of the country determinants: economic mass, economic distance, banking system, corporate endowment, as well as legal, political, and institutional system on the transactions. A new method is developed to examine countries in their dual roles as investor and target. This approach verifies their global importance as source and host, and also makes possible an analysis of overall private equity investment. For private equity-specific multi-investor deals, a scheme is designed to measure cross-border activity with more precision by participation, proportional deal participation, and deal flow. The analysis identifies intense level of affinity between country pairs and reveals that no single country is ideal for private equity activity. Instead, the findings show that the specific push and pull factors within each country constellation define the optimal country as trading partner. The results verify a correlation between cross-border deals and economic masses and reduced economic distance of countries. Geographic distance and cultural similarities, such as language and legal system, intensify the likelihood of initiating transactions. International trade-oriented countries with a high level of development lower the entrance barriers and increase the chances of deal success. A well-funded financial system for the investor and an efficient and competitive banking system of target countries enhance the probability of investment between countries. Also relevant for the likelihood of starting cross-border deals are low corporate tax burdens and advanced scientific competitiveness, and a well-developed stock market in the investor country. Fundamental to frequency and likelihood of success are well-established, high standards of a country- social, political, and legal systems with widespread confidence in the rules of society. In particular, the reliability of contract enforcement, with proven quality of regulations that promote private sector development, proves to be crucial for deal success.
In this study, candidate loci for periodic catatonia (SCZD10, OMIM #605419) on chromosome 15q15 and 22q13.33 have been fine mapped and investigated. Previously, several studies found evidences for a major susceptibility locus on chromosome 15q15 and a further potential locus on 22q13.33 pointing to genetic heterogeneity. Fine mapping was done in our multiplex families through linkage and mutational analysis using genomic markers selected from public databases. Positional candidate genes like SPRED1 and BRD1, and ultra-conserved elements were investigated by direct sequencing in these families. The results narrow down the susceptibility locus on chromosome 15q14-15q15.1 to a region between markers D15S1042 and D15S968, as well as exclusion of SPRED1 and ultra-conserved elements as susceptibility candidates. Fine mapping for two chromosome 23q13.33-linked families showed that the recombination events would place the disease-causing gene to a telomeric ~577 Kb interval and SNP rs138880 investigation revealed an A-allele in the affected person, therefore excludes BRD1 as well as confirmed MLC1 to be the candidate gene for periodic catatonia.
In Beloved, Jazz and Paradise, Toni Morrison negotiates ways of individual and collective identity formation through figurations of space and trauma. In geographical spaces that are public and private, open and closed, inclusive and exclusive, space of the past and spaces of the present, Morrison writes discursive spaces in which to create individual and communal African American history and identity, based on the traumatic hi-stories at the core of the Black American experience: the Middle Passage, slavery, Jim Crow and the Civil Rights Movement, just to name a few. In the three novels, Toni Morrison subscribes to a postmodern notion of space and place, presenting it as relative to the individual- frame of mind. Places are used as metonymies for the protagonists" traumatized minds and their different ways of dealing with trauma. Trauma that is not worked through and transcended is presented by Morrison as impacting the protagonists- ability to fashion a home out of a vast and often hostile space. The physical and mental space of Morrison- protagonists is occupied by historical traumata that disables the protagonists to find a place in the present without revisiting the places of their troubled past. While this burdens their lives, it also opens up a historical and metahistorical discourse that allows the revision of mainstream historiography to include minority histories of oppression and trauma. Morrison reconfigures the American historical landscape by emphasizing the subjectivity of any history and offering alternatives to historical grand narratives through her historiographic metafiction. All three novels explore the possibility of reconciliation between past trauma and present life. Doing so requires Morrison to send her protagonists on strenuous journeys through time and space in order to visit the past trauma that keeps them from making a home in the here and now. The protagonists venture back to the primal scenes that bear major significance for their lives but have been suppressed for being too painful to remember. Their pain thus awakens anew, but out of it grow the possibility of a life in the present and the hope for a future. The pasts Morrison thus digs up serve as anchors to situate the African American place in the American historical landscape. Those primal places have a geographical as well as a historical and psychological quality, as places in Morrison- novels are often used as metonymies for the protagonists" traumatized minds, containing the memory of the traumatic past. By spatializing time, Morrison makes history accessible to a communal working through, thus countering the modernist impulse to treat memory as a private faculty embedded in the individual- psyche. This makes it difficult, for African Americans with individual recollections of slavery and racist oppression for example, to use traumatic memory as the basis for a common sense of identity. Morrison uses spatialized time as a forum to discover this basis, to allow for the establishment of a common historical bond. At the same time, she warns against instrumentalizing a common history to exclude those who do not share it. Any history, for Morrison, should be open and flexible enough to accommodate different perspectives. Essentially, Morrison suggests that western historiography is a discursive construct. By allowing, in all three novels, a polyphonic weaving of different equal histories to destablize a single, authoritative, hegemonic historiography, Morrison gives African Americans the power to construct her own past, her own present, and thereby claim back her identity. Moreover, Morrison destabilizes the duality of private space and public space that has long served to distinguish subjective individual memory from objective communal history and thus to legitimize certain accounts of history at the expense of others. The gendered as well as the racial other, by virtue of being excluded from the public sphere, have been excluded from their own historicization. By opening up the private sphere of personal trauma and loss, Morrison spatializes personal memory in a way that it forms a parallel public sphere in which African Americans may negotiate their historicity, move out of the timelessness of the private into the historicized public. By opening up the traditionally private sphere of the home to the public and turning it into a deeply political place, Morrison redefines home in a way that it does not necessarily conform to the classic view of a closed-off shelter but rather a transient place with flexible boundaries that allows for the formation of liberated individual and communal identities out of (hi)stories of pain and trauma.
One mechanism underlying the acquisition of interpersonal attitudes is the formation of an association between a valenced unconditioned stimulus (US) and an affectively neutral conditioned stimulus (CS). However, a stimulus (e.g., a person) is not always and necessarily perceived to be unambiguously positive or negative. An individual can be negative regarding abstract (trait) information but at the same time display a positive (concrete) behavior. The present research deals with the question of whether the valence of abstract or concrete information about a US is encoded and subsequently transferred to an associated CS. The central assumptions are that the valence of the concrete information is more important for the evaluation of the US, whereas the abstract information is more important for the evaluation of the CS. The rationale behind these assumptions is that the US is a psychologically proximal stimulus because it elicits a more direct affective reaction. The CS, however, is psychologically more distal because it is merely associated with the US and is therefore only experienced indirectly. It is postulated that the associative relation between US and CS constitutes a dimension of psychological distance. In four studies, the valence of abstract and concrete information about a number of USs was manipulated. Within an evaluative learning paradigm, these stimuli were associated with affectively neutral CSs. As predicted, ambivalent USs were evaluated according to the valence of the concrete information. The evaluation of CSs, however, was influenced more strongly by the valence of the abstract information. Moreover, in a subsequent lexical decision task, participants were faster to categorize abstract (vs. concrete) stimuli when the stimuli were preceded by a CS prime as compared to a US prime. The results provide first evidence that perceived psychological distance influences the evaluations of US and CS in an associative evaluative learning paradigm.
The reduction of information contained in model time series through the use of aggregating statistical performance measures is very high compared to the amount of information that one would like to draw from it for model identification and calibration purposes. It is readily known that this loss imposes important limitations on model identification and -diagnostics and thus constitutes an element of the overall model uncertainty as essentially different model realizations with almost identical performance measures (e.g. r-² or RMSE) can be generated. In three consecutive studies the present work proposes an alternative approach towards hydrological model evaluation based on the application of Self-Organizing Maps (SOM; Kohonen, 2001). The Self-Organizing Map is a type of artificial neural network and unsupervised learning algorithm that is used for clustering, visualization and abstraction of multidimensional data. It maps vectorial input data items with similar patterns onto contiguous locations of a discrete low-dimensional grid of neurons. The iterative training of the SOM causes the neurons to form a discrete, data-compressed representation of the high-dimensional input data. Using appropriate visualization techniques, information on distributions, patterns and relationships in complex data sets can be extracted. Irrespective of their potential, SOM applications have earned very little attention in hydrological modelling compared to other artificial neural network techniques. Therefore, the aim of the present work is to demonstrate that the application of Self-Organizing Maps has very high potential to address fundamental issues of model evaluation: It is shown that the clustering and classification of model time series by means of SOM can provide useful insights into model behaviour. In combination with the diagnostic properties of Signature Indices (Gupta et al., 2008; Yilmaz et al., 2008) SOM provides a novel tool for interpreting the model parameters in the hydrological context and identifying parameter sets that simultaneously meet multiple objectives, even if the corresponding model realizations belong to different models. Moreover, the presented studies and reviews also encourage further studies on the application of SOM in hydrological modelling.