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The midcingulate cortex has become the focus of scientific interest as it has been associated with a wide range of attentional phenomena. This survey found evidence indicating the relevance of gender and handedness for measures of regional cortical morphology. Although gender was associated with structural variations concerning the neuroanatomy of the midcingulum bundle as well, handedness did not emerge in the analyses of white matter characteristics as significant factor. Hemispheric differences were found at the level of both gray and white matter. Turning to the functional implications of neuroanatomical variations and comparing subjects with a pronounced and a low degree of midcingulate folding, which indicates differential expansions of cytoarchitectural areas, behavioral and electrophysiological differences in the processing of interference became evident. A high degree of leftward midcingulate fissurization was associated with better behavioral performance, presumably caused by a more effective conflict-monitoring system triggering fast and automatic attentional filtering mechanisms. Subjects exhibiting a lower degree of midcingulate fissurization rather seem to rely on more effortful control processes. These results carry implications not only concerning neuronal representations of individual differences in attentional processes, but might also be of relevance for the refinement of models for mental disorders.
As a target for condemnation, the thematic prevalence of racism in African American novels of satire is not surprising. In order to confront this vice in its shifting manifestations, however, the African American satirist has to employ special techniques. This thesis examines some of these devices as they occur in George Schuyler- Black No More, Charles Wright- The Wig, and Percival Everett- Erasure. Given the reciprocity of target and technique in the satiric context, close attention is paid to how the authors under study locate and interrogate racism in their narratives. In this respect, the significance of anti-essentialist Marxist criticism in Schuyler- Black No More and the author- portrayal of the society of his time as capitalist machinery is examined. While Schuyler is concerned with exposing the general socioeconomic workings of the 1920s from a Marxist perspective, Wright offers the reader perspective into how this oppressive machinery psychologically manipulates and corrupts the individual in the historic context of Lyndon B. Johnson- political vision of the Great Society. Everett then elaborates on the epistemological concern which is traceable in Wright- work and addresses the role media representation plays in manufacturing images and rigid categories that shape systematic racism. As such, the present study not only highlights the versatility of satire as a rhetorical secret weapon and thus ventures toward the idiosyncrasies of the African American novel of satire, it also makes an effort to trace the ever-changing face of racial discrimination.
Mental processes are filters which intervene in the literary presentation of nature. This article will take you on a journey through literary landscapes, starting from Joseph Furphy and end-ing with Gerald Murnane. It will try to show the development of Australian literary landscape depiction. The investigation of this extensive topic will show that the perception of the Aus-tralian landscape as foreign and threatening is a coded expression of the protagonists" crisis of identity due to their estrangement from European cultural roots. Only a feeling of being at home enables the characters to perceive landscapes in a positive way and allows the author to depict intimate and familiar views of nature. This topic will be investigated with a range of novels to reveal the development of this theme from the turn of the nineteenth century (the time of Furphy- novel Such is Life) up to the present (i.e. novels by Malouf, Foster, Hall, Murnane).
ENGLISH ACADEMIC LITERARY DISCOURSE IN SOUTH AFRICA 1958-2004: A REVIEW OF 11 ACADEMIC JOURNALS
(2007)
This study examines the discipline of English studies in South Africa through a review of articles published in 11 academic journals over the period 1958"2004. The aims are to gain a better understanding of the functions of peer-reviewed journals, to reveal the presence of rules governing discursive production, and to uncover the historical shifts in approach and choice of disciplinary objects. The Foucauldian typology of procedures determining discursive production, that is: exclusionary, internal and restrictive procedures, is applied to the discipline of English studies in order to elucidate the existence of such procedures in the discipline. Each journal is reviewed individually and comparatively. Static and chronological statistical analyses are undertaken on the articles in the 11 journals in order to provide empirical evidence to subvert the contention that the discipline is unruly and its choice of objects random. The cumulative results of this analysis are used to describe the major shifts primarily in ranges of disciplinary objects, but also in metadiscursive and thematic debates. Each of the journals is characterised in relation to what the overall analysis reveals about the mainstream developments. The two main findings are that, during the period under review, South African imaginative written artefacts have moved from a marginal position to the centre of focus of the discipline; and that the conception of what constitutes the "literary" has returned to a pre-Practical criticism definition, broadly inclusive of a variety of types of artefact including imaginative writing, such as autobiography, letters, journals and orature.
There is ample evidence that the personality trait of extraversion is associated with frequent experiences of positive affect whereas introversion is associated with less frequent experiences of positive affect. According to a theory of Watson et al. (1997), these findings demonstrate that positive affect forms the conceptual core of extraversion. In contrast, several other researchers consider sociability - and not positive affect - as the core of extraversion. The aim of the present work is to examine the relation between extraversion and dispositional positive affect on the neurobiological level. In 38 participants resting cerebral blood flow was measured with continuous arterial spin labeling (CASL). Each participant was scanned on two measurement occasions separated by seven weeks. In addition, questionnaire measures of extraversion and dispositional positive affect were collected. To employ CASL for investigating the biological basis of personality traits, the psychometric properties of CASL blood flow measurements were examined in two studies. The first study was conducted to validate the CASL technique. Using a visual stimulation paradigm, the expected pattern of activity was found, i.e. there were specific differences in blood flow in the primary and secondary visual areas. Moreover, the results in the first measurement occasion could be reproduced in the second. Thus, these results suggest that CASL blood flow measurements have a high degree of validity. The aim of the second psychometric study was to examine whether resting blood flow measurements are characterized by a sufficient trait stability to be used as a marker for personality traits. Employing the latent state-trait theory developed by Steyer and colleagues, it was shown that about 70 % of the variance of regional blood flow could be explained by individual differences in a latent trait. This suggests that blood flow measurements have sufficient trait stability for investigating the biological basis of personality traits. In the third study, the relation between extraversion and dispositional positive affect was investigated on the neurobiological level. Voxel-based analyses showed that dispositional positive affect was correlated with resting blood flow in the ventral striatum, i.e. a brain structure that is associated with approach behavior and reward processing. This biological basis was also found for extraversion. In addition, when extraversion was statistically controlled, the association between dispositional positive affect and blood flow in the ventral striatum was still present. However, when dispositional positive affect was statistically controlled, the relation between extraversion and the ventral striatum disappeared. Taken together, these results suggest that positive affect forms a core of extraversion on the neurobiological level. The present findings thus add psychophysiological evidence to the theory of Watson et al. (1997), which suggests that positive affect forms the conceptual core of extraversion.
Memory consists of multiple anatomically and functionally distinct systems. Animal studies suggest that stress modulates multiple memory systems in a manner that favors nucleus caudatus-based stimulus-response learning at the expense of hippocampus-based spatial learning. The present work aimed (i) to translate these findings to humans, (ii) to determine the involvement of the stress hormone cortisol in this effect, and (iii) to assess whether the use of stimulus-response and spatial strategies is a long lasting person characteristic. To address these issues we developed a new paradigm that differentiates the use of spatial and stimulus-response learning in humans. Our findings indicate that (i) psychosocial stress (Trier Social Stress Test) modulates the use of spatial and stimulus-response learning in humans, (ii) cortisol plays a key role in this modulatory effect of stress, and (iii) the use of spatial and stimulus-response learning is affected by situational rather than long lasting person factors.
In addition to flood disasters on major rivers, damage caused by the flooding of smaller and medium-sized tributaries is also of considerable significance. To ensure that flood protection measures are effective, engineering flood prevention measures on the rivers must be supported by integrated catchment management. This includes decentralised water retention measures implemented in the sectors of forestry, agriculture and in residential areas. Within this scope new instruments have to be elaborated and introduced, such as GIS-based systems and systems for the evaluation of economic consequences and eco-efficiency of flood damage precaution measures associated with land-use. These are extremely significant for improving information management, the prevention of advice to the general public and for the acceptance of flood precaution measures. The conference intends to promote scientific exchange between specialists working on all areas concerning integrated catchment management. This includes the methodology for identification of catchment types prone to flooding hazards, the control and validation of land-use concepts for decentralised water retention as well as its combination and upscaling procedures up to mesoscale catchments. As catchment management is not only the concern of natural scientists the strategies for enhancing catchment management and the development of decision-support tools will also be important topics of the conference. ***Addenda *1. The articles from page 136 to 161 belong to session 5 *2. Article page 107: Ancient irrigation strategies: land use and hazard mitigation in Ma-´rib, Yemen (New list of authors: Ueli Brunner (a) , Michael Schütz (b), Dana Pietsch (c), Peter Kühn (c), Thomas Scholten (c), Iris Gerlach (d))
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.
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.
In this thesis, we investigate the quantization problem of Gaussian measures on Banach spaces by means of constructive methods. That is, for a random variable X and a natural number N, we are searching for those N elements in the underlying Banach space which give the best approximation to X in the average sense. We particularly focus on centered Gaussians on the space of continuous functions on [0,1] equipped with the supremum-norm, since in that case all known methods failed to achieve the optimal quantization rate for important Gauss-processes. In fact, by means of Spline-approximations and a scheme based on the Best-Approximations in the sense of the Kolmogorov n-width we were able to attain the optimal rate of convergence to zero for these quantization problems. Moreover, we established a new upper bound for the quantization error, which is based on a very simple criterion, the modulus of smoothness of the covariance function. Finally, we explicitly constructed those quantizers numerically.
The aim of the thesis was to investigate the role of the immune system in fibromyalgia (FM), as part of a dynamic co-regulation between different bodily systems. FM is a chronic musculoskeletal disorder characterized by widespread pain and specific tender points, combined with other symptoms including fatigue, sleep disturbances, morning stiffness and anxiety. The main goal of the work was to identify possible dysregulation of peripheral immune and endocrine parameters in patients with FM compared to matched healthy controls. Moreover, the possible relation between symptom complaints and the specific parameters measured was also evaluated. A first approach was to investigate possible differences between FM patients and controls in the expression of cytokines, as they have been implicated in the occurrence of several of the symptoms associated with FM. Furthermore, adhesion molecules which are involved in cell-to-cell communication and immune cell trafficking were also studied. The latter are known to be regulated by both cytokines and glucocorticoids (GCs) and their expression is often found altered in patients with immune dysregulation. It was expected that subjects with FM would have an increased production of proinflammatory cytokines and/or a reduced antiinflammatory cytokine production and that certain cytokines and/or adhesion molecules would be differently regulated by dexamethasone (DEX). Unstimulated blood was used in the analysis of adhesion molecule expression by flow cytometry while stimulated whole blood cell cultures were used in cytokine flow cytometry assays. Peripheral blood mononuclear cells (PBMCs) were also cultured and the supernatants collected to determine the concentration of cytokines by biochip protein array. In addition, serum samples were used in enzyme-linked immunosorbent assays (ELISA) for quantification of soluble adhesion molecules. L-selectin was found elevated on monocytes and neutrophils of FM patients. A bias toward lower IL-4 levels was observed in FM patients. Based on studies showing differences in glucocorticoid receptor (GR) affinity and disturbances associated with loss of hypothalamic-pituitary-adrenal (HPA) axis resiliency in FM, it was hypothesized whether FM would be associated with abnormalities in glucocorticoid sensitivity. Total plasma cortisol and salivary free cortisol were quantified by ELISA and time-resolved fluorescence immunoassay, respectively. GR sensitivity through DEX inhibition of IL-6, in stimulated whole blood, was evaluated after cytokine quantification by ELISA. The corticosteroid receptors, GR alpha and mineralocorticoid receptor (MR), as well as the glucocorticoid-induced leucine zipper (GILZ) and the FK506 binding protein 5 mRNA expression were assessed in PBMCs by real-time reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, sequencing of RT-PCR products and/or genomic DNA was used for mutational analysis of the corticosteroid receptors. We observed lower basal plasma cortisol levels (borderline statistical significance) and a lower expression of corticosteroid receptors and GILZ in FM patients when compared to healthy controls. The minor allele of the MR single nucleotide polymorphism (SNP) rs5522 was found more often in FM patients than in controls. In addition, female carriers of this SNP seemed to have reduced salivary cortisol responses to a strong psychological stressor (Trier Social Stress Test) compared to non-carriers. FM patient carriers of an MR intronic SNP (rs17484245), before exon 3, were associated with significantly higher scores of depression symptoms compared to patient non-carriers. The thesis includes also a comprehensive analysis of the complexity of GR regulation and the role of alternative mRNA splicing. It focuses on the differential expression of the untranslated GR first exons, their high sequence homology among different species and how genetic determinants, without apparent relevance, may have implications in health and disease. In FM patients, GR exon 1-C expression was found lower and a significant difference was observed when comparing GR 1-C expression between antidepressant-free and patients who had taken antidepressants until two weeks before sample collection. In summary, the study shows a slight disturbance of some components of the innate immune system of FM patients and suggests an enhanced adhesion and possible recruitment of leukocytes to inflammatory sites. The reduced expression of corticosteroid receptors and possibly the reduced MR function may be associated with an impaired function of the HPA axis in these patients. A hyporesponsiveness of the HPA axis under stress or disturbances of the stress response could make these patients more vulnerable to cytokines and inflammation which, compounded by lower antiinflammatory mediators, may sustain some of the symptoms that contribute to the clinical picture of FM.
During the last decade, anatomic and physiological neuroscience research has yielded extensive information on the physiological regulators of short-term satiety, visceral and interoceptive sensation. Distinct neural circuits regulate the elements of food ingestion physiologically. The general aim of the current studies is to elucidate the peripheral neural pathways to the brain in healthy subjects to establish the groundwork for the study of the pathophysiology of bulimia nervosa (BN). We aimed to define the central activation pattern during non-nutritive gastric distension in humans, and aimed to define the cognitive responses to this mechanical gastric distension. We estimated regional cerebral blood flow with 15O-water positron emission tomography during intragastric balloon inflation and deflation in 18 healthy young women of normal weight. The contrast between inflated minus deflated in the exploratory analysis revealed activation in more than 20 brain regions. The analysis confirmed several well known areas in the central nervous system that contribute to visceral processing: the inferior frontal cortex, representing a zone of convergence for food related stimuli; the insula and operculum referred to as "visceral cortex"; the anterior cingulate gyrus (and insula), processing affective information; and the brainstem, a site of vagal relay for visceral afferent stimuli. Brain activation in the left ventrolateral prefrontal cortex was reproducible. This area is well known for higher cognitive processing, especially reward-related stimuli. The ventrolateral prefrontal cortex with the insular regions may provide a link between the affective and rewarding components of eating and disordered eating as observed in BN and binge-eating obesity. Gastric distension caused a significant rapid, reversible, and reproducible increase in the feelings of fullness, sleepiness, and gastric discomfort as well as a significant rapid, reversible, and reproducible decrease in the feeling of hunger. We showed that mechanical activation of the neurocircuitry involved in meal termination led to the described phenomena. The current brain activation studies of non-painful, proximal gastric distension could provide groundwork in the field of abnormal eating behavior by suggesting a link between visceral sensation and abnormal eating patterns. A potential treatment for disordered eating and obesity could alter the conscious and unconscious perception and interoceptive awareness of gastric distension contributing to meal termination.
The human brain is characterised by two apparently symmetrical cerebral hemispheres. However, the functions attributed to each half of the brain are very distinct with a relative specialisation of the left hemisphere for language processing. Most laterality research has been performed on a behavioural level, using techniques such as visual half-field presentation. The visual half-field technique involves the presentation of stimuli in the left or right visual field for a very short time (about 200 ms). During the presentation of lateralized stimuli, the gaze of the participants is fixated on a centrally presented fixation cross. This technique takes advantage of the anatomy of the visual pathway as the temporal hemiretinae project ipsilateral, while the nasal hemiretinae project contralateral. Thus, stimuli presented in the left or right visual field are initially processed in the contralateral hemisphere. Language organisation can also be directly investigated using functional magnetic resonance imaging (fMRI). Both behavioural and neuroimaging studies showed that about 95% of right-handed men have a left hemispheric specialisation for language. In contrast, data on language organisation in women are ambiguous. It is supposed that this ambivalent picture might be associated with changes in gonadal steroid levels in blood during the menstrual cycle. However, gonadal steroid effects are complex and their role in functional cerebral lateralization is still open to discussion. The aim of this PhD project was to investigate, using fMRI: (1) the processing of linguistic information initially received in the specialised, non-specialised or both hemispheres; (2) linking the associated brain activation pattern with progesterone levels during the menstrual cycle. Firstly, brain activation was measured in 16 right-handed, healthy males during processing of different components of language (orthography, phonology and semantics) after reception in the left, right or both hemispheres. Secondly, to investigate changes in language organisation during the menstrual cycle, we conducted an event-related fMRI study during semantic and phonological processing also using visual half-field and central presentation of linguistic stimuli. Our results revealed higher BOLD signal intensity change in the visual cortex contralateral to the visual field of stimulus presentation compared to the ipsilateral visual cortex reflecting the crossing of visual pathways. We also found support for the hypothesis that the superiority of word recognition in the left VWFA is the result of a reduced activity in the right VWFA under left hemispheric control. Further, linguistic information received in the subdominant RH, is interhemispheric transferred to the left hemisphere for phonological processing. Semantic processing in contrast occurs in the specialised and in the non-specialised hemisphere. For the group of women, data analysis revealed that during semantic processing, salivary progesterone levels correlated positively with brain activity of the left superior frontal gyrus, left middle and inferior occipital gyri and bilateral fusiform gyrus. In contrast, the brain activation pattern for phonological processing did not change significantly across the menstrual cycle. In conclusion, the effect of serum progesterone levels on brain activity is task and region specific.
The glucocorticoid (GC) cortisol, main mediator of the hypothalamic-pituitary-adrenal axis, has many implications in metabolism, stress response and the immune system. GC function is mediated mainly via the glucocorticoid receptor (GR) which binds as a transcription factor to glucocorticoid response elements (GREs). GCs are strong immunosuppressants and used to treat inflammatory and autoimmune diseases. Long-term usage can lead to several irreversible side effects which make improved understanding indispensable and warrant the adaptation of current drugs. Several large scale gene expression studies have been performed to gain insight into GC signalling. Nevertheless, studies at the proteomic level have not yet been made. The effects of cortisol on monocytes and macrophages were studied in the THP-1 cell line using 2D fluorescence difference gel electrophoresis (2D DIGE) combined with MALDI-TOF mass spectrometry. More than 50 cortisol-modulated proteins were identified which belonged to five functional groups: cytoskeleton, chaperones, immune response, metabolism, and transcription/translation. Multiple GREs were found in the promoters of their corresponding genes (+10 kb/-0.2 kb promoter regions including all alternative promoters available within the Database for Transcription Start Sites (DBTSS)). High quality GREs were observed mainly in cortisol modulated genes, corroborating the proteomics results. Differential regulation of selected immune response related proteins were confirmed by qPCR and immuno-blotting. All immune response related proteins (MX1, IFIT3, SYWC, STAT3, PMSE2, PRS7) which were induced by LPS were suppressed by cortisol and belong mainly to classical interferon target genes. Mx1 has been selected for detailed expression analysis since new isoforms have been identified by proteomics. FKBP51, known to be induced by cortisol, was identified as the strongest differentially expressed protein and contained the highest number of strict GREs. Genomic analysis of five alternative FKBP5 promoter regions suggested GC inducibility of all transcripts. 2D DIGE combined with 2D immunoblotting revealed the existence of several previously unknown FKBP51 isoforms, possibly resulting from these transcripts. Additionally multiple post-translational modifications were found, which could lead to different subcellular localization in monocytes and macrophages as seen by confocal microscopy. Similar results were obtained for the different cellular subsets of human peripheral blood mononuclear cells (PBMCs). FKBP51 was found to be constitutively phosphorylated with up to 8 phosphosites in CD19+ B lymphocytes. Differential Co-immunoprecipitation for cytoplasm and nucleus allowed us to identify new potential interaction partners. Nuclear FKBP51 was found to interact with myosin 9, whereas cytosolic FKBP51 with TRIM21 (synonym: Ro52, Sjögren`s syndrome antigen). The GR has been found to interact with THOC4 and YB1, two proteins implicated in mRNA processing and transcriptional regulation. We also applied proteomics to study rapid non-genomic effects of acute stress in a rat model. The nuclear proteome of the thymus was investigated after 15 min restraint stress and compared to the non-stressed control. Most of the identified proteins were transcriptional regulators found to be enriched in the nucleus probably to assist gene expression in an appropriate manner. The proteomic approach allowed us to further understand the cortisol mediated response in monocytes/macrophages. We identified several new target proteins, but we also found new protein variants and post-translational modifications which need further investigation. Detailed study of FKBP51 and GR indicated a complex regulation network which opened a new field of research. We identified new variants of the anti-viral response protein MX1, displaying differential expression and phosphorylation in the cellular compartments. Further, proteomics allowed us to follow the very early effects of acute stress, which happen prior to gene expression. The nuclear thymocyte proteome of restraint stressed rats revealed an active preparation for subsequent gene expression. Proteomics was successfully applied to study differential protein expression, to identify new protein variants and phosphorylation events as well as to follow translocation. New aspects for future research in the field of cortisol-mediated immune modulation have been added.
In this psycho-neuro-endocrine study the molecular basis of different variants of steroid receptors as well as highly conserved non steroidal receptors was investigated. These nuclear receptors (NRs) are important key regulators of a wide variety of different physiological and pathophysiological challenges ranging from inflammation and stress to complex behaviour and disease. NRs control gene transcription in a ligand dependent manner and are embedded in the huge interaction network of the neuroendocrine and immune system. Two receptors, the glucocorticoid receptor (GR) and the chicken ovalbumin upstream promoter-transcription factorII (Coup-TFII), both expressed in the immune and nervous system, were investigated regarding possible splice variants and their implication in the control of gene transcription. Both NRs are known to interact and modulate each other- target gene regulation. This study could be shown that both NRs have different splice variants that are expressed in a tissue specific manner. The different 5-´alternative transcript variants of the human GR were in silico identified in other species and evidence for a highly conserved and tightly controlled function was provided. Investigations of the N-terminal transactivation domain of the GR showed a deletion suggesting an altered glucocorticoid-dependent transactivation profile. The newly identified alternative transcript variant of Coup-TFII leads to a DNA binding deficient Coup-TFII isoform that is highly expressed in the brain. This Coup-TFII isoform alters Coup-TFII target gene expression and is suggested to interact with GR via its ligand binding domain resulting in an impaired GR target gene regulation in the nervous system. In this thesis it was demonstrated that NR variants are important for the understanding of the enormous regulatory potential of this receptor family and have to be taken into account for the development of therapeutic strategies for complex diseases such as stress related and neurodegenerative disorders.
Considering the numerical simulation of mathematical models it is necessary to have efficient methods for computing special functions. We will focus our considerations in particular on the classes of Mittag-Leffler and confluent hypergeometric functions. The PhD Thesis can be structured in three parts. In the first part, entire functions are considered. If we look at the partial sums of the Taylor series with respect to the origin we find that they typically only provide a reasonable approximation of the function in a small neighborhood of the origin. The main disadvantages of these partial sums are the cancellation errors which occur when computing in fixed precision arithmetic outside this neighborhood. Therefore, our aim is to quantify and then to reduce this cancellation effect. In the next part we consider the Mittag-Leffler and the confluent hypergeometric functions in detail. Using the method we developed in the first part, we can reduce the cancellation problems by "modifying" the functions for several parts of the complex plane. Finally, in in the last part two other approaches to compute Mittag-Leffler type and confluent hypergeometric functions are discussed. If we want to evaluate such functions on unbounded intervals or sectors in the complex plane, we have to consider methods like asymptotic expansions or continued fractions for large arguments z in modulus.
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.
The skin is continuously challenged by environmental antigens that may penetrate and elicit a skin sensitization, which can develop into allergic contact dermatitis. Medical treatment for allergic contact dermatitis is limited - in fact only acute symptoms can be cured and for secondary prevention of the disease a lifelong avoidance of the allergen(s) is necessary. Therefore, the screening of the sensitization potential of substance used in commercially available products is indispensable to prevent such diseases. Hence, risk assessment is deduced from data obtained by murine local lymph node assay predominantly, but there exists a need to develop methods capable of providing the same information that do not require the use of animals in view of legislative initiatives such as REACH (registration, evaluation, authorization of chemicals) as well as the 7th Amendment to the Cosmetics Directive (2003/15/EC). Therefore, a number of promising in silico and in vitro approaches are being developed to address this need. In vitro test systems using the response of dendritic cells, which are the key player in the elicitation process of contact dermatitis, are established, but, although these novel methods for hazard identification might find application in the context of screening, it is not clear whether these approaches are useful for the purposes of risk assessment and risk management to predict allergic potency. Therefore, it was investigated whether on the one hand in vitro generated dendritic cells from primary blood monocytes (MoDC) and on the other hand a continuous monocytic cell line, the THP-1 cells, suggested as dendritic cell surrogate, react to a presumably weak allergen. Ascaridol, predicted as one of the possible causes for tea tree oil contact dermatitis, was studied and its effects in these two in vitro skin sensitization models were explored. Thus, the surface expression of CD86, HLADR, CD54, and CD40, which are known as activation markers in both in vitro models, were measured via flow cytometry. For MoDC, an augmented CD86 and HLADR surface expression in comparison to untreated cells were determined after 24 h exposure with ascaridol. An increased CD54 and CD40 surface expression were found only in some donors. After long term incubation of 96 h, ascaridol-treated MoDC still up-regulated CD86 and additionally an augmented CD40 expression was measured in all studied donors. An enhanced CD54 expression was determined for 50 percentage of all investigated donors. Furthermore, CD80, CD83 and CD209 protein expression were up-regulated in MoDC after 96 h of ascaridol incubation. In addition, it was determined that after 24 h ascaridol-treated MoDC showed an increased capacity to uptake antigens, whereas after 96 h this capacity got lost and antigen-capturing devices were reduced in comparison to non-treated MoDC. Moreover, the cytokine release of ascaridol-treated MoDC were measured after 24 h. Tumor necrosis factor (TNF)alpha, interleukin (IL)-1beta and IL 6 secretion were determined in some donors. Furthermore, IL-8 release was clearly increased after 24 h ascaridol treatment. By the same token, THP-1 cells were analyzed after ascaridol treatment for several activation markers. We found a similar response pattern as measured in MoDC. Ascaridol induced CD86 expression as well as CD54 after 24 h incubation. Additionally, the impact of ascaridol on phosphorylation of p38 mitogen-activated protein kinase, which had been shown to be involved in increased expression of activation markers like CD86 by others, were studied via Western blot analysis. A phosphorylation of p38 was determined after 15 min of ascaridol stimulation. Moreover, an augmented CD40 and HLADR surface expression were measured in a dose-response manner after 24 h ascaridol treatment. Also similar to MoDC an enhanced IL-8 secretion after ascaridol stimulation was observed in THP-1 cells. Hence, for the first time it was shown that ascaridol has immuno-modulating effects. The obtained data from both in vitro systems, MoDC and THP-1 cells, identified ascaridol as a sensitizer. Although for both systems there remain significant challenges to overcome for potency assessment, ascaridol is presumed to be a weak sensitizer probably. Interestingly, ascaridol treatment of THP-1 cells resulted also in an increased augmentation of CD184 and CCR2, two chemokine receptors expressed on monocyte. Therefore, these data encouraged the exploration of chemokine receptors as tools in skin sensitization prediction. Consequently, the combination of chemical assays with in vitro techniques may provide a useful surrogate to animal testing for skin sensitization. Due to the continuously changing environmental conditions, it is necessary to regularly monitor and update the spectrum of sensitizers that elicit contact dermatitis. Therefore, both debated in vitro test systems will become indispensable tools.
As an interface between an individual and its environment, the skin is a major site of direct exposure to exogenous substances. Once absorbed, these substances may interact with different biomolecules within the skin. The aryl hydrocarbon receptor (AhR) signaling pathway is one mechanism whereby the skin responds to exposures, predominantly through the induction or upregulation of metabolizing enzymes. One known physiological role of the AhR in many tissues is its involvement in the control of cell cycle progression. In skin, almost nothing is known about this physiological function. Moreover, the question whether frequently used naturally occurring phenolic derivatives like eugenol and isoeugenol impact on the AhR within the skin has rarely been studied so far. Eugenol and isoeugenol are due to their odour referred to as fragrances. The ubiquitous distribution of eugenol and isoeugenol results in an almost unavoidable contact with these substances in our daily lives. Despite this fact, their molecular mechanisms of action in skin are poorly understood. There is evidence supporting the hypothesis that these substances may impact on the AhR. On the one hand, eugenol is shown to induce cytochrome P450 1A1 (CYP1A1), a well-known target gene of the AhR. On the other hand, their known anti-proliferative properties might also be mediated by the AhR, based on its physiological function. In order to proof this hypothesis, it was investigated whether eugenol and isoeugenol impact on the AhR signaling pathway in skin cells. Results revealed that eugenol as well as isoeugenol impact on the AhR signaling pathway in skin cells. Both substances caused the translocation of the AhR into the nucleus, induced the expression of the well-known AhR target genes CYP1A1 and AhR repressor (AhRR) and exhibited impact on cell cycle progression. Both substances caused an AhR-dependent cell cycle arrest in skin cells, modulated protein levels of several cell cycle regulatory proteins, inhibited DNA synthesis and thereby reduced cell numbers. The comparison of wildtype cells to AhR knockdown cells revealed an influence of the AhR on cell cycle progression in skin cells in the absence of exogenous ligands. AhR knockdown cells exhibited a slower progression through the cell cycle caused by an accumulation of cells in the G0/G1 phase of the cell cycle and a decreased DNA synthesis rate. Modulation of cell cycle regulatory proteins involved in the transition from the G0/G1 to the S phase of the cell cycle was altered in AhR knockdown cells as well. To conclude, eugenol as well as isoeugenol were able to impact on the AhR signaling pathway in skin cells. Their molecular mechanisms of action are similar to those of classical AhR ligands, although their structural characteristics strongly differ from that of these ligands. In the absence of exogenous ligands the AhR promotes cell cycle progression in many tissues and this knowledge could be expanded on skin-derived cells within the scope of this thesis.
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.
This thesis presents a study of the visual change detection mechanism. This mechanism is thought to be responsible for the detection of sudden and unexpected changes in our visual environment. As the brain is a capacity limited system and has to deal with a continuous stream of information from its surroundings only a part of the vast amount of information can be completely processed and be brought to conscious awareness. This information, which passes through attentional filters, is used for goal-directed behaviour. Therefore, the change detection mechanism is a very useful aid to cope with important information which is outside the focus of our attention. rnIt is thought that a neural memory trace of repetitive visual information is stored. Each new information input is compared to this existing memory trace by a so-called change or mismatch detection system. Following a sudden change, the comparison process leads to a mismatch and the detection system elicits a warning signal, to which an orienting response can follow. This involves a change in the focus of attention towards this sudden environmental change which can then be evaluated for potential danger and allows for a behavioural adaptation to the new situation. rnTo this purpose a paradigm was developed combining a 2-choice response time task with in the background a mismatch detection task of which the subjects were not aware. This paradigm was implemented in an ERP and an fMRI study and was used to study the the change detection mechanism and its relationship with impulsivity.rnIn previous studies a change detection system for auditory information had already been established. As the brain is a very efficient system it was thought to be unlikely that this change detection system is only available for the processing of auditory information. rnIndeed, a modality specific mismatch response at the sensory specific occipital cortex and a more general response at the frontocentral midline, both resembling the components shown in auditory research, were found in the ERP study.rnAdditionally, magnetic resonance imaging revealed a possible functional network of regions, which responded specifically to the processing of a deviant. These regions included the occipital gyrus, premotor cortex, inferior frontal cortex, thalamas, insula, and parts of the cingular cortex. rnThe relationship between impulsivity measures and visual change detection was established in an additional study. More impulsive subjects showed less detection of deviant stimuli, which was most likely due to too fast and imprecise information processing.rnIn summary it can be said, that the work presented in this thesis demonstrates that visual mismatch negativity was established, a number of regions could be associated with change detection and additionally the relevance of change detection in information processing was shown.rn
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.
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.
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.
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
The thesis studies the question how universal behavior is inherited by the Hadamard product. The type of universality that is considered here is universality by overconvergence; a definition will be given in chapter five. The situation can be described as follows: Let f be a universal function, and let g be a given function. Is the Hadamard product of f and g universal again? This question will be studied in chapter six. Starting with the Hadamard product for power series, a definition for a more general context must be provided. For plane open sets both containing the origin this has already been done. But in order to answer the above question, it becomes necessary to have a Hadamard product for functions that are not holomorphic at the origin. The elaboration of such a Hadamard product and its properties are the second central part of this thesis; chapter three will be concerned with them. The idea of the definition of such a Hadamard product will follow the case already known: The Hadamard product will be defined by a parameter integral. Crucial for this definition is the choice of appropriate integration curves; these will be introduced in chapter two. By means of the Hadamard product- properties it is possible to prove the Hadamard multiplication theorem and the Borel-Okada theorem. A generalization of these theorems will be presented in chapter four.
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.
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.
This thesis presents a study of tsunami deposits created by the 2004 Indian Ocean tsunami at the Thai Andaman coast. The outcomes of a study are the characteristics of tsunami deposit for paleo-tsunami database, the identification of major sediment layers in tsunami deposit and the reconstructing tsunami run-ups from the characteristics of tsunami deposit for a coastal development program. The investigations of tsunami deposit are made almost 3 years after the event. Field investigations characterize the tsunami deposit as a distinct sediment layer variable in thickness of gray sand deposited with an erosional basis on a pre-existing soil. The best location for the observation of recent tsunami deposit is the area located about 50-200 m inland from the coastline. In most cases, the deposit layer is normally graded. In some cases, the deposit contains rip-up clasts of muddy soils and/or organic matters. The tsunami deposits are compared with three deposits from coastal sub-environments. The mean grain-size and standard deviation of deposits show that the shoreface deposits are fine to very fine sand, poorly to moderately well sorted; the swash zone deposits are coarse to fine sand, poorly to well sorted; the berm/dune deposits are medium to fine sand, poorly to well sorted; and the tsunami deposits are coarse to very fine sand, poorly to moderately well sorted. The plots of deposit mean grain-size versus sorting indicate that the tsunami deposits are composed of shoreface deposits, swash zone deposits and berm/dune deposits as well. The vertical variation of the texture of tsunami deposit shows that the mean grain-size fines upward and fining landward. The analysis and interpretation of the run-up numbers from the characteristics of tsunami deposits get three run-ups for the 2004 Indian Ocean tsunami at the Thai Andaman coast. It corresponds to field observations from the eye-witness reports and local people- affirmations. The total deposition is a major transportation pattern of onshore tsunami sediments. The sediments must fine in the direction of transport. In general, the major origins of the sediment are the swash zone and berm/dune zone where coarse to medium sand is a significant material, the minor origin of tsunami sediment is a shoreface where a significant material is fine to very fine sand. Only at an area with flat slope shorface, the major origin of tsunami sediment is the shoreface. The thicknesses, the mean grain-sizes, and the standard deviations of tsunami deposits are used to evaluate the influences of coastal morphology on the sediment characteristics. The evaluations show that the tsunami affected areas were attacked by the variable energy waves. Wave energies at the direct tsunami wave affected areas are higher than at the indirect tsunami wave affected areas. Tsunami wave energy is highly dissipated at an area with steep slope shoreface. In the same way, tsunami run-up energy is highly dissipated at an area with steep slope onshore. A channel paralleled to the coastline decreases the run-up velocity, slightly dissipates run-up energy. The road and pond highly influence the characteristics of tsunami deposit and tsunami run-up. A road obstructs the run-up velocity, dissipates run-up energy. A pond decreases run-up velocity, dissipates run-up energy. The characteristics of tsunami deposit can be interpreted for reconstructing the characteristics of tsunami run-up such as a run-up height and a flow velocity. Soulsby et al.(2007)- model is applied for reconstructing tsunami run-up at the study areas. The input parameters are sediment grain-size and sediment inundation distance. Ao Kheuy beach and Khuk Khak beach, Phang Nga province, Thailand are the areas listed for reconstructing tsunami run-up. The evaluated run-up heights are 4.2-4.9 m at Ao Kheuy beach, and 5.4-9.4 m at Khuk Khak beach. The evaluated run-up velocities are 12.8-19.2 m/s (maximum) and 0.2-1.9 m/s (mean) at the coastline and onshore, respectively. Hence, a reasonably good agreement between the evaluated and observed run-up is found. Tsunami run-up height and velocity can be used for coastal development and risk management in the tsunami affected areas. The case studies from the Thai Andaman coast suggest that in the area from coastline to about 70-140 m inland was flooded by the high velocity (high energy) run-ups, and those run-up energies were dissipated there. That area ought to be a non-residential area or a physical protection construction area (flood barrier, forest planting, etc.).
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.
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.
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.
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.
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.
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).
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.
We are living in a connected world, surrounded by interwoven technical systems. Since they pervade more and more aspects of our everyday lives, a thorough understanding of the structure and dynamics of these systems is becoming increasingly important. However - rather than being blueprinted and constructed at the drawing board - many technical infrastructures like for example the Internet's global router network, the World Wide Web, large scale Peer-to-Peer systems or the power grid - evolve in a distributed fashion, beyond the control of a central instance and influenced by various surrounding conditions and interdependencies. Hence, due to this increase in complexity, making statements about the structure and behavior of tomorrow's networked systems is becoming increasingly complicated. A number of failures has shown that complex structures can emerge unintentionally that resemble those which can be observed in biological, physical and social systems. In this dissertation, we investigate how such complex phenomena can be controlled and actively used. For this, we review methodologies stemming from the field of random and complex networks, which are being used for the study of natural, social and technical systems, thus delivering insights into their structure and dynamics. A particularly interesting finding is the fact that the efficiency, dependability and adaptivity of natural systems can be related to rather simple local interactions between a large number of elements. We review a number of interesting findings about the formation of complex structures and collective dynamics and investigate how these are applicable in the design and operation of large scale networked computing systems. A particular focus of this dissertation are applications of principles and methods stemming from the study of complex networks in distributed computing systems that are based on overlay networks. Here we argue how the fact that the (virtual) connectivity in such systems is alterable and widely independent from physical limitations facilitates a design that is based on analogies between complex network structures and phenomena studied in statistical physics. Based on results about the properties of scale-free networks, we present a simple membership protocol by which scale-free overlay networks with adjustable degree distribution exponent can be created in a distributed fashion. With this protocol we further exemplify how phase transition phenomena - as occurring frequently in the domain of statistical physics - can actively be used to quickly adapt macroscopic statistical network parameters which are known to massively influence the stability and performance of networked systems. In the case considered in this dissertation, the adaptation of the degree distribution exponent of a random, scale-free overlay allows - within critical regions - a change of relevant structural and dynamical properties. As such, the proposed scheme allows to make sound statements about the relation between the local behavior of individual nodes and large scale properties of the resulting complex network structures. For systems in which the degree distribution exponent cannot easily be derived for example from local protocol parameters, we further present a distributed, probabilistic mechanism which can be used to monitor a network's degree distribution exponent and thus to reason about important structural qualities. Finally, the dissertation shifts its focus towards the study of complex, non-linear dynamics in networked systems. We consider a message-based protocol which - based on the Kuramoto model for coupled oscillators - achieves a stable, global synchronization of periodic heartbeat events. The protocol's performance and stability is evaluated in different network topologies. We further argue that - based on existing findings about the interrelation between spectral network properties and the dynamics of coupled oscillators - the proposed protocol allows to monitor structural properties of networked computing systems. An important aspect of this dissertation is its interdisciplinary approach towards a sensible and constructive handling of complex structures and collective dynamics in networked systems. The associated investigation of distributed systems from the perspective of non-linear dynamics and statistical physics highlights interesting parallels both to biological and physical systems. This foreshadows systems whose structures and dynamics can be analyzed and understood in the conceptual frameworks of statistical physics and complex systems.
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.
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.
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.
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.
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.
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
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.
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.
1.The Discursive Construction of Black Masculinity: Intersections of Race, Gender, and Sexuality
1.1.The Plight of Black Men: A History of Lynchings and Castrations
1.2.The Discursive Construction of the Black Man as Otherrn
1.3.Black Corporeality and the Scopic Regime of Racism
2. Ralph Ellison's 'Invisible man'
2.1.Invisible Black Men: Between Emasculation and Hypermasculinityrn
2.2.Transcending Invisibility
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.
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.
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 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 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.
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.
Variational inequality problems constitute a common basis to investigate the theory and algorithms for many problems in mathematical physics, in economy as well as in natural and technical sciences. They appear in a variety of mathematical applications like convex programming, game theory and economic equilibrium problems, but also in fluid mechanics, physics of solid bodies and others. Many variational inequalities arising from applications are ill-posed. This means, for example, that the solution is not unique, or that small deviations in the data can cause large deviations in the solution. In such a situation, standard solution methods converge very slowly or even fail. In this case, so-called regularization methods are the methods of choice. They have the advantage that an ill-posed original problem is replaced by a sequence of well-posed auxiliary problems, which have better properties (like, e.g., a unique solution and a better conditionality). Moreover, a suitable choice of the regularization term can lead to unconstrained auxiliary problems that are even equivalent to optimization problems. The development and improvement of such methods are a focus of current research, in which we take part with this thesis. We suggest and investigate a logarithmic-quadratic proximal auxiliary problem (LQPAP) method that combines the advantages of the well-known proximal-point algorithm and the so-called auxiliary problem principle. Its exploration and convergence analysis is one of the main results in this work. The LQPAP method continues the recent developments of regularization methods. It includes different techniques presented in literature to improve the numerical stability: The logarithmic-quadratic distance function constitutes an interior point effect which allows to treat the auxiliary problems as unconstrained ones. Furthermore, outer operator approximations are considered. This simplifies the numerical solution of variational inequalities with multi-valued operators since, for example, bundle-techniques can be applied. With respect to the numerical practicability, inexact solutions of the auxiliary problems are allowed using a summable-error criterion that is easy to implement. As a further advantage of the logarithmic-quadratic distance we verify that it is self-concordant (in the sense of Nesterov/Nemirovskii). This motivates to apply the Newton method for the solution of the auxiliary problems. In the numerical part of the thesis the LQPAP method is applied to linearly constrained, differentiable and nondifferentiable convex optimization problems, as well as to nonsymmetric variational inequalities with co-coercive operators. It can often be observed that the sequence of iterates reaches the boundary of the feasible set before being close to an optimal solution. Against this background, we present the strategy of under-relaxation, which robustifies the LQPAP method. Furthermore, we compare the results with an appropriate method based on Bregman distances (BrPAP method). For differentiable, convex optimization problems we describe the implementation of the Newton method to solve the auxiliary problems and carry out different numerical experiments. For example, an adaptive choice of the initial regularization parameter and a combination of an Armijo and a self-concordance step size are evaluated. Test examples for nonsymmetric variational inequalities are hardly available in literature. Therefore, we present a geometric and an analytic approach to generate test examples with known solution(s). To solve the auxiliary problems in the case of nondifferentiable, convex optimization problems we apply the well-known bundle technique. The implementation is described in detail and the involved functions and sequences of parameters are discussed. As far as possible, our analysis is substantiated by new theoretical results. Furthermore, it is explained in detail how the bundle auxiliary problems are solved with a primal-dual interior point method. Such investigations have by now only been published for Bregman distances. The LQPAP bundle method is again applied to several test examples from literature. Thus, this thesis builds a bridge between theoretical and numerical investigations of solution methods for variational inequalities.
This thesis centers on formal tree languages and on their learnability by algorithmic methods in abstractions of several learning settings. After a general introduction, we present a survey of relevant definitions for the formal tree concept as well as special cases (strings) and refinements (multi-dimensional trees) thereof. In Chapter 3 we discuss the theoretical foundations of algorithmic learning in a specific type of setting of particular interest in the area of Grammatical Inference where the task consists in deriving a correct formal description for an unknown target language from various information sources (queries and/or finite samples) in a polynomial number of steps. We develop a parameterized meta-algorithm that incorporates several prominent learning algorithms from the literature in order to highlight the basic routines which regardless of the nature of the information sources have to be run through by all those algorithms alike. In this framework, the intended target descriptions are deterministic finite-state tree automata. We discuss the limited transferability of this approach to another class of descriptions, residual finite-state tree automata, for which we propose several learning algorithms as well. The learnable class by these techniques corresponds to the class of regular tree languages. In Chapter 4we outline a recent range of attempts in Grammatical Inference to extend the learnable language classes beyond regularity and even beyond context-freeness by techniques based on syntactic observations which can be subsumed under the term 'distributional learning', and we describe learning algorithms in several settings for the tree case taking this approach. We conclude with some general reflections on the notion of learning from structural information.
This dissertation focuses on the link between labour market institutions and precautionary savings. It is evaluated whether private households react to changes in social insurance provision such as the income replacement in case of unemployment by increased savings for precautionary reasons. The dissertation consists of three self-contained chapters, each focusing on slightly different aspects of the topic. The first chapter titled "Precautionary saving and the (in)stability of subjective earnings uncertainty" empirically looks at the influence of future income uncertainty on household saving behavior. Numerous cross-section studies on precautionary saving use subjective expectations regarding the income variance one year ahead as a proxy for income uncertainty. Using such proxies observed only at one point in time, however, may give rise to biased estimates for precautionary wealth if expectations are not stable over time. Survey data from the Dutch DNB Household Survey suggest that subjective future income distributions are not stable over the mid-term. Moreover, in this study I contrast estimates of precautionary wealth using the variation coefficient observed at one point in time with those using a simple mid-term average. Estimates of precautionary wealth based on the average are about 40% to 80% higher than the estimates using the variation coefficient observed only once. In addition to that, wealth accumulation for precautionary reasons is estimated for different parts of the income distribution. The share of precautionary wealth is highest for households at the center of the income distribution. By linking saving behaviour with unemployment insurance, the following chapters then shed some light on an issue that has largely been neglected in the literature on labour market institutions so far. Whereas the third chapter models the relevance of unemployment insurance for income uncertainty and intertemporal decision making during institutional reform processes, chapter 4 seeks to establish empirically a relationship between saving behavior and unemployment insurance. Social insurance, especially unemployment insurance, provides agents with income insurance against not marketable income risks. Since the early 1990s, reform measures like more activating policies as suggested by the OECD Jobs Study in 1994 have been observed in Europe. In the third chapter it is argued that such changes in unemployment insurance reduce public insurance and increase income uncertainty. Moreover, a simple three period model is discussed which shows a link between a welfare state reform and agents' saving decisions as one possible reaction of agents to self-insure against income risk. Two sources of uncertainty seem to be important in this context: (1) uncertain results of the reform process concerning the replacement rate, and (2) uncertainty regarding the timing of information about the content of the reform. It can be shown that the precautionary motive for saving explains an increased accumulation of capital in times of reform activities. In addition to that, early information about the expected replacement rate increases agents' utility and reduces under and oversaving. Following the argument of the previous chapters, that an important feature of labour market institutions in modern welfare states is to provide cash transfers as income replacement in case of unemployment, it is hypothesised that unemployment benefits reduce the motive to save for precautionary reasons. Based on consumer sentiment data from the European Commission's Consumer Survey, chapter four finally provides some evidence that aggregate saving intentions are significantly influenced by unemployment benefits. It can be shown that higher benefits lower the intention to save.
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.
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.
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.
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.
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.
On the Influence of Ignored Stimuli: Generalization and Application of Distractor-Response Binding.
(2011)
In selection tasks where target stimuli are accompanied by distractors, responses to target stimuli, target stimuli and the distractor stimuli can be encoded together as one episode in memory. Subsequent repetition of any aspect of such an episode can lead to the retrieval of the whole episode including the response. Thus, repeating a distractor can retrieve responses given to previous targets; this mechanism was labeled distractor-response binding and has been evidenced in several visual setups. Three experiments of the present thesis implemented a priming paradigm with an identification task to generalize this mechanism to auditory and tactile stimuli as well as to stimulus concepts. In four more experiments the possible effect of distractor-response binding on drivers' reactions was investigated. The same paradigm was implemented using more complex stimuli, foot responses, go/no-go responses, and a dual task setup with head-up and head-down displays. The results indicate that distractor-response binding effects occur with auditory and tactile stimuli and that the process is mediated by a conceptual representation of the distractor stimuli. Distractor-response binding effects also revealed for stimuli, responses, and framework conditions likely to occur in a driving situation. It can be concluded that the effect of distractor-response binding needs to be taken into account for the design of local danger warnings in driver assistance systems.
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.
In addition to the well-recognised effects of both, genes and adult environment, it is now broadly accepted that adverse conditions during pregnancy contribute to the development of mental and somatic disorders in the offspring, such as cardiovascular disorders, endocrinological disorders, metabolic disorders, schizophrenia, anxious and depressive behaviour and attention deficit hyperactivity disorder (ADHD). Early life events may have long lasting impact on tissue structure and function and these effects appear to underlie the developmental origins of vulnerability to chronic diseases. The assumption that prenatal adversity, such as maternal emotional states during pregnancy, may have adverse effects on the developing infant is not new. Accordant references can be found in an ancient Indian text (ca. 1050 before Christ), in biblical texts and in documents originating during the Middle Ages. Even Hippocrates stated possible effects of maternal emotional states on the developing fetus. Since the mid-1950s, research examining the effects of maternal psychosocial stress during pregnancy appeared in the literature. Extensive research in this field has been conducted since the early 1990s. Thus, the relationship between early life events and long-term health outcomes was already postulated over 20 years ago. David Barker and colleagues demonstrated that children of lower birth weight - which represents a crude marker of an adverse intrauterine environment - were at increased risk of high blood pressure, cardiovascular disorders, and type-2 diabetes later in life. These provocative findings led to a large amount of subsequent research, initially focussing on the role of undernutrition in determining fetal outcomes. The phenomenon of prenatal influences that determine in part the risk of suffering from chronic disease later in life has been named the "fetal origins of health and disease" paradigm. The concept of "prenatal programming" has now been extended to many other domains, such as the effects of prenatal maternal stress, prenatal tobacco exposure, alcohol intake, medication, toxins, as well as maternal infection and diseases. During the process of prenatal programming, environmental agents are transmitted across the placenta and act on specific fetal tissues during sensitive periods of development. Thus, developmental trajectories are changed and the organisation and function of tissue structure and organ system is altered. The biological purpose of those "early life programming" may consist in evolutionary advantages. The offspring adapts its development to the expected extrauterine environment which is forecast by the clues available during fetal life. If the fetus receives signals of a challenging environment, e.g. due to maternal stress hormones or maternal undernutrition, its survival may be promoted due to developmental adaptation processes. However, if the expected environment does not match with the real environment, maladapation and later disease risk may result. For example, a possible indicator of a "response ready" trait, such as hyperactivity/inattention may have been advantageous in an adverse ancient environment. However, it is of disadvantage when the postnatal environment demands oppositional skills, such as attention and concentration " e.g. in the classroom, at school, to achieve academic success. Borderline personality disorder (BPD) is a prevalent psychiatric disorder, characterized by impulsivity, affective instability, dysfunctional interpersonal relationships and identity disturbance. Although many studies report different risk factors, the exact etiologic mechanisms are not yet understood. In addition to the well-recognised effects of genetic components and adverse childhood experiences, BPD may potentially be co-determined by further environmental influences, acting very early in life: during pre- and perinatal period. There are several hints that may suggest possible prenatal programming processes in BPD. For example, patients with BPD are characterized by elevated stress sensitivity and reactivity and dysfunctions of the neuroendocrine stress system, such as the hypothalamic pituitary adrenal (HPA) axis. Furthermore, patients with BPD show a broad range of somatic comorbidities " especially those disorders for which prenatal programming processes have been described. During infancy and childhood, BPD patients already show behavioural and emotional abnormalities as well as pronounced temperamental traits, such as impulsivity, emotional dysregulation and inattention that may potentially be co-determined by prenatal programming processes. Such temperamental traits - similar to those, seen in patients with ADHD - have been described to be associated with low birthweight which indicates a suboptimal intrauterine environment. Moreover, the functional and structural alterations in the central nervous system (CNS) in patients with BPD might also be mediated in part by prenatal agents, such as prenatal tobacco exposure. Prenatal adversity may thus constitute a further, additional component in the multifactorial genesis of BPD. The association between BPD and prenatal risk factors has not yet been studied in such detail. We are not aware of any further study that assessed pre- and perinatal risk factors, such as maternal psychoscocial stress, smoking, alcohol intake, obstetric complications and lack of breastfeeding in patients with BPD.
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 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.
Psychiatric/Behavioral disorders/traits are usually polygenic in nature, where a particular phenotype is the manifestation of multiple genes. However, the existence of large families with numerous members who are affected by these disorders/traits steers us towards a Mendelian (or monogenic) possibility, where the phenotype is caused by a single gene. In order to better understand the genetic architecture of general psychiatric/behavioral disorders/traits, this thesis investigates large pedigrees that display a Mendelian pattern for attention-deficit/hyperactivity disorder, schizophrenia and bipolar disorder. Numerous challenges in the field of psychiatric and behavioral sciences have impeded the genetic investigation of such disorders/traits. Examples include frequent cross-disorders, genetic heterogeneity across subjects as well as the use of diagnostic tools that can be subjective at times. To overcome these challenges, this thesis investigates large multi-generational pedigrees, which comprise a significant number of members who exhibit specific psychiatric/behavioral phenotypes. These pedigrees provide high-resolution experimental setups that can dissect the genetic complexities of psychiatric/behavioral disorders/traits. This thesis adopts a classical two-stage genetic approach to investigate the various psychiatric/behavioral disorders/traits in large pedigrees. The classical two-stage genetic approach is commonly used by many human geneticists to study a wide spectrum of human physiological disorders but is only being applied to the field of psychiatric and behavioral genetics recently. Through the study of large pedigrees, this thesis discovers the genomic regions that may play a causative role in the expression of certain psychiatric/behavioral disorders/traits within the vast genome.
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.
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.
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.
Religion, churches and religious communities have growing importance in the Law of the European Union. Since long a distinct law on religion of the European Union is developing.rnThis collection of those norms of European Union Law directly concerning religion mirrors today's status of this dynamic process.
The main topic of this treatise is the solution of two problems from the general theory of linear partial differential equations with constant coefficients. While surjectivity criteria for linear partial differential operators in spaces of smooth functions over an open subset of euclidean space and distributions were proved by B. Malgrange and L. Hörmander in 1955, respectively 1962, concrete evaluation of these criteria is still a highly non-trivial task. In particular, it is well-known that surjectivity in the space of smooth functions over an open subset of euclidean space does not automatically imply surjectivity in the space of distributions. Though, examples for this fact all live in three or higher dimensions. In 1966, F. Trèves conjectured that in the two dimensional setting surjectivity of a linear partial differential operator on the smooth functions indeed implies surjectivity on the space of distributions. An affirmative solution to this problem is presented in this treatise. The second main result solves the so-called problem of (distributional) parameter dependence for solutions of linear partial differential equations with constant coefficients posed by J. Bonet and P. Domanski in 2006. It is shown that, in dimensions three or higher, this problem in general has a negative solution even for hypoelliptic operators. Moreover, it is proved that the two dimensional case is again an exception, because in this setting the problem of parameter dependence always has a positive solution.
In this thesis, we mainly investigate geometric properties of optimal codebooks for random elements $X$ in a seperable Banach space $E$. Here, for a natural number $ N $ and a random element $X$ , an $N$-optimal codebook is an $ N $-subset in the underlying Banach space $E$ which gives a best approximation to $ X $ in an average sense. We focus on two types of geometric properties: The global growth behaviour (growing in $N$) for a sequence of $N$-optimal codebooks is described by the maximal (quantization) radius and a so-called quantization ball. For many distributions, such as central-symmetric distributions on $R^d$ as well as Gaussian distributions on general Banach spaces, we are able to estimate the asymptotics of the quantization radius as well as the quantization ball. Furthermore, we investigate local properties of optimal codebooks, in particular the local quantization error and the weights of the Voronoi cells induced by an optimal codebook. In the finite-dimensional setting, we are able to proof for many interesting distributions classical conjectures on the asymptotic behaviour of those properties. Finally, we propose a method to construct sequences of asymptotically optimal codebooks for random elements in infinite dimensional Banach spaces and apply this method to construct codebooks for stochastic processes, such as fractional Brownian Motions.
One of the main tasks in mathematics is to answer the question whether an equation possesses a solution or not. In the 1940- Thom and Glaeser studied a new type of equations that are given by the composition of functions. They raised the following question: For which functions Ψ does the equation F(Ψ)=f always have a solution. Of course this question only makes sense if the right hand side f satisfies some a priori conditions like being contained in the closure of the space of all compositions with Ψ and is easy to answer if F and f are continuous functions. Considering further restrictions to these functions, especially to F, extremely complicates the search for an adequate solution. For smooth functions one can already find deep results by Bierstone and Milman which answer the question in the case of a real-analytic function Ψ. This work contains further results for a different class of functions, namely those Ψ that are smooth and injective. In the case of a function Ψ of a single real variable, the question can be fully answered and we give three conditions that are both sufficient and necessary in order for the composition equation to always have a solution. Furthermore one can unify these three conditions to show that they are equivalent to the fact that Ψ has a locally Hölder-continuous inverse. For injective functions Ψ of several real variables we give necessary conditions for the composition equation to be solvable. For instance Ψ should satisfy some form of local distance estimate for the partial derivatives. Under the additional assumption of the Whitney-regularity of the image of Ψ, we can give sufficient conditions for flat functions f on the critical set of Ψ to possess a solution F(Ψ)=f.
The 23rd Annual Congress of the European Consortium for Church and State Research took place in Oxford, United Kingdom from 29 September to 2 October 2011. Founded in 1989, the Consortium unites experts in law and religion from Member States of the European Union. The Oxford conference took as its theme Religion and Discrimination Law focusing on the manner in which State governments had sought to implement the non-discrimination policy of the EU by legislation and through courts and tribunals. The proceedings comprise three introductory papers considering the historical, cultural and social background; the prohibition on discrimination, and the exemptions to the general prohibition. This is followed by national reports from twenty-three countries describing the reach of discrimination law in the field of religion. These are supplemented by further papers analysing the jurisprudence of the Strasbourg Court and the background to EU Directive 2000/78/EC and by some concluding reflections. The proceedings begin with the text of a public lecture given at the opening of the Congress by Sir Nicolas Bratza, President of the European Court of Human Rights on the subject of freedom of religion under Article 9 of the Convention.
In this thesis, in order to shed light on the biological function of the membrane-bound Glucocorticoid Receptor (mGR), proteomic changes induced by 15 min in vivo acute stress and by short in vitro activation of the mGR were analyzed in T-lymphocytes. The numerous overlaps between the two datasets suggest that the mGR mediates physiologically relevant actions and participates in the early stress response, triggering rapid early priming events that pave the way for the slower genomic GC activities. In addition, a new commercially available method with suitable sensitivity to detect the human mGR is reported and the transcriptional origin of this protein investigated. Our results indicates that specific GR-transcripts, containing exon 1C and 1D, are associated with the expression of this membrane isoform.
The stress hormone cortisol as the end-product of the hypothalamic-pituitary-adrenal (HPA) axis has been found to play a crucial role in the release of aggressive behavior (Kruk et al., 2004; Böhnke et al., 2010). In order to further explore potential mechanisms underlying the relationship between stress and aggression, such as changes in (social) information processing, we conducted two experimental studies that are presented in this thesis. In both studies, acute stress was induced by means of the Socially Evaluated Cold Pressor Test (SECP) designed by Schwabe et al. (2008). Stressed participants were classified as either cortisol responders or nonresponders depending on their rise in cortisol following the stressor. Moreover, basal HPA axis activity was measured prior to the experimental sessions and EEG was recorded throughout the experiments. The first study dealt with the influence of acute stress on cognitive control processes. 41 healthy male participants were assigned to either the stress condition or the non-stressful control procedure of the SECP. Before as well as after the stress induction, all participants performed a cued task-switching paradigm in order to measure cognitive control processes. Results revealed a significant influence of acute and basal cortisol levels, respectively, on the motor preparation of the upcoming behavioral response, that was reflected in changes in the magnitude of the terminal Contingent Negative Variation (CNV). In the second study, the effect of acute stress and subsequent social provocation on approach-avoidance motivation was examined. 72 healthy students (36 males, 36 females) took part in the study. They performed an approach-avoidance task, using emotional facial expressions as stimuli, before as well as after the experimental manipulation of acute stress (again via the SECP) and social provocation realized by means of the Taylor Aggression Paradigm (Taylor, 1967). Additionally to salivary cortisol, testosterone samples were collected at several points in time during the experimental session. Results indicated a positive relationship between acute testosterone levels and the motivation to approach social threat stimuli in highly provoked cortisol responders. Similar results were found when the testosterone-to-cortisol ratio at baseline was taken into account instead of acute testosterone levels. Moreover, brain activity during the approach-avoidance task was significantly influenced by acute stress and social provocation, as reflected in reductions of early (P2) as well as of later (P3) ERP components in highly provoked cortisol responders. This may indicate a less accurate, rapid processing of socially relevant stimuli due to an acute increase in cortisol and subsequent social provocation. In conclusion, the two studies presented in this thesis provide evidence for significant changes in information processing due to acute stress, basal cortisol levels and social provocation, suggesting an enhanced preparation for a rapid behavioral response in the sense of a fight-or-flight reaction. These results confirm the model of Kruk et al. (2004) proposing a mediating role of changed information processes in the stress-aggression-link.
Magnet Resonance Imaging (MRI) and Electroencephalography (EEG) are tools used to investigate the functioning of the working brain in both humans and animal studies. Both methods are increasingly combined in separate or simultaneous measurements under the assumption to benefit from their individual strength while compensating their particular weaknesses. However, little attention has been paid to how statistical analyses strategies can influence the information that can be retrieved from a combined EEG fMRI study. Two independent studies in healthy student volunteers were conducted in the context of emotion research to demonstrate two approaches of combining MRI and EEG data of the same participants. The first study (N = 20) applied a visual search paradigm and found that in both measurements the assumed effects were absent by not statistically combining their results. The second study (N = 12) applied a novelty P300 paradigm and found that only the statistical combination of MRI and EEG measurements was able to disentangle the functional effects of brain areas involved in emotion processing. In conclusion, the observed results demonstrate that there are added benefits of statistically combining EEG-fMRI data acquisitions by assessing both the inferential statistical structure and the intra-individual correlations of the EEG and fMRI signal.
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.
Optimal control problems are optimization problems governed by ordinary or partial differential equations (PDEs). A general formulation is given byrn \min_{(y,u)} J(y,u) with subject to e(y,u)=0, assuming that e_y^{-1} exists and consists of the three main elements: 1. The cost functional J that models the purpose of the control on the system. 2. The definition of a control function u that represents the influence of the environment of the systems. 3. The set of differential equations e(y,u) modeling the controlled system, represented by the state function y:=y(u) which depends on u. These kind of problems are well investigated and arise in many fields of application, for example robot control, control of biological processes, test drive simulation and shape and topology optimization. In this thesis, an academic model problem of the form \min_{(y,u)} J(y,u):=\min_{(y,u)}\frac{1}{2}\|y-y_d\|^2_{L^2(\Omega)}+\frac{\alpha}{2}\|u\|^2_{L^2(\Omega)} subject to -\div(A\grad y)+cy=f+u in \Omega, y=0 on \partial\Omega and u\in U_{ad} is considered. The objective is tracking type with a given target function y_d and a regularization term with parameter \alpha. The control function u takes effect on the whole domain \Omega. The underlying partial differential equation is assumed to be uniformly elliptic. This problem belongs to the class of linear-quadratic elliptic control problems with distributed control. The existence and uniqueness of an optimal solution for problems of this type is well-known and in a first step, following the paradigm 'first optimize, then discretize', the necessary and sufficient optimality conditions are derived by means of the adjoint equation which ends in a characterization of the optimal solution in form of an optimality system. In a second step, the occurring differential operators are approximated by finite differences and the hence resulting discretized optimality system is solved with a collective smoothing multigrid method (CSMG). In general, there are several optimization methods for solving the optimal control problem: an application of the implicit function theorem leads to so-called black-box approaches where the PDE-constrained optimization problem is transformed into an unconstrained optimization problem and the reduced gradient for these reduced functional is computed via the adjoint approach. Another possibilities are Quasi-Newton methods, which approximate the Hessian by a low-rank update based on gradient evaluations, Krylov-Newton methods or (reduced) SQP methods. The use of multigrid methods for optimization purposes is motivated by its optimal computational complexity, i.e. the number of required computer iterations scales linearly with the number of unknowns and the rate of convergence, which is independent of the grid size. Originally multigrid methods are a class of algorithms for solving linear systems arising from the discretization of partial differential equations. The main part of this thesis is devoted to the investigation of the implementability and the efficiency of the CSMG on commodity graphics cards. GPUs (graphic processing units) are designed for highly parallelizable graphics computations and possess many cores of SIMD-architecture, which are able to outperform the CPU regarding to computational power and memory bandwidth. Here they are considered as prototype for prospective multi-core computers with several hundred of cores. When using GPUs as streamprocessors, two major problems arise: data have to be transferred from the CPU main memory to the GPU main memory, which can be quite slow and the limited size of the GPU main memory. Furthermore, only when the streamprocessors are fully used to capacity, a remarkable speed-up comparing to a CPU is achieved. Therefore, new algorithms for the solution of optimal control problems are designed in this thesis. To this end, a nonoverlapping domain decomposition method is introduced which allows the exploitation of the computational power of many GPUs resp. CPUs in parallel. This algorithm is based on preliminary work for elliptic problems and enhanced for the application to optimal control problems. For the domain decomposition into two subdomains the linear system for the unknowns on the interface is solved with a Schur complement method by using a discrete approximation of the Steklov-Poincare operator. For the academic optimal control problem, the arising capacitance matrix can be inverted analytically. On this basis, two different algorithms for the nonoverlapping domain decomposition for the case of many subdomains are proposed in this thesis: on the one hand, a recursive approach and on the other hand a simultaneous approach. Numerical test compare the performance of the CSMG for the one domain case and the two approaches for the multi-domain case on a GPU and CPU for different variants.
This study focuses on the representation of British South Asian identities in contemporary British audiovisual media. It attempts to answer the question, whether these identities are represented as hybrid, heterogeneous and ambivalent, or whether these contemporary representations follow in the tradition of colonial and postcolonial racialism. Racialised depictions of British South Asians have been the norm not only in the colonial but also in the postcolonial era until the rise of the Black British movement, whose successes have been also acknowledged in the field of representation. However these achievements have to be scrutinized again, especially in the context of the post 9/11 world, rising Islamophobia, and new forms of institutionalized discrimination on the basis of religion. Since the majority of British Muslims are of South Asian origin, this study tries to answer the question whether the marker of religious origin is racial belonging, i.e. skin colour, and old stereotypes associated with the racialised representation are being perpetuated into current depictions through an examination of the varied genre of popular audio visual media texts.
The contribution of three genes (C15orf53, OXTR and MLC1) to the etiology of chromosome 15-bound schizophrenia (SCZD10), bipolar disorder (BD) and autism spectrum disorder (ASD) were studied. At first, the uncharacterized gene C15orf53 was comprehensively analyzed. Previous genome-wide association studies (GWAS) in bipolar disorder samples have identified an association signal in close vicinity to C15orf53 on chromosome 15q14. This gene is located in exactly the genomic region, which is segregating in our SCZD10 families. An association study with bipolar disorder (BD) and SCZD10 individual samples did not reveal any association of single nucleotide polymorphisms (SNPs) in C15orf53. Mutational analysis of C15orf53 in SCZD10-affected individuals from seven multiplex families did not show any mutations in the 5'-untranslated region, the coding region and the intron-exon boundaries. Gene expression analysis revealed that C15orf53 was expressed in a subpopulation of leukocytes, but not in human post-mortem limbic brain tissue. Summarizing these studies, C15orf53 is unlikely to be a strong candidate gene for the etiology of BD or SCZD10. The second investigated gene was the human oxytocin receptor gene (OXTR). Five well described SNPs located in the OXTR gene were taken for a transmission-disequilibrium test (TDT) in parents-child trios with ASD-affected children. Neither in the complete sample nor in a subgroup with children that had an intelligence quotient (IQ) above 70, association was found, independent from the application of Haploview or UNPHASED for analysis. The third gene, MLC1, was investigated with regards to its implication in the etiology of SCZD10. Mutations in the MLC1 gene lead to megalencephalic leukoencephalopathy with subcortical cysts (MLC) and one variant coding for the amino acid methionine (Met) instead of leucine (Leu) at position 309 was identified to segregate in a family affected with SCZD10. For further investigation of MLC1 and its possible implication in the etiology of SCZD10, a constitutive Mlc1 knockout mouse model should be created. Mouse embryonic stem cells (mES) were electroporated with a knockout vector construct and analyzed with respect to homologous recombination of the knockout construct with the genomic DNA (gDNA) of the mES. Polymerase chain reaction (PCR) on the available stem cell clones did not reveal any homologous recombined ES. Additionally, we conducted experiments to knockdown MLC1 and using microRNAs. The 3'-untranslated region of the MLC1 gene was analyzed with the bioinformatics tool TargetScan to screen for potential microRNA target sites. In the 3'-untranslated region of the MLC1 gene, a potential binding site for miR-137 was identified. The gene expression level of genes that had been linked to psychiatric disorders and carried a predicated miR-137 binding site has been proven to be immediately responsive to miR-137. Thus, there is new evidence that MLC1 is a candidate gene for the etiology of SCZD10.
The main objective of the present thesis was to investigate whether antibody effects observed in earlier in vitro studies can translate into the protection against chemical carcinogenesis in vivo as the basis of an immunoprophylactic approach against carcinogens. As model for chemical carcinogenesis, we selected B[a]P the prototype polycyclic aromatic hydrocarbon (PAH), an environmental pollutant emanating from both natural and anthropogenic sources. Many in vivo models conveniently use high doses of carcinogens mostly given as single bolus, which provides simple surrogate readouts, but poorly reflects chronic exposure to the low concentrations found in the environment. In addition, these concentrations cannot be matched with equimolar antibody concentrations obtained by immunisation. However, low B[a]P concentrations do not permit to directly measure chemical carcinogenesis. Therefore, in the present thesis, the pharmacokinetic, metabolism and B[a]P mediated immunotoxicity were chosen as experimental read-outs. B[a]P conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to actively immunise mice against B[a]P. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. In order to further improve the vaccination, we replaced the protein carrier by promiscuous T-helper cell epitopes to induce higher antibody titer with increased specificity for the B[a]P hapten. We hypothesised that a reduction of B cell binding sites on the carrier, compared to whole protein carrier, should favour the activation of B cells recognising the hapten instead of the carrier protein. An internal processing of the carrier and cleavage of the B[a]P-BA and subsequent presentation of the carrier peptide by MHC II molecules to T cell receptor should induce a B cell dependent immune response by activating B cells capable to recognise B[a]P. We demonstrated that a vaccination against B[a]P using promiscuous T-helper cell epitopes as a carrier is feasible and some tested peptide conjugates were more immunogenic as whole protein conjugates with increased specificity. We showed that vaccination against B[a]P reduces immunotoxicity. B[a]P suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice the immunotoxic effect of B[a]P on IFN-γ, Il-12, TNF-ï¡ production and B cell activation was restored. In addition, specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. In order to replace Freund adjuvant and to improve the immunisation strategy in terms of antibody quantity and quality, several adjuvants that are potentially compatible with their use in humans were tested. In combination with Freund adjuvant, the conjugate-vaccine induced high levels of B[a]P-specific antibodies. We showed that all adjuvants tested induced specific antibodies against B[a]P and 7,8-diol-B[a]P, its carcinogenic metabolite. The highest antibody levels were obtained with Quil A, MF-59 and Alum. Biological activity in terms of enhanced retention of B[a]P was confirmed in mice immunised with Quil A, Montanide, Alum and MF-59. Our findings demonstrate that a vaccination against B[a]P is feasible in combination with adjuvants licensed in humans. Based on these results and with the current understanding of the mechanisms of chemical carcinogenesis of the ubiquitous carcinogen B[a]P and of the effects of specific antibodies, an immunoprophylactic approach against chemical carcinogenesis is absolutely warranted. Nevertheless, the direct effects of B[a]P-specific antibodies on the different stages of carcinogenesis (e.g. adduct formation) and whether these effects may translate into long-term protective effect against tumourigenesis needs to be proven in further experiments.
Time series archives of remotely sensed data offer many possibilities to observe and analyse dynamic environmental processes at the Earth- surface. Based on these hypertemporal archives, which offer continuous observations of vegetation indices, typically at repetition rates from one to two weeks, sets of phenological parameters or metrics can be derived. Examples of such parameters are the beginning and end of the annual growing period, as well as its length. Even though these parameters do not correspond exactly to conventional observations of phenological events, they nevertheless provide indications of the dynamic processes occurring in the biosphere. The development of robust algorithms for the derivation of phenological metrics can be challenging. Currently, such algorithms are most commonly based on digital filters or the Fourier analysis of time series. Polynomial spline models offer a useful alternative to existing methods. The possibilities of using spline models in the analytical description of time series are numerous, and their specific mathematical properties may help to avoid known problems occurring with the more common methods for deriving phenological metrics. Based on a selection of different polynomial spline models suitable for the analysis of remotely sensed time series of vegetation indices, a method to derive various phenological parameters from such time series was developed and implemented in this work. Using an example data set from an intensively used agricultural area showing highly dynamic variations in vegetation phenology, the newly developed method was verified by a comparison of the results of the spline based approach to the results of two alternative, well established methods.
This dissertation focuses on e-marketing strategy's effective elements in tourism industry. As case study, research focus is on Airlines, tour operator, chain hotels in Iran and Germany. It aims to show various possibilities to enhance the company- e-marketing strategy and successfully performance e-marketing strategies with recognition effective elements and their important during the strategy designing and implementation process. For the purpose of this research due to the nature of the research, Explanatory -exploratory-applicable; after studying and consulting, Delphi technique has been chosen. In results, we have some effective elements and their important according the Delphi and AHP method. For example between elements "Tourists' Needs, Experience and Expects" with the importance coefficient of %204 is the most remarkable elements and "Customer satisfactions' elements group" with average value 5.54 according the research results have more important than other groups.
Arctic and Antarctic polynya systems are of high research interest since extensive new ice formation takes place in these regions. The monitoring of polynyas and the ice production is crucial with respect to the changing sea-ice regime. The thin-ice thickness (TIT) distribution within polynyas controls the amount of heat that is released to the atmosphere and has therefore an impact on the ice-production rates. This thesis presents an improved method to retrieve thermal-infrared thin-ice thickness distributions within polynyas. TIT with a spatial resolution of 1 km × 1 km is calculated using the MODIS ice-surface temperature and atmospheric model variables within the Laptev Sea polynya for the winter periods 2007/08 and 2008/09. The improvement of the algorithm is focused on the surface-energy flux parameterizations. Furthermore, a thorough sensitivity analysis is applied to quantify the uncertainty in the thin-ice thickness results. An absolute mean uncertainty of -±4.7 cm for ice below 20 cm of thickness is calculated. Furthermore, advantages and drawbacks using different atmospheric data sets are investigated. Daily MODIS TIT composites are computed to fill the data gaps arising from clouds and shortwave radiation. The resulting maps cover on average 70 % of the Laptev Sea polynya. An intercomparison of MODIS and AMSR-E polynya data indicates that the spatial resolution issue is essential for accurately deriving polynya characteristics. Monthly fast-ice masks are generated using the daily TIT composites. These fast-ice masks are implemented into the coupled sea-ice/ocean model FESOM. An evaluation of FESOM sea-ice concentrations is performed with the result that a prescribed high-resolution fast-ice mask is necessary regarding the accurate polynya location. However, for a more realistic simulation of other small-scale sea-ice features further model improvements are required. The retrieval of daily high-resolution MODIS TIT composites is an important step towards a more precise monitoring of thin sea ice and sea-ice production. Future work will address a combined remote sensing " model assimilation method to simulate fully-covered thin-ice thickness maps that enable the retrieval of accurate ice production values.
Religion, churches and religious communities have growing importance in the Law of the European Union. Since long a distinct law on religion of the European Union is developing. This collection of those norms of European Union Law directly concerning religion mirrors today's status of this dynamic process.
In his article, the author asks how legitimacy of law and the concept of rules of law can be described taking into account the interaction between aspects of philosophy and sociology as well as the will of the state in states' constitutions. As the rule of law, versus other kinds of rules in our society, should be regarded as a rule of &amp;quot;three-dimensionality&amp;quot; " an interaction between the will of the state, the social, historical, and economic factors, and the idea or concept of justice ", the author focuses his interest on the examination of these three factors always taking into account that law is the will of the state, but that not every decision of the state can be considered as law.
Cortisol exhibits typical ultradian and circadian rhythm and disturbances in its secretory pattern have been described in stress-related pathology. The aim of this thesis was to dissect the underlying structure of cortisol pulsatility and to develop tools to investigate the effects of this pulsatility on immune cell trafficking and the responsiveness of the neuroendocrine system and GR target genes to stress. Deconvolution modeling was set up as a tool for investigation of the pulsatile secretion underlying the ultradian cortisol rhythm. This further allowed us to investigate the role of the single cortisol pulses on the immune cell trafficking and the role of induced cortisol pulses on the kinetics of expression of GR target genes. The development of these three tools, would allow to induce and investigate in future the significance of single cortisol pulses for health and disease.
Copositive programming is concerned with the problem of optimizing a linear function over the copositive cone, or its dual, the completely positive cone. It is an active field of research and has received a growing amount of attention in recent years. This is because many combinatorial as well as quadratic problems can be formulated as copositive optimization problems. The complexity of these problems is then moved entirely to the cone constraint, showing that general copositive programs are hard to solve. A better understanding of the copositive and the completely positive cone can therefore help in solving (certain classes of) quadratic problems. In this thesis, several aspects of copositive programming are considered. We start by studying the problem of computing the projection of a given matrix onto the copositive and the completely positive cone. These projections can be used to compute factorizations of completely positive matrices. As a second application, we use them to construct cutting planes to separate a matrix from the completely positive cone. Besides the cuts based on copositive projections, we will study another approach to separate a triangle-free doubly nonnegative matrix from the completely positive cone. A special focus is on copositive and completely positive programs that arise as reformulations of quadratic optimization problems. Among those we start by studying the standard quadratic optimization problem. We will show that for several classes of objective functions, the relaxation resulting from replacing the copositive or the completely positive cone in the conic reformulation by a tractable cone is exact. Based on these results, we develop two algorithms for solving standard quadratic optimization problems and discuss numerical results. The methods presented cannot immediately be adapted to general quadratic optimization problems. This is illustrated with examples.
The startle response in psychophysiological research: modulating effects of contextual parameters
(2013)
Startle reactions are fast, reflexive, and defensive responses which protect the body from injury in the face of imminent danger. The underlying reflex is basic and can be found in many species. Even though it consists of only a few synapses located in the brain stem, the startle reflex offers a valuable research method for human affective, cognitive, and psychological research. This is because of moderating effects of higher mental processes such as attention and emotion on the response magnitude: affective foreground stimulation and directed attention are validated paradigms in startle-related research. This work presents findings from three independent research studies that deal with (1) the application of the established "affective modulation of startle"-paradigm to the novel setting of attractiveness and human mating preferences, (2) the question of how different components of the startle response are affected by a physiological stressor and (3) how startle stimuli affect visual attention towards emotional stimuli. While the first two studies treat the startle response as a dependent variable by measuring its response magnitude, the third study uses startle stimuli as an experimental manipulation and investigates its potential effects on a behavioural measure. The first chapter of this thesis describes the basic mechanisms of the startle response as well as the body of research that sets the foundation of startle research in psychophysiology. It provides the rationale for the presented studies, and offers a short summary of the obtained results. Chapter two to four represent primary research articles that are published or in press. At the beginning of each chapter the contribution of all authors is explained. The references for all chapters are listed at the end of this thesis. The overall scope of this thesis is to show how the human startle response is modulated by a variety of factors, such as the attractiveness of a potential mating partner or the exposure to a stressor. In conclusion, the magnitude of the startle response can serve as a measure for such psychological states and processes. Beyond the involuntary, physiological startle reflex, startle stimuli also affect intentional behavioural responses, which we could demonstrate for eye movements in a visual attention paradigm.
This study examines the relationship between media content, its production, and its reception in Japanese popular culture with the example of the so-called yuri ("lily") genre that centers on representations of intimate relationships between female characters. Based on contemporary genre theory, which posits that genres are not inherent properties of texts, the central question of this study is how the yuri genre is discursively produced in Japan. To examine this question, the study takes a variety of sources into consideration: Firstly, it discusses ten exemplary texts from the 1910s to 2010s that in the Japanese discourse on the yuri genre are deemed the milestone texts of the yuri genre's historical development (Hana monogatari, Otome no minato, Secret Love, Shiroi heya no futari, BishÅjo senshi Sailor Moon, Maria-sama ga miteru, ShÅjo Sect, Aoi hana, Yuru yuri, and Yuri danshi). Secondly, interviews with ten editors working for Japanese manga magazines shed light on their assessment of the yuri genre. Finally, the results of an online survey among Japanese fans of the yuri genre, which returned 1,352 completed questionnaires, question hitherto assumptions about the fans and their reasons for liking the yuri genre. The central argument of this study is that the yuri genre is for the most part constructed not through assignments on part of the genre's producers but through interpretations on part of the genre's fans. The intimacy portrayed in the texts ranges from "friendship" to "love," and often the ideas of "innocence" and "beauty" are emphasized. Nevertheless, the formation of the yuri genre occurs outside the bounds of the texts, most importantly in fan works, i.e. derivative texts created by fans. The actual content of the originals merely serves as a starting point for these interpretations. Located at the intersection of Japanese studies, cultural studies, media studies, and sociology, this study contributes to our understanding of contemporary Japanese popular culture by showing the mutual dependencies between media content, production, and reception. It provides a deeper look at these processes through first-hand accounts of both producers and fans of the yuri genre.
This work investigates the industrial applicability of graphics and stream processors in the field of fluid simulations. For this purpose, an explicit Runge-Kutta discontinuous Galerkin method in arbitrarily high order is implemented completely for the hardware architecture of GPUs. The same functionality is simultaneously realized for CPUs and compared to GPUs. Explicit time steppings as well as established implicit methods are under consideration for the CPU. This work aims at the simulation of inviscid, transsonic flows over the ONERA M6 wing. The discontinuities which typically arise in hyperbolic equations are treated with an artificial viscosity approach. It is further investigated how this approach fits into the explicit time stepping and works together with the special architecture of the GPU. Since the treatment of artificial viscosity is close to the simulation of the Navier-Stokes equations, it is reviewed how GPU-accelerated methods could be applied for computing viscous flows. This work is based on a nodal discontinuous Galerkin approach for linear hyperbolic problems. Here, it is extended to non-linear problems, which makes the application of numerical quadrature obligatory. Moreover, the representation of complex geometries is realized using isoparametric mappings. Higher order methods are typically very sensitive with respect to boundaries which are not properly resolved. For this purpose, an approach is presented which fits straight-sided DG meshes to curved geometries which are described by NURBS surfaces. The mesh is modeled as an elastic body and deformed according to the solution of closest point problems in order to minimize the gap to the original spline surface. The sensitivity with respect to geometry representations is reviewed in the end of this work in the context of shape optimization. Here, the aerodynamic drag of the ONERA M6 wing is minimized according to the shape gradient which is implicitly smoothed within the mesh deformation approach. In this context a comparison to the classical Laplace-Beltrami operator is made in a Stokes flow situation.
Design and structural optimization has become a very important field in industrial applications over the last years. Due to economical and ecological reasons, the efficient use of material is of highly industrial interest. Therefore, computational tools based on optimization theory have been developed and studied in the last decades. In this work, different structural optimization methods are considered. Special attention lies on the applicability to three-dimensional, large-scale, multiphysic problems, which arise from different areas of the industry. Based on the theory of PDE-constraint optimization, descent methods in structural optimization require knowledge of the (partial) derivatives with respect to shape or topology variations. Therefore, shape and topology sensitivity analysis is introduced and the connection between both sensitivities is given by the Topological-Shape Sensitivity Method. This method leads to a systematic procedure to compute the topological derivative by terms of the shape sensitivity. Due to the framework of moving boundaries in structural optimization, different interface tracking techniques are presented. If the topology of the domain is preserved during the optimization process, explicit interface tracking techniques, combined with mesh-deformation, are used to capture the interface. This techniques fit very well the requirements in classical shape optimization. Otherwise, an implicit representation of the interface is of advantage if the optimal topology is unknown. In this case, the level set method is combined with the concept of the topological derivative to deal with topological perturbation. The resulting methods are applied to different industrial problems. On the one hand, interface shape optimization for solid bodies subject to a transient heat-up phase governed by both linear elasticity and thermal stresses is considered. Therefore, the shape calculus is applied to coupled heat and elasticity problems and a generalized compliance objective function is studied. The resulting thermo-elastic shape optimization scheme is used for compliance reduction of realistic hotplates. On the other hand, structural optimization based on the topological derivative for three-dimensional elasticity problems is observed. In order to comply typical volume constraints, a one-shot augmented Lagrangian method is proposed. Additionally, a multiphase optimization approach based on mesh-refinement is used to reduce the computational costs and the method is illustrated by classical minimum compliance problems. Finally, the topology optimization algorithm is applied to aero-elastic problems and numerical results are presented.
Krylov subspace methods are often used to solve large-scale linear equations arising from optimization problems involving partial differential equations (PDEs). Appropriate preconditioning is vital for designing efficient iterative solvers of this type. This research consists of two parts. In the first part, we compare two different kinds of preconditioners for a conjugate gradient (CG) solver attacking one partial integro-differential equation (PIDE) in finance, both theoretically and numerically. An analysis on mesh independence and rate of convergence of the CG solver is included. The knowledge of preconditioning the PIDE is applied to a relevant optimization problem. The second part aims at developing a new preconditioning technique by embedding reduced order models of nonlinear PDEs, which are generated by proper orthogonal decomposition (POD), into deflated Krylov subspace algorithms in solving corresponding optimization problems. Numerical results are reported for a series of test problems.
In politics and economics, and thus in the official statistics, the precise estimation of indicators for small regions or parts of populations, the so-called Small Areas or domains, is discussed intensively. The design-based estimation methods currently used are mainly based on asymptotic properties and are thus reliable for large sample sizes. With small sample sizes, however, this design based considerations often do not apply, which is why special model-based estimation methods have been developed for this case - the Small Area methods. While these may be biased, they often have a smaller mean squared error (MSE) as the unbiased design based estimators. In this work both classic design-based estimation methods and model-based estimation methods are presented and compared. The focus lies on the suitability of the various methods for their use in official statistics. First theory and algorithms suitable for the required statistical models are presented, which are the basis for the subsequent model-based estimators. Sampling designs are then presented apt for Small Area applications. Based on these fundamentals, both design-based estimators and as well model-based estimation methods are developed. Particular consideration is given in this case to the area-level empirical best predictor for binomial variables. Numerical and Monte Carlo estimation methods are proposed and compared for this analytically unsolvable estimator. Furthermore, MSE estimation methods are proposed and compared. A very popular and flexible resampling method that is widely used in the field of Small Area Statistics, is the parametric bootstrap. One major drawback of this method is its high computational intensity. To mitigate this disadvantage, a variance reduction method for parametric bootstrap is proposed. On the basis of theoretical considerations the enormous potential of this proposal is proved. A Monte Carlo simulation study shows the immense variance reduction that can be achieved with this method in realistic scenarios. This can be up to 90%. This actually enables the use of parametric bootstrap in applications in official statistics. Finally, the presented estimation methods in a large Monte Carlo simulation study in a specific application for the Swiss structural survey are examined. Here problems are discussed, which are of high relevance for official statistics. These are in particular: (a) How small can the areas be without leading to inappropriate or to high precision estimates? (b) Are the accuracy specifications for the Small Area estimators reliable enough to use it for publication? (c) Do very small areas infer in the modeling of the variables of interest? Could they cause thus a deterioration of the estimates of larger and therefore more important areas? (d) How can covariates, which are in different levels of aggregation be used in an appropriate way to improve the estimates. The data basis is the Swiss census of 2001. The main results are that in the author- view, the use of small area estimators for the production of estimates for areas with very small sample sizes is advisable in spite of the modeling effort. The MSE estimates provide a useful measure of precision, but do not reach in all Small Areas the level of reliability of the variance estimates for design-based estimators.
The present thesis addresses the validity of Binge Eating Disorder (BED) as well as underlying mechanisms of BED from three different angles. Three studies provide data discriminating obesity with BED from obesity without BED. Study 1 demonstrates differences between obese individuals with and without BED regarding eating in the natural environment, psychiatric comorbidity, negative affect as well as self reported tendencies in eating behavior. Evidence for possible psychological mechanisms explaining increased intake of BED individuals in the natural environment was given by analyzing associations of negative affect, emotional eating, restrained eating and caloric intake in obese BED compared to NBED controls. Study 2 demonstrated stress-induced changes in the eating behavior of obese individuals with BED. The impact of a psychosocial stressor, the Trier Social Stress Test (TSST, Kirschbaum, Pirke, &amp;amp; Hellhammer, 1993), on behavioral patterns of eating behavior in laboratory was investigated. Special attention was given to stress-induced changes in variables that reflect mechanisms of appetite regulation in obese BED individuals compared to controls. To further explore by which mechanisms stress might trigger binge eating, study 3 investigated differences in stress-induced cortisol secretion after a socially evaluated cold pressure test (SECPT, Schwabe, Haddad, &amp;amp; Schachinger, 2008) in obese BED as compared to obese NBED individuals.