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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.