Im Rahmen des FACETS-Projektes ist die optimierte Abbildung neuronaler Netzwerke durch spezielle Algorithmen auf dafür konzipierte Hardware notwendig, um die Simulation plastischer und pulsierender Modelle zu ermöglichen. Die Erstellung der biologischen und Hardware- Modelle sowie die Konzeptionierung und Analyse der Algorithmen werden in dieser Arbeit vorgestellt.

Recurrent processes are a general feature of living systems, from the cell cycle to circadian day-night rhythms to hibernation and flowering cycles. During development and life, numerous recurrent processes are controlled by genetic oscillators, a specific class of genetic regulatory networks that generates oscillations in the level of gene products. A vital mechanism controlled by genetic oscillators is the rhythmic and sequential segmentation of the elongating body axis of vertebrate embryos. During this process, a large collection of coupled genetic oscillators gives rise to spatio-temporal wave patterns of oscillating gene expression at tissue level, forming a dynamic prepattern for the precursors of the vertebrae. While such systems of genetic oscillators have been studied extensively over the past years, many fundamental questions about their collective behavior remain unanswered. In this thesis, we study the behavior and the properties of genetic oscillators from the single oscillator scale to the complex pattern forming system involved in vertebrate segmentation. Genetic oscillators are subject to fluctuations because of the stochastic nature of gene expression. To study the effects of noisy biochemical coupling on genetic oscillators, we propose a theory in which both the internal dynamics of the oscillators as well as the coupling process are inherently stochastic. We find that stochastic coupling of oscillators profoundly affects their precision and synchronization properties, key features for their viability as biological pacemakers. Moreover, stochasticity introduces phenomena not known from deterministic systems, such as stochastic switching between different modes of synchrony. During vertebrate segmentation, genetic oscillators play a key role in establishing a segmental prepattern on tissue scale. We study the spatio-temporal patterns of oscillating gene expression using a continuum theory of coupled phase oscillators. We investigate the effects of different biologically relevant factors such as delayed coupling due to complex signaling processes, local tissue growth, and tissue shortening on pattern formation and segmentation. We find that the decreasing tissue length induces a Doppler effect that contributes to the rate of segment formation in a hitherto unanticipated way. Comparison of our theoretical findings with experimental data reveals the occurrence of such a Doppler effect in vivo. To this end, we develop quantification methods for the spatio-temporal patterns of gene expression in developing zebrafish embryos. On a cellular level, tissues have a discrete structure. To study the interplay of cellular processes like cell division and random cell movement with pattern formation, we go beyond the coarse-grained continuum theories and develop a three-dimensional cell-based model of vertebrate segmentation, in which the dynamics of the segmenting tissue emerges from the collective behavior of individual cells. We show that this model is able to describe tissue formation and segmentation in a self-organized way. It provides the first step of theoretically describing pattern formation and tissue dynamics during vertebrate segmentation in a unified framework involving a three-dimensional tissue with cells as distinct mechanical entities. Finally, we study the synchronization dynamics of generic oscillator systems whose coupling is subject to phase shifts and time delays. Such phase shifts and time delays are induced by complex signaling processes as found, e.g., between genetic oscillators. We show how phase shifts and coupling delays can alter the synchronization dynamics while leaving the collective frequency of the synchronized oscillators invariant. We find that in globally coupled systems, fastest synchronization occurs for non-vanishing coupling delays while in spatially extended systems, fastest synchronization can occur on length scales larger than the coupling range, giving rise to novel synchronization scenarios. Beyond their potential relevance for biological systems, these results have implications for general oscillator systems, e.g., in physics and engineering. In summary, we use discrete and continuous theories of genetic oscillators to study their dynamic behavior, comparing our theoretical results to experimental data where available. We cover a wide range of different topics, contributing to the general understanding of genetic oscillators and synchronization and revealing a hitherto unknown mechanism regulating the timing of embryonic pattern formation.

In dieser Arbeit wird die Eignung eines Haarwurzelsystems (HR) aus transgenen Sonnenblumen-hairy roots zur biotechnologischen Produktion von α-Tocopherol untersucht. Es wurden hairy roots mit und ohne Transgene erzeugt. Transgene HR exprimieren Tocopherolbiosynthesegene aus Arabidopsis thaliana. Die HR wurden unterschiedlichen Stressoren unterworfen, um die α-Tocopherolproduktion binnen eines Zeitraums zu überprüfen. Stressoren waren verringerte Kohlenstoffquelle, Beleuchtung und der Zusatz von Zytokininen. Die Produktionsleistung des Systems ist schlussendlich ungenügend zur kostengünstigen Produktion von α-Tocopherol.

In der vorliegenden Arbeit untersuchten wir an einer europäischen Population ausgewählte Polymorphismen zweier Gene auf eine Assoziation zu IA. Beide Gene FIGF und ACE2 sind lokalisiert auf Chromosom Xp22 und stellen damit positionelle Kandidatengene dar, aber auch funktionell sind sie von Interesse, da sie v.a. in Prozesse des Gefäßwachstums (FIGF) und der Blutdruckregulierung (ACE2) involviert sind; Vorgänge also, die möglicherweise in die pathophysiologische Erklärung der IA Entstehung mit hineinspielen. In keinem der insgesamt neun analysierten Polymorphismen konnten wir jedoch eine signifikante Assoziation zu IA finden. Auch eine Analyse möglicher intra- und intergenetischer Haplotypen aller untersuchten Varianten erbrachte kein signifikantes Ergebnis.

Social anxiety disorder, also known as social phobia, is one of the most prevalent anxiety disorders, affecting 7-13% of subjects in the community at some time in their lives. Despite being eminently treatable, it remains largely under-recognised and, therefore, undertreated. The disorder is characterized by a fear of scrutiny by others, with sufferers experiencing excessive anxiety in social and performance situations. This excessive anxiety usually leads to avoidance behaviour that can severely affect normal daily living. With onset commonly occurring during childhood or adolescence, social anxiety disorder may disrupt normal patterns of development of social and personal relationships, often having a long-term impact on emotional stability in social or working life. If left untreated, the course of social anxiety disorder is frequently complicated with comorbid conditions, particularly major depression or substance abuse. This review assesses the size of the clinical problem by evaluating current and lifetime prevalence estimates, age of onset, risk factors and evolution of the clinical course; thereby providing the rationale for early recognition and prompt treatment.

The research project “Beethovens Werkstatt” is intended as a contribution to basic musicological research. Methods, concepts and digital components developed in this project using the example of Beethoven are meant to be transferable to other composers. In my paper, I choose Robert Schumann as an example to test this transferability. Concepts that were developed in the course of the first module of “Beethovens Werkstatt” aim at the reconstruction and digital representation of genetic variants. They are based on research on the composer’s work processes. Fundamental aspects of this research include, for example, the temporality of the writing process; the composer’s self-critical dialogue with what he has already written; the work routines that may lie behind it (can certain compositional strategies be derived from them?). These questions are not only specific to Beethoven. They can generally be asked in connection with other composers. However, a prerequisite for an insightful research is a good record of handwritten texts and manuscripts. Due to the rich source material and Schumann’s habit of documenting many details in his diaries and working manuscripts, a text-genetic and digital analysis of his working methods is particularly suitable.

Die Broschüre beschreibt den erreichten Sachstand der forstlichen Generhaltung und zeigt die Wege auf, die in Zukunft im Freistaat Sachsen beschritten werden sollen. Die Veröffentlichung richtet sich an die Beschäftigten in der Forstwirtschaft, dem Naturschutz und den Umweltwissenschaften, an interessierte Bürgerinnen und Bürger sowie an Entscheidungsträger in Politik und Verwaltung. Redaktionsschluss: 30.06.2021

Gegenstand: Seit der vollständigen Entschlüsselung des menschlichen Genoms ist es mit geringem Aufwand möglich, Menschen über das Vorliegen erblich (mit-)bedingter Erkrankungen - sogar vor deren Ausbruch - zu informieren. „Gentests“ sind jedoch umstritten. Neben Vorteilen wie der Ermöglichung präventiver medizinischer Maßnahmen oder möglichst frühzeitiger Interventionen werden auch immense Nachteile für das Individuum, wie z.B. eine hohe psychosoziale Belastung, deutlich. Die tatsächliche Inanspruchnahme genetischer Untersuchungen hängt in erheblichem Maße von den persönlichen Einstellungen ab. Besonders große Bedeutung wird hierbei den behandelnden Ärzten zuteil, die Patienten hinsichtlich der Möglichkeiten und Einschränkungen von genetischen Untersuchungen beraten. Ziel dieser Studie war es, die Einstellungen zu genetischen Untersuchungen bei angehenden Medizinern zu erfragen und die Ergebnisse über mehrere Jahre hinweg miteinander zu vergleichen. Zusätzlich wurde der Einfluss verschiedener Determinanten auf die Einstellungen zu genetischen Untersuchungen erfasst. Untersuchungsmethoden: In drei unabhängigen Fragebogenerhebungen wurden in den Jahren 2001 (N = 129), 2010 (N = 196) und 2016/17 (N = 134) Medizinstudierende zu ihren Einstellungen zu genetischen Untersuchungen befragt. Hierfür wurde ein 13 Items umfassender Fragebogen genutzt, der aus einer finnischen Studie übernommen wurde und positive und negative Aspekte sowie Befürchtungen und Vertrauen bzgl. genetischer Untersuchungen erfasst. Zusätzlich wurden die Variablen Religion, Politik, Geschlecht, Alter und Persönlichkeit erfasst. Ergebnisse: Medizinstudierende sind genetischen Untersuchungen gegenüber sowohl kritisch als auch befürwortend eingestellt. Sie sehen tendenziell jedoch mehr positive Effekte. Die Berechnungen von ANOVAs ergaben, dass im Jahresverlauf positive Aspekte konstant bleiben, negative Aspekte und Befürchtungen abnehmen und das Vertrauen zunimmt. Regressionsanalysen ergaben, dass die Einstellungen zu genetischen Untersuchungen durch die Religion (religiöse Menschen sind Gentests gegenüber kritischer eingestellt) und die Persönlichkeit (verträgliche Menschen sind positiver eingestellt, emotional stabile haben mehr Befürchtungen), nicht jedoch durch die politische Orientierung, Geschlecht und Alter beeinflusst werden. Geschlecht und Alter bedingten ausschließlich den Einfluss der Persönlichkeit auf die Einstellungen zu genetischen Untersuchungen. Schlussfolgerung: Die Zunahme Gentests befürwortender Einstellungen von Medizinstudierenden während der vergangenen 16 Jahre bei gleichzeitiger kritischer Auseinandersetzung mit der Thematik ist positiv zu bewerten. Nur so kann eine patientenorientierte, non-direktive Beratung bzgl. genetischer Untersuchungen gelingen. Um diese zu unterstützen, sollten psychosoziale Aspekte humangenetischer Beratung ausnahmslos Gegenstand der universitären Ausbildung Medizinstudierender sein. / Purpose: Since the advent of whole-genome sequencing, little effort is necessary to individually inform people about the presence of hereditary diseases, even before symptoms appear. However varying opinions exist regarding the application of genetic testing. There are various recognizable advantages, such as enabling early medical interventions or preventive measures, as well as immense disadvantages e.g. high psychosocial strain. The actual use of genetic testing depends, to a considerable extent, on the personal attitudes of respective individuals. Of particular importance are the attending physicians, advising the patients on possibilities and limitations of genetic testing. The objective of this study was to investigate future physician’s attitudes towards genetic testing, and to observe potential changes in their attitudes over a certain period of time. Additionally, the influence of different determinants on the attitude towards genetic testing was examined. Methods: Medicine students were questioned on three independent measurements in 2001 (N = 129), 2010 (N = 196) and 2016/17 (N = 134) on their attitudes towards genetic testing. For this purpose a German version of a Finnish questionnaire consisting of 13 items covering approval, disapproval, concern and trust regarding genetic testing was used. Additionally religiosity, political opinion, sex, age and personality were determined. Results: In general medicine students show positive as well as negative attitudes regarding genetic testing. There is a tendency towards a slightly more positive opinion. ANOVA results indicate no changes in approval regarding genetic testing during the different measurements. In contrast to these results disapproval and concerns decreased whereas trust increased. Regression analysis demonstrated that people with a religious affiliation held a less favorable view of genetic testing. People with a higher level in Agreeableness demonstrate a higher level of approval whereas people with a higher level in Emotional Stability show more concerns regarding genetic testing. There was no influence in the categories of political opinion, sex and age. The effect of the personality on the attitudes towards genetic testing was influenced by sex and age. Conclusions: The increase of approving opinions of medicine students towards genetic testing during the last 16 years, despite simultaneous and critical debate regarding the same topic, can be evaluated as a positive development. It can help to ensure a patient-centered and non-directive genetic counseling. In support of this development, psychosocial aspects of genetic counseling should, without exception, be included in university education.

Spreadsheets are very successful content generation tools, used in almost every enterprise to create a wealth of information. However, this information is often intermingled with various formatting, layout, and textual metadata, making it hard to identify and interpret the tabular payload. Previous works proposed to solve this problem by mainly using heuristics. Although fast to implement, these approaches fail to capture the high variability of user-generated spreadsheet tables. Therefore, in this paper, we propose a supervised approach that is able to adapt to arbitrary spreadsheet datasets. We use a graph model to represent the contents of a sheet, which carries layout and spatial features. Subsequently, we apply genetic-based approaches for graph partitioning, to recognize the parts of the graph corresponding to tables in the sheet. The search for tables is guided by an objective function, which is tuned to match the specific characteristics of a given dataset. We present the feasibility of this approach with an experimental evaluation, on a large, real-world spreadsheet corpus.

Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. - Design: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case–control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). - Results: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10⁻⁹, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10⁻⁵, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10⁻⁴⁴). - Conclusion: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.