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Wolfgang Kopp Diagnostikzentrum Graz, Graz, 8043, AustriaCorrespondence: Wolfgang KoppFormer Head of Diagnostikzentrum (retired), Mariatrosterstraße 41, Graz 8043, AustriaEmail w.kopp@weiz.ccAbstract: Obesity has reached epidemic proportions and is one of the greatest challenges for public health in the twenty-first century. The macronutrient composition of diets, in particular the amount and ratio of carbohydrates, fat and protein, have received considerable attention in recent decades due to its potential relevance to the development of obesity and weight loss. The effects of various macronutrients on body weight regulation are still under debate. High-carbohydrate diets, and particularly high-fat diets, have been blamed for the increase in the prevalence of obesity. This paper shows that neither fat nor carbohydrates are fattening per se. Mixed diets with substantial amounts of fat and high-glycemic carbohydrates, like current WDs, are required to promote weight gain and obesity. High-glycemic carbohydrates are the active partner (the “driver”), which promotes fat storage through its insulinogenic effect, while fat is the passive partner (the “passenger”) on the way to obesity. Elevated insulin levels (postprandial, but more importantly due to hypersecretion and hyperinsulinemia) promote fat storage and play a key role in obesogenesis and the obesity epidemic. Furthermore, mixed diets high in high-glycemic carbohydrates and fat promote fetal programming, with long-term adverse impacts on the offspring, including insulin hypersecretion, (childhood) obesity and metabolic diseases. Maternal obesity and high weight gain during pregnancy have also been linked to deleterious effects on fetal programming. As the global obesity epidemic increasingly affects women of reproductive age, a significant percentage of fetuses will experience fetal programming with a tendency towards obesity – a self-reinforcing process that further fuels the epidemic. A change in lifestyle and diet composition is needed to prevent or limit the development of obesity and related diseases.Keywords: hypersecretion, hyperinsulinemia, fetal programming, weight gain, insulinogenic Western diet

Wolfgang Kopp Retired Head, Diagnostikzentrum Graz, Graz 8043, AustriaCorrespondence: Wolfgang Kopp Mariatrosterstraße 41, Graz 8043, AustriaEmail w.kopp@weiz.ccAbstract: Westernized populations are plagued by a plethora of chronic non-infectious degenerative diseases, termed as “civilization diseases”, like obesity, diabetes, cardiovascular diseases, cancer, autoimmune diseases, Alzheimer’s disease and many more, diseases which are rare or virtually absent in hunter-gatherers and other non-westernized populations. There is a growing awareness that the cause of this amazing discrepancy lies in the profound changes in diet and lifestyle during recent human history. This paper shows that the transition from Paleolithic nutrition to Western diets, along with lack of corresponding genetic adaptations, cause significant distortions of the fine-tuned metabolism that has evolved over millions of years of human evolution in adaptation to Paleolithic diets. With the increasing spread of Western diet and lifestyle worldwide, overweight and civilization diseases are also rapidly increasing in developing countries. It is suggested that the diet-related key changes in the developmental process include an increased production of reactive oxygen species and oxidative stress, development of hyperinsulinemia and insulin resistance, low-grade inflammation and an abnormal activation of the sympathetic nervous system and the renin-angiotensin system, all of which play pivotal roles in the development of diseases of civilization. In addition, diet-related epigenetic changes and fetal programming play an important role. The suggested pathomechanism is also able to explain the well-known but not completely understood close relationship between obesity and the wide range of comorbidities, like type 2 diabetes mellitus, cardiovascular disease, etc., as diseases of the same etiopathology. Changing our lifestyle in accordance with our genetic makeup, including diet and physical activity, may help prevent or limit the development of these diseases.Keywords: diabetes, obesity, metabolic syndrome, insulin hypersecretion, oxidative stress, paleolithic diet, pathogenesis

In this thesis, we discuss methods for analyzing the non-coding sequence of the genome (e.g promoters) with respect to the identification and enrichment of transcription factor binding sites (TFBSs), as they are related to gene regulation. The identification of pu- tative TFBSs is based on the log- likelihood ratio between a TF motif, which describes the binding affinity of a TF towards the DNA, and a background model, which is im- plemented by an order-d Markov models with d ≥ 0, in conjunction with a pre-defined log- likelihood ratio threshold. Chapter 2 reviews algorithms for computing the false positive probability of calling motif hits for a given threshold. As putative TFBSs can self-overlap one another, which affects the enrichment test of the number of TFBSs, we discuss the quantification of overlapping TFBS predictions in Chapter 3. In Chapter 4, we discuss a compound Poisson model for modeling the distribution of the number of TFBSs in both strands of the DNA sequence, which represents an extension of Pape et al. [36]. The main advance of our model regards the use of newly derived princi- pal overlapping hit probabilities, which are motivated by the discussion of principal periods in Reinert et al. [41], as well as by facilitating the use higher-order Markov models for the background. In Chapter 5 we discuss a novel Markov model which is utilized to determine the probability of a TFBS occurrence that does not overlap a previ- ous TFBS occurrences, termed clump start probability, which mark the beginning of a clump. The resulting clump start probability then serves as an important building block for the subsequent Chapter 6. Finally, in Chapter 6 we present a novel combinatorial model for the distribution of the number of motif hit. To that end, we efficiently sum up the probabilities of all realizations of placing x TFBSs in a finite-length sequence of length N. We systematically compared the accuracy of the combinatorial model, the compound Poisson model and the binomial model. An implementation of the algo- rithms that were discussed in this thesis is provided as an R package that is available at https://github.com/wkopp/mdist., In dieser Dissertation beschäftigen wir uns mit der statistischen Analyse von nicht- kodierenden Segmenten des Genoms. Insbesondere betrachten wir Verfahren zur Identifikation und Anreicherungsanalyse von Transkriptionsfaktorbindungsstellen (TFBSen) in DNA Segmenten (z.B. in Promotoren), da das Binden von Transkriptionsfaktoren regulatorisch auf die Geneexpression benachbarter Gene wirkt. Die Identifikation von TFBSen basiert auf dem Log-likelihood Verhältnis zwischen einem bekanntem Tran- skriptionsfaktormotiv, welches die DNA Bindungsaffinität des Transkriptionsfaktors beschreibt, und einem Hintergrundmodel, z.B. einem Markov Model der Ordnung d, unter Verwendung eines festgelegten Schwellwerts. Kapitel 2 beschreibt die Berech- nung der falsch-positiv Wahrscheinlichkeit für den gewählten Schwellwert. Da die Iden- tifikation von TFBSen zu selbst- überlappenden Vorhersagen führen kann, welche die Anreicherungsanalyse beeinflussen, behandeln wir in Kapitel 3 die Quantifizierung der selbst- überlappenden Vorhersagen. In Kapitel 4 behandeln wir die Compound Poisson Verteilung als analytisches Model für die Anreicherungsanalyse welche selbst- überlap- pende TFBSen auf beiden DNA-Strängen berücksichtigt und eine direkte Weiteren- twicklung von Pape et al. [36] darstellt. Der zentrale Fortschritt in diesem Kapi- tel wurde durch die Verwendung der neuer Überlappwahrscheinlichkeiten und durch die Verwendung von DNA- Hintergrundmodellen höherer Ordnung geleistet. In Kapi- tel 5 führen wir eine Markov Model ein, welches die Wahrscheinlichkeit einer TFBS, die nicht von einer vorhergehenden TFBSen überlappt wird, modelliert. Jene TFBSen markieren immer den Beginn eines oder mehrerer selbst-überlappender TFBS Vorher- sagen (auch motif clumps benannt). Das Ergebnis von Kapitel 5 spielt eine wichtige Hilfsrolle für das darauffolgende Kapitel 6. Schließlich stellen wir ein neues kombi- natorischen Model für die Anreicherungsanalyse in Kapitel 6 vor, welches effizient die Wahrscheinlichkeiten aller möglich Kombinationen x TFBSen in einer endlichen Se- quenz der Länge N zu platzieren aufsummiert. Vergleiche mit dem Compound Pois- son Model zeigten, dass das kombinatorische Model insbesondere für niedrige Log- likelihood-Schwellwerte wesentlich genauere Ergebnisse erzielt. Eine Implementierung der diskutierten Methoden ist als R Paket unter https://github.com/wkopp/mdist verfügbar.

durch Wolfgang Kopp Zsfassung in engl. Sprache. - Literaturverz. Bl. 90 Wien, FH-Campus, FH-StG Technisches Projekt- und Prozessmanagement, Dipl.-Arb., 2005

In the first part a short history of prostitution is given and some examples of its influence on fine arts and music are mentioned. As the general attitudeconcerning prostitution is changing, present practices of Viennese Health Authorities in respect to prostitutes (female sex-workers, FSW) are outlined. FSWs are recruited out of different social categories and nationalities, their legal status varies. The epidemiological and diagnosticalproblems as well as the quality of medical and social assistance are assessed. Good contacts to the female patients already exist, contacts areoffered also to the male sex providers, but these are less cooperative.