Social phobia is a disabling, lifelong disorder characterised by fear in social settings. The aim of the present study was to gain more knowledge about diagnostic, neurobiologic and epidemiologic aspects of social phobia. Thirty-two individuals were assessed by the Structured Clinical Interview for DSM-IV Axis I and II psychiatric disorders, the Karolinska Scales of Personality and the Temperament and Character Inventory. Social phobia was accompanied by concurrent axis I disorders in about 28% of individuals, lifetime axis I disorders in 54%, personality disorders in 60%, and avoidant personality disorder (APD) in 47%. This suggests that there is a high comorbidity between social phobia and APD according to the DSM-IV criteria. The personality profiles associated with social phobia were dominated by anxiety-related traits that were primarily related to social phobia itself and not to the presence of concurrent personality disorders. Eighteen subjects with social phobia and eighteen controls were investigated with positron emission tomography and the radiolabeled serotonin precursor, [3 -11C]–5-HTP (5-HTP). Individuals with social phobia demonstrated proportionally lower regional relative whole brain accumulation of 5-HTP in areas of the frontal and temporal cortices as well as the striatum, but higher accumulation in the cerebellum. This suggests that there are imbalances in presynaptic serotonin function in individuals with social phobia, although this could only be confirmed in men, and not in women. By means of a postal survey, distributed to 2000 randomly selected individuals, social phobia in Sweden was found to be common, with a point prevalence of 15.6%.

The main intention of the author consisted in understandable presentation of the application of Structural and Cohesion Funds in a member state of the European Union, particularly in the case of a small-sized company. The purpose of the diploma thesis was to provide the reader with an overview of European Union Structural and Cohesion Funds in general and of those available in the Czech Republic as well. The opportunities to gain funding from European Union of one small sized Czech firm were examined in the last part of the essay. The case study of Czech enterprise proved that the co-financing of projects in a member state can be cumbersome but also very beneficial when approached properly.

The mining, processing, and use of finite natural resources is associated with significant interventions in the natural environment. Thus, these and other negative consequences make it necessary to reduce resource consumption. An important field of action is the more efficient use of biogenic residues as secondary raw materials. However, high water containing biomasses are still a problem since they need an energy- and cost-intensive pre-treatment for many conversion processes, which can make their use uneconomical. Hydrothermal processes (HTP) seem to be promising, since they require an aqueous environment for optimal processing anyway. Although technological progress within the industry is recognisable, however, to date HTP have not been established in industrial continuous operation in Germany. The core of this work is identifying reasons for this sluggish development and deriving appropriate recommendations for action. Based on the hypothesis that HTP can contribute to the efficient utilisation of biogenic residues in the future, potentials and obstacles for the development of HTP in Germany are identified using a literature review, expert survey, expert workshop, and SWOT analysis. To estimate the future potential of HTP in a systematic and structured way, a multi-criteria technology assessment approach is developed based on the results. To this end, assessment criteria for HTP are derived, weighted by expert judgment, and integrated into a transparent and structured procedure. In addition, mainly based on a Delphi-survey key factors of HTP development by 2030 in Germany are identified and three development alternatives for HTP in Germany by 2030 are derived. Using a system analysis and a comparative multi-criteria analysis at plant level, these scenarios are analysed for their possible future impact. Based on this methodology, the work shows that the production costs for the end products, the energy efficiency of the process, and the proportion of recycled phosphorus are of high relevance to the techno-economic success of HTP compared to reference systems, and they are therefore of high importance for its future development on the plant level. In addition, further key factors for the future development of HTP in Germany on the system level are found to be mainly in the political-legal (e.g. legal waste status of products from HTP) and techno-economic (e.g. cost-effective process water treatment) areas. According to this, important fields of action are the identification and use of cost reduction potentials (e.g. heat waste use), the development of system integrated decentralised plant concepts with integrated nutrient recycling (e.g. phosphorus), and the development of cost-effective ways to treat process water. System integration, cost-effective process water treatment, and nutrient recycling are all closely linked to production costs, investment costs, and potential revenues, and can contribute to improved process economics. For these areas, there is promising future potential to achieve higher competitiveness with reference technologies that are currently more economical.:Bibliographic description Curriculum Vitae Selbstständigkeitserklärung Danksagung List of Publications Contribution to the Publications Contents List of Acronyms List of Tables List of Figures Part I Introductory Chapters 1 Introduction and Background Hydrothermal processes: Introduction and status quo State of the art in the research field and knowledge gaps Objective and research framework Expected value added of this work 2 Materials and methods Derivation of HTP evaluation metrics and technology assessment tool Derivation of key HTP development factors and scenarios Performing the system-level scenario analysis Plant-level scenario analysis and test application of the assessment tool Derivation of core recommendations 3 Results and discussion Key development factors for HTP in Germany and scenarios System-level scenario analysis Test application of the assessment tool on plant level scenarios Recommendations Discussion 4 Conclusion and outlook Future research Further fields for the application of the developed methods 5 References Part II Appended Articles Paper I Paper II Paper III Paper IV Paper V Paper VI / Der Abbau, die Verarbeitung und die Nutzung endlicher natürlicher Ressourcen sind mit erheblichen Eingriffen in die natürliche Umwelt verbunden. Diese und andere negative Folgen machen es daher erforderlich, den Ressourcenverbrauch zu senken. Ein wichtiges Handlungsfeld ist die effizientere Nutzung biogener Reststoffe als Sekundärrohstoffe. Stark wasserhaltige Biomassen sind jedoch ein Problem, da sie für viele Umwandlungsprozesse eine energie- und kostenintensive Vorbehandlung benötigen, was ihre Verwendung unwirtschaftlich machen kann. Hydrothermale Prozesse (HTP) scheinen für diese Reststoffe allerdings vielversprechend zu sein, da sie ohnehin eine wässrige Umgebung für eine optimale Verarbeitung benötigen. Obwohl der technologische Fortschritt innerhalb der Branche erkennbar ist, wurde HTP in Deutschland bisher nicht im industriellen Dauerbetrieb etabliert. Der Kern dieser Arbeit besteht darin, Gründe für diese schleppende Entwicklung zu ermitteln und geeignete Handlungsempfehlungen abzuleiten. Basierend auf der Hypothese, dass HTP in Zukunft zur effizienten Nutzung biogener Reststoffe beitragen können, werden Potenziale und Hindernisse für deren Entwicklung in Deutschland anhand einer Literaturrecherche, einer Expertenumfrage, eines Expertenworkshops und einer SWOT-Analyse ermittelt. Um das zukünftige Potenzial von HTP systematisch und strukturiert abzuschätzen, wird basierend auf den Ergebnissen ein multi-kriterieller Technologiebewertungsansatz entwickelt. Zu diesem Zweck werden Bewertungskriterien für HTP abgeleitet, nach Expertenmeinung gewichtet und in ein transparentes und strukturiertes Verfahren integriert. Darüber hinaus werden hauptsächlich auf der Grundlage einer Delphi-Umfrage Schlüsselfaktoren für die HTP-Entwicklung bis 2030 in Deutschland identifiziert und drei Entwicklungsalternativen für HTP in Deutschland bis 2030 abgeleitet. Mithilfe einer Systemanalyse und einer vergleichenden multi-kriteriellen Analyse auf Anlagenebene werden diese Szenarien auf ihre möglichen zukünftigen Auswirkungen hin analysiert. Basierend auf dieser Methodik zeigen sich als Ergebnisse, dass die Produktionskosten für die Endprodukte, die Energieeffizienz der Prozesse und der Anteil an recyceltem Phosphor für den techno-ökonomischen Erfolg von HTP im Vergleich zu Referenzsystemen von hoher Relevanz und daher auch von hoher Bedeutung für die zukünftige Entwicklung auf Anlagenebene sind. Darüber hinaus liegen weitere Schlüsselfaktoren für die künftige Entwicklung von HTP in Deutschland auf Systemebene hauptsächlich im politisch-rechtlichen (z. B. legalen Abfallstatus von Produkten aus HTP) und techno-ökonomischen (z. B. kostengünstige Prozesswasseraufbereitung)) Bereichen. Wichtige Handlungsfelder sind demnach die Ermittlung und Nutzung von Kostensenkungspotentialen (zB Abwärmenutzung), die Entwicklung systemintegrierter dezentraler Anlagenkonzepte mit integriertem Nährstoffrecycling (z.B. Phosphor) und die Entwicklung kostengünstiger Wege zur Prozesswasserbehandlung. Systemintegration, kostengünstige Prozesswasseraufbereitung und Nährstoffrecycling hängen eng mit Produktionskosten, Investitionskosten und potenziellen Einnahmen zusammen und können zu einer verbesserten Wirtschaftlichkeit der Prozesse beitragen. Für diese Bereiche besteht ein vielversprechendes Zukunftspotenzial für eine höhere Wettbewerbsfähigkeit zu Referenztechnologien, die derzeit noch wirtschaftlicher sind.:Bibliographic description Curriculum Vitae Selbstständigkeitserklärung Danksagung List of Publications Contribution to the Publications Contents List of Acronyms List of Tables List of Figures Part I Introductory Chapters 1 Introduction and Background Hydrothermal processes: Introduction and status quo State of the art in the research field and knowledge gaps Objective and research framework Expected value added of this work 2 Materials and methods Derivation of HTP evaluation metrics and technology assessment tool Derivation of key HTP development factors and scenarios Performing the system-level scenario analysis Plant-level scenario analysis and test application of the assessment tool Derivation of core recommendations 3 Results and discussion Key development factors for HTP in Germany and scenarios System-level scenario analysis Test application of the assessment tool on plant level scenarios Recommendations Discussion 4 Conclusion and outlook Future research Further fields for the application of the developed methods 5 References Part II Appended Articles Paper I Paper II Paper III Paper IV Paper V Paper VI

<p>Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s.</p><p>We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s. </p><p>Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection.</p><p>A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s).</p><p>Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s. </p>

Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s. We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in &gt;50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s. Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p&lt;0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection. A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s). Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s.

Monocytes exhibiting a pro-inflammatory phenotype play a key role in adhesion and development of atherosclerotic plaques. As an alternative to smoking, next-generation tobacco and nicotine products (NGP) are now widely used. However, little is known about their pro-inflammatory effects on monocytes. We investigated cell viability, anti-oxidant and pro-inflammatory gene and protein expression in THP-1 monocytes after exposure to aqueous smoke extracts (AqE) of a heated tobacco product (HTP), an electronic cigarette (e-cig), a conventional cigarette (3R4F) and pure nicotine (nic). Treatment with 3R4F reduced cell viability in a dose-dependent manner, whereas exposure to alternative smoking products showed no difference to control. At the highest non-lethal dose of 3R4F (20%), the following notable mRNA expression changes were observed for 3R4F, HTP, and e-cig respectively, relative to control; HMOX1 (6-fold, < 2-fold, < 2-fold), NQO1 (3.5-fold, < 2-fold, < 2-fold), CCL2 (4-fold, 3.5-fold, 2.5-fold), IL1B (4-fold, 3-fold, < 2-fold), IL8 (5-fold, 2-fold, 2-fold), TNF (2-fold, 2-fold, < 2-fold) and ICAM1 was below the 2-fold threshold for all products. With respect to protein expression, IL1B (3-fold, < 2-fold, < 2-fold) and IL8 (3.5-fold, 2-fold, 2-fold) were elevated over the 2-fold threshold, whereas CCL2, TNF, and ICAM1 were below 2-fold expression for all products. At higher doses, greater inductions were observed with all extracts; however, NGP responses were typically lower than 3R4F. In conclusion, anti-oxidative and pro-inflammatory processes were activated by all products. NGPs overall showed lower responses relative to controls than THP-1 cells exposed to 3R4F AqE.