Highly debilitating natural Trypanosoma vivax infections in Brazilian calves: epidemiology, pathology, and probable transplacental transmission

Clinical, epidemiological, and pathological aspects of trypanosomiasis caused by Trypanosoma vivax in calves were reported for the first time in northeast Brazil. Clinical and epidemiological data, packed cell volumes (PCV), and parasitemia were assessed in 150 calves in May 2009 (rainy season-survey 1) and in 153 calves in November 2009 (dry season-survey 2) in three farms (A, B, and C). Prevalence of T. vivax in calves examined in the survey 1 was 63.3%, 65.0%, and 80.0% in farms A, B, and C, respectively. Morbidity varied from 63.3% to 80%, mortality from 15% to 30% and lethality from 23% to 37.5%. In survey 1, for all farms, high parasitemia (from 30.3 to 26.2x10(6) parasites/mL), fever (from 39.8 to 40.3 degrees C), low PCV (from 15.7% to 18.1%), and body score (from 2.5 to 3.5) were detected. Calves showed depression, weight loss, pale mucous membranes, enlarged lymph nodes, edema of the dewlap, cough, coryza, and diarrhea. The animals from farms A and B were treated with diminazene aceturate. Six months after, in survey 2, non-treated calves from farm C showed values for prevalence (81.82), morbidity (81.82), mortality (12.73), and lethality (15.55) similar to those in survey 1 (P>0.05). Also in survey 2, four calves aging merely 1-3 days old presented high parasitemia levels (from 32x10(6) to 74x10(6) parasites/mL), suggesting transplacental transmission. In conclusion, trypanosomiasis by T. vivax constitutes high prevalent disease for calves raised in Brazilian semiarid and may have transplacental transmission.

Seeking tools for image fusion between computed tomography, structural and functional magnetic resonance methods for applications in neurosurgery

OBJECTIVE: To evaluate tools for the fusion of images generated by tomography and structural and functional magnetic resonance imaging. METHODS: Magnetic resonance and functional magnetic resonance imaging were performed while a volunteer who had previously undergone cranial tomography performed motor and somatosensory tasks in a 3-Tesla scanner. Image data were analyzed with different programs, and the results were compared. RESULTS: We constructed a flow chart of computational processes that allowed measurement of the spatial congruence between the methods. There was no single computational tool that contained the entire set of functions necessary to achieve the goal. CONCLUSION: The fusion of the images from the three methods proved to be feasible with the use of four free-access software programs (OsiriX, Register, MRIcro and FSL). Our results may serve as a basis for building software that will be useful as a virtual tool prior to neurosurgery.

Essays in Applied Health Economics: Evidence on Health and Health Care in Italy and UK

This thesis is the result of my experience as a PhD student taking part in the Joint Doctoral Programme at the University of York and the University of Bologna. In my thesis I deal with topics that are of particular interest in Italy and in Great Britain. Chapter 2 focuses on the empirical test of the existence of the relationship between technological profiles and market structure claimed by Sutton’s theory (1991, 1998) in the specific economic framework of hospital care services provided by the Italian National Health Service (NHS). In order to test the empirical predictions by Sutton, we identify the relevant markets for hospital care services in Italy in terms of both product and geographic dimensions. In particular, the Elzinga and Hogarty (1978) approach has been applied to data on patients’ flows across Italian Provinces in order to derive the geographic dimension of each market. Our results provide evidence in favour of the empirical predictions of Sutton. Chapter 3 deals with the patient mobility in the Italian NHS. To analyse the determinants of patient mobility across Local Health Authorities, we estimate gravity equations in multiplicative form using a Poisson pseudo maximum likelihood method, as proposed by Santos-Silva and Tenreyro (2006). In particular, we focus on the scale effect played by the size of the pool of enrolees. In most of the cases our results are consistent with the predictions of the gravity model. Chapter 4 considers the effects of contractual and working conditions on selfassessed health and psychological well-being (derived from the General Health Questionnaire) using the British Household Panel Survey (BHPS). We consider two branches of the literature. One suggests that “atypical” contractual conditions have a significant impact on health while the other suggests that health is damaged by adverse working conditions. The main objective of our paper is to combine the two branches of the literature to assess the distinct effects of contractual and working conditions on health. The results suggest that both sets of conditions have some influence on health and psychological well-being of employees.

Copper(I) phenanthroline complexes and supramolecular systems containing fullerenes: Photophysics, photochemistry and potential applications in sustainable energy technologies.

Chemistry can contribute, in many different ways to solve the challenges we are facing to modify our inefficient and fossil-fuel based energy system. The present work was motivated by the search for efficient photoactive materials to be employed in the context of the energy problem: materials to be utilized in energy efficient devices and in the production of renewable electricity and fuels. We presented a new class of copper complexes, that could find application in lighting techhnologies, by serving as luminescent materials in LEC, OLED, WOLED devices. These technologies may provide substantial energy savings in the lighting sector. Moreover, recently, copper complexes have been used as light harvesting compounds in dye sensitized photoelectrochemical solar cells, which offer a viable alternative to silicon-based photovoltaic technologies. We presented also a few supramolecular systems containing fullerene, e.g. dendrimers, dyads and triads.The most complex among these arrays, which contain porphyrin moieties, are presented in the final chapter. They undergo photoinduced energy- and electron transfer processes also with long-lived charge separated states, i.e. the fundamental processes to power artificial photosynthetic systems.

Use of solvents and environmental friendly materials for applications in Green Chemistry

The present Thesis studies three alternative solvent groups as sustainable replacement of traditional organic solvents. Some aspects of fluorinated solvents, supercritical fluids and ionic liquids, have been analysed with a critical approach and their effective “greenness” has been evaluated from the points of view of the synthesis, the properties and the applications. In particular, the attention has been put on the environmental and human health issues, evaluating the eco-toxicity, the toxicity and the persistence, to underline that applicability and sustainability are subjects with equal importance. The “green” features of fluorous solvents and supercritical fluids are almost well-established; in particular supercritical carbon dioxide (scCO2) is probably the “greenest” solvent among the alternative solvent systems developed in the last years, enabling to combine numerous advantages both from the point of view of industrial/technological applications and eco-compatibility. In the Thesis the analysis of these two classes of alternative solvents has been mainly focused on their applicability, rather than the evaluation of their environmental impact. Specifically they have been evaluated as alternative media for non-aqueous biocatalysis. For this purpose, the hydrophobic ion pairing (HIP), which allows solubilising enzymes in apolar solvents by an ion pairing between the protein and a surfactant, has been investigated as effective enzymatic derivatisation technique to improve the catalytic activity under homogeneous conditions in non conventional media. The results showed that the complex enzyme-surfactant was much more active both in fluorous solvents and in supercritical carbon dioxide than the native form of the enzyme. Ionic liquids, especially imidazolium salts, have been proposed some years ago as “fully green” alternative solvents; however this epithet does not take into account several “brown” aspects such as their synthesis from petro-chemical starting materials, their considerable eco-toxicity, toxicity and resistance to biodegradation, and the difficulty of clearly outline applications in which ionic liquids are really more advantageous than traditional solvents. For all of these reasons in this Thesis a critical analysis of ionic liquids has been focused on three main topics: i) alternative synthesis by introducing structural moieties which could reduce the toxicity of the most known liquid salts, and by using starting materials from renewable resources; ii) on the evaluation of their environmental impact through eco-toxicological tests (Daphnia magna and Vibrio fischeri acute toxicity tests, and algal growth inhibition), toxicity tests (MTT test, AChE inhibition and LDH release tests) and fate and rate of aerobic biodegradation in soil and water; iii) and on the demonstration of their effectiveness as reaction media in organo-catalysis and as extractive solvents in the recovery of vegetable oil from terrestrial and aquatic biomass. The results about eco-toxicity tests with Daphnia magna, Vibrio fischeri and algae, and toxicity assay using cultured cell lines, clearly indicate that the difference in toxicity between alkyl and oxygenated cations relies in differences of polarity, according to the general trend of decreasing toxicity by decreasing the lipophilicity. Independently by the biological approach in fact, all the results are in agreement, showing a lower toxicity for compounds with oxygenated lateral chains than for those having purely alkyl lateral chains. These findings indicate that an appropriate choice of cation and anion structures is important not only to design the IL with improved and suitable chemico-physical properties but also to obtain safer and eco-friendly ILs. Moreover there is a clear indication that the composition of the abiotic environment has to be taken into account when the toxicity of ILs in various biological test systems is analysed, because, for example, the data reported in the Thesis indicate a significant influence of salinity variations on algal toxicity. Aerobic biodegradation of four imidazolium ionic liquids, two alkylated and two oxygenated, in soil was evaluated for the first time. Alkyl ionic liquids were shown to be biodegradable over the 6 months test period, and in contrast no significant mineralisation was observed with oxygenated derivatives. A different result was observed in the aerobic biodegradation of alkylated and oxygenated pyridinium ionic liquids in water because all the ionic liquids were almost completely degraded after 10 days, independently by the number of oxygen in the lateral chain of the cation. The synthesis of new ionic liquids by using renewable feedstock as starting materials, has been developed through the synthesis of furan-based ion pairs from furfural. The new ammonium salts were synthesised in very good yields, good purity of the products and wide versatility, combining low melting points with high decomposition temperatures and reduced viscosities. Regarding the possible applications as surfactants and biocides, furan-based salts could be a valuable alternative to benzyltributylammonium salts and benzalkonium chloride that are produced from non-renewable resources. A new procedure for the allylation of ketones and aldehydes with tetraallyltin in ionic liquids was developed. The reaction afforded high yields both in sulfonate-containing ILs and in ILs without sulfonate upon addition of a small amount of sulfonic acid. The checked reaction resulted in peculiar chemoselectivity favouring aliphatic substrates towards aromatic ketones and good stereoselectivity in the allylation of levoglucosenone. Finally ILs-based systems could be easily and successfully recycled, making the described procedure environmentally benign. The potential role of switchable polarity solvents as a green technology for the extraction of vegetable oil from terrestrial and aquatic biomass has been investigated. The extraction efficiency of terrestrial biomass rich in triacylglycerols, as soy bean flakes and sunflower seeds, was comparable to those of traditional organic solvents, being the yield of vegetable oils recovery very similar. Switchable polarity solvents as been also exploited for the first time in the extraction of hydrocarbons from the microalga Botryococcus braunii, demonstrating the efficiency of the process for the extraction of both dried microalgal biomass and directly of the aqueous growth medium. The switchable polarity solvents exhibited better extraction efficiency than conventional solvents, both with dried and liquid samples. This is an important issue considering that the harvest and the dewatering of algal biomass have a large impact on overall costs and energy balance.

Polymer controlled mineralization of zinc phosphate hydrates and applications in corrosion protection, catalysis and biomedicine

ZUSAMMENFASSUNG Die Tauglichkeit von Hybridmaterialien auf der Basis von Zinkphosphathydrat-Zementen zum Einsatz als korrosionshemmende anorganische Pigmente oder zur prothetischen und konservierenden Knochen- und Zahntherapie wird weltweit empirisch seit den neunziger Jahren intensiv erforscht. In der vorliegenden Arbeit wurden zuerst Referenzproben, d.h. alpha-und beta-Hopeite (Abk. a-,b-ZPT) dank eines hydrothermalen Kristallisationsverfahrens in wässerigem Milieu bei 20°C und 90°C hergestellt. Die Kristallstruktur beider Polymorphe des Zinkphosphattetrahydrats Zn3(PO4)2  4 H2O wurde komplett bestimmt. Einkristall-strukturanalyse zeigt, daß der Hauptunterschied zwischen der alpha-und beta-Form des Zinkphosphattetrahydrats in zwei verschiedenen Anordnungen der Wasserstoffbrücken liegt. Die entsprechenden drei- und zweidimensionalen Anordnungen der Wasserstoffbrücken der a-und b-ZPT induzieren jeweils unterschiedliches thermisches Verhalten beim Aufwärmen. Während die alpha-Form ihr Kristallwasser in zwei definierten Stufen verliert, erzeugt die beta-Form instabile Dehydratationsprodukt. Dieses entspricht zwei unabhängigen, aber nebeneinander ablaufenden Dehydratationsmechanismen: (i) bei niedrigen Heizraten einen zweidimensionalen Johnson-Mehl-Avrami (JMA) Mechanismus auf der (011) Ebene, der einerseits bevorzugt an Kristallkanten stattfindet und anderseits von existierenden Kristalldefekten auf Oberflächen gesteuert wird; (ii) bei hohen Heizraten einem zweidimensionalen Diffusionsmechanismus (D2), der zuerst auf der (101) Ebene und dann auf der (110) Ebene erfolgt. Durch die Betrachtung der ZPT Dehydratation als irreversibele heterogene Festkörperstufenreaktion wurde dank eines „ähnlichen Endprodukt“-Protokolls das Dehydratationsphasendiagramm aufgestellt. Es beschreibt die möglichen Zusammenhänge zwischen den verschiedenen Hydratationszuständen und weist auf die Existenz eines Übergangszustandes um 170°C (d.h. Reaktion b-ZPT  a-ZPT) hin. Daneben wurde auch ein gezieltes chemisches Ätzverfahren mit verdünnten H3PO4- und NH3 Lösungen angewendet, um die ersten Stufe des Herauslösens von Zinkphosphat genau zu untersuchen. Allerdings zeigen alpha- und beta-Hopeite charakteristische hexagonale und kubische Ätzgruben, die sich unter kristallographischer Kontrolle verbreitern. Eine zuverlässige Beschreibung der Oberfächenchemie und Topologie konnte nur durch AFM und FFM Experimente erfolgen. Gleichzeitig konnte in dieser Weise die Oberflächendefektdichte und-verteilung und die Volumenauflösungsrate von a-ZPT und b-ZPT bestimmt werden. Auf einem zweiten Weg wurde eine innovative Strategie zur Herstellung von basischen Zinkphosphatpigmenten erster und zweiter Generation (d.h. NaZnPO4  1H2O und Na2ZnPO4(OH)  2H2O) mit dem Einsatz von einerseits oberflächenmodifizierten Polystyrolatices (z.B. produziert durch ein Miniemulsionspolymerisationsverfahren) und anderseits von Dendrimeren auf der Basis von Polyamidoamid (PAMAM) beschritten. Die erhaltene Zeolithstruktur (ZPO) hat in Abhängigkeit von steigendem Natrium und Wassergehalt unterschiedliche kontrollierte Morphologie: hexagonal, würfelförmig, herzförmig, sechsarmige Sterne, lanzettenförmige Dendrite, usw. Zur quantitativen Evaluierung des Polymereinbaus in der Kristallstruktur wurden carboxylierte fluoreszenzmarkierte Latices eingesetzt. Es zeigt sich, daß Polymeradditive nicht nur das Wachstum bis zu 8 µm.min-1 reduzierten. Trotzdem scheint es auch als starker Nukleationsbeschleuniger zu wirken. Dank der Koordinationschemie (d.h. Bildung eines sechszentrigen Komplexes L-COO-Zn-PO4*H2O mit Ligandenaustausch) konnten zwei einfache Mechanismen zur Wirkung von Latexpartikeln bei der ZPO Kristallisation aufgezeigt werden: (i) ein Intrakorona- und (ii) ein Extrakorona-Keimbildungsmechanismus. Weiterhin wurde die Effizienz eines Kurzzeit- und Langzeitkorrosionschutzes durch maßgeschneiderte ZPO/ZPT Pigmente und kontrollierte Freisetzung von Phosphationen in zwei Näherungen des Auslösungsgleichgewichts abgeschätzt: (i) durch eine Auswaschungs-methode (thermodynamischer Prozess) und (ii) durch eine pH-Impulsmethode (kinetischer Prozess. Besonders deutlich wird der Ausflösungs-Fällungsmechanismus (d.h. der Metamorphismus). Die wesentliche Rolle den Natriumionen bei der Korrosionshemmung wird durch ein passendes zusammensetzungsabhängiges Auflösungsmodell (ZAAM) beschrieben, das mit dem Befund des Salzsprühteste und der Feuchtigkeitskammertests konsistent ist. Schließlich zeigt diese Arbeit das herausragende Potential funktionalisierter Latices (Polymer) bei der kontrollierten Mineralisation zur Herstellung maßgeschneiderter Zinkphosphat Materialien. Solche Hybridmaterialien werden dringend in der Entwicklung umweltfreundlicher Korrosionsschutzpigmente sowie in der Dentalmedizin benötigt.

Sustainable inorganic Binders and Their Applications in Building Engineering: A Green Alternative to Ordinary Portland Cement

In the last decades, the building materials and construction industry has been contributing to a great extent to generate a high impact on our environment. As it has been considered one of the key areas in which to operate to significantly reduce our footprint on environment, there has been widespread belief that particular attention now has to be paid and specific measures have to be taken to limit the use of non-renewable resources.The aim of this thesis is therefore to study and evaluate sustainable alternatives to commonly used building materials, mainly based on ordinary Portland Cement, and find a supportable path to reduce CO2 emissions and promote the re-use of waste materials. More specifically, this research explores different solutions for replacing cementitious binders in distinct application fields, particularly where special and more restricting requirements are needed, such as restoration and conservation of architectural heritage. Emphasis was thus placed on aspects and implications more closely related to the concept of non-invasivity and environmental sustainability. A first part of the research was addressed to the study and development of sustainable inorganic matrices, based on lime putty, for the pre-impregnation and on-site binding of continuous carbon fiber fabrics for structural rehabilitation and heritage restoration. Moreover, with the aim to further limit the exploitation of non-renewable resources, the synthesis of chemically activated silico-aluminate materials, as metakaolin, ladle slag or fly ash, was thus successfully achieved. New sustainable binders were hence proposed as novel building materials, suitable to be used as primary component for construction and repair mortars, as bulk materials in high-temperature applications or as matrices for high-toughness fiber reinforced composites.

Thin nanostructured crystalline TiO 2 films and their applications in solar cells

Research on thin nanostructured crystalline TiO2 films has attracted considerable interests because of their intriguing physical properties and potential applications in photovoltaics. Nanostructured TiO2 film plays an important role in the TiO2 based dye-sensitized solar cells because they act as a substrate for the adsorption of dye molecules and a matrix for the transportation of electrons as well. Thus they can influence the solar cell performance significantly. Consequently, the control of the morphology including the shape, size and size distribution of the TiO2 nanostructures is critical to tune and optimize the performance of the solar cells. To control the TiO2 morphology, a strategy using amphiphilic block copolymer as templating agent coupled with sol-gel chemistry has been applied. Especially, a good-poor solvent pair induced phase separation process has been developed to guide the microphase separation behavior of the block copolymers. The amphiphilic block copolymers used include polystyrene-block-poly (ethylene oxide) (PS-b-PEO), poly (methyl methacrylate)-block-poly (ethylene oxide) (PMMA-b-PEO), and poly (ethylene oxide)-block-polystyrene-block-poly (ethylene oxide) (PEO-b-PS-b-PEO). The block copolymer undergoes a good-poor-solvent pair induced phase separation in a mixed solution of 1, 4-dioxane or N, N’-dimethyl formamide (DMF), concentrated hydrochloric acid (HCl) and Titanium tetraisopropoxide (TTIP). Specifically, in the system of PS-b-PEO, a morphology phase diagram of the inorganic-copolymer composite films was mapped by adjusting the weight fractions among 1, 4-dioxane, HCl, and TTIP in solution. The amorphous TiO2 within the titania-block copolymer composite films was crystallized by calcination at temperatures above 400C, where the organic block copolymer was simultaneously burned away. This strategy is further extended to other amphiphilic block copolymers of PMMA-b-PEO and PEO-b-PS-b-PEO, where the morphology of TiO2 films can also be controlled. The local and long range structures of the titania films were investigated by the combination of imaging techniques (AFM, SEM) and x-ray scattering techniques (x-ray reflectivity and grazing incidence small-angle x-ray scattering). Based on the knowledge of the morphology control, the crystalline TiO2 nanostructured films with different morphologies were introduced into solid state dye-sensitized solar cells. It has been found that all of the morphologies help to improve the performance of the solar cells. Especially, clustered nanoparticles, worm-like structures, foam-like structures, large collapsed nanovesicles show more pronounced performance improvement than other morphologies such as nanowires, flakes, and nanogranulars.

Evaluation of Microbial Contamination in Bivalve Mollusks: Epidemiology and Diagnosis

Shellfish are filter-feeding organisms that can accumulate many bacteria and viruses. Considering that depuration procedures are not effective in removal of certain microorganisms, shellfish-borne diseases are frequent in many parts of the world, and their control must rely primarily on investigation of prevalence of human pathogens in shellfish and water environment. However, the diffusion of enteric viruses and Vibrio bacteria is not known in many geographical areas, for example in Sardinia, Italy. A survey aimed at investigating the prevalence of Norovirus (NoV), hepatitis A virus (HAV), V. parahaemolyticus, V. cholerae and V. vulnificus was carried out, analyzing both local and imported purified, non-purified and retail shellfish from North Italy and Sardinia. Shellfish from both areas were found contaminated by NoVs, HAV and Vibrio, including retail and purified animals. Molecular analysis evidenced different NoV genogroups and genotypes, including bovine NoVs, as well as pathogenic Vibrio strains, underlining the risk for shellfish consumers. However, also other approaches are needed to control the diffusion of shellfish-borne diseases. It was originally thought that enteric viruses are passively accumulated by shellfish. Recently, it was proven that NoVs bind to specific carbohydrate ligands in oysters, and various NoV strains are characterized by a different bioaccumulation pattern. To deepen the knowledge on this argument, a study was carried out, analyzing bioaccumulation of up to 8 different NoV strains in four different species of shellfish. Different bioaccumulation patterns were observed for each shellfish species and NoV strain used, potentially important in setting up effective shellfish purification protocols. Finally, a novel study of evaluation of viral contamination in shellfish from the French Atlantic coast was carried out following the passage of Xynthia tempest over Western Europe which caused massive destruction. Different enteric viruses were found over a one month period, evidencing the potential of these events of contaminating shellfish.

Essays in Household and Demographic Economics

This dissertation consists of three empirical studies that are believed to provide new contributions to the literature exploring the determinants of children/adolescents achievement test scores (Chapter 2), adolescent health risk behaviors (Chapter 3), and children time use patterns (Chapter 4). The second and third studies look at the separate roles of fathers and of mothers in influencing outcomes, wherein parental time is the resource input of interest quantitatively measured and directly derived from time diaries. The last chapter looks at the time allocation of children and how it varies according to child and household characteristics.

Variation of stable silicon isotopes: Analytical developments and applications in Precambrian geochemistry

Die vorliegende Dissertation behandelt die Gesamtgesteinsanalyse stabiler Siliziumisotope mit Hilfe einer „Multi Collector-ICP-MS“. Die Analysen fanden in Kooperation mit dem „Royal Museum for Central Africa“ in Belgien statt. Einer der Schwerpunkte des ersten Kapitels ist die erstmalige Analyse des δ30Si –Wertes an einem konventionellen Nu PlasmaTM „Multi-Collector ICP-MS“ Instrument, durch die Eliminierung der den 30Si “peak” überlagernden 14N16O Interferenz. Die Analyse von δ30Si wurde durch technische Modifikationen der Anlage erreicht, welche eine höherer Massenauflösung ermöglichten. Die sorgsame Charakterisierung eines adäquaten Referenzmaterials ist unabdingbar für die Abschätzung der Genauigkeit einer Messung. Die Bestimmung der „U.S. Geological Survey“ Referenzmaterialien bildet den zweiten Schwerpunkt dieses Kapitales. Die Analyse zweier hawaiianischer Standards (BHVO-1 and BHVO-2), belegt die präzise und genaue δ30Si Bestimmung und bietet Vergleichsdaten als Qualitätskontrolle für andere Labore. Das zweite Kapitel befasst sich mit kombinierter Silizium-/Sauerstoffisotope zur Untersuchung der Entstehung der Silizifizierung vulkanischer Gesteine des „Barberton Greenstone Belt“, Südafrika. Im Gegensatz zu heute, war die Silizifizierung der Oberflächennahen Schichten, einschließlich der „Chert“ Bildung, weitverbreitete Prozesse am präkambrischen Ozeanboden. Diese Horizonte sind Zeugen einer extremen Siliziummobilisierung in der Frühzeit der Erde. Dieses Kapitel behandelt die Analyse von Silizium- und Sauerstoffisotopen an drei unterschiedlichen Gesteinsprofilen mit unterschiedlich stark silizifizierten Basalten und überlagernden geschichteten „Cherts“ der 3.54, 3.45 und 3.33 Mill. Jr. alten Theespruit, Kromberg und Hooggenoeg Formationen. Siliziumisotope, Sauerstoffisotope und die SiO2-Gehalte demonstrieren in allen drei Gesteinsprofilen eine positive Korrelation mit dem Silizifizierungsgrad, jedoch mit unterschiedlichen Steigungen der δ30Si-δ18O-Verhältnisse. Meerwasser wird als Quelle des Siliziums für den Silizifizierungsprozess betrachtet. Berechnungen haben gezeigt, dass eine klassische Wasser-Gestein Wechselwirkung die Siliziumisotopenvariation nicht beeinflussen kann, da die Konzentration von Si im Meerwasser zu gering ist (49 ppm). Die Daten stimmen mit einer Zwei-Endglieder-Komponentenmischung überein, mit Basalt und „Chert“ als jeweilige Endglieder. Unsere gegenwärtigen Daten an den „Cherts“ bestätigen einen Anstieg der Isotopenzusammensetzung über der Zeit. Mögliche Faktoren, die für unterschiedliche Steigungen der δ30Si-δ18O Verhältnisse verantwortlich sein könnten sind Veränderungen in der Meerwasserisotopie, der Wassertemperatur oder sekundäre Alterationseffekte. Das letzte Kapitel beinhaltet potentielle Variationen in der Quellregion archaischer Granitoide: die Si-Isotopen Perspektive. Natriumhaltige Tonalit-Trondhjemit-Granodiorit (TTG) Intrusiva repräsentieren große Anteile der archaischen Kruste. Im Gegensatz dazu ist die heutige Kruste kaliumhaltiger (GMS-Gruppe: Granit-Monzonite-Syenite). Prozesse, die zu dem Wechsel von natriumhaltiger zu kaliumhaltiger Kruste führten sind die Thematik diesen Kapitels. Siliziumisotopenmessungen wurden hier kombiniert mit Haupt- und Spurenelementanalysen an unterschiedlichen Generationen der 3.55 bis 3.10 Mill. Yr. alten TTG und GMS Intrusiva aus dem Arbeitsgebiet. Die δ30Si-Werte in den unterschiedlichen Plutonit Generationen zeigen einen leichten Anstieg der Isotopie mit der Zeit, wobei natriumhaltige Intrusiva die niedrigste Si-Isotopenzusammensetzung aufweisen. Der leichte Anstieg in der Siliziumisotopenzusammensetzung über die Zeit könnte auf unterschiedliche Temperaturbedingungen in der Quellregion der Granitoide hinweisen. Die Entstehung von Na-reichen, leichten d30Si Granitoiden würde demnach bei höheren Temperaturen erfolgen. Die Ähnlichkeit der δ30Si-Werte in archaischen K-reichen Plutoniten und phanerozoischen K-reichen Plutoniten wird ebenfalls deutlich.

Computational Methods in Biophysics and Medicinal Chemistry: Applications and Challenges

In this thesis I described the theory and application of several computational methods in solving medicinal chemistry and biophysical tasks. I pointed out to the valuable information which could be achieved by means of computer simulations and to the possibility to predict the outcome of traditional experiments. Nowadays, computer represents an invaluable tool for chemists. In particular, the main topics of my research consisted in the development of an automated docking protocol for the voltage-gated hERG potassium channel blockers, and the investigation of the catalytic mechanism of the human peptidyl-prolyl cis-trans isomerase Pin1.