Bøker utgitt av Cuvillier

In chemical biology, the fluorescent labeling of molecules and usage of fluorescence-based imaging techniques for visualizing molecular interactions at a subcellular level is a key feature and contributes significantly to the elucidation of disease mechanisms. Furthermore, potential drug target sites can be identified, drugs acting on such sites can be developed, and by their labeling, the interactions of drugs and targets can be uncovered. In this work, innovative approaches for the fluorescent labeling of proteins, nucleic acids, and drugs are presented. A novel methodology for the facile synthesis of a versatile, functionalized, water-soluble, and tunable fluorescent probe has been developed. As a class of promising drug candidates, oligonucleotides were labeled in a dual-color readout DNA/RNA ¿Traffic Lights¿ concept that allows reliable tracking of cellular delivery, target binding, and structural integrity of nucleic acids. To ensure efficient early detection of diseases, a melanocyte-specific compound has been synthesized with the goal of enabling melanoma detection via non-invasive fluorescence microscopy. Once a cancerous disease with a solid tumor is detected, the efficient transport of a drug to the tumor site and local accumulation is of meaningful impact. A polymeric nanocarrier system for targeted tumor transport and triggered drug release has been developed.

The separation of isotopes has always been a challenge because of their identical size, shape and thermodynamic properties. Nowadays, the extraction of deuterium is performed e.g. by the Girdler Sulfid process or cryogenic distillation, which lead to low separation factors (below 2.5) in combination with high energy costs. The standard way to produce helium-3 is to skim it as a byproduct of the radioactive tritium decay.In this thesis, two alternative approaches have been investigated for the separation of light isotopes, Quantum Sieving and Chemical Affinity Sieving . While Quantum Sieving is based on confinement in small pores, Chemical Affinity Sieving relies on strong adsorption sites. Both methods use the mass difference of the isotopes, which is related to their zero-point energy.The microporous metal-organic frameworks are excellent candidates for studying these quantum effects due to their well-defined pore structure and the possibility to introduce strong adsorption sites directly into the framework. The samples have been exposed to an isotope mixture and the adsorbed quantity of each isotope was detected by low-temperature thermal desorption spectroscopy (TDS). The ratio of the desorbed amount of the isotopes leads directly to the selectivity (separation factor). The selectivity is determined as a function of exposure time and temperature and exhibits the highest value of 25 observed for hydrogen isotopes at temperatures well above the boiling point of liquid nitrogen.

Variations in insulin regulation reflect either as tissue insulin resistance or insulin dysregulation result in moderate to severe hyperinsulinemia in horses and ponies suffering from the Equine Metabolic Syndrome (EMS). Several pathomechanisms provoking equine insulin resistance have been suggested, but insulin signaling in healthy horses has not been studied in detail so far. Thus the objective of this PhD project was to investigate equine insulin sensitivity, glucose homeostasis and lipid metabolism by combining examinations of insulin signaling on a protein level in different main metabolic tissues and analyses of dynamic hormone and metabolite changes during acute stimulations by either oral glucose application or IV insulin and glucose injection. Furthermore, systemic markers of insulin resistance were analyzed by an innovative targeted metabolomics approach to provide better understanding of potential pathomechanisms involved in impaired insulin regulation in horses. In conclusion, equine-specific insulin signaling, the marginal relationship of insulin sensitivity to obesity and strong associations of high plasma insulin concentration to cellular oxidative stress depicted not only a special physiological condition but also indicate novel pathophysiological conditions underlying EMS.

Magnetic nanostructures in thin films and their behavior have seen a drastic increase in scientific interest in the last decades. Similarly, X-ray microscopy has moved into the spotlight since the turn of the century. This thesis combines both topics with the investigation of magnetic vortex structures under pulsed field excitation using both micromagnetic simulations and time resolved magnetic X-ray microscopy. This allowed the observation of vortex core polarization switches with

This dissertation investigates the impact of the European regulatory measures MAD (Market Abuse Directive, introduced in 2003) and MiFID (Markets in Financial Instruments Directive, introduced in 2004) on the behaviour and information environment of sell-side financial analysts. The MAD and the MiFID are, amongst other objectives, geared up for the mitigation of conflicts of interest in the field of the financial analysts' investment research and the prohibition of selective disclosures. The impact of the regulatory measures is examined by using the common sell-side financial analysts' quantitative outputs target prices, earnings forecasts and stock recommendations. The main results of the empirical analysis imply that the regulatory measures induced conflicted sell-side analysts to avoid the intended impacts of the regulatory measures when issuing target prices. Moreover, the regulatory measures, which should prevent selective disclosures, can have unintended consequences, too.