Doctor of Philosophy

dissertationSemiconductor nanocrystal quantum dots are a relatively recent area of study in materials science and engineering, but their unique, size-dependent properties have resulted in active growth over the past three decades. The motivation for this thesis has been exploiting the ability to tune the energy band gap and develop new families of geothermal reservoir tracers. While colloid transport in porous media has been studied extensively for groundwater systems, there is little existing research appropriate to high temperature geothermal systems. In this research, a multitiered approach is used to characterize quantum dot behavior at temperatures above 100 °C. First, a model system of cadmium selenide (CdSe) quantum dots is used to investigate fundamental aspects of nanocrystal growth and dissolution. Observing quantum dot dissolution and modeling the kinetic parameters yields critically important thermodynamic properties. These parameters are necessary for optimizing large-scale reactor conditions and design, and predicting fluid-phase quantum dot behavior. Insight into these thermodynamic properties provides the basis for experimentally studying transport in high temperature porous media that are surrogates for a geothermal reservoir. Core/shell quantum dots were pumped through Ottawa sand columns under a range of temperatures and salinities. Retardation and deposition were investigated as the principal transport parameters, while also considering the dynamics of quantum dot solubility and the interaction energy between quantum dots and the sand surfaces. Elevated temperatures increased the amount of quantum dot retention, following a multilayer deposition model. Finally, a novel method for detecting optically active species is introduced. Existing techniques for optical detection of quantum dots fail in turbid or high temperature environments. We demonstrate how the characteristic absorption - coupled with a long-wavelength overtone band - can be used to detect QDs in a variety of industrially relevant mixtures

Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker

Background: The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor alpha beta-positive CD8(+) memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples. Results: We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation. Conclusions: DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed

Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides

Bacterial endotoxins (lipopolysaccharides (LPS)) are strong elicitors of the human immune system by interacting with serum and membrane proteins such as lipopolysaccharide-binding protein (LBP) and CD14 with high specificity. At LPS concentrations as low as 0.3 ng/ml, such interactions may lead to severe pathophysiological effects, including sepsis and septic shock. One approach to inhibit an uncontrolled inflammatory reaction is the use of appropriate polycationic and amphiphilic antimicrobial peptides, here called synthetic anti-LPS peptides (SALPs). We designed various SALP structures and investigated their ability to inhibit LPS-induced cytokine secretion in vitro, their protective effect in a mouse model of sepsis, and their cytotoxicity in physiological human cells. Using a variety of biophysical techniques, we investigated selected SALPs with considerable differences in their biological responses to characterize and understand the mechanism of LPS inactivation by SALPs. Our investigations show that neutralization of LPS by peptides is associated with a fluidization of the LPS acyl chains, a strong exothermic Coulomb interaction between the two compounds, and a drastic change of the LPS aggregate type from cubic into multilamellar, with an increase in the aggregate sizes, inhibiting the binding of LBP and other mammalian proteins to the endotoxin. At the same time, peptide binding to phospholipids of human origin (e.g., phosphatidylcholine) does not cause essential structural changes, such as changes in membrane fluidity and bilayer structure. The absence of cytotoxicity is explained by the high specificity of the interaction of the peptides with LPS

Health and social problems associated with recent Novel Psychoactive Substance (NPS) use amongst marginalised, nightlife and online users in six European countries.

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland (n = 3023). Some respondents were unable to categorise NPS they had used. Use of ‘herbal blends’ and ‘synthetic cannabinoids obtained pure’ was most reported in Germany, Poland and Hungary, and use of ‘branded stimulants’ and ‘stimulants/empathogens/nootropics obtained pure’ was most reported in the Netherlands. Increased heart rate and palpitation, dizziness, anxiety, horror trips and headaches were most commonly reported acute side effects. Marginalised users reported substantially more acute side effects, more mid- and long-term mental and physical problems, and more social problems. Development of country-specific NPS awareness raising initiatives, health and social service needs assessments, and targeted responses are warranted

High energy synchrotron diffraction study of a transformation induced plasticity steel during tensile deformation

Energy-dispersive x-ray diffraction offers the possibility for measurement and evaluation of diffraction spectra containing information of various diffraction lines of all contributing crystalline phases of a material. Combined strain imaging and diffraction analysis was conducted during the tensile test of a low alloyed transformation-induced plasticity (TRIP) steel in order to investigate the transformation induced plasticity, strain hardening, and load partitioning effects. Optical strain imaging allowed for determination of localized true strains from three-dimensional deformations measured in situ. High-energy synchrotron radiation has permitted diffraction analysis in transmission mode to gather information from the material interior. Phase-specific stress evolution during loading could be observed applying the sin2ψ technique during certain load steps. The strains of the individual lattice planes were determined in different locations under varying angles between loading and perpendicular direction. Using energy-dispersive methods it was also possible to determine the transformation behaviour during elastic and plastic regime taking into account a large number of diffraction lines. The results show that the approach practised here enables one to pull together macroscopic and phase-specific microscopic material behaviour in order to improve existing models for prediction of complex load situations. </jats:p

Methods to obtain weld discontinuities in spot-welded joints made of advanced high-strength steels

Resistance spot welding is the major joining technique in mass car production. This applies in particular to high-strength steel and advanced high-strength steel (AHSS) joining of thin sheet steel components for lightweight body shell structures. Joining of AHSS in mass production might lead to weld discontinuities under certain circumstances. Those discontinuities in form of cracks might be an initial start of cracking in the spot-welded joints regarding fatigue loads. It is of great interest to figure out, if, in comparison to specimens without weld discontinuities, the crack initiating point changes and if the fatigue resistance might be reduced by the discontinuities. In this contribution, an overview of potential discontinuities is given. Their possible causes are discussed and means for their detection are highlighted. Among the possible causes of weld discontinuities, two major groups are distinguished: the welding parameters as primary influences in the welding process, and the production-specific influences as secondary ones. With emphasis on major cracks penetrating the weld nugget, these influences are analysed. Finally, a combination of extreme welding parameters with production-specific influences is chosen in order to establish a method which enables the preparation of fatigue test specimens with reproducible major cracks in different locations of the spot-welded joints. This method is than applied in order to prepare spot weld specimens for fatigue tests

Thermal stability of retained austenite in low alloyed TRIP steel determined by high energy synchrotron radiation

TRIP-steels offer a good combination between strength and ductility. Therefore TRIP-steels are widely used in the automobile industries. The aim of this work is to study the stability of involved phases during heating and to identify the kinetics of the occuring phase transformations. For that purpose, in-situ diffraction measurements, using high energy synchrotron radiation were conducted. The analysis revealed the decomposition of the metastable austenitic phase into carbide and ferrite along the heating process and the regeneration of the austenite by further heating of the sample.</jats:p

Determination of local stress-strain properties of spot welded joints using the instrumented indentation test

Determination of Local Stress-Strain Properties of Spot Welded Joints Using the Instrumented Indentation Test. The local strength properties in the region of weld joints are essential for their resistance to mechanical stress. In contrast to an alternative method of determining the local stress strain behaviour i.e. the preparation intensive, destructive micro tensile test the instrumented indentation test (ITT) provides gradients of strength properties with excellent local resolution. Two methods of determining true stress strain curves from cyclic indentation test have been used in order to investigate the strength behaviour in the region of resistance spot welded joints (region of base metal and weld nugget) of two high strength steels, a TRIP steel, and a martensitic steel and on the other hand a mild steel. Exemplary for the TRIP steel the results were compared and discussed with stress-strain-curves obtained by tensile tests on specimens made of the base metal and on specimens which were heat-treated corresponding to the welding process