MRI and histologic studies on early markers of Alzheimer's disease

This thesis adresses a variety of early markers of Alzheimer's disease, using MRI, histology and MRS. MRS is found to be promising for early diagnosis of AD. However this study is done on mice and should be replicated on AD patients over time. Besides the early markers the thesis descibes a potential difference between male and female in the development of AD in the brain. LUMC / Geneeskund

Production of narrowband tunable extreme-ultraviolet radiation by noncollinear resonance-enhanced four-wave mixing

Fourier-transform-limited extreme-ultraviolet (XUV) radiation (bandwidth ≲300 MHz) tunable around 91 nm is produced by use of two-photon resonance-enhanced four-wave mixing on the Kr resonance at 94 093 c

A Genomic Background Based Method for Association Analysis in Related Individuals

Background. Feasibility of genotyping of hundreds and thousands of single nucleoticle polymorphisms (SNPs) in thousands of study subjects have triggered the need for fast, powerful, and reliable methods for genome-wide association analysis. Here we consider a situation when study participants are genetically related (e.g. due to systematic sampling of families or because a study was performed in a genetically isolated population). Of the available methods that account for relatedness, the Measured Genotype (MG) approach is considered the 'gold standard'. However, MG is not efficient with respect to time taken for the analysis of genome-wide data. In this context we proposed a fast two-step method called Genome-wide Association using Mixed Model and Regression (GRAMMAR) for the analysis of pedigree-based quantitative traits. This method certainly overcomes the drawback of time limitation of the measured genotype (MG) approach, but pays in power. One of the major drawbacks of both MG and GRAMMAR, is that they crucially depend on the availability of complete and correct pedigree data, which is rarely available. Methodology. In this study we first explore type 1 error and relative power of MG, GRAMMAR, and Genomic Control (GCC) approaches for genetic association analysis. Secondly, we propose an extension to GRAMMAR i.e. GRAMMAR-GC. Finally, we propose application of GRAMMAR-GC using the kinship matrix estimated through genomic marker data, instead of (possibly missing and/or incorrect) genealogy. Conclusion. Through simulations we show that MG approach maintains high power across a range of heritabilities and possible pedigree structures, and always outperforms other contemporary methods. We also show that the power of our proposed GRAMMAR-GC approaches to that of the 'gold standard' MG for all models and pedigrees studied. We show that this method is both feasible and powerful and has correct type 1 error in the context of genome-wide association analysis in related individuals

Third-harmonic generation of a continuous-wave Ti : Sapphire laser in external resonant cavities

An all-solid-state tunable continuous-wave (cw) laser operating near 272 nm with a bandwidth Gamma approximate to 3 MHz has been developed. The third harmonic of light from a single-cw Ti:Sapphire laser has been generated using two external enhancement cavities. An output power of 175 mW has been produced, corresponding to an overall conversion efficiency of 8%. (C) 2003 American Institute of Physics

Оцінювання закону розподілу величини збитків унаслідок реалізації загрози “Відсутність або недостатність технічного обслуговування”

The problem of estimation of size distribution law of damages in the absence or insufficient sample size of the universe and the initial data suggested approach to finding the most expected value of losses due to information security threats

Crystal Structure of 3-Hydroxybenzoate 6-Hydroxylase Uncovers Lipid-assisted Flavoprotein Strategy for Regioselective Aromatic Hydroxylation.

3-Hydroxybenzoate 6-hydroxylase (3HB6H) from Rhodococcus jostii RHA1 is a dimeric flavoprotein that catalyzes the NADH- and oxygen-dependent para-hydroxylation of 3-hydroxybenzoate to 2,5-dihydroxybenzoate. In this study, we report the crystal structure of 3HB6H as expressed in Escherichia coli. The overall fold of 3HB6H is similar to that of p-hydroxybenzoate hydroxylase and other flavoprotein aromatic hydroxylases. Unexpectedly, a lipid ligand is bound to each 3HB6H monomer. Mass spectral analysis identified the ligand as a mixture of phosphatidylglycerol and phosphatidylethanolamine. The fatty acid chains occupy hydrophobic channels that deeply penetrate into the interior of the substrate-binding domain of each subunit, whereas the hydrophilic part is exposed on the protein surface, connecting the dimerization domains via a few interactions. Most remarkably, the terminal part of a phospholipid acyl chain is directly involved in the substrate-binding site. Co-crystallized chloride ion and the crystal structure of the H213S variant with bound 3-hydroxybenzoate provide hints about oxygen activation and substrate hydroxylation. Essential roles are played by His-213 in catalysis and Tyr-105 in substrate binding. This phospholipid-assisted strategy to control regioselective aromatic hydroxylation is of relevance for optimization of flavin-dependent biocatalysts

Global implications of the European Food System : A food systems approach

The EU is a major player in the world market for agricultural products, both dependent on commodity imports from many countries, and exporting high-value agricultural products. There is a need to better understand the impact - on people, planet and profit - of the EU trade on food systems outside the EU, with a focus on Low- and Middle-Income Countries (LMIC). This will help the EU to steer its actions and policies in other directions where this is deemed necessary to achieve the Sustainable Development Goals (SDGs)

Direct in vivo assessment of sex-related metabolic differences in a mouse model of Alzheimer's disease by MRI

Solid state NMR/Biophysical Organic Chemistr