High harmonic generation and ion acceleration with high-intensity laser pulses

This thesis reports on research performed on high harmonic generation and ion acceleration, processes that are based on the interaction of gaseous and solid media with high-intensity laser pulses. High harmonic generation leads to the production of beams of ultrashort, laser-like radiation in the wavelength range reaching from the extreme ultraviolet (XUV) to soft X-rays. Ion acceleration generates highly energetic protons and ions in the form of highly directional and pulsed beams with an ultrashort duration. The scope of this thesis is to present novel investigations and methods towards an enhancement of the flux and maximum energy of the accelerated ions and the harmonic radiation via an improved understanding of the underlying physics and, to provide a more complete identification of the actual requirements of the laser and the target for optimum output.\ud The first part of this work concerns the construction and testing of a setup to generate high harmonics in gaseous media. The setup employs a capillary waveguide in which we implemented a novel manner of differential pumping. We performed an experiment on an enhancement technique, called Harmonic Excitation, and demonstrated for the first time that this technique can be applied in a capillary waveguide.\ud The second part of the research concerns ion acceleration and high-order harmonic generation from solid-state targets using high-intensity laser pulses with ultra-high contrast. We investigated the coherence properties of high-order harmonic generation via coherent wake emission. Special attention was given to the preparation and investigation of extremely thin foils, i.e. freestanding nanofoils, to enter a very promising, but largely unexplored, regime. We experimentally investigated ion acceleration in this, so-called, transparent regime for the first time, and compared the results with predictions from improved numerical calculations. We also investigated for the first time high-order harmonic generation in the transparent regime, experimentally and via numerical modeling

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and alpha-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates further exert toxicity leading to the dysfunction, degeneration and loss of cells in the affected organs. Due to the disordered structure of the amyloid proteins, endogenous molecules, such as lipids, are prone to interact with amyloid proteins at a low concentration and influence amyloid cytotoxicity. The heterogeneity of amyloid proteinscomplicates the understanding of the amyloid cytotoxicity when relying only on conventional bulk and ensemble techniques. As complementary tools, single-molecule techniques (SMTs) provide novel insights into the different subpopulations of a heterogeneous amyloid mixture as well as the cytotoxicity, in particular as involved in lipid membranes. This review focuses on the recent advances of a series of SMTs, including single-molecule fluorescence imaging, single-molecule force spectroscopy and single-nanopore electrical recording, for the understanding of the amyloid molecular mechanism. The working principles, benefits and limitations of each technique are discussed and compared in amyloid protein related studies.. We also discuss why SMTs show great potential and are worthy of further investigation with feasibility studies as diagnostic tools of neurodegenerative diseases and which limitations are to be addressed

Cross interactions between Apolipoprotein E and amyloid proteins in neurodegenerative diseases

Three common Apolipoprotein E isoforms, ApoE2, ApoE3, and ApoE4, are key regulators of lipid homeostasis, among other functions. Apolipoprotein E can interact with amyloid proteins. The isoforms differ by one or two residues at positions 112 and 158, and possess distinct structural conformations and functions, leading to isoform-specific roles in amyloid-based neurodegenerative diseases. Over 30 different amyloid proteins have been found to share similar characteristics of structure and toxicity, suggesting a common interactome. The molecular and genetic interactions of ApoE with amyloid proteins have been extensively studied in neurodegenerative diseases, but have not yet been well connected and clarified. Here we summarize essential features of the interactions between ApoE and different amyloid proteins, identify gaps in the understanding of the interactome and propose the general interaction mechanism between ApoE isoforms and amyloid proteins. Perhaps more importantly, this review outlines what we can learn from the interactome of ApoE and amyloid proteins; that is the need to see both ApoE and amyloid proteins as a basis to understand neurodegenerative diseases