28 research outputs found
Ultrafast Electron Diffraction Studies of Optically Excited Thin Bismuth Films
This thesis contains work on the design and the realization of an experimental setup capable of providing sub-picosecond electron pulses for ultrafast electron diffraction experiments, and performing the study of ultrafast dynamics in bismuth after optical excitation using this setup
An endstation for resonant inelastic X-ray scattering studies of solid and liquid samples
Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelinâs nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the methodâs sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures
Probing the Hofmeister Effect with Ultrafast Core Hole Spectroscopy
In the current work, X-ray emission spectra of aqueous solutions of different inorganic salts within the Hofmeister series are presented. The results reflect the direct interaction of the ions with the water molecules and therefore, reveal general properties of the salt-water interactions. Within the experimental precision a significant effect of the ions on the water structure has been observed but no ordering according to the structure maker/structure breaker concept could be mirrored in the results indicating that the Hofmeister effect-if existent-may be caused by more complex interactions
Dynamic discrete choice models: forecasting of competitive events through optimal linear filtering of choice persistence effects
This thesis presents a new modelling framework for dynamic discrete decision-making problem settings, in which persistence in preferences, derived from previously made ranked choices, is taken into account. The endorsed framework leverages trends of the revealed preferences to model the evolution of the temporal persistence of unobserved attributes of alternatives, and it effectively incorporates changing choice sets and irregular time durations between the repeated availability of alternatives in consecutive decision events. The new model structure eliminates effect-confounding problems inherent in incumbent models, and it highlights the effects of time duration bias and the unreliability of lower ranked choices on the probabilities of future choice selections. Following a post-positivistic research paradigm, empirical validation of the models in a naturalistic market environment (UK horse-betting markets), which integrates behavioural (decisionmaker-related) and economic (betting-market-related) information sets, is carried out. The proposed methodology centres around a two-stage model structure, which includes elements of the classical Conditional Logit approach, revealed order of preferences, and the Kalman filtering of the latent states, aimed at providing forecasts of choice probabilities. These probabilities are subsequently used for implementation of a Kelly betting strategy, which, together with standard statistical tests of significance, assesses the merits of the modelling approach. In particular, it is shown that a novel Kalman filter algorithm, developed for filter divergence mitigation, outperforms traditional Kalman filtering algorithms.The empirical results and the associated analysis confirm that forecasted trend variables add statistically significant information over public market information (betting odds) and that incorporating trend variable forecasts in a betting strategy yields above-average monetary gains. Analysis of the evidence collected in the study leads to the conclusion that persistence in preference effects are significant and have to be controlled for, in order to mitigate the effects of the considered biases. In a wider context, obtained evidence confirms the propensity of vested decision makers to time duration bias in a revealed preference setup and that importance weighting of the ranked choice data may be used to mitigate the effects of lower ranked alternativesâ unreliability
The effects of some nutritional parameters on rubratoxin biosynthesis by Penicillium rubrum.
Penicillium rubrum Stoll, a toxigenic mould, was first implicated in a mycotoxicosis in 1956 when it was suspected to be one of the causal agents of swine poisoning. Since then a number of studies have been performed on the toxins elaborated by this organism and on the effects of the external environment on their synthesis. The present study was performed using the CMI 112715 strain of this mould and several nutritional factors have been examined. A chemically defined medium has been developed during the course of this study which gave rise to toxin yields comparable with those of the enriched Raulin-Thom medium. Of special interest were the effects of carbon and nitrogen content of the medium on toxin synthesis and some interesting results have been obtained through the use of metabolic inhibitors such as malonate and ferrocyanide. The secondary metabolic nature of the toxins has been established and attempts have been made to establish the relative importance of the various primary metabolic pathways in generating the intermediates required in rubratoxin synthesis, by use of the above mentioned inhibitors. This study confirmed the importance of the C/N ratio in secondary metabolic activity of fungi and in the case of rubratoxin synthesis indicated a possible indirect effect of absence of zinc on toxin synthesis. Effects of some other nutritional factors are discussed in connection with the biosynthesis of rubratoxins by this mould
Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI
Disentangling human brain connectivity requires an accurate description of nerve fiber trajectories, unveiled via detailed mapping of axonal orientations. However, this is challenging because axons can cross one another on a micrometer scale. Diffusion magnetic resonance imaging (dMRI) can be used to infer axonal connectivity because it is sensitive to axonal alignment, but it has limited spatial resolution and specificity. Scattered light imaging (SLI) and small-angle X-ray scattering (SAXS) reveal axonal orientations with microscopic resolution and high specificity, respectivelyHere, we apply both scattering techniques on the same samples and cross-validate them, laying the groundwork for ground-truth axonal orientation imaging and validating dMRI. We evaluate brain regions that include unidirectional and crossing fibers in human and vervet monkey brain sections. SLI and SAXS quantitatively agree regarding in-plane fiber orientations including crossings, while dMRI agrees in the majority of voxels with small discrepancies. We further use SAXS and dMRI to confirm theoretical predictions regarding SLI determination of through-plane fiber orientations. Scattered light and X-ray imaging can provide quantitative micrometer 3D fiber orientations with high resolution and specificity, facilitating detailed investigations of complex fiber architecture in the animal and human brain.</p
Insights into open/closed conformations of the catalytically active human guanylate kinase as investigated by small-angle X-ray scatteringand DAAD
Bio-catalysis is the outcome of a subtle interplay between internal motions in enzymes and chemical kinetics. Small-angle X-ray scattering (SAXS) investigation of an enzymeâs internal motions during catalysis offers an integral view of the proteinâs structural plasticity, dynamics, and function, which is useful for understanding allosteric effects and developing novel medicines. Guanylate kinase (GMPK) is an essential enzyme involved in the guanine nucleotide metabolism of unicellular and multicellular organisms. It is also required for the intracellular activation of numerous antiviral and anticancer purine nucleoside analog prodrugs. Catalytically active recombinant human GMPK (hGMPK) was purified for the first time and changes in the size and shape of open/closed hGMPK were tracked by SAXS. The binding of substrates (GMP+AMPPNP or Ap5G or GMP+ADP) resulted in the compaction of size and shape of hGMPK. The structural changes between open and completely closed hGMPK conformation were confirmed by observing differences in the hGMPK secondary structures with circular dichroism spectroscopy
Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering
Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons.
X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods.ISSN:1742-7061ISSN:1878-756
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Viscoelastic analysis of mussel threads reveals energy dissipative mechanisms
Mussels use byssal threads to secure themselves to rocks and as shock absorbers during cyclic loading from wave motion. Byssal threads combine high strength and toughness with extensibility of nearly 200%. Researchers attribute tensile properties of byssal threads to their elaborate multi-domain collagenous protein cores. Because the elastic properties have been previously scrutinized, we instead examined byssal thread viscoelastic behaviour, which is essential for withstanding cyclic loading. By targeting protein domains in the collagenous core via chemical treatments, stress relaxation experiments provided insights on domain contributions and were coupled with in situ small-angle X-ray scattering to investigate relaxation-specific molecular reorganizations. Results show that when silk-like domains in the core were disrupted, the stress relaxation of the threads decreased by nearly 50% and lateral molecular spacing also decreased, suggesting that these domains are essential for energy dissipation and assume a compressed molecular rearrangement when disrupted. A generalized Maxwell model was developed to describe the stress relaxation response. The model predicts that maximal damping (energy dissipation) occurs at around 0.1 Hz which closely resembles the wave frequency along the California coast and implies that these materials may be well adapted to the cyclic loading of the ambient conditions