Relationship between synaptic dysfunction and degeneration in a rodent model of dementia

Synaptic degeneration is currently the best biomarker correlate of cognitive decline in dementia. In the years prior to dementia onset, many neurophysiological changes are occurring hypothesised to preserve cognitive function, including alterations in synaptic and neuronal function. This thesis aims to characterise the early synaptic and neurophysiological alterations occurring in a mouse model of tauopathy-driven neurodegeneration (rTg4510). This work was performed in the somatosensory cortex, a well characterised region of the brain in the mouse, which serves as a prototypical model of the neocortex. The work presented in Chapters two and three revealed alterations in synaptic glutamatergic receptor function (reduced NMDA:AMPA receptor ratio) and intrinsic neuronal properties in prodromal tauopathy in rTg4510 mice, using in vitro whole-cell patch clamp electrophysiology. Increased dendritic branching proximal to the soma was seen in these recorded neurons following post hoc imaging of their structure. In more advanced stages of tauopathy, reductions in putative AMPA receptor-mediated spontaneous synaptic activity was observed. Significant reductions in glutamatergic receptor expression and synaptic markers was detected in both prodromal and more advanced tauopathy, quantified from isolated synaptosomes. To characterise how glutamatergic receptor dysfunction manifested in vivo, recording paradigms were optimised for in vivo two-photon targeted whole-cell patch clamp electrophysiology, outlined in Chapter four. This technique was used to simultaneously record subthreshold synaptic properties, network activity, and evoked synaptic responses in the rTg4510 model in early neurodegeneration in Chapter five. Whilst spontaneous network activity was similar between genotypes, there was an observable increase in the fast peak response of evoked activity. This work suggests that synaptic dysfunction is a feature of both prodromal and advanced tauopathy, with different functional and biochemical correlates manifesting at different stages of disease progression. Further characterisation of these processes, and how this contributes to symptomatic decline, can provide a basis to develop novel therapeutic strategies to alleviate tau-mediated synaptic and neuronal dysfunction prior to widespread cell loss

Correlation function and electronic spectral line broadening in relativistic plasmas

The electrons dynamics and the time autocorrelation function Cee(t) for the total electric microfield of the electrons on positive charge impurity embedded in a plasma are considered when the relativistic dynamic of the electrons is taken into account. We have, at first, built the effective potential governing the electrons dynamics. This potential obeys a nonlinear integral equation that we have solved numerically. Regarding the electron broadening of the line in plasma, we have found that when the plasma parameters change, the amplitude of the collision operator changes in the same way as the time integral of Cee(t). The electron-impurity interaction is taken at first time as screened Deutsh interaction and at the second time as Kelbg interaction. Comparisons of all interesting quantities are made with respect to the previous interactions as well as between classical and relativistic dynamics of electrons

A finite element modelling of thermo-hydro-mechanical behaviour and numerical simulations of progressing spalling front

This paper presents a coupled thermo-hydro-mechanical (THM) model enriched with a buckling-type criterion for progressive spalling. In the first part of the paper, a general fully coupled multi-phase THM model describing the behaviour of concrete at moderate and high temperatures is presented. Then the spalling criterion and its numerical implementation in the framework of the finite element method are presented. Finally, a simple 1D numerical example will illustrate the effectiveness of the implemented numerical approach

Helioseismology with PICARD

PICARD is a CNES micro-satellite launched in June 2010 (Thuillier at al. 2006). Its main goal is to measure the solar shape, total and spectral irradiance during the ascending phase of the activity cycle. The SODISM telescope onboard PICARD also allows us to conduct a program for helioseismology in intensity at 535.7 nm (Corbard et al. 2008). One-minute cadence low-resolution full images are available for a so-called medium-$l$ program, and high-resolution images of the limb recorded every 2 minutes are used to study mode amplification near the limb in the perspective of g-mode search. First analyses and results from these two programs are presented here.Comment: 6 pages, 6 figures, Eclipse on the Coral Sea: Cycle 24 Ascending, GONG 2012 / LWS/SDO-5 / SOHO 27, November 12 - 16, 2012, Palm Cove, Queensland. Accepted for publication in Journal of Physics Conference Series on March 1st 201

Does investment stimulate or inhibit CSR transparency? The moderating role of CSR committee, board monitoring and CEO duality

open access articleThis study examined the potential relationship between different facets of firm investment (i.e., sales growth, R&D intensity, and total tangible and intangible assets) and CSR reporting, assurance and GRI adoption. Also, it further explored the conditions under which investing firms can encourage or discourage their CSR transparency. Our sample included 44,996 firm-year observations from 2004 to 2019 across 61 countries. Using a random-effects logistic model, our results indicate that corporate investments reduce firms’ CSR reporting and assurance tendency, which implies that a tradeoff exists between these two aspects of firm investment worldwide. Our moderation analysis outlined the contingent role of board-specific characteristics in the link between firm investment and CSR transparency. It appears that the CSR committee generates greater moderating effects on the firm investment–CSR transparency nexus than board monitoring and CEO duality. This empirical evidence also suggests several practical implications and future research agendas