Applications of EPR with an Emphasis on Tau Fibril Structure

Substances containing unpaired electrons have been studied by electron paramagnetic resonance (EPR) for nearly 70 years. With continual development and enhancement of EPR techniques, questions have arisen regarding optimum method selection for a given sample based on its properties. In this work, radiation defects, natural lattice defects, solid organic radicals, radicals in solution, and spin-labeled proteins were analyzed using CW, pulse, and rapid scan EPR to compare methods. Studies of solid BDPA, EOe in quartz, Ns0 in diamond, and a-Si:H, showed that rapid scan could overcome many obstacles presented by other techniques, cementing rapid scan as an effective alternative to CW and pulse methods. Relaxation times of six nitroxide radicals were characterized from 0.25-34 GHz, guiding synthesis of improved nitroxides for in vivo imaging experiments. Processes contributing to T1 of DPPH in polystyrene were found through variable temperature measurements at X- and Q-band, resolving previously-reported discrepancies in relaxation properties and providing new insight into this commonly-used standard. In the history of EPR, the study of proteins is relatively new. Double electron-electron resonance (DEER) has emerged as a powerful technique for the study of amyloid fibrils, a class of protein aggregates implicated in a number of neurodegenerative disorders. Microtubule-associated protein tau forms fibrils linked to Alzheimerfs disease through seeded conversion of monomer. Self-assembly is mediated by the microtubule binding repeats in tau, and there are either three or four repeats present depending on the isoform. DEER was used to show that filaments of 3R and 4R tau are conformationally distinct and that 4R fibrils adopt a heterogeneous mixture of conformations. Populations of 4R fibril conformations, which were independently validated using a model system, can be modulated by introduction of mutations to the primary sequence or by varying fibril growth conditions. These findings provided unprecedented insights into the seed selection of tau monomers and established conformational compatibility as an important driving force in tau fibril propagation. Lastly, DEER acquisition was improved through addition of paramagnetic metal to spin-labeled protein, decreasing collection time, and through use of a novel spin label with increased T2, thereby lengthening the available acquisition window.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Bio-based PLA_PHB plasticized blend films: Processing and structural characterization

Bio-based films formed by poly(lactic acid) (PLA) and poly(3-hydroxybutyrate) (PHB) plasticized with an oligomer of the lactic acid (OLA) were used as supporting matrices for an antibacterial agent (carvacrol). This paper reports the main features of the processing and physico-chemical characterization of these innovative biodegradable material based films, which were extruded and further submitted to filmature process. The effect of the addition of carvacrol and OLA on their microstructure, chemical, thermal and mechanical properties was assessed. The presence of these additives did not affect the thermal stability of PLA_PHB films, but resulted in a decrease in their crystallinity and in the elastic modulus for the active formulations. The obtained results showed the effective presence of additives in the PLA or the PLA_PHB matrix after processing at high temperatures, making them able to be used in active and bio-based formulations with antioxidant/antimicrobial performance.

Enhanced removal of 8-quinolinecarboxylic acid in an activated carbon cloth by electroadsorption in aqueous solution

The effect of the electrochemical treatment (potentiostatic treatment in a filter-press electrochemical cell) on the adsorption capacity of an activated carbon cloth (ACC) was analyzed in relation with the removal of 8-quinolinecarboxylic acid pollutant from water. The adsorption capacity of an ACC is quantitatively improved in the presence of an electric field (electroadsorption process) reaching values of 96% in comparison to 55% in absence of applied potential. In addition, the cathodic treatment results in higher removal efficiencies than the anodic treatment. The enhanced adsorption capacity has been proved to be irreversible, since the removed compound remains adsorbed after switching the applied potential. The kinetics of the adsorption processes is also improved by the presence of an applied potential.

The Financialization of Food: An Inquiry into the 2008-2011 Food Price Spikes

This dissertation investigates the question: has financial speculation contributed to global food price volatility since the mid 2000s? I problematize the mainstream academic literature on the 2008-2011 food price spikes as being dominated by neoclassical economic perspectives and offer new conceptual and empirical insights into the relationship between financial speculation and food. Presented in three journal style manuscripts, manuscript one uses circuits of capital to conceptualize the link between financial speculators in the global north and populations in the global south. Manuscript two argues that what makes commodity index speculation (aka ‘index funds’ or index swaps) novel is that it provides institutional investors with what Clapp (2014) calls “financial distance” from the biopolitical implications of food speculation. Finally, manuscript three combines Gramsci’s concepts of hegemony and ‘the intellectual’ with the concept of performativity to investigate the ideological role that public intellectuals and the rhetorical actor the market play in the proliferation and governance of commodity index speculation. The first two manuscripts take an empirically mixed method approach by combining regression analysis with discourse analysis, while the third relies on interview data and discourse analysis. The findings show that financial speculation by index swap dealers and hedge funds did indeed significantly contribute to the price volatility of food commodities between June 2006 and December 2014. The results from the interview data affirm these findings. The discourse analysis of the interview data shows that public intellectuals and rhetorical characters such as ‘the market’ play powerful roles in shaping how food speculation is promoted, regulated and normalized. The significance of the findings is three-fold. First, the empirical findings show that a link does exist between financial speculation and food price volatility. Second, the findings indicate that the post-2008 CFTC and the Dodd-Frank reforms are unlikely to reduce financial speculation or the price volatility that it causes. Third, the findings suggest that institutional investors (such as pension funds) should think critically about how they use commodity index speculation as a way of generating financial earnings.

The Effects of Civic Education on Political Knowledge

Traditionally political knowledge was regarded as an important potential outcome for civic education efforts. Most of the currently available research, however, tends to focus on non-cognitive goals, despite the fact that studies repeatedly have shown that political knowledge is an important resource for enlightened and engaged citizenship. In this article, we investigate whether civic education contributes to political knowledge levels. The analysis is based on the Belgian Political Panel Survey, a two year panel study among 2,988 Belgian late adolescents. The analysis shows that experiences with group projects at school contribute significantly to political knowledge levels two years later on. Furthermore, we can observe an interaction effect as those who are already most knowledgeable about politics, gain most from these group projects. Classes about politics, on the other hand, did not have an effect on knowledge levels. In the discussion, it is argued that civic education can have strong cognitive effects, but that these effects are not always related to classical civic education efforts.

Geochemistry and isotopic ratios of basalts from ODP Leg 163 sites

Voluminous, subaerial magmatism resulted in the formation of extensive seaward-dipping reflector sequences (SDRS) along the Paleogene Southeast Greenland rifted margin. Drilling during Leg 163 recovered basalts from the SDRS at 66ºN (Site 988) and 63ºN (Sites 989 and 990). The basalt from Site 988 is light rare-earth-element (REE) enriched (La(n)/Yb(n) = 3.4), with epsilon-Nd(t=60) = 5.3, 87Sr/86Sr = 0.7034, and 206Pb/204Pb = 17.98. It is similar to tholeiites recovered from the Irminger Basin during Leg 49 and to light-REE-enriched tholeiites from Iceland. Drilling at Site 989, the innermost of the sites on the 63ºN transect, was proposed to extend recovery of the earliest part of the SDRS initiated during Leg 152. These basalts are, however, younger than those from Site 917 and are compositionally similar to basalts from the more seaward Sites 990 and 915. Many of the basalts from Sites 989 and 990 show evidence of contamination by continental crust (e.g., epsilon-Nd(t=60) extends down to -3.7, 206Pb/204Pb extends down to 15.1). We suggest that the contaminant is a mixture of Archean granulite and amphibolite and that the most contaminated basalts have assimilated ~5% of crust. Uncontaminated basalts are isotopically similar to basalts from Site 918, on the main body of the SDRS, and are light-REE depleted. Consistent with previous models of the development of this margin, we show that at the time of formation of the basalts from Sites 989 and 990 (1) melting was at relatively shallow levels in a fully-fledged rift zone; (2) fragments of continental crust were present in the lithosphere above the zones of melt generation; and (3) the sublithospheric mantle was dominated by a depleted Icelandic plume component.

(Table 1) Clay minerals at DSDP Hole 93-603B

Cretaceous sediments encountered in Hole 603B contain a 17 Å smectite as the principal clay mineral, with lesser amounts of illite, kaolinite, and randomly interstratified illite/smectite (I/S). No evidence of smectite to I/S transformation with depth is seen in the interval between 1040 and 1570 m below the sediment surface. Although the presence of some volcanic ash suggests a volcanic origin for the smectite, the nature of associated organic matter together with prevailing sedimentological models for Cretaceous sedimentation on the lower continental rise argue more strongly for a dominantly terrestrial origin for the clays.

Rukovodstvo po istorii Russkoi T S erkvi /

I. Domongol skii period (988-1237) -- II. Period severno-russkoi mitropolii (1237-1588) -- III. Patriarshii period (1589-1700) -- IV. Sinodal nyi period (1700-1890).