Combining 10Be surface exposure and OSL dating to reconstruct Holocene lake-level fluctuations: a case study at Tangra Yumco (southern Tibet)

Abstract HKT-ISTP 2013 B

Сложность алгоритмов криптографической системы Эль–Гамаля и ихэффективность

Objective. - Electrical remodeling as well as atrial contractile dysfunction after the conversion of atrial fibrillation (AF) to sinus rhythm (SR) are mainly caused by a reduction of the inward L-type Ca2+ current (ICaL). We investigated whether the expression of L-type Ca2+-channel subunits was reduced in atrial myocardium of AF patients. Methods. - Right atrial appendages were obtained from patients undergoing coronary artery bypass graft surgery (CAD, n = 35) or mitral valve surgery (MVD, n = 37). Seventeen of the CAD patients and 18 of the MVD patients were in chronic (>3 months) AF, whereas the others were in SR. The protein expression of the L-type Ca2+-channel subunits {alpha}1C and {beta}2 was quantified by western blot analysis. Furthermore, we measured the density of dihydropyridine (DHP)-binding sites of the L-type Ca2+ channel using 3H-PN220-100 as radioligand. Results. - Surprisingly, the {alpha}1C and the {beta}2-subunit expression was not altered in atrial myocardium of AF patients. Also, the DHP-binding site density was unchanged. Conclusion. - The protein expression of the L-type Ca2+-channel subunits {alpha}1C or {beta}2 is not reduced in atrial myocardium of AF patients. Therefore, the reduced ICaL might be due to downregulation of other accessory subunits ({alpha}2{delta}), expression of aberrant subunits, changes in channel trafficking or alterations in channel function

Chronology of Cauvery Delta Sediments from Shallow Subsurface Cores Using Elevated-Temperature Post-IR IRSL Dating of Feldspar

We present the results of luminescence dating of sediments from two cores from the Cauvery Delta in south-east India. Since all natural quartz OSL signals except one sample were in saturation, the elevated temperature post-IR IRSL protocol for K-feldspar was applied to establish a chronology. Internal dose rates of K-feldspar grains were calculated from the measured internal content of potassium, uranium, thorium and rubidium in the bulk of K-feldspar grains using solution ICP-OES and ICP-MS analysis. A substantial scatter in single-aliquot De values was observed which is most probably due to the effect of incomplete bleaching of fluvial sediments before burial. A minimum age model was applied to extract possible depositional ages. The study revealed that except an upper layer of Holocene sediments (< 5m), the majority of the upper ~50m of Cauvery delta sediments were deposited between marine isotope stage MIS-5 and MIS-10 or older. The feldspar luminescence ages also indicate the existence of a period of non deposition or erosion in the upper part of the cores. © 2010 GADAM Centre Institute of Physics, Silesian University of Technology. All rights reserved

Physiologically-based pharmacokinetic modeling of quinidine to establish a CYP3A4, P-gp, and CYP2D6 drug-drug-gene interaction network

The antiarrhythmic agent quinidine is a potent inhibitor of cytochrome P450 (CYP) 2D6 and P-glycoprotein (P-gp) and is therefore recommended for use in clinical drug-drug interaction (DDI) studies. However, as quinidine is also a substrate of CYP3A4 and P-gp, it is susceptible to DDIs involving these proteins. Physiologically-based pharmacokinetic (PBPK) modeling can help to mechanistically assess the absorption, distribution, metabolism, and excretion processes of a drug and has proven its usefulness in predicting even complex interaction scenarios. The objectives of the presented work were to develop a PBPK model of quinidine and to integrate the model into a comprehensive drug-drug(-gene) interaction (DD(G)I) network with a diverse set of CYP3A4 and P-gp perpetrators as well as CYP2D6 and P-gp victims. The quinidine parent-metabolite model including 3-hydroxyquinidine was developed using pharmacokinetic profiles from clinical studies after intravenous and oral administration covering a broad dosing range (0.1-600 mg). The model covers efflux transport via P-gp and metabolic transformation to either 3-hydroxyquinidine or unspecified metabolites via CYP3A4. The 3-hydroxyquinidine model includes further metabolism by CYP3A4 as well as an unspecific hepatic clearance. Model performance was assessed graphically and quantitatively with greater than 90% of predicted pharmacokinetic parameters within two-fold of corresponding observed values. The model was successfully used to simulate various DD(G)I scenarios with greater than 90% of predicted DD(G)I pharmacokinetic parameter ratios within two-fold prediction success limits. The presented network will be provided to the research community and can be extended to include further perpetrators, victims, and targets, to support investigations of DD(G)Is.Horizon 2020 (H2020)Personalised Therapeutic

Global sea-level rise in the early Holocene revealed from North Sea peats

Rates of relative sea-level rise during the final stage of the last deglaciation, the early Holocene, are key to understanding future ice melt and sea-level change under a warming climate1. Data about these rates are scarce2, and this limits insight into the relative contributions of the North American and Antarctic ice sheets to global sea-level rise during the early Holocene. Here we present an early Holocene sea-level curve based on 88 sea-level data points (13.7–6.2 thousand years ago (ka)) from the North Sea (Doggerland3,4). After removing the pattern of regional glacial isostatic adjustment caused by the melting of the Eurasian Ice Sheet, the residual sea-level signal highlights two phases of accelerated sea-level rise. Meltwater sourced from the North American and Antarctic ice sheets drove these two phases, peaking around 10.3 ka and 8.3 ka with rates between 8 mm yr−1 and 9 mm yr−1. Our results also show that global mean sea-level rise between 11 ka and 3 ka amounted to 37.7 m (2σ range, 29.3–42.2 m), reconciling the mismatch that existed between estimates of global mean sea-level rise based on ice-sheet reconstructions and previously limited early Holocene sea-level data. With its broad spatiotemporal coverage, the North Sea dataset provides critical constraints on the patterns and rates of the late-stage deglaciation of the North American and Antarctic ice sheets, improving our understanding of the Earth-system response to climate change

Geoarchaeological studies on Roman time harbour sediments in Cologne - Comparison of different OSL dating techniques

Due to the construction of a new North-South subway in Cologne, Roman time harbour sediments were exposed and were sampled for luminescence dating. A very good independent age control was given by the precise knowledge of the chronology of Roman activity and by radiocarbon ages of charcoal samples. Hence, different methodological approaches within luminescence dating were applied for Holocene heterogeneously bleached fluvial samples and were compared to the known ages. For one sample, optically stimulated luminescence (OSL) dating was applied to coarse-grained quartz using a single aliquot regenerative-dose (SAR) protocol. After De-measurements, dif-ferent statistical approaches were tested (i.e. arithmetic mean, median, minimum age model, finite mixture model, leading edge method and the Fuchs and Lang approach). It is demonstrated that the Fuchs and Lang approach along with the leading edge method yielded the best matching OSL ages with respect to the known ages. For the other sample which showed feldspar contamination within the quartz signal, the post-IR blue stimulated luminescence (double SAR protocol) was measured in three different ways to calculate the De-value: with continuous wave (CW) stimulation with an IR-bleach at 50°C and at 225°C for 100 s prior to the OSL, and pulsed OSL (POSL). It was demonstrated that the IR-stimulation at 225°C has very good potential to remove the feldspar signal contribution as well as pulsed OSL, but the former might deplete parts of the quartz OSL signal