519 research outputs found

    Титульні сторінки та зміст

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    Histoire et agronomie : entre ruptures et durée

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    CD4+ T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines

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    There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4+^+ T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require direct CD4+^+ T-cell recognition of latently infected cells through epitopes derived from endogenously expressed viral proteins and presented on the target cell surface in association with HLA class II molecules. It is therefore important to know how often these conditions are met. Here we provide CD4+^+ epitope maps for four EBV nuclear antigens, EBNA1, -2, -3A, and -3C, and establish CD4+^+ T-cell clones against 12 representative epitopes. For each epitope we identify the relevant HLA class II restricting allele and determine the efficiency with which epitope-specific effectors recognize the autologous EBV-transformed B-lymphoblastoid cell line (LCL). The level of recognition measured by gamma interferon release was consistent among clones to the same epitope but varied between epitopes, with values ranging from 0 to 35% of the maximum seen against the epitope peptide-loaded LCL. These epitope-specific differences, also apparent in short-term cytotoxicity and longer-term outgrowth assays on LCL targets, did not relate to the identity of the source antigen and could not be explained by the different functional avidities of the CD4+^+ clones; rather, they appeared to reflect different levels of epitope display at the LCL surface. Thus, while CD4+^+ T-cell responses are detectable against many epitopes in EBV latent proteins, only a minority of these responses are likely to have therapeutic potential as effectors directly recognizing latently infected target cells

    Self-Pulsating Semiconductor Lasers: Theory and Experiment

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    We report detailed measurements of the pump-current dependency of the self-pulsating frequency of semiconductor CD lasers. A distinct kink in this dependence is found and explained using rate-equation model. The kink denotes a transition between a region where the self-pulsations are weakly sustained relaxation oscillations and a region where Q-switching takes place. Simulations show that spontaneous emission noise plays a crucial role for the cross-over.Comment: Revtex, 16 pages, 7 figure

    Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors

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    <p>Abstract</p> <p>Background</p> <p>The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as <it>ATM </it>(Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity.</p> <p>Results</p> <p>Using a replication-free assay in <it>Xenopus </it>extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells.</p> <p>Conclusions</p> <p>These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.</p

    Wave: A New Family of Trapdoor One-Way Preimage Sampleable Functions Based on Codes

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    We present here a new family of trapdoor one-way Preimage Sampleable Functions (PSF) based on codes, the Wave-PSF family. The trapdoor function is one-way under two computational assumptions: the hardness of generic decoding for high weights and the indistinguishability of generalized (U,U+V)(U,U+V)-codes. Our proof follows the GPV strategy [GPV08]. By including rejection sampling, we ensure the proper distribution for the trapdoor inverse output. The domain sampling property of our family is ensured by using and proving a variant of the left-over hash lemma. We instantiate the new Wave-PSF family with ternary generalized (U,U+V)(U,U+V)-codes to design a "hash-and-sign" signature scheme which achieves existential unforgeability under adaptive chosen message attacks (EUF-CMA) in the random oracle model. For 128 bits of classical security, signature sizes are in the order of 15 thousand bits, the public key size in the order of 4 megabytes, and the rejection rate is limited to one rejection every 10 to 12 signatures.Comment: arXiv admin note: text overlap with arXiv:1706.0806

    High pressure water pyrolysis of coal to evaluate the role of pressure on hydrocarbon generation and source rock maturation at high maturities under geological conditions

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    This study investigates the effect of water pressure on hydrocarbon generation and source rock maturation at high maturities for a perhydrous Tertiary Arctic coal, Svalbard. Using a 25 ml Hastalloy vessel, the coal was pyrolysed under low water pressure (230–300 bar) and high water pressure (500, 700 and 900 bar) conditions between 380 °C and 420 °C for 24 h. At 380 °C and 420 °C, gas yields were not affected by pressure up to 700 bar, but were reduced slightly at 900 bar. At 380 °C, the expelled oil yield was highest at 230 bar, but reduced significantly at 900 bar. At 420 °C cracking of expelled oil to gas was retarded at 700 and 900 bar. As well as direct cracking of the coal, the main source of gas generation at high pressure at both 380 °C and 420 °C is from bitumen trapped in the coal, indicating that this is a key mechanism in high pressure geological basins. Vitrinite reflectance (VR) was reduced by 0.16 %Ro at 380 °C and by 0.27 %Ro at 420 °C at 900 bar compared to the low pressure runs, indicating that source rock maturation will be more retarded at higher maturities in high pressure geological basins

    Past temperature reconstructions from deep ice cores: relevance for future climate change

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    Ice cores provide unique archives of past climate and environmental changes based only on physical processes. Quantitative temperature reconstructions are essential for the comparison between ice core records and climate models. We give an overview of the methods that have been developed to reconstruct past local temperatures from deep ice cores and highlight several points that are relevant for future climate change. We first analyse the long term fluctuations of temperature as depicted in the long Antarctic record from EPICA Dome C. The long term imprint of obliquity changes in the EPICA Dome C record is highlighted and compared to simulations conducted with the ECBILT-CLIO intermediate complexity climate model. We discuss the comparison between the current interglacial period and the long interglacial corresponding to marine isotopic stage 11, about 400 kyr BP. Previous studies had focused on the role of precession and the thresholds required to induce glacial inceptions. We suggest that, due to the low eccentricity configuration of MIS 11 and the Holocene, the effect of precession on the incoming solar radiation is damped and that changes in obliquity must be taken into account. The EPICA Dome C alignment of terminations I and VI published in 2004 corresponds to a phasing of the obliquity signals. A conjunction of low obliquity and minimum northern hemisphere summer insolation is not found in the next tens of thousand years, supporting the idea of an unusually long interglacial ahead. As a second point relevant for future climate change, we discuss the magnitude and rate of change of past temperatures reconstructed from Greenland (NorthGRIP) and Antarctic (Dome C) ice cores. Past episodes of temperatures above the present-day values by up to 5°C are recorded at both locations during the penultimate interglacial period. The rate of polar warming simulated by coupled climate models forced by a CO2 increase of 1% per year is compared to ice-core-based temperature reconstructions. In Antarctica, the CO2-induced warming lies clearly beyond the natural rhythm of temperature fluctuations. In Greenland, the CO2-induced warming is as fast or faster than the most rapid temperature shifts of the last ice age. The magnitude of polar temperature change in response to a quadrupling of atmospheric CO2 is comparable to the magnitude of the polar temperature change from the Last Glacial Maximum to present-day. When forced by prescribed changes in ice sheet reconstructions and CO2 changes, climate models systematically underestimate the glacial-interglacial polar temperature change
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