Laser-pulsed atom-probe tomography has been used to study the nanoscale features present in an ODS-Eurofer 97 alloy. A core/shell structure was found for particles 5-10 nm in diameter. The particle cores were primarily Y and O, enriched with Mn and Si resulting in a metal (Y, Mn and Si) to oxygen ratio of M:O ∼2:3. The ∼2 nm thick outer-shell region of the particles exhibited partitioning of V, Cr, Ta, C and N together with the core elements in many cases. Detailed compositional measurements have also been made on the smallest of the yttria-based oxide clusters down to 2 nm in diameter. The 2 nm clusters were found to have a non-stoichiometric oxide composition, enriched in oxygen compared to Y2O3, and evidence for the existence of a shell around these smaller particles was found. 相似文献
INTRODUCTION: Police crash data, which are the basis for safety research in most countries, are incomplete and biased. We focus here on the extent of under-reporting in France, and how it is related to casualty and crash characteristics. METHODS: Police data are compared with a road trauma registry, on the Rh?ne county, after record-linkage. The study covers the 1997-2001 period, totalling 59,714 casualties. A multivariate analysis is conducted, modelling the probability of being police-reported among casualties in the registry, as a function of crash and casualty characteristics. Results are expressed as relative risks (RR) and adjusted probabilities. RESULTS: Police reporting rate is 37.7%. Under-reporting varies mainly according to injury severity (RR=0.35 for slightly injured versus severely injured), to road user type and third party involvement (yes/no): comparing casualties with no third party versus those with one, RR=0.32 among motorcyclists whereas RR=0.78 among car occupants. Under-reporting also varies with road type, road environment (metropole/rural) and type of police force, all of which are structurally dependent. CONCLUSION: Any study based on police crash data may be quite misleading. We are therefore working on obtaining unbiased estimates of road casualties figures, by extrapolating the Rh?ne road trauma registry to the nation-wide level. 相似文献
To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). By revealing three structural snapshots of the enzyme catalytic cycle, each associated with a distinct conformational state, and details about the interactions with N-BPs, these structures provide a novel understanding of the mechanism of FPPS catalysis and inhibition. In particular, the accumulating substrate, IPP, was found to bind to and stabilize the FPPS-N-BP complexes rather than to compete with and displace the N-BP inhibitor. Stabilization of the FPPS-N-BP complex through IPP binding is supported by differential scanning calorimetry analyses of a set of representative N-BPs. Among other factors such as high binding affinity for bone mineral, this particular mode of FPPS inhibition contributes to the exceptional in vivo efficacy of N-BP drugs. Moreover, our data form the basis for structure-guided design of optimized N-BPs with improved pharmacological properties. 相似文献
CDC25 inhibition by thiazolopyrimidines : CDC25 is an attractive target for cancer therapy, as it is overexpressed in numerous cancers and is often associated with tumor aggressiveness and poor prognosis. Based on an in silico/in vitro screen, we developed a series of thiazolopyrimidines to further improve inhibitory activity and cytotoxic properties.
Within the framework of a general survey of the water quality of the river Dadou (Tarn, France), different physico-chemical parameters were measured and an inventory of the fish population was made along the water course, around the Rassisse dam. With the aim of monitoring the potential genotoxic effects and the detoxifying activities induced in organisms exposed to the river water, two in vivo bioassays were performed in laboratory experiments, using larvae of the amphibian Xenopus laevis. The first was the micronucleus test, using red blood cells, and the second the assay of ethoxyresorufin-O-deethylase (EROD) induction in the liver of exposed animals. Eight water samples were taken from the river and at outlet points from the two major industrial activities of the studied section of the water course: a spar-fluor mine and a water treatment plant. Genotoxic impact and EROD induction were measured in the larvae. The effluent of the filter-washing process from the water treatment plant was found to be particularly genotoxic, even after dilution in pure reconstituted water, but no particular genotoxicity was found, either in Dadou river water, or in the effluents from the mine. On the other hand, most of the water samples tested produced a clear induction of EROD activity compared to the level of enzymatic activity found in the liver of larvae reared in the river water sampled upstream of the industrial activities. These results were interpreted taking into account (i) the high concentrations of pollutants (fluorine and manganese) measured in the river water, (ii) the very low population levels inventoried in the downstream section of the river and (iii) the possible interactions between the substances present in the river water, particularly the classical EROD inducers PAHs and PCBs. 相似文献
A new concept of immunoassay based on the use of a trifunctional reagent (tripod) and fluorescence resonance energy transfer (FRET) phenomenon is described. This procedure involves differential steps: (1) the tripod bearing (i) a fluorophore, (ii) a molecule structurally close to the target, and (iii) a linker reacts with the solid phase; (2) the solid phase is further activated with an anti-target antibody labeled with a quencher molecule, generating the decrease of the fluorophore emission via FRET; (3) FRET being distance dependent, the presence of the target by competing with the tripod for binding the quencher-labeled antibody leads to a rise of the fluorescence signal; (4) the solid phase is reactivated simply, by adding the quencher-labeled antibody. This method was evaluated in microtiter plates using the susbtance P as model while fluorescein and TAMRA were used as donor and acceptor, respectively. Results clearly illustrated the interest of the method, by allowing (i) a simple regeneration procedure, without requiring any drastic treatment, (ii) a direct fluorescence measurement onto the solid support, leading to a localized and cumulative signal, (iii) an increase of the signal when detecting the target, unlike classical competitive immunoassays, and (iv) a real-time monitoring of the competition and regeneration steps. 相似文献
The nucleotide sequence of a 29·425 kb fragment localized on the left arm of chromosome XV from Saccharomyces cerevisiae has been determined. The sequence contains 13 open reading frames (ORFs) of which four encode the known genes ADH1, COQ3, MSH2 and RCF4. Predictions are made concerning the functions of the unknown ORFs. Some of the ORFs contain sequences similar to expressed sequences tags (EST) found in the database made available by TIGR. In particular, the highly expressed ADH1 gene is represented in this database by no less than 20 EST sequences. Two ARS sequences and a putative functional GCN4 motif have also been detected. One ORF (O0953) containing nine putative transmembrane segments is similar to a hypothetical membrane protein of Arabidopsis thaliana. Characteristic features of the other ORFs include ATP/GTP binding sites, a fungal Zn(2)-Cys(6) binuclear centre, an endoplasmic reticulum targeting sequence, a β-transducin repeat signature and in two instances, good similarity to the prokaryotic lipoprotein signal peptide motif. The sequence has been deposited in the EMBL data library under Accession Number X83121. 相似文献
Extracellular polymeric substances were extracted from activated sludge using a resin exchange method and analyzed. The separation and identification of EPS were carried out by size exclusion chromatography and Fourier transform infrared micro-spectroscopy. Chromatograms of extracted EPS exhibited seven peaks. Proteins varying in molecular weights from 670 to 45 kDa were present in all the peaks. Polysaccharides corresponding to molecular weights of approximately 1 and approximately 0.5 kDa were present in only three peaks. Strong association of polysaccharides and proteins was observed. Infrared results revealed the presence of one type of polysaccharide and two types of proteins (A and B). Proteins differed mainly in the length of their associated alkyl chains and in the ratio of ester/acidic functionalities. 相似文献
The authors showed previously that when time intervals around two sec are reproduced concurrently with a memory task, intervals are positively related to duration of memory processing. However, some data in research on timing as well as in memory research suggest that 2 sec might be a critical duration beyond which different mechanisms or structures would support performance. This implies that the interference observed between memory processing and 2-sec productions could be specific to these durations, and would not be obtained with longer durations. In this experiment, intervals ranging from 1.85 to 6.45 sec were reproduced by participants (16 females and 12 males, aged 18-33 yrs), who were searching simultaneously for a memory probe. At all durations, reproductions were positively related to memory set size. These findings have implications with regards to previous research indicating a discontinuity around 2-3 sec in time perception. They suggest in particular that the role of memory is similar in reproduction of durations around 2 sec and of longer durations. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献