Accurate measurement of absolute experimental inelastic mean free paths and EELS differential cross-sections

Methods are described for measuring accurate absolute experimental inelastic mean free paths and differential cross-sections using DualEELS. The methods remove the effects of surface layers and give the results for the bulk materials. The materials used are VC0.83,TiC0.98,VN0.97and TiN0.88but the method should be applicable to a wide range of materials. The data were taken at 200 keVusing a probe half angle of 29mradand a collection angle of 36mrad. The background can be subtracted from under the ionisation edges, which can then be separated from each other. This is achieved by scaling Hartree-Slater calculated cross-sections to the edges in the atomic regions well above the threshold. The average scaling factors required are 1.00 for the non-metal K-edges and 1.01 for the metal L-edges (with uncertainties of a few per cent). If preliminary measurements of the chromatic effects in the post-specimen lenses are correct, both drop to 0.99. The inelastic mean free path for TiC0.98 was measured as 103.6±0.5 nm compared to the prediction of 126.9 nm based on the widely used Iakoubovskii parameterisation

Scanning transmission electron microscopy characterisation of carbide precipitates in steel

High strength micro-alloyed steels are used extensively in a number of industries such as car manufacturing. The properties of these steels, including their high strength, are caused in part by the formation of nanoscale precipitates during thermomechanical processing. In the case of the steels examined in the work reported in this thesis, the microalloying elements added to the steel were titanium, vanadium and niobium. During hot rolling, these combined with carbon and nitrogen to form stable carbides, nitrides and carbonitrides. Many steel properties depend on the size, distribution and chemistry of these precipitates, which in turn depend on the exact thermomechanical processing steps used during manufacture. The overall aim of the project was to understand how the combination of Ti, V and Nb influences the properties of bainitic steels and characterise the precipitation at different stages during manufacture. Electron microscopy techniques have been used to characterise the distribution, size and chemistry of these precipitates. This involved two different approaches, both using electron energy loss spectroscopy (EELS). First, large areas of steels were mapped using low-loss EELS. This allowed us to identify areas rich in precipitates, image their distribution and obtain a measurement of their size distribution as absolute volume fractions. The results from this are presented in Chapter 4 of this thesis. To process this data and obtain results from precipitates smaller than 1nm in diameter, a method to analyse the low-loss datasets has been developed as part of this PhD. This is detailed in Chapter 3. Once areas containing precipitates had been found, some of these were picked for more in-depth quantitative chemical analysis using DualEELS. A series of results for different types of precipitates found in a range of steel samples is detailed in Chapter 6. Again, the method used to analyse these datasets was partly developed as part of this PhD and is described in Chapter 3. It uses a multiple linear least squares fitting approach where experimentally obtained cross-sections are fitted to the precipitate data. The results of this are then used to quantify the exact chemistry of the precipitates. The details of the measurement of these cross-sections, and the method used to obtain them, are presented in Chapter 5. For the first time, we have been able to perform large area volumetric analysis coupled with detailed analysis of the chemistry of individual precipitates. This gave us the ability to track the precipitate formation resulting from the manufacturing process while while obtaining both a statistically significant overview and fine chemical detail. This has clear applications to the future of steel processing and other reactions involving precipitation or formation of nanoscale chemical inhomogeneity in materials

Spectrum imaging of complex nanostructures using DualEELS: II. Absolute quantification using standards

Nanometre-sized TixV(1−x)CyNz precipitates in an Fe20%Mn steel matrix with a thickness range from 14 to 40 nm are analysed using DualEELS. Their thicknesses, volumes and compositions are quantified using experimental binary standards and the process used to give robust results is described. Precisions of a few percent are achieved with accuracies that are estimated to be of a similar magnitude. Sensitivities are shown to be at 0.5–1 unit cells range in the thinnest matrix region, based on the assumption that a sub-lattice is fully populated by the element. It rises to the 1–2 unit cell range for the metals and 2–3 unit cells for the non-metal in the thickest matrix region. The sensitivities for Ti and N are greater than those for V and C respectively because the O K-edge from surface oxide needs to be separated from the V L2,3-edge, and the C K-edges from C in the matrix and amorphous C on the surface have to be separated from the C in the precipitate itself. Separation of the contributions from the bulk and the surface is demonstrated, showing that there is significant and detectable C in the matrix but no O, while there is significant O but little C in the surface oxide. Whilst applied to precipitates in steel in this work, the approach can be adapted to many multi-phase systems

DOLOMITIC SEDIMENTS IN CORE BAN 89-22 GC FROM THE DEEP-SEATED BRINES OF BANNOCK BASIN, EASTERN MEDITERRANEAN

Core Ban 89-22 GC has been recovered in the Bannock Basin (Eastern Mediterranean) on the large sill separaring Borea and Maestro sub-basins in an area covered by high density brines. The interest of this core consists in its dolomitic composition, for this reason the core has been studied in its sedimentological and micropaleontological characters with great detail. The use of particular analyses (C.A.T. Computerized axial tomography, carbonate percentage, smear-slides observations of all samples for the identification of nannofossil Zones and for the mineralogic composition of the sediments, EDAX) allows to explain the dolomitic composition as secondary diagenization due to the upward molecular diffusion or advection of Mg++ ions from the dissolution of primary dolomite of Messinian age, recovered in the core-catcher thus in contact with the Pleistocene-Holocene core sediments

Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion

Background: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. Results: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 Kaplan–Meier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. Conclusions: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion.Supported by FundaciónMutuaMadrileña (AP102962012), SpanishMINECO(SAF 2011-28150; SAF2014-55399R; SAF2014-58920) and ISCIII (CP12/03304, FIS 15/1492)

Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

Addiction is regarded as a disorder of inflexible choice with behavior dominated by immediate positive rewards over longer-term negative outcomes. However, the psychological mechanisms underlying the effects of self-administered drugs on behavioral flexibility are not well understood. To investigate whether drug exposure causes asymmetric effects on positive and negative outcomes we used a reversal learning procedure to assess how reward contingencies are utilized to guide behavior in rats previously exposed to intravenous cocaine self-administration (SA). Twenty-four rats were screened for anxiety in an open field prior to acquisition of cocaine SA over six daily sessions with subsequent long-access cocaine SA for 7 days. Control rats (n = 24) were trained to lever-press for food under a yoked schedule of reinforcement. Higher rates of cocaine SA were predicted by increased anxiety and preceded impaired reversal learning, expressed by a decrease in lose-shift as opposed to win-stay probability. A model-free reinforcement learning algorithm revealed that rats with high, but not low cocaine escalation failed to exploit previous reward learning and were more likely to repeat the same response as the previous trial. Eight-day withdrawal from high cocaine escalation was associated, respectively, with increased and decreased dopamine receptor D2 (DRD2) and serotonin receptor 2C (HTR2C) expression in the ventral striatum compared with controls. Dopamine receptor D1 (DRD1) expression was also significantly reduced in the orbitofrontal cortex of high cocaine-escalating rats. These findings indicate that withdrawal from escalated cocaine SA disrupts how negative feedback is used to guide goal-directed behavior for natural reinforcers and that trait anxiety may be a latent variable underlying this interaction.Pinsent Darwin Studentship, Cambridge University Swedish Research Council AXA Research Fund National Health and MRC of Australia Cambridge Isaac Newton Trust Boehringer Ingelheim Pharma GmbH, German

Correction: Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org