Determinants of cerebral extracellular potassium after severe human head injury

The key role players of brain swelling seen after severe human head injury have only been partly determined. We used our human head injury data base to determine relationships between potassium, glutamate, lactate and cerebral blood flow (CBF). A total of 70 severely head injured patients (GCS < or = 8) were studied using intracerebral microdialysis to measure extracellular glutamate, potassium and lactate. Xenon CT was used to determine regional cerebral blood flow (rCBF). The mean +/- SEM of the r value of all patients, between potassium and glutamate, and potassium and lactate was 0.25 +/- 0.04 (p < 0.0001) and 0.17 +/- 0.06 (p = 0.006), respectively, demonstrating in both cases a positive relationship. rCBF was negatively correlated with potassium with marginal significance (r = -0.35, p = 0.08). When separated into two groups, patients with contusion had higher potassium levels than patients without contusion (1.55 +/- 0.03 mmol/l versus 1.26 +/- 0.02 mmol/l, respectively). These results in severely head injured patients confirm previous in vitro and animal studies in which relationships between potassium, glutamate, lactate and CBF were found. Potassium efflux is a major determinant of cell swelling leading to clinically significant cytotoxic edema due to increased glutamate release during reduced cerebral blood flow.

Magnetic properties of two cores from the Iberian Margin

Magnetic properties of late Quaternary sediments on the SW Iberian Margin are dominated by bacterial magnetite, observed by transmission electron microscopy (TEM), with contributions from detrital titanomagnetite and hematite. Reactive hematite from eolian dust, together with low organic matter concentrations and the lack of sulfate reduction, lead to dissimilatory iron reduction and availability of Fe(II) for abundant magnetotactic bacteria. Magnetite grain-size proxies (kARM/k and ARM/IRM) and S-ratios (sensitive to hematite) vary on stadial/interstadial timescales, contain orbital power, and mimic planktic d18O. The detrital/biogenic magnetite ratio and hematite concentration are greater during stadials and glacial isotopic stages, reflecting increased detrital (magnetite) input during times of lowered sea level, coinciding with atmospheric conditions favoring hematitic dust supply. Magnetic susceptibility, on the other hand, has a very different response being sensitive to coarse detrital multidomain (MD) magnetite associated with ice-rafted debris (IRD). High susceptibility and/or magnetic grain size coarsening, mark Heinrich stadials (HS), particularly HS2, HS3, HS4, HS5, HS6 and HS7, as well as older Heinrich-like detrital layers, indicating the sensitivity of this region to fluctuations in the position of the polar front. Relative paleointensity (RPI) records have well-constrained age models based on planktic d18O correlation to ice-core chronologies, however, they differ from reference records (e.g. PISO) particularly in the vicinity of glacial maxima, mainly due to inefficient normalization of RPI records in intervals of enhanced detrital/eolian hematite input.

Seawater carbonate chemistry and calcification during a study of barrier reef flat in Moorea, French Polynesia, 1998

The relative contribution of soft bottoms to the community metabolism (primary production, respiration and net calcification) of a barrier reef flat has been investigated at Moorea (French Polynesia). Community metabolism of the sedimentary area was estimated using in situ incubations in perspex chambers, and compared with estimates of community metabolism of the whole reef flat obtained using a Lagrangian technique (Gattuso et al., 1996. Carbon flux in coral reefs. 1. Lagrangian measurement of community metabolism and resulting air-sea CO2 disequilibrium. Mar. Ecol. Prog. Ser. 145, 109-121). Net organic carbon production (E), respiration (R) and net calcification (G) of sediments were measured by seven incubations performed in triplicate at different irradiance. Respiration and environmental parameters were also measured at four randomly selected additional stations. A model of Photosynthesis-irradiance allowed to calculate oxygen (O2), organic carbon (CO2) and calcium carbonate (CaCO3) evolution from surface irradiance during a diel cycle. As chlorophyll a content of the sediment was not significantly different between stations, primary production of the sediment was considered as homogeneous for the whole lagoon. Thus, carbon production at the test station can be modelled from surface light irradiance. The modelled respiration was two times higher at the test station than the mean respiration of the barrier reef, and thus underestimated sediment contribution to excess production. Sediments cover 40-60% of the surface and accounted for 2.8-4.1% of organic carbon excess production estimated with the modelled R and 21-32% when mean R value was considered. The sedimentary CaCO3 budget was a very minor component of the whole reef budget.

Pollen spectra and relative pollen productivity estimates for common taxa of the northern Siberian Arctic

Pollen productivity estimates (PPE) are used to quantitatively reconstruct variations in vegetation within a specific distance of the sampled pollen archive. Here, for the first time, PPEs from Siberia are presented. The study area (Khatanga region, Krasnoyarsk territory, Russia) is located in the Siberian Sub-arctic where Larixis the sole forest-line forming tree taxon. Pollen spectra from two different sedimentary environments, namely terrestrial mosses (n=16) and lakes (n=15, median radius ~100 m) and their surrounding vegetation were investigated to extract PPEs. Our results indicate some differences in pollen spectra between moss and lake pollen. Larix and Cyperaceae for example obtained higher representation in the lacustrine than in terrestrial moss samples. This highlights that in calibration studies modern and fossil dataset should be of similar sedimentary origin. The results of the Extended R-Value model were applied to assess the relevant source area of pollen (RSAP) and to calculate the PPEs for both datasets. As expected, the RSAP of the moss samples was very small (about 10 m) compared to the lacustrine samples (about 25 km). Calculation of PPEs for the six most common taxa yielded generally similar results for both datasets. Relative to Poaceae (reference taxon, PPE=1) Betula nana-type (PPEmoss: 1.8, PPElake: 1.8) and Alnusfruticosa-type (PPEmoss: 6.4, PPElake: 2.9) were overrepresented while Cyperaceae (PPEmoss: 0.5, PPElake: 0.1), Ericaceae (PPEmoss: 0.3, PPElake <0.01), Salix (PPEmoss: 0.03, PPElake <0.01) and Larix (PPEmoss <0.01, PPElake: 0.2) were under-represented in the pollen spectra compared to the vegetation in the RSAP. The estimation for the dominant tree in the region, Larixgmelinii, is the first published result for this species, but need to be considered very preliminary. The inferred sequence from over- to under-representation is mostly consistent with results from Europe; however, still the absolute values show some differences. Gathering vegetation data was limited by flowering season and low resolute satellite imagery and accessibility of the remote location of our study area. Therefore, our estimate may serve as first reference to strengthen future vegetation reconstructions in this climate-sensitive region.

On the Controversy About the Presence of Grain Boundary Sliding in Mg AZ31

Highly-textured, rolled AZ31 sheet material shows a significant drop in the plastic anisotropy (r-value; r=εw/εt) in tension between 25°C and 200°C. This behavior was initially explained as a result of the increased activity of non-basal slip with increased temperature. Other authors suggested, however, that the mechanism resp onsible for this phenomenon was the activation of grain boundary sliding (GBS). Here, in-situ ten sile tests have been carried out in an SEM at various temperatures in order to obtain further evi dence of the role of GBS during moderate to high temperature deformation of Mg alloys, which remains highly controversial.

Substrate-induced conformational change in a trimeric ornithine transcarbamoylase

The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-l-ornithine (PALO) has been determined at 2.8-Å resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides new insights into the linkages between substrate binding, protein–protein interactions, and conformational change. The structure was solved by molecular replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad. Sci. USA 92, 10762–10766; Protein Data Bank reference pdb 1otc) as the model and refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into two domains, a carbamoyl phosphate binding domain and an l-ornithine binding domain. The bound inhibitor interacts with the side chains and/or backbone atoms of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231, Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain. Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates that binding of the substrate analog results in closure of the two domains of each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes the largest conformational change upon substrate binding. The clinical implications for human OTCase deficiency are discussed.

Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug

Triabin, a 142-residue protein from the saliva of the blood-sucking triatomine bug Triatoma pallidipennis, is a potent and selective thrombin inhibitor. Its stoichiometric complex with bovine α-thrombin was crystallized, and its crystal structure was solved by Patterson search methods and refined at 2.6-Å resolution to an R value of 0.184. The analysis revealed that triabin is a compact one-domain molecule essentially consisting of an eight-stranded β-barrel. The eight strands A to H are arranged in the order A-C-B-D-E-F-G-H, with the first four strands exhibiting a hitherto unobserved up-up-down-down topology. Except for the B-C inversion, the triabin fold exhibits the regular up-and-down topology of lipocalins. In contrast to the typical ligand-binding lipocalins, however, the triabin barrel encloses a hydrophobic core intersected by a unique salt-bridge cluster. Triabin interacts with thrombin exclusively via its fibrinogen-recognition exosite. Surprisingly, most of the interface interactions are hydrophobic. A prominent exception represents thrombin’s Arg-77A side chain, which extends into a hydrophobic triabin pocket forming partially buried salt bridges with Glu-128 and Asp-135 of the inhibitor. The fully accessible active site of thrombin in this complex is in agreement with its retained hydrolytic activity toward small chromogenic substrates. Impairment of thrombin’s fibrinogen converting activity or of its thrombomodulin-mediated protein C activation capacity upon triabin binding is explained by usage of overlapping interaction sites of fibrinogen, thrombomodulin, and triabin on thrombin. These data demonstrate that triabin inhibits thrombin via a novel and unique mechanism that might be of interest in the context of potential therapeutic applications.

Crystal structure of Pseudomonas aeruginosa catabolic ornithine transcarbamoylase at 3.0-A resolution: a different oligomeric organization in the transcarbamoylase family.

The crystal structure of the Glu-105-->Gly mutant of catabolic ornithine transcarbamoylase (OTCase; carbamoyl phosphate + L-ornithine = orthophosphate + L-citrulline, EC 2.1.3.3) from Pseudomonas aeruginosa has been determined at 3.0-A resolution. This mutant is blocked in the active R (relaxed) state. The structure was solved by the molecular replacement method, starting from a crude molecular model built from a trimer of the catalytic subunit of another transcarbamoylase, the extensively studied aspartate transcarbamoylase (ATCase) from Escherichia coli. This model was used to generate initial low-resolution phases at 8-A resolution, which were extended to 3-A by noncrystallographic symmetry averaging. Four phase extensions were required to obtain an electron density map of very high quality from which the final model was built. The structure, including 4020 residues, has been refined to 3-A, and the current crystallographic R value is 0.216. No solvent molecules have been added to the model. The catabolic OTCase is a dodecamer composed of four trimers organized in a tetrahedral manner. Each monomer is composed of two domains. The carbamoyl phosphate binding domain shows a strong structural homology with the equivalent ATCase part. In contrast, the other domain, mainly implicated in the binding of the second substrate (ornithine for OTCase and aspartate for ATCase) is poorly conserved. The quaternary structures of these two allosteric transcarbamoylases are quite divergent: the E. coli ATCase has pseudo-32 point-group symmetry, with six catalytic and six regulatory chains; the catabolic OTCase has 23 point-group symmetry and only catalytic chains. However, both enzymes display homotropic and heterotropic cooperativity.

The mechanical properties and formability of dual-phase steel

In recent years dual phase steels comprising of 5-20% martensite in a ferrite matrix have come into the limelight of high strength cold formable steels because of their potential for vehicle weight saving. They show the following features: no yield point; relatively low initial flow stress; high initial workhardening rate; well sustained work hardening. As a consequence of these characteristics, dual phase steels exhibit a better combination of strength and elongation than other HSLA steels. In this thesis, a broad view of the factors which influence their properties is presented. Mechanical properties and forming ability of a commercially available dual phase steel and an AL-Si killed steel processed to dual phase form are investigated to ascertain the effect of their microstructure on their properties. It is found that the yield phenomena are masked by the transformation induced stresses present during processing and so yield point could be recovered under suitable ageing treatment; that apart from giving the above properties dual phasing gives rise to very low strain-rate sensitivity and a low R value ~ 1; that the mechanical response under rolling conditions is not different from those under tension; that there is a danger of damage to tooling during forming operations of these steels if fracture should precede instability as a result of grain size dependent strength found for these steels. It is also found that very little deformation of the martensite islands took place during deformation except at high strains. The work-hardening and the strength levels can be controlled by either decreasing the grain size or increasing the martensite volume fraction, but it is found that increasing martensite has a detrimental effect on ductility and the ductility and fracture strength can be controlled better by refining the grain size. A remarkable effect found in the dual phase steel tested is that the compressive strength is higher than the tensile strength. The reason for this observation is not yet clear but it is suggested that it might be due to the introduction of emissary type dislocations into the ferrite lattice as a result of twins formed in the martensite during transformation from austenite. The twins are envisaged to be {111} <112> in character.

Study on yield function and plastic potential under non-associated flow for accurate earing prediction in cup drawing

Prediction of more than four ears in a cup drawing process can be successfully achieved by considering r-value and stress directionalities. Yld2004-18p based on associated flow rule and Yld2000-2D based on non-associated flow rule are the examples. The former, however, is more costly in terms of computational efficiency than the latter. In this work, an anisotropic constitutive model based on non-associated flow rule which combines two different functions, Hill (1948) and Yld2000-2d, is implemented to a user defined material model. The accuracy of the anisotropic directionalities (yield stresses and plastic strain ratios) is evaluated. Simulation of a mini-die cup drawing with a body stock alloy predicted eight ears, in good agreement with the experimental results. The use of Hill (1948) model for the yield function and Yld2000-2d for plastic potential under the framework of non-associated flow rule led to accurate prediction of up to eight ears at the lower computational cost.

Retrospective evaluation and prospective value-add : a review of R&D investment in Australia

This paper describes a lead project currently underway through Australia’s Sustainable Built Environment National Research Centre evaluating diffusion mechanisms and impacts of R&D investment in the Australian built environment. Through a retrospective analysis of R&D investment trends and industry outcomes, and a prospective assessment of industry futures using strategic foresighting, a future-focussed industry R&D roadmap and pursuant policy guidelines will be developed. This research aims to build new understandings and knowledge relevant to R&D funding strategies, research team formation and management, dissemination of outcomes and industry uptake. Each of these issues are critical due to: the disaggregated nature of the built environment industry; intense competition; limited R&D investment; and new challenges (e.g. IT, increased environmental expectations). This paper details the context within which this project is being undertaken and the research design. Findings of the retrospective analysis of past R&D investment in Australia will be presented at this conference.

Variable selection by orthogonal descriptors and prediction of R-f value of phenol and aniline derivatives

Orthogonal descriptors is a viable method for variable selection, but this method strongly depend on the orthogonalisation ordering of the descriptors. In this paper, we compared the different methods used for order the descriptors. It showed that better results could be achieved with the use of backward elimination ordering. We predicted R-f value of phenol and aniline derivatives by this method, and compared it with classical algorithms such as forward selection, backward elimination, and stepwise procedure. Some interesting hints were obtained.