934 resultados para Free R-value


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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.

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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.

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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.

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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.

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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.

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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.

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Gaussian processes provide natural non-parametric prior distributions over regression functions. In this paper we consider regression problems where there is noise on the output, and the variance of the noise depends on the inputs. If we assume that the noise is a smooth function of the inputs, then it is natural to model the noise variance using a second Gaussian process, in addition to the Gaussian process governing the noise-free output value. We show that prior uncertainty about the parameters controlling both processes can be handled and that the posterior distribution of the noise rate can be sampled from using Markov chain Monte Carlo methods. Our results on a synthetic data set give a posterior noise variance that well-approximates the true variance.

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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.

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Pearl millet flour was utilized in kibbeh formulations instead of whole-wheat flour. Physicochemical properties, oxidation stability and sensorial characteristics of control kibbeh made with whole-wheat flour (CT) were compared with kibbehs prepared with millet flour (roasted or wet) and stored for 90 days (–18 °C). Kibbeh prepared with millet flour presented good oxidation stability (TBARS concentration). Baked kibbehs (with roasted millet flour) presented good acceptability and kibbeh samples did not differ significantly (p > 0.05) from the whole-wheat flour sample, when global appearance, texture and flavor were evaluated. Millet flour could be a suitable ingredient for kibbeh formulations, maintaining their nutritional value and sensorial quality in addition to being a gluten-free product.

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PURPOSE Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria. PATIENTS AND METHODS Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS). RESULTS Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment. CONCLUSION Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients.

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Mode of access: Internet.

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Purpose: To evaluate the effects of Triesence (R) (TRI), a new preservative-free triamcinolone approved by the U. S. Food and Drug Administration (FDA) for intraocular use, on human retina pigment epithelial (ARPE-19) and rat neurosensory (R28) cells in culture. Methods: ARPE-19 and R28 cell cultures were treated 24 h with 1,000, 500, 200, or 100 mu g/mL of crystalline (cTRI) or 1,000, 500, or 200 mu g/mL of solubilized (sTRI). TRI was solubilized by centrifuging the drug, discarding the supernatant containing the vehicle and then resuspending the drug pellet in an equivalent amount of Dimethyl sulfoxide to achieve the same concentration as the commercial preparation. Percentage of cell viability (CV) was evaluated by a trypan blue dye-exclusion assay. The mitochondrial membrane potential (Delta Psi m) was analyzed with the JC-1 assay. The caspase-3/7 activity was measured by a fluorochrome assay. Results: In the ARPE-19 cultures, the cTRI caused a decrease in CV at 1,000 mg/mL (13.03 +/- 6.51; P < 0.001), 500 mu g/mL (28.87 +/- 9.3; P < 0.001), 200 mu g/mL (54.93 +/- 5.61; P < 0.001), and 100 mu g/mL (82.53 +/- 0.65; P < 0.005) compared with the untreated controls (96.98 +/- 0.16). In R28 cultures, the cTRI treatment also reduced CV values significantly (P < 0.001) for the 1,000 mu g/mL (22.73 +/- 2.44), 500 mu g/mL (34.63 +/- 1.91), 200 mu g/mL (58.70 +/- 1.39), and 100 mu g/m (75.33 +/- 2.47) compared with the untreated controls (86.08 +/- 3.54). Once the TRI was solubilized (sTRI), the CV and Delta Psi m remained similar to the untreated controls for both ARPE-19 and R28 cells. The sTRI treatment with 1,000, 500, and 200 mu g/mL increased in caspase-3/7 activity in ARPE-19 cells (P < 0.01) and in R28 cells (P < 0.05) compared with dimethyl sulfoxide equivalent controls. Conclusion: The crystalline form of TRI (cTRI) can cause a significant decrease in CV to cultured retinal cells. Once the TRI is solubilized (sTRI), at the same concentrations, the cells remain viable with no decrease in CV or Delta Psi m. The sTRI can, however, increase caspase-3/7 activity, thus suggesting some degree of apoptosis.

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The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.