In this work, the results of interpreting the variation of the magnetic signal of iron-rich marine sedimentary rocks were presented by the example of the Cretaceous–Paleogene section of the Bakchar ...iron ore deposit (Western Siberia). The anomalous values of the magnetic susceptibility are determined by two factors: first, a superimposed diagenetic process accompanied by the formation of pyrrhotite, greigite, and siderite among ooidal ironstones; and second, an increase in the continental runoff, causing the accumulation of terrigenous magnetite and ilmenite in the siltstone as the climate becomes increasingly humid and the weathering intensifies. It was shown that the elevated values of the magnetic susceptibility in iron-rich deposits can be due to the formation of ferrimagnetic iron sulfides, which is indicative of methane mobilization through ancient bottom sediments.
Characteristics of a new antithrombin DNA-aptamer RE31 were studied. This aptamer inhibited thrombin formation in human plasma catalyzed by exogenous (lengthening of thrombin time) and endogenous ...thrombin (lengthening of partial prothrombin time and activated partial thromboplastin time). In addition, the aptamer completely suppressed thrombin-induced aggregation of human platelets. On the other hand, RE31 did not reduce amidolytic activity of thrombin towards the short peptide substrate, in other words, did not modify the state of enzyme active center. By the capacity to inhibit clotting reactions, RE31 was superior to the previously described highly effective 31-component antithrombin aptamer 31TBA (thrombin binding aptamer, TBA). The effect of RE31 was species-specifi c: it inhibited human thrombin activity more effectively than activities of rat and rabbit thrombins.
The discharge of major cations and dissolved organic carbon (C
org
) with water of the Ob River and its tributaries along the natural zones within the Ob River basin was calculated, and the ...contribution of the underground component to the volumes of total discharge of the Ob River basin was estimated. It was demonstrated that the total chemical composition of river water and the geochemical discharge in the Ob River basin were consistent with the zoned hydroclimatic conditions controlling the character and duration of interaction in the water–rock system. It was established that the average ionic discharge of the Ob River increased from 6–7 × 10
6
t/year near Barnaul to 46–47 × 10
6
t/year near Salekhard; the discharge of dissolved C
org
increased from 0.1 × 10
6
to 3.8 × 10
6
t/year. Multiple enrichment of underground waters of the Ob River in dissolved organic matter from the upper to the lower reaches was revealed.
This article describes the investigation in the behavior and structure features of the iron-ore sequence in Bakchar ore deposit. Five facies characterizing the typical sedimentation environments were ...identified based on the analysis of typomorphic attributes of ore-bearing and barren deposits. The facies where oolitic ores are localized have been determined. A conceptual sedimentation model of the Bakchar ore mineralization has been proposed. Two facies- littoral argillo-arenaceous ferriferous sediments and mobile shallow alluvium oolitics were proposed as prospecting indicators of oolite hydrogoethite ore deposits.
The LHCb software is based on the Gaudi framework, on top of which are built several large and complex software applications. As the LHCb experiment is now in the active phase of collecting and ...analyzing data, performance problems arise in various parts of the software, from the High Level Trigger (HLT) programs to data analysis frameworks. It is not easy to find hotspots in the code — only specialized tools can help to understand where CPU or memory usage are not reasonable. There exist many performance analyzing tools, but the main problem is that they show reports in terms of class and function names and such information usually is not very useful — the majority of algorithm developers use the Gaudi framework abstractions and usually do not know about functions which lie at the lower level. We will show a new approach which adds to performance reports a higher abstraction level based on knowledge of framework architecture and run-time object properties. A set of profiling tools (based on Intel® VTune™ Amplifier XE) and visualization interfaces has been developed and deployed.
Glycoprotein (GP) IIb-IIIa (αIIbβ3-integrin) is the central receptor of platelet aggregation. Activated GP IIb-IIIa binds fibrinogen or von Willebrand factor, which forms molecular bridges between ...aggregating platelets. This review summarizes data on the relationship between GP IIb-IIIa expression on the platelet surface and platelet aggregating activity. GP IIb-IIIa number, measured as maximal binding of complex-specific monoclonal antibody, varied by approximately two fold in both healthy volunteers (n = 35) and patients with acute coronary syndrome (ACS) (n = 65). In healthy volunteers positive associations were observed between GP IIb-IIIa number and the level of ADP-induced aggregation when this relationship was analysed in untreated platelet-rich plasma (PRP) as well as upon in vitro addition of aspirin or non-saturating concentrations of GP IIb-IIIa blockers. In the same group of volunteers almost no differences in aggregating activity were detected between donors carrying the GP IIIa Pro33 allele (n = 15) and those with the GP IIIa Leu33Leu33 genotype (n = 20). No significant relationships were revealed between platelet aggregability and variations of plasma fibrinogen concentration. Positive correlation of the level of ADP-induced aggregation and GP IIb-IIIa content was detected in patients with ACS within the first hour upon admission to the hospital when they had already received aspirin, but not clopidogrel. However, there were no correlations between these parameters at days 3-5 and days 8-12 (before discharge). At these time points patients were treated not only with aspirin but were saturated with clopidogrel as well. In ACS patients we also evaluated the expression of another platelet adhesive receptor, GP Ib, and found a significant positive correlation between GP IIb-IIIa and GP Ib content. A strong association was also revealed between the number of both receptors and mean platelet volume. The latter observation indicated that individual variations of the number of glycoprotein molecules are mainly affected by platelet size but not the density of their expression on the platelet membrane. Possible usefulness of measuring GP IIb-IIIa content as a marker of increased platelet reactivity is discussed.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Methods for suppression of scattered X-ray radiation and related methods for improvement of X-ray image are discussed. The concept of method selectivity is suggested by analogy with the concept of ...X-ray raster selectivity. The selectivity of each method is quantitatively estimated.
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Membrane microparticles (MP), produced upon cell activation and/or damage, exhibit coagulation activity, i.e. ability to accelerate blood clotting. They contain on their surface phosphatidylserine ...(PS), a substrate for assembling coagulation enzymatic complexes, and some of them tissue factor (TF), the initiator of clotting cascade reactions. In this study coagulation properties of MP derived from erythrocytes have been investigated. These MP were obtained from donor’s erythrocytes activated with ionophore A23187 as well as from outdated erythrocyte concentrates for transfusion. MP were counted by flow cytometry and their coagulation activity was examined by the modified plasma recalcification assay. Involvement of PS and TF in this reaction was assessed using PS blocker lactadherin and anti-TF antibodies. TF activity in MP was measured by its ability to activate factor X in the chromogenic assay. Size of MP was evaluated by dynamic light scattering. Properties of erythrocyte MP were compared with previously characterized (using the same methodological approaches) MP derived from platelets and monocytic THP-1 cells, lacking and containing TF, respectively. Erythrocyte MP accelerated plasma clotting, but less actively than MP from platelets and MP from THP-1 cells, which demonstrated maximal activity. Lactadherin completely inhibited coagulation activity of all MP. Anti-TF antibodies did not affect clotting parameters in the presence of platelet and erythrocyte MP, but slowed clotting in the presence of MP from THP-1 cells. In contrast to MP from THP-1 cells expressing active TF, the TF activity was not detected in erythrocyte and platelet MP. MP derived from erythrocytes were smaller than MP from platelets and THP-1 cells, with average diameter about 200 nm and 400 nm, respectively. Thus, MP from erythrocytes exhibit lower ability to accelerate plasma clotting in comparison with MP from platelet and THP-1 cells. The data obtained suggest that lower coagulation activity of erythrocyte MP in comparison with MP from THP-1 cells is due to the absence of TF in erythrocyte MP (in contrast to MP from THP-1 cells) and to their smaller size, and in comparison with MP from platelets (which as erythrocyte MP do not express TF) is due to their smaller size only.
In this review we described the properties of reticulated platelets (RP) and showed how variations of their content might influence platelet activity, efficacy of antiplatelet drugs and the rate of ...thrombotic events in patients with cardiovascular diseases. RP represent a minor platelet fraction containing residual RNA from megakaryocytes. Platelets have no nucleus and do not synthesize RNA de novo, and RNA of megakaryocytic origin is destroyed during their circulation. That is why only recently produced “young” platelets contain RNA. In healthy donors RP are identified by staining with the RNA specific fluorescent dyes by flow cytofluorimetry or using standard protocols in modern flow haematological analyzers. RP content in blood reflects the level of thrombocytopoesis in the bone marrow. RP on average amounted from 3 to 10% of all platelets in the circulation depending on the method applied for their determination. RP absolute amount and/or their percentage is changed in haematological diseases associated with the alterations of megakaryocyte productive properties. RT measurements in patients with cardiovascular diseases have shown that their content is increased in acute coronary syndrome patients. RP are larger and functionally more active in comparison with not reticulated forms. They more frequently incorporate into the platelet aggregates and contain more intracellular granules. Increase of RT content in the circulation correlates with the increase of the average size and functional activity in the whole platelet population. High RP content in patients with cardiovascular diseases reduces antiaggregative effects of aspirin and P2Y12 APD receptor antagonists and increases the risk of atherothrombotic events.
The pharmacokinetic and safety profiles of clinical drug candidates are greatly influenced by their requisite physicochemical properties. In particular, it has been shown that 2D molecular ...descriptors such as fraction of Sp3 carbon atoms (Fsp3) and number of stereo centers correlate with clinical success. Using the proteomic off-target hit rate of nicotinic ligands, we found that shape-based 3D descriptors such as the radius of gyration and shadow indices discriminate off-target promiscuity better than do Fsp3 and the number of stereo centers. We have deduced the relevant descriptor values required for a ligand to be nonpromiscuous. Investigating the MDL Drug Data Report (MDDR) database as compounds move from the preclinical stage toward the market, we have found that these shape-based 3D descriptors predict clinical success of compounds at preclinical and phase1 stages vs compounds withdrawn from the market better than do Fsp3 and LogD. Further, these computed 3D molecular descriptors correlate well with experimentally observed solubility, which is among well-known physicochemical properties that drive clinical success. We also found that about 84% of launched drugs satisfy either Shadow index or Fsp3 criteria, whereas withdrawn and discontinued compounds fail to meet the same criteria. Our studies suggest that spherical compounds (rather than their elongated counterparts) with a minimal number of aromatic rings may exhibit a high propensity to advance from clinical trials to market.
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