Влияние коагуляции капель воды на их распределение по размерам в рабочей части аэрохолодильной установки

Mathematical simulation of coagulation of droplets of finite number of size fractions of a polydisperse mixture, injected by a nozzle into the region of an air-cooler unit along air flux motion direction, was performed. Sets of differential equations describing dependences of droplet fraction concentrations, their densities, as well as masses of droplets in each fraction on time, were solved using the fourth-order Runge–Kutta method. Negligibility of the impact of heat-mass exchange between the substance of droplets and surrounding air on changing their sizes during motion from the nozzle to the operating part of the device is shown. Decomposition of droplets is not simulated, since the critical Weber number is not reached in the considered operating regime of the air-cooler. Results of simulation of droplet coagulation in turbulent air flux show that distributions of droplets by sizes near the surface of a spraying nozzle do not coincide, which proves the necessity of accounting this process in simulation of ice coating of aircrafts in ground conditions.

A pilot interlaboratory comparison of protocols that simulate aging of nanocomposites and detect released fragments

Environmental context Nanoparticles are contained in many commercialised products, but the lack of validated methods to assess their potential release into the environment hampers our ability to perform a reliable risk assessment. Equipment to simulate aging is available, but the challenge is to sample released entities, and to analyse those fragments with suitable nano-analytics. We describe methods to characterise the degradation and surface accumulation of nanoparticles, and to quantify fragments released during UV irradiation of polymer nanocomposites. Abstract The safe use of nanoparticles as fillers in nanocomposite materials depends, in part, on a good understanding of what is released from aging nanocomposites, and at which rate. Here we investigated the critical parameters of the nanoparticle release phenomenon by a pilot inter-laboratory study of a polyamide containing 4mass% of silica nanoparticles (nanosilica). The main focus is on the validity range of the aging and release protocols. Both induced release by mechanical shear after dry weathering at different UV intensities and spontaneous release during wet weathering were investigated. We propose a combined protocol based on the finding that the characteristics of released fragments – which are the essential input for fate, transport and (eco-)toxicological testing – were reproducible between laboratories and between different aging, sampling and analysis protocols: the released fragments were a polydisperse mixture of predominantly composite fragments from the nanometre up to several micrometre diameter, and of clustered or individual nanosilica unbound to polymer. The unbound fraction was microscopically observed but could not be quantified. We found that aging conditions are very critical for the release rates, not for release characteristics. The sampling protocol tolerates some differences. Simplified aging + immersion protocols can at least partially replace, complement and extend dedicated weathering apparatus with run-off collection.

Selectins, Heparins, and Cancer: Rationale for Clinical Trials.

Heparin has been in use as an anticoagulant for many decades, based on its ability to enhance antithrombin activity. However, heparin is a natural product, comprising a complex polydisperse mixture of highly sulfated glycosaminoglycan chains, only a fraction of which bind antithrombin. We reported that heparin has an unrelated biological effect in inhibiting P- and L-selectin binding to their natural ligands. Meanwhile, animal studies and analyses of human clinical data suggest that heparin therapy increases survival in various cancers. In contrast, clinical trials using Vitamin K antagonists showed no major effect on survival in most studies. Thus, the heparin effect on cancer may not be due primarily to its anticoagulant function, but rather to inhibition of P- and L-selectin. Indeed, we have demonstrated that the selectins play critical roles in animal models of the hematogeneous phase of carcinoma metastasis and of the platelet-rich microthromboses typical of classical Trousseau’s syndrome. This involves interactions of selectins with pathological ligands produced by carcinoma cells, particularly sialylated, fucosylated, and sulfated mucins. The critical selectin-mediated interactions blocked by heparin occur early in the metastatic cascade. Also, inhibition occurs at concentrations in the clinically acceptable range. Furthermore, there are many other salutary actions of heparin in cancer, including adsorption of cytokines and growth factors, inhibition of thrombin generation, and inhibition of heparanases. We, therefore, suggest that heparin therapy for metastasis prevention in humans be revisited, with these new paradigms in mind. Most of the above studies used unfractionated heparin. We found that selectin-inhibiting effects of low molecular weight heparins (LMWH) are varied and that the synthetic heparinoid pentasaccharide that specifically binds antithrombin does not block at clinically relevant levels. Optimal dosing to sustain clinically acceptable levels of all these drugs in mice gave congruent results. These data suggest a rational clinical trial comparing an optimal LMWH with the pentasaccharide in the pre-/peri- and immediate post-operative periods of newly diagnosed carcinomas. Notably, heparin can also attenuate inflammatory pathologies in animal models by blocking L- and P-selectin.

AVE5026: A New Hemisynthetic Ultra Low Molecular Weight Heparin with Enriched Anti-Xa Activity and Enhanced Antithrombotic Activity for Management of Cancer Associated Thrombosis

AVE5026 is an ULMWH with a high anti-Xa activity associated with residual anti-IIa activity (ratio anti-Xa/IIa>30). This ratio may be favorable for use in cancer patients as it may have a higher therapeutic window. This agent is a polydisperse mixture of oligomeric heparin fragments (molecular weight 2000–3000 daltons) prepared by partial and controlled depolymerization of porcine mucosal heparin (UFH).. The anticoagulant profile of AVE5026 has been previously reported (Hoppensteadt, et al. Blood 2007). To validate the hypothesis that AVE5026 is an appropriate antithrombotic in cancer, studies were carried out to determine its antithrombotic, bleeding, tumor growth, angiogenesis and apoptosis effects in animal models. AVE5026 produced a dose-dependent antithrombotic response in the rat laser model of microvascular thrombosis (2.5 mg/kg IV, 9±1.7 laser shots; 5.0 mg/kg SC, 8±1.6 laser shots; control 3±0.8 laser shots). The relative bleeding effects of AVE5026 in a rat tail bleeding model were negligible in comparison to enoxaparin (E) and UFH (all 5 mg/kg IV; UFH >1000 sec; E 360±57 sec; AVE5026 209±29 sec; Control 215±32 seconds). Repeated administration of AVE5026 in dose ranges of 1–5 mg/kg od, SC for 14 days did not result in accumulation of the anti-Xa activity. Furthermore, in contrast to E, there was no enhancement of the hemorrhagic profile. Both E and AVE5026 inhibited tumor growth by regulating angiogenesis and apoptosis in a Lewis Lung carcinoma (14% vs. 22% decrease) rat model and in a Walker 256 carcinosarcoma model (21% vs. 30% decrease) Although comparable results to E were demonstrated in animal models of arterial thrombosis, the bleeding effect of AVE5026 were disproportionately lower. This superior safety-efficacy ratio may translate into improved antithrombotic efficacy with decreased bleeding risk, suggesting that AVE5026 may provide the optimal treatment strategy for the management of cancer associated thrombosis.

Exogenous Nucleic Acids - A Potential Source of Resistance to Nucleoside Analogues in Cancer and Antiviral Therapy.

The metabolism of exogenous nucleic acids is not well defined. Moreover, there is little information whether there might be interference with chemically and structurally related drugs, e.g. nucleoside analogues (NA) widely used in cancer or in antiviral therapy. In the present report we provide evidence, that nucleic-acid based drugs might antagonize fludarabine or acyclovir. In vitro, fludarabine treated lymphocytes or myeloid blasts where rescued from apoptosis when incubated with defibrotide (DF), a polydisperse mixture of single-stranded oligodeoxyribonucleotides (15 to 30 kD) or singular deoxynucleotides. Thereby deoxycytidine (dCTP) turned out to be the key substrate competing with fludarabine for phosphorylation by deoxycitidine kinase (dCK) and suggested interference with nucleic acid metabolism rather than direct competition with the drug. To further prove this hypothesis the influence of defibrotide on HSV replication was evaluated. In standard drug resistance assays performed with acyclovir sensitive herpes simplex virus (HSV) strains (V0631508) 4 mM of DF restored viral replication in presence of 50 mM acyclovir. This was confirmed by quantitative PCR of viral DNA. Moreover, in this case deoxythymidine (dTTP) turned out to be the competitor for intracellular phosphorylation mediated by virus thymidine kinase. We conclude that treatment with DF and other nucleic-acid-based drugs interfere with the efficacy of NA used for cancer and antiviral therapy. Prospective clinical trials are required to confirm these in vitro findings.