The toxic effects of four cationic porphyrins on various human cells were studied in vitro. It was found that, under dark conditions, porphyrins are almost nontoxic, while, under the action of light, the toxic effect was observed starting from nanomolar concentrations. At a concentration of 100 nM, porphyrins caused inhibition of metabolism in the MTT test in normal and cancer cells. Furthermore, low concentrations of porphyrins inhibited colony formation. The toxic effect was nonlinear; with increasing concentrations of various porphyrins, up to about 1 μM, the effect reached a plateau. In addition to the MTT test, this was repeated in experiments examining cell permeability to trypan blue, as well as survival after 24 h. The first visible manifestation of the toxic action of porphyrins is blebbing and swelling of cells. Against the background of this process, permeability to porphyrins and trypan blue appears. Subsequently, most cells (even mitotic cells) freeze in this swollen state for a long time (24 and even 48 h), remaining attached. Cellular morphology is mostly preserved. Thus, it is clear that the cells undergo mainly necrotic death. The hypothesis proposed is that the concentration dependence of membrane damage indicates a limited number of porphyrin targets on the membrane. These targets may be any ion channels, which should be considered in photodynamic therapy.
Hair follicles normally regenerate cyclically and this makes them a popular model for investigations of regeneration and aging.We studied the effects on mouse hair follicles of the Satura ® Rosta remedy manufactured from plant extracts and used to stimulate hair growth restoration.A prolonged application of the remedy to the skin of various strains of mice and of outbred white mice did not induce detectable negative effects and caused a significant increase of mean hair follicle size and hair root volume as well as skin thickening due to adipose elaboration.The volume increase took place mainly among the largest hair follicles.Mouse skin thickness is known to fluctuate cyclically in coordination with the waves of hair growth; anagen regions are thicker due to adipose increase.Satura ® Rosta did not abrogate hair growth waves.Apparently the observed effects could be explained by the remedy-induced prolongation of the anagen phase.Although the effect of Satura ® Rosta on fur appearance was insignificant in young animals, experiments with old mice exhibiting alopecia resulted in hair regrowth in alopecia regions.Transcriptome analysis of Satura ® Rosta action on dermal fibroblasts in vitro revealed significant changes of the expression of genes associated with the cell cycle, developmental processes and lipid metabolism.
An experimental study of the kinetics of the initial stages of the pyrolysis of high-density polyethylene (PE) was performed. Quantitative yields of gas-phase products (C1-C8 alkanes and alkenes) and functional groups within the remaining polyethylene melt (methyl, vinyl, vinylene, vinylidene, and branching sites) were obtained as a function of time (0-20 min) at five temperatures in the 400-440 °C range. Gas chromatography and NMR ((1)H and (13)C) were used to detect the gas- and condensed-phase products, respectively. Modeling of polyethylene pyrolysis was performed, with the primary purpose of determining the rate constants of several critical reaction types important at the initial pyrolysis stages. Detailed chemical mechanisms were created (short and extended mechanisms) and used with both the steady-state approximation and numerical integration of the differential kinetic equations. Rate constants of critical elementary reactions (C-C backbone scission, two kinds of H-atom transfer, radical addition to the double bond, and beta-scission of tertiary alkyl radicals) were adjusted, resulting in an agreement between the model and the experiment. The values of adjusted rate constants are in general agreement with those of cognate reactions of small molecules in the gas phase, with the exception of the rate constants of the backbone C-C scission, which is found to be approximately 1-2 orders of magnitude lower. This observation provides tentative support to the hypothesis that congested PE melt molecular environment impedes the tumbling motions of separating fragments in C-C bond scission, thus resulting in less "loose" transition state and lower rate constant values. Sensitivity of the calculations to selected uncertainties in model properties was studied. Values and estimated uncertainties of four combinations of rate constants are reported as derived from the experimental results via modeling. The dependence of the diffusion-limited rate constant for radical recombination on the changing molecular mass of polyethylene was explicitly quantified and included in the extended kinetic mechanism, which appears critical for the agreement between modeling and experiment, particularly the agreement between the experimental and the calculated activation energies for product formation rates. Calculations were performed to estimate the contribution to the overall rate of radical recombination of the "reaction diffusion" phenomenon, where recombination is driven not by the actual motion of the recombining radical sites but rather by the migration of the radical site through PE melt due to rapid hydrogen transfer; this contribution was shown to be negligible for the conditions of the current work.
The paper provides an overview of systems for scientometric analysis and considers methods for identifying current research directions. The new method for research directions detection based on full-text clustering is proposed. The results of experiments on the detection of the directions of the field "regenerative medicine" are presented. The prospects of method, its drawbacks and directions for further research are discussed.
To estimate patients risks and make clinical decisions, evidence based medicine (EBM) relies upon the results of reproducible trials and experiments supported by accurate mathematical methods. Experimental and clinical evidence is crucial, but laboratory testing and especially clinical trials are expensive and time-consuming. On the other hand, a new medical product to be evaluated may be similar to one or many already tested. Results of the studies hitherto performed with similar products may be a useful tool to determine the extent of further pre-clinical and clinical testing. This paper suggests a workflow design aimed to support such an approach including methods for information collection, assessment of research reliability, extraction of structured information about trials and meta-analysis. Additionally, the paper contains a discussion of the issues emering during development of an integrated software system that implements the proposed workflow.
The kinetics of the self-reaction of cyclopentadienyl radicals (c-C5H5) was studied by laser photolysis/photoionization mass spectroscopy. Overall rate constants were obtained in direct real-time experiments in the temperature region 304-600 K and at bath gas densities of (3.00-12.0) × 10(16) molecules cm(-3). The room-temperature value of the rate constant, (3.98 ± 0.41) × 10(-10) cm(3) molecule(-1) s(-1), is significantly higher than the rate constants for most hydrocarbon radical-radical reactions and coincides with the estimated collision rate. The observed overall c-C5H5 + c-C5H5 rate constant demonstrates an unprecedented strong negative temperature dependence: k1 = 2.9 × 10(-12) exp(+1489 K/T) cm(3) molecule(-1) s(-1), with estimated uncertainty increasing with temperature, from 13% at 304 to 32% at 600 K. Formation of C10H10 as the primary product of cyclopentadienyl self-reaction was observed. In additional experiments performed at the temperature of 800 K, formation of C10H10, C10H9, and C10H8 was observed. Final product analysis by gas chromatography/mass spectrometry detected two isomers of C10H8 at 800 K: naphthalene (major) and azulene (minor).
The paper contains a brief overview of full-text clustering methods for current research directions detection. A novel full-text clustering method is proposed. A dataset is created and experimental results are verified by problem domain “Regenerative medicine” experts with PhD degrees. The proposed method is well applicable for research directions detection according to experimental results. Finally, prospects and drawbacks of the proposed method are discussed. * The research is supported by Russian Foundation for Basic Research, project �14 -29-05008-ofi_m
The reaction of C-C bond scission in polyethylene chains of various lengths was studied using molecular dynamics under the conditions of vacuum and condensed phase (polymer melt). A method of assigning meaningful rate constant values to condensed-phase bond scission reactions based on a kinetic mechanism accounting for dissociation, reverse recombination, and diffusional separation of fragments was developed. The developed method accounts for such condensed-phase phenomena as cage effects and diffusion of the decay products away from the reaction site. The results of C-C scission simulations indicate that per-bond rate constants decrease by an order of magnitude as the density of the system increases from vacuum to the normal density of a polyethylene melt. Additional calculations were performed to study the dependence of the rate constant on the length of the polymer chain under the conditions of the condensed phase. The calculations demonstrate that the rate constant is independent of the degree of polymerization if polyethylene samples of different lengths are kept at the same pressure. However, if instead molecular systems of different polyethylene chain lengths decompose under the conditions of the same density, shorter chains result in higher pressures and lower rate constants. The observed effect is attributed to a higher degree of molecular crowding (lower fraction of free intermolecular space available for molecular motion) in the case of shorter molecules.
Karyotypes of species sects. Linum and Adenolinum have been studied using C/DAPI-banding, Ag-NOR staining, FISH with 5S and 26S rDNA and RAPD analysis. C/DAPI-banding patterns enabled identification of all homologous chromosome pairs in the studied karyotypes. The revealed high similarity between species L. grandiflorum (2n = 16) and L. decumbens by chromosome and molecular markers proved their close genome relationship and identified the chromosome number in L. decumbens as 2n = 16. The similarity found for C/DAPI-banding patterns between species with the same chromosome numbers corresponds with the results obtained by RAPD-analysis, showing clusterization of 16-, 18- and 30-chromosome species into three separate groups. 5S rDNA and 26S rDNA were co-localized in NOR-chromosome 1 in the genomes of all species investigated. In 30-chromosome species, there were three separate 5S rDNA sites in chromosomes 3, 8 and 13. In 16-chromosome species, a separate 5S rDNA site was also located in chromosome 3, whereas in 18-chromosome species it was found in the long arm of NOR-chromosome 1. Thus, the difference in localization of rDNA sites in species with 2n = 16, 2n = 30 and 2n = 18 confirms taxonomists opinion, who attributed these species to different sects. Linum and Adenolinum, respectively. The obtained results suggest that species with 2n = 16, 2n = 18 and 2n = 30 originated from a 16-chromosome ancestor.
The C2H3+C2H4 reaction was studied using the laser photolysis/photoionization mass spectrometry technique at T=625–950K and bath gas (helium) densities of (6–12)×1016atomcm−3. Reaction rate constants can be described by the expression k1=10−11.69±0.44exp(−(2830±790)K/T)cm3molecule−1s−1. C4H6 and C4H7 were detected as primary products; thermal stability of C4H7 at 950K indicates that it is a delocalized radical. The experimental results are compared with predictions obtained in master equation modeling based on the potential energy surface of Miller (J. Phys. Chem. A 108 (2004) 2268).
The thermal decomposition of the 2-chloroallyl radical, CH(2)CClCH(2) --> CH(2)CCH(2) + Cl (1), was studied using the laser photolysis/photoionization mass spectrometry technique. Rate constants were determined in time-resolved experiments as a function of temperature (720-840 K) and bath gas density ([He] = (3-12) x 10(16), [N(2)] = 6 x 10(16) molecule cm(-3)). C(3)H(4) was observed as a primary product of reaction 1. The rate constants of reaction 1 are in the falloff, close to the low-pressure limit, under the conditions of the experiments. The potential energy surface (PES) of reaction 1 was studied using a variety of quantum chemical methods. The results of the study indicate that the minimum energy path of the CH(2)CClCH(2) dissociation proceeds through a PES plateau corresponding to a weakly bound Cl-C(3)H(4) complex; a PES saddle point exists between the equilibrium CH(2)CClCH(2) structure and the Cl-C(3)H(4) complex. The results of quantum chemical calculations, the rate constant values obtained in the experimental study, and literature data on the reverse reaction of addition of Cl to allene were used to create a model of reactions 1 and -1. The experimental dependences of the rate constants on temperature and pressure were reproduced in RRKM/master equation calculations. The reaction model provides expressions for the temperature dependences of the high-pressure-limit and the low-pressure-limit rate constants and the falloff broadening factors (at T = 300-1600 K): k(infinity)(1) = 1.45 x 10(20)T(-1.75) exp(-19609 K/T) s(-1), k(infinity)(-)(1) = 8.94 x 10(-10)T(-0.40) exp(481 K/T) cm(3) molecule(-1) s(-1), k(1)(0)(He) = 5.01 x 10(-32)T(-12.02) exp(-22788 K/T) cm(3) molecule(-1) s(-1), k(1)(0)(N(2)) = 2.50 x 10(-32)T(-11.92) exp(-22756 K/T) cm(3) molecule(-1) s(-1), F(cent)(He) = 0.46 exp(-T/1001 K) + 0.54 exp(-T/996 K) + exp(-4008 K/T), and F(cent)(N(2)) = 0.37 exp(-T/2017 K) + 0.63 exp(-T/142 K) + exp(-4812 K/T). The experimental data are not sufficient to specify all the parameters of the model; consequently, some of the model parameters were obtained from quantum chemical calculations and from analogy with other reactions of radical decomposition. Thus, the parametrization is most reliable under conditions close to those used in the experiments.
The CH2Cl + CH3 (1) and CHCl2 + CH3 (2) cross-radical reactions were studied by laser photolysis/photoionization mass spectroscopy. Overall rate constants were obtained in direct real-time experiments in the temperature region 301-800 K and bath gas (helium) density (6-12) x 10(16) atom cm(-3). The observed rate constant of reaction 1 can be represented by an Arrhenius expression k1 = 3.93 x 10(-11) exp(91 K/T) cm3 molecule(-1) s(-1) (+/-25%) or as an average temperature-independent value of k1= (4.8 +/- 0.7) x 10(-11) cm3 molecule(-1) s(-1). The rate constant of reaction 2 can be expressed as k2= 1.66 x 10(-11) exp(359 K/T) cm3 molecule(-1) s(-1) (+/-25%). C2H4 and C2H3Cl were detected as the primary products of reactions 1 and 2, respectively. The experimental values of the rate constant are in reasonable agreement with the prediction based on the "geometric mean rule." A separate experimental attempt to determine the rate constants of the high-temperature CH2Cl + O2 (10) and CHCl2 + O2 (11) reaction resulted in an upper limit of 1.2 x 10(-16) cm(3) molecule(-1) s(-1) for k10 and k11 at 800 K.
5′-Hydrogenphosphonate of 3′-azido-2′,3′-dideoxythymidine (HpAZT), a novel anti-HIV drug approved for the treatment of HIV-infected patients in Russia, displays some clinical advantages over azidothymidine (AZT). Metabolism in the HL-60 cell culture and pharmacokinetics in mice of [6-3H]-HpAZT (in comparison with [6-3H]-AZT) were studied to elucidate the metabolic basis of its lower clinical toxicity. Accumulation of [6-3H]-HpAZT-derived products in cells with time, distribution of its radioactive metabolites among blood and different mouse organs and dependence of drug accumulation on the route of administration were investigated. The rate of accumulation of [3H]-HpAZT metabolites in cells was slower than the rate of accumulation of [3H]-AZT metabolites. [3H]-AZTMP was the dominating metabolite at all time points, achieving the level of 15±3pmol/106 cells after 25h incubation. After oral or intravenous administrations of [3H]-HpAZT, the (radioactive) metabolites were rapidly distributed among blood, stomach, intestine and liver and were not found in brain, muscles and spleen. [3H]-HpAZT underwent rapid and extensive metabolism, [3H]-AZT being the dominating product at all time points. Administration of 180nmol of [3H]-HpAZT resulted in an AZT concentration in blood of 1–3μM after 5min, which remained practically constant during the next 25min and did not depend on the route of administration.
Chromosomes of some species are very small (few microns in length), so only high magnification lenses (x100) with high aperture (typically 1.3) are used to study them. Investigators had developed methods of staining that permit chromosome identification (chromosome banding). To have a higher contrast investigators use green filters. We substituted the tungsten-halogen bulb in our microscope with a set of LEDs of different colours and compared the images of chromosomes. We used direct observation or a B&W CCD camera. Green LED illumination produced images of the same quality as those obtained with the halogen bulb and a set of filters (green and hot mirror). The differences in images obtained with different LEDs are visible and different LEDs can be used to improve contrast or to study spectral characteristics of the objects. Our LED illumination device is 10 times cheaper than the halogen, consume 5 times less energy, has 10 times longer lifetime, is 10 times lighter, and it is safer.