Разработка состава и методик анализа таблеток ладастена, полученных прямым прессованием

Ladasten is original anxiolytic medicine with the psychostimulant action that increases human resistance to unfavorable factors of the environment. As the result of the investigation the optimal composition was found and the methods of analysis were elaborated for the direct compression tablets.Ладастен - оригинальное лекарственное средство, проявляющее анксиолитическую активность, обладающее психостимулирующим действием, повышающим устойчивость организма к действию неблагоприятных факторов среды обитания и деятельности. В результате проведенных исследований разработан оптимальный состава и методики анализа таблеток ладастена, полученных прямым прессованием

Measurement of the atmospheric neutrino-induced upgoing muon flux using MACRO

We present a measurement of the flux of neutrino-induced upgoing muons (~100 GeV) using the MACRO detector. The ratio of the number of observed to expected events integrated over all zenith angles is 0.74 +/- 0.036 (stat) +/- 0.046(systematic) +/- 0.13 (theoretical). The observed zenith distribution for -1.0 < cos(theta) < -0.1 does not fit well with the no oscillation expectation, giving a maximum probability for chi^2 of 0.1%. The acceptance of the detector has been extensively studied using downgoing muons, independent analyses and Monte-Carlo simulations. The other systematic uncertainties cannot be the source of the discrepancies between the data and expectations. We have investigated whether the observed number of events and the shape of the zenith distribution can be explained by a neutrino oscillation hypothesis. Fitting either the flux or zenith distribution independently yields mixing parameters of sin^2 (2theta)=1.0 and delta m^2 of a few times 10^-3 eV^2. However, the observed zenith distribution does not fit well with any expectations giving a maximum probability for chi^2 of 5% for the best oscillation hypothesis, and the combined probability for the shape and number of events is 17%. We conclude that these data favor a neutrino oscillation hypothesis, but with unexplained structure in the zenith distribution not easily explained by either the statistics or systematics of the experiment.Comment: 7 pages (two-column) with 4 figure

Global sensitivity analysis of stochastic computer models with joint metamodels

The global sensitivity analysis method used to quantify the influence of uncertain input variables on the variability in numerical model responses has already been applied to deterministic computer codes; deterministic means here that the same set of input variables gives always the same output value. This paper proposes a global sensitivity analysis methodology for stochastic computer codes, for which the result of each code run is itself random. The framework of the joint modeling of the mean and dispersion of heteroscedastic data is used. To deal with the complexity of computer experiment outputs, nonparametric joint models are discussed and a new Gaussian process-based joint model is proposed. The relevance of these models is analyzed based upon two case studies. Results show that the joint modeling approach yields accurate sensitivity index estimatiors even when heteroscedasticity is strong

Explorations of the application of cyanine dyes for quantitative α-synuclein detection

We examined the practical aspects of using fluorescent mono (T-284) and trimethinecyanine (SH-516) dyes for detecting and quantifying fibrillar α-synuclein (ASN). We studied the interaction of cyanine dyes with fibrillar proteins using fluorescence spectroscopy and atomic force microscopy. The commercially available classic amyloid stain thioflavin T (Thio T) was used as the reference dye. T-284 and SH-516 dyes can be used for fluorometric quantification of fibrillar wild-type ASN at concentrations of ∼1.5–20 µg/ml. Both dyes appeared suitable for step-wise monitoring of ASN variants (wild-type and mutants A30P and A53T) aggregation into fibrils in vitro, demonstrating good reproducibility, exceeding that for the commonly used Thio T. Our assay may be used for screening in vitro of agents capable of affecting the aggregation of ASN. In addition, T-284 and SH-516 cyanine dyes were shown to recognize amyloid proteins of various amino acid compositions selectively. T-284 demonstrated particular sensitivity to wild-type and A53T ASN, while for SH 516, the fluorescence response to fibrillar proteins was nearly the same except for lysozymes. T-284 and SH-516 cyanine dyes are sensitive and specific fluorescent probes for monitoring ASN fibril formation process in vitro, quantification of fibrillar ASN in solution, and fluorescent detection of various fibrillar protein specie

Studies of Interaction Between Cyanine Dye T-284 and Fibrillar Alpha-Synuclein

A key feature of Parkinson’s disease is the formation and accumulation of amyloid fibrils of the natively unfolded protein α-synuclein (ASN) inside neurons. Recently we have proposed novel sensitive monomethinecyanine dye T-284 as fluorescent probe for quantitative detection of ASN amyloid fibrils. In this study the T-284 dye complex with ASN fibril was characterized by means of fluorescence anisotropy, atomic force microscopy and time-resolved fluorescence techniques to give further insights into the mode of dye interaction with amyloid fibrils. The fluorescence anisotropy of T-284 was shown to noticeably increase upon addition of aggregated proteins indicating on stable dye/amyloid fibril complex formation. AFM imaging of fibrillar wild-type ASN revealed differences in heights between ASN fibrils alone and in presence of the T-284 dye (6.37 ± 1.0 nm and 8.0 ± 1.1 nm respectively), that is believed to be caused by embedding of T-284 dye molecules in the “binding channel” running along the fibril. Fluorescence decay analysis of the T-284 in complexes with fibrillar ASN variants revealed the fluorescence lifetime values for T-284/fibril complexes to be an order of magnitude higher as compared to the free dye. Also, the fluorescence decay of free T-284 was bi-exponential, while dye bound to protein yields tri-exponential decay. We suppose that in complexes with fibrillar ASN variants T-284 dye might exist in different “populations” due to interaction with fibrils in different conformers and ways. The exact binding mode of T-284 with ASN fibrils needs further studies. Studied parameters of dye/amyloid fibril complexes are important for the characterization and screening of newly-developed amyloid-sensitive dyes

Quantum control of dressed state population for four-level ladder Li2 molecules in femtosecond laser fields

Using the time-dependent wave packet method, Aulter-Townes splitting in the photoelectron spectra of four-level ladder Li2 molecules is theoretically investigated by two pump and one probe femtosecond laser pulses. Structure of the triple splitting is presented to analyze the information about a selective population of dressed states. It is found that regulating the intensity of laser pulse can control Rabi oscillation and thus tailor the splitting of three peaks. The population and energy of dressed states can be manipulated by changing the wavelength of the second pulse which can be interpreting using doubly dressed states. By adjusting the delay time between pump and probe pulse, one can control the population of the dressed states