DETECTION OF DNA-PSORALEN PHOTOADDUCTS in situ

Abstract— An immunological method, with the use of specific immune serum, has been developed for detection of 8-methoxypsoralen (8-MOP) photoadducts to DNA, formed in situ in cell nuclei, after combined treatment with 8MOP and UV-A irradiation (Zarçbska et al. , 1978). Lymphocytes fixed on slides or in suspension, and cryostat sections of different mammalian tissues, served as antigenic substrate, after treatment with 8-MOP and UV-A in vitro. Specific fluorescence in these substrates was detected in the nuclei after treatment with 30 ˜ 140 kJ/m² UV-A in the presence of 0.1-0.3 μg/cm² 8-MOP. PHA-stimulated-lymphocytes appeared to be the most sensitive substrate.
However, hairless mice treated with high doses of UV-A in vivo , 70 ˜ 360 kJ/m² did not reveal a specific fluorescence of epidermal nuclei, unless a high local concentration of 8-MOP was attained.
The apparent discrepancy in the level of photoadduct detection between the in vitro and in vivo treated specimens was explained by the low number of DNA-8-MOP-photoadducts formed in vivo under these experimental conditions. The relevance of these findings to the role of DNA-8-MOP-photoadducts formed during PUVA photochemotherapy is discussed.     

Newtonian plane Couette flow with dynamic wall slip

Meccanica - The occurrence of slip complicates the estimation of the viscosity in rheometric flows. Thus, special analyses and experimental protocols are needed in order to obtain reliable...     

ON QUOTIENTS OF BRAID GROUPS

ABSTRACT.

Let G be the group ?[t, t ^?1] x ?. By studying the action of the braid group B_n on the set Gⁿ , we obtain representations of B_n into a wreath product of the symmetric group and the general linear group over ?[t, t ^?1]. This in particular recovers the Burau representation of the braid group. Furthermore, some quotients of the braid group are obtained by using the representations found.     

Structural basis of pyrazolopyrimidine derivatives as CAMKIIδ kinase inhibitors: insights from 3D QSAR,docking studies and in silico ADMET evaluation

Ca²⁺/calmodulin-dependent protein kinase II (CAMKIIδ) belongs to the serine/threonine kinase family, which is involved in a broad range of cellular events in cell survival and proliferation as well as a number of other signal transduction pathways. Thus, it is regarded a promising target for treatment of cancers. In the present paper, a three-dimensional quantitative structure–activity relationship and molecular docking were applied to investigate a series of new CAMKIIδ inhibitors of pyrazolopyrimidine derivatives. The determination coefficient (R²) and leave-one-out cross-validation coefficient (Q²) of CoMSIA model are 0.676 and 0.956, respectively. The predictive ability of this model was evaluated by the external validation using a test set of eight compounds with a predicted determination coefficient \(R^{ 2}_{\text{test}}\) of 0.80, besides the mean absolute error of the test set was 0.328 log units. Docking results are in concordance with CoMSIA contour maps, gave the information for interactive mode exploration. Based on those satisfactory results, newly designed molecules were predicted with highly potent CAMKIIδ inhibitory activity, additionally, they have showed promising results in the preliminary in silico ADMET evaluations. This study could expand our understanding of pyrazolopyrimidine derivatives as inhibitors of CAMKIIδ and would be of great help in lead optimization for early drug discovery of highly potent CAMKIIδ inhibitors.     

Further investigation of the mechanism of Doxorubicin release from P105 micelles using kinetic models

The kinetics of the release of Doxorubicin from Pluronic P105 micelles during ultrasonication and its subsequent re-encapsulation upon cessation of insonation were investigated. Four mechanisms are proposed to explain the acoustically-triggered Doxorubicin (Dox) release and re-encapsulation from Pluronic P105 micelles. The four mechanisms are: micelle destruction; destruction of cavitating nuclei; reassembly of micelles, and the re-encapsulation of Dox. The first mechanism, the destruction of micelles during insonation, causes the release of Dox into solution. The micelles are destroyed because of cavitation events produced by collapsing nuclei, or bubbles in the insonated solution. The second mechanism, the slow destruction of cavitating nuclei, results in a slow partial recovery phase, when a small amount of Dox is re-encapsulated. The third and fourth mechanisms, the reassembly of micelles and the re-encapsulatin of Dox, are independent of ultrasound. These two mechanism are responsible for maintaining the drug release at a partial level, and for recovery after insonation ceases. A normal distribution was used to describe micellar size. Parameters for the model were determined based upon the best observed fit to experimental data. The resulting model provides a good approximation to experimental data for the release of Dox from Pluronic P105 micelles.     

Phase transitions of nanoemulsions using ultrasound: experimental observations

The ultrasound-induced transformation of perfluorocarbon liquids to gases is of interest in the area of drug and gene delivery. In this study, three independent parameters (temperature, size, and perfluorocarbon species) were selected to investigate the effects of 476-kHz and 20-kHz ultrasound on nanoemulsion phase transition. Two levels of each factor (low and high) were considered at each frequency. The acoustic intensities at gas bubble formation and at the onset of inertial cavitation were recorded and subsequently correlated with the acoustic parameters. Experimental data showed that low frequencies are more effective in forming and collapsing a bubble. Additionally, as the size of the emulsion droplet increased, the intensity required for bubble formation decreased. As expected, perfluorohexane emulsions require greater intensity to form cavitating bubbles than perfluoropentane emulsions.     

Theoretical Study of Copper Acetonitrile Effects on Parr Functions Indices and Regioselectivity Using Density Functional Theory (DFT)

Russian Journal of Physical Chemistry A - Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a straightforward way for making covalent connections between building blocks containing...     

Signal optimisation in cw-laser crossed-beam photothermal spectrometry: influence of the chopping frequency, sample size and flow rate

Optimisation of the optical design for cw-laser crossed-beam thermal lens spectrometry in infinite and finite samples has been investigated using different excitation beam waists and various lens combinations. The characteristics of the photothermal signal depending on the position of the sample with respect to the probe beam waist, the chopping frequency, the sample size and the flow rate have been considered. Depending on the irradiation duration, the size of the thermal element at the measurement time can be much greater than the waist of the excitation beam. As a result, the optimum sample position is closely related to the probe beam to thermal element size ratio and therefore depends on the chopping frequency and of the sample size. At low frequencies, the size of the thermal element is almost independent of the degree of focusing of the excitation beam because a smaller beam waist induces a faster thermal expansion. As a result, the amplitude of the optimum signal does not depend on the waist of the excitation beam. In contrast, at high frequency, the size of the thermal element remains closer to the size of the excitation beam and the signal is inversely proportional to the waist of the excitation beam as previously demonstrated under pulsed-laser excitation. Moreover, at moderate flow velocities, the signal is significantly enhanced because the negative effect produced by the displacement of the thermal element across the probe beam axis is more than compensated by a decrease of the effective thermal time constant due to radial mixing.     

Characterization of partially transesterified poly(beta-hydroxyalkanoate)s using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was used for the characterization of a partially transesterified poly(beta-hydroxyalkanoate), PHA, polymer produced by the bacterial strain Alcaligenes eutrophus using saponified vegetable oils as the sole carbon sources. The transesterification was carried out separately under acidic and basic conditions to obtain PHA oligomers weighing less than 10 kDa. The intact oligomers were detected in their cationized [M + Na](+) and [M + K](+) forms by MALDI-TOFMS. A composition analysis, using the MALDI-TOF spectra, indicate that the oligomers obtained via acid catalysis were terminated with a methyl 3-hydroxybutyrate end group, and those obtained by base catalysis had a methyl crotonate (olefinic) termination. In addition to HB (hydroxy butyrate), the oligomers were found to contain a small percentage of HV (hydroxy valerate). This was independently confirmed using gas chromatography/mass spectrometry (GC/MS). In comparison, the analysis of a commercial PHA polymer, transesterified under identical conditions, only showed the presence of HB, i.e. a pure PHB homopolymer. Copyright 1999 John Wiley & Sons, Ltd.