Cis-trans isomerization in cyclosporin C dissolved in acetonitrile.

Cyclosporin is an 11-amino acid cyclic peptide with pharmacologically valuable properties which has a variety of actual and potential applications. Its activity relies on the cell membrane permeability which, in turn, depends on the structure of cyclosporin and its ability to change the conformation. In this work, conformational exchange processes occurring in cyclosporin C were studied using one- and two-dimensional nuclear magnetic resonance spectroscopy. The free energy barrier separating two major conformers observed in polar solution (acetonitrile) was found to be 77 ± 2 kJ/mol. Less populated conformation states are also present in the solution, which agrees with the ease of formation of multiple forms revealed by MD simulations of cyclosporin C.

Compact high-current pulse generator for laboratory studies of high energy density matter.

We present the design and parameters of a compact and mobile high-current pulse generator, which can be applied in the study of warm dense matter in university laboratories. The generator dimensions are 550 × 570 × 590 mm3, the weight is ∼70 kg, and it consists of four "bricks" connected in parallel. Each brick, made up of 2 × 40 nF, 100 kV low-inductance capacitors connected in parallel, has its own multi-gap and multichannel ball gas spark switch, triggered via a capacitively coupled triggering by a positive polarity pulse of ∼80 kV amplitude and ∼15 ns rise time. At a charging voltage of ∼70 kV, the generator produces a ∼155 kA current pulse with a rise time of ∼220 ns on a ∼15 nH inductive short-circuit load and a ∼90 kA amplitude current pulse in the underwater electrical explosion of a copper wire.

Comparison of cyclosporin variants B-E based on their structural properties and activity in mitochondrial membranes.

Cyclosporins B, C, D, and E were characterized by NMR spectroscopy, and backbone flexibility was studied by molecular dynamics simulation. Structures of the molecules were characterized by nuclear Overhauser effect spectroscopy, which revealed that the studied peptides have many common features. Molecular dynamics simulation showed that the backbone of cyclosporin E is relatively more rigid than in other peptides. Calcium-dependent swelling of liver mitochondria under the influence of four considered compounds was also investigated. Three of them were found to have the activity similar to cyclosporin A, inhibiting opening of the mitochondrial pore at concentrations within 100-300 nM. However, cyclosporin E did not show any biological effect at concentrations up to 1 µM. Results of this study agree with the idea on the correlation between the peptide chain flexibility and its bioavailability.

Polyurethane ionomers based on amino ethers of ortho-phosphoric acid.

The etherification of ortho-phosphoric acid with triethanolamine and polyoxypropylene glycol is studied. The reaction process is accompanied by the formation of hyperbranched amino ethers of ortho-phosphoric acid terminated by hydroxyl groups. A specific feature of the chemical structure of the compounds obtained is the existence of ion pairs in their structure separated in space. The reaction of the etherification of ortho-phosphoric acid with glycols becomes possible through the use of tertiary amines. The amino ethers of ortho-phosphoric acid are investigated as a polyol component for the synthesis of polyurethanes with high adhesion characteristics and strength properties. The experimental results presented allow us to relate polyurethanes obtained on the basis of ortho-phosphoric acid amino ethers to polymers of ionomeric nature.

Evidence of oligomerization of bovine insulin in solution given by NMR.

The protein hormone insulin exists in several forms in nature, and a large number of modified sequences are used in pharmacy. They differ by physicochemical properties and efficiency of biological action. Pancreatic bovine insulin was studied in an acidic solution by nuclear magnetic resonance spectroscopy. [Formula: see text]H and [Formula: see text]C NMR signal assignment of backbone and side chains was made by analysis of a set of 2D spectra obtained on a sample with natural isotope abundance. The presence of certain secondary structure elements was revealed on a qualitative level based on nuclear Overhauser effect spectroscopy, which are similar to those observed in the crystal structure. The C-terminus of the B-chain possessed a remarkable flexibility. The molecule was shown to exist in exchange with oligomers based on its self-diffusion coefficient and correlation time measurements performed at different concentrations. Certain signals in the NOESY and HSQC spectra are consistent with the presence of minor conformers; this is an obstacle in simulating the molecular structure under the conditions used in the experiment.

Commissioning of the PRIOR proton microscope.

Recently, a new high energy proton microscopy facility PRIOR (Proton Microscope for FAIR Facility for Anti-proton and Ion Research) has been designed, constructed, and successfully commissioned at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany). As a result of the experiments with 3.5-4.5 GeV proton beams delivered by the heavy ion synchrotron SIS-18 of GSI, 30 µm spatial and 10 ns temporal resolutions of the proton microscope have been demonstrated. A new pulsed power setup for studying properties of matter under extremes has been developed for the dynamic commissioning of the PRIOR facility. This paper describes the PRIOR setup as well as the results of the first static and dynamic proton radiography experiments performed at GSI.

[Choosing the method of reconstruction for lower-limb critical ischemia].

Presented herein are long-term outcomes of surgical treatment of 74 patients with atherosclerotic occlusive-stenotic lesions of the femoral-popliteal-tibial segment and critical ischaemia. 51 (68.92%) patients underwent femoropopliteal shunting into the isolated segment of the reversed great saphenous vein. Of these, three patients were subjected to a hybrid operation consisting of femoropopliteal bypass grafting and balloon angioplasty of the popliteal and one tibial artery. 23 (31.08%) patients endured percutaneous balloon angioplasty with stenting of the superficial femoral artery and balloon angioplasty of one tibial artery. Two-year patency of the zone of reconstruction of the femoropopliteal segment in these groups was identical, amounting to 64.71 and 56.52%, respectively. However, the group of patients with endovascular intervention demonstrated rather a high rate of intraoperative complications--21.74%, technical success in balloon angioplasty of arteries of the crus amounted to 65.22%. Once the method of operative treatment is chosen, preference is given to shunting in the isolated popliteal artery with sufficient collateral blood flow. Further studies are required to determine angiographic indications for endovascular intervention on tibial arteries.

Antimicrobial peptide protegrin-3 adopt an antiparallel dimer in the presence of DPC micelles: a high-resolution NMR study.

A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel ß-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric ß-barrels.

High-resolution NMR structure of the antimicrobial peptide protegrin-2 in the presence of DPC micelles.

PG-1 adopts a dimeric structure in dodecylphosphocholine (DPC) micelles, and a channel is formed by the association of several dimers but the molecular mechanisms of the membrane damage by non-α-helical peptides are still unknown. The formation of the PG-1 dimer is important for pore formation in the lipid bilayer, since the dimer can be regarded as the primary unit for assembly into the ordered aggregates. It was supposed that only 12 residues (RGGRL-CYCRR-RFCVC-V) are needed to endow protegrin molecules with strong antibacterial activity and that at least four additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin (PG-2) represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi. As the peptide conformation and peptide-to-membrane binding properties are very sensitive to single amino acid substitutions, the solution structure of PG-2 in solution and in a membrane mimicking environment are crucial. In order to find evidence if the oligomerization state of PG-1 in a lipid environment will be the same or not for another protegrins, we investigate in the present work the PG-2 NMR solution structure in the presence of perdeuterated DPC micelles. The NMR study reported in the present work indicates that PG-2 form a well-defined structure (PDB: 2MUH) composed of a two-stranded antiparallel ß-sheet when it binds to DPC micelles.

Determination of preferred conformations of ibuprofen in chloroform by 2D NOE spectroscopy.

Solution of an anti-inflammatory drug ibuprofen ((RS)-2-(4-isobutylphenyl) propionic acid) in chloroform was studied by nuclear magnetic resonance spectroscopy. A set of 2D NOESY spectra was analyzed in order to obtain atom-atom distances. Since ibuprofen is known to exist as an ensemble of different conformations, these distances are averaged over the ensemble. To compare experimental and calculated distances, three models of averaging were concerned. Our data allowed to determine the dominant conformers of ibuprofen dissolved in chloroform. The population of conformers in the saturated solution leads to a certain crystal morphology formed within the nucleation process. Observed and calculated (13)C chemical shifts (at the DFT/B3LYP/6-311+G(2d,p) level) were in good agreement.

Diagnostics of underwater electrical wire explosion through a time- and space-resolved hard x-ray source.

A time- and space-resolved hard x-ray source was developed as a diagnostic tool for imaging underwater exploding wires. A ~4 ns width pulse of hard x-rays with energies of up to 100 keV was obtained from the discharge in a vacuum diode consisting of point-shaped tungsten electrodes. To improve contrast and image quality, an external pulsed magnetic field produced by Helmholtz coils was used. High resolution x-ray images of an underwater exploding wire were obtained using a sensitive x-ray CCD detector, and were compared to optical fast framing images. Future developments and application of this diagnostic technique are discussed.

[Unusual alternations of floral organs in Paeonia: structure and possible mechanism of formation].

Morphological analysis of flowers was carried out in Paeonia cultivars. Some unusual alternations of floral organs were described: sepal-(petal-stamen) x N-carpel, where 2 < or = n < or = 4 (appearance of an additional zone of petal and stamen formation in the medial flower part). The identity of floral organs was not affected in the flowers with this unusual alternation. It was shown on the basis of mathematical simulation of the genes responsible for flower development that these alternations may be determined by increased pool of stem cells, which may lead to delayed termination of flower development.

Strongly coupled copper plasma generated by underwater electrical wire explosion.

A number of theoretical approaches to the analysis of the parameters of a discharge channel consisting of strongly coupled plasma generated in the process of underwater electrical wire explosion are presented. The analysis is based on experimental results obtained from discharges employing Cu wire. The obtained experimental data included electrical measurements and optical observations from which information about the dynamics of the water flow was extrapolated. Numerical calculation based on a 1D magnetohydrodynamic model was used to simulate the process of underwater wire explosion. A wide range conductivity model was applied in this calculation and good agreement with a set of experimental data was obtained. A method of determining the average temperature of the discharge channel based on this model and experimental results is proposed, and the limits of this method's applicability are discussed.

[Immunological disorders in vibration-related illness among miners of Northern regions]. / Immunologicheskie narusheniia pri vibratsionnoi bolezni u gornorabochikh severnykh regionov.

Evaluation of miners in Northern and East Siberian regions revealed disorders of humoral immunity: increased B-lymphocytes count, higher production of autologic antibodies to peripheral nerves, greater serum concentration of circulating immune complexes and cryoglobulins. Cytostatic medications suppressed antibodies production and considerably increased efficiency of complex therapy of severe vibration disease.

[The characteristics of the corticosteroid receptors in the hormonal modification of the stress reactivity of rats]. / Kharakteristika kortikosteroidnykh retseptorov pri gormonal'noi modifikatsii stress-reaktivnosti u krys.

After neonatal administration of hydrocortisone the rat litter preserve inhibition of function of the hypophyseal-adrenal system at the age under 2 months. During the inhibition period, the number of corticosteroid receptors was decreased in the hypothalamus and hippocampus and increased in the hypophysis. At the 3-month age, binding of corticosteroids in these structures is restored.

[The evaluation of corticosteroid hormone receptor status in the brain structures of stressed and adrenalectomized rats]. / Otsenka sostoianiia retseptorov kortikosteroidnykh gormonov v strukturakh mozga stressirovannykh i adrenaléktomirovannykh krys.

The value of receptor capacity in respect to cytosol concentration was shown to vary, therefore two criteria are proposed for estimation of condition of the cytosol corticosteroid receptors: the density of the receptors in tissue and the range of intermediate (active) complex. The number of receptors in the hypophysis was shown to reduce after adrenalectomy whereas in the hypothalamus, hippocampus and striatum it increased. The range of intermediate complex was shown to change differently in different structures after stress.

[Method of detecting excitability of skin receptors in the diagnosis of vibration disease]. / Metodika opredeleniia vozbudimosti kozhnykh retseptorov pri diagnostike vibratsionnoi bolezni.

The follow-up studies of patients with vibration disease caused by local vibration proved diagnostic value of minor skin response of dorsal hand surface and anterior surface of arm or forearm, if subjected to irritation with mixture of chloroform and ethanol. Depressed skin receptors during the disease are diagnosed through longer latent period of burning sensation in two of three points irritated on skin of the upper limb. The diagnostic method based on chemical stimulation of skin receptors is highly sensitive (86.9%) and specific (94.4%), especially for early stages of the disease, promoting detection of subclinical peripheral neuropathy caused by vibration. Due to its simplicity and availability the method could replace algesimetry in mass screening among workers exposed to vibration.