Stabilization of optical characteristics of DNA cholesteric liquid-crystalline dispersions

Abnormal optical properties of liquid-crystalline dispersions (phases) formed as a result of phase exclusion of double-stranded DNA and RNA from water-salt poly(ethylene glycol) solutions and X-ray parameters of these phases are compared. It is shown that the cholesteric packing of nucleic acid molecules is realized at the certain osmotic pressure of a solvent only. A comparison of the optical properties of liquid-crystalline phases (dispersions) to their X-ray parameters allows one to put forward a suggestion on various hydratation (fluctuation) regimes of the nucleic acid behaviour under the condensed phases formation and factors, influencing the mode of packing of these molecules in phases formed. It is shown as well, that immobilization of DNA cholesteric liquid-crystalline particles in the content of polymeric matrix is accompanied by the stabilization of these particles and, hence, their specific abnormal optical activity as well as by formation of particles having a structure, which corresponds to the "optically isotropic ordered liquid" without abnormal optical activity. Data on stabilization of the cholesteric structure of liquid-crystalline DNA dispersions by creation of polymeric chelate bridges between the neighbouring DNA molecules, fixed in the structure of liquid-crystalline dispersions, are shown.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

Experimental and clinical validation of auto- and allodermoplasty using transverse dermal micrografts in deep burns

A new method of autoallodermoplasty is proposed which is as follows: a patient's skin band is cut out 40 times less than the total area of the wound surface. The wound in the donor area is sutured tightly. The skin flap is dissected to thin transverse rectangular pieces with a special microdermatome or with a razor and then they are laid with their lateral side onto the wound and covered with the allo-skin. Experimental and clinical observations have shown that at remote terms both the anatomical and functional restitution of the integument occurred. The method is indicated for huge dermal defects of the "functionally passive" areas in patients with restricted, not big resources of the donor sites, especially in patients with high operative risk.     

Modelling the dynamics of the tilt-casting process and the effect of the mould design on the casting quality

All titanium alloys are highly reactive in the molten condition and so are usually melted in a water-cooled copper crucible to avoid contamination using processes such as Induction Skull Melting (ISM). These provide only limited superheat which, coupled with the surface turbulence inherent in most conventional mould filling processes, results in entrainment defects such as bubbles in the castings. To overcome these problems, a novel tilt-casting process has been developed in which the mould is attached directly to the ISM crucible holding the melt and the two are then rotated together to achieve a tranquil transfer of the metal into the mould. From the modelling point of view, this process involves complex three-phase flow, heat transfer and solidification. In this paper, the development of a numerical model of the tilt-casting process is presented featuring several novel algorithm developments introduced into a general CFD package (PHYSICA) to model the complex dynamic interaction of the liquid metal and melting atmosphere. These developments relate to the front tracking and heat transfer representations and to a casting-specific adaptation of the turbulence model to account for an advancing solid front. Calculations have been performed for a 0.4 m long turbine blade cast in a titanium aluminide alloy using different mould designs. It is shown that the feeder/basin configuration has a crucial influence on the casting quality. The computational results are validated against actual castings and are used to support an experimental programme. Although fluid flow and heat transfer are inseparable in a casting, the emphasis in this paper will be on the fluid dynamics of mould filling and its influence on cast quality rather than heat transfer and solidification which has been reported elsewhere.     

Role of primate medial vestibular nucleus in long-term adaptive plasticity of vestibuloocular reflex

1. Fifteen hundred and thirty cells were recorded in the medial vestibular nucleus (MVN) of alert monkeys whose vestibuloocular reflex (VOR) had been adapted to one of two kinds of spectacles. The "high-gain" sample was recorded from monkeys that had worn 2.0 x telescopic spectacles; the gain of the VOR in the dark (eye velocity divided by head velocity) was greater than 1.5. The "low-gain" sample was recorded from monkeys that had worn goggles providing a visual field that was fixed with respect to the freely turning head; the gain of the VOR was less than 0.4. 2. Cells showing modulation of firing rate related to imposed head velocity were grouped into four categories: pure vestibular (10), vestibular-plus-saccade (10), vestibular-plus-position (10), and vestibular-plus-head/body (24). Sensitivity to head velocity was measured from averaged responses to sinusoidal, 0.4-Hz whole-body oscillation in the horizontal plane. Almost all cells (98%) having increased firing during ipsilateral head rotation received inputs from the horizontal semicircular canals. Conversely, 82% of cells having increased firing during contralateral head rotation received inputs from the vertical canals. 3. There were no statistically significant differences in resting discharge rate, phase shift, or sensitivity to head velocity between the high- and low-gain samples of any of the cell types. Nonetheless, there was a consistent tendency, evident in all the functionally defined cell groups, for the sensitivity to be about 20% greater in the high-gain samples. However, this difference is small by comparison with the fourfold difference in VOR gain. 4. Detailed scrutiny of the response properties of individual cells suggested that the small differences in sensitivity reflect small changes distributed throughout the population, rather than large and potentially significant changes within a small sub-population. 5. Our data indicate that large, adaptive changes in the gain of the VOR are accompanied by only minor changes in the vestibular sensitivity and no changes in the phase shift or resting discharge rates of cells in the MVN. It remains possible that large changes in vestibular sensitivity occurred in cells we did not sample or in subgroups we could not identify. We argue that this is unlikely and that the major changes underlying VOR plasticity occur after the first central synapse in the VOR pathways.     

Effect of moditen-depot therapy on the duration and quality of remissions in schizophrenia patients

The authors studied the effectiveness of out-patient treatment by Moditen-Deppt of 128 schizophrenic patients. A comparison of the previous remissions appearing during usual pharmacotherapy and remissions seen during Moditen-Depot treatment depicted statistically significant differences, indicating a distinct prevention of exacerbations due to this preparation, an increase in the duration and improved quality of remissions. Such improved remissions were expressed in lesser severity, in a decrease of psychopathological disturbances, changes qualified as a "mollification of a defect" and an improvement of some socio-clinical indices.     

Effect of argon pressure on the optical properties of sputtered solar selective surfaces

The influence of argon gas pressure (0.15-40 Pa) on the refractive indices n,k of dc planar-magnetron reactively sputtered cermet and amorphous semiconductor films has been investigated for a layer thickness of approximately 50 nm. Stainless steel-carbon and amorphous hydrogenated carbon layers with relatively low index n and stainless steel-silicon and amorphous hydrogenated silicon layers with relatively high index n are examined with a view to solar selective surface applications. The development of structural porosity with associated reduction in n for layers deposited at high argon pressure significantly improves the solar absorptance of surfaces incorporating stainless steel-silicon or amorphous hydrogenated silicon layers.     

Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity

Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment.