Localization of deformation and its effect on the course of processes of pressure working metals

The author examines the problems of spontaneous and stationary localization of deformation on the development of plastic yielding in pressure working of metals. It is established that localization of plastic yielding results in the dispersion of the geometrical dimensions, structure, texture and properties, and also in changes in their general level. Possible methods of affecting the deformation region are discussed with special reference to controlling the development of localization of plastic yielding and properties of the component.Translated from Problemy Prochnosti, No. 2, pp. 89–92, February, 1994.     

Metal diffraction gratings as laser power or energy dividers

The authors survey published results on the application of metal diffraction gratings as laser power or energy dividers when the laser beam is split into two approximately equal pans. The normal incidence of laser radiation on metal diffraction gratings of various profiles in the case of three propagating diffraction orders n=0, ±1 is discussed, along with the case of oblique incidence with only two propagating diffraction orders n=0 and n =–1.Translated from Izmeritel'naya Tekhnika, No. 2, pp. 22–26, February, 1994.     

Effects of error variation in means of measurement on reliability parameters in engineering-system monitoring

A method is given for calculating the monitoring reliability parameters (MRP) for an engineering system with allowance for the drift in the measurement error of the means of measurement (MM). The approach is based on introducing a biased MM error distribution into the traditional formulas for the conditional probabilities of spurious and unobserved failure. The bias at the center of the distribution is determined by the systematic error at the given instant. An example is given to illustrate the performance in MRP calculation.Translated from Izmeritel'naya Tekhnika, No. 1, pp. 12–13, January, 1994.     

Effect of pulse time gate on CsI(T1) light output

The mass and charge identification of secondary particles with Z < 4 by a large CsI(T1) scintillation detector is performed using pulse shape analysis and time-of-flight methods. The dependence of the light output on E, A and Z is studied in the energy range of 1–20 MeV/A and special attention is paid to the integration time of the photomultiplier anode signal. It is found that the behaviour of the calibration curves strongly depends on the choice of the integration time interval.     

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.