Differentiation between sources of mechanoluminescence and acoustic emission in impact‐loaded ZnSe and ZnS ceramics

Ductile semiconductor ceramics ZnSe and ZnS were damaged by a falling weight, and the time series of mechanoluminescence (ML) and acoustic emission (AE) pulses were recorded with the nanosecond resolution. The ML lighting appeared in the instance of shock but the AE generation emerged with a delay of 50–100 μsec; however, the maxima of the light and sound emissions coincided in time. This difference in temporal profiles was explained by the difference in prevailing sources of emissions of two types. The detected luminescence in A₂B₆ compounds was excited, mainly, by moving and multiplying dislocations, while the sound was generated by nucleating and growing cracks. The statistical analysis showed that at the stage of pre‐failure deformation, the ensemble of dislocations exhibited a trend to self‐organizing; the cracking was fully random. The effect of intergranular boundaries on the dislocation motion manifested itself in the statistics of mechanoluminescence generation.     

Development of Search Strategy for Peptide Inhibitors of Immune Checkpoints

Current strategy for the blockade of molecules inhibiting T-cell immunity, the immune checkpoints (ICP), such as CTLA-4, PD-1, and B7-H1(PD-L1), using monoclonal antibodies (mAbs), showed significant clinical effects in cancer immunotherapy. In this kind of therapy, antibodies do not kill tumor cells directly, but block inhibitory signals for T lymphocytes, resulting in activation of the immune response cascade that eliminate malignant cells and lead to tumor degradation. However, the mAb preparations have some limitations, and the development of new low-molecular-weight antagonists (for example, peptides) is an important issue. In this study, we used peptide microarrays and phage display libraries to search for peptides that interact with the immune checkpoints. We found peptides that specifically bind CTLA-4, PD-1, B7-1, B7-2 and B7-H1(PD-L1) which play important role in the regulation of the immune responses. These synthetic peptides can be applied to the development of new immunomodulating drugs for cancer immunotherapy.     

Genetic recombination: Formal implications of a crossed strand-exchange between two homologous DNA molecules

Formal genetic consequences of generation and break-up of a structure with cross connection have been studied on the basis of a simple quantitative model with a symmetric exchange of two strands between parental DNA molecules. In recombination analysis, this intermediate structure gives rise to a critical frequency R(ξ) (see Fig. 3), which corresponds to recombination between two markers separated by a distance equal to the mean genetic length ξ of the hybrid region at the time of scission of the cross connection. As concerns the routine mapping practice, a fundamental inference emerges: since genetic exchange has no invariable equivalent on molecular level it fails basically to serve as statistically independent elementary event in fine scale mapping. Instead of the number of exchanges between markers (or proportional metrics) the use of the number of the sites of initiation of hybrid regions (or proportional metrics) as a measure of map distance is suggested. Usage of the mean length of hybrid region ξ as a natural unit of map distance is shown to be of particular interest.In the case of bacteriophage T4 under the conditions of standard crosses, the structure with cross connection is characterized by the value R(ξ) equal to 3·0.10^?2, at the time of scission of the cross connection this structure acquiring either of the two alternative isomeric configurations with equal probability. About four percent of the total number of mismatches emerging as a result of formation of hybrid regions were repaired.     

13C tracer experiments and metabolite balancing for metabolic flux analysis: comparing two approaches

Conventional metabolic flux analysis uses the information gained from determination of measurable fluxes and a steady-state assumption for intracellular metabolites to calculate the metabolic fluxes in a given metabolic network. The determination of intracellular fluxes depends heavily on the correctness of the assumed stoichiometry including the presence of all reactions with a noticeable impact on the model metabolite balances. Determination of fluxes in complex metabolic networks often requires the inclusion of NADH and NADPH balances, which are subject to controversial debate. Transhydrogenation reactions that transfer reduction equivalents from NADH to NADPH or vice versa can usually not be included in the stoichiometric model, because they result in singularities in the stoichiometric matrix. However, it is the NADPH balance that, to a large extent, determines the calculated flux through the pentose phosphate pathway. Hence, wrong assumptions on the presence or activity of transhydrogenation reactions will result in wrong estimations of the intracellular flux distribution. Using 13C tracer experiments and NMR analysis, flux analysis can be performed on the basis of only well established stoichiometric equations and measurements of the labeling state of intracellular metabolites. Neither NADH/NADPH balancing nor assumptions on energy yields need to be included to determine the intracellular fluxes. Because metabolite balancing methods and the use of 13C labeling measurements are two different approaches to the determination of intracellular fluxes, both methods can be used to verify each other or to discuss the origin and significance of deviations in the results. Flux analysis based entirely on metabolite balancing and flux analysis, including labeling information, have been performed independently for a wild-type strain of Aspergillus oryzae producing alpha-amylase. Two different nitrogen sources, NH4+ and NO3-, have been used to investigate the influence of the NADPH requirements on the intracellular flux distribution. The two different approaches to the calculation of fluxes are compared and deviations in the results are discussed. Copyright 1998 John Wiley & Sons, Inc.     

Genetic Recombination in Bacteriophage T4: Single-Burst Analysis of Cosegregants and Evidence in Favor of a Splice/Patch Coupling Model

To reveal the structure of penultimate DNA intermediates in T4 bacteriophage recombination, resolution of which produces free recombinant molecules, a single-burst analysis of the recombinant progeny was made in multifactor crosses, enabling one to determine quantitatively the different recombinants generated by one or two exchanges within the same chromosome segment. It was found that double and single exchanges are highly correlated in T4 recombination. These results were interpreted as evidence for simultaneous formation of a splice/patch pair as the primary recombination products. A recombination model called here the "splice/patch coupling model" is presented according to which resolution of a single DNA intermediate results in two linear heterozygous molecules containing a patch and a splice, respectively, in homologous positions.     

Application of electron-donor properties of glucose oxidase and xanthine oxidase for reduction of microsomal NAD(P)H-dependent electron-transport chains

The reduction of cytochromes b5 and P-450 in mammalian hepatic microsomes by glucose oxidase and xanthine oxidase has been investigated. Under anaerobic conditions cytochrome b5 is reduced by glucose oxidase to the "dithionite" level, while cytochrome P-450 remains oxidized. Under the same conditions xanthine oxidase completely reduces both hemoproteins. Besides, neither glucose oxidase nor xanthine oxidase reduces isolated cytochromes. They can be reduced only after addition of microsomes to incubation media. Only in this case are the cytochromes, both isolated and included in microsomal membranes, reduced. The participation of microsomal flavoproteins in the reduction reaction is discussed. The method suggested makes it possible to substantially decrease the rates of reduction of microsomal hemoproteins, thus permitting the investigation of interactions between microsomal NADH- and NADPH-dependent electron-transport chains and electron carriers.     

Microbial ecology and the state of the gastrointestinal mucosa in patients with allergic diseases

Patients with allergic diseases of the skin and the respiratory system were found to have a high rate of disturbances in the microbial ecology of the gastrointestinal tract and the involvement of all its sections into the pathological process. On the mucous membrane of different sections of the digestive tract spiral-like bacteria were detected in a large percentage of cases. The possibility of the fact that the development and maintenance of the allergic process were evidently linked with the detected changes in the microbial ecology and pathomorphological features of the gastrointestinal mucosa could hardly be excluded, which made it necessary to make corrections in the therapeutic process.