The Effect of Hydrogen on the Parameters of Plastic Deformation Localization in Low Carbon Steel

In the present study, the effect of interstitial hydrogen atoms on the mechanical properties and plastic strain localization patterns in tensile tested polycrystals of low-carbon steel Fe-0.07%C has been studied using double exposure speckle photography technique. The main parameters of plastic flow localization at various stages of deformation hardening have been determined in polycrystals of steel electrolytically saturated with hydrogen in a three-electrode electrochemical cell at a controlled constant cathode potential. Also, the effect of hydrogen on changing of microstructure by using optical microscopy has been demonstrated

Pharmacokinetic Studies of Radiopharmaceuticals

Pharmacokinetic (PK) studies of radiopharmaceuticals (RPs) are distinctive because of small concentrations of active ingredients. Whereas methods applicable to non-RP medicinal products cannot be used for RPs, radionuclide methods can provide an insight into radionuclide behaviour. The aim of the study was to compare approaches to pre-clinical PK evaluation of RPs and other medicinal products. The article describes the main aspects of PK studies of RPs and non-RPs, defining similarities and differences in the conduction of these studies. The authors provided examples from their own PK studies of RPs: one investigating the possibility of using 99mTc–Zoledronic acid to visualise bone pathologies in patients receiving Zometa©; and the other demonstrating the advantage of orthotopic xenograft models over heterotopic ones. According to the conclusions, methods based on ionising radiation are undeniably superior to other methods used to study the PK of medicinal products (for example, the former offer a possibility of non-invasive detection of active ingredients in the nano and/or pico range). The data obtained during PK studies can be used to characterise both the safety and functional suitability of RPs

Methodological Approaches to Preclinical Evaluation of General Toxicity of Therapeutic Radiopharmaceuticals

Radiopharmaceuticals differ from other medicines mainly by the specific nature of their pharmacological action based on radioactivity, by absence of multiple-dose regimens, and by miniscule concentrations of the active pharmaceutical ingredient (10-9–10-12 mol/L). However, the official regulations and standards do not contain specific requirements for preclinical evaluation of radiopharmaceuticals. The aim of the study was to summarise preclinical data on general toxicity of therapeutic radiopharmaceuticals, which were obtained by the Laboratory of Preclinical and Clinical Studies of Radiopharmaceuticals of the Federal State Budgetary Institution ‘State Research Center of the Russian Federation¾Burnasyan Federal Medical Biophysical Center’ of the Federal Medical Biological Agency. Results: the authors analysed criteria for: selection of the study design based on physico-chemical nature of the active pharmaceutical ingredient; calculation of doses and selection of dosage regimens for radiopharmaceuticals with different administration routes; radiation safety for personnel performing the study. The authors used the data on three therapeutic radiopharmaceuticals to formulate methodological approaches to preclinical evaluation of their general toxic properties. The analysis of long-term experience in preclinical studies of therapeutic radiopharmaceuticals demonstrated the need for a judicious individual approach to the development of a preclinical study design. The authors proposed methodological approaches to preclinical evaluation of general toxic properties of therapeutic radiopharmaceuticals, which make it possible to adequately assess potential toxic effects and obtain meaningful study results. Conclusions: there is a need for a specific guideline for preclinical studies of therapeutic radiopharmaceuticals, which would take into account specific pharmacological action and nuclear-physical characteristics of radionuclides

About the Poisson Structure for D4 Spinning String

The model of D4 open string with non-Grassmann spinning variables is considered. The non-linear gauge, which is invariant both Poincar\'e and scale transformations of the space-time, is used for subsequent studies. It is shown that the reduction of the canonical Poisson structure from the original phase space to the surface of constraints and gauge conditions gives the degenerated Poisson brackets. Moreover it is shown that such reduction is non-unique. The conseption of the adjunct phase space is introduced. The consequences for subsequent quantization are discussed. Deduced dependence of spin $J$ from the square of mass $\mu^2$ of the string generalizes the ''Regge spectrum`` for conventional theory.Comment: 23 page

Dynamic and structural properties of oxyethylated isononylphenols

© 2016Diffusion coefficients, dielectric relaxation times and refraction coefficients were measured, and activation energies of translational and rotational mobilities were determined for a series of oxyethylated phenols (neonols AF9-n) p-C9H19C6H4-O(CH2CH2O)nH, n = 4, 6, 8, 9, 10, 12, at different temperatures. The results demonstrated the existence of contraction and transition phenomena that changed the structure of neonol molecules at n ∼ 9 from a zigzag to a meander form

New directions in antimalarial target validation

Introduction: Malaria is one of the most prevalent human infections worldwide with over 40% of the world's population living in malaria-endemic areas. In the absence of an effective vaccine, emergence of drug-resistant strains requires urgent drug development. Current methods applied to drug target validation, a crucial step in drug discovery, possess limitations in malaria. These constraints require the development of techniques capable of simplifying the validation of Plasmodial targets. Areas covered: The authors review the current state of the art in techniques used to validate drug targets in malaria, including our contribution - the protein interference assay (PIA) - as an additional tool in rapid in vivo target validation. Expert opinion: Each technique in this review has advantages and disadvantages, implying that future validation efforts should not focus on a single approach, but integrate multiple approaches. PIA is a significant addition to the current toolset of antimalarial validation. Validation of aspartate metabolism as a druggable pathway provided proof of concept of how oligomeric interfaces can be exploited to control specific activity in vivo. PIA has the potential to be applied not only to other enzymes/pathways of the malaria parasite but could, in principle, be extrapolated to other infectious diseases

On the non-Abelian Stokes theorem for SU(2) gauge fields

We derive a version of non-Abelian Stokes theorem for SU(2) gauge fields in which neither additional integration nor surface ordering are required. The path ordering is eliminated by introducing the instantaneous color orientation of the flux. We also derive the non-Abelian Stokes theorem on the lattice and discuss various terms contributing to the trace of the Wilson loop.Comment: Latex2e, 0+14 pages, 3 figure

Differential Equations for Definition and Evaluation of Feynman Integrals

It is shown that every Feynman integral can be interpreted as Green function of some linear differential operator with constant coefficients. This definition is equivalent to usual one but needs no regularization and application of $R$-operation. It is argued that presented formalism is convenient for practical calculations of Feynman integrals.Comment: pages, LaTEX, MSU-PHYS-HEP-Lu2/9

Effect of rotary swaging on structure and properties of low-carbon steel

The structural transformation and mechanical properties of a low-carbon 0.2% C steel and a 0.09% C-Mn-V steel in coarse- and ultrafine-grained (UFG) states were studied. The UFG structure with structural elements about 210-375 nm in size was obtained by rotary swaging (RS) and equal-channel angular pressing (ECAP). ECAP was used to compare the influence of the industrial deformation and SPD methods on the microstructure and properties of low-carbon steel

Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase

Aspartate transcarbamoylase catalyzes the second step of de-novo pyrimidine biosynthesis. As malarial parasites lack pyrimidine salvage machinery and rely on de-novo production for growth and proliferation, this pathway is a target for drug discovery. Previously, an apo crystal structure of aspartate transcarbamoylase from Plasmodium falciparum (PfATC) in its T-state has been reported. Here we present crystal structures of PfATC in the liganded R-state as well as in complex with the novel inhibitor, 2,3-napthalenediol, identified by high-throughput screening. Our data shows that 2,3-napthalediol binds in close proximity to the active site, implying an allosteric mechanism of inhibition. Furthermore, we report biophysical characterization of 2,3-napthalenediol. These data provide a promising starting point for structure based drug design targeting PfATC and malarial de-novo pyrimidine biosynthesis