The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Migration of Point Defects in the Field of a Temperature Gradient

The influence of the temperature gradient over the thickness of the cladding of a fuel element of a fast-neutron reactor on the migration of point defects formed in the cladding material due to neutron irradiation has been studied. It has been shown that, under the action of the temperature gradient, the flux of vacancies onto the inner surface of the cladding is higher than the flux of interstitial atoms, which leads to the formation of a specific concentration profile in the cladding with a vacancy-depleted zone near the inner surface. The experimental results on the spatial distribution of pores over the cladding thickness have been presented with which the data on the concentration profiles and vacancy fluxes have been compared.     

A Giant Frequency Shift in the Raman Spectrum of Water Adsorbed on a Metallic Silver Surface

The Raman spectrum of water adsorbed on a metallic silver surface reveals an anomalously large shift of the vibrational frequency as compared to that in the bulk. The results are compared to data reported by other researchers, and possible interpretations of the observed phenomenon are discussed.     

Strain Concentration Effect in Cu–Al–Ni Single Crystals under a Longitudinal Bending Force

The behavior of a superelastic Cu?14.2% Al?4%Ni single crystal in the case of high reversible strains under a longitudinal bending force was investigated. The effect of strain confinement along the crystal length was revealed and studied. The highest reversible strains (up to 10%) were shown to be confined within the central part of the bent crystal.     

Role of Elastic Interphase Deformations in the Formation of Crystal Structure of β-Nb Particles Precipitating in a Zr–2.5% Nb Alloy

X-ray diffraction analysis has been used to study the structure of the α-Zr matrix phase and the precipitation of β-Nb particles upon the annealing of a Zr–2.5% Nb deformed alloy. It has been found that the process of the precipitation of the strengthening β-Nb particles in the alloy is accompanied by the appearance of fields of elastic interphase deformations in the matrix α phase of the alloy due to the difference in the specific atomic volumes of the crystal structures of the matrix and precipitated phases. It has been shown experimentally that, as a result of the presence of interphase deformations in the alloy, the bcc crystal structure of the precipitating β-Nb particles undergoes monoclinic distortions.     

Performance Analysis of Pulse Generators on Residual Stress of Machined Silicon Steel Using the EDM Process

The cracks in the workpiece specimens can reduce the fatigue life of any machine components. Since the residual stress has a considerable amount of influence on determining crack formation over the machined surface, it is very essential to analyze the residual stress developed in any machining process. However, it is a very tedious process to compute the residual stress over the machined surface. In the present study, an endeavor has been made to measure and analyze the residual stress of machined silicon steel as a workpiece using the EDM process with different energy distribution. The nano-indentation method was used to compute the residual stress produced over the machined surface. From the experimental results, it was found that the uniform energy distribution has produced higher compressive residual stress owing to the tiny and uniform spark energy distribution. It has also been observed that the tool electrode has a considerable amount of influence on determining development of residual stress in the EDM process.