Local Mechanical Behavior of Steel Exposed to Nonlinear Harmonic Oscillation

The local mechanical behavior of fatigued steel specimens was probed using nanoindentation. High-carbon steel cantilevers were exposed to nonlinear harmonic oscillation. The indentation modulus on the beam surface and plastic work during indentation decreased as a function of cycles, which was attributed to grain fragmentation and reorientation as well as the continuous reduction in inherent energy dissipation capacity of the material. X-ray diffraction, electron backscatter diffraction, and atomic force microscopy were used to characterize this microstructural evolution during early stages of the beam fatigue life, which altered 1) the local mechanical properties and 2) the global structural dynamic response. The results provide insight into fatigue damage precursors and provides a framework for connecting materials evolution with nonlinear structural dynamics.     

Radiation response behaviour of Al codoped germano-silicate SM fiber at high radiation dose

Radiation response behaviour of Ge + Al doped SM fiber fabricated by the solution doping process has been studied at room temperature with respect to 1310 nm transmission wavelength under three different dose rates of 200, 400 and 600 Rad/min to compare with that of standard Er doped as well as Ge doped SM fibers. Their radiation sensitivity has been observed with variation of dose rates, transmission wavelength along with their recovery nature. Radiation response behaviour of Al doped SM fiber is found to be slightly non-linear in nature with very low dose rate dependency. No saturation level was found upto 13 Krad cumulative dose. Thermobleaching as well as photobleaching phenomena have also been studied. Gamma irradiated Al doped preform shows an absorption peak at around 300 nm due to generation of Al (E′) defect center and gets annihilated after thermobleaching process. Gamma irradiated Al doped SM fiber shows prominent photobleaching effect on their optical attenuation with respect to the 850 nm transmission wavelength. From ESR study resonance signals for Al³⁺ related radiation-induced defect centers are not clearly observed in this study. A very weak hyperfine pattern has been observed for gamma irradiated Al doped preform sample. The high radiation sensitivity along with linear response behaviour, low recovery and almost dose rate independence behaviour of the material system of Ge + Al codoped SM core optical fiber under gamma radiation shows their potential for application as fiber optic radiation sensor in comparison to the universal standard erbium doped SM fiber.     

Effect of counterions on the activity of lipase in cationic water-in-oil microemulsions

This paper delineates how the different counterions affect the physicochemical properties of the aqueous aggregates and thereby the lipase activities at the interface of cationic water-in-oil microemulsions. To this end, we have synthesized a series of cetyltrimethylammonium-based surfactants, 1-14, having aliphatic, aliphatic with aromatic substitution at the alpha position, and aromatic carboxylate anion as the counterion. The physicochemical characterizations of these aqueous aggregates were done by conductometric, tensiometric, fluorometric techniques to determine counterion binding (beta), critical micelle concentration (cmc), and micropolarity at the microenvironment. It has been found that the activity of lipase mainly increases with hydrophobicity (which is directly proportional to the counterion binding (beta) of the surfactant) of the counterion and reaches a maximum when the beta value is around 0.5. Increase in hydrophobicity as well as beta leads to the attachment of more counterions at interface resulting in enhancement of interfacial area. Consequently, the enzyme may attain flexible secondary conformation at the augmented surface area and also allow larger population of substrates and enzyme molecules at the interface leading to the enhancement in lipase activity. After an optimum value of beta, further increase probably produces a steric crowding at the interface, hindering the smooth occupancy of enzyme and the substrate in this region leading to decrease of enzyme activity, while molecular surface area of the counterion did not show any virtual influence on the lipase activity. Thus, the variation in the counterion structure and hydrophobicity plays a crucial role in modulating the lipase activity.     

Protecting-group-free synthesis of glycosyl 1-phosphates

Glycosyl 1-phosphates enriched in the α-anomer are obtained without the use of protecting groups in two steps starting from the free hemiacetal. Condensation of free hemiacetals with toluenesulfonylhydrazide yields a range of glycosylsulfonohydrazide donors which can be oxidized using cupric chloride in the presence of phosphoric acid and the coordinating additive 2-methyl-2-oxazoline to give useful yields of the fully deprotected glycosyl 1-phosphates.     

Dinucleosides with non-natural backbones: a new class of ribonuclease A and angiogenin inhibitors

Ribonuclease?A (RNase A) serves as a convenient model enzyme in the identification and development of inhibitors of proteins that are members of the ribonuclease superfamily. This is principally because the biological activity of these proteins, such as angiogenin, is linked to their catalytic ribonucleolytic activity. In an attempt to inhibit the biological activity of angiogenin, which involves new blood vessel formation, we employed different dinucleosides with varied non-natural backbones. These compounds were synthesized by coupling aminonucleosides with dicarboxylic acids and amino- and carboxynucleosides with an amino acid. These molecules show competitive inhibition with inhibition constant (K(i)) values of (59±3) and (155±5) μM for RNase A. The compounds were also found to inhibit angiogenin in a competitive fashion with corresponding K(i) values in the micromolar range. The presence of an additional polar group attached to the backbone of dinucleosides was found to be responsible for the tight binding with both proteins. The specificity of different ribonucleolytic subsites were found to be altered because of the incorporation of a non-natural backbone in between the two nucleosidic moieties. In spite of the replacement of the phosphate group by non-natural linkers, these molecules were found to selectively interact with the ribonucleolytic site residues of angiogenin, whereas the cell binding site and nuclear translocation site residues remain unperturbed. Docked conformations of the synthesized compounds with RNase A and angiogenin suggest a binding preference for the thymine-adenine pair over the thymine-thymine pair.     

Environmental DNA-encoded antibiotics fasamycins A and B inhibit FabF in type II fatty acid biosynthesis

In a recent study of polyketide biosynthetic gene clusters cloned directly from soil, we isolated two antibiotics, fasamycins A and B, which showed activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. To identify the target of the fasamycins, mutants with elevated fasamycin A minimum inhibitory concentrations were selected from a wild-type culture of E. faecalis OG1RF. Next-generation sequencing of these mutants, in conjunction with in vitro biochemical assays, showed that the fasamycins inhibit FabF of type II fatty acid biosynthesis (FASII). Candidate gene overexpression studies also showed that fasamycin resistance is conferred by fabF overexpression. On the basis of comparisons with known FASII inhibitors and in silico docking studies, the chloro-gem-dimethyl-anthracenone substructure seen in the fasamycins is predicted to represent a naturally occurring FabF-specific antibiotic pharmacophore. Optimization of this pharmacophore should yield FabF-specific antibiotics with increased potencies and differing spectra of activity. This study demonstrates that culture-independent antibiotic discovery methods have the potential to provide access to novel metabolites with modes of action that differ from those of antibiotics currently in clinical use.     

Dinucleosides with Non‐Natural Backbones: A New Class of Ribonuclease A and Angiogenin Inhibitors

Ribonuclease A (RNase A) serves as a convenient model enzyme in the identification and development of inhibitors of proteins that are members of the ribonuclease superfamily. This is principally because the biological activity of these proteins, such as angiogenin, is linked to their catalytic ribonucleolytic activity. In an attempt to inhibit the biological activity of angiogenin, which involves new blood vessel formation, we employed different dinucleosides with varied non‐natural backbones. These compounds were synthesized by coupling aminonucleosides with dicarboxylic acids and amino‐ and carboxynucleosides with an amino acid. These molecules show competitive inhibition with inhibition constant (K_i) values of (59±3) and (155±5) μM for RNase A. The compounds were also found to inhibit angiogenin in a competitive fashion with corresponding K_i values in the micromolar range. The presence of an additional polar group attached to the backbone of dinucleosides was found to be responsible for the tight binding with both proteins. The specificity of different ribonucleolytic subsites were found to be altered because of the incorporation of a non‐natural backbone in between the two nucleosidic moieties. In spite of the replacement of the phosphate group by non‐natural linkers, these molecules were found to selectively interact with the ribonucleolytic site residues of angiogenin, whereas the cell binding site and nuclear translocation site residues remain unperturbed. Docked conformations of the synthesized compounds with RNase A and angiogenin suggest a binding preference for the thymine–adenine pair over the thymine–thymine pair.     

Effect of dispersion on the diffusion zone in two-phase laminar flows in microchannels

Aim of the present work is to investigate the reaction–diffusion process of a two species system under laminar flow in a T-shaped microchannel. A zone formed at the interface between the aqueous solutions of these two species is affected by advection and diffusion. Through theoretical analyses and experimental results, the effect of dispersion has been shown to influence this diffusion zone. We have defined a parameter called effective diffusivity, to account for the dispersion effects and observed it to be a function of the channel Peclet number. In the limiting case of low Peclet number, this parameter is constant and turns out to be equal to the molecular diffusivity. We have also related effective diffusivity and the dispersion coefficient through scaling estimates.     

Cobinamide chemistries for photometric cyanide determination. A merging zone liquid core waveguide cyanide analyzer using cyanoaquacobinamide

Diaquacobinamide (H₂O)₂Cbi²⁺ or its conjugate base hydroxyaquacobinamide (OH(H₂O)Cbi⁺)) can bind up to two cyanide ions, making dicyanocobinamide. This transition is accompanied by a significant change in color, previously exploited for cyanide determination. The reagent OH(H₂O)Cbi⁺ is used in excess; when trace amounts of cyanide are added, CN(H₂O)Cbi⁺ should be formed. But the spectral absorption of CN(H₂O)Cbi⁺ is virtually the same as that of OH(H₂O)Cbi⁺. It has been inexplicable how trace amounts of cyanide are sensitively measured by this reaction. It is shown here that even with excess OH(H₂O)Cbi⁺, (CN)₂Cbi is formed first due to kinetic reasons; this only slowly forms CN(H₂O)Cbi⁺. This understanding implies that CN(H₂O)Cbi⁺ will itself be a better reagent.