Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment-Based Approach

Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the Maybridge^TM fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action.     

Increased in vitro Anti-HIV Activity of Caffeinium-Functionalized Polyoxometalates

Polyoxometalates (POMs), molecular metal oxide anions, are inorganic clusters with promising antiviral activity. Herein we report increased anti-HIV-1 activity of a POM when electrostatically combined with organic counter-cations. To this end, Keggin-type cerium tungstate POMs have been combined with organic methyl-caffeinium (Caf) cations, and their cytotoxicity, antiviral activity and mode of action have been studied. The novel compound, Caf₄K[β₂-CeSiW₁₁O₃₉]×H₂O, exhibits sub-nanomolar antiviral activity and inhibits HIV-1 infectivity by acting on an early step of the viral infection cycle. This work demonstrates that combination of POM anions and organic bioactive cations can be a powerful new strategy to increase antiviral activity of these inorganic compounds.     

Er3+-Yb3+ ions doped fluoro-aluminosilicate glass-ceramics as a temperature-sensing material

The transparent Er³⁺-Yb³⁺-doped fluoro-aluminosilicate glass-ceramic (GC) was prepared by melt-quenching. The crystal phase, morphology, and up-conversion (UC) luminescence of as-produced GC were characterized by X-ray diffraction, scanning electron microscopy, and fluorescence spectrophotometry, respectively. The results show that BaYF₅ nanocrystals were uniformly distributed in the glass matrix of the as-produced GC. When the as-produced GC was subjected to heat treatment, the crystallinity was increased, but the crystal identity remains unchanged. Such heat-treatment doubled the intensity of the UC luminescence, and this enhancement was ascribed to the increased incorporation of both Er³⁺ and Yb³⁺ ions into the lower phonon energy environment of BaYF₅ nanocrystals. Furthermore, the heat-treated GC was stable against further crystallization, and consequently its UC luminescence was stable at the application temperature. The heat-treated GC was found to possess an outstanding temperature-sensing capability.     

Phase locked loop-based clock synthesizer for reconfigurable analog-to-digital converters

Analog Integrated Circuits and Signal Processing - This paper presents the complete design of a phase locked loop-based clock synthesizer for reconfigurable analog-to-digital converters. The...     

Quantum-Confinement Effect in Silicon Nanocrystals during Their Dissolution in Model Biological Fluids

Semiconductors - In present work, we studied the mechanisms of dissolution of porous silicon nanoparticles (PSi NPs) during their incubation in model liquids, i.e. water and phosphate buffered...     

Analytical Conditions for Equalizing and Reducing the Amplitudes of the Time Response Components in the Meander Line Turn

Journal of Communications Technology and Electronics - In this study, we note the relevance of protecting radio electronic equipment against conductive excitation, in particular ultrashort pulses...     

Traceability of Measurements of the Energy Parameters of Laser Beams

Measurement Techniques - A conceptual approach to the traceability of measurements of the energy (power) of laser beams during calibration of means of measurement to standards is formulated,...     

Experimental Investigation of Oblique Impact Behavior of Adhesively Bonded Composite Single-Lap Joints

Applied Composite Materials - Determining the impact behavior of adhesive joints allows the designing of high-strength joints. Therefore, the dynamic behavior of adhesive joints has recently become...     

Solar-blind ultraviolet photodetector based on Ti-doped Ga2O3/Si p–n heterojunction

A solar-blind ultraviolet photodetector based on Ti-doped Ga₂O₃/Si p–n heterojunction is demonstrated for the first time. It is found that the heterojunction quality forming between Ga₂O₃ and Si becomes better after Ti incorporation in Ga₂O₃. The current–voltage and temporal response measurements show that the detector based on Ti-doped Ga₂O₃/Si p–n heterojunction has a responsivity of 0.382 A/W and a fast rise time of 73 ms as well, which are much better than those undoped Ga₂O₃/Si p–n heterojunction analogues.