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.     

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...     

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.

     

Rheological and viscoelastic properties of colloidal solutions based on gelatins and chitosan as affected by pH

The objective of this study was to evaluate the influence of pH on rheological and viscoelastic properties of solutions based on blends of type A (GeA) or type B (GeB) gelatin and chitosan (CH). Solutions of GeA, GeB, CH, GeA:CH, and GeB:CH were prepared in several pH (3.5–6.0) and analyzed for determination of zeta-potential. Rheological analyses (stationary and dynamic essays) were carried out with blends allowing to study the effect of pH on shear stress, apparent viscosity, loss (G”) and storage (G’) moduli, and angle phase (Tanδ). Zeta potential of all biopolymers decreased linearly as a function of pH. CH presented higher values, and GeB, the lowest one, being the only having negative values at pH > 5. Overall, the pH influenced the rheological and viscoelastic properties of the colloidal solutions: shear stress and apparent viscosity increased as a function of pH. Other assays were carried out at 3% and 5% strain, for GeA:CH and GeB:CH, respectively. In the sol domain, G’ and G” (1 Hz) increased linearly for GeA:CH. But for GeB:CH, they increased in two linear different regions: one function between pH 3.5 and 5.0 and another one between 5.0 and 6.0, being a more important effect was visible in this last domain probably due to the negative net charge of gelatin, above it pI. An effect in two domains was also visible for Tanδ, explained in the same manner as previously. The GeB:CH blends behaved like diluted solutions, and transition temperatures increased as a function of pH.     

Effects of Agaricus bisporus on gel properties of chicken myofibrillar protein

The gel-forming ability of myofibrillar protein (MP) is highly correlated with the characteristics of emulsified meat products. Incorporation of Agaricus bisporus (Ab) powder into MP gels may enhance its gel properties to facilitate the development of a novel and safe meat product. Therefore, this study investigated the effects of Ab powder on gel strength, water holding capacity (WHC), texture, rheological behaviour, LF-NMR spin–spin relaxation (T₂), microstructure and protein secondary structure of the MP gel system. The results indicated that the gel strength, WHC, G' value and G" value were significantly improved when the addition of Ab powder increased from 0% to 6% (P < 0.05). Meanwhile, the T₂ relaxation time was shortened, and free water was transformed into immobilised water. The texture of the gel was improved when 1%–4% Ab powder was added compared to the control. Furthermore, Ab filled in the gel network and promoted the unfolding of MP α-helix and the formation of MP β-sheet during the thermal denaturation of MP, leading to a dense aggregated network structure. The study suggested that Ab could be a promising ingredient in improving chicken MP's gel properties and developing fat-reduced meat products.