Development of Stability Indicating HPLC–UV Method for Determination of Daclatasvir and Characterization of Forced Degradation Products

A simple and sensitive stability indicating high performance liquid chromatography method was developed for quantification of Daclatasvir hydrochloride in bulk and tablet dosage forms. The analysis was performed on water symmetry analytical column (150 mm?×?3.9 mm, 5 µm), packing octyl silica (Si-[CH₂]₇-CH₃) C8. Mobile phase containing potassium phosphate buffer (pH 2.0) and acetonitrile (38: 62) v/v was used at flow rate 0.7 mL min^?1 for isocratic elution. Detection was performed on 304 nm using UV detector. The method was validated appropriately according to the requirements of United State Pharmacopeia and International Conference on Harmonization guideline Q2 (R1). Recovery, precision, linearity and specificity of the method were assured. The correlation coefficient for linearity ranged from 2 to 24 µg mL^?1 was (r?>?0.9999). The limits of detection and quantification of Daclatasvir were 0.08 and 0.28 µg mL^?1, respectively. Stability studies of Daclatasvir were performed under various stressed conditions, i.e., hydrolytic (acidic, basic and neutral), oxidation, photolytic and thermal conditions, according to International Conference on Harmonization Q1A (R2) and QIB Guidelines. The degradation products were resolved using proposed method and further characterized by MS, NMR and IR spectroscopic analyses. The proposed method was successfully applied to assay determination of bulk drugs and tablet dosage forms.     

Thermostability of Cromobacterium viscosum lipase in AOT/isooctane reverse micelle

The thermostability of Cromobacterium viscosum lipase (EC 3.1.1.3) entrapped in AOT (sodium bis-[2-ethylhexyl] sulfosuccinate) reverse micelles was increased by the addition of short-chain polyethylene glycol (PEG 400). Two different approaches were considered: (1) the determination of half-life time and (2) the mechanistic analysis of deactivation kinetics. The half-life of lipase entrapped in AOT/isooctane reverse micelles with PEG 400 at 60 degrees C was 28 h, ninefold higher than that in reverse micelles without PEG 400. The lipase entrapped in both reverse micellar systems followed a series-type deactivation mechanism involving two first-order steps. The deactivation constant for the first step at 60 degrees C in PEG containing reverse micelles was 0.055 h!1, 11-fold lower than that in reverse micelles without PEG, whereas it remained almost constant for the second step. The inactivation energy of the lipase entrapped in reverse micelles with and without PEG 400 was 88.12 and 21.97 kJ/mol, respectively.     

Free energy landscape of receptor-mediated cell adhesion

Receptor-mediated cell adhesion plays a critical role in cell migration, proliferation, signaling, and survival. A number of diseases, including cancer, show a strong correlation between integrin activation and metastasis. A better understanding of cell adhesion is highly desirable for not only therapeutic but also a number of tissue engineering applications. While a number of computational models and experimental studies have addressed the issue of cell adhesion to surfaces, no model or theory has adequately addressed cell adhesion at the molecular level. In this paper, the authors present a thermodynamic model that addresses receptor-mediated cell adhesion at the molecular level. By incorporating the entropic, conformational, solvation, and long- and short-range interactive components of receptors and the extracellular matrix molecules, they are able to predict adhesive free energy as a function of a number of key variables such as surface coverage, interaction distance, molecule size, and solvent conditions. Their method allows them to compute the free energy of adhesion in a multicomponent system where they can simultaneously study adhesion receptors and ligands of different sizes, chemical identities, and conformational properties. The authors' results not only provide a fundamental understanding of adhesion at the molecular level but also suggest possible strategies for designing novel biomaterials.     

Biological Efficacy of Compounds from Stingless Honey and Sting Honey against Two Pathogenic Bacteria: An In Vitro and In Silico Study

Honey inhibits bacterial growth due to the high sugar concentration, hydrogen peroxide generation, and proteinaceous compounds present in it. In this study, the antibacterial activity of stingless and sting honey against foodborne pathogenic bacteria isolated from spoiled milk samples was examined. The isolated bacterial strains were confirmed as Bacillus cereus and Listeria monocytogenes through morphological, biochemical, and 16 s RNA analysis. Physiochemical characterizations of the honey samples revealed that both of the honey samples had an acidic pH, low water content, moderate reducing sugar content, and higher proline content. Through the disc diffusion method, the antibacterial activities of the samples were assayed and better results were observed for the 50 mg/disc honey. Both stingless and sting honey showed the most positive efficacy against Bacillus cereus. Therefore, an in silico study was conducted against this bacterium with some common compounds of honey. From several retrieved constituents of stingless and sting honey, 2,4-dihydroxy-2,5-dimethyl 3(2H)-furan-3-one (furan) and 4H-pyran-4-one,2,3-dihydro of both samples and beta.-D-glucopyranose from the stingless revealed high ligand-protein binding efficiencies for the target protein (6d5z, hemolysin II). The root-mean-square deviation, solvent-accessible surface area, the radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation and confirmed their stability. The combined effort of wet and dry lab-based work support, to some extent, that the antimicrobial properties of honey have great potential for application in medicine as well as in the food industries.     

Generalizing reduction-based algebraic multigrid

Algebraic multigrid (AMG) methods are often robust and effective solvers for solving the large and sparse linear systems that arise from discretized PDEs and other problems, relying on heuristic graph algorithms to achieve their performance. Reduction-based AMG (AMGr) algorithms attempt to formalize these heuristics by providing two-level convergence bounds that depend concretely on properties of the partitioning of the given matrix into its fine- and coarse-grid degrees of freedom. MacLachlan and Saad (SISC 2007) proved that the AMGr method yields provably robust two-level convergence for symmetric and positive-definite matrices that are diagonally dominant, with a convergence factor bounded as a function of a coarsening parameter. However, when applying AMGr algorithms to matrices that are not diagonally dominant, not only do the convergence factor bounds not hold, but measured performance is notably degraded. Here, we present modifications to the classical AMGr algorithm that improve its performance on matrices that are not diagonally dominant, making use of strength of connection, sparse approximate inverse (SPAI) techniques, and interpolation truncation and rescaling, to improve robustness while maintaining control of the algorithmic costs. We present numerical results demonstrating the robustness of this approach for both classical isotropic diffusion problems and for non-diagonally dominant systems coming from anisotropic diffusion.     

Thermally stratified flow of hybrid nanofluids with radiative heat transport and slip mechanism: multiple solutions

Research on flow and heat transfer of hybrid nanofluids has gained great significance due to their efficient heat transfer capabilities.In fact,hybrid nanofluids are a novel type of fluid designed to enhance heat transfer rate and have a wide range of engineering and industrial applications.Motivated by this evolution,a theoretical analysis is performed to explore the flow and heat transport characteristics of Cu/Al₂O₃ hybrid nanofluids driven by a stretching/shrinking geometry.Further,this work focuses on the physical impacts of thermal stratification as well as thermal radiation during hybrid nanofluid flow in the presence of a velocity slip mechanism.The mathematical modelling incorporates the basic conservation laws and Boussinesq approximations.This formulation gives a system of governing partial differential equations which are later reduced into ordinary differential equations via dimensionless variables.An efficient numerical solver,known as bvp4c in MATLAB,is utilized to acquire multiple(upper and lower)numerical solutions in the case of shrinking flow.The computed results are presented in the form of flow and temperature fields.The most significant findings acquired from the current study suggest that multiple solutions exist only in the case of a shrinking surface until a critical/turning point.Moreover,solutions are unavailable beyond this turning point,indicating flow separation.It is found that the fluid temperature has been impressively enhanced by a higher nanoparticle volume fraction for both solutions.On the other hand,the outcomes disclose that the wall shear stress is reduced with higher magnetic field in the case of the second solution.The simulation outcomes are in excellent agreement with earlier research,with a relative error of less than 1%.     

Selective CO2 Reduction to Ethylene Mediated by Adaptive Small-molecule Engineering of Copper-based Electrocatalysts

Electrochemical CO₂ reduction reaction (CO₂RR) over Cu catalysts exhibits enormous potential for efficiently converting CO₂ to ethylene (C₂H₄). However, achieving high C₂H₄ selectivity remains a considerable challenge due to the propensity of Cu catalysts to undergo structural reconstruction during CO₂RR. Herein, we report an in situ molecule modification strategy that involves tannic acid (TA) molecules adaptive regulating the reconstruction of a Cu-based material to a pathway that facilitates CO₂ reduction to C₂H₄ products. An excellent Faraday efficiency (FE) of 63.6 % on C₂H₄ with a current density of 497.2 mA cm⁻² in flow cell was achieved, about 6.5 times higher than the pristine Cu catalyst which mainly produce CH₄. The in situ X-ray absorption spectroscopy and Raman studies reveal that the hydroxyl group in TA stabilizes Cu^δ+ during the CO₂RR. Furthermore, theoretical calculations demonstrate that the Cu^δ+/Cu⁰ interfaces lower the activation energy barrier for *CO dimerization, and hydroxyl species stabilize the *COH intermediate via hydrogen bonding, thereby promoting C₂H₄ production. Such molecule engineering modulated electronic structure provides a promising strategy to achieve highly selective CO₂ reduction to value-added chemicals.     

Applying a new method for analyzing experimental data on nuclear reactions at high energies

A new statistical method is proposed for the analysis of experimental data obtained in nucleus-nucleus collisions at high energies which borrows from ideas developed using the Random Matrix Theory. The method allows us to detect regions with correlation effects in the momentum distributions of secondary particles.     

Unsteady wake vortices in jets in cross-flow

Abstract  

The current flow visualization study investigates unsteady wake vortices of jets in cross-flow in order to (1) advance the understanding of their origin and characteristics and (2) explore various excitation techniques for organizing and accentuating them. An isolated circular jet passed through a nozzle and entered the cross-flow normal to the wall. Free stream velocities up to 5 m/s and jet-to-cross-flow velocity ratio range between 1 and 10 were covered. While mechanical perturbation did not result in any significant periodic organization of the wake vortices, the database obtained for the unperturbed flow provided further insight into their behavior. The key finding was that the wake vortices always originated from the lee-side of the jet where the jet efflux boundary layer and the wall boundary layer intersected. In no case these vortices were seen to form either from the wall boundary layer or the jet shear layer at downstream locations. After formation the wake vortex twists and stretches as it convects downstream with the base still attached to the near-wall region on the jet’s lee side. The top remains connected to the underside of the jet where the tracer particles dissipate due to high turbulence in the shear layer.