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(R)-[3,5-bis(trifluoromethyl) phenyl] ethanol [(R)-3,5-BTPE] is a crucial chiral intermediate for the synthesis of the NK-1 receptor antagonists aprepitant, rolapitant and fosaprepitant. The carbonyl reductase KR01 from Leifsonia sp. S749, discovered by protein sequence alignment, could convert 3′,5′-bis(trifluoromethyl) acetophenone (3,5-BTAP) into (R)-3,5-BTPE with excellent activity and enantioselectivity. In order to enhance the conversion efficiency at high substrate concentrations, the reaction conditions were optimized by response surface analysis. The results showed that 600 g/L 3,5-BTAP was bioreduced to (R)-3,5-BTPE (> 99.9% enantiomeric excess) by the recombinant Escherichia coli/pET-28a (+)-KR01 whole cells, with a 98.3% conversion and 59 g/L/h productivity under the optimized reaction conditions. In addition, the recombinant E. coli cells could be repeatedly used up to seven times in the reaction mixture containing 90% isopropanol (IPA). This is the highest substrate loading and productivity for the bioreduction of 3,5-BTAP by carbonyl reductase ever reported, and this method represents an efficient and cost-effective process for production of (R)-3,5-BTPE.

The momentum method was considered to be not applicable for a fine grid adjacent to the diffuser. However, the reason underlying this phenomenon has not been clarified until now. This paper explains this issue from the viewpoint of discretization. The momentum equation is integrated in the first cell adjacent to the diffuser and is expressed as the diffuser-related term and the diffuser nonrelated term. The direct momentum method and the convective-flux momentum method use different diffuser-related terms. A large error may be introduced for the convective-flux momentum method when the first grid interval adjacent to the diffuser is very small. The total-flux momentum method is presented to include both the convective flux and the diffusion flux in the momentum source. Good agreement between the total-flux momentum method and experiment is obtained. The total-flux momentum method helps to minimize the computational error and facilitates the determination of an optimal grid.

(S)-2-Chloro-1-(3,4-difluorophenyl)ethanol (1) is a vital chiral intermediate for the synthesis of Ticagrelor—an effective treatment for acute coronary syndromes. A ketoreductase (KRED) KR-01 in our KRED library was screened to transform 2-chloro-1-(3,4-difluorophenyl)ethanone (2) into the chiral alcohol 1. During process optimization, the bioreduction procedure was performed at a substrate concentration of 500 g/L, giving a near 100% conversion with >99.9% ee. The product 1 was directly obtained by extraction and can be used for the synthesis of (1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxylic acid ethyl ester (3) with a yield of 98% and >99.9% de, greatly simplifying the original process operation and reducing the safety risk. This process is green and environmentally sound with high productivity of biocatalysis and a space–time yield of 145.8 mmol/L/h. It has an opportunity to be very useful in industrial applications. Additional studies have indicated that KR-01 can also be used to prepare (R)-1-(...

Commonly, the strong heterogeneity leads to poorer sweep efficiency for poor reservoir. So, liquid production rate optimization was often used to improve development effect, especially liquid production rate increasing in high water cut stage. However, the quantitative relationship between the rising law of water cut and the main control factors is not clear, which results in the uncertainty of water cut changing after liquid increasing. This paper proposed a theoretical prediction model of water cut presenting the correlations between water cut and formation parameters, fluid property parameters, relative permeability parameters and production control conditions. Furthermore, the water cut rising law is theoretically divided into three types (continuous rising type, stable type and step type). Moreover, the theoretical equation of water cut change after liquid increasing is established, and the critical mathematical conditions were clarified for different kinds of water cut changing law such as water cut rising, unchanged or decreasing in complex multi-layer reservoirs. Then, oil rate increment and liquid rate changing can be predicted quantitatively further. The proposed method could be used for the working system optimization, stimulation optimization and development plan adjustment. It has been proved to have a high accuracy based on the actual dynamic data.

Extensive research papers of three-dimensional computational techniques are widely used for the investigation of human brain pathophysiology. Eddy current analyzing could provide an indication of conductivity change within a biological body. A significant obstacle to current trend analyses is the development of a numerically stable and efficiency-finite element scheme that performs well at low frequency and does not require a large number of degrees of freedom. Here, a custom finite element method (FEM) solver based on edge elements is proposed using the weakly coupled theory, which separates the solution into two steps. First, the background field (the magnetic vector potential on each edge) is calculated and stored. Then, the electric scalar potential on each node is obtained by FEM based on Galerkin formulations. Consequently, the electric field and eddy current distribution in the object can be obtained. This solver is more efficient than typical commercial solvers since it reduces the vector eddy current equation to a scalar one, and reduces the meshing domain to just the eddy current region. It can therefore tackle complex eddy current calculations for models with much larger numbers of elements, such as those encountered in eddy current computation in biological tissues. An example is presented with a realistic human brain mesh of 2 million elements. In addition, with this solver, the equivalent magnetic field induced from the excitation coil is applied, and therefore there is no need to mesh the excitation coil. In combination, these significantly increase the efficiency of the solver.

Blockchain es una tecnológica que se ha puesto de moda en estos últimos años, uno de los productos creados por esta tecnología es Bitcoin, el motivo principal de este TFG es desarrollar un monedero de Bitcoin y desde este punto enseñar al lector como funciona Bitcoin y los conocimientos que tiene que saber para desarrollar un monedero Bitcoin. Este TFG concretamente es desarrollar un monedero Bitcoin que cumple los requisitos básicos de un monedero: crear un monedero nuevo, enviar Bitcoin, recibir Bitcoin y mantener Bitcoin de forma segura. Este documento describe el diseño y la implementación de este sistema, usando patrones de diseño MVC junto con Singleton, en la parte de desarrollo se ha establecido el uso de lenguaje de programación TypeScript, acompañado con frameworks: Angular6, Ionic3 y Electron, y algunas librerías de NodeJs: BitcoinJs-lib y Crypto, para desarrollar la lógica interna del monedero de Bitcoin. El resultado final es obtener un monedero de Bitcoin diseñado como una aplicación hibrida, que es capaz de ejecutar en todas las plataformas ya sea dispositivo móvil o computadores, en tiempo real.