Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Experimental and numerical simulation of lignite chemical looping gasification with phosphogypsum as oxygen carrier in a fluidized bed

Phosphogypsum (PG) is a solid waste produced in the wet process of producing phosphoric acid.Lignite is a kind of promising chemical raw material.However,the high sulfur of lignite limits the utilization of lig-nite as a resource.Based on fluidized bed experiments,the optimal reaction conditions for the production syngas by lignite chemical looping gasification (CLG) with PG as oxygen carrier were studied.The study found that the optimal reaction temperature should not exceed 1123 K;the mole ratio of water vapor to lignite should be about 0.2;the mole ratio of PG oxygen carrier to lignite should be about 0.6.Meanwhile,commercial software Comsol was used to establish a fuel reaction kinetics model.Through computational fluid dynamics (CFD) numerical simulation,the process of reaction in fluidized bed were well captured.The model was based on a two-fluid model and coupled mass transfer,heat transfer and chemical reac-tions.This study showed that the fluidized bed presents a flow structure in which gas and solid coexist.There was a high temperature zone in the middle and lower parts of the fluidized bed.It could be seen from the results of the flow field simulated that the fluidized bed was beneficial to the progress of the gasification reaction.     

Strength, strain-rate sensitivity and ductility of copper with nanoscale twins

We present a comprehensive computational analysis of the deformation of ultrafine crystalline pure Cu with nanoscale growth twins. This physically motivated model benefits from our experimental studies of the effects of the density of coherent nanotwins on the plastic deformation characteristics of Cu, and from post-deformation transmission electron microscopy investigations of dislocation structures in the twinned metal. The analysis accounts for high plastic anisotropy and rate sensitivity anisotropy by treating the twin boundary as an internal interface and allowing special slip geometry arrangements that involve soft and hard modes of deformation. This model correctly predicts the experimentally observed trends of the effects of twin density on flow strength, rate sensitivity of plastic flow and ductility, in addition to matching many of the quantitative details of plastic deformation reasonably well. The computational simulations also provide critical mechanistic insights into why the metal with nanoscale twins can provide the same level of yield strength, hardness and strain rate sensitivity as a nanostructured counterpart without twins (but of grain size comparable to the twin spacing of the twinned Cu). The analysis also offers some useful understanding of why the nanotwinned Cu with high strength does not lead to diminished ductility with structural refinement involving twins, whereas nanostructured Cu normally causes the ductility to be compromised at the expense of strength upon grain refinement.     

冲压成形仿真过程中有限元网格模型的建立

网格模型对冲压成形模拟的精度和效率影响极大 ,文中阐述了有限元网格模型建立的方法 ,并从单元尺寸、单元类型、自适应网格再划分技术等方面论述了如何解决精度与效率的问题。     

Efficient multiple-precision integer division algorithm

Design and implementation of division algorithm is one of the most complicated problems in multi-precision arithmetic. Huang et al. [1] proposed an efficient multi-precision integer division algorithm, and experimentally showed that it is about three times faster than the most popular algorithms proposed by Knuth [2] and Smith [3]. This paper reports a bug in the algorithm of Huang et al. [1], and suggests the necessary corrections. The theoretical correctness proof of the proposed algorithm is also given. The resulting algorithm remains as fast as that of [1].     

Optimum sweeps of simple polygons with two guards

A polygon P admits a sweep if two mobile guards can detect an unpredictable, moving target inside P  , no matter how fast the target moves. Two guards move on the polygon boundary and are required to always be mutually visible. The objective of this study is to find an optimum sweep such that the sum of the distances travelled by the two guards in the sweep is minimized. We present an O(n²)$O(n^2)$ time and O(n)$O(n)$ space algorithm for optimizing this metric, where n   is the number of vertices of the given polygon. Our result is obtained by reducing this problem to finding a shortest path between two nodes in a graph of size O(n)$O(n)$.     

Human interaction with policy flight simulators

Policy flight simulators are designed for the purpose of exploring alternative management policies at levels ranging from individual organizations to national strategy. This article focuses on how such simulators are developed and on the nature of how people interact with these simulators. These interactions almost always involve groups of people rather than individuals, often with different stakeholders in conflict about priorities and courses of action. The ways in which these interactions are framed and conducted are discussed, as well as the nature of typical results.     

Smart pricing scheme: A multi-layered scoring rule application

Defining appropriate pricing strategy for smart environment is important and complex task at the same time. It holds the primal fraction in Demand Response (DR) program. In our work, we devise an incentive based smart dynamic pricing scheme for consumers facilitating a multi-layered scoring rule. The proposed strategy characterizes both incentive based DR and price based DR programs facilities. This mechanism is applied between consumer agents (CA) to electricity provider agent (EP) and EP to Generation Company (GENCO). Based on the Continuous Ranked Probability Score (CRPS), a hierarchical scoring system is formed among these entities, CA–EP–GENCO. As CA receives the dynamic day-ahead pricing signal from EP, it will schedule the household appliances to lower price period and report the prediction in a form of a probability distribution function to EP. EP, in similar way reports the aggregated demand prediction to GENCO. Finally, GENCO computes the base discount after running a cost-optimization problem. GENCO will reward EP with a fraction of discount based on their prediction accuracy. EP will do the same to CA based on how truthful they were reporting their intentions on device scheduling. The method is tested on real data provided by Ontario Power Company and we show that this scheme is capable to reduce energy consumption and consumers’ payment.     

计算思维影响下的应用型本科计算机基础教学改革探索

当前以计算思维能力培养为切入点的大学计算机课程改革工作已进入一个新的阶段,如何改革计算机基础教学以适应当前形势的发展,是计算机基础教学面临的挑战。以计算思维为导向,对应用型本科院校大学计算机基础课程的目标定位、教学内容、教学过程等教学环节作改革式探索。