Two Methods,One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes.     

Chemical Bonding by the Chemical Orthogonal Space of Reactivity

The fashionable Parr–Pearson (PP) atoms-in-molecule/bonding (AIM/AIB) approach for determining the exchanged charge necessary for acquiring an equalized electronegativity within a chemical bond is refined and generalized here by introducing the concepts of chemical power within the chemical orthogonal space (COS) in terms of electronegativity and chemical hardness. Electronegativity and chemical hardness are conceptually orthogonal, since there are opposite tendencies in bonding, i.e., reactivity vs. stability or the HOMO-LUMO middy level vs. the HOMO-LUMO interval (gap). Thus, atoms-in-molecule/bond electronegativity and chemical hardness are provided for in orthogonal space (COS), along with a generalized analytical expression of the exchanged electrons in bonding. Moreover, the present formalism surpasses the earlier Parr–Pearson limitation to the context of hetero-bonding molecules so as to also include the important case of covalent homo-bonding. The connections of the present COS analysis with PP formalism is analytically revealed, while a numerical illustration regarding the patterning and fragmentation of chemical benchmarking bondings is also presented and fundamental open questions are critically discussed.     

基于QoE感知的星地一体化网络公平资源分配策略

星地一体化网络是卫星网络和地面网络互联，实现卫星网络和地面网络优势互补的一体化网络。随着无线通信的快速发展，卫星网络和地面网络的同频复用技术可有效提升资源利用效率，满足日益增长的无线数据业务需求。但由于无线数据业务类型的多样化和频谱资源的稀缺性，如何实现用户数据服务的服务体验质量（Quality of experience， QoE）和公平性提升也成为星地一体化网络亟待解决的关键问题。本文综合考虑信道时变性、服务体验多样性和服务公平性，提出了一种基于QoE感知的星地一体化网络资源分配策略。为此，将目标问题描述为基于时间平均的服务体验质量的网络公平效用最大化，并利用李雅普诺夫优化理论，将复杂的动态原始优化问题进一步转化并分解为3个瞬时优化子问题，每个子问题可以在每个时隙独立求解。同时，由于无线资源分配为典型的非凹混合组合优化问题，推导了一个低复杂度的两步算法来求解第三个资源分配子问题。仿真结果揭示了在不同的公平性参数下用户的长时QoE与公平性之间的折衷情况。     

Flow state monitoring of gas-water two-phase flow using multi-Gaussian mixture model based on canonical variate analysis

As a highly complex and time-varying process, gas-water two-phase flow is commonly encountered in industries. It has a variety of typical flow states and transition flow states. Accurate identification and monitoring of flow states is not only beneficial to further study of two-phase flow but also helpful for stable operation and economic efficiency of process industry. Combining canonical variate analysis (CVA) and Gaussian mixture model (GMM), a strategy called multi-CVA-GMM is proposed for flow state monitoring in gas-water two-phase flow. CVA is used to extract flow state features from the perspective of correlation between historical data and future data, which solves the cross correlation and temporal correlation of multi-sensor measurement data. GMM calculates the possibility that the current flow state belongs to each typical flow pattern and judges the current flow state by probability indicators. It is conducive to follow-up use of Bayesian inference probability and Mahalanobis distance-based (BID) indicator for flow state monitoring, which avoids repeated traversal of multiple CVA-GMM models and improves the efficiency of the monitoring process. The probability indicators can also be used to analyze transition flow states. The method combining the probabilistic idea of GMM with the deterministic idea of multimodal modeling can accurately identify the current flow state and effectively monitor the evolution of flow state. The multi-CVA-GMM method is validated by using the measured data of the horizontal flow loop of gas-water two-phase flow experimental facility, and its effectiveness is proved.     

Flow modeling of high-viscosity fluids in pipeline infrastructure of oil and gas enterprises

Today, the issues related to solving the problem of finding an effective distribution of oil flows through the system of oil pipelines in order to reduce the total energy consumption are relevant. The solution to this problem is connected with selection of rational pumping modes for various technological sections of oil pipelines using modern methods of mathematical programming or new techniques for improving the energy and transport characteristics of oil.Reducing energy consumption during pumping of crude through oil trunk pipelines can be achieved by various methods. Numerous investigations in this direction are mainly carried out to save energy on separate single-line pipelines. However, due to the development of the network of trunk oil pipelines in the world over the past decades, the issues of energy efficient management of oil flows throughout the entire oil pipeline system of oil and gas enterprises become urgent.This paper analyses parameters for pipeline transport of high-viscosity and heavy oils. The article proposes a method for assessing the rheological properties of oil for further planning of pumping taking into account the preservation of oil quality and an increase in energy and transport characteristics. The proposed solutions and tasks for predicting changes in the viscosity-temperature characteristics of the flow for blends of different oil types are especially relevant in the current conditions of an increase in the share of oil production with complex rheological characteristics. Results of the presented investigations may be used for planning the measures of efficient transportation of high-viscosity and heavy oils.     

Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.     

42CrMo钢加热过程中的奥氏体晶粒尺寸演变

通过金相试验方法测定42CrMo钢在890~930 ℃下保温10~240 min后的晶粒尺寸。结果表明,42CrMo钢在加热到试验温度890~930 ℃时已经完全奥氏体化,保温过程中的晶粒生长属于正常生长;加热温度对晶粒尺寸的影响较大,保温时间对晶粒尺寸的影响较小;随保温时间的延长晶粒生长缓慢,晶粒尺寸与保温时间满足指数小于1的函数关系。基于试验数据,通过线性回归得到晶粒长大的Beck模型参数,通过非线性回归得到Sellars和Anelli模型参数,3个模型的预测精度都较好,而Anelli模型的适用性要高于Beck模型和Sellars模型,故在预测42CrMo钢的奥氏体晶粒长大规律时宜使用Anelli模型。     

Towards artificial intelligence at scale in the chemical industry

In the Industry 4.0 era, the chemical industry is embracing broad adoption of artificial intelligence (AI) and machine learning (ML) methods. This article provides a holistic view of how the industry is transforming digitally towards AI at scale. First, a historical perspective on how the industry used AI to aid humans in better decision-making is shown. Then state-of-the-art AI research addressing industrial needs on reliability and safety, process optimization, supply chain, material discovery, and reaction engineering is highlighted. Finally, a vision of the plant of the future is illustrated with critical components of AI-ready culture, model life cycle management, and renewed role of humans in chemical manufacturing.     

An automated treatment planning strategy for highly noncoplanar radiotherapy arc trajectories

Radiation therapy is a technology-driven cancer treatment modality that has experienced significant advances over the last decades, due to multidisciplinary contributions that include engineering and computing. Recent technological developments allow the use of noncoplanar volumetric modulated arc therapy (VMAT), one of the most recent photon treatment techniques, in clinical practice. In this work, an automated noncoplanar arc trajectory optimization framework designed in two modular phases is presented. First, a noncoplanar beam angle optimization algorithm is used to obtain a set of noncoplanar irradiation directions. Then, anchored in these directions, an optimization strategy is proposed to compute an optimal arc trajectory. The computational experiments considered a pool of twelve difficult head-and-neck tumor cases. It was possible to observe that, for some of these cases, the optimized noncoplanar arc trajectories led to significant treatment planning quality improvements, when compared with coplanar VMAT treatment plans. Although these experiments were done in a research environment treatment planning software (matRad), the conclusions can be of interest for a clinical setting: automated procedures can simplify the current treatment workflow, produce high-quality treatment plans, making better use of human resources and allowing for unbiased comparisons between different treatment techniques.