Accelerating Factor Xa inhibitor discovery with a de novo drug design pipeline

Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug design framework, Drug CAMD, that integrates a deep learning model with a mixed-integer nonlinear programming model is used for designing drug candidates. Within this framework, a virtual chemical library is specifically tailored to inhibit Factor Xa. To further filter and narrow down the lead compounds from the designed compounds, comprehensive approaches involving molecular docking,binding pose metadynamics(BPMD), binding free energy calculations, and enzyme activity inhibition analysis are utilized. To maximize efficiency in terms of time and resources, molecules for in vitro activity testing are initially selected from commercially available portions of customized virtual chemical libraries. In vitro studies assessing inhibitor activities have confirmed that the compound EN300-331859shows potential Factor Xa inhibition, with an IC_(50)value of 34.57 μmol·L^(-1). Through in silico molecular docking and BPMD, the most plausible binding pose for the EN300-331859-Factor Xa complex are identified. The estimated binding free energy values correlate well with the results obtained from biological assays. Consequently, EN300-331859 is identified as a novel and effective sub-micromolar inhibitor of Factor Xa.

The Study on Landscape Factors,Pattern and Design in New Countryside Construction in Mountainous Areas of China

With the vigorous development of China urbanization and increase of people's environmental consciousness,landscape design had received more and more attentions in urban construction and planning.However,the planning for mountainous new countryside construction and landscape design had not been emphasized.Hence,how to make use of natural and cultural landscape factors in mountainous areas to conduct landscape design in new countryside construction was an issue needed to be highlighted.According to the field study of natural villages and residences of Longnan City in Gansu Province,the paper had discussed the composition of mountainous settlements and residences,the composition of mountainous rural landscape factors and landscape planning principles,hoping to provide reference for rural landscape design and new countryside construction.

Impact of Improving Design Factor over 0.72 on the Safety and Reliability of Gas Pipelines and Feasibility Justification

Many years experience of the operation of high stress (>72% specified minimum yield strength, SMYS) gas pipelines and statistical analysis results of pipeline incidents showed that the operating pipelines at stress levels over 72% SMYS have not presented problems in USA and Canada, and design factor does not control incidents or the safety of pipelines. Enhancing pipeline safety management level is most important for decreasing incident rate. The application history of higher design factors in the U.S and Canada was reviewed. And the effect of higher factors to the critical flaw size, puncture resistance, change of reliability with time, risk level and the arrest toughness requirements of pipeline were analyzed here. The comparison of pipeline failure rates and risk levels between two design factors (0.72 and 0.8) has shown that a change in design factor from 0.72 to 0.8 would bring little effect on failure rates and risk levels. On the basis of the analysis result, the application feasibility of design factor of 0.8 in China was discussed and the related suggestions were proposed. When an operator wishes to apply design factor 0.8 to gas pipeline, the following process is recommended: stress level of line pipe hydro test should be up to 100% SMYS, reliability and risk assessment at the design feasibility or conceptual stage should be conducted, Charpy impact energy should meet the need of pipeline crack arrest; and establish and execute risk based integrity management plan. The technology of pipeline steel metallurgy, line pipe fabrication and pipeline construction, and line pipe quality control level in China achieved tremendous progresses, and line pipe product standards and property indexes have come up to international advanced level. Furthermore, pipeline safety management has improved greatly in China. Consequently, the research for the feasibility of application of design factor of 0.8 in China has fundamental basis.

PHASE STRUCTURE FACTOR AND INTERFACE CONJUNCTION FACTOR OF CAST IRON AND ITS COMPOSITION DESIGN

Theempiricalelectrontheory of solidsand molecules( EET) and theimproved TFDtheory wereapplied tocalculatethe phasestructurefactorsand interfaceconjunction factorsofcom mon alloying elementsincastiron. Akind of Si- Mo- Cu ductileiron with rareearth Mg asnodularizer was designed accordingtothese valenceelectron structure parameters. Actual applicationtestsshow thatthelongevity of thisiron is 1.5 timesof thatof high manganesesteel. This accordance of theoretical results and actual effectsshows the composition design methodcan beused in othercastiron research.

Design of Full-Ocean-Depth Self-Floating Sampler and Analysis of Factors Affecting Core Penetration Depth

The hadal zone(ocean depths of 6 – 11 km) is one of the least-understood habitats on Earth because of its extreme conditions such as high pressure, darkness, and low temperature. With the development of deep-sea vehicles such as China's 7000 m manned submersible Jiaolong, abyssal science has received greater attention. For decades, gravity-piston corers have been widely used to collect loose subsea-sediment long-core samples. However, the weight and length of the gravity sampler cables and the operating environment limit sampling capacity at full ocean depths. Therefore, a new self-floating sediment sampler with a spring-loaded auto-trigger release and that incorporates characteristics from traditional gravity-driven samplers is designed. This study analyzes the process by which a gravity-piston corer penetrates the sediment and the factors that affect it. A formula for obtaining the penetration depth is deduced. A method of optimizing the sampling depth is then developed based on structure design and parametric factor modeling. The parameters considered in the modeling include the sampling depth, balance weight, ultimate stress friction coefficient, dimensions of the sampler, and material properties. Thus, a new deep-sea floating parametric sampler designed based on virtual prototyping is proposed. Accurate values for all the design factors are derived from calculations based on the conservation of energy with penetration depth, analyses of the factors affecting the penetration depth, and analyses of the pressure bar stability. Finally, experimental data are used to verify the penetration-depth function and to provide theoretical guidance for the design of sediment samplers.

Design optimization of composite egg-shaped submersible pressure hull for minimum buoyancy factor

This paper describes a design optimization study of the composite egg-shaped submersible pressure hull employing optimization and finite element analysis(FEA)tools as a first attempt to provide an optimized design of the composite egg-shaped pressure hull for manufacturing or further investigations.A total of 15 optimal designs for the composite egg-shaped pressure hull under hydrostatic pressure are obtained in terms of fibers’angles and the number of layers for 5 lay-up arrangements and 3 unidirectional(UD)composite materials.The optimization process is performed utilizing a genetic algorithm and FEA in ANSYS.The minimization of the buoyancy factor eB:FT is selected as the objective for the optimization under constraints on both material failure and buckling strength.Nonlinear buckling analysis is conducted for one optimal design considering both geometric nonlinearity and imperfections.A sensitivity study is also conducted to further investigate the influence of the design variables on the optimal design of the egg-shaped pressure hull.

Seismic design factors for RC special moment resisting frames in Dubai,UAE

This study investigates the seismic design factors for three reinforced concrete （RC） framed buildings with 4, 16 and 32-stories in Dubai, UAE utilizing nonlinear analysis. The buildings are designed according to the response spectrum procedure defined in the 2009 International Building Code （IBC＇09）. Two ensembles of ground motion records with 10% and 2% probability of exceedance in 50 years （10/50 and 2/50, respectively） are used. The nonlinear dynamic resPonses to the earthquake records are computed using IDARC-2D. Key seismic design parameters are evaluated; namely, response modification factor （R）, deflection amplification factor （Cd）, system overstrength factor （Ωo）, and response modification factor for ductility （Rd） in addition to inelastic interstory drift. The evaluated seismic design factors are found to significantly depend on the considered ground motion （10/50 versus 2/50）. Consequently, resolution to the controversy of Dubai seismicity is urged. The seismic design factors for the 2/50 records show an increase over their counterparts for the 10/50 records in the range of 200%-400%, except for the D~ factor, which shows a mere 30% increase. Based on the observed trends, perioddependent R and Cd factors are recommended if consistent collapse probability （or collapse prevention performance） in moment frames with varying heights is to be expected.

Study on strength reduction factors consid-ering the effect of classification of design earthquake

The strength reduction factors are not only the key factors in determining seismic action for force-based seismic design, but also the key parameters to derive the inelastic response spectra for performance-based seismic design. In this paper, with a high quality ground motion database that includes a reasonable-sized set of records from China, a statistical study on the strength reduction factors is conducted and a new expression of strength reduction factors involving classification of design earthquake, which is an important concept to determine design spectra in Chinese seismic design code, is proposed. The expression of strength reduction factors can reflect the ground motion characteristics of China to a certain extent and is particularly suitable for Chinese seismic design. Then, the influence effects of site condition, classification of design earthquake, period of vibration, ductility level, earthquake magnitude and distance to fault on strength reduction factors are investigated. It is concluded that the effect of site condition on the strength reduction factors cannot be neglected, especially for the short-period structures of higher ductility. The classification of design earthquake also has an important effect on strength reduction factors and it may be unsuitable to use the existing expressions of strength reduction factors to the design spectra of current Chinese seismic code. The earthquake magnitude has no practical effect on strength reduction factors and if the near-fault records with forward directivity effect are not taken into consideration, the effect of distance to fault on strength reduction factors can also be neglected.

Assessment of seismic design response factors of concrete wall buildings

To verify the seismic design response factors of high-rise buildings, five reference structures, varying in height from 20- to 60-stories, were selected and designed according to modern design codes to represent a wide range of concrete wall structures. Verified fiber-based analytical models for inelastic simulation were developed, considering the geometric nonlinearity and material inelasticity of the structural members. The ground motion uncertainty was accounted for by employing 20 earthquake records representing two seismic scenarios, consistent with the latest understanding of the tectonic setting and seismicity of the selected reference region （UAE）. A large number of Inelastic Pushover Analyses （IPAs） and Incremental Dynamic Collapse Analyses （IDCAs） were deployed for the reference structures to estimate the seismic design response factors. It is concluded that the factors adopted by the design code are adequately conservative. The results of this systematic assessment of seismic design response factors apply to a wide variety of contemporary concrete wall buildings with various characteristics.

Ce掺杂0.94MgTiO_(3)-0.06(Ca_(0.8)Sr_(0.2))TiO_(3)陶瓷的制备及微波介电性能

为了提高MgTiO_(3)-(Ca_(0.8)Sr_(0.2))TiO_(3)(MT-CST)微波介质陶瓷的品质因数,通过SEM、XRD、拉曼光谱仪与XPS分析手段,研究了Ce掺杂对MT-CST陶瓷成分晶体结构和微波介电性能的影响.结果表明:高价Ce^(3+)取代Mg^(2+)可使氧空位缺陷得到有效抑制,从而降低了微波介质损耗,可使品质因数得到较大提升.制备的陶瓷具有优异的微波介电性能:介电常数为20.8,品质因数为61000 GHz,谐振频率温度系数为-4.99×10^(-6)/℃.

Characterization of Six Categories of Systematic 2^{<i>n</i>-(<i>n</i>-<i>k</i>)}Fractional Factorial Designs

Six categories of systematic 2n-(n-k) designs derivable from the full 2k factorial experiment by the interactions-main effects assignment are available for carrying out 2n-(n-k) factorial experiments sequentially run after the other such that main effects are protected against the linear/quadratic time trend and/or such that the number of factor level changes (i.e. cost) between the runs is minimal. Three of these six categories are of resolution at least III and three are of resolution at least IV. The three categories of designs within each resolution are: 1) minimum cost 2n-(n-k) designs, 2) minimum cost linear trend free 2n-(n-k) designs and 3) minimum cost linear and quadratic trend free 2n-(n-k) designs. This paper characterizes these six categories and documents their differences with regard to either time trend resistance of factor effects and/or the number of factor level changes. The paper introduces the last category of systematic 2n-(n-k) designs (i.e. the sixth) for the purpose of extending the design resolution from III into IV and also for raising the level of protection of main effects from the linear time trend into the quadratic, where a catalog of minimum cost linear and quadratic trend free 2n-(n-k) designs (of resolution at least IV) will be proposed. The paper provides for each design in any of the six categories: 1) the sequence of its runs in minimum number of factor level changes 2) the defining relation or its 2n-(n-k) alias structure and 3) the k independent generators needed for sequencing the 2n-(n-k) runs by the generalized foldover scheme. A comparison among these six categories of designs reveals that when the polynomial degree of the time trend increases from linear into quadratic and/or when the design’s resolution increases from III to IV, the number of factor level changes between the 2n-(n-k) runs increases. Also as the number of factors (i.e. n) increases, the design’s resolution decreases.

Development of Product Design Projects Applying Specifications and Factors Matrix (SFM) as a Support Tool in Higher Education

The application of work strategies taking into account, from the initial stages, all the factors involved in the product design process is considered essential by the researches to generate higher quality products, assess users’ needs and anticipate design problems. This paper presents two approaches of design project development, denominated respectively: projects with imposed specifications and projects with derived specifications and proposes the use of the matrix that integrates specifications and design factors (SFM). This design support tool complements others already used in the development of product concepts by higher education students, increasing the capacity of synthesis and structuring of information in order to facilitate decision-making into the design process. Its elaboration implies understanding of objectives, identifying of factors and establishing of specifications. At the same time, it aims to foster the reflection process and an integrated information analysis. The application of SFM and its contribution to different project approaches are shown in this paper.

On Several Reflection Factors during the Interior Design of Green Residence

Nowadays, with the rapid development of the society and economy, the living standards of people increase rapidly. People are gradually pursuing green and environmental living concepts rather than the extensive type living modes. Due to the increase of people＇ s cognition of scientific development concept as well as the gradually increasing demands on residential interior design, the concept of green residence comes into people＇ s mind. As the development tendency of future interior design, green residence can be environmental-friendly and increase the greenery and comfort to the house, thus being more and more welcomed in the home market. This paper analyzes and explores some questions concerned during the green residential interior design by starting from the concept of green residential interior design.

The investigation of multiple factors on elastic anisotropy of artificial shale based on the orthogonal experiment

Elastic anisotropy of shales is critical to accurate constraints for rock physical models,quantitative interpretation and hydraulic fracturing.However,the causes of elastic anisotropy of shales are very complicated,and the understanding of how multiple influence factors affect the elastic anisotropy of shales is still not clear.Hence,the orthogonal experiment,as an effective multiple factors experimental method,is adopted in this study to analyze the effect of multiple factors for shale elastic anisotropy.Three factors,clay content,organic matter(OM)content and compaction stress are selected as independent variables,the orthogonal test table L_(16)(4^(3))with four levels for each factor is adopted.According to the designed orthogonal table,sixteen artificial shales are constructed based on the cold-pressing method,and all the dry artificial shales are measured by the ultrasonic measurements.The influence of each factor on the elastic anisotropy and the sensitivity orders of three factors are obtained using the range analysis.The orders of sensitivity for selected factors follow the sequence clay content>compaction stress>OM content for velocity anisotropy parameters.The compaction mechanism of artificial shales is also discussed by the compaction factor,which are positively correlated with the velocity anisotropy parameters.The clay platelets orientation distribution function(ODF)of samples is evaluated by a theoretical model,the ODF coefficients are significantly affected by the clay content and compaction stress,and W200 are much more sensitive to these factors than W400.The results can provide a critical rock physics basis for quantitative interpretation and reservoir prediction of the low-maturity or maturity shale reservoir.

Inelastic displacement ratio of low-to mid-rise BRBFs designed under variable levels of seismicity

Buckling-restrained braces(BRBs)have shown their capability to provide building structures with stiffness,strength,and ductility.Estimating the seismic drifts of buckling-restrained braced frames(BRBFs)is an important design step to control structural and non-structural damage.In current practice of seismic design,the estimation of seismic drifts of BRBFs is performed by using empirical calculations that are independent upon either the type of the structural system or the design level of seismicity.In these empirical calculations,the seismic drifts are estimated by amplifying the reduced elastic drifts obtained under design lateral loading with a displacement amplification factor(DAF).The value of DAF is considered equal to the product of the response modification factor R and the inelastic displacement ratioρ.The goal of the current research is to assess the value ofρfor low-to mid-rise BRBFs designed under low and high levels of seismicity.This goal has been achieved by conducting a series of elastic and inelastic time-history analyses pertaining to an ensemble of earthquake records on 3-,6-and 9-story BRBFs.The results indicate that theρ-ratio increases with an increase in design seismic intensity and an increase in experienced inelasticity.The range ofρfor low seismicity designs ranges from 0.63 to 0.9,while for high seismicity designs this range stretches from 0.83 to 1.29.It has been found that the consideration of a generalρ-ratio of 1.0 is a reasonable estimation for the design of the BRBFs considered in this study.

基于Design-expert的醋酸纤维/煤基分级多孔炭制备优化

当前煤层气利用的主要方式是直接燃烧,该过程会产生大量温室气体(CO_(2))排放,且会造成稀缺资源的低附加值利用。为实现煤层气的高附加值利用,拟通过在煤中原位添加醋酸纤维和KOH活化的方法制备一种醋酸纤维/煤基分级多孔炭材料,并将其应用于煤层气直接裂解制氢,不仅可以获得高纯氢气,还能得到一定数量的纳米碳材料。醋酸纤维/煤基分级多孔炭在制备过程中需要考虑温度、碱碳质量比、溶剂量和其他碳源添加量对制备过程和转化率的影响,利用Design-expert软件对试验方案进行优化设计。通过响应曲面法和部分试验数据对各影响因素与转化率的关系进行分析,建立相应拟合回归方程,得出理论最优解。通过将最优解与试验结果进行对比分析,验证Design-expert软件在多因素多水平条件下的预测可靠性,同时也阐明最优条件下炭材料催化裂解煤层气的机理。结果表明,温度和碱碳质量比是醋酸纤维/煤基分级多孔炭制备过程的最大影响因素,建立相关因素与转化率之间的拟合回归方程并求出理论最优解。理论最优解与试验值之间的最大误差为3.05%,说明Design-expert软件对制备过程的优化准确可靠。醋酸纤维/煤基分级多孔炭催化裂解煤层气较原煤炭材料具有高的转化率和稳定性,前者反应后表面生成大量碳球,而后者表面则生成少量碳纤维和大量碳球。

载人航天人机交互界面色彩设计方法研究

目的对载人航天人机交互界面的色彩设计方法流程进行了梳理和分析。方法遵循“以人为中心”的设计原则,从色彩空间与模型、色彩设计与人因、航天色彩设计范围、载人航天器色彩设计模型,以及载人航天器色彩设计与人因评价体系等方面,对载人航天器人机交互界面色彩设计方法流程体系进行了探讨。结果构建了载人航天色彩设计模型,阐述了完整的载人航天色彩设计方法流程体系。结论针对载人航天人机交互色彩设计方法的研究为航天员在轨环境中的生活品质及工作效能等相关领域的提高提供了有力支持,进一步增强了航天领域色彩设计与人因工程的重要性。

基于关联规则的发射系统敏捷响应要素辨识

当今高性能发射系统追求的大负载、轻量化、低成本、敏捷响应等设计要求通常是相互矛盾的,必须考虑多种约束条件下,多参数匹配的综合优化,才能突破系统各性能指标相互制约的瓶颈。针对以上问题,采用关联规则挖掘方法研究了发射系统设计因素的影响,建立了发射系统设计因素关联规则挖掘模型。在“支持度-置信度”模式的基础上,引入附加评估度量Kulc和IR,提高挖掘结果的准确性。通过工程算例,研究了设计参数对发射系统敏捷响应能力的影响。算例结果表明,提出的方法能够识别对敏捷响应能力起关键作用的设计变量,实现精炼设计空间、简化优化问题,以及提高设计优化效率的目的。

引入重要度修正因子的复杂光电系统可靠性分配研究

以某新型复杂光电系统为研究对像,针对传统评分分配法客观性差、分配偏差大的缺点,构建重要度修正因子,提出了一种引入重要度修正因子的可靠性评分分配法。首先,运用模糊层次分析法,得到功能单元对上级功能单元/系统可靠性影响的相对重要度;然后,基于相对重要度,按照专家评分规则,得到功能单元对上级功能单元/系统可靠性影响的绝对重要度;最后,基于相对重要度和绝对重要度,构建功能单元重要度修正因子,以此修正各功能单元的评分结果。经对比验证,关重功能单元可靠性分配值较传统评分分配值至少提高6%,引入重要度修正因子的评分分配法能有效削弱传统评分分配法的主观影响,释放关重功能单元可靠性余量,提高功能单元可靠性分配的科学性、合理性,进而提高复杂系统可靠性设计水平。

基于DEMATEL-ISM的公共设施可持续设计提升策略研究

目的 为探索可持续设计需求在公共设施设计中的重要性问题,准确全面地推进公共设施的可持续设计,构建覆盖公共设施生命全周期的多指标设计体系模型,对设计阶段前期的因素重要性需求及相关性进行评估。从而支持在后续的公共设施设计过程中的可持续设计评估。方法 以可持续设计的环境价值、经济价值和社会价值为目标层,对美景度、环保度等9个影响因素进行分析,获取公共设施在可持续设计方面的各种影响因素,构建研究体系。在此基础上,提出运用DEMATEL-ISM组合模型探究各制约因素间的复杂影响关系,利用排序和重要性结果,寻找关键要素,绘制层级关系示意图,使各种因素之间的关系更加条理化、层次化。根据计算结果提出有助于在设计阶段提高公共设施设计可持续的策略及建议。结果 研究表明,在公共设施的可持续设计中,实用度和可控度的中心度最高,为重要的影响因素。公共设施可持续设计需要以提高美景度及和谐度为改善基础,实用度、可控度和体验度为调节因素,最终通过控制环保度、耐久度等因素,保障公共设施设计的可持续运行。结论 基于DEMATEL-ISM可以直观清晰地展现公共设施可持续设计影响因素之间的相互关系。通过对模型信息的理性分析,能够促使后期设计方案在公共设施生命全周期的各个维度上具有可持续性,并在理论层面为设计环节的决策提供参考依据。