Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission

The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1 , a molecular scaffold with a carbazole–pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant K_a=6.04×10⁵ M⁻¹. Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π–π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure.     

地质—工程—经济一体化页岩气水平井井距优化——以国家级页岩气开发示范区宁209井区为例

为了最大限度地提高资源动用率,通常都采用一次性井网整体部署的方式开发页岩气,而水平井井距设计则是页岩气井网部署的关键。在确定最优井距时,既需要掌握地质特征和钻井压裂工艺,也必须考虑气价、成本等经济因素的影响,目前国内外均没有形成较为可靠的页岩气水平井井距设计方法。为此,首次建立了一种基于地质—工程—经济一体化的页岩气水平井井距分析方法,通过地质建模、数值模拟、现金流分析3种技术手段,使用最终可采储量(EUR)、采收率和内部收益率(IRR)等3项指标对四川盆地长宁—威远国家级页岩气示范区宁209井区的页岩气开发井距进行了综合评价。研究结果表明:①宁209井区在当前的地质、工程、经济条件下,井距大于240 m可以确保页岩气平台开发的内部收益率大于8%;②井距控制在330～380 m时,可以同时兼顾单井EUR、平台采收率和经济效益。结论认为,该研究成果支撑了该井区页岩气开发技术政策的制定,为其实现页岩气规模效益开发奠定了基础。     

Ab initio calculations of the NO2 fission for CL-20 conformers

NO₂ fission is regarded to be the most important initial decomposition process of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). In this study, four CL-20 conformers based on the ε-CL-20 were obtained after the optimization at m062x/cc-pvtz level, and the bond length, bond order and bond dissociation energy of the N-N bonds were examined to investigate the stability of these bonds. In addition, the rate constants and activation energy of the NO₂ fission were evaluated using the microcanonical variational transition state theory (μVT). The calculation results have shown that N-N bonds in the case of pseudo-equatorial and axial of nitro groups are the most stable and the least stable, respectively, by evaluating the bond length, bond order and minimum energy path (MEP). The NO₂ fission rate constants are affected by not only the stability of N-N bonds but also the repulsion forces from the other nitro groups, and the fission process for pseudo-equatorial positioning of nitro groups is easier to be accelerated due to the increase of the repulsion forces. The decomposition of CL-20 conformer may mainly originate from the fission of the pseudo-equatorial positioning of nitro groups, especially for CL-20 III conformer because of the significant low activation energy.     

A practical data-flow verification scheme for business processes

Data in business processes becomes more and more important. Current standard languages for process modeling like BPMN 2.0 which include the data flow reflect this. Ensuring the correctness of the data flow in processes is challenging. Model checking, i.e., verifying properties of process models, is a well-known technique to this end. An important part of model checking is the construction of the state space of the model. However, state-space explosion typically is in the way of an effective verification. We study how to overcome this problem in our context by means of reduction. More specifically, we propose a reduction on the level of the process model. To our knowledge, this is new for the data-flow analysis of processes. The core of our approach are so-called regions of the process model that are relevant for the verification of properties describing the data flow. Non-relevant regions are candidates for reduction of the process model, yielding a smaller state space. Our evaluation shows that our approach works well on industrial process models.     

Digital twin-based assembly data management and process traceability for complex products

Complex products such as satellites, missiles, and aircraft typically have demanding requirements for dynamic data management and process traceability. The assembly process for these complex products involves high complexity, strong dynamics, many uncertainties, and frequent rework and repair, especially in the model development stage. Achieving assembly data management and process traceability for complex products has always been a challenge. A recently proposed solution involves one-to-one mapping of the corresponding physical entity, also known as the digital twin method. This paper proposes a digital twin-based assembly data management and process traceability approach for complex products. First, the dynamic evolutionary process of complex product assembly data was analyzed from three dimensions: granularity, period and version. Then, a framework of digital twin-based assembly data management and process traceability for complex products was constructed. Some core techniques are: 1) workflow-based product assembly data organization and version management; 2) synchronous modeling of the product assembly process based on digital twin; and 3) hierarchical management and traceability of product assembly data based on digital twin. On this basis, an algorithm flowchart for generating a product assembly data package was created, which includes product assembly data management, assembly process traceability, and generation of a product assembly data package. Furthermore, the Digital Twin-based Assembly Process Management and Control System (DT-APMCS) was designed to verify the efficiency of the proposed approach. Some aerospace-related assembly enterprises are currently using DT-APMCS and achieving satisfactory results. Finally, a summary of our work is given, and the future research work is also discussed.     

高压下CL-20拉曼光谱和红外光谱相变研究

为了更好地认识和了解CL-20晶体结构演变规律和相变行为,利用金刚石对顶砧超高压实验技术,在0~50GPa下,研究了高压下ε-CL-20的原位拉曼光谱和红外光谱。结果表明,CL-20晶体在整个加压过程中存在两个相变,第一个相变发生在4.2~7.5GPa,认为是ε相到对称性更低的γ相转变,相变产生的原因是在压强的作用下,笼环外的硝基方向发生改变,电子云密度重置导致的分子构型转变;第二个相变发生在14.2~18.9GPa,属于γ相到ζ相的晶体结构转变;卸压后,拉曼和红外光谱恢复常压状态,表明CL-20晶体在研究压强范围内的相变过程是可逆的。     

How hydrogen-storage material affects the decomposition of nitramine explosive: CPMD investigations of LAB-doped CL20

As the most popular high-energy explosives, 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazatetracyclo [5.5.0.0.0] dodecane (Simplified as HNIW or CL20) attracts many attentions for improving its detonation appearance in the application. Here we introduce hydrogen-storage compounds into explosives to estimate the possible improved detonation performances by Car-Parrinello molecular dynamics (CPMD) simulation, where we construct lithium amidoborane (LAB) doped CL20 as the initial structure. Almost all the interactions between hydrogen and CL20 appear exothermic properties, which indicate LAB increases the enthalpies of detonation. The results suggest explosive mixed with hydrogen-storage material is possibly a new field of energetic compound.     

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

Materials aspects associated with the addition of up to 20 mol% hydrogen into an existing natural gas distribution network

The introduction of hydrogen into the UK natural gas main has been reviewed in terms of how materials within the gas distribution network may be affected by contact with up to 80% Natural Gas (NG)/20 mol% hydrogen blend at up to 2 barg. A range of metallic, polymeric and elastomeric materials in the gas distribution network (GDN) were assessed via a combination of literature review and targeted practical test programmes.The work considered:? The effect of hydrogen on metallic materials identified in the network.? The effect of hydrogen on polymeric materials identified in the network.? The effect of hydrogen exposure on polyethylene pipeline joining and repair techniques (squeeze-off, and socket and saddle electrofusion joints)The experimental work involved soaking materials, under pressure conditions representative of the network, in 100% hydrogen, 20% hydrogen in methane, and 100% methane. For the metal samples, the test programme involved the assessment of hydrogen uptake on the tensile properties. For the polyethylene samples, the test programme looked at the assessment of possible hydrogen absorption/desorption and its effect on electrofusion jointing.The trials concluded that the majority of metallic materials showed no significant deterioration in mechanical (tensile) properties when stored in hydrogen environments compared to those stored in analogous methane or blended gas atmospheres up to 2 barg. Polymeric materials showed no deterioration to efficiency of squeeze-off or collar electrofusion in socket or shoulder orientations following soaking in hydrogen, methane or hydrogen blends.     

增进核电焊材用钢508 Ⅲ洁净度的工艺实践

核电焊材用钢508 Ⅲ（/%:0.09~0.12C,0.30~0.40Si,1.45~1.65Mn,≤0.008P,≤0.008S,0.45~0.60Mo,0.60~0.75Ni）的生产工艺流程为20t EAF-LF-VD-4t铸锭-锻造150 mm×150 mm坯-轧制Φ5.5mm盘条。采用精选炉料,以及高碱度渣、高FeO含量,钢水温度1550~1570℃等措施控制,电弧炉终点[P]≤0.002%,并选用低磷合金,使钢中磷含量≤0.006%;LF采用硅钙合金沉淀脱氧,SiC粉扩散脱氧、CaO-Al₂O₃-SiO₂渣系,碱度5.0~5.5,VD真空度≤67Pa,Ar流量30~50 L/min,保护浇铸等措施后,3炉钢的分析结果表明,钢中气体含量为1.3×10^-6~1.5×10^-6[H],10×10^-6~14×10^-6[O]和44×10^-6~58×10^-6[N],满足核电焊材用钢508Ⅲ洁净度的要求。