A Box of Chemistry to Inhibit the MEN1 Tumor Suppressor Gene Promoting Leukemia

Targeting protein-protein interactions (PPIs) with small-molecule inhibitors has become a hotbed of modern drug development. In this review, we describe a new class of PPI inhibitors that block menin from binding to MLL proteins. Menin is encoded by the MEN1 tumor suppressor, but acts as an essential cofactor for MLL/KMT2A-rearranged leukemias. The most promising menin-MLL inhibitors belong to the thienopyrimidine class and have recently entered phase I/II clinical trials for treating acute leukemias characterized by MLL/KMT2A translocations or NPM1 mutations. As single agents, thienopyrimidine compounds eradicate leukemia in a xenograft models of primary leukemic cells belonging to the MLL-rearranged or NPM1-mutant subtypes. These compounds are well tolerated with few or no side effects, which is remarkable given the tumor-suppressor function of menin. The menin-MLL inhibitors highlight how leukemia patients could benefit from a targeted epigenetic therapy with novel PPI inhibitors obtained by directed chemical evolution.     

地表径流速度对城市内涝影响规律

为分析地表径流速度对城市内涝的影响,采用一维地下排水管网与二维城区地形的动态耦合模型,选取大连市某排水区块作为研究区域,设置4种地表径流速度10种设计降雨场景,模拟分析在不同重现期设计降雨及不同地表径流速度下研究区的内涝积水特性。结果表明:随着地表径流速度降低,管道排水压力变小,管道排水达标率最高可提升48.05%,且降雨重现期越短,地表径流流速对管道排水压力的削减效果越明显;地表径流流速对检查井溢流量影响显著,随着地表径流速度降低,检查井溢流量峰值最高可减小2 750 m~3,峰现时间最长可滞后56 min,同时随着降雨重现期增长,地表径流流速对检查井溢流量的削减效果减弱;研究区低、高风险区淹没面积随地表径流速度降低,最高可分别减小1.64万、8.37万m~2,但中风险区淹没面积变化反复。     

南水北调中线总干渠藻类的生态调度

南水北调中线总干渠无在线调蓄水库,对藻类生态调度过程中出现的问题开展生态调度实现策略和实施方式研究。主要实现策略包括:划定自身的调蓄区,隔离生态调度对下游的影响;采用高效的渠池运行方式,减少生态调度时蓄量的反复调整;综合考虑安全、快速、平稳等需求,设定生态调度实施进程和方式。具体实施方式包括:将总干渠划分为流速调控区、调蓄区和正常运行区,分别实施等体积、控制蓄量和闸前常水位方式运行;将生态调度过程划分为充水阶段和泄水阶段,基于流速调控目标值、持续时长和水位降幅约束条件,确定各阶段时长和各分区的闸门群调控方案等。基于2018年3月输水工况,采用明渠一维非恒定流模型,仿真总干渠上游15个渠池的藻类生态调度过程。结果表明,生态调度可在3.5 d内完成,各渠池的平均流速由0.48 m/s增至0.93 m/s,持续时间超过2 h。在整个生态调度过程中,水位变化平稳,水位变幅符合安全阈值要求,下游渠道的正常运行未受生态调度明显影响。     

基于分形理论的黄河内蒙古段河势演变特征及其与凌汛灾害关联研究

寒区河道凌汛灾害河势“弯道效应”的量化评估十分重要。基于分形理论提出河道横断面-纵剖面-平面多维度河势分形维数计算方法及其物理机制，并探讨黄河内蒙古段不同维度河势演变分形特征及其与凌汛灾害的关联关系。结果表明，黄河内蒙古段不同维度河势均具有多尺度自相似分形特征，且具有多年记忆周期的长程相关性；冰坝（严重性冰塞）发生频次与河道主槽弯曲分形维数呈正相关指数型函数关系，与河相系数、深泓点高程和河段平均底坡分形维数负相关，与水深-面积分形维数正相关，总体表明冰坝灾害更易发生于主槽偏移摆动大、蜿蜒曲折、河湾发育程度高的宽浅型弯曲河道，研究成果可为凌汛期冰塞冰坝灾害易发河段诊断及预测提供重要理论依据。     

Analysis of operating limits and combustion state regulation for low-calorific value gases in industrial burners

The effective and efficient utilization of low-calorific value (LCV) gases has gained increasing attention in scientific research and industrial fields. In this study, the combustion characteristics of three LCV gases in practical devices are analyzed by using a nonadiabatic perfectly stirred reactor model. The complete steady-state solution in the temperature-residence time parameter space is obtained with arc-length continuation. The stable operation region is quantified by the eigenvalue analysis. The transition of solution curves is quantified with heat loss coefficient. Five key system parameters are systematically investigated on their effects on stability limits. With the combustion performance being quantified by a combustion state index, a combustion state regulation method is proposed to find the optimal regulation path of system parameters. Active subspace method is further applied to shorten the regulation step by identifying the active direction. The proposed method and findings are useful for optimal regulation of burning LCV gases in industrial burners.     

Laboratory Studies to Determine Suitable Chemicals to Improve Oil Recovery from Garzan Oil Field

Garzan oil field is located at the south east of Turkey. It is a mature oil field and the reservoir is fractured carbonate reservoir. After producing about 1% original oil in place (OOIP) reservoir pressure started to decline. Waterflooding was started in order to support reservoir pressure and also to enhance oil production in 1960. Waterflooding improved the oil recovery but after years of flooding water breakthrough at the production wells was observed. This increased the water/oil ratio at the production wells. In order to enhance oil recovery again different techniques were investigated. Chemical enhanced oil recovery (EOR) methods are gaining attention all over the world for oil recovery. Surfactant injection is an effective way for interfacial tension (IFT) reduction and wettability reversal. In this study, 31 different types of chemicals were studied to specify the effects on oil production. This paper presents solubility of surfactants in brine, IFT and contact angle measurements, imbibition tests, and lastly core flooding experiments. Most of the chemicals were incompatible with Garzan formation water, which has high divalent ion concentration. In this case, the usage of 2-propanol as co-surfactant yielded successful results for stability of the selected chemical solutions. The results of the wettability test indicated that both tested cationic and anionic surfactants altered the wettability of the carbonate rock from oil-wet to intermediate-wet. The maximum oil recovery by imbibition test was reached when core was exposed 1-ethly ionic liquid after imbibition in formation water. Also, after core flooding test, it is concluded that considerable amount of oil can be recovered from Garzan reservoir by waterflooding alone if adverse effects of natural fractures could be eliminated.     

Tuning of emission by effect of local symmetry in BaLaLiWO6:Dy3+/Eu3+ for WLEDs

The luminescence center energy transfer, crystal field strength, and covalency are limited by the crystal structure of the host and subsequently affect the luminescence efficiency, color, and intensity. Here, we report an excellent red phosphor BaLaLiWO₆:0.40Eu³⁺ and the dependence between symmetry and luminous performance. A model for changing symmetry is drawn by analyzing the Coulomb potential and structure for the application of a double-perovskite phosphor BLLWO: Dy³⁺, Eu³⁺ in white light LEDs. The addition of Dy³⁺/Eu³⁺ makes the W-O bond formed by the B-site and oxygen ion longer and the Li-O bond shorter, and the difference between the eight octahedral around the A-site is reduced, increasing the symmetry of the A-site. Local symmetry was successfully modulated by changing the Eu³⁺ concentration to control the Y/B ratio of Dy³⁺ and the R/O ratio of Eu³⁺ and smoothly achieved (0.382, 0.373) warm white light color coordinate. The phosphor has excellent thermal stability and still has 92.3% intensity at 475 K. The above results show that the wavelength composition of the luminescence is tunable by changing the symmetry of the environment in which the doped ions are located. It applies to single hosts for the regulation of white light emission.     

Interface regulation effects on mechanical behavior of heterostructure Ti6Al4V/TiAl-based laminated composite sheets

Design of architectured composites with layered-ordered structure can solve the strength-toughness mismatch problem of structural materials. In the present study, heterostructure Ti6Al4V/TiAl laminated composite sheets with different thicknesses of interface layer and TiAl composite layer were successfully produced by hot-pressing technology. The effects of interface regulation and laminated structure on their mechanical properties, crack propagation, and fracture behavior were studied. The results indicated that compressive strength of the sheets increased with the decrease in interface thickness. Compressive strength of TiAl composite sheet with thicker composite layer reached 1481.55 MPa at the arrester orientation with sintering holding time of 40 min, which was 25.96% higher than that of the sheet obtained at 120 min. Analysis indicated that the interface area transferred stress through slip bands and through-interface cracks. Compressive strength at the divider orientation reached 1443.06 MPa, which was 45.78% higher than that of the sheet obtained at 120 min. In this case, the interface area transferred stress through slip bands and along-interface cracks. For TiAl composite sheets with thinner composite layer, compressive strength was further improved to 1631.01 MPa and 1594.66 MPa at the arrester and divider orientations with sintering holding time of 40 min, respectively. The ductile metal layer exerted a significant toughening effect. Both interface regulation and laminated structure transformation could enhance the hetero-deformation induced (HDI) strengthening and improve the comprehensive mechanical properties of the composite sheets.     

Genome-Wide Analyses of the Temperature-Responsive Genetic Loci of the Pectinolytic Plant Pathogenic Pectobacterium atrosepticum

Temperature is one of the critical factors affecting gene expression in bacteria. Despite the general interest in the link between bacterial phenotypes and environmental temperature, little is known about temperature-dependent gene expression in plant pathogenic Pectobacterium atrosepticum, a causative agent of potato blackleg and tuber soft rot worldwide. In this study, twenty-nine P. atrosepticum SCRI1043 thermoregulated genes were identified using Tn5-based transposon mutagenesis coupled with an inducible promotorless gusA gene as a reporter. From the pool of 29 genes, 14 were up-regulated at 18 °C, whereas 15 other genes were up-regulated at 28 °C. Among the thermoregulated loci, genes involved in primary bacterial metabolism, membrane-related proteins, fitness-corresponding factors, and several hypothetical proteins were found. The Tn5 mutants were tested for their pathogenicity in planta and for features that are likely to remain important for the pathogen to succeed in the (plant) environment. Five Tn5 mutants expressed visible phenotypes differentiating these mutants from the phenotype of the SCRI1043 wild-type strain. The gene disruptions in the Tn5 transposon mutants caused alterations in bacterial generation time, ability to form a biofilm, production of lipopolysaccharides, and virulence on potato tuber slices. The consequences of environmental temperature on the ability of P. atrosepticum to cause disease symptoms in potato are discussed.     

Cross-sector collaboration within Dutch flood risk governance: historical analysis of external triggers

ABSTRACT

This article synthesizes the literature on Dutch flood risk governance to analyze how external conditions shaped past and present dynamics of cross-sector collaboration for integrated flood risk management in the Netherlands. It traces the extent to which policy and legal frameworks, socio-economic circumstances, political realities, power relations and conflict situations have influenced attempts at collaboration between flood safety, spatial planning, environmental protection and other sectors. Despite the growing interdependences, existing power relations between the sectors are characterized by the dominance of the water sector. Hence, cross-sector collaboration can develop as long as it does not compromise flood safety.