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.     

Degradation analysis of the core components of metal plate proton exchange membrane fuel cell stack under dynamic load cycles

The durability of metal plate proton exchange membrane fuel cell (PEMFC) stack is still an important factor that hinders its large-scale commercial application. In this paper, we have conducted a 1000 h durability test on a 1 kW metal plate PEMFC stack, and explored the degradation of the core components. After 1000 h of dynamic load cycles, the voltage decay percentage of the stack under the current densities of 1000 mA cm^?2 is 5.67%. By analyzing the scanning electron microscopy (SEM) images, the surfaces of the metal plates are contaminated locally by organic matter precipitated from the membrane electrode assembly (MEA). The SEM images of the catalyst coated membrane (CCM) cross section indicate that the MEA has undergone severe degradation, including the agglomeration of the catalyst layer, and the thinning and perforation of the PEM. These are the main factors that cause the rapid increase in hydrogen crossover flow rate and performance decay of the PEMFC stack.     

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。     

“灰绿”协同措施对银川市合流制溢流污染的影响EI北大核心CSCD

针对合流制管网系统在雨天溢流污染严重,造成城市水体黑臭现象的问题,以银川市某高密度城区合流制管网系统为例,基于SWMM模型,在短历时设计降雨和长历时设计降雨两种条件下,模拟分析了合流制溢流(CSO)调蓄池、雨污管道混错接改造、绿化带海绵化改造等“灰绿”协同措施对CSO污染的影响。结果表明:CSO调蓄池、雨污管道混错接改造、绿化带海绵化改造及“灰绿”措施结合4种方案在短历时、长历时设计降雨条件下,随着降水量的增加,溢流水量及溢流污染物负荷均增加,溢流削减率均逐渐减小,其中“灰绿”措施结合方案对溢流污染的削减效果最为显著;重现期小于5 a时,溢流水量削减率与溢流污染物负荷削减率基本达到80%;降雨条件为中雨时,污染物负荷削减率基本达到75%;重现期为20 a时,溢流水量削减率及TSS、COD、TP、NH^(+)_(4)-N负荷削减率分别达到64%、70%、70%、70%、70%;降雨条件为大雨时,溢流水量削减率及TSS、COD、TP、NH^(+)_(4)-N负荷削减率分别达到28%、32%、26%、31%、33%。     

基于跨临界CO2热泵的茶叶生产能源系统负荷削减潜力

乡村产业中的化石能源设备逐渐被电能技术替代，引起了乡村负荷波动增大、部分时段产生集中高负荷的问题。为了解决以上问题，将低品位清洁能源应用至乡村的茶叶生产中，针对烘茶全过程的工艺要求提出了跨临界CO₂热泵烘茶技术；并以某茶叶生产乡村为对象，对其代表台区的全年日用电量及产茶日负荷进行了分析，得出采用CO₂热泵烘茶后其负荷得到大幅度削减，整体可降低至原负荷的39.6%~46.8%，峰值负荷与平时负荷的比值由原本的13.6降至5.4~6.2。跨临界CO₂热泵应用至农产品生产中可有效缓解乡村供电压力。     

Thermomechanical stability and inelastic energy dissipation as durability criteria for fuel cell gas diffusion media with pre-assembly effects

In this article, pre-assembly hot-press pressure and thermal expansion effects in gas-diffusion layers (GDLs) are addressed to explore the practicalities of the constitutive model reported in the companion article. A facile technique is proposed to include deformation history dependent residual strain effects. The model is implemented in the numerical environment and compared with widely followed conventional models such as isotropic and orthotropic material models. With the normal and accelerated thermal expansion effects no significant variation in stresses or strains is reported with the compressible GDL model in contrast to the conventional incompressible form of the GDL model. The present work identifies the critical differences with advanced and extended variants of the model along with conventional GDL material models in terms of planar stress/strain distribution and the membrane response. Finally, the model is simulated for micro-cyclic stress loads of varying amplitudes that imitate the real working conditions of fuel cell. The inelastic energy dissipation in GDLs is predicted using the proposed model, which is utilized further to distinguish the safe (elastic) and unsafe (inelastic shakedown) operating limits. The inelastic collapse of GDLs is shown to be a active function of high amplitude micro-cyclic load with high initial clamping load.     

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.     

Effect of heat treatment and zircon addition on the properties of low-cement castables based on recycled alumina grog

In this investigation, low-cement castables were prepared using 70% alumina grog aggregates obtained from crushed alumina brick waste. The aggregates were thermally treated at 1550 °C for 3 h. Four types of low-cement castables were prepared with various types of aggregates (alumina grog with or without thermal treatment) and fillers (with or without zircon addition), and they were evaluated in terms of their physical, thermal, and chemical properties. Microstructural analysis via scanning electron microscopy (SEM) was performed on the castables before and after slag attack. Compared to the other fabricated castables, the thermally treated alumina grog castables with zircon showed better physical properties, such as a higher bulk density, cold crushing strength, and modulus of rupture and a lower apparent porosity and water absorption. In addition, they had a higher positive linear thermal expansion, refractoriness under load, permanent linear change, and hot modulus of rupture. The results of the SEM with energy dispersive X-ray analysis of the prepared castables confirmed that the mullite and anorthite phases were predominant when zircon was not added and the zircon–mullite phase additionally appeared upon the incorporation of zircon. A quantitative elemental analysis via X-ray fluorescence spectroscopy was employed to determine the composition of the castables. X-ray diffraction analysis showed that the alumina grog castables had a high mullite and low anorthite content, and the thermally treated alumina grog had a high anorthite, low mullite, and high zircon content. The improvement in the mechanical and thermo-mechanical properties of the castables with thermally treated alumina grog and added zircon can be attributed to the formation of the zircon–mullite phase with a low mullite phase content.     

Generation,validation and application of dynamic load profiles in flow measurement using cavitating Herschel–Venturi nozzles

Today, utility meters for water are tested for measurement behavior at stable operating conditions at specified flow rates as part of the approval process. The measurement error that occurs during start and stop or when changing between flow rates may not be taken into account. In addition, there are new technologies whose measuring behavior under real-world conditions is only known to a limited extend. To take these facts into account, a new method has been developed and tested to determine the measurement behavior of water meters under dynamic load profiles as they occur in the real application. For this purpose, a test rig for flow rate measurement was extended by a cavitation nozzle apparatus and the generation of dynamic load profiles was validated. For the cavitation nozzles used, possible factors influencing the flow rate, such as temperature and purity of the water as well as the upstream pressure were investigated. Using different types of domestic water meters, the applicability of the dynamic test procedure was demonstrated and the measurement behavior of the meters was characterised.     

Simulations of NBI fast ion loss in the presence of toroidal field ripple on EAST

NBI fast ion losses in the presence of the toroidal field ripple on EAST have been investigated by using the orbit code GYCAVA and the NBI code TGCO. The ripple effect was included in the upgraded version of the GYCAVA code. It is found that loss regions of NBI fast ions are mainly on the low field side near the edge in the presence of ripple. For co-current NBIs, the synergy effect of ripple and Coulomb collision on fast ion losses is dominant, and fast trapped ions located on the low field side are easily lost. The ripple well loss and the ripple stochastic loss of fast ions have been identified from the heat loads of co-current NBI fast ions. The ripple stochastic loss and the collisioninduced loss are much larger than the ripple well loss. Heat loads of lost fast ions are mainly localized on the right side of the radio frequency wave antennas from the inside view toward the first wall. For counter-current NBIs, the first orbit loss due to the magnetic drift is the dominant loss channel. In addition, fast ion loss fraction with ripple and collision for each NBI linearly increases with the effective charge number, which is related to the pitch angle scattering effect.