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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.  相似文献   
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Abstract

This paper explores automatic generation control (AGC) of a more realistic 2-area multi-source power system comprising hydro, thermal, gas, and wind energy sources-based power plants in each control area. The wind power plants (WPPs) have been growing continuously worldwide due to their inherent feature of providing eco-friendly sustainable energy. But, operations of WPPs are associated with system stability problems due to lack of inertia. However, WPPs do not participate in the elimination of mismatch between generation and demand by AGC but disturbance can be injected by the WPPs due to the stochastic nature of wind energy. An optimal controller based on full state feedback control theory is designed to conduct the study. The system dynamic performance analysis is carried out for 1% step load disturbance in corresponding control areas. It is observed that the system dynamic graphs of deviation in area frequency and tie-line power are significantly improved with the implementation of optimal AGC controller compared to GA tuned classical controller. It has also been shown that the WPPs aid the increase in load disturbance when the input wind power reduces but it negates the effect of increase in load disturbance for increase in wind energy to the WPPs.  相似文献   
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Wireless Networks - Wireless body area network (WBAN) routing protocols are primarily designed for improvement of network performance parameters such as network lifetime, throughput and latency....  相似文献   
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This paper presents a study of the effects of harsh outdoor weather and warm sea water on the tensile behavior of Glass-Fiber Reinforced Vinylester (GFRV) pipe materials destined for sea water handling and transportation. The effect of Dhahran’s outdoor weather for exposure periods ranging from 3 to 36 months revealed an improvement in tensile strength when compared with the as received GFRV sample. A significant increasing trend of tensile strength from 3 to 12 months was noted. This is attributed mainly to the post curing effects resulting in higher cross linking density. After 12 months of exposure the tensile strength showed a decreasing trend, but remaining still higher than the average tensile strength of as received (baseline) GFRV sample. Similar results of enhanced tensile strength were noted after immersion of GFRV pipes in warm Gulf sea water for 12 months. Fractographic analysis was performed on the tensile tested GFRV samples using optical microscope followed by scanning electron microscope (SEM). The characterization of the controlling failure mechanisms involved from fracture initiation to fracture propagation through the gage section of the specimen were predicted and were justified by correlating the optical and SEM pictures.  相似文献   
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A parametric study of pyrolysis and steam gasification of rice straw (RS) was performed to investigate the effect of the presence of K2CO3 on the behavior of gas evolution, gas component distribution, pyrolysis/gasification reactivity, the quality and volume of synthetic gas. During pyrolysis, with the increase in K2CO3 content in RS (i) the instantaneous CO2 concentration was increased while CO concentration was relatively stable; (ii) the yield of CO2 and H2 increased on the cost of CH4. During steam gasification of RS, with the increase in K2CO3 content in RS (i) the instantaneous concentration of CO2 and H2 increased while instantaneous concentration of CO and CH4 decreased; (ii) the yield of CO2 and H2 production and total yield increased; and (iii) yield of CO and CH4 production followed the order: 9% K2CO3 RS<6% K2CO3 RS<raw RS<3% K2CO3 RS<water-leached RS. Water-leached RS showed the highest pyrolysis reactivity, while stream gasification reactivity was proportional to K2CO3 content in RS. The results of this study reveal that the presence of K2CO3 during pyrolysis and steam gasification of RS effectively improves production of H2 rich gas.  相似文献   
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Journal of Computational Electronics - Nanosheet field effect transistors (NS-FET) are a most promising candidate for next-generation semiconductor devices for sub-7-nm technology nodes. This work...  相似文献   
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Journal of Porous Materials - Aerogel is a special type of porous material with many outstanding physical and chemical properties, such as low density, high porosity, high surface area, and...  相似文献   
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This paper presents a study of the effects of harsh outdoor weather and warm sea water on the tensile behavior of Glass-Fiber Reinforced Vinylester (GFRV) pipe materials destined for sea water handling and transportation. The effect of Dhahran’s outdoor weather for exposure periods ranging from 3 to 36 months revealed an improvement in tensile strength when compared with the as received GFRV sample. A significant increasing trend of tensile strength from 3 to 12 months was noted. This is attributed mainly to the post curing effects resulting in higher cross linking density. After 12 months of exposure the tensile strength showed a decreasing trend, but remaining still higher than the average tensile strength of as received (baseline) GFRV sample. Similar results of enhanced tensile strength were noted after immersion of GFRV pipes in warm Gulf sea water for 12 months. Fractographic analysis was performed on the tensile tested GFRV samples using optical microscope followed by scanning electron microscope (SEM). The characterization of the controlling failure mechanisms involved from fracture initiation to fracture propagation through the gage section of the specimen were predicted and were justified by correlating the optical and SEM pictures.  相似文献   
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