Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99673/1/8545_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99673/2/ange_201302313_sm_miscellaneous_information.pd

Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/1/8387_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/2/anie_201302313_sm_miscellaneous_information.pd

Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Low-carbon transportation scheduling of open-pit mine based on GWO-NSGA-Ⅱ hybrid algorithm

In order to improve truck transport efficiency, reduce carbon emissions and save transport costs in open-pit mines, pure electric trucks are taken as the research object. The objective function is transportation cost, total queuing time (including truck charging time, operation time and maintenance waiting time in the production process), and ore grade deviation. The constraints include the crushing capacity of the crushing site, mining capacity of the mining site, loading capacity, ore grade error limit, vehicle charging pile selection and charging limit. The optimization model of low carbon transportation scheduling of open-pit is established. The gray wolf optimization (GWO) and non-dominated sorting genetic algorithm-II (NSGA-II) have been used to solve the low-carbon transportation scheduling model for pure electric mining trucks in open-pit mines. The former is prone to get trapped in local optimum while the latter is likely to achieve a global optimum but converges slowly. In order to solve the above problems, a GWO-NSGA-II hybrid algorithm is proposed. The hybrid algorithm introduces three genetic operations of NSGA-II, selection, crossover and mutation, into the GWO algorithm to effectively prevent the algorithm from falling into local optimum. In order to improve the stability of the global convergence of the algorithm, hunting and attack operations are introduced into the elite retention strategy of NSGA-II. Five standard test functions are used to verify that the hybrid algorithm improves the stability while ensuring the convergence. The example analysis shows that, compared with NSGA-II and GWO, the hybrid algorithm improves the optimization speed by 48.7% and 27.1% respectively. The hybrid algorithm improves the optimization precision by 17.1% and 9.3% respectively. The hybrid algorithm reduces the number of trucks, carbon emissions, transportation distance and transportation costs

Performance and mechanism research of hierarchically structured Li-rich cathode materials for advanced lithium–ion batteries

The hierarchically structured cathode material Li1.165Mn0.501Ni0.167Co0.167O2 (LMNCO) is successfully synthesized via a facile ultrasonic-assisted co-precipitation method with a two-step heat treatment by adopting graphene and carbon nanotubes (CNTs) as functional framework and modified material. The structure and electrochemical performance degeneration mechanism were systematically investigated in this work. The obtained LMNCO microspheres possess a hierarchical nano-micropore structure assembled with nanosized building blocks, which originates from the oxidative decomposition of the transition metal carbonate precursor and carbonaceous materials accompanied with the release of CO2 (but still remain carbon residue). What’s more, the positive electrode exhibits enhanced specific capacities (276.6 mAh g−1 at 0.1 C), superior initial coulombic efficiency (80.3 %), remarkable rate capability (60.5 mAh g−1 at 10 C) and high Li+ diffusion coefficient (~10−9 cm2 s−1). The excellent performances can be attributed to the pore structure, small particle sizes, large specific surface area and enhanced electrical conductivity. (1 C = 250 mA g−1).Department of Electrical Engineerin