Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.

Lonafarnib (SCH66336) is a farnesyl transferase inhibitor (FTI) that inhibits the post-translational lipid modification of H-

With the exploration of ferroelectric materials, researchers have a strong desire to explore the next generation of non‐volatile ferroelectric memory with silicon‐based epitaxy, high‐density storage, and algebraic operations. Herein, a silicon‐based memristor with an epitaxial vertically aligned nanostructures BaTiO3–CeO2 film based on La0.67Sr0.33MnO3/SrTiO3/Si substrate is reported. The ferroelectric polarization reversal is optimized through the continuous exploring of growth temperature, and the epitaxial structure is obtained, thus it improves the resistance characteristic, the multi‐value storage function of five states is achieved, and the robust endurance characteristic can reach 109 cycles. In the synapse plasticity modulated by pulse voltage process, the function of the spiking‐time‐dependent plasticity and paired‐pulse facilitation is simulated successfully. More importantly, the algebraic operations of addition, subtraction, multiplication, and division are realized by using fast speed pulse of the width ≈50 ns. Subsequently, a convolutional neural network is constructed for identifying the CIFAR‐10 dataset, to simulate the performance of the device; the online and offline learning recognition rate reach 90.03% and 92.55%, respectively. Overall, this study paves the way for memristors with silicon‐based epitaxial ferroelectric films to realize multi‐value storage, algebraic operations, and neural computing chip applications.

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