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The lack of predictive preclinical models is a fundamental barrier to translating knowledge about the molecular pathogenesis of cancer into improved therapies. Insertional mutagenesis (IM) in mice is a robust strategy for generating malignancies that recapitulate the extensive inter- and intra-tumoral genetic heterogeneity found in advanced human cancers. While the central role of "driver" viral insertions in IM models that aberrantly increase the expression of proto-oncogenes or disrupt tumor suppressors has been appreciated for many years, the contributions of cooperating somatic mutations and large chromosomal alterations to tumorigenesis are largely unknown. Integrated genomic studies of T lineage acute lymphoblastic leukemias (T-ALLs) generated by IM in wild-type (WT) and Kras mutant mice reveal frequent point mutations and other recurrent non-insertional genetic alterations that also occur in human T-ALL. These somatic mutations are sensitive and specific markers for defining clonal dynamics and identifying candidate resistance mechanisms in leukemias that relapse after an initial therapeutic response. Primary cancers initiated by IM and resistant clones that emerge during in vivo treatment close key gaps in existing preclinical models, and are robust platforms for investigating the efficacy of new therapies and for elucidating how drug exposure shapes tumor evolution and patterns of resistance.

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With the popularization of wide band-gap power modules in offshore wind power systems and water surface photovoltaic power stations, packaging materials face challenges of corrosion by salt, blended with high humidity. Copper-silver (Cu-Ag) composite sintered paste was proposed by researchers as a novel die-attach material for a lower cost and antielectromigration ability. However, the potential difference between copper and silver forms galvanic corrosion in a highhumidity environment, resulting in accelerated failure combined with salt mist. To further promote the application of composite sintered materials, a copper-silver double-sphere galvanic corrosion model based on finite element simulation was proposed in this paper. The relationship between corrosion rate and time of different Cu-Ag particle size combinations under different sintering degrees was predicted by initial exchange current density. Through the electrochemical characterization of the sintered samples, the optimal combination of materials was further discussed. The accuracy of the model was also verified. The conclusions obtained from both the experiments and simulation work provide guidance for future anti-corrosion analysis, as well as the reliability improvement of novel composite sintered materials.