Cancer research has previously focused on the identification of specific genes and pathways responsible for cancer initiation and progression based on the prevailing viewpoint that cancer is caused by a stepwise accumulation of genetic aberrations. This viewpoint, however, is not consistent with the clinical finding that tumors display high levels of genetic heterogeneity and distinctive karyotypes. We show that chromosomal instability primarily generates stochastic karyotypic changes leading to the random progression of cancer. This was accomplished by tracing karyotypic patterns of individual cells that contained either defective genes responsible for genome integrity or were challenged by onco-proteins or carcinogens that destabilized the genome. Analysis included the tracing of patterns of karyotypic evolution during different stages of cellular immortalization. This study revealed that non-clonal chromosomal aberrations (NCCAs) (both aneuploidy and structural aberrations) and not recurrent clonal chromosomal aberrations (CCAs) are directly linked to genomic instability and karyotypic evolution. Discovery of "transitional CCAs" during in vitro immortalization clearly demonstrates that karyotypic evolution in solid tumors is not a continuous process. NCCAs and their dynamic interplay with CCAs create infinite genomic combinations leading to clonal diversity necessary for cancer cell evolution. The karyotypic chaos observed within the cell crisis stage prior to establishment of the immortalization further supports the ultimate importance of genetic aberrations at the karyotypic or genome level. Therefore, genomic instability generated NCCAs are a key driving force in cancer progression. The dynamic relationship between NCCAs and CCAs provides a mechanism underlying chromosomal based cancer evolution and could have broad clinical applications.
The establishment of the correct conceptual framework is vital to any scientific discipline including cancer research. Influenced by hematologic cancer studies, the current cancer concept focuses on the stepwise patterns of progression as defined by specific recurrent genetic aberrations. This concept has faced a tough challenge as the majority of cancer cases follow non-linear patterns and display stochastic progression. In light of the recent discovery that genomic instability is directly linked to stochastic non-clonal chromosome aberrations (NCCAs), and that cancer progression can be characterized as a dynamic relationship between NCCAs and recurrent clonal chromosome aberrations (CCAs), we propose that the dynamics of NCCAs is a key element for karyotypic evolution in solid tumors. To support this viewpoint, we briefly discuss various basic elements responsible for cancer initiation and progression within an evolutionary context. We argue that even though stochastic changes can be detected at various levels of genetic organization, such as at the gene level and epigenetic level, it is primarily detected at the chromosomal or genome level. Thus, NCCA-mediated genomic variation plays a dominant role in cancer progression. To further illustrate the involvement of NCCA/CCA cycles in the pattern of cancer evolution, four cancer evolutionary models have been proposed based on the comparative analysis of karyotype patterns of various types of cancer.
Coefficient of restitution is regarded as a dominating parameter in rockfall research. Generally, small-scale experiments were developed without considering interactions between boulder and slope. However, preimpact moving statuses are essential to evaluate rockfall behaviors. To reveal the effect of preimpact interactions on coefficient of restitution, energy dissipation considering initial velocity, surface type, and slope angle is executed based on medium-scale tests. The results show that (1) as the inclination of initial velocity, higher rebound height, and the declining normal coefficient of restitution occur, a determinable linear function could demonstrate relationships among energy dissipation and all coefficient of restitution; when initial velocity exceeds 5 m/s, the recovery ability shows and produces an increasing trend with respect to the variation of kinematic coefficient of restitution and kinetic energy coefficient of restitution. (2) As the surface material varies, slope hardness and rebound ability influence normal coefficient of restitution, and the surface roughness and rotation feature dominate tangential coefficient of restitution; considering preimpact slope and boulder interactions, four types of coefficient of restitution follow declining trend with different material sequence. (3) Slope angle affects normal coefficient of restitution, and tangential coefficient of restitution relatively descends 18% and inclines 10% when the angle ranges from 30° to 75°; regarding preimpact moving status, it differs from bounce times. The correlation between preimpact energy dissipation and four coefficients of restitution can be represented by the same decreasing linear function, when increasing the slope angle.
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