The collision of a probe laser pulse with a relativistic ionization front is analyzed via two-dimensional ray-tracing theory and simulations. It is shown that collisions in higher dimensions lead to new regimes for the frequency upshift of the probe photons; the frequency upshift can be considerably higher for particular collision angles that maximize the interaction length with the ionization front gradient. Finite ionization fronts also lead to angle-dependent frequency upshifts, thus acting as diffraction gratings.
Sequencing studies of Diffuse Large B Cell Lymphoma (DLBCL) have identified hundreds of recurrently altered genes. However, it remains largely unknown whether and how these mutations may contribute to lymphomagenesis, either individually or in combination.Existing strategies to address this problem predominantly utilize cell lines, which are limited by their initial characteristics and subsequent adaptions to prolonged in vitro culture. Here, we describe a novel co-culture system that enables the ex vivo expansion and viral transduction of primary human germinal center B cells. The incorporation of CRISPR/Cas9 technology enables high-throughput functional interrogation of genes recurrently mutated in DLBCL. Using a backbone of BCL2 with either BCL6 or MYC we have identified cooperating oncogenes that promote growth and survival, or even full transformation into synthetically engineered models of DLBCL. The resulting tumors can be expanded and sequentially transplanted in vivo, providing a scalable platform to test putative cancer genes and for the creation of mutation-directed, bespoke lymphoma models.
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