Surface effects of vapour-liquid-solid driven Bi surface droplets formed during molecular-beam-epitaxy of GaAsBi

Herein we investigate a (001)-oriented GaAs1−xBix/GaAs structure possessing Bi surface droplets capable of catalysing the formation of nanostructures during Bi-rich growth, through the vapourliquid-solid mechanism. Specifically, self-aligned “nanotracks” are found to exist trailing the Bi droplets on the sample surface. Through cross-sectional high-resolution transmission electron microscopy the nanotracks are revealed to in fact be elevated above surface by the formation of a subsurface planar nanowire, a structure initiated mid-way through the molecular-beam-epitaxy growth and embedded into the epilayer, via epitaxial overgrowth. Electron microscopy studies also yield the morphological, structural, and chemical properties of the nanostructures. Through a combination of Bi determination methods the compositional profile of the film is shown to be graded and inhomogeneous. Furthermore, the coherent and pure zincblende phase property of the film is detailed. Optical characterisation of features on the sample surface is carried out using polarised micro-Raman and micro-photoluminescence spectroscopies. The important light producing properties of the surface nanostructures are investigated through pump intensity-dependent micro PL measurements, whereby relatively large local inhomogeneities are revealed to exist on the epitaxial surface for important optical parameters. We conclude that such surface effects must be considered when designing and fabricating optical devices based on GaAsBi alloys

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Strongly interacting photons in asymmetric quantum well via resonant tunneling

10.1364/OE.20.008485Optics Express2088485-849

Copper ionophore elesclomol selectively targets GNAQ/11-mutant uveal melanoma

Unlike cutaneous melanoma, uveal melanoma (UM) is characterized by mutations in GNAQ and GNA11 and remains a fatal disease because there is essentially no effective targeted therapy or immunotherapy available. We report the discovery of the copper ionophore elesclomol as a GNAQ/11-specific UM inhibitor. Elesclomol was identified in a differential cytotoxicity screen of an in-house tool compound library, and its in vivo pharmacological efficacy was further confirmed in zebrafish and mouse UM models. Mechanistically, elesclomol transports copper to mitochondria and produces a large amount of reactive oxygen species (ROS) as Cu(II) is reduced to Cu(I) in GNAQ/11-mutant UM cells, which selectively activates LATS1 kinase in the Hippo signaling pathway and consequently promotes YAP phosphorylation and inhibits its nuclear accumulation. The inactivation of YAP downregulates the expression of SNAI2, which in turn suppresses the migration of UM cells. These findings were cross validated by our clinical observation that YAP activation was found specifically in UM samples with a GNAQ/11 mutation. Furthermore, addition of binimetinib, a MEK inhibitor, to elesclomol increased its synthetic lethality to GNAQ/11-mutant UM cells, thereby overriding drug resistance. This effect was confirmed in an orthotopic xenograft model and in a patient-derived xenograft model of UM. These studies reveal a novel mechanistic basis for repurposing elesclomol by showing that copper homeostasis is a GNAQ/11-specific vulnerability in UM. Elesclomol may provide a new therapeutic path for selectively targeting malignant GNAQ/11-mutant UM.Ophthalmic researc