7 research outputs found
Ultrafast Plasmonic Control of Second Harmonic Generation
Efficient frequency conversion techniques are crucial to the development of
plasmonic metasurfaces for information processing and signal modulation. In
principle, nanoscale electric-field confinement in nonlinear materials enables
higher harmonic conversion efficiencies per unit volume than those attainable
in bulk materials. Here we demonstrate efficient second-harmonic generation
(SHG) in a serrated nanogap plasmonic geometry that generates steep electric
field gradients on a dielectric metasurface. An ultrafast pump is used to
control plasmon-induced electric fields in a thin-film material with inversion
symmetry that, without plasmonic enhancement, does not exhibit an an even-order
nonlinear optical response. The temporal evolution of the plasmonic near-field
is characterized with ~100as resolution using a novel nonlinear interferometric
technique. The ability to manipulate nonlinear signals in a metamaterial
geometry as demonstrated here is indispensable both to understanding the
ultrafast nonlinear response of nanoscale materials, and to producing active,
optically reconfigurable plasmonic device
Efficient forward second-harmonic generation from planar archimedean nanospirals
The enhanced electric field at plasmonic resonances in nanoscale antennas can
lead to efficient harmonic generation, especially when the plasmonic geometry is
asymmetric on either inter-particle or intra-particle levels. The planar
Archimedean nanospiral offers a unique geometrical asymmetry for second-harmonic
generation (SHG) because the SHG results neither from arranging centrosymmetric
nanoparticles in asymmetric groupings, nor from non-centrosymmetric
nanoparticles that retain a local axis of symmetry. Here, we report forward SHG
from planar arrays of Archimedean nanospirals using 15 fs pulses from a
Ti:sapphire oscillator tuned to 800 nm wavelength. The measured
harmonic-generation efficiencies are 2.6·10−9, 8·10−9 and
1.3·10−8 for left-handed circular, linear, and right-handed
circular polarizations, respectively. The uncoated nanospirals are stable under
average power loading of as much as 300 μWper nanoparticle. The nanospirals also
exhibit selective conversion between polarization states. These experiments show
that the intrinsic asymmetry of the nanospirals results in a highly efficient,
two-dimensional harmonic generator that can be incorporated into metasurface
optics
Keap1 loss promotes Kras-driven lung cancer and results in a dependence on glutaminolysis
Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein1. One approach to addressing this challenge is to define frequently co-occurring mutations with KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function (LOF) mutations in Kelch-like ECH-associated protein 1 (KEAP1)2-4, a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response5-10. The high frequency of mutations in KEAP1 suggests an important role for the oxidative stress response in lung tumorigenesis. Using a CRISPR/Cas9-based approach in a mouse model of Kras-driven LUAD we examined the effects of Keap1 loss in lung cancer progression. We show that loss of Keap1 hyper-activates Nrf2 and promotes Kras-driven LUAD. Combining CRISPR/Cas9-based genetic screening and metabolomic analyses, we show that Keap1/Nrf2-mutant cancers are dependent on increased glutaminolysis, and this property can be therapeutically exploited through the pharmacological inhibition of glutaminase. Finally, we provide a rationale for sub-stratification of human lung cancer patients with KRAS-KEAP1 or -NRF2-mutant tumors as likely to respond to glutaminase inhibition