Dynamics of Citrate Coordination on Gold Nanoparticles Under Low Specific Power Laser-Induced Heating.

SERS evolution recorded over a drop-coated coffee-ring pattern of citrate-capped gold colloids was investigated as a function of time under low-specific laser power. Spectral changes caused by plasmon-induced reaction could not be detected, but a long-term transient original spectral profile showing additional lines was observed. We performed deep qualitative and quantitative SERS intensity variation analysis based on the complementary use of extreme deviation and cross-correlation statistics, which provided further insights on the behavior of citrate-capping layers of gold nanoparticles upon laser illumination. More precisely, the cross-correlation analysis made possible to follow the so-called individual events denoting particular resonance structures, in which groups of modes were assigned to an evolution of citrate coordination on gold surface driven by photo-activation. As a consequence, the detection limit was increased and new lines were related to the presence of a very low amount of dicarboxy-acetone (DCA), which was already present in the system.

ATR represents a therapeutic vulnerability in clear cell renal cell carcinoma.

Metastatic clear cell renal cell carcinomas (ccRCCs) are resistant to DNA-damaging chemotherapies, limiting therapeutic options for patients whose tumors are resistant to tyrosine kinase inhibitors and/or immune checkpoint therapies. Here we show that mouse and human ccRCCs were frequently characterized by high levels of endogenous DNA damage and that cultured ccRCC cells exhibited intact cellular responses to chemotherapy-induced DNA damage. We identify that pharmacological inhibition of the DNA damage-sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) with the orally administered, potent, and selective drug M4344 (gartisertib) induced antiproliferative effects in ccRCC cells. This effect was due to replication stress and accumulation of DNA damage in S phase. In some cells, DNA damage persisted into subsequent G2/M and G1 phases, leading to the frequent accumulation of micronuclei. Daily single-agent treatment with M4344 inhibited the growth of ccRCC xenograft tumors. M4344 synergized with chemotherapeutic drugs including cisplatin and carboplatin and the poly(ADP-ribose) polymerase inhibitor olaparib in mouse and human ccRCC cells. Weekly M4344 plus cisplatin treatment showed therapeutic synergy in ccRCC xenografts and was efficacious in an autochthonous mouse ccRCC model. These studies identify ATR inhibition as a potential novel therapeutic option for ccRCC.

Trajectory selection in high harmonic generation by controlling the phase between orthogonal two-color fields.

We demonstrate control of short and long quantum trajectories in high harmonic emission through the use of an orthogonally polarized two-color field. By controlling the relative phase ϕ between the two fields we show via classical and quantum calculations that we can steer the two-dimensional trajectories to return, or not, to the core and so control the relative strength of the short or long quantum trajectory contribution. In experiments, we demonstrate that this leads to robust control over the trajectory contributions using a drive field from a femtosecond laser composed of the fundamental ω at 800 nm (intensity ∼1.2×10(14) W cm(-2)) and its weaker orthogonally polarized second harmonic 2ω (intensity ∼0.3×10(14) W cm(-2)) with the relative phase between the ω and 2ω fields varied simply by tilting a fused silica plate. This is the first demonstration of short and long quantum trajectory control at the single-atom level.

Enhancement of high harmonics generated by field steering of electrons in a two-color orthogonally polarized laser field.

We demonstrate enhancement by 1 order of magnitude of the high-order harmonics generated in argon by combining a fundamental field at 1300 nm (10(14) W cm(-2)) and its orthogonally polarized second harmonic at 650 nm (2 × 10(13) W cm(-2)) and by controlling the relative phase between them. This extends earlier work by ensuring that the main effect is the combined field steering the electron trajectory with negligible contribution from multiphoton effects compared to the previous schemes with 800/400 nm fields. We access a broad energy range of harmonics (from 20 eV to 80 eV) at a low laser intensity (far below the ionization saturation limit) and observe deep modulation of the harmonic yield with a period of π in the relative phase. Strong field theoretical analysis reveals that this is principally due to the steering of the recolliding electron wave packet by the two-color field. Our modeling also shows that the atto chirp can be controlled, leading to production of shorter pulses.