Enhanced generation of VUV radiation by four-wave mixing in mercury using pulsed laser vaporization

The efficiency of a coherent VUV source at 125 nm, based on 2-photon resonant four-wave mixing in mercury vapor, has been enhanced by up to 2 orders of magnitude. This enhancement was obtained by locally heating a liquid Hg surface with a pulsed excimer laser, resulting in a high density vapor plume in which the nonlinear interaction occurred. Energies up to 5 μJ (1 kW peak power) have been achieved while keeping the overall Hg cell at room temperature, avoiding the use of a complex heat pipe. We have observed a strong saturation of the VUV yield when peak power densities of the fundamental beams exceed the GW/cm2 range, as well as a large intensity-dependant broadening (up to ~30 cm-1) of the two-photon resonance. The source has potential applications for high resolution interference lithography and photochemistry

Applications to regional tectonics: [chapter 11] /

Despite the interesting fundamental science of SERS, the promise of the technique as the basis for portable chemical sensors has not been fully realized yet. The reason for this gap between the science and engineering lies in the formidable nanofabrication challenges, which can be summed up as the need to prepare large numbers of very small yet highly controlled “hot spots” for the sensing device. In this work, we will describe newly-developed techniques for forming dense periodic two-dimensional plasmonic arrays for SERS sensing applications. These techniques utilize 157-nm interference lithography on a 90-nm pitch grid for 1) direct patterning of Ag nanocones and 2) convective assembly of Au nanoparticles into pre-patterned PMMA templates. Both fabrication methods result in a high areal density of plasmonic nano-gap “hot spots.” These arrays were used to achieve area-averaged Raman enhancement factor of adsorbed benzenethiol of ≥5 x 106. The fabrication process employed here is scalable to large areas, and therefore it can enable the manufacturing of highly sensitive chemical sensors that detect the greatly enhanced Raman scattering signal

Transcriptome Analysis of Tumor-Infiltrating Lymphocytes Identifies NK Cell Gene Signatures Associated With Lymphocyte Infiltration and Survival in Soft Tissue Sarcomas.

PurposeClinical successes using current T-cell based immunotherapies have been limited in soft tissue sarcomas (STS), while pre-clinical studies have shown evidence of natural killer (NK) cell activity. Since tumor immune infiltration, especially tumor-infiltrating lymphocytes, is associated with improved survival in most solid tumors, we sought to evaluate the gene expression profile of tumor and blood NK and T cells, as well as tumor cells, with the goal of identifying potential novel immune targets in STS.Experimental designUsing fluorescence-activated cell sorting, we isolated blood and tumor-infiltrating CD3-CD56+ NK and CD3+ T cells and CD45- viable tumor cells from STS patients undergoing surgery. We then evaluated differential gene expression (DGE) of these purified populations with RNA sequencing analysis. To evaluate survival differences and validate primary DGE results, we also queried The Cancer Genome Atlas (TCGA) database to compare outcomes stratified by bulk gene expression.ResultsSorted intra-tumoral CD3+ T cells showed significant upregulation of established activating (CD137) and inhibitory genes (TIM-3) compared to circulating T cells. In contrast, intra-tumoral NK cells did not exhibit upregulation of canonical cytotoxic genes (IFNG, GZMB), but rather significant DGE in mitogen signaling (DUSP4) and metabolic function (SMPD3, SLC7A5). Tumors with higher NK and T cell infiltration exhibited significantly increased expression of the pro-inflammatory receptor TLR4 in sorted CD45- tumor cells. TCGA analysis revealed that tumors with high TLR4 expression (P = 0.03) and low expression of STMN1 involved in microtubule polymerization (P < 0.001) were associated with significantly improved survival.ConclusionsUnlike T cells, which demonstrate significant DGE consistent with upregulation of both activating and inhibiting receptors in tumor-infiltrating subsets, NK cells appear to have more stable gene expression between blood and tumor subsets, with alterations restricted primarily to metabolic pathways. Increased immune cell infiltration and improved survival were positively correlated with TLR4 expression and inversely correlated with STMN1 expression within tumors, suggesting possible novel therapeutic targets for immunotherapy in STS