Model for quantitative tip-enhanced spectroscopy and the extraction of nanoscale-resolved optical constants

Near-field infrared spectroscopy by elastic scattering of light from a probe tip resolves optical contrasts in materials at dramatically sub-wavelength scales across a broad energy range, with the demonstrated capacity for chemical identification at the nanoscale. However, current models of probe-sample near-field interactions still cannot provide a sufficiently quantitatively interpretation of measured near-field contrasts, especially in the case of materials supporting strong surface phonons. We present a model of near-field spectroscopy derived from basic principles and verified by finite-element simulations, demonstrating superb predictive agreement both with tunable quantum cascade laser near-field spectroscopy of SiO$_2$ thin films and with newly presented nanoscale Fourier transform infrared (nanoFTIR) spectroscopy of crystalline SiC. We discuss the role of probe geometry, field retardation, and surface mode dispersion in shaping the measured near-field response. This treatment enables a route to quantitatively determine nano-resolved optical constants, as we demonstrate by inverting newly presented nanoFTIR spectra of an SiO$_2$ thin film into the frequency dependent dielectric function of its mid-infrared optical phonon. Our formalism further enables tip-enhanced spectroscopy as a potent diagnostic tool for quantitative nano-scale spectroscopy.Comment: 19 pages, 9 figure

Mesoscale acid deposition modeling studies

The work performed in support of the EPA/DOE MADS (Mesoscale Acid Deposition) Project included the development of meteorological data bases for the initialization of chemistry models, the testing and implementation of new planetary boundary layer parameterization schemes in the MASS model, the simulation of transport and precipitation for MADS case studies employing the MASS model, and the use of the TASS model in the simulation of cloud statistics and the complex transport of conservative tracers within simulated cumuloform clouds. The work performed in support of the NASA/FAA Wind Shear Program included the use of the TASS model in the simulation of the dynamical processes within convective cloud systems, the analyses of the sensitivity of microburst intensity and general characteristics as a function of the atmospheric environment within which they are formed, comparisons of TASS model microburst simulation results to observed data sets, and the generation of simulated wind shear data bases for use by the aviation meteorological community in the evaluation of flight hazards caused by microbursts

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies

Phenology of western flower thrips Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) on plant species in and near apple orchards in Washington State

Both orchard and adjacent native vegetation harboured adult western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), from early spring until fall. Frankliniella occidentalis made up the great majority of adults collected in flowers of most plant species sampled, including apple. Other species found on apple flowers included Anaphothrips obscurus Muller, which lives on grasses, and Thrips brevipilosus Moulton. A mixture of thrips species, including F. occidentalis, Scirtothrzps citri (Moulton), Thrips tabaci Lindeman, and Thrips treherni Preisner, occurred on apple shoots. Thrips were found in orchards as early as green tip (early April), with the highest concentrations of F. occidentalis in shoots occurring in June and July. Thrips declined in late summer as shoots formed dormant buds; however, some F. occidentalis adults were still found in early September. Five common woody plants and forbs selected for sampling in the sagebrush-steppe habitat had F. occidentalis adults present, especially during bloom. Western flower thrips can exploit open flowers or young shoots from spring through fall in native vegetation because of the diversity of plants and their different growth habits

The Kondo Dynamics of YbIn(1-x)AgxCu4

We present an infrared/optical study of the dynamics of the strongly correlated electron system YbIn(1-x)AgxCu4 as a function of doping and temperature for x ranging from 0 to 1, and T between 20 and 300 K. This study reveals information about the unusual phase transition as well as the phases themselves. Scaling relations emerge from the data and are investigated in detail using a periodic Anderson model based calculation. We also provide a picture in which to view both the low and high-energy x-dependent features of the infrared data, including identification of high energy, temperature dependent features.Comment: 12 pages, 11 figures, submitted Phys. Rev.

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement