Pharmacologic Activities of 3’-Hydroxypterostilbene: Cytotoxic, Anti- Oxidant, Anti-Adipogenic, Anti-Inflammatory, Histone Deacetylase and Sirtuin 1 Inhibitory Activity

Purpose: Delineate the selected pharmacodynamics of a naturally occurring stilbene 3’- Hydroxypterostilbene. Objective: Characterize for the first time the pharmacodynamics bioactivity in several in-vitro assays with relevant roles in heart disease, inflammation, cancer, and diabetes etiology and pathophysiology. Methods: 3’-Hydroxypterostilbene was studied in in-vitro assays to identify possible bioactivity. Results: 3’-Hydroxypterostilbene demonstrated anti-oxidant, anti-inflammatory, cytotoxic, antiadipogenic, histone deacetylase, and sirtuin-1 inhibitory activity. Conclusions: The importance of understanding individual stilbene pharmacologic activities were delineated. Small changes in chemical structure of stilbene compounds result in significant pharmacodynamic differences

The High Arctic in Extreme Winters: Vortex, Temperature, and MLS and ACE-FTS Trace Gas Evolution

The first three Canadian Arctic Atmospheric Chemistry Experiment (ACE) Validation Campaigns at Eureka (80° N, 86° W) were during two extremes of Arctic winter variability: Stratospheric sudden warmings (SSWs) in 2004 and 2006 were among the strongest, most prolonged on record; 2005 was a record cold winter. New satellite measurements from ACE-Fourier Transform Spectrometer (ACE-FTS), Sounding of the Atmosphere using Broadband Emission Radiometry, and Aura Microwave Limb Sounder (MLS), with meteorological analyses and Eureka lidar and radiosonde temperatures, are used to detail the meteorology in these winters, to demonstrate its influence on transport and chemistry, and to provide a context for interpretation of campaign observations. During the 2004 and 2006 SSWs, the vortex broke down throughout the stratosphere, reformed quickly in the upper stratosphere, and remained weak in the middle and lower stratosphere. The stratopause reformed at very high altitude, above where it could be accurately represented in the meteorological analyses. The 2004 and 2006 Eureka campaigns were during the recovery from the SSWs, with the redeveloping vortex over Eureka. 2005 was the coldest winter on record in the lower stratosphere, but with an early final warming in mid-March. The vortex was over Eureka at the start of the 2005 campaign, but moved away as it broke up. Disparate temperature profile structure and vortex evolution resulted in much lower (higher) temperatures in the upper (lower) stratosphere in 2004 and 2006 than in 2005. Satellite temperatures agree well with Eureka radiosondes, and with lidar data up to 50–60 km. Consistent with a strong, cold upper stratospheric vortex and enhanced radiative cooling after the SSWs, MLS and ACE-FTS trace gas measurements show strongly enhanced descent in the upper stratospheric vortex during the 2004 and 2006 Eureka campaigns compared to that in 2005

From LIMS to OMPS-LP: Limb Ozone Observations for Future Reanalyses

High vertical resolution and accuracy of ozone data from satellite-borne limb sounders has made them an invaluable tool in scientific studies of the middle and upper atmosphere. However, it was not until recently that these measurements were successfully incorporated in atmospheric reanalyses: of the major multidecadal reanalyses only ECMWF's (European Centre for Medium-Range Weather Forecasts') ERA (ECMWF Re-Analysis)-Interim/ERA5 and NASA's MERRA-2 (Modern-Era Retrospective Analysis for Research and Applications-2) use limb ozone data. Validation and comparison studies have demonstrated that the addition of observations from the Microwave Limb Sounder (MLS) on EOS (Earth Observing System) Aura greatly improved the quality of ozone fields in MERRA-2 making these assimilated data sets useful for scientific research. In this presentation, we will show the results of test experiments assimilating retrieved ozone from the Limb Infrared Monitor of the Stratosphere (LIMS, 1978/1979) and Ozone Mapping Profiler Suite Limb Profiler (OMPS-LP, 2012 to present). Our approach builds on the established assimilation methodology used for MLS in MERRA-2 and, in the case of OMPS-LP, extends the excellent record of MLS ozone assimilation into the post-EOS era in Earth observations. We will show case studies, discuss comparisons of the new experiments with MERRA-2, strategies for bias correction and the potential for combined assimilation of multiple limb ozone data types in future reanalyses for studies of multidecadal stratospheric ozone changes including trends

Atmospheric Effects of Energetic Particle Precipitation in the Arctic Winter 1978-1979 Revisted

[1] The Limb Infrared Monitor of the Stratosphere (LIMS) measured polar stratospheric enhancements of NO2 mixing ratios due to energetic particle precipitation (EPP) in the Arctic winter of 1978–1979. Recently reprocessed LIMS data are compared to more recent measurements from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and the Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) to place the LIMS measurements in the context of current observations. The amount of NOx (NO + NO2) entering the stratosphere that has been created by EPP in the mesosphere and lower thermosphere (EPP-NOx) has been quantified for the 1978–1979 and 2002–2003 through 2008–2009 Arctic winters. The NO2 enhancements in the LIMS data are similar to those in MIPAS and ACE-FTS data in the Arctic winters of 2002–2003, 2004–2005, 2006–2007, and 2007–2008. The largest enhancement by far is in 2003–2004 (∼2.2 Gmol at 1500 K), which is attributed to a combination of elevated EPP and unusual dynamics that led to strong descent in the upper stratosphere/lower mesosphere in late winter. The enhancements in 2005–2006 and 2008–2009, during which large stratospheric NOx enhancements were caused by a dynamical situation similar to that in 2003–2004, are larger than in all the other years (except 2003–2004) at 3000 K. However, by 2000 K the enhancements in 2005–2006 (2008–2009) are on the same order of magnitude as (smaller than) all other years. These results highlight the importance of the timing of the descent in determining the potential of EPP-NOx for reaching the middle stratosphere

Thermal excitation of heavy nuclei with 5-15 GeV/c antiproton, proton and pion beams

Excitation-energy distributions have been derived from measurements of 5.0-14.6 GeV/c antiproton, proton and pion reactions with $^{197}$Au target nuclei, using the ISiS 4$\pi$ detector array. The maximum probability for producing high excitation-energy events is found for the antiproton beam relative to other hadrons, $^3$He and $\bar{p}$ beams from LEAR. For protons and pions, the excitation-energy distributions are nearly independent of hadron type and beam momentum above about 8 GeV/c. The excitation energy enhancement for $\bar{p}$ beams and the saturation effect are qualitatively consistent with intranuclear cascade code predictions. For all systems studied, maximum cluster sizes are observed for residues with E*/A $\sim$ 6 MeV.Comment: 14 pages including 5 figures and 1 table. Accepted in Physics Letter B. also available at http://nuchem.iucf.indiana.edu

Vorinostat with Sustained Exposure and High Solubility in Poly(ethylene glycol)-b-poly(DL-lactic acid) Micelle Nanocarriers: Characterization and Effects on Pharmacokinetics in Rat Serum and Urine

The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anti-cancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat’s pharmacokinetics in rats were investigated after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) micellar administrations and compared to a conventional PEG400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 mg/ml to 8.15 ± 0.60 mg/ml and 10.24 ± 0.92 mg/ml at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 nm and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19 %, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the oral and intravenous pharmacokinetics and bioavailability of vorinostat, which warrants further investigation

Signals for a Transition from Surface to Bulk Emission in Thermal Multifragmentation

Excitation-energy-gated two-fragment correlation functions have been studied between 2 to 9A MeV of excitation energy for equilibrium-like sources formed in $\pi^-$ and p + $^{197}$Au reactions at beam momenta of 8,9.2 and 10.2 GeV/c. Comparison of the data to an N-body Coulomb-trajectory code shows a decrease of one order of magnitude in the fragment emission time in the excitation energy interval 2-5A MeV, followed by a nearly constant breakup time at higher excitation energy. The observed decrease in emission time is shown to be strongly correlated with the increase of the fragment emission probability, and the onset of thermally-induced radial expansion. This result is interpreted as evidence consistent with a transition from surface-dominated to bulk emission expected for spinodal decomposition.Comment: 11 pages including 3 postscript figures (1 color

Semi-Inclusive Lambda and Kshort Production in p-Au Collisions at 17.5 GeV/c

The first detailed measurements of the centrality dependence of strangeness production in p-A collisions are presented. Lambda and Kshort dn/dy distributions from 17.5 GeV/c p-Au collisions are shown as a function of "grey" track multiplicity and the estimated number of collisions, nu, made by the proton. The nu dependence of the Lambda yield deviates from a scaling of p-p data by the number of participants, increasing faster than this scaling for nu<=5 and saturating for larger nu. A slower growth in Kshort multiplicity with nu is observed, consistent with a weaker nu dependence of K-Kbar production than Y-K production.Comment: 5 pages, 3 figures, formatted with RevTex, current version has enlarged figure catpion