Paint it Black -- A Combinatorial Yawp

No abstract provided in this paper

The Metagalactic Ionizing Radiation Field at Low Redshift

We compute the ionizing radiation field at low redshift, arising from Seyferts, QSOs, and starburst galaxies. This calculation combines recent Seyfert luminosity functions, extrapolated ultraviolet fluxes from our IUE-AGN database, and a new intergalactic opacity model based on Hubble Space Telescope and Keck Ly-alpha absorber surveys. At z = 0 for AGN only, our best estimate for the specific intensity at 1 Ryd is I_0 = 1.3 (+0.8/-0.5) x 10^-23 ergs/cm^2/s/Hz/sr, independent of H_0, Omega_0, and Lambda. The one-sided ionizing photon flux is Phi_ion = 3400 (+2100/-1300) photons/cm^2/s, and the H I photoionization rate is Gamma_HI = 3.2 (+2.0/-1.2) x 10^-14 s^-1 for alpha_s = 1.8. We also derive Gamma_ HI for z = 0 - 4. These error ranges reflect uncertainties in the spectral indexes for the ionizing EUV (alpha_s = 1.8 +/- 0.3) and the optical/UV (alpha_UV = 0.86 +/- 0.05), the IGM opacity model, the range of Seyfert luminosities (0.001 - 100 L*) and the completeness of the luminosity functions. Our estimate is a factor of three lower than the most stringent upper limits on the ionizing background (Phi_ion < 10^4 photons/cm^2/s) obtained from H-alpha observations in external clouds, and it lies within the range implied by other indirect measures. Starburst galaxies with a sufficiently large Lyman continuum escape fraction, f_ esc > 0.05, may provide a comparable background to AGN, I_0 (z=0) = 1.1 (+1.5/-0.7) x 10^{-23). An additional component of the ionizing background of this magnitude would violate neither upper limits from H-alpha observations nor the acceptable range from other measurements.Comment: 30 pages, 9 figures, accepted for Astronomical J. (Oct. 1999

Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses

The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease

A homogeneous method for investigation of methylation-dependent protein–protein interactions in epigenetics

Methylation of lysine residues on the tails of histone proteins is a major determinant of the transcription state of associated DNA coding regions. The interplay among methylation states and other histone modifications to direct transcriptional outcome is referred to as the histone code. In addition to histone methyltransferases and demethylases which function to modify the methylation state of lysine sidechains, other proteins recognize specific histone methylation marks essentially serving as code readers. While these interactions are highly specific with respect to site and methylation state of particular lysine residues, they are generally weak and therefore difficult to monitor by traditional assay techniques. Herein, we present the design and implementation of a homogeneous, miniaturizable, and sensitive assay for histone methylation-dependent interactions. We use AlphaScreen, a chemiluminescence-based technique, to monitor the interactions of chromodomains (MPP8, HP1β and CHD1), tudor domains (JMJD2A) and plant homeodomains (RAG2) with their cognate trimethyllysine histone partners. The utility of the method was demonstrated by profiling the binding specificities of chromo- and tudor domains toward several histone marks. The simplicity of design and the sensitive and robust nature of this assay should make it applicable to a range of epigenetic studies, including the search for novel inhibitors of methylation-dependent interactions

Effects of NADPH oxidase inhibitor in diabetic nephropathy

Effects of NADPH oxidase inhibitor in diabetic nephropathy.BackgroundWe used apocynin to test the hypothesis that superoxide anion (O−2) from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase underlies the development of diabetic nephropathy in the rat.MethodsRats received apocynin (16 mg/kg/day) from 2 to 8 weeks after inducing diabetes mellitus (DM) with streptozotocin.ResultsDM increased excretion of hydrogen peroxide (H2O2), lipid peroxidation products (LPO), nitric oxide products (NOx), and protein. The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), and increased mesangial matrix with expression of fibronectin and collagen I. Apocynin prevented the increase in excretion of H2O2, LPO, and protein in diabetic rats, increased renal NOx generation, and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox, and reverted the mesangial matrix expansion.ConclusionActivation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO generation, despite enhanced eNOS expression in a model of diabetic nephropathy. Apocynin prevents these changes and the associated proteinuria

Dynamic adjustment of the ocean circulation to self-attraction and loading effects

The oceanic response to surface loading, such as that related to atmospheric pressure, freshwater exchange, and changes in the gravity field, is essential to our understanding of sea level variability. In particular, so-called self-attraction and loading (SAL) effects caused by the redistribution of mass within the land–atmosphere–ocean system can have a measurable impact on sea level. In this study, the nature of SAL-induced variability in sea level is examined in terms of its equilibrium (static) and nonequilibrium (dynamic) components, using a general circulation model that implicitly includes the physics of SAL. The additional SAL forcing is derived by decomposing ocean mass anomalies into spherical harmonics and then applying Love numbers to infer associated crustal displacements and gravitational shifts. This implementation of SAL physics incurs only a relatively small computational cost. Effects of SAL on sea level amount to about 10% of the applied surface loading on average but depend strongly on location. The dynamic component exhibits large-scale basinwide patterns, with considerable contributions from subweekly time scales. Departures from equilibrium decrease toward longer time scales but are not totally negligible in many places. Ocean modeling studies should benefit from using a dynamical implementation of SAL as used here

Synthesis and pharmacological evaluation of indole derivatives as deaza analogues of potent human neutrophil elastase inhibitors

A number of N-benzoylindoles were designed and synthesized as deaza analogues of our previously reported potent and selective HNE inhibitors with an indazole scaffold. The new compounds containing substituents and functions that were most active in the previous series were active in the micromolar range (the most potent had IC(50)=3.8 µM) or inactive. These results demonstrated the importance of N-2 in the indazole nucleus. Docking studies performed on several compounds containing the same substituents but with an indole or an indazole scaffold, respectively, highlight interesting aspects concerning the molecule orientation and H-bonding interactions, which could help to explain the lower activity of this new series