A New Star-Formation Rate Calibration from Polycyclic Aromatic Hydrocarbon Emission Features and Application to High Redshift Galaxies

We calibrate the integrated luminosity from the polycyclic aromatic hydrocarbon (PAH) features at 6.2\micron, 7.7\micron\ and 11.3\micron\ in galaxies as a measure of the star-formation rate (SFR). These features are strong (containing as much as 5-10\% of the total infrared luminosity) and suffer minimal extinction. Our calibration uses \spitzer\ Infrared Spectrograph (IRS) measurements of 105 galaxies at $0 < z < 0.4$, infrared (IR) luminosities of 10^9 - 10^{12} \lsol, combined with other well-calibrated SFR indicators. The PAH luminosity correlates linearly with the SFR as measured by the extinction-corrected \ha\ luminosity over the range of luminosities in our calibration sample. The scatter is 0.14 dex comparable to that between SFRs derived from the \paa\ and extinction-corrected \ha\ emission lines, implying the PAH features may be as accurate a SFR indicator as hydrogen recombination lines. The PAH SFR relation depends on gas-phase metallicity, for which we supply an empirical correction for galaxies with 0.2 < \mathrm{Z} \lsim 0.7~\zsol. We present a case study in advance of the \textit{James Webb Space Telescope} (\jwst), which will be capable of measuring SFRs from PAHs in distant galaxies at the peak of the SFR density in the universe ($z\sim2$) with SFRs as low as $\sim$~10~\sfrunits. We use \spitzer/IRS observations of the PAH features and \paa\ emission plus \ha\ measurements in lensed star-forming galaxies at $1 < z < 3$ to demonstrate the ability of the PAHs to derive accurate SFRs. We also demonstrate that because the PAH features dominate the mid-IR fluxes, broad-band mid-IR photometric measurements from \jwst\ will trace both the SFR and provide a way to exclude galaxies dominated by an AGN.Comment: Accepted for publication in Ap

Etiopathogenesis of Insulin Autoimmunity

Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity

Increasing the Net Charge and Decreasing the Hydrophobicity of Bovine Carbonic Anhydrase Decreases the Rate of Denaturation with Sodium Dodecyl Sulfate

AbstractThis study compares the rate of denaturation with sodium dodecyl sulfate (SDS) of the individual rungs of protein charge ladders generated by acylation of the lysine ε−NH3+ groups of bovine carbonic anhydrase II (BCA). Each acylation decreases the number of positively charged groups, increases the net negative charge, and increases the hydrophobic surface area of BCA. This study reports the kinetics of denaturation in solutions containing SDS of the protein charge ladders generated with acetic and hexanoic anhydrides; plotting these rates of denaturation as a function of the number of modifications yields a U-shaped curve. The proteins with an intermediate number of modifications are the most stable to denaturation by SDS. There are four competing interactions—two resulting from the change in electrostatics and two resulting from the change in exposed hydrophobic surface area—that determine how a modification affects the stability of a rung of a charge ladder of BCA to denaturation with SDS. A model based on assumptions about how these interactions affect the folded and transition states has been developed and fits the experimental results. Modeling indicates that for each additional acylation, the magnitude of the change in the activation energy of denaturation (ΔΔG‡) due to changes in the electrostatics is much larger than the change in ΔΔG‡ due to changes in the hydrophobicity, but the intermolecular and intramolecular electrostatic effects are opposite in sign. At the high numbers of acylations, hydrophobic interactions cause the hexanoyl-modified BCA to denature nearly three orders of magnitude more rapidly than the acetyl-modified BCA

Is it the shape of the cavity, or the shape of the water in the cavity?

Historical interpretations of the thermodynamics characterizing biomolecular recognition have marginalized the role of water. An important (even, perhaps, dominant) contribution to molecular recognition in water comes from the “hydrophobic effect,” in which non-polar portions of a ligand interact preferentially with non-polar regions of a protein. Water surrounds the ligand, and water fills the binding pocket of the protein: when the protein-ligand complex forms, and hydrophobic surfaces of the binding pocket and the ligand approach one another, the molecules (and hydrogen-bonded networks of molecules) of water associated with both surfaces rearrange and, in part, entirely escape into the bulk solution. It is now clear that neither of the two most commonly cited rationalizations for the hydrophobic effect—an entropy-dominated hydrophobic effect, in which ordered waters at the surface of the ligand, and water at the surface of the protein, are released to the bulk upon binding, and a “lock-and-key” model, in which the surface of a ligand interacts directly with a surface of a protein having a complementary shape–can account for water-mediated interactions between the ligand and the protein, and neither is sufficient to account for the experimental observation of both entropy- andenthalpy-dominated hydrophobic effects. What is now clear is that there is no single hydrophobic effect, with a universally applicable, common, thermodynamic description: different processes (i.e., partitioning between phases of different hydrophobicity, aggregation in water, and binding) with different thermodynamics, depend on the molecular-level details of the structures of the molecules involved, and of the aggregates that form. A “water-centric” description of the hydrophobic effect in biomolecular recognition focuses on the structures of water surrounding the ligand, and of water filling the binding pocket of the protein, both before and after binding. This view attributes the hydrophobic effect to changes in the free energy of the networks of hydrogen bonds that are formed, broken, or re-arranged when two hydrophobic surfaces approach (but do not necessarily contact) one another. The details of the molecular topography (and the polar character) of the mole- cular surfaces play an important role in determining the structure of these networks of hydrogen-bonded waters, and in the thermodynamic description of the hydrophobic effect(s). Theorists have led the formulation of this “water-centric view”, although experiments are now supplying support for it. It poses complex problems for would-be “designers” of protein-ligand interactions, and for so-called “rational drug design”.Chemistry and Chemical Biolog

Spitzer Spectroscopy of Infrared-Luminous Galaxies: Diagnostics of AGN and Star Formation and Contribution to Total Infrared Luminosity

We use Spitzer IRS spectroscopy to study the nature 65 IR-luminous galaxies at 0.02 1.2mJy. The IRS spectra cover wavelengths spanning the PAH features and important atomic diagnostic lines. Our sample corresponds to L(IR) = L(8-1000micron) = 10^10-10^12 Lsun. We divide our galaxies into those with Spitzer IRAC colors indicative of warm dust heated by an AGN (IRAGN) and those whose colors indicate star-formation processes (non-IRAGN). Compared to the non-IRAGN, the IRAGN show smaller PAH emission EWs, which we attribute to an increase in mid-IR continuum from the AGN. We find that in both the IRAGN and non-IRAGN samples, the PAH luminosities correlate strongly with the [Ne II] emission, from which we conclude that the PAH luminosity directly traces the instantaneous SFR in both the IRAGN and non-IRAGN galaxies. We compare the ratio of PAH luminosity to the total IR luminosity and show that for most IRAGN star-formation accounts for 10-50% of the L(IR). We also find no measurable difference between the PAH luminosity ratios of L(11.3)/L(7.7) and L(6.2)/L(7.7) for the IRAGN and non-IRAGN, suggesting that AGN do not significantly excite or destroy PAH molecules on galaxy-wide scales. A small subset of galaxies show excess of [O IV] emission compared to their PAH emission, which indicates the presence of heavily-obscured AGN, including 3 galaxies that are not otherwise selected as IRAGN. The low PAH emission and low [Ne II] emission of the IRAGN and [O IV]-excess objects imply they have low SFRs and their IR luminosity is dominated by processes associated with the AGN.Comment: 22 pages, 18 figures, accepted for publication in Ap

The Most Powerful Lenses in the Universe: Quasar Microlensing as a Probe of the Lensing Galaxy

Optical and X-ray observations of strongly gravitationally lensed quasars (especially when four separate images of the quasar are produced) determine not only the amount of matter in the lensing galaxy but also how much is in a smooth component and how much is composed of compact masses (e.g., stars, stellar remnants, primordial black holes, CDM sub-halos, and planets). Future optical surveys will discover hundreds to thousands of quadruply lensed quasars, and sensitive X-ray observations will unambiguously determine the ratio of smooth to clumpy matter at specific locations in the lensing galaxies and calibrate the stellar mass fundamental plane, providing a determination of the stellar $M/L$. A modest observing program with a sensitive, sub-arcsecond X-ray imager, combined with the planned optical observations, can make those determinations for a large number (hundreds) of the lensing galaxies, which will span a redshift range of $\sim$$0.25<z<1.5$Comment: Astro2020 Science White Pape

Dependence of Avidity on Linker Length for a Bivalent Ligand–Bivalent Receptor Model System

This paper describes a synthetic dimer of carbonic anhydrase, and a series of bivalent sulfonamide ligands with different lengths (25 to 69 Å between the ends of the fully extended ligands), as a model system to use in examining the binding of bivalent antibodies to antigens. Assays based on analytical ultracentrifugation and fluorescence binding indicate that this system forms cyclic, noncovalent complexes with a stoichiometry of one bivalent ligand to one dimer. This dimer binds the series of bivalent ligands with low picomolar avidities (Kdavidity = 3–40 pM). A structurally analogous monovalent ligand binds to one active site of the dimer with Kdmono = 16 nM. The bivalent association is thus significantly stronger (Kdmono/Kdavidity ranging from 500 to 5000 unitless) than the monovalent association. We infer from these results, and by comparison of these results to previous studies, that bivalency in antibodies can lead to associations much tighter than monovalent associations (although the observed bivalent association is much weaker than predicted from the simplest level of theory: predicted Kdavidity of 0.002 pM and Kdmono/Kdavidity 8 × 106 unitless).Chemistry and Chemical Biolog

Subaru Spectroscopy of the Gravitational Lens HST 14176+5226: Implications for a Large Cosmological Constan

We present new optical spectroscopy of the lens elliptical galax in the ``Einstein Cross'' lens system HST 14176+5226, using the Faint Object Camera and Spectrograph (FOCAS) of the Subaru t Our spectroscopic observations are aimed at measuring the stella dispersion of the lens galaxy, located at high redshift of z_L= as an important component to lens models. We have measured this 230 +- 14 km s^{-1} (1 sigma) inside 0.35 effective radi based on the comparison between the observed galaxy spectrum and templates of three G-K giants by means of the Fourier cross-corr To extract the significance of this information on the geometry universe which also affects the lensing of the background image, to fit three different lens models to the available data of the Provided that the lens galaxy has the structural and dynamical p (i.e., its radial density profile, core radius, and velocity ani similar to those of local elliptical galaxies, we calculate the function for the simultaneous reproduction of both the observed and newly measured velocity dispersion of the lens. Although the interval depends rather sensitively on the adopted lens models o parameters, our experiments suggest the larger likelihood for a cosmological constant, Omega_Lambda: formal 1 sigma lower Omega_Lambda in the flat universe ranges 0.73 to 0.97, where lower limit is basically unavailable. This method for determinin model is thus dependent on lens models but is insensitive to oth ambiguities, such as the dust absorption or the evolutionary eff galaxies. Exploring spectroscopic observations of more lens gala redshift may minimize the model uncertainties and thus place a m constraint on Omega_Lambda.Comment: 23 pages, 5 figures, accepted for publication in The Astronomical Journa