Conformational Variability in Ground-State CFTR Lipoprotein Particle Cryo-EM Ensembles

Cystic fibrosis transmembrane regulator (CFTR) is a dynamic membrane protein belonging to the ABC transporter family. It is unusual within this family as it is an ion channel, as opposed to a transporter. Activation of CFTR requires ATP and phosphorylation by PKA, and dysregulation of CFTR mediated salt and water homeostasis can lead to cystic fibrosis. Recent advancements in structural biological methods have led to more than 10 published CFTR structures, and, so far, all of these structures of CFTR, determined by cryo-EM, have been limited to detergent-purified protein preparations. To visualize CFTR in an environment that more closely represents its native membranous environment, we utilized two different lipoprotein particle encapsulation techniques: one in which the ion channel is first purified and then reconstituted using the membrane scaffolding protein Saposin A and another that uses the solubilizing polymer Sokalan CP9 (DIBMA) to extract CFTR directly from membranes. Structures derived from these types of preparations may better correlate to their function, for instance, the single-channel measurements from membrane vesicles

Discovery of Two Gravitationally Lensed Quasars with Image Separations of 3 Arcseconds from the Sloan Digital Sky Survey

We report the discovery of two doubly-imaged quasars, SDSS J100128.61+502756.9 and SDSS J120629.65+433217.6, at redshifts of 1.838 and 1.789 and with image separations of 2.86'' and 2.90'', respectively. The objects were selected as lens candidates from the Sloan Digital Sky Survey (SDSS). Based on the identical nature of the spectra of the two quasars in each pair and the identification of the lens galaxies, we conclude that the objects are gravitational lenses. The lenses are complicated; in both systems there are several galaxies in the fields very close to the quasars, in addition to the lens galaxies themselves. The lens modeling implies that these nearby galaxies contribute significantly to the lens potentials. On larger scales, we have detected an enhancement in the galaxy density near SDSS J100128.61+502756.9. The number of lenses with image separation of ~3'' in the SDSS already exceeds the prediction of simple theoretical models based on the standard Lambda-dominated cosmology and observed velocity function of galaxies.Comment: 24 pages, 9 figures, accepted for publication in Ap

Spectroscopic Target Selection in the Sloan Digital Sky Survey: The Quasar Sample

We describe the algorithm for selecting quasar candidates for optical spectroscopy in the Sloan Digital Sky Survey. Quasar candidates are selected via their non-stellar colors in "ugriz" broad-band photometry, and by matching unresolved sources to the FIRST radio catalogs. The automated algorithm is sensitive to quasars at all redshifts lower than z=5.8. Extended sources are also targeted as low-redshift quasar candidates in order to investigate the evolution of Active Galactic Nuclei (AGN) at the faint end of the luminosity function. Nearly 95% of previously known quasars are recovered (based on 1540 quasars in 446 square degrees). The overall completeness, estimated from simulated quasars, is expected to be over 90%, whereas the overall efficiency (quasars:quasar candidates) is better than 65%. The selection algorithm targets ultraviolet excess quasars to i^*=19.1 and higher-redshift (z>3) quasars to i^*=20.2, yielding approximately 18 candidates per square degree. In addition to selecting ``normal'' quasars, the design of the algorithm makes it sensitive to atypical AGN such as Broad Absorption Line quasars and heavily reddened quasars.Comment: 62 pages, 15 figures (8 color), 8 tables. Accepted by AJ. For a version with higher quality color figures, see http://archive.stsci.edu/sdss/quasartarget/RichardsGT_qsotarget.preprint.p

High-Redshift Quasars Found in Sloan Digital Sky Survey Commissioning Data II: The Spring Equatorial Stripe

This is the second paper in a series aimed at finding high-redshift quasars from five-color (u'g'r'i'z') imaging data taken along the Celestial Equator by the Sloan Digital Sky Survey (SDSS) during its commissioning phase. In this paper, we present 22 high-redshift quasars (z>3.6) discovered from ~250 deg^2 of data in the spring Equatorial Stripe, plus photometry for two previously known high-redshift quasars in the same region of sky. Our success rate of identifying high-redshift quasars is 68%. Five of the newly discovered quasars have redshifts higher than 4.6 (z=4.62, 4.69, 4.70, 4.92 and 5.03). All the quasars have i* < 20.2 with absolute magnitude -28.8 < M_B < -26.1 (h=0.5, q_0=0.5). Several of the quasars show unusual emission and absorption features in their spectra, including an object at z=4.62 without detectable emission lines, and a Broad Absorption Line (BAL) quasar at z=4.92.Comment: 28 pages, AJ in press (Jan 2000), final version with minor changes; high resolution finding charts available at http://www.astro.princeton.edu/~fan/paper/qso2.htm

The Luminosity Function of Galaxies in SDSS Commissioning Data

During commissioning observations, the Sloan Digital Sky Survey (SDSS) has produced one of the largest existing galaxy redshift samples selected from CCD images. Using 11,275 galaxies complete to r^* = 17.6 over 140 square degrees, we compute the luminosity function of galaxies in the r^* band over a range -23 < M < -16 (for h=1). The result is well-described by a Schechter function with parameters phi_* = 0.0146 +/- 0.0012 h^3 Mpc^{-3}, M_* = -20.83 +/- 0.03, and alpha = -1.20 +/- 0.03. The implied luminosity density in r^* is j = (2.6 +/- 0.3) x 10^8 h L_sun Mpc^{-3}. The surface brightness selection threshold has a negligible impact for M < -18. We measure the luminosity function in the u^*, g^*, i^*, and z^* bands as well; the slope at low luminosities ranges from alpha=-1.35 to alpha=-1.2. We measure the bivariate distribution of r^* luminosity with half-light surface brightness, intrinsic color, and morphology. High surface brightness, red, highly concentrated galaxies are on average more luminous than low surface brightness, blue, less concentrated galaxies. If we synthesize results for R-band or b_j-band using the Petrosian magnitudes with which the SDSS measures galaxy fluxes, we obtain luminosity densities 2.0 times that found by the Las Campanas Redshift Survey in R and 1.4 times that found by the Two-degree Field Galaxy Redshift Survey in b_j. We are able to reproduce the luminosity functions obtained by these surveys if we also mimic their isophotal limits for defining galaxy magnitudes, which are shallower and more redshift dependent than the Petrosian magnitudes used by the SDSS. (Abridged)Comment: 49 pages, including 23 figures, accepted by AJ; some minor textual changes, plus an important change in comparison to LCR

The Sloan Digital Sky Survey Quasar Lens Search. II. Statistical lens sample from the third data release

We report the first results of our systematic search for strongly lensed quasars using the spectroscopically confirmed quasars in the Sloan Digital Sky Survey (SDSS). Among 46,420 quasars from the SDSS Data Release 3 (~4188 deg^2), we select a subsample of 22,683 quasars that are located at redshifts between 0.6 and 2.2 and are brighter than the Galactic extinction-corrected i-band magnitude of 19.1. We identify 220 lens candidates from the quasar subsample, for which we conduct extensive and systematic follow-up observations in optical and near-infrared wavebands, in order to construct a complete lensed quasar sample at image separations between 1" and 20" and flux ratios of faint to bright lensed images larger than 10^(−0.5). We construct a statistical sample of 11 lensed quasars. Ten of these are galaxy-scale lenses with small image separations (~ 1"-2") and one is a large separation (15") system which is produced by a massive cluster of galaxies, representing the first statistical sample of lensed quasars including both galaxy- and cluster-scale lenses. The Data Release 3 spectroscopic quasars contain an additional 11 lensed quasars outside the statistical sample

A Phase 1a/1b Clinical Trial Design to Assess Safety, Acceptability, Pharmacokinetics and Tolerability of Intranasal Q-Griffithsin for COVID-19 Prophylaxis

Background: The COVID-19 pandemic remains an ongoing threat to global public health. Q-Griffithsin (Q-GRFT) is a lectin that has demonstrated potent broad-spectrum inhibitory activity in preclinical studies in models of Nipah virus and the beta coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2. Methods: Here, we propose a clinical trial design to test the safety, pharmacokinetics (PK), and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection as a prophylaxis strategy. The initial Phase 1a study will assess the safety and PK of a single dose of intranasally administered Q-GRFT. If found safe, the safety, PK, and tolerability of multiple doses of intranasal Q-GRFT will be assessed in a Phase 1b study. Group 1 participants will receive 3 mg of intranasal Q-GRFT (200 μL/nostril) once daily for 7 days. If this dose is tolerated, participants will be enrolled in Group 2 to receive 3 mg twice daily for 7 days. Secondary endpoints of the study will be user perceptions, acceptability, and the impact of product use on participants’ olfactory sensation and quality of life. Discussion: Results from this study will support further development of Q-GRFT as a prophylactic against respiratory viral infections in future clinical trials

Photometric Redshifts of Quasars

We demonstrate that the design of the Sloan Digital Sky Survey (SDSS) filter system and the quality of the SDSS imaging data are sufficient for determining accurate and precise photometric redshifts (``photo-z''s) of quasars. Using a sample of 2625 quasars, we show that photo-z determination is even possible for z<=2.2 despite the lack of a strong continuum break that robust photo-z techniques normally require. We find that, using our empirical method on our sample of objects known to be quasars, approximately 70% of the photometric redshifts are correct to within delta z = 0.2; the fraction of correct photometric redshifts is even better for z>3. The accuracy of quasar photometric redshifts does not appear to be dependent upon magnitude to nearly 21st magnitude in i'. Careful calibration of the color-redshift relation to 21st magnitude may allow for the discovery of on the order of 10^6 quasars candidates in addition to the 10^5 quasars that the SDSS will confirm spectroscopically. We discuss the efficient selection of quasar candidates from imaging data for use with the photometric redshift technique and the potential scientific uses of a large sample of quasar candidates with photometric redshifts.Comment: 29 pages, 8 figures, submitted to A