Biochemical characterization of the retinoid isomerase system of the eye

Journal ArticleWe have previously shown that membranes from the retinal pigment epithelium can transform added all-trans-retinol into a mixture of 11-cis-retinoids, demonstrating the "missing reaction" in the visual cycle for the first time (Bernstein, P. S., Law, W. C., and Rando, R. R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1849-1853). In this article, this isomerase activity is further characterized. Double-label experiments with [15-3H]- and [15-14C]all-trans-retinol as the substrate show that the tritium label is retained in the 11-cis-retinol and 11-cis-retinyl palmitate products. This requires that isomerization occur at the alcohol level of oxidation. All-trans-retinyl esters, such as the palmitate, acetate, butyrate, and hexanoate esters, are not directly transformed into their 11-cis counterparts by the membranes. The data are consistent with the presence of an all-trans-retinol isomerase enzyme system or enzyme complex, which produces 11-cis-retinol. Other isomeric retinols were tested for substrate activity. Neither 9-cis-retinol(al) nor 13-cis-retinol were processed by the isomerase. Since the membranes containing the isomerase possess other retinol metabolizing activities, such as retinyl ester synthetase and dehydrogenase activities, further purification was attempted. Appreciable quantities of all detergents tested led to the disappearance of isomerase activity, and high salt or EDTA did not dissociate isomerase activity from the membranes. However, extensive sonication of the membranes did produce a 100,000 x g supernatant fraction of light membranes depleted of other all-trans-retinol processing activities. The isomerase activity in these membranes was saturable with all-trans-retinol, as required for a biologically significant process, and showed a Vmax of 5 pmol/h/mg of protein, a KM of 0.8 microM, and a pH optimum of 8. The isomerase was destroyed by proteinase K, by phospholipase C, by heating, or by ethanol at concentrations greater than 1%. The addition of high energy compounds, such as MgATP, MgGTP, or palmitoyl-CoA, did not appear to stimulate isomerase activity in the 100,000 x g supernatant

Effects of head-movement on theories of subjacency and proper government

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Linguistics and Philosophy, 1991.Includes bibliographical references (leaves 336-345).by Paul S. Law.Ph.D

Scattering of relativistic particles with Aharonov-Bohm-Coulomb interaction in two dimensions

The Aharonov-Bohm-Coulomb potentials in two dimensions may describe the interaction between two particles carrying electric charge and magnetic flux, say, Chern--Simons solitons, or so called anyons. The scattering problem for such two-body systems is extended to the relativistic case, and the scattering amplitude is obtained as a partial wave series. The electric charge and magnetic flux is ($-q$, $-\phi/Z$) for one particle and ($Zq$, $\phi$) for the other. When $(Zq^2/\hbar c)^2\ll 1$, and $q\phi/2\pi\hbar c$ takes on integer or half integer values, the partial wave series is summed up approximately to give a closed form. The results exhibit some nonperturbative features and cannot be obtained from perturbative quantum electrodynamics at the tree level.Comment: revtex, 11 pages, no figur

Beyond shareholder primacy? Reflections on the trajectory of UK corporate governance.

Core institutions of UK corporate governance, in particular the City Code on Takeovers and Mergers, the Combined Code on Corporate Governance and the law on directors’ duties, are strongly orientated towards the norm of shareholder primacy. Beyond the core, however, stakeholder interests are better represented, in particular at the intersection of insolvency and employment law. This reflects the influence of European Community laws on information and consultation of employees. In addition, there are signs that some institutional shareholders are redirecting their investment strategies, under government encouragement, away from a focus on short-term returns, in such a way as to favour stakeholder-inclusive practices by firms. On this basis we suggest that the UK system is currently in a state of flux and that the debate over shareholder primacy has not been concluded

Astro2020 Project White Paper: The Cosmic Accelerometer

We propose an experiment, the Cosmic Accelerometer, designed to yield velocity precision of $\leq 1$ cm/s with measurement stability over years to decades. The first-phase Cosmic Accelerometer, which is at the scale of the Astro2020 Small programs, will be ideal for precision radial velocity measurements of terrestrial exoplanets in the Habitable Zone of Sun-like stars. At the same time, this experiment will serve as the technical pathfinder and facility core for a second-phase larger facility at the Medium scale, which can provide a significant detection of cosmological redshift drift on a 6-year timescale. This larger facility will naturally provide further detection/study of Earth twin planet systems as part of its external calibration process. This experiment is fundamentally enabled by a novel low-cost telescope technology called PolyOculus, which harnesses recent advances in commercial off the shelf equipment (telescopes, CCD cameras, and control computers) combined with a novel optical architecture to produce telescope collecting areas equivalent to standard telescopes with large mirror diameters. Combining a PolyOculus array with an actively-stabilized high-precision radial velocity spectrograph provides a unique facility with novel calibration features to achieve the performance requirements for the Cosmic Accelerometer

Mediating punitiveness: understanding public attitudes towards work-related fatality cases

This paper concerns an empirical investigation into public attitudes towards work-related fatality cases, where organizational offenders cause the death of workers or members of the public. This issue is particularly relevant following the introduction of the Corporate Manslaughter and Corporate Homicide Act 2007 into UK law. Here, as elsewhere, the use of criminal law against companies reflects governmental concerns over public confidence in the law’s ability to regulate risk. The empirical findings demonstrate that high levels of public concern over these cases do not translate into punitive attitudes. Such cases are viewed rationally and constructively, and lead to instrumental rather than purely expressive enforcement preferences

A Neutron Star with a Massive Progenitor in Westerlund 1

We report the discovery of an X-ray pulsar in the young, massive Galactic star cluster Westerlund 1. We detected a coherent signal from the brightest X-ray source in the cluster, CXO J164710.2-455216, during two Chandra observations on 2005 May 22 and June 18. The period of the pulsar is 10.6107(1) s. We place an upper limit to the period derivative of Pdot<2e-10 s/s, which implies that the spin-down luminosity is Edot<3e33 erg/s. The X-ray luminosity of the pulsar is L_X = 3(+10,-2)e33 (D/5 kpc)^2 erg/s, and the spectrum can be described by a kT = 0.61+/-0.02 keV blackbody with a radius of R_bb = 0.27+/-0.03 (D/5 kpc}) km. Deep infrared observations reveal no counterpart with K1 Msun. Taken together, the properties of the pulsar indicate that it is a magnetar. The rarity of slow X-ray pulsars and the position of CXO J164710.2-455216 only 1.6' from the core of Westerlund 1 indicates that it is a member of the cluster with >99.97% confidence. Westerlund 1 contains 07V stars with initial masses M_i=35 Msun and >50 post-main-sequence stars that indicate the cluster is 4+/-1 Myr old. Therefore, the progenitor to this pulsar had an initial mass M_i>40 Msun. This is the most secure result among a handful of observational limits to the masses of the progenitors to neutron stars.Comment: 4 pages, 5 figures. Final version to match ApJL (added one figure since v2

GARP and EARP are required for efficient BoHV-1 replication as identified by a genome wide CRISPR knockout screen

The advances in gene editing bring unprecedented opportunities in high throughput functional genomics to animal research. Here we describe a genome wide CRISPR knockout library, btCRISPRko.v1, targeting all protein coding genes in the cattle genome. Using it, we conducted genome wide screens during Bovine Herpes Virus type 1 (BoHV-1) replication and compiled a list of pro-viral and anti-viral candidates. These candidates might influence multiple aspects of BoHV-1 biology such as viral entry, genome replication and transcription, viral protein trafficking and virion maturation in the cytoplasm. Some of the most intriguing examples are VPS51, VPS52 and VPS53 that code for subunits of two membrane tethering complexes, the endosome-associated recycling protein (EARP) complex and the Golgi-associated retrograde protein (GARP) complex. These complexes mediate endosomal recycling and retrograde trafficking to the trans Golgi Network (TGN). Simultaneous loss of both complexes in MDBKs resulted in greatly reduced production of infectious BoHV-1 virions. We also found that viruses released by these deficient cells severely lack VP8, the most abundant tegument protein of BoHV-1 that are crucial for its virulence. In combination with previous reports, our data suggest vital roles GARP and EARP play during viral protein packaging and capsid re-envelopment in the cytoplasm. It also contributes to evidence that both the TGN and the recycling endosomes are recruited in this process, mediated by these complexes. The btCRISPRko.v1 library generated here has been controlled for quality and shown to be effective in host gene discovery. We hope it will facilitate efforts in the study of other pathogens and various aspects of cell biology in cattle.</p

Development of a Passive and Slope Adaptable Prosthetic Foot

Historically, users of prosthetic ankles have relied on actively operated systems to provide effective slope adaptability. However, there are many drawbacks to these systems. This research builds upon work previously completed by Hansen et al. as it develops a passive, hydraulically operated prosthetic ankle with the capability of adapting to varying terrain in every step. Using gait cycle data and an analysis of ground reaction forces, the team determined that weight activation was the most effective way to activate the hydraulic circuit. Evaluations of the system pressure and energy showed that although the spring damper system results in a loss of 9J of energy to the user, the footplate stores 34J more than a standard prosthesis. Therefore, the hydraulic prosthetic provides a 54% increase in stored energy when compared to a standard prosthesis. The hydraulic circuit manifold prototype was manufactured and tested. Through proof of concept testing, the prototype proved to be slope adaptable by successfully achieving a plantarflexion angle of 16 degrees greater than a standard prosthetic foot currently available on the market.Massachusetts Institute of Technology. Tata Center for Technology and Desig

The Host Galaxy and Redshift of the Repeating Fast Radio Burst FRB 121102

The precise localization of the repeating fast radio burst (FRB 121102) has provided the first unambiguous association (chance coincidence probability $p\lesssim3\times10^{-4}$) of an FRB with an optical and persistent radio counterpart. We report on optical imaging and spectroscopy of the counterpart and find that it is an extended ($0.6^{\prime\prime}-0.8^{\prime\prime}$) object displaying prominent Balmer and [OIII] emission lines. Based on the spectrum and emission line ratios, we classify the counterpart as a low-metallicity, star-forming, $m_{r^\prime} = 25.1$ AB mag dwarf galaxy at a redshift of $z=0.19273(8)$, corresponding to a luminosity distance of 972 Mpc. From the angular size, the redshift, and luminosity, we estimate the host galaxy to have a diameter $\lesssim4$ kpc and a stellar mass of $M_*\sim4-7\times 10^{7}\,M_\odot$, assuming a mass-to-light ratio between 2 to 3$\,M_\odot\,L_\odot^{-1}$. Based on the H$\alpha$ flux, we estimate the star formation rate of the host to be $0.4\,M_\odot\,\mathrm{yr^{-1}}$ and a substantial host dispersion measure depth $\lesssim 324\,\mathrm{pc\,cm^{-3}}$. The net dispersion measure contribution of the host galaxy to FRB 121102 is likely to be lower than this value depending on geometrical factors. We show that the persistent radio source at FRB 121102's location reported by Marcote et al (2017) is offset from the galaxy's center of light by $\sim$200 mas and the host galaxy does not show optical signatures for AGN activity. If FRB 121102 is typical of the wider FRB population and if future interferometric localizations preferentially find them in dwarf galaxies with low metallicities and prominent emission lines, they would share such a preference with long gamma ray bursts and superluminous supernovae.Comment: 12 pages, 3 figures, Published in ApJ Letters. V2: Corrected mistake in author lis