Alcohol and HIV Decrease Proteasome and Immunoproteasome Function in Macrophages: Implications for Impaired Immune Function During Disease

Proteasomes (proteinase complexes, PR) and immunoproteasomes (IPR) degrade damaged proteins and affect protein processing required for antigen presentation by mononuclear phagocytes. These critical immune processes are attenuated during progressive HIV-1 infection and are affected by alcohol abuse. To investigate the mechanisms underlying these functional changes, we measured PR and CYP2E1 activities [an ethanol (EtOH) metabolizing enzyme] and reactive oxygen species (ROS) in human monocyte-derived macrophages (MDM) following HIV-1 infection and EtOH treatment. We observed progressive declines of PR activity and PR/IPR contents in HIV-1-infected MDM. PR activity and IPR expression increased after IFN-γ stimulation but reduced after HIV-1 infection. EtOH inhibited both IFN-γ -induced PR and IPR. Paradoxically, EtOH attenuated PR catalytic activity in infected MDM and suppressed viral replication. Elevated ROS followed EtOH exposure and paralleled decreased PR activity. The latter was restored by anti-oxidant. The data support the notion that HIV-1 infection and EtOH may work in concert to affect immune function including antigen presentation and thereby affect disease progression

Dynamics of Simple Balancing Models with State Dependent Switching Control

Time-delayed control in a balancing problem may be a nonsmooth function for a variety of reasons. In this paper we study a simple model of the control of an inverted pendulum by either a connected movable cart or an applied torque for which the control is turned off when the pendulum is located within certain regions of phase space. Without applying a small angle approximation for deviations about the vertical position, we see structurally stable periodic orbits which may be attracting or repelling. Due to the nonsmooth nature of the control, these periodic orbits are born in various discontinuity-induced bifurcations. Also we show that a coincidence of switching events can produce complicated periodic and aperiodic solutions.Comment: 36 pages, 12 figure

Bright z~9 Galaxies in Parallel: The Bright End of the Rest-UV Luminosity Function from HST Parallel Programs

The abundance of bright galaxies at z>8 can provide key constraints on models of galaxy formation and evolution, as the predicted abundance varies greatly when different physical prescriptions for gas cooling and star formation are implemented. We present the results of a search for bright z=9-10 galaxies selected from pure-parallel Hubble Space Telescope imaging programs. We include 132 fields observed as part of the Brightest of Reionizing Galaxies survey, the Hubble Infrared Pure Parallel Imaging Extragalactic Survey, and the WFC3 Infrared Spectroscopic Parallel survey. These observations cover a total of 620 sq. arcmin, about 70% of which is also covered with Spitzer Space Telescope infrared imaging. We identify thirteen candidate galaxies in the range 8.3<z<11 with 24.5 < m_H < 26.5 (-22.9 < M_UV < -21.2). This sample capitalizes on the uncorrelated nature of pure parallel observations to overcome cosmic variance and leverages a full multi-wavelength selection process to minimize contamination without sacrificing completeness. We perform detailed completeness and contamination analyses, and present measurements of the bright end of the UV luminosity function using a pseudo-binning technique. We find a number density consistent with results from Finkelstein et al. (2022) and other searches in HST parallel fields. These bright candidates likely reside in overdensities, potentially representing some of the earliest sites of cosmic reionization. These new candidates are excellent targets for follow-up with JWST, and four of them will be observed with the NIRSpec prism in Cycle 1.Comment: Submitted to AAS Journals; key results in Fig 17; 45 pages, 19 figure

Matrix dependence of blue light emission from a novel NH2-functionalized dicyanoquinodimethane derivative

The reactions of primary and secondary amines with (cyclohexa-2,5-diene-1,4-diylidene)-dimalononitrile (TCNQ) lead to mono- and disubstituted dicyanoquinodimethane derivatives and fluorescence emission has been observed for several of these compounds. We report the luminescence properties, synthesis and crystal structure of the novel dicyanoquinodimethane derivative 2-{4-[amino-(2,6-dimethyl-morpholin-4-yl)-methylene]-cyclohexa-2,5- dienylidene}-malononitrile (Ammor), a unique example of an asymmetric dicyanoquinodimethane derivative in which one of the nitrile groups has been replaced with an NH2 moiety, which provides a reactive centre for potential further substitution or tethering to larger molecules or polymers. The luminescence properties of the title compound were investigated in a variety of environments, including alcohol solutions at room temperature and a glass-forming solvent at low temperature. The fluorescence quantum yields and Stokes' shifts of the blue emission were found to be very sensitive to the matrix. The crystal structure of the subject compound was determined, revealing that the molecules are non-planar in the ground state. The environmentally sensitive emission is discussed in terms of the conformational change during photoexcitation and the constraint imposed on this by the matrix. This behaviour is also compared with that of other related amino-functionalized dicyanoquinodimethane derivatives