Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within ...resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.
ABSTRACT
We present observations of ASASSN-19dj, a nearby tidal disruption event (TDE) discovered in the post-starburst galaxy KUG 0810+227 by the All-Sky Automated Survey for Supernovae (ASAS-SN) at ...a distance of d ≃ 98 Mpc. We observed ASASSN-19dj from −21 to 392 d relative to peak ultraviolet (UV)/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From the ASAS-SN g-band data, we determine that the TDE began to brighten on 2019 February 6.8 and for the first 16 d the rise was consistent with a flux ∝t2 power law. ASASSN-19dj peaked in the UV/optical on 2019 March 6.5 (MJD = 58548.5) at a bolometric luminosity of L = (6.2 ± 0.2) × 1044 erg s−1. Initially remaining roughly constant in X-rays and slowly fading in the UV/optical, the X-ray flux increased by over an order of magnitude ∼225 d after peak, resulting from the expansion of the X-ray emitting region. The late-time X-ray emission is well fitted by a blackbody with an effective radius of ∼1 × 1012 cm and a temperature of ∼6 × 105 K. The X-ray hardness ratio becomes softer after brightening and then returns to a harder state as the X-rays fade. Analysis of Catalina Real-Time Transient Survey images reveals a nuclear outburst roughly 14.5 yr earlier with a smooth decline and a luminosity of LV ≥ 1.4 × 1043 erg s−1, although the nature of the flare is unknown. ASASSN-19dj occurred in the most extreme post-starburst galaxy yet to host a TDE, with Lick HδA = 7.67 ± 0.17 Å.
The Earth’s thermosphere and ionosphere constitute a dynamic system that varies daily in response to energy inputs from above and from below. This system can exhibit a significant response within an ...hour to changes in those inputs, as plasma and fluid processes compete to control its temperature, composition, and structure. Within this system, short wavelength solar radiation and charged particles from the magnetosphere deposit energy, and waves propagating from the lower atmosphere dissipate.
Understanding the global-scale response of the thermosphere-ionosphere
(
T-I
)
system to these drivers is essential to advancing our physical understanding of coupling between the space environment and the Earth’s atmosphere
. Previous missions have successfully determined how the “climate” of the T-I system responds. The Global-scale Observations of the Limb and Disk (GOLD) mission will determine how the “weather” of the T-I responds, taking the next step in understanding the coupling between the space environment and the Earth’s atmosphere. Operating in geostationary orbit, the GOLD imaging spectrograph will measure the Earth’s emissions from 132 to 162 nm. These measurements will be used image two critical variables—thermospheric temperature and composition, near 160 km—on the dayside disk at half-hour time scales. At night they will be used to image the evolution of the low latitude ionosphere in the same regions that were observed earlier during the day. Due to the geostationary orbit being used the mission observes the same hemisphere repeatedly, allowing the unambiguous separation of spatial and temporal variability over the Americas.
ABSTRACT
We present high-cadence multifrequency radio observations of the long gamma-ray burst (GRB) 190829A, which was detected at photon energies above 100 GeV by the High Energy Stereoscopic ...System (H.E.S.S.). Observations with the Meer Karoo Array Telescope (MeerKAT, 1.3 GHz) and Arcminute Microkelvin Imager – Large Array (AMI-LA, 15.5 GHz) began one day post-burst and lasted nearly 200 d. We used complementary data from Swift X-Ray Telescope (XRT), which ran to 100 d post-burst. We detected a likely forward shock component with both MeerKAT and XRT up to over 100 d post-burst. Conversely, the AMI-LA light curve appears to be dominated by reverse shock emission until around 70 d post-burst when the afterglow flux drops below the level of the host galaxy. We also present previously unpublished observations of the other H.E.S.S.-detected GRB, GRB 180720B from AMI-LA, which shows likely forward shock emission that fades in less than 10 d. We present a comparison between the radio emission from the three GRBs with detected very high energy (VHE) gamma-ray emission and a sensitivity-limited radio afterglow sample. GRB 190829A has the lowest isotropic radio luminosity of any GRB in our sample, but the distribution of luminosities is otherwise consistent, as expected, with the VHE GRBs being drawn from the same parent distribution as the other radio-detected long GRBs.
Chemical components of organic aerosol (OA) selectively absorb light at short wavelengths. In this study, the prevalence, sources, and optical importance of this so-called brown carbon (BrC) aerosol ...component are investigated throughout the North American continental tropospheric column during a summer of extensive biomass burning. Spectrophotometric absorption measurements on extracts of bulk aerosol samples collected from an aircraft over the central USA were analyzed to directly quantify BrC abundance. BrC was found to be prevalent throughout the 1 to 12 km altitude measurement range, with dramatic enhancements in biomass-burning plumes. BrC to black carbon (BC) ratios, under background tropospheric conditions, increased with altitude, consistent with a corresponding increase in the absorption Aangstrom exponent (AAE) determined from a three-wavelength particle soot absorption photometer (PSAP). The sum of inferred BC absorption and measured BrC absorption at 365 nm was within 3 % of the measured PSAP absorption for background conditions and 22 % for biomass burning. A radiative transfer model showed that BrC absorption reduced top-of-atmosphere (TOA) aerosol forcing by ~ 20 % in the background troposphere. Extensive radiative model simulations applying this study background tropospheric conditions provided a look-up chart for determining radiative forcing efficiencies of BrC as a function of a surface-measured BrC : BC ratio and single scattering albedo (SSA). The chart is a first attempt to provide a tool for better assessment of brown carbon's forcing effect when one is limited to only surface data. These results indicate that BrC is an important contributor to direct aerosol radiative forcing.
In common parlance, moral transgressions "leave a bad taste in the mouth." This metaphor implies a link between moral disgust and more primitive forms of disgust related to toxicity and disease, yet ...convincing evidence for this relationship is still lacking. We tested directly the primitive oral origins of moral disgust by searching for similarity in the facial motor activity evoked by gustatory distaste (elicited by unpleasant tastes), basic disgust (elicited by photographs of contaminants), and moral disgust (elicited by unfair treatment in an economic game). We found that all three states evoked activation of the levator labii muscle region of the face, characteristic of an oralnasal rejection response. These results suggest that immorality elicits the same disgust as disease vectors and bad tastes.
Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing ...these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.
Single photons and entangled photon pairs are a key resource of many quantum secure communication and quantum computation protocols, and non-Poissonian sources emitting in the low-loss wavelength ...region around 1,550 nm are essential for the development of fibre-based quantum network infrastructure. However, reaching this wavelength window has been challenging for semiconductor-based quantum light sources. Here we show that quantum dot devices based on indium phosphide are capable of electrically injected single photon emission in this wavelength region. Using the biexciton cascade mechanism, they also produce entangled photons with a fidelity of 87 ± 4%, sufficient for the application of one-way error correction protocols. The material system further allows for entangled photon generation up to an operating temperature of 93 K. Our quantum photon source can be directly integrated with existing long distance quantum communication and cryptography systems, and provides a promising material platform for developing future quantum network hardware.
ABSTRACT
We present radio and optical afterglow observations of the TeV-bright long gamma-ray burst 190114C at a redshift of z = 0.425, which was detected by the Major Atmospheric Gamma Imaging ...Cherenkov telescope. Our observations with Atacama Large Millimeter/submillitmeter Array, Australia Telescope Compact Array, and upgraded Giant Metre-wave Radio Telescope were obtained by our low frequency observing campaign and range from ∼1 to ∼140 d after the burst and the optical observations were done with three optical telescopes spanning up to ∼25 d after the burst. Long-term radio/mm observations reveal the complex nature of the afterglow, which does not follow the spectral and temporal closure relations expected from the standard afterglow model. We find that the microphysical parameters of the external forward shock, representing the share of shock-created energy in the non-thermal electron population and magnetic field, are evolving with time. The inferred kinetic energy in the blast-wave depends strongly on the assumed ambient medium density profile, with a constant density medium demanding almost an order of magnitude higher energy than in the prompt emission, while a stellar wind-driven medium requires approximately the same amount energy as in prompt emission.
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