The gravitationally lensed, luminous infrared galaxy IRAS F10214+4724 observed with XMM-Newton

We report on a short XMM-Newton observation of the gravitationally-lensed, luminous infrared galaxy IRAS F10214+4724 at z=2.3. A faint X-ray source is detected at 4 sigma. The observed 0.5-2 keV (1.7-6.6 keV in the rest-frame) flux is 1.3e-15 erg/s/cm2 and the spectral slope in the rest-frame 1-10 keV band is Gamma~2. These results agree with those obtained from the Chandra X-ray Observatory, given the large uncertainties in both measurements. While possible evidence for excess emission above 5 keV is seen, we suspect this excess might be either spurious or not related to the infrared galaxy.Comment: 4 pages, 2 figures, New Astronomy in pres

Neuroinflammation in Multiple System Atrophy: Response to and Cause of α-Synuclein Aggregation

Multiple system atrophy (MSA) is a progressive neurodegenerative disease presenting with combinations of autonomic dysfunction, parkinsonism, cerebellar ataxia and/or pyramidal signs. Oligodendroglial cytoplasmic inclusions (GCIs) rich in α-synuclein (α-syn) constitute the disease hallmark, accompanied by neuronal loss and activation of glial cells which indicate neuroinflammation. Recent studies demonstrate that α-syn may be released from degenerating neurons to mediate formation of abnormal inclusion bodies and to induce neuroinflammation which, interestingly, might also favor the formation of intracellular α-syn aggregates as a consequence of cytokine release and the shift to a pro-inflammatory environment. Here, we critically review the relationships between α-syn and astrocytic and microglial activation in MSA to explore the potential of therapeutics which target neuroinflammation.9 page(s

Deep Submillimeter Surveys: Luminous Infrared Galaxies at High Redshift

Deep surveys at 850microns from Mauna Kea using the SCUBA camera on the JCMT appear to have discovered a substantial population of ultraluminous infrared galaxies (ULIGs: L_ir > 10^{12} L_sun). The cumulative space density of these sources (~10,000 per sq.deg with S_850 > 1mJy) is sufficient to account for nearly all of the extragalactic background light at submillimeter wavelengths. Current estimates of the redshift distribution suggest a peak in the comoving space density of SCUBA sources at z = 1-3, similar to what is observed for QSOs and radio galaxies. The luminosity density in the far-infrared/submillimeter exceeds that in the UV by factors of 3-10 over this redshift range, implying that as much as 80-90% of the "activity" in galaxies at z < 4 is hidden by dust. The SCUBA sources plausibly represent the primary epoch in the formation of spheroids and massive black holes triggered by major mergers of large gas-rich disks.Comment: LaTex, 14 pages with 9 embedded .eps figures. To appear in ``Space Infrared Telescopes and Related Science", 32nd COSPAR workshop, Nagoya, Japan 1998, ed. T. Matsumoto, T. de Graau

The CO line SED and atomic carbon in IRAS F10214+4724

Using the IRAM 30m telescope and the Plateau de Bure interferometer we have detected the \ctwo and the CO 3$-$2, 4$-$3, 6$-$5, 7$-$6 transitions as well as the dust continuum at 3 and 1.2 mm towards the distant luminous infrared galaxy IRAS F10214+4724 at $z=2.286$. The \ctwo line is detected for the first time towards this source and IRAS F10214+4724 now belongs to a sample of only 3 extragalactic sources at any redshift where both of the carbon fine structure lines have been detected. The source is spatially resolved by our \ctwo\ observation and we detect a velocity gradient along the east-west direction. The CI line ratio allows us to derive a carbon excitation temperature of 42$^{+12}_{-9}$ K. The carbon excitation in conjunction with the CO ladder and the dust continuum constrain the gas density to n(\hh) = $10^{3.6-4.0}$ cm$^{-3}$ and the kinetic temperature to $T\rm_{kin}$ = 45--80 K, similar to the excitation conditions found in nearby starburst galaxies. The rest-frame 360 $\mu$m dust continuum morphology is more compact than the line emitting region, which supports previous findings that the far infrared luminosity arises from regions closer to the active galactic nucleus at the center of this system.Comment: 11 pages, 9 figures, accepted by A&

Highly-excited CO emission in APM08279+5255 at z=3.9

We report the detection of the CO 4-3, 6-5, 9-8, 10-9, and 11-10 lines in the Broad Absorption Line quasar APM08279+5255 at z=3.9 using the IRAM 30m telescope. We also present IRAM PdBI high spatial resolution observations of the CO 4-3 and 9-8 lines, and of the 1.4mm dust radiation as well as an improved spectrum of the HCN(5-4) line. Unlike CO in other QSO host galaxies, the CO line SED of APM08279+5255 rises up to the CO(10-9) transition. The line fluxes in the CO ladder and the dust continuum fluxes are best fit by a two component model, a "cold" component at ~65K with a high density of n(H2)= 1x10^5 cm^-3, and a "warm", ~220K component with a density of 1x10^4 cm^-3. We show that IR pumping via the 14 micron bending mode of HCN is the most likely channel for the HCN excitation. From our models we find, that the CO(1-0) emission is dominated by the {\it dense} gas component which implies that the CO conversion factor is higher than usually assumed for high-z galaxies with alpha~5 SM/(K km/s pc^2). Using brightness temperature arguments, the results from our high-resolution mapping, and lens models from the literature, we argue that the molecular lines and the dust continuum emission arise from a very compact (r~100-300 pc), highly gravitationally magnified (m= 60-110) region surrounding the central AGN. Part of the difference relative to other high-$z$ QSOs may therefore be due to the configuration of the gravitational lens, which gives us a high-magnification zoom right into the central 200-pc radius of APM08279+5255 where IR pumping plays a significant role for the excitation of the molecular lines.Comment: 18 pages, 14 figures, accepted for publication in A&

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Environmental Factors Controlling the Distribution of Symbiodinium Harboured by the Coral Acropora millepora on the Great Barrier Reef

Background: The Symbiodinium community associated with scleractinian corals is widely considered to be shaped by seawater temperature, as the coral's upper temperature tolerance is largely contingent on the Symbiodinium types harboured. Few studies have challenged this paradigm as knowledge of other environmental drivers on the distribution of Symbiodinium is limited. Here, we examine the influence of a range of environmental variables on the distribution of Symbiodinium associated with Acropora millepora collected from 47 coral reefs spanning 1,400 km on the Great Barrier Reef (GBR), Australia

Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged &lt;65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.ObjectiveThis study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD.MethodsParticipants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional impairment (ie, prodromal FTLD), 43 (18.6%) with neurobehavioral changes and functional impairment (ie, symptomatic FTLD), and 139 (60.2%) clinically normal adults, of whom 55 (39.6%) harbored heterozygous pathogenic or likely pathogenic variants in an autosomal dominant FTLD gene. Participants completed the Clinical Dementia Rating plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Behavior and Language Domains (CDR+NACC FTLD) scale, a neuropsychological battery; the Neuropsychiatric Inventory; and brain magnetic resonance imaging. The ALLFTD Mobile App was installed on participants' smartphones for remote, passive, and continuous monitoring of smartphone use. Battery percentage was collected every 15 minutes over an average of 28 (SD 4.2; range 14-30) days. To determine whether temporal patterns of battery percentage varied as a function of disease severity, linear mixed effects models examined linear, quadratic, and cubic effects of the time of day and their interactions with each measure of disease severity on battery percentage. Models covaried for age, sex, smartphone type, and estimated smartphone age.ResultsThe CDR+NACC FTLD global score interacted with time on battery percentage such that participants with prodromal or symptomatic FTLD demonstrated less change in battery percentage throughout the day (a proxy for less smartphone use) than clinically normal participants (P&lt;.001 in both cases). Additional models showed that worse performance in all cognitive domains assessed (ie, executive functioning, memory, language, and visuospatial skills), more neuropsychiatric symptoms, and smaller brain volumes also associated with less battery use throughout the day (P&lt;.001 in all cases).ConclusionsThese findings support a proof of concept that passively collected data about smartphone use behaviors associate with clinical impairment in FTLD. This work underscores the need for future studies to develop and validate passive digital markers sensitive to longitudinal clinical decline across neurodegenerative diseases, with potential to enhance real-world monitoring of neurobehavioral change

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice