NFIRAOS: TMT facility adaptive optics with conventional DMs

Although many of the instruments planned for the TMT (Thirty Meter Telescope) have their own closely-coupled adaptive optics systems, TMT will also have a facility Adaptive Optics (AO) system feeding three instruments on the Nasmyth platform. For this Narrow-Field Infrared Adaptive Optics System, NFIRAOS (pronounced nefarious), the TMT project considered two architectures. One, described in this paper, employs conventional deformable mirrors with large diameters of about 300 mm and this is the reference design adopted by the TMT project. An alternative design based on MEMS was also studied, and is being presented separately in this conference. The requirements for NFIRAOS include 0.8-5 microns wavelength range, 30 arcsecond diameter output field of view (FOV), excellent sky coverage, and diffraction- limited atmospheric turbulence compensation (specified at 133 nm RMS including residual telescope and science instrument errors.) The reference design for NFIRAOS includes multiple sodium laser guide stars over a 70 arcsecond FOV, and an infrared tip/tilt/focus/astigmatism natural guide star sensor within instruments. Larger telescopes require greater deformable mirror (DM) stroke. Although initially NFIRAOS will correct a 10 arcsecond science field, it uses two deformable mirrors in series, partly to provide sufficient stroke for atmospheric correction over the 30 m telescope aperture, but mainly to partially correct a 2 arcminute diameter "technical" field to sharpen near-IR natural guide stars and improve sky coverage. The planned upgrade to full performance includes replacing the groundconjugated DM with a higher actuator density, and using a deformable telescope secondary mirror as a "woofer." NFIRAOS incorporates an instrument rotator and selection of three live instruments: a near-Infrared integral field Imaging spectrograph, a near-infrared echelle spectrograph, and after upgrading NFIRAOS to full multi-conjugation, a wide field (30 arcsecond) infrared camera

Relating jet structure to photometric variability: the Herbig Ae star HD 163296

Herbig Ae/Be stars are intermediate-mass pre-main sequence stars surrounded by circumstellar dust disks. Some are observed to produce jets, whose appearance as a sequence of shock fronts (knots) suggests a past episodic outflow variability. This "jet fossil record" can be used to reconstruct the outflow history. We present the first optical to near-infrared (NIR) VLT/X-shooter spectra of the jet from the Herbig Ae star HD 163296. We determine physical conditions in the knots, as well as their kinematic "launch epochs". Knots are formed simultaneously on either side of the disk, with a regular interval of ~16 yr. The velocity dispersion versus jet velocity and the energy input are comparable in both lobes. However, the mass loss rate, velocity, and shock conditions are asymmetric. We find Mjet/Macc ~ 0.01-0.1, consistent with magneto-centrifugal jet launching models. No evidence for dust is found in the high-velocity jet, suggesting it is launched within the sublimation radius (<0.5 au). The jet inclination measured from proper motions and radial velocities confirms it is perpendicular to the disk. A tentative relation is found between the structure of the jet and the photometric variability of the source. Episodes of NIR brightening were previously detected and attributed to a dusty disk wind. We report for the first time significant optical fadings lasting from a few days up to a year, coinciding with the NIR brightenings. These are likely caused by dust lifted high above the disk plane; this supports the disk wind scenario. The disk wind is launched at a larger radius than the high-velocity atomic jet, although their outflow variability may have a common origin. No significant relation between outflow and accretion variability could be established. Our findings confirm that this source undergoes periodic ejection events, which may be coupled with dust ejections above the disk plane.Comment: 20 pages, 11 figures, accepted for publication in Astronomy & Astrophysic

The VLT-FLAMES Tarantula Survey XV. VFTS 822: A candidate Herbig B[e] star at low metallicity

We report the discovery of the B[e] star VFTS 822 in the 30 Doradus star-forming region of the Large Magellanic Cloud, classified by optical spectroscopy from the VLT-FLAMES Tarantula Survey and complementary infrared photometry. VFTS 822 is a relatively low-luminosity (log L = 4.04 ± 0.25 L⊙) B8[e] star. In this Letter, we evaluate the evolutionary status of VFTS 822 and discuss its candidacy as a Herbig B[e] star. If the object is indeed in the pre-main sequence phase, it would present an exciting opportunity to spectroscopically measure mass accretion rates at low metallicity, to probe the effect of metallicity on accretion rates

Targeted Proteomics Reveals Inflammatory Pathways that Classify Immune Dysregulation in Common Variable Immunodeficiency

Patients with common variable immunodeficiency (CVID) can develop immune dysregulation complications such as autoimmunity, lymphoproliferation, enteritis, and malignancy, which cause significant morbidity and mortality. We aimed to (i) assess the potential of serum proteomics in stratifying patients with immune dysregulation using two independent cohorts and (ii) identify cytokine and chemokine signaling pathways that underlie immune dysregulation in CVID. A panel of 180 markers was measured in two multicenter CVID cohorts using Olink Protein Extension Assay technology. A classification algorithm was trained to distinguish CVID with immune dysregulation (CVIDid, n = 14) from CVID with infections only (CVIDio, n = 16) in the training cohort, and validated on a second testing cohort (CVIDid n = 23, CVIDio n = 24). Differential expression in both cohorts was used to determine relevant signaling pathways. An elastic net classifier using MILR1, LILRB4, IL10, IL12RB1, and CD83 could discriminate between CVIDid and CVIDio patients with a sensitivity of 0.83, specificity of 0.75, and area under the curve of 0.73 in an independent testing cohort. Activated pathways (fold change > 1.5, FDR-adjusted p < 0.05) in CVIDid included Th1 and Th17-associated signaling, as well as IL10 and other immune regulatory markers (LAG3, TNFRSF9, CD83). Targeted serum proteomics provided an accurate and reproducible tool to discriminate between patients with CVIDid and CVIDio. Cytokine profiles provided insight into activation of Th1 and Th17 pathways and indicate a possible role for chronic inflammation and exhaustion in immune dysregulation. These findings serve as a first step towards the development of biomarkers for immune dysregulation in CVID

Immune Responses 6 Months After mRNA-1273 COVID-19 Vaccination and the Effect of a Third Vaccination in Patients with Inborn Errors of Immunity

Purpose: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective long-term protection against COVID-19 is therefore of great importance in these patients, but little is known about the decay of the immune response after primary vaccination. We studied the immune responses 6 months after two mRNA-1273 COVID-19 vaccines in 473 IEI patients and subsequently the response to a third mRNA COVID-19 vaccine in 50 patients with common variable immunodeficiency (CVID).Methods: In a prospective multicenter study, 473 IEI patients (including X-linked agammaglobulinemia (XLA) (N = 18), combined immunodeficiency (CID) (N = 22), CVID (N = 203), isolated or undefined antibody deficiencies (N = 204), and phagocyte defects (N = 16)), and 179 controls were included and followed up to 6 months after two doses of the mRNA-1273 COVID-19 vaccine. Additionally, samples were collected from 50 CVID patients who received a third vaccine 6 months after primary vaccination through the national vaccination program. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T cell responses were assessed.Results: At 6 months after vaccination, the geometric mean antibody titers (GMT) declined in both IEI patients and healthy controls, when compared to GMT 28 days after vaccination. The trajectory of this decline did not differ between controls and most IEI cohorts; however, antibody titers in CID, CVID, and isolated antibody deficiency patients more often dropped to below the responder cut-off compared to controls. Specific T cell responses were still detectable in 77% of controls and 68% of IEI patients at 6 months post vaccination. A third mRNA vaccine resulted in an antibody response in only two out of 30 CVID patients that did not seroconvert after two mRNA vaccines.Conclusion: A similar decline in IgG titers and T cell responses was observed in patients with IEI when compared to healthy controls 6 months after mRNA-1273 COVID-19 vaccination. The limited beneficial benefit of a third mRNA COVID-19 vaccine in previous non-responder CVID patients implicates that other protective strategies are needed for these vulnerable patients.</p

Tunable beam shaping with a phased array acousto-optic modulator

We demonstrate the generation of Bessel beams using an acousto-optic array based on a liquid filled cavity surrounded by a cylindrical multi-element ultrasound transducer array. Conversion of a Gaussian laser mode into a Bessel beam with tunable order and position is shown. Also higher-order Bessel beams up to the fourth order are successfully generated with experimental results very closely matching simulations

The InfraRed Imaging Spectrograph (IRIS) for TMT: Overview of innovative science programs

IRIS (InfraRed Imaging Spectrograph) is a first light near-infrared diffraction limited imager and integral field spectrograph being designed for the future Thirty Meter Telescope (TMT). IRIS is optimized to perform astronomical studies across a significant fraction of cosmic time, from our Solar System to distant newly formed galaxies (Barton et al. [1]). We present a selection of the innovative science cases that are unique to IRIS in the era of upcoming space and ground-based telescopes. We focus on integral field spectroscopy of directly imaged exoplanet atmospheres, probing fundamental physics in the Galactic Center, measuring 10^4 to 10^10 Msun supermassive black hole masses, resolved spectroscopy of young star-forming galaxies (1 < z < 5) and first light galaxies (6 < z < 12), and resolved spectroscopy of strong gravitational lensed sources to measure dark matter substructure. For each of these science cases we use the IRIS simulator (Wright et al. [2], Do et al. [3]) to explore IRIS capabilities. To highlight the unique IRIS capabilities, we also update the point and resolved source sensitivities for the integral field spectrograph (IFS) in all five broadband filters (Z, Y, J, H, K) for the finest spatial scale of 0.004" per spaxel. We briefly discuss future development plans for the data reduction pipeline and quicklook software for the IRIS instrument suite.Comment: Proceedings of the SPIE, 9147-36

NFIRAOS: TMT facility adaptive optics with conventional DMs

Although many of the instruments planned for the TMT (Thirty Meter Telescope) have their own closely-coupled adaptive optics systems, TMT will also have a facility Adaptive Optics (AO) system feeding three instruments on the Nasmyth platform. For this Narrow-Field Infrared Adaptive Optics System, NFIRAOS (pronounced nefarious), the TMT project considered two architectures. One, described in this paper, employs conventional deformable mirrors with large diameters of about 300 mm and this is the reference design adopted by the TMT project. An alternative design based on MEMS was also studied, and is being presented separately in this conference. The requirements for NFIRAOS include 0.8-5 microns wavelength range, 30 arcsecond diameter output field of view (FOV), excellent sky coverage, and diffraction- limited atmospheric turbulence compensation (specified at 133 nm RMS including residual telescope and science instrument errors.) The reference design for NFIRAOS includes multiple sodium laser guide stars over a 70 arcsecond FOV, and an infrared tip/tilt/focus/astigmatism natural guide star sensor within instruments. Larger telescopes require greater deformable mirror (DM) stroke. Although initially NFIRAOS will correct a 10 arcsecond science field, it uses two deformable mirrors in series, partly to provide sufficient stroke for atmospheric correction over the 30 m telescope aperture, but mainly to partially correct a 2 arcminute diameter "technical" field to sharpen near-IR natural guide stars and improve sky coverage. The planned upgrade to full performance includes replacing the groundconjugated DM with a higher actuator density, and using a deformable telescope secondary mirror as a "woofer." NFIRAOS incorporates an instrument rotator and selection of three live instruments: a near-Infrared integral field Imaging spectrograph, a near-infrared echelle spectrograph, and after upgrading NFIRAOS to full multi-conjugation, a wide field (30 arcsecond) infrared camera

VLT/X-shooter spectroscopy of the candidate black-hole X-ray binary MAXI J1659-152 in outburst

We present the optical to near-infrared spectrum of MAXI J1659-152, during the onset of its 2010 X-ray outburst. The spectrum was obtained with X-shooter on the ESO - Very Large Telescope (VLT) early in the outburst simultaneous with high quality observations at both shorter and longer wavelengths. At the time of the observations, the source was in the low-hard state. The X-shooter spectrum includes many broad (~2000 km/s), double-peaked emission profiles of H, HeI, HeII, characteristic signatures of a low-mass X-ray binary during outburst. We detect no spectral signatures of the low-mass companion star. The strength of the diffuse interstellar bands results in a lower limit to the total interstellar extinction of Av ~ 0.4 mag. Using the neutral hydrogen column density obtained from the X-ray spectrum we estimate Av ~1 mag. The radial-velocity structure of the interstellar NaI D and CaII H & K lines results in a lower limit to the distance of ~ 4 +/- 1 kpc, consistent with previous estimates. With this distance and Av, the dereddened spectral energy distribution represents a flat disk spectrum. The two subsequent 10 minute X-shooter spectra show significant variability in the red wing of the emission-line profiles, indicating a global change in the density structure of the disk, though on a timescale much shorter than the typical viscous timescale of the disk.Comment: Accepted for publication in ApJ Letter

Long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin 10%: a European post-authorization study

Aim: To assess the long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in European routine clinical practice. Materials & methods: This prospective, noninterventional, open-label, post-authorization safety study (EUPAS5812) sourced data on adverse events, immunogenicity, treatment regimens and product administration for 106 adult patients prescribed fSCIG 10% across 17 sites in six European countries from July 2014 to February 2020. Results: In total, 1171 treatment-emergent adverse events were reported in 94 patients (88.7%); 25.5% of these events were considered related to fSCIG 10%. Positive binding antibody titers developed in three patients; no neutralizing antibodies to recombinant human hyaluronidase were detected. Conclusion: This real-world study of fSCIG 10% is the longest to date and confirms its long-term safety and tolerability in adults with antibody deficiency diseases