Actuators and Sensors Based on Tensegrity D-bar Structures

Tensegrity offers lightweight deployable structures for use in many engineering disciplines. Among all of the available tensegrity forms, D-Bar has a potential for combined applications of sensing, actuation, and structural support. In this paper, we enhance the minimal mass formulation of the D-Bar by including yielding of the compressive members as a design constraint in contrast to the previous assumption which considers buckling as the sole failure mechanism. In addition, we analyze the length and force gains of a D-bar system analytically by considering the minimal mass D-bar as the design constraint. Furthermore, we calculate the stiffness of the D-Bar and when appropriate use as design constraints as well. To enhance the minimal mass properties of the D-Bar, we combine T-bar and D-bar systems. The analysis shows that these structures are the basis for effective force transducers, force-controlled actuators, and efficient deployable compressive structures

Galectin-3 inhibitor GB0139 protects against acute lung injury by inhibiting neutrophil recruitment and activation

Rationale: Galectin-3 (Gal-3) drives fibrosis during chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Effective pharmacological therapies available for ALI are limited; identifying novel concepts in treatment is essential. GB0139 is a Gal-3 inhibitor currently under clinical investigation for the treatment of idiopathic pulmonary fibrosis. We investigate the role of Gal-3 in ALI and evaluate whether its inhibition with GB0139 offers a protective role. The effect of GB0139 on ALI was explored in vivo and in vitro. Methods: The pharmacokinetic profile of intra-tracheal (i.t.) GB0139 was investigated in C57BL/6 mice to support the daily dosing regimen. GB0139 (1–30 µg) was then assessed following acute i.t. lipopolysaccharide (LPS) and bleomycin administration. Histology, broncho-alveolar lavage fluid (BALf) analysis, and flow cytometric analysis of lung digests and BALf were performed. The impact of GB0139 on cell activation and apoptosis was determined in vitro using neutrophils and THP-1, A549 and Jurkat E6 cell lines. Results: GB0139 decreased inflammation severity via a reduction in neutrophil and macrophage recruitment and neutrophil activation. GB0139 reduced LPS-mediated increases in interleukin (IL)-6, tumor necrosis factor alpha (TNFα) and macrophage inflammatory protein-1-alpha. In vitro, GB0139 inhibited Gal-3-induced neutrophil activation, monocyte IL-8 secretion, T cell apoptosis and the upregulation of pro-inflammatory genes encoding for IL-8, TNFα, IL-6 in alveolar epithelial cells in response to mechanical stretch. Conclusion: These data indicate that Gal-3 adopts a pro-inflammatory role following the early stages of lung injury and supports the development of GB0139, as a potential treatment approach in ALI

Cryogenic detector preamplifer developments at the ANU

We present a summary of the cryogenic detector preamplifier development programme under way at the ANU. Cryogenic preamplifiers have been demonstrated for both near-infrared detectors (Teledyne H1RG and Leonardo SAPHIRA eAPD as part of development for the GMTIFS instrument) and optical CCDs (e2v CCD231-84 for use with the AAT/Veloce spectrograph). This approach to detector signal conditioning allows low-noise instrument amplifiers to be placed very close to an infra-red detector or optical CCD, isolating the readout path from external interference noise sources. Laboratory results demonstrate effective isolation of the readout path from external interference noise sources. Recent progress has focussed on the first on-sky deployment of four cryogenic preamp channels for the Veloce Rosso precision radial velocity spectrograph. We also outline future evolution of the current design, allowing higher speeds and further enhanced performance for the demanding applications required for the on instrument wavefront sensor on the Giant Magellan Integral Field Spectrograph (GMTIFS).This research was supported under Australian Research Council's Linkage Project funding scheme (LP150100620) in partnership with the Australian National University and Giant Magellan Telescope Organisation

An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE):A Phase Ib/IIa Randomised Controlled Trial

RATIONALE: High circulating galectin-3 is associated with poor outcomes in patients with coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with antiinflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis. OBJECTIVES: Primary outcomes were safety and tolerability of inhaled GB0139 as an add-on therapy for patients hospitalized with COVID-19 pneumonitis. METHODS: We present the findings of two arms of a phase Ib/IIa randomized controlled platform trial in hospitalized patients with confirmed COVID-19 pneumonitis. Patients received standard of care (SoC) or SoC plus 10 mg inhaled GB0139 twice daily for 48 hours, then once daily for up to 14 days or discharge. MEASUREMENTS AND MAIN RESULTS: Data are reported from 41 patients, 20 of which were assigned randomly to receive GB0139. Primary outcomes: the GB0139 group experienced no treatment-related serious adverse events. Incidences of adverse events were similar between treatment arms (40 with GB0139 + SoC vs. 35 with SoC). Secondary outcomes: plasma GB0139 was measurable in all patients after inhaled exposure and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc analysis of covariance [ANCOVA] over days 2–7; P = 0.0099 vs. SoC). Plasma biomarkers associated with inflammation, fibrosis, coagulopathy, and major organ function were evaluated. CONCLUSIONS: In COVID-19 pneumonitis, inhaled GB0139 was well-tolerated and achieved clinically relevant plasma concentrations with target engagement. The data support larger clinical trials to determine clinical efficacy. Clinical trial registered with ClinicalTrials.gov (NCT04473053) and EudraCT (2020–002230–32)

Veloce Rosso: Australia's new precision radial velocity spectrograph

Veloce is an ultra-stable fibre-fed R4 echelle spectrograph for the 3.9 m Anglo-Australian Telescope. The first channel to be commissioned, Veloce ‘Rosso’, utilises multiple low-cost design innovations to obtain Doppler velocities for sun-like and M-dwarf stars at 75,000 spectra over a 580-930 nm range for the Rosso channel. Simultaneous calibration is provided by a single-mode pulsed laser frequency comb in tandem with a traditional arc lamp. A bundle of 19 object fibres ensures full sampling of stellar targets from the AAT site. Veloce is housed in dual environmental enclosures that maintain positive air pressure at a stability of ±0.3 mbar, with a thermal stability of ±0.01 K on the optical bench. We present a technical overview and early performance data from Australia's next major spectroscopic machine

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)

GMTIFS: Challenging optical design problems and their solutions for the GMT integral-field spectrograph

GMTIFS is a first generation instrument for the Giant Magellan Telescope (GMT). It is a combined Imager and Integral Field Spectrograph (IFS) designed to work with the Adaptive Optics (AO) Systems of the GMT. Working at the diffraction limit of the GMT and satisfying the challenging AO interface requirements and constraints results in unique optical challenges. We describe two of these challenges and how we have addressed them. The GMT has a direct feed architecture that maximizes transmission and reduces emissivity. This means that the cryostat window is tilted to reflect visual wavelengths to the external Visual Wave Front Subsystem (VWS). For a plane-parallel window, this tilt causes astigmatism in the transmitted beam that must be corrected. A corrective system using two plates, tilted and slightly wedged in opposite directions, is used. Geometry and performance of the system is described. Another challenging problem is the optical design of the anamorphic field projector. The Integral Field Unit of GMTIFS requires that a small field delivered to it be projected onto an Image Slicer at much larger scale, with the magnification in the spectral direction being twice that in the spatial direction so that the spaxels are square when referred to the sky. Output images must be coincident in the spectral and spatial projections in both the field and pupil domains. Additionally, field and pupil image locations must be independently controllable so that they can be made coincident for interchangeable units that provide a range of output field scales. A two-mirror system that satisfies these requirements is described

The adaptive optics beam steering mirror for the GMT Integral-Field Spectrograph, GMTIFS

To achieve the high adaptive optics sky coverage necessary to allow the GMT Integral-Field Spectrograph to access key scientific targets, the on-instrument adaptive-optics wavefront-sensing system must patrol the full 180 arcsecond diameter guide field passed to the instrument. Starlight must be held stationary on the wavefront sensor (accounting for flexure, differential refraction and non-sidereal tracking rates) to ∼ 1 milliarcsecond to provide the stable position reference signal for deep AO observations and avoid introducing image blur. Hence a tight tolerance of 1/180,000 is placed on the positioning and encoding accuracy for the cryogenic On-Instrument Wave-Front Sensor feed. GMTIFS will achieve this requirement using a beam-steering mirror system as an optical relay for starlight from across the accessible guide field. The system avoids hysteresis and backlash by eliminating friction and avoiding gearing while maintaining high setting speed and accuracy with a precision feedback loop. Here we present the design of the relay system and the technical solution deployed to meet the challenging specifications for drive rate, accuracy and positional encoding of the beam-steering system

GMTIFS: Deformable mirror environmental testing for the on-instrument wavefront sensor

GMTIFS requires a deformable mirror (DM) as part of its on-instrument wavefront sensor (OIWFS). The DM facilitates wavefront correction for the off-axis natural guide star, with the objective being to maximize the energy in the diffraction core and improve the signal-to-noise ratio of the guide star position measurement. It is essential that the OIWFS be positionally stable with respect to the science field. The use of J–K to observe the guide star, and thus the need to limit thermal background, essentially requires the DM in the OIWFS to be operated at or below −40°C. This is below the standard operating temperature range of currently available DMs. In cooperation with the manufacturers we are testing the performance of three DMs at temperatures from ambient to −45°C, or cooler. In the context of the OIWFS adequate stroke, open-loop positioning stability, hysteresis, interactuator surface figure and dynamic response are key performance criteria. A test system based around high spatial sampling of the DM aperture with a Shack-Hartmann wavefront sensor has been built. The opto-mechanical design permits a DM to be contained in a cryostat so that it may be cooled in isolation. We describe this test system and the test cases that are applied to the ALPAO DM-69, Boston MicroMachines 492DM and the IrisAO PTT111 deformable mirrors. Preliminary results at ambient temperatures are presented