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A critical role of vascular endothelium is as a semi-permeable barrier, dynamically regulating the flux of solutes between blood and the surrounding tissue. Existing platforms that quantify endothelial function in vitro are either significantly throughput limited or overlook physiologically relevant extracellular matrix (ECM) interactions and thus do not recapitulate in vivo function. Leveraging droplet microfluidics, we developed a scalable platform to measure endothelial function in nanoliter-volume, ECM-based microtissues. In this study, we describe our high-throughput method for fabricating endothelial-coated collagen microtissues that incorporate physiologically relevant cell–ECM interactions. We showed that the endothelial cells had characteristic morphology, expressed tight junction proteins, and remodeled the ECM via compaction and deposition of basement membrane. We also measured macromolecular permeability using two optical modalities, and found the cell layers: (1) had permeability values comparable to in vivo measurements and (2) were responsive to physiologically-relevant modulators of endothelial permeability (TNF-α and TGF-β). This is the first demonstration, to the authors’ knowledge, of high-throughput assessment ( n > 150) of endothelial permeability on natural ECM. Additionally, this technology is compatible with standard cell culture equipment ( e.g. multi-well plates) and could be scaled up further to be integrated with automated liquid handling systems and automated imaging platforms. Overall, this platform recapitulates the functions of traditional transwell inserts, but extends application to high-throughput studies and introduces new possibilities for interrogating cell–cell and cell–matrix interactions.
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Heterostructure design to achieve high quality, high density GaAs 2D electron system with g -factor tending to zero
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ABSTRACT Drosophila’s innate response to gravity, geotaxis, has been used to assess the impact of aging and disease on motor performance. Despite its rich history, fly geotaxis continues to be largely measured manually and assessed through simplistic metrics, limiting analytic insights into the behavior. Here, we have constructed a fully programmable apparatus and developed a multi-object tracking software capable of following sub-second movements of individual flies, thus allowing quantitative analysis of geotaxis. The apparatus monitors 10 fly cohorts simultaneously, with each cohort consisting of up to 7 flies. The software tracks single flies during the entire run with ∼97% accuracy, yielding detailed climbing curve, speed and movement direction with 1/30 s resolution. Our tracking permits the construction of multi-variable metrics and the detection of transitory movement phenotypes, such as slips and falls. The platform is therefore poised to advance Drosophila geotaxis assay into a comprehensive assessment of locomotor behavior.more » « less
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Context.Since 2019, GRAVITY has provided direct observations of giant planets and brown dwarfs at separations of down to 95 mas from the host star. Some of these observations have provided the first direct confirmation of companions previously detected by indirect techniques (astrometry and radial velocities). Aims.We want to improve the observing strategy and data reduction in order to lower the inner working angle of GRAVITY in dual-field on-axis mode. We also want to determine the current limitations of the instrument when observing faint companions with separations in the 30–150 mas range. Methods.To improve the inner working angle, we propose a fiber off-pointing strategy during the observations to maximize the ratio of companion-light-to-star-light coupling in the science fiber. We also tested a lower-order model for speckles to decouple the companion light from the star light. We then evaluated the detection limits of GRAVITY using planet injection and retrieval in representative archival data. We compare our results to theoretical expectations. Results.We validate our observing and data-reduction strategy with on-sky observations; first in the context of brown dwarf follow-up on the auxiliary telescopes with HD 984 B, and second with the first confirmation of a substellar candidate around the starGaiaDR3 2728129004119806464. With synthetic companion injection, we demonstrate that the instrument can detect companions down to a contrast of 8 × 10−4(ΔΚ= 7.7 mag) at a separation of 35 mas, and a contrast of 3 × 10−5(ΔΚ= 11 mag) at 100 mas from a bright primary (K< 6.5), for 30 min exposure time. Conclusions.With its inner working angle and astrometric precision, GRAVITY has a unique reach in direct observation parameter space. This study demonstrates the promising synergies between GRAVITY andGaiafor the confirmation and characterization of substellar companions.more » « less
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ABSTRACT High-fidelity radio interferometric data calibration that minimizes spurious spectral structure in the calibrated data is essential in astrophysical applications, such as 21 cm cosmology, which rely on knowledge of the relative spectral smoothness of distinct astrophysical emission components to extract the signal of interest. Existing approaches to radio interferometric calibration have been shown to impart spurious spectral structure to the calibrated data if the sky model used to calibrate the data is incomplete. In this paper, we introduce BayesCal: a novel solution to the sky-model incompleteness problem in interferometric calibration, designed to enable high-fidelity data calibration. The BayesCal data model supplements the a priori known component of the forward model of the sky with a statistical model for the missing and uncertain flux contribution to the data, constrained by a prior on the power in the model. We demonstrate how the parameters of this model can be marginalized out analytically, reducing the dimensionality of the parameter space to be sampled from and allowing one to sample directly from the posterior probability distribution of the calibration parameters. Additionally, we show how physically motivated priors derived from theoretical and measurement-based constraints on the spectral smoothness of the instrumental gains can be used to constrain the calibration solutions. In a companion paper, we apply this algorithm to simulated observations with a HERA-like array and demonstrate that it enables up to four orders of magnitude suppression of power in spurious spectral fluctuations relative to standard calibration approaches.more » « less
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0013938
