The vascular glycocalyx is not a mechanosensor in conduit arteries in the anesthetized pig.

The role of the glycocalyx as the endothelial sensor of an increase in blood flow was assessed in the iliac artery in vivo. Acetylcholine-induced flow mediated dilation was evaluated before and after vascular glycocalyx disruption. This was accomplished by exposing the iliac lumen to the chemotactic agent fMLP (1 μM; = 6 pigs), concomitant heparinase III (100 mU ml) and hyaluronidase (14 mg ml) ( = 4), and neuraminidase (140 mU ml; = 5), for 20 min in separate iliac artery preparations. Only one lumen intervention per iliac was conducted. For the heparinase III + hyaluronidase experiment, the iliac diameter increased by an average of 0.54 ± 0.11 mm before and 0.45 ± 0.03 mm after the enzymes ( = 0.42; paired Student's test). The iliac diameter increased by 0.31 ± 0.02 mm before and 0.29 ± 0.07 mm after fMLP exposure ( = 0.7) and the diameter increased by 0.54 ± 0.11 mm before and 0.54 ± 0.09 mm after neuraminidase exposure ( = 0.98). In all cases, the shear stress changes before and after lumen exposure were not significantly different to each other. There was no significant reduction in flow mediated dilation of the iliac in response to any of the interventions conducted. Therefore, the vascular endothelial glycocalyx as whole is not required for flow mediated dilation in conduit arteries in the intact animal

Heparan sulphate and hyaluronic acid components of the glycocalyx do not play a role in flow-mediated dilation of the iliac in the anaesthetized pig

The shear-stress sensor function of vascular glycocalyx heparan sulphate and hyaluronic acid was investigated in vivo by assessing flow-mediated dilation before and after their removal. Heparinase III exposure (100 mU·mL−1 for 20 min;n = 6) did not significantly affect flow-mediated dilation of the iliac, from 0.42 ± 0.08 mm (mean ± SEM) to 0.34 ± 0.07 mm after (P = 0.12; paired Student’s t test) for a statistically similar increase in shear stress; 18.24 ± 4.2 N·m−2 for the control and 15.8 ± 3.6 N·m−2 for the heparinase III experiment (P = 0.18). Hyaluronidase exposure (0.14–1.4 mg·mL−1 for 20 min; n = 8) also did not significantly reduce flow-mediated dilation of the iliac, which averaged 0.39 ± 0.08 mm before and 0.38 ± 0.09 mm after (P = 0.11) for a statistically similar increase in shear stress; 11.90 ± 3.20 N·m−2 for the control and 9.8 ± 3.33 N·m−2 for the hyaluronidase experiment (P = 0.88). Removal of both heparan sulphate and hyaluronic acid was confirmed using immunohistochemistry. Neither the heparan sulphate nor the hyaluronic acid components of the glycocalyx mediate shear-stress-induced vasodilation in conduit arteries in vivo.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Reference Star Differential Imaging of Close-in Companions and Circumstellar Disks with the NIRC2 Vortex Coronagraph at the W. M. Keck Observatory

Reference star differential imaging (RDI) is a powerful strategy for high-contrast imaging. Using example observations taken with the vortex coronagraph mode of Keck/NIRC2 in L′ band, we demonstrate that RDI provides improved sensitivity to point sources at small angular separations compared to angular differential imaging (ADI). Applying RDI to images of the low-mass stellar companions HIP 79124 C (192 mas separation, ∆L′ = 4.01) and HIP 78233 B (141 mas separation, ∆L′ = 4.78), the latter a first imaging detection, increases the significance of their detections by up to a factor of 5 with respect to ADI. We compare methods for reference frame selection and find that pre- selection of frames improves detection significance of point sources by up to a factor of 3. In addition, we use observations of the circumstellar disks around MWC 758 and 2MASS J16042165-2130284 to show that RDI allows for accurate mapping of scattered light distributions without self-subtraction artifacts

Reference Star Differential Imaging of Close-in Companions and Circumstellar Disks with the NIRC2 Vortex Coronagraph at the W. M. Keck Observatory

© 2019. The American Astronomical Society. All rights reserved. Reference star differential imaging (RDI) is a powerful strategy for high-contrast imaging. Using example observations taken with the vortex coronagraph mode of Keck/NIRC2 in L′ band, we demonstrate that RDI provides improved sensitivity to point sources at small angular separations compared to angular differential imaging (ADI). Applying RDI to images of the low-mass stellar companions HIP 79124 C (192 mas separation, ΔL′ = 4.01) and HIP 78233 B (141 mas separation, ΔL′ = 4.78), the latter a first imaging detection, increases the significance of their detections by up to a factor of 5 with respect to ADI. We compare methods for reference frame selection and find that pre-selection of frames improves detection significance of point sources by up to a factor of 3. In addition, we use observations of the circumstellar disks around MWC 758 and 2MASS J16042165-2130284 to show that RDI allows for accurate mapping of scattered light distributions without self-subtraction artifacts.status: publishe

Characterizing the performance of the NIRC2 vortex coronagraph at W. M. Keck Observatory

International audienceThe NIRC2 vortex coronagraph is an instrument on Keck II designed to directly image exoplanets and circumstellar disks at mid-infrared bands L′ (3.4–4.1 μm) and Ms (4.55–4.8 μm). We analyze imaging data and corresponding adaptive optics telemetry, observing conditions, and other metadata over a three-year time period to characterize the performance of the instrument and predict the detection limits of future observations. We systematically process images from 359 observations of 304 unique stars to subtract residual starlight (i.e., thecoronagraphic point-spread function) of the target star using two methods: angular differential imaging (ADI) and reference star differential imaging (RDI). We find that for the typical parallactic angle (PA) rotation of our data set (∼10°), RDI provides gains over ADI for angular separations smaller than 0 25. Furthermore, we find a power-law relation between the angular separation from the host star and the minimum PA rotation required for ADI to outperform RDI, with a power-law index of −1.18 ± 0.08. Finally, we use random forest models to estimate ADI and RDI post-processed detection limits a priori. These models, which we provide publicly on a website, explain 70%–80% of the variance in ADI detection limits and 30%–50% of the variance in RDI detection limits. Averaged over a range of angular separations, our models predict both ADI and RDI contrast to within a factor of 2. These results illuminate important factors in high-contrast imaging observations with the NIRC2 vortex coronagraph, help improve observing strategies, and inform future upgrades to the hardware

Neonatal Systemic AAV Induces Tolerance to CNS Gene Therapy in MPS I Dogs and Nonhuman Primates

The potential host immune response to a nonself protein poses a fundamental challenge for gene therapies targeting recessive diseases. We demonstrate in both dogs and nonhuman primates that liver-directed gene transfer using an adeno-associated virus (AAV) vector in neonates induces a persistent state of immunological tolerance to the transgene product, substantially improving the efficacy of subsequent vector administration targeting the central nervous system (CNS). We applied this approach to a canine model of mucopolysaccharidosis type I (MPS I), a progressive neuropathic lysosomal storage disease caused by deficient activity of the enzyme α-l-iduronidase (IDUA). MPS I dogs treated systemically in the first week of life with a vector expressing canine IDUA did not develop antibodies against the enzyme and exhibited robust expression in the CNS upon intrathecal AAV delivery at 1 month of age, resulting in complete correction of brain storage lesions. Newborn rhesus monkeys treated systemically with AAV vector expressing human IDUA developed tolerance to the transgene, resulting in high cerebrospinal fluid (CSF) IDUA expression and no antibody induction after subsequent CNS gene therapy. These findings suggest that inducing tolerance to the transgene product during a critical period in immunological development can improve the efficacy and safety of gene therapy