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Disturbed fluid flow is well understood to have significant ramifications on endothelial function, but the impact disturbed flow has on endothelial biomechanics is not well understood. In this study, we measured tractions, intercellular stresses, and cell velocity of endothelial cells exposed to disturbed flow using a custom-fabricated f low chamber. Our flow chamber exposed cells to disturbed fluid flow within the following spatial zones: zone 1 (inlet; length 0.676–2.027 cm): 0.0037 ± 0.0001 Pa; zone 2 (middle; length 2.027–3.716 cm): 0.0059 ± 0.0005 Pa; and zone 3 (outlet; length 3.716–5.405 cm): 0.0051 ± 0.0025 Pa. Tractions and intercellular stresses were observed to be highest in the middle of the chamber (zone 2) and lowest at the chamber outlet (zone 3), while cell velocity was highest near the chamber inlet (zone 1), and lowest near the middle of the chamber (zone 2). Our findings suggest endothelial biomechanical response to disturbed fluid flow to be dependent on not only shear stress magnitude, but the spatial shear stress gradient as well. We believe our results will be useful to a host of fields including endothelial cell biology, the cardiovascular field, and cellular biomechanics in general.more » « less
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WISE J224607.6–052634.9 (W2246–0526) is a hot dust-obscured galaxy atz = 4.601, and the most luminous obscured quasar known to date. W2246–0526 harbors a heavily obscured supermassive black hole that is most likely accreting above the Eddington limit. We present observations with the Atacama Large Millimeter/submillimeter Array (ALMA) in seven bands, including band 10, of the brightest far-infrared (FIR) fine-structure emission lines of this galaxy: [OI]63 μm, [OIII]88 μm, [NII]122 μm, [OI]145 μm, [CII]158 μm, [NII]205 μm, [CI]370 μm, and [CI]609 μm. A comparison of the data to a large grid of CLOUDYradiative transfer models reveals that a high hydrogen density (nH ∼ 3 × 103cm−3) and extinction (AV ∼ 300 mag), together with extreme ionization (log(U) = − 0.5) and a high X-ray to UV ratio (αox ≥ −0.8) are required to reproduce the observed nuclear line ratios. The values ofαoxandUare among the largest found in the literature and imply the existence of an X-ray-dominated region (XDR). In fact, this component explains the a priori very surprising non-detection of the [OIII]88 μmemission line, which is actually suppressed, instead of boosted, in XDR environments. Interestingly, the best-fitted model implies higher X-ray emission and lower CO content than what is detected observationally, suggesting the presence of a molecular gas component that should be further obscuring the X-ray emission over larger spatial scales than the central region that is being modeled. These results highlight the need for multiline infrared observations to characterize the multiphase gas in high redshift quasars and, in particular, W2246–0526 serves as an extreme benchmark for comparisons of interstellar medium conditions with other quasar populations at cosmic noon and beyond.more » « less
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We report results of a project to map HCN and HCO+ J=1→0 emission toward a sample of molecular clouds in the inner Galaxy, all containing dense clumps that are actively engaged in star formation. We compare these two molecular line tracers with millimeter continuum emission and extinction, as inferred from 13CO, as tracers of dense gas in molecular clouds. The fraction of the line luminosity from each tracer that comes from the dense gas, as measured by AV>8 mag, varies substantially from cloud to cloud. In all cases, a substantial fraction (in most cases, the majority) of the total luminosity arises in gas below the AV>8 mag threshold and outside the region of strong millimeter continuum emission. Measurements of L(HCN) toward other galaxies will likely be dominated by such gas at lower surface densities. Substantial, even dominant, contributions to the total line luminosity can arise in gas with densities typical of the cloud as a whole (n ∼ 100 cm-3). Defining the dense clump from the HCN or HCO+ emission itself, similarly to previous studies, leads to a wide range of clump properties, with some being considerably larger and less dense than in previous studies. HCN and HCO+ have a similar ability to trace dense gas for the clouds in this sample. For the two clouds with low virial parameters, 13CO is definitely a worse tracer of the dense gas, but for the other four, it is equally good (or bad) at tracing dense gas.more » « less
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Abstract The human brain microvasculature is constantly exposed to variable fluid flow regimes and their influence on the endothelium depends in part on the synchronous cooperative behavior between cell–cell junctions and the cytoskeleton. In this study, we exposed human cerebral microvascular endothelial cells to a low laminar flow (1 dyne⋅cm−2), high laminar flow (10 dyne⋅cm−2), low oscillatory flow (±1 dyne⋅cm−2), or high oscillatory flow (±10 dyne⋅cm−2) for 24 hr. After this time, endothelial cell–cell junction and cytoskeletal structural response was characterized through observation of zonula occludens‐1 (ZO‐1), claudin‐5, junctional adhesion molecule‐A (JAM‐A), vascular endothelial cadherin (VE‐Cad), and F‐actin. In addition, we also characterized cell morphology through measurement of cell area and cell eccentricity. Our results revealed the greatest change in junctional structure reorganization for ZO‐1 and JAM‐A to be observed under low laminar flow conditions while claudin‐5 exhibited the greatest change in structural reorganization under both low and high laminar flow conditions. However, VE‐Cad displayed the greatest structural response under a high laminar flow, reflecting the unique responses each cell–cell junction protein had to each fluid flow regime. In addition, cell area and cell eccentricity displayed most significant changes under the high laminar flow and low oscillatory flow, respectively. We believe this study will be useful to the field of cell mechanics and mechanobiology.more » « less
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