GalSim is a collaborative, open-source project aimed at providing an image simulation tool of enduring benefit to the astronomical community. It provides a software library for generating images of ...astronomical objects such as stars and galaxies in a variety of ways, efficiently handling image transformations and operations such as convolution and rendering at high precision. We describe the GalSim software and its capabilities, including necessary theoretical background. We demonstrate that the performance of GalSim meets the stringent requirements of high precision image analysis applications such as weak gravitational lensing, for current datasets and for the Stage IV dark energy surveys of the Large Synoptic Survey Telescope, ESA’s Euclid mission, and NASA’s WFIRST-AFTA mission. The GalSim project repository is public and includes the full code history, all open and closed issues, installation instructions, documentation, and wiki pages (including a Frequently Asked Questions section). The GalSim repository can be found at https://github.com/GalSim-developers/GalSim.
Background: Tight junctions form a continuous belt‐like structure between cells and act to regulate paracellular signaling. Protein kinase C (PKC) has been shown to regulate tight junction assembly ...and disassembly and is activated by alcohol. Previous research has shown that alcohol increases the permeability of tight junctions in lung alveolar cells. However, little is known about alcohol’s effect on tight junctions in epithelium of the conducting airways. We hypothesized that long‐term alcohol exposure reduces zonula occluden‐1 (ZO‐1) and claudin‐1 localization at the cell membrane and increases permeability through a PKC‐dependent mechanism.
Methods: To test this hypothesis, we exposed normal human bronchial epithelial (NHBE) cells, cells from a human bronchial epithelial transformed cell line (Beas‐2B), and Beas‐2B expressing a PKCα dominant negative (DN) to alcohol (20, 50, and 100 mM) for up to 48 hours. Immunofluorescence was used to assess changes in ZO‐1, claudin‐1, claudin‐5, and claudin‐7 localization. Electric cell–substrate impedance sensing was used to measure the permeability of tight junctions between monolayers of NHBE, Beas‐2B, and DN cells.
Results: Alcohol increased tight junction permeability in a concentration‐dependent manner and decreased ZO‐1, claudin‐1, claudin‐5, and claudin‐7 localization at the cell membrane. To determine a possible signaling mechanism, we measured the activity of PKC isoforms (alpha, delta, epsilon, and zeta). PKCα activity significantly increased in Beas‐2B cells from 1 to 6 hours of 100 mM alcohol exposure, while PKCζ activity significantly decreased at 1 hour and increased at 3 hours. Inhibiting PKCα with Gö‐6976 prevented the alcohol‐induced protein changes in both ZO‐1 and claudin‐1 at the cell membrane. PKCα DN Beas‐2B cells were resistant to alcohol‐induced protein alterations.
Conclusions: These results suggest that alcohol disrupts ZO‐1, claudin‐1, claudin‐5, and claudin‐7 through the activation of PKCα, leading to an alcohol‐induced “leakiness” in bronchial epithelial cells. Such alcohol‐induced airway‐leak state likely contributes to the impaired airway host defenses associated with acute and chronic alcohol ingestion.
During the initial COVID‐19 shutdown, in the spring of 2020, dissection videos were created to meet the ongoing needs of all our student populations. In total, thirty‐one dissection videos were ...created, corresponding to each laboratory dissection. Videos were linked to an online Interactive Dissecting Guide, which students could access through a secure network. Dissection videos were initially utilized for virtual laboratory sessions and as a supplementary resource for students. Upon the return of in‐person courses, the videos were then primarily used as supplemental resources. The purpose of this study was to retroactively determine student usage and feedback.
Methods
An anonymous survey was sent to students in the Colleges of Medicine, Allied Health, and Graduate Studies who had access to dissection videos during their gross anatomy courses. Data regarding video views was extracted from Echo360 and mapped to student populations covering the specific content at that time.
Results
Initial analysis showed that students tended to watch the videos more at the beginning of a unit and then tapered off toward the end of the unit. Additionally, videos that accompanied faculty lab demonstrations were viewed the least. Survey analysis of student feedback demonstrated that 77.6% of the respondents found the videos to be “very useful” and the remaining students ranked them as “somewhat useful.” Of the students that viewed the videos, 86.2% of them indicated that they viewed them frequently.
Conclusions
Students utilized and valued high quality dissection videos created specifically for their laboratory dissection content. Students had a tendency to utilize the videos in higher numbers at the beginning of each unit and less at the end of each unit.
Major embryonic hand development occurs in approximately the fifth week of gestation. The normal course of limb development can be affected by environmental or genetic factors leading to various ...congenital anomalies. The variability and severity of the anomalies could lead to functional deficits, truncated development, or absence of development. The present study aimed to investigate the anatomical composition of a cadaveric limb presenting with a complex congenital hand malformation.
Plain film x-rays and CT scans were obtained prior to dissection of the hand. Then forearm and hand dissections were completed. Digital images were captured throughout the dissection process.
Imaging and dissection revealed normal osteology of the distal radius, ulna, carpal, and phalanx of the first digit. The second, third and fourth digits were truncated, brachydactyly, with syndactyly of the distal phalanx and integument of these digits. Interestingly, the fifth digit presented with clinodactyly. Examination of the flexor and extensor musculature revealed an abnormal distribution pattern as well. The proximal and distal attachments of the flexor and extensor tendons of the first and fifth digits appeared relatively normal. The extensors of the second, third, and fourth digits attached to the base of the metacarpals. The distribution of the flexor digitorum superficialis and profundus appeared to interweave with each other and have an altered insertion pattern, with some digits lacking all or some of the typical tendons.
Based on the osteology and neurovascular results we suspect the congenital malformation observed was symbrachydactyly.
•Tissue analysis of symbrachydactyly.•Hand malformation in cadaveric donor.•Combined hand malformations in symbrachydactyly.
Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. ...However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell-substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2-related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension.
Exposure to cigarette smoke is associated with airway epithelial mucus cell hyperplasia and a decrease in cilia and ciliated cells. Few models have addressed the long-term effects of chronic ...cigarette smoke exposure on ciliated epithelial cells. Our previous in vitro studies showed that cigarette smoke decreases ciliary beat frequency (CBF) via the activation of protein kinase C (PKC). We hypothesized that chronic cigarette smoke exposure in an in vivo model would decrease airway epithelial cell ciliary beating in a PKC-dependent manner. We exposed C57BL/6 mice to whole-body cigarette smoke 2 hours/day, 5 days/week for up to 1 year. Tracheal epithelial cell CBF and the number of motile cells were measured after necropsy in cut tracheal rings, using high-speed digital video microscopy. Tracheal epithelial PKC was assayed according to direct kinase activity. At 6 weeks and 3 months of smoke exposure, the baseline CBF was slightly elevated (~1 Hz) versus control mice, with no change in β-agonist-stimulated CBF between control mice and cigarette smoke-exposed mice. By 6 months of smoke exposure, the baseline CBF was significantly decreased (2-3 Hz) versus control mice, and a β-agonist failed to stimulate increased CBF. The loss of β-agonist-increased CBF continued at 9 months and 12 months of smoke exposure, and the baseline CBF was significantly decreased to less than one third of the control rate. In addition to CBF, ciliated cell numbers significantly decreased in response to smoke over time, with a significant loss of tracheal ciliated cells occurring between 6 and 12 months. In parallel with the slowing of CBF, significant PKC activation from cytosol to the membrane of tracheal epithelial cells was detected in mice exposed to smoke for 6-12 months.
Alcohol impairs resolution of respiratory viral infections. Numerous immune response pathways are altered in response to alcohol misuse, including alcohol-induced ciliary dysfunction in the lung. We ...hypothesized that mucociliary clearance-mediated innate immunity to respiratory syncytial virus (RSV) would be compromised by alcohol exposure. Cilia were assayed using Sisson-Ammons Video Analysis by quantitating the average number of motile points in multiple whole field measurements of mouse tracheal epithelial cells grown on an air-liquid interface. Pretreatment with ethanol alone (100 mM for 24 hours) had no effect on the number of motile cilia. A single dose (TCID50 1 × 105) of RSV resulted in a significant (p < 0.05) decrease in motile cilia after 2 days. Ethanol pretreatment significantly (p < 0.05) potentiated RSV-induced cilia loss by 2 days. Combined RSV and ethanol treatment led to a sustained activation-induced auto-downregulation of PKC epsilon (PKCε). Ethanol-induced enhancement of ciliated cell detachment was confirmed by dynein ELISA and LDH activity from the supernates. RSV-induced cilia loss was evident until 7 days, when RSV-only infected cells demonstrated no significant cilia loss vs. control cells. However, cells pretreated with ethanol showed significant cilia loss until 10 days post-RSV infection. To address the functional significance of ethanol-enhanced cilia detachment, mice fed alcohol ad libitum (20% for 12 weeks) were infected once with RSV, and clearance was measured by plaque-forming assay from lung homogenates for up to 7 days. After 3 days, RSV plaque formation was no longer detected from the lungs of control mice, while significant (p < 0.01) RSV plaque-forming units were detected at 7 days in alcohol-fed mice. Alcohol-fed mice demonstrated enhanced cilia loss and delayed cilia recovery from tracheal measurements in wild-type C57BL/6 mice, but not PKCε KO mice. These data suggest that alcohol worsens RSV-mediated injury to ciliated epithelium in a PKCε-dependent manner.
•RSV infection results in loss of cilia; alcohol potentiates this injury.•Alcohol enhancement of RSV cilia slowing and detachment involves PKCε.•Resolution of RSV infection is delayed in mice fed alcohol.
Background
Cilia are finger‐like motor‐driven organelles, which propel inhaled particles and mucus from the lung and airways. We have previously shown that brief alcohol exposure stimulates ciliary ...motility through an endothelial nitric oxide synthase (eNOS)‐dependent pathway localized in the ciliary metabolon. However, the signaling molecules of the ciliary metabolon involved in alcohol‐triggered ciliary beat frequency (CBF) stimulation upstream of eNOS activation remain unknown.
Methods
We hypothesized that brief alcohol exposure alters threonine and serine phosphorylation of proteins involved in stimulating CBF. Two‐dimensional electrophoresis indicated both increases and decreases in the serine and threonine phosphorylation states of several proteins. One of the proteins identified was heat shock protein 90 (HSP90), which undergoes increased threonine phosphorylation after brief alcohol exposure. Because HSP90 has been shown to associate with eNOS in lung tissue, we hypothesized that HSP90 is a key component in alcohol‐triggered eNOS activation and that these 2 proteins co‐localize within the ciliary metabolon.
Results
Immunofluorescence experiments demonstrate that eNOS and HSP90 co‐localize within basal bodies of the ciliary metabolon and partially translocate to the axoneme upon brief alcohol exposure. Pretreatment with geldanamycin, which disrupts HSP90 chaperone functions, prevented eNOS‐HSP90 association and prevented the translocation of eNOS from the ciliary metabolon to the axoneme. Functional cilia motility studies revealed that geldanamycin blocked alcohol‐stimulated ciliary motility in bovine bronchial epithelial cells and mouse tracheal rings.
Conclusions
On the basis of the HSP90 localization with eNOS, alcohol activation of HSP90 phosphorylation, and geldanamycin's ability to inhibit HSP90‐eNOS association, prevent eNOS translocation to the axoneme, and block alcohol‐stimulated ciliary motility, we conclude that alcohol‐induced cilia stimulation occurs through the increased association of HSP90 with eNOS. These data help further elucidate the mechanism through which brief alcohol exposure stimulates CBF.
ABSTRACT
We implement the first blind analysis of cluster abundance data to derive cosmological constraints from the abundance and weak lensing signal of redMaPPer clusters in the Sloan Digital Sky ...Survey (SDSS). We simultaneously fit for cosmological parameters and the richness–mass relation of the clusters. For a flat Λ cold dark matter cosmological model with massive neutrinos, we find $S_8 \equiv \sigma _{8}(\Omega _\mathrm{ m}/0.3)^{0.5}=0.79^{+0.05}_{-0.04}$. This value is both consistent and competitive with that derived from cluster catalogues selected in different wavelengths. Our result is also consistent with the combined probes analyses by the Dark Energy Survey (DES), the Kilo-Degree Survey (KiDS), and with the cosmic microwave background (CMB) anisotropies as measured by Planck. We demonstrate that the cosmological posteriors are robust against variation of the richness–mass relation model and to systematics associated with the calibration of the selection function. In combination with baryon acoustic oscillation data and big bang nucleosynthesis data (Cooke et al.), we constrain the Hubble rate to be h = 0.66 ± 0.02, independent of the CMB. Future work aimed at improving our understanding of the scatter of the richness–mass relation has the potential to significantly improve the precision of our cosmological posteriors. The methods described in this work were developed for use in the forthcoming analysis of cluster abundances in the DES. Our SDSS analysis constitutes the first part of a staged-unblinding analysis of the full DES data set.
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