Vitamin A as a Transcriptional Regulator of Cardiovascular Disease

Vitamin A is a micronutrient and signaling molecule that regulates transcription, cellular differentiation, and organ homeostasis. Additionally, metabolites of Vitamin A are utilized as differentiation agents in the treatment of hematological cancers and skin disorders, necessitating further study into the effects of both nutrient deficiency and the exogenous delivery of Vitamin A and its metabolites on cardiovascular phenotypes. Though vitamin A/retinoids are well-known regulators of cardiac formation, recent evidence has emerged that supports their role as regulators of cardiac regeneration, postnatal cardiac function, and cardiovascular disease progression. We here review findings from genetic and pharmacological studies describing the regulation of both myocyte- and vascular-driven cardiac phenotypes by vitamin A signaling. We identify the relationship between retinoids and maladaptive processes during the pathological hypertrophy of the heart, with a focus on the activation of neurohormonal signaling and fetal transcription factors (Gata4, Tbx5). Finally, we assess how this information might be leveraged to develop novel therapeutic avenues

Dark matter to dark energy transition in k-essence cosmologies

We implement the transition from dark matter to dark energy in k-essence cosmologies for a very large set of kinetic functions $F$, in a way alternative to recent proposals which use generalized Chaplygin gas and transient models. Here we require that the pressure admits a power-law expansion around some value of the kinetic energy where the pressure vanishes. In addition, for suitable values of the parameters of the model, the speed of sound of the dark matter will be low. We first present the discussion in fairly general terms, and later consider for illustration two examples.Comment: 5 pages, revte

Neptune at Summer Solstice: Zonal Mean Temperatures from Ground-Based Observations 2003-2007

Imaging and spectroscopy of Neptune's thermal infrared emission is used to assess seasonal changes in Neptune's zonal mean temperatures between Voyager-2 observations (1989, heliocentric longitude Ls=236) and southern summer solstice (2005, Ls=270). Our aim was to analyse imaging and spectroscopy from multiple different sources using a single self-consistent radiative-transfer model to assess the magnitude of seasonal variability. Globally-averaged stratospheric temperatures measured from methane emission tend towards a quasi-isothermal structure (158-164 K) above the 0.1-mbar level, and are found to be consistent with spacecraft observations of AKARI. This remarkable consistency, despite very different observing conditions, suggests that stratospheric temporal variability, if present, is $\pm$5 K at 1 mbar and $\pm$3 K at 0.1 mbar during this solstice period. Conversely, ethane emission is highly variable, with abundance determinations varying by more than a factor of two. The retrieved C2H6 abundances are extremely sensitive to the details of the T(p) derivation. Stratospheric temperatures and ethane are found to be latitudinally uniform away from the south pole (assuming a latitudinally-uniform distribution of stratospheric methane). At low and midlatitudes, comparisons of synthetic Voyager-era images with solstice-era observations suggest that tropospheric zonal temperatures are unchanged since the Voyager 2 encounter, with cool mid-latitudes and a warm equator and pole. A re-analysis of Voyager/IRIS 25-50 {\mu}m mapping of tropospheric temperatures and para-hydrogen disequilibrium suggests a symmetric meridional circulation with cold air rising at mid-latitudes (sub-equilibrium para-H2 conditions) and warm air sinking at the equator and poles (super-equilibrium para-H2 conditions). The most significant atmospheric changes are associated with the polar vortex (absent in 1989).Comment: 35 pages, 19 figures. Accepted for publication in Icaru

A novel dual reporter embryonic stem cell line for toxicological assessment of teratogen-induced perturbation of anterior-posterior patterning of the heart

Reliable in vitro models to assess developmental toxicity of drugs and chemicals would lead to improvement in fetal safety and a reduced cost of drug development. The validated embryonic stem cell test (EST) uses cardiac differentiation of mouse embryonic stem cells (mESCs) to predict in vivo developmental toxicity, but does not take into account the stage-specific patterning of progenitor populations into anterior (ventricular) and posterior (atrial) compartments. In this study, we generated a novel dual reporter mESC line with fluorescent reporters under the control of anterior and posterior cardiac promoters. Reporter expression was observed in nascent compartments in transgenic mouse embryos, and mESCs were used to develop differentiation assays in which chemical modulators of Wnt (XAV939: 3, 10 mu M), retinoic acid (all-trans retinoic acid: 0.1, 1, 10 mu M; 9-cis retinoic acid: 0.1, 1, 10 mu M; bexarotene 0.1, 1, 10 mu M), and Tgf-beta (SB431542: 3, 10 mu M) pathways were tested for stage- and dose-dependent effects on in vitro anterior-posterior patterning. Our results suggest that with further development, the inclusion of anterior-posterior reporter expression could be part of a battery of high-throughput tests used to identify and characterize teratogens.Peer reviewe

Applied Remote Sensing Program (ARSP)

There are no author-identified significant results in this report

Fiber Breakage Model for Carbon Composite Stress Rupture Phenomenon: Theoretical Development and Applications

Stress rupture failure of Carbon Composite Overwrapped Pressure Vessels (COPVs) is of serious concern to Science Mission and Constellation programs since there are a number of COPVs on board space vehicles with stored gases under high pressure for long durations of time. It has become customary to establish the reliability of these vessels using the so called classic models. The classical models are based on Weibull statistics fitted to observed stress rupture data. These stochastic models cannot account for any additional damage due to the complex pressure-time histories characteristic of COPVs being supplied for NASA missions. In particular, it is suspected that the effects of proof test could significantly reduce the stress rupture lifetime of COPVs. The focus of this paper is to present an analytical appraisal of a model that incorporates damage due to proof test. The model examined in the current paper is based on physical mechanisms such as micromechanics based load sharing concepts coupled with creep rupture and Weibull statistics. For example, the classic model cannot accommodate for damage due to proof testing which every flight vessel undergoes. The paper compares current model to the classic model with a number of examples. In addition, several applications of the model to current ISS and Constellation program issues are also examined

Bayes Analysis and Reliability Implications of Stress-Rupture Testing a Kevlar/Epoxy COPV using Temperature and Pressure Acceleration

Composite Overwrapped Pressure Vessel (COPVs) that have survived a long service time under pressure generally must be recertified before service is extended. Sometimes lifetime testing is performed on an actual COPV in service in an effort to validate the reliability model that is the basis for certifying the continued flight worthiness of its sisters. Currently, testing of such a Kevlar49(registered TradeMark)/epoxy COPV is nearing completion. The present paper focuses on a Bayesian statistical approach to analyze the possible failure time results of this test and to assess the implications in choosing between possible model parameter values that in the past have had significant uncertainty. The key uncertain parameters in this case are the actual fiber stress ratio at operating pressure, and the Weibull shape parameter for lifetime; the former has been uncertain due to ambiguities in interpreting the original and a duplicate burst test. The latter has been uncertain due to major differences between COPVs in the data base and the actual COPVs in service. Any information obtained that clarifies and eliminates uncertainty in these parameters will have a major effect on the predicted reliability of the service COPVs going forward. The key result is that the longer the vessel survives, the more likely the more optimistic stress ratio is correct. At the time of writing, the resulting effect on predicted future reliability is dramatic, increasing it by about one nine , that is, reducing the probability of failure by an order of magnitude. However, testing one vessel does not change the uncertainty on the Weibull shape parameter for lifetime since testing several would be necessary

Reliability of recommended non-invasive chairside screening tests for diabetes-related peripheral neuropathy : a systematic review with meta-analyses

The objective is to determine, by systematic review, the reliability of testing methods for diagnosis of diabetes-related peripheral neuropathy (DPN) as recommended by the most recent guidelines from the International Diabetes Foundation, International Working Group on the Diabetic Foot and American Diabetes Association. Electronic searches of Cochrane Library, EBSCO Megafile Ultimate and EMBASE were performed to May 2021. Articles were included if they reported on the reliability of recommended chairside tests in diabetes cohorts. Quality appraisal was performed using a Quality Appraisal of Reliability Studies checklist and where possible, meta-analyses, with reliability reported as estimated Cohen's kappa (95% CI). Seventeen studies were eligible for inclusion. Pooled analysis found acceptable inter-rater reliability of vibration perception threshold (VPT) (κ=0.61 (0.50 to 0.73)) and ankle reflex testing (κ=0.60 (0.55 to 0.64)), but weak inter-rater reliability for pinprick (κ=0.45 (0.22 to 0.69)) and 128 Hz tuning fork (κ=0.42 (0.15 to 0.70)), though intra-rater reliability of the 128 Hz tuning fork was moderate (κ=0.54 (0.37 to 0.73)). Inter-rater reliability of the four-site monofilament was acceptable (κ=0.61 (0.45 to 0.77)). These results support the clinical use of VPT, ankle reflexes and four-site monofilament for screening and ongoing monitoring of DPN as recommended by the latest guidelines. The reliability of temperature perception, pinprick, proprioception, three-site monofilament and Ipswich touch test when performed in people with diabetes remains unclear