ABSTRACT There is an ≈9 ± 2.5 per cent tension between the value of Hubble’s Constant, H0 = 67.4 ± 0.5 km s−1 Mpc−1, implied by the Planck microwave background power spectrum and that given by the ...distance scale of H0 = 73.4 ± 1.7 km s−1Mpc−1. But with a plausible assumption about a Gaia DR2 parallax systematic offset, we find that Gaia parallax distances of Milky Way Cepheid calibrators are ≈12–15 per cent longer than previously estimated. Similarly, Gaia also implies ≈4.7 ± 1.7 per cent longer distances for 46 Cepheids than previous distances on the scale of Riess et al. Then we show that the existence of an ≈150 h−1Mpc ‘Local Hole’ in the galaxy distribution implies an outflow of ≈500 km s−1. Accounting for this in the recession velocities of SNIa standard candles out to z ≈ 0.15 reduces H0 by a further ≈1.8 per cent. Combining the above two results would reduce the distance scale H0 estimate by ≈7 per cent from H0 ≈ 73.4 ± 1.7 to ≈68.9 ± 1.6 km s−1Mpc−1, in reasonable agreement with the Planck value. We conclude that the discrepancy between distance scale and Planck H0 measurements remains unconfirmed due to uncertainties caused by Gaia systematics and an unexpectedly inhomogeneous local galaxy distribution.
ABSTRACT
We investigate the kinematics of the molecular gas in a sample of seven edge-on (i > 60°) galaxies identified as hosting large-scale outflows of ionized gas, using ALMA CO(1–0) observations ...at ∼1 kpc resolution. We build on Hogarth et al., where we find that molecular gas is more centrally concentrated in galaxies which host winds than in control objects. We perform full three-dimensional kinematic modelling with multiple combinations of kinematic components, allowing us to infer whether these objects share any similarities in their molecular gas structure. We use modelling to pinpoint the kinematic centre of each galaxy, in order to interpret their minor- and major-axis position velocity diagrams (PVDs). From the PVDs, we find that the bulk of the molecular gas in our galaxies is dynamically cold, tracing the rotation curves predicted by our symmetric, rotation-dominated models, but with minor flux asymmetries. Most notably, we find evidence of radial gas motion in a subset of our objects, which demonstrate a characteristic ‘twisting’ in their minor-axis PVDs generally associated with gas flow along the plane of a galaxy. In our highest S/N object, we include bi-symmetric radial flow in our kinematic model, and find (via the Bayesian Information Criterion) that the presence of radial gas motion is strongly favoured. This may provide one mechanism by which molecular gas and star formation are centrally concentrated, enabling the launch of massive ionized gas winds. However, in the remainder of our sample, we do not observe evidence that gas is being driven radially, once again emphasizing the variety of physical processes that may be powering the outflows in these objects, as originally noted in H21.
ABSTRACT
We revisit our mapping of the ‘Local Hole’, a large underdensity in the local galaxy redshift distribution that extends out to redshift z ≈ 0.05 and a potential source of outflows that may ...perturb the global expansion rate and thus help mitigate the present ‘H0 tension’. First, we compare local peculiar velocities measured via the galaxy average redshift–magnitude Hubble diagram, $\overline{z}(m)$, with a simple dynamical outflow model based on the average underdensity in the Local Hole. We find that this outflow model is in good agreement with our peculiar velocity measurements from $\overline{z}(m)$ and not significantly inconsistent with Type Ia supernova peculiar velocity measurements from at least the largest previous survey. This outflow could cause an ≈2–3 per cent increase in the local value of Hubble’s constant. Second, considering anisotropic motions, we find that the addition of the outflow model may improve the $\overline{z}(m)$ fit of a bulk flow where galaxies are otherwise at rest in the Local Group frame. We conclude that the Local Hole plus neighbouring overdensities such as the Shapley Supercluster may cause outflow and bulk motions out to ≈150 h−1 Mpc that are cosmologically significant and that need to be taken into account in estimating Hubble’s constant.
ABSTRACT
We investigate whether barred galaxies are statistically more likely to harbour radial molecular gas flows and what effect those flows have on their global properties. Using 46 galaxies from ...the ALMA-MaNGA QUEnching and STar formation (ALMaQUEST) survey, we identify galaxies hosting optical bars using a combination of the morphological classifications in Galaxy Zoo 2 and HyperLEDA. In order to detect radial molecular gas flows, we employ full 3D kinematic modelling of the ALMaQUEST 12CO(1–0) data cubes. By combining our bar classifications with our radial bar-driven flow detections, we find that galaxies classed as barred are statistically more likely to host large-scale radial gas motions compared to their un-barred and edge-on galaxy counterparts. Moreover, the majority of barred galaxies require multicomponent surface brightness profiles in their best-fitting models, indicative of the presence of resonance systems. We find that galaxies classed as barred with radial bar-driven flows (‘barred + radial flow’ subset) have significantly suppressed global star-formation efficiencies compared to barred galaxies without radial bar-driven flows and galaxies in the other morphological sub-samples. Our ‘barred + radial flow’ subset galaxies also possess consistently centrally concentrated molecular gas distributions, with no indication of depleted gas mass fractions, suggesting that gas exhaustion is not the cause of their suppressed star formation. Furthermore, these objects have higher median gas mass surface densities in their central 1 kpc, implying that central gas enhancements do not fuel central starbursts in these objects. We propose that dynamical effects, such as shear caused by large-scale inflows of gas, act to gravitationally stabilize the inner gas reservoirs.
ABSTRACT
We perform a joint analysis of high spatial resolution molecular gas and star-formation rate (SFR) maps in main-sequence star-forming galaxies experiencing galactic-scale outflows of ionized ...gas. Our aim is to understand the mechanism that determines which galaxies are able to launch these intense winds. We observed CO(1→0) at 1-arcsec resolution with ALMA in 16 edge-on galaxies, which also have 2-arcsec spatial-resolution optical integral field observations from the SAMI Galaxy Survey. Half the galaxies in the sample were previously identified as harbouring intense and large-scale outflows of ionized gas (‘outflow types’) and the rest serve as control galaxies. The data set is complemented by integrated CO(1→0) observations from the IRAM 30-m telescope to probe the total molecular gas reservoirs. We find that the galaxies powering outflows do not possess significantly different global gas fractions or star-formation efficiencies when compared with a control sample. However, the ALMA maps reveal that the molecular gas in the outflow-type galaxies is distributed more centrally than in the control galaxies. For our outflow-type objects, molecular gas and star-formation are largely confined within their inner effective radius (reff), whereas in the control sample, the distribution is more diffuse, extending far beyond reff. We infer that outflows in normal star-forming galaxies may be caused by dynamical mechanisms that drive molecular gas into their central regions, which can result in locally enhanced gas surface density and star-formation.
all-trans retinoic acid (atRA), the active metabolite of vitamin A, is an essential signaling molecule. Specifically the concentrations of atRA are spatiotemporally controlled in target tissues such ...as the liver and the testes. While the enzymes of the aldehyde dehydrogenase 1A family (ALDH1A) are believed to control the synthesis of atRA, a direct relationship between altered ALDH1A activity and tissue atRA concentrations has never been shown. To test whether inhibition of ALDH1A enzymes decreases atRA concentrations in a tissue specific manner, the potent ALDH1A inhibitor WIN 18,446 was used to inhibit ALDH1A activity in mice. The ALDH1A expression, atRA formation kinetics, ALDH1A inhibition by WIN 18,446 and WIN 18,446 disposition were used to predict the time course and extent of inhibition of atRA formation in the testis and liver. The effect of WIN 18,446 on atRA concentrations in testis, liver and serum were measured following single and multiple doses of WIN 18,446. ALDH1A1 and ALDH1A2 were responsible for the majority of atRA formation in the testis while ALDH1A1 and aldehyde oxidase contributed to atRA formation in the liver. Due to the different complement of enzymes contributing to atRA formation in different tissues and different inhibition of ALDH1A1 and ALDH1A2 by WIN 18,446, WIN 18,446 caused only a 50% decrease in liver atRA but testicular atRA decreased over 90%. Serum atRA concentrations were also reduced. These data demonstrate that inhibition of ALDH1A enzymes will decrease atRA concentrations in a tissue specific manner and selective ALDH1A inhibition could be used to alter atRA concentrations in select target tissues.
All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in ...human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whetheratRA regulates hepatic mitochondrial activity.atRA treatment increased the mRNA and protein expression of multiple components of mitochondrialβ-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally,atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1αand 1βand nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification.atRA also increasedβ-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARα, RARβ, and PPARδrevealed that the enhancement of mitochondrial biogenesis andβ-oxidation byatRA requires peroxisome proliferator activated receptor delta. In vivo in mice,atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition ofatRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects ofatRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show thatatRA regulates mitochondrial function and lipid metabolism and that increasingatRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acidβ-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction.
Objective, portable measures of motor function for out-of-office assessments are needed in Parkinson's Disease (PD). This study had 3 objectives. First, to examine change in objective motor ...measurements in PD (as assessed with the Objective PD Measurement (OPDM) system). Second, to correlate objective measures with clinical features and putative PD cerebrospinal fluid (CSF) and dopaminergic imaging biomarkers. Third, to assess participant compliance with and perceptions of serial in-home motor assessments.
De novo PD subjects participating in this pilot study of the Parkinson Progression Markers Initiative (PPMI) completed OPDM assessments at home weekly for 3 months and in the clinic at baseline and 3-, 6-, and 12-months. Tasks included (i)digitography (ii)a repetitive hand tapping task and (iii)timed pegboard task. A global objective motor score (OMS) was derived from the latter three. MDS-UPDRS-III score was obtained at each time point, and CSF and dopamine transporter (DAT) SPECT at baseline.
27 participants, mean age 62.6 years, 19 male were included. A mean of 10.5 in-home assessments were completed. There was no significant change in in-home OMS over 12 weeks (p = 0.48). There was strong correlation between mean baseline OMS and MDS-UPDRS-III scores (spearman's rho = 0.60, p=<0.0001). Baseline OMS predicted 6-month MDS-UPDRS-III (β = 0.80, p = 0.0002) but not change in MDS-UPDRS-III score, DAT SPECT, or putative CSF biomarkers.
This study suggests that administration of in-home motor tasks as part of a large multi-center study is feasible and scores derived from these assessments may serve as surrogates of in-person clinician-assessed motor score.
•In-home quantitative motor testing is feasible and acceptable to participants.•The objective motor score is a good proxy of physical exam (MDS-UPDRS-III score).•The objective motor score at baseline predicts MDS-UPDRS-III score 6-months later.
Abstract Digital measures may provide objective, sensitive, real-world measures of disease progression in Parkinson’s disease (PD). However, multicenter longitudinal assessments of such measures are ...few. We recently demonstrated that baseline assessments of gait, tremor, finger tapping, and speech from a commercially available smartwatch, smartphone, and research-grade wearable sensors differed significantly between 82 individuals with early, untreated PD and 50 age-matched controls. Here, we evaluated the longitudinal change in these assessments over 12 months in a multicenter observational study using a generalized additive model, which permitted flexible modeling of at-home data. All measurements were included until participants started medications for PD. Over one year, individuals with early PD experienced significant declines in several measures of gait, an increase in the proportion of day with tremor, modest changes in speech, and few changes in psychomotor function. As measured by the smartwatch, the average (SD) arm swing in-clinic decreased from 25.9 (15.3) degrees at baseline to 19.9 degrees (13.7) at month 12 ( P = 0.004). The proportion of awake time an individual with early PD had tremor increased from 19.3% (18.0%) to 25.6% (21.4%; P < 0.001). Activity, as measured by the number of steps taken per day, decreased from 3052 (1306) steps per day to 2331 (2010; P = 0.16), but this analysis was restricted to 10 participants due to the exclusion of those that had started PD medications and lost the data. The change of these digital measures over 12 months was generally larger than the corresponding change in individual items on the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale but not greater than the change in the overall scale. Successful implementation of digital measures in future clinical trials will require improvements in study conduct, especially data capture. Nonetheless, gait and tremor measures derived from a commercially available smartwatch and smartphone hold promise for assessing the efficacy of therapeutics in early PD.
In patients with advanced idiopathic pulmonary fibrosis, treatment with sildenafil was compared with placebo. In the sildenafil group, there was a nonsignificant trend toward improvement and some ...benefit in other physiological measures and symptom scores.
Idiopathic pulmonary fibrosis is a chronic, progressive lung disease of unknown cause that is characterized by the histopathologic pattern of usual interstitial pneumonia.
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Progression to end-stage respiratory insufficiency and death within 5 years after the onset of symptoms is characteristic.
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To date, no pharmacologic therapies have definitively been shown to improve survival or quality of life in patients with this disease.
Patients with severe idiopathic pulmonary fibrosis have abnormalities of the pulmonary vasculature leading to decreased levels of resting and exercise-induced production of nitric oxide. Since nitric oxide is a potent pulmonary vasodilator, reduced levels are associated with pulmonary . . .
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