Ariel - Volume 7 Number 2

Editors Mark Dembert Frank Chervanek John Lammie Jim Burke Curt Cumming

The Clinical Utility of a Precision Medicine Blood Test Incorporating Age, Sex, and Gene Expression for Evaluating Women with Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Analysis from the PRESET Registry.

Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry. Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing. Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1-40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16). Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation

Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge

Research Funding Wellcome Trust, UK. Grant Numbers: 086827, 080088 NIH. Grant Number: DE022550Peer reviewedPublisher PD

A survey of X-ray emission from 100 kpc radio jets

We have completed a Chandra snapshot survey of 54 radio jets that are extended on arcsec scales. These are associated with flat spectrum radio quasars spanning a redshift range z=0.3 to 2.1. X-ray emission is detected from the jet of approximately 60% of the sample objects. We assume minimum energy and apply conditions consistent with the original Felten-Morrison calculations in order to estimate the Lorentz factors and the apparent Doppler factors. This allows estimates of the enthalpy fluxes, which turn out to be comparable to the radiative luminosities.Comment: Conference Proceedings IAU Symposium No. 313, Extragalactic jets from every angle, pp. 219-224, 4 figure

Drosophila Apc2 Is a Cytoskeletally-Associated Protein That Regulates Wingless Signaling in the Embryonic Epidermis

The tumor suppressor adenomatous polyposis coli (APC) negatively regulates Wingless (Wg)/Wnt signal transduction by helping target the Wnt effector β-catenin or its Drosophila homologue Armadillo (Arm) for destruction. In cultured mammalian cells, APC localizes to the cell cortex near the ends of microtubules. Drosophila APC (dAPC) negatively regulates Arm signaling, but only in a limited set of tissues. We describe a second fly APC, dAPC2, which binds Arm and is expressed in a broad spectrum of tissues. dAPC2's subcellular localization revealed colocalization with actin in many but not all cellular contexts, and also suggested a possible interaction with astral microtubules. For example, dAPC2 has a striking asymmetric distribution in neuroblasts, and dAPC2 colocalizes with assembling actin filaments at the base of developing larval denticles. We identified a dAPC2 mutation, revealing that dAPC2 is a negative regulator of Wg signaling in the embryonic epidermis. This allele acts genetically downstream of wg, and upstream of arm, dTCF, and, surprisingly, dishevelled. We discuss the implications of our results for Wg signaling, and suggest a role for dAPC2 as a mediator of Wg effects on the cytoskeleton. We also speculate on more general roles that APCs may play in cytoskeletal dynamics

Forecast dataset associated with “From Random Forests to Flood Forecasts: A Research to Operations Success Story”

Gridded forecasts from the Colorado State University-Machine Learning Probabilities (CSU-MLP) system for excessive rainfall prediction over the continental United States. The dataset includes probabilistic forecasts for days 1, 2, and 3 from the 2017, 2019, and 2020 versions of the CSU-MLP forecast system. For the day 2 and 3 forecasts, daily forecasts are included from 19 June 2018 through 15 October 2020; for day-1 forecasts a period from 15 March 2019 through 15 October 2020 is used.Because excessive rainfall is poorly defined and difficult to forecast, there is a need for tools for Weather Prediction Center (WPC) forecasters to use when generating Excessive Rainfall Outlooks (EROs), which are issued for the contiguous United States at lead times of 1--3 days. To address this need, a probabilistic forecast system for excessive rainfall, known as the Colorado State University-Machine Learning Probabilities (CSU-MLP) system, was developed based on ensemble reforecasts, precipitation observations, and machine learning algorithms, specifically random forests. The CSU-MLP forecasts were designed to emulate the EROs, with the goal being a tool that forecasters can use as a ``first guess'' in the ERO forecast process. Resulting from close collaboration between CSU and WPC and evaluation at the Flash Flood and Intense Rainfall experiment, iterative improvements were made to the forecast system and it was transitioned into operational use at WPC. Quantitative evaluation shows that the CSU-MLP forecasts are skillful and reliable, and they are now being used as a part of the WPC forecast process. This project represents an example of a successful research-to-operations transition, and highlights the potential for machine learning and other post-processing techniques to improve operational predictions.This research and operational transition was supported by NOAA Joint Technology Transfer Initiative grants NA16OAR4590238 and NA18OAR4590378

Polarimetry and the High-Energy Emission Mechanisms in Quasar Jets. The Case of PKS 1136-135

Since the discovery of kiloparsec-scale X-ray emission from quasar jets, the physical processes responsible for their high-energy emission have been poorly defined. A number of mechanisms are under active debate, including synchrotron radiation, inverse-Comptonized CMB (IC/CMB) emission, and other Comptonization processes. In a number of cases, the optical and X-ray emission of jet regions are inked by a single spectral component, and in those, high- resolution multi-band imaging and polarimetry can be combined to yield a powerful diagnostic of jet emission processes. Here we report on deep imaging photometry of the jet of PKS 1136$-$135 obtained with the {\it Hubble Space Telescope.} We find that several knots are highly polarized in the optical, with fractional polarization $\Pi>30$. When combined with the broadband spectral shape observed in these regions, this is very difficult to explain via IC/CMB models, unless the scattering particles are at the lowest-energy tip of the electron energy distribution, with Lorentz factor $\gamma \sim 1$, and the jet is also very highly beamed ($\delta \geq 20$) and viewed within a few degrees of the line of sight. We discuss both the IC/CMB and synchrotron interpretation of the X-ray emission in the light of this new evidence, presenting new models of the spectral energy distribution and also the matter content of this jet. The high polarizations do not completely rule out the possibility of IC/CMB optical-to-X-ray emission in this jet, but they do strongly disfavor the model. We discuss the implications of this finding, and also the prospects for future work.Comment: 14 pages, 8 figures, ApJ in pres