Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors.

Allosteric modulation is a central mechanism for metabolic regulation but has yet to be described for a gut microbiota-host interaction. Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, has previously been clinically associated with and mechanistically linked to cardiovascular disease (CVD) and heart failure (HF). Here, using cells expressing β1- versus β2-adrenergic receptors (β1AR and β2AR), PAGln is shown to act as a negative allosteric modulator (NAM) of β2AR, but not β1AR.

Establishing flood thresholds for sea level rise impact communication.

Sea level rise (SLR) affects coastal flood regimes and poses serious challenges to flood risk management, particularly on ungauged coasts. To address the challenge of monitoring SLR at local scales, we propose a high tide flood (HTF) thresholding system that leverages machine learning (ML) techniques to estimate SLR and HTF thresholds at a relatively fine spatial resolution (10 km) along the United States' coastlines. The proposed system, complementing conventional linear- and point-based estimations of HTF thresholds and SLR rates, can estimate these values at ungauged stretches of the coast.

Development of an x-ray radiography platform to study laser-direct-drive energy coupling at the National Ignition Facility.

A platform has been developed to study laser-direct-drive energy coupling at the National Ignition Facility (NIF) using a plastic sphere target irradiated in a polar-direct-drive geometry to launch a spherically converging shock wave. To diagnose this system evolution, eight NIF laser beams are directed onto a curved Cu foil to generate He line emission at a photon energy of 8.4 keV.

Mere Nuisance or Growing Threat? The Physical and Economic Impact of High Tide Flooding on US Road Networks.

High tide flooding (HTF) already affects traffic in many US coastal areas, but the issue will worsen significantly in the future. While studies show that large storm surge events threaten to be ever more costly, less damaging, but more frequent HTF events remain understudied and potentially carry a comparable economic impact. This study advances our understanding of the risks and impacts of HTF on vulnerable traffic corridors using hourly tide gauge water levels, sea-level rise projections, and link-level spatial analysis.

High-yield magnetic recoil neutron spectrometer on the National Ignition Facility for operation up to 60 MJ.

Recent progress at the National Ignition Facility (NIF), with neutron yields of order 1 × 10, places new constraints on diagnostics used to characterize implosion performance. The Magnetic Recoil neutron Spectrometer (MRS), which is routinely used to measure yield, ion temperature (T), and down-scatter ratio (dsr), has been adapted to allow measurements of dsr up to 5 × 10, and yield and T up to 2 × 10 in the near term with new data processing techniques and conversion foil solutions. This paper presents a solution for extending MRS operation up to a yield of 2 × 10 (60 MJ) by moving the spectrometer outside of the NIF shield wall.

Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart.

Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart.

Methods And Results: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia.

Understanding of Contemporary Regional Sea-Level Change and the Implications for the Future.

Global sea level provides an important indicator of the state of the warming climate, but changes in regional sea level are most relevant for coastal communities around the world. With improvements to the sea-level observing system, the knowledge of regional sea-level change has advanced dramatically in recent years. Satellite measurements coupled with in situ observations have allowed for comprehensive study and improved understanding of the diverse set of drivers that lead to variations in sea level in space and time.

A measurement of the equation of state of carbon envelopes of white dwarfs.

White dwarfs represent the final state of evolution for most stars. Certain classes of white dwarfs pulsate, leading to observable brightness variations, and analysis of these variations with theoretical stellar models probes their internal structure. Modelling of these pulsating stars provides stringent tests of white dwarf models and a detailed picture of the outcome of the late stages of stellar evolution.

Design and implementation of the infection prevention program into risk management: Managing high level disinfection and sterilization in the outpatient setting.

Reusable, invasive medical devices within the outpatient setting pose a risk for patient harm. Ineffective disinfection of medical devices can potentially lead to transmission of pathogens between patients; and improper handling can lead to patient injury. A risk assessment was conducted, and the results strongly supported the necessity to develop a robust infection prevention program within the risk management department.

Usable Science for Managing the Risks of Sea-Level Rise.

Sea-level rise sits at the frontier of usable climate climate change research, because it involves natural and human systems with long lags, irreversible losses, and deep uncertainty. For example, many of the measures to adapt to sea-level rise involve infrastructure and land-use decisions, which can have multigenerational lifetimes and will further influence responses in both natural and human systems. Thus, sea-level science has increasingly grappled with the implications of (1) deep uncertainty in future climate system projections, particularly of human emissions and ice sheet dynamics; (2) the overlay of slow trends and high-frequency variability (e.

Rising Sea Levels: Helping Decision-Makers Confront the Inevitable.

Sea-level rise (SLR) is not just a future trend; it is occurring now in most coastal regions across the globe. It thus impacts not only long-range planning in coastal environments, but also emergency preparedness. Its inevitability and irreversibility on long time scales, in addition to its spatial non-uniformity, uncertain magnitude and timing, and capacity to drive non-stationarity in coastal flooding on planning and engineering timescales, create unique challenges for coastal risk-management decision processes.

Cardiac CRFR1 Expression Is Elevated in Human Heart Failure and Modulated by Genetic Variation and Alternative Splicing.

Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)-1, Ucn2, and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured the levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors.

The rs11515 Polymorphism Is More Frequent and Associated With Aggressive Breast Tumors with Increased ANRIL and Decreased p16 (INK4a) Expression.

Chromosome position 9p21 encodes three-tumor suppressors p16(INK4a), p14(ARF), and p15(INK4b) and the long non-coding RNA ANRIL (antisense non-coding RNA in the INK4 locus). The rs11515 single-nucleotide polymorphism in the p16 (INK4a) /p14 (ARF) 3'-untranslated region is associated with glioblastoma, melanoma, and other cancers. This study investigated the frequency and effect of rs11515 genotypes in breast cancer.

In Situ Conductance Analysis of Zinc Oxide Nucleation and Coalescence during Atomic Layer Deposition on Metal Oxides and Polymers.

Real time in situ conductance is collected continuously during atomic layer deposition (ALD) of zinc oxide films, and trends are used to study ALD nucleation on polypropylene, nylon-6, SiO2, TiO2, and Al2O3 substrates. The detailed conductance change during the ALD cycle is ascribed to changes in surface band bending upon precursor/reactant exposure. Conductive pathways form earlier on the inorganic surfaces than on the polymers, with Al2O3 substrates showing more rapid nucleation than SiO2 or TiO2, consistent with the expected density of nucleation sites (e.

Association of noninvasively measured left ventricular mechanics with in vitro muscle contractile performance: a prospective study in hypertrophic cardiomyopathy patients.

Background: Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in which regional left ventricular dysfunction may exist without overt global left ventricular dysfunction. In obstructive HCM patients who underwent surgical myectomy (SM), we sought to determine if there is a significant association between echocardiographic longitudinal strain, histopathology, and in vitro myocardial performance (resting tension and developed tension) of the surgical specimen.

Methods And Results: HCM patients (n=122, 54±14 years, 54% men) undergoing SM were prospectively recruited.

Atomic layer deposition of metal oxide patterns on nonwoven fiber mats using localized physical compression.

Patterning is an essential part of many industrial processes from printing to semiconductor manufacturing. In this work, we demonstrate a new method to pattern and selectively coat nonwoven textiles by atomic layer deposition (ALD) using compressive mask patterning. A physical mask combined with mechanical compression allows lateral definition and fidelity of the ALD coating to be controlled.

S100A1 in human heart failure: lack of recovery following left ventricular assist device support.

Background: We hypothesized that S100A1 is regulated during human hypertrophy and heart failure and that it may be implicated in remodeling after left ventricular assist device. S100A1 is decreased in animal and human heart failure, and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling.

An animal model of stress-induced cardiomyopathy utilizing the social defeat paradigm.

Stress-induced cardiomyopathy (SIC) is a form of acute heart disease triggered by extreme psychological stress. In patients who develop SIC, the outward symptoms are almost indistinguishable from acute myocardial infarction (AMI). However, some important criteria differentiate patients with SIC from those with AMI.

Highly conductive and flexible nylon-6 nonwoven fiber mats formed using tungsten atomic layer deposition.

Low-temperature vapor-phase tungsten atomic layer deposition (ALD) using WF6 and dilute silane (SiH4, 2% in Ar) can yield highly conductive coatings on nylon-6 microfiber mats, producing flexible and supple nonwovens with conductivity of ∼1000 S/cm. We find that an alumina nucleation layer, reactant exposure, and deposition temperature all influence the rate of W mass uptake on 3D fibers, and film growth rate is calibrated using high surface area anodic aluminum oxide. Transmission electron microscopy (TEM) reveals highly conformal tungsten coatings on nylon fibers with complex "winged" cross-section.

The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues.

Genome-wide association studies have identified a coronary artery disease (CAD) risk locus in a non-coding region at 9p21.3, the nearest genes being CDKN2A and CDKN2B. To understand the pathways by which this locus might influence CAD susceptibility, we investigated associations between the 9p21.

Pulmonary hypertension associated with advanced systolic heart failure: dysregulated arginine metabolism and importance of compensatory dimethylarginine dimethylaminohydrolase-1.

Objectives: This study sought to examine the hemodynamic determinants of dysregulated arginine metabolism in patients with acute decompensated heart failure and to explore possible mechanisms of arginine dysregulation in human heart failure.

Background: Accumulating methylated arginine metabolites and impaired arginine bioavailability have been associated with heart failure, but the underlying pathophysiology remains unclear.

Methods: This study prospectively determined plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and global arginine bioavailability ratio [GABR = arginine/(ornithine + citrulline)] by tandem mass spectrometry in subjects with advanced decompensated heart failure in the intensive care unit (n = 68) and with stable chronic heart failure (n = 57).