Optimal parameters for radiation reaction experiments

As new laser facilities are developed with intensities on the scale of 10^22 - 10^24 W cm^-2 , it becomes ever more important to understand the effect of strong field quantum electrodynamics processes, such as quantum radiation reaction, which will play a dominant role in laser-plasma interactions at these intensities. Recent all-optical experiments, where GeV electrons from a laser wakefield accelerator encountered a counter-propagating laser pulse with a_0 > 10, have produced evidence of radiation reaction, but have not conclusively identified quantum effects nor their most suitable theoretical description. Here we show the number of collisions and the conditions required to accomplish this, based on a simulation campaign of radiation reaction experiments under realistic conditions. We conclude that while the critical energy of the photon spectrum distinguishes classical and quantum-corrected models, a better means of distinguishing the stochastic and deterministic quantum models is the change in the electron energy spread. This is robust against shot-to-shot fluctuations and the necessary laser intensity and electron beam energies are already available. For example, we show that so long as the electron energy spread is below 25%, collisions at a_0 = 10 with electron energies of 500 MeV could differentiate between different quantum models in under 30 shots, even with shot to shot variations at the 50% level.Comment: 12 pages, 7 figure

Shedding Light on Chemically Mediated Tri-Trophic Interactions: A 1H-NMR Network Approach to Identify Compound Structural Features and Associated Biological Activity

Diverse mixtures of plant natural products play an important role in plant-herbivore-parasitoid interactions. In the pursuit of understanding these chemically-mediated interactions, we are often faced with the challenge of determining ecologically and biologically relevant compounds present in complex phytochemical mixtures. Using a network-based approach, we analyzed binned 1H-NMR data from 196 prepared mixtures of commonly studied secondary metabolites including alkaloids, amides, terpenes, iridoid glycosides, saponins, phenylpropanoids, flavonoids and phytosterols. The mixtures included multiple dimensions of chemical diversity, including molecular complexity, mixture complexity and differences in relative compound concentrations. This approach yielded modules of co-occurring chemical shifts that were correlated with specific compounds or common structural features shared across compounds. This approach was then applied to crude phytochemical extracts of 31 species in the phytochemically diverse tropical plant genus Piper (Piperaceae). Combining the activity of crude plant extracts in an array of bioassays with our 1H-NMR network approach, we identified a potential prenylated benzoic acid from these mixtures that exhibits antifungal properties and identified small structural differences that were potentially responsible for antifungal activity. In an intraspecific analysis of individual Piper kelleyi plants, we also found ontogenetic differences in chemistry that may affect natural plant enemies. In sum, this approach allowed us to characterize mixtures as useful network modules and to combine chemical and ecological datasets to identify biologically important compounds from crude extracts

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Receptor activity-modifying proteins 2 and 3 generate adrenomedullin receptor subtypes with distinct molecular properties

Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM1 and AM2 receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins (RAMP) 2 and 3, respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMPs 2 and 3 on the activation and conformation of the CLR subunit of AM receptors we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors and determined the effects on cAMP signalling. Sixteen CLR mutations had differential effects between the AM1 and AM2 receptors. Accompanying this, independent molecular modelling of the full-length AM-bound AM1 and AM2 receptors predicted differences in the binding pocket, and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function

Measurement of magnetic cavitation driven by heat flow in a plasma

We describe the direct measurement of the expulsion of a magnetic field from a plasma driven by heat flow. Using a laser to heat a column of gas within an applied magnetic field, we isolate Nernst advection and show how it changes the field over a nanosecond timescale. Reconstruction of the magnetic field map from proton radiographs demonstrates that the field is advected by heat flow in advance of the plasma expansion. This changes the dynamics of high energy density plasmas, in which heat flows and fields are strongly coupled, and may disrupt magnetised inertial confinement fusion schemes

Impacts of Social Distancing Policies on Mobility and COVID-19 Case Growth in the US

Social distancing remains an important strategy to combat the COVID-19 pandemic in the United States. However, the impacts of specific state-level policies on mobility and subsequent COVID-19 case trajectories have not been completely quantified. Using anonymized and aggregated mobility data from opted-in Google users, we found that state-level emergency declarations resulted in a 9.9% reduction in time spent away from places of residence. Implementation of one or more social distancing policies resulted in an additional 24.5% reduction in mobility the following week, and subsequent shelter-in-place mandates yielded an additional 29.0% reduction. Decreases in mobility were associated with substantial reductions in case growth 2 to 4 weeks later. For example, a 10% reduction in mobility was associated with a 17.5% reduction in case growth 2 weeks later. Given the continued reliance on social distancing policies to limit the spread of COVID-19, these results may be helpful to public health officials trying to balance infection control with the economic and social consequences of these policies.Comment: Co-first Authors: GAW, SV, VE, and AF contributed equally. Corresponding Author: Dr. Evgeniy Gabrilovich, [email protected] 32 pages (including supplemental material), 4 figures in the main text, additional figures in the supplemental materia