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DOE OSTI2023

Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils

The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson’s disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic target for treatment of these diseases. We identify two small molecules capable of disassembling preformed alpha-synuclein fibrils. The compounds, termed CNS-11 and CNS-11g, disaggregate recombinant alpha-synuclein fibrils in vitro, prevent the intracellular seeded aggregation of alpha-synuclein fibrils, and mitigate alpha-synuclein fibril cytotoxicity in neuronal cells. Furthermore, we demonstrate that both compounds disassemble fibrils extracted from MSA patient brains and prevent their intracellular seeding. They also reduce in vivo alpha-synuclein aggregates in C. elegans . Both compounds also penetrate brain tissue in mice. A molecular dynamics–based computational model suggests the compounds may exert their disaggregating effects on the N terminus of the fibril core. These compounds appear to be promising therapeutic leads for targeting alpha-synuclein for the treatment of synucleinopathies.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2013

NEW TECHNIQUES FOR HIGH-CONTRAST IMAGING WITH ADI: THE ACORNS-ADI SEEDS DATA REDUCTION PIPELINE

We describe Algorithms for Calibration, Optimized Registration, and Nulling the Star in Angular Differential Imaging (ACORNS-ADI), a new, parallelized software package to reduce high-contrast imaging data, and its application to data from the SEEDS survey. We implement several new algorithms, including a method to register saturated images, a trimmed mean for combining an image sequence that reduces noise by up to {approx}20%, and a robust and computationally fast method to compute the sensitivity of a high-contrast observation everywhere on the field of view without introducing artificial sources. We also include a description of image processing steps to remove electronic artifacts specific to Hawaii2-RG detectors like the one used for SEEDS, and a detailed analysis of the Locally Optimized Combination of Images (LOCI) algorithm commonly used to reduce high-contrast imaging data. ACORNS-ADI is written in python. It is efficient and open-source, and includes several optional features which may improve performance on data from other instruments. ACORNS-ADI requires minimal modification to reduce data from instruments other than HiCIAO. It is freely available for download at www.github.com/t-brandt/acorns-adi under a Berkeley Software Distribution (BSD) license.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2013

ON THE REMOTE DETECTION OF SUPRATHERMAL IONS IN THE SOLAR CORONA AND THEIR ROLE AS SEEDS FOR SOLAR ENERGETIC PARTICLE PRODUCTION

Forecasting large solar energetic particle (SEP) events associated with shocks driven by fast coronal mass ejections (CMEs) poses a major difficulty in the field of space weather. Besides issues associated with CME initiation, the SEP intensities are difficult to predict, spanning three orders of magnitude at any given CME speed. Many lines of indirect evidence point to the pre-existence of suprathermal seed particles for injection into the acceleration process as a key ingredient limiting the SEP intensity of a given event. This paper outlines the observational and theoretical basis for the inference that a suprathermal particle population is present prior to large SEP events, explores various scenarios for generating seed particles and their observational signatures, and explains how such suprathermals could be detected through measuring the wings of the H I Ly{alpha} line.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2014

Seed photon fields of blazars in the internal shock scenario

We extend our approach of modeling spectral energy distribution (SED) and light curves of blazars to include external Compton (EC) emission due to inverse Compton scattering of an external anisotropic target radiation field. We describe the time-dependent impact of such seed photon fields on the evolution of multifrequency emission and spectral variability of blazars using a multi-zone time-dependent leptonic jet model, with radiation feedback, in the internal shock model scenario. We calculate accurate EC-scattered high-energy (HE) spectra produced by relativistic electrons throughout the Thomson and Klein-Nishina regimes. We explore the effects of varying the contribution of (1) a thermal Shakura-Sunyaev accretion disk, (2) a spherically symmetric shell of broad-line clouds, the broad-line region (BLR), and (3) a hot infrared emitting dusty torus (DT), on the resultant seed photon fields. We let the system evolve to beyond the BLR and within the DT and study the manifestation of the varying target photon fields on the simulated SED and light curves of a typical blazar. The calculations of broadband spectra include effects of γ-γ absorption as γ-rays propagate through the photon pool present inside the jet due to synchrotron and inverse Compton processes, but neglect γ-γ absorption by the BLR and DT photon fields outside the jet. Thus, our account of γ-γ absorption is a lower limit to this effect. Here, we focus on studying the impact of parameters relevant for EC processes on HE emission of blazars.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2014

The moving group targets of the seeds high-contrast imaging survey of exoplanets and disks: Results and observations from the first three years

We present results from the first three years of observations of moving group (MG) targets in the Strategic Exploration of Exoplanets and Disks with Subaru (SEEDS) high-contrast imaging survey of exoplanets and disks using the Subaru telescope. We achieve typical contrasts of ∼10{sup 5} at 1'' and ∼10{sup 6} beyond 2'' around 63 proposed members of nearby kinematic MGs. We review each of the kinematic associations to which our targets belong, concluding that five, β Pictoris (∼20 Myr), AB Doradus (∼100 Myr), Columba (∼30 Myr), Tucana-Horogium (∼30 Myr), and TW Hydrae (∼10 Myr), are sufficiently well-defined to constrain the ages of individual targets. Somewhat less than half of our targets are high-probability members of one of these MGs. For all of our targets, we combine proposed MG membership with other age indicators where available, including Ca II HK emission, X-ray activity, and rotation period, to produce a posterior probability distribution of age. SEEDS observations discovered a substellar companion to one of our targets, κ And, a late B star. We do not detect any other substellar companions, but do find seven new close binary systems, of which one still needs to be confirmed. A detailed analysis of the statistics of this sample, and of the companion mass constraints given our age probability distributions and exoplanet cooling models, will be presented in a forthcoming paper.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2021

Experimental study of the influence of gas puff locations on H-mode boundary plasmas with argon seeding on EAST

To investigate the optimal scenario of impurity seeding to obtain divertor plasma detachment for target protection, experiments with Ar&D 2 seeding from two different poloidal locations, the upper outer (UO) divertor target and lower outer (LO) target, were carried out on EAST. Partial energy detachment (the electron temperature near the strike point T e,spt ≤ 10 eV) were obtained with Ar&D 2 mixture puffing from the UO target and, for the first time, from the LO target into H-mode plasmas in the upper single null (USN) configuration. The peak heat flux q t on the UO target was significantly reduced (by ~80%). The rollover of ion flux density j s did not appear probably due to insufficient momentum loss, which is independent of the puff locations. The poloidal asymmetries of particle and heat fluxes on the targets have also been investigated. The UO-dominant asymmetry of particle flux was reversed, while the UO-dominant asymmetry of heat flux was mitigated but not reversed. The plasma confinement dropped by only 14% and 8.2% in the LO-puff case and UO-puff case, respectively, during detachment. The high level of C may contributed greatly to the higher radiation in the bulk plasma region and the greater decline in W MHD in the LO-puff case.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2015

An optical parametric chirped-pulse amplifier for seeding high repetition rate free-electron lasers

High repetition rate free-electron lasers (FEL), producing highly intense extreme ultraviolet and x-ray pulses, require new high power tunable femtosecond lasers for FEL seeding and FEL pump-probe experiments. A tunable, 112 W (burst mode) optical parametric chirped-pulse amplifier (OPCPA) is demonstrated with center frequencies ranging from 720–900 nm, pulse energies up to 1.12 mJ and a pulse duration of 30 fs at a repetition rate of 100 kHz. Since the power scalability of this OPCPA is limited by the OPCPA-pump amplifier, we also demonstrate a 6.7–13.7 kW (burst mode) thin-disk OPCPA-pump amplifier, increasing the possible OPCPA output power to many hundreds of watts. Furthermore, third and fourth harmonic generation experiments are performed and the results are used to simulate a seeded FEL with high-gain harmonic generation.

43 PARTICLE ACCELERATORS↗

DOE OSTI2012

Towards a formal description of the collapse approach to the inflationary origin of the seeds of cosmic structure

Inflation plays a central role in our current understanding of the universe. According to the standard viewpoint, the homogeneous and isotropic mode of the inflaton field drove an early phase of nearly exponential expansion of the universe, while the quantum fluctuations (uncertainties) of the other modes gave rise to the seeds of cosmic structure. However, if we accept that the accelerated expansion led the universe into an essentially homogeneous and isotropic space-time, with the state of all the matter fields in their vacuum (except for the zero mode of the inflaton field), we can not escape the conclusion that the state of the universe as a whole would remain always homogeneous and isotropic. It was recently proposed in [A. Perez, H. Sahlmann and D. Sudarsky, {sup O}n the quantum origin of the seeds of cosmic structure{sup ,} Class. Quant. Grav. 23 (2006) 2317–2354] that a collapse (representing physics beyond the established paradigm, and presumably associated with a quantum-gravity effect à la Penrose) of the state function of the inflaton field might be the missing element, and thus would be responsible for the emergence of the primordial inhomogeneities. Here we will discuss a formalism that relies strongly on quantum field theory on curved space-times, and within which we can implement a detailed description of such a process. The picture that emerges clarifies many aspects of the problem, and is conceptually quite transparent. Nonetheless, we will find that the results lead us to argue that the resulting picture is not fully compatible with a purely geometric description of space-time.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2017

Globular cluster seeding by primordial black hole population

Primordial black holes (PBHs) that form in the early Universe in the modified Affleck-Dine (AD) mechanism of baryogenesis should have intrinsic log-normal mass distribution of PBHs. We show that the parameters of this distribution adjusted to provide the required spatial density of massive seeds (≥ 10{sup 4} M {sub ⊙}) for early galaxy formation and not violating the dark matter density constraints, predict the existence of the population of intermediate-mass PBHs with a number density of 0∼ 100 Mpc{sup −3}. We argue that the population of intermediate-mass AD PBHs can also seed the formation of globular clusters in galaxies. In this scenario, each globular cluster should host an intermediate-mass black hole with a mass of a few thousand solar masses, and should not obligatorily be immersed in a massive dark matter halo.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2017

Constraints on the production of primordial magnetic seeds in pre-big bang cosmology

We study the amplification of the electromagnetic fluctuations, and the production of 'seeds' for the cosmic magnetic fields, in a class of string cosmology models whose scalar and tensor perturbations reproduce current observations and satisfy known phenomenological constraints. We find that the condition of efficient seeds production can be satisfied and compatible with all constraints only in a restricted region of parameter space, but we show that such a region has significant intersections with the portions of parameter space where the produced background of relic gravitational waves is strong enough to be detectable by aLIGO/Virgo and/or by eLISA.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2021

SMBH seeds from dissipative dark matter

The existence of supermassive black holes (SMBHs) with masses greater than ~ 10 9 M ⊙ at high redshift ( z ≳ 7) is difficult to accommodate in standard astrophysical scenarios. We study the possibility that (nearly) totally dissipative self-interacting dark matter (tdSIDM)–in rare, high density dark matter fluctuations in the early Universe — produces SMBH seeds through catastrophic collapse. We use a semi-analytic model, tested and calibrated by a series of N-body simulations of isolated dark matter halos, to compute the collapse criteria and timescale of tdSIDM halos, where dark matter loses nearly all of its kinetic energy in a single collision in the center-of-momentum frame. Applying this model to halo merger trees, we empirically assign SMBH seeds to halos and trace the formation and evolution history of SMBHs. We make predictions for the quasar luminosity function, the M BH -σ v * relation, and cosmic SMBH mass density at high redshift and compare them to observations. We find that a dissipative dark matter interaction cross-section of σ/ m ~ 0.05 cm 2 /g is sufficient to produce the SMBHs observed in the early Universe while remaining consistent with ordinary SMBHs in the late Universe.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2022

Disruptive neoclassical tearing mode seeding in DIII-D with implications for ITER

New studies identify the critical parameters and physics governing disruptive neoclassical tearing mode (NTM) onset. An m/n = 2/1 mode in DIII-D that begins to grow robustly after a seeding event (edge localized mode ELM or sawtooth precursor and crash) causes the mode rotation to drop close to the plasma's Er = 0 rest frame; this condition opens the stabilizing ion-polarization current 'gate' and destabilizes an otherwise marginally stable NTM. Our new experimental and theoretical insights and novel toroidal theory-based modeling are benchmarked and scalable to ITER and other future experiments. Here, the nominal ITER rotation at q = 2 is found to be stabilizing ('gate closed') except for MHD-induced transients that could 'open the gate'. Extrapolating from the DIII-D ITER baseline scenario (IBS) discharges, MHD transients are much more likely to destabilize problematic robustly growing 2/1 NTMs in ITER; this makes predictions of seeding and control of both ELMs and sawteeth imperative for more than just minimizing divertor pulsed-heat loading.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2021

Beyond 4D tracking: using cluster shapes for track seeding

Tracking is one of the most time consuming aspects of event reconstruction at the Large Hadron Collider (LHC) and its high-luminosity upgrade (HL-LHC). Innovative detector technologies extend tracking to four-dimensions by including timing in the pattern recognition and parameter estimation. However, present and future hardware already have additional information that is largely unused by existing track seeding algorithms. The shape of pixel-clusters provides an additional dimension for track seeding that can significantly reduce the combinatorial challenge of track finding. We use neural networks to show that cluster shapes can reduce significantly the rate of fake combinatorical backgrounds while preserving a high efficiency. We demonstrate this using the information in cluster singlets, doublets and triplets. Numerical results are presented with simulations from the TrackML challenge.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2024

Towards rational control of seed oil composition: dissecting cellular organization and flux control of lipid metabolism

Plant lipids represent a fascinating field of scientific study, in part due to a stark dichotomy in the limited fatty acid (FA) composition of cellular membrane lipids vs the huge diversity of FAs that can accumulate in triacylglycerols (TAGs), the main component of seed storage oils. With few exceptions, the strict chemical, structural, and biophysical roles imposed on membrane lipids since the dawn of life have constrained their FA composition to predominantly lengths of 16–18 carbons and containing 0–3 methylene-interrupted carbon-carbon double bonds in cis-configuration. However, over 450 “unusual” FA structures can be found in seed oils of different plants, and we are just beginning to understand the metabolic mechanisms required to produce and maintain this dichotomy. Here we review the current state of plant lipid research, specifically addressing the knowledge gaps in membrane and storage lipid synthesis from 3 angles: pathway fluxes including newly discovered TAG remodeling, key acyltransferase substrate selectivities, and the possible roles of “metabolons.”

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Minijet clustering algorithm using transverse-momentum seeds in high-energy nuclear collisions

We propose an algorithm to detect mini-jet clusters in high-energy nuclear collisions, by selecting a high-transverse-momentum (pT) particle as a seed and assigning a clustering radius (R) in the pseudorapidity and azimuthal-angle space. Our PYTHIA simulations for p+p collisions show that a scheme with a seeding p T of around 0.5 GeV/c and R of approximately 0.6 satisfactorily identifies mini-jet clusters. The correlation between clusters obtained in PYTHIA calculations using the algorithm exhibits the proper behavior of hard-scattering-like processes, suggesting its usefulness in isolating mini-jet-like clusters from non-hard-scattering soft processes when applied to actual nuclear-collision data, thereby allowing a closer examination of both the mini-jet and the soft mechanisms.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

DOE OSTI2012

Evidence of High Harmonics from Echo-Enabled Harmonic Generation for Seeding X-ray Free Electron Lasers

Echo-enabled harmonic generation free electron lasers hold great promise for the generation of fully coherent radiation in x-ray wavelengths. Here we report the first evidence of high harmonics from the echo-enabled harmonic generation technique in the realistic scenario where the laser energy modulation is comparable to the beam slice energy spread. In this experiment, coherent radiation at the seventh harmonic of the second seed laser is generated when the energy modulation amplitude is about 2-3 times the slice energy spread. The experiment confirms the underlying physics of echo-enabled harmonic generation and may have a strong impact on emerging seeded x-ray free electron lasers that are capable of generating laserlike x rays which will advance many areas of science.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2024

Wave-packet manipulation of He Rydberg states by a seeded free-electron laser

We report a two-dimensional pump-control-probe spectroscopic study of the dynamics of singly excited He Rydberg-state wave packets with a seeded extreme ultraviolet (XUV) free-electron laser (FEL) source. A pair of coherent XUV pulses, defined by their coarse time separation and relative phase, created and manipulated the wave packets. The He atoms were postionized by infrared (IR) pulses, and the ion yield was measured as a function of XUV phase and IR arrival time. We tagged and sorted the relative phase of the XUV pulse pair on a single-shot basis by fitting each FEL spectrum with a suitable function that accounts for nonidealities of the XUV pulse pairs, associated with the seeding process; more generally, the fit returns the time-dependent electric field of the FEL spectra. The experimental two-dimensional maps of ion yields, measured as a function of IR (probe) delay and of XUV (pump-control) phase, were compared with the solution of the first-order time-dependent Schrödinger equation for this field. Despite the fact that the experimental conditions imply strong excitation, beyond the approximations of first-order perturbation theory, the simulated map satisfactorily reproduces the experimental one for temporally well-separated pulses. We show that by selecting data at appropriate values of pump-control phase, we enhance or suppress the amplitude of chosen wave-packet components consisting of two or more Rydberg states. When the temporal overlap of the pulse pair cannot be neglected, the phase reconstruction is underdetermined, and we provide a simplified comparison between data and simulations. Published by the American Physical Society 2024

Dumergue, Mathieu (ORCID:0000000236984406)↗

DOE OSTI2017

Pulse Duration of Seeded Free-Electron Lasers

The pulse duration, and, more generally, the temporal intensity profile of free-electron laser (FEL) pulses, is of utmost importance for exploring the new perspectives offered by FELs; it is a nontrivial experimental parameter that needs to be characterized. We measured the pulse shape of an extreme ultraviolet externally seeded FEL operating in high-gain harmonic generation mode. Two different methods based on the cross-correlation of the FEL pulses with an external optical laser were used. The two methods, one capable of single-shot performance, may both be implemented as online diagnostics in FEL facilities. The measurements were carried out at the seeded FEL facility FERMI. The FEL temporal pulse characteristics were measured and studied in a range of FEL wavelengths and machine settings, and they were compared to the predictions of a theoretical model. Finally, the measurements allowed a direct observation of the pulse lengthening and splitting at saturation, in agreement with the proposed theory.

74 ATOMIC AND MOLECULAR PHYSICS↗