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DOE OSTI2025

Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel K Ca 3.1

The 1,4-dihydropyridines, drugs with well-established bioavailability and toxicity profiles, have proven efficacy in treating human hypertension, peripheral vascular disorders, and coronary artery disease. Every 1,4-dihydropyridine in clinical use blocks L-type voltage-gated calcium channels. We now report our development, using selective optimization of a side activity (SOSA), of a class of 1,4-dihydropyridines that selectively and potently inhibit the intermediate-conductance calcium-activated K + channel K Ca 3.1, a validated therapeutic target for diseases affecting many organ systems. One of these 1,4-dihydropyridines, DHP-103, blocked K Ca 3.1 with an IC 50 of 6 nM and exhibited exquisite selectivity over calcium channels and a panel of >100 additional molecular targets. Using high-resolution structure determination by cryogenic electron microscopy together with mutagenesis and electrophysiology, we delineated the drug binding pocket for DHP-103 within the water-filled central cavity of the K Ca 3.1 channel pore, where bound drug directly impedes ion permeation. DHP-103 inhibited gain-of-function mutant K Ca 3.1 channels that cause hereditary xerocytosis, suggesting its potential use as a therapeutic for this hemolytic anemia. In a rat model of acute ischemic stroke, the second leading cause of death worldwide, DHP-103 administered 12 h postischemic insult in proof-of-concept studies reduced infarct volume, improved balance beam performance (measure of proprioception) and decreased numbers of activated microglia in infarcted areas. K Ca 3.1-selective 1,4-dihydropyridines hold promise for the many diseases for which K Ca 3.1 has been experimentally confirmed as a therapeutic target.

Ong, Seow Theng [Lee Kong Chian School of Medicine↗

DOE OSTI2025

Laser wakefield acceleration driven by a discrete flying focus

Laser wakefield acceleration (LWFA) may enable the next generation of TeV-scale lepton colliders. Reaching such energies will likely require multiple LWFA stages to overcome limitations on the energy gain achievable in a single stage. The use of stages, however, introduces challenges such as alignment, adiabatic matching between stages, and a lower average accelerating gradient. Here, we propose a discrete flying focus that can deliver higher energy gain in a single stage, thereby reducing the number of stages required for a target energy. A sequence of laser pulses with staggered focal points and delays drives a plasma wave in which an electron beam experiences a near-constant accelerating gradient over distances beyond those attainable with a conventional pulse. Simulations demonstrate that a discrete flying focus with a total energy of 150 J can transfer 40 GeV per electron to a 50-pC beam in a single 30-cm stage, corresponding to 50 dephasing lengths.

laser wakefield acceleration↗

DOE OSTI2026

Phase Drifts and Signal Dispersion in Coaxial Cables

Phase reference distribution is a critical challenge in modern linear particle accelerators, such as European Spallation Source (ESS), European X-ray Free Electron Laser (E-XFEL), or Proton Improvement Plan II (PIP-II). Similar issues may also arise in other RF systems that need to synchronize many independent circuits. Achieving low phase drift of the reference signal requires careful selection of cables and their environmental operating conditions. Due to the limited data provided by cable manufacturers, it is necessary to characterize the cable performance. This article investigates the phase drifts in coaxial cables and presents a dedicated measurement methodology. The dispersion characteristics of the cables are also examined. The measurement results of various coaxial cables are presented, along with conclusions and practical guidelines for designers of phase reference distribution lines.

coaxial cables↗

DOE OSTI2026

Data for "Depth of nutrient uptake by deep-rooted plants is regulated by water availability"

The data set consists of strontium (Sr) isotope ratios (87Sr/86Sr), water isotopes, soil cation concentrations, soil water potential sensor data, and results of 87Sr/86Sr mixing model. The plant canopy size files include the dataset of canopy dimension of sagebrush, lupine, and sunflower. The soil and plant ICPMS (Inductively Coupled Plasma Mass Spectrometry) data file includes both of 87Sr/86Sr, and cation concentration dataset from soil exchangeable pool, apatite pool, silicate extract, atmospheric rain deposition, and plant leaf and stem tissues. The plant dendrochronology file includes the dendrochronogical ring width of several sagebrush, and dendrochemical sample data includes the 87Sr/86Sr for each separated growth ring. The modeling result gives the proportion of nutrient sources of each plants (based on their 87Sr/86Sr in leaf tissues and growth rings) from atmospheric deposition and mineral weathering. Soil water potential data includes continuous collection of soil water potential dataset at 2 depths (30 cm and 60 cm, from Nov 24 - Jun 25) of the sampling site. All the samples were collected from 2 sampling campaign June and July 2023, and rain water is a separate sampling from Aug - Sept 2023, at north-facing hillslope near pumphouse site. The data showed that the depth of cation nutrient acquisition is thus tightly coupled with, and likely determined by, water availability in soil, saprolite and bedrock. The enhanced uptake of cations and water from regions of mineral weathering could confer plant and ecosystem resilience during low water years and may impact the rate of bedrock weathering and watershed chemistry during drought. This dataset includes a file-level metadata (flmd.csv) file that lists each file contained in the dataset with associated metadata; a data dictionary (dd.csv) file that contains column/row headers used throughout the files along with a definition, units, and data type; a location metadata file (locations.csv); and a samples metadata file (samples.csv). All files are provided as comma-separated values (CSV) files (.csv). This work was supported by the Watershed Function Science Focus Area at Lawrence Berkeley National Laboratory funded by the US Department of Energy, Office of Science, Biological and Environmental Research under Contract No. DE-AC02-05CH11231.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2026

Design of a 915 MHz conduction-cooled cryomodule

High-power, compact, continuous-wave (CW) linear electron accelerators with beam energies of up to 10 MeV are being considered for possible industrial applications. Conduction-cooled, superconducting radio-frequency (SRF) technology allows operating such machines at high electrical efficiency, thereby reducing the operating cost significantly. A prototype conduction-cooled SRF cryomodule has been designed and components are currently being manufactured. The cryomodule features a two-cell, 915 MHz SRF cavity, two cryocoolers, a fundamental power coupler, two magnetic shields, a thermal shield and warm-to-cold transitions. The cryomodule has been designed to be able to provide an energy gain of 3.5 MeV to a CW electron beam with a current of 5 mA. This contribution focusses on thermal and mechanical design aspects of the cryomodule.

Ciovati, G. [Old Dominion Univ., Norfolk, VA (Unit↗

DOE OSTI2025

DARHT Axis 1 Bremsstrahlung Dose Measurements

he Dual-Axis Radiographic Hydrodynamic Test (DARHT) facility provides flash radiography ca pabilities using two electron Linear Induction Accelerators (LIA’s). Axis-1 of DARHT produces, nominally, a 20-MeV, 1.5-kA, 80-ns-Full Width at Half Max (FWHM) electron beam. The elec tron beam is focused on to a tantalum target to produce a Bremsstrahlung x-ray dose for flash radiography of dynamic systems. This paper will describe and compare a variety of techniques for determining the x-ray dose for two different beam currents produced by a 55mm and 70mm diameter cathode. The data was taken in November of 2022 on DARHT Axis 1. The experimen tal measurement techniques include a platinum calorimeter, a diamond radiation detector (DRD), and a Compton diode (CD). Gafchromic EBT3 self-developing dosimetry film was also used, but no useful results were obtained. Beam charge and energy were recorded and dose was calculated with this information using xtr with Dosecalcx, and simple dose charge-energy scaling. In this pa per, we will discuss the target geometry and experimental layout, the methods of measuring dose, dose diagnostics and measurement of beam charge and energy, and the comparisons of data and calculations.

43 PARTICLE ACCELERATORS↗

DOE OSTI2025

Design of a 915 MHz conduction-cooled cryomodule

Ciovati, G. [Old Dominion Univ., Norfolk, VA (Unit↗

DOE OSTI2025

A Performance Portable, Fully Implicit Landau Collision Operator with Batched Linear Solvers

Modern accelerators use hierarchical parallel programming models that enable massive multithreading within a processing element (PE), with multiple PEs per device driven by traditional processes. Batching is a technique for exposing PE-level parallelism in algorithms that have traditionally run on MPI processes or multiple threads within a single process. Opportunities for batching arise in, for example, kinetic discretizations of magnetized plasmas where collisions are advanced in velocity space at each spatial point independently. This paper builds on previous work on a high-performance, fully nonlinear, Landau collision operator by batching the linear solver, as well as batching the spatial point problems and adding new support for multiple grids for multiscale, multispecies problems. An anisotropic relaxation verification test that agrees well with previously published results and analytical models is presented. The performance results from NVIDIA A100 and AMD MI250X nodes are presented with hardware utilization analysis for each architecture. Finally, the entire implicit Landau operator time advance is implemented in Kokkos for performance portability, running entirely on the device and is available in the PETSc numerical library.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2026

First results from a high-frame-rate, multi-GHz ionizing particle detection system geared toward accelerator diagnostic applications

An integrated detection system, consists of a thin diamond sensor incorporated into a compact signal loop, coupled in turn to an application-specific integrated circuit readout chip, has been tested for the first time, using ps-duration electron pulses from the Next Linear Collider Test Accelerator at the SLAC National Accelerator Laboratory. For readout frame rates as high as 120 kHz, the detection system is shown to achieve a linear dynamic range of 10 3 and a bandwidth of 4–5 GHz, with no ringing seen on the tail of the output pulse. These results represent the best-performing multi-GHz ionizing particle detection system achieved to date.

Ferezghi, Mohammadreza Mohseni [University of Cali↗

DOE OSTI2025

A two-level GPU-accelerated incomplete LU preconditioner for general sparse linear systems

This paper presents a parallel preconditioning approach based on incomplete LU (ILU) factorizations in the framework of Domain Decomposition (DD) for general sparse linear systems. We focus on distributed memory parallel architectures, specifically, those that are equipped with graphic processing units (GPUs). In addition to block-Jacobi, we present general purpose two-level ILU Schur complement-based approaches, where different strategies are presented to solve the coarse-level reduced system. These strategies are combined with modified ILU methods in the construction of the coarse-level operator, in order to effectively remove smooth errors by targeting an algebraically smooth vector. We leverage available GPU-based sparse matrix kernels to accelerate the setup and the solve phases of the proposed ILU preconditioner. We evaluate the efficiency of the proposed methods as a smoother for algebraic multigrid (AMG) and as a preconditioner for Krylov subspace methods on challenging anisotropic diffusion problems and a collection of general sparse matrices.

97 MATHEMATICS AND COMPUTING↗

DOE OSTI2025

Hardware acceleration for HPS algorithms in two and three dimensions

We provide a flexible, open-source framework for hardware acceleration, namely massively-parallel execution on general-purpose graphics processing units (GPUs), applied to the hierarchical Poincaré–Steklov (HPS) family of algorithms for building fast direct solvers for linear elliptic partial differential equations. To take full advantage of the power of hardware acceleration, we propose two variants of HPS algorithms to improve performance on two- and three-dimensional problems. In the two-dimensional setting, we introduce a novel recomputation strategy that minimizes costly data transfers to and from the GPU; in three dimensions, we modify and extend the adaptive discretization technique of Geldermans and Gillman [1] to greatly reduce peak memory usage. We provide an open-source implementation of these methods written in JAX, a high-level accelerated linear algebra package, which allows for the first integration of a high-order fast direct solver with automatic differentiation tools. We conclude with extensive numerical examples showing our methods are fast and accurate on two- and three-dimensional problems.

Fast direct solvers↗

DOE OSTI2025

The positron arm of a plasma-based linear collider

Plasma-based acceleration of electrons has produced high-energy beams at high accelerating gradients with a narrow energy spread and high efficiency both in experiments and simulations. Furthermore, it is now being considered as a complementary approach to the use of radiofrequency cavities in next-generation lepton accelerators. However, compared with electrons, plasma-based positron acceleration is at the present time much less advanced. Although high-gradient positron acceleration in a plasma has been achieved, we are one to three orders of magnitude away from delivering the high-quality positron beams needed for a future high-energy linear collider. Here we review the status of plasma-based acceleration of electrons and positrons and discuss the prospects for substantial progress towards developing the positron arm of a plasma-based electron–positron linear collider in the next decade.

Plasma-based accelerators↗

DOE OSTI2025

Capacitated p -hub approach for park-and-ride facility location problem under nested logit demand function: polyhedral approaches

By generalizing the unconstrained p-hub approach for the park-and-ride (P&R) facility location problem under the multinomial logit demand function, the capacitated p-hub approach for the problem under the nested logit demand function captures a broader range of real-world cases. To solve this problem optimally, we introduce a mixed-integer linear program and accelerate its solution by enhancing the branch-and-cut procedure. To address the problem at a large scale, we introduce two other polyhedral approaches: variable neighborhood search (VNS) and adaptive randomized rounding (ARR). Downtown areas in Seoul have a high modal share of public transportation and congested road traffic, yet P&R has not been widely implemented. Therefore, we apply the ARR procedure to solve a real-world problem using traffic and geographic data from the Seoul metropolitan area. ARR performs better than VNS and addresses real-world cases. The solutions obtained by ARR present a phased expansion plan that encourages policymakers to start installing a small number of P&Rs immediately.

Capacitated p-hub approach↗

DOE OSTI2024

Image plate multi-scan response to fusion protons in the range of 1–14 MeV

Image plates (IPs) are a quickly recoverable and reusable radiation detector often used to measure proton and x-ray fluence in laser-driven experiments. Recently, IPs have been used in a proton radiography detector stack on the OMEGA laser, a diagnostic historically implemented with CR-39, or radiochromic film. The IPs used in this and other diagnostics detect charged particles, neutrons, and x-rays indiscriminately. IPs detect radiation using a photo-stimulated luminescence (PSL) material, often phosphor, in which electrons are excited to metastable states by ionizing radiation. Protons at MeV energies deposit energy deeper into the IP compared with x rays below ∼20 keV due to the Bragg peak present for protons. This property is exploited to discriminate between radiation types. Doses of mono-energetic protons between 1.7 and 14 MeV are applied to IPs using the MIT linear electrostatic ion accelerator. This paper presents the results from consecutive scans of IPs irradiated with different proton energies. The PSL ratios between subsequent scans are shown to depend on proton energy, with higher energy protons having lower PSL ratios for each scan. This finding is separate from the known energy dependence in the absolute sensitivity of IPs. The results can be compared to complimentary work on x rays, showing a difference between protons and x rays, forging a path to discriminate between proton and x-ray fluence in mixed radiation environments.

Instruments & Instrumentation↗

DOE OSTI2025

Experimental and computational study of phase space dynamics in strongly coupled plasmas with steep density gradients

Understanding how plasmas thermalize when density gradients are steep remains a fundamental challenge in plasma physics, with direct implications for fusion experiments and astrophysical phenomena. Standard hydrodynamic models break down in these regimes, and kinetic theories make predictions that have never been directly tested. Here, we present the first detailed phase-space measurements of a strongly coupled plasma as it evolves from sharp density gradients to thermal equilibrium. Using laser-induced fluorescence imaging of an ultracold calcium plasma, we track the complete ion distribution function f(x,v,t). We discover that commonly used kinetic models (Bhatnagar–Gross–Krook and Lenard–Bernstein) overpredict thermalization rates, even while correctly capturing the initial counterstreaming plasma formation. Our measurements reveal that the initial ion acceleration response scales linearly with electron temperature, and that the simulations underpredict the initial ion response. In our geometry we demonstrate the formation of well-controlled counterpropagating plasma beams. This experimental platform enables precision tests of kinetic theories and opens new possibilities for studying plasma stopping power and flow-induced instabilities in strongly coupled systems.

Bergeson, Scott (ORCID:0000000231249226)↗

DOE OSTI2025

ORNL/Restricted-Alternating-Anderson-Picard

Implementation in the programming language Julia of the Restricted Alternating Anderson Picard (AAP) acceleration for (non)-linear fixed point iterations.

Barnafi, NicolásAlejandro [Pontifica Universidad C↗

DOE OSTI2025

Monte Carlo simulation analysis for radiation damage on Glidcop Al-15 caused by 17-20 MeV/u heavy ions

The Facility for Rare Isotope Beams (FRIB) SRF linear heavy-ion accelerator is designed to accelerate all ions up to uranium to a maximum beam power of 400 kW. Several beam intercepting devices (BIDs) are essential to the successful operation of the accelerator, including a low power charge selector (LPCS) made of copper containing 0.15% precipitated aluminum oxide by weight called Glidcop Al-15. As FRIB ramps up the primary beam power beyond the current 20 kW level, the charge selector must withstand higher radiation damage rates, typically measured in displacements per atom (dpa). Significant beam induced radiation damage including significant deformation, like swelling, blistering, and cracking has been observed on a recently removed LPCS. We also observed physical features up to about 5.5 mm wide and appear to be deeper than the projected range of any ions. This paper presents the results of Monte Carlo simulations carried out using the Particle and Heavy Ion Transport code System (PHITS), quantifying the total damage dose and ion concentration, etc. Simulating an accurate irradiation history is essential to determining the scope of post irradiation examination (PIE) work.

Fletcher, Ethan [Michigan State U.]↗

DOE OSTI2025

Summary of Working Group 7: Linear colliders

The contributions presented during the Working Group 7: Linear Colliders (WG7) sessions at the 2024 Advanced Accelerator Concepts Workshop are briefly summarized, as well as the discussions regarding a design initiative for a linear collider based on wakefield accelerator technology.

Advanced Accelerator Concepts↗