Morphology of Copper Nanofoams for Radiation Hydrodynamics and Fusion Applications Investigated by 3D Ptychotomography.

The performance of metal and polymer foams used in inertial confinement fusion (ICF), inertial fusion energy (IFE), and high-energy-density (HED) experiments is currently limited by our understanding of their nanostructure and its variation in bulk material. We utilized an X-ray-free electron laser (XFEL) together with lensless X-ray imaging techniques to probe the 3D morphology of copper foams at nanoscale resolution (28 nm). The observed morphology of the thin shells is more varied than expected from previous characterizations, with a large number of them distorted, merged, or open, and a targeted mass density 14% less than calculated.

Room temperature X-ray absorption spectroscopy of metalloenzymes with drop-on-demand sample delivery at XFELs.

X-ray crystallography and X-ray spectroscopy using X-ray free electron lasers plays an important role in understanding the interplay of structural changes in the protein and the chemical changes at the metal active site of metalloenzymes through their catalytic cycles. As a part of such an effort, we report here our recent development of methods for X-ray absorption spectroscopy (XAS) at XFELs to study dilute biological samples, available in limited volumes. Our prime target is Photosystem II (PS II), a multi subunit membrane protein complex, that catalyzes the light-driven water oxidation reaction at the MnCaO cluster.

Prediction on X-ray output of free electron laser based on artificial neural networks.

Knowledge of x-ray free electron lasers' (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs' self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges.

Simultaneous bright- and dark-field X-ray microscopy at X-ray free electron lasers.

The structures, strain fields, and defect distributions in solid materials underlie the mechanical and physical properties across numerous applications. Many modern microstructural microscopy tools characterize crystal grains, domains and defects required to map lattice distortions or deformation, but are limited to studies of the (near) surface. Generally speaking, such tools cannot probe the structural dynamics in a way that is representative of bulk behavior.

Real-time imaging of acoustic waves in bulk materials with X-ray microscopy.

The dynamics of lattice vibrations govern many material processes, such as acoustic wave propagation, displacive phase transitions, and ballistic thermal transport. The maximum velocity of these processes and their effects is determined by the speed of sound, which therefore defines the temporal resolution (picoseconds) needed to resolve these phenomena on their characteristic length scales (nanometers). Here, we present an X-ray microscope capable of imaging acoustic waves with subpicosecond resolution within mm-sized crystals.

Detection of a Geminate Photoproduct of Bovine Cytochrome Oxidase by Time-Resolved Serial Femtosecond Crystallography.

Cytochrome oxidase (CO) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme group in their active sites, CO has a unique binuclear center (BNC) composed of a copper atom (Cu) and a heme iron, where O binds and is reduced to water. CO is a versatile O surrogate in ligand binding and escape reactions.

Optical control of ultrafast structural dynamics in a fluorescent protein.

The photoisomerization reaction of a fluorescent protein chromophore occurs on the ultrafast timescale. The structural dynamics that result from femtosecond optical excitation have contributions from vibrational and electronic processes and from reaction dynamics that involve the crossing through a conical intersection. The creation and progression of the ultrafast structural dynamics strongly depends on optical and molecular parameters.

Exploring fingerprints of ultrafast structural dynamics in molecular solutions with an X-ray laser.

We apply ultrashort X-ray laser pulses to track optically excited structural dynamics of [Ir(dimen)] molecules in solution. In our exploratory study we determine angular correlations in the scattered X-rays, which comprise a complex fingerprint of the ultrafast dynamics. Model-assisted analysis of the experimental correlation data allows us to elucidate various aspects of the photoinduced changes in the excited molecular ensembles.

Dosimetric patterns of failure in the era of novel chemoradiotherapy in newly-diagnosed glioblastoma patients.

Background: Patterns of failure (POF) may provide an alternative quantitative endpoint to overall survival for evaluation of novel chemoradiotherapy regimens with glioblastoma.

Materials And Methods: POF of 109 newly-diagnosed glioblastoma patients per 2016 WHO classification who received conformal radiotherapy with concomitant and adjuvant temozolomide were reviewed. Seventy-five of those patients also received an investigational chemotherapy agent (everolimus, erlotinib, or vorinostat).

Towards a wavefront-preservation X-ray crystal monochromator for high-repetition-rate FELs.

The wavefront preservation of coherent X-ray free-electron laser beams is pushing the requirement on the quality and performance of X-ray optics to an unprecedented level. The Strehl ratio can be used to quantify this requirement. In this paper, the criteria for thermal deformation of the X-ray optics are formulated, especially for crystal monochromators.

Detection of a geminate photoproduct of bovine cytochrome c oxidase by time-resolved serial femtosecond crystallography.

Cytochrome oxidase (C O) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme group in their active sites, C O has a unique binuclear center (BNC) comprised of a copper atom (Cu ) and a heme iron, where O binds and is reduced to water. CO is a versatile O surrogate in ligand binding and escape reactions.

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

Objective: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors.

Methods: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303).

Rational Control of Off-State Heterogeneity in a Photoswitchable Fluorescent Protein Provides Switching Contrast Enhancement.

Reversibly photoswitchable fluorescent proteins are essential markers for advanced biological imaging, and optimization of their photophysical properties underlies improved performance and novel applications. Here we establish a link between photoswitching contrast, one of the key parameters that dictate the achievable resolution in nanoscopy applications, and chromophore conformation in the non-fluorescent state of rsEGFP2, a widely employed label in REversible Saturable OpticaL Fluorescence Transitions (RESOLFT) microscopy. Upon illumination, the cis chromophore of rsEGFP2 isomerizes to two distinct off-state conformations, trans1 and trans2, located on either side of the V151 side chain.

The time-resolved atomic, molecular and optical science instrument at the Linac Coherent Light Source.

The newly constructed time-resolved atomic, molecular and optical science instrument (TMO) is configured to take full advantage of both linear accelerators at SLAC National Accelerator Laboratory, the copper accelerator operating at a repetition rate of 120 Hz providing high per-pulse energy as well as the superconducting accelerator operating at a repetition rate of about 1 MHz providing high average intensity. Both accelerators power a soft X-ray free-electron laser with the new variable-gap undulator section. With this flexible light source, TMO supports many experimental techniques not previously available at LCLS and will have two X-ray beam focus spots in line.

Enhanced charge density wave coherence in a light-quenched, high-temperature superconductor.

Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBaCuO after the quench of superconductivity by an infrared laser pulse.

Cooperative allostery and structural dynamics of streptavidin at cryogenic- and ambient-temperature.

Multimeric protein assemblies are abundant in nature. Streptavidin is an attractive protein that provides a paradigm system to investigate the intra- and intermolecular interactions of multimeric protein complexes. Also, it offers a versatile tool for biotechnological applications.

Acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models.

Background: Uncontrolled immune response with T cell activation has a key role in the pathogenesis of systemic sclerosis (SSc), a disorder that is characterized by generalized fibrosis affecting particularly the lungs and skin. Costimulatory molecules are key players during immune activation, and recent evidence supports a role of CD28 and ICOS in the development of fibrosis. We herein investigated the efficacy of acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, in two complementary SSc-related mouse models recapitulating skin fibrosis, interstitial lung disease, and pulmonary hypertension.

Absolute contrast estimation for soft X-ray photon fluctuation spectroscopy using a variational droplet model.

X-ray photon fluctuation spectroscopy using a two-pulse mode at the Linac Coherent Light Source has great potential for the study of quantum fluctuations in materials as it allows for exploration of low-energy physics. However, the complexity of the data analysis and interpretation still prevent recovering real-time results during an experiment, and can even complicate post-analysis processes. This is particularly true for high-spatial resolution applications using CCDs with small pixels, which can decrease the photon mapping accuracy resulting from the large electron cloud generation at the detector.

Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing.

The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int).

Initial Results of a Phase 2 Trial of F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma.

Purpose: Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (F-DOPA) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. The purpose of this prospective phase 2 study was to determine the safety and efficacy of biologic-guided, dose-escalated radiation therapy (DERT) using F-DOPA PET in patients with glioblastoma.

Methods And Materials: Patients with newly diagnosed, histologically confirmed glioblastoma aged ≥18 years without contraindications to F-DOPA were eligible.

ICOSL plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist.

Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs).

Investigating off-Hugoniot states using multi-layer ring-up targets.

Laser compression has long been used as a method to study solids at high pressure. This is commonly achieved by sandwiching a sample between two diamond anvils and using a ramped laser pulse to slowly compress the sample, while keeping it cool enough to stay below the melt curve. We demonstrate a different approach, using a multilayer 'ring-up' target whereby laser-ablation pressure compresses Pb up to 150 GPa while keeping it solid, over two times as high in pressure than where it would shock melt on the Hugoniot.

Wavefront preserving and high efficiency diamond grating beam splitter for x-ray free electron laser.

X-ray free electron lasers (XFELs) provide femtosecond high-power x-ray beams with high spatial coherence, resulting in numerous influential discoveries. Diffractive optics allow for the easy manipulation and measurement of an x-ray beam's wavefront and enable the realization of complex designed properties and specifications. For example, phase gratings can be used as x-ray beam splitters to enable beam sharing by multiple end stations or in-situ beam monitoring, including spectrum and wavefront measurements.