A5056060411- Advanced X-ray Imaging Techniques
- Enzyme Structure and Function
- Advanced Electron Microscopy Techniques and Applications
- X-ray Spectroscopy and Fluorescence Analysis
- Protein Structure and Dynamics
- Advanced MRI Techniques and Applications
- Particle Accelerators and Free-Electron Lasers
- Receptor Mechanisms and Signaling
- HIV Research and Treatment
- Machine Learning in Materials Science
- Medical Imaging Techniques and Applications
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- Advanced X-ray and CT Imaging
- Electron and X-Ray Spectroscopy Techniques
- Crystallography and Radiation Phenomena
- Laser-Plasma Interactions and Diagnostics
- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- Biochemical and Molecular Research
- Distributed and Parallel Computing Systems
- Advanced Data Storage Technologies
- Digital Holography and Microscopy
- Cardiomyopathy and Myosin Studies
- Astrophysical Phenomena and Observations
SLAC National Accelerator Laboratory
2016-2024
Linac Coherent Light Source
2016-2024
Deutsches Elektronen-Synchrotron DESY
2014-2022
Stanford University
2021-2022
University of Canterbury
2004-2021
Stanford Synchrotron Radiation Lightsource
2021
University of Nebraska–Lincoln
2021
Lawrence Berkeley National Laboratory
2021
Los Alamos National Laboratory
2021
University of California, San Francisco
2021
The emerging technique of serial X-ray diffraction, in which diffraction data are collected from samples flowing across a pulsed source at repetition rates 100 Hz or higher, has necessitated the development new software order to handle large volumes produced. Sorting according different criteria and rapid filtering events retain only patterns interest results significant reductions volume, thereby simplifying subsequent analysis management tasks. Meanwhile generation reduced form virtual...
CrystFEL is a suite of programs for processing data from `serial crystallography' experiments, which are usually performed using X-ray free-electron lasers (FELs) but also increasingly with other sources. The software has been under development since 2009, just before the first hard FEL experiments were performed, and significantly updated improved then. This article describes most important improvements have made to release version. These changes include addition new suite, ability resolve...
A new approach for collecting data from many hundreds of thousands microcrystals using X-ray pulses a free-electron laser has recently been developed. Referred to as serial crystallography, diffraction patterns are recorded at constant rate suspension protein crystals flows across the path an beam. Events that by chance contain single-crystal retained, then indexed and merged form three-dimensional set reflection intensities structure determination. This relies upon several innovations:...
Architectural and technological trends of systems used for scientific computing call a significant reduction data sets that are composed mainly floating-point data. This article surveys presents experimental results currently identified use cases generic lossy compression to address the different limitations systems. The shows from collection experiments run on parallel leadership facility not only can reduce footprint storage but also I/O checkpoint/restart times, accelerate computation,...
We use extremely bright and ultrashort pulses from an x-ray free-electron laser (XFEL) to measure correlations in x rays scattered individual bioparticles. This allows us go beyond the traditional crystallography single-particle imaging approaches for structure investigations. employ angular recover three-dimensional (3D) of nanoscale viruses diffraction data measured at Linac Coherent Light Source. Correlations provide with a comprehensive structural fingerprint 3D virus, which we both...
This article describes a free and open-source data analysis utility designed for fast online feedback during serial X-ray diffraction scattering experiments: OnDA (online analysis). Three complete real-time monitors common types of imaging experiments are presented. These capable providing the essential information required quick decision making in face extreme rates collection. In addition, set modules, functions algorithms that allow developers to modify provided or develop new ones...
MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed the TIR domain of (MAL
Single-particle experiments using X-ray Free Electron Lasers produce more than 10(5) snapshots per hour, consisting of an admixture blank shots (no particle intercepted), and exposures one or particles. Experimental data sets also often contain unintentional contamination with different species. We present unsupervised method able to sort experimental without recourse templates, specific noise models, user-directed learning. The results show 90% agreement manual classification.
The analysis of a single-particle imaging (SPI) experiment performed at the AMO beamline LCLS as part SPI initiative is presented here. A workflow for three-dimensional virus reconstruction PR772 bacteriophage from measured data developed. It consists several well defined steps including single-hit diffraction classification, refined filtering classified data, scattered intensity experimental patterns by orientation determination and final electron density without symmetry constraints....
Abstract Single particle diffractive imaging data from Rice Dwarf Virus (RDV) were recorded using the Coherent X-ray Imaging (CXI) instrument at Linac Light Source (LCLS). RDV was chosen as it is a well-characterized model system, useful for proof-of-principle experiments, system optimization and algorithm development. RDV, an icosahedral virus of about 70 nm in diameter, aerosolized injected into approximately 0.1 μm diameter focused hard beam CXI LCLS. Diffraction patterns with signal to...
Psana ( Photon Science Analysis ) is a software package that used to analyze data produced by the Linac Coherent Light Source X-ray free-electron laser at SLAC National Accelerator Laboratory. The project began in 2011, written primarily C++ with some Python, and provides user interfaces both Python. Most users use Python interface. same code can be run real time while are being taken as well offline, executing on many nodes/cores using MPI for parallelization. It publicly available...
Abstract Single-particle diffraction from X-ray Free Electron Lasers offers the potential for molecular structure determination without need crystallization. In an effort to further develop technique, we present a dataset of coherent soft images Coliphage PR772 virus, collected at Atomic Molecular Optics (AMO) beamline with pnCCD detectors in LAMP instrument Linac Coherent Light Source. The diameter ranges 65–70 nm, which is considerably smaller than previously reported ~600 nm Mimivirus....
Cytochrome c oxidase (CcO) is an essential enzyme in mitochondrial and bacterial respiration. It catalyzes the four-electron reduction of molecular oxygen to water harnesses chemical energy translocate four protons across biological membranes. The turnover CcO reaction involves oxidative phase, which reduced (R) oxidized metastable O
The advent of newer, brighter, and more coherent X-ray sources, such as Free-Electron Lasers (XFELs), represents a tremendous growth in the potential to apply X-rays determine structure materials from micron-scale down Angstrom-scale. There is significant need for multi-physics simulation framework perform source-to-detector simulations single particle imaging experiment, including (i) multidimensional source; (ii) wave-optics propagation XFEL beams; (iii) atomistic modelling photon-material...
The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for includes: (1) designing a vaccine future protection; (2) de novo drug discovery; (3) identifying existing drugs repurpose them immediate treatments. To assist repurposing design, we determine two apo structures severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial...
We show that the symmetries of image formation by scattering enable graph-theoretic manifold-embedding techniques to extract structural and timing information from simulated experimental snapshots at extremely low signal. The approach constitutes a physically-based, computationally efficient, noise-robust route analyzing large varied datasets generated existing emerging methods for studying structure dynamics scattering. demonstrate three-dimensional recovery X-ray diffraction cryo-electron...
Abstract Structural information about biological macromolecules near the atomic scale provides important insight into functions of these molecules. To date, X-ray crystallography has been predominant method used for macromolecular structure determination. However, challenges exist when solving structures with X-rays, including phase problem and radiation damage. X-ray-free electron lasers (X-ray FELs) have enabled collection diffraction before onset damage, yet majority solved at FELs phased...
Single-particle imaging with X-ray free-electron lasers (XFELs) has the potential to provide structural information at atomic resolution for non-crystalline biomolecules. This exists because ultra-short intense pulses can produce interpretable diffraction data notwithstanding radiation damage. paper explores impact of pulse duration on interpretability using comprehensive and realistic simulations an experiment European Free-Electron Laser. It is found that optimal molecules a few thousand...
The Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS) is seventh and newest world's first hard X-ray free-electron laser. It was designed with a primary focus on structural biology, employing ultrafast pulses of X-rays from LCLS atmospheric conditions to overcome radiation damage limitations in biological measurements. also capable performing various time-resolved MFX design consists versatile base system supporting multiple methods,...
An outstanding question in X-ray single particle imaging experiments has been the feasibility of sub 10-nm-sized biomolecules under realistic experimental conditions where very few photons are expected to be measured a snapshot and instrument background may significant relative scattering. While analyses simulated data have shown that determination an average image should feasible using Bayesian methods such as EMC algorithm, this yet demonstrated containing non-isotropic background, sample...
Using X-ray free-electron lasers (XFELs), it is possible to determine three-dimensional structures of nanoscale particles using single-particle imaging methods. Classification algorithms are needed sort out the diffraction patterns from large amount XFEL experimental data. However, different methods often yield inconsistent results. This study compared performance three classification algorithms: convolutional neural network, graph cut and diffusion map manifold embedding The identified data...
Abstract Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5’-monophosphate dehydrogenase (IMPDH) has been proposed as potential drug target, since it maintains balance between guanylate deoxynucleotide and ribonucleotide levels that pivotal for parasite. Here we report structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution reveals presence ATP GMP...
Abstract The data systems for X-ray free-electron laser (FEL) experiments at the Linac coherent light source (LCLS) are described. These designed to acquire and reliably transport shot-by-shot a peak throughput of 5 GB/s offline storage where experimental relevant metadata archived made available user analysis. analysis monitoring implementation (AMI) Photon Science ANAlysis (psana) software packages Psana is open freely available.