Effects of radiation damage and inelastic scattering on single-particle imaging of hydrated proteins with an X-ray Free-Electron Laser

We present a computational case study of X-ray single-particle imaging of hydrated proteins on an example of 2-Nitrogenase–Iron protein covered with water layers of various thickness, using a start-to-end simulation platform and experimental parameters of the SPB/SFX instrument at the European X-ray Free-Electron Laser facility. The simulations identify an optimal thickness of the water layer at which the effective resolution for imaging the hydrated sample becomes significantly higher than for the non-hydrated sample. This effect is lost when the water layer becomes too thick. Even though the detailed results presented pertain to the specific sample studied, the trends which we identify should also hold in a general case. We expect these findings will guide future single-particle imaging experiments using hydrated proteins

VINYL: The VIrtual Neutron and x-raY Laboratory and its applications

Experiments conducted in large scientific research infrastructures, such as synchrotrons, free electron lasers and neutron sources become increasingly complex. Such experiments, often investigating complex physical systems, are usually performed under strict time limitations and may depend critically on experimental parameters. To prepare and analyze these complex experiments, a virtual laboratory which provides start-to-end simulation tools can help experimenters predict experimental results under real or close to real instrument conditions. As a part of the PaNOSC (Photon and Neutron Open Science Cloud) project, the VIrtual Neutron and x-raY Laboratory (VINYL) is designed to be a cloud service framework to implement start-to-end simulations for those scientific facilities. In this paper, we present an introduction of the virtual laboratory framework and discuss its applications to the design and optimization of experiment setups as well as the estimation of experimental artifacts in an X-ray experiment

Expected resolution limits of x-ray free-electron laser single-particle imaging for realistic source and detector properties

The unprecedented intensity of x-ray free-electron laser sources has enabled single-particle x-ray diffraction imaging (SPI) of various biological specimens in both two-dimensional projection and three dimensions (3D). The potential of studying protein dynamics in their native conditions, without crystallization or chemical staining, has encouraged researchers to aim for increasingly higher resolutions with this technique. The currently achievable resolution of SPI is limited to the sub-10 nanometer range, mainly due to background effects, such as instrumental noise and parasitic scattering from the carrier gas used for sample delivery. Recent theoretical studies have quantified the effects of x-ray pulse parameters, as well as the required number of diffraction patterns to achieve a certain resolution, in a 3D reconstruction, although the effects of detector noise and the random particle orientation in each diffraction snapshot were not taken into account. In this work, we show these shortcomings and address limitations on achievable image resolution imposed by the adaptive gain integrating pixel detector noise

Reproducible Science with Jupyter

The Jupyter notebook format enables seamless coexistence of computer program code, documentation, and execution, as well as interactive visualization and discussion of results in one document and provides a user-friendly work environment. We will give an overview of the Jupyter ecosystem of tools and services and discuss how Jupyter enhances reproducibility in data intensive research

Effects of multistrain Bifidobacteria and Lactobacillus probiotics on HMO compositions after supplementation to pregnant women at threatening preterm delivery: design of the randomized clinical PROMO trial

Abstract Background As an indigestible component of human breast milk, Human Milk Oligosaccharides (HMOs) play an important role as a substrate for the establishing microbiome of the newborn. They have further been shown to have beneficial effects on the immune system, lung and brain development. For preterm infants HMO composition of human breast milk may be of particular relevance since the establishment of a healthy microbiome is challenged by multiple disruptive factors associated with preterm birth, such as cesarean section, hospital environment and perinatal antibiotic exposure. In a previous study it has been proposed that maternal probiotic supplementation during late stages of pregnancy may change the HMO composition in human milk. However, there is currently no study on pregnancies which are threatened to preterm birth. Furthermore, HMO composition has not been investigated in association with clinically relevant outcomes of vulnerable infants including inflammation-mediated diseases such as sepsis, necrotizing enterocolitis (NEC) or chronic lung disease. Main body A randomized controlled intervention study (PROMO = probiotics for human milk oligosaccharides) has been designed to analyze changes in HMO composition of human breast milk after supplementation of probiotics (Lactobacillus acidophilus, Bifidobacterium lactis and Bifidobacterium infantis) in pregnancies at risk for preterm birth. The primary endpoint is HMO composition of 3-fucosyllactose and 3’-sialyllactose in expressed breast milk. We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. As secondary outcomes we will measure preterm infants’ clinical outcomes (preterm birth, sepsis, weight gain growth, gastrointestinal complications) and effects on microbiome composition in the rectovaginal tract of mothers at delivery and in the gut of term and preterm infants by sequencing at high genomic resolution. Therefore, we will longitudinally collect bio samples in the first 4 weeks after birth as well as in follow-up investigations at 3 months, one year, and five years of age. Conclusions We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. The PROMO study will gain insight into the microbiome-HMO interaction at the fetomaternal interface and its consequences for duration of pregnancy and outcome of infants

Start-to-end simulation of single-particle imaging using ultra-short pulses at the European X-ray Free-Electron Laser

10.1107/S2052252517009496IUCrJ4560-56

Simulations of ultrafast x–ray laser experiments

Simulations of experiments at modern light sources, such as optical laser laboratories, synchrotrons, and free electron lasers, become increasingly important for the successful preparation, execution, and analysis of these experiments investigating ever more complex physical systems, e.g. biomolecules, complex materials, and ultra–short lived states of matter at extreme conditions. We have implemented a platform for complete start–to–end simulations of various types of photon science experiments, tracking the radiation from the source through the beam transport optics to the sample or target under investigation, its interaction with and scattering from the sample, and registration in a photon detector. This tool allows researchers and facility operators to simulate their experiments and instruments under real life conditions, identify promising and unattainable regions of the parameter space and ultimately make better use of valuable beamtime. In this paper, we present an overview about status and future development of the simulation platform and discuss three applications: 1.) Single–particle imaging of biomolecules using x–ray free electron lasers and optimization of x–ray pulse properties, 2.) x–ray scattering diagnostics of hot dense plasmas in high power laser–matter interaction and identification of plasma instabilities, and 3.) x–ray absorption spectroscopy in warm dense matter created by high energy laser–matter interaction and pulse shape optimization for low–isentrope dynamic compression