The FRagment Separator FRS at GSI is a versatile spectrometer and separator for experiments with relativistic in-flight separated short-lived exotic beams. One branch of the FRS is connected to the target hall where the bio-medical cave (Cave M) is located. Recently a joint activity between the experimental groups of the FRS and the biophysics at the GSI and Department of physics at LMU was started to perform biomedical experiments relevant for hadron therapy with positron emitting carbon and oxygen beams. This paper presents the new ion-optical mode and commissioning results of the FRS-Cave M branch where positron emitting O-ions were provided to the medical cave for the first time. An overall conversion efficiency of 2.9±0.2×10 O fragments per primary O ion accelerated in the synchrotron SIS18 was reached.

Proton interactions with O or C nuclei are frequent nuclear interaction leading to secondary radiation in tissues for space radiation and cancer therapy with protons or ion beams. The fragmentation of these ions by protons produces a large number of heavy ion (A>4) target or projectile fragments often with high ionization density. Here we develop an analytical model of energy dependent proton-O and proton-C cross sections for isotopic nuclei production. Using experimental data and a 2 order optical model an accurate formula for the absorption cross section from <10 MeV/u to >10 GeV/u is obtained. The energy dependence of the elemental and isotopic cross sections is modeled as multiplicities scaled to absorption cross section with average isotopic fractions estimated from experimental data. We show that this approach results in accurate analytic formulae for isotopic fragmentation cross sections over the full energy range in hadron therapy and space radiation protection studies.

The Lawrence Livermore National Laboratory - Center for Accelerator Mass Spectrometry (LLNL/CAMS) 1 MV AMS system was converted from a biomedical AMS instrument to a natural abundance C spectrometer. The system is equipped with a gas-accepting hybrid ion source capable of measuring both solid (graphite) and gaseous (CO) samples. Here we describe a series of experiments intended to establish and optimize CO measurement capabilities at natural abundance levels. A maximum instantaneous ionization efficiency of 8 % was achieved with 3 % CO in helium at a flow rate of approximately 220 μL/min (3.5 μg C/min). For modern materials (e.g., OX I) we measured an average of 240 ± 50 14C counts/μg C, equivalent to a total system efficiency of approximately 3 %. Experimental CO samples with FC values ranging from 0.20 to 1.05 measured as both graphite and directly as CO gas produced equivalent values with an average offset of < 2σ.

Light ion breakup cross sections are important for studies of cosmic ray interactions in the inter-stellar medium or radiation protection considerations of energy deposition in shielding and tissues. Abrasion cross sections for heavy ion reactions have been modeled using the Glauber model in the large mass limit or Eikonal form of the optical potential model. Here we formulate an abrasion model for He fragmentation on protons using the Glauber model avoiding the large mass limit and include a model for final state interactions. Calculations of energy dependent total, absorption, elastic and breakup cross sections for He into He or H with proton targets are shown to be in good agreement with experiments for energies from 100 to 100,000 MeV/u. The Glauber model for light nuclei with and without a large mass limit approximation is shown to be in fair agreement above 300 MeV/u, however important differences occur at lower energies.

The Lawrence Livermore National Laboratory - Center for Accelerator Mass Spectrometry compact 1 MV biomedical accelerator mass spectrometer was repurposed and optimized for the semi-automated radiocarbon measurement of natural abundance environmental samples. Substantial efforts were made to greatly improve instrument precision and develop semi-automation capabilities for unattended operation. Here we present results from 15 months of routine system operation and evaluate the system performance based on 30 sample wheels measured with directly comparable operating conditions over 7 months from August 2019 to March 2020. Unattended operation was enabled through software that tracks specific error conditions and can initiate a complete instrument shutdown when specific criteria were met. The average measurement precision was found to be 2.7 ± 0.7 ‰ based on repeated measurements of OX I standards. Accuracy was assessed with measurements of standard materials with known C-content, spanning 0.5 to 1.5 modern, and by comparison to split samples measured with the 10 MV FN AMS system. We also assessed sample size and age limitations using C-free materials, finding that we can routinely analyze samples as small as 300 μg C and less than 33000 years without the need for size-specific correction protocols.

Intense X-rays available at powerful synchrotron beamlines provide macromolecular crystallographers with an incomparable tool for investigating biological phenomena on an atomic scale. The resulting insights into the mechanism's underlying biological processes have played an essential role and shaped biomedical sciences during the last 30 years, considered the "golden age" of structural biology. In this review, we analyze selected aspects of the impact of synchrotron radiation on structural biology. Synchrotron beamlines have been used to determine over 70% of all macromolecular structures deposited into the Protein Data Bank (PDB). These structures were deposited by over 13,000 different research groups. Interestingly, despite the impressive advances in synchrotron technologies, the median resolution of macromolecular structures determined using synchrotrons has remained constant throughout the last 30 years, at about 2 Å. Similarly, the median times from the data collection to the deposition and release have not changed significantly. We describe challenges to reproducibility related to recording all relevant data and metadata during the synchrotron experiments, including diffraction images. Finally, we discuss some of the recent opinions suggesting a diminishing importance of X-ray crystallography due to impressive advances in Cryo-EM and theoretical modeling. We believe that synchrotrons of the future will increasingly evolve towards a life science center model, where X-ray crystallography, Cryo-EM, and other experimental and computational resources and knowledge are encompassed within a versatile research facility. The recent response of crystallographers to the COVID-19 pandemic suggests that X-ray crystallography conducted at synchrotron beamlines will continue to play an essential role in structural biology and drug discovery for years to come.

Vitamin B12 deficiency and depletion are common world-wide, particularly in populations that consume low amounts of animal source foods. WHO and the Food Fortification Initiative recommend that wheat flour be fortified with vitamin B12 in regions where intake of B12 is low. The purpose of this pilot study in five participants was to determine if fortification of flour with B12 produced a bread product with intact B12 still present and to determine if healthy elderly absorb sufficient B12 from bread fortified in this manner. High-purity crystalline C-B12 was dissolved in water and added to flour (2 μg B12 /100 g flour) in a bread maker and made into rolls (average 1.17 kBq (31.5 nCi) C-B12 in a total of 0.8 µg B12 per roll). Excess C first appeared in plasma 4 h after ingestion of the C fortified bread and plasma levels returned almost to background by 72 h. Measurement of C in plasma verified that the dose was absorbed into the systemic circulation. The cumulative % dose recovered in urine was 4.8-37.0% (mean = 20.1%). Most of the C label in the stool appeared by day 4, and the cumulative % dose recovered in stool was 24.5- 43.0% (mean = 31.8%). Bioavailability among the 5 participants, calculated by subtracting the sum of urinary and fecal C excretion from the administered dose, was 28.4-63.7% (mean = 48.0%). This study showed that when B12 is added as a fortificant to flour it survives the fermentation and baking processes, and retains ~ 50% bioavailability when fed in small doses to healthy subjects. The Recommended Dietary Allowance of B12 for adults is 2.4 μg/d. This recommendation assumes that usual bioavailability of low doses of the vitamin in the crystalline form is 60%, while for the same amount in foods such as meat and fish it is 50%. Our pilot study shows that B12 added to bread as a fortificant in flour was absorbed as well as it is from endogenous food sources such as meat and fish.

Naphthalene (NA) is a respiratory toxicant and possible human carcinogen. NA is a ubiquitous combustion product and significant component of jet fuel. The National Toxicology Program found that NA forms tumors in two species, in rats (nose) and mice (lung). However, it has been argued that NA does not pose a cancer risk to humans because NA is bioactivated by cytochrome P450 monooxygenase enzymes that have very high efficiency in the lung tissue of rodents but low efficiency in the lung tissue of humans. It is thought that NA carcinogenesis in rodents is related to repeated cycles of lung epithelial injury and repair, an indirect mechanism. Repeated exposure to NA leads to development of tolerance, with the emergence of cells more resistant to NA insult. We tested the hypothesis that tolerance involves reduced susceptibility to the formation of NA-DNA adducts. NA-DNA adduct formation in tolerant mice was examined in individual, metabolically-active mouse airways exposed to 250 μΜ C-NA. dosing was used since it had been done previously and the act of creating a radioactive aerosol of a potential carcinogen posed too many safety and regulatory obstacles. Following extensive rinsing to remove unbound C-NA, DNA was extracted and C-NA-DNA adducts were quantified by AMS. The tolerant mice appeared to have slightly lower NA-DNA adduct levels than non-tolerant controls, but intra-group variations were large and the difference was statistically insignificant. It appears the tolerance may be more related to other mechanisms, such as NA-protein interactions in the airway, than DNA-adduct formation.

We report on the first several years of operation of our recently installed 250 kV SSAMS at LLNL, purchased to replace our 1-MV AMS system for the measurement of C from labeled biochemical samples. We have modified the ion source region to improve ion output. Additionally, the SSAMS required significant software modifications to the data acquisition system in order to accurately measure C at the high-count rates typically encountered with labeled biochemical samples. We found that the data can be corrected assuming a nonparalyzable dead time response with a single event dead time of 6 µs. Since operation began, we have measured over 13,000 graphitic unknowns and over 1900 standards with an overall precision of 1.0%. We have optimized our system for the analysis of CO2 gas samples. We compared aliquots of identical samples measured as solid graphite and as liquid drops. Excellent agreement was found between the two, although the average precision of the graphite targets was an order of magnitude better than the liquid drop analysis due to the much larger number of C atoms available for measurement.

Dichlorodifluoromethane (R-12) has been widely used as a radiator gas in pressure threshold Cherenkov detectors for high-energy particle physics. However, that compound is becoming unavailable due to the Montreal Protocol. To find a replacement with suitably high refractive index, we use a combination of theory and experiment to examine the polarizability and refractivity of several non-ozone-depleting compounds. Our measurements show that the fourth-generation refrigerants R-1234yf (2,3,3,3-tetrafluoropropene) and R-1234ze(E) (-1,3,3,3-tetrafluoropropene) have sufficient refractivity to replace R-12 in this application. If the slight flammability of these compounds is a problem, two nonflammable alternatives are R-218 (octafluoropropane), which has a high Global Warming Potential, and R-13I1 (trifluoroiodomethane), which has low Ozone Depletion Potential and Global Warming Potential but may not be sufficiently inert.

A program of comparing American (NASA) and Russian (ROSCOSMOS) space radiation transport codes has recently begun, and the first paper directly comparing the NASA and ROSCOSMOS space radiation transport codes, HZETRN and SHIELD respectively has recently appeared. The present work represents the second time that NASA and ROSCOSMOS calculations have been directly compared, and the focus here is on models of pion production cross sections used in the two transport codes mentioned above. It was found that these models are in overall moderate agreement with each other and with experimental data. Disagreements that were found are discussed.

Phasing of novel macromolecular crystal structures has been challenging since the start of structural biology. Making use of anomalous diffraction of natively present elements, such as sulfur and phosphorus, for phasing has been possible for some systems, but hindered by the necessity to access longer X-ray wavelengths in order to make most use of the anomalous scattering contributions of these elements. Presented here are the results from a first successful experimental phasing study of a macromolecular crystal structure at a wavelength close to the sulfur K edge. This has been made possible by the in-vacuum setup and the long-wavelength optimised experimental setup at the I23 beamline at Diamond Light Source. In these early commissioning experiments only standard data collection and processing procedures have been applied, in particular no dedicated absorption correction has been used. Nevertheless the success of the experiment demonstrates that the capability to extract phase information can be even further improved once data collection protocols and data processing have been optimised.

Fe, Cu, and Al stacked foils were irradiated by 90 MeV protons at the Los Alamos Neutron Science Center's Isotope Production Facility to measure nuclear cross sections for the production of medically relevant isotopes, such as Mn, Mn, Cr, Co, Co and Ni. The decay of radioactive isotopes produced during irradiation was monitored using high-purity germanium gamma spectroscopy over the months following irradiation. Proton fluence was determined using the Al(p,x)Na, Cu(p,x)Zn Cu(p,x)Zn, and Cu(p,x)Co monitor reactions. Calculated cross sections were compared against literature values and theoretical TALYS predictions. Notably this work includes the first reported independent cross section measurements of Cu(p,x)Co and Cu(p,x)Co.

A summary of results from the solid samples run on our compact 1 MV AMS system over its 13.5 years of operation is presented. On average 7065 samples per year were measured with that average dropping to 3278 samples per year following the deployment of our liquid sample capability. Although the dynamic range of our spectrometer is 4.5 orders in magnitude, most of the measured graphitic samples had C/C concentrations between 0.1 and 1 modern. The measurements of our ANU sucrose standard followed a Gaussian distribution with an average of 1.5082 ± 0.0134 modern. The LLNL biomedical AMS program supported many different types of experiments, however, the large majority of samples measured were derived from animal model systems. We have transitioned all of our biomedical AMS measurements to the recently installed 250 kV SSAMS instrument with good agreement compared in measured C/C isotopic ratios between sample splits. Finally, we present results from replacement of argon stripping gas with helium in the SSAMS with a 22% improvement in ion transmission through the accelerator and high-energy analyzing magnet.

We describe the moving wire interface attached to the 1-MV AMS system at LLNL's Center for Accelerator Mass Spectrometry for the analysis of nonvolatile liquid samples as either discrete drops or from the direct output of biochemical separatory instrumentation, such as high-performance liquid chromatography. Discrete samples containing at least a few 10s of nanograms of carbon and as little as 50 zmol C can be measured with a 3-5% precision in a few minutes. The dynamic range of our system spans approximately 3 orders in magnitude. Sample to sample memory is minimized by the use of fresh targets for each discrete sample or by minimizing the amount of carbon present in a peak generated by an HPLC containing a significant amount of C. Liquid Sample AMS provides a new technology to expand our biomedical AMS program by enabling the capability to measure low-level biochemicals in extremely small samples that would otherwise be inaccessible.

Trophallaxis between individual worker ants and the toxicant load in dead and live Argentine ants () in colonies exposed to fipronil and hydramethylnon experimental baits were examined using accelerator mass spectrometry (AMS). About 50% of the content of the crop containing trace levels of C-sucrose, C-hydramethylnon, and C-fipronil was shared between single donor and recipient ants. Dead workers and queens contained significantly more hydramethylnon (122.7 and 22.4 amol/μg ant, respectively) than did live workers and queens (96.3 and 10.4 amol/μg ant, respectively). Dead workers had significantly more fipronil (420.3 amol/μg ant) than did live workers (208.5 amol/μg ant), but dead and live queens had equal fipronil levels (59.5 and 54.3 amol/μg ant, respectively). The distribution of fipronil differed within the bodies of dead and live queens; the highest amounts of fipronil were recovered in the thorax of dead queens whereas live queens had the highest levels in the head. Resurgence of polygynous ant colonies treated with hydramethylnon baits may be explained by queen survival resulting from sublethal doses due to a slowing of trophallaxis throughout the colony. Bait strategies and dose levels for controlling insect pests need to be based on the specific toxicant properties and trophic strategies for targeting the entire colony.

Accelerator Mass Spectrometry (AMS) is the most sensitive method for quantitation of C in biological samples. This technology has been used in a variety of low dose, human health related studies over the last 20 years when very high sensitivity was needed. AMS helped pioneer these scientific methods, but its expensive facilities and requirements for highly trained technical staff have limited their proliferation. Quantification of C by cavity ring-down spectroscopy (CRDS) offers an approach that eliminates many of the shortcomings of an accelerator-based system and would supplement the use of AMS in biomedical research. Our initial prototype, using a non-ideal wavelength laser and under suboptimal experimental conditions, has a 3.5-modern, 1- precision for detection of milligram-sized, carbon-14-elevated samples. These results demonstrate proof of principle and provided a starting point for the development of a spectrometer capable of biologically relevant sensitivities.

For control of influenza, firstly it is important to find the real virus transmission media. Atmospheric aerosol particles are presumably one of the media. In this study, three typical atmospheric inhaled particles in Shanghai were studied by the synchrotron based transmission X-ray microscopes (TXM). Three dimensional microstructure of the particles reveals that there are many pores contained in, particularly the coal combustion fly particles which may be possible virus carrier. The particles can transport over long distance and cause long-range infections due to its light weight. We suggest a mode which is droplet combining with aerosol mode. By this mode the transmission of global and pandemic influenzas and infection between inland avian far from population and poultry or human living in cities along coast may be explained.

The effects of high cumulative radiation dose on the luminescence properties of KCl:Eu are investigated. Pellet samples of KCl:Eu were given doses of up to 200 kGy at the Louisiana State University Synchrotron facility. After synchrotron irradiation, samples were optically bleached and given a clinical dose of 2 Gy from a 6 MV medical linear accelerator. Optical properties were evaluated using photostimulated luminescence (PSL), photoluminescence (PL), and temperature-dependent PSL measurements. For a cumulated dose of up to 5-10 kGy, the PSL emission intensity increased by 15% compared to the PSL signal with no radiation history. For doses higher than 10 kGy, the PSL emission intensity retained at least 70% of the original intensity. Spatial correlation of the charge storage centers increased for doses up to 5 kGy and then decreased for higher cumulative doses. Emission band at 975 nm was attributed to transitions of Eu. PL spectra showed an intense peak centered at 420 nm for all cumulative doses. The results of this work show that KCl:Eu storage phosphors are excellent reusable materials for radiation therapy dosimetry.

The goal of this work is to understand the physical mechanism behind the signal stabilization process in KCl:Eu, a storage phosphor material that has generated renewed interest due to its potential in radiation therapy dosimetry application. The temperature dependency of the photostimulated luminescence (PSL) spectra and intensity vs. time post x ray irradiation was measured. Commercial BaFBr:Eu materials were included in this study for comparison. Unlike BaFBr:Eu, broadening of the F(Cl) stimulation band and red-shift of the peak were observed for KCl:Eu with increasing temperature. For irradiations at temperatures lower than 200 K, PSL intensity of KCl:Eu showed recuperation behavior in the first 2 hrs post-irradiation and stayed almost constant with time thereafter. Moreover, spatially-correlated storage centers increased from 24% for irradiation at 50 K to 31% at 195 K and almost 100% at room temperature. The data suggest that certain types of charge storage-centers were mobile and contribute to the fast fading in PSL.

Application of visible or infrared (IR) lasers for spectroscopy of highly-charged ions (HCI) has not been particularly extensive so far due to a mismatch in typical energies. We show here that the energy difference between the two lowest levels within the first excited configuration 3 4 in Ni-like ions of heavy elements from = 60 to = 92 is within the range of visible or near-IR lasers. The wavelengths of these transitions are calculated within the relativistic model potential formalism and compared with other theoretical and limited experimental data. Detailed collisional-radiative simulations of non-Maxwellian and thermal plasmas are performed showing that photopumping between these levels using relatively moderate lasers is sufficient to provide a two-order of magnitude increase of the pumped level population. This accordingly results in a similar rise of the X-ray line intensity thereby allowing control of X-ray emission with visible/IR lasers.