Neutron dose coefficients for the lens of the eye.

The International Commission on Radiation Units and Measurements (ICRU) Report Number 95 (2020 Operational quantities for external radiation exposureICRU Rep. 95 J. ICRU20) recommends new definitions ffor operational quantities as estimators of the International Commission on Radiological Protection radiation protection quantities. As part of this report, dose coefficients for neutron fluences are included for energies from 10-9-50 MeV. For lens of the eye dosimetry, several changes in the ICRU recommended quantities are of particular interest. First, an updated eye model is used that includes segmentation of the sensitive lens region. In addition, the use of absorbed dose instead of dose equivalent has been selected as the appropriate operational quantity since deterministic (i.e. non-stochastic) effects are of primary importance for the lens of the eye. The ICRU report also addresses computational parameters, such as absorbed dose tally volumes, depths, source areas and source rotational angles. In this work, neutron dose coefficients calculated for the lens of the eye in support of the ICRU report are presented. Dose coefficients for mono-energetic neutrons and reference neutron spectra are presented. The source is a parallel beam, and the mono-energetic dose coefficients are provided for rotational angles with respect to the front face of the head ranging from 0°-90°. In addition, monoenergetic dose coefficients for the parallel beam incident on the back of the head (180°) and for a rotational source geometry where the head is irradiated from all angles are reported. For all scenarios, absorbed doses to the complete lens and the sensitive volume of each eye were calculated. Eye lens absorbed dose coefficients,Dp,slab(3,0)/Φ, were also calculated in an ICRU tissue slab phantom at a depth of 3 mm for a parallel beam irradiating the slab perpendicular to the front face, and these results are compared to the values determined using the eye phantom.

A biokinetic model for trivalent or hexavalent chromium in adult humans.

Chromium exists in several oxidation states, with the trivalent state (Cr(III)) being the dominant naturally occurring form. Chromium in other oxidation states tends to be converted to the trivalent oxide in the natural environment and in biological systems. Chromium(III) has been shown to be an essential nutrient for humans and several non-human species. Chromium(VI), the second most stable form of chromium, is an important environmental contaminant that is mostly of industrial origin and is associated with lung cancer and nose tumours in chromium workers. This paper proposes a biokinetic model for chromium that addresses the distinctive behaviours of Cr(III) and Cr(VI) following uptake to blood of an adult human. The model is based on biokinetic data derived from relatively short-term studies involving administration of chromium tracers to adult human subjects or laboratory animals, supplemented with data on the long-term distribution of chromium in adult humans as estimated from autopsy measurements. The model is part of a comprehensive update of biokinetic models of the International Commission on Radiological Protection, used to project or evaluate radiation doses from occupational intake of radionuclides.

Neutron dose coefficients for local skin.

A draft report by the International Commission on Radiation Units and Measurements (ICRU) Report Committee 26 (RC26) will recommend alternative definitions of the operational quantities that are better estimators of radiation protection quantities. Dose coefficients for use with physical field quantities-fluence and, for photons, air kerma-are given for various particle types over a broad energy range. For the skin dosimetry, several changes are of particular interest. Specifically, the use of absorbed dose instead of dose equivalent has been selected as the operational quantity since deterministic effects are of primary interest in the skin. In addition, newly recommended phantoms are specified for computing the operational dose coefficients. The report also addresses computational approaches such as tally volumes, depths, source areas, and rotational angles. In this work, dose coefficients calculated for local skin in support of the ICRU report are presented. Energy-dependent dose coefficients were calculated in phantoms specified for the trunk (slab), the ankle or wrist (pillar), and the finger (rod). The phantom specifications in this work were taken directly from the draft report. Full transport of secondary charged particles from neutron interactions was performed and an analysis of the depth-dose profiles in the slab phantom is presented, The last complete set of neutron dose coefficients for the extremities was published more than 25 years ago. Given the limited data available, it is difficult for many facilities to obtain clear guidance on how monitoring should be performed and how dosimeters should be calibrated so spectra from commonly encountered neutron sources were used to generate source-specific dose coefficients in each of the phantoms. Both energy-dependent and source-specific dose coefficients are provided for rotational angles up to 180 degrees for the rod and pillar phantoms and up to 75 degrees for the slab phantom.

Organ and effective dose rate coefficients for submersion exposure in occupational settings.

External dose coefficients for environmental exposure scenarios are often computed using assumption on infinite or semi-infinite radiation sources. For example, in the case of a person standing on contaminated ground, the source is assumed to be distributed at a given depth (or between various depths) and extending outwards to an essentially infinite distance. In the case of exposure to contaminated air, the person is modeled as standing within a cloud of infinite, or semi-infinite, source distribution. However, these scenarios do not mimic common workplace environments where scatter off walls and ceilings may significantly alter the energy spectrum and dose coefficients. In this paper, dose rate coefficients were calculated using the International Commission on Radiological Protection (ICRP) reference voxel phantoms positioned in rooms of three sizes representing an office, laboratory, and warehouse. For each room size calculations using the reference phantoms were performed for photons, electrons, and positrons as the source particles to derive mono-energetic dose rate coefficients. Since the voxel phantoms lack the resolution to perform dose calculations at the sensitive depth for the skin, a mathematical phantom was developed and calculations were performed in each room size with the three source particle types. Coefficients for the noble gas radionuclides of ICRP Publication 107 (e.g., Ne, Ar, Kr, Xe, and Rn) were generated by folding the corresponding photon, electron, and positron emissions over the mono-energetic dose rate coefficients. Results indicate that the smaller room sizes have a significant impact on the dose rate per unit air concentration compared to the semi-infinite cloud case. For example, for Kr-85 the warehouse dose rate coefficient is 7% higher than the office dose rate coefficient while it is 71% higher for Xe-133.

External dose reconstruction for the former village of Metlino (Techa River, Russia) based on environmental surveys, luminescence measurements, and radiation transport modelling.

In the first years of its operation, the Mayak Production Association, a facility part of the Soviet nuclear weapons program in the Southern Urals, Russia, discharged large amounts of radioactively contaminated effluent into the nearby Techa River, thus exposing the people living at this river to external and internal radiations. The Techa River Cohort is a cohort intensely studied in epidemiology to investigate the correlation between low-dose radiation and health effects on humans. For the individuals in the cohort, the Techa River Dosimetry System describes the accumulated dose in human organs and tissues. In particular, organ doses from external exposure are derived from estimates of dose rate in air on the Techa River banks which were estimated from measurements and Monte Carlo modelling. Individual doses are calculated in accordance with historical records of individuals' residence histories, observational data of typical lifestyles for different age groups, and age-dependent conversion factors from air kerma to organ dose. The work here describes an experimentally independent assessment of the key input parameter of the dosimetry system, the integral air kerma, for the former village of Metlino, upper Techa River region. The aim of this work was thus to validate the Techa River Dosimetry System for the location of Metlino in an independent approach. Dose reconstruction based on dose measurements in bricks from a church tower and Monte Carlo calculations was used to model the historic air kerma accumulated in the time from 1949 to 1956 at the shoreline of the Techa River in Metlino. Main issues are caused by a change in the landscape after the evacuation of the village in 1956. Based on measurements and published information and data, two separate models for the historic pre-evacuation geometry and for the current geometry of Metlino were created. Using both models, a value for the air kerma was reconstructed, which agrees with that obtained in the Techa River Dosimetry System within a factor of two.

Effective dose rate coefficients for exposure to contaminated soil.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose rate calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. The coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.

[Pest control in your garden - a case series of severe hand injuries caused by privately used explosives and shot traps]. / Schädlingsbekämpfung im eigenen Garten - Fallserie schwerer Handverletzungen durch Spreng- und Schussfallen in privatem Gebrauch.

Booby traps and gun-like devices for vole control can lead to complex trauma requiring emergency medical care. We present a case series of patients who suffered severe hand and facial trauma through detonation of booby traps and paraphernalia (n = 9, Ø 60 years of age). All patients were admitted to the emergency department of Hannover Medical School for primary care. Between 2011 and 2015 we treated six patients with hand trauma due to gun-like devices, two patients with hand trauma due to booby traps, and one patient with injury to the face including eyes due to a gas cartridge explosion. All hand trauma patients (n = 8) showed injuries of the soft tissue. Six of these patients also presented fractures or lesions of capsular or tendon structures. Therapies included debridement as well as skin grafts or flaps for tissue defect coverage. We informed the Department for Commercial Safety (Gewerbeaufsicht Hannover) in 2014 because we believe that these traps pose a serious safety hazard.

Luminescence dosimetry for evaluation of the external exposure in Metlino, upper Techa River valley, Southern Urals, Russia: Analysis of new results.

Luminescence dosimetry was applied in the former settlement of Metlino, Southern Urals, Russia as part of a full-scale study to validate the Techa River Dosimetry System (TRDS) 2016 for the upper Techa River region. The village, which was evacuated in 1956, was located 7 km downstream of the release point of liquid radioactive waste by the Mayak plutonium facility. Several brick samples were taken from north-eastern and south-eastern walls of the granary, facing the former Techa river shoreline and floodplain. Samples were all taken at the same height and measured at different depths into the brick. For the majority of brick samples, good Optically Stimulated Luminescence properties of the quartz grains were observed. In some cases, however, strong levels of sensitization and/or signal recuperation were encountered which necessitated adjustment in the measurement protocols. Anthropogenic doses in bricks varied from 1.5 to 6.6 Gy and the horizontal profiles along both walls showed significant variation, which is explained on a qualitative basis. A dose depth profile is observed for selected samples, which is different from the dose depth profile measured and simulated for samples from the north-western wall of the granary in previous studies. This is qualitatively explained by the differences in source configuration.

Bayesian optimization to estimate hyperfine couplings from 19F ENDOR spectra.

ENDOR spectroscopy is a fundamental method to detect nuclear spins in the vicinity of paramagnetic centers and their mutual hyperfine interaction. Recently, site-selective introduction of 19F as nuclear labels has been proposed as a tool for ENDOR-based distance determination in biomolecules, complementing pulsed dipolar spectroscopy in the range of angstrom to nanometer. Nevertheless, one main challenge of ENDOR still consists of its spectral analysis, which is aggravated by a large parameter space and broad resonances from hyperfine interactions. Additionally, at high EPR frequencies and fields (⩾94 GHz/3.4 Tesla), chemical shift anisotropy might contribute to broadening and asymmetry in the spectra. Here, we use two nitroxide-fluorine model systems to examine a statistical approach to finding the best parameter fit to experimental 263 GHz 19F ENDOR spectra. We propose Bayesian optimization for a rapid, global parameter search with little prior knowledge, followed by a refinement by more standard gradient-based fitting procedures. Indeed, the latter suffer from finding local rather than global minima of a suitably defined loss function. Using a new and accelerated simulation procedure, results for the semi-rigid nitroxide-fluorine two and three spin systems lead to physically reasonable solutions, if minima of similar loss can be distinguished by DFT predictions. The approach also delivers the stochastic error of the obtained parameter estimates. Future developments and perspectives are discussed.

Nitroxide Derivatives for Dynamic Nuclear Polarization in Liquids: The Role of Rotational Diffusion.

Polarization transfer efficiency in liquid-state dynamic nuclear polarization (DNP) depends on the interaction between polarizing agents (PAs) and target nuclei modulated by molecular motions. We show how translational and rotational diffusion differently affect the DNP efficiency. These contributions were disentangled by measuring 1H-DNP enhancements of toluene and chloroform doped with nitroxide derivatives at 0.34 T as a function of either the temperature or the size of the PA. The results were employed to analyze 13C-DNP data at higher fields, where the polarization transfer is also driven by the Fermi contact interaction. In this case, bulky nitroxide PAs perform better than the small TEMPONE radical due to structural fluctuations of the ring conformation. These findings will help in designing PAs with features specifically optimized for liquid-state DNP at various magnetic fields.

Luminescence dosimetry for evaluation of the external exposure in Metlino, upper Techa River valley, due to the shore of the Metlinsky Pond: A feasibility study.

Luminescence dosimetry was performed using bricks from the former settlement of Metlino, Southern Urals, Russia, to investigate the feasibility of validating the Techa River Dosimetry System (TRDS) 2016 for the shore of the Metlinsky Pond, upper Techa River region. TRDS is a code for estimating external and internal doses for members of the Extended Techa River Cohort. Several brick samples were taken from the north-western wall of the granary, facing the Metlinsky Pond. Samples were measured at different heights and at different depths into the bricks. Dating of the granary was performed by analyzing well shielded bricks. Assessment of the gamma dose-rate at the sample positions was done by thermoluminescent dosimeters and the dose-rate in front of the granary mapped with a dose-rate meter. Anthropogenic doses in bricks vary from 0.8 to 1.7 Gy and show an increase with sampling height. A similar height profile is observed for the current gamma dose-rate, which is compatible with the results of the dose-rate mapping. Implications for validating the TRDS are discussed.

Separate domains of KAR1 mediate distinct functions in mitosis and nuclear fusion.

The yeast KAR1 gene is essential for mitotic growth and important for nuclear fusion. Mutations in KAR1 prevent duplication of the spindle pole body (SPB), and affect functions associated with both the nuclear and cytoplasmic microtubules. The localization of hybrid Kar1-lacZ proteins, described elsewhere (Vallen, E. A., T. Y. Scherson, T. Roberts, K. van Zee, and M. D. Rose. 1992. Cell. In press), suggest that the protein is associated with the SPB. In this paper, we report a deletion analysis demonstrating that the mitotic and karyogamy functions of KAR1 are separate and independent, residing in discrete functional domains. One region, here shown to be essential for mitosis, coincided with a part of the protein that is both necessary and sufficient to target Karl-lacZ hybrid proteins to the SPB (Vallen, E. A., T. Y. Scherson, T. Roberts, K. van Zee, and M. D. Rose. 1992. Cell. In press). Complementation testing demonstrated that deletions in this interval did not affect nuclear fusion. A second region, required only for karyogamy, was necessary for the localization of a Kar3-lacZ hybrid protein to the SPB. These data suggest a model for the roles of Kar1p and Kar3p, a kinesin-like protein, in nuclear fusion. Finally, a third region of KAR1 was found to be important for both mitosis and karyogamy. This domain included the hydrophobic carboxy terminus and is sufficient to target a lacZ-Kar1 hybrid protein to the nuclear envelope (Vallen E. A., T. Y. Scherson, T. Roberts, K. van Zee, and M. D. Rose. 1992. Cell. In press). Altogether, the essential mitotic regions of KAR1 comprised 20% of the coding sequence. We propose a model for Kar1p in which the protein is composed of several protein-binding domains tethered to the nuclear envelope via its hydrophobic tail.

ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway.

Secretion of proteins is initiated by their uptake into the endoplasmic reticulum (ER), which possesses a proteolytic system able to degrade misfolded and nonassembled proteins. The ER degradation system was studied with yeast mutants defective in the breakdown of a mutated soluble vacuolar protein, carboxypeptidase yscY (CPY*). The ubiquitin-conjugating enzyme Ubc7p participated in the degradation process, which was mediated by the cytosolic 26S proteasome. It is likely that CPY* entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it was conjugated with ubiquitin and degraded.

Monte Carlo simulation of dose coefficients for a fish eye lens model exposed to monoenergetic electrons.

Vision is an important sense for the majority of the wildlife species, affecting their ability to find food and escape predation. Currently, no study on radiation induced cataract frequency on the fish eyes lens has been done. However, any thorough future study of this subject will require more accurate dose estimates for the fish eye lens than those currently available. For this purpose, the eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using the MCNPX Monte Carlo radiation transport code package. All results were validated against three different fish voxel models. The discrepancies between model results mainly originate from the different fish eye dimensions used in the different studies and in two of the cases the lack of a defined eye lens region. The dose conversion coefficients calculated in this work can be used to estimate the dose to the fish eye lens based on the activity concentration of the surrounding water. The model developed in this work has also demonstrated that the mathematical models still have several advantages over the voxel models.

ORGAN AND EFFECTIVE DOSE COEFFICIENTS FOR CRANIAL AND CAUDAL IRRADIATION GEOMETRIES: NEUTRONS.

Dose coefficients based on the recommendations of International Commission on Radiological Protection (ICRP) Publication 103 were reported in ICRP Publication 116, the revision of ICRP Publication 74 and ICRU Publication 57 for the six reference irradiation geometries: anterior-posterior, posterior-anterior, right and left lateral, rotational and isotropic. In this work, dose coefficients for neutron irradiation of the body with parallel beams directed upward from below the feet (caudal) and downward from above the head (cranial) using the ICRP 103 methodology were computed using the MCNP 6.1 radiation transport code. The dose coefficients were determined for neutrons ranging in energy from 10-9 MeV to 10 GeV. At energies below about 500 MeV, the cranial and caudal dose coefficients are less than those for the six reference geometries reported in ICRP Publication 116.

Reducing Statistical Uncertainties in Simulated Organ Doses of Phantoms Immersed in Water.

In this article, methods are addressed to reduce the computational time to compute organ-dose rate coefficients using Monte Carlo techniques. Several variance reduction techniques are compared including the reciprocity method, importance sampling, weight windows and the use of the ADVANTG software package. For low-energy photons, the runtime was reduced by a factor of 105 when using the reciprocity method for kerma computation for immersion of a phantom in contaminated water. This is particularly significant since impractically long simulation times are required to achieve reasonable statistical uncertainties in organ dose for low-energy photons in this source medium and geometry. Although the MCNP Monte Carlo code is used in this paper, the reciprocity technique can be used equally well with other Monte Carlo codes.

Effective Dose Rate Coefficients for Immersions in Radioactive Air and Water.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge (CRPK) has undertaken a number of calculations in support of a revision to the United States Environmental Protection Agency (US EPA) Federal Guidance Report on external exposure to radionuclides in air, water and soil (FGR 12). Age-specific mathematical phantom calculations were performed for the conditions of submersion in radioactive air and immersion in water. Dose rate coefficients were calculated for discrete photon and electron energies and folded with emissions from 1252 radionuclides using ICRP Publication 107 decay data to determine equivalent and effective dose rate coefficients. The coefficients calculated in this work compare favorably to those reported in FGR12 as well as by other authors that employed voxel phantoms for similar exposure scenarios.

Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne.

Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients.

COMPARISON OF MONOENERGETIC PHOTON ORGAN DOSE RATE COEFFICIENTS FOR STYLIZED AND VOXEL PHANTOMS SUBMERGED IN AIR.

As part of a broader effort to calculate effective dose rate coefficients for external exposure to photons and electrons emitted by radionuclides distributed in air, soil or water, age-specific stylized phantoms have been employed to determine dose coefficients relating dose rate to organs and tissues in the body. In this article, dose rate coefficients computed using the International Commission on Radiological Protection reference adult male voxel phantom are compared with values computed using the Oak Ridge National Laboratory adult male stylized phantom in an air submersion exposure geometry. Monte Carlo calculations for both phantoms were performed for monoenergetic source photons in the range of 30 keV to 5 MeV. These calculations largely result in differences under 10 % for photon energies above 50 keV, and it can be expected that both models show comparable results for the environmental sources of radionuclides.

vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.

We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants that inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B). A single nuclear mutation, designated cev1 for calcineurin essential for viability, is responsible for the CsA-FK506-sensitive phenotype. The peptidyl-prolyl cis-trans isomerases cyclophilin A and FKBP12, respectively, mediate CsA and FK506 toxicity in the cev1 mutant strain. We demonstrate that cev1 is an allele of the VPH6 gene and that vph6 mutant strains fail to assemble the vacuolar H(+)-ATPase (V-ATPase). The VPH6 gene was mapped on chromosome VIII and is predicted to encode a 181-amino acid (21 kD) protein with no identity to other known proteins. We find that calcineurin is essential for viability in many mutant strains with defects in V-ATPase function or vacuolar acidification. In addition, we find that calcineurin modulates extracellular acidification in response to glucose, which we propose occurs via calcineurin regulation of the plasma membrane H(+)-ATPase PMA1. Taken together, our findings suggest calcineurin plays a general role in the regulation of cation transport and homeostasis.