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The main goal of the radiation monitor RADEM flying onboard the ESA JUICE mission is to provide continuous information on particle fluxes and their energy spectra. The monitor measures electrons up to 40 MeV and protons up to 250 MeV. Such a range of energies detected by RADEM enables covering the most hazardous regimes in terms of radiation damage. Spectroscopic information on particle energies is provided using eight quasi-logarithmic energy bins. RADEM has also a dedicated heavy-ion detector designed to measure a variety of heavy ion species with their LET between 0.1 and 10 MeV/cm/mg-1. Moreover, the monitor contains an additional detector sensitive to the direction of incoming radiation. It expands the instrument's angular coverage up to 35% of the sky. Apart from its spectroscopic and angular distribution functions, RADEM will continuously provide values of the radiation dose deposited by each particle species. Its telemetry data will be stored in the data center for the JUICE mission operated by the European Space Astronomy Centre. After preprocessing the higher-level data will become available to the JUICE scientific team. RADEM will be switched on shortly after the JUICE launch planned for April 2023 and after a short commissioning phase will start its nominal operation. Apart from regular and short tuning and calibration periods, it will remain operating for the rest of the mission i.e. almost 10 years. While its primary purpose is to monitor the mission levels for safety concerns of the spacecraft and its scientific payload, its measurements open a unique opportunity for conducting real-time, continuous observations during its full cruise to Jupiter. RADEM will study all aspects of the radiation phenomena characteristic to the Earth and Solar System. Correlations with other instruments will allow for advanced observations of particle event propagation and a better understanding of processes related to the dynamics of particle environments including their links with solar activity and magnetic fields across the solar system. In particular, during its first two years of the cruise to Jupiter, RADEM will precisely map the radiation environment between Venus and Mars, providing uninterrupted time-resolved spectroscopy and dosimetry data from Solar Energetic Particles and Cosmic Rays.

Brachial vascular function after acute aerobic exercise in older adults with and without type 2 diabetes Purpose: The acute exercise model provides clinical insights regarding vascular dysfunction in adults with type 2 Diabetes Mellitus (T2DM), as it uncovers abnormalities not normally present at rest. However, whether vascular responses to acute exercise in adults with T2DM are intensity-dependent, and whether response patterns differ with aging and disease, remains unknown. Thus, we examined brachial artery flow-mediated dilation (FMD) and flow-mediated slowing (FMS) of pulse wave velocity (PWV), 10 and 60-min after an acute bout of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in middle-aged and older men with and without T2DM compared to young men without T2DM. Hypothesis: HIIE would induce a larger decrease in FMD immediately after exercise cessation compared to MICE in older men with and without T2DM. Methods: Twelve males with (57-84 yr) and without (57-76 yr) T2DM, and 12 healthy young adults (20-40 yr), completed an isocaloric acute exercise bout of HIIE, MICE, and a non-exercise condition in randomized order. FMD and FMS were evaluated and offline analyzed by the same researcher following standard guidelines. Central and peripheral arterial stiffness were measured via applanation tonometry estimates of carotid-femoral PWV (cfPWV) and carotid dorsalis pedis PWV (cdPWV), respectively. Statistical inferences were performed using linear mixed models. Results: %FMD was reduced (d= - 5.94, 95% CI: -10.50 to -1.38 %, p=0.002), whereas %FMS was increased (d= 4.55, 95% CI: 0.62 to 8.48%, p=0.01), 10-min after HIIE only in older adults with T2DM, returning to resting values 60-min into recovery. Conversely, %FMD was increased (d= 5.33, 95% CI: 0.76 to 9.89%, p=0.009) 10-min after MICE only in older adults with T2DM, while cfPWV and cdPWV remained unchanged following HIIE and MICE in all groups. There were no group differences at rest in brachial %FMD and %FMS, while cfPWV and cdPWV were higher in older adults with T2DM compared to age-matched controls (cfPWV: d= 1.94, 95% CI: 0.44 to 3.44 m. s-1, p=0.009). Conclusions: We found evidence of intensity- and disease-dependent vascular responses to acute aerobic exercise. These findings suggest that high-intensity acute exercise transiently impairs vascular function in older adults with T2DM, which may constitute an important trigger for exercise-based long-term improvements in vascular function. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: Proteins are biomolecules that consist of sequences of amino acids (primary structure) which can further interact and cause the backbone to fold into more complex arrangements (secondary and tertiary structures). Any chemical alterations of the molecules after the translation of the messenger RNA code into a protein primary sequence are known as posttranslational modifications (PTMs). PTMs may affect the protein’s functionality; thus it is necessary to identify them. PTMs of particular interest to the pharmaceutical industry include deamidation, oxidation, deglycosylation and isomerization, which may occur due to environmental stressors. However, they have proved challenging to identify quickly. Electronic and vibrational spectroscopies have proved valuable tools for studying higher-order structure and stability of proteins. Materials & Methods: In this work, circular dichroism (CD), infrared absorbance (IR) and Raman spectroscopies were applied to characterize antibody (mAb NIP 228) PTMs as a result of different stressors. Mass spectrometry was used to confirm the identity of modifications including the targeted ones. Room temperature CD showed that the secondary structure was the same after all treatments, and temperature-controlled CD showed how protein stability was affected by modifications. Both Raman and IR analysis detected small differences between the reference and deglycosylated proteins, and clearly indicated the presence of other PTMs. Conclusion: This work required some novel computational approaches to pre-process Raman and IR spectra and a review of the band assignments for proteins existing in the literature.

Owing to the favorable depth-dose distribution and the radiobiological properties of heavy ion radiation, ion beam therapy shows an improved success/toxicity ratio compared to conventional radiotherapy. The sharp dose gradients and very high doses in the Bragg peak region, which represent the larger physical advantage of ion beam therapy, make it also extremely sensitive to range uncertainties. The use of

BepiColombo is a joint mission of the European Space Agency (ESA) and the Japan Aerospace Exploration Agency (JAXA) to the planet Mercury. It was launched in October 2018 and it is due to arrive at Mercury in late 2025. It consists of two spacecraft, the Mercury Planetary Orbiter (MPO) built by ESA, and the Mercury Magnetospheric Orbiter (MMO) built by JAXA, as well as a Mercury Transfer Module (MTM) for propulsion built by ESA. The cruise phase to Mercury will last ~7 years and constitutes an exceptional opportunity for studying the evolution of the solar wind, solar transients, as well as for planetary science and planetary space weather. On this last topic, BepiColombo is proving to be an important upstream solar wind monitor for the terrestrial planets. This is especially important for case of Mars where we currently do not have many observations of the upstream interplanetary magnetic field or solar wind. As consequence, the analysis and interpretation of ionospheric observations is challenging, especially when coronal mass ejections and solar energetic particles hit Mars and we do not have Earth plasma observatories in good alignment with Mars to provide the space weather context. While Mars missions such as Mars Express or MAVEN are able to investigate the impact of the solar wind on the ionosphere, BepiColombo can be the solar wind sentinel for Mars, so we can see the cause and effect. Therefore, this work focuses on the response of the Martian ionosphere to solar transient events which have been previously detected by BepiColombo, and for which we can provide the right upstream solar wind context, such as during the last months of 2021. The objective is to evaluate the response of the Martian ionosphere and its dynamics with more accuracy knowing the exact energy inputs from the solar wind as detected in-situ in the solar wind by BepiColombo.

December 2019 marked the beginning of Solar Cycle 25. Since then, the Sun´s activity has been ramping up with multiple Coronal Mass Ejections (CMEs), Solar Flares, and Solar Energetic Particle (SEP) events having been registered in the past few years. These events are extremely hazardous to both spacecraft and biological systems. However, due to the lack of multi-point measurements, it is still impossible to predict their occurrence and to accurately model their propagation. BepiColombo, the first European mission to the Hermean System, was launched in 2018 and is predicted to enter Mercury’s orbit in 2025. It is composed of two spacecraft, ESA’s Mercury Planetary Orbiter (MPO) and JAXA’s Mercury Magnetospheric Orbiter (nicknamed Mio). Given the mission´s close proximity to the Sun, reaching 0.3 AU at multiple points of its trajectory, BepiColombo will provide critical measurements to characterize and model Solar Events. While BepiColombo carries a plethora of scientific instruments, most of them are turned-off during a large part of the cruise phase. However, the BepiColombo Environment Radiation Monitor (BERM) aboard the MPO, is always operational since it is part of the mission´s housekeeping, with the objetive of monitoring radiation hazards so they can be managed in order to prevent possible damage on the spacecraft and instruments. Being in operation during all phases of the mission allows it to detect and characterize SEP events, even when other instruments are switched off. BERM is based on standard silicon stack detectors. It consists of a single telescope stack with 11 Silicon detectors interleaved by aluminum and tantalum absorbers. It can detect electrons with energies from ~0.1 to ~10 MeV, protons with energies from ~1 MeV to ~200 MeV, and heavy ions with a Linear Energy Transfer from 1 to 50 MeV/mg/cm2. Particle species and energies are determined by the track and signal registered in the stack. Because of the limited bandwidth, particle events are processed in-flight before being sent to Earth. Particles are assigned to 18 channels, five are dedicated to electrons, eight to protons, and five to heavy ions. BERM provides daily files with the number of registered counts in each channel integrated over 30 seconds sampling intervals. To provide useful information for scientists, BERM data must be converted into physical units. This work presents the results of applying the bow-tie method, first introduced by Van Allen in 1979, to obtain the fluxes from BERM’s count rates. assuming a power law for the electron and proton spectra. The method considers energy spectra with a range of power-law indices and finds the effective energy measured by each channel and its corresponding geometric factor. We have used this method to analyze the data collected by BERM during the Earth flyby of BepiColombo. We apply the bow tie method to estimate the fluxes of particles during the already detected solar events. So far, two events are worthy of special attention. During the event on April 17th, 2021, BERM and the Solar Intensity X-ray and Particle Spectrometer (SIXS) instrument were simultaneously operating onboard BepiColombo. The particle detector of SIXS (SIXS-P) can measure electrons from approximately 50 keV to 3 MeV and protons from 1 to 30 MeV. The two instruments measure overlapping particle energy ranges, which allows for validating the results of bow tie analysis of BERM particle channels. The second event of interest happened on February 16th, 2022. It exhibited fluxes of such high energies that all 8 proton bins registered a signal above the noise levels strong enough to be analyzed. Results for other events will also be shown.

The BepiColombo Environment Radiation Monitor (BERM) on board the European Space Agency’s Mercury Planetary Orbiter (MPO), is designed to measure the radiation environment encountered by BepiColombo. The instrument measures electrons with energies from $\sim150~\text{keV}$ ∼ 150 keV to $\sim10~\text{MeV}$ ∼ 10 MeV , protons with energies from $\sim1.5~\text{MeV}$ ∼ 1.5 MeV to $\sim100~\text{MeV}$ ∼ 100 MeV , and heavy ions with Linear Energy Transfer from 1 to $50~\text{MeV}\cdot\text{mg}^{-1}\cdot\text{cm}^{2}$ 50 MeV ⋅ mg − 1 ⋅ cm 2 . BERM is operated continuously, being responsible for monitoring the radiation levels during all phases of the mission, including the cruise, the planetary flybys of Earth, Venus and Mercury, and the Hermean environment. In this paper, we describe the scientific objectives, instrument design and calibration, and the in-flight scientific performance of BERM. Moreover, we provide the first scientific results obtained by BERM during the BepiColombo flyby of Earth in April 2020, and after the impact of a solar energetic particle event during the cruise phase in May 2021. We also discuss the future plans of the instrument including synergies with other instruments on the BepiColombo and on other missions.

Introduction: The hygienic and sanitary conditions of vessels carrying passengers and cargo requires constant diagnosis and monitoring for disease prevention. Objective: The objective of this study was to identify health hazards in food preparation conditions and water potability in mixed vessels in the State of Amazonas-Brazil. Method: 33 vessels were analyzed with qualitative detection analysis of Escherichia coli by chromogenic substrate for water potability and environmental evaluation with questionnaire application. Results: There was microbiological contamination in 13 (39.39%) drinking water samples and 31 (93.93%) sink samples for E. coli. The structural and operational conditions of kitchen handlers mostly did not meet the minimum percentages of safety in food production. Conclusions: This is the first report on the structural and operational conditions of food preparation in mixed vessels in Manaus-AM and we conclude that intervention is necessary with public policies regarding hygienic and sanitary issues involving the supply of water served in vessels for the protection of passenger health and training of food handlers and inspection of environments.

Para caracterizar a resposta de um trecho do quebra-mar de taludes do porto da Ericeira à agitação marítima nele incidente, realizaram-se no canal de ondas irregulares do LNEC um conjunto de ensaios com um modelo reduzido desse mesmo trecho. Nesta comunicação descreve-se a instalação experimental, incluindo os diversos instrumentos utilizados para medir as séries temporais das várias grandezas de interesse e o programa de ensaios, apresentando-se as grandezas medidas num subconjunto dos ensaios considerado mais interessante. Nestas grandezas incluem-se a elevação da superfície livre associada à agitação incidente, o espraiamento ao longo do talude, o volume de água de água galgado, a pressão em vários pontos da superestrutura e a erosão do manto protetor utilizando um sensor cujo funcionamento se baseia na tecnologia Time of Flight. Palavras-chave: agitação marítima; espraiamento; galgamento; superestrutura; dano.

We compared response patterns of cardiovagal modulation through heart-rate variability (HRV) and baroreflex sensitivity (BRS) indices at 10 and 60 min after an acute bout of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in active young and older adults. Twelve young (aged 20–40 years) and older (aged 57–76 years) healthy and active male adults performed an isocaloric acute bout of HIIE, MICE, or a non-exercise condition in a randomized order. HRV and BRS indices were analyzed offline with R-R intervals obtained from a supine position. HIIE decreased natural logarithm (Ln) standard deviation of NN intervals (d=−0.53; 95% CI: −0.77 to −0.30 ms, p

Objective. CT-mesh hybrid phantoms (or ‘hybrid(s)’) made from integrated patient CT data and mesh-type reference computational phantoms (MRCPs) can be beneficial for patient-specific whole-body dose evaluation, but this benefit has yet to be evaluated for second cancer risk prediction. The purpose of this study is to compare the hybrid’s ability to predict risk throughout the body with a patient-scaled MRCP against ground truth whole-body CTs (WBCTs). Approach. Head and neck active scanning proton treatment plans were created for and simulated on seven hybrids and the corresponding scaled MRCPs and WBCTs. Equivalent dose throughout the body was calculated and input into five second cancer risk models for both excess absolute and excess relative risk (EAR and ERR). The hybrid phantom was evaluated by comparing equivalent dose and risk predictions against the WBCT. Main results. The hybrid most frequently provides whole-body second cancer risk predictions which are closer to the ground truth when compared to a scaled MRCP alone. The performance of the hybrid relative to the scaled MRCP was consistent across ERR, EAR, and all risk models. For all in-field organs, where the hybrid shares the WBCT anatomy, the hybrid was better than or equal to the scaled MRCP for both equivalent dose and risk prediction. For out-of-field organs across all patients, the hybrid’s equivalent dose prediction was superior than the scaled MRCP in 48% of all comparisons, equivalent for 34%, and inferior for 18%. For risk assessment in the same organs, the hybrid’s prediction was superior than the scaled MRCP in 51.8% of all comparisons, equivalent in 28.6%, and inferior in 19.6%. Significance. Whole-body risk predictions from the CT-mesh hybrid have shown to be more accurate than those from a reference phantom alone. These hybrids could aid in risk-optimized treatment planning and individual risk assessment to minimize second cancer incidence.

The detailed Martian Energetic Radiation Environment Model (dMEREM) is a Geant4 based model developed for the European Space Agency, which enables to predict the radiation environment expected at different locations on the Martian orbit, atmosphere and surface, as a function of epoch, latitude and longitude, taking into account the specific atmospheric and soil composition, based on different particle propagation codes for primary Galactic Cosmic Rays or Solar Particle Events. This work describes the validation of dMEREM with differential proton fluxes measured with the NASA Curiosity rover Radiation Assessment Detector (RAD) at the Gale Crater, at the surface of Mars, from 15 November 2015 to 15 January 2016 and in the beginning of September 2017, using two different Galactic Cosmic Ray (GCR) models, the ISO-15 390 and the Badhwar-O’Neill 2014 models. This work includes a comparative study of the available Geant4 physics lists in describing the RAD measured proton spectrum, and an investigation of the proton directional spectrum at the Martian surface, and on its effect on the comparisons between models and data, which are necessarily measured within a limited field-of-view. For both GCR models and data periods there was a good agreement between the proton fluxes in the energy range between 10 and 90 MeV measured at the surface of Mars with RAD and the corresponding dMEREM predictions. Therefore, although the RAD only measures a limited field-of-view in zenith angle of the Martian Particle Radiation Field, and this effect has to be taken into account, the results obtained constitute an important benchmark in the use of dMEREM in the assessment of the expected ionising radiation field on the surface of Mars.

Description, A local charged particle source in Jupiter’s inner radiation belts generates oxygen ions of cosmic ray energies., Jupiter hosts the most hazardous radiation belts of our solar system that, besides electrons and protons, trap an undetermined mix of heavy ions. The details of this mix are critical to resolve because they can reveal the role of Jupiter’s moons relative to other less explored energetic ion sources. Here, we show that with increasing energy and in the vicinity of Jupiter’s moon Amalthea, the belts’ ion composition transitions from sulfur- to oxygen-dominated due to a local source of ≳50 MeV/nucleon oxygen. Contrary to Earth’s and Saturn’s radiation belts, where their most energetic ions are supplied through atmospheric and ring interactions with externally accelerated cosmic rays, Jupiter’s magnetosphere powers this oxygen source internally. The underlying source mechanism, involving either Jovian ring spallation by magnetospheric sulfur or stochastic oxygen heating by low-frequency plasma waves, puts Jupiter’s ion radiation belt in the same league with that of astrophysical particle accelerators.

This paper presents a general framework for modeling dependence in multivariate time series. Its fundamental approach relies on decomposing each signal in a system into various frequency components and then studying the dependence properties through these oscillatory activities.The unifying theme across the paper is to explore the strength of dependence and possible lead-lag dynamics through filtering. The proposed framework is capable of representing both linear and non-linear dependencies that could occur instantaneously or after some delay(lagged dependence). Examples for studying dependence between oscillations are illustrated through multichannel electroencephalograms. These examples emphasized that some of the most prominent frequency domain measures such as coherence, partial coherence,and dual-frequency coherence can be derived as special cases under this general framework.This paper also introduces related approaches for modeling dependence through phase-amplitude coupling and causality of (one-sided) filtered signals.

In this paper, we present the results of a 6-year experiment in space that studied the effects of radiation in Gallium Nitride (GaN) electronics in geostationary orbit. Four GaN transistors in a Colpitts oscillator configuration were flown in the Component Technology Test-Bed aboard the Alphasat telecommunication satellite. A heuristic analysis was performed by observing the variation in the power output of the oscillators with the total ionizing dose gathered during the mission. The total ionizing dose was measured with a Radiation Sensing Field Effect Transistors (RadFET) placed close to the GaN devices. The experiment showed that GaN is a robust technology that can be used in the space radiation environment of a geostationary orbit. The work presented here starts with a brief introduction of the subject, the motivation, and the main goal. This is followed by the description of the experimental setup, including the details of the oscillator design and simulations, as well as the implementation of the test-bed and the Components Technology Test-Bed. Finally, the results obtained during the 6 years of experience in space are discussed.

Objective. As cancer survivorship increases, there is growing interest in minimizing the late effects of radiation therapy such as radiogenic second cancer, which may occur anywhere in the body. Assessing the risk of late effects requires knowledge of the dose distribution throughout the whole body, including regions far from the treatment field, beyond the typical anatomical extent of clinical computed tomography (CT) scans. Approach. A hybrid phantom was developed which consists of in-field patient CT images extracted from ground truth whole-body CT scans, out-of-field mesh phantoms scaled to basic patient measurements, and a blended transition region. Four of these hybrid phantoms were created, representing male and female patients receiving proton therapy treatment in pelvic and cranial sites. To assess the performance of the hybrid approach, we simulated treatments using the hybrid phantoms, the scaled and unscaled mesh phantoms, and the ground truth whole-body CTs. We calculated absorbed dose and equivalent dose in and outside of the treatment field, with a focus on neutrons induced in the patient by proton therapy. Proton and neutron dose was calculated using a general purpose Monte Carlo code. Main results. The hybrid phantom provided equal or superior accuracy in calculated organ dose and equivalent dose values relative to those obtained using the mesh phantoms in 78% in all selected organs and calculated dose quantities. Comparatively the default mesh and scaled mesh were equal or superior to the other phantoms in 21% and 28% of cases respectively. Significance. The proposed methodology for hybrid synthesis provides a tool for whole-body organ dose estimation for individual patients without requiring CT scans of their entire body. Such a capability would be useful for personalized assessment of late effects and risk-optimization of treatment plans.

Detailed radiation analysis of instruments flown in space is critical to ensure mission safety, often requiring the use of state-of-the-art particle transport simulation tools. Geant4 is one of the most powerful toolkits to simulate the interaction and the passage of particles through matter, but it is not prepared to receive Standard for The Exchange of Product data (STEP) files, the most versatile Computer-Aided Design (CAD) format, as input, requiring previous conversion to other CAD formats. This may lead to loss of detail and under or overestimation of the quantities under study, especially when the instruments have complex shapes, and/or a large number of volumes. Though several solutions have been proposed to import complex geometries from STEP files into Geant4, so far, only commercial options are available. In this paper we present a new tool, GUIMesh, that embeds FreeCAD libraries, an open-source CAD editor, to tessellate volumes, and convert them to Geometry Description Markup Language (GDML), a Geant4 readable format , in a straightforward way. Several degrees of freedom are given to the user regarding mesh precision and choice of material. Different geometries were tested for material definition, geometry and navigation errors, and the method used was successfully validated. Program Summary Program Title: GUIMesh Program Files doi: http://dx.doi.org/10.17632/c3c9xbspzp.1 Licensing provisions : GNU General Public License 3 (GPLv3) Programming language: Python Nature of problem: No open-source software allows to import STEP geometries intro Geant4, one of the most powerful toolkits to simulate radiation interaction with matter. Since CAD software is extensively used in the design of particle and radiation detection instruments, it is highly desirable for physicists that STEP geometries can be imported to Geant4 with little effort instead of having to code structures made of a very large number of solid volumes which are difficult to accurately reproduce with Geant4 C++ classes. Solution method : STEP geometries are converted to tessellated volumes (with some margin of error) using FreeCAD libraries. A Python script then writes GDML files based on the results allowing users to import these geometries with Geant4. A graphical user interface provides several options to the user, including material assignment and mesh precision setting for each volume.

Jupiter's radiation belts constitute a multi-component system, trapping high intensities of electrons, protons and heavier ions. We revisit measurements from Galileo's Heavy Ion Counter (HIC) instrument, a high-quality dataset that extends considerably the energy range covered by Galileo/EPD and Juno/JEDI (

The Space environment is known to be populated by highly energetic particles. These particles originate from three main sources: (1) Galactic Cosmic Rays (GCRs), a low flux of protons (90%), heavy ions, and to some extent electrons, with energies up to 1021 eV, arriving from outside of the Solar System; (2) Solar Energetic Particles (SEPs), sporadic and unpredictable bursts of electrons, protons, and heavy ions, travelling much faster than the Space plasma, accelerated in Solar Flares and Coronal Mass Ejections; and (3) planetary trapped particles, a dynamic population of protons and electrons trapped around planetary magnetospheres first discovered at Earth by Van Allen. Solar activity is responsible for transient and long-term variation of the radiation environment. During periods of low activity, the GCR flux increases as a result of the lower heliospheric modulation exerted on charged particle from outside the solar system and the probability of SEP events decreases; vice-versa, during high activity, GCR fluxes decrease, and the probability of SEP events increases. Extreme Solar Events also affect the Earth’s magnetosphere and the radiation belts which can lead to ground-level enhancements. These three components of radiation in space combine into a hazardous environment for both manned and unmanned missions and are responsible for several processes in planetary bodies. Therefore, it is important to monitor and comprehend the dynamics of energetic particles in space. BepiColombo is the first mission of the European Space Agency to the Hermean System. It was launched in 2018 and will enter Mercury’s orbit in 2025 with the first flyby to Mercury planned for 2021. It is composed of two Spacecraft, ESA’s Mercury Planetary Orbiter (MPO) and JAXA’s Mercury Magnetospheric Orbiter (MMO). Both Spacecraft carry a rich suite of scientific instruments to study the planet geology, exosphere, and magnetosphere. In particular, the MPO spacecraft carries the BepiColombo Radiation Monitor (BERM), which is capable of measuring electrons with energies from ~100 keV to ~10 MeV, protons with energies from 1 MeV to ~200 MeV, and heavy ions with a Linear Energy Transfer from 1 to 50 MeV/mg/cm2. While BERM is part of the mission housekeeping, it will provide valuable scientific data of the energetic particle population in interplanetary space and at Mercury. Because BERM is in operation during most of the cruise phase, it is able to detect and characterize SEP events. In fact, two events were already registered and will be included in a multi-spacecraft analysis. BERM is based on standard silicon stack detectors such as the SREM and the MFS. It consists of a single telescope stack with 11 Silicon detectors interleaved by aluminum and tantalum absorbers. Particle species and energies are determined by charged particle track signals registered in the Si stack. Because of the limited bandwidth, particle events are processed in-flight before being sent to Earth. Particles are then assigned to 18 channels, five corresponding to electrons, eight to protons, and five to heavy ions. In this work, we will present the response of the 18 detector channels obtained by comparing Geant4 simulations with the BERM beam calibration data. The response functions are validated using measurements made during of the BepiColombo Earth flyby and during the cruise phase. Special focus is given to the synergies between BERM and the Solar intensity X-ray and particle Spectrometer (SIXS) instrument signals. The latter measures electrons from ~50 keV to ~3 MeV and protons from ~1 to ~30 MeV. The availability of two instruments with overlapping energy ranges allows to validate and cross-calibrate their data, namely during Earth flyby at the radiation belts, and to maximize the scientific output of the mission. In fact, lessons learned during this joint analysis are expected to set the basis for a similar collaboration between the RADiation hard Electron Monitor (RADEM) and the Particle Environment Package (PEP) instruments aboard the future JUICE mission.

BepiColombo is a joint mission of the European Space Agency (ESA) and the Japan Aerospace Exploration Agency (JAXA) to the planet Mercury, that was launched in October 2018 and it is due to arrive at Mercury in late 2025. It consists of two spacecraft, the Mercury Planetary Orbiter (MPO) built by ESA, and the Mercury Magnetospheric Orbiter (MMO) built by JAXA, as well as a Mercury Transfer Module (MTM) for propulsion built by ESA. The cruise phase to Mercury will last ~7 years and constitutes an exceptional opportunity for studying the evolution of the solar wind, solar transients, as well as for planetary science and planetary space weather. Some important aspects to consider during the cruise are the close distances to the Sun that BepiColombo will face, the near half-solar activity cycle that will cover, as well as the several flybys to Earth, Venus and Mercury that will perform. So far, BepiColombo has accomplished a flyby to Earth in April 2020 and a flyby to Venus in October 2020, with a second flyby to Venus programmed for August 2021 and the first Mercury flyby in October 2021.This work focuses on the flyby to Earth, and in particular, on the radiation belt observations performed by several instruments onboard BepiColombo. The flyby occurred on 10 April 2020 under relatively steady solar wind conditions. BepiColombo crossed the outer radiation belt on the terrestrial dawn side when moving from the day side to the night side. It skimmed the inner radiation belt on the night side sector after dawn, and then crossed again the outer belt at night (behind the dusk terminator region). Two instruments onboard the MPO spacecraft were able to take measurements of the belts: the BepiColombo Radiation Monitor (BERM) and the Solar Intensity X-Ray and Particle Spectrometer (SIXS). In this work, we report the particle species, radiation and energies observed by these two instruments, as well as we perform a cross-calibration of their detections, which is an important activity in preparation for joint-observations of the Hermean environment. Moreover, using magnetic field observations from MPO-MAG, we also investigate the trajectory of the particles within the radiation belts. This work is complemented with data from other missions that give us the state of the terrestrial system and frame our observations into the right context. It includes data from Cluster-II, Themis, and Arase/ERG missions.

The characterisation of the Martian radiation environment is essential to understand if the planet can sustain life and ultimately if its human exploration is feasible. The major components of the radiation environment in the Mars orbit, are Galactic Cosmic Rays (GCRs) and Solar Energetic Particle (SEP) events. Since Mars has a negligible magnetic field and a much thinner atmosphere compared to the Earth’s, its surface is exposed to GCR and eventual SEP events, as well as to secondary particles produced in the atmosphere and in the shallow layers of the planet. The Curiosity rover that has been exploring the surface of Mars since August 2012, carries in its Mars Science Laboratory (MSL), the Radiation Assessment Detector (RAD) which measures high-energy radiation, such as protons, energetic ions of various elements, neutrons, and gamma rays. That includes not only direct radiation from space, but also secondary radiation produced by the interaction of space radiation with the atmosphere and surface rocks and soil. The detailed Martian Energetic Radiation Environment Model (dMEREM) is a GEometry ANd Tracking (GEANT4) based model developed for ESA which enables to predict the radiation environment expected at different locations on the Martian orbit, atmosphere and surface, as a function of epoch, latitude and longitude, taking into account the specific atmospheric and soil composition. dMEREM can be interfaced to different Primary Particle Models, such as the ISO-15390 and the Badhwar - O'Neill (BON) 2014 or 2020 Galactic Cosmic Ray Flux Models, or the National Aeronautics and Space Administration (NASA) Emission of Solar Protons (ESP) model for solar energetic proton fluences. dMEREM is interfaced with the European Mars Climate Database from where it retrieves information on the atmosphere composition and density at specific locations and solar longitudes and Gamma Ray Spectrometer data aboard Mars Odyssey, for the description of Mars soil composition, although soil compositions for specific locations, including those locally sampled by Martian rovers can also be defined by the user. dMEREM provides the kinetic energy and directional spectra of all particle types produced in the interactions of energetic particles with the Martian Atmosphere and Soil. The dMEREM validation results using differential proton fluxes stopping in the RAD sensor head as measured by MSL/RAD in Gale crater from November 15, 2015 to January 15, 2016 and in the begin of September 2017 is presented. Although the RAD only measures a limited field-of-view in zenith angle of the Martian Particle Radiation Field, the good agreement between the RAD data and the dMEREM predictions for protons within the RAD field of-view, are used as the basis for the use of dMEREM in the assessment of the expected ionizing radiation field on the surface of Mars for particles coming from all directions, including albedo particles. This assessment is also used to make predictions of dosimetric quantities, such as Ambient Dose Equivalent and Effective Dose, relevant for Human Space Flight, for the considered data periods.

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

Prompt gamma (PG) imaging is widely investigated as one of the most promising methods for proton range verification in proton therapy. The performance of this technique is affected by several factors like tissue heterogeneity, number of protons in the considered pencil beam and the detection device. Our previous work proposed a new treatment planning concept which boosts the number of protons of a few PG monitoring-friendly pencil beams (PBs), selected on the basis of two proposed indicators quantifying the conformity between the dose and PG at the emission level, above the desired detectability threshold. To further explore this method at the detection level, in this work we investigated the response of a knife-edge slit PG camera which was deployed in the first clinical application of PG to proton therapy monitoring. The REGistration Graphical User Interface (REGGUI) is employed to simulate the PG emission, PG detection as well as the corresponding dose distribution. As the PG signal detected by this kind of PG camera is sensitive to the relative position of the camera and PG signal falloff, we optimized our PB selection method for this camera by introducing a new camera position indicator identifying whether the expected falloff of the PG signal is centered in the field of view of the camera or not. Our camera-adapted PB selection method is investigated using computed tomography (CT) scans at two different treatment time points of a head and neck, and a prostate cancer patient under scenarios considering different statistics level. The results show that a precision of 0.8 mm for PG falloff identification can be achieved when a PB has more than 2 × 108 primary protons. Except for one case due to unpredictable and comparably large anatomical changes, the PG signals of most of the PBs recommended by all our indicators are observed to be reliable for proton range verification with deviations between the inter-fractional shift of proton range (as deduced from the PB dose distribution) and the detected PG signal within 2.0 mm. In contrast, a shift difference up to 9.6 mm has been observed for the rejected PBs. The magnitude of the proton range shift due to the inter-fractional anatomical changes is observed to be up to 23 mm. The proposed indicators are shown to be valuable for identifying and recommending reliable PBs to create new PG monitoring-friendly TPs. Comparison between our PB boosting method and the alternative PB aggregation, which combines the signal of nearby PBs to reach the desired counting statistics, is also discussed.

A deeper understanding of biological mechanisms to promote more efficient treatment strategies in proton therapy demands advances in preclinical radiation research. However this is often limited by insufficient availability of adequate infrastructures for precision image guided small animal proton irradiation. The project SIRMIO aims at filling this gap by developing a portable image-guided research platform for small animal irradiation, to be used at clinical facilities and allowing for a precision similar to a clinical treatment, when scaled down to the small animal size. This work investigates the achievable dosimetric properties of different lowest energy clinical proton therapy beams, manipulated by a dedicated portable beamline including active focusing after initial beam energy degradation and collimation. By measuring the lateral beam size in air close to the beam nozzle exit and the laterally integrated depth dose in water, an analytical beam model based on the beam parameters of the clinical beam at the Rinecker Proton Therapy Center was created for the lowest available clinical beam energy. The same approach was then applied to estimate the lowest energy beam model of different proton therapy facilities, Paul Scherrer Institute, Centre Antoine Lacassagne, Trento Proton Therapy Centre and the Danish Centre for Particle Therapy, based on their available beam commissioning data. This comparison indicated similar beam properties for all investigated sites, with emittance values of a few tens of mm·mrad. Finally, starting from these beam models, we simulated propagation through a novel beamline designed to manipulate the beam energy and size for precise small animal irradiation, and evaluated the resulting dosimetric properties in water. For all investigated initial clinical beams, similar dosimetric results suitable for small animal irradiation were found. This work supports the feasibility of the proposed SIRMIO beamline, promising suitable beam characteristics to allow for precise preclinical irradiation at clinical treatment facilities.

Within the project “Small animal proton Irradiator for Research in Molecular Image-guided radiation-Oncology” (SIRMIO) we have designed an in-beam PET scanner for preclinical application. The system is based on a novel spherical geometry, and in order to fully exploit its potential we are developing an integrated computational framework for simulation, image reconstruction and range verification. The software comprises a full Monte Carlo engine to simulate the proton treatment with related detector response, and an image reconstruction tool for simulated and experimental data. The platform is designed to integrate robust analytical reconstruction algorithms and new statistical approaches based on deep learning. The core of the framework is based on MEGAlib (The Medium Energy Gamma-ray Astronomy software library). The physical simulation is based on GEANT4. The machine learning method for the event classification is implemented with the ROOT based Toolkit for Multivariate Data Analysis (TMVA). The first prototype of the SIRMIO irradiation platform foresees a fixed beam, thus requiring the movement of the mouse for scanned beam delivery. Hence, we have extended the MEGAlib image reconstruction algorithm based on maximum-likelihood expectation-maximization (ML-EM) to correct for geometrical efficiency and attenuation taking into account the mouse motion. The goal is to be able to discriminate proton range shifts of ~ 0.5 mm. Moreover, we are augmenting the image reconstruction framework with a new approach based on machine learning, which aims at using all photon events collected during irradiation (dominated by prompt gamma) to retrieve on-the-fly the range of the beam, to complement the PET information.

The JUpiter ICy moons Explorer (JUICE) is the European Space Agency (ESA) next large class mission to the Jovian system. The mission, scheduled to launch in 2022, will investigate Jupiter and characterize its icy moons, Callisto, Europa and Ganymede for a period of 3.5 years after a 7.5-year cruise to the planet. JUICE is planned to flyby Europa and Callisto, perform a high latitude tour of the Jovian system, and finally, at the end of the mission, it will orbit Ganymede at different altitudes inside the moon’s intrinsic magnetosphere.While radiation is one of the major threats for all Space missions, in the Jovian system this problem is exacerbated due to the existent of very large fluxes of energetic electrons, with energies up to dozens of MeV, which can damage and eventually destroy the spacecraft systems. The existence of this electron population, and to a lesser extent of a proton and heavy ion population, is a consequence of Jupiter’s huge magnetosphere which can accelerate these particles to energies higher than those found in other known planetary magnetospheres. Although the Galileo mission, and to a lesser extent the Cassini, Pioneer and Voyager missions have provided ample information about the radiation environment in the Jovian, several questions about particle origin, acceleration mechanisms, Jovian-Solar magnetosphere coupling, and overall dynamics of the system still need to be answered with implications in magnetospheric physics, astrobiology and others, as well as in development of future manned and unmanned missions to both the inner and outer Solar System.For these reasons, the JUICE mission will include the RADiation hard Electron Monitor (RADEM), a low power, low mass radiation monitor, that will increase the range of long-term spectral measurements acquired by the Energetic Particle Detector (EPD) aboard the Galileo spacecraft, from 11 to 40 MeV for electrons and from 55 to 250 MeV for protons. RADEM consists of three detector heads based on traditional silicon stack detector technologies: the Electron Detector Head (EDH), the Proton Detector Head (PDH), and the Heavy Ion Detector Head (HIDH), that will measure electrons from 0.3 MeV to 40 MeV, protons from 5 MeV to 250 MeV and Heavy Ions from Helium to Oxygen with energies from 8 to 670 MeV, respectively. Because the detectors have limited Field-Of-View, a fourth detector, the Directionality Detector Head (DDH) will measure electron angular distributions which can vary greatly along the Jovian System as observed by the Galileo spacecraft.Although RADEM is a housekeeping instrument that will provide in-situ Total Ionizing Dose (TID) measurements and serve as a radiation level alarm, it has a broad scientific potential. Besides the Jovian system, the instrument will be fully operated during the cruise of the Solar System, which includes three Earth flybys, a Venus flyby and a Mars flyby, that offer additional scientific opportunities including but not limited to studying the cosmic ray gradient in the Solar System, characterizing Solar Energetic Particle (SEP) events, and others. In this work, we will present RADEM from a technical point-of-view, as well as the scientific opportunities that will be addressed by the radiation monitor during the JUICE mission.

Dual-energy computed tomography (DECT) has been shown to allow for more accurate ion therapy treatment planning by improving the estimation of tissue stopping power ratio (SPR) relative to water, among other tissue properties. In this study, we measured and compared the accuracy of SPR values derived using both dual- and single-energy CT (SECT) based on different published conversion algorithms. For this purpose, a phantom setup containing either fresh animal soft tissue samples (beef, pork) and a water reference or tissue equivalent plastic materials was designed and irradiated in a clinical proton therapy facility. Dosimetric polymer gel was positioned downstream of the samples to obtain a three-dimensional proton range distribution with high spatial resolution. The mean proton range in gel for each tissue relative to the water sample was converted to a SPR value. Additionally, the homogeneous samples were probed with a variable water column encompassed by two ionization chambers to benchmark the SPR accuracy of the gel dosimetry. The SPR values measured with both methods were consistent with a mean deviation of 0.2%, but the gel dosimetry captured range variations up to 5 mm within individual samples. Across all fresh tissue samples the SECT approach yielded significantly greater mean absolute deviations from the SPR deduced using gel range measurements, with an average difference of 1.2%, compared to just 0.3% for the most accurate DECT-based algorithm. These results show a significant advantage of DECT over SECT for stopping power prediction in a realistic setting, and for the first time allow to compare a large set of methods under the same conditions.

The southern right whale dolphin (Lissodelphis peronii) is a seldom seen cetacean of southern latitudes. In the eastern South Pacific, there are less than 73 confirmed records of live and stranded animals. Moreover, all live individual records have been sighted in offshore and deep waters, but not in the shallow water of the channels and fjords of southern Chile. Two sightings of southern right whale dolphins were made on March 21 and April 7, 2018 at Ballena Sound and Charles Islands in the western area of Magellan Strait. All individuals were identified as putative adults. Both sightings may correspond to the same group of animals and, if this assumption is correct, the dolphins would have stayed at least 17 days in the area. Even though it is not clear whether the southern right whale dolphins were initially present in the Magellan Strait, or what route they took from the open sea and what biological and physical properties were determinants for this presence, without a doubt, the occurrence of southern right whale dolphins in the eastern South Pacific channel systems is unusual.

Positron emission tomography (PET) and prompt gamma (PG) detection are promising proton therapy monitoring modalities. Fast calculation of the expected distributions is desirable for comparison to measurements and to develop/train algorithms for automatic treatment error detection. A filtering formalism was used for positron-emitter predictions and adapted to allow for its use for the beamline of any proton therapy centre. A novel approach based on a filtering formalism was developed for the prediction of energy-resolved PG distributions for arbitrary tissues. The method estimates PG yields and their energy spectra in the entire treatment field. Both approaches were implemented in a research version of the RayStation treatment planning system. The method was validated against PET monitoring data and Monte Carlo simulations for four patients treated with scanned proton beams. Longitudinal shifts between profiles from analytical and Monte Carlo calculations were within -1.7 and 0.9 mm, with maximum standard deviation of 0.9 mm and 1.1 mm, for positron-emitters and PG shifts, respectively. Normalized mean absolute errors were within 1.2 and 5.3%. When comparing measured and predicted PET data, the same more complex case yielded an average shift of 3 mm, while all other cases were below absolute average shifts of 1.1 mm. Normalized mean absolute errors were below 7.2% for all cases. A novel solution to predict positron-emitter and PG distributions in a treatment planning system is proposed, enabling calculation times of only a few seconds to minutes for entire patient cases, which is suitable for integration in daily clinical routine.

Purpose One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. Methods and Materials The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Results Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. Conclusions We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame.

Proton computed tomography (pCT) promises to reduce or even eliminate range uncertainties inherent in the conversion of Hounsfield units into relative stopping power (RSP) for proton therapy treatment planning. This is of particular interest for proton irradiation studies in animal models due to the high precision required and uncertainties in tissue properties. We propose a dedicated single-particle tracking pCT system consisting of low material budget floating strips Micromegas detectors for tracking and a segmented time-projection-chamber with vertical Mylar absorbers, functioning as a range telescope. Based on Monte Carlo simulations of a realistic in silico beam and detector implementation, a geometrical optimization of the system components was conducted to safeguard an ideal operation close to intrinsic performance limits at 75 MeV. Moreover, the overall imaging capabilities relevant for pre-clinical proton therapy treatment planning were evaluated for a mouse model. In order to minimize extrinsic uncertainties in the estimated proton trajectories, a spacing of the two tracking planes of at least 7 cm is required in both tracking detectors. Additionally, novel in-house developed and produced aluminum-based readout electrodes promise superior performance with around 3mm-1 spatial resolution due to the reduced material budget. Concerning the range telescope, an absorber thickness within 500 µm to 750 µm was found to yield the best compromise between water-equivalent path length resolution and complexity of the detector instrumentation, still providing sub-0.5% RSP accuracy. The optimized detector configuration enables better than 2% range accuracy for proton therapy treatment planning in pre-clinical data sets. This work outlines the potential of pCT for small animal imaging. The performance of the proposed and optimized system provides superior treatment planning accuracy compared to conventional X-ray CT. Thus, pCT can play an important role in translational and pre-clinical cancer research.

In presence of inter-fractional anatomical changes, clinical benefits are anticipated from image-guided adaptive radiotherapy. Nowadays, cone-beam CT (CBCT) imaging is mostly utilized during pre-treatment imaging for position verification. Due to various artifacts, image quality is typically not sufficient for photon or proton dose calculation, thus demanding accurate CBCT correction, as potentially provided by deep learning techniques. This work aimed at investigating the feasibility of utilizing a cycle-consistent generative adversarial network (cycleGAN) for prostate CBCT correction using unpaired training. Thirty-three patients were included. The network was trained to translate uncorrected, original CBCT images (CBCT org) into planning CT equivalent images (CBCT cycleGAN). HU accuracy was determined by comparison to a previously validated CBCT correction technique (CBCT cor). Dosimetric accuracy was inferred for volumetric-modulated arc photon therapy (VMAT) and opposing single-field uniform dose (OSFUD) proton plans, optimized on CBCT cor and recalculated on CBCT cycleGAN. Single-sided SFUD proton plans were utilized to assess proton range accuracy. The mean HU error of CBCT cycleGAN with respect to CBCT cor decreased from 24 HU for CBCT org to -6 HU. Dose calculation accuracy was high for VMAT, with average pass-rates of 100%/89% for a 2%/1% dose difference criterion. For proton OSFUD plans, the average pass-rate for a 2% dose difference criterion was 80%. Using a (2%, 2 mm) gamma criterion, the pass-rate was 96%. 93% of all analyzed SFUD profiles had a range agreement better than 3 mm. CBCT correction time was reduced from 6-10 min for CBCT cor to 10 s for CBCT cycleGAN. Our study demonstrated the feasibility of utilizing a cycleGAN for CBCT correction, achieving high dose calculation accuracy for VMAT. For proton therapy, further improvements may be required. Due to unpaired training, the approach does not rely on anatomically consistent training data or potentially inaccurate deformable image registration. The substantial speed-up for CBCT correction renders the method particularly interesting for adaptive radiotherapy.

Range verification is one of the most relevant tasks in ion beam therapy. In the case of carbon ion therapy, positron emission tomography (PET) is the most widely used method for this purpose, which images the -activation following nuclear interactions of the ions with the tissue nuclei. Since the positron emitter activity profile is not directly proportional to the dose distribution, until today only its comparison to a prediction of the PET profile allows for treatment verification. Usually, this prediction is obtained from time-consuming Monte Carlo simulations of high computational effort, which impacts the clinical workflow. To solve this issue in proton therapy, a convolution approach was suggested to predict positron emitter activity profiles from depth dose distributions analytically. In this work, we introduce an approach to predict positron emitter distributions from depth dose profiles in carbon ion therapy. While the distal fall-off position of the positron emitter profile is predicted from a convolution approach similar to the one suggested for protons, additional analytical functions are introduced to describe the characteristics of the positron emitter distribution in tissue. The feasibility of this approach is demonstrated with monoenergetic depth dose profiles and spread out Bragg peaks in homogeneous and heterogeneous phantoms. In all cases, the positron emitter profile is predicted with high precision and the distal fall-off position is reproduced with millimeter accuracy.