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Risk and Performance Assessment of Generic Mission Architectures: Showcasing the Artemis Mission

A has initiated a strong push to return face. In this work, we astronaut assess performance and risk for proposed mission architectures using a new Mission Architecture Risk Assessment (MARA) tool. The MARA tool can produce statistics about the availability of components and overall performance of the mission considering potential failures of any of its components. In a Monte Carlo approach, the tool repeats the mission simulation multiple times while a random generator lets modules fail according to their failure rates. The results provide statistically meaningful insights into the overall performance of the chosen architecture. A given mission architecture can be freely replicated in the tool, with the mission timeline and basic characteristics of employed mission modules (habitats, rovers, power generation units, etc.) specified in a configuration file. Crucially, failure rates for each module need to be known or estimated. The tool performs an event-driven simulation of the mission and accounts for random failure events. Failed modules can be repaired, which takes crew time but restores operations. In addition to tracking individual modules, MARA can assess the availability of predefined functions throughout the mission. For instance, the function of resource collection would require a rover to collect the resources, a power generation unit to charge the rover, and a resource processing module. Together, the modules that are required for a given function are called a functional group. Similarly, we can assess how much crew time is available to achieve a mission benefit (e.g. research, building a base, etc) as opposed to spending crew time on repairs. Here we employ the method on the proposed NASA Artemis mission. Artemis aims to return United States astronauts to the lunar surface by 2024. Results provide insights into mission failure probabilities, up- and downtime for individual modules and crew-time resources spent on the repair of failed modules. The tool also allows us to tweak the mission architecture in order to find setups that produce more favorable mission performance. As such, the tool can be an aid in improving the mission architect abling cost-benefit analysis for mission improvement.

Rumpf, Clemens M.↗

Uncrewed Lunar Surface Operations and Support Activities

Sustained human presence on the surface of the Moon and future missions to Mars require increased independence from surface crews and Earth-based mission control to operate efficiently, safely, and reliably. The time for surface crews to perform tasks will be limited. Extravehicular activities by surface personnel are burdensome and time-consuming, even when a continuous human presence on the surface occurs. Identifying and balancing human/automation roles and tasks and infusing automation and autonomy practices early in a system’s lifecycle will be essential to achieve mission objectives. Among these objectives are attaining a sustained human presence, improving performance and mission effectiveness, reducing operations and maintenance (O&M) costs, and ensuring operations that are robust to communication delays. To achieve these objectives, an operational shift toward increased automation and autonomy with less reliance on humans is needed. Uncrewed lunar surface operations and support activities occur when surface crews are not present or are independent of surface crew timeline activities requiring no surface crew oversight or intervention. These uncrewed surface opportunities can also be planned to minimize crew workload that avoids routine maintenance and support tasks, thus maximizing crew exploration time. Uncrewed preparations such as staging and prepositioning equipment and materials before the crew arrives could improve crew task efficiency. Additional opportunities exist to conduct uncrewed science, exploration, and utilization. Uncrewed surface architecture functions can include science and exploration; habitation; launch and landing support; surface communication and navigation; surface power generation and distribution; human surface mobility; lifting, handling, manipulating; excavation, construction, and site preparation; logistics management; maintenance and repair; surface resource utilization; integrated site operations and shared support services (e.g., site scheduling/prioritization, dust mitigation/contamination control, and surface safety). Early robotic lunar surface campaigns will provide information on the availability of resources, such as oxygen and water, and demonstrate surface-based technologies. After the Artemis III human lunar return mission, a series of landers will deliver surface systems, cargo, supplies, science packages, spare parts, and commodities. A balance of crewed and uncrewed surface operations will enable a sustained lunar surface presence at the South Pole of the Moon at a site that will be known as the Artemis Base Camp (ABC). It is envisioned that base camp operations on and around the Moon will then help prepare for the mission durations and activities needed to support the first human mission to Mars. Before long-duration crew missions to the base camp can occur, the necessary surface infrastructure will be pre-deployed and verified operational. Surface assets will be teleoperated and remotely managed from Earth. Additionally, robotic and short-duration crewed missions to the ABC will ensure the site’s merit to achieve long-term science objectives, availability of usable resources, and that terrain, seasonal variations, and illumination conditions are acceptable. ABC will consist of different areas where specific functions and services are rendered, including: • Launch and Landing Area • Habitation Area • Power Production Area • Resource Areas Launch and Landing Area—The launch and landing area will support associated functions for the arrival and departure of vehicles, such as crewed landing and ascent and uncrewed cargo deliveries and offloading. It will evolve from an unimproved site at the beginning of the exploration campaign to a more sustainable landing and launch area that can support repeated arrivals and departures. Initial uncrewed Lunar Terrain Vehicle (LTV) surface operations may include emplacement of navigation beacons and communication equipment, real-time video and photography of landing/liftoff events, and element repositioning, such as portable utility power (PUP) (applicable for other landed assets at other areas). Site preparations, such as surface leveling, soil compaction, and berm/path construction, may be needed for a more sustainable launch and landing area capable of accommodating vehicles that are increasingly more reusable and reduce the effects of plume surface interactions and ejecta impacts on nearby surface assets. During the ABC missions, cargo and logistics will be delivered to the lunar surface via robotic cargo landers before the crew arrives. These shipments, which can arrive in pressurized logistics carriers, will deliver the logistics necessary to support a crewed mission and include items such as food, water, equipment spares, etc. Providing the capability to retrieve, offload, and transport the logistics closer to the ABC site before the arrival of the crew will increase the overall efficiency of crew operations once they arrive. In the sustained phase of exploration, other supporting services may be needed, such as lander propellant servicing, surface power services, commodity refreshes, and additional inspection, maintenance, and repair capabilities, to sustain a cadence of extended personnel stays and cargo arrivals and departures. Habitation Area—Uncrewed support to surface habitation could involve supporting activation and pre-entry operations of the habitat while the crew is in orbit at the Gateway outpost preparing for a surface landing. Surface Habitat (SH) uncrewed operations may include bringing the cabin environment to a habitable temperature and air mix and activating other critical crew support systems. Potential crop production uncrewed tasks in the SH could also include autonomous watering and tending. Additionally, when the crew departs, the SH enters dormancy for the long period of uncrewed operation. A logistical staging area could also be collocated near the SH. If so, staging operations for crew supplies, waste re-location, and recycling operations may be opportunities for uncrewed operations. Power Production Area—The Fission Surface Power (FSP) element and its supporting distribution equipment provide power to surface elements as needed across the ABC to supplement day-to-day operations and survive lunar nights. Uncrewed support of this power system includes any initial LTV-assisted deployments of cables and other distributed equipment, associated electrical connections, and system testing and activation operations. Robotically performing some inspections, maintenance, or repair tasks on the power distribution equipment could reduce the surface crew workload. Resource Area— Uncrewed resource prospecting, mapping, and characterizing possible resource sites is likely to be time-consuming and represents an opportunity for uncrewed operations between crewed missions. Uncrewed mobile equipment operations will be needed in the extreme environments of permanently shadowed locations where resource extractions occur. As In-Situ Resource Utilization (ISRU) pilot plant operations begin, uncrewed surface support activities with available mobile and portable assets (LTV, PUP, etc.) will better support these operations. Any produced commodities can be stored at a centralized storage location for future use. Also associated with these operations is the use of mobile robotic excavators for resource acquisition and robotic/autonomous regolith processing. The waste tailings generated during excavation and regolith processing would also need to be transported and deposited at a dedicated location. Surface assets will continue operating between crew visits to maintain surface capabilities, conduct lunar surface science, technology demonstrations, and public outreach opportunities. Additionally, certain sustaining tasks that would consume valuable crew time could be performed before crew arrival, or after their departure. This capability may offer more affordable options to construct, activate, test, and maintain a broad set of surface assets. Telerobotically operated human surface mobility systems, such as the LTV and Pressurized Rover (PR), can be utilized for various tasks. Surface environmental conditions pose a distinct challenge for all these activities. Surface illumination and localized shadows are one such factor. Night-survival operations could consist of thermal management, battery pre-charging, and load shedding. Some surface systems may hibernate through the night and then awake and continue nominal operations. Uncrewed mobile assets may use a more adaptive approach to optimize their power and operations; one method is to follow the sunlight. Night-survival operations may be initiated remotely by teleoperation, automated, or accomplished by supervised autonomous operation. The ability to pre-deploy and control remote assets in orbit or on Mars before the arrival of the mission crew is a key capability that can be simulated on the moon. The base camp provides a venue where these advanced operational concepts, technologies, and autonomous methods and techniques, including the incorporation of time delays to simulate Earth-Mars latency can be replicated to help buy down future Mars mission risks. This paper will examine the evolution of uncrewed lunar surface operations and support activities. It will also discuss the lunar surface environmental conditions (thermal, lighting, terrain, topography, communications) along with the challenges they pose on uncrewed surface operations, and the performance of these activities with limited to minimal human interaction and/or teleoperation. Since lunar missions include Mars mission analogs, such investigation provides the framework for future uncrewed Mars mission support.

Mark E Lewis↗

NextSTEP Appendix A Modular ECLSS Effort Lessons Learned

NASA’s Artemis program provides the first steps for earth-independent exploration starting with crewed habitats in cislunar space and progressing toward crewed landings on the lunar surface that will prepare systems and crews for the exploration of Mars. The Next Space Technology for Exploration Partnerships (NextSTEP) is a public-private partnership model that facilitates commercial development of deep space exploration capabilities in support of more extensive human spaceflight missions in and beyond cislunar space. NASA issued the original NextSTEP Broad Agency Announcement (BAA) to U.S. industry in late 2014 and issued the second BAA (NextSTEP-2) in April 2016. The first appendix under NextSTEP-2, Appendix A, focused on developing deep space habitation concepts, engineering design and development, and risk reduction efforts leading to a habitation capability in cislunar space. NASA solicited concepts to develop and refine the evolvable, modular architecture, functional allocation options, standards, and common interfaces required to enable interoperability of the aggregate system to provide long duration deep space transit habitation, specifically enhancements and testing of deep space Environmental Control and Life Support Systems (ECLSS). Collins Aerospace, formerly UTC Aerospace Systems (UTAS), was awarded a Phase 1 and subsequent Phase 2 contract to “develop concepts that group ECLS systems into logical modules maximizing the use of common components and the development of unique methods and design concepts that support in-flight maintenance and repair for future exploration systems.” This paper summarizes the work accomplished under this effort, the lessons that can be applied to development of forthcoming habitation elements, and the gaps remaining to achieve a more resilient, maintainable, repairable and adaptable system capable of installation on a wide variety of habitat platforms. A primary accomplishment of this effort is the development and maturation of a modular palletization concept to enable standard rack interfaces, post-launch outfitting, and decoupling of structural supports that withstand launch environments from those needed for lower on-orbit loads in order to reduce installed mass and repurposing of panels within the habitat. In the course of the effort, Collins assessed numerous architecture trades, including the use of condensing and noncondensing heat exchangers, the ability of modular units to accommodate various habitat volumes and thermal loading, and the most appropriate order of and timing of delivery of regenerative ECLSS hardware to orbital habitats. In addition to the modularity of hardware elements, Collins developed software approaches for distributed/modular command, control, and communication systems and innovative Bayesian fault detection and isolation techniques. Finally, the effort explored advanced maintainability and supportability concepts including the definition of maintenance units (MUs) in place of the traditional Orbital Replacement Units (ORUs), increasing parts commonality to reduce the number and type of spare parts, the use of augmented reality to guide crews during maintenance and repair procedures, and how crews would prepare for and recover from long durations of habitat dormancy. Now that the NextSTEP Modular ECLSS effort has come to a close, it’s important to identify the lessons learned and where they can be leveraged to improve NASA’s broader program of ECLSS technology development and demonstration and ultimately how they can increase the performance of future surface and orbital habitats.

NextSTEP↗

NextSTEP Appendix A Modular ECLSS Effort Lessons Learned

NASA’s Artemis program provides the first steps for earth-independent exploration starting with crewed habitats in cislunar space and progressing toward crewed landings on the lunar surface that will prepare systems and crews for the exploration of Mars. The Next Space Technology for Exploration Partnerships (NextSTEP) is a public-private partnership model that facilitates commercial development of deep space exploration capabilities in support of more extensive human spaceflight missions in and beyond cislunar space. NASA issued the original NextSTEP Broad Agency Announcement (BAA) to U.S. industry in late 2014 and issued the second BAA (NextSTEP-2) in April 2016. The first appendix under NextSTEP-2, Appendix A, focused on developing deep space habitation concepts, engineering design and development, and risk reduction efforts leading to a habitation capability in cislunar space. NASA solicited concepts to develop and refine the evolvable, modular architecture, functional allocation options, standards, and common interfaces required to enable interoperability of the aggregate system to provide long duration deep space transit habitation, specifically enhancements and testing of deep space Environmental Control and Life Support Systems (ECLSS). Collins Aerospace, formerly UTC Aerospace Systems (UTAS), was awarded a Phase 1 and subsequent Phase 2 contract to “develop concepts that group ECLS systems into logical modules maximizing the use of common components and the development of unique methods and design concepts that support in-flight maintenance and repair for future exploration systems.” This paper summarizes the work accomplished under this effort, the lessons that can be applied to development of forthcoming habitation elements, and the gaps remaining to achieve a more resilient, maintainable, repairable and adaptable system capable of installation on a wide variety of habitat platforms. A primary accomplishment of this effort is the development and maturation of a modular palletization concept to enable standard rack interfaces, post-launch outfitting, and decoupling of structural supports that withstand launch environments from those needed for lower on-orbit loads in order to reduce installed mass and repurposing of panels within the habitat. In the course of the effort, Collins assessed numerous architecture trades, including the use of condensing and noncondensing heat exchangers, the ability of modular units to accommodate various habitat volumes and thermal loading, and the most appropriate order of and timing of delivery of regenerative ECLSS hardware to orbital habitats. In addition to the modularity of hardware elements, Collins developed software approaches for distributed/modular command, control, and communication systems and innovative Bayesian fault detection and isolation techniques. Finally, the effort explored advanced maintainability and supportability concepts including the definition of maintenance units (MUs) in place of the traditional Orbital Replacement Units (ORUs), increasing parts commonality to reduce the number and type of spare parts, the use of augmented reality to guide crews during maintenance and repair procedures, and how crews would prepare for and recover from long durations of habitat dormancy. Now that the NextSTEP Modular ECLSS effort has come to a close, it’s important to identify the lessons learned and where they can be leveraged to improve NASA’s broader program of ECLSS technology development and demonstration and ultimately how they can increase the performance of future surface and orbital habitats.

NextSTEP↗

Lessons Learned from Astrobee Operations on the International Space Station

Since its launch in 2019, NASA has been operating three Astrobee free-flying robots providing an autonomous and adaptable research platform aboard the International Space Station (ISS). These robots have not only facilitated a myriad of national and international research endeavors in microgravity but have also served as a STEM outreach platform for student competitions aboard the ISS. Amidst its extensive operational tenure, spanning over five years and exceeding 1200 hours of cumulative free-flyer operation as of April 2024, the Astrobee robots have encountered software and hardware anomalies. Despite its inherent design for on-orbit repair or replacement, certain anomalies have proven to be complex, necessitating remote resolution via software and firmware updates or, in extreme cases, hardware replacements or the return of faulty units to NASA's ground facilities for repair. Such challenges underscore the delicate balance between the autonomous functionality of Astrobee and the occasional need for human intervention to maintain optimal performance. One recurring point of failure identified during Astrobee's operational lifespan has been the SD card, a critical component utilized by the different Astrobee processors and the Dock Station. The occurrence of SD card anomalies, both on orbit and within ground units, has provided invaluable insights into the improvement of Astrobee's systems and mitigation to future faults. This presentation will focus on four key areas: 1. Overview of Faults and Anomalies: A comprehensive examination of the diverse array of faults and anomalies encountered by Astrobee and its associated systems both in orbit and on the ground. From software glitches to hardware malfunctions, this section provides insights into the challenges faced during Astrobee's operational tenure. 2. Resolution Processes and Procedures: An in-depth discussion of the methodologies and procedures implemented to resolve the encountered anomalies. This includes remote troubleshooting, software patches, firmware updates, and, when necessary, the logistics involved in hardware replacements or down-massing for repair. 3. Implementation of Software Updates and Hardware Upgrades: A detailed exploration of the strategies employed to mitigate the risk of recurring anomalies through the implementation of software updates and hardware upgrades. This section highlights the iterative nature of Astrobee's development, emphasizing the continuous pursuit of robustness and reliability. 4. Lessons Learned and Future Directions: Reflecting on the insights gained from addressing anomalies, this section examines the lessons learned and outlines future directions for enhancing Astrobee's robustness and resilience. It underscores the iterative nature of space exploration and the importance of adaptability and continuous improvement in the pursuit of scientific discovery. Through a nuanced examination of Astrobee's operational challenges and the strategies employed to overcome them, this presentation sheds light on the complexities of operating autonomous robotic systems in the ISS environment. It underscores NASA's commitment to pushing the boundaries of exploration and innovation while navigating the inherent challenges of space exploration.

Astrobee↗

Lessons Learned from Astrobee Operations on the International Space Station

Since its launch in 2019, NASA has been operating three Astrobee free-flying robots providing an autonomous and adaptable research platform aboard the International Space Station (ISS). These robots have not only facilitated a myriad of national and international research endeavors in microgravity but have also served as a STEM outreach platform for student competitions aboard the ISS. Amidst its extensive operational tenure, spanning over five years and exceeding 1200 hours of cumulative free-flyer operation as of April 2024, the Astrobee robots have encountered software and hardware anomalies. Despite its inherent design for on-orbit repair or replacement, certain anomalies have proven to be complex, necessitating remote resolution via software and firmware updates or, in extreme cases, hardware replacements or the return of faulty units to NASA's ground facilities for repair. Such challenges underscore the delicate balance between the autonomous functionality of Astrobee and the occasional need for human intervention to maintain optimal performance. One recurring point of failure identified during Astrobee's operational lifespan has been the SD card, a critical component utilized by the different Astrobee processors and the Dock Station. The occurrence of SD card anomalies, both on orbit and within ground units, has provided invaluable insights into the improvement of Astrobee's systems and mitigation to future faults. This presentation will focus on four key areas: 1. Overview of Faults and Anomalies: A comprehensive examination of the diverse array of faults and anomalies encountered by Astrobee and its associated systems both in orbit and on the ground. From software glitches to hardware malfunctions, this section provides insights into the challenges faced during Astrobee's operational tenure. 2. Resolution Processes and Procedures: An in-depth discussion of the methodologies and procedures implemented to resolve the encountered anomalies. This includes remote troubleshooting, software patches, firmware updates, and, when necessary, the logistics involved in hardware replacements or down-massing for repair. 3. Implementation of Software Updates and Hardware Upgrades: A detailed exploration of the strategies employed to mitigate the risk of recurring anomalies through the implementation of software updates and hardware upgrades. This section highlights the iterative nature of Astrobee's development, emphasizing the continuous pursuit of robustness and reliability. 4. Lessons Learned and Future Directions: Reflecting on the insights gained from addressing anomalies, this section examines the lessons learned and outlines future directions for enhancing Astrobee's robustness and resilience. It underscores the iterative nature of space exploration and the importance of adaptability and continuous improvement in the pursuit of scientific discovery. Through a nuanced examination of Astrobee's operational challenges and the strategies employed to overcome them, this presentation sheds light on the complexities of operating autonomous robotic systems in the ISS environment. It underscores NASA's commitment to pushing the boundaries of exploration and innovation while navigating the inherent challenges of space exploration.

Astrobee↗

Comparison of Geant4-DNA and RITRACKS/RITCARD: Microdosimetry, Nanodosimetry and DNA Damage Predictions for Low to High LET Ions

Low linear energy transfer (LET) ionizing radiations induce homogeneously distributed DNA damage at the cellular scale, while high LET ionizing radiations are well known to create complex biological damage including clustered double strand breaks (DSB). Clustered DSB are critical events that are difficult to repair, leading to increased biological outcomes compared to low LET radiation exposure. Recent studies have shown that DNA compaction, which can be actively modified by the cell to allow DNA repair, influences the yield of DSB [1]. The goal of this work is to determine the impact of DNA compaction on chromosome aberration formation, a biomarker of radiation-induced cancer risk. The RITRACKS track structure code [2], together with the RITCARD code [3], allow one to simulate the transport of high LET ions, calculate DNA damage and repair, and chromosome aberration formation, but does not include detailed geometrical models of DNA. The Geant4-DNA toolkit provides such detailed models with different levels of DNA compaction [1,4], but does not model chromosome aberration formation. In this work, these highly detailed DNA geometries are used to compute DNA breaks with Geant4-DNA and combine the results with the RITCARD tool to compute chromosome aberrations. As a first step, we compared the transport models used in RITRACKS and Geant4-DNA and newly released heavy ion model transport (G4DNARuddIonisationExtendedModel Geant4 v11.2) to ensure consistency between the physical stage of the two radiation transport codes. We compared energy deposition at the micrometric and nanometric scales for different ions (H 250 MeV, H 150 Me, He 250 MeV/n, C 290 MeV/n, O 350 MeV/n, O 55 MeV/n, Si 170MeV/n, Ti 300 MeV/n, Ti 300 MeV/n, Fe 600 MeV/n, Fe 450 MeV/n and Fe 300 MeV/n) with LET ranging from ~0.4 keV/μm up to 235 keV/μm. Excellent agreement is found for both microdosimetric and nanodosimetric spectra for all ion types and energies. The calculation of DNA breaks and their complexity with the Geant4-DNA is an ongoing work, and comparison with RITCARD will be presented based on result availability at the time of the conference. [1] Tang et al. (2019). Med. Phys., 46(3), 1501-1511. [2] Plante et al. (2008). NJP, 10(12), 125020. [3] Plante et al. (2019). Rad. Res., 192(3), 282-298. [4] Incerti et al. (2018). Med. Phys., 45(8), e722-e739.

Floriane Poignant↗

Calcium- Silicate-Cement Based Blends with Natural Zeolites - Self-Healing Performance under Conditions of High-Temperature Geothermal Wells

Geothermal cements are subjects to thermal and mechanical shocks, high temperatures and aggressive environments that can cause cement damage and compromise well integrity, contaminate underground waters and, if not repaired in time, lead to the well collapse. Repairs of the damaged areas are problematic for subterranean constructions. Self-repairing cements are especially attractive for such applications.

15 GEOTHERMAL ENERGY↗

Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm ± 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. Conclusions: With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Ruptured Aortic Aneurysm From Late Type II Endoleak Treated by Transarterial Embolization

Endoleak is the most common complication after endovascular aneurysm repair. The most common type of endoleak, a type II endoleak, typically follows a benign course and is only treated when associated with increasing aneurysm size. In this case report, we describe a ruptured abdominal aortic aneurysm due to a late, type II endoleak occurring 10 years after endovascular aneurysm repair that was successfully treated by transarterial embolization.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

ChEVAS: Combining Suprarenal EVAS with Chimney Technique

Endovascular sealing with the Nellix{sup ®} endoprosthesis (EVAS) is a new technique to treat infrarenal abdominal aortic aneurysms. We describe the use of endovascular sealing in conjunction with chimney stents for the renal arteries (chEVAS) in two patients, one with a refractory type Ia endoleak and an expanding aneurysm, and one with a large juxtarenal aneurysm unsuitable for fenestrated endovascular repair (EVAR). Both aneurysms were successfully excluded. Our report confirms the utility of chEVAS in challenging cases, where suprarenal seal is necessary. We suggest that, due to lack of knowledge on its durability, chEVAS should only been considered when more conventional treatment modalities (open repair and fenestrated EVAR) are deemed difficult or unfeasible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice

PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to procedure type; these included among others cerebral interventions (n = 112), iliac and/or caval venous recanalization procedures (n = 68), endovascular aortic repair procedures (n = 63), biliary duct interventions (n = 58), and percutaneous gastrostomy procedure (n = 28).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gy cm{sup 2} (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0) μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1 μSv/Gy cm{sup 2} in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

RBMK Neutron-Physical Characteristics and Nuclear Safety

The neutron-physical characteristics of RBMK at the Kursk, Leningradskaya, and Smolensk NPPs for 2015–2017, as determined from calculations of more than 6000 actual states at nominal power, are presented. The results of computational modeling of shutdown regimes upon actuation of the shutdown systems of the emergency protection and fast power reduction are presented. It is shown that the physical characteristics, efficiency, and fast response of the shutdown systems of the emergency protection and fast power reduction ensure the nuclear safety of RBMK. The effect of repair of the graphite stack with a sharp graphite blocks on the neutron-physical characteristics of the reactor is determined. It is shown that the removal of some of the graphite during the repair of 500–600 graphite columns results in a reduction of the steam coefficient of reactivity and partial or complete removal of additional absorbers from the core while maintaining the neutronic characteristics and nuclear safety of RBMK.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs

Highlights: ► PES1 was overexpressed in diverse cancer cell lines. ► PES1-ablation enhances DNA damage response by decreasing DNA repair. ► PES1-ablation increases the sensitivity of HCT116 cells to chemotherapeutic agents. ► PES1-ablation is associated with diminished nuclear entry of RAD51. -- Abstract: PES1 (also known as Pescadillo), a nucleolar protein, was involved in biogenesis of ribosomal RNA. Up-regulation of PES1 has been documented in some human cancers, indicating that PES1 may play some crucial roles in tumorigenesis. In our previous study, it was found that silencing of PES1 resulted in decreased proliferation of colorectal cancer cells. We also noticed that depletion of PES1 altered expression profiles of diverse genes. In the present study, we validated the expression changes of a subset of genotoxic stress-related genes in PES1-silenced HCT116 cells by quantitative RT-PCR. The steady and etoposide-induced phosphorylated H2AX (γ-H2AX) were higher in PES1-silenced cells than in control cells. Besides, etoposide-induced γ-H2AX persisted longer in PES1-silenced cells after removing the etoposide. Next, results of comet assay revealed decreased DNA repair after PES1-ablation. PES1-ablated cells were more sensitive to chemotherapeutic agents, which could be reversed by reconstitution with exogenous PES1. Furthermore, deletion of PES1 diminished steady and DNA damage-induced levels of nuclear RAD51. Our results uncover a potential role of PES1 in chemoresistance by regulating DNA damage response in colorectal cancer cells.

60 APPLIED LIFE SCIENCES↗

The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is important for the physiological function of Rad52 not only at a late stage following irradiation, but also at an early stage.

60 APPLIED LIFE SCIENCES↗

C-terminal region of DNA ligase IV drives XRCC4/DNA ligase IV complex to chromatin

Highlights: •Chromatin binding of XRCC4 is dependent on the presence of DNA ligase IV. •C-terminal region of DNA ligase IV alone can recruit itself and XRCC4 to chromatin. •Two BRCT domains of DNA ligase IV are essential for the chromatin binding of XRCC4. -- Abstract: DNA ligase IV (LIG4) and XRCC4 form a complex to ligate two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). It is not fully understood how these proteins are recruited to DSBs. We recently demonstrated radiation-induced chromatin binding of XRCC4 by biochemical fractionation using detergent Nonidet P-40. In the present study, we examined the role of LIG4 in the recruitment of XRCC4/LIG4 complex to chromatin. The chromatin binding of XRCC4 was dependent on the presence of LIG4. The mutations in two BRCT domains (W725R and W893R, respectively) of LIG4 reduced the chromatin binding of LIG4 and XRCC4. The C-terminal fragment of LIG4 (LIG4-CT) without N-terminal catalytic domains could bind to chromatin with XRCC4. LIG4-CT with W725R or W893R mutation could bind to chromatin but could not support the chromatin binding of XRCC4. The ability of C-terminal region of LIG4 to interact with chromatin might provide us with an insight into the mechanisms of DSB repair through NHEJ.

60 APPLIED LIFE SCIENCES↗

Down-regulation of PERK enhances resistance to ionizing radiation

Highlights: •PERK enhances the sensitivity of cancer cells to ionizing radiation. •Down-regulation of PERK results in enhanced DNA repair. •Ionizing radiation-induced apoptosis is inhibited in PERK-down regulated cancer cells. -- Abstract: Although, ionizing radiation (IR) has been implicated to cause stress in endoplasmic reticulum (ER), how ER stress signaling and major ER stress sensors modulate cellular response to IR is unclear. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER transmembrane protein which initiates unfolded protein response (UPR) or ER stress signaling when ER homeostasis is disturbed. Here, we report that down-regulation of PERK resulted in increased clonogenic survival, enhanced DNA repair and reduced apoptosis in irradiated cancer cells. Our study demonstrated that PERK has a role in sensitizing cancer cells to IR.

60 APPLIED LIFE SCIENCES↗

Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.

60 APPLIED LIFE SCIENCES↗