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Astronauts on deep space missions face chronic exposure to galactic cosmic radiation (GCR). However, it remains unknown whether mission-relevant multi-ion GCR produces global or circuit-selective cognitive vulnerabilities and whether candidate countermeasures protect uniformly or show domain-dependent trade-offs. Here we used a 33-ion GCR simulation with concurrent countermeasure treatment to address both questions in male and female mice. C57BL/6J mice received 33-GCR (0.75 Gy) or sham radiation with the Nrf2-activating compound CDDO-EA or vehicle, followed by multi-domain behavioral assessment across the hippocampal-nucleus accumbens-prefrontal circuit. Under very high memory load, male Veh/33-GCR mice showed enhanced pattern separation compared to Veh/Sham males, an effect normalized by CDDO-EA. Female mice showed no radiation-induced changes in pattern separation but weighed more than Veh/Sham females and had reduced locomotor activity. Reward-based learning differed by sex: males showed no changes, while female Veh/33-GCR mice displayed enhanced reward anticipation, with both treatments contributing to elevated goal-tracking. For behavioral flexibility, CDDO-EA impaired reversal learning in males regardless of radiation, while 33-GCR impaired reversal learning in females regardless of CDDO-EA. Principal component analysis revealed CDDO-EA under 33-GCR specifically disrupted the balance between stimulus-driven and executive control processes and altered goal-directed behavior, while hippocampal-dependent discrimination maintained its functional relationships with other cognitive domains - confirming circuit-selective rather than global vulnerability. In a preliminary fiber photometry cohort, irradiated males showed enhanced dentate gyrus encoding activity under high memory load. At the cellular level, combined CDDO-EA/33-GCR selectively reduced dentate gyrus progenitors in females. Together, these findings reveal distinct, circuit-selective vulnerability patterns in males and females that would have been invisible to single-sex, single-endpoint designs. CDDO-EA proved a double-edged sword: protecting one cognitive domain while impairing another, a trade-off invisible to single-endpoint assessment and directly relevant to astronaut risk assessment.

Spaceflight stressors, including microgravity-induced unloading and galactic cosmic radiation (GCR), acutely disrupt mitochondrial function and contribute to skeletal muscle atrophy. The long-term remodeling of skeletal muscle following combined unloading and radiation exposure remains poorly understood. We investigated protein abundance changes 9-mo postexposure to combined unloading and radiation exposure. Female, 6-mo-old, C57Bl/6J mice underwent 5 days of hindlimb unloading (HU) or weight-bearing (WB) conditions, followed by 0, 0.5, or 1.5 Gy of simulated GCR exposure using the simplified 5-ion beam exposure (simGCRsim) (n = 5/group). The gastrocnemius muscle was collected after 9 mo of WB and analyzed by data-independent acquisition mass spectrometry. Differentially abundant proteins were identified and evaluated using pathway enrichment analyses. WB mice exposed to 0.5 Gy exhibited increased abundance of electron transport system proteins and mitochondrial transport proteins, suggesting increased mitochondrial activity relative to control mice. HU mice exposed to 0.5 Gy displayed decreased glycolytic proteins, increased reliance on oxidative pathways, and reduced antioxidant proteins (glutaredoxins and peroxiredoxin) compared with WB0.5. In HU mice, a higher radiation dose (HU1.5 vs. HU0.5) led to the downregulation of 26S proteasome subunits and the upregulation of peroxisomal antioxidant, tricarboxylic acid cycle, and β-oxidation proteins, indicating dose-dependent mitochondrial adaptations. Long-term muscular remodeling after simGCRsim exposure is influenced by both muscle-loading status and radiation dose, with prolonged shifts toward oxidative metabolism and altered protein quality control persisting months after exposure. These findings provide new insights into skeletal muscle adaptation to spaceflight stressors and have important implications for astronaut health during and after long-duration missions.NEW & NOTEWORTHY Acute simGCRsim exposure causes changes in metabolic and mitochondrial protein abundance that are observable after 9 mo. Weight-bearing and unloaded muscle show unique metabolic protein profiles, with unloaded muscle experiencing reduced expression of glycolytic proteins relative to weight-bearing muscle after 9 mo. Significant dose-dependent response to acute simGCRsim exposure, with higher doses having more profound effects on metabolic and antioxidant protein abundance.

High-energy heavy-ion particle accelerators have long served as proxies for the harsh space radiation environment, enabling both fundamental life-science research and applied testing of flight hardware. Traditionally, monoenergetic high-energy heavy-ion beams have been employed for practicality, providing valuable datasets that underpin radiation risk and predictive computational models. However, such beams cannot fully reproduce the mixed-field nature of space radiation, motivating the development of realistic analogs for improved risk assessment and countermeasure evaluation in preparation for future deep-space missions to Moon or Mars. Spearheaded by developments at the NASA Space Radiation Laboratory, the GSI Helmholtzzentrum für Schwerionenforschung, supported by the European Space Agency (ESA), has established advanced space radiation simulation capabilities in Europe. Here, we present the design, optimization, and in-silico benchmarking of GSI's hybrid active-passive Galactic Cosmic Ray (GCR) simulator, together with a computationally optimized phase-space particle source for Geant4, which is available to external users for their own simulation studies and experimental planning.

In this paper for the first time the frequency of complex double strand breaks (DSB) and non-DSB clustered damage behind spacecraft and tissue shielding from exposure to galactic cosmic rays (GCR) and secondary radiation are predicted. Elementary DNA lesions produced by ionizing radiation include single strand breaks (SSB) and various forms of base damages (BD) (e.g. abasic or oxidative sites). Clustered DNA damage is defined by the occurence of 2 or more elementary lesions within 10 base-pairs (bp), and complex clustered damage as 3 or more elementary lesions within 10 bp. Clustered DNA damage is more difficult to repair compared to simple forms of DNA damage, while the relative contribution of clustered to simple DNA damage increases with ionization density or linear energy transfer (LET), and therefore imporant for space radiation exposures. The author has developed the multinominal model of clustered DNA damage that uses nanoscopic energy imparted spectra in DNA volumes and damage location probability operators to predict clustered DNA damage frequencies. In this paper, I combine the results of the multinomial model with GCR particle energy spectra to predict the probabilities of complex DSB, and tandem and bistranded non-DSB clustered damage. Predictions for the local interstellar (LIS), solar mininum, and solar maximum environments are discussed. Results show that the frequency of DSB and non-DSB clusters attenuates slowly with aluminum and tissue shielding, and that non-DSB clusters are >4 times more frequent than prompt DSBs. This is an important finding which quantifies a prediction of the dominance of delayed formation of DSBs created in non-DSB clusters repair processes over prompt DSBs in the initial GCR DNA damage in tissues.

Space radiation is one of the major obstacles to space exploration. If not mitigated, radiation can interact both with biological and electronic systems, inducing damage and posing significant risk to space missions. Countermeasures can only be studied effectively with ground-based accelerators that act as a proxy for space radiation. Following an in-silico design and optimization process, we have developed a galactic cosmic ray (GCR) simulator using a hybrid active-passive methodology. In this approach, the primary beam energy is actively switched and the beam interacts with specifically designed passive modulators. In this paper, we present the implementation of such a GCR simulator and its experimental microdosimetric characterization. Measuring the GCR field is of paramount importance, both before providing it to the user as a validated radiation field and for achieving the best possible radiation description. The issue is addressed in this paper by using a tissue equivalent proportional counter to measure radiation quality and by comparing experimental measurements with Monte Carlo simulations. In conclusion, we will demonstrate the GCR simulator's capability to reproduce a GCR field.

Galactic cosmic rays (GCR) are a principal source of ionizing radiation exposure for astronauts during deep space missions. Given the ambition to expand manned space exploration to distant destinations like Mars, it is essential to accurately predict the radiation doses astronauts are likely to encounter and the consequent biological impacts. Accurate dose predictions are important for operational radiation safety, ensuring that risk assessments and protective measures are appropriately calibrated to the myriad of challenges of deep space travel. The GCRsim facility at the NASA Space Radiation Laboratory enables small animal radiobiology studies of GCR exposure, offering a controlled setting to mimic the complex radiation conditions found in deep space. This manuscript introduces a series of Dose Conversion Factors (DCFs) which enable rigorous absorbed dose calculations for mice irradiated at the GCRsim. A formalism was introduced for calculating organ-level and voxel-level radiation dose to a representative mouse phantom, based on DCFs quantifying radiation absorbed dose per unit fluence of different GCRsim beam components for different irradiation orientations. The PHITS Monte Carlo code was employed to compute the DCFs in units of Gy∙cm2∙ion-1. A library of murine DCFs were derived using the PHITS Monte Carlo code for six irradiation orientations: right-left, anterior-posterior, superior-inferior, and their opposed variations. Absorbed doses to the murine total body were calculated with the method and compared with ion chamber measurements, which agreed within 10 %. A library of dose conversion factors for mouse irradiation at GCRsim was developed and validated against physical measurements. These DCFs account for organ-specific variations in radiation dose from different GCRsim beam components, enabling improved assessments of potential radiogenic effects, toward improving astronaut safety measures for future deep space missions.

The active galactic nucleus (AGN) accretion disks are ideal sites for hierarchical black hole (BH) mergers. To robustly probe such a possibility, we analyze binary black hole mergers in the GWTC-4 with a flexible mixture population model for component masses, spin magnitudes, and spin tilt angles, and identify two distinct subpopulations. In the second subpopulation characterized by high spin magnitudes χ∼0.8 as well as the broad mass distribution up to ≳150M_{⊙}, we find a pronounced preference for spins aligned with the orbital angular momentum: an isotropic tilt distribution is strongly disfavored (logarithmic Bayes factor =4.5). The aligned events account for ∼0.57_{-0.31}^{+0.23} of the second subpopulation, corresponding to a local rate of ∼0.25_{-0.16}^{+0.38}  Gpc^{-3} yr^{-1} (all values reflect central 90% credible intervals). These notable features naturally arise from hierarchical mergers embedded in AGN disks, where gas torques may effectively align spins. Our results suggest that AGN-disk hierarchical assembly may be one important channel for the present gravitational-wave sample, and provide concrete, testable predictions for future detection.

In regions of the Solar System distant from planetary magnetic fields, galactic cosmic rays (GCRs) have generally been assumed to be uniformly distributed over the Earth-Moon distance. However, our analysis of data from the LND (Lunar Lander Neutron and Dosimetry) experiment onboard the Chang'E-4 lander revealed a region of reduced GCR flux in the prenoon sector of the lunar orbit. Further investigation suggests the presence of an energetic particle cavity, formed by Earth's magnetic field acting as an obstacle to GCR propagation. This cavity indicates that the influence of Earth's magnetic field within the space environment extends unexpectedly up to and far beyond the lunar orbit. This finding offers the potential to avoid high radiation levels during future lunar exploration and deep-space missions.

Cellular senescence is a stress response that prevents the proliferation of damaged cells. As senescence has evolved in the near-surface biosphere, where cosmic background radiation (CBR) continuously delivers a low flux of highly penetrating muon particles, we investigated whether this persistent abiotic stress contributes to senescence thresholding. At the Canfranc Deep Underground Laboratory, an astrophysical facility located 800 meters beneath granite rock in the Spanish Pyrenees (~2,450 meters of water-equivalent depth), cosmic muons are suppressed by five orders of magnitude. There, we examined the senescence-induction dynamics in human cancer cells exposed to G0/G1- or G2/M-targeting chemotherapeutics and compared them to cells in adjacent, above-ground conditions with natural CBR. Muon depletion significantly reduced the acquisition of the senescence-associated β-gal-positive phenotype under conditions favoring a G0/G1 arrest with the CDK4/6 inhibitor palbociclib. SA-β-gal-positive states driven by G2/M arrest in response to the mitotic kinase inhibitor alisertib and the DNA-damaging radiomimetic bleomycin were insensitive to muon suppression. While the SENCAN classifier, which uses RNA-seq data to determine whether cell samples are senescent, and the senescence-associated secretory phenotype profiles were largely unaffected by the absence of cosmic-ray muons, muon depletion caused small variations at a transcriptome-wide level in the two pathways to senescence. Our hypothesis-generating study suggests that muons might act as abiotic signal-to-noise calibrators that facilitate the consolidation of senescence trajectories specifically associated with G0/G1 withdrawal. Our exploratory findings shed light on how life incorporated CBR evolutionarily to sense and respond to cellular damage, which could inform senescence operability in low-muon extraterrestrial habitats.

The Galactic Center Excess (GCE) may yet herald the discovery of annihilating dark matter. Weighing against that conclusion are analyses showing evidence for dim point sources within the spatial structure of the emission. Because of technical limitations these analyses are purely spatial with all spectral information that could disentangle the excess from astrophysical backgrounds discarded. Here, we demonstrate that a neural network simulation-based inference approach can jointly analyze the spatial and spectra data. The addition is profound: energy information drives the putative point sources to be significantly dimmer, indicating either the GCE is truly diffuse in nature or made of an exceptionally large number of sources. Quantitatively, for our best fit background model, the excess is essentially consistent with Poisson emission as predicted by dark matter. If due to point sources, our median prediction is O(10^{5}) sources, or more than 35 000 at 90% confidence-both orders of magnitude larger than the hundreds preferred by earlier point-source analyses of the GCE, although variations allowed by background systematics could reduce the required number of sources by roughly an order of magnitude.

This corrects the article DOI: 10.1103/PhysRevLett.133.231401.

We study the formation of stellar bars using 145 simulations of disc galaxies embedded in live and static dark matter haloes. We use the exponential bar growth time-scale, [Formula: see text], to quantify how disc structure and kinematics regulate the onset and rate of secular bar formation. We extend previous work to thicker and more turbulent discs, motivated by those observed at high redshift ([Formula: see text]). By revisiting several commonly used disc stability criteria - the Efstathiou-Lake-Negroponte parameter ([Formula: see text]), the Ostriker-Peebles ratio ([Formula: see text]), and the disc stellar mass fraction within 2.2 disc scale radii ([Formula: see text]) - we find that [Formula: see text], when expressed in terms of the disc's orbital period, follows a tight power law with each criteria. In Milky Way-like discs embedded in live haloes, bars form within a Hubble time if [Formula: see text], [Formula: see text], and [Formula: see text]. We show discs with higher velocity dispersion experience delayed bar growth and introduce an empirical relation that correctly describes the bar formation time-scales of all our live halo models. Bars in static haloes grow at roughly half the rate of those in live haloes and require substantially greater disc instability to do so.