Mutational signatures and their association with cancer survival and gene expression in multiple cancer types.

Different endogenous and exogenous mutational processes cause specific patterns of somatic mutations and mutational signatures. Although their biological research has been intensive, there are only rare studies assessing the possible prognostic role of mutational signatures. We used data from The Cancer Genome Atlas to study the associations between the activity of the mutational signatures and four survival endpoints in 18 types of malignancies. We further explored the prognostic differences according to, for example, the HPV status in head and neck squamous cell carcinomas and smoking status in lung cancers. The predictive power of the signatures over time was evaluated with a dynamic area under the curve model, and the links between mutational signature activities and differences in gene expression patterns were analyzed. In 12 of 18 studied cancer types, we identified at least one mutational signature whose activity predicted survival outcomes after adjusting for the established prognostic factors. For example, overall survival was associated with the activity of mutational signatures in nine cancer types and disease-specific survival in seven cancer types. The clock-like signatures SBS5 and SBS40 were most commonly associated with survival endpoints. The genes of the myosin binding protein and melanoma antigen families were among the most substantially dysregulated genes between the signatures of low and high activity. The differences in gene expression also revealed various enriched pathways. Based on these data, specific mutational signatures associate with the gene expression and have the potential to serve as strong prognostic factors in several cancer types.

Evidence for particle acceleration approaching PeV energies in the W51 complex.

The γ-ray emission from the W51 complex is widely acknowledged to be attributed to the interaction between the cosmic rays (CRs) accelerated by the shock of supernova remnant (SNR) W51C and the dense molecular clouds in the adjacent star-forming region, W51B. However, the maximum acceleration capability of W51C for CRs remains elusive. Based on observations conducted with the Large High Altitude Air Shower Observatory (LHAASO), we report a significant detection of γ rays emanating from the W51 complex, with energies from 2 to 200 TeV. The LHAASO measurements, for the first time, extend the γ-ray emission from the W51 complex beyond 100 TeV and reveal a significant spectrum bending at tens of TeV. By combining the "π0-decay bump" featured data from Fermi-LAT, the broadband γ-ray spectrum of the W51 region can be well-characterized by a simple pp-collision model. The observed spectral bending feature suggests an exponential cutoff at ∼400 TeV or a power-law break at ∼200 TeV in the CR proton spectrum, most likely providing the first evidence of SNRs serving as CR accelerators approaching the PeV regime. Additionally, two young star clusters within W51B could also be theoretically viable to produce the most energetic γ rays observed by LHAASO. Our findings strongly support the presence of extreme CR accelerators within the W51 complex and provide new insights into the origin of Galactic CRs.

Effect of Biomass Water Dynamics in Cosmic-Ray Neutron Sensor Observations: A Long-Term Analysis of Maize-Soybean Rotation in Nebraska.

Precise soil water content (SWC) measurement is crucial for effective water resource management. This study utilizes the Cosmic-Ray Neutron Sensor (CRNS) for area-averaged SWC measurements, emphasizing the need to consider all hydrogen sources, including time-variable plant biomass and water content. Near Mead, Nebraska, three field sites (CSP1, CSP2, and CSP3) growing a maize-soybean rotation were monitored for 5 (CSP1 and CSP2) and 13 (CSP3) years. Data collection included destructive biomass water equivalent (BWE) biweekly sampling, epithermal neutron counts, atmospheric meteorological variables, and point-scale SWC from a sparse time domain reflectometry (TDR) network (four locations and five depths). In 2023, dense gravimetric SWC surveys were collected eight (CSP1 and CSP2) and nine (CSP3) times over the growing season (April to October). The N0 parameter exhibited a linear relationship with BWE, suggesting that a straightforward vegetation correction factor may be suitable (fb). Results from the 2023 gravimetric surveys and long-term TDR data indicated a neutron count rate reduction of about 1% for every 1 kg m-2 (or mm of water) increase in BWE. This reduction factor aligns with existing shorter-term row crop studies but nearly doubles the value previously reported for forests. This long-term study contributes insights into the vegetation correction factor for CRNS, helping resolve a long-standing issue within the CRNS community.

Understanding the Phase of Responsivity and Noise Sources in Frequency-Domain Multiplexed Readout of Transition Edge Sensor Bolometers.

Cosmic microwave background (CMB) experiments have deployed focal planes with O ( 10 4 ) transition edge sensor (TES) bolometers cooled to sub-Kelvin temperatures by multiplexing the readout of many TES channels onto a single pair of wires. Digital Frequency-domain Multiplexing (DfMux) is a multiplexing technique used in many CMB polarization experiments, such as the Simons Array, SPT-3 G, and EBEX. The DfMux system studied here uses LC filters with resonant frequencies ranging from 1.5 to 4.5 MHz connected to an array of TESs. Each detector has an amplitude-modulated carrier tone at the resonant frequency of its accompanying LC resonator. The signal is recovered via quadrature demodulation where the in-phase (I) component of the demodulated current is in phase with the complex admittance of the circuit and the quadrature (Q) component is orthogonal to I. Observed excess current noise in the Q component is consistent with fluctuations in the resonant frequency. This noise has been shown to be non-orthogonal to the phase of the detector's responsivity. We present a detailed analysis of the phase of responsivity of the TES and noise sources in our DfMux readout system. Further, we investigate how modifications to the TES operating resistance and bias frequency can affect the phase of noise relative to the phase of the detector responsivity, using data from Simons Array to evaluate our predictions. We find that both the phase of responsivity and phase of noise are functions of the two tuning parameters, which can be purposefully selected to maximize signal-to-noise (SNR) ratio.

Cosmos MIND and matter: Is mind in spacetime?

We attempt in this article to formulate a conceptual and testable framework weaving Cosmos, Mind and Matter into a whole. We build on three recent discoveries, each requiring more evidence: i. The particles of the Standard Model, SU(3) x SU(2) x U(1), are formally capable of collective autocatalysis. This leads us to ask what roles such autocatalysis may have played in Cosmogenesis, and in trying to answer, Why our Laws? Why our Constants? A capacity of the particles of SU(3) x SU(2) x U(1) for collective autocatalysis may be open to experimental test, stunning if confirmed. ii. Reasonable evidence now suggests that matter can expand spacetime. The first issue is to establish this claim at or beyond 5 sigma if that can be done. If true, this process may elucidate Dark Matter, Dark Energy and Inflation and require alteration of Einstein's Field Equations. Cosmology would be transformed. iii. Evidence at 6.49 Sigma suggests that mind can alter the outcome of the two-slit experiment. If widely and independently verified, the foundations of quantum mechanics must be altered. Mind plays a role in the universe. That role may include Cosmic Mind. OUR CONSIDERATIONS CONCERN: 1. Ontologically Real Potentia and the Unmanifest; 2. Nonlocality as Fundamental; 3. Res potentia, Res extensa, and Actualization; 4. Mind and Qualia, Mind is not in Spacetime; 5. Quantum Vacuum = Potentia not in Spacetime = Mind not in Spacetime; 6. Mind can Actualize Potentia; 7. The emergence of the classical world; 8. Co-evolution of evermore complex matter; 9. Why "My Mind"?; 10. Each embodied mind is coupled bilaterally to the Quantum Vacuum that is Cosmic Mind; 11. Responsible Free Will.

Cosmic Ionizing Radiation: A DNA Damaging Agent That May Underly Excess Cancer in Flight Crews.

In the United States, the Federal Aviation Administration has officially classified flight crews (FC) consisting of commercial pilots, cabin crew, or flight attendants as "radiation workers" since 1994 due to the potential for cosmic ionizing radiation (CIR) exposure at cruising altitudes originating from solar activity and galactic sources. Several epidemiological studies have documented elevated incidence and mortality for several cancers in FC, but it has not yet been possible to establish whether this is attributable to CIR. CIR and its constituents are known to cause a myriad of DNA lesions, which can lead to carcinogenesis unless DNA repair mechanisms remove them. But critical knowledge gaps exist with regard to the dosimetry of CIR, the role of other genotoxic exposures among FC, and whether possible biological mechanisms underlying higher cancer rates observed in FC exist. This review summarizes our understanding of the role of DNA damage and repair responses relevant to exposure to CIR in FC. We aimed to stimulate new research directions and provide information that will be useful for guiding regulatory, public health, and medical decision-making to protect and mitigate the risks for those who travel by air.

Experimentation in cosmology: Intervening on the whole universe.

There are many arguments against the possibility of experimenting on the whole universe. This system seems to be too big to be manipulated, it exists in only one exemplar and its evolution is a non-repeatable process. In this paper, I claim that we can nonetheless talk about experimentation in cosmology if we use Woodward's non-anthropocentric notion of intervention. However, Woodward and other interventionists argued that an intervention was necessarily an exogenous causal process and thus that no intervention on a closed system such as the universe was possible. I discuss their argument and I determine the conditions under which a consistent notion of endogenous intervention on the universe can be defined. Then, I show that there is at least one cosmic phenomenon satisfying these conditions: the photon decoupling. Finally, I draw some conclusions from this analysis regarding a realist approach of cosmology.

Variable and Large Losses of Diagnostic Biomarkers After Simulated Cosmic Radiation Exposure in Clay- and Carbonate-Rich Mars Analog Samples.

Mars has been exposed to ionizing radiation for several billion years, and as part of the search for life on the Red Planet, it is crucial to understand the impact of radiation on biosignature preservation. Several NASA and ESA missions are looking for evidence of ancient life in samples collected at depths shallow enough that they have been impacted by galactic cosmic rays (GCRs). In this study, we exposed a diverse set of Mars analog samples to 0.9 Megagray (MGy) of gamma radiation to mimic 15 million years of exposure on the Martian surface. We measured no significant impact of GCRs on the total organic carbon (TOC) and bulk stable C isotopes in samples with initial TOC concentration > 0.1 wt. %; however, diagnostic molecular biosignatures presented a wide range of degradation that didn't correlate to factors like mineralogy, TOC, water content, and surface area. Exposure dating suggests that the surface of Gale crater has been irradiated at more than five times our dose, yet using this relatively low dose and "best-case scenario" geologically recalcitrant biomarkers, large and variable losses were nevertheless evident. Our results empasize the importance of selecting sampling sites at depth or recently exposed at the Martian surface.

Galactic Cosmic Ray Particle Exposure Does Not Increase Protein Levels of Inflammation or Oxidative Stress Markers in Rat Microglial Cells In Vitro.

Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk of neurodegenerative disease. As key regulators of inflammation and OS in the CNS, microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to helium (4He) and iron (56Fe) particles on inflammation and OS in microglia in vitro, to establish a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) 4He or 2 Gy 56Fe (600 MeV/n), while the control cells were not exposed (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated IκB-α [pIκB-α], tumor necrosis factor-α [TNFα], and nitrite [NO2-]) and OS (NADPH oxidase [NOX2]) were assessed 24 h later using standard immunochemical techniques. Results showed that radiation did not increase levels of NO2- or protein levels of COX-2, iNOS, pIκB-α, TNFα, or NOX2 compared to non-irradiated control conditions in microglial cells (p > 0.05). Therefore, microglia in isolation may not be the primary cause of neuroinflammation and OS following exposures to helium or iron GCR particles.

Integrating Cosmic Microwave Background Readings with Celestial Navigation to Enhance Deep Space Navigation.

This research unveils a cutting-edge navigation system for deep space missions that utilizes cosmic microwave background (CMB) sensor readings to enhance spacecraft positioning and velocity estimation accuracy significantly. By exploiting the Doppler-shifted CMB spectrum and integrating it with optical measurements for celestial navigation, this approach employs advanced data processing through the Unscented Kalman Filter (UKF), enabling precise navigation amid the complexities of space travel. The simulation results confirm the system's exceptional precision and resilience in deep space missions, marking a significant advancement in astronautics and paving the way for future space exploration endeavors.

[Genome Stability of Bacillus velezensis after Two-Year Exposure in Open Space].

Spore-forming bacteria have a unique resistance to negative environmental conditions, including aggressive space factors, and are an excellent model for studying adaptation mechanisms and survival strategies at the molecular level. The study analyzed the genome of Bacillus velezensis, which remained viable after a 2-year exposure in outer space on the outer surface of the ISS as part of the Test space experiment. A comparative analysis of the draft genomes of the exhibit strain and the ground control did not reveal significant changes; the average nucleotide identity was 99.98%, which indicates the ability of microorganisms to maintain genome stability in space conditions, due to both increased stress resistance of bacterial spores and efficient operation of the system of repair of accumulated changes. The study of a single nucleotide polymorphism in the genome of B. velezensis revealed nine point substitutions, three of which are in intergenic regions, six in protein-coding genes, three of them are missense mutations, two nucleotide deletions leading to a shift in the reading frame, and one synonymous substitution. The profiles of the housekeeping genes were determined during MLST typing and it was found that the allelic profiles obtained for B. velezensis T15.2 and 924 strains do not correspond to any of the previously described sequence types. The presented results indicate the ability of B. velezensis bacteria to maintain the viability of spores and the integrity of the genome for a long time under extreme conditions of outer space, which is important for the problem of planetary protection, as well as the potential possibility of performing biotechnological processes based on B. velezensis during space exploration.

Combined Ionizing Radiation Exposure by Gamma Rays and Carbon-12 Nuclei Increases Neurotrophic Factor Content and Prevents Age-Associated Decreases in the Volume of the Sensorimotor Cortex in Rats.

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.

Micrometeorite collections: a review and their current status.

Micrometeorites are estimated to represent the main part of the present flux of extraterrestrial matter found on the Earth's surface and provide valuable samples to probe the interplanetary medium. Here, we describe large and representative collections of micrometeorites currently available to the scientific community. These include Antarctic collections from surface ice and snow, as well as glacial sediments from the eroded top of nunataks-summits outcropping from the icesheet-and moraines. Collections extracted from deep-sea sediments (DSS) produced a large number of micrometeorites, in particular, iron-rich cosmic spherules that are rarer in other collections. Collections from the old and stable surface of the Atacama Desert show that finding large numbers of micrometeorites is not restricted to polar regions or DSS. The advent of rooftop collections marks an important step into involving citizen science in the study of micrometeorites, as well as providing potential sampling locations over all latitudes to explore the modern flux. We explore their strengths of the collections to address specific scientific questions and their potential weaknesses. The future of micrometeorite research will involve the finding of large fossil micrometeorite collections and benefit from recent advances in sampling cosmic dust directly from the air. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Sharp Rise in Cosmic Ray Irradiation of Organisms on Earth Caused by a Nearby SN Shockwave Passage.

The work considers the modelling of nearby supernova (SN) effects on Earth's biosphere via cosmic rays (CRs) accelerated by shockwaves. The rise of the radiation background on Earth resulted from the external irradiation by CR high-energy particles and internal radiation in organisms by the decay of cosmogenic 14C is evaluated. We have taken into account that the CR flux near Earth goes up steeply when the shockwave crosses the Solar System, while in previous works the CR transport was considered as purely diffusive. Our simulations demonstrate a high rise of the external ionization of the environments at Earth's surface by atmospheric cascade particles that penetrate the first 70-100 m of water depth. Also, the cosmogenic 14C decay is able to irradiate the entire biosphere and deep ocean organisms. We analyzed the probable increase in mutation rate and estimated the distance between Earth and an SN, where the lethal effects of irradiation are possible. Our simulations demonstrate that for SN energy of around 1051 erg the lethal distance could be ∼18 pc.

The DESTINY+ Dust Analyser - a dust telescope for analysing cosmic dust dynamics and composition.

The DESTINY+(Demonstration and Experiment of Space Technology for INterplanetary voYage with Phaethon fLyby and dUst Science) Dust Analyser (DDA) is a state-of-the-art dust telescope for the in situ analysis of cosmic dust particles. As the primary scientific payload of the DESTINY+ mission, it serves the purpose of characterizing the dust environment within the Earth-Moon system, investigating interplanetary and interstellar dust populations at 1 AU from the Sun and studying the dust cloud enveloping the asteroid (3200) Phaethon. DDA features a two-axis pointing platform for increasing the accessible fraction of the sky. The instrument combines a trajectory sensor with an impact ionization time-of-flight mass spectrometer, enabling the correlation of dynamical, physical and compositional properties for individual dust grains. For each dust measurement, a set of nine signals provides the surface charge, particle size, velocity vector, as well as the atomic, molecular and isotopic composition of the dust grain. With its capabilities, DDA is a key asset in advancing our understanding of the cosmic dust populations present along the orbit of DESTINY+. In addition to providing the scientific context, we are presenting an overview of the instrument's design and functionality, showing first laboratory measurements and giving insights into the observation planning. This article is part of a theme issue 'Dust in the Solar System and beyond'.

The unresolved mystery of dust particle swarms within the magnetosphere.

Early-generation in situ dust detectors in near-Earth space have reported the occurrence of clusters of sub-micron dust particles that seemed unrelated to human spaceflight activities. In particular, data from the impact ionization detector onboard the HEOS-2 satellite indicate that such swarms of particles occur throughout the Earth's magnetosphere up to altitudes of 60 000 km-far beyond regions typically used by spacecraft. Further account of high-altitude clusters has since been given by the GEO-deployed GORID detector, however, explanations for the latter have so far only been sought in GEO spaceflight activity. This perspective piece reviews dust cluster detections in near-Earth space, emphasizing the natural swarm creation mechanism conjectured to explain the HEOS-2 data-i.e. the electrostatic disruption of meteoroids. Highlighting this mechanism offers a novel viewpoint on more recent near-Earth dust measurements. We further show that the impact clusters observed by both HEOS-2 and GORID are correlated with increased geomagnetic activity. This consistent correlation supports the notion that both sets of observations stem from the same underlying phenomenon and aligns with the hypothesis of the electrostatic breakup origin. We conclude that the nature of these peculiar swarms remains highly uncertain, advocating for their concerted investigation by forthcoming dust science endeavours, such as the JAXA/DLR DESTINY+ mission. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Seasonal variation of background counting rates in liquid scintillation counting.

A liquid scintillation background sample was measured daily in a custom-built TDCR counter for more than 17 months. The double and triple coincidence counting rates exhibit an annual sinusoidal fluctuation with a maximum in winter and a minimum in summer. Possible correlations with air temperature, air humidity, radon concentration and secondary cosmic radiation were investigated. The observation of a correlation with the ambient dose equivalent rate [Formula: see text] originating from the charged component of secondary cosmic radiation and an anti-correlation with the effective atmospheric temperature Teff suggest that the seasonal fluctuations in the background counting rate may be primarily driven by temporal variations in the muon flux at ground level. Additionally, a correlation was found with the indoor 222Rn concentration in air.

Proteomic and phosphoproteomic characterization of cardiovascular tissues after long term exposure to simulated space radiation.

Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environment unlike that experienced on Earth, it is unresolved whether there is a risk to cardiovascular health during long-term space exploration missions. Previously, we have described that mice exposed to a single dose of simplified Galactic Cosmic Ray (GCR5-ion) develop cardiovascular dysfunction by 12 months post-radiation. Methods: To investigate the biological basis of this dysfunction, here we performed a quantitative mass spectrometry-based proteomics analysis of heart tissue (proteome and phosphoproteome) and plasma (proteome only) from these mice at 8 months post-radiation. Results: Differentially expressed proteins (DEPs) for irradiated versus sham irradiated samples (fold-change ≥1.2 and an adjusted p-value of ≤0.05) were identified for each proteomics data set. For the heart proteome, there were 87 significant DEPs (11 upregulated and 76 downregulated); for the heart phosphoproteome, there were 60 significant differentially phosphorylated peptides (17 upregulated and 43 downregulated); and for the plasma proteome, there was only one upregulated protein. A Gene Set Enrichment Analysis (GSEA) technique that assesses canonical pathways from BIOCARTA, KEGG, PID, REACTOME, and WikiPathways revealed significant perturbation in pathways in each data set. For the heart proteome, 166 pathways were significantly altered (36 upregulated and 130 downregulated); for the plasma proteome, there were 73 pathways significantly altered (25 upregulated and 48 downregulated); and for the phosphoproteome, there were 223 pathways significantly affected at 0.1 adjusted p-value cutoff. Pathways related to inflammation were the most highly perturbed in the heart and plasma. In line with sustained inflammation, neutrophil extracellular traps (NETs) were demonstrated to be increased in GCR5-ion irradiated hearts at 12-month post irradiation. NETs play a fundamental role in combating bacterial pathogens, modulating inflammatory responses, inflicting damage on healthy tissues, and escalating vascular thrombosis. Discussion: These findings suggest that a single exposure to GCR5-ion results in long-lasting changes in the proteome and that these proteomic changes can potentiate acute and chronic health issues for astronauts, such as what we have previously described with late cardiac dysfunction in these mice.

The role of nuclear fragmentations in high energy transfers to a micro-object exposed to primary space radiation.

This paper describes events of anomalously high energy transfer to a micro-object by fragments of nuclei generated in nuclear interactions in the environment on board a spacecraft in flight in low-Earth orbit. An algorithm has been developed that allows for the calculation of the absorbed energy from one or more fragments - products of nuclear interaction. With this algorithm the energy distributions for a spherical micro-volume in an aqueous medium were calculated. And the resulting absorbed energy spectra from nuclear fragments and from primary cosmic rays were compared. The role of nuclear interactions in events of large energy transfers in micro-objects in the field of primary cosmic radiation has been evaluated. The calculations performed in this study showed that the energy in a micro-volume from nuclear events can be several times higher compared to the energy imparted by primary space radiation.