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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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223 records · Page 13

Solar Modulation of Cosmic Nuclei over a Solar Cycle: Results from the Alpha Magnetic Spectrometer

We report the properties of precision time structures of cosmic nuclei He, Li, Be, B, C, N, and O fluxes over an 11-year solar cycle from May 2011 to November 2022 in the rigidity range from 1.92 to 60.3 GV. The nuclei fluxes show similar but not identical time variations with amplitudes decreasing with increasing rigidity. In particular, below 3.64 GV the Li, Be, and B fluxes, and below 2.15 GV the C, N, and O fluxes, are significantly less affected by solar modulation than the He flux. We observe that these differences in solar modulation are linearly correlated with the differences in the spectral indices of the cosmic nuclei fluxes. This shows, in a model-independent way, that solar modulation of galactic cosmic nuclei depends on their spectral shape. In addition, solar modulation differences due to nuclei velocity dependence on the mass-to-charge ratio (𝐴/𝑍) are not observed.

cosmic ray composition & spectra↗

Antiprotons and Elementary Particles over a Solar Cycle: Results from the Alpha Magnetic Spectrometer

We present results over an 11-year Solar cycle of cosmic antiprotons based on 1.1 × 10 6 events in the rigidity range from 1.00 to 41.9 GV. The $\bar{𝑝}$ fluxes exhibit distinct properties. The magnitude of the $\bar{𝑝}$ flux temporal variation is significantly smaller than those of 𝑝, 𝑒 − , and 𝑒 + . A hysteresis between the $\bar{𝑝}$ fluxes and the 𝑝 fluxes is observed, whereas the $\bar{𝑝}$ and 𝑒 − fluxes show a linear correlation. With a model-independent analysis, we found a universal relation between the shape of the rigidity spectrum and the magnitude of flux temporal variation over an 11-year Solar cycle for both positively and negatively charged particles. The simultaneous results on $\bar{𝑝}$ and 𝑝, 𝑒 − , and 𝑒 + provide unique information for understanding particle transport in the Solar System as a function of mass, charge, and spectral shape.

cosmic ray composition & spectra↗

Properties of Cosmic Lithium Isotopes Measured by the Alpha Magnetic Spectrometer

We present the first measurement of cosmic-ray fluxes of 6 Li and 7 Li isotopes in the rigidity range from 1.9 to 25 GV. The measurements are based on 9.7 × 10 5 6 Li and 1.04 × 10 6 7 Li nuclei collected by the Alpha Magnetic Spectrometer on the International Space Station from May 2011 to October 2023. We observe that over the entire rigidity range the 6 Li and 7 Li fluxes exhibit nearly identical time variations and, above ∼4 GV, the time variations of 6 Li , 7 Li , He, Be, B, C, N, and O fluxes are identical. Above ∼7 GV, we find an identical rigidity dependence of the 6 Li and 7 Li fluxes. This shows that they are both produced by collisions of heavier cosmic-ray nuclei with the interstellar medium and, in particular, excludes the existence of a sizable primary component in the 7 Li flux.

cosmic ray acceleration↗

A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution

Abstract Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer, potentially explaining ∼40% of relapses. If other mechanisms underlie the evolution of hormone-dependent breast cancer under adjuvant therapy is currently unknown. In this work, we employ functional genomics to dissect the contribution of cis-regulatory elements (CRE) to cancer evolution by focusing on 12 megabases of noncoding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Parallel epigenetic perturbation (CRISPRi) in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies a limited set of noncoding changes potentially involved in therapy resistance. Overall, our data uncover how endocrine therapies trigger the emergence of transient features which could ultimately be exploited to hinder the adaptive process. Significance: This study shows that cells adapting to endocrine therapies undergo changes in the usage or regulatory regions. Dormant cells are less vulnerable to regulatory perturbation but gain transient dependencies which can be exploited to decrease the formation of dormant persisters.

Oncology↗

Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells

Patients with estrogen receptor–positive breast cancer receive adjuvant endocrine therapies (ET) that delay relapse by targeting clinically undetectable micrometastatic deposits. Yet, up to 50% of patients relapse even decades after surgery through unknown mechanisms likely involving dormancy. To investigate genetic and transcriptional changes underlying tumor awakening, we analyzed late relapse patients and longitudinally profiled a rare cohort treated with long-term neoadjuvant ETs until progression. Next, we developed an in vitro evolutionary study to record the adaptive strategies of individual lineages in unperturbed parallel experiments. Our data demonstrate that ETs induce nongenetic cell state transitions into dormancy in a stochastic subset of cells via epigenetic reprogramming. Single lineages with divergent phenotypes awaken unpredictably in the absence of recurrent genetic alterations. Targeting the dormant epigenome shows promising activity against adapting cancer cells. Overall, this study uncovers the contribution of epigenetic adaptation to the evolution of resistance to ETs.

60 APPLIED LIFE SCIENCES↗

SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds.

59 BASIC BIOLOGICAL SCIENCES↗