Inositol pyrophosphates have been implicated in numerous biological processes. Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol pyrophosphate, diphosphoinositol ...pentakisphosphate (IP7), influences apoptotic cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a transcriptional program leading to cell cycle arrest or apoptosis. We demonstrate that IP6K2 is required for p53- mediated apoptosis and modulates the outcome of the p53 response. Gene disruption of IP6K2 in colorectal cancer cells selectively impairs p53-mediated apoptosis, instead favoring cell-cycle arrest. IP6K2 acts by binding directly to p53 and decreasing expression of pro-arrest gene targets such as the cyclin-dependent kinase inhibitor p21.
Fluences of solar energetic particles (SEPs) are not easy to evaluate, especially for high-energy events (i.e. ground-level enhancements, GLEs). Earlier estimates of event-integrated SEP fluences for ...GLEs were based on partly outdated assumptions and data, and they required revisions. Here, we present the results of a full revision of the spectral fluences for most major SEP events (GLEs) for the period from 1956 -- 2017 using updated low-energy flux estimates along with greatly revisited high-energy flux data and applying the newly invented reconstruction method including an improved neutron-monitor yield function. Low- and high-energy parts of the SEP fluence were estimated using a revised space-borne/ionospheric data and ground-based neutron monitors, respectively. The measured data were fitted by the modified Band function spectral shape. The best-fit parameters and their uncertainties were assessed using a direct Monte Carlo method. As a result, a full reconstruction of the event-integrated spectral fluences was performed in the energy range above 30 MeV, parametrised, and tabulated for easy use along with estimates of the 68% confidence intervals. This forms a solid basis for more precise studies of the physics of solar eruptive events and the transport of energetic particles in the interplanetary medium, as well as the related applications.
Tibet-AS\(\gamma\) collaboration has recently reported a measurement of diffuse \(\gamma\)-ray flux from the outer Galactic disk in the energy range reaching PeV. We complement this measurement with ...the Fermi/LAT measurement of the diffuse flux from the same sky region and study the pion decay model of the combined Fermi/LAT+Tibet-AS\(\gamma\) spectrum. We find that within such a model the average cosmic ray spectrum in the outer Galactic disk has the same characteristic features as the local cosmic ray spectrum. In particular, it experiences a hardening at several hundred GV rigidity and a knee feature in the PV rigidity range. The slope of the average cosmic ray spectrum above the break is close to the locally observed slope of the helium spectrum \(\gamma\simeq 2.5\), but is harder than the slope of the local proton spectrum in the same rigidity range. Although the combination of Fermi/LAT and Tibet-AS\(\gamma\) data points to the presence of the knee in the average cosmic ray spectrum, the quality of the data is not yet sufficient for the study of knee shape and cosmic ray composition.
In May 2024, the scientific community observed intense solar eruptions that resulted in an extreme geomagnetic storm and auroral extension, highlighting the need to document and quantify these ...events. This study mainly focuses on their quantification. The source active region (AR 13664) evolved from 113 to 2761 millionths of the solar hemisphere between 4 May and 14 May 2024. AR 13664's magnetic free energy surpassed 1033 erg on 7 May 2024, triggering 12 X-class flares. Multiple interplanetary coronal mass ejections (ICMEs) came out from this AR, accelerating solar energetic particles toward Earth. At least four ICMEs seemingly piled up to disturb the interplanetary space, according to the satellite data and interplanetary scintillation data. The shock arrival at 17:05 UT on 10 May 2024 significantly compressed the magnetosphere down to ~ 5.04 R_E, and triggered a deep Forbush decrease. GOES satellite data and ground-based neutron monitors confirmed a ground-level enhancement from 2 UT to 10 UT on 11 May 2024. The ICMEs induced extreme geomagnetic storms, peaking at a Dst index of -412 nT at 2 UT on 11 May 2024, marking the sixth-largest storm since 1957. The AE and AL indices showed extreme auroral extensions that located the AE/AL stations into the polar cap. We gathered auroral records at that time and reconstructed the equatorward boundary of the visual auroral oval to 29.8{\deg} invariant latitude. We compared naked-eye and camera auroral visibility, providing critical caveats on their difference. We also confirmed global enhancements of storm-enhanced density of the ionosphere.
The newly published spectra of protons and helium over time directly measured in space by the AMS-02 experiment for the period 2011--2017 provide a unique opportunity to calibrate ground-based ...neutron monitors (NMs). Here, calibration of several stable sealevel NMs (Inuvik, Apatity, Oulu, Newark, Moscow, Hermanus, Athens) was performed using these spectra. Four modern NM yield functions were verified: Mi13 (Mishev et al., 2013), Ma16 (Mangeard et al., 2016), CM12 (Caballero-Lopez & Moraal, 2012) and CD00 (Clem & Dorman, 2000), on the basis of the cosmic-ray spectra measured by AMS-02. The Mi13 yield function was found to realistically represent the NM response to galactic cosmic rays. CM12 yield function leads to a small skew in the solar cycle dependence of the scaling factor. In contrast, Ma16 and CD00 yield functions tend to overestimate the NM sensitivity to low-rigidity (<10 GV) cosmic rays. This effect may be important for an analysis of ground level enhancements, leading to a potential underestimate of fluxes of solar energetic particles as based on NM data. The Mi13 yield function is recommended for quantitative analyses of NM data, especially for ground-level enhancements. The validity the force-field approximation was studied, and it was found that it fits well the directly measured proton spectra, within a few % for periods of low to moderate activity and up to ~10% for active periods. The results of this work strengthen and validate the method of the cosmic-ray variability analysis based on the NM data and yield-function formalism, and improves its accuracy.
Our direct knowledge of solar eruptive events is limited to several decades and does not include extreme events, which can only be studied by the indirect proxy method over millennia, or by a large ...number of sun-like stars. There is a gap, spanning 1--2 orders of magnitude, in the strength of events between directly observed and reconstructed ones. Here, we study the proxy-method sensitivity to identify extreme solar particle events (SPEs). First, the strongest directly observed SPE (23-Feb-1956), used as a reference for proxy-based reconstructions, was revisited using the newly developed method. Next, the sensitivity of the cosmogenic-isotope method to detect a reference SPE was assessed against the precision and number of individual isotopic records, showing that it is too weak by a factor \(\approx\)30 to be reliably identified in a single record. Uncertainties of 10Be and 14C data are shown to be dominated by local/regional patterns and measurement errors, respectively. By combining several proxy records, an SPE 4--5 times stronger than the reference one can be potentially detected, increasing the present-day sensitivity by an order of magnitude. This will allow filling the observational gap in SPE strength distribution, thus enriching statistics of extreme events from 3--4 presently known ones to several tens. This will provide a solid basis for research in the field of extreme events, both for fundamental science, viz. solar and stellar physics, and practical applications, such as the risk assessments of severe space-based hazards for the modern technological society.
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