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Energetic particles constitute an important component of the heliospheric plasma environment. They range from solar energetic particles in the inner heliosphere to the anomalous cosmic rays accelerated at the interface of the heliosphere with the local interstellar medium. Although stochastic acceleration by fluctuating electric fields and processes associated with magnetic reconnection may account for some of the particle populations, the majority are accelerated by the variety of shock waves present in the solar wind. This review focuses on “gradual” solar energetic particle (SEP) events including their energetic storm particle (ESP) phase, which is observed if and when an associated shock wave passes Earth. Gradual SEP events are the intense long-duration events responsible for most space weather disturbances of Earth’s magnetosphere and upper atmosphere. The major characteristics of gradual SEP events are first described including their association with shocks and coronal mass ejections (CMEs), their ion composition, and their energy spectra. In the context of acceleration mechanisms in general, the acceleration mechanism responsible for SEP events, diffusive shock acceleration, is then described in some detail including its predictions for a planar stationary shock, shock modification by the energetic particles, and wave excitation by the accelerating ions. Finally, some complexities of shock acceleration are addressed, which affect the predictive ability of the theory. These include the role of temporal and spatial variations, the distinction between the plasma and wave compression ratios at the shock, the injection of thermal plasma at the shock into the process of shock acceleration, and the nonlinear evolution of ion-excited waves in the vicinity of the shock.

We present a review of Anomalous Cosmic Rays (ACRs), including the history of their discovery and recent insights into their acceleration and transport in the heliosphere. We focus on a few selected topics including a discussion of mechanisms of their acceleration, escape from the heliosphere, their effects on the dynamics of the heliosheath, transport in the inner heliosphere, and their solar cycle dependence. A discussion concerning their name is also presented towards the end of the review. We note that much is known about ACRs and perhaps the term Anomalous Cosmic Ray is not particularly descriptive to a non specialist. We suggest that the more-general term: “Heliospheric Energetic Particles”, which is more descriptive, for which ACRs and other energetic particle species of heliospheric origin are subsets, might be more appropriate.

This paper reviews our current understanding of the acceleration mechanism of anomalous cosmic rays (ACRs). ACRs were first discovered in the early 1970s and soon afterwards it was recognized that they were accelerated interstellar pickup ions that obtained most of their energization in the outer heliosphere. Their observed composition and charge state suggest they are accelerated to over 200 MeV total energy in about a year. Diffusive shock acceleration at the solar-wind termination shock, which provided a natural explanation for spacecraft observations prior to the Voyager crossings of the termination shock in 2004 and 2007, was the long-held paradigm for the acceleration mechanism. But when both Voyagers crossed the shock, the ACR energy spectrum remained modulated, suggesting a source more distant than the shock. While shock acceleration remains a popular mechanism, other ideas have emerged recently to explain the observations. This review focuses on three main acceleration mechanisms that have been proposed: (a) acceleration at the termination shock including new effects such as the global blunt-shape of the shock and large-scale turbulence, (b) acceleration by magnetic reconnection in the heliosheath, and (c) acceleration by diffusive compression acceleration in the heliosheath.

During mid‐May 2024, active region (AR) 13664 produced a series of M‐ and X‐class flares along with several coronal mass ejections (CMEs) that resulted in exceptionally strong aurora at Earth. This study presents in situ solar energetic particle (SEP) ion composition data from Solar Terrestrial Relations Observatory Ahead (STA), Advanced Composition Explorer (ACE), and Parker Solar Probe (PSP) as their magnetic connectivity to AR 13664 varied throughout the event period. Between 08 and 24 May, STA was separated by 12° in longitude from ACE at 0.96 AU. SEP intensities rose gradually due to merged CMEs from AR 13664. On 13 May, an M6 flare was followed by a rapid‐onset SEP event at STA, although velocity dispersion analysis yielded no clear path length or release time. Parker Solar Probe, 95° longitudinally separated from Earth at 0.74 AU, observed gradually increasing SEP intensities beginning 11 May, followed by a jump in both SEP intensity and magnetic field (>100 nT) on 16 May. These early event intervals display stepwise SEP increases, consistent with the passage of successive CMEs. On 20 May, an X16.5 flare from AR 13664 produced an Fe‐rich SEP event observed at all three spacecraft despite their wide longitudinal separations. Throughout the period, Fe/O ratios ranged from <0.01 to >0.8 and increased with energy between 1 and 100 MeV/nuc. This trend deviates from the typical energy‐dependent decrease expected from diffusive shock acceleration and suggests more complex scenarios, possibly involving variable suprathermal seed populations or species‐dependent transport.

Our understanding of the interaction of the large-scale heliosphere with the local interstellar medium (LISM) has undergone a profound change since the very earliest analyses of the problem. In part, the revisions have been a consequence of ever-improving and widening observational results, especially those that identified the entrance of interstellar material and gas into the heliosphere. Accompanying these observations was the identification of the basic underlying physics of how neutral interstellar gas and interstellar charged particles of different energies, up to and including interstellar dust grains, interacted with the temporal flows and electromagnetic fields of the heliosphere. The incorporation of these various basic effects into global models of the interaction, whether focused on neutral interstellar gas and pickup ions, energetic particles such as anomalous and galactic cosmic rays, or magnetic fields and large-scale flows, has profoundly changed our view of how the heliosphere and LISM interact. This article presents a brief history of the conceptual and observation evolution of our understanding of the interaction of the heliosphere with the local interstellar medium, up until approximately 1996.

BackgroundImmunologically cold tumors with an ‘immune desert’ phenotype lack tumor-infiltrating lymphocytes (TILs) and are typically impervious to systemic immune checkpoint blockade (ICB). Intratumoral treatment of tumors with immunomodulatory agents can promote local tumor inflammation leading to improved T cell responses in injected tumors. Addition of systemic ICB increases response frequency and immune-mediated clearance of injected and distal non-injected lesions, and this promising approach is being widely investigated clinically. In this work, we evaluate and characterize the local and systemic antitumor immunotherapeutic activity of VAX014, a novel non-viral targeted oncolytic agent based on recombinant bacterial minicells, following intratumoral administration and in combination with systemic ICB.MethodsThe immunotherapeutic activity of VAX014 following weekly intratumoral administration was investigated in multiple preclinical tumor models with B16F10 murine melanoma serving as the primary model for evaluation of immune desert tumors. Mice bearing a single intradermal tumor were used to evaluate tumor response and overall survival (OS), assess changes in immune cell populations, and explore global changes to immunotranscriptomes of injected tumors. Mice bearing bilateral intradermal tumors were then used to evaluate non-injected tumors for changes in TIL populations and phenotypes, compare immunotranscriptomes across treatment groups, and assess distal non-injected tumor response in the context of monotherapy or in combination with ICB.ResultsVAX014 demonstrated strong immune-mediated tumor clearance of injected tumors coinciding with significantly elevated CD8+ TILs and upregulation of multiple immune pathways essential for antitumor immune responses. Modest activity against distal non-injected immune desert tumors was observed despite elevated levels of systemic antitumor lymphocytes. Combination with systemic CTLA-4 blockade improved survival and elevated TILs but did not improve clearance rates of non-injected tumors. Immunotranscriptomes of non-injected tumors from this treatment combination group exhibited upregulation of multiple immune pathways but also identified upregulation of PD-1. Further addition of systemic PD-1 blockade led to rapid clearance of non-injected tumors, enhanced OS, and provided durable protective immunological memory.ConclusionsIntratumoral administration of VAX014 stimulates local immune activation and robust systemic antitumor lymphocytic responses. Combination with systemic ICB deepens systemic antitumor responses to mediate clearance of injected and distal non-injected tumors.

WEST is an upgrade of the Tore Supra tokamak to test ITER like divertor elements over very long pulses. For the studies of MHD instabilities affected by tungsten impurities, two microwave imaging diagnostics have been developed to obtain density and temperature fluctuation maps. The core reflectometer was refurbished and now measures the core density profiles in few microseconds. Measurements of several thousand profiles in sequence with microsecond dead time (burst mode) will be available in 2019 enabling the reconstruction of density maps with unprecedented time resolution. The major issue for the implementation of an electron cyclotron emission imaging diagnostic was the heat radiation during long pulses on the large vacuum window and the first optics. Two metallic in-vessel mirrors inside the personnel access tube solved this issue. The first mirror can withstand the heat radiation without water cooling, the second mirror redirects the beam toward the personnel access port. The oblique and small view angle of this access eases also the thermomechanical constraints on the vacuum window. As the space between the port flange and the tokamak access lobby was tight, a compact optical enclosure with vertical aligned optics was designed. To ensure a good reproducibility of the mirrors and the optical enclosure positions after a maintenance period and thus avoid re-alignment, different mechanical systems are used to manipulate the mirrors and the optical enclosure and to fine tune their position and their orientation. The first channel covers the low field side and will provide 192 pixel images of temperature fluctuations with 1–2 microsecond time resolution. The installation of the in-vessel mirrors is scheduled during March 2019. Diagnostic qualification tests will be done before the restart of the experiments late May 2019.

We present solar energetic particle events observed at 1 AU from the Sun for which the proton energy spectra at energies between ∼50 keV to ∼1 MeV flatten during a period of at least ∼12 hours prior to the passage of the associated interplanetary shock. The flattening of the proton energy spectra occurs when the source of the particles (presumably the traveling interplanetary shock) is still downwind from the spacecraft and particle intensities are still continuously increasing. The arrival of the shock at the spacecraft is then characterized by a steepening of the spectra, where low-energy proton intensities show a more pronounced enhancement than the high-energy proton intensities. We discuss the mechanisms that may result in this flattening of the spectra in terms of current models presented in the literature.

The physics of collisionless shocks is a very broad topic, which has been well studied for many decades. However, there are a number of important issues which remain unresolved. Moreover, there have been new findings, which cast doubt on well-established ideas. The purpose of this review is to address a subset of unresolved problems in collisionless shock physics from a theoretical and/or numerical modeling point of view. The topics which are addressed are: the nonstationarity of the shock front, the heating and dynamics of electrons through the shock layer, particle diffusion in turbulent electric and magnetic fields, particle acceleration, and the interaction of pickup ions with collisionless shocks.

Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. Although most cases are accompanied by MLL rearrangements and harbor very few somatic mutations, less is known about the genetics of the cases without MLL translocations. We performed the largest exome-sequencing study to date on matched non-cancer DNA from pairs of mothers and IL patients to characterize congenital variation that may contribute to early leukemogenesis. Using the COSMIC database to define acute leukemia-associated candidate genes, we find a significant enrichment of rare, potentially functional congenital variation in IL patients compared with randomly selected genes within the same patients and unaffected pediatric controls. IL acute myeloid leukemia (AML) patients had more overall variation than IL acute lymphocytic leukemia (ALL) patients, but less of that variation was inherited from mothers. Of our candidate genes, we found that MLL3 was a compound heterozygote in every infant who developed AML and 50% of infants who developed ALL. These data suggest a model by which known genetic mechanisms for leukemogenesis could be disrupted without an abundance of somatic mutation or chromosomal rearrangements. This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins.