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Schumann resonances are electromagnetic resonances generally associated with lightning. If they exist on Mars, Schumann resonances are expected to resonate within the ionospheric cavity at a fundamental frequency of 7–14 Hz. We conducted a search for 5–16 Hz signals below 400 km in magnetic field data from the Mars Global Surveyor (MGS) and Mars Atmosphere and Volatile Evolution (MAVEN) missions. Fast Fourier transforms and wavelet analysis were used to find these signals and investigate their characteristics further. We discuss our null results and the required steps forward to continue and improve this search. Future studies will require higher sensitivity instruments and would benefit from additional missions that reach into the lower ionosphere of Mars.

We present an event observed by Parker Solar Probe (PSP) at ∼0.2 au on 2022 March 2 in which imaging and in situ measurements coincide. During this event, PSP passed through structures on the flank of a streamer blowout coronal mass ejection (CME) including an isolated flux tube in front of the CME, a turbulent sheath, and the CME itself. Imaging observations and in situ helicity and principal variance signatures consistently show the presence of flux ropes internal to the CME. In both the sheath and the CME interval, the distributions are more isotropic, the spectra are softer, and the abundance ratios of Fe/O and He/H are lower than those in the isolated flux tube, and yet elevated relative to typical plasma and solar energetic particle abundances. These signatures in the sheath and the CME indicate that both flare populations and those from the plasma are accelerated to form the observed energetic particle enhancements. In contrast, the isolated flux tube shows large streaming, hard spectra, and large Fe/O and He/H ratios, indicating flare sources. Energetic particle fluxes are most enhanced within the CME interval from suprathermal through energetic particle energies (∼keV to >10 MeV), indicating particle acceleration, as well as confinement local to the closed magnetic structure. The flux-rope morphology of the CME helps to enable local modulation and trapping of energetic particles, in particular along helicity channels and other plasma boundaries. Thus, the CME acts to build up energetic particle populations, allowing them to be fed into subsequent higher-energy particle acceleration throughout the inner heliosphere where a compression or shock forms on the CME front.

On 2022 September 5, Parker Solar Probe (Parker) observed a large solar energetic particle (SEP) event at the unprecedented distance of only 15 R _S from the Sun. The observations from the Integrated Science Investigation of the Sun (IS⊙IS) obtained over the course of this event are remarkably rich, and an overview is presented here. IS⊙IS is capable of measuring ions from 20 keV to over 100 MeV nuc ^−1 and electrons from 30 keV to 6 MeV; here, we primarily focus on the proton and helium measurements above 80 keV. Among the surprising results are evidence of inverse velocity dispersion at energies above 1 MeV during the onset of the event, a sharp decrease in the energetic particle intensities at all energies at the interplanetary shock crossing, and repeated short durations of highly anisotropic sunward flow. Many changes in the SEP intensities, anisotropy, and spectral steepness are coincident with solar wind structure boundaries identified using the Parker solar wind magnetic field and plasma data. However, there are significant changes that are not correlated with any clearly visible solar wind variation. The observations presented here serve as an introduction to a complex event with numerous opportunities for future, more in-depth studies.

Parker Solar Probe (PSP) observations of a small dispersive event on 2022 February 27 and 28 indicate scatter-free propagation as the dominant transport mechanism between the low corona and greater than 35 solar radii. The event occurred during unique orbital conditions that prevailed along specific flux tubes that PSP encountered repeatedly between 25 and 35 R _s during outbound orbit 11. This segment of the PSP orbit exhibits almost stationary angular motion relative to the rotating solar surface, such that in the rotating frame, PSP’s motion is essentially radial. The time dispersion often observed in impulsive solar energetic particle (SEP) events continues in this case down to velocities including the core solar-wind ion velocities. Especially at the onset of this event, the ^3 He content is much larger than the usual SEP abundances seen in the energy range from ∼100 keV to several MeV for helium. Later in the event, iron is enhanced. The compositional signatures suggest this to be an example of an acceleration mechanism for generating the seed energetic particles required by shock (or compression) acceleration models in SEP events to account for the enrichment of various species above solar abundances in such events. A preliminary search of similar orbital conditions over the PSP mission has not revealed additional such events, although favorable conditions (isolated impulsive acceleration and well-ordered magnetic field connection with minimal magnetic field fluctuation) that would be required are infrequently realized, given the small fraction of the PSP trajectory that meets these observation conditions.

On 2022 February 15–16, multiple spacecraft measured one of the most intense solar energetic particle (SEP) events observed so far in Solar Cycle 25. This study provides an overview of interesting observations made by multiple spacecraft during this event. Parker Solar Probe (PSP) and BepiColombo were close to each other at 0.34–0.37 au (a radial separation of ∼0.03 au) as they were impacted by the flank of the associated coronal mass ejection (CME). At about 100° in the retrograde direction and 1.5 au away from the Sun, the radiation detector on board the Curiosity surface rover observed the largest ground-level enhancement on Mars since surface measurements began. At intermediate distances (0.7–1.0 au), the presence of stream interaction regions (SIRs) during the SEP arrival time provides additional complexities regarding the analysis of the distinct contributions of CME-driven versus SIR-driven events in observations by spacecraft such as Solar Orbiter and STEREO-A, and by near-Earth spacecraft like ACE, SOHO, and WIND. The proximity of PSP and BepiColombo also enables us to directly compare their measurements and perform cross-calibration for the energetic particle instruments on board the two spacecraft. Our analysis indicates that energetic proton measurements from BepiColombo and PSP are in reasonable agreement with each other to within a factor of ∼1.35. Finally, this study introduces the various ongoing efforts that will collectively improve our understanding of this impactful, widespread SEP event.

The Voyager 2 crossing of the termination shock indicated that most of the upstream energy from the thermal solar wind ions was transferred to pickup ions (PUIs) and other energetic particles downstream of the shock. We use hybrid simulations at the termination shock for the Voyager 2, flank, and tail directions to evaluate the distributions of different ion species downstream of the shock over the energy range of 0.52–55 keV. Here, we extend the work of Gkioulidou et al., which showed an energy-dependent discrepancy between modeled and energetic neutral atom (ENA) observations, and fit distributions to a hybrid model to show that a population of PUIs accelerated via diffusive shock acceleration (DSA) to become low-energy anomalous cosmic rays (ACRs) can bridge the gap between modeled and observed ENA fluxes. Our results with the inclusion of DSA via hybrid fitting give entirely new and novel evidence that DSA at the termination shock is likely to be an important physical process. These ACRs carry a significant fraction of the energy density at the termination shock (22%, 13%, and 19% in the Voyager 2, flank, and tail directions, respectively). Using these ACRs in global ENA modeling of the heliosphere from 0.52 to 55 keV, we find that scaling factors as large as 1.8–2.5 are no longer required to match ENA observations at energies of ∼1–4 keV. Large discrepancies between modeled and observed ENAs only remain over energies of 4–20 keV, indicating that there may be a further acceleration mechanism in the heliosheath at these energies.

The shape of the heliosphere is currently under active debate. Energetic neutral atoms (ENAs) offer the best method for investigating the global structure of the heliosphere. To date, the Interstellar Boundary Explorer (IBEX) and the Ion and Neutral Camera (INCA) that was on board Cassini provide the only global ENA observations of the heliosphere. While extensive modeling has been done at IBEX-Hi energies (0.52–6 keV), no global ENA modeling has been conducted for INCA energies (5.2–55 keV). Here, we use an ENA model of the heliosphere based on hybrid results that capture the heating and acceleration of pickup ions (PUIs) at the termination shock to compare modeled global ENA results with IBEX-Hi and INCA observations using both a long- and short-tail model of the heliosphere. We find that the modeled ENA results for the two heliotail configurations produce similar results from the IBEX-Hi through the INCA energies. We conclude from our modeled ENAs, which only include PUI acceleration at the termination shock, that ENA observations in currently available energy ranges are insufficient for probing the shape and length of the heliotail. However, as a prediction for the future IMAP-Ultra mission (3–300 keV) we present modeled ENA maps at 80 keV, where the cooling length (∼600 au) is greater than the distance where the long- and short-heliotail models differ (∼400 au), and find that IMAP-Ultra should be able to identify the shape of the heliotail, predicting differences in the north lobe to downwind flux ratio between the models at 48%.

We compare hybrid (kinetic proton, fluid electron) and particle-in-cell (kinetic proton, kinetic electron) simulations of the solar wind termination shock with parameters similar to those observed by Voyager 2 during its crossing. The steady-state results show excellent agreement between the downstream variations in the density, plasma velocity, and magnetic field. The quasi-perpendicular shock accelerates interstellar pickup ions to a maximum energy limited by the size of the computational domain, with somewhat higher fluxes and maximal energies observed in the particle-in-cell simulation, likely due to differences in the cross-shock electric field arising from electron kinetic-scale effects. The higher fluxes may help address recent discrepancies noted between observations and large-scale hybrid simulations.

We study the transport of fast charged particles, such as galactic cosmic rays, in the very local interstellar medium (VLISM), which is currently being explored by the two Voyager space probes. Guided by the observations of magnetic fluctuations, the paper develops a simple theoretical framework for computing scattering rates and spatial diffusion coefficients that can be used to model cosmic-ray transport in the VLISM. The local interstellar magnetic turbulence is represented as a superposition of (a) Alfvénic, (b) transverse 2D, and (c) longitudinal components obeying distinctive geometry rules in the plasma frame. The model is based on the weakly nonlinear formalism where particle trajectory’s deviation from the unperturbed helix is caused primarily by guiding-center diffusion across the mean magnetic field. The transverse component plays the dominant role in perpendicular diffusion, while the longitudinal component has only a minor effect. Pitch-angle scattering is extremely weak in the VLISM, so that cosmic-ray transport can be considered essentially scatter-free on heliospheric scales. We test our theoretical model with the help of particle orbit simulations to find good agreement for perpendicular diffusion. We also find that cosmic rays disperse faster than in a conventional random walk (diffusive) process if the turbulence power spectrum contains fluctuations whose wavelength is larger than the size of the heliosphere.

We construct artificial "software" spacecraft consisting of magnetometers and 3D thermal and energetic ion detectors. Four such spacecraft are "flown" through a 1D simulation of a quasi-parallel shock. We analyze the resulting time series from the spacecraft, and then use the more complete simulational information to evaluate our interpretations based on the limited times series information. The separation strategy used, with two closely spaced spacecraft pairs separated by a large distance, was helpful in the interpretation, since a variety of important processes operate over several different scale lengths. This work highlights the ability to draw inferences about spatially and temporally varying phenomena based on multiple-spacecraft time series data, and suggests that many spacecraft configurations which bear little resemblance to the classic Cluster tetrahedron may be necessary when multiple scale lengths are present.

We construct artificial "software" spacecraft consisting of magnetometers and 3D thermal and energetic ion detectors. Four such spacecraft are "flown" through a 1D simulation of a quasi-parallel shock. We analyze the resulting time series from the spacecraft, and then use the more complete simulational information to evaluate our interpretations based on the limited times series information. The separation strategy used, with two closely spaced spacecraft pairs separated by a large distance, was helpful in the interpretation, since a variety of important processes operate over several different scale lengths. This work highlights the ability to draw inferences about spatially and temporally varying phenomena based on multiple-spacecraft time series data, and suggests that many spacecraft configurations which bear little resemblance to the classic Cluster tetrahedron may be necessary when multiple scale lengths are present.

Purpose: Many improvements in head and neck cancer (HNC) outcomes are related to optimization of radiation therapy (RT) dose, fractionation, normal-tissue sparing, and technology. However, prior work has shown that the literature of randomized controlled trials is dominated by industry-sponsored trials that have lower rates of incorporating RT. We characterized HNC clinical trials, hypothesizing that RT-specific research questions may be relatively underrepresented among HNC randomized controlled trials. Methods and Materials: A web query of all open interventional trials on www.ClinicalTrials.gov was performed using search terms “head and neck cancer” and specific HNC subsites. Trial details were captured including the modality used, principal investigator (PI) specialty, funding, and whether the study tested a RT-modality specific hypothesis. Chi-square testing and logistic regression were used to compare groups. Results: There were 841 open HNC trials, including definitive (47.6%) and recurrent/metastatic (41.9%) populations. Most trials (71.7%) were phase I or nonrandomized phase II studies, rather than phase III or randomized phase II (28.3%). Among single-arm studies, most (79.6%) incorporated systemic therapy (ST), and fewer (25.2%) incorporated RT. Even fewer phase III and randomized phase II trials tested an RT-specific hypothesis (11.1%), compared with ST-related hypotheses (77.1%; P < .001); trials were more likely to test an RT-hypothesis if the study PI was a radiation oncologist (20.9% vs 6.0%; P < .001). Among RT trials, most early-phase studies tested novel modalities (eg, stereotactic body radiation therapy, proton therapy), whereas most later-phase studies tested dose and fractionation. RT-focused trials had low rates of federal (10.4%) or industry (2.6%) funding. Conclusions: RT-specific research hypotheses are a minority of phase II-III HNC trials, which mostly focus on incorporating ST in the definitive or recurrent/metastatic setting and have higher rates of industry funding. Radiation oncologist PI leadership and increased nonindustry funding access may ensure that RT-specific hypotheses are incorporated into trial design.

The refinement of tightly regulated prokaryotic expression systems that permit functional expression of toxic recombinant proteins is a continually evolving process. Unfortunately, the current best promoter options are either tightly repressed and produce little protein, or produce substantial protein but lack the necessary repression to avoid mutations stimulated by leaky expression in the absence ofinducer. In this report, we present three novel prokaryotic expression constructs that are tightly regulated by L-rhamnose and D-glucose. These expression vectors utilize the Escherichia coli rhaT promoter and corresponding regulatory genes to provide titratable, high-level protein yield without compromising clone integrity. Together, these components may enable the stable cloning and functional expression of otherwise toxic proteins.

Background Immunologically 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.Methods The 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.Results VAX014 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.Conclusions Intratumoral 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.