Mercury's Magnetopause and Bow Shock from MESSENGER Magnetometer Observations

We have established the average shape and location of Mercury's magnetopause and bow shock from orbital observations by the MESSENGER Magnetometer. We fit empirical models to midpoints of boundary crossings and probability density maps of the magnetopause and bow shock positions. The magnetopause was fit by a surface for which the position R from the planetary dipole varies as [1 + cos(theta)]-alpha, where theta is the angle between R and the dipole-Sun line, the subsolar standoff distance Rss is 1.45 RM (where RM is Mercury's radius), and the flaring parameter alpha = 0.5. The average magnetopause shape and location were determined under a mean solar wind ram pressure PRam of 14.3 nPa. The best fit bow shock shape established under an average Alfvén Mach number (MA) of 6.6 is described by a hyperboloid having Rss = 1.96 RM and an eccentricity of 1.02. These boundaries move as PRam and MA vary, but their shapes remain unchanged. The magnetopause Rss varies from 1.55 to 1.35 RM for PRam in the range of 8.8-21.6 nPa. The bow shock Rss varies from 2.29 to 1.89 RM for MA in the range of 4.12-11.8. The boundaries are well approximated by figures of revolution. Additional quantifiable effects of the interplanetary magnetic field are masked by the large dynamic variability of these boundaries. The magnetotail surface is nearly cylindrical, with a radius of ~2.7 RM at a distance of 3 RM downstream of Mercury. By comparison, Earth's magnetotail flaring continues until a downstream distance of ~10 Rss

Plasma pressure in Mercury's equatorial magnetosphere derived from MESSENGER Magnetometer observations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95264/1/grl28621-sup-0002-txts01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/95264/2/grl28621.pd

Spatial Distribution and Spectral Characteristics of Energetic Electrons in Mercury's Magnetosphere

The Energetic Particle Spectrometer (EPS) on the MESSENGER spacecraft, in orbit about Mercury since March 2011, has detected bursts of low- and moderate-energy (tens to hundreds of keV) electrons during portions of most orbits. There have been periods when such bursts were observed regularly on every orbit over a span of several weeks, and other periods when electrons were not observed for several days at a time. We have systematically characterized these energetic events on the basis of particle intensity over the 12-month period since MESSENGER began orbital operations. Now that MESSENGER has sampled most Mercury longitudes and local times, it is evident that the largest burst events were either at high northern latitudes or near local midnight. Lower-energy events were also seen near the equator but were mostly absent in both the dawn and dusk local time sectors. The high-latitude and nightside events are similar in particle intensity, spectra, and pitch angle and are interpreted to be the result of acceleration by the same mechanism. Another group of events occurred upstream of Mercury's bow shock. For two examples of this group of upstream events with good pitch angle coverage, the particles were field-aligned and traveling away from the bow shock. This group of events is interpreted to be similar to upstream events found at Earth during which particles are accelerated at the bow shock and subsequently travel upstream into the solar wind

MESSENGER observations of Mercury's magnetic field structure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96229/1/jgre3136.pd

Solar wind forcing at Mercury: WSA‐ENLIL model results

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97237/1/jgra50070.pd

Solar wind forcing at Mercury: WSA-ENLIL model results

Analysis and interpretation of observations from the MESSENGER spacecraft in orbit about Mercury require knowledge of solar wind “forcing” parameters. We have utilized the Wang-Sheeley-Arge (WSA)-ENLIL solar wind modeling tool in order to calculate the values of interplanetary magnetic field (IMF) strength (B), solar wind velocity (V) and density (n), ram pressure (~nV2), cross-magnetosphere electric field (V × B), Alfvén Mach number (MA), and other derived quantities of relevance for solar wind-magnetosphere interactions. We have compared upstream MESSENGER IMF and solar wind measurements to see how well the ENLIL model results compare. Such parameters as solar wind dynamic pressure are key for determining the Mercury magnetopause standoff distance, for example. We also use the relatively high-time-resolution B-field data from MESSENGER to estimate the strength of the product of the solar wind speed and southward IMF strength (Bs) at Mercury. This product VBs is the electric field that drives many magnetospheric dynamical processes and can be compared with the occurrence of energetic particle bursts within the Mercury magnetosphere. This quantity also serves as input to the global magnetohydrodynamic and kinetic magnetosphere models that are being used to explore magnetospheric and exospheric processes at Mercury. Moreover, this modeling can help assess near-real-time magnetospheric behavior for MESSENGER or other mission analysis and/or ground-based observational campaigns. We demonstrate that this solar wind forcing tool is a crucial step toward bringing heliospheric science expertise to bear on planetary exploration programs

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

etuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9–11.4) and 8.9 (90% CI = 2.7–15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6–40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8+ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC

An evaluation of the appropriateness of advice and healthcare contacts made following calls to NHS Direct Wales

Background: An evaluation of NHS Direct Wales (NHSDW), a national telephone-based healthcare advice and information service, was undertaken. A key objective was to describe the actions of callers and assess the appropriateness of advice and healthcare contacts made following calls, results of which are reported here. Methods: Postal questionnaires were sent to consecutive callers to NHSDW in May 2002 and February 2004 to determine 1) callers' actions following calls and 2) their views about the appropriateness of: advice given; and when to seek further care. An independent clinical panel agreed and applied a set of rules about healthcare sites where examinations, investigations, treatments and referrals could be obtained. The rules were then applied to the subsequent contacts to healthcare services reported by respondents and actions were classified in terms of whether they had been necessary and sufficient for the care received. Results: Response rates were similar in each survey: 1033/1897 (54.5%); 606/1204 (50.3%), with 75% reporting contacting NHSDW. In both surveys, nearly half of all callers reported making no further healthcare contact after their call to NHSDW. The most frequent subsequent contacts made were with GPs. More than four fifths of callers rated the advice given - concerning any further care needed and when to seek it - as appropriate (further care needed: survey 1: 673/729, 82.3%; survey 2: 389/421, 92.4%; when to seek further care - survey 1: 462/555, 83.2%; survey 2: n = 295/346, 85.3%). A similar proportion of cases was also rated through the rule set and backed up by the clinical panel as having taken necessary and sufficient actions following their calls to NHSDW (survey 1: 624/729, 80.6%; survey 2: 362/421, 84.4%), with more unnecessary than insufficient actions identified at each survey (survey 1: unnecessary 132/729, 17.1% versus insufficient 11/729, 1.4%; survey 2: unnecessary 47/421, 11.0% versus insufficient 14/421, 3.3%). Conclusion: Based on NHSDW caller surveys responses and applying a transparent rule set to caller actions a large majority of subsequent actions were assessed as appropriate, with insufficient contacts particularly infrequent. The challenge for NHSDW is to reduce the number of unnecessary contacts made following calls to the service, whilst maintaining safety.</p

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC