A series of solar energetic particle (SEP) events was observed by the Integrated Science Investigation of the Sun (IS IS) on the Parker Solar Probe (PSP) during the period from 2019 April 18 through ...24. The PSP spacecraft was located near 0.48 au from the Sun on Parker spiral field lines that projected out to 1 au within ∼25° of the near-Earth spacecraft. These SEP events, though small compared to historically large SEP events, were among the largest observed thus far in the PSP mission and provide critical information about the space environment inside 1 au during SEP events. During this period, the Sun released multiple coronal mass ejections (CMEs). One of these CMEs observed was initiated on 2019 April 20 at 01:25 UTC, and the interplanetary CME (ICME) propagated out and passed over the PSP spacecraft. Observations by the Electromagnetic Fields Investigation show that the magnetic field structure was mostly radial throughout the passage of the compression region and the plasma that followed, indicating that PSP did not directly observe a flux rope internal to the ICME, consistent with the location of PSP on the ICME flank. Analysis using relativistic electrons observed near Earth by the Electron, Proton and Alpha Monitor on the Advanced Composition Explorer demonstrates the presence of electron seed populations (40-300 keV) during the events observed. The energy spectrum of the IS IS-observed proton seed population below 1 MeV is close to the limit of possible stationary-state plasma distributions out of equilibrium. IS IS observations reveal the enhancement of seed populations during the passage of the ICME, which likely indicates a key part of the preacceleration process that occurs close to the Sun.
Several fast solar wind streams and stream interaction regions (SIRs) were observed by the Parker Solar Probe (PSP) during its first orbit (2018 September-2019 January). During this time, several ...recurring SIRs were also seen at 1 au at both L1 (Advanced Composition Explorer (ACE) and Wind) and the location of the Solar Terrestrial Relations Observatory-Ahead (STEREO-A). In this paper, we compare four fast streams observed by PSP at different radial distances during its first orbit. For three of these fast stream events, measurements from L1 (ACE and Wind) and STEREO-A indicated that the fast streams were observed by both PSP and at least one of the 1 au monitors. Our associations are supported by simulations made by the ENLIL model driven by GONG-(ADAPT-)WSA, which allows us to contextualize the inner heliospheric conditions during the first orbit of PSP. Additionally, we determine which of these fast streams are associated with an SIR and characterize the SIR properties for these events. From these comparisons, we find that the compression region associated with the fast-speed streams overtaking the preceding solar wind can form at various radial distances from the Sun in the inner heliosphere inside 0.5 au, with the suprathermal ion population (energies between 30 and 586 keV) observed as isolated enhancements suggesting localized acceleration near the SIR stream interface at ∼0.3 au, which is unlike those seen at 1 au, where the suprathermal enhancements extend throughout and behind the SIR. This suprathermal enhancement extends further into the fast stream with increasing distance from the Sun.
Abstract
Energetic electrons of Jovian origin have been observed for decades throughout the heliosphere, as far as 11 au, and as close as 0.5 au, from the Sun. The treatment of Jupiter as a ...continuously emitting point source of energetic electrons has made Jovian electrons a valuable tool in the study of energetic electron transport within the heliosphere. We present observations of Jovian electrons measured by the EPI-Hi instrument in the Integrated Science Investigation of the Sun instrument suite on Parker Solar Probe at distances within 0.5 au of the Sun. These are the closest measurements of Jovian electrons to the Sun, providing a new opportunity to study the propagation and transport of energetic electrons to the inner heliosphere. We also find periods of nominal connection between the spacecraft and Jupiter in which expected Jovian electron enhancements are absent. Several explanations for these absent events are explored, including stream interaction regions between Jupiter and Parker Solar Probe and the spacecraft lying on the opposite side of the heliospheric current sheet from Jupiter, both of which could impede the flow of the electrons. These observations provide an opportunity to gain a greater insight into electron transport through a previously unexplored region of the inner heliosphere.
Summary Background Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute ...stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. Methods We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18–83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8–20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24–48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov , number NCT01436487. Findings The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 99% of 65 patients in the multipotent adult progenitor cell group vs 59 97% of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 95% CI 0·55–2·09, p=0·83). Interpretation Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Funding Athersys Inc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This paper is a phenomenological description of the ionospheric plasma and induced magnetospheric boundary (IMB) response to two different types of upstream solar wind events impacting Mars in March ...2008, at the solar minimum. A total of 16 Mars Express orbits corresponding to five consecutive days is evaluated. Solar TErrestrial RElations Observatory‐B (STEREO‐B) at 1 AU and Mars Express and Mars Odyssey at 1.644 AU detected the arrival of a small transient interplanetary coronal mass ejection (ICME‐like) on the 6 and 7 of March, respectively. This is the first time that this kind of small solar structure is reported at Mars's distance. In both cases, it was followed by a large increase in solar wind velocity that lasted for ~10 days. This scenario is simulated with the Wang‐Sheeley‐Arge (WSA) ‐ ENLIL + Cone solar solar wind model. At Mars, the ICME‐like event caused a strong compression of the magnetosheath and ionosphere, and the recovery lasted for ~3 orbits (~20 h). After that, the fast stream affected the upper ionosphere and the IMB, which radial and tangential motions in regions close to the subsolar point are analyzed. Moreover, a compression in the Martian plasma system is also observed, although weaker than after the ICME‐like impact, and several magnetosheath plasma blobs in the upper ionosphere are detected by Mars Express. We conclude that, during solar minimum and at aphelion, small solar wind structures can create larger perturbations than previously expected in the Martian system.
Key Points
Martian plasma system response to space weather disturbances during low solar activity
Propagation of an ICME‐like transient and a fast solar wind stream from STEREO‐B to Mars
Longitudinal and radial inner boundary movements at Mars
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Urban environments are the primary contributors to global anthropogenic carbon emissions. Because much of the growth in CO2 emissions will originate from cities, there is a need to develop, assess, ...and improve measurement and modeling strategies for quantifying and monitoring greenhouse gas emissions from large urban centers. In this study the uncertainties in an aircraft-based mass balance approach for quantifying carbon dioxide and methane emissions from an urban environment, focusing on Indianapolis, IN, USA, are described. The relatively level terrain of Indianapolis facilitated the application of mean wind fields in the mass balance approach. We investigate the uncertainties in our aircraft-based mass balance approach by (1) assessing the sensitivity of the measured flux to important measurement and analysis parameters including wind speed, background CO2 and CH4, boundary layer depth, and interpolation technique, and (2) determining the flux at two or more downwind distances from a point or area source (with relatively large source strengths such as solid waste facilities and a power generating station) in rapid succession, assuming that the emission flux is constant. When we quantify the precision in the approach by comparing the estimated emissions derived from measurements at two or more downwind distances from an area or point source, we find that the minimum and maximum repeatability were 12 and 52%, with an average of 31%. We suggest that improvements in the experimental design can be achieved by careful determination of the background concentration, monitoring the evolution of the boundary layer through the measurement period, and increasing the number of downwind horizontal transect measurements at multiple altitudes within the boundary layer.
Background & Aims: Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response.
Methods: A placebo-controlled study was conducted in patients with ...active Crohn's disease despite prednisone treatment. Patients were randomized to a 36-hour infusion of azathioprine, 40 mg/kg (51 patients), or placebo (45 patients) followed by oral azathioprine, 2 mg/kg, for 16 weeks. Prednisone was tapered over 5 weeks. The primary outcome measure was complete remission at week 8, defined by discontinuation of prednisone and a Crohn's Disease Activity Index of ≤150 points. Erythrocyte concentrations of the azathioprine active metabolite, 6-thioguanine nucleotide, were measured.
Results: At week 8, 13 patients (25%) were in complete remission in the azathioprine-loaded group compared with 11 patients (24%) in the placebo group. The frequency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, and no differences were found in mean concentrations between the groups. There were no significant differences in the frequency of adverse events between the groups.
Conclusions: A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported.
GASTROENTEROLOGY 1999;117:527-535
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder and is a major risk factor for colorectal cancer (CRC). Hypoxia is a feature of IBD and modulates cellular and mitochondrial ...metabolism. However, the role of hypoxic metabolism in IBD is unclear. Because mitochondrial dysfunction is an early hallmark of hypoxia and inflammation, an unbiased proteomics approach was used to assess the mitochondria in a mouse model of colitis. Through this analysis, we identified a ferrireductase: six-transmembrane epithelial antigen of prostate 4 (STEAP4) was highly induced in mouse models of colitis and in IBD patients. STEAP4 was regulated in a hypoxia-dependent manner that led to a dysregulation in mitochondrial iron balance, enhanced reactive oxygen species production, and increased susceptibility to mouse models of colitis. Mitochondrial iron chelation therapy improved colitis and demonstrated an essential role of mitochondrial iron dysregulation in the pathogenesis of IBD. To address if mitochondrial iron dysregulation is a key mechanism by which inflammation impacts colon tumorigenesis, STEAP4 expression, function, and mitochondrial iron chelation were assessed in a colitis-associated colon cancer model (CAC). STEAP4 was increased in human CRC and predicted poor prognosis. STEAP4 and mitochondrial iron increased tumor number and burden in a CAC model. These studies demonstrate the importance of mitochondrial iron homeostasis in IBD and CRC.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In this trial, 27,564 patients with cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter or higher on statin therapy were assigned to either evolocumab or placebo. At 2.2 years, ...the evolocumab group had a significantly lower rate of major adverse cardiovascular events.
Low-density lipoprotein (LDL) cholesterol is a well-established and modifiable risk factor for cardiovascular disease. Monoclonal antibodies that inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9) have emerged as a new class of drugs that effectively lower LDL cholesterol levels.
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Evolocumab, a member of this class, is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%.
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Genetic studies have shown that carriage of
PCSK9
loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction.
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Moreover, exploratory data from longer-term follow-up in phase 2 and phase 3 trials of PCSK9 inhibitors . . .
MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) measurements taken during passes over Mercury's dayside hemisphere indicate that on four occasions the spacecraft remained in ...the magnetosheath even though it reached altitudes below 300 km. During these disappearing dayside magnetosphere (DDM) events, the spacecraft did not encounter the magnetopause until it was at very high magnetic latitudes, ~66 to 80°. These DDM events stand out with respect to their extremely high solar wind dynamic pressures, Psw ~140 to 290 nPa, and intense southward magnetic fields, Bz ~ −100 to −400 nT, measured in the magnetosheath. In addition, the bow shock was observed very close to the surface during these events with a subsolar altitude of ~1,200 km. It is suggested that DDM events, which are closely associated with coronal mass ejections, are due to solar wind compression and/or reconnection‐driven erosion of the dayside magnetosphere. The very low altitude of the bow shock during these events strongly suggests that the solar wind impacts much of Mercury's sunlit hemisphere during these events. More study of these disappearing dayside events is required, but it is likely that solar wind sputtering of neutrals from the surface into the exosphere maximizes during these intervals.
Key Points
The dayside magnetosphere of Mercury is observed to disappear at MESSENGER's orbit during some coronal mass ejection impacts
The cause appears to be extreme solar wind compression and/or reconnection‐driven erosion of Mercury's dayside magnetic field
The low altitude of the bow shock during these events strongly suggests that Mercury's dayside surface experiences direct solar wind impact
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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