Distinct Scaling Regimes of Energy Release Dynamics in the Nighttime Magnetosphere

Based on a spatiotemporal analysis of POLAR UVI images, we show that the auroral emission events that initiate equatorward of the isotropic boundary (IB) obtained from a time-dependent empirical model, have systematically steeper power-law slopes of energy, power, area and lifetime probability distributions compared to the events that initiate poleward of the IB. The low-latitude group of events contains a distinct subpopulation of substorm-scale disturbances violating the power-law behavior, while the high latitude group is described by nearly perfect power-law statistics over the entire range of scales studied. The results obtained indicate that the inner and outer portions of the plasma sheet are characterized by substantially different scaling regimes of bursty energy dissipation suggestive of different physics in these regions.Comment: 11 pages, 2 figures, 2 table

Quasi-parallel electron beams and their possible application in inferring the auroral arc's root in the magnetosphere

In this study we investigate the upgoing electron beams at the topside ionosphere and their counterpart feature, the bidirectional quasi-parallel electron beams (QPEB) in the equatorial magnetosphere, with highlight on their potential application in estimating the location of the arc's root (AR) in the magnetotail central plasma sheet (CPS). We infer from FAST data that the upgoing electron beam is often found in the equatorward vicinity of the inverted-V arc. On the premise of such a scenario, we propose a method to estimate the location of the AR from available magnetospheric measurements by assuming that the tailward boundary of the QPEB demarcates the earthward boundary of the AR. We report two events with THEMIS observations of QPEBs in the magnetotail CPS, and demonstrate how to use the QPEB features, together with the magnetic signatures of the current circuit constituted by the QPEB and arc, to estimate the earthward boundary of the AR. We find that the estimated earthward boundary of AR is situated at the periphery of a quasi-dipolar magnetosphere characterized by a strong Bz gradient. This finding is consistent with previously existing proposals on the possible AR location in the tail (e.g., Lui and Burrows, 1978; Sergeev et al., 2012)

Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients

Gemcitabine and treosulfan are DNA-damaging agents. Preclinical studies suggest that synergism exists when melanoma cells are exposed to both drugs concurrently. We conducted a phase I trial in advanced melanoma patients to determine the optimal dose of gemcitabine to be combined with treosulfan. Cohorts of three patients received increasing doses of gemcitabine, commencing at 0.5 g m−2, followed by a fixed dose of 5.0 g m−2 treosulfan on day one of a 21-day cycle. Patients alternately received a first cycle of single-agent gemcitabine or treosulfan before subsequent cycles of both drugs. Peripheral blood lymphocytes were collected in cycles 1 and 2 at various time points until 48 h post-treatment. The single-cell gel electrophoresis (Comet) assay was used to measure chemotherapy-induced DNA damage. A total of 27 patients were enrolled, no objective responses were observed, but two uveal melanoma patients had minor responses. Dose-limiting myelosuppression was reached at 3.0 g m−2 gemcitabine. DNA single-strand breaks were detected 4 h post-gemcitabine, repaired by 24 h. DNA interstrand crosslinks were detected 4 h post-treosulfan, fully removed by 48 h. Following combination chemotherapy, treosulfan-induced DNA crosslinks persisted, still being detectable 48 h post-treatment, supporting the hypothesis that gemcitabine potentiates treosulfan-induced cytotoxicity. The recommended regimen for further study is 2.5 g m−2 gemcitabine combined with 5.0 g m−2 treosulfan

Longitudinal development of a substorm brightening arc

We present simultaneous THEMIS-ground observations of longitudinal (eastward) extension of a substorm initial-brightening arc at Gillam (magnetic latitude: 65.6°) at 08:13 UT on 10 January 2008. The speed of the eastward arc extension was ~2.7 km/s. The extension took place very close to the footprints of the longitudinally separated THEMIS E and D satellites at ~12 <I>R<sub>E</sub></I>. The THEMIS satellites observed field dipolarization, weak earthward flow, and pressure increase, which propagated eastward from E to D at a speed of ~50 km/s. The THEMIS A satellite, located at 1.6 <I>R<sub>E</sub></I> earthward of THEMIS E, observed fluctuating magnetic field during and after the dipolarization. The THEMIS E/D observations suggest that the longitudinal extension of the brightening arc at substorm onset is caused by earthward flow braking processes which produce field dipolarization and pressure increase propagating in longitude in the near-earth plasma sheet

Interhemispheric comparison of GPS phase scintillation at high latitudes during the magnetic-cloud-induced geomagnetic storm of 5–7 April 2010

Arrays of GPS Ionospheric Scintillation and TEC Monitors (GISTMs) are used in a comparative scintillation study focusing on quasi-conjugate pairs of GPS receivers in the Arctic and Antarctic. Intense GPS phase scintillation and rapid variations in ionospheric total electron content (TEC) that can result in cycle slips were observed at high latitudes with dual-frequency GPS receivers during the first significant geomagnetic storm of solar cycle 24 on 5–7 April 2010. The impact of a bipolar magnetic cloud of north-south (NS) type embedded in high speed solar wind from a coronal hole caused a geomagnetic storm with maximum 3-hourly Kp = 8- and hourly ring current Dst =−73 nT. The interhemispheric comparison of phase scintillation reveals similarities but also asymmetries of the ionospheric response in the northern and southern auroral zones, cusps and polar caps. In the nightside auroral oval and in the cusp/cleft sectors the phase scintillation was observed in both hemispheres at about the same times and was correlated with geomagnetic activity. The scintillation level was very similar in approximately conjugate locations in Qiqiktarjuaq (75.4° N; 23.4° E CGM lat. and lon.) and South Pole (74.1° S; 18.9° E), in Longyearbyen (75.3° N; 111.2° E) and Zhongshan (74.7° S; 96.7° E), while it was significantly higher in Cambridge Bay (77.0° N; 310.1° E) than at Mario Zucchelli (80.0° S; 307.7° E). In the polar cap, when the interplanetary magnetic field (IMF) was strongly northward, the ionization due to energetic particle precipitation was a likely cause of scintillation that was stronger at Concordia (88.8° S; 54.4° E) in the dark ionosphere than in the sunlit ionosphere over Eureka (88.1° N; 333.4° E), due to a difference in ionospheric conductivity. When the IMF tilted southward, weak or no significant scintillation was detected in the northern polar cap, while in the southern polar cap rapidly varying TEC and strong phase scintillation persisted for many hours. This interhemispheric asymmetry is explained by the difference in the location of solar terminator relative to the cusps in the Northern and Southern Hemisphere. Solar terminator was in the immediate proximity of the cusp in the Southern Hemisphere where sunlit ionospheric plasma was readily convected into the central polar cap and a long series of patches was observed. In contrast, solar terminator was far poleward of the northern cusp thus reducing the entry of sunlit plasma and formation of dense patches. This is consistent with the observed and modeled seasonal variation in occurrence of polar cap patches. The GPS scintillation and TEC data analysis is supported by data from ground-based networks of magnetometers, riometers, ionosondes, HF radars and all-sky imagers, as well as particle flux measurements by DMSP satellites

An interhemispheric comparison of GPS phase scintillation with auroral emission observed at the South Pole and from the DMSP satellite

The global positioning system (GPS) phase scintillation caused by highlatitude ionospheric irregularities during an intense high-speed stream (HSS) of the solar wind from April 29 to May 5, 2011, was observed using arrays of GPS ionospheric scintillation and total electron content monitors in the Arctic and Antarctica. The one-minute phase-scintillation index derived from the data sampled at 50 Hz was complemented by a proxy index (delta phase rate) obtained from 1-Hz GPS data. The scintillation occurrence coincided with the aurora borealis and aurora australis observed by an all-sky imager at the South Pole, and by special sensor ultraviolet scanning imagers on board satellites of the Defense Meteorological Satellites Program. The South Pole (SP) station is approximately conjugate with two Canadian High Arctic Ionospheric Network stations on Baffin Island, Canada, which provided the opportunity to study magnetic conjugacy of scintillation with support of riometers and magnetometers. The GPS ionospheric pierce points were mapped at their actual or conjugate locations, along with the auroral emission over the South Pole, assuming an altitude of 120 km. As the aurora brightened and/or drifted across the field of view of the all-sky imager, sequences of scintillation events were observed that indicated conjugate auroras as a locator of simultaneous or delayed bipolar scintillation events. In spite of the greater scintillation intensity in the auroral oval, where phase scintillation sometimes exceeded 1 radian during the auroral break-up and substorms, the percentage occurrence of moderate scintillation was highest in the cusp. Interhemispheric comparisons of bipolar scintillation maps show that the scintillation occurrence is significantly higher in the southern cusp and polar cap

Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

PURPOSE Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL. METHODS Patients age ≥ 16 years with r/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years. RESULTS Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had ≥ 50% bone marrow blasts. No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease–negative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4-84.4) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies/µg genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up. CONCLUSION AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL