Space Borne and Ground-Based Observations of Transient Processes Occurring Around Substorm Onset

The combined THEMIS five spacecraft in-situ and ground magnetic and visible camera arrays have advanced considerably our understanding of the causal relationship between midtail plasma flows, transient ionospheric features, and ground magnetic signatures. In particular recent work has shown a connection between equatorward moving visible ionospheric transients and substorm onset, in both white-light and 6300 nm emissions. These observations, together with THEMIS in-situ measurements of bulk flows, provides strict constraints on the sequence of events leading to substorm auroral onset.We first provide a brief summary of these observations, highlighting in particular areas where the two observations differ, and suggest reasons for the differences. Next, by combining the observed correlation of flow and Pi2 waveform with a unified model of global Pi2 generation and substorm current wedge initiation we present a self-consistent description of the dynamical processes and communicative pathways that occur just prior to and during substorm expansion onset

Large-Scale Aspects and Temporal Evolution of Pulsating Aurora

Pulsating aurora is a common phenomenon generally believed to occur mainly in the aftermath of a, substorm, where dim long-period pulsating patches appear. The study determines the temporal and spatial evolution of pulsating events using two THEN IIIS ASI stations, at Gillam (66.18 mlat, 332.78 mlon, magnetic midnight at 0634 UT) and Fort Smith, (67.38 mlat, 306.64 mlon, magnetic midnight at, 0806 UT) along roughly the same invariant latitude. Parameters have been calculated from a database of 74 pulsating aurora events from 119 days of good optical data within the period from September 2007 through March 2008 as identified with the Gillam camera. It is shown that the source region of pulsating aurora drifts or expands eastward, away from magnetic midnight, for pre-midnight onsets and that the spatial evolution is more complicated for post midnight onsets, which has implications for the source mechanism. The most probable duration of a pulsating aurora event is roughly 1.5 hours while the distribution of possible event durations includes many long (several hours) events. This may suggest that pulsating aurora is not strictly a substorm recovery phase phenomenon but rather a persistent, long-lived phenomenon that may be temporarily disrupted by auroral substorms. Observations from the Gillam station show that in fact, pulsating aurora is quite common with the occurrence rate increasing to around 60% for morning hours, with 6910 of pulsating aurora onsets occurring after substorm breakup

A Statistical Analysis of STEVE

There has been an exciting recent development in auroral research associated with the discovery of a new subauroral phenomenon called STEVE (Strong Thermal Emission Velocity Enhancement). Although STEVE has been documented by amateur night sky watchers for decades, it is as yet an unidentified upper atmosphere phenomenon. Observed first by amateur auroral photographers, STEVE appears as a narrow luminous structure across the night sky over thousands of kilometers in the east‐west direction. In this paper, we present the first statistical analysis of the properties of 28 STEVE events identified using Time History of Events and Macroscale Interactions during Substorms (THEMIS) all‐sky imager and the Redline Emission Geospace Observatory (REGO) database. We find that STEVE occurs about 1 hr after substorm onset at the end of a prolonged expansion phase. On average, the AL index magnitude is larger and the expansion phase has a longer duration for STEVE events compared to subauroral ion drifts or substorms. The average duration for STEVE is about 1 hr, and its latitudinal width is ~20 km, which corresponds to ~¼ of the width of narrow auroral structures like streamers. STEVE typically has an equatorward displacement from its initial location of about 50 km and a longitudinal extent of 2,145 km

Persistent, Widespread Pulsating Aurora: A Case Study

Observations of a pulsating aurora event occurring on February 11, 2008, using the THEMIS all-sky imager array, indicate a spatially and temporally continuous event with a duration of greater than 15 hours and covering a region with a maximum size of greater than 9 hours MLT. The optical pulsations are at times locally interrupted or drowned out by auroral substorm activity, but are observed in the same location once the discrete aurora recedes. The pulsations following the auroral breakup appear to be brighter and have a larger patch size than pre-substorm. This suggests that, while the onset of pulsating aurora is not necessarily dependent upon a substorm precursor, the pulsations are affected and possibly enhanced by the substorm process. The long duration of such pulsating aurora events, enduring for several hours without interruption, is far longer than the expected recovery phase of a substorm, suggesting that pulsating aurora is not strictly a recovery phase phenomenon

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

SMILE: A joint ESA/CAS mission to investigate the interaction between the solar wind and Earth's magnetosphere

The Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) is a collaborative science mission between ESA and the Chinese Academy of Sciences (CAS). SMILE is a novel self-standing mission to observe the coupling of the solar wind and Earth's magnetosphere via X-Ray imaging of the solar wind -- magnetosphere interaction zones, UV imaging of global auroral distributions and simultaneous in-situ solar wind, magnetosheath plasma and magnetic field measurements. The SMILE mission proposal was submitted by a consortium of European, Chinese and Canadian scientists following a joint call for mission by ESA and CAS. It was formally selected by ESA's Science Programme Committee (SPC) as an element of the ESA Science Program in November 2015, with the goal of a launch at the end of 2021. In order to achieve its scientific objectives, the SMILE payload will comprise four instruments: the Soft X-ray Imager (SXI), which will spectrally map the Earth's magnetopause, magnetosheath and magnetospheric cusps; the UltraViolet Imager (UVI), dedicated to imaging the auroral regions; the Light Ion Analyser (LIA) and the MAGnetometer (MAG), which will establish the solar wind properties simultaneously with the imaging instruments. We report on the status of the mission and payload developments and the findings of a design study carried out in parallel at the concurrent design facilities (CDF) of ESA and CAS in October/November 2015. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

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

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). METHODS: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage. RESULTS: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed. CONCLUSIONS: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01862003