The IPC-81 cell line is derived from the transplantable BNML model of acute myelogenic leukemia (AML), known to be a reliable predictor of the clinical efficiency of antileukemic agents, like the first-line AML anthracycline drug daunorubicin (DNR). We show here that cAMP acted synergistically with DNR to induce IPC cell death. The DNR-induced death differed from that induced by cAMP by (1) not involving Bim induction, (2) being abrogated by GSK3β inhibitors, (3) by being promoted by the HSP90/p23 antagonist geldanamycin and truncated p23 and (4) by being insensitive to the CRE binding protein (CREB) antagonist ICER and to cyclin-dependent protein kinase (CDK) inhibitors. In contrast, the apoptosis induced by cAMP correlated tightly with Bim protein expression. It was abrogated by Bim (BCL2L11) downregulation, whether achieved by the CREB antagonist ICER, by CDK inhibitors, by Bim-directed RNAi, or by protein synthesis inhibitor. The forced expression of BimL killed IPC-81(WT) cells rapidly, Bcl2-overexpressing cells being partially resistant. The pivotal role of CREB and CDK activity for Bim transcription is unprecedented. It is also noteworthy that newly developed cAMP analogs specifically activating PKA isozyme I (PKA-I) were able to induce IPC cell apoptosis. Our findings support the notion that AML cells may possess targetable death pathways not exploited by common anti-cancer agents.
Newly acquired, sequentially spaced, high-resolution near-infrared spectra across the central section of crater Copernicus' interior have been analyzed using a range of complementary techniques and indexes.We have developed a new interpretative method based on a multiple stage normalization process that appears to both confirm and expand on previous mineralogical estimations and mapping. In broad terms, the interpreted distribution of the principle mafic species suggests an overall composition of surface materials dominated by calcium-poor pyroxenes and minor olivine but with notable exceptions: the southern rim displays strong ca-rich pyroxene absorption features and five other locations, the uppermost northern crater wall, opposite rim sections facing the crater floor, and the central peak Pk1 and at the foot of Pk3, show instead strong olivine signatures.We also propose impact glass an alternative interpretation to the source of the weak but widespread olivine-like spectral signature found in low-reflectance samples, since it probably represents a major regolith constituent and component in large craters such as Copernicus.The high quality and performance of the SIR-2 data allows for the detection of diagnostic key mineral species even when investigating spectral samples with very subdued absorption features, confirming the intrinsic high-quality value of the returned data. (C) 2011 Elsevier Inc. All rights reserved.
This paper presents a computer architecture developed for the instrument control unit (ICU) of the Spectrometer Infrared 2 (SIR-2) instrument onboard the Chandrayaan-1 mission to the Moon. Characteristic features of this architecture are its high autonomy, its high reliability, and its high performance, which are obtained by the following methods: 1) adopting state-of-the-art digital-construction techniques using one single radiation-tolerant field-programmable gate array for implementing an embedded system with a 32-bit central processing unit, commercial intellectual-property cores, and custom-specified logic; 2) implementing two independent communication buses, one for instrument commanding and instrument health monitoring and another one for transferring scientific and housekeeping data to the spacecraft; 3) implementing simple and well-arranged hardware, firmware, and software; and 4) implementing in-flight software-reconfiguration capabilities available from ground command. The SIR-2 ICU performs data acquisition, data processing, and temperature regulation. Per-spectrum averaging and per-pixel oversampling are supported to reduce measurement noise. A temperature regulator for the instrument sensor unit is also implemented, with the purpose of reducing dark current noise from the detector. The embedded real-time software is implemented as a multirate cyclic executive with interrupts. Five different tasks are maintained, running with a 10-ms base cycle time. A safe mode is implemented in the boot-loader, allowing in-flight software patching through the MIL-STD-1553B bus. The advanced features of this architecture make it an excellent choice for the control unit of the scientific SIR-2 instrument, compared with architectures from previous heritage.
Chandrayaan-1, the first Indian mission to the Moon, will provide an opportunity for in situ lunar observations over a two-year period from a 100 km polar orbit. A comprehensive suite of onboard instruments will include the SIR-2 near-infrared grating spectrometer. SIR-2, a pointing spectrometer, will observe the Moon in the spectral range 900-2400 nm, with a unique spectral resolution of 6 nm over a wide range of phase angles. The high resolution SIR-2 observations, particularly of the lunar far side and polar region, are expected to have a large impact on our understanding of the mineralogy and composition of the Moon.
Measurements with the Magnetospheric Ion Composition Spectrometer (MICS) onboard the polar orbiting Swedish satellite VIKING clearly show a strong asymmetry between the dusk‐ and dawnside ion distributions obtained after the onset of a magnetic storm on May 2‐3, 1986. The eveningside of the inner ring current region is quickly filled by protons with energies of some tens of keV. The morningside continues for several hours to show the quiet‐time inner ring current proton spectra in which protons below ∼100 keV have been removed due to charge‐exchange processes. The data obtained at high latitudes will be compared with measurements of the CHEM instrument on the AMPTE/CCE spacecraft near the equatorial plane. The observations are discussed in context of the convection of injected ions into the inner magnetosphere during magnetically active periods.
A pulsation event with a period of 6–8 min has been observed simultaneously by the geostationary satellite GEOS 2 and two balloons located in the area magnetically conjugate to the satellite. The balloons were equipped with electric field and X ray instruments. The pulsation event occurred in the magnetic local time sector 0600–1100 determined by ground‐based measurements. The satellite instruments observed the signature of a magnetosonic wave having a radially inward directed Poynting vector. The electric field associated with the wave was closely correlated with the electric field detected by the balloon instrument near the footprint of the magnetic field line through GEOS 2. The ground‐based observations show that the wave phase pattern was north‐south striated and that it moved from east to west. The balloon X ray measurements showed a strongly pulsating particle precipitation, in close correlation with the intensity of the energetic electron flux and the VLF electromagnetic radiation measured on the satellite, suggesting a wave‐particle interaction process. The pulsations seem to originate beyond the geosynchronous orbit. The study demonstrates the usefulness of simultaneous measurements with a geostationary satellite and instruments in the ground area magnetically conjugate to the satellite.
This chapter contains sections titled: Telemetry Information Description of Payloads MEP - Multiexperiment Payload SAP - Special Auroral X-Ray Payload CEP - Payload for the Combined Measurements of Omnidirectional X-rays and Electric Fields XOP - Payload for Measuring Auroral X-rays Only Event on June 23, 1979 at ˜ 21 UT
Coordinated observations of electron precipitation via X ray measurements from three simultaneously flown balloons, and of energetic particles at the geosynchronous satellite GEOS 2, were used to investigate variations of the distribution of energetic charged particles at the onset of a magnetospheric substorm on July 3, 1979. The electron precipitation started shortly after the onset of the substorm. It was accompanied by the injection of energetic electrons and ions at GEOS 2. The intensity of the injected particles increased without any observable energy dispersion. The electron pitch angle distributions were characterized by strong intensity increases toward the geomagnetic field direction. Azimuthal anisotropies of the ion intensity around the geomagnetic field lines occurred and were interpreted as spatial density gradients. The temporal variations of the gradients indicated that a region of intense ion fluxes was located near the satellite during the period of field‐aligned electron fluxes. It is concluded that the electron precipitation was directly related to the injection of electrons and that the injection took place well earthward of the near‐earth reconnection region postulated in some substorm models. A possible mechanism that would connect injection to reconnection is proposed. The influence of parallel electric fields on the particle distribution is discussed.
Observations of electron precipitation via X-ray measurements with balloon-borne instruments and electron measurements onboard the geostationary satellite GEOS-2 are used to analyse the relationship between electron precipitation and magnetospheric processes at the onset of a magnetospheric substorm. The observations are interpreted in terms of electron scattering and different acceleration processes at the outer boundary of the plasma sheet and simultaneous movements of its inner boundary.
Simultaneous balloon recordings of auroral-zone X-rays from precipitating electrons, covering a range of L-values from ≈5 to ≈7.5, are presented. The precipitation event was observed in the early morning sector (from about 0200 to 0500 local magnetic time), and was associated with a negative magnetic bay. Before the bay, precipitation associated with the growth phase of the substorm was observed at high L-values. After bay onset, precipitation was observed over the whole range of L-values covered, but with a delayed onset in the southern part of the precipitation region as compared with the onset of cosmic noise absorption in the local midnight sector. At high L-values the X-ray flux was completely unstructured and drizzle-like, both before and after bay onset. At low L-values, where precipitation occurred only after bay onset, the event was splash-like with X-ray bursts of typically 4–6 sec duration apparently rising out of the cosmic-ray background. The precipitation bursts had spatial extensions of 300–400 km. They were accompanied by weak magnetic impulses which were, both temporally and spatially, closely related to the X-ray bursts. The unstructured precipitation at high L-values was apparently associated with and extending along the auroral electrojet, presumably representing freshly accelerated particles. The highly structured and burst-like precipitation to the south seems to have come from a cloud of electrons drifting out from the acceleration region, from which wave-particle instabilities or some other mechanism caused electrons to be precipitated.
Multiple balloon recordings of bremsstrahlung X-rays from a large scale auroral-zone electron precipitation event are presented. Additional riometer recordings show that it extended from noon, via dusk, to midnight. The X-ray observations show electron precipitation over a range of L-values from ∼− 5.5 to 7.5. This was briefly interrupted during a negative sudden impulse in the geomagnetic field. A close similarity between variations in the X-ray fluxes and locally recorded variations in the geomagnetic field was observed. Magnetic records from around the auroral zone suggest that the precipitation was related to an asymmetric magnetospheric convection system.
Simultaneous balloon measurements of bremsstrahlung X-rays from electron precipitation over Iceland and Scandinavia indicate that ⪆ 30 keV electron precipitation events in the geomagnetic midnight-to-morning sector extend for more than 2000 km in the west-east direction. Some events are spatially directly associated with the auroral electrojet, whereas others occur along the auroral zone, south of the electrojet. Precipitation of the former type seems to start almost simultaneously over the whole region studied, whereas precipitation of the latter type starts progressively later as one goes eastwards from the midnight sector. According to previous studies, precipitation along the electrojet is believed to be directly associated with the acceleration of electrons, whereas precipitation south of the electrojet comes from clouds of electrons drifting in the Earth's magnetic field. The large-scale observations presented here tend to confirm this model.
Auroral-zone electron precipitation during early morning hours (0200–0600 hr magnetic local time) has been analysed with the aid of X-ray measurements from northern Scandinavia together with recordings of geomagnetic variations and cosmic noise absorption (CNA). The electron precipitation can be divided in two parts: one occurring close to the location of the electrojet, the other, when the electrojet is far away or absent. The main features of these two types of precipitation distinctly resemble those found earlier in the midnight hours and in the late-morning (SVA-events), respectively. Both types of precipitation may occur simultaneously in the early morning hours. The SVA-type precipitation may extend to very early local times, and the midnight-type precipitation towards dawn. Fast pulsations of the X-ray intensity were found in both types. The midnight-type precipitation apparently stems directly from the acceleration process. The SVA-precipitation was observed to be delayed with respect to the break-up phase in the midnight sector and showed characteristic variations of the energy spectrum in a sense as to support the assumption that drifting electrons were the cause of this phenomenon. It is proposed to call the part characteristic for local times around midnight ‘direct precipitation’ and the SVA-like part ‘drift precipitation’.