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Accurate determination of thermal resistances having a clear physical interpretation is crucial for analyzing self-heating effects (SHEs) in bulk FinFETs and ensuring reliable circuit operation. In this article, we use extensive electrothermal simulations, calibrated against experiments, to validate a popular method to monitor SHEs based on the measured AC output conductance. The results confirm that nanoscale silicon fins exhibit degraded thermal conductivity compared with the bulk silicon case. Then, we explore the relationship between the temperature extracted by the output conductance method and the maximum temperature inside the fin (which is a useful parameter to study device reliability) as a function of device bias and dimensions, providing a few projections toward scaled technology nodes. Our results show that the following hold: 1) the overtemperature extracted with the AC output conductance method represents an average overtemperature across the device active area and 2) the AC conductance method largely underestimates the peak temperature of long-channel devices; less so for short-channel ones. In this latter case, however, the difference between the above temperatures changes appreciably as a function of gate voltage.

The Arase satellite observed the precipitation of monoenergetic electrons accelerated from a very high altitude above 32,000 km altitude on 16 September 2017. The event was selected in the period when the high‐angular resolution channel of the electron detector looked at pitch angles within ∼5° from the ambient magnetic field direction, and thereby was the first to examine the detailed distribution of electron flux near the energy‐dependent loss cone at such high altitudes. The potential energy below the satellite estimated from the observed energy‐dependence of the loss cone was consistent with the energy of the upgoing ion beams, indicating that ionospheric ions were accelerated by a lower‐altitude acceleration region. The accelerated electrons inside the loss cone carried a significant net field‐aligned current (FAC) density corresponding to ionospheric‐altitude FAC of up to ∼3μA/m2. Based on the anisotropy of the accelerated electrons, we estimated the height of the upper boundary of the acceleration region to be >∼2 REabove the satellite. The height distribution of the acceleration region below the satellite, estimated from the frequency of auroral kilometric radiation, was ∼4,000–13,000 km altitude, suggesting that the very‐high‐altitude acceleration region was separated from the lower acceleration region. Additionally, we observed time domain structure (TDS) electric fields on a subsecond time scale with a thin FAC indicated by magnetic deflections. Such a TDS may be generated by the formation of double layers in the magnetotail, and its potential drop could significantly contribute (∼40%–60%) to the parallel energization of precipitating auroral electrons. The auroral arc is produced by electrons in the magnetosphere accelerated downward by a quasi‐static electric field. The region of the electric field, so called the auroral acceleration region, is typically located just above the ionosphere, at altitudes of a few thousand kilometers. However, recent studies have shown that it can be extended to altitudes higher than 30,000 km. The mechanism and impact of such a very‐high‐altitude acceleration region remain a mystery. The high‐angular resolution electron detector on board the Arase satellite successfully measured current and energy flows carried by the electron accelerated at the very‐high‐altitude acceleration region above the satellite altitude of 32,000 km. This acceleration at very‐high‐altitudes contributed significantly to the energy flow into the ionosphere. Based on the anisotropy of the accelerated electrons, the frequency of auroral kilometric radiation, and the presence of spiky electrostatic waves, we estimate that the very‐high‐altitude acceleration region was located more than 12,000 km above the satellite as a thin charge separation layer, apart from the acceleration region below the satellite. Our results suggest that localized electric fields at very high altitudes, which were not previously associated with the aurora, can energize auroral electrons and affect auroral visibility. We comprehensively analyzed a very‐high‐altitude (>32,000 km) auroral acceleration eventNet precipitation of accelerated electrons significantly contributes to the field‐aligned current and energy flux into the ionosphereDouble layers in the magnetotail are possible candidates for very‐high‐altitude auroral accelerations We comprehensively analyzed a very‐high‐altitude (>32,000 km) auroral acceleration event Net precipitation of accelerated electrons significantly contributes to the field‐aligned current and energy flux into the ionosphere Double layers in the magnetotail are possible candidates for very‐high‐altitude auroral accelerations

Super Dual Auroral Radar Network (SuperDARN) observations show that ionospheric flow fluctuations of millihertz or lower‐frequency range with horizontal velocities of a few hundred meters per second appeared in the subauroral to midlatitude region during a magnetic storm on 27 March 2017. A set of the radars have provided the first ever observations that the fluctuations propagate azimuthally both westward and eastward simultaneously, showing bifurcated phase propagation associated with substorm expansion. Concurrent observations near the conjugate site in the inner magnetosphere made by the Arase satellite provide evidence that multiple drifting clouds of electrons in the near‐Earth equatorial plane were associated with the electric field fluctuations propagating eastward in the ionosphere. We interpret this event in terms of mesoscale pressure gradients carried by drifting ring current electrons that distort field lines one after another as they drift through the inner magnetosphere, causing eastward propagating ionospheric electric field fluctuations. Midlatitude ionospheric radars called SuperDARN observed azimuthally propagating fluctuations of ionospheric plasma flow in association with substorm expansion during a magnetic storm on 27 March 2017. The radar observations have shown for the first time that the flow fluctuations bifurcate toward eastward and westward simultaneously. The Arase satellite in the near‐conjugate site of the eastward propagating ionospheric flow fluctuations in the inner magnetosphere saw repeated flux enhancement of energetic electrons. The good satellite‐radar conjunction gives observational evidence that the eastward propagating ionospheric flow fluctuations are driven by eastward drifting pressure bumps of electrons injected into the inner magnetosphere upon substorm expansion. This study shows the first ever comprehensive observation of azimuthal bifurcation of substorm‐associated ionospheric flow fluctuationsThe eastward propagating portion of the flow fluctuations can be mapped to electron pressure enhancements in the inner magnetosphereWe propose that multiple pressure bumps of drifting energetic electrons directly cause the observed ionospheric flow fluctuations

Although many substorm‐related observations have been made, we still have limited insight into propagation of the plasma and field perturbations in Pi2 frequencies (∼7–25 mHz) in association with substorm aurora, particularly from the auroral source region in the inner magnetosphere to the ground. In this study, we present conjugate observations of a substorm brightening aurora using an all‐sky camera and an inner‐magnetospheric satellite Arase at L∼ 5. A camera at Gakona (62.39°N, 214.78°E), Alaska, observed a substorm auroral brightening on 28 December 2018, and the footprint of the satellite was located just equatorward of the aurora. Around the timing of the auroral brightening, the satellite observed a series of quasi‐periodic variations in the electric and magnetic fields and in the energy flux of electrons and ions. We demonstrate that the diamagnetic variations of thermal pressure and medium‐energy ion energy flux in the inner magnetosphere show approximately one‐to‐one correspondence with the oscillations in luminosity of the substorm brightening aurora and high‐latitudinal Pi2 pulsations on the ground. We also found their anti‐correlation with low‐energy electrons. Cavity‐type Pi2 pulsations were observed at mid‐ and low‐latitudinal stations. Based on these observations, we suggest that a wave phenomenon in the substorm auroral source region, like ballooning type instability, play an important role in the development of substorm and related auroral brightening and high‐latitude Pi2, and that the variation of the auroral luminosity was directly driven by keV electrons which were modulated by Alfven waves in the inner magnetosphere. One of the most frequent disturbances in the Earth's magnetosphere is called substorm. Through Earth's magnetic field line, the development of a magnetospheric substorm is projected onto Earth's high‐latitude ionosphere as auroral evolution. During a substorm, the energy in the tail of the magnetosphere is released to the earth, and quite a part of this energy is transmitted as different types of wave phenomena. These wave oscillations can be observed by magnetometers on the ground and satellites in the magnetosphere. It is still uncertain what mechanisms trigger these substorm‐related waves, how these waves correlate with other substorm phenomena, and how they transmit and dissipate, especially for the wave phenomena at ∼4–7 Earth radii away from the Earth. This paper presents a case study of such substorm event, where we show the variation of magnetic field and auroral luminosity on the ground, and the electromagnetic wave that is called as Pi2 pulsations and oscillation of plasma flux in the inner magnetosphere. We demonstrate that there are one‐to‐one correspondences in these oscillations. We suggest the possibility that a ballooning plasma instability triggers the observed oscillations in particle flux, as well as the electromagnetic wave that modulates the auroral luminosity. Observations of plasma and field characteristics near the source region of a substorm auroral brightening at L∼ 5Pi2, auroral luminosity variation and fluctuations of in‐situ electromagnetic field and particle flux were observed during substorm onsetCorrespondence between these fluctuations suggest waves in the magnetosphere like ballooning instability control auroral intensity Observations of plasma and field characteristics near the source region of a substorm auroral brightening at L∼ 5 Pi2, auroral luminosity variation and fluctuations of in‐situ electromagnetic field and particle flux were observed during substorm onset Correspondence between these fluctuations suggest waves in the magnetosphere like ballooning instability control auroral intensity

Security in quantum cryptography is continuously challenged by inventive attacks targeting the real components of a cryptographic set-up, and duly restored by new countermeasures to foil them. Owing to their high sensitivity and complex design, detectors are the most frequently attacked components. It was recently shown that two-photon interference from independent light sources can be used to remove any vulnerability from detectors. This new form of detection-safe quantum key distribution (QKD), termed measurement-device-independent (MDI), has been experimentally demonstrated but with modest key rates. Here, we introduce a new pulsed laser seeding technique to obtain high-visibility interference from gain-switched lasers and thereby perform MDI-QKD with unprecedented key rates in excess of 1 megabit per second in the finite-size regime. This represents a two to six orders of magnitude improvement over existing implementations and supports the new scheme as a practical resource for secure quantum communications.

Kinetic effects due to wave-particle interactions and suprathermal electrons have been suggested in the literature as possible solar wind acceleration mechanisms. Ion cyclotron resonant heating, in particular, has been associated with some qualitative features observed in the solar wind. In terms of solar wind acceleration, however, it is interesting to compare the kinetic effects of suprathermal electrons with those due to the wave-particle interactions. The combined effects of the two acceleration mechanisms on the fast solar wind have been studied by Tam & Chang (1999a,b). In this study, we investigate the role of the suprathermal electron population in the acceleration of the solar wind. Our model follows the global kinetic evolution of the fast solar wind under the influence of ion cyclotron resonant heating, while taking into account Coulomb collisions, and the ambipolar electric field that is consistent with the particle distributions themselves. The kinetic effects due to the suprathermal electrons, which we define to be the tail of the electron distributions, can be included in the model as an option. By comparing the results with and without the inclusion of the suprathermal electron effects, we determine the relative importance of suprathermal electrons and wave-particle interactions in driving the solar wind. We find that although suprathermal electrons enhance the ambipolar electric potential in the solar wind considerably, their overall influence as an acceleration mechanism is relatively insignificant in a wave-driven solar wind.

The 9977 package is a certified type B transportation packaging that was designed to transport radioactive materials with a decay heat load of up to 19W. The packaging was recently modified to accommodate increased content heat load (up to 38W) by employing an aluminium heat dissipating sleeve outside the containment vessel (CV), as well as an aluminium spacer inside the CV holding two 3013 containers. This paper provides highlights of thermal analyses of the modified 9977 package that were performed to evaluate its compliance with the 10 CFR 71 regulatory safety requirements. Parametric studies were also performed to examine effects of (i) surface properties, e.g. light absorptivity and emissivity, of the packaging; (ii) total decay heat loads, ranging from 18 to 38W; and (iii) distribution of decay heat load inside the CV on the temperature of the Viton O-ring seal. The results of thermal analyses show that for the normal condition of transport with insolation, increasing absorptivity and decreasing emissivity increase the temperature of the O-ring; decreasing heat load decreases the temperature of the O-ring, whereas changing heat load distribution has little effect on the temperature of the O-ring. Likewise, changing the thermal conductivity of the spacer inside the CVhas little effect on the temperature of the O-ring. Briefly discussed is the possible extension of the annual maintenance interval of the 9977 package, based on previous work and the data obtained in the long-term leak performance tests conducted by the Savannah River National Laboratory.

Auroral brightening is one of the most common phenomena that occur during substorm onset and is usually recognized as a projection of the substorm‐associated magnetospheric plasma dynamics to the ionosphere. However, electromagnetic fields and plasma features associated with the substorm brightening arc have not been well understood. In this study, we present a comprehensive observation of the source plasma and field variations of a substorm brightening aurora in the inner magnetosphere. We performed a unique conjugate observation of a substorm brightening auroral arc observed by a ground‐based camera and by the Arase satellite in the magnetospheric source region at L∼ 6. The event was observed at Tromsø (69.6°N, 19.2°E), Norway, on 12 October 2017. The brightening arc indicates east‐west structures with longitudinal scales of ∼0.5°–2.0°. Field‐aligned bi‐directional electrons with an energy range between 66 and 1,800 eV were detected by the satellite, simultaneously with the appearance of the brightening arc in the camera. These electrons were probably supplied from the auroral brightening region in the ionosphere, indicating that the satellite was on the same field line of the brightening aurora. The magnetic and electric field data show characteristic fluctuations and earthward Poynting flux around the time that the satellite crossed the aurora. Anti‐phase oscillations between the thermal pressure and the magnetic pressure are also reported. Based on these observations, we suggest the possibility that a ballooning instability occurred in the source region of the substorm brightening arc in the inner magnetosphere at L∼ 6. A frequently occurring source of variations in the magnetosphere is the substorm, a process that causes energy dissipation into the atmosphere. Substorm is presented as the development of aurorae at high latitudes in the ionosphere. The study of substorm processes helps in understanding the near‐Earth space environment and the space weather. Along Earth's magnetic field lines, the aurora at a latitude of ∼65°N can be traced to ∼4–7 Earth radii away from the Earth at the equatorial plane in space. Using a ground‐based auroral camera, we can construct the correspondence between auroral motion and field and plasma variation at the satellite. This study reports such a unique event of substorm brightening arc observed at Tromsø, Norway, on 12 October 2017. Satellite observed bi‐directional electrons prove the connection between aurora break‐up at ∼100 km altitude and its source region in the magnetosphere at ∼30,000 km away from Earth. Based on the magnetic wave spectrograms, auroral bead‐like structures and other observational results, we suggest the possibility that a ballooning plasma instability occurred in the source region of the substorm brightening arc in the inner magnetosphere. Observation of plasma and field features in the source region of a sudden brightening auroral arc during a minor substorm onset at L∼ 6Energization of particles, field‐aligned electrons, and electromagnetic field fluctuations were observed during the arc crossing by AraseSeveral observational facts indicate the possibility of ballooning instability occurring at this substorm onset Observation of plasma and field features in the source region of a sudden brightening auroral arc during a minor substorm onset at L∼ 6 Energization of particles, field‐aligned electrons, and electromagnetic field fluctuations were observed during the arc crossing by Arase Several observational facts indicate the possibility of ballooning instability occurring at this substorm onset

Plasmaspheric hiss can cause energetic electron precipitation from the magnetosphere to the Earth's upper atmosphere and affect the ionospheric electron density profiles. In this study, we use Arase satellite measurements in the dayside plasmasphere to model the electron precipitation and the resultant ionospheric response, and compare the results to the electron density measured by the Poker Flat Incoherent Scatter Radar (PFISR). We analyzed two close conjunction events between Arase and PFISR at L∼ 6 in the afternoon sector, when Arase was in the outer plasmasphere and traveled into the plasmaspheric plumes. Modest or strong hiss waves were observed with amplitudes higher than 50 pT during both events. Quasilinear modeling suggests that the hiss waves could cause intense electron precipitation ranging from several keV to several hundred keV energies. The electron density profiles at 60–90 km modeled by the Boulder Electron Radiation to Ionization (BERI) model suggest significant electron density enhancements due to the precipitating electrons. PFISR simultaneously observed electron density enhancements during both events, and provided evidence for the electron precipitation at altitudes down to <70 km. The temporal modulation of hiss caused the modulated density profiles in BERI modeling, but was not evident in PFISR observations. The modeled altitude profiles of the perturbed electron density overall agree with PFISR observation. At altitudes below 75 km, the modeled electron densities are lower than the observation, suggesting additional high energy electron precipitation possibly due to low frequency (<50 Hz) waves or hiss wave powers ducted to high latitudes. Two Poker Flat Incoherent Scatter Radar (PFISR)‐Arase conjunction events are identified at the dayside plasmasphere when hiss wave amplitudes reach 50–100 pT at L∼ 6Hiss‐driven electron precipitation obtained from quasilinear simulation is used to model ionospheric density profiles at 60–90 km altitudeModeled electron densities overall agree with PFISR observations with differences in the temporal modulation and at altitudes below 75 km Two Poker Flat Incoherent Scatter Radar (PFISR)‐Arase conjunction events are identified at the dayside plasmasphere when hiss wave amplitudes reach 50–100 pT at L∼ 6 Hiss‐driven electron precipitation obtained from quasilinear simulation is used to model ionospheric density profiles at 60–90 km altitude Modeled electron densities overall agree with PFISR observations with differences in the temporal modulation and at altitudes below 75 km

Inner magnetospheric electrons are precipitated in the ionosphere via pitch‐angle (PA) scattering by lower band chorus (LBC), upper band chorus (UBC), and electrostatic electron cyclotron harmonic (ECH) waves. However, the PA scattering efficiency of low‐energy electrons (0.1–10 keV) has not been investigated via in situobservations because of difficulties in flux measurements within loss cones at the magnetosphere. In this study, we demonstrate that LBC, UBC, and ECH waves contribute to PA scattering of electrons at different energy ranges using the Arase (ERG) satellite observation data and successively detected the moderate loss cone filling, that is, approaching strong diffusion. Approaching strong diffusion by LBC, UBC, and ECH waves occurred at ∼2–20 keV, ∼1–10 keV, and ∼0.1–2 keV, respectively. The occurrence rate of the approaching strong diffusion by high‐amplitude LBC (>50 pT), UBC (>20 pT), and ECH (>10 mV/m) waves, respectively, reached ∼70%, ∼40%, and ∼30% higher than that without simultaneous wave activity. The energy range in which the occurrence rate was high agreed with the range where the PA diffusion rate of each wave exceeded the strong diffusion level based on the quasilinear theory. The pitch‐angle scattering efficiencies by plasma waves are statistically investigated using in situobservationsLower band chorus waves caused approaching strong diffusion with the highest occurrence rate in the energy range of ∼2–20 keVElectrostatic electron cyclotron harmonic waves could contribute approaching strong diffusion in the ∼0.1–1 keV energy range The pitch‐angle scattering efficiencies by plasma waves are statistically investigated using in situobservations Lower band chorus waves caused approaching strong diffusion with the highest occurrence rate in the energy range of ∼2–20 keV Electrostatic electron cyclotron harmonic waves could contribute approaching strong diffusion in the ∼0.1–1 keV energy range

The combination of a nitric oxide (NO) donor and a paclitaxel−NO donor conjugate coated on a vascular stent was tested in a rabbit iliac artery model of stenosis as a potential therapy for restenosis. Paclitaxel was conjugated with a NO donor at the 7-position to give compound 7. An adamantane-based NO donor 14 was synthesized and combined with 7 to provide a burst of NO in the first few critical hours following injury to the vessel wall. Both 7 and 14 demonstrated antiproliferative activity (IC50 = 20 nM and 15 μM, respectively) and antiplatelet activity (IC50 = 10 and 1 μM, respectively). Stents were coated with a layer of a polymer containing test compounds. The total amount of NO eluted from the stents after a 6 h implantation in the rabbit iliac artery was 35%, 95%, and 69% of the original content for the stents coated with 7, 14, and the combination of 7 and 14, respectively. The antistenotic activity of 7 and 14 was determined in a 28-day rabbit model with two control groups (uncoated stents and polymer-coated stents) and two study groups (paclitaxel-coated stents and stents coated with the combination of 7 and 14). Polymer-coated stents caused inflammation and increased stenosis by 39% when compared to the uncoated stents. The stents coated with 7 plus 14 were as good as the uncoated stents, 41% better than the polymer-coated stents and 34% better than the paclitaxel-coated stents. These data indicate a beneficial effect of adding NO to an antiproliferative agent (paclitaxel) and suggest a potential therapeutic combination for the treatment of stenotic vessel disease.

The synthesis of a series of novel pyrazoles containing a nitrate (ONO2) moiety as a nitric oxide (NO)-donor functionality is reported. Their COX-1 and COX-2 inhibitory activities in human whole blood are profiled. Our data demonstrate that pyrazole ring substituents play an important role in COX-2 selective inhibition, such that a cycloalkyl pyrazole (6b) was found to be a potent and selective COX-2 inhibitor. Other modifications at the 3 position of the central pyrazole ring (17b, 23b, 26b-I) enhanced COX-2 inhibitory potency. Among the pyrazoles synthesized, the oxime (23b) was identified as the most potent COX-2 selective inhibitor. Accordingly, 23b was profiled pharmacologically in the rat after oral administration and shown to possess potent antiinflammatory activity in the carrageenan-induced air-pouch model and less gastric toxicity than a standard COX-2 inhibitor when administered with background aspirin treatment. We suggest that the enhanced gastric tolerance of an NO-donor COX-2 selective inhibitor has the potential to augment the clinical profile of this drug class.

A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in human whole blood (HWB). In the present study, structure−activity relationships (SAR) in the metharyl analogues were investigated. The spacer group and substitutions in the spacer group were found to be quite important for potent COX-2 inhibition. Compounds in which a methylene group (8a−c), carbonyl group (12a−c), or methylidene group (7a−c) connected cycloalkyl groups to the central benzo-1,3-dioxolane template were found to be potent and selective COX-2 inhibitors. Aryl-substituted compounds linked to the central ring by either a methylene or a carbonyl spacer resulted in potent, highly selective COX-2 inhibitors. In this series of substituted-(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-1-(methylsulfonyl)benzene compounds, SAR studies demonstrated that substitution at the 3-position of the aryl group optimized COX-2 selectivity and potency, whereas substitution at the 4-position attenuated COX-2 inhibition. Mono- or difluoro substitution at meta position(s), as in 22c and 22h, was advantageous for both in vitro COX-2 potency and selectivity (e.g., COX-2 IC50 for 22c = 1 μM and COX-1 IC50 for 22c = 20 μM in HWB assay). Several novel compounds in the (2H-benzo[3,4-d]1,3-dioxolan-5-yl))-1-(methylsulfonyl)benzene series, as shown in structures 7c, 8a, 12a, 21c, 22c, 22e, and 22h, selectively inhibited COX-2 activity by 40−50% at a test concentration of 1 μM in an in vitro HWB assay.

Despite its widespread use, diclofenac has gastrointestinal liabilities common to nonsteroidal antiinflammatory drugs (NSAIDs) that might be reduced by concomitant administration of a gastrointestinal cytoprotectant such as nitric oxide (NO). A series of novel diclofenac esters containing a nitrosothiol (−S-NO) moiety as a NO donor functionality has been synthesized and evaluated in vivo for bioavailability, pharmacological activity, and gastric irritation. All S-NO-diclofenac derivatives acted as orally bioavailable prodrugs, producing significant levels of diclofenac in plasma within 15 min after oral administration to mice. At equimolar oral doses, S-NO-diclofenac derivatives (20a−21b) displayed rat antiinflammatory and analgesic activities comparable to those of diclofenac in the carrageenan-induced paw edema test and the mouse phenylbenzoquinone-induced writhing test, respectively. All tested S-NO-diclofenac derivatives (20a−21b) were gastric-sparing in that they elicited markedly fewer stomach lesions as compared to the stomach lesions caused by a high equimolar dose of diclofenac in the rat. Nitrosothiol esters of diclofenac comprise a novel class of NO-donating compounds having therapeutic potential as nonsteroidal antiinflammatory agents with an enhanced gastric safety profile.

We present observations of an equatorward detachment of the auroral arc from the main oval and magnetically conjugate measurements made by the Arase satellite in the inner magnetosphere. The all‐sky imager at Gakona (magnetic latitude = 63.6°N), Alaska, shows the detachment of the auroral arc in both red and green lines at local midnight (∼0130–0230 MLT) on 30 March 2017. The electron density derived from the Arase in‐situ observations shows that this arc occurred outside the plasmapause. At the arc crossing, the electron flux of energies ∼0.1–2 keV is found to be locally enhanced at L∼4.3–4.5. We estimated auroral intensities for both red and green lines by using the Arase low‐energy (0.1–19 keV) electron flux data. The peak latitude of the estimated intensity shows reasonably good correspondence with the observed intensity mapped at the ionospheric footprints of the Arase satellite. These findings indicate that the observed arc detachment at Gakona was associated with the localized enhancement of low‐energy electrons (∼0.1–2 keV) at the inner edge of the electron plasma sheet. Further, we employ the simulation results of the Community Coordinated Modeling Center (CCMC), the BATS‐R‐US–CIMI 3‐D MHD code to understand the conditions in the inner magnetosphere around the time of detachment. Although the simulation could not reproduce the lower‐energy component responsible for the arc detachment, it successfully reproduced two earthward convection events at the lower radial distance (R) (R ≤ ∼4) around the time of arc detachment and the features of enhanced convection in similarity with the observations. Conjugate measurements of an equatorward detachment of the auroral arc from the main oval and the Arase satellite in the inner magnetosphereEquatorward detachment of the auroral arc coincided with a localized enhancement of electrons of energies ∼0.1–2 keV deeper down to L∼4.3–4.5BATS‐R‐US–CIMI model successfully reproduced the enhancement of lower‐energy electrons (∼8–40 keV) at a lower radial distance (R < 4) Conjugate measurements of an equatorward detachment of the auroral arc from the main oval and the Arase satellite in the inner magnetosphere Equatorward detachment of the auroral arc coincided with a localized enhancement of electrons of energies ∼0.1–2 keV deeper down to L∼4.3–4.5 BATS‐R‐US–CIMI model successfully reproduced the enhancement of lower‐energy electrons (∼8–40 keV) at a lower radial distance (R < 4)

Medium‐scale traveling ionospheric disturbances (MSTIDs) are a phenomenon widely and frequently observed over the ionosphere from high to low latitudes. Night time MSTIDs are caused generally by the polarization electric field in the ionosphere. However, propagation of this polarization electric field to the magnetosphere has not yet been identified. Here, we report the first observation of the polarization electric field and associated density variations of a night time MSTID in the magnetosphere. The MSTID event was observed by an all‐sky airglow imager at Gakona (geographical latitude: 62.39°N, geographical longitude: 214.78°E, magnetic latitude: 63.20°N), Alaska. The Arase satellite passed over the MSTID in the inner magnetosphere at 0530–0800 UT (2030–2300 LT) on November 3, 2018. This MSTID, observed in 630 nm airglow images, was propagating westward with a horizontal wavelength of ∼165 km, a north–south phase front, and a phase velocity of ∼80 m/s. The Arase satellite footprint on the ionosphere crossed the MSTID in the direction nearly perpendicular to the MSTID phase fronts. The electric field and electron density observed by the Arase satellite showed periodic variation associated with the MSTID structure with amplitudes of ∼2 mV/m and ∼150 cm−3, respectively. The electric field variations projected to the ionosphere are mainly in the east‐west direction and are consistent with the direction of the polarization electric field expected from MSTID growth by E× Bdrift. This observation indicates that the polarization electric field associated with the MSTID in the ionosphere is projected onto the magnetosphere, causing plasma density fluctuations in the magnetosphere. Medium‐scale traveling ionospheric disturbances (MSTIDs) are propagation of electron density fluctuation in the ionospheric F‐layer. MSTIDs are a common phenomenon from high to low latitudes. From simultaneous observations of airglow imagers in both hemispheres, MSTIDs are known to have a mirror structure at magnetic conjugate hemispheres. If an MSTID is generated by ionospheric instabilities, the polarization electric field associated with the MSTID should propagate along the magnetic field lines. In this paper, we report the first simultaneous observation of an MSTID using a ground‐based airglow imager and the Arase satellite in the magnetosphere. The electric field variations and plasma density fluctuations observed by Arase showed periodic variations associated with the MSTID structure. This result indicates that the spatial inhomogeneity of the ionospheric Pedersen conductivity associated with the MSTID yields the polarization electric field in the ionosphere, and that this polarization electric field was projected onto the magnetosphere. First simultaneous observation of an medium‐scale traveling ionospheric disturbance (MSTID) using a ground‐based airglow imager and the Arase satellite in the magnetosphereThe polarization electric field associated with the MSTID in the ionosphere was projected to the magnetosphere and observed by AraseThe electric field and electron density observed by the Arase satellite showed a periodic variation associated with the MSTID structure First simultaneous observation of an medium‐scale traveling ionospheric disturbance (MSTID) using a ground‐based airglow imager and the Arase satellite in the magnetosphere The polarization electric field associated with the MSTID in the ionosphere was projected to the magnetosphere and observed by Arase The electric field and electron density observed by the Arase satellite showed a periodic variation associated with the MSTID structure

Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [¹²⁵I]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist α-helical CRH(9−41) (Ki = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than α-helical CRH(9−41) (IC50 = 20 000 nM vs 250 nM). Systematic structure−activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH1 receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure−activity studies which improved hCRH1 receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH1 Ki = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

Linopirdine is a compound being assessed for value in reversing the dementia associated with Alzheimer's disease. The drug improves learning and memory performance in several rodent behavioral paradigms. Its proposed mechanism of action is the enhancement of neurotransmitter release, but the molecular site which mediates this action is unknown. The present study examines the possible involvement of channels which mediate the movement of K+, Cl- and Na+, which are important to the polarization state of excitable membranes, in the release-enhancing effects of linopirdine. Linopirdine causes a shift in the K+ dose response for the release of tritium from cerebral cortical slices preloaded with [3H]choline ([3H]acetylcholine (ACh) released) to the left, consistent with the blockade of a site, such as a K+ channel, involved in dampening the response of neuronal terminals to depolarizing stimuli. Linopirdine does not appear to act at aminopyridine-sensitive K+ channels, inasmuch as the aminopyridines and linopirdine have different patterns of effects regarding [3H]ACh release. Tetraethylamonium (TEA), on the other hand, does share common effects with linopirdine. TEA enhances K(+)-evoked [3H]ACh release to as much as 620% of control without affecting basal efflux of the neurotransmitter. Experiments using the muscarinic agonist carbachol indicate that linopirdine does not affect the cholinergic autoreceptor influence on [3H]ACh release. Linopirdine also does not appear to act at tetrodotoxin-sensitive Na+ channels. The anion channel blocker 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid and Cl(-)-deficient media do not affect the level of linopirdine release enhancement.

Recent in situ observations have revealed novel features in the polar wind. Measurements between 5000 and 9000 km altitude by the Akebono satellite indicate that both H+ and O+ ions can have remarkably higher outflow velocities in the sunlit region than on the nightside. Electrons also display an asymmetric behavior: the dayside difference in energy spread, greater for upward-moving than downward-moving electrons, is absent on the nightside. Here, we discuss the further development of a theory by Tam et al. that can explain most of these observed peculiar properties by properly taking into account the global, kinetic, collisional effects of the sunlit photoelectrons, on the background polar wind and the electric field. Quantitative comparisons of the calculated results with actual data will be described. In addition, transition from the daytime photoelectron-driven polar wind to the night-time polar wind will be discussed.

This paper reviews the status of underground pumped hydro storage (UPHS) for electric utility peaking and energy-storage applications. The salient features of major recent studies are reviewed. Turbomachinery options and advances in high-head pump/turbines are discussed. The effect of head, capacity, turbomachinery unit size and type, and other performance variables on die cost of a UPHS plant are presented. Market potential, siting criteria, lower reservoir construction, and geologically-related issues are addressed. The environmental impact of a UPHS plant is deduced from comparable facilities, and these issues and other safety concerns are presented. UPHS is an economically viable scheme for energy-storage and peaking applications in which considerable savings in premium fuels can be achieved through the replacement of combustion gas turbines. The technology for UPHS is available, but additional research and development are required for high-head turbomachinery, motor/generators, cavern geology, and system optimization.

In an effort to improve the pharmacokinetic and pharmacodynamic properties of the cognition-enhancer linopirdine (DuP 996), a number of core structure analogues were prepared in which the 4-pyridyl pendant group was systematically replaced with 2-fluoro-4-pyridyl. This strategy resulted in the discovery of several compounds with improved activity in acetylcholine (ACh) release-enhancing assays, in vitro and in vivo. The most effective compound resulting from these studies, 10,10-bis[(2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (9), is between 10 and 20 times more potent than linopirdine in increasing extracellular hippocampal ACh levels in the rat with a minimum effective dose of 1 mg/kg. In addition to superior potency, 9 possesses an improved pharmacokinetic profile compared to that of linopirdine. The half-life of 9 (2 h) in rats is 4-fold greater than that of linopirdine (0.5 h), and it showed a 6-fold improvement in brain−plasma distribution over linopirdine. On the basis of its pharmacologic, pharmacokinetic, absorption, and distribution properties, 9 (DMP543) has been advanced for clinical evaluation as a potential palliative therapeutic for treatment of Alzheimer's disease.

1-(Cyclopropylmethyl)-4-(2-(4-fluorophenyl)-2-oxoethyl) piperidine HBr (DuP 734) is a novel sigma receptor ligand which exhibits promise in preclinical animal models as an antipsychotic agent without motor side effects. In vitro and in vivo receptor binding profiles of DuP 734 in mouse brain using [3H]DuP 734 and [3H]N-allylnormetazocine ((+)-SKF 10,047) were studied. The pharmacology and stereospecificity of [3H]DuP 734-labeled sites in mouse brain, both in vitro and in vivo, was consistent with sigma receptor pharmacology. Specific in vivo binding of [3H]DuP 734 in brain peaked 1 hr after i.v. injection and this level of binding was maintained up to 4 hr. On the other hand, plasma concentration of [3H]DuP 734 decreased rapidly within 20 min after injection, indicating different pharmacokinetics between brain and plasma levels. Nonspecific binding, defined using 1 mg/kg (2.66 mumol/kg) of haloperidol, was approximately 30% of total binding 1 hr after injection of radiotracer. Administration of DuP 734 potently antagonized the binding of [3H]DuP 734 and [3H](+)-SKF 10,047 to brain sigma receptors in vivo with ID50 values of 0.02 and 0.07 mg/kg (0.07 and 0.25 mumol/kg), respectively. However, (+)-SKF 10,047, which possess a high affinity (IC50 = 22.5 nM) for [3H]DuP 734 binding in vitro, failed to displace [3H]DuP 734 binding in vivo. Thus in vitro receptor binding data may not predict in vivo receptor occupancy. Overall, the data suggest [3H] DuP 734 is a good ligand for in vivo imaging of sigma receptors.

It has been suggested that sigma receptors may be involved in the etiology of psychosis and that 5-hydroxytryptamine2 (5-HT2) antagonists may have utility in treating the negative symptoms of psychosis as well as reducing the side effects associated with the typical antipsychotic haloperidol. We have evaluated the potential antipsychotic effects of 1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'-oxoethyl)piper i din e HBr (DuP 734), a selective and potent sigma and 5-HT2 receptor ligand with weak affinity for D2 receptors, in behavioral animal models that are not necessarily dependent on dopamine antagonism. DuP 734 potently blocked mescaline-induced scratching (ED50 = 0.35 mg/kg, p.o.) and aggressive activity (ED50 = 1.9 mg/kg, p.o.) and was relatively much weaker as an apomorphine antagonist (ED50 = 12 mg/kg, p.o.). This was in contrast to the typical antipsychotic agents such as haloperidol and chlorpromazine, which were very potent in all three tests. In rats, DuP 734 did not antagonize avoidance behavior or induce catalepsy, and, therefore, differed from the potent dopamine receptor antagonist antipsychotics. It did, however, reduce lever response rates in a random interval 60-sec food reward schedule of reinforcement (ED50 = 6.0 mg/kg, p.o.) in rats. The results suggest that DuP 734 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics. Although DuP 734 itself did not antagonize avoidance activity, it significantly enhanced the potency of haloperidol in blocking avoidance behavior by 3-fold (by shifting the ED50 from 0.94 to 0.36 mg/kg, p.o.), whereas the ED50 of haloperidol for blockade of escape behavior and induction of catalepsy was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs and that 5-hydroxytryptamine (5-HT2) receptor antagonists produce improvements of the negative symptoms of schizophrenia. [1-(Cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'- oxoethyl)-piperidine HBr] (DuP 734) is a novel compound with high affinity for the sigma (Ki = 10 nM) and 5-HT2 (Ki = 15 nM) receptors, but low affinity for dopamine receptors (Ki > 1000 nM) as well as 33 other receptors, ion channels and second messenger systems in vitro. DuP 734 did not inhibit the synaptosomal uptake of dopamine, 5-HT or norepinephrine. Oral administration of DuP 734 potently blocked 5-hydroxy-L-trytophan (5-HTP)-induced head twitch in the rat (ED50 = 6.5 mumol/kg), indicating 5-HT2 antagonist activity. Extracellular single-unit recording studies demonstrated that DuP 734 antagonized the effect of the selective sigma ligand (+)-3-(3-hydroxyphenyl-N-(1-propyl) piperidine [(+)-3-PPP] on dopamine neuronal activity in the substantia nigra of the rat with an ED90 of 3.6 mumol/kg i.v. The sigma receptor agonists (+)-SKF 10,047 and phencyclidine both elicited rotational behavior in rats with unilateral lesion of the substantia nigra. The rotational behavior induced by either (+)-SKF 10,047 or phencyclidine was dose-dependently antagonized by DuP 734 with oral ED50 of 8.7 and 19.6 mumol/kg, respectively. The 5-HT2 receptor antagonist ICI 169,369, even at high doses (up to 33 mumol/kg, s.c.), did not antagonize the rotational behavior induced by (+)-SKF 10,047.(ABSTRACT TRUNCATED AT 250 WORDS)

The in vitro binding properties of 1-(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'-oxoethyl)pipe ridi ne HBr, [3H]DuP 734, a novel sigma receptor ligand, were examined in homogenates of guinea pig brain. Specific [3H]DuP 734 binding (10 microM haloperidol-displaceable) in cerebellum was dependent on pH, temperature and membrane protein concentration, reversible, saturable and of high affinity (KD = 228 +/- 34 pM; Bmax = 3856 +/- 340 fmol/mg protein). [3H]DuP 734 binding was substantially reduced by treating the membrane with proteases and completely abolished by heat denaturation. [3H]DuP 734 binding was unaffected by the presence of ions or guanine nucleotides. The pharmacological characteristics of [3H]DuP 734 binding in cerebellum displayed the same rank order and stereospecificity as previously reported for sigma receptors in brain. [3H]DuP 734-labeled sigma receptors were heterogeneously distributed throughout the central nervous systems with highest densities present in pons/medulla, hypothalamus, spinal cord and cerebellum. In addition to labeling sigma receptors, a second, lower affinity, haloperidol-insensitive [3H] DuP 734 binding site was observed in the cerebral cortex. This second site could not be positively identified as a neuronal receptor because a series of standard compounds were unable to displace [3H]DuP 734 from the haloperidol-insensitive site; only structural analogs of DuP 734 proved effective in displacing [3H]DuP 734 from the haloperidol-insensitive site. In summary, [3H]DuP 734 is a novel ligand that binds with high affinity to sigma receptors in brain.

To investigate the role of distance between two opioid peptide pharmacophores on binding activities to delta, mu and kappa receptor in vitro, a number of new dimeric enkephalin analogues were synthesized in which two identical tetrapeptides: Tyr-D-Ala-Gly-Phe were connected together at their C-termini by α,ω-diamino-α,ω-dideoxyalditols. The length of the hydrophilic spacer (3 -6 carbons) did not affect the affinities for delta receptors, whereas the affinities for mu and kappa receptors were dependent on the length as well as the configuration of the spacer. The analogues had high affinities, and some of them possessed moderate delta selectivity.

Phospholipases A1 and A2 catalyze the hydrolysis of acyl groups of phospholipids at C-1 and C-2, respectively. These phospholipases are important in phospholipid catabolism and the remodeling of the acyl groups of phospholipids. Phospholipase A from hamster heart cytosol was purified by a combination of ion-exchange and gel filtration chromatography. The purity of the enzyme was assessed by nondenaturing polyacrylamide gel electrophoresis, two-dimension polyacrylamide gel electrophoresis, and immunological studies. The purified enzyme exhibited both phospholipase A1 and A2 activities toward phosphatidylcholine and had the ability to hydrolyze the acyl groups of phosphatidylethanolamine. However, the enzyme was not active toward lysophosphatidylcholine, diacylglycerol, or triacylglycerol. By Sepharose 6B chromatography, the molecular weight of the purified enzyme was estimated to be 140,000. Analysis of the purified enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the enzyme was composed of identical Mr 14,000 subunits. At least six subunits in the native enzyme could be cross-linked by dimethyl suberimidate. Both phospholipase A1 and A2 activities showed similar pH profiles, exhibited no absolute requirements for divalent metallic cations, but displayed a high degree of specificity for the acyl groups of phosphatidylcholine at both C-1 and C-2. The Km of phospholipases A1 and A2 for 1-palmitoyl-2-arachidon-ylglycerophosphocholine was found to be identical (0.5 mM).

The effect of beta-funaltrexamine (beta-FNA), an irreversible mu receptor blocker in isolated tissue bioassays, on mu, kappa and delta opioid receptor binding and the binding of beta-[3H]FNA were determined in guinea pig brain membranes. beta-FNA inhibited the binding of mu, kappa and delta opioid ligands to their receptors with Ki values of 2.2, 14 and 78 nM, respectively. Pretreatment of brain membranes with beta-FNA (less than 2 microM) followed by extensive washing inhibited mu binding and to a lesser degree delta binding, without changing kappa binding. The extent of the irreversible inhibition was dependent on the concentration of beta-FNA, and this inhibition on mu binding could be observed with as little as 1 nM beta-FNA. The irreversible inhibition of mu binding by beta-FNA pretreatment was due to a decrease in the number of binding sites with little change in Kd, and was more pronounced in the presence of increasing concentrations of NaCl. Specific binding of beta-[3H]FNA to opioid receptors was demonstrated. The rate of specific binding with 2 nM beta-[3H]FNA was rapid in the initial 10 min and did not reach maximum in 90 min. The dissociation of bound beta-[3H]FNA (5 nM added) by the addition of excess unlabeled naloxone reached maximum at 30 min with approximately 35% of specifically bound beta-[3H]FNA remaining. Mu opioids were most effective in preventing specific binding of beta-[3H]FNA when added before beta-[3H]FNA. Opioids added 1 hr after 2 nM beta-[3H]FNA could displace maximally only 70 to 75% of specific binding.(ABSTRACT TRUNCATED AT 250 WORDS)

The cognitive enhancer DuP 996 [3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one] and its structural analogs enhance the K(+)-stimulated release of acetylcholine, dopamine, and serotonin in brain slices, without effect on basal release. A novel receptor site labeled by [3H]DuP 996 has been identified. The [3H]DuP 996 binding site has a Kd of 19 nM and a Bmax of 102 fmol/mg of protein. Binding to this site is specific, saturable, reversible, and time, pH, and temperature dependent. Specific binding is decreased by treatment with trypsin and not affected by phospholipase C. Specific binding is inhibited by Ca2+ and increased by Mn2+ but not affected by Na+, K+, or Mg2+. The [3H]DuP 996 binding sites are heterogeneously distributed in brain, with striatum and hypothalamus having highest density and cerebellum lowest. The [3H]DuP 996 binding site does not belong to any known class of receptor site, because [3H]DuP 996 binding could not be displaced by a broad variety of standard pharmacological agents and neuropeptides. Physiological significance of this binding site is suggested by the excellent correlation between the binding affinity for this site and the potency to enhance K(+)-stimulated release of acetylcholine for a series of DuP 996 analogs. Ligands for this receptor site may have therapeutic potential for the treatment of cognitive deficits and neurodegenerative diseases.

It has been postulated that the psychotomimetic effects of opiates of the benzomorphan series are due to their activity at the sigma receptor. Therefore, the binding of (+/-)-[3H]ethylketocyclazocine ( [3H]EKC), a benzomorphan, to synaptosomal membranes of rat central nervous tissue was studied. Surprisingly, high concentrations of naloxone, a mu, delta, and kappa receptor antagonist, only inhibited about 80% of the specifically bound [3H]EKC in the spinal cord. This suggested that the remaining 20% of the binding sites were not mu, delta, or kappa. The Scatchard plot of the binding of [3H]EKC was nonlinear but became linear in the presence of naloxone (1 microM), suggesting a single class of naloxone-inaccessible receptor sites. This biochemically readily distinguishable receptor type bound the dextrorotatory isomer of EKC stereoselectively. The sigma agonist N-allylnormetazocine [(+)-SKF 10,047] stereoselectively competed with the binding of [3H]EKC to this naloxone-inaccessible binding site. A number of opiates that have psychotomimetic activity also competed for binding to this binding site. This binding site is designated as sigma binding site according to the nomenclature originally suggested by Martin et al. [Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E. & Gilbert, P. E. (1976) J. Pharmacol. Exp. Ther. 197, 517-532]. The drug selectivity and regional distribution of this sigma binding site in the rat central nervous system are different from that of the mu and delta opioid receptors and phencyclidine receptors. The concentration of the sigma binding site is highest in the spinal cord, pons and medulla, and cerebellum.

EXP063 (4-[[4-[[3-(N-isopropylamino)-2-hydroxypropyl]oxy]- indole-2-carboxamido]methyl]-2-propyl-1-[(2'-(1H-tetrazol-5-yl)bip henyl-4 - yl)methyl]imidazole-5-carboxylic acid) was designed to possess both the angiotensin II (Ang II) and beta adrenergic receptor antagonistic properties. EXP063 inhibited the specific binding of [125I]Sar1,lle8-Ang II in rat adrenal membranes with Ki values of 3.9 +/- 0.6 nM for the Ang II type 1 and > 1 microM for the Ang II type 2 receptor binding sites. It displaced [3H]dihydroalprenolol in the rat cerebral frontal cortex with a Ki of 80 +/- 13 nM. EXP063 antagonized the contractile effect of Ang II competitively (pA2 = 8.9 +/- 0.1) and selectively in rabbit aorta and guinea pig ileum. EXP063 appears to be a partial beta adrenoceptor agonist as it increased heart rate in vitro and in vivo. At 1 and 10 microM, it inhibited the positive inotropic effect of isoproterenol in guinea pig atria. In pithed rats, EXP063 was more potent in blocking the pressor effect of Ang II than the positive chronotropic effect of isoproterenol. In renal hypertensive rats, EXP063 given i.v. produced a long-lasting decrease in blood pressure for at least 6 hr with an ED30 of 0.53 mg/kg. In summary, this study demonstrates that EXP063 is a novel chemical entity possessing both the Ang II and beta adrenergic receptor blocking properties and, thus, represents a promising agent for the treatment of hypertension and congestive heart failure.

Apoptosis was induced in S-phase-arrested HeLa cells by staurosporine, caffeine, 6-dimethylaminopurine, and okadaic acid, agents that activate M-phase-promoting factor and induce premature mitosis in similarly treated hamster cell lines. Addition of these agents to asynchronously growing HeLa cells or to cells arrested in early G1 phase with lovastatin had little or no effect. S-phase arrest also promoted tumor necrosis factor alpha-induced apoptosis, eliminating the normal requirement for simultaneous cycloheximide treatment. For all of the apoptosis-inducing agents tested, the appearance of condensed chromatin was accompanied by 2- to 7-fold increases in cyclin A-associated histone H1 kinase activity, levels approximating the mitotic value. Where examined, both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. Stable overexpression of bcl-2 suppressed the apoptosis-inducing activity of all agents tested and reduced the amount of Cdc2 and Cdk2 in the nucleus, suggesting a possible mechanism by which bcl-2 inhibits the chromatin condensation characteristic of apoptosis. These findings suggest that at least one of the biochemical steps required for mitosis, activation of cyclin A-dependent protein kinases, is also an important event during apoptosis.

The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[3H]SKF 10,047 (N-allylnormetazocine) and to dopamine D2 sites was investigated. In guinea pig brain membranes, (+)-[3H]SKF 10,047 bound to a single class of sites with a Kd of 4 X 10(-8) M and a Bmax of 333 fmol/mg of protein. This binding was different from mu, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[3H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol greater than perphenazine greater than fluphenazine greater than acetophenazine greater than trifluoperazine greater than molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[3H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[3H]SKF 10,047 binding sites did not correlate with those for [3H]spiperone (dopamine D2) sites. [3H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-SKF 10,047. In the striatum, about half of the saturable [3H]haloperidol binding was to [3H]spiperone (D2) sites and the other half was to sites similar to (+)-[3H]SKF 10,047 binding sites.

This study reports a relation between electron flux modulations and chorus emissions by using correlation analysis. On April 18, 2017, Arase observed an enhancement of electron fluxes and intensification of banded chorus emissions at the same time. A result of the analysis shows that both the upper‐band and lower‐band chorus emissions have good correlations with field‐aligned electron fluxes that satisfy their resonance conditions. This indicates simultaneous interactions with both the emission bands and electrons, resulting in electron pitch‐angle scattering toward the magnetic field direction. In addition, low‐energy electron fluxes in the perpendicular direction also show positive correlations with the chorus intensities, probably because the chorus emissions are modulated by a fluctuation of perpendicular low‐energy electron fluxes. Scientists have believed that pulsating auroras in the polar regions originate in precipitating electrons that are caused by a wave‐particle interaction in the magnetosphere. Recent observational studies show direct evidence that chorus waves near the magnetic equator scatter local magnetospheric electrons, which are then streaming along the field line down to the ionosphere to generate aurora pulsation in response to modulation of the chorus emissions. Chorus waves usually have two distinct frequency bands, that is, upper band and lower band, but it had not been investigated that how two emission bands interact with electrons. In this study, we analyzed Arase satellite's observation data and identified good correlations between field‐aligned electron fluxes and intensities of the upper‐band and lower‐band emissions. This result indicates that pitch‐angle scattering of electrons takes place by both chorus emission bands simultaneously. Arase observed intense banded chorus emissions near the magnetic equator simultaneously with an electron flux enhancementParallel electron fluxes show good correlations with intensities of both the upper‐band and the lower‐band chorus wavesThe positive correlation indicates pitch‐angle scattering of electrons by the chorus waves toward the magnetic field direction Arase observed intense banded chorus emissions near the magnetic equator simultaneously with an electron flux enhancement Parallel electron fluxes show good correlations with intensities of both the upper‐band and the lower‐band chorus waves The positive correlation indicates pitch‐angle scattering of electrons by the chorus waves toward the magnetic field direction

This report describes electron beams observed at high latitudes in the magnetosphere by the Arase satellite. According to fine angular channel measurements, beam electrons are mainly flowing away from the Earth, and are well collimated to within a few degrees. A statistical study indicates that the beams are seen when Arase is located at Lm> ∼5, and more frequently as the magnetosphere becomes active. The field lines of the beam events are traced back to the typical auroral ovals. The statistical properties of the beams are consistent with the interpretation that ionospheric electrons are accelerated by a parallel electric field of an auroral potential structure and are streaming upward to the high latitude magnetosphere. It is well accepted that discrete aurora is generated by precipitating electrons that are accelerated by an upward electric field. As a counterpart, a downward electric field exists in the vicinity of the upward electric field, accelerating ionospheric electrons upward to the magnetosphere. Such electron beams have been already reported by spacecraft observations in low altitudes and also in the magnetosphere. It is known that electron beams observed in the magnetosphere are collimated, but the pitch angle widths of the collimated beams have not been well resolved yet. In this report, we describe results of electron beam observations in the high latitude magnetosphere based on fine angular channel measurements of electrons by the Arase satellite. Arase observes electron beams extremely collimated to within a few degrees in the high latitude magnetosphereElectron beams flow away from the Earth along the field lines connected to the auroral ovalsBeam electrons originate from a return current region of auroras in the ionosphere Arase observes electron beams extremely collimated to within a few degrees in the high latitude magnetosphere Electron beams flow away from the Earth along the field lines connected to the auroral ovals Beam electrons originate from a return current region of auroras in the ionosphere

Electrostatic electron cyclotron harmonic (ECH) waves are generally excited in the magnetic equator region, in the sector from nightside to dayside during geomagnetically active conditions, and cause the pitch angle scattering by cyclotron resonance. The scattered electrons precipitate into the Earth's atmosphere and cause auroral emission. However, there is no observational evidence that ECH waves actually scatter electrons into the loss cone in the magnetosphere. In this study, from simultaneous wave and particle observation data obtained by the Arase satellite equipped with a high‐pitch angular resolution electron analyzer, we present evidence that the ECH wave intensity near the magnetic equator is correlated with an electron flux inside the loss cone with an energy of about 5 keV. The simulation suggests that this electron flux contributes to the auroral emission at 557.7 nm with an intensity of about 200 R. Wave‐particle interaction via electrostatic electron cyclotron harmonic (ECH) waves is a promising generation mechanism for precipitating electrons into Earth's atmosphere and producing diffuse auroras. However, there is no observational evidence that ECH waves scatter electrons to cause auroral emissions. In this study, based on observation data obtained by the Arase satellite equipped with a high‐angular resolution electron analyzer, we identified an event during which the ECH wave intensity near the magnetic equator was correlated with the electron flux that precipitated into the Earth's atmosphere. Our simulation suggests that this electron flux contributes to visible oxygen green‐line auroral emission. We found an event that electron cyclotron harmonic wave intensity correlated with electron flux in a loss cone with ~5 keV energyThe pitch‐angle diffusion coefficient of 5 keV is larger than those of other energies when the electron temperature is 8 eV and the wave normal angle is 88.5°The electron flux correlated with the ECH wave intensity can cause 557.7 nm auroral emission with ~200 R intensity

Auroral arcs and diffuse auroras are common phenomena at high latitudes, though characteristics of their source plasma and fields have not been well understood. We report the first observation of fields and particles including their pitch‐angle distributions in the source region of auroral arcs and diffuse auroras, using data from the Arase satellite at L~ 6.0–6.5. The auroral arcs appeared and expanded both poleward and equatorward at local midnight from ~0308 UT on 11 September 2018 at Nain (magnetic latitude: 66°), Canada, during the expansion phase of a substorm, while diffuse auroras covered the whole sky after 0348 UT. The top part of auroral arcs was characterized by purple/blue emissions. Bidirectional field‐aligned electrons with structured energy‐time spectra were observed in the source region of auroral arcs, while source electrons became isotropic and less structured in the diffuse auroral region afterwards. We suggest that structured bidirectional electrons at energies below a few keV were caused by upward field‐aligned potential differences (upward electric field along geomagnetic field) reaching high altitudes (~30,000 km) above Arase. The bidirectional electrons above a few keV were probably caused by Fermi acceleration associated with the observed field dipolarization. Strong electric‐field fluctuations and earthward Poynting flux were observed at the arc crossing and are probably also caused by the field dipolarization. The ions showed time‐pitch‐angle dispersion caused by mirror reflection. These results indicate a clear contrast between auroral arcs and diffuse auroras in terms of source plasma and fields and generation mechanisms of auroral arcs in the inner magnetosphere. Auroral arcs or curtains are a familiar phenomenon seen at high latitudes, and aurora is also present in diffuse form. In near‐Earth space, plasmas and electric and magnetic fields are known to have interactions that cause the auroral phenomena, but a direct link between measurements in space and the corresponding auroras near the surface has been hard to make. The Arase satellite carries advanced plasma and field instruments allowing detailed study of conditions in space, so campaign observations were carried out at Nain, Canada, in September 2018, at a time when it was expected to be connected to the region by following magnetic field lines. Both discrete and diffuse auroras were observed from the ground, while in space electrons and ions were observed, whose characteristics changed depending on whether the spacecraft was lined up with discrete auroras, or later, with diffuse auroras. The auroras and particles changed with time due to a “substorm,” which made the auroras brighten while making the particles more energetic. The observations suggest mechanisms by which the particles may be energized during substorms, with direct measurements in the source region. This is the first observation of the source plasma features of auroral arcs and diffuse auroras in the inner magnetosphere by AraseUnique purple/blue auroral arcs appeared in association with an arrival of corotating interaction region (CIR) in the solar windDuring the arc crossing, field‐aligned electrons, time‐pitch‐angle dispersion of ions, and strong electric field variations were observed

In this study, we describe small‐scale density depletions of cold electrons associated with electrostatic electron cyclotron harmonic (ECH) waves observed by the ERG (Exploration of energization and Radiation in Geospace) spacecraft during a plasmapause crossing near the magnetic equator in the postmidnight sector. The total electron density was roughly 2 orders of magnitude larger than that of the hot electrons, indicating existence of a cold and dense electron population below ∼20 eV. The cold electron density profile showed small‐scale density depletion regions, in which the ECH emissions were intensified. Moreover, a flux enhancement of hot electrons in the perpendicular direction was also associated with the ECH emissions intensity. This relation suggests perpendicular energization of electrons by electric field oscillation of the ECH waves. This study clarifies a relation of cold‐electron density irregularities and electron cyclotron harmonic (ECH) waves, both of which are frequently observed in the inner magnetosphere but their relation had not been clearly indicated by observations. We analyzed a plasmapause crossing event on 12 April 2017 observed by the ERG spacecraft and found that the plasmapause had small‐scale density depletions of cold electrons and ECH emissions were intensified inside the depletion regions. This suggests that an ECH emission intensity can be controlled by a background cold‐electron population. In addition, enhancements of hot‐electron fluxes in the direction perpendicular to the local magnetic field were also observed in response to the ECH emissions. This is probably due to perpendicular energization of cold electrons by the oscillating electric field of the ECH waves. The close relation between cold electrons and ECH emission intensification, shown in this analysis, gives indication of leakage of ionospheric cold electrons and its control of equatorial ECH waves just outside the plasmapause. The ERG spacecraft observes density depletions associated with ECH waves during a plasmapause crossingThe ECH waves are intensified inside the density depletion regionsThe electric field of the ECH waves energizes electrons in the perpendicular directions

The synthesis and the structural and electrochemical characterization of a flavinophane in its oxidized (cf.