Global electric field determination in the Earth's outer magnetosphere using charged particles

Although many properties of the Earth's magnetosphere have been measured and quantified in the past 30 years since it was discovered, one fundamental (for a zeroeth order magnetohydrodynamic (MHD) equilibrium) measurement was made infrequently and with poor spatial coverage: the global electric field. This oversight is in part due to the difficulty of measuring a plasma electric field, and in part due to the difficulty of measuring a plasma electric field, and in part due to the neglect of theorists. However, there is renewed interest in the convection electric field, since it has been realized that it is vital for understanding many aspects of the magnetosphere: the global MHD equilibrium, reconnection rates, Region 2 Birkeland currents, magnetosphere-ionosphere coupling, ring current and radiation belt transport, substorm injections, acceleration mechanisms, etc. Unfortunately the standard experimental methods have not been able to synthesize a global field (excepting the pioneering work of McIlwain's geostationary models), and we are left with an overly simplistic theoretical field, the Volland-Stern electric field mode. Again, single point measurements of the plasma pause were used to infer the appropriate amplitudes of the model, parameterized by Kp (Maynard & Chen, JGR 1975). Although this result was never intended to be the definitive electric field model, it has gone nearly unchanged for 15 years. However, the data sets being taken today require a great deal more accuracy than can be provided by the Volland-Stern model. Nor has the variability of the electric field shielding been properly addressed, although effects of penetrating magnetospheric electric fields has been seen in mid- and low-latitude ionospheric data sets. The growing interests in substorm dynamics also requires a much better assessment of the electric fields responsible for particle injections. Thus, we proposed and developed algorithms for extracting electric fields from particle data taken in the earth's magnetosphere. As a test of the effectiveness of these techniques, we analyzed data taken by the AMPTE/CCE spacecraft in equatorial orbit between 1984-1988. Some analytic tools had to be developed before construction of computer algorithms, and they are discussed

Periodic substorm activity in the geomagnetic tail

On 19 May 1978 an anusual series of events is observed with the Quadrispherical LEPEDEA on board the ISEE-1 satellite in the Earth's geomagnetic tail. For 13 hours periodic bursts of both ions and electrons are seen in all the particle detectors on the spacecraft. On this day periodic activity is also seen on the ground, where multiple intensifications of the electrojets are observed. At the same time the latitudinal component of the interplanetary magnetic field shows a number of strong southward deflections. It is concluded that an extended period of substorm activity is occurring, which causes repeated thinnings and recoveries of the plasma sheet. These are detected by ISEE, which is situated in the plasma sheet boundary layer, as periodic dropouts and reappearances of the plasma. Comparisons of the observations at ISEE with those at IMP-8, which for a time is engulfed by the plasma sheet, indicate that the activity is relatively localized in spatial extent. For this series of events it is clear that a global approach to magnetospheric dynamics, e.g., reconnection, is inappropriate

A simplified procedure for correcting both errors and erasures of a Reed-Solomon code using the Euclidean algorithm

It is well known that the Euclidean algorithm or its equivalent, continued fractions, can be used to find the error locator polynomial and the error evaluator polynomial in Berlekamp's key equation needed to decode a Reed-Solomon (RS) code. A simplified procedure is developed and proved to correct erasures as well as errors by replacing the initial condition of the Euclidean algorithm by the erasure locator polynomial and the Forney syndrome polynomial. By this means, the errata locator polynomial and the errata evaluator polynomial can be obtained, simultaneously and simply, by the Euclidean algorithm only. With this improved technique the complexity of time domain RS decoders for correcting both errors and erasures is reduced substantially from previous approaches. As a consequence, decoders for correcting both errors and erasures of RS codes can be made more modular, regular, simple, and naturally suitable for both VLSI and software implementation. An example illustrating this modified decoding procedure is given for a (15, 9) RS code

A systematic and prospectively validated approach for identifying synergistic drug combinations against malaria.

BACKGROUND: Nearly half of the world's population (3.2 billion people) were at risk of malaria in 2015, and resistance to current therapies is a major concern. While the standard of care includes drug combinations, there is a pressing need to identify new combinations that can bypass current resistance mechanisms. In the work presented here, a combined transcriptional drug repositioning/discovery and machine learning approach is proposed. METHODS: The integrated approach utilizes gene expression data from patient-derived samples, in combination with large-scale anti-malarial combination screening data, to predict synergistic compound combinations for three Plasmodium falciparum strains (3D7, DD2 and HB3). Both single compounds and combinations predicted to be active were prospectively tested in experiment. RESULTS: One of the predicted single agents, apicidin, was active with the AC50 values of 74.9, 84.1 and 74.9 nM in 3D7, DD2 and HB3 P. falciparum strains while its maximal safe plasma concentration in human is 547.6 ± 136.6 nM. Apicidin at the safe dose of 500 nM kills on average 97% of the parasite. The synergy prediction algorithm exhibited overall precision and recall of 83.5 and 65.1% for mild-to-strong, 48.8 and 75.5% for moderate-to-strong and 12.0 and 62.7% for strong synergies. Some of the prospectively predicted combinations, such as tacrolimus-hydroxyzine and raloxifene-thioridazine, exhibited significant synergy across the three P. falciparum strains included in the study. CONCLUSIONS: Systematic approaches can play an important role in accelerating discovering novel combinational therapies for malaria as it enables selecting novel synergistic compound pairs in a more informed and cost-effective manner

Photon-weighted barycentric correction and its importance for precise radial velocities

When applying the barycentric correction to a precise radial velocity measurement, it is common practice to calculate its value only at the photon-weighted midpoint time of the observation instead of integrating over the entire exposure. However, since the barycentric correction does not change linearly with time, this leads to systematic errors in the derived radial velocities. The typical magnitude of this second-order effect is of order 10 cm s$^{-1}$, but it depends on several parameters, e.g. the latitude of the observatory, the position of the target on the sky, and the exposure time. We show that there are realistic observing scenarios, where the errors can amount to more than 1 ms$^{-1}$. We therefore recommend that instruments operating in this regime always record and store the exposure meter flux curve (or a similar measure) to be used as photon-weights for the barycentric correction. In existing data, if the flux curve is no longer available, we argue that second-order errors in the barycentric correction can be mitigated by adding a correction term assuming constant flux.Comment: 9 pages, 7 figures, accepted to MNRA

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites <i>Trypanosoma brucei rhodesiense</i> or <i>Trypanosoma brucei gambiense</i>, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. <i>In vitro</i> assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherap

Working group report on beam plasmas, electronic propulsion, and active experiments using beams

The JPL Workshop addressed a number of plasma issues that bear on advanced spaceborne technology for the years 2000 and beyond. Primary interest was on the permanently manned space station with a focus on identifying environmentally related issues requiring early clarification by spaceborne plasma experimentation. The Beams Working Group focused on environmentally related threats that platform operations could have on the conduct and integrity of spaceborne beam experiments and vice versa. Considerations were to include particle beams and plumes. For purposes of definition it was agreed that the term particle beams described a directed flow of charged or neutral particles allowing single-particle trajectories to represent the characteristics of the beam and its propagation. On the other hand, the word plume was adopted to describe a multidimensional flow (or expansion) of a plasma or neutral gas cloud. Within the framework of these definitions, experiment categories included: (1) Neutral- and charged-particle beam propagation, with considerations extending to high powers and currents. (2) Evolution and dynamics of naturally occurring and man-made plasma and neutral gas clouds. In both categories, scientific interest focused on interactions with the ambient geoplasma and the evolution of particle densities, energy distribution functions, waves, and fields