Jovian Injections Observed at High Latitude.

The polar orbit of Juno at Jupiter provides a unique opportunity to observe high-latitude energetic particle injections. We measure energy-dispersed impulsive injections of protons and electrons. Ion injection signatures are just as prevalent as electron signatures, contrary to previous equatorial observations. Included are previously unreported observations of high-energy banded structures believed to be remnants of much earlier injections, where the particles have had time to disperse around Jupiter. A model fit of the injections used to estimate timing fits the shape of the proton signatures better than it does the electron shapes, suggesting that electrons and protons are different in their abilities to escape the injection region. We present ultaviolet observations of Jupiter's aurora and discuss the relationship between auroral injection features and in situ injection events. We find, unexpectedly, that the presence of in situ particle injections does not necessarily result in auroral injection signatures.

High-Energy (>10 MeV) Oxygen and Sulfur Ions Observed at Jupiter From Pulse Width Measurements of the JEDI Sensors.

The Jovian polar regions produce X-rays that are characteristic of very energetic oxygen and sulfur that become highly charged on precipitating into Jupiter's upper atmosphere. Juno has traversed the polar regions above where these energetic ions are expected to be precipitating revealing a complex composition and energy structure. Energetic ions are likely to drive the characteristic X-rays observed at Jupiter (Haggerty et al., 2017, https://doi.org/10.1002/2017GL072866; Houston et al., 2018, https://doi.org/10.1002/2017JA024872; Kharchenko et al., 2006, https://doi.org/10.1029/2006GL026039). Motivated by the science of X-ray generation, we describe here Juno Jupiter Energetic Particle Detector Instrument (JEDI) measurements of ions above 1 MeV and demonstrate the capability of measuring oxygen and sulfur ions with energies up to 100 MeV. We detail the process of retrieving ion fluxes from pulse width data on instruments like JEDI (called "puck's"; Clark, Cohen, et al., 2016, https://doi.org/10.1002/2017GL074366; Clark, Mauk, et al., 2016, https://doi.org/10.1002/2015JA022257; Mauk et al., 2013, https://doi.org/10.1007/s11214-013-0025-3) as well as details on retrieving very energetic particles (>20 MeV) above which the pulse width also saturates.

Discrete and broadband electron acceleration in Jupiter's powerful aurora.

The most intense auroral emissions from Earth's polar regions, called discrete for their sharply defined spatial configurations, are generated by a process involving coherent acceleration of electrons by slowly evolving, powerful electric fields directed along the magnetic field lines that connect Earth's space environment to its polar regions. In contrast, Earth's less intense auroras are generally caused by wave scattering of magnetically trapped populations of hot electrons (in the case of diffuse aurora) or by the turbulent or stochastic downward acceleration of electrons along magnetic field lines by waves during transitory periods (in the case of broadband or Alfvénic aurora). Jupiter's relatively steady main aurora has a power density that is so much larger than Earth's that it has been taken for granted that it must be generated primarily by the discrete auroral process. However, preliminary in situ measurements of Jupiter's auroral regions yielded no evidence of such a process. Here we report observations of distinct, high-energy, downward, discrete electron acceleration in Jupiter's auroral polar regions. We also infer upward magnetic-field-aligned electric potentials of up to 400 kiloelectronvolts, an order of magnitude larger than the largest potentials observed at Earth. Despite the magnitude of these upward electric potentials and the expectations from observations at Earth, the downward energy flux from discrete acceleration is less at Jupiter than that caused by broadband or stochastic processes, with broadband and stochastic characteristics that are substantially different from those at Earth.

The "Puck" energetic charged particle detector: Design, heritage, and advancements.

Energetic charged particle detectors characterize a portion of the plasma distribution function that plays critical roles in some physical processes, from carrying the currents in planetary ring currents to weathering the surfaces of planetary objects. For several low-resource missions in the past, the need was recognized for a low-resource but highly capable, mass-species-discriminating energetic particle sensor that could also obtain angular distributions without motors or mechanical articulation. This need led to the development of a compact Energetic Particle Detector (EPD), known as the "Puck" EPD (short for hockey puck), that is capable of determining the flux, angular distribution, and composition of incident ions between an energy range of ~10 keV to several MeV. This sensor makes simultaneous angular measurements of electron fluxes from the tens of keV to about 1 MeV. The same measurements can be extended down to approximately 1 keV/nucleon, with some composition ambiguity. These sensors have a proven flight heritage record that includes missions such as MErcury Surface, Space ENvironment, GEochemistry, and Ranging and New Horizons, with multiple sensors on each of Juno, Van Allen Probes, and Magnetospheric Multiscale. In this review paper we discuss the Puck EPD design, its heritage, unexpected results from these past missions and future advancements. We also discuss high-voltage anomalies that are thought to be associated with the use of curved foils, which is a new foil manufacturing processes utilized on recent Puck EPD designs. Finally, we discuss the important role Puck EPDs can potentially play in upcoming missions.

Prospective evaluation of the fetal heart using Fetal Intelligent Navigation Echocardiography (FINE).

OBJECTIVE: To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. METHODS: In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. RESULTS: One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. CONCLUSIONS: In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Bidirectional modulation of hippocampal gamma (20-80 Hz) frequency activity in vitro via alpha(α)- and beta(ß)-adrenergic receptors (AR).

Noradrenaline (NA) in the hippocampus plays an important role in memory function and has been shown to modulate different forms of synaptic plasticity. Oscillations in the gamma frequency (20-80 Hz) band in the hippocampus have also been proposed to play an important role in memory functions and, evidence from both in vitro and in vivo studies, has suggested this activity can be modulated by NA. However, the role of different NA receptor subtypes in the modulation of gamma frequency activity has not been fully elucidated. We have found that NA (30 µM) exerts a bidirectional control on the magnitude of kainate-evoked (50-200 nM) gamma frequency oscillations in the cornu Ammonis (CA3) region of the rat hippocampus in vitro via activation of different receptor subtypes. Activation of alpha-adrenergic receptors (α-AR) reduced the power of the gamma frequency oscillation. In contrast, activation of beta-adrenergic receptors (ß-AR) caused an increase in the power of the gamma frequency oscillations. Using specific agonists and antagonists of AR receptor subtypes we demonstrated that these effects are mediated specifically via α1A-AR and ß1-AR subtypes. NA activated both receptor subtypes, but the α1A-AR-mediated effect predominated, resulting in a reversible suppression of gamma frequency activity. These results suggest that NA is able to differentially modulate on-going gamma frequency oscillatory activity that could result in either increased or decreased information flow through the hippocampus.

A case series of patients with lamotrigine toxicity at one center from 2003 to 2012.

INTRODUCTION: Lamotrigine is a phenyltriazine compound that inhibits voltage-gated sodium channels, decreasing release of glutamate and aspartate, and inhibits serotonin, norepinephrine and dopamine reuptake. Reports of toxicity in the literature are limited to case reports and primarily involve coingestants. This case series is intended to report the clinical manifestations of lamotrigine toxicity. METHODS: This retrospective case series from 2003 to 2012 studies the effects of lamotrigine toxicity when not confounded by coingestants. Admission records at an inpatient toxicology center were reviewed for lamotrigine-only exposure based on history with supporting laboratory data when available. After identification, these charts were reviewed again to characterize vital signs, neurological examination findings, specific laboratory and electrocardiography parameters, and complications. RESULTS: Fifty-seven patients were identified with possible lamotrigine toxicity. Nine patients, including three toddlers, had lamotrigine-only ingestions. Three of these patients had seizures, four were hypertensive, five were tachycardic, and four experienced tachypnea. Mental status was altered in all nine (depressed (n = 4), agitated (n = 5) or both (n = 3)). Five patients were hyperreflexic and experienced intermittent myoclonus, and two had inducible clonus. On electrocardiogram, two patients experienced QRS prolongation (114-116 ms), and four had QTc prolongation (463-586 ms). No patient had life-threatening symptoms or signs. Serum levels of lamotrigine were available in seven patients, and averaged 35.4 mg/L (17-90 mg/L). The therapeutic range for sLTG is 3-14 mg/L. CONCLUSIONS: Lamotrigine toxicity manifested with minor-moderate neurologic and/or electrocardiographic effects. Toxicity reflects the known pharmacologic actions of lamotrigine: serotonin, norepinephrine and dopamine reuptake inhibition, and sodium channel blockade.

Energetic particles in the jovian magnetotail.

When the solar wind hits Jupiter's magnetic field, it creates a long magnetotail trailing behind the planet that channels material out of the Jupiter system. The New Horizons spacecraft traversed the length of the jovian magnetotail to >2500 jovian radii (RJ; 1 RJ identical with 71,400 kilometers), observing a high-temperature, multispecies population of energetic particles. Velocity dispersions, anisotropies, and compositional variation seen in the deep-tail (greater, similar 500 RJ) with a approximately 3-day periodicity are similar to variations seen closer to Jupiter in Galileo data. The signatures suggest plasma streaming away from the planet and injection sites in the near-tail region (approximately 200 to 400 RJ) that could be related to magnetic reconnection events. The tail structure remains coherent at least until it reaches the magnetosheath at 1655 RJ.

Phylogenetic characterization of novel transport protein families revealed by genome analyses.

As a result of recent genome sequencing projects as well as detailed biochemical, molecular genetic and physiological experimentation on representative transport proteins, we have come to realize that all organisms possess an extensive but limited array of transport protein types that allow the uptake of nutrients and excretion of toxic substances. These proteins fall into phylogenetic families that presumably reflect their evolutionary histories. Some of these families are restricted to a single phylogenetic group of organisms and may have arisen recently in evolutionary time while others are found ubiquitously and may be ancient. In this study we conduct systematic phylogenetic analyses of 26 families of transport systems that either had not been characterized previously or were in need of updating. Among the families analyzed are some that are bacterial-specific, others that are eukaryotic-specific, and others that are ubiquitous. They can function by either a channel-type or a carrier-type mechanism, and in the latter case, they are frequently energized by coupling solute transport to the flux of an ion down its electrochemical gradient. We tabulate the currently sequenced members of the 26 families analyzed, describe the properties of these families, and present partial multiple alignments, signature sequences and phylogenetic trees for them all.

Age-related differences in adults' macrospatial cognitive processes.

Young and elderly adults' performance was compared on the Landmark Selection Task, designed to assess perceptual selection, and the Scrambled Route Task, designed to assess temporospatial integration. Age-related performance decrements were found on both tasks. Subjects' scores on psychometric tests hypothesized as involving some of the same processes as these experimental tasks yielded positive correlations to measures of task performance. Unexpectedly, self-estimates of wayfinding and distance estimation skills were negatively correlated to experimental task performance for elderly adults. Results were discussed in the context of declines in the effectiveness of selective attention, which is considered critical to perceptual selection, and in the proficiency of working memory, which is considered central to temporospatial integration.

Abnormalities of carbohydrate metabolism and of OCT gene function in the Rett syndrome.

The pathogenetic basis of the Rett syndrome (RS) is unknown: an X-linked dominant, male-lethal gene defect is thought likely. We present a girl with RS who has defects both of the urea cycle and of carbohydrate metabolism resulting in fasting hypoglycaemia, post-prandial hyperlactataemia and excess urinary orotic acid excretion after alanine load. Her sister has a similar clinical picture, but less marked metabolic anomalies. The mother of these sisters has abnormal urinary orotic acid excretion; she transmitted opposite ornithine carbomoyltransferase (OCT) alleles to the two girls. Another girl with RS has similar metabolic responses to fasting and to carbohydrate load. We conclude that RS may be an aetiologically homogeneous condition, but that it includes a variable pattern of metabolic anomalies, and that the gene defect is distinct from the OCT locus.

Differential expression of multiple forms of arginase in cultured cells.

Arginase (EC 3.5.3.1), the final enzyme in the urea cycle, catalyzes the cleavage of arginine to orthinine and urea. At least two forms of this enzyme, AI and AII, have been described and are probably encoded by discrete genetic loci. The expression of these separate genes has been studied in mammalian cells grown in culture. The permanent rat-hepatoma line H4-II-E-C3 contained exclusively the AI enzyme; the form in mammals comprising about 98% of the arginase activity in liver and erythrocytes but catalyzing only about one half of that reaction in kidney, gastrointestinal tract, and brain. By contrast, human-embryonic-kidney and -brain cells, after transformation with the human papovavirus BK, contained only the AII species of arginase, which form contributes the remaining half of that catalysis in those mammalian tissues in vivo. We report here the results of an extensive study on the properties of these two forms of arginase in the three cell lines, including Km values for arginine, behavior on polyacrylamide gels under non-denaturing conditions, and cross-reactivity with lapine antibodies against the arginases from either rat or human liver.

Regulation by glucocorticoids of rat-liver phenylalanine hydroxylase in vivo.

Phenylalanine hydroxylase, a liver-associated enzyme, is induced markedly by glucocorticoids in two permanent rat-hepatoma cell lines. In order to gain evidence that this phenomenon also occurs in vivo, we examined the effect of adrenalectomy and/or hormone supplementation on the levels of phenylalanine hydroxylase in the livers of adult rats: glucocorticoid administration increases, and adrenal ablation reduces, the activity of the hepatic enzyme, and the diminution occurring in the latter instance is entirely prevented by concurrent hormone replacement. These results thus corroborate earlier findings from a single experiment and are consistent with the hypothesis that adrenal corticosteroid hormones participate in modulating phenylalanine-hydroxylase levels within the diploid hepatocyte.

Regulation of expression of genes for enzymes of the mammalian urea cycle in permanent cell-culture lines of hepatic and non-hepatic origin.

We present here the results of investigations conducted by ourselves and others on the regulation of the expression of genes encoding the enzymes of the mammalian urea cycle as manifest in cultured cells of both hepatic and extrahepatic origin. Upon consideration of the recently discovered discrete non-hepatic arginase genetic locus in man and our consequent hypothesis that the form of arginase thus transcribed in such extrahepatic cells functions principally in providing ornithine for protein anabolism and polyamine biosynthesis, rather than in detoxifying ammonia through urea formation, we have chosen instead to study permanent cell lines that are derived from liver and continue to perform a variety of hepatic functions in culture as experimental models for probing the molecular mechanisms underlying the control of ureagenesis within the mature liver cell. Of two such arginase-positive rat-hepatoma lines, we have characterized extensively in one (H4-II-E-C3) the mode of action of glucocorticoids in augmenting the cellular levels of this enzyme as well as of argininosuccinate synthetase. To this end, we have recently demonstrated that these stimulations are both mediated by binding of the hormones to classical cytoplasmic steroid receptors in a specific and saturable fashion and have thus concluded that the H4-II-E-C3 line will provide a suitable cell culture system for subsequent more detailed experiments from which the information garnered will continue to be relevant to the ureagenic pathway as modulated in the differentiated hepatocyte in vivo.

Regulation of glucocorticoids of arginase and argininosuccinate synthetase in cultured rat hepatoma cells.

We have examined and characterized the regulation by glucocorticoids of the levels of arginase and argininosuccinate synthetase in two rat hepatoma cell lines (H4-II-E-C3 and MH1C1). Hydrocortisone elevates the activity of both enzymes in a time- and dose-dependent fashion. This effect was blunted markedly by small amounts of ethanol (0.1 to 0.9% [v/v]) and blocked substantially by a high molar excess of the "anti-inducer" steroid fluoxymesterone. The other "optimal" inducers dexamethasone and corticosterone were as effective as hydrocortisone in elevating the levels of these enzymes at saturating concentrations. Inhibition of these stimulations by cycloheximide indicated that ongoing cellular protein synthesis was required for both effects, and the admixture of extracts from fully stimulated and basal cells gave no evidence for the existence of direct inhibitors or activators of either enzyme. The results corroborate findings from earlier whole-animal studies and provide evidence for the following conclusions. (i) This stimulation by hydrocortisone of urea-cycle enzymes in the cultured hepatoma cells is mediated by a classical glucocorticoid mechanism involving initial binding to specific cytoplasmic steroid receptors and the eventual accumulation of new enzyme molecules. (ii) These cell lines thus constitute valid experimental models for use in further detailed studies on the molecular mechanism(s) through which glucocorticoids and intermediary metabolites effect a selective modulation of arginase and argininosuccinate-synthetase gene expression in the differentiated mammalian liver.

Translation of phenylalanine hydroxylase-specific mRNA in vitro: evidence for pretranslational control by glucocorticoids.

We have found that the induction of phenylalanine hydroxylase by hydrocortisone and serum in confluent cultures of H4-II-E-C3 rat hepatoma cells is accompanied by an increase in polysomal mRNA specific for phenylalanine hydroxylase, as measured by translation in a cell-free protein-synthesizing system. Thus, the induction is mediated largely, if not entirely, by a pretranslational mechanism, possibly by stimulation of the transcription of the phenylalanine hydroxylase gene.

The Escherichia coli L-arabinose operon: binding sites of the regulatory proteins and a mechanism of positive and negative regulation.

The locations of DNA binding by the proteins involved with positive and negative regulation of transcription initiation of the L-arabinose operon in Escherichia coli have been determined by the DNase I protection method. Two cyclic AMP receptor protein sites were found, at positions -78 to -107 and -121 to -146, an araC protein--arabinose binding site was found at position -40 to -78, and an araC protein-fucose binding site was found at position -106 to -144. These locations, combined with in vivo data on induction of the two divergently oriented arabinose promoters, suggest the following regulatory mechanism: induction of the araBAD operon occurs when cyclic AMP receptor protein, araC protein, and RNA polymerase are all present and able to bind to DNA. Negative regulation is accomplished by the repressing form of araC protein binding to a site in the regulatory region such that it stimultaneously blocks access of cyclic AMP receptor protein to two sites on the DNA, one site of which serves each of the two promoters. Thus, from a single operator site, the negative regulator represses the two outwardly oriented ara promoters. This regulatory mechanism explains the known positive and negative regulatory properties of the ara promoters.