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The MAss Spectrometer for Planetary EXploration (MASPEX) is a high-mass-resolution, high-sensitivity, multi-bounce time-of-flight mass spectrometer (MBTOF) capable of measuring minor species with abundances of sub-parts-per-million in Europa's sputter-produced and radiolytically modified exosphere and in its oceanic plumes. The goal of the MASPEX-Europa investigation is to determine, through in-situ measurement of the exosphere and plume composition, whether the conditions for habitability exist or have existed on Europa. As conventionally defined, based on our knowledge of Earth life, the three fundamental conditions for habitability are: (1) the presence of liquid water; (2) the presence of organic compounds and the biogenic elements CHNOPS; and (3) a source of energy available for metabolic processes, which for Europa will most probably be chemosynthetic rather than photosynthetic. Condition (1) is already established by previous indirect (magnetic field) measurements, while MASPEX will contribute directly to the evaluation of condition (2) through highly specific compositional measurements in the Europan exosphere and plumes. The composition measurements will also contribute to the test of condition (3) through disequilibrium states of chemical reactions. Thus, the primary goal of MASPEX for Europa Clipper is to assess the habitability of Europa and specifically of its interior ocean. MASPEX has been developed successfully, and its calibration has demonstrated that it meets its specified requirements for sensitivity, dynamic range, and mass resolution. This paper reports the development of the MASPEX scientific investigation, the instrument, its performance, and calibration. [ABSTRACT FROM AUTHOR]

A concise review is given on the past two decades' results from laboratory experiments on collisionless magnetic reconnection in direct relation with space measurements, especially by the Magnetospheric Multiscale (MMS) mission. Highlights include spatial structures of electromagnetic fields in ion and electron diffusion regions as a function of upstream symmetry and guide field strength, energy conversion and partitioning from magnetic field to ions and electrons including particle acceleration, electrostatic and electromagnetic kinetic plasma waves with various wavelengths, and plasmoid-mediated multiscale reconnection. Combined with the progress in theoretical, numerical, and observational studies, the physics foundation of fast reconnection in collisionless plasmas has been largely established, at least within the parameter ranges and spatial scales that were studied. Immediate and long-term future opportunities based on multiscale experiments and space missions supported by exascale computation are discussed, including dissipation by kinetic plasma waves, particle heating and acceleration, and multiscale physics across fluid and kinetic scales. [ABSTRACT FROM AUTHOR]

As a universal structure in space plasma, electron holes represent an obvious signature of nonlinear process. Although the theory has a 60-year history, whether electron hole can finally accelerate ambient electrons (or ions) is quite controversial. Previous theory for one-dimensional holes predicts that net velocity change of passing electrons (or ions) occurs only if the holes have non-zero acceleration. However, the prediction has not yet been demonstrated in observations. Here, we report four electron holes whose acceleration/deceleration is obtained by fitting the spatial separations and detection time delays between different Magnetospheric Multiscale spacecraft. We find that electron hole acceleration/deceleration is related to the ion velocity distribution gradient at the hole's velocity. We observe net velocity changes of ions passing through the accelerating/decelerating holes, in accordance with theoretical predictions. Therefore, we show that electron holes with non-zero acceleration can cause the velocity of passing ions to increase in the acceleration direction. Electron holes with drift speeds comparable to local ion thermal velocity are called slow electron holes. Here, the authors show slow electron holes with non-zero acceleration can cause net velocity change of ions passing through. [ABSTRACT FROM AUTHOR]

In Western Europe, the transition from the middle Iron Age to the early Roman period implied changes in livestock practices, with the emergence of a specialized and selective animal husbandry. These changes have been related in Italy and south of France with changes in livestock management involving their mobility between ecologically complementary areas. The study of this question in the Iberian Peninsula has only been partially investigated through palaeoenvironmental analyses, and the information about the origin and significance of this phenomenon is very scarce. To shed new light on this topic we used an archaeozoological approach, with the application of geometric morphometrics. They were used to study size and shape variability in sheep astragali from 9 sites dating from the middle Iron Age to the early Roman period (5th c. BC–3rd c. AD) and located on the Pyrenees and on the north-eastern Iberian coast as a case study. The results we obtained, combined with Number of Identified Specimens (NISP) and kill-off patterns, showed local specificities in terms of breeding methods and sheep morphologies between the two areas during the middle Iron Age. On the contrary, sheep with similar size and the implementation and development of similar sheep husbandry practices in the Pyrenees and the north-eastern Iberian coast were documented during the early Roman period. These results suggest the existence of livestock links between these two areas during the Roman period, that could be involved a possible movement of sheep between the lowlands and the Pyrenees for the first time. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70-90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation. Methods: Patients recruited from a local endoscopy clinic provided informed consent and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios (ORs) and 95 % confidence intervals (95% CIs) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders. Results: Complete data were available for 107 participants; 36 % had adenomas (men 40 %, women 31 %). Hypomethylation of the MINT1 locus (OR 5.3, 95% CI 1.0-28.2) and the PER1 (OR 2.9, 95% CI 1.1-7.7) and PER3 (OR 11.6, 95% CI 1.6-78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71-97 %), sensitivity was relatively low (18-45 %). Conclusion: Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance. [ABSTRACT FROM AUTHOR]

This paper describes the science motivation, measurement objectives, performance requirements, detailed design, approach and implementation, and calibration of the four Hot Plasma Composition Analyzers (HPCA) for the Magnetospheric Multiscale mission. The HPCA is based entirely on electrostatic optics combining an electrostatic energy analyzer with a carbon-foil based time-of-flight analyzer. In order to fulfill mission requirements, the HPCA incorporates three unique technologies that give it very wide dynamic range capabilities essential to measuring minor ion species in the presence of extremely high proton fluxes found in the region of magnetopause reconnection. Dynamic range is controlled primarily by a novel radio frequency system analogous to an RF mass spectrometer. The RF, in combination with capabilities for high TOF event processing rates and high current micro-channel plates, ensures the dynamic range and sensitivity needed for accurate measurements of ion fluxes between ∼1 eV and 40 keV that are expected in the region of reconnection events. A third technology enhances mass resolution in the presence of high proton flux. In order to calibrate the four HPCA instruments we have developed a unique ion calibration system. The system delivers a multi-species beam resolved to M/Δ M∼100 and current densities between 0.05 and 200 pA/cm with a stability of ±5 %. The entire system is controlled by a dedicated computer synchronized with the HPCA ground support equipment. This approach results not only in accurate calibration but also in a comprehensive set of coordinated instrument and auxiliary data that makes analysis straightforward and ensures archival of all relevant data. [ABSTRACT FROM AUTHOR]

Magnetospheric Multiscale (MMS), a NASA four-spacecraft constellation mission launched on March 12, 2015, will investigate magnetic reconnection in the boundary regions of the Earth's magnetosphere, particularly along its dayside boundary with the solar wind and the neutral sheet in the magnetic tail. The most important goal of MMS is to conduct a definitive experiment to determine what causes magnetic field lines to reconnect in a collisionless plasma. The significance of the MMS results will extend far beyond the Earth's magnetosphere because reconnection is known to occur in interplanetary space and in the solar corona where it is responsible for solar flares and the disconnection events known as coronal mass ejections. Active research is also being conducted on reconnection in the laboratory and specifically in magnetic-confinement fusion devices in which it is a limiting factor in achieving and maintaining electron temperatures high enough to initiate fusion. Finally, reconnection is proposed as the cause of numerous phenomena throughout the universe such as comet-tail disconnection events, magnetar flares, supernova ejections, and dynamics of neutron-star accretion disks. The MMS mission design is focused on answering specific questions about reconnection at the Earth's magnetosphere. The prime focus of the mission is on determining the kinetic processes occurring in the electron diffusion region that are responsible for reconnection and that determine how it is initiated; but the mission will also place that physics into the context of the broad spectrum of physical processes associated with reconnection. Connections to other disciplines such as solar physics, astrophysics, and laboratory plasma physics are expected to be made through theory and modeling as informed by the MMS results. [ABSTRACT FROM AUTHOR]

The Fast Plasma Investigation (FPI) was developed for flight on the Magnetospheric Multiscale (MMS) mission to measure the differential directional flux of magnetospheric electrons and ions with unprecedented time resolution to resolve kinetic-scale plasma dynamics. This increased resolution has been accomplished by placing four dual 180-degree top hat spectrometers for electrons and four dual 180-degree top hat spectrometers for ions around the periphery of each of four MMS spacecraft. Using electrostatic field-of-view deflection, the eight spectrometers for each species together provide 4pi-sr field-of-view with, at worst, 11.25-degree sample spacing. Energy/charge sampling is provided by swept electrostatic energy/charge selection over the range from 10 eV/q to 30000 eV/q. The eight dual spectrometers on each spacecraft are controlled and interrogated by a single block redundant Instrument Data Processing Unit, which in turn interfaces to the observatory's Instrument Suite Central Instrument Data Processor. This paper describes the design of FPI, its ground and in-flight calibration, its operational concept, and its data products. [ABSTRACT FROM AUTHOR]

The Magnetospheric Multiscale (MMS) mission and operations are designed to provide the maximum reconnection science. The mission phases are chosen to investigate reconnection at the dayside magnetopause and in the magnetotail. At the dayside, the MMS orbits are chosen to maximize encounters with the magnetopause in regions where the probability of encountering the reconnection diffusion region is high. In the magnetotail, the orbits are chosen to maximize encounters with the neutral sheet, where reconnection is known to occur episodically. Although this targeting is limited by engineering constraints such as total available fuel, high science return orbits exist for launch dates over most of the year. The tetrahedral spacecraft formation has variable spacing to determine the optimum separations for the reconnection regions at the magnetopause and in the magnetotail. In the specific science regions of interest, the spacecraft are operated in a fast survey mode with continuous acquisition of burst mode data. Later, burst mode triggers and a ground-based scientist in the loop are used to determine the highest quality data to downlink for analysis. This operations scheme maximizes the science return for the mission. [ABSTRACT FROM AUTHOR]

Interplanetary scintillation observations, as well as the ENLIL 3D-MHD model when employed either separately or in combination with the observations, enable the making of predictions of the solar wind density and speed at locations in the inner heliosphere. Both methods are utilized here to predict the arrival at the Rosetta spacecraft and its adjacent comet 67P/Churyumov-Gerasimenko of, flare related, interplanetary propagating shocks and coronal mass ejections in September 2014. The predictions of density and speed variations at the comet are successfully matched with signatures recorded by the magnetometer and the ion and electron sensor instruments in the Rosetta Plasma Package, thereby providing confidence that the signatures recorded aboard the spacecraft were solar related. The plasma perturbations which were detected some 9-10 days after significant flaring in September 2014 are interpreted to have been signatures of the arrivals of three coronal mass ejection related shocks at the comet. Also, a solar energetic particle event was recorded at 3.7 AU within ~30 min of the onset of a flare by the Standard Radiation Monitor aboard Rosetta. [ABSTRACT FROM AUTHOR]

Following a licence extension to include those aged 6-11 years, the National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of omalizumab (Novartis Pharmaceuticals UK) to submit evidence for the clinical and cost effectiveness of this drug for patients with severe persistent allergic asthma in this age bracket. NICE had previously considered the use of omalizumab in patients aged 12 years and over. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) at the University of York were commissioned as the Evidence Review Group (ERG) to critically appraise the evidence presented by the manufacturer. This article summarizes that review of the evidence, the deliberations of the NICE Appraisal Committee and the resulting NICE guidance. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The relevant patient population was patients aged 6-11 years of age with severe persistent allergic immunoglobulin E-mediated asthma whose condition remained uncontrolled despite best standard care with high-dose inhaled corticosteroids and a long-acting inhaled β₂-agonist. The main clinical effectiveness data were derived from a pre-planned subgroup analysis of a single randomized controlled trial comparing omalizumab plus standard therapy against standard therapy alone. At a 52-week follow-up, the only outcome to show a statistically significant benefit of omalizumab compared with placebo was the number of exacerbations defined as 'clinically significant' [CS] (relative risk [RR] 0.504; 95% CI 0.350, 0.725; p < 0.001). At the ERG's request, the manufacturer provided analyses stratified by baseline exacerbation rate, which indicated the effect of omalizumab on CS exacerbations was statistically significant only for those children with ≥3 exacerbations as baseline. The ERG identified a number of issues relating to the clinical effectiveness results: it was unclear whether the pre-planned subgroup analysis had sufficient power; the definition of CS exacerbation was less severe than that used in UK clinical practice; and the method for imputing exacerbations for those who withdrew from treatment may have underestimated the exacerbation rate. The incremental cost-effectiveness ratio based on the manufacturer's results was considerably above the threshold range stated in the NICE Guide to the Methods of Technology Appraisal. The ERG identified numerous issues relating to the cost-effectiveness results, which included the following: the 10-year time horizon for treatment may exceed that in clinical practice; the assumption of constant exacerbation rates over a lifetime given that adolescence is expected to impact on the severity of asthma; and whether it is appropriate to use health-related quality-of-life data collected in adults for children. The ERG concluded that omalizumab appears to reduce CS exacerbations but there was no evidence of improvement in daily symptoms, CS severe (CSS) exacerbations or hospitalization rates. The main driver of cost effectiveness was the reduction in asthma-related mortality associated with a reduction in CSS exacerbations. As the number of CSS exacerbations avoided was low, as is asthma-related mortality in children, the potential small gain in QALYs associated with omalizumab was not sufficient to compensate for the high treatment cost even under the most favourable scenario analyses. The Appraisal Committee recommended that omalizumab should not be routinely provided for the treatment of severe persistent allergic asthma in children aged 6-11 years. [ABSTRACT FROM AUTHOR]

Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) is a NASA Explorer Mission-of-Opportunity to stereoscopically image the Earth’s magnetosphere for the first time. TWINS extends our understanding of magnetospheric structure and processes by providing simultaneous Energetic Neutral Atom (ENA) imaging from two widely separated locations. TWINS observes ENAs from 1–100 keV with high angular (∼4°×4°) and time (∼1-minute) resolution. The TWINS Ly- α monitor measures the geocoronal hydrogen density to aid in ENA analysis while environmental sensors provide contemporaneous measurements of the local charged particle environments. By imaging ENAs with identical instruments from two widely spaced, high-altitude, high-inclination spacecraft, TWINS enables three-dimensional visualization of the large-scale structures and dynamics within the magnetosphere for the first time. This “instrument paper” documents the TWINS design, construction, calibration, and initial results. Finally, the appendix of this paper describes and documents the Southwest Research Institute (SwRI) instrument calibration facility; this facility was used for all TWINS instrument-level calibrations. [ABSTRACT FROM AUTHOR]

The Plasma Experiment for Planetary Exploration (PEPE) flown on Deep Space 1 combines an ion mass spectrometer and an electron spectrometer in a single, low-resource instrument. Among its novel features PEPE incorporates an electrostatically swept field-of-view and a linear electric field time-of-flight mass spectrometer. A significant amount of effort went into developing six novel technologies that helped reduce instrument mass to 5.5 kg and average power to 9.6 W. PEPE’s performance was demonstrated successfully by extensive measurements made in the solar wind and during the DS1 encounter with Comet 19P/Borrelly in September 2001. [ABSTRACT FROM AUTHOR]

The ion and electron sensor (IES) is part of the Rosetta Plasma Consortium (RPC). The IES consists of two electrostatic plasma analyzers, one each for ions and electrons, which share a common entrance aperture. Each analyzer covers an energy/charge range from 1 eV/e to 22 keV/e with a resolution of 4%. Electrostatic deflection is used at the entrance aperture to achieve a field of view of 90°× 360° (2.8π sr). Angular resolution is 5°× 22.5° for electrons and 5°× 45° for ions with the sector containing the solar wind being further segmented to 5°× 5°. The three-dimensional plasma distributions obtained by IES will be used to investigate the interaction of the solar wind with asteroids Steins and Lutetia and the coma and nucleus of comet 67P/Churyumov–Gerasimenko (CG). In addition, photoelectron spectra obtained at these bodies will help determine their composition. [ABSTRACT FROM AUTHOR]

The Rosetta Plasma Consortium (RPC) will make in-situ measurements of the plasma environment of comet 67P/Churyumov-Gerasimenko. The consortium will provide the complementary data sets necessary for an understanding of the plasma processes in the inner coma, and the structure and evolution of the coma with the increasing cometary activity. Five sensors have been selected to achieve this: the Ion and Electron Sensor (IES), the Ion Composition Analyser (ICA), the Langmuir Probe (LAP), the Mutual Impedance Probe (MIP) and the Magnetometer (MAG). The sensors interface to the spacecraft through the Plasma Interface Unit (PIU). The consortium approach allows for scientific, technical and operational coordination, and makes optimum use of the available mass and power resources. [ABSTRACT FROM AUTHOR]

The Ion Composition Analyzer (ICA) is part of the Rosetta Plasma Consortium (RPC). ICA is designed to measure the three-dimensional distribution function of positive ions in order to study the interaction between the solar wind and cometary particles. The instrument has a mass resolution high enough to resolve the major species such as protons, helium, oxygen, molecular ions, and heavy ions characteristic of dusty plasma regions. ICA consists of an electrostatic acceptance angle filter, an electrostatic energy filter, and a magnetic momentum filter. Particles are detected using large diameter (100 mm) microchannel plates and a two-dimensional anode system. ICA has its own processor for data reduction/compression and formatting. The energy range of the instrument is from 25 eV to 40 keV and an angular field-of-view of 360° × 90° is achieved through electrostatic deflection of incoming particles. [ABSTRACT FROM AUTHOR]

The Earth's radiation belts-also known as the Van Allen belts-contain high-energy electrons trapped on magnetic field lines. The centre of the outer belt is usually 20,000-25,000?km from Earth. The region between the belts is normally devoid of particles, and is accordingly favoured as a location for spacecraft operation because of the benign environment. Here we report that the outer Van Allen belt was compressed dramatically by a solar storm known as the‘Hallowe'en storm’of 2003. From 1 to 10 November, the outer belt had its centre only~10,000?km from Earth's equatorial surface, and the plasmasphere was similarly displaced inwards. The region between the belts became the location of high particle radiation intensity. This remarkable deformation of the entire magnetosphere implies surprisingly powerful acceleration and loss processes deep within the magnetosphere. [ABSTRACT FROM AUTHOR]

The Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) is the first satellite mission that is dedicated to imaging the Earth's magnetosphere. Using advanced multispectral imaging techniques along with omnidirectional radio sounding, IMAGE has provided the first glimpses into the global structure and behavior of plasmas in the inner magnetosphere. Scientific results from the two-year prime mission include the confirmation of the theory of plasmaspheric tails and the discovery of several new and unpredicted features of the plasmasphere. Neutral-atom imaging has shown how the ring current develops during magnetic storms and how ionospheric ions are injected into the ring current during sub storms. The first global imaging of proton auroras has allowed the identification of the ionospheric footprint of the polar cusp and its response to changes in the interplanetary magnetic field. Detached subauroral proton arcs have been found to appear in the afternoon sector following south-north and east-west rotations of the IMF. Low-energy neutral atom imaging has shown global-scale ionospheric outflow to be an immediate response to solar-wind pressure pulses. Such imaging has also provided the first measurements of solar wind and interstellar neutral atoms from inside the magnetosphere. Radio sounding has revealed the internal structure of the plasmasphere and identified plasma cavities as the source of kilometric continuum radiation. These and numerous other scientific results now set the stage for the extended mission of IMAGE in which the imaging perspective will change markedly owing to orbital evolution while the magnetospheric environment undergoes a transition from solar maximum toward solar minimum. [ABSTRACT FROM AUTHOR]

Background: We formulated a clinical pathway (CP) for elective laparoscopic cholecystectomy (LC), which included the following preoperative evaluation: history and physical (H&P), right upper quadrant ultrasound (US), and liver function tests (LFTs). We hypothesized that routine LFTs did not alter management beyond that dictated by H&P and US, and could be excluded from the CP. Methods: The study involved 387 consecutive patients undergoing elective LC. Abnormalities in the preoperative evaluation were compared with the finding of choledocholithiasis or other unexpected outcomes. Results: In 187 (48%) patients, abnormalities were found by H&P (n = 7), US (n = 13), and LFTs (n = 177). Seven patients (2%) had documented choledocholithiasis; two had abnormal H&P; three had abnormal US; and four had abnormal LFTs. No patient with choledocholithiasis had abnormal LFTs but normal H&P and US. Conclusions: Routine LFTs before elective LC are not cost effective. Before LC H&P and US are warranted, but LFTs do not add any useful information and should not be routinely measured. [ABSTRACT FROM AUTHOR]

In preparation for a possible large epidemiological study of radiation-related leukemia in Chernobyl clean-up workers of Ukraine, histologic evaluation of 62 cases of leukemia and related disorders was conducted by a panel of expert hematologists and hematopathologists from the United States, France, and Ukraine. All cases were randomly selected from a surrogate population of men in the general population of 6 regions of Ukraine who were between the ages of 20 and 60 years in 1986 and were reported to have developed leukemia, myelodysplasia, or multiple myeloma between the years 1987 and 1998. The hematologists and hematopathologists on the panel were in agreement with one another and with the previously reported diagnoses and classifications of about 90% of the cases of acute and chronic leukemia in the study. These results suggest that strong reliance can be placed on the clinical diagnoses of acute and chronic forms of leukemia and multiple myeloma that have occurred in Ukrainian Chernobyl clean-up workers providing that the diagnoses are supported by records of the patients having had adequate histologic bone marrow studies. The number of cases in this study with the diagnosis of myelodysplasia, however, was too small to draw firm conclusions. [ABSTRACT FROM AUTHOR]

The Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) mission uses a suite of imaging instruments to investigate the global response of the magnetosphere to changing solar wind conditions. Detailed science questions that fall under this broad objective include plasma processes that occur on the dayside, flanks, and nightside of the magnetosphere. The IMAGE orbit has been carefully designed to optimize the investigation of these plasma processes as the orbit precesses through the magnetospheric regions. We discuss here the phasing of the IMAGE orbit during the two-year prime mission and the relationship between the orbit characteristics and the critical science objectives of the mission. [ABSTRACT FROM AUTHOR]

Seventy-four depressed patients were treated with amitriptyline for 4-6 weeks. Their doses were individually adjusted to maintain the sum of the plasma levels of amitriptyline (AT) and nortriptyline (NT) within one of three different ranges, randomly allocated. Allowance was made for individual plasma binding of the drugs. In the 50 patients between 25 and 65 years of age, the antidepressive response at low plasma drug levels was somewhat poorer than at medium or high levels, which were equally effective. In this age group an association was found between outcome and the individual rate of AT metabolism, expressed as 'reciprocal clearance' (RC), the steady-state plasma concentration of AT plus NT divided by the daily AT dose. Good antidepressive outcome was associated with high RC. The implications of these findings for patient treatment and for the interpretation of other studies are discussed. The 18 patients between 65 and 80 years of age showed no significant differences between the effectiveness of treatment at different plasma drug levels, and no significant associations between outcome and RC. [ABSTRACT FROM AUTHOR]

Myosins providing the motors for the actin-based motility that occurs in diverse plants have proved difficult to study. To facilitate those studies, we describe polymerase chain reaction primers that reliably amplify part of the myosin head from diverse plants, consensus sequences that characterise the amplified product as encoding a class V or class VIII myosin, and a monoclonal antibody that recognises an epitope conserved in the head of most plant, fungal, and animal myosins. A pair of stringent oligonucleotide primers was designed that, when used in the polymerase chain reaction, amplified at least eleven different myosins from five species of angiosperms and one sequence from each of the fern Azolla and the algae Nitella and Phaeodactylum. The amplified products, comprising 126 to 135 nucleotides encoding part of the myosin head domain, can be used as myosin-specific probes to screen genomic and cDNA libraries. To identify the products of plant myosin genes, we raised a monoclonal antibody (anti-CHE) to a nine amino acid peptide matching a conserved head epitope showing not more than single amino acid substitutions in most published myosin genes. This antibody recognises rabbit skeletal myosin and multiple polypeptides of >100 kDa in four angiosperms and in the alga Nitella. Relating the Mr values of immunoreactive bands in Arabidopsis extracts to the predicted Mr values of the products of five myosin genes supports the view that the antibody recognises both myosins V and VIII together with the products of some as yet unsequenced genes. The previously described MB170 antibodies may, in contrast, be specific for one or more type V myosins. Together, the polymerase chain reaction primers and the antibody represent versatile tools for identifying and categorising myosins in diverse plants. [ABSTRACT FROM AUTHOR]

The science objectives of the Toroidal Imaging Mass-Angle Spectrograph (TIMAS) are to investigate the transfer of solar wind energy and momentum to the magnetosphere, the interaction between the magnetosphere and the ionosphere, the transport processes that distribute plasma and energy throughout the magnetosphere, and the interactions that occur as plasma of different origins and histories mix and interact. In order to meet these objectives the TIMAS instrument measures virtually the full three-dimensional velocity distribution functions of all major magnetospheric ion species with one-half spin period time resolution. The TIMAS is a first-order double focusing (angle and energy), imaging spectrograph that simultaneously measures all mass per charge components from 1 AMU e to greater than 32 AMU e over a nearly 360° by 10° instantaneous field-of-view. Mass per charge is dispersed radially on an annular microchannel plate detector and the azimuthal position on the detector is a map of the instantaneous 360° field of view. With the rotation of the spacecraft, the TIMAS sweeps out very nearly a 4π solid angle image in a half spin period. The energy per charge range from 15 eV e to 32 keV e is covered in 28 non-contiguous steps spaced approximately logarithmically with adjacent steps separated by about 30%. Each energy step is sampled for approximately 20 ms; 14 step (odd or even) energy sweeps are completed 16 times per spin. In order to handle the large volume of data within the telemetry limitations the distributions are compressed to varying degrees in angle and energy, log-count compressed and then further compressed by a lossless technique. This data processing task is supported by two SA3300 microprocessors. The voltages (up to 5 kV) for the tandem toroidal electrostatic analyzers and preacceleration sections are supplied from fixed high voltage supplies using optically controlled series-shunt regulators. [ABSTRACT FROM AUTHOR]

The Thermal Ion Dynamics Experiment (TIDE) and the Plasma Source Instrument (PSI) have been developed in response to the requirements of the ISTP Program for three-dimensional (3D) plasma composition measurements capable of tracking the circulation of low-energy (0-500 eV) plasma through the polar magnetosphere. This plasma is composed of penetrating magnetosheath and escaping ionospheric components. It is in part lost to the downstream solar wind and in part recirculated within the magnetosphere, participating in the formation of the diamagnetic hot plasma sheet and ring current plasma populations. Significant obstacles which have previously made this task impossible include the low density and energy of the outflowing ionospheric plasma plume and the positive spacecraft floating potentials which exclude the lowest-energy plasma from detection on ordinary spacecraft. Based on a unique combination of focusing electrostatic ion optics and time of flight detection and mass analysis, TIDE provides the sensitivity (seven apertures of ∼ 1 cm effective area each) and angular resolution (6°×18°) required for this purpose. PSI produces a low energy plasma locally at the POLAR spacecraft that provides the ion current required to balance the photoelectron current, along with a low temperature electron population, regulating the spacecraft potential slightly positive relative to the space plasma. TIDE/PSI will: (a) measure the density and flow fields of the solar and terrestrial plasmas within the high polar cap and magnetospheric lobes; (b) quantify the extent to which ionospheric and solar ions are recirculated within the distant magnetotail neutral sheet or lost to the distant tail and solar wind; (c) investigate the mass-dependent degree energization of these plasmas by measuring their thermodynamic properties; (d) investigate the relative roles of ionosphere and solar wind as sources of plasma to the plasma sheet and ring current. [ABSTRACT FROM AUTHOR]

The temperature field of starting thermal plumes were measured in a rotating annulus with various rotation rates and buoyancies. The experiments revealed many details of the internal structure of these convective phenomena and also significant horizontal displacements from their source. Measurements show an increase in the maximum temperature observed in the thermal caps with increasing rotation and a more rapid cooling of the buoyancy source. [ABSTRACT FROM AUTHOR]

Recent research into the effects of the interplanetary magnetic field (IMF) on the Earth's auroral oval and plasmapause are reviewed. While the IMF sector structure has been known for some time to produce asymmetries in polar-cap convection, recent work has shown these effects to extend into the dayside auroral oval. A restricted region of local times referred to as the convection 'throat' is found to move to either side of the noon meridian in response to changes in the IMF B component. The question of the entry of solar-wind plasma into the magnetosphere continues to be a prime area of research. While it is generally felt that magnetic merging must play some significant role, evidence continues to mount that it does not occur at the subsolar magnetopause, as previously supposed, and that other driving forces for antisunward convection must occur on closed field lines. A suggestion is made that many of the seemingly conflicting observations that have been made in the region of the dayside cusps can be explained if significant distortions of closed field lines near the dayside magnetopause are allowed and if closed and open field lines coexist in the cusp, particularly near the entry layer. Effects of the IMF on the nightside auroral oval and on the plasmapause stem chiefly from the expansion of the oval to lower latitudes which is produced by southward IMF components and from the impulsive substorm phenomena that become stronger and more probable with increasingly southward IMF. [ABSTRACT FROM AUTHOR]

A single intramuscular (IM) dose of 50 mg amitriptyline (AT) was given to each of two healthy subjects who had previously taken three oral doses of AT tablets. The concentration-time curves of plasma nortriptyline (NT) arising from IMAT were fitted by computer to an equation based on the assumptions that NT is produced at a rate proportional to plasma AT concentration and is eliminated at a rate proportional to plasma NT concentration. The total amount of systemic NT produced was approximately equal for IM and oral AT doses, suggesting that the hepatic elimination of a given quantity of AT produces a constant amount of systemic NT, whether the AT is metabolised in the first pass or from the systemic circulation. This conclusion is supported by analysis of the time course of plasma NT concentration arising from oral AT doses. A large early production had previously been demonstrated and attributed to first-pass metabolism. The proportion of each oral AT dose eliminated in the first pass could now be estimated. values ranged from 51% to 70% and were approximately equal to the proportion of the total NT apparently formed in the first pass. [ABSTRACT FROM AUTHOR]

Five elderly depressed patients were treated with amitriptyline (AT) and nortriptyline (NT) in turn, in a crossover design. Steady-state plasma drug levels were compared with those calculated for eight healthy subjects of previous single-dose studies. Plasma clearances were on average about 2.5 times lower in the patients than the healthy subjects, but the ratios of the different reaction rates did not differ significantly between the two groups. The interpretation of the ratio of NT levels during AT treatment and NT treatment, in terms of the fraction of AT that is metabolised by demethylation, is discussed. The ratio of NT level to AT level during AT treatment was particularly variable between individuals. This was apparently due to independent variation in (a) the ratio of plasma clearances of AT and NT and (b) the fraction of AT metabolised to NT. [ABSTRACT FROM AUTHOR]

Fourteen depressed in-patients were treated with 150 mg clomipramine (CLO) daily, given as one oral dose. Using a gas-chromatographic method, concentrations of CLO and desmethyl clomipramine (DMCLO) were determined in plasma samples taken at frequent intervals during 24h. The plasma level of each compound 12 h after the dose correlated well with the average value in the same patient, calculated over the whole 24-h period. Levels at other times gave poorer correlations, and at 24 h it was particularly poor. Plasma DMCLO concentrations were usually maximum 4-6 h after the dose. The ratios of maximum to minimum levels averaged only 1.31±0.15 SD. Peak CLO levels occurred 3 or 4 h after the dose. Maximum: minimum ratios averaged 2.72±0.73 SD, contrasting with the much smaller fluctuations of plasma nortriptyline (NT) levels observed in patients given this drug once daily. The difference is not due to a shorter half-life of CLO, but to the absorption and/or distribution behaviour of the two drugs. Although not fully understood, this difference between tertiary and secondary amines appears to hold generally among the tricyclic antidepressants. [ABSTRACT FROM AUTHOR]

In a new method for the measurement of plasma binding, amitriptyline (AT) and nortriptyline (NT) were allowed to reach equilibrium distribution between the cells and plasma of whole blood. A separate sample of the cells was equilibrated with a buffer solution containing the drugs. From the two distribution ratios for each drug, the fraction free in the plasma was calculated. Equilibria were achieved rapidly, avoiding denaturation of binding proteins. The pH was adequately controlled and the composition of the plasma was not altered by the experimental procedures. Large volumes of buffer solution gave amounts of free drug readily measurable by gas chromatography. Duplicate determinations showed coefficients of variation of 6% and 4.8% respectively for the free fractions of AT and NT in a given plasma sample. In 51 subjects the mean percentage of AT free in plasma was 4.31±0.59 SD and, of NT, 8.59±0.86. Binding was independent of drug concentration in the therapeutic range and did not differ between males and females nor between patients and normal subjects. It increased slightly with age. It was not affected by chylomicrons in the blood. [ABSTRACT FROM AUTHOR]

Six healthy volunteers were given single doses of amitriptyline (AT) and of nortriptyline (NT) separated by at least 10 days. Plasma concentrations of both compounds were measured at intervals for 48 or 72 h. the total areas under the concentration-time curves for the ingested drug were greater for NT, but AT concentrations showed much higher peak values and took more than 12 h to reach the terminal β phase of elimination. Doses of 50 mg AT produced areas averaging slightly less than half those for 100 mg AT in the same subject, suggesting some saturation of the elimination process. The consumption of a large, fatty meal just before taking the AT tablets had little effect on the plasma drug concentration curves. NT half-lives, measured after ingestion of NT tablets, were used in analysing the production of NT from doses of AT in the same subject. There was a rapid early production, amounting to 30-67% of the total and presumably resulting from the first pass of AT through the liver. NT was then formed continuously at a rate always, proportional to the simultaneous rate of AT elimination. The total amount of NT entering the systemic circulation was about one-quarter of the AT dose. [ABSTRACT FROM AUTHOR]

Two separate single doses of Lentizol (W. R. Warner, Pontypool, U.K.) a sustained-release preparation of amitriptyline (AT) were taken by each of six healthy subjects. Plasma concentrations of AT and of nortriptyline (NT) were determined at intervals over a period of 48 or 72 h. Faeces were collected and their drug content measured. Results were compared with those obtained when the same subjects took ordinary AT tabets. AT was found in the faeces after the ingestion of Lentizol or of ordinary AT tablets. However, after NT tablets negligible amounts of NT appeared in the faeces. AT was sometimes absorbed slowly from Lentizol, but on other occasions it was absorbed as rapidly as from ordinary tablets. Plasma levels of AT 24 h after the dose were usually not higher after Lentizol than after an equal dose of ordinary tablets. The systemic bioavailability of Lentizol as judged by areas under the plasma concentration-time curves, both for AT and for the NT formed metabolically, was on average lower than that of the ordinary tablets. However, the amounts of AT found in the faeces were not large enough to account for the AT area reduction by simple failure of absorption. Possible explanations of the discrepancy are discussed. [ABSTRACT FROM AUTHOR]

A foreword to "Space Science Reviews" is presented.

Rotating at over twice the angular speed of Earth, Saturn imposes a rapid spin on its magnetosphere. As a result, cold, dense plasma is believed to be flung outward from the inner magnetosphere by centrifugal force and replaced by hotter, more tenuous plasma from the outer magnetosphere. The centrifugal interchange of plasmas in rotating magnetospheres was predicted many years ago and was conclusively demonstrated by observations in Jupiter’s magnetosphere, which—like that of Saturn (but unlike that of Earth)—is rotationally dominated. Recent observations in Saturn’s magnetosphere have revealed narrow injections of hot, tenuous plasma believed to be the inward-moving portion of the centrifugal interchange cycle. Here we report observations of the distribution of the angle between the electron velocity vector and the magnetic field vector (‘pitch angle’) obtained in the cold, dense plasma adjacent to these inward injection regions. The observed pitch-angle distributions are indicative of outward plasma flow and consistent with centrifugal interchange in Saturn’s magnetosphere. Further, we conclude that the observed double-peaked (‘butterfly’) pitch-angle distributions result from the transport of plasma from regions near the orbits of Dione and Tethys, supporting the idea of distinct plasma tori associated with these moons. [ABSTRACT FROM AUTHOR]

Change history: In this Letter, the y-axis values in Fig. 3f should go from 4 to −8 (rather than from 4 to −4), the y-axis values in Fig. 3h should appear next to the major tick marks (rather than the minor ticks), and in Fig. 1b, the arrows at the top and bottom of the electron-scale current sheet were going in the wrong direction; these errors have been corrected online. [ABSTRACT FROM AUTHOR]

Magnetic cavities (sometimes referred to as magnetic holes) at electron kinetic scale are thought to be one of the extremely small intermittent structures formed in magnetized turbulent plasmas, where the turbulence energy cascaded down to electron scale may finally be dissipated and consequently energize the electrons. However, the geometry and formation of these structures remain not definitively resolved. Here we discuss an electron scale magnetic cavity embedded in a proton scale magnetic cavity observed by the MMS spacecraft in the magnetosheath. By applying an innovative particle sounding technique, we directly depict the boundary of the electron scale magnetic cavity and uncover the geometry. We find that this structure is nearly circular with a radius of 10.0 km and its formation is due to the diamagnetic current. Investigation of the electron scale structure is only recently made possible by the high spatial and temporal resolution provided by MMS observations. Magnetic cavities are universal phenomena existing in cosmic plasma environments. Here Liu et al. show electron scale magnetic cavities in proton scale magnetic cavities observed by Magnetospheric Multiscale (MMS) spacecraft in the Earth's magnetosheath, and depict the boundary of the electron scale magnetic cavity using particle sounding technique. [ABSTRACT FROM AUTHOR]