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The ongoing development of avionics to support the Spectral Imaging of the Coronal Environment (SPICE) Electronics Box (SEB) program as part of the European Space Agency's (ESA) Solar Orbiter mission has resulted in the development of an Image Processing Field Programmable Gate Array (FPGA) (IPF). The IPF is a single FPGA containing functions to communicate with a Front End Electronics (FEE) assembly/extreme ultraviolet camera, to apply data corrections on incoming pixels, and to compress the final image product for transmission to the ground. The IPF is used as part of a larger science “observation” campaign envisaged as a series of “studies” that are scheduled using a macro execution engine maintained by the Flight Software (FSW). A macro is a lookup table (LUT) stored in memory which contains a series of SPICE commands with relative time tags for each, which determines when each command is executed. This paper discusses the design and architecture of the IPF and associated controlling software employed to meet the various engineering and science requirements of the SPICE instrument.

Fused carbocyclic systems containing seven- and eight-membered rings can be constructed from allylic ethers in a stereoselective manner by tandem carbenoid generation, ylide formation and [2,3] rearrangement. Exceptionally high yields are obtained in cases where the substrate possesses favourable relative stereochemistry. The dienes resulting from [2,3] rearrangement of gem-divinyl ylides undergo Diels–Alder cycloaddition with reactive dienophiles at room temperature. Ylide formation, rearrangement and cycloaddition can be performed in a one-pot process to generate complex tetracyclic systems in a highly stereoselective manner. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The author notes that, overall, he and White seem to agree on many important issues that she writes about in her commentary, such as the necessity of recognizing both our shared humanity and the agency of separate, subjective selves. He argues, however, that White mischaracterizes what it means to think of the self as socially constructed, and he clarifies his views of how the concept of a socially constructed self may be related to individual differences in the same culture, and to personal agency. He responds to White's imputation that his paper implicitly prescribes a type of intervention or mandates some particular view of the Truth as a new theology, substituting a concrete environmental or social determinism for the abstract (intrapsychic) determinism that he criticizes. Finally, he responds to some interesting and insightful questions White raises about the case vignette of Mr. J that was presented in his essay.

In light of the contemporary shift away from the universalizing of the Eurocentric perspective, brought into focus with the advent of globalization, it may be useful to consider reorienting traditional psychoanalytic assumptions about human nature to those that are more appropriate to the recognition of a culturally pluralistic world. The author argues that ego psychology originated in the Western Enlightenment's emphasis on liberal individualism, which has limited its applicability across races, classes, and cultures. Relational theories, in their capacity to include the examination of the socially constructed dimensions of the analytic dyad (including race, class, gender, ethnicity, and sexual orientation), offer crucial theoretical and clinical possibilities, lacking in traditional psychoanalysis, that may help analysts to address some of the important cultural sources of psychological suffering. In the relational view expressed here, the unconscious—as made manifest in everyday life and in the transfe...

The aim of this study was to audit the degree of compliance with new health and safety legislation 5 years after enactment in a typical cross-section of New Zealand manufacturing industries. To this end, 299 randomly selected enterprises using a welding process were visited by Occupational Safety and Health Officers of the Department of Labour. An interviewer-administered questionnaire concerning the nature of the hazards encountered in that enterprise and the chosen control measures employed to protect the health of their employees was undertaken and analysed. Only 40% of New Zealand businesses in this sample undertaking welding had adopted the most basic of regulatory requirements to control health and safety risks. This percentage seemed independent of employer size. Fundamental safety issues (e.g. welding in confined spaces) were ignored by >50% of enterprises. In conclusion, self-management of health and safety risks had not occurred in over half the enterprises surveyed.

The advent of NASA-JPL's X2000 architecture has brought CompactPCI (cPCI) to the forefront as the system bus of choice for space data processing. This paper presents a hybrid architecture allowing the inclusion of new, high performance cPCI modules with heritage VME based modules. The hybrid system yields a cost effective, performance optimized processing solution for space.

The operation of a glutamine-glutamate/GABA cycle in the brain consisting of the transfer of glutamine from astrocytes to neurons and neurotransmitter glutamate or GABA from neurons to astrocytes is a well-known concept. In neurons, glutamine is not only used for energy production and protein synthesis, as in other cells, but is also an essential precursor for biosynthesis of amino acid neurotransmitters. An excellent tool for the study of glutamine transfer from astrocytes to neurons is [(14)C]acetate or [(13)C]acetate and the glial specific enzyme inhibitors, i.e. the glutamine synthetase inhibitor methionine sulfoximine and the tricarboxylic acid cycle (aconitase) inhibitors fluoro-acetate and -citrate. Acetate is metabolized exclusively by glial cells, and [(13)C]acetate is thus capable when used in combination with magnetic resonance spectroscopy or mass spectrometry, to provide information about glutamine transfer. The present review will give information about glutamine trafficking and the tools used to map it as exemplified by discussions of published work employing brain cell cultures as well as intact animals. It will be documented that considerably more glutamine is transferred from astrocytes to glutamatergic than to GABAergic neurons. However, glutamine does have an important role in GABAergic neurons despite their capability of re-utilizing their neurotransmitter by re-uptake.

Glycogen phosphorylase (GP) is activated to degrade glycogen in response to different stimuli, to support both the astrocyte's own metabolic demand and the metabolic needs of neurons. The regulatory mechanism allowing such a glycogenolytic response to distinct triggers remains incompletely understood. In the present study, we used siRNA-mediated differential knockdown of the two isoforms of GP expressed in astrocytes, muscle isoform (GPMM), and brain isoform (GPBB), to analyze isoform-specific regulatory characteristics in a cellular setting. Subsequently, we tested the response of each isoform to phosphorylation, triggered by incubation with norepinephrine (NE), and to AMP, increased by glucose deprivation in cells in which expression of one GP isoform had been silenced. Successful knockdown was demonstrated on the protein level by Western blot, and on a functional level by determination of glycogen content showing an increase in glycogen levels following knockdown of either GPMM or GPBB. NE triggered glycogenolysis within 15 min in control cells and after GPBB knockdown. However, astrocytes in which expression of GPMM had been silenced showed a delay in response to NE, with glycogen levels significantly reduced only after 60 min. In contrast, allosteric activation of GP by AMP, induced by glucose deprivation, seemed to mainly affect GPBB, as only knockdown of GPBB, but not of GPMM, delayed the glycogenolytic response to glucose deprivation. Our results indicate that the two GP isoforms expressed in astrocytes respond to different physiological triggers, therefore conferring distinct metabolic functions of brain glycogen.

An eleven stage flat top type output Marx utilizing sparkgap switches is operated to produce a desired 500 kV output at 10 Hz rep-rate with > 500 J pulse energy to drive a ∼ 20 Ohm load. While this Marx generator utilizes custom-designed spark gaps, the significant progress in semi-conductor pulsed switching technology is evaluated through PSICE modeling of the semiconductor switches integrated into the Marx electrical model. The switches are experimentally evaluated at conditions that a single switch (stack) would experience in a full Marx generator. Alternatively to the Marx topology, the potential benefits of choosing a linear transformer driver (LTD) as a HPM pulsed power driver are evaluated. We note that the main advantage for the LTD is the savings in insulation material and size; the same semiconductor switches are utilized. The potential benefits of such a generator include significant reduction of electromagnetic noise, increased lifetime, improved reliability, and reduced maintenance.

Many thyristor models exist that are either impractical to implement in a SPICE simulator, or do not model transient turn-on performance accurately. An empirical SPICE model is developed for thyristors to model turn-on performance. Silicon Power's CCS SC 14N40 is selected for simulation. The process of model determination is detailed and simulation results are compared to experiments.

The ongoing development of avionics to support the Spectral Imaging of the Coronal Environment (SPICE) Electronics Box (SEB) program as part of the European Space Agency's (ESA) Solar Orbiter program has presented numerous design and verification challenges. A unique challenge in the development of the SPICE electronics is the validation of the system due to its multi-national elements and their concurrent development timelines. The practical application of a systems engineering process has reduced and mitigated these risks through requirements flow-down to subsystems and a comprehensive verification program to ensure all specifications are met. This paper discusses the lessons learned from requirements development and verification and validation activities. These lessons have resulted in a substantial risk reduction as the program has moved forward with flight model design development and testing activities.

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-13C]acetate and [1-13C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-13C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and 13C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.

A flexible, practical, and stereoselective synthesis of enantiomerically pure trans-5-oxohexahydropyrrolo[3,2-b]pyrroles (pyrrolidine-trans-lactams) is described. The key reaction involves addition of Z-ketene acetal 24 to the acyliminium ion derived from 48. This reaction is mediated by BF3·OEt2 and introduces the 6S and 6aS stereocenters stereoselectively. The acyliminium precursor was prepared in four different ways: from racemic 2,4-diaminobutyric acid 8, from (R)-asparagine, from (R)-methionine, and via a crystallization-induced dynamic resolution of a salt of the racemic amine 56. (R)-Methionine is the preferred starting material for the preparation of enantiomerically pure material. The best conditions for addition of the ketene acetal to the acyliminium ion derived from 48 were determined by systematically screening a range of ketene acetals and Lewis acids. The best ketene acetal was Z-(1-ethoxy-3-methylbut-1-enyloxyl)triisopropylsilane 24. In this series, the bulk of the silyl group of the Z-ke...

SPICE is a high resolution imaging spectrometer operating at extreme ultraviolet wavelengths, 70.4 – 79.0 nm and 97.3 - 104.9 nm. It is a facility instrument on the Solar Orbiter mission. SPICE will address the key science goals of Solar Orbiter by providing the quantitative knowledge of the physical state and composition of the plasmas in the solar atmosphere, in particular investigating the source regions of outflows and ejection processes which link the solar surface and corona to the heliosphere. By observing the intensities of selected spectral lines and line profiles, SPICE will derive temperature, density, flow and composition information for the plasmas in the temperature range from 10,000 K to 10MK. The instrument optics consists of a single-mirror telescope (off-axis paraboloid operating at near-normal incidence), feeding an imaging spectrometer. The spectrometer is also using just one optical element, a Toroidal Variable Line Space grating, which images the entrance slit from the telescope focal plane onto a pair of detector arrays, with a magnification of approximately x5. Each detector consists of a photocathode coated microchannel plate image intensifier, coupled to active-pixel-sensor (APS). Particular features of the instrument needed due to proximity to the Sun include: use of dichroic coating on the mirror to transmit and reject the majority of the solar spectrum, particle-deflector to protect the optics from the solar wind, and use of data compression due to telemetry limitations.

The Cyclone Global Navigation Satellite System (CYGNSS), which was recently selected as the Earth Venture-2 investigation by NASA's Earth Science System Pathfinder (ESSP) Program, measures the ocean surface wind field with unprecedented temporal resolution and spatial coverage, under all precipitating conditions, and over the full dynamic range of wind speeds experienced in a tropical cyclone (TC). The CYGNSS flight segment consists of 8 microsatellite-class observatories, which represent SwRI's first spacecraft bus design, installed on a Deployment Module for launch. They are identical in design but provide their own individual contribution to the CYGNSS science data set. Subsystems include the Attitude Determination and Control System (ADCS), the Communication and Data Subsystem (CDS), the Electrical Power Supply (EPS), and the Structure, Mechanisms, and Thermal Subsystem (SMT). This paper will present an overview of the mission and the avionics, including the ADCS, CDS, and EPS, in detail. Specifically, we will detail how off-the-shelf components can be utilized to do ADCS and will highlight how SwRI's existing avionics solutions will be adapted to meet the requirements and cost constraints of microsat applications. Avionics electronics provided by SwRI include a command and data handling computer, a transceiver radio, a low voltage power supply (LVPS), and a peak power tracker (PPT).

Southwest Research Institute® (SwRI®) has designed a wireless transceiver to provide inter-satellite communications as part of the Defense Advanced Research Projects Agency (DARPA) System F6 program. System F6 (Future, Fast, Flexible, Fractionated, Free-Flying Spacecraft United by Information Exchange) seeks to demonstrate the feasibility and benefits of a satellite architecture wherein the functionality of a traditional “monolithic” spacecraft is delivered by a cluster of wirelessly-interconnected modules capable of sharing their resources and utilizing resources found elsewhere in the cluster. SwRI's System F6 Wireless Inter-module Communication System (F6WICS) provides the data link and physical layers of the network stack that are specifically designed to meet the needs of fractionated space missions. F6WICS provides deterministic, real-time media access mechanisms that make efficient use of limited communications bandwidth over a wide range of spacecraft separation distances and network populations. The data link protocol is highly robust to module failure. The physical layer waveform provides robust communication, precision time transfer throughout the network, and continuous estimation of distance between spacecraft for use in navigation. The views expressed are those of the author and do not reflect the official policy or position of the Department of Defense or the U.S. Government. Distribution Statement “A”: Approved for Public Release, Distribution Unlimited.

The brain is highly susceptible to oxidative injury, and the pentose phosphate pathway (PPP) has been shown to be affected by pathological conditions, such as Alzheimer's disease and traumatic brain injury. While this pathway has been investigated in the intact brain and in astrocytes, little is known about the PPP in neurons. The activity of the PPP was quantified in cultured cerebral cortical and cerebellar neurons after incubation in the presence of [2-13C]glucose or [3-13C]glucose. The activity of the PPP was several fold lower than glycolysis in both types of neurons. While metabolism of 13C-labeled glucose via the PPP does not appear to contribute to the production of releasable lactate, it contributes to labeling of tricarboxylic acid (TCA) cycle intermediates and related amino acids. Based on glutamate isotopomers, it was calculated that PPP activity accounts for ∼6% of glucose metabolism in cortical neurons and ∼4% in cerebellar neurons. This is the first demonstration that pyruvate generated from glucose via the PPP contributes to the synthesis of acetyl CoA for oxidation in the TCA cycle. Moreover, the fact that 13C labeling from glucose is incorporated into glutamate proves that both the oxidative and the nonoxidative stages of the PPP are active in neurons.

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA ( N-methyl-D-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate–aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling.

Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies—it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on (1) the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP), (2) alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and (3) a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g., turnover) is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology.

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA ( N -methyl-D-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca 2+ during activation cause influx of Ca 2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate–aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca 2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13 C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca 2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca 2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca 2+ -induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca 2+ signalling.

We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.

Pyruvate carboxylation (PC) is thought to be the major anaplerotic reaction for the tricarboxylic acid cycle and is necessary for de novo synthesis of amino acid neurotransmitters. In the brain, the main enzyme involved is pyruvate carboxylase, which is predominantly located in astrocytes. Carboxylation leads to the formation of oxaloacetate, which condenses with acetyl coenzyme A to form citrate. However, oxaloacetate may also be converted to malate and fumarate before being regenerated. This pathway is termed the oxaloacetate-fumarate-flux or backflux. Carbon isotope-based methods for quantification of activity of PC lead to underestimation when backflux is not taken into account and critical errors have been made in the interpretation of results from metabolic studies. This study was conducted to establish the degree of backflux after PC in cerebellar and neocortical astrocytes. Astrocyte cultures from cerebellum or neocortex were incubated with either [3- 13 C] or [2- 13 C]glucose, and extracts were analyzed using mass spectrometry or nuclear magnetic resonance spectroscopy. Substantial PC compared with pyruvate dehydrogenase activity was observed, and extensive backflux was demonstrated in both types of astrocytes. The extent of backflux varied between the metabolites, reaffirming that metabolism is highly compartmentalized. By applying our calculations to published data, we demonstrate the existence of backflux in vivo in cat, rat, mouse, and human brain. Thus, backflux should be taken into account when calculating the magnitude of PC to allow for a more precise evaluation of cerebral metabolism. V

An O(N/sup 3/) algorithm for partitioning and allocating N Datalog procedural bundles among K distributed or dedicated processors is presented. The algorithm determines a static distribution of the bundles to all K processors. The independent variables of the objective function include both processing and communication costs, and the goal is to balance the processing requirements of the K processors while allocating bundles in such a way as to reduce the communication costs. The algorithm can be used with heterogeneous systems of processors, and it can accommodate a two-tier communication model in which both local area networks and more expensive wide area networks are used. The algorithm can be used interactively with a programmer or system designer. Example results from its implementation are given, and a comparison with another technique is shown. >

GABA is synthesized from glutamate by glutamate decarboxylase (GAD), which exists in two isoforms, that is, GAD65 and GAD67. In line with GAD65 being located in the GABAergic synapse, several studies have demonstrated that this isoform is important during sustained synaptic transmission. In contrast, the functional significance of GAD65 in the maintenance of GABA destined for extrasynaptic tonic inhibition is less well studied. Using GAD65-/- and wild type GAD65+/+ mice, this was examined employing the cortical wedge preparation, a model suitable for investigating extrasynaptic GABA(A) receptor activity. An impaired tonic inhibition in GAD65-/- mice was revealed demonstrating a significant role of GAD65 in the synthesis of GABA acting extrasynaptically. The correlation between an altered tonic inhibition and metabolic events as well as the functional and metabolic role of GABA synthesized by GAD65 was further investigated in vivo. Tonic inhibition and the demand for biosynthesis of GABA were augmented by injection of kainate into GAD65-/- and GAD65+/+ mice. Moreover, [1-(13) C]glucose and [1,2-(13) C]acetate were administered to study neuronal and astrocytic metabolism concomitantly. Subsequently, cortical and hippocampal extracts were analyzed by NMR spectroscopy and mass spectrometry, respectively. Although seizure activity was induced by kainate, neuronal hypometabolism was observed in GAD65+/+ mice. In contrast, kainate evoked hypermetabolism in GAD65-/- mice exhibiting deficiencies in tonic inhibition. These findings underline the importance of GAD65 for synthesis of GABA destined for extrasynaptic tonic inhibition, regulating epileptiform activity.

It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate. The importance of this as well as the significance of ATP formed in glycolysis versus that formed by the concerted action of the tricarboxylic acid (TCA) cycle processes and oxidative phosphorylation for maintenance of glutamate transport capacity in astrocytes is discussed. It is argued that glycolytically derived energy in the form of ATP may be of particular functional importance in this context.

Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential molecular therapeutic agents for the treatment of cancer. Here we describe novel 2-aminothieno[2,3-d]pyrimidine ATP competitive Hsp90 inhibitors, which were designed by combining structural elements of distinct low affinity hits generated from fragment-based and in silico screening exercises in concert with structural information from X-ray protein crystallography. Examples from this series have high affinity (IC50 = 50-100 nM) for Hsp90 as measured in a fluorescence polarization (FP) competitive binding assay and are active in human cancer cell lines where they inhibit cell proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Several examples (34a, 34d and 34i) caused tumor growth regression at well tolerated doses when administered orally in a human BT474 human breast cancer xenograft model.

Although the brain utilizes glucose for energy production, individual brain cells may to some extent utilize substrates derived from glucose. Thus, it has been suggested that neurons consume extracellular lactate during synaptic activity. However, the precise role of lactate for fueling neuronal activity is still poorly understood. Recently, we demonstrated that glucose metabolism is up-regulated in cultured glutamatergic neurons during neurotransmission whereas that of lactate is not. Here, we show that utilization of glucose but not lactate correlates with NMDA-induced neurotransmitter glutamate release in cultured cerebellar neurons from mice. Pulses of NMDA at 30, 100, and 300 microM, leading to a progressive increase in both cytosolic [Ca2+] and release of glutamate, increased uptake and metabolism of glucose but not that of lactate as evidenced by mass spectrometric measurement of 13C incorporation into intracellular glutamate. In this manuscript, a cascade of events for the preferential neuronal utilization of glucose during neurotransmission is suggested and discussed in relation to our current understanding of neuronal energy metabolism.

We report the discovery of a novel, chiral azetidine urea inhibitor of Fatty Acid Amide Hydrolase (FAAH,) and describe the surprising species selectivity of VER-156084 versus rat and human FAAH and also hCB1.

The pharmacological properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), a potent inhibitor of glycogen phosphorylase and synthase activity in liver preparations, were characterized in different brain tissue preparations as a prerequisite for using it as a tool to investigate brain glycogen metabolism. Its inhibitory effect on glycogen phosphorylase was studied in homogenates of brain tissue and astrocytes and IC50-values close to 400 nM were found. However, the concentration of DAB needed for inhibition of glycogen shunt activity, i.e. glucose metabolism via glycogen, in intact astrocytes was almost three orders of magnitude higher. Additionally, such complete inhibition required a pre-incubation period, a finding possibly reflecting a limited permeability of the astrocytic membrane. DAB did not affect the accumulation of 2-deoxyglucose-6-phosphate indicating that the transport of DAB is not mediated by the glucose transporter. DAB had no effect on enzymes involving glucose-6-phosphate, i.e. glucose-6-phosphate dehydrogenase, phosphoglucoisomerase and hexokinase. Furthermore, DAB was evaluated in a functional preparation of the isolated mouse optic nerve, in which its presence severely reduced the ability to sustain evoked compound action potentials in the absence of glucose, a condition in which glycogen serves as an important energy substrate. Based on the experimental findings, DAB can be used to evaluate glycogen shunt activity and its functional importance in intact brain tissue and cells at a concentration of 300-1000 muM and a pre-incubation period of 1 h.

Neuronal activity is tightly coupled with brain energy metabolism. Numerous studies have suggested that lactate is equally important as an energy substrate for neurons as glucose. Lactate production is reportedly triggered by glutamate uptake, and independent of glutamate receptor activation. Here we show that climbing fibre stimulation of cerebellar Purkinje cells increased extracellular lactate by 30% within 30 s of stimulation, but not for briefer stimulation periods. To explore whether lactate production was controlled by pre- or postsynaptic events we silenced AMPA receptors with CNQX. This blocked all evoked rises in postsynaptic activity, blood flow, and glucose and oxygen consumption. CNQX also abolished rises in lactate concomitantly with marked reduction in postsynaptic currents. Rises in lactate were unaffected by inhibition of glycogen phosphorylase, suggesting that lactate production was independent of glycogen breakdown. Stimulated lactate production in cerebellum is derived directly from glucose uptake, and coupled to neuronal activity via AMPA receptor activation.

Introduction Insomnia is a risk factor (odds ratio 39,8) as well as symptom of depressive disorder and other psychiatric conditions. Therefore, psychiatrists require appropriate training in diagnosing and treating insomnia. To date, there is no data available in Europe on training in sleep medicine for early career psychiatrists. Aims To establish how accessible training in insomnia management is to European early career Psychiatrists, and how confident they feel in treating this disorder. Methods Europe wide survey carried out jointly by the European and World Psychiatric Associations Early Career Psychiatrists Committees. Representatives of Early career Psychiatrists from each participating European country filled in a questionnaire about training in sleep medicine in their country. Early Career Psychiatrists were also invited to fill out a questionnaire at the EPA congress in Nice in 2013. Results 55 participants from 27 European countries responded. Only 24% had sleep medicine training mandatorily included in their national training curriculum. A majority (60%) felt that the quality of training they did receive was either average or below average. 88% felt either very or fairly confident in treating insomnia. However, when asked to select the correct management options for insomnia from a provided list of 6 options, only 19% and 33% of respondents chose the two correct options. Conclusions There is a clear gap between the level of confidence and the clinical judgements being made to treat insomnia among European Early Career Psychiatrists. There is a definite need to improve the availability and structure of insomnia training in Europe.

As the measurement techniques in the space science community rapidly evolve, the demand for multi-channeled, high-speed, radiation tolerant data acquisitioning systems gets increasingly higher. The high volume and resolution of data, and the complexity of the in-situ processing and analysis requirements, have triggered the need for faster, smaller, and easily reconfigurable designs. In response to this demand, Southwest Research Institute has developed a high-speed, multi-channel, versatile data acquisitioning architecture. This new architecture can perform reconfigurable DSP algorithms and subsequent data processing on instrument analog input signals. The overall architecture and topology was developed as part of a SwRI science instrumentation trade study and then implemented on the NASA gamma-ray large area space telescope (GLAST) data processing unit (DPU). It can easily be reconfigured for other space missions and instrument applications. This paper presents an architectural view of the design and gives examples of its tremendous versatility. It also addresses the evolution of analog DSP data acquisition systems in general and emphasizes the advantages and tradeoffs between today's approaches versus older heritage methods.

SpaceWire is a switched network designed for space environments. To support the Internet protocol (IP) and other high level network protocols, SpaceWire requires a method for mapping the physical interface addresses to global network protocol addresses. Standard address resolution protocol (ARP) cannot be used because SpaceWire does not have a broadcast mechanism. This paper describes a non-broadcast SpaceWire ARP (SW-ARP) that supports any higher network protocol, including IPv4, IPv6, and the CCSDS SCPS-NP address family. Our protocol includes forward and reverses ARP mappings, and is applicable to all devices that conform to the SpaceWire standard specification. SW-ARP can be implemented in node software drivers and requires no changes to the interface hardware, SpaceWire routing switches, or the SpaceWire standard specification.

A 59-year-old man presented with chest pain and single-vessel coronary disease on angiography. Left ventricular function was normal with mild hypertrophy. He was treated for coronary disease but represented 18 months later with biventricular heart failure. There had been a striking ECG evolution: ST-segment change; reduced QRS amplitude; increased P-wave width and amplitude; and progressive increase in PR interval (196–276 ms) (Panel A). Echocardiography now …

The US Army Corps of Engineers, San Francisco District (USACE), is evaluating the suitability of sites for ocean disposal of dredged material from several projects in the San Francisco Bay area. In conjunction with those efforts, the USACE maintained current meter moorings at two candidate disposal sites (Sites B1B and 1M) on the California continental shelf. Optical backscatterance (OBS) sensors mounted on these moorings near the sea bed were used to determine suspended sediment concentrations. The initial deployments at Site 1M (42 m) and Site B1B (86 m) occurred in April 1988; data were recovered in June and September 1988, and January 1989. Final instrument recovery was scheduled for May 1989, and the program should provide a full year of information on tidal and low-frequency shelf currents and near-bed suspended sediment concentrations. This is a preliminary report of the data from the 86-m site. The data showed evidence of strong vertical coherence in the currents, net southward flow at all depths during upwelling season, frequent flow reversals in fall and winter, and more frequent resuspension of sediment during the winter months. 9 refs., 5 figs., 2 tabs.

This paper presents Southwest Research Institute's continuing development of flexible CCSDS compatible command and telemetry collection hardware. Results of the requirements analysis, systems design and hardware fabrication and test are presented in detail. The objective of this development effort was to provide an FPGA core module that could be used in a variety of spacecraft with minimal modification. The module must provide command decoding and BCH error detection and correction for the spacecraft's main computer. The module must also serve as a level-0 "safe" mode processor and be able to immediately execute commands received from the ground. The FPGA core module designed as a result of this effort will be used in those applications where a critical need exists for a level-0 command capability along with normal spacecraft commanding. The design may also be used to speed up system throughput by off loading the command process from the main computer's tasks.

The Space Station Module Power Management and Distribution (SSM/PMAD) Breadboard is a test facility designed for advanced development of space power automation. Originally designed for 20 kHz power, the system is being converted to work with direct current (DC). Power levels are on a par with those expected for a Space Station module. Some of the strengths and weaknesses of the SSM/PMAD system in design and function are examined, and the future directions foreseen for the system are outlined. >

Speech coders such as those based on multiband excitation (MBE) and STC models depend on having available an accurate representation of a discrete set of significant spectral amplitudes. Normal linear predictive (LP) spectrum representations model adequately only the general spectral envelope, not individual spectral amplitudes. A technique for enhancing the accuracy of a LP spectrum representation through the use of cubic spline interpolation and amplitude compression is described. The technique is applied to a 2400 bps MBE-type coder (EMBE 2400) and shown to result in significantly lower spectral distortion than a simple LP model alone.

A Level-0 processor is a low-level command processor intended to control the spacecraft whenever the main processor is off-line. Such an event can happen during early orbit activities, during load shedding operations or during an anomaly (like the upset of the main processor due to cosmic radiation). During these periods, the safe mode processor collects a subset of normal housekeeping telemetry, formats it, and downlinks it along with the command link control word information required by the CCSDS Telecommand recommendations. This subset of normal telemetry collection includes housekeeping telemetry from critical spacecraft subsystems such as attitude control, power regulation, solar array control, and payload maintenance. To determine the optimal number of interfaces and telemetry points, SwRI polled several spacecraft vendors and used this information to implement Level-0 CCSDS command processing/telemetry collection. This paper presents Southwest Research Institute's continuing development of flexible Level-0 command and telemetry collection hardware.

This paper presents the continuing development of flexible Level-0 command and telemetry collection hardware. Results of the requirements analysis, systems design and hardware fabrication and test are presented in detail. The objective of this research program was to provide a module that could handle a variety of interfaces accessible from either a spacecraft's main computer or an on-board microcontroller. The module must serve as a level-0 "safe" mode processor and be able to execute commands received from the ground. The system designed as a result of this IR&D will be used in those applications where a critical need exists for a level-0 "safe" mode processor. The design may also be used to speed up system throughput by way of parallel processing with the main computer.

This paper presents a radiation hardened digital oscilloscope tailored for space applications. The waveform capture system (WCS) was designed as a data acquisition system for a time of flight instrument on the European Rosetta cometary mission. The WCS is a radiation hardened low power, single board solution, providing 11 bits of accuracy, sub-nanosecond resolution, and complete command and data handling. This paper details the design and evolution of the WCS, as well as presenting results from recent testing of the engineering qualification module with the time of flight instrument.

A microdischarge is driven by short pulses (80 ns FWHM) with peak current levels up to 80 A, with a repetition frequency of 1 MHz (1 pulse/μs) allowing for ∼550 W input power. Experiments in pure argon (Ar2*, 127 nm) and argon-hydrogen (Lyman-α, 121.6 nm) were conducted. Using short pulses, the argon excimer emission was not observed. Alternatively, Ar-H2 operated at both higher power and efficiency (0.63%) whenever pulsed. Using Ar-H2, the experiments result in an average generated vacuum ultraviolet power just above 3.4 W with a peak power of 42.8 W, entirely at Lyman-α.

Occupations of two geographically distinct populations of patients with upper limb pain were examined. Relative risks for being in an occupation were calculated for subjects with epicondylitis, carpal tunnel syndrome, and pain syndromes in one population and nonspecific occupational overuse syndrome (OOS) in the other. Population A subjects (806 female, 154 male Auckland clinic referrals) with epicondylitis and carpal tunnel syndrome had higher rates of manual occupations compared with the Auckland employed population, consistent with previous research. Both Population A and Population B subjects (1,188 female, 499 male national notifications to the Department of Labour) with pain syndrome or nonspecific OOS had increased rates of clerical occupations. Relative risks ranged from 2.24 (95% CI 1.69,2.97) to 3.92 (3.50 ,4.40). Word processor operators, data-entry operators, and mail sorters were overrepresented in both populations. An unexplained association between nonspecific upper arm pain and being in some clerical occupations requires further research.

To establish the degree of compliance with health and safety standards in New Zealand mortuaries.A mortuary audit tool was developed based mainly on British mortuary health and safety standards. This was tested and then applied to all identified mortuaries.Less than 50% (seven out of 15 institutions) met the standards required to carry out "basic" autopsies. Only one institution had mortuary facilities that were deemed suitable for "high risk" procedures. Where necessary, recommendations for improvements were made.New Zealand (and preferably Australasian-wide) standards need to be established and adopted for mortuaries. Some rationalisation of mortuary services so as to isolate risk (and improve quality control?) is necessary. People working in mortuaries need to adhere to stricter work practices while working in purpose-designed environments that minimise their risk.