Development Status of the NASA 30-cm Ion Thruster and Power Processor

Xenon ion propulsion systems are being developed by NASA Lewis Research Center and the Jet Propulsion Laboratory to provide flight qualification and validation for planetary and earth-orbital missions. In the ground-test element of this program, light-weight (less than 7 kg), 30 cm diameter ion thrusters have been fabricated, and preliminary design verification tests have been conducted. At 2.3 kW, the thrust, specific impulse, and efficiency were 91 mN, 3300 s, and 0.65, respectively. An engineering model thruster is now undergoing a 2000 h wear-test. A breadboard power processor is being developed to operate from an 80 V to 120 V power bus with inverter switching frequencies of 50 kHz. The power processor design is a pathfinder and uses only three power supplies. The projected specific mass of a flight unit is about 5 kg/kW with an efficiency of 0.92 at the full-power of 2.5 kW. Preliminary integration tests of the neutralizer power supply and the ion thruster have been completed. Fabrication and test of the discharge and beam/accelerator power stages are underway

How to treat patients with ST-elevation acute myocardial infarction and multi-vessel disease?

Over 50% of ST-segment elevation myocardial infarction (STEMI) patients suffer multi-vessel coronary artery disease, which is known to be associated with worse prognosis. Treatment strategies used in clinical practice vary from acute multi-vessel percutaneous coronary intervention (PCI), through staged PCI procedures to a conservative approach with primary PCI of only the infarct-related artery (IRA) and subsequent medical therapy unless recurrent ischaemia occurs. Each approach has advantages and disadvantages. This review paper summarizes the international experience and authors’ opinion on this clinically important question. Multi-vessel disease in STEMI is not a single entity and thus the treatment approach should be individualized. However, the following general rules can be proposed till future large randomized trials prove otherwise

Protection by the NDI1 Gene against Neurodegeneration in a Rotenone Rat Model of Parkinson's Disease

It is widely recognized that mitochondrial dysfunction, most notably defects in the NADH-quinone oxidoreductase (complex I), is closely related to the etiology of sporadic Parkinson's disease (PD). In fact, rotenone, a complex I inhibitor, has been used for establishing PD models both in vitro and in vivo. A rat model with chronic rotenone exposure seems to reproduce pathophysiological conditions of PD more closely than acute mouse models as manifested by neuronal cell death in the substantia nigra and Lewy body-like cytosolic aggregations. Using the rotenone rat model, we investigated the protective effects of alternative NADH dehydrogenase (Ndi1) which we previously demonstrated to act as a replacement for complex I both in vitro and in vivo. A single, unilateral injection of recombinant adeno-associated virus carrying the NDI1 gene into the vicinity of the substantia nigra resulted in expression of the Ndi1 protein in the entire substantia nigra of that side. It was clear that the introduction of the Ndi1 protein in the substantia nigra rendered resistance to the deleterious effects caused by rotenone exposure as assessed by the levels of tyrosine hydroxylase and dopamine. The presence of the Ndi1 protein also prevented cell death and oxidative damage to DNA in dopaminergic neurons observed in rotenone-treated rats. Unilateral protection also led to uni-directional rotation of the rotenone-exposed rats in the behavioral test. The present study shows, for the first time, the powerful neuroprotective effect offered by the Ndi1 enzyme in a rotenone rat model of PD

Imaging crustal structure in South-Central Costa Rica with Receiver Functions

An array of broadband seismometers transecting the Talamanca Range in southern Costa Rica was operated from 2005 until 2007. In combination with data from a short‐period network near Quepos in central Costa Rica, this data is analyzed by the receiver function method to image the crustal structure in south‐central Costa Rica. Two strong positive signals are seen in the migrated images, interpreted as the Moho (at around 35 km depth) and an intra‐crustal discontinuity (15 km depth). A relatively flat crustal and Moho interface underneath the north‐east flank of the Talamanca Range can be followed for a lateral distance of about 50 km parallel to the trench, with only slight changes in the overall geometry. Closer to the coast, the topography of the discontinuities shows several features, most notably a deeper Moho underneath the Talamanca Mountain Range and volcanic arc. Under the highest part of the mountain ranges, the Moho reaches a depth of about 50 km, which indicates that the mountain ranges are approximately isostatically compensated. Local deviations from the crustal thickness expected for isostatic equilibrium occur under the active volcanic arc and in south Costa Rica. In the transition region between the active volcanic arc and the Talamanca Range, both the Moho and intracrustal discontinuity appear distorted, possibly related to the southern edge of the active volcanic zone and deformation within the southern part of the Central Costa Rica Deformed Belt. Near the volcanoes Irazu and Turrialba, a shallow converter occurs, correlating with a low‐velocity, low‐density body seen in tomography and gravimetry. Applying a grid search for the crustal interface depth and vp/vs ratio cannot constrain vp/vs values well, but points to generally low values (<1.7) in the upper crust. This is consistent with quartz‐rich rocks forming the mountain range

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.

Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies

We All Know How, Don’t We? On the Role of Scrum in IT-Offshoring

Part 2: Creating Value through Software DevelopmentInternational audienceOffshoring in the IT-industry involves dual interactions between a mother company and an external supplier, often viewed with an implicit perspective from the mother company. This article review general off shoring and IT offshoring literature, focusing on the proliferation of a globally available set of routines; Scrum and Agile. Two cases are studied; a small company and short process and a large mother company with a long process. The interactions of the set ups shows that global concepts like Scrum and Agile are far from a common platform. The “well known” concepts are locally shaped and the enterprises have mixed experiences

Reduction of Hydrophilic Ubiquinones by the Flavin in Mitochondrial NADH:Ubiquinone Oxidoreductase (Complex I) and Production of Reactive Oxygen Species†

ABSTRACT: NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a complicated, energy-transducing, membrane-bound enzyme that contains 45 different subunits, a non-covalently bound flavin mononucleotide, and eight iron-sulfur clusters. The mechanisms of NADH oxidation and intramolecular electron transfer by complex I are gradually being defined, but the mechanism linking ubiquinone reduction to proton translocation remains unknown. Studies of ubiquinone reduction by isolated complex I are problematic because the extremely hydrophobic natural substrate, ubiquinone-10, must be substituted with a relatively hydrophilic analogue (such as ubiquinone-1). Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway (which is insensitive to inhibitors such as rotenone and piericidin A). Here, we show that inhibitor-insensitive ubiquinone reduction occurs by a ping-pong type mechanism, catalyzed by the flavin mononucleotide cofactor in the active site for NADH oxidation. Moreover, semiquinones produced at the flavin site initiate redox cycling reactions with molecular oxygen, producing superoxide radicals and hydrogen peroxide. The ubiquinone reactant is regenerated, so the NADH:Q reaction becomes superstoichiometric. Idebenone, an artificial ubiquinone showing promise in the treatment of Friedreich’s Ataxia, reacts at the flavin site. The factors which determine the balance of reactivity between the two sites of ubiquinone reduction (the energy-transducing site and the flavi

The immunopathology of ANCA-associated vasculitis.

The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control