323 research outputs found

    Investigation of a pulsed electrothermal thruster system

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    The performance of an ablative wall Pulsed Electrothermal (PET) thruster is accurately characterized on a calibrated thrust stand, using polyethylene propellant. The thruster is tested for four configurations of capillary length and pulse length. The exhaust velocity is determined with twin time-of-flight photodiode stagnation probes, and the ablated mass is measured from the loss over ten shots. Based on the measured thrust impulse and the ablated mass, the specific impulse varies from 1000 to 1750 seconds. The thrust to power varies from .05 N/kW (quasi-steady mode) to .10 N/kW (unsteady mode). The thruster efficiency varies from .56 at 1000 seconds to .42 at 1750 seconds. A conceptual design is presented for a 40 kW PET propulsion system. The point design system performance is .62 system efficiency at 1000 seconds specific impulse. The system's reliability is enhanced by incorporating 20, 20 kW thruster modules which are fired in pairs. The thruster design is non-ablative, and uses water propellant, from a central storage tank, injected through the cathode

    The Tumor Suppressor HHEX Inhibits Axon Growth when Prematurely Expressed in Developing Central Nervous System Neurons

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    Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present only in trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension

    Condensation of microturbulence-generated shear flows into global modes

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    In full flux-surface computer studies of tokamak edge turbulence, a spectrum of shear flows is found to control the turbulence level and not just the conventional (0,0)-mode flows. Flux tube domains too small for the large poloidal scale lengths of the continuous spectrum tend to overestimate the flows, and thus underestimate the transport. It is shown analytically and numerically that under certain conditions dominant (0,0)-mode flows independent of the domain size develop, essentially through Bose-Einstein condensation of the shear flows.Comment: 5 pages, 4 figure

    Investigation of a repetitive pulsed electrothermal thruster

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    A pulsed electrothermal (PET) thruster with 1000:1 ratio nozzle is tested in a repetitive mode on water propellant. The thruster is driven by a 60J pulse forming network at repetition rates up to 10 Hz (600W). The pulse forming network has a .31 ohm impedance, well matched to the capillary discharge resistance of .40 ohm, and is directly coupled to the thruster electrodes without a switch. The discharge is initiated by high voltage breakdown, typically at 2500V, through the water vapor in the interelectrode gap. Water is injected as a jet through a .37 mm orifice on the thruster axis. Thruster voltage, current and impulse bit are recorded for several seconds at various power supply currents. Thruster to power ratio is typically T/P = .07 N/kW. Tank background pressure precludes direct measurement of exhaust velocity which is inferred from calculated pressure and temperature in the discharge to be about 14 km/sec. Efficiency, based on this velocity and measured T/P is .54 + or - .07. Thruster ablation is zero at the throat and becomes measurable further upstream, indicating that radiative ablation is occurring late in the pulse

    Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes

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    Pseudomonas is a metabolically-diverse genus of bacteria known for its flexibility and leading free living to pathogenic lifestyles in a wide range of hosts. The Pseudomonas Genome Database (http://www.pseudomonas.com) integrates completely-sequenced Pseudomonas genome sequences and their annotations with genome-scale, high-precision computational predictions and manually curated annotation updates. The latest release implements an ability to view sequence polymorphisms in P. aeruginosa PAO1 versus other reference strains, incomplete genomes and single gene sequences. This aids analysis of phenotypic variation between closely related isolates and strains, as well as wider population genomics and evolutionary studies. The wide range of tools for comparing Pseudomonas annotations and sequences now includes a strain-specific access point for viewing high precision computational predictions including updated, more accurate, protein subcellular localization and genomic island predictions. Views link to genome-scale experimental data as well as comparative genomics analyses that incorporate robust genera-geared methods for predicting and clustering orthologs. These analyses can be exploited for identifying putative essential and core Pseudomonas genes or identifying large-scale evolutionary events. The Pseudomonas Genome Database aims to provide a continually updated, high quality source of genome annotations, specifically tailored for Pseudomonas researchers, but using an approach that may be implemented for other genera-level research communities

    Development of an inflammatory bowel disease (IBD) Patient‐Reported Experience Measure (PREM): A patient‐led consensus work and ‘think aloud’ study for a quality improvement programme

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    Background Patient-Reported Experience Measures (PREMs) are key in improving healthcare quality, but no PREM exists for inflammatory bowel disease (IBD). This study aimed to co-produce a PREM with IBD service users for IBD service evaluation and quality improvement programme. Methods A pool of 75 items was drawn from published survey instruments covering interactions with services and aspects of living with IBD. In Stage 1, during two workshops, eight expert service users reduced candidate items through a ranked-choice voting exercise and suggested further items. During Stage 2, 18 previously uninvolved people with IBD assessed the face and content validity of the candidate items in ‘Think Aloud’ interviews. During two final workshops (Stage 3), the expert service users removed, modified and added items based on the interview findings to produce a final version of the PREM. Results Stage 1 generated a draft working PREM mapped to the following four domains: Patient-Centred Care; Quality; Accessibility; Communication and Involvement. The PREM included a set of nine items created by the expert group which shifted the emphasis from ‘self-management’ to ‘living with IBD’. Stage 2 interviews showed that comprehension of the PREM was very good, although there were concerns about the wording, IBD-relevance and ambiguity of some items. During the final two workshops in Stage 3, the expert service users removed 7 items, modified 15 items and added seven new ones based on the interview findings, resulting in a 38-item PREM. Conclusions This study demonstrates how extensive service user involvement can inform PREM development. Patient or Public Contribution Patients were involved as active members of the research team and as research participants to co-produce and validate a PREM for IBD services. In Stage 1, eight expert service users (‘the expert group’) reduced candidate items for the PREM through a voting exercise and suggested new items. During Stage 2, 18 previously uninvolved people with IBD (the ‘think aloud’ participants) assessed the validity of the candidate items in ‘Think Aloud’ interviews as research participants. In Stage 3, the expert group removed, changed and added items based on the interview findings to produce a final version of the 38-item PREM. This study shows how service user involvement can meaningfully inform PREM development

    Взаємозв’язок великих кондратьєвських циклів розвитку економіки і системних світових конфліктів

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    Однією з найважливіших проблем, що постала перед сучасною наукою у зв’язку із стрімким розгортанням глобальної економічної кризи, загостренням світових конфліктів, є вироблення науково обґрунтованих «метричних» експрес прогнозів розвитку суспільства на ближчу і далеку перспективу

    The Importance of Context and Cognitive Agency in Developing Police Knowledge: Going Beyond the Police Science Discourse

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    This paper argues the current exposition of police knowledge through the discourses of police science and evidenced based policing (EBP) leads to exaggerated claims about what is, and can be, known in policing. This new orthodoxy underestimates the challenges of applying knowledge within culturally-mediated police practice. The paper draws upon virtue epistemology highlighting the role cognitive agency plays in establishing knowledge claims. We challenge the assumption that it is possible to derive what works in all instances of certain aspects of policing and suggest it would be more apt to speak about what worked within a specific police context

    Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

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    Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease
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