8,564 research outputs found
Innovation and failure in mechatronics design education
Innovative engineering design always has associated with it the risk of failure, and it is the role of the design engineer to mitigate the possibilities of failure in the final system. Education should however provide a safe space for students to both innovate and to learn about and from failures. However, pressures on course designers and students can result in their adopting a conservative, and risk averse, approach to problem solving. The paper therefore considers the nature of both innovation and failure, and looks at how these might be effectively combined within mechatronics design education
Delineating neuroinflammation, parasite CNS invasion, and blood-brain barrier dysfunction in an experimental murine model of human African trypanosomiasis
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness. In addition, we have measured the trypanosome load present in the brain using quantitative Taqman PCR and assessed the severity of the neuroinflammatory reaction at specific time points over the course of the infection.
Contrast enhanced – MRI detected a significant degree of BBB impairment in mice at 14 days following trypanosome infection, which increased in a step-wise fashion as the disease progressed. Parasite DNA was present in the brain tissue on day 7 after infection. This increased significantly in quantity by day 14 post-infection and continued to rise as the infection advanced. A progressive increase in neuroinflammation was detected following trypanosome infection, reaching a significant level of severity on day 14 post-infection and rising further at later time-points. In this model stage-2 disease presents at 21 days post-infection.
The combination of the three methodologies indicates that changes in the CNS become apparent prior to the onset of established stage-2 disease. This could in part account for the difficulties associated with defining specific criteria to distinguish stage-1 and stage-2 infections and highlights the need for improved staging diagnostics
Simplifying the construction of domain-specific automatic programming systems: The NASA automated software development workstation project
An overview is presented of the Automated Software Development Workstation Project, an effort to explore knowledge-based approaches to increasing software productivity. The project focuses on applying the concept of domain specific automatic programming systems (D-SAPSs) to application domains at NASA's Johnson Space Center. A version of a D-SAPS developed in Phase 1 of the project for the domain of space station momentum management is described. How problems encountered during its implementation led researchers to concentrate on simplifying the process of building and extending such systems is discussed. Researchers propose to do this by attacking three observed bottlenecks in the D-SAPS development process through the increased automation of the acquisition of programming knowledge and the use of an object oriented development methodology at all stages of the program design. How these ideas are being implemented in the Bauhaus, a prototype workstation for D-SAPS development is discussed
A learning apprentice for software parts composition
An overview of the knowledge acquisition component of the Bauhaus, a prototype computer aided software engineering (CASE) workstation for the development of domain-specific automatic programming systems (D-SAPS) is given. D-SAPS use domain knowledge in the refinement of a description of an application program into a compilable implementation. The approach to the construction of D-SAPS was to automate the process of refining a description of a program, expressed in an object-oriented domain language, into a configuration of software parts that implement the behavior of the domain objects
Nova Aquilae 1918 (V603 Aql) Faded by 0.44 mag/century from 1938-2013
We present the light curve of the old nova V603 Aql (Nova Aql 1918) from
1898-1918 and 1934-2013 using 22,721 archival magnitudes. All of our magnitudes
are either in, or accurately transformed into, the Johnson and
magnitude systems. This is vital because offsets in old sequences and the
visual-to- transformation make for errors from 0.1-1.0 magnitude if not
corrected. Our V603 Aql light curve is the first time that this has been done
for any nova. Our goal was to see the evolution of the mass accretion rate on
the century time scale, and to test the long-standing prediction of the
Hibernation model that old novae should be fading significantly in the century
after their eruption is long over. The 1918 nova eruption was completely
finished by 1938 when the nova decline stopped, and when the star had faded to
fainter than its pre-nova brightness of mag. We find that
the nova light from 1938-2013 was significantly fading, with this being seen
consistently in three independent data sets (the Sonneberg plates in , the
AAVSO light curve, and the non-AAVSO light curve). We find that V603
Aql is declining in brightness at an average rate of mag per
century since 1938. This work provides remarkable confirmation of an important
prediction of the Hibernation model.Comment: 13 pages, 1 figure, 2 electronic online data tables, Accepted for
publication ApJLet
Synthesis and Evaluation of New Ligands for Gallium Radiolabelling
A series of N3O3 triaza-tricarboxylate hexadentate ligands, based on the 6-amino-1,4-diazepine scaffold, has been designed and synthesised. An investigation of the suitability of these ligands towards application in 68Ga-PET has been conducted, with particular focus on the efficiency and efficacy of radiolabelling. Subsequently, selectivity for Ga(III) over other relevant cations has been studied, along with exploration of the kinetics of radiolabelling, stability and in vivo behaviour of the radiolabelled complexes in healthy rats. The four best candidates quantitatively radiolabel within three minutes at room temperature over the pH range 4 – 7, to give a single 68Ga-radiolabelled species which is sufficiently stable for in vivo application. As a result, these compounds are very promising candidates for use as ligands in 68Ga-PET.
Decoration of the AMPED scaffold amine functionalities yielded a series of chelators, which allowed the 68Ga-radiolabelling properties of this family of ligands to be investigated. The ligands have a mixture of acyclic and cyclic properties, which facilitated rapid binding of the metal and formation of a stable complex. Synthetic details and 1H NMR solution state properties are described. With respect to radiolabelling, the best ligands were those with the least sterically demanding exocyclic amine substituents. However, ligands featuring a mono-alkylated exocyclic amine were prone to internal lactamisation under acidic conditions, which rendered these compounds ineffectual as ligands for 68Ga.
The synthesis and radiochemical evaluation of an additional series of ligands, featuring a modified core structure, designed to inhibit the lactamisation reaction and promote ‘pre-organisation’ of the ligand donors were undertaken. The synthetic methodology developed allows for selective functionalisation of the different amine groups of the ring. Modification of the AMPED core by substitution of the tertiary methyl group for a phenyl moiety increased the steric bulk close to exocyclic amine, which inhibited internal lactamisation. Critically, the methyl-for-phenyl substitution does not have a detrimental effect on the complexation properties.
Finally a study was undertaken of the radiolabelled complex speciation, using NMR spectroscopy and X-ray crystallography. The presence of multiple radiolabelled complex species was attributed to the formation of kinetically trapped complexes of differing stability. The relative population of the two major ligand conformations is controlled by the relative steric demand of the substituents at the quaternary site. The exocyclic amine is subject to protonation (pKa 5.7), and therefore the relative population of the ligand conformers is pH dependent over the range 3 – 7. By substituting the methyl group for a more sterically demanding phenyl group, the population of the ligand conformation favouring fast and stable gallium binding was increased
Computational and Analytic Time-Dependent Ginzburg-Landau Theory for High-Resistivity High-Field Superconducting Josephson Junctions
In this thesis, we study the building block for the description of the granular structure of polycrystalline superconductors - the Josephson junction. We investigate the critical current density as a function of applied magnetic field both analytically and computationally, through the lens of time-dependent Ginzburg-Landau theory (TDGL) in 2D. We derive new analytic expressions for the order parameter distribution near interfaces of arbitrary material properties in 2D, validate them using TDGL simulations and use them to extract the effective upper critical field. These results represent a generalization of the famous work from Saint James and de Gennes to arbitrary grain boundary properties. We then extend this framework to include the transport current flowing across the grain boundary, and obtain analytic expressions for the maximum current density that can flow across the grain boundary, providing a generalization of the in-field work in the literature, to high resistivity grain boundaries. We provide a framework to predict the critical current density across the 2D grain boundary over the entire applied magnetic field range, again validated using TDGL simulations. Crucially, our derived expressions consider arbitrary width in detail, but require no additional free parameters, since the derivation formally includes the complexity near interfaces with arbitrary material parameters. We demonstrate how our analytic extension and treatment is necessary for systems with geometries and material parameters which are representative of commercial high-field superconducting materials. Finally, we address how to apply our understanding of a single Josephson junction to 3D polycrystalline materials
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