1,511 research outputs found
Molecular characteristics of the scrapie agent.
The prion diseases of humans and animals, including Creutzfeld-Jakob disease (CJD) and Kuru of humans, scrapie of sheep and Bovine Spongiform Encephalopothy (BSE), are a family of closely linked neurodegenerative disorders that have proved to be both heritable and transmittable. The aetiology of these disorders has been shown to be intrinsically linked to a novel infectious particle made up either solely or overwhelmingly of protein, the major component of which is the prion precursor protein (PrP). PrP is a 253 amino acid protein modified during synthesis by the addition of a glycophosphatidinol (GPI) anchor and either one or two N-linked sugar chains. PrP normally exists within the cell in a predominantly a-helical conformation (PrPc), but can adopt an alternative, predominantly p-sheet structure closely linked to the disease state. In this thesis, investigations into two of the molecular characteristics of the scrapie agent are described: the impact of the GPI anchor on infectivity and the biochemical effect of the codon 129 M/V polymorphism. The M/V polymorphism plays a major role in the disease process---with the codon 129 status of an individual modifying both susceptibility to disease and disease course. No alterations were observed in the stability, structure, protease resistance or copper binding properties of the a-helical form of PrP due to this polymorphism. Both forms had a similar propensity to form the P-rich isoform of PrP and, once in the P-rich conformation, no differences in structure, protease resistance or stability were observed between the two polymorphic variants. The codon 129 polymorphism was found, however, to have a dramatic impact on the ability of the prion protein to form ordered aggregates. To investigate the contribution of the GPI anchor to the infectivity of PrPSc, a novel proteolytic treatment was used to remove the C-terminal and GPI from the prion protein. The infectious properties of PrP80 lacking the GPI were examined using in vitro, cell based and in vivo models of prion replication. No alteration in the ability of C-terminally truncated PrP80 to propagate was observed
Neural correlates of processing valence and arousal in affective words
Psychological frameworks conceptualize emotion along 2 dimensions, "valence" and "arousal." Arousal invokes a single axis of intensity increasing from neutral to maximally arousing. Valence can be described variously as a bipolar continuum, as independent positive and negative dimensions, or as hedonic value (distance from neutral). In this study, we used functional magnetic resonance imaging to characterize neural activity correlating with arousal and with distinct models of valence during presentation of affective word stimuli. Our results extend observations in the chemosensory domain suggesting a double dissociation in which subregions of orbitofrontal cortex process valence, whereas amygdala preferentially processes arousal. In addition, our data support the physiological validity of descriptions of valence along independent axes or as absolute distance from neutral but fail to support the validity of descriptions of valence along a bipolar continuum
A systemic approach to the design of cellular manufacturing systems
Cellular manufacturing is widely acknowledged as one of the key approaches to achieving world-class performance in batch manufacturing operations. The design of cellular manufacturing systems (CMS) is therefore crucial in determining a company's competitiveness. This thesis postulated that, in order to be effective the design of CMS should not only be systematic but also systemic. A systemic design uses the concepts of the body of work known as the 'systems approach' to ensure that a truly effective CMS is defined. The thesis examined the systems approach and created a systemic framework against which existing approaches to the design of CMS were evaluated. The most promising of these, Manufacturing Systems Engineering (MSE), was further investigated using a series of cross-sectional case-studies. Although, in practice, MSE proved to be less than systemic, it appeared to produce significant benefits. This seemed to suggest that CMS design did not need to be systemic to be effective. However, further longitudinal case-studies showed that the benefits claimed were at an operational level not at a business level and also that the performance of the whole system had not been evaluated. The deficiencies identified in the existing approaches to designing CMS were then addressed by the development of a novel CMS design methodology that fully utilised systems concepts. A key aspect of the methodology was the use of the Whole Business Simulator (WBS), a modelling and simulation tool that enabled the evaluation of CMS at operational and business levels. The most contentious aspects of the methodology were tested on a significant and complex case-study. The results of the exercise indicated that the systemic methodology was feasible
Two decades of pulsar timing of Vela
Pulsar timing at the Mt Pleasant observatory has focused on Vela, which can
be tracked for 18 hours of the day. These nearly continuous timing records
extend over 24 years allowing a greater insight into details of timing noise,
micro glitches and other more exotic effects. In particular we report the
glitch parameters of the 2004 event, along with the reconfirmation that the
spin up for the Vela pulsar occurs instantaneously to the accuracy of the data.
This places a lower limit of about 30 seconds for the acceleration of the
pulsar to the new rotational frequency. We also confirm of the low braking
index for Vela, and the continued fall in the DM for this pulsar.Comment: Isolated Neutron Stars conference, London, April 24-28 200
Systematic Study of Electron Localization in an Amorphous Semiconductor
We investigate the electronic structure of gap and band tail states in
amorphous silicon. Starting with two 216-atom models of amorphous silicon with
defect concentration close to the experiments, we systematically study the
dependence of electron localization on basis set, density functional and spin
polarization using the first principles density functional code Siesta. We
briefly compare three different schemes for characterizing localization:
information entropy, inverse participation ratio and spatial variance. Our
results show that to accurately describe defect structures within self
consistent density functional theory, a rich basis set is necessary. Our study
revealed that the localization of the wave function associated with the defect
states decreases with larger basis sets and there is some enhancement of
localization from GGA relative to LDA. Spin localization results obtained via
LSDA calculations, are in reasonable agreement with experiment and with
previous LSDA calculations on a-Si:H models.Comment: 16 pages, 11 Postscript figures, To appear in Phys. Rev.
The Complexity of Reasoning for Fragments of Default Logic
Default logic was introduced by Reiter in 1980. In 1992, Gottlob classified
the complexity of the extension existence problem for propositional default
logic as \SigmaPtwo-complete, and the complexity of the credulous and
skeptical reasoning problem as SigmaP2-complete, resp. PiP2-complete.
Additionally, he investigated restrictions on the default rules, i.e.,
semi-normal default rules. Selman made in 1992 a similar approach with
disjunction-free and unary default rules. In this paper we systematically
restrict the set of allowed propositional connectives. We give a complete
complexity classification for all sets of Boolean functions in the meaning of
Post's lattice for all three common decision problems for propositional default
logic. We show that the complexity is a hexachotomy (SigmaP2-, DeltaP2-, NP-,
P-, NL-complete, trivial) for the extension existence problem, while for the
credulous and skeptical reasoning problem we obtain similar classifications
without trivial cases.Comment: Corrected versio
Physical tests for Random Numbers in Simulations
We propose three physical tests to measure correlations in random numbers
used in Monte Carlo simulations. The first test uses autocorrelation times of
certain physical quantities when the Ising model is simulated with the Wolff
algorithm. The second test is based on random walks, and the third on blocks of
n successive numbers. We apply the tests to show that recent errors in high
precision simulations using generalized feedback shift register algorithms are
due to short range correlations in random number sequences. We also determine
the length of these correlations.Comment: 16 pages, Post Script file, HU-TFT-94-
Wound healing and hyper-hydration - a counter intuitive model
Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration
A twin-disc study of the role of the surface quality achieved by grinding on the wear resistance and rolling contact fatigue behavior of wheel/rail pairs
The tribological behavior of wheel and rail material twin-disc samples prepared under laboratory-controlled grinding operations was studied. A laboratory grinding device was designed and validated to produce similar results to those found in the field in terms of surface quality and presence of white etching layer (WEL). The test samples were evaluated in a twin-disc machine under dry and lubricated conditions. The results showed that the surface finishing parameters and the microstructure change greatly depending on the surface preparation procedure, and that such changes affect the tribological response of the samples. The wear rates of the tribological tests for the different rail surface qualities showed a reduction of 47.4% for the lubricated tests and 7.3% for the dry tests when the surfaces of the rail specimens were finished by grinding. This is only applied when the WEL thickness was less than 4 μm
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General techniques for constrained motion planning
This report presents automatic motion planning algorithms for robotic manipulators performing a variety of tasks. Given a task and a robot manipulator equipped with a tool in its hand, the motion planners compute robot motions to complete the task while respecting manipulator kinematic constraints and avoiding collisions with objects in the robot`s work space. To handle the high complexity of the motion planning problem, a sophisticated search strategy called SANDROS is developed and used to solve many variations of the motion planning problem. To facilitate systematic development of motion planning algorithms, robotic tasks are classified into three categories according to the dimension of the manifold the robot tool has to travel: visit-point (0 dimensional), trace-curve (1 dimensional) and cover-surface (2 dimensional) tasks. The motion planner for a particular dimension is used as a sub-module by the motion planner for the next-higher dimension. This hierarchy of motion planners has led to a set of compact and systematic algorithms that can plan robot motions for many types of robotic operations. In addition, an algorithm is developed that determines the optimal robot-base configuration for minimum cycle time. The SANDROS search paradigm is complete in that it finds a solution path if one exists, up to a user specified resolution. Although its worst-case time complexity is exponential in the degrees of freedom of the manipulator, its average performance is commensurate with the complexity of the solution path. Since solution paths for most of motion planning problems consist of a few monotone segments, the motion planners based on SANDROS search strategy show approximately two-orders of magnitude improvements over existing complete algorithms
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