Biophysics of Purkinje computation

Although others have reported and characterised different patterns of Purkinje firing (Womack and Khodakhah, 2002, 2003, 2004; McKay and Turner, 2005) this thesis is the first study that moves beyond their description and investigates the actual basis of their generation. Purkinje cells can intrinsically fire action potentials in a repeating trimodal or bimodal pattern. The trimodal pattern consists of tonic spiking, bursting and quiescence. The bimodal pattern consists of tonic spiking and quiescence. How these firing patterns are generated, and what ascertains which firing pattern is selected, has not been determined to date. We have constructed a detailed biophysical Purkinje cell model that can replicate these patterns and which shows that Na+/K+ pump activity sets the model’s operating mode. We propose that Na+/K+ pump modulation switches the Purkinje cell between different firing modes in a physiological setting and so innovatively hypothesise the Na+/K+ pump to be a computational element in Purkinje information coding. We present supporting in vitro Purkinje cell recordings in the presence of ouabain, which irreversibly blocks the Na+/K+ pump. Climbing fiber (CF) input has been shown experimentally to toggle a Purkinje cell between an up (firing) and down (quiescent) state and set the gain of its response to parallel fiber (PF) input (Mckay et al., 2007). Our Purkinje cell model captures these toggle and gain computations with a novel intracellular calcium computation that we hypothesise to be applicable in real Purkinje cells. So notably, our Purkinje cell model can compute, and importantly, relates biophysics to biological information processing. Our Purkinje cell model is biophysically detailed and as a result is very computationally intensive. This means that, whilst it is appropriate for studying properties of the 8 individual Purkinje cell (e.g. relating channel densities to firing properties), it is unsuitable for incorporation into network simulations. We have overcome this by deploying mathematical transforms to produce a simpler, surrogate version of our model that has the same electrical properties, but a lower computational overhead. Our hope is that this model, of intermediate biological fidelity and medium computational complexity, will be used in the future to bridge cellular and network studies and identify how distinctive Purkinje behaviours are important to network and system function

Studies in analytical luminescence spectrometry

Imperial Users onl

Small scale tectonism on Venus: An experimental and image based study

Closely spaced parallel lineations in the plains of Venus are interpreted as extensional rubble-filled fractures because they show no structure and are radar-bright irrespective of look angle. Their formation was investigated using a new methodology which combines material science and fracture mechanics principles together with experimental measurement and the analysis of Magellan data. Mapping in the Guinevere and Sedna Planitia regions shows that the closely spaced parallel fractures (CSPF) follow a concentric pattern around the edge of the large topographic rise of Western Eistla Regio. 13 spacing profiles show that most of the CSPF have spacings of between 0.8 and 1.2km. Using a new fracture mechanics apparatus designed to simulate Venusian surface conditions (90bar of CO2, 450°C), the fracture toughness of basalt was measured from atmospheric to 200 bar confining pressure and from room temperature to 600°C. 1 /2 Fracture toughness was found to increase from -2.4 MPam1/2 at ambient pressure to about -3.0 MPam1/2 at 50 bar confining pressure. Higher confining pressures have no further effect. Fracture toughness shows no clear trend with temperature, rising from an ambient level of -2.4MPam1/2 to -3.0MPa1/2 at 150°C and returning to -2.4MPam1/2 at higher temperatures. A new, two-dimensional model based upon fracture mechanics is described. The depth of the CSPF is controlled by the stress intensity factor but their spacing is controlled by the initiation of new cracks. Application of a faulting criterion to limit the conditions under which the CSPF can form shows that the spacing is consistent with a regional tensile stress of 5.5-8.5MPa. This stress could have resulted from uplift of Western Eistla Regio by -2km

Fat and water signals in nuclear magnetic resonance imaging

This thesis is intended to explore fat and water differentiation in nuclear magnetic resonance imaging. The need to create separate fat and water images is discussed and a critical review of current practices in the field is presented. These techniques include chemical shift imaging, coupled spin mapping and methods based on relaxation time differences. As an extension of this review, alternative slice cycling procedures are proposed that afford an improvement in the conventional chemical shift selective presaturation sequence. A new, hybrid fat or water suppression sequence is studied in detail, including a theoretical description of the role of the sequence parameters, as well as direct experimental comparison with its most closely related conventional fat and water differentiation techniques. The proposed scheme is shown to be robust in normal use and more tolerant than the conventional methods to mis-settings of experimental parameters. In vivo demonstration of the method is also performed. Further work involves the generation of differential fat and water relaxation time maps. A critical review of current, conventional techniques that allow production of longitudinal relaxation calculated images is presented. Novel pulse sequence schemes for the measurement of fat and water longitudinal relaxation times are described, and the accuracy of these measurements is evaluated using phantoms. The results obtained are also being compared with conventional spectroscopic and imaging methods

SINGLE MOLECULE FLUORESCENCE INVESTIGATION OF PROTEIN FOLDING

In addition to the well known two-state folding scenario, the energy landscape theory of protein folding predicts the possibility of downhill folding under native conditions. This intriguing prediction was extended by Victor Muñoz and coworkers to include global downhill folding. i.e. a barrierless free energy surface and unimodal conformational distributions at all degrees of unfolding stress. A small protein, BBL, has been shown to follow this behavior as evidenced from experiments and simulations. However, the identification of BBL as a global downhill folder has raised a significant amount of controversy with some groups claiming that it still folds in a two-state fashion. The objective of this thesis is to characterize the conformational distribution of BBL using single molecule Förster resonance energy transfer (SM-FRET) to obtain direct evidence for the downhill folding in BBL. We carried out SM-FRET measurements at 279 K to slow down the protein dynamics to 150 μs thus enabling the use of a 50 μs binning time (the short binning time being a first in SM measurements). By optimizing the microscope system setup and employing a novel Trolox-cysteamine fluorophore protection system, we obtained sufficient signal to construct reliable 50 μs SM-FRET histograms. The data show clear unimodal conformational distributions at varying denaturant concentrations thus demonstrating the downhill folding nature of BBL. Further SM-FRET measurements on a two-state folder, α-spectrin SH3 produced bimodal histograms indicating that our experimental setup works well and that the unimodal distributions of BBL are not due to instrumental errors. The comparison of ensemble FRET measurements on labeled proteins (both BBL and α-spectrin SH3) with CD measurements on the corresponding unlabeled proteins shows that the fluorophores do not affect the protein stability. We also simulated the expected histograms if BBL were a two-state folder using Szabo's photon statistics theory of SM-FRET. The two-state simulation results are inconsistent with the experimental histograms even under very conservative assumptions about BBL's relaxation time. Therefore, all the control experiments and simulations exclude any possible artifacts, which shows our results are quite robust. Additionally, we estimated the relaxation time of BBL from the histogram width analysis to be consistent with independent kinetic measurements

Low-cost Interference Mitigation and Relay Processing for Cooperative DS-CDMA Systems

In wireless communications, propagation aspects such as fading, shadowing and path loss are the major constraints that seriously limit the overall performance of systems. Indeed, severe fading has a detrimental effect on the received signals and can lead to a degradation of the transmission of information and the reliability of the network. In this case, diversity techniques are introduced in order to mitigate fading. Among various kinds of diversity techniques, cooperative diversity with relaying nodes is a modern technique that has been widely considered in recent years as an effective tool to deal with this problem. Several cooperative protocols have been proposed in the literature, and among the most effective ones are Amplify-and-Forward (AF) and Decode-and-Forward (DF). Cooperative diversity can be combined with direct sequence code division multiple access (DS-CDMA) systems to further enhance the information security. However, due to the multiple access interference (MAI) that arises from nonorthogonal received waveforms in the DS-CDMA systems, the system performance may easily be affected. To deal with this issue, novel multiuser detection (MUD) technique is introduced as a useful relay processing strategy for the uplink of cooperative DS-CDMA systems. Apart from that, distributed space-time coding (DSTC) is another effective approach that can be combined with cooperative diversity to further improve the transmission performance. Moreover, in order to increase the throughput of the cooperative DS-CDMA network, physical-layer network coding (PNC) scheme is then adopted together with the cooperative DS-CDMA network. Clearly, better performance gain and lower power consumption can be obtained when appropriate relaying strategies are applied

Acoustic and Elastic Waves: Recent Trends in Science and Engineering

The present Special Issue intends to explore new directions in the field of acoustics and ultrasonics. The interest includes, but is not limited to, the use of acoustic technology for condition monitoring of materials and structures. Topics of interest (among others): • Acoustic emission in materials and structures (without material limitation) • Innovative cases of ultrasonic inspection • Wave dispersion and waveguides • Monitoring of innovative materials • Seismic waves • Vibrations, damping and noise control • Combination of mechanical wave techniques with other types for structural health monitoring purposes. Experimental and numerical studies are welcome

Proceedings : mechanics and mitigation of violent failure in coal and hard-rock mines

Papers presented at a U.S. Bureau of Mines (USBM) technology transfer seminar describe the causes of violent material failure in U.S. mines, measurement techniques for monitoring events that result in violent failure, and mitigation techniques for controlling failure. Specific factors contributing to violent failure are identified on the basis of geotechnical monitoring in 16 U.S. hard-rock and coal mines and on statistical analyses of 172 coal bump events. New monitoring and analysis techniques developed as tools for assessing violent failure; geotomographic methods that provide new capabilities for the study of material failure and stress changes over large areas; and seismic methods for determining source locations, calculating energy release, and determining source mechanisms are described. Fair correlations have been established among seismic parameters, elastic stresses, face support load, and violent events. USBM studies have identified the advantages using both yielding and stable pillars for coal bump control. A computer program has been developed as an aid for selecting room-and-pillar layouts. The practical aspects of implementing a destressing program is outlined for coal mines, while the importance of mine orientation and timely support installation in controlling buckling-type failure is identified for hard-rock mines.Papers presented at technology transfer seminars held May 1995 in Coeur d'Alene, ID, Price, UT, and Norton, VA.NIOSHTIC no. 2002460