Characterization of the structure of RAMP1 by mutagenesis and molecular modeling

Receptor activity modifying proteins (RAMPs) are a family of single-pass transmembrane proteins that dimerize with G-protein-coupled receptors. They may alter the ligand recognition properties of the receptors (particularly for the calcitonin receptor-like receptor, CLR). Very little structural information is available about RAMPs. Here, an ab initio model has been generated for the extracellular domain of RAMP1. The disulfide bond arrangement (Cys 27-Cys82, Cys40-Cys72, and Cys 57-Cys104) was determined by site-directed mutagenesis. The secondary structure (a-helices from residues 29-51, 60-80, and 87-100) was established from a consensus of predictive routines. Using these constraints, an assemblage of 25,000 structures was constructed and these were ranked using an all-atom statistical potential. The best 1000 conformations were energy minimized. The lowest scoring model was refined by molecular dynamics simulation. To validate our strategy, the same methods were applied to three proteins of known structure; PDB:1HP8, PDB:1V54 chain H (residues 21-85), and PDB:1T0P. When compared to the crystal structures, the models had root mean-square deviations of 3.8 Å, 4.1 Å, and 4.0 Å, respectively. The model of RAMP1 suggested that Phe93, Tyr 100, and Phe101 form a binding interface for CLR, whereas Trp74 and Phe92 may interact with ligands that bind to the CLR/RAMP1 heterodimer. © 2006 by the Biophysical Society.

The influence of cutting tool geometry upon aspects of chip flow and tool wear:a theoretical, three dimensional examination of the cutting geometry and the shape of the twist drill

This work is undertaken in the attempt to understand the processes at work at the cutting edge of the twist drill. Extensive drill life testing performed by the University has reinforced a survey of previously published information. This work demonstrated that there are two specific aspects of drilling which have not previously been explained comprehensively. The first concerns the interrelating of process data between differing drilling situations, There is no method currently available which allows the cutting geometry of drilling to be defined numerically so that such comparisons, where made, are purely subjective. Section one examines this problem by taking as an example a 4.5mm drill suitable for use with aluminium. This drill is examined using a prototype solid modelling program to explore how the required numerical information may be generated. The second aspect is the analysis of drill stiffness. What aspects of drill stiffness provide the very great difference in performance between short flute length, medium flute length and long flute length drills? These differences exist between drills of identical point geometry and the practical superiority of short drills has been known to shop floor drilling operatives since drilling was first introduced. This problem has been dismissed repeatedly as over complicated but section two provides a first approximation and shows that at least for smaller drills of 4. 5mm the effects are highly significant. Once the cutting action of the twist drill is defined geometrically there is a huge body of machinability data that becomes applicable to the drilling process. Work remains to interpret the very high inclination angles of the drill cutting process in terms of cutting forces and tool wear but aspects of drill design may already be looked at in new ways with the prospect of a more analytical approach rather than the present mix of experience and trial and error. Other problems are specific to the twist drill, such as the behaviour of the chips in the flute. It is now possible to predict the initial direction of chip flow leaving the drill cutting edge. For the future the parameters of further chip behaviour may also be explored within this geometric model.

Point-by-point inscription of 250-nm-period structure in bulk fused silica by tightly-focused femtosecond UV pulses: experiment and numerical modeling

By conducting point-by-point inscription in a continuously moving slab of a pure fused silica at the optimal depth (170 μm depth below the surface), we have fabricated a 250-nm-period nanostructure with 30 nJ, 300 fs, 1 kHz pulses from frequency-tripled Ti:sapphire laser. This is the smallest value for the inscribed period yet reported, and has been achieved with radical improvement in the quality of the inscribed nanostructures in comparison with previous reports. The performed numerical modeling confirms the obtained experimental results.

Bandwidth management of WiMAX systems and performance modeling

WiMAX has been introduced as a competitive alternative for metropolitan broadband wireless access technologies. It is connection oriented and it can provide very high data rates, large service coverage, and flexible quality of services (QoS). Due to the large number of connections and flexible QoS supported by WiMAX, the uplink access in WiMAX networks is very challenging since the medium access control (MAC) protocol must efficiently manage the bandwidth and related channel allocations. In this paper, we propose and investigate a cost-effective WiMAX bandwidth management scheme, named the WiMAX partial sharing scheme (WPSS), in order to provide good QoS while achieving better bandwidth utilization and network throughput. The proposed bandwidth management scheme is compared with a simple but inefficient scheme, named the WiMAX complete sharing scheme (WCPS). A maximum entropy (ME) based analytical model (MEAM) is proposed for the performance evaluation of the two bandwidth management schemes. The reason for using MEAM for the performance evaluation is that MEAM can efficiently model a large-scale system in which the number of stations or connections is generally very high, while the traditional simulation and analytical (e.g., Markov models) approaches cannot perform well due to the high computation complexity. We model the bandwidth management scheme as a queuing network model (QNM) that consists of interacting multiclass queues for different service classes. Closed form expressions for the state and blocking probability distributions are derived for those schemes. Simulation results verify the MEAM numerical results and show that WPSS can significantly improve the network's performance compared to WCPS.

Investigation of a binding model for anti-cancer cyclohexadienones by computational chemistry and crystallography

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Experimental and theoretical studies on molecular geometry and polymorphism in crystalline drug substances

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Hydrogen production by steam reforming of DME in a large scale CFB reactor. Part I:computational model and predictions

This study presents a computational fluid dynamic (CFD) study of Dimethyl Ether steam reforming (DME-SR) in a large scale Circulating Fluidized Bed (CFB) reactor. The CFD model is based on Eulerian-Eulerian dispersed flow and solved using commercial software (ANSYS FLUENT). The DME-SR reactions scheme and kinetics in the presence of a bifunctional catalyst of CuO/ZnO/Al2O3+ZSM-5 were incorporated in the model using in-house developed user-defined function. The model was validated by comparing the predictions with experimental data from the literature. The results revealed for the first time detailed CFB reactor hydrodynamics, gas residence time, temperature distribution and product gas composition at a selected operating condition of 300 °C and steam to DME mass ratio of 3 (molar ratio of 7.62). The spatial variation in the gas species concentrations suggests the existence of three distinct reaction zones but limited temperature variations. The DME conversion and hydrogen yield were found to be 87% and 59% respectively, resulting in a product gas consisting of 72 mol% hydrogen. In part II of this study, the model presented here will be used to optimize the reactor design and study the effect of operating conditions on the reactor performance and products.

Bioactive sol-gel glasses at the atomic scale:the complementary use of advanced probe and computer modeling methods

Sol-gel-synthesized bioactive glasses may be formed via a hydrolysis condensation reaction, silica being introduced in the form of tetraethyl orthosilicate (TEOS), and calcium is typically added in the form of calcium nitrate. The synthesis reaction proceeds in an aqueous environment; the resultant gel is dried, before stabilization by heat treatment. These materials, being amorphous, are complex at the level of their atomic-scale structure, but their bulk properties may only be properly understood on the basis of that structural insight. Thus, a full understanding of their structure-property relationship may only be achieved through the application of a coherent suite of leading-edge experimental probes, coupled with the cogent use of advanced computer simulation methods. Using as an exemplar a calcia-silica sol-gel glass of the kind developed by Larry Hench, in the memory of whom this paper is dedicated, we illustrate the successful use of high-energy X-ray and neutron scattering (diffraction) methods, magic-angle spinning solid-state NMR, and molecular dynamics simulation as components to a powerful methodology for the study of amorphous materials.

Words and intelligence I:selected papers by Yorick Wilks

Yorick Wilks is a central figure in the fields of Natural Language Processing and Artificial Intelligence. His influence extends to many areas and includes contributions to Machines Translation, word sense disambiguation, dialogue modeling and Information Extraction. This book celebrates the work of Yorick Wilks in the form of a selection of his papers which are intended to reflect the range and depth of his work. The volume accompanies a Festschrift which celebrates his contribution to the fields of Computational Linguistics and Artificial Intelligence. The papers include early work carried out at Cambridge University, descriptions of groundbreaking work on Machine Translation and Preference Semantics as well as more recent works on belief modeling and computational semantics. The selected papers reflect Yorick’s contribution to both practical and theoretical aspects of automatic language processing.

The detection and identification of extraneous metals in material conveyance systems

The aim of this work was to design and build an equipment which can detect ferrous and non-ferrous objects in conveyed commodities, discriminate between them and locate the object along the belt and on the width of the belt. The magnetic induction mechanism was used as a means of achieving the objectives of this research. In order to choose the appropriate geometry and size of the induction field source, the field distributions of different source geometries and sizes were studied in detail. From these investigations it was found the square loop geometry is the most appropriate as a field generating source for the purpose of this project. The phenomena of field distribution in the conductors was also investigated. An equipment was designed and built at the preliminary stages of thework based on a flux-gate magnetometer with the ability to detect only ferrous objects.The instrument was designed such that it could be used to detect ferrous objects in the coal conveyors of power stations. The advantages of employing this detector in the power industry over the present ferrous metal electromagnetic separators were also considered. The objectives of this project culminated in the design and construction of a ferrous and non-ferrous detector with the ability to discriminate between ferrous and non-ferrous metals and to locate the objects on the conveying system. An experimental study was carried out to test the performance of the equipment in the detection of ferrous and non-ferrous objects of a given size carried on the conveyor belt. The ability of the equipment to discriminate between the types of metals and to locate the object on the belt was also evaluated experimentally. The benefits which can be gained from the industrial implementations of the equipment were considered. Further topics which may be investigated as an extension of this work are given.

Flow field analysis of some mixing and conveying screw element regions, within a closely intermeshing, co-rotating twin-screw extruder.

Grafting of antioxidants and other modifiers onto polymers by reactive extrusion, has been performed successfully by the Polymer Processing and Performance Group at Aston University. Traditionally the optimum conditions for the grafting process have been established within a Brabender internal mixer. Transfer of this batch process to a continuous processor, such as an extruder, has, typically, been empirical. To have more confidence in the success of direct transfer of the process requires knowledge of, and comparison between, residence times, mixing intensities, shear rates and flow regimes in the internal mixer and in the continuous processor.The continuous processor chosen for the current work in the closely intermeshing, co-rotating twin-screw extruder (CICo-TSE). CICo-TSEs contain screw elements that convey material with a self-wiping action and are widely used for polymer compounding and blending. Of the different mixing modules contained within the CICo-TSE, the trilobal elements, which impose intensive mixing, and the mixing discs, which impose extensive mixing, are of importance when establishing the intensity of mixing. In this thesis, the flow patterns within the various regions of the single-flighted conveying screw elements and within both the trilobal element and mixing disc zones of a Betol BTS40 CICo-TSE, have been modelled using the computational fluid dynamics package Polyflow. A major obstacle encountered when solving the flow problem within all of these sets of elements, arises from both the complex geometry and the time-dependent flow boundaries as the elements rotate about their fixed axes. Simulation of the time dependent boundaries was overcome by selecting a number of sequential 2D and 3D geometries, used to represent partial mixing cycles. The flow fields were simulated using the ideal rheological properties of polypropylene and characterised in terms of velocity vectors, shear stresses generated and a parameter known as the mixing efficiency. The majority of the large 3D simulations were performed on the Cray J90 supercomputer situated at the Rutherford-Appleton laboratories, with pre- and postprocessing operations achieved via a Silicon Graphics Indy workstation. A mechanical model was constructed consisting of various CICo-TSE elements rotating within a transparent outer barrel. A technique has been developed using coloured viscous clays whereby the flow patterns and mixing characteristics within the CICo-TSE may be visualised. In order to test and verify the simulated predictions, the patterns observed within the mechanical model were compared with the flow patterns predicted by the computational model. The flow patterns within the single-flighted conveying screw elements in particular, showed good agreement between the experimental and simulated results.

Investigating viscous fluid flow in an internal mixer using computational fluid dynamics

This thesis presents an effective methodology for the generation of a simulation which can be used to increase the understanding of viscous fluid processing equipment and aid in their development, design and optimisation. The Hampden RAPRA Torque Rheometer internal batch twin rotor mixer has been simulated with a view to establishing model accuracies, limitations, practicalities and uses. As this research progressed, via the analyses several 'snap-shot' analysis of several rotor configurations using the commercial code Polyflow, it was evident that the model was of some worth and its predictions are in good agreement with the validation experiments, however, several major restrictions were identified. These included poor element form, high man-hour requirements for the construction of each geometry and the absence of the transient term in these models. All, or at least some, of these limitations apply to the numerous attempts to model internal mixes by other researchers and it was clear that there was no generally accepted methodology to provide a practical three-dimensional model which has been adequately validated. This research, unlike others, presents a full complex three-dimensional, transient, non-isothermal, generalised non-Newtonian simulation with wall slip which overcomes these limitations using unmatched ridding and sliding mesh technology adapted from CFX codes. This method yields good element form and, since only one geometry has to be constructed to represent the entire rotor cycle, is extremely beneficial for detailed flow field analysis when used in conjunction with user defined programmes and automatic geometry parameterisation (AGP), and improves accuracy for investigating equipment design and operation conditions. Model validation has been identified as an area which has been neglected by other researchers in this field, especially for time dependent geometries, and has been rigorously pursued in terms of qualitative and quantitative velocity vector analysis of the isothermal, full fill mixing of generalised non-Newtonian fluids, as well as torque comparison, with a relatively high degree of success. This indicates that CFD models of this type can be accurate and perhaps have not been validated to this extent previously because of the inherent difficulties arising from most real processes.

Live 3D shape reconstruction, recognition and registration

We present a video-based system which interactively captures the geometry of a 3D object in the form of a point cloud, then recognizes and registers known objects in this point cloud in a matter of seconds (fig. 1). In order to achieve interactive speed, we exploit both efficient inference algorithms and parallel computation, often on a GPU. The system can be broken down into two distinct phases: geometry capture, and object inference. We now discuss these in further detail. © 2011 IEEE.