Histidine hydrogen bonding in MHC at pH 5 and pH 7 modeled by molecular docking and molecular dynamics simulations

Hydrogen bonds play important roles in maintaining the structure of proteins and in the formation of most biomolecular protein-ligand complexes. All amino acids can act as hydrogen bond donors and acceptors. Among amino acids, Histidine is unique, as it can exist in neutral or positively charged forms within the physiological pH range of 5.0 to 7.0. Histidine can thus interact with other aromatic residues as well as forming hydrogen bonds with polar and charged residues. The ability of His to exchange a proton lies at the heart of many important functional biomolecular interactions, including immunological ones. By using molecular docking and molecular dynamics simulation, we examine the influence of His protonation/deprotonation on peptide binding affinity to MHC class II proteins from locus HLA-DP. Peptide-MHC interaction underlies the adaptive cellular immune response, upon which the next generation of commercially-important vaccines will depend. Consistent with experiment, we find that peptides containing protonated His residues bind better to HLA-DP proteins than those with unprotonated His. Enhanced binding at pH 5.0 is due, in part, to additional hydrogen bonds formed between peptide His+ and DP proteins. In acidic endosomes, protein His79β is predominantly protonated. As a result, the peptide binding cleft narrows in the vicinity of His79β, which stabilizes the peptide - HLA-DP protein complex. © 2014 Bentham Science Publishers.

Computer control of chemical process plants with special reference to distillation

A sieve plate distillation column has been constructed and interfaced to a minicomputer with the necessary instrumentation for dynamic, estimation and control studies with special bearing on low-cost and noise-free instrumentation. A dynamic simulation of the column with a binary liquid system has been compiled using deterministic models that include fluid dynamics via Brambilla's equation for tray liquid holdup calculations. The simulation predictions have been tested experimentally under steady-state and transient conditions. The simulator's predictions of the tray temperatures have shown reasonably close agreement with the measured values under steady-state conditions and in the face of a step change in the feed rate. A method of extending linear filtering theory to highly nonlinear systems with very nonlinear measurement functional relationships has been proposed and tested by simulation on binary distillation. The simulation results have proved that the proposed methodology can overcome the typical instability problems associated with the Kalman filters. Three extended Kalman filters have been formulated and tested by simulation. The filters have been used to refine a much simplified model sequentially and to estimate parameters such as the unmeasured feed composition using information from the column simulation. It is first assumed that corrupted tray composition measurements are made available to the filter and then corrupted tray temperature measurements are accessed instead. The simulation results have demonstrated the powerful capability of the Kalman filters to overcome the typical hardware problems associated with the operation of on-line analyzers in relation to distillation dynamics and control by, in effect, replacirig them. A method of implementing estimator-aided feedforward (EAFF) control schemes has been proposed and tested by simulation on binary distillation. The results have shown that the EAFF scheme provides much better control and energy conservation than the conventional feedback temperature control in the face of a sustained step change in the feed rate or multiple changes in the feed rate, composition and temperature. Further extensions of this work are recommended as regards simulation, estimation and EAFF control.

Computer control of machines utilising independent drive mechanisms

The thesis describes an investigation into methods for the specification, design and implementation of computer control systems for flexible manufacturing machines comprising multiple, independent, electromechanically-driven mechanisms. An analysis is made of the elements of conventional mechanically-coupled machines in order that the operational functions of these elements may be identified. This analysis is used to define the scope of requirements necessary to specify the format, function and operation of a flexible, independently driven mechanism machine. A discussion of how this type of machine can accommodate modern manufacturing needs of high-speed and flexibility is presented. A sequential method of capturing requirements for such machines is detailed based on a hierarchical partitioning of machine requirements from product to independent drive mechanism. A classification of mechanisms using notations, including Data flow diagrams and Petri-nets, is described which supports capture and allows validation of requirements. A generic design for a modular, IDM machine controller is derived based upon hierarchy of control identified in these machines. A two mechanism experimental machine is detailed which is used to demonstrate the application of the specification, design and implementation techniques. A computer controller prototype and a fully flexible implementation for the IDM machine, based on Petri-net models described using the concurrent programming language Occam, is detailed. The ability of this modular computer controller to support flexible, safe and fault-tolerant operation of the two intermittent motion, discrete-synchronisation independent drive mechanisms is presented. The application of the machine development methodology to industrial projects is established.

An investigation into the use of knowledge representation in computer-integrated manufacturing

In a certain automobile factory, batch-painting of the body types in colours is controlled by an allocation system. This tries to balance production with orders, whilst making optimally-sized batches of colours. Sequences of cars entering painting cannot be optimised for easy selection of colour and batch size. `Over-production' is not allowed, in order to reduce buffer stocks of unsold vehicles. Paint quality is degraded by random effects. This thesis describes a toolkit which supports IKBS in an object-centred formalism. The intended domain of use for the toolkit is flexible manufacturing. A sizeable application program was developed, using the toolkit, to test the validity of the IKBS approach in solving the real manufacturing problem above, for which an existing conventional program was already being used. A detailed statistical analysis of the operating circumstances of the program was made to evaluate the likely need for the more flexible type of program for which the toolkit was intended. The IKBS program captures the many disparate and conflicting constraints in the scheduling knowledge and emulates the behaviour of the program installed in the factory. In the factory system, many possible, newly-discovered, heuristics would be awkward to represent and it would be impossible to make many new extensions. The representation scheme is capable of admitting changes to the knowledge, relying on the inherent encapsulating properties of object-centres programming to protect and isolate data. The object-centred scheme is supported by an enhancement of the `C' programming language and runs under BSD 4.2 UNIX. The structuring technique, using objects, provides a mechanism for separating control of expression of rule-based knowledge from the knowledge itself and allowing explicit `contexts', within which appropriate expression of knowledge can be done. Facilities are provided for acquisition of knowledge in a consistent manner.

Computer automation of land evaluation procedures

This study was concerned with the computer automation of land evaluation. This is a broad subject with many issues to be resolved, so the study concentrated on three key problems: knowledge based programming; the integration of spatial information from remote sensing and other sources; and the inclusion of socio-economic information into the land evaluation analysis. Land evaluation and land use planning were considered in the context of overseas projects in the developing world. Knowledge based systems were found to provide significant advantages over conventional programming techniques for some aspects of the land evaluation process. Declarative languages, in particular Prolog, were ideally suited to integration of social information which changes with every situation. Rule-based expert system shells were also found to be suitable for this role, including knowledge acquisition at the interview stage. All the expert system shells examined suffered from very limited constraints to problem size, but new products now overcome this. Inductive expert system shells were useful as a guide to knowledge gaps and possible relationships, but the number of examples required was unrealistic for typical land use planning situations. The accuracy of classified satellite imagery was significantly enhanced by integrating spatial information on soil distribution for Thailand data. Estimates of the rice producing area were substantially improved (30% change in area) by the addition of soil information. Image processing work on Mozambique showed that satellite remote sensing was a useful tool in stratifying vegetation cover at provincial level to identify key development areas, but its full utility could not be realised on typical planning projects, without treatment as part of a complete spatial information system.

How do practitioners understand? Practitioner perceptions of an object-oriented programming.

In the computer science community, there is considerable debate about the appropriate sequence for introducing object-oriented concepts to novice programmers. Research into novice programming has struggled to identify the critical aspects that would provide a consistently successful approach to teaching introductory object-oriented programming. Starting from the premise that the conceptions of a task determine the type of output from the task, assisting novice programmers to become aware of what the required output should be, may lay a foundation for improving learning. This study adopted a phenomenographic approach. Thirty one practitioners were interviewed about the ways in which they experience object-oriented programming and categories of description and critical aspects were identified. These critical aspects were then used to examine the spaces of learning provided in twenty introductory textbooks. The study uncovered critical aspects that related to the way that practitioners expressed their understanding of an object-oriented program and the influences on their approach to designing programs. The study of the textbooks revealed a large variability in the cover of these critical aspects.