Forced retroevolution of an RNA bacteriophage

The operator hairpin ahead of the replicase gene in RNA bacteriophage MS2 contains overlapping signals for binding the coat protein and ribosomes. Coat protein binding inhibits further translation of the gene and forms the first step in capsid formation. The hairpin sequence was partially randomized to assess the importance of this structure element for the bacteriophage and to monitor alternative solutions that would evolve on the passaging of mutant phages. The evolutionary reconstruction of the operator failed in the majority of mutants. Instead, a poor imitation developed containing only some of the recognition signals for the coat protein. Three mutants were of particular interest in that they contained double nonsense codons in the lysis reading frame that runs through the operator hairpin. The simultaneous reversion of two stop codons into sense codons has a very low probability of occurring. Therefore the phage solved the problem by deleting the nonsense signals and, in fact, the complete operator, except for the initiation codon of the replicase gene. Several revertants were isolated with activities ranging from 1% to 20% of wild type. The operator, long thought to be a critical regulator, now appears to be a dispensable element. In addition, the results indicate how RNA viruses can be forced to step back to an attenuated form.

An integrated scheduling problem of PCB components on sequential pick-and-place machines:mathematical models and heuristic solutions

This paper formulates several mathematical models for determining the optimal sequence of component placements and assignment of component types to feeders simultaneously or the integrated scheduling problem for a type of surface mount technology placement machines, called the sequential pick-andplace (PAP) machine. A PAP machine has multiple stationary feeders storing components, a stationary working table holding a printed circuit board (PCB), and a movable placement head to pick up components from feeders and place them to a board. The objective of integrated problem is to minimize the total distance traveled by the placement head. Two integer nonlinear programming models are formulated first. Then, each of them is equivalently converted into an integer linear type. The models for the integrated problem are verified by two commercial packages. In addition, a hybrid genetic algorithm previously developed by the authors is adopted to solve the models. The algorithm not only generates the optimal solutions quickly for small-sized problems, but also outperforms the genetic algorithms developed by other researchers in terms of total traveling distance.

A genetic algorithm approach to optimising component placement and retrieval sequence for chip shooter machines

A chip shooter machine in printed circuit board (PCB) assembly has three movable mechanisms: an X-Y table carrying a PCB, a feeder carrier with several feeders holding components and a rotary turret with multiple assembly heads to pick up and place components. In order to get the minimal placement or assembly time for a PCB on the machine, all the components on the board should be placed in a perfect sequence, and the components should be set up on a right feeder, or feeders since two feeders can hold the same type of components, and additionally, the assembly head should retrieve or pick up a component from a right feeder. The entire problem is very complicated, and this paper presents a genetic algorithm approach to tackle it.

A multi-depot travelling salesman problem and its iterative and integrated approaches

This paper formulates a logistics distribution problem as the multi-depot travelling salesman problem (MDTSP). The decision makers not only have to determine the travelling sequence of the salesman for delivering finished products from a warehouse or depot to a customer, but also need to determine which depot stores which type of products so that the total travelling distance is minimised. The MDTSP is similar to the combination of the travelling salesman and quadratic assignment problems. In this paper, the two individual hard problems or models are formulated first. Then, the problems are integrated together, that is, the MDTSP. The MDTSP is constructed as both integer nonlinear and linear programming models. After formulating the models, we verify the integrated models using commercial packages, and most importantly, investigate whether an iterative approach, that is, solving the individual models repeatedly, can generate an optimal solution to the MDTSP. Copyright © 2006 Inderscience Enterprises Ltd.

Promoting creativity at work:the role of problem-solving demand

We propose that problem-solving demand (PSD) is an important job attribute for employees' creative performance. Applying job design theory, we examined the relationship between PSD and employee creativity. The theorised model was tested with data obtained from a sample of 270 employees and their supervisors from three Chinese organisations. Regression results revealed that PSD was positively related to creativity, and this relationship was mediated by creative self-efficacy. Additionally, intrinsic motivation moderated the relationship between PSD and creative self-efficacy such that the relationship was stronger for individuals with high rather than low intrinsic motivation. We discuss our findings, implications for practice, and future research.

The influence of high contrast acuity and normalised low contrast acuity upon self-reported situation avoidance and driving crashes

The aim of this study was to determine the cues used to signal avoidance of difficult driving situations and to test the hypothesis that drivers with relatively poor high contrast visual acuity (HCVA) have fewer crashes than drivers with relatively poor normalised low contrast visual acuity (NLCVA). This is because those with poorer HCVA are well aware of their difficulties and avoid dangerous driving situations while those poorer NLCVA are often unaware of the extent of their problem. Age, self-reported situation avoidance and HCVA were collected during a practice based study of 690 drivers. Screening was also carried out on 7254 drivers at various venues, mainly motorway sites, throughout the UK. Age, self-reported situation avoidance and prior crash involvement were recorded and Titmus vision screeners were used to measure HCVA and NLCVA. Situation avoidance increased in reduced visibility conditions and was influenced by age and HCVA. Only half of the drivers used visual cues to signal situation avoidance and most of these drivers used high rather than low contrast cues. A statistical model designed to remove confounding interrelationships between variables showed, for drivers that did not report situation avoidance, that crash involvement decreased for drivers with below average HCVA and increased for those with below average NLCVA. These relationships accounted for less than 1% of the crash variance, so the hypothesis was not strongly supported. © 2002 The College of Optometrists.

Investigation of the effects of low energy high dose ion bombardment in metals and compound semiconductors

The effect of low energy nitrogen molecular ion beam bombardment on metals and compound semiconductors has been studied, with the aim to investigate at the effects of ion and target properties. For this purpose, nitrogen ion implantation in aluminium, iron, copper, gold, GaAs and AIGaAs is studied using XPS and Angle Resolve XPS. A series of experimental studies on N+2 bombardment induced compositional changes, especially the amount of nitrogen retained in the target, were accomplished. Both monoenergetic implantation and non-monoenergetic ion implantation were investigated, using the VG Scientific ESCALAB 200D system and a d. c. plasma cell, respectively. When the samples, with the exception of gold, are exposed to air, native oxide layers are formed on the surfaces. In the case of monoenergetic implantation, the surfaces were cleaned using Ar+ beam bombardment prior to implantation. The materials were then bombarded with N2+ beam and eight sets of successful experiments were performed on each sample, using a rastered N2+ ion beam of energy of 2, 3, 4 and 5 keV with current densities of 1 μA/cm2 and 5 μA/cm22 for each energy. The bombarded samples were examined by ARXPS. After each complete implantation, XPS depth profiles were created using Ar+ beam at energy 2 ke V and current density 2 μA/cm2 . As the current density was chosen as one of the parameters, accurate determination of current density was very important. In the case of glow discharge, two sets of successful experiments were performed in each case, by exposing the samples to nitrogen plasma for the two conditions: at low pressure and high voltage and high pressure and low voltage. These samples were then examined by ARXPS. On the theoretical side, the major problem was prediction of the number of ions of an element that can be implanted in a given matrix. Although the programme is essentially on experimental study, but an attempt is being made to understand the current theoretical models, such as SATVAL, SUSPRE and TRIM. The experimental results were compared with theoretical predictions, in order to gain a better understanding of the mechanisms responsible. From the experimental results, considering possible experimental uncertainties, there is no evidence of significant variation in nitrogen saturation concentration with ion energy or ion current density in the range of 2-5 ke V, however, the retention characteristics of implantant seem to strongly depend on the chemical reactivity between ion species and target material. The experimental data suggests the presence of at least one thermal process. The discrepancy between the theoretical and experimental results could be the inability of the codes to account for molecular ion impact and thermal processes.

Identification of nonlinear systems by correlation using pseudorandom signals

This thesis is concerned with the measurement of the characteristics of nonlinear systems by crosscorrelation, using pseudorandom input signals based on m sequences. The systems are characterised by Volterra series, and analytical expressions relating the rth order Volterra kernel to r-dimensional crosscorrelation measurements are derived. It is shown that the two-dimensional crosscorrelation measurements are related to the corresponding second order kernel values by a set of equations which may be structured into a number of independent subsets. The m sequence properties determine how the maximum order of the subsets for off-diagonal values is related to the upper bound of the arguments for nonzero kernel values. The upper bound of the arguments is used as a performance index, and the performance of antisymmetric pseudorandom binary, ternary and quinary signals is investigated. The performance indices obtained above are small in relation to the periods of the corresponding signals. To achieve higher performance with ternary signals, a method is proposed for combining the estimates of the second order kernel values so that the effects of some of the undesirable nonzero values in the fourth order autocorrelation function of the input signal are removed. The identification of the dynamics of two-input, single-output systems with multiplicative nonlinearity is investigated. It is shown that the characteristics of such a system may be determined by crosscorrelation experiments using phase-shifted versions of a common signal as inputs. The effects of nonlinearities on the estimates of system weighting functions obtained by crosscorrelation are also investigated. Results obtained by correlation testing of an industrial process are presented, and the differences between theoretical and experimental results discussed for this case;

Present perspectives on the automated classification of the G-protein coupled receptors (GPCRs) at the protein sequence level

The G-protein coupled receptors--or GPCRs--comprise simultaneously one of the largest and one of the most multi-functional protein families known to modern-day molecular bioscience. From a drug discovery and pharmaceutical industry perspective, the GPCRs constitute one of the most commercially and economically important groups of proteins known. The GPCRs undertake numerous vital metabolic functions and interact with a hugely diverse range of small and large ligands. Many different methodologies have been developed to efficiently and accurately classify the GPCRs. These range from motif-based techniques to machine learning as well as a variety of alignment-free techniques based on the physiochemical properties of sequences. We review here the available methodologies for the classification of GPCRs. Part of this work focuses on how we have tried to build the intrinsically hierarchical nature of sequence relations, implicit within the family, into an adaptive approach to classification. Importantly, we also allude to some of the key innate problems in developing an effective approach to classifying the GPCRs: the lack of sequence similarity between the six classes that comprise the GPCR family and the low sequence similarity to other family members evinced by many newly revealed members of the family.

Sequence distributions in free-radical polymers

This thesis is concerned with demonstrating how the visual representation of the sequence distribution of individual monomer units, of a polymer, that would be observed upon polymerisation, may be utilised in designing and synthesizing polymers with relatively low cell adhesion characteristics, The initial part of this thesis is concerned with demonstrating the use of a computer simulation technique, in illustrating the sequence distribution that would be observed upon the polymerisation of a set of monomers. The power of the computer simulation technique has been demonstrated through the simulation of the sequence distributions of some generic contact lens materials. These generic contact lens materials were chosen simply because in the field of biomaterials their compositions are amongst the most systematically regulated and they present a wide range of compositions. The validity of the computer simulation technique has been assessed through the synthesis and analysis of linear free-radical polymers at different conversions. Two main parameters were examined, that of composition and the number-average sequence lengths of individual monomer units, at various conversions. The polymers were synthesized through the solution polymerisation process. The monomer composition was determined by elemental analysis and 13C nuclear magnetic analysis (NMR). Number-average sequence lengths were determined exclusively through 13C NMR. Although the computer simulation technique provides a visual representation of the monomer sequence distribution up to 100% conversion, these assessments were made on linear polymers at a reasonably high conversion (above 50%) but below 100% conversion of ease for analysis. The analyses proved that the computer simulation technique was reasonably accurate in predicting the sequence distribution of monomer units, upon polymerisation, in the polymer.An approach has been presented which allows one to manipulate the use of monomers, with their reactivity ratios, thereby enabling us to design polymers with controlled sequence distributions.Hydrogel membranes, with relatively controlled sequence distributions and polymerised to 100% conversion, were synthesized to represent prospective biomaterials. Cell adhesion studies were used as a biological probe to investigate the susceptibility of the surface of these membranes to cell adhesion. This was necessary in order to assess the surface biocompatibility or biotolerance of these prospective biomaterials.

Enhancing creativity in a general work environment : the role of problem-solving demand

Prior research suggests management can employ cognitively demanding job attributes to promote employee creativity. However, it is not clear what specific type of cognitive demand is particularly important for creativity, what processes underpin the relationship between demanding job conditions and creativity and what factors lead to employee perceptions of demanding job attributes. This research sets out to address the aforementioned issues by examining: (i) problem-solving demand (PDS), a specific type of cognitive demand, and the processes that link PSD to creativity, and (ii) antecedents to PSD. Based on social cognitive theory, PSD was hypothesized to be positively related to creativity through the motivational mechanism of creative self-efficacy. However, the relationship between PSD and creative self-efficacy was hypothesized to be contingent on levels of intrinsic motivation. Social information processing perspective and the job crafting model were used to identify antecedents of PSD. Consequently, two social-contextual factors (supervisor developmental feedback and job autonomy) and one individual factor (proactive personality) were hypothesized to be precursors to PSD perceptions. The theorized model was tested with data obtained from a sample of 270 employees and their supervisors from 3 organisations in the People’s Republic of China. Regression results revealed that PSD was positively related to creativity but this relationship was partially mediated by creative self-efficacy. Additionally, intrinsic motivation moderated the relationship between PSD and creative self-efficacy such that the relationship was stronger for individuals high rather than low in intrinsic motivation. The findings represent a productive first step in identifying a specific cognitive demand that is conducive to employee creativity. In addition, the findings contribute to the literature by identifying a psychological mechanism that may link cognitively demanding job attributes and creativity.

The development of constrained source localisation algorithms for human brain imaging

This work sets out to evaluate the potential benefits and pit-falls in using a priori information to help solve the Magnetoencephalographic (MEG) inverse problem. In chapter one the forward problem in MEG is introduced, together with a scheme that demonstrates how a priori information can be incorporated into the inverse problem. Chapter two contains a literature review of techniques currently used to solve the inverse problem. Emphasis is put on the kind of a priori information that is used by each of these techniques and the ease with which additional constraints can be applied. The formalism of the FOCUSS algorithm is shown to allow for the incorporation of a priori information in an insightful and straightforward manner. In chapter three it is described how anatomical constraints, in the form of a realistically shaped source space, can be extracted from a subject’s Magnetic Resonance Image (MRI). The use of such constraints relies on accurate co-registration of the MEG and MRI co-ordinate systems. Variations of the two main co-registration approaches, based on fiducial markers or on surface matching, are described and the accuracy and robustness of a surface matching algorithm is evaluated. Figures of merit introduced in chapter four are shown to given insight into the limitations of a typical measurement set-up and potential value of a priori information. It is shown in chapter five that constrained dipole fitting and FOCUSS outperform unconstrained dipole fitting when data with low SNR is used. However, the effect of errors in the constraints can reduce this advantage. Finally, it is demonstrated in chapter six that the results of different localisation techniques give corroborative evidence about the location and activation sequence of the human visual cortical areas underlying the first 125ms of the visual magnetic evoked response recorded with a whole head neuromagnetometer.

Gravity field recovery using two low satellites in different orbital planes

This study is concerned with gravity field recovery from low-low satellite to satellite range rate data. An improvement over a coplanar mission is predicted in the errors associated with certain parts of the geopotential by the separation of the orbital planes of the two satellites. Using Hill's equations an analytical scheme to model the range rate residuals is developed. It is flexible enough to model equally well the residuals between pairs of satellites in the same orbital plane or whose planes are separated in right ascension. The possible benefits of such an orientation to gravity field recovery from range rate data can therefore be analysed, and this is done by means of an extensive error analysis. The results of this analysis show that for an optimal planar mission improvements can be made by separating the satellites in right ascension. Gravity field recoveries are performed in order to verify and gauge the limitations of the analytical model, and to support the results of the error analysis. Finally the possible problem of the differential decay rates of two satellites due to the diurnal bulge are evaluated.

Antibacterial activity of low amperage and low voltage electric current (DC)

Infection is a major clinical problem associated with the use of intravenous catheters.The efficacy of a direct electric current (10µA, 9V) via electrode-conducting carbon impregnated catheters to prevent colonisation of catheters by micro-organisms was investigated. The range of organisms susceptible to 10µA was determined by a zone of inhibition test. The catheters acting as the anode and the cathode were inserted into a nutrient agar plate inoculated with a lawn of bacteria. There was no zone of inhibition observed around the anode. Organisms susceptible to 10µA at the cathode were Staphylococcus aureus (2 strains), Staphylococcus epidermidis (5 strains), Escherichia coli and Klebsiella pneumoniae (2 strains each), and one strain of the following micro-organisms: Staphylococcus hominis, Proteus mirabilis, Pseudomonas aeruginosa and Candida albicans. The zones ranged from 6 to 16 mm in diameter according to the organisms under test. The zone size was proportional to the amperage (10 - 100 µA) and the number of organisms on the plate. Ten µA did not prevent adhesion of staphylococci to the cathode nor did it affect their growth in nutrient broth. However, it was bactericidal to adherent bacteria on the cathodal catheter and significantly reduced the number of bacteria on the catheter after 4 to 24 h application of electricity. The antimicrobial activity of low amperage electric current under anaerobic conditions and in the absence of chloride ions against bacteria attached to the surface of a current carrying electrode was also investigated.The mechanisms of the bactericidal activity associated with the cathode were investigated with S. epidermidis and S. aureus. The inhibition zone was greatly reduced in the presence of catalase. There was no zone around the cathode when the test was carried out under anaerobic conditions. Hydrogen peroxide was produced at the cathode surface under aerobic conditions, but not in the absence of oxygen. A salt-bridge apparatus was used to demonstrate further that hydrogen peroxide was produced at the cathode, and chlorine at the anode. The antimicrobial activity of low amperage electric current under anaerobic conditions and in the absence of chloride ions against bacteria attached to the surface of a current carrying electrode was also investigated. Antibacterial activity was reduced under anaerobic conditions, which is compatible with the role of hydrogen peroxide as a primary bactericidal agent of electricity associated with the cathode. A reduction in chloride ions did not significantly reduce the antibacterial activity suggesting chlorine plays only a minor role in the bactericidal activity against organisms attached to anodal electrode surfaces. The bactericidal activity of electric current associated with the cathode and H202 was greatly reduced in the presence of 50 μM to 0.5 mM magnesium ions in the test menstrum. Ten μA applied via the catheters did not prevent the initial biofilm growth by the adherent bacteria but reduced the number of bacteria in the biofilm by 2 log order aiter 24 h. The results suggested that 10 μA may prevent the colonisation of catheters by both the extra~ and intra-luminal routes. The localised production of hydrogen peroxide and chlorine and the intrinsic activity due to electric current may offer a useful method for the eradication of bacteria from catheter surfaces.

An integral equation method for a mixed initial boundary value problem for unsteady Stokes system in a doubly-connected domain

We present a novel numerical method for a mixed initial boundary value problem for the unsteady Stokes system in a planar doubly-connected domain. Using a Laguerre transformation the unsteady problem is reduced to a system of boundary value problems for the Stokes resolvent equations. Employing a modied potential approach we obtain a system of boundary integral equations with various singularities and we use a trigonometric quadrature method for their numerical solution. Numerical examples are presented showing that accurate approximations can be obtained with low computational cost.