Removing the redundancy from randomised gene libraries

Amino acid substitution plays a vital role in both the molecular engineering of proteins and analysis of structure-activity relationships. High-throughput substitution is achieved by codon randomisation, which generates a library of mutants (a randomised gene library) in a single experiment. For full randomisation, key codons are typically replaced with NNN (64 sequences) or NNG CorT (32 sequences). This obligates cloning of redundant codons alongside those required to encode the 20 amino acids. As the number of randomised codons increases, there is therefore a progressive loss of randomisation efficiency; the number of genes required per protein rises exponentially. The redundant codons cause amino acids to be represented unevenly; for example, methionine is encoded just once within NNN, whilst arginine is encoded six times. Finally, the organisation of the genetic code makes it impossible to encode functional subsets of amino acids (e.g. polar residues only) in a single experiment. Here, we present a novel solution to randomisation where genetic redundancy is eliminated; the number of different genes equals the number of encoded proteins, regardless of codon number. There is no inherent amino acid bias and any required subset of amino acids may be encoded in one experiment. This generic approach should be widely applicable in studies involving randomisation of proteins. © 2003 Elsevier Ltd. All rights reserved.

Overcoming network overload and redundancy in inter-organizational networks:the roles of potential and latent ties

This paper builds on Granovetter's distinction between strong and weak ties [Granovetter, M. S. 1973. The strength of weak ties. Amer. J. Sociol. 78(6) 1360–1380] in order to respond to recent calls for a more dynamic and processual understanding of networks. The concepts of potential and latent tie are deductively identified, and their implications for understanding how and why networks emerge, evolve, and change are explored. A longitudinal empirical study conducted with companies operating in the European motorsport industry reveals that firms take strategic actions to search for potential ties and reactivate latent ties in order to solve problems of network redundancy and overload. Examples are given, and their characteristics are examined to provide theoretical elaboration of the relationship between the types of tie and network evolution. These conceptual and empirical insights move understanding of the managerial challenge of building effective networks beyond static structural contingency models of optimal network forms to highlight the processes and capabilities of dynamic relationship building and network development. In so doing, this paper highlights the interrelationship between search and redundancy and the scope for strategic action alongside path dependence and structural influences on network processes.

A quick guide to surviving redundancy:your essential legal guide

What do you do if your boss calls you in to talk about job cuts? What are your rights? What are his or her rights? Do you know the procedures that should be followed? If redundancy looms, or you just want to be prepared for the worst,you need to know where you stand.Author Kathy Daniels is well placed to help. She writes and lectures extensively on human resources and employee rights, and as a member of the Employment Tribunal she regularly comes face-to-face with redundancy claims. In this easy-to-understand guide she answers all the important questions on redundancy and its aftermath, including: How are staff selected for redundancy? What is voluntary redundancy? Are full-time,part-time and agency staff treated differently? What is the consultation process bosses must adhere to? How much redundancy pay can you expect? How do you take a claim to the Employment Tribunal? As well as covering all the legal dos and don'ts, helpful guidance is provided on: Budgets and personal finances after redundancy Benefits you may be able to claim Coping with stress and strain Finding a new job or changing career The Quick Guide to Surviving Redundancy is full of real-life case studies and top tips on your employment rights. It also includes template letters for a range of redundancy situations.

Second life battery energy storage systems:converter topology and redundancy selection

Battery energy storage systems have traditionally been manufactured using new batteries with a good reliability. The high cost of such a system has led to investigations of using second life transportation batteries to provide an alternative energy storage capability. However, the reliability and performance of these batteries is unclear and multi-modular power electronics with redundancy have been suggested as a means of helping with this issue. This paper reviews work already undertaken on battery failure rate to suggest suitable figures for use in reliability calculations. The paper then uses reliability analysis and a numerical example to investigate six different multi-modular topologies and suggests how the number of series battery strings and power electronic module redundancy should be determined for the lowest hardware cost using a numerical example. The results reveal that the cascaded dc-side modular with single inverter is the lowest cost solution for a range of battery failure rates.

Self-organising zooms for decentralised redundancy management in visual sensor networks

When visual sensor networks are composed of cameras which can adjust the zoom factor of their own lens, one must determine the optimal zoom levels for the cameras, for a given task. This gives rise to an important trade-off between the overlap of the different cameras’ fields of view, providing redundancy, and image quality. In an object tracking task, having multiple cameras observe the same area allows for quicker recovery, when a camera fails. In contrast having narrow zooms allow for a higher pixel count on regions of interest, leading to increased tracking confidence. In this paper we propose an approach for the self-organisation of redundancy in a distributed visual sensor network, based on decentralised multi-objective online learning using only local information to approximate the global state. We explore the impact of different zoom levels on these trade-offs, when tasking omnidirectional cameras, having perfect 360-degree view, with keeping track of a varying number of moving objects. We further show how employing decentralised reinforcement learning enables zoom configurations to be achieved dynamically at runtime according to an operator’s preference for maximising either the proportion of objects tracked, confidence associated with tracking, or redundancy in expectation of camera failure. We show that explicitly taking account of the level of overlap, even based only on local knowledge, improves resilience when cameras fail. Our results illustrate the trade-off between maintaining high confidence and object coverage, and maintaining redundancy, in anticipation of future failure. Our approach provides a fully tunable decentralised method for the self-organisation of redundancy in a changing environment, according to an operator’s preferences.

Introducing a pilot data collection model for real-time evaluation of data redundancy

In order to reduce serious health incidents, individuals with high risks need to be identified as early as possible so that effective intervention and preventive care can be provided. This requires regular and efficient assessments of risk within communities that are the first point of contacts for individuals. Clinical Decision Support Systems CDSSs have been developed to help with the task of risk assessment, however such systems and their underpinning classification models are tailored towards those with clinical expertise. Communities where regular risk assessments are required lack such expertise. This paper presents the continuation of GRiST research team efforts to disseminate clinical expertise to communities. Based on our earlier published findings, this paper introduces the framework and skeleton for a data collection and risk classification model that evaluates data redundancy in real-time, detects the risk-informative data and guides the risk assessors towards collecting those data. By doing so, it enables non-experts within the communities to conduct reliable Mental Health risk triage.

+Psychometric evaluation of the MacDQoL individualised measure of the impact of macular degeneration on quality of life

Background: The MacDQoL is an individualised measure of the impact of macular degeneration (MD) on quality of life (QoL). There is preliminary evidence of its psychometric properties and sensitivity to severity of MD. The aim of this study was to carry out further psychometric evaluation with a larger sample and investigate the measure's sensitivity to MD severity. Methods: Patients with MD (n = 156: 99 women, 57 men, mean age 79 ± 13 years), recruited from eye clinics (one NHS, one private) completed the MacDQoL by telephone interview and later underwent a clinic vision assessment including near and distance visual acuity (VA), comfortable near VA, contrast sensitivity, colour recognition, recovery from glare and presence or absence of distortion or scotoma in the central 10° of the visual field. Results: The completion rate for the MacDQoL items was 99.8%. Of the 26 items, three were dropped from the measure due to redundancy. A fourth was retained in the questionnaire but excluded when computing the scale score. Principal components analysis and Cronbach's alpha (0.944) supported combining the remaining 22 items in a single scale. Lower MacDQoL scores, indicating more negative impact of MD on QoL, were associated with poorer distance VA (better eye r = -0.431 p < 0.001; worse eye r = -0.350 p < 0.001; binocular vision r = -0.419 p < 0.001) and near VA (better eye r -0.326 p < 0.001; worse eye r = -0.226 p < 0.001; binocular vision r = -0.326 p < 0.001). Poorer MacDQoL scores were associated with poorer contrast sensitivity (better eye r = 0.392 p < 0.001; binocular vision r = 0.423 p < 0.001), poorer colour recognition (r = 0.417 p < 0.001) and poorer comfortable near VA (r = -0.283, p < 0.001). The MacDQoL differentiated between those with and without binocular scotoma (U = 1244 p < 0.001). Conclusion: The MacDQoL 22-item scale has excellent internal consistency reliability and a single-factor structure. The measure is acceptable to respondents and the generic QoL item, MD-specific QoL item and average weighted impact score are related to several measures of vision. The MacDQoL demonstrates that MD has considerable negative impact on many aspects of QoL, particularly independence, leisure activities, dealing with personal affairs and mobility. The measure may be valuable for use in clinical trials and routine clinical care. © 2005 Mitchell et al; licensee BioMed Central Ltd.

The impact of organizational change on the perceptions of UK managers change

Redundancy, delayering, downsizing, and various other forms of organizational change have become increasingly prevalent. This article focuses on the impact of different forms of organizational change on managers' perceptions of the organizations they work within and the comparison between changes that involve redundancy and/or delayering and those that do not involve such changes. The literature has many accounts of the negative effects associated with redundancy and delayering, but are these effects unique to these types of change or are they a consequence of negative experiences of a range of organizational changes? Hypotheses were tested to assess, first, whether there are differences between different levels of management, notably between directors and nondirectors in the way they perceive organizational change, second, to assess how change has affected managers' perceptions of their organizations and their working lives, and third, to explore if different forms of change are associated with differences in managers' perceptions of their organizations “as a place to work”. Hypotheses were tested with data from a cross-sectional survey with 830 managers from the UK. Organizational changes include cost reduction and culture change programmes, delayering, mergers/demergers, outsourcing, redundancy programmes, and contract/ temporary workers. The analyses reported here indicate clearly that specific forms of change are associated with managers' reports of their experiences at work; some forms of change (notably redundancy and delayering) seem to have particularly damaging implications for managers' experiences in the workplace. The analyses also show that there is a difference in the way directors and nondirectors perceive the changes. Finally, the article considers strategies for ameliorating the effects of change including the role of HR.

AC self-bearing motors with a bridge configured winding

Magnetic levitation bearings eliminate friction, wear and the need for lubrication and so have high speed capability and potential for vibration control. One noteworthy development in the realm of magnetic levitation is the self-bearing or bearingless motor - an electromagnetic machine that supports its own rotor by way of magnetic forces generated by windings on its stator. Accordingly, various winding schemes have been proposed to accomplish the task of force production. This thesis proposes a novel concept of winding based on a bridge connection for polyphase self-bearing rotating electrical machines with the following advantages: • the connection uses a single set of windings and thus power loss is relatively low when compared with self-bearing motors with conventional dual set of windings. • the motor and levitation controls are segregated such that only one motor inverter is required for the normal torque production and levitation forces are produced by using auxiliary power supplies of relatively low current and voltage rating. The usual way of controlling the motor is retained. • there are many variant winding schemes to meet special needs. • independent power supplies for levitation control offer redundancy for fault tolerance. This thesis dwells specifically on the conceptual design and implementation of the proposed single set of windings scheme. The new connection has been verified to exhibit characteristics of a self-bearing motor via coupled-field finite element analysis: results are crosschecked analytically. Power loss and other aspects such as cost, design implementation are compared to support the newly proposed connection as a potential alternative to present designs.

Spatial and temporal dependencies of cross-orientation suppression in human vision.

A well-known property of orientation-tuned neurons in the visual cortex is that they are suppressed by the superposition of an orthogonal mask. This phenomenon has been explained in terms of physiological constraints (synaptic depression), engineering solutions for components with poor dynamic range (contrast normalization) and fundamental coding strategies for natural images (redundancy reduction). A common but often tacit assumption is that the suppressive process is equally potent at different spatial and temporal scales of analysis. To determine whether it is so, we measured psychophysical cross-orientation masking (XOM) functions for flickering horizontal Gabor stimuli over wide ranges of spatio-temporal frequency and contrast. We found that orthogonal masks raised contrast detection thresholds substantially at low spatial frequencies and high temporal frequencies (high speeds), and that small and unexpected levels of facilitation were evident elsewhere. The data were well fit by a functional model of contrast gain control, where (i) the weight of suppression increased with the ratio of temporal to spatial frequency and (ii) the weight of facilitatory modulation was the same for all conditions, but outcompeted by suppression at higher contrasts. These results (i) provide new constraints for models of primary visual cortex, (ii) associate XOM and facilitation with the transient magno- and sustained parvostreams, respectively, and (iii) reconcile earlier conflicting psychophysical reports on XOM.

Evolutionary neural networks : models and applications

The scaling problems which afflict attempts to optimise neural networks (NNs) with genetic algorithms (GAs) are disclosed. A novel GA-NN hybrid is introduced, based on the bumptree, a little-used connectionist model. As well as being computationally efficient, the bumptree is shown to be more amenable to genetic coding lthan other NN models. A hierarchical genetic coding scheme is developed for the bumptree and shown to have low redundancy, as well as being complete and closed with respect to the search space. When applied to optimising bumptree architectures for classification problems the GA discovers bumptrees which significantly out-perform those constructed using a standard algorithm. The fields of artificial life, control and robotics are identified as likely application areas for the evolutionary optimisation of NNs. An artificial life case-study is presented and discussed. Experiments are reported which show that the GA-bumptree is able to learn simulated pole balancing and car parking tasks using only limited environmental feedback. A simple modification of the fitness function allows the GA-bumptree to learn mappings which are multi-modal, such as robot arm inverse kinematics. The dynamics of the 'geographic speciation' selection model used by the GA-bumptree are investigated empirically and the convergence profile is introduced as an analytical tool. The relationships between the rate of genetic convergence and the phenomena of speciation, genetic drift and punctuated equilibrium arc discussed. The importance of genetic linkage to GA design is discussed and two new recombination operators arc introduced. The first, linkage mapped crossover (LMX) is shown to be a generalisation of existing crossover operators. LMX provides a new framework for incorporating prior knowledge into GAs.Its adaptive form, ALMX, is shown to be able to infer linkage relationships automatically during genetic search.

Development of the MAX randomisation technique

During the last decade the use of randomised gene libraries has had an enormous impact in the field of protein engineering. Such libraries comprise many variations of a single gene in which codon replacements are used to substitute key residues of the encoded protein. The expression of such libraries generates a library of randomised proteins which can subsequently be screened for desired or novel activities. Randomisation in this fashion has predominantly been achieved by the inclusion of the codons NNN or NNGCor T, in which N represents any of the four bases A,C,G, or T. The use of thesis codons however, necessities the cloning of redundant codons at each position of randomisation, in addition to those required to encode the twenty possible amino acid substitutions. As degenerate codons must be included at each position of randomisation, this results in a progressive loss of randomisation efficiency as the number of randomised positions is increased. The ratio of genes to proteins in these libraries rises exponentially with each position of randomisation, creating large gene libraries, which generate protein libraries of limited diversity upon expression. In addition to these problems of library size, the cloning of redundant codons also results in the generation of protein libraries in which substituted amino acids are unevenly represented. As several of the randomised codons may encode the same amino acid, for example serine which is encoded six time using the codon NNN, an inherent bias may be introduced into the resulting protein library during the randomisation procedure. The work outlined here describes the development of a novel randomisation technique aimed at a eliminating codon redundancy from randomised gene libraries, thus addressing the problems of library size and bias, associated with the cloning of redundant codons.

Minority enterprise in the clothing industry: an analysis of Asian jeans manufacturers in Birmingham

This thesis discusses and assesses the resources available to Asian entrepreneurs in the West Midlands' clothing industry and how they are used by these small businessmen in order to address opportunities in the market economy within the constraints imposed. The fashion industry is volatile and is dependent upon flexible firms which can respond quickly to shortrun production schedules. Small firms are best able to respond to this market environment. Production of jeans presents an interesting departure from the mainstream fashion industry. It is traditionally gared towards longrun production schedules where multinational enterprises have artificially diversified the market, promoting the 'right' brand name and have established control of the upper end of the market, whilst imports from Newly Developing Countries have catered for cheap copies at the lower end of the market. In recent years, a fashion element to jeans has emerged, thus opening a market gap for U.K. manufacturers to respond in the same way as for other fashion articles. A large immigrant population, previously serving the now declining factories and foundries of the West Midlands but, through redundancy, no longer a part of this employment sector, has ~5ponded to economic constraints and market opportunities by drawing on ethnic network resources for competitive access to labour, finance and contacts, to attack the emergent market gap. Two models of these Asian entrepreneurs are developed. One being somecne who has professionally and actively tackled the market gap and become established. These entrepreneurs are usually educated and have personal experience in business and were amongst the first to perceive opportunities to enter the industry, actively utilising their ethnicity as a resource upon which to draw for favorable access to cheap, flexible labour and capital. The second model is composed of later entrants to jeans manufacturing. They have less formal education and experience and have been pushed into self-employment by constraints of unemployment. Their ethnicity is passively used as a resource. They are more likely confined to the marginal activity of 'cut make and trim' and have little opportunity to increase profit margins, become estalished or expand.

Watermarking biomedical time series data

This thesis addresses the problem of information hiding in low dimensional digital data focussing on issues of privacy and security in Electronic Patient Health Records (EPHRs). The thesis proposes a new security protocol based on data hiding techniques for EPHRs. This thesis contends that embedding of sensitive patient information inside the EPHR is the most appropriate solution currently available to resolve the issues of security in EPHRs. Watermarking techniques are applied to one-dimensional time series data such as the electroencephalogram (EEG) to show that they add a level of confidence (in terms of privacy and security) in an individual’s diverse bio-profile (the digital fingerprint of an individual’s medical history), ensure belief that the data being analysed does indeed belong to the correct person, and also that it is not being accessed by unauthorised personnel. Embedding information inside single channel biomedical time series data is more difficult than the standard application for images due to the reduced redundancy. A data hiding approach which has an in built capability to protect against illegal data snooping is developed. The capability of this secure method is enhanced by embedding not just a single message but multiple messages into an example one-dimensional EEG signal. Embedding multiple messages of similar characteristics, for example identities of clinicians accessing the medical record helps in creating a log of access while embedding multiple messages of dissimilar characteristics into an EPHR enhances confidence in the use of the EPHR. The novel method of embedding multiple messages of both similar and dissimilar characteristics into a single channel EEG demonstrated in this thesis shows how this embedding of data boosts the implementation and use of the EPHR securely.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.