Improved production of industrially relevant recombinant proteins: application of multi-factorial design of experiments and scalable process modelling

The work described in this thesis focuses on the use of a design-of-experiments approach in a multi-well mini-bioreactor to enable the rapid establishments of high yielding production phase conditions in yeast, which is an increasingly popular host system in both academic and industrial laboratories. Using green fluorescent protein secreted from the yeast, Pichia pastoris, a scalable predictive model of protein yield per cell was derived from 13 sets of conditions each with three factors (temperature, pH and dissolved oxygen) at 3 levels and was directly transferable to a 7 L bioreactor. This was in clear contrast to the situation in shake flasks, where the process parameters cannot be tightly controlled. By further optimisating both the accumulation of cell density in batch and improving the fed-batch induction regime, additional yield improvement was found to be additive to the per cell yield of the model. A separate study also demonstrated that improving biomass improved product yield in a second yeast species, Saccharomyces cerevisiae. Investigations of cell wall hydrophobicity in high cell density P. pastoris cultures indicated that cell wall hydrophobin (protein) compositional changes with growth phase becoming more hydrophobic in log growth than in lag or stationary phases. This is possibly due to an increased occurrence of proteins associated with cell division. Finally, the modelling approach was validated in mammalian cells, showing its flexibility and robustness. In summary, the strategy presented in this thesis has the benefit of reducing process development time in recombinant protein production, directly from bench to bioreactor.

Computer simulation for tube-making by the cold roll-forming process

The conventional design of forming rolls depends heavily on the individual skill of roll designers which is based on intuition and knowledge gained from previous work. Roll design is normally a trial an error procedure, however with the progress of computer technology, CAD/CAM systems for the cold roll-forming industry have been developed. Generally, however, these CAD systems can only provide a flower pattern based on the knowledge obtained from previously successful flower patterns. In the production of ERW (Electric Resistance Welded) tube and pipe, the need for a theoretical simulation of the roll-forming process, which can not only predict the occurrence of the edge buckling but also obtain the optimum forming condition, has been recognised. A new simulation system named "CADFORM" has been devised that can carry out the consistent forming simulation for this tube-making process. The CADFORM system applied an elastic-plastic stress-strain analysis and evaluate edge buckling by using a simplified model of the forming process. The results can also be visualised graphically. The calculated longitudinal strain is obtained by considering the deformation of lateral elements and takes into account the reduction in strains due to the fin-pass roll. These calculated strains correspond quite well with the experimental results. Using the calculated strains, the stresses in the strip can be estimated. The addition of the fin-pass roll reduction significantly reduces the longitudinal compressive stress and therefore effectively suppresses edge buckling. If the calculated longitudinal stress is controlled, by altering the forming flower pattern so it does not exceed the buckling stress within the material, then the occurrence of edge buckling can be avoided. CADFORM predicts the occurrence of edge buckling of the strip in tube-making and uses this information to suggest an appropriate flower pattern and forming conditions which will suppress the occurrence of the edge buckling.

“I didn’t mean to steal someone else’s words!”:a forensic linguistic approach to detecting intentional plagiarism

The concept of plagiarism is not uncommonly associated with the concept of intellectual property, both for historical and legal reasons: the approach to the ownership of ‘moral’, nonmaterial goods has evolved to the right to individual property, and consequently a need was raised to establish a legal framework to cope with the infringement of those rights. The solution to plagiarism therefore falls most often under two categories: ethical and legal. On the ethical side, education and intercultural studies have addressed plagiarism critically, not only as a means to improve academic ethics policies (PlagiarismAdvice.org, 2008), but mainly to demonstrate that if anything the concept of plagiarism is far from being universal (Howard & Robillard, 2008). Even if differently, Howard (1995) and Scollon (1994, 1995) argued, and Angèlil-Carter (2000) and Pecorari (2008) later emphasised that the concept of plagiarism cannot be studied on the grounds that one definition is clearly understandable by everyone. Scollon (1994, 1995), for example, claimed that authorship attribution is particularly a problem in non-native writing in English, and so did Pecorari (2008) in her comprehensive analysis of academic plagiarism. If among higher education students plagiarism is often a problem of literacy, with prior, conflicting social discourses that may interfere with academic discourse, as Angèlil-Carter (2000) demonstrates, we then have to aver that a distinction should be made between intentional and inadvertent plagiarism: plagiarism should be prosecuted when intentional, but if it is part of the learning process and results from the plagiarist’s unfamiliarity with the text or topic it should be considered ‘positive plagiarism’ (Howard, 1995: 796) and hence not an offense. Determining the intention behind the instances of plagiarism therefore determines the nature of the disciplinary action adopted. Unfortunately, in order to demonstrate the intention to deceive and charge students with accusations of plagiarism, teachers necessarily have to position themselves as ‘plagiarism police’, although it has been argued otherwise (Robillard, 2008). Practice demonstrates that in their daily activities teachers will find themselves being required a command of investigative skills and tools that they most often lack. We thus claim that the ‘intention to deceive’ cannot inevitably be dissociated from plagiarism as a legal issue, even if Garner (2009) asserts that generally plagiarism is immoral but not illegal, and Goldstein (2003) makes the same severance. However, these claims, and the claim that only cases of copyright infringement tend to go to court, have recently been challenged, mainly by forensic linguists, who have been actively involved in cases of plagiarism. Turell (2008), for instance, demonstrated that plagiarism is often connoted with an illegal appropriation of ideas. Previously, she (Turell, 2004) had demonstrated by comparison of four translations of Shakespeare’s Julius Caesar to Spanish that the use of linguistic evidence is able to demonstrate instances of plagiarism. This challenge is also reinforced by practice in international organisations, such as the IEEE, to whom plagiarism potentially has ‘severe ethical and legal consequences’ (IEEE, 2006: 57). What plagiarism definitions used by publishers and organisations have in common – and which the academia usually lacks – is their focus on the legal nature. We speculate that this is due to the relation they intentionally establish with copyright laws, whereas in education the focus tends to shift from the legal to the ethical aspects. However, the number of plagiarism cases taken to court is very small, and jurisprudence is still being developed on the topic. In countries within the Civil Law tradition, Turell (2008) claims, (forensic) linguists are seldom called upon as expert witnesses in cases of plagiarism, either because plagiarists are rarely taken to court or because there is little tradition of accepting linguistic evidence. In spite of the investigative and evidential potential of forensic linguistics to demonstrate the plagiarist’s intention or otherwise, this potential is restricted by the ability to identify a text as being suspect of plagiarism. In an era with such a massive textual production, ‘policing’ plagiarism thus becomes an extraordinarily difficult task without the assistance of plagiarism detection systems. Although plagiarism detection has attracted the attention of computer engineers and software developers for years, a lot of research is still needed. Given the investigative nature of academic plagiarism, plagiarism detection has of necessity to consider not only concepts of education and computational linguistics, but also forensic linguistics. Especially, if intended to counter claims of being a ‘simplistic response’ (Robillard & Howard, 2008). In this paper, we use a corpus of essays written by university students who were accused of plagiarism, to demonstrate that a forensic linguistic analysis of improper paraphrasing in suspect texts has the potential to identify and provide evidence of intention. A linguistic analysis of the corpus texts shows that the plagiarist acts on the paradigmatic axis to replace relevant lexical items with a related word from the same semantic field, i.e. a synonym, a subordinate, a superordinate, etc. In other words, relevant lexical items were replaced with related, but not identical, ones. Additionally, the analysis demonstrates that the word order is often changed intentionally to disguise the borrowing. On the other hand, the linguistic analysis of linking and explanatory verbs (i.e. referencing verbs) and prepositions shows that these have the potential to discriminate instances of ‘patchwriting’ and instances of plagiarism. This research demonstrates that the referencing verbs are borrowed from the original in an attempt to construct the new text cohesively when the plagiarism is inadvertent, and that the plagiarist has made an effort to prevent the reader from identifying the text as plagiarism, when it is intentional. In some of these cases, the referencing elements prove being able to identify direct quotations and thus ‘betray’ and denounce plagiarism. Finally, we demonstrate that a forensic linguistic analysis of these verbs is critical to allow detection software to identify them as proper paraphrasing and not – mistakenly and simplistically – as plagiarism.

Non-English-speaking defendants in the magistrates court:a comparative study of face-to-face and prison video link interpreter-mediated hearings in England

This study compares interpreter-mediated face-to-face Magistrates Court hearings with those conducted through prison video link in which interpreters are located in court and non- English-speaking defendants in prison. It seeks to examine the impact that the presence of video link has on court actors in terms of interaction and behaviour. The data comprises 11 audio-recordings of face-to-face hearings, 10 recordings of prison video link hearings, semistructured interviews with 27 court actors, and ethnographic observation of hearings as viewed by defendants in Wormwood Scrubs prison in London. The over-arching theme is the pervasive influence of the ecology of the courtroom upon all court actors in interpretermediated hearings and thus on the communication process. Close analysis of the court transcripts shows that their relative proximity to one another can be a determinant of status, interpreting role, mode and volume. The very few legal protocols which apply to interpretermediated cases (acknowledging and ratifying the interpreter, for example), are often forgotten or dispensed with. Court interpreters lack proper training in the specific challenges of court interpreting, whether they are co-present with the defendant or not. Other court actors often misunderstand the interpreter’s role. This has probably come about because courts have adjusted their perceptions of what they think interpreters are supposed to do based on their own experiences of working with them, and have gradually come to accept poor practice (the inability to perform simultaneous interpreting, for example) as the norm. In video link courts, mismatches of sound and image due to court clerks’ failure to adequately track current speakers, poor image and sound quality and the fact that non-English-speaking defendants in pre-and post-court consultations can see and hear interpreters but not their defence advocates are just some of the additional layers of disadvantage and confusion already suffered by non- English-speaking defendants. These factors make it less likely that justice will be done.

Evaluation of options for energy recovery from municipal solid waste in India using the hierarchical analytical network process

In this paper a Hierarchical Analytical Network Process (HANP) model is demonstrated for evaluating alternative technologies for generating electricity from MSW in India. The technological alternatives and evaluation criteria for the HANP study are characterised by reviewing the literature and consulting experts in the field of waste management. Technologies reviewed in the context of India include landfill, anaerobic digestion, incineration, pelletisation and gasification. To investigate the sensitivity of the result, we examine variations in expert opinions and carry out an Analytical Hierarchy Process (AHP) analysis for comparison. We find that anaerobic digestion is the preferred technology for generating electricity from MSW in India. Gasification is indicated as the preferred technology in an AHP model due to the exclusion of criteria dependencies and in an HANP analysis when placing a high priority on net output and retention time. We conclude that HANP successfully provides a structured framework for recommending which technologies to pursue in India, and the adoption of such tools is critical at a time when key investments in infrastructure are being made. Therefore the presented methodology is thought to have a wider potential for investors, policy makers, researchers and plant developers in India and elsewhere. © 2013 Elsevier Ltd. All rights reserved.

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.

The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Process improvement and quality management systems in the financial services industry:the case for the OPEX quality management system and framework

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

The opportunity recognition process:the mechanisms by which entrepreneurial opportunities are recognised and the role played by social networks in this process

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

The aquisition process in mutinational food companies in Europe

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

Mean field methods for Gaussian process classifiers

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

Land use change and the planning process in historic town centres

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

The investigation into the mechanics and inducement of residual torsion within the beadwire production process

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

The effects of the punching process upon the magnetic properties of steel laminations

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

Managing project risk using combined analytic hierarchy process and risk map

The main purpose of the study is to develop an integrated framework for managing project risks by analyzing risk across project, work package and activity levels, and developing responses. Design/methodology/approach: The study first reviews the literature of various contemporary risk management frameworks in order to identify gaps in project risk management knowledge. Then it develops a conceptual risk management framework using combined analytic hierarchy process (AHP) and risk map for managing project risks. The proposed framework has then been applied to a 1500 km oil pipeline construction project in India in order to demonstrate its effectiveness. The concerned project stakeholders were involved through focus group discussions for applying the proposed risk management framework in the project under study. Findings: The combined AHP and risk map approach is very effective to manage project risks across project, work package and activity levels. The risk factors in project level are caused because of external forces such as business environment (e.g. customers, competitors, technological development, politics, socioeconomic environment). The risk factors in work package and activity levels are operational in nature and created due to internal causes such as lack of material and labor productivity, implementation issues, team ineffectiveness, etc. Practical implications: The suggested model can be applied to any complex project and helps manage risk throughout the project life cycle. Originality/value: Both business and operational risks constitute project risks. In one hand, the conventional project risk management frameworks emphasize on managing business risks and often ignore operational risks. On the other hand, the studies that deal with operational risk often do not link them with business risks. However, they need to be addressed in an integrated way as there are a few risks that affect only the specific level. Hence, this study bridges the gaps. © 2010 Elsevier B.V. All rights reserved.