• Gandhi as a political organiser. An analysis of Iocal and national campaigns in India 1915-1922.

      Young, Nigel; Overy, Bob (University of BradfordPostgraduate School of Studies in Peace Studies., 2009-11-09)
      By examining Gandhi as a political organiser it may be possible to bridge the gap between two interpretations of his importance -- one which focuses on his propagation of nonviolence "as a way of life", the other- which treats him as a pioneer in the use of nonviolence "as a conflict technique. " Gandhi named his philosophy and his method of action, "satyagraha". Between 1915 and 1922 he emerged as the organiser of local satyagraha campaigns in Bihar and Gujarat. He moved quickly, however, to leadership of further struggles at a national level, in particular the hoxlatt Satyagraha in 1919 and Noncooperation eighteen months later. The thesis explores, through a series of case studies, how Gandhi developed his methods as he moved over a period of about five years from local to national scale. At the national level, Gandhi failed to take India by storm as he had hoped through organisations founded by himself to propagate his principles like the Satyagraha Sabha and the Swadeshi Sabha. He therefore forged alliances with political figures from other perspectives within the Khilafat movement and the Indian Rational Congress who nonetheless were prepared to follow his direction. A principal means which Gandhi developed for generating solidarity between the nation's educated "classes" and the "masses" and for mobilising people short of civil disobedience, was the promotion of campaigns of constructive work. This is particularly clear in his planning and leadership of the Noncooperation movement. Presentation of nonviolent action in the West, by overstressing the "conflict" aspect of satyagraha and neglecting the "constructive", has been one-sided. The importance in Gandhi's method as an organiser of a concept of constructive programme and its application in practice suggests that advocates of nonviolent action as a technique should look more closely at the balance between the two aspects in his approach. The thesis concludes with a review'of the rules and stages in Gandhi's satyagraha campaigns which have been proposed in the work of Joan Bondurant.
    • Gas assisted injection moulding: Experiment and simulation. Industrial machine experimental studies of the effect of process variables on gas bubble formation, and with simulation based upon a pseudo-concentration method.

      Olley, Peter; Coates, Philip D.; Mulvaney-Johnson, Leigh (University of BradfordDepartment of Mechanical and Medical Engineering, 2011-08-01)
      The gas assisted injection moulding process is an important extension to conventional injection moulding. Gas assist can be applied in a number of ways, but here the penetration of a gas bubble through the polymer melt is of interest. A 3D fi nite element implementation of a pseudo concentration method is employed to simulate the primary penetration of the gas bubble. The wall thickness prediction is an important result since the extent of bubble penetration is sensitive to the remaining melt fraction. A number of methods for experimental measurement are developed to measure characteristics of the gas assisted injection moulding process dynamics and product. Key process variables, on an industrial gas-assist machine, were measured and analysed, leading to an empirical model for wall thickness prediction. Gas delay time and injection velocity are shown to be most influential in controlling residual wall thickness. Simulation results are evaluated against the empirical model. The trends observed, for simulation and experiment, in wall thickness after changes in process variable settings are found to agree qualitatively. The wall thickness prediction is found to be within 10% of the experimentally obtained measurements.
    • Gas purification by short cycle pressure swing adsorption. Experimental and theoretical studies of a fixed bed adsorption process for the separation of carbon dioxide from air at ambient temperatures using molecular sieve 5A and activated charcoal adsorbents.

      Granville, W.H.; Ellis, David I. (University of BradfordPostgraduate School of Studies in Chemical Engineering, 2010-06-30)
      An experimental pressure swing adsorption unit has been constructed and used to investigate the separation of carbon dioxide from carbon dioxide enriched air using both an activated carbon and a type 5A molecular sieve adsorbent. Continuous, cyclic operation was achievedusing a pair of fixed bed adsorbers. At any one time the feed gas entered one bed at a high pressure and part of the purified gas was returned to the other bed at a reduced pressure to provide countercurrent regeneration of the adsorbent. The beds of adsorbent used were each nominally 0.165m diameter and Im. deep. Separations were carried out at approximately ambient temperature using air flow rates in the range 0.15 to 0.95 kg/m2s and inlet carbon dioxide concentrations'in the range 0.1 to 1.5% v/v. Adsorption pressures of 2 to 6.4 bar were examined, the desorption pressure being maintained throughout at essentially 1.0 bar. The period time was varied from 30 to 900 seconds and the revert ratio (i. e. the ratio of the product gas returned for desorption to the total feed rate to the unit) was varied from 0 to 1.0. The carbon dioxide separation efficiency was found to increase markedly as the adsorption pressure and the revert ratio were increased whereas it was relatively insensitive to variations in feed rate and, more particularly, feed concentration. The performance of the molecular sieve adsorbent was found to be very sensitive to the presence of moisture in the feed gas. In contrast the carbon dioxide efficiencies observed with Lhe activated carbon were unaffected by the presence of small amounts (circa 100 ppm) of moisture in the feed. A theoretical model has been proposed for predicting the performance of pressure swing adsorption systems of the type investigated and approximate analytical equations and more precise numerical techniques have been established to represent its solution. The approximate analytical solutions were found to give close agreement with the more precise methods examined under conditions corresponding to low values of a dimensionless period time parameter. The proposed theoretical model incorporates an effective irean mass transfer coefficient to represent the diffusion process within the adsorbent particles. Methods for estimation of the value of this coefficient based on the limiting conditions of a periodic constant surface flux or a periodic constant surface concentration are presented. The experimental performance data were analysed in terms of the proposed analytical solution to give values of the apparent solid phase mass transfer coefficient for comparison with those predicted theoretically. In general the apparent experimental values were consistently less than the predicted values. In addition the relationship between the experimental and predicted coefficients was found to be dependent on both the nature of the adsorbent and a parameter formed by the product of the revert ratio and the adsorption to desorption pressure ratio. Empirical correlating equations which incorporate this dependence are presented.
    • Gate-Turn-Off thyristor commutation of DC machines : The development of a rotating DC machine with static commutation of armature coil current using Gate-Turn-Off thyristor devices.

      Gray, Clifford B.; Karim, A.H.M. (University of BradfordPostgraduate School of Studies in Electrical and Electronic Engineering., 2009-09-01)
      The thesis Is concerned with the development of a separately excited DC machine In which gate turn-off thyristor devices with their associated firing and protective circuits are used to provide the static commutation of armature coil current. The developed machine has Its armature winding with 24 tapping points located on the stator and Interconnected In "Lop" configuration. The Initiation of the conduction periods of armature switching devices Is defined by a digital control logic circuit. In conjunction with an Incremental rotary encoder which provides the necessary feedback Information relating to shaft speed and shaft angular position. This Is arranged such that, under normal running conditions of the machine, the axis of the radial field of the armature winding maintains the normal space-quadrature relationship with that of the main field winding, giving the optimal torque angle of 000. Provision Is made, however, within the digital control circuit for controlled departure of the armature switch tapping points from the quadrature axis positions, and the effect of this, In Improving commutation Is Investigated. The effect of Interpoles Is also explored. On the basis of the analysis carried out, a proposal Is made for the future development of the machine employing a reduced number of armature switching devices without the need for Interpole windings.
    • Gender differences in mathematics performance. Analysis of attainment and attitudes in mathematics of girls and boys; detailed appraisal of theories and pressures that influence girls' underachievement and underparticipation in the subject.

      Murray, Russell; Bradberry, John S. (University of BradfordDepartment of Social and Economic Studies, 2010-06-18)
      Statistics show that boys perform better in mathematics tests than girls. In order to make a refined assessment of the magnitude of gender differences in mathematics performance, a study was made of one thousand 16+ mathematics scripts to find the precise topics on which girls and boys differ significantly in performance. These concepts were found to be concerned with scale or ratio, spatial problems, space-time relationships and probability questions. Differences were found in performance between girls and boys at each ten-percentile level through the ability range. A longitudinal study also revealed differences in mathematics 'performance through the years of secondary education. There is no convincing evidence that the discrepancy can be accounted for by innate or genetic reasons. Intervention programmes have been found to improve the performance of girls in the weak areas of spatial awareness, proportionality and problem solving. In addition, a study was made of gender attitudes towards mathematics. Ten secondary schools were surveyed and the results revealed a marked decrease in the attitudes of third and fourth form girls. During these difficult adolescent years girls and boys are susceptible to strong internal and external pressures. Corresponding differences were also found across the ability range. These social pressures are concerned with teacher influence, social interaction, type of grouping, sex stereotyping, choices, teaching materials and careers advice.
    • A Gendered Analysis of Formal Vocational Education, Skills Development, and Self-employment in Accra, Ghana: Exploring enterprise development and outcomes of women’s self-employment in the feminized trades

      Kusi-Mensah, Rita
      This research is an exploration of the extent to which formal vocational education in the domestic trades (catering and dressmaking) for women in Ghana leads to sustainable self-employment in the urban informal sector (UIS) in Accra. The research adopts a qualitative methodological approach using interpretive analysis to gain an in-depth understanding of the primary data collected. A case study approach is adopted to articulate emerging themes in a manner that is comprehensive and intelligible. Two conceptual frameworks are employed: firstly, the research builds on the work of McCauley et al (1995), to ascertain the developmental dimensions of VE catering job roles that provide graduates with the capabilities and opportunities needed for sustainable self-employment. Secondly, the concept of Gender Role Socialization is drawn on to ascertain the gender-specific factors that influence women’s engagement in VE and constrain women’s MSE growth. The research identified three key factors which affect VE graduates gaining employment and prospects for sustainable self-employment. They are: 1) The VE programme pursued and the presence or absence of a transformative environment of skill utilization. 2) The attainment of post-graduation specialist training or advanced certification which provide VE graduates with enhanced prospects for employment. 3) Post-graduation quality workplace development experience (QWDE). Gender-specific factors include traditional Ghanaian expectations of “womanhood”, and the streaming of women towards occupational paths that maintain their gendered role obligations within the household and family. These include ‘domestic provisioning’; male prerogative as principal decision-maker in the household; weak inheritance rights and access to property.
    • Gendered moral rationalities in combining motherhood and employment. A case study of Sri Lanka

      Duncan, Simon; Beckett-Wrighton, Clare; Kodagoda, Delapolage T.D. (University of BradfordDepartment of Social Sciences and Humanities, 2012-02-13)
      Over the last three decades, the impact of dramatic change in the social, religious, political and economic environment has led to a rapid expansion in the number of women entering the paid labour force in Sri Lanka as elsewhere. However, their identities and workload continue to be defined around caring work, especially for children. Not surprisingly, employed mothers endeavour to balance these two central spheres of their life, family and work. This research focuses on the contradictions of mothers¿ work-life balance. It does so through an analysis of how successfully (or unsuccessfully) professional and managerial mothers in Sri Lanka combine motherhood with paid work, and how they understand this in terms of gendered identities and social norms. This example also allows an evaluation of western derived theories about mothers¿ decision making in the context of a developing, Asian country. Grounded theory was used to examine mothers¿ narratives about life in the family and at work, drawn from in-depth qualitative interviews, along with data from some representative secondary sources, in order to explore these questions. This thesis demonstrates that working women¿s mothering leads to the formation of a gendered identity which varies according to different socio-cultural and religious opportunities and constraints. Using the Bourdieu approach the research suggests how everyday life operates in terms of habitus, field and capital. However, these working mothers have low capacity to achieve a work-life balance and this may lead to complex social problems.
    • General method for the synthesis of pseudodisaccharides. Diels-Alder approach to the synthesis of pseudodisaccharides

      Afarinkia, Kamyar; Patterson, Laurence H.; Abdullahi, Mohamed H. (University of BradfordInstitute of Cancer Therapeutics, 2011-05-20)
      This thesis describes a new method for the synthesis of pseudodisaccharides containing a carbasugar analogue attached to a "true" sugar. The methodology is based on a Diels-Alder cycloaddition of vinyl sugars and appropriately substituted pyran-2-ones, followed by chemical manipulation of the resulting cycloadducts. The thesis also describes the synthesis of inhibitors of Golgi ¿-mannosidase II and glucokinase. The first chapter is a comprehensive survey of the reported synthetic routes to pseudodisaccharides from the literature. The results and discussions are presented in chapter 2. This chapter starts by discussion of the preparation of vinyl sugars and pyran-2-ones and the regio- and stereoselectivity of their cycloadditions. This is followed by reporting the chemical manipulations of these cycloadducts and the synthesis of a pseudodisaccharide. Cycloadducts are shown to lose carbon dioxide at elevated temperatures to afford dihydrobenzenes. The loss of the bridging carbon dioxide from the cycloadducts is experimentally and computationally investigated. The resulting dihydrobenzenes are shown to also be useful as precursors in the synthesis of pseudodisaccharides. The chemical manipulation of these dihydrobenzenes is used towards the synthesis of a pseudodisaccharide. The third and fourth chapters focus on the synthesis of new inhibitors of Golgi ¿-mannosidase II and glucokinase respectively. A range of 6-aminoglucose and mannose derivatives were prepared and tested for the inhibition of Jack bean ¿-mannosidase, but were found to lack any inhibition. Similarly, a range of 6-triazologlucose derivatives were prepared but were found to lack any cytotoxicity. The fifth chapter contains the details of the preparation, experimental procedures and spectroscopic characterisation of the synthesised chemical compounds. Rate calculations are reported in Appendix I and the X-ray crystallographic data are presented in the Appendix II.
    • General queueing network models for computer system performance analysis. A maximum entropy method of analysis and aggregation of general queueing network models with application to computer systems.

      Kouvatsos, Demetres D.; El-Affendi, Mohamed A. (University of BradfordPostgraduate School of Studies in Computing, 2009-10-23)
      In this study the maximum entropy formalism [JAYN 57] is suggested as an alternative theory for general queueing systems of computer performance analysis. The motivation is to overcome some of the problems arising in this field and to extend the scope of the results derived in the context of Markovian queueing theory. For the M/G/l model a unique maximum entropy solution., satisfying locALl balance is derived independent of any assumptions about the service time distribution. However, it is shown that this solution is identical to the steady state solution of the underlying Marko-v process when the service time distribution is of the generalised exponential (CE) type. (The GE-type distribution is a mixture of an exponential term and a unit impulse function at the origin). For the G/M/1 the maximum entropy solution is identical in form to that of the underlying Markov process, but a GE-type distribution still produces the maximum overall similar distributions. For the GIG11 model there are three main achievements: first, the spectral methods are extended to give exaft formulae for the average number of customers in the system for any G/G/l with rational Laplace transform. Previously, these results are obtainable only through simulation and approximation methods. (ii) secondly, a maximum entropy model is developed and used to obtain unique solutions for some types of the G/G/l. It is also discussed how these solutions can be related to the corresponding stochastic processes. (iii) the importance of the G/GE/l and the GE/GE/l for the analysis of general networks is discussed and some flow processes for these systems are characterised. For general queueing networks it is shown that the maximum entropy solution is a product of the maximum entropy solutions of the individual nodes. Accordingly, existing computational algorithms are extended to cover general networks with FCFS disciplines. Some implementations are suggested and a flow algorithm is derived. Finally, these results are iised to improve existing aggregation methods. In addition, the study includes a number of examples, comparisons, surveys, useful comments and conclusions.
    • General queueing networks with priorities. Maximum entropy analysis of general queueing network models with priority preemptive resume or head-of-line and non-priority based service disciplines.

      Kouvatsos, Demetres D.; Tabet Aouel, Nasreddine (University of BradfordDepartment of Computing, 2010-02-08)
      Priority based scheduling disciplines are widely used by existing computer operating systems. However, the mathematical analysis and modelling of these systems present great difficulties since priority schedulling is not compatible with exact product form solutions of queueing network models (QNM's). It is therefore, necessary to employ credible approximate techniques for solving QNM's with priority classes. The principle of maximum entropy (ME) is a method of inference for estimating a probability distribution given prior information in the form of expected values. This principle is applied, based on marginal utilisation, mean queue length and idle state probability constraints, to characterise new product-form approximations for general open and closed QNM's with priority (preemptive-resume, non-preemtive head-of-line) and non-priority (first-come-first-served, processor-sharing, last-come-first-served with, or without preemtion) servers. The ME solutions are interpreted in terms of a decomposition of the original network into individual stable GIG11 queueing stations with assumed renewal arrival processes. These solutions are implemented by making use of the generalised exponential (GE) distributional model to approximate the interarrival-time and service-time distributions in the network. As a consequence the ME queue length distribution of the stable GE/GEzl priority queue, subject to mean value constraints obtained via classical queueing theory on bulk queues, is used as a 'building block' together with corresponding universal approximate flow formulae for the analysis of general QNM's with priorities. The credibility of the ME method is demonstrated with illustrative numerical examples and favourable comparisons against exact, simulation and other approximate methods are made.
    • Generalised analytic queueing network models. The need, creation, development and validation of mathematical and computational tools for the construction of analytic queueing network models capturing more critical system behaviour.

      Kouvatsos, Demetres D.; Almond, John (University of BradfordPostgraduate School of Studies in Computing, 2009-10-22)
      Modelling is an important technique in the comprehension and management of complex systems. Queueing network models capture most relevant information from computer system and network behaviour. The construction and resolution of these models is constrained by many factors. Approximations contain detail lost for exact solution and/or provide results at lower cost than simulation. Information at the resource and interactive command level is gathered with monitors under ULTRIX'. Validation studies indicate central processor service times are highly variable on the system. More pessimistic predictions assuming this variability are in part verified by observation. The utility of the Generalised Exponential (GE) as a distribution parameterised by mean and variance is explored. Small networks of GE service centres can be solved exactly using methods proposed for Generalised Stochastic Petri Nets. For two centre. systems of GE type a new technique simplifying the balance equations is developed. A very efficient "building bglloocbka"l. is presented for exactly solving two centre systems with service or transfer blocking, Bernoulli feedback and load dependent rate, multiple GE servers. In the tandem finite buffer algorithm the building block illustrates problems encountered modelling high variability in blocking networks. ': . _. A parametric validation study is made of approximations for single class closed networks of First-Come-First-Served (FCFS) centres with general service times. The multiserver extension using the building block is validated. Finally the Maximum Entropy approximation is extended to FCFS centres with multiple chains and implemented with computationally efficient convolution.
    • Generation of Software Test Data from the Design Specification Using Heuristic Techniques. Exploring the UML State Machine Diagrams and GA Based Heuristic Techniques in the Automated Generation of Software Test Data and Test Code.

      Dahal, Keshav P.; Hossain, M. Alamgir; Doungsa-ard, Chartchai (University of BradfordDepartment of Computing, 2012-02-10)
      Software testing is a tedious and very expensive undertaking. Automatic test data generation is, therefore, proposed in this research to help testers reduce their work as well as ascertain software quality. The concept of test driven development (TDD) has become increasingly popular during the past several years. According to TDD, test data should be prepared before the beginning of code implementation. Therefore, this research asserts that the test data should be generated from the software design documents which are normally created prior to software code implementation. Among such design documents, the UML state machine diagrams are selected as a platform for the proposed automated test data generation mechanism. Such diagrams are selected because they show behaviours of a single object in the system. The genetic algorithm (GA) based approach has been developed and applied in the process of searching for the right amount of quality test data. Finally, the generated test data have been used together with UML class diagrams for JUnit test code generation. The GA-based test data generation methods have been enhanced to take care of parallel path and loop problems of the UML state machines. In addition the proposed GA-based approach is also targeted to solve the diagrams with parameterised triggers. As a result, the proposed framework generates test data from the basic state machine diagram and the basic class diagram without any additional nonstandard information, while most other approaches require additional information or the generation of test data from other formal languages. The transition coverage values for the introduced approach here are also high; therefore, the generated test data can cover most of the behaviour of the system.
    • Generator Maintenance Scheduling Models in Power Systems. Integrated Cost Models for Generator Maintenance Strategy under Market Environment.

      Dahal, Keshav P.; Al-Arfaj, Khalid A. (University of BradfordDepartment of Computing, 2010-05-28)
      Change from a regulated to deregulated structure means that, the centralized maintenance system is not valid any more. In the surveyed published literature, there is not a single model which incorporates all maintenance cost components to analyze the effect of different maintenance strategies for generator companies (GENCOs). The work enclosed in this thesis demonstrates that there is a considerable requirement for accurately modelling cost components of the maintenance model, to be used in maintenance scheduling for deregulated power system, in order to attain a superior schedule with major financial and operational impact. This research investigates and models most cost factors that affect the maintenance activities of the deregulated GENCOs, and demonstrates the utilization of the developed cost models in maintenance scheduling. It also presents the data gathering process for the developed maintenance cost model. A generator maintenance scheduling model that considers direct and indirect maintenance costs, opportunity costs (i.e. loss of customer goodwill), effective maintenance strategies, failures, and interruptions is developed. A Genetic Algorithm (GA) based approach is employed to achieve maintenance schedules to various generators maintenance scenarios. An Analytical Hierarchy Process (AHP) approach is proposed for modelling customer goodwill. The maintenance model was redeveloped under the Reliability Centred Maintenance (RCM) strategy to analyze the effect of a maintenance strategy on maintenance costs. Case studies are presented to demonstrate the utilisation of the developed models.The investigation shows that the market prices, opportunity costs and maintenance strategy have an effect on the final maintenance schedule. The research demonstrates that the cost components are critical factors to achieve an effective maintenance schedule, and they must be considered and carefully modelled in order to reflect more realistic situation for maintenance scheduling of generator units in deregulation environment.
    • Genoprotective effect of aspirin and ibuprofen in human lymphocyte cells. Effect of nano and bulk forms of aspirin and ibuprofen on lymphocytes from breast cancer patients compared with those from healthy females

      Anderson, Diana; Baumgartner, Adolf; Dandah, Osama M.M. (University of BradfordFaculty of Life Sciences, 2017)
      Various recent studies have suggested that regular intake of some non-steroidal anti-inflammatory drugs (NSAIDs) have a preventative effect against several types of tumours including breast cancer. The term nanotechnology refers to technology in which one-billionth of a meter is used as a scale for chemical particle size. This work aims to study the effect of both ibuprofen and aspirin on DNA damage using peripheral blood lymphocytes from breast cancer patients and comparing the results with those from healthy females as a control using the Comet and micronucleus assays. Western blot analysis (WBA) was used to investigate the effect of these drugs on XRCC3 and p53 proteins, whereas QPCR was to evaluate this effect on p53, cox1 and cox2 genes. Two hundred fifty ng/ml of ibuprofen (NP and bulk) and 500 ng/ml of aspirin (NP and bulk) were used to treat the lymphocytes. Both aspirin and ibuprofen caused a reduction in DNA damage and micronucleus formation. Aspirin, both forms, showed a reduction in DNA damage in the Comet and micronucleus assays. Ibuprofen both forms, by contrast, showed a statistically significant reduction in micronucleus frequency in the micronucleus assay, while its preventative effect with the Comet assay was weak or insignificant. NPs of both agents were more effective than bulk sizes. Using the Comet repair assay, aspirin and ibuprofen nano form catalysed DNA repair to a greater extent than their bulk forms. Also, both sizes showed better repair with NSAIDs compared to samples repaired without NSAIDs. In WBA aspirin increased the expression of XRCC3 protein in healthy cells. However, both NSAIDs decreased that expression in cells from BC patients. Furthermore, aspirin increased p53 expression in BC patients lymphocytes. With the QPCR method, results of both aspirin forms increased the expression of the p53 gene in BC patient cells statistically significantly. Both drugs reduced cox1 expression in healthy volunteers and cancer patients lymphocytes. Moreover, cox2 reduction was only in lymphocytes from BC patients. The results of this work are consistent with the view that NSAIDs, particularly aspirin and ibuprofen, could have a promising role in cancer treatment including breast cancer.
    • Genotoxic effects of nano and bulk forms of aspirin and ibuprofen on blood samples from prostate cancer patients compared to those from healthy individuals: The protective effects of NSAIDs against oxidative damage, quantification of DNA repair capacity and major signal transduction pathways in lymphocytes from healthy individuals and prostate cancer patients

      Anderson, Diana; Baumgartner, Adolf; Guma, Azeza S.S.
      Inhibiting inflammatory processes or eliminating inflammation represents a logical role in the suppression and treatment strategy of cancer. Several studies have shown that anti-inflammatory drugs (NSAIDs) have promise as anticancer agents while reducing metastases and mortality. NSAIDs are seriously limited by side effects and their toxicity, which can become cumulative with their long-term administration for chemoprevention. The huge development in nanotechnology allows the drugs to exhibit novel and significantly improved properties compared to the large particles of the respective bulk compound, leading to more targeted therapy and reduced dosage. The overall aim of this thesis is to add to our understanding of cancer prevention and treatment through studying the genotoxicity mechanisms of NSAIDs agents in lymphocytes. In this study, the genotoxicity mechanisms of NSAID in bulk and nanoparticles forms a strategy to prevent and minimise the damage in human lymphocytes. Aspirin nano (ASP N) caused a significant decrease in deoxyribonucleic acid (DNA) damage compared to aspirin bulk (ASP B). Also, ibuprofen nano (IBU N) showed a significant reduction in DNA damage compared to ibuprofen bulk (IBU B). Micronuclei (MNi) decreased after ASP N, ASP B and IBU N in prostate cancer patients and healthy individuals, and the ibuprofen bulk showed a significant increase of MNi formation in lymphocytes from healthy and prostate cancer patients when compared to untreated lymphocytes from prostate cancer patients. In order to study the geno-protective properties of these drugs, the protective effect of NSAIDs and the quantification of the DNA repair capacity in lymphocytes was studied. ASP N was found to increase the DNA repair capacity and reduced the reactive oxygen species (ROS) formation significantly more than ASP B. Finally, the role of NSAIDs on some key regulatory signal transduction pathways in isolated lymphocyte cells was investigated by studying their effect on ataxia-telangiectasia-mutated kinase (ATM) and ataxia-telangiectasia and Rad3-related kinase (ATR) mRNA. ATM mRNA significantly increased after treatment with ASP B, ASP N and IBU N. ATR expression also increased after treatment with IBU B and IBU N, but was only significant with IBU N. These findings indicate that a reduction in particle size had an impact on the reactivity of the drug, further emphasising the potential of nanoparticles as improvement to current treatment options.
    • Genotoxic effects of NSAIDs and hydrocortisone in bulk and nano forms in lymphocytes from patients with haematological cancers

      Anderson, Diana; Normington, Charmaine
      Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.
    • Genotoxic effects of NSAIDs and hydrocortisone on bulk and nano forms in lymphocytes from patients with haematological cancers

      Anderson, Diana; Normington, Charmaine (University of BradfordFaculty of Life Sciences, 2017)
      Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.
    • Genotoxic effects of oestrogens and nano-NSAIDs: Genotoxic effects of oestrogens in vivo and nano- and bulk forms of NSAIDs on blood samples from prostate cancer patients

      Anderson, Diana; Gopalan, Rajendran C.; Rathore, Dildar S. (University of BradfordFaculty of Life Sciences, 2014)
      The genotoxicological effects of five intra-peritoneal administered oestrogens (17β- oestradiol, daidzein, diethylstilboestrol, genistein, and equol), were examined. Male hooded- Lister rats were used to examine to what extent DNA damage occurred. The alkaline Comet assay was the chosen method used to assess double-strand DNA breakage by examining the Olive tail moment and %age tail DNA. Tissues from the testis, bone marrow, liver and blood were analysed after an 8-day duration of exposure. Statistically significant increases in DNA damage were observed in the testis with daidzein and in the blood with diethylstilboestrol. In addition, a further study was carried out to examine the effects of bulk and nanotised forms of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and ibuprofen, in the Comet and micronucleus assays, on whole blood taken from prostate cancer patients or volunteers. These were used because it is known that the sensitivity of DNA to genotoxins can be heightened in patients with cancer. Patients’ and volunteers’ blood was cultured with either the bulk or nano-forms for 44 hours at 37°C, 5% CO2. Data were obtained for the Comet assay as above and the number of binucleated cells scored for the micronucelus assay. The results show the nanotised forms of the NSAIDs decreased the levels of strand breakage and lowered the numbers of micronuclei generated compared with their bulk forms. There was no clear difference between the sensitivity of the healthy controls and the prostate cancer patients, with only one individual showing evidence of heightened sensitivity.
    • Genotoxicity of haloacetic acids, aspirin and ibuprofen in human cells. Genotoxic effects of water disinfectant- by-products in human blood and sperm and bulk and nano forms of aspirin and ibuprofen in human blood of respiratory disease patients

      Anderson, Diana; Gopalan, Rajendran C.; Ali, Aftab H.M. (University of BradfordFaculty of Life Sciences, 2014)
      This project focuses on two important topics which may pose hazards to human health. Firstly, drinking water disinfection by-products (DBPs), which are generated by the chemical disinfection of water have been investigated. What has not been shown is the effect of DBPs in human germ cells as well as somatic cells and whether oxidative stress is involved in the mechanism of genotoxic action. Three different DBPs (halo acetic acids: HAAs), together with the antioxidants – catalase and butylated hydroxyanisole (BHA), were investigated in peripheral blood cells and sperm from healthy individuals using the Comet assay and lymphocytes only using the micronucleus assay. Secondly, nanoparticles of the non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and ibuprofen, have been investigated in patients with respiratory diseases, in the micronucleus assay and the Comet repair assay. NSAIDs inhibit cyclooxygenase enzyme activity, which plays part in tumour progression. In the Comet assay, BHA and catalase were able to reduce DNA damage in both cell types compared to HAAs alone. Similarly, in the micronucleus assay, micronuclei were reduced with the antioxidants, suggesting oxygen radical involvement in both assays. With the NSAIDs, reductions were seen for DNA damage in the micronucleus assay with aspirin and ibuprofen nanoparticles compared to their bulk forms. Using the Comet repair assay, aspirin and ibuprofen nanoparticles aided repair of DNA to a greater extent than their bulk counterparts, which in turn showed better repair compared to samples repaired without NSAIDs. These observations show the importance of DBPs and NSAIDs in genotoxic public health issues.
    • Geometric modelling and shape optimisation of pharmaceutical tablets. Geometric modelling and shape optimisation of pharmaceutical tablets using partial differential equations.

      Ugail, Hassan; Gonzalez Castro, Gabriela; Ahmat, Norhayati (University of BradfordSchool of Computing, Informatics and Media, 2013-11-21)
      Pharmaceutical tablets have been the most dominant form for drug delivery and they need to be strong enough to withstand external stresses due to packaging and loading conditions before use. The strength of the produced tablets, which is characterised by their compressibility and compactibility, is usually deter-mined through a physical prototype. This process is sometimes quite expensive and time consuming. Therefore, simulating this process before hand can over-come this problem. A technique for shape modelling of pharmaceutical tablets based on the use of Partial Differential Equations is presented in this thesis. The volume and the sur-face area of the generated parametric tablet in various shapes have been es-timated numerically. This work also presents an extended formulation of the PDE method to a higher dimensional space by increasing the number of pa-rameters responsible for describing the surface in order to generate a solid tab-let. The shape and size of the generated solid tablets can be changed by ex-ploiting the analytic expressions relating the coefficients associated with the PDE method. The solution of the axisymmetric boundary value problem for a finite cylinder subject to a uniform axial load has been utilised in order to model a displace-ment component of a compressed PDE-based representation of a flat-faced round tablet. The simulation results, which are analysed using the Heckel model, show that the developed model is capable of predicting the compressibility of pharmaceutical powders since it fits the experimental data accurately. The opti-mal design of pharmaceutical tablets with particular volume and maximum strength has been obtained using an automatic design optimisation which is performed by combining the PDE method and a standard method for numerical optimisation.