• Investigation of a solvent-free continuous process to produce pharmaceutical co-crystals. Understanding and developing solvent-free continuous cocrystallisation (SFCC) through study of co-crystal formation under the application of heat, model shear and twin screw extrusion, including development of a near infrared spectroscopy partial least squares quantification method

      Kelly, Adrian L.; Paradkar, Anant R.; Gough, Timothy D.; Wood, Clive John (University of BradfordSchool of Life Sciences, 2016)
      This project utilised a novel solvent-free continuous cocrystallisation (SFCC) method to manufacture pharmaceutical co-crystals. The objectives were to optimize the process towards achieving high co-crystal yields and to understand the behaviour of co-crystals under different conditions. Particular attention was paid to the development of near infrared (NIR) spectroscopy as a process analytical technology (PAT). Twin screw, hot melt extrusion was the base technique of the SFCC process. Changing parameters such as temperature, screw speed and screw geometry was important for improving the co-crystal yield. The level of mixing and shear was directly influenced by the screw geometry, whilst the screw speed was an important parameter for controlling the residence time of the material during hot melt extrusion. Ibuprofen – nicotinamide 1:1 cocrystals and carbamazepine – nicotinamide 1:1 co-crystals were successfully manufactured using the SFCC method. Characterisation techniques were important for this project, and NIR spectroscopy proved to be a convenient, accurate analytical technique for identifying the formation of co-crystals along the extruder barrel. Separate thermal and model shear deformation studies were also carried out to determine the effect of temperature and shear on co-crystal formation for several different pharmaceutical co-crystal pairs. Finally, NIR spectroscopy was used to create two partial least squares regression models, for predicting the 1:1 co-crystal yield of ibuprofen – nicotinamide and carbamazepine – nicotinamide, when in a powder mixture with the respective pure API. It is believed that the prediction models created in this project can be used to facilitate future in-line PAT studies of pharmaceutical co-crystals during different manufacturing processes.
    • An investigation of corporate responsibility practices amongst MNCs' subsidiaries in Sri Lanka. Implementation and influencing factors.

      Fairbrass, Jenny M.; Mohr, Alexander T.; Beddewela, Eshani S. (University of BradfordBradford University School of Management, 2013-11-20)
      This thesis examines the implementation of Community Corporate Responsibility (CCR) practices among ten subsidiaries of Multinational Corporations (MNCs) in Sri Lanka and the different factors which influence such implementation. Within this context, it specifically focuses on examining the internal factors residing within the MNC as an organisation and those factors which exist outside in the institutional environment of the host country. The study combines three broad theoretical domains: Corporate Responsibility implementation literature, International Business Strategy literature and Neo-Institutional theory. It uses a qualitative research methodology based upon the interview method. Qualitative interview data collected through sixty-two in-depth interviews with managers of the ten subsidiaries and key institutional actors in the host country were analysed using descriptive coding, interpretive coding and conceptualisation to arrive at the findings. The findings showed that non-specialist functional departments were mainly responsible for implementing CCR practices, indicating a lack of strategic and structural integration of CCR practices. The findings reinforces the dominant role of the MNC headquarters in implementing CCR practices within subsidiaries operating in a developing country, indicating that ¿power¿ relationships between subsidiary and parent is an important denominator in internal organisational practices implementation. Furthermore, dynamic and complex relationships were found between the subsidiaries and the Sri Lankan government and other institutional actors indicating the existence of a strategic approach towards legitimisation by iii subsidiaries, using CCR practices. Based upon these findings, this research proposes the need to conduct future studies across different MNCs and their subsidiaries located in multiple developing countries to further examine the implementation of CCR practices as it would enable public policy makers and business managers to better influence the global CSR of MNCs.
    • Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer. Probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursors

      Patterson, Laurence H.; McCaul, Jim; Pors, Klaus; Presa, Daniela (University of BradfordInstitute of Cancer Therapeutics, Faculty of Life Sciences, 2018)
      Cytochrome P450 enzymes such as CYP1A1 and CYP2W1 have been shown to be overexpressed in tumour tissue compared to surrounding normal tissue, providing an opportunity to develop targeted therapies. Recent studies have shown that re-engineered duocarmycins can be activated selectively by cancer cells expressing CYP1A1 and/or CYP2W1 to potent cytotoxins that damage DNA. This study aimed to explore CYP expression in HNC tissue, and link CYP1A1, 1B1 and 2W1 expression with capacity to bioactivate duocarmycin bioprecursors. A panel of HNC cell lines was investigated for CYP gene expression using Real Time PCR (RT-PCR), and protein expression by Western blot and/or immunofluorescence. The cell lines were also evaluated for anti proliferative activity using lead duocarmycin bioprecursor compounds (ICT2700, ICT2706 and ICT2726) and novel analogues. Various levels of mRNA expression were observed for CYP1A1 and 1B1, but not for CYP2W1, which was only detected at very low levels, contrasting with the moderate-to high CYP2W1 expression found in clinical tissues and xenografts. FaDu and Detroit-562 were identified as sensitive cell lines to several duocarmycins, and hence useful for assessing compound activity. Two novel compounds, ICT2700S and ICT11003, were shown to be the most potent duocarmycins evaluated in FaDu and Detroit-562, which primarily expressed CYP1A1. Using the comet assay and γH2AX, ICT2700S cytotoxic activity was correlated with DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), while one benzofuran-based duocarmycin (ICT2724) was shown to cause more inter stand crosslinks (ICLs). The significance of target CYP expression and compound activity warrants further investigations in preclinical models to ascertain the clinical potential of duocarmycin-based bioprecursors.
    • Investigation of drug ionic liquid salts for topical delivery systems

      Paradkar, Anant R.; Brown, Elaine C.; Karodia, Nazira; Bansiwal, Mukesh (University of BradfordFaculty of Life Sciences, 2017)
      Pharmaceutical companies and FDA (Federal Drug Administration) rules rely heavily on crystalline active pharmaceutical ingredients delivered as tablets and powders in the form of neutral compounds, salts and solvates of neutral compounds and salts. About half of all drugs sold in the market are in the form of salts which are held together by ionic bonds along with some other forces. Recently, Ionic liquids (ILs) an interesting class of chemical compounds have offered potential opportunity for exploration as novel drug ionic liquid salts, particularly in the field of transdermal/topical drug delivery. Due to the multifunctional nature of these salts they could allow generation of new pathway to manipulate the transport and deposition behaviour of the drug molecule. It is this modular approach of IL that forms the basis of the research presented here, in which pharmaceutically acceptable compounds are combined with selected drugs with known problems. IL salts were generated by combining at least one drug molecule with FDA approved compounds and were assessed for physicochemical properties, skin deposition and permeation studies. Skin deposition data suggested that these systems exhibit high skin retention, which was found to correlate with the molecular weight. On the other hand, permeation data displayed an inverse relationship between flux values and molecular weight of the permeant. Similar work was extended with ILs with mixed anions containing two drugs. The benzalkonium-sulfacetamide ILs were investigated for synergism and the biological studies data display no synergistic effect. It was also illustrated that in-situ IL based ibuprofen hydrogels systems could be manipulated via IL approach for topical application. These findings suggest the potential applicability of IL based formulations for topical delivery of drugs.
    • Investigation of Energy Demand Modeling and Management for Local Communities. Investigation of the electricity demand modeling and management including consumption behaviour, dynamic tariffs, and use of renewable energy.

      Rajamani, Haile S.; Abd-Alhameed, Raed A.; Ihbal, Abdel-Baset M.I. (University of BradfordSchool of Engineering, Design and Technology, 2013-11-20)
      Various forecasting tools, based on historical data, exist for planners of national networks that are very effective in planning national interventions to ensure energy security, and meet carbon obligations over the long term. However, at a local community level, where energy demand patterns may significantly differ from the national picture, planners would be unable to justify local and more appropriate intervention due to the lack of appropriate planning tools. In this research, a new methodology is presented that initially creates a virtual community of households in a small community based on a survey of a similar community, and then predicts the energy behaviour of each household, and hence of the community. It is based on a combination of the statistical data, and a questionnaire survey. The methodology therefore enables realistic predictions and can help local planners decide on measures such as embedding renewable energy and demand management. Using the methodology developed, a study has been carried out in order to understand the patterns of electricity consumption within UK households. The methodology developed in this study has been used to investigate the incentives currently available to consumers to see if it would be possible to shift some of the load from peak hours. Furthermore, the possibility of using renewable energy (RE) at community level is also studied and the results presented. Real time pricing information was identified as a barrier to understanding the effectiveness of various incentives and interventions. A new pricing criteria has therefore been developed to help developers and planners of local communities to understand the cost of intervention. Conclusions have been drawn from the work. Finally, suggestions for future work have been presented.
    • An investigation of forecasting methods for a purchasing decision support system. A real-world case study of modelling, forecasting and decision support for purchasing decisions in the rental industry.

      Dahal, Keshav P.; Cowling, Peter I.; Yang, Ruohui (University of BradfordDepartment of Computing, 2013-11-15)
      This research designs a purchasing decision support system (PDSS) to assist real-world decision makings on whether to purchase or to sub-hire for equipment shortfalls problem, and to avoid shortage loss for rental business. Research methodology includes an extensive literature review on decision support systems, rental industry, and forecasting methods. A case study was conducted in a rental company to learn the real world problem and to develop the research topics. A data converter is developed to recover the missing data and transform data sets to the accumulative usage data for the forecasting model. Simulations on a number of forecasting methods was carried out to select the best method for the research data based on the lowest forecasting errors. A hybrid forecasting approach is proposed by adding company revenue data as a parameter, in addition to the selected regression model to further reduce the forecasting error. Using the forecasted equipment usage, a two stage PDSS model was constructed and integrated to the forecasting model and data converter. This research fills the gap between decision support system and rental industry. The PDSS now assists the rental company on equipments buy or hire decisions. A hybrid forecasting method has been introduced to improve the forecasting accuracy significantly. A dada converter is designed to efficiently resolve data missing and data format problems, which is very common in real world.
    • Investigation of Indoor Propagation Algorithms for Localization Purposes: Simulation and Measurements of Indoor Propagation Algorithms for Localization Applications using Wall Correction Factors, Local Mean Power Estimation and Ray Tracing Validations

      Abd-Alhameed, Raed A.; Noras, James M.; Jones, Steven M.R.; Obeidat, Huthaifa A.N.
      The objective of this work is to enhance the awareness of the indoor propagation behaviour, by a set of investigations including simulations and measurements. These investigations include indoor propagation behaviour, local mean power estimation, proposing new indoor path loss model and introducing a case study on 60 GHz propagation in indoor environments using ray tracing and measurements. A summary of propagation mechanisms and manifestations in the indoor environment is presented. This comprises the indoor localization techniques using channel parameters in terms of angle of arrival (AOA), time of arrival (TOA) and received signal strength (RSS). Different models of path loss, shadowing and fast fading mechanisms are explored. The concept of MIMO channels is studied using many types of deterministic channel modelling such as Finite Difference Time Domain, Ray tracing and Dominant path model. A comprehensive study on estimating local average of the received signal strength (RSS) for indoor multipath propagation is conducted. The effect of the required number of the RSS data and their Euclidian distances between the neighbours samples are investigated over 1D, 2D and 3D configurations. It was found that the effect of fast fading was reduced sufficiently using 2D horizontal’s arrangement with larger spacing configuration. A modified indoor path loss prediction model is presented namely effective wall loss model (EWLM). The modified model with wall correction factors is compared to other indoor path loss prediction models using simulation data (for 2.4, 5, 28, 60 and 73.5 GHz) and real-time measurements (for 2.4 and 5 GHz). Different operating frequencies and antenna polarizations are considered to verify the observations. In the simulation part, EWLM shows the best performance among other models. Similar observations were recorded from the experimental results. Finally, a detailed study on indoor propagation environment at 60 GHz is conducted. The study is supported by Line of Sight (LoS) and Non-LoS measurements data. The results were compared to the simulated ones using Wireless-InSite ray tracing software. Several experiments have confirmed the reliability of the modelling process based on adjusted material properties values from measurements.
    • Investigation of inhibitors of polysialyltransferase as novel therapeutics for neuroblastoma. Development of in vitro assays to assess the functionality and selectivity of novel small-molecule inhibitors of polysialyltransferases for use in neuroblastoma therapy

      Shnyder, Steven D.; Falconer, Robert A.; Saeed, Rida F. (University of BradfordInstitute of Cancer Therapeutics, Faculty of Life Sciences, 2015)
      Polysialic acid is aunique carbohydrate that decorates the surface of the neural cell adhesion molecule. Polysialic acidis an onco-developmental antigen, expressed in tumours principally of neuroendocrine origin, notably neuroblastoma,strongly correlating with invasion and metastasis. Polysialylation is regulated by two polysialyltransferase enzymes, PST(ST8SiaIV)and STX(ST8SiaII),withSTX dominant in cancer. Post-development polysialic acid expression is only found at low levels in the brain, thus this could be a novel target for cancer therapy. It is hypothesized that inhibition of polysialyltransferasecould lead to control of tumour dissemination and metastasis.The aims of this thesis were to develop tools and in vitro assays to screen novel polysialyltransferaseinhibitors. A panel of tumour cell lines were characterised in terms of growth parameters (using the MTT assay) and polysialic acid expression. This includes a pair of isogenic C6 rat glioma cells (C6-STX and C6-WT) and naturally polysialic acid expressing neuroblastoma cells(SH-SY5Y). Following this, an in vitro assay was validated to screen modulation of polysialic acid expression by removing pre-existing polysialic acid expression using endoneuraminidase N and evaluated the amount of re-expression of polysialic acid using immunocytochemistry. Then, a functional assay was developed and validated for invasion, the matrigel invasion assay. Cytidine monophosphate (tool compound) significantly reduced polysialic acidsurface expression and invasion. A panel of six novel polysialyltransferase inhibitors was screened for cytotoxicity, polysialic acidsurface expression and invasion. Of the potential polysialyltransferase inhibitorsevaluated, ICT3176 and ICT3172 were identified from virtual screening of Maybridge library and were emerged as the most promising inhibitors, demonstrating significant (p<0.05)reduction in cell-surface polysialic acidre-expression and invasion in polysialic acid expressing cells.Furthermore, the specificity of compounds for polysialyltransferase (α-2,8-sialyltransferase) over othermembers of the wider sialyltransferase family (α-2,3-and α-2,6-sialyltransferases) was confirmed using differential lectin staining. These results demonstrated that small molecule inhibitors as STX is possible and provides suitable in vitrocell based assays to discovery more potent derivatives.
    • Investigation of injection moulding for novel drug delivery systems. An investigation into the use of injection moulding to produce pharmaceutical dosage forms and to understand the relationship between materials, processing conditions and performance, in particular drug release and stability

      Kelly, Adrian L.; Paradkar, Anant R.; Deshmukh, Shivprasad S. (University of BradfordSchool of Life Sciences, 2015)
      The feasibility of the injection moulding (IM) was explored for the development of novel drug delivery systems. Controlled release formulations were developed using a substituted cellulose derivative, hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and a graft co-polymer (Soluplus®). BCS class II drugs ibuprofen and the felodipine were selected based on their physicochemical properties. In the present work, a homogenous dispersion of drugs in the polymer matrices was achieved using Hot Melt Extrusion (HME) and extruded pellets obtained were used for the development of the injection moulded systems. Four systems were developed using the IM consisting of ibuprofen-HPMCAS, ibuprofen-Soluplus®, felodipine-PEO-HPMCAS and felodipine-Soluplus®. The ibuprofen acts as a good plasticiser compared to felodipine therefore, felodipine containing IM systems required a plasticiser (PEO) when processed with HPMCAS. The analysis of extruded pellets and injection moulded systems using modulated DSC (MDSC) and Raman spectroscopy confirmed the formation of an amorphous molecular dispersion (i.e solid solution) in the case of all four systems. The phase separation behaviour and the amorphous stability of the systems was studied at various stress conditions. This revealed the “surface crystallisation” behaviour of the ibuprofen-HPMCAS systems. Temperature-composition phase diagram constructed based on the melting point depression and the Flory-Huggins lattice solution theory provided the explanation for the phase separation and crystallisation behaviour of ibuprofen-HPMCAS systems. The advanced characterisation techniques like DMA, 2D XRD and 3D laser microscopy provided the detailed understanding of crystal habits, phase seperation and surface crystallisation. The significant effect of the stress conditions on the rate of shrinkage was observed where, higher shrinkage tendency of a HPMCAS IM system was observed compared to Soluplus® IM systems. The extruded pellets provided the faster drug release compared to the moulded tablets suggests the effect of particle size as well as the densification during IM on the dissolution rate of the dosage form. The nature of the polymer and processing history were the contributing factors for the dissolution of the dosage forms.
    • An investigation of intellectual capital disclosure in annual reports of UK firms. Practices and determinants.

      Pike, Richard H.; Haniffa, Roszaini M.; Li, Jing (University of BradfordSchool of Management, 2010-06-14)
      This study examines the intellectual capital (IC) disclosure practices in the annual reports of 100 listed UK firms selected from sectors considered to be IC-intensive. It also investigates the possible determinants of such disclosure practices from the three perspectives of corporate governance structure, company characteristics and market factors. IC disclosures were captured using content analysis, and were measured by a disclosure index, supported by word count and percentage of word count metrics to assess the variety, volume and focus of IC disclosure respectively, at both overall and subcategory levels. The presentational formats and locations of IC disclosures were also recorded. The results indicate that the UK firms sampled provide considerable IC information in their annual reports, mainly in text form, with popular use of numerical information, while the use of graphs and pictures for many IC elements remains low. The distribution of IC disclosures, captured in three categories, varies by the three measures of disclosure applied. IC information was found in virtually all sections of the annual report and was most concentrated in the Operating and Financial Review section. IC terms typically used in the academic literature do not feature in the sampled annual reports. The results of the statistical analyses based on the three measures of IC disclosure indicate significant associations with a number of corporate governance factors (i.e. board composition, share concentration, audit committee size and frequency of meeting, board directors¿ shareholding, audit committee directors¿ shareholding, and board directors with cross-directorships), company characteristics (i.e. firm size, profitability, and listing age), and market factors (i.e. `hidden value¿, share price volatility, share turnover, and multiple listing). These findings offer support for a number of theories, such as information asymmetry, agency and signalling theory. The influence of these explanatory factors on human, structural and relational capital disclosures, based on all three disclosure measure metrics, as well as on the format of IC disclosure, was also explored. The study also finds that its IC framework is more effective than a less detailed framework used in prior studies for the purpose of examining IC disclosure practice and its determinants. The study contributes to the further advancement of the state of knowledge in relation to IC disclosure both empirically and methodologically. It provides information users, preparers, regulatory bodies and academics with a state-of-the-art understanding of IC disclosure practices in the annual report. The transparent content analysis process enables future replication and comparison of results. The rigorous measurements of IC disclosure, the greater specificity of disclosure about the location and presentational format, and the more detailed IC research framework can be usefully applied by other studies. By examining the relationship between explanatory factors and IC disclosure, it helps shareholders and other groups of information users as well as the regulatory bodies to identify factors that may encourage IC disclosure in the annual report.
    • Investigation of mechanisms of drug resistance in colorectal cancer: a proteomic and pharmacological study using newly developed drug-resistant human cell line subclones

      Shnyder, Steven D.; Sutton, Chris W.; Duran, M. Ortega (University of BradfordFaculty of Life Sciences, 2017)
      Despite therapeutic advances, colorectal cancer still has a 45% mortality rate, and one of the most crucial problems is the development of acquired resistance to treatment with anticancer drugs. Thus the aims of this project are to develop drug-resistant colon cancer cell lines in order to identify mechanisms of resistance for the most commonly drugs used in colorectal cancer: 5-fluorouracil, oxaliplatin, and irinotecan. Following evaluation of drug sensitivity to these agents in an initial panel of eight colorectal cancer cell lines, 3 lines (DLD-1, KM-12 and HT-29) were selected for the development of 5-FU (3 lines), oxaliplatin (2) and irinotecan (1) resistant sublines by continuous drug exposure, with resistance confirmed using the MTT assay. Consistently resistant sublines were subject to a „stable isotope labelling with amino acids in cell culture‟ (SILAC) approach and a MudPIT proteomics strategy, employing 2D LC and Orbitrap Fusion mass spectrometric analysis, to identify novel predictive biomarkers for resistance. An average of 3622 proteins was quantified for each resistant and parent cell line pair, with on average 60-70 proteins up-regulated and 60-70 down-regulated in the drug resistant sublines. The validity of this approach was further confirmed using immunodetection techniques. These studies have provided candidate proteins which can be assessed for their value as predictive biomarkers, or as therapeutic targets for the modulation of acquired drug resistance in colorectal cancer.
    • An investigation of oriented polymers for power transmission applications

      Caton-Rose, Philip D.; Day, Andrew J.; Vgenopoulos, Dimitrios (University of BradfordSchool of Engineering & Informatics, 2014-05-30)
      The feasibility of using oriented polymer technology in the design and manufacture of mechanical power transmission belts has been investigated. Working from an initial selection of polymers a die-drawing technique for orienting the polymers was devised, and the static and dynamic mechanical properties of the oriented polymers were investigated. These results indicated that PP, PBT, PPS and PEEK were suitable for further research. Of these 4 materials PBT was selected as the most appropriate material for belt manufacture based on cost, processability (drawing temperature, natural draw ratio) and limitations of laboratory equipment. A technique based on free-tensile drawing combined with simultaneous rotational motion was designed and used to manufacture oriented PBT flat belts from cylindrical injection moulded preforms. The technique used a tensile machine with two pulley-clamps, a fitted heated chamber and an electric motor to provide rotational motion to the belt during drawing. Two types of oriented PBT flat belts with different cross sections were produced successfully, termed 'thick' and 'thin'. These belts were tested on a purpose-built rig comprising two equal diameter pulleys, one driven by an electric motor and the other connected to a generator to provide load. The belt life and power transmission performance was investigated at various conditions of speed, transmitted torque and tension, and the results indicated that despite their smaller cross section 'thin' flat belts demonstrated up to 3 times longer life. However life was only 100 hours, which was very low compared with conventional flat belts that last for many thousands of hours at higher speeds and much greater power transmission capacity. Synchronous belts were then produced through the same manufacturing method used for flat belts. This aspect of the research concentrated on the initial pitch design and size, i. e. the timing. Initially a rectangular tooth profile was selected for its simplicity in terms of manufacture. The produced belts exhibited high pitch length variation as well as deformed teeth and were not usable for synchronous power transmission. An extra timing feature was included to control orientation; reducing the pitch length variation enabling consistent tooth production. It was observed that the areas between the extra timing feature and the tooth edges did not orient completely with some regions remaining undrawn. Finite Element Analysis (FEA) was used to predict the drawing behaviour of different shapes and dimensions of the timing features. The results suggested that a 4mm wide and 7mm long slot provided the highest possible extension and the minimum non-oriented regions on the groove. Whilst, the thickness and width of the drawn belt timing features showed differences to the FEA predictions, manufactured synchronous belts based on that design had much better controlled dimensions and the lowest achieved pitch length variation ( ±1%), compared to initial attempts. It is concluded that oriented polymers have the potential to be used in power transmission belts since they offer higher stiffness, tensile strength and creep resistance compared with isotropic polymers that are currently used in commercially available belts such as thermoplastic polyurethane (TPU) and polyvinyl chloride (PVC). The main disadvantages were the lack of dimensional stability and number of cycle to failure.
    • Investigation of regulatory functions of micrornas in skin and hair follicle development and cycling. A role of microRNA-214 in skin and hair follicle homeostasis.

      Botchkareva, Natalia V.; Alam, Majid A. (University of BradfordMedical Biosciences, School of Life Sciences, 2014-10-20)
      miRNAs are important post-transcriptional regulators of gene expression which play vital roles in the arrays of physiological processes, including skin and hair follicle (HF) development. In this study, the role for miR-214 in the skin and HF development and their postnatal physiological regeneration was investigated. miR-214 exhibits discrete expression patterns in the epidermis and HF in developing and postnatal skin, and is highly expressed in the epithelial stem cells and their lineage-committed progenies. The effects of miR-214 on HF morphogenesis and cycle progression were evaluated by using doxycyclineinducible miR-214 transgenic mice (K14-rtTA/TRE-miR-214). Keratinocyte specific miR-214 overexpression during skin embryogenesis resulted in the partial inhibition of HF induction and formation of the HF reduced in size producing thinner hair. Overexpression of miR-214 in telogen skin caused retardation of the anagen progression and HF growth. Inhibitory effects of miR- 214 on HF development and cycling were associated with supressed activity of stem cells, reduced proliferation in the hair matrix, and altered differentiation. miR-214 induced complex changes in gene expression programs in keratinocytes, including inhibition of cyclins and cyclin-dependent kinases and several essential components of Wnt, Edar, Shh and Bmp signalling pathways, whereas 􀁅-catenin acts as a novel conserved miR-214 target. Indeed, the inhibitory effects of miR-214 on HF development were rescued by intracutaneous delivery of pharmacological Wnt activator. Thus, this study demonstrated that by targeting 􀁅-catenin and, therefore, interfering with Wnt signalling activity miR-214 may act as one of the upstream effectors of the signalling cascades which govern HF morphogenesis and cycling.
    • Investigation of selected Nigerian medicinal plants as a source of new antimalarial agents. Isolation of phytochemicals from some Nigerian medicinal plants using chromatographic techniques and their evaluation for antiplasmodial activity.

      Wright, Colin W.; Okpako, Larry Commander (University of BradfordBradford School of Pharmacy, 2014-05-02)
      Malaria affects hundreds of millions of people worldwide and equally claims hundreds of thousands of lives each year. With the current spread of drug resistance to standard antimalarial drugs like chloroquine and the emergence of artemisinin-resistant parasites, new antimalarial drugs and formulations are urgently needed. An ethnobotanical survey was carried out in this study in search of novel compounds with promising antiplasmodial activity. Using the ethnobotanical approach, a total of 61 plant species from 59 genera distributed in 34 plant families were found to be used traditionally for the treatment of malaria in Nigeria. Biological evaluation of the plant¿s methanolic extracts was assessed using the parasite lactate dehydrogenase (pLDH) assay against the chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. A total of five (5) plant species showed more potent antiplasmodial activities against the malaria parasites. These are Acanthospermum hispidum, Cassia occidentalis, Kaempferia aethiopica Prosopis africana and Physalis angulata with MIC values ranging between 7.815µg/ml to 31.25µg/ml (3D7 strain) and 15.63µg/ml to 62.50µg/ml (K1 strain) against the malaria parasites, respectively. Two plants, Prosopis africana (Leguminosae-mimosoideae) and Physalis angulata (Solanaceae) were selected for further study. The phytochemical investigation of the active chloroform extracts of P. africana and P. angulata yielded several compounds with three known alkaloids, namely, prosopinine (I), prosopine (II) and acetamide (III). Their structures were confirmed by MS, 1D and 2D NMR spectroscopy. Compounds I, II and III have moderate in vitro antiplasmodial activity against the malaria parasites. Both chloroquine and artemether were used as standard control.
    • Investigation of the application of UPFC controllers for weak bus systems subjected to fault conditions. An investigation of the behaviour of a UPFC controller: the voltage stability and power transfer capability of the network and the effect of the position of unsymmetrical fault conditions.

      Rajamani, Haile S.; Abd-Alhameed, Raed A.; Jalboub, Mohamed K. (University of BradfordSchool of Engineering, Design and Technology, 2013-11-21)
      In order to identify the weakest bus in a power system so that the Unified Power Flow Controller could be connected, an investigation of static and dynamic voltage stability is presented. Two stability indices, static and dynamic, have been proposed in the thesis. Multi-Input Multi-Output (MIMO) analysis has been used for the dynamic stability analysis. Results based on the Western System Coordinate Council (WSCC) 3-machine, 9-bus test system and IEEE 14 bus Reliability Test System (RTS) shows that these indices detect with the degree of accuracy the weakest bus, the weakest line and the voltage stability margin in the test system before suffering from voltage collapse. Recently, Flexible Alternating Current Transmission systems (FACTs) have become significant due to the need to strengthen existing power systems. The UPFC has been identified in literature as the most comprehensive and complex FACTs equipment that has emerged for the control and optimization of power flow in AC transmission systems. Significant research has been done on the UPFC. However, the extent of UPFC capability, connected to the weakest bus in maintaining the power flows under fault conditions, not only in the line where it is installed, but also in adjacent parallel lines, remains to be studied. In the literature, it has normally been assumed the UPFC is disconnected during a fault period. In this investigation it has been shown that fault conditions can affect the UPFC significantly, even if it occurred on far buses of the power system. This forms the main contribution presented in this thesis. The impact of UPFC in minimizing the disturbances in voltages, currents and power flows under fault conditions are investigated. The WSCC 3-machine, 9-bus test system is used to investigate the effect of an unsymmetrical fault type and position on the operation of UPFC controller in accordance to the G59 protection, stability and regulation. Results show that it is necessary to disconnect the UPFC controller from the power system during unsymmetrical fault conditions.
    • An investigation of the influence of radiographic malpositioning and image processing algorithm selection on ICU/CCU chest radiographs

      Hardy, Maryann L.; Scally, Andy J.; Small, Neil A.; Elhain, Ahmed M.S.B. (University of BradfordSchool of Health Studies, 2015-07-15)
      Mobile chest radiography remains the most appropriate test for critical care patients with cardiorespiratory changes and with patients who have chest tubes and lines as a monitoring tool, and to detect complications related to their use. However, one of the most frequent issues recognized radiographically with patients in critical care is chest tubes and lines malposition. This can be related to technical quality reasons which can affect their appearance in the chest radiography. This research considers how the technical quality of the ICU/CCU chest radiography can impact upon the appearance of chest tubes/lines and how that appearance can impact on the decision making. Results show that the methods used in the chest phantom experiment to estimate the degree of angulation have a large effect upon the appearance of anatomical structures, but it does not have a particularly large effect upon the apparent changes of tube/line position central venous catheter and endotracheal tube (CVC, ETT). The study also shows that there was a little difference between the two image processing algorithms, apart from the visualisation of sharp reproduction of the trachea and proximal bronchi, which was significantly better using the standard algorithm compared to the inverted algorithm. The two methods used to estimate the degree of angulation and the apparent position of the CVC/ETT on 17 mobile chest radiographs provide limited useful information to the image interpreter in estimating the degree of angulation and degree of malpositioning of the tube and line.
    • Investigation of the prevalence of opportunistic gram negative pathogens in the water supply of a haematology unit, and the application of point-of-use filtration as an intervention.

      Snelling, Anna M.; Wright, Claire Louise (University of BradfordSchool of Medical Sciences, 2013-11-21)
      Gram-negative infection has been linked to hospital water although few studies have examined whether water systems are reservoirs of nosocomial pathogens. This study investigated longitudinal recovery of the opportunistic pathogens Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii from water outlets of a haematology unit and evaluated Point-Of-Use Filtration (POU-F) as a control measure. In a two-year double cross-over trial, water samples and swabs were taken weekly from 39 showers/taps on the unit. Four study phases alternated between non-filtered (Phases 1 & 3), and filtered outlets (Phases 2 & 4) using Pall AquasafeTM 14-day filters. In Phases 1 & 3; 99% of 1396 samples yielded bacterial growth, with colonies generally too numerous to count. Target species were isolated from 22% of water samples (P. aeruginosa 14%; S. maltophilia 10%) and 10% of swabs. P. aeruginosa was particularly associated with handwash stations and S. maltophilia with showers. A. baumannii was not isolated. With POU-F; 22% of 1242 samples yielded bacterial growth (mean CFU/100ml ,4.6). S. maltophilia was isolated only once from water but never from outlet swabs. PCR typing identified clusters of isolates colonizing different outlets over time but no clear association between water and patient isolates was identified. The incidence of Gram negative infections remained low throughout the study. Without POU-F, water from taps/showers represented a source of bacteria including the target species. POU-F substantially reduced the frequency and number of target species from every outlet, and merits further investigation as an intervention to protect immunocompromised patients from opportunistic pathogens.
    • An investigation of the relationship between the structure and function of the myopic eye. Correlating the optical, functional and structural aspects of ametropia in young adult humans.

      Mallen, Edward A.H.; Chisholm, Catharine M.; Pacey, Ian E.; Ehsaei, Asieh (University of BradfordBradford School of Optometry and Vision Science, 2013-04-09)
      The increasing prevalence of myopia over the past few decades and its association with potential ocular complications make myopia an important research topic. The present work is concerned with the structural and functional characteristics of a group of myopic and emmetropic individuals. The technical experiments in this work investigated firstly the effect of instrument alignment on peripheral refraction measurements and revealed that the corneal vertex was an acceptable alignment position of the Shin-Nippon NVision-K 5001 autorefractor, allowing consistent alignment with other instruments used in this research. Secondly, spectacles could be used to provide comparable vision to contact lenses in the visual performance studies. In the main experimental parts of this work, visual performance and multiple aspects of ocular structure were assessed across a wide range of eccentricities along the horizontal and vertical meridians within the same eyes. The structural properties of the myopic eye were measured through central and peripheral autorefraction, and through cornea to retina dimensions using non-contact biometry. In addition, the central and peripheral resolution acuities of myopic and emmetropic eyes for high and low contrast levels were investigated. Our structural and functional measurements revealed relatively prolate myopic eyes with reduced high contrast resolution acuity, compared to emmetropic eyes. Moreover, multiple regression analyses were performed at the fovea and outermost retinal eccentricities common to all core experiments but revealed no strong relationship between the structure and function of the myopic eye. Finally, regarding asymmetry, the nasal and superior retinae were found to be longer and to perform better in comparison to the temporal and superior retinae respectively.
    • Investigation, design and implementation of circular-polarised antennas for satellite mobile handset and wireless communications. Simulation and measurement of microstrip patch and wire antennas for handheld satellite mobile handsets and investigations of polarization polarity, specific absorption rate, and antenna design optimization using genetic algorithms.

      Abd-Alhameed, Raed A.; Excell, Peter S.; Khalil, Khaled (University of BradfordSchool of Engineering, Design and Technology, 2010-06-01)
      The objectives of this research work are to investigate, design and implement circularly-polarized antennas to be used for handheld satellite mobile communication and wireless sensor networks. Several antennas such as Quadrifilar Spiral Antennas (QSAs), two arm Square Spiral and stripline or coaxially-fed microstrip patch antennas are developed and tested. These antennas are investigated and discussed to operate at L band (1.61-1.6214GHz) and ISM band (2.4835-2.5GHz) A substantial size reduction was achieved compared to conventional designs by introducing special modifications to the antenna geometries. Most of the antennas are designed to produce circularly-polarized broadside-beam except for wireless sensor network application a circularly-polarized conical-beam is considered. The polarization purity and Specific Absorption Rate (SAR) of two dual-band antennas for satellite-mobile handsets next to the human head are investigated and discussed, using a hybrid computational method. A small distance between the head and the handset is chosen to highlight the effects of the relatively high-radiated power proposed from this particular antenna. A Genetic Algorithm in cooperation with an electromagnetic simulator has been introduced to provide fast, accurate and reliable solutions for antenna design structures. Circularly-polarized quadrifilar helical antenna handset and two air-dielectric microstrip antennas were studied. The capabilities of GA are shown as an efficient optimisation tool for selecting globally optimal parameters to be used in simulations with an electromagnetic antenna design code, seeking convergence to designated specifications. The results in terms of the antenna size and radiation performance are addressed, and compared to measurements and previously published data.