Dissertations / Theses on the topic 'Limit of Detection (LOD)'
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Jin, Yan. "Bayesian Solution to the Analysis of Data with Values below the Limit of Detection (LOD)." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1227293204.
Full textRodríguez, Cuesta Mª José. "Limit of detection for second-order calibration methods." Doctoral thesis, Universitat Rovira i Virgili, 2006. http://hdl.handle.net/10803/9013.
Full textThe lowest quantity of a substance that can be distinguished from the absence of that substance (a blank value) is called the detection limit or limit of detection (LOD). Traditionally, in the context of simple measurements where the instrumental signal only depends on the amount of analyte, a multiple of the blank value is taken to calculate the LOD (traditionally, the blank value plus three times the standard deviation of the measurement). However, the increasing complexity of the data that analytical instruments can provide for incoming samples leads to situations in which the LOD cannot be calculated as reliably as before.
Measurements, instruments and mathematical models can be classified according to the type of data they use. Tensorial theory provides a unified language that is useful for describing the chemical measurements, analytical instruments and calibration methods. Instruments that generate two-dimensional arrays of data are second-order instruments. A typical example is a spectrofluorometer, which provides a set of emission spectra obtained at different excitation wavelengths.
The calibration methods used with each type of data have different features and complexity. In this thesis, the most commonly used calibration methods are reviewed, from zero-order (or univariate) to second-order (or multi-linears) calibration models. Second-order calibration models are treated in details since they have been applied in the thesis.
Concretely, the following methods are described:
- PARAFAC (Parallel Factor Analysis)
- ITTFA (Iterative Target Transformation Analysis)
- MCR-ALS (Multivariate Curve Resolution-Alternating Least Squares)
- N-PLS (Multi-linear Partial Least Squares)
Analytical methods should be validated. The validation process typically starts by defining the scope of the analytical procedure, which includes the matrix, target analyte(s), analytical technique and intended purpose. The next step is to identify the performance characteristics that must be validated, which may depend on the purpose of the procedure, and the experiments for determining them. Finally, validation results should be documented, reviewed and maintained (if not, the procedure should be revalidated) as long as the procedure is applied in routine work.
The figures of merit of a chemical analytical process are 'those quantifiable terms which may indicate the extent of quality of the process. They include those terms that are closely related to the method and to the analyte (sensitivity, selectivity, limit of detection, limit of quantification, ...) and those which are concerned with the final results (traceability, uncertainty and representativity) (Inczédy et al., 1998). The aim of this thesis is to develop theoretical and practical strategies for calculating the limit of detection for complex analytical situations. Specifically, I focus on second-order calibration methods, i.e. when a matrix of data is available for each sample.
The methods most often used for making detection decisions are based on statistical hypothesis testing and involve a choice between two hypotheses about the sample. The first hypothesis is the "null hypothesis": the sample is analyte-free. The second hypothesis is the "alternative hypothesis": the sample is not analyte-free. In the hypothesis test there are two possible types of decision errors. An error of the first type occurs when the signal for an analyte-free sample exceeds the critical value, leading one to conclude incorrectly that the sample contains a positive amount of the analyte. This type of error is sometimes called a "false positive". An error of the second type occurs if one concludes that a sample does not contain the analyte when it actually does and it is known as a "false negative". In zero-order calibration, this hypothesis test is applied to the confidence intervals of the calibration model to estimate the LOD as proposed by Hubaux and Vos (A. Hubaux, G. Vos, Anal. Chem. 42: 849-855, 1970).
One strategy for estimating multivariate limits of detection is to transform the multivariate model into a univariate one. This strategy has been applied in this thesis in three practical applications:
1. LOD for PARAFAC (Parallel Factor Analysis).
2. LOD for ITTFA (Iterative Target Transformation Factor Analysis).
3. LOD for MCR-ALS (Multivariate Curve Resolution - Alternating Least Squares)
In addition, the thesis includes a theoretical contribution with the proposal of a sample-dependent LOD in the context of multivariate (PLS) and multi-linear (N-PLS) Partial Least Squares.
La Química Analítica es pot dividir en dos tipus d'anàlisis, l'anàlisi quantitativa i l'anàlisi qualitativa. La gran part de la química analítica moderna és quantitativa i fins i tot els govern fan ús d'aquesta ciència per establir regulacions que controlen, per exemple, nivells d'exposició a substàncies tòxiques que poden afectar la salut pública. El concepte de mínima quantitat d'un analit o component que es pot detectar apareix en moltes d'aquestes regulacions, en general com una part de la validació dels mètodes per tal de garantir la qualitat i la validesa dels resultats.
La mínima quantitat d'una substància que pot ser diferenciada de l'absència d'aquesta substància (el que es coneix com un blanc) s'anomena límit de detecció (limit of detection, LOD). En procediments on es treballa amb mesures analítiques que són degudes només a la quantitat d'analit present a la mostra (situació d'ordre zero) el LOD es pot calcular com un múltiple de la mesura del blanc (tradicionalment, 3 vegades la desviació d'aquesta mesura). Tanmateix, l'evolució dels instruments analítics i la complexitat creixent de les dades que generen, porta a situacions en les que el LOD no es pot calcular fiablement d'una forma tan senzilla. Les mesures, els instruments i els models de calibratge es poden classificar en funció del tipus de dades que utilitzen. La Teoria Tensorial s'ha utilitzat en aquesta tesi per fer aquesta classificació amb un llenguatge útil i unificat. Els instruments que generen dades en dues dimensions s'anomenen instruments de segon ordre i un exemple típic és l'espectrofluorímetre d'excitació-emissió, que proporciona un conjunt d'espectres d'emissió obtinguts a diferents longituds d'ona d'excitació.
Els mètodes de calibratge emprats amb cada tipus de dades tenen diferents característiques i complexitat. En aquesta tesi, es fa una revisió dels models de calibratge més habituals d'ordre zero (univariants), de primer ordre (multivariants) i de segon ordre (multilinears). Els mètodes de segon ordre estan tractats amb més detall donat que són els que s'han emprat en les aplicacions pràctiques portades a terme.
Concretament es descriuen:
- PARAFAC (Parallel Factor Analysis)
- ITTFA (Iterative Target Transformation Analysis)
- MCR-ALS (Multivariate Curve Resolution-Alternating Least Squares)
- N-PLS (Multi-linear Partial Least Squares)
Com s'ha avançat al principi, els mètodes analítics s'han de validar. El procés de validació inclou la definició dels límits d'aplicació del procediment analític (des del tipus de mostres o matrius fins l'analit o components d'interès, la tècnica analítica i l'objectiu del procediment). La següent etapa consisteix en identificar i estimar els paràmetres de qualitat (figures of merit, FOM) que s'han de validar per, finalment, documentar els resultats de la validació i mantenir-los mentre sigui aplicable el procediment descrit.
Algunes FOM dels processos químics de mesura són: sensibilitat, selectivitat, límit de detecció, exactitud, precisió, etc. L'objectiu principal d'aquesta tesi és desenvolupar estratègies teòriques i pràctiques per calcular el límit de detecció per problemes analítics complexos. Concretament, està centrat en els mètodes de calibratge que treballen amb dades de segon ordre.
Els mètodes més emprats per definir criteris de detecció estan basats en proves d'hipòtesis i impliquen una elecció entre dues hipòtesis sobre la mostra. La primera hipòtesi és la hipòtesi nul·la: a la mostra no hi ha analit. La segona hipòtesis és la hipòtesis alternativa: a la mostra hi ha analit. En aquest context, hi ha dos tipus d'errors en la decisió. L'error de primer tipus té lloc quan es determina que la mostra conté analit quan no en té i la probabilitat de cometre l'error de primer tipus s'anomena fals positiu. L'error de segon tipus té lloc quan es determina que la mostra no conté analit quan en realitat si en conté i la probabilitat d'aquest error s'anomena fals negatiu. En calibratges d'ordre zero, aquesta prova d'hipòtesi s'aplica als intervals de confiança de la recta de calibratge per calcular el LOD mitjançant les fórmules d'Hubaux i Vos (A. Hubaux, G. Vos, Anal. Chem. 42: 849-855, 1970)
Una estratègia per a calcular límits de detecció quan es treballa amb dades de segon ordre es transformar el model multivariant en un model univariant. Aquesta estratègia s'ha fet servir en la tesi en tres aplicacions diferents::
1. LOD per PARAFAC (Parallel Factor Analysis).
2. LOD per ITTFA (Iterative Target Transformation Factor Analysis).
3. LOD per MCR-ALS (Multivariate Curve Resolution - Alternating Least Squares)
A més, la tesi inclou una contribució teòrica amb la proposta d'un LOD que és específic per cada mostra, en el context del mètode multivariant PLS i del multilinear N-PLS.
Nqakala, Noniko Civilized. "Construction of an enzyme-free electrochemical sensor based on Ag-Fe2O3/POM/RGO novel nanocomposite for hydrogen peroxide detection." University of the Western Cape, 2018. http://hdl.handle.net/11394/6762.
Full textThe motivation to determine H2O2 lies in the fact that this chemical species plays a crucial role in diverse fields of practise such as cosmetic, food, diagnostic, pharmaceutical, clinical and environmental protection industries. Several methods such as chromatography, colorimetry, titrimetry and spectrophotometry have been developed for its detection. However, these methods are known to manifest underlying disadvantages such as high cost, time consuming, instability and complicated immobilization procedures. In this present study an enzyme-less electrochemical sensor based on Ag-Fe2O3/POM/RGO nanocomposite (POM stands for polyoxometalate and RGO stands for reduced graphene oxide) was successfully synthesised via a hydrothermal method and a photochemical reduction method for the detection of hydrogen peroxide (H2O2).
Oranzie, Marlon. "Electrochemical Aptasensing of B-Type Natriuretic Peptide-A Biomarker for Myocardial Infarction." University of the Western Cape, 2019. http://hdl.handle.net/11394/7707.
Full textinfarction (MI) affects many parts of the western world and in South Africa alone it is estimated that MI is responsible for 1 in 6 deaths (17.3%). Traditional diagnostic methods for MI include an electrocardiograms and blood tests. The problem with these diagnostic methods are that they are time consuming, require large sample volumes, expensive equipment and complicated machinery. To achieve early detection of MI the discovery of specific, sensitive and reliable biomarkers are required. Brain natriuretic peptide (BNP) has been identified as a reliable biomarker for MI due to the fact that it has a defined cutoff of 100 pg/ml and it is not susceptible to patient‘s age which could make early detection of BNP complicated. Early detection methods for BNP has been based on immunoradiometric assays but problems associated with immunoradiometric assays are that there is a restricted availability of antigens and incubation of the labeled antibody could take up to two weeks which affects the patients waiting time on results. Electrochemical biosensors are emerging as early detection method for MI because they can be designed to be sensitive, specific to BNP at a low cost. This research study reported for the first the successful fabrication and implementation of highly sensitive mercaptosuccinic acid capped nickel selenide quantum dots (MSA-NiSe2 QDs) aptasensor for the detection of BNP. The poly-dispersed MSA-NiSe2 QDs were synthesized via an inexpensive, simple and reproducible aqueous microwave assisted irradiation method. The prepared MSA-NiSe2 QDs were characterized by Ultraviolet spectroscopy (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), High Resolution Transmission/Scanning Electron Microscopy (HR TEM/SEM) and Small Angle X-ray Scattering (SAXSpace). The electrochemical properties of the MSA-NiSe2 QDs were investigated by Cylic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). HR-TEM revealed the formation of small sized MSA-NiSe2 QDs about 4 nm in diameter which was complemented by SAXSpace. UV-Vis studies showed absorption peaks in the ultraviolet region (100-400 nm) confirming the small size of these QDs as well confirming the direct and indirect bandgap of the QDs. XRD confirmed that the QDs are crystalline and belong to the bulk cubic MSA-NiSe2 QDs phase. FTIR studies confirmed the successful capping of MSA on the QDs due to the disappearance of the thiol peak at 2652 cm-1. Electrochemical studies revealed that the MSA-NiSe2 QDs showed good electrochemical properties on screen printed carbon electrodes (SPCE) which allowed them to be used as a mediating platform between the aptamer and SPCE. The successful detection of BNP was achieved by an incubation process between the aptamer drop coated on the MSA-NiSe2 QDs/SPCE surface overnight. The response of the MSA-NiSe2 QDs based aptasensor towards different concentrations of BNP was studied by differential pulse voltammetry (DPV). DPV showed a good linearly with correlation coefficient of R2 = 0.98. DPV also showed a high sensitivity (0.4513 μA/ pg/mL) towards detecting BNP with a detection limit of 11.93 pg/ml. The value of 11.93 pg/ml falls within the negative predictive value range of 10-100 pg/ml for early-stage diagnosis of BNP.
Mahmood, Rahimi. "Karatärisering av XRF-mätning med 120kV röntgenrör." Thesis, Mittuniversitetet, Institutionen för elektronikkonstruktion, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-42590.
Full textNgwanya, Olwethu. "Molecularly imprinted polymers for detection of volatile organics associated with fuel combustion." University of the Western Cape, 2018. http://hdl.handle.net/11394/6363.
Full textPollutants such as polycyclic aromatic hydrocarbons (PAHs) are known for their toxic effects which may lead to the cause of degenerative diseases in both humans and animals. PAHs are widespread in the environment, and may be found in water, food, automotive industry and petrochemical industries to name but a few sources. Literature reports have highlighted industrial workplace exposure to PAHs as a leading cause for development of cancer in workers. Particularly, workers in the petrochemical industry are adversely affected and the incidence of skin and lung cancer in this population group is high. The United States of America in its guidelines developed by environmental protection agency (EPA) has identified 18 PAHs as priority pollutants. Among these are anthracene, benzo[a]pyrene and pyrene which have been selected as the focal point of this study due to their significance in the petrochemical industry. Due to the carcinogenic and mutagenic properties reported in literature for certain PAHs, there have been monitoring procedures taken in most countries around the world. The commonly used analytical methods for the detection of PAHs from industrial samples are high performance liquid chromatography (HPLC) coupled to fluorescence detection, membrane filtration, ozonation and reverse osmosis. Analysis of PAHs from the petrochemical industry is typically performed by HPLC method as well as sono-degredation in the presence of oxygen and hydrogen peroxide.
Guo, Jing. "MULTI-MODE SELF-REFERENCING SURFACE PLASMON RESONANCE SENSORS." UKnowledge, 2013. http://uknowledge.uky.edu/ece_etds/13.
Full textFeleni, Usisipho. "Quantum dots-amplified electrochemical cytochrome P450 phenotype sensor for tamoxifen, a breast cancer drug." University of the Western Cape, 2017. http://hdl.handle.net/11394/5505.
Full textBreast cancer is regarded as the most common cancer in South Africa and its rate of occurrence is increasing. About one in every 31 South African women are at the risk of developing breast cancer and early diagnosis and treatment guarantee 90% survival rate. Tamoxifen is the drugs of choice for the treatment of all stages of breast cancer. The drug binds with estrogen receptor (ER) to minimize the transcription of estrogen dependent genes. However, nearly 50% of ER-positive breast cancer patients either become resistant or fail to respond to tamoxifen resulting in a serious clinical challenge in breast cancer management. The Grand Health Challenges of South Africa includes the development of cost effective diagnostic systems suitable for early detection of diseases and drug resistivity for timely invention and better patient management.
2020-08-31
Yavrucuk, Ilkay. "Adaptive limit margin detection and limit avoidance." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/12354.
Full textHorn, Joe. "Flight envelope limit detection and avoidance." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/12435.
Full textTallawi, Reham. "FPGA-based Speed Limit Sign Detection." Master's thesis, Universitätsbibliothek Chemnitz, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-qucosa-229018.
Full textLeutenegger, Anne-Louise B. "Estimation of random genome sharing : consequences for linkage detection." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/9574.
Full textRens, Bram Antonius Philomena van. "Detection of magnetic monopoles below the Cherenkov limit." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2006. http://dare.uva.nl/document/23682.
Full textHermansson, Albin. "View-Dependent Collision Detection and Response Using Octrees." Thesis, Blekinge Tekniska Högskola, Institutionen för kreativa teknologier, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-12751.
Full textKirwa, Abraham Tuwei. "Self-referenced evanescent wave sensor for low limit of detection applications." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22475/.
Full textHeaney, S. F. "Development of a low detection limit Cu(II) ISE for complexation studies." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419362.
Full textDick, Nicole Marie. "Methods for handling missing data due to a limit of detection in longitudinal lognormal data." Manhattan, Kan. : Kansas State University, 2008. http://hdl.handle.net/2097/867.
Full textSharma, Siddhartha Mohan. "Optimizing the lower limit of detection of proteins for use in a novel diagnostic device for cancer." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12620.
Full textCancer is a major health concern throughout the United States and around the world. It is the second most common cause of death in the United States. However, since the 1970's survivorship has increased for many types of cancer. Cancer diagnostics, in addition to better and more targeted treatment, have been critical to this success. Current gold standard methods have significant limitations which can lead to delays in treatment or require more invasive procedures that need a significant amount of tissue for accurate diagnosis. One approach to improve current diagnostic methods is to use proteomics and microfluidic devices to create an integrated diagnostic device. A microfluidic device, built as a porous polymer monolith, can be utilized for solid phase extraction for protein biomarkers that are indicative of cancer. Microfluidic devices have already been used to extract RNA from bacteria, viruses and, in a previous study, for extracting miRNA from human cancer cells in large enough quantities to be useful as a diagnostic assay and require a significant amount of tissue. The aim of this study is to validate the presence of select protein biomarkers, to determine the lower limit of detection of these biomarkers and to quantify them from two cancer cell lines. This study is being conducted in support of a larger project's goal to design a cheap, disposable, plastic microfluidic chip for the analysis of protein biomarkers that are indicative of cancer and intended for use in a bench top machine. Ultimately, the chip's utility will be validated by analyzing small volume human specimens. BCPAP, a thyroid cancer cell line, and MCF-7, a breast cancer cell line, will be used to demonstrate the chips ability to extract, from whole cell lysates, the following protein biomarkers: Estrogen Receptor-alpha, Estrogen Receptor-beta, Thyroid Transcription Factor-1, Thyroglobulin, Human Epidermal Growth Factor Receptor-2, and E-cadherin from whole celllysates.
Muro, Claire K. "Further Development of Raman Spectroscopy for Body Fluid Investigation| Forensic Identification, Limit of Detection, and Donor Characterization." Thesis, State University of New York at Albany, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10275358.
Full textThe challenges to forensic body fluid analysis have placed limitations on the type of information that investigators can acquire and how that information can be collected. In recent years, Raman spectroscopy has proven itself useful for characterizing body fluids. In 2008, a large-scale investigation was undertaken to explore the use of Raman spectroscopy as a means of identifying body fluids. This work resulted in multidimensional Raman spectroscopic signatures for the five main body fluids: semen, peripheral blood, saliva, vaginal fluid, and sweat. These studies were incredibly successful and created the foundation for years of continued research. Accordingly, the studies included in this thesis have been specifically chosen to frame the previous research projects. They include a suite of projects aimed to advance and validate the developed method.
First, a statistical model was developed to automatically identify and differentiate body fluids based on their Raman spectra. The multidimensional spectroscopic signatures mentioned above are very effective at identification, but they are body fluid-specific. In other words, they individually evaluate whether or not an unknown spectrum is from a particular body fluid, such as blood. Additionally, each signature was built on spectra from a limited number of donors. To improve on this capability, a single classification model was built on the Raman spectra from 60 donors (12 for each body fluid). This model was externally validated with an additional 15 donors in order to objectively assess the model’s performance. All of the external validation donors were correctly identified, illustrating how accurate and robust the model is.
Second, the limit of detection (LOD) for the classification model was explored as a form of validation. It is vitally important that a method’s limits be established before deploying it into use. The LOD of peripheral blood was investigated. Peripheral blood is unique from other body fluids because its Raman spectrum has been attributed almost entirely to one molecule- hemoglobin. Because hemoglobin is only found in red blood cells (RBCs), the Raman spectrum of peripheral blood essentially results purely from RBCs. Given this, we chose to start with a single RBC, and then increase the volume until identification was successful. We found that we were able to conclusively and confidently identify peripheral blood using a single red blood cell. This limit is 5000X smaller than the amount of blood required for DNA analysis, demonstrating the sensitivity of the developed method.
Finally, the method was further advanced by incorporating donor characterization into the process. Besides identifying body fluids, the method can now extract “phenotypic” information about the donor. Raman spectroscopy and multivariate data analysis were used to determine the biological sex of saliva donors, and the race of semen donors. These studies will help forensic investigators extract incredibly useful information about a potential suspect or victim, and can be performed directly at a crime scene for instant results.
Altogether, these studies combine to strengthen the method previously developed by our research group. More importantly, they help to bridge the gap between research and application. Creating a universal method to differentiate and identify body fluids, investigating the method’s LOD, and developing additional techniques to characterize body fluids represents a significant contribution to the field of forensic chemistry. The universal method created within this thesis will be adapted to perform on-site analysis of physical evidence at crime scenes. The methods’ incredible sensitivity has been demonstrated by determining that it can identify peripheral blood based on a single RBC. Finally, by developing models to characterize body fluid donors, investigators will be able to extract useful information about individuals that may have been present at a crime scene. Additional studies are already being conducted to make further improvements, and our method is poised to make a significant contribution to the field of crime scene investigation.
Urbano, Simone. "Detection and diagnostic of freeplay induced limit cycle oscillation in the flight control system of a civil aircraf." Thesis, Toulouse, INPT, 2019. http://www.theses.fr/2019INPT0023/document.
Full textThis research study is the result of a 3 years CIFRE PhD thesis between the Airbus design office(Aircraft Control domain) and TéSA laboratory in Toulouse. The main goal is to propose, developand validate a software solution for the detection and diagnosis of a specific type of elevator andrudder vibration, called limit cycle oscillation (LCO), based on existing signals available in flightcontrol computers on board in-series aircraft. LCO is a generic mathematical term defining aninitial condition-independent periodic mode occurring in nonconservative nonlinear systems. Thisstudy focuses on the LCO phenomenon induced by mechanical freeplays in the control surface ofa civil aircraft. The LCO consequences are local structural load augmentation, flight handlingqualities deterioration, actuator operational life reduction, cockpit and cabin comfort deteriorationand maintenance cost augmentation. The state-of-the-art for freeplay induced LCO detection anddiagnosis is based on the pilot sensitivity to vibration and to periodic freeplay check on the controlsurfaces. This study is thought to propose a data-driven solution to help LCO and freeplaydiagnosis. The goal is to improve even more aircraft availability and reduce the maintenance costsby providing to the airlines a condition monitoring signal for LCO and freeplays. For this reason,two algorithmic solutions for vibration and freeplay diagnosis are investigated in this PhD thesis. Areal time detector for LCO diagnosis is first proposed based on the theory of the generalized likeli hood ratio test (GLRT). Some variants and simplifications are also proposed to be compliantwith the industrial constraints. In a second part of this work, a mechanical freeplay detector isintroduced based on the theory of Wiener model identification. Parametric (maximum likelihoodestimator) and non parametric (kernel regression) approaches are investigated, as well as somevariants to well-known nonparametric methods. In particular, the problem of hysteresis cycleestimation (as the output nonlinearity of a Wiener model) is tackled. Moreover, the constrainedand unconstrained problems are studied. A theoretical, numerical (simulator) and experimental(flight data and laboratory) analysis is carried out to investigate the performance of the proposeddetectors and to identify limitations and industrial feasibility. The obtained numerical andexperimental results confirm that the proposed GLR test (and its variants/simplifications) is a very appealing method for LCO diagnostic in terms of performance, robustness and computationalcost. On the other hand, the proposed freeplay diagnostic algorithm is able to detect relativelylarge freeplay levels, but it does not provide consistent results for relatively small freeplay levels. Moreover, specific input types are needed to guarantee repetitive and consistent results. Further studies should be carried out in order to compare the GLRT results with a Bayesian approach and to investigate more deeply the possibilities and limitations of the proposed parametric method for Wiener model identification
Láznička, Jan. "Analýza spolehlivosti měření látek pomocí biosenzorů - návrh robustní metody stanovení limitu detekce." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2008. http://www.nusl.cz/ntk/nusl-217622.
Full textSherman, Brook W. "The Examination and Evaluation of Dynamic Ship Quiescence Prediction and Detection Methods for Application in the Ship-Helicopter Dynamic Interface." Thesis, Virginia Tech, 2007. http://hdl.handle.net/10919/32436.
Full textThis thesis defines and examines the use of two methodical approaches to evaluating Landing Period Indicators (LPIs) and their subject ship-helicopter dynamic interface system. First a methodology utilizing the comparison of a basic transparent algorithm is detailed and a case study employing this methodology is examined. Second, a system dynamics approach is taken to pilot workload analysis, utilizing a dynamic systems model characterizing a subset of the Dynamic Interface. This approach illustrates the realistic gains in understanding and development that can be accomplished by utilizing system dynamics in the analysis of the Dynamic Interface and LPI insertion.
Master of Science
Schreiber, Emil [Verfasser]. "Gravitational-wave detection beyond the quantum shot-noise limit : the integration of squeezed light in GEO 600 / Emil Schreiber." Hannover : Gottfried Wilhelm Leibniz Universität Hannover, 2018. http://d-nb.info/1172414548/34.
Full textZosiwe, Mlandeli Siphelele Ernest. "Cytochrome P450 2E1/Nickel-Poly(propylene imine) dendrimeric nanobiosensor for pyrazinamide - A first line TB Drug." University of the Western Cape, 2015. http://hdl.handle.net/11394/4703.
Full textThe tuberculosis (TB) disease to this day remains one of the world’s prominent killerdiseases. Pyrazinamide (PZA) is one of the most commonly prescribed anti- tuberculosis (anti-TB) drugs due to its ability to significantly shorten the TB treatment period from the former nine months to the current six months duration. However, excess PZA in the body causes hepatotoxicity and damages the liver. This hepatotoxicity, together with the resistance of the bacteria to treatment drugs, poor medication and inappropriate dosing, greatly contribute to the high incidents of TB deaths and diseases that are due to side effects (such as liver damage). This brings about the calls for alternative methods for ensuring reliable dosing of the drug, which will be specific from person to person due to inter-individual differences in drug metabolism. A novel biosensor system for monitoring the metabolism of PZA was prepared with a Ni-PPI-PPy star copolymer and cytochrome P450 2E1 (CYP2E1) deposited onto a platinum electrode. The nanobiosensor system exhibited enhanced electro-activity that is attributed to the catalytic effect of the incorporated star copolymer. The biosensor had a sensitivity of 0.142 µA.nM-1, and a dynamic linear range (DLR) of 0.01 nM-0.12 nM (1.231 – 7.386 ng/L PZA). The limit of detection of the biosensor was found to be 0.00114 nM (0.14 ng/L) PZA. From the HPLC peakconcentration (Cmax) of PZA determined 2 h after drug intake is 2.79 – 3.22 ng.L-1,which is very detectable with the nanobiosensor as it falls within the dynamic linear range.
Gutiérrez, Arenas Omar. "Sensitivity, Noise and Detection of Enzyme Inhibition in Progress Curves." Doctoral thesis, Uppsala University, Department of Biochemistry, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6886.
Full textStarting with the development of an enzymatic assay, where an enzyme in solution hydrolysed a solid-phase bound peptide, a model for the kinetics of enzyme action was introduced. This model allowed the estimation of kinetic parameters and enzyme activity for a system that has the peculiarity of not being saturable with the substrate, but with the enzyme. In a derivation of the model, it was found that the sensitivity of the signal to variations in the enzyme concentration had a transient increase along the reaction progress with a maximum at high substrate conversion levels.
The same behaviour was derived for the sensitivity in classical homogeneous enzymatic assays and experimental evidence of this was obtained. The impact of the transient increase of the sensitivity on the error structure, and on the ability of homogeneous end-point enzymatic assays to detect competitive inhibition, came into focus. First, a non-monotonous shape in the standard deviation of progress curve data was found and it was attributed to the random dispersion in the enzyme concentration operating through the transient increase in the sensitivity. Second, a model for the detection limit of the quantity Ki/[I] (the IDL-factor) as a function of the substrate conversion level was developed for homogeneous end-point enzymatic assays.
It was found that the substrate conversion level where the IDL-factor reached an optimum was beyond the initial velocity range. Moreover, at this optimal point not only the ability to detect inhibitors but also the robustness of the assays was maximized. These results may prove to be relevant in drug discovery for optimising end point homogeneous enzymatic assays that are used to find inhibitors against a target enzyme in compound libraries, which are usually big (>10000) and crowded with irrelevant compounds.
Willemse, Chandre Monique. "Nanocomposite-graphene based platform for heavy metal detection." Thesis, University of the Western Cape, 2010. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_8123_1323852117.
Full textLiu, Jun. "Biomarker Detection at Risk Forecasting Level Using Metal-Enhanced Fluorescence Combined with Surface Acoustic Wave." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6534.
Full textGutierrez, Arenas Omar. "Sensitivity, Noise and Detection of Enzyme Inhibition in Progress Curves." Doctoral thesis, Uppsala universitet, Institutionen för naturvetenskaplig biokemi, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6886.
Full textPanahi, Tayyebeh. "Glutamic Acid Resorcinarene-based Molecules and Their Application in Developing New Stationary Phases in Ion Chromatography." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6436.
Full textKeathley, Phillip Donald. "DESIGN AND ANALYSIS OF NANO-GAP ENHANCED SURFACE PLASMON RESONANCE SENSORS." UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_theses/643.
Full textMartin-Rémy, Aurélie. "Analyse de données de biométrologie : aspects méthodologiques et applications." Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0223/document.
Full textMany biomonitoring studies are conducted at INRS, in order to assess occupational exposure to chemicals in France, and to propose reference values to protect workers exposed to these substances. These studies consist in measuring simultaneously biological and airborne exposure of workers exposed to a toxic substance. The relationship between these biological and airborne measurements is then estimated through a linear regression model. When this relationship exists and the route of absorption of the toxic is essentially inhalatory, it is possible to derive a Biological Limit Value (BLV) from the Occupational Exposure Limit Value (OEL) of the toxic substance. However, two characteristics of these data have been identified, which are not or only partially taken into account in the current statistical modelling: the left-censoring due to limits of detection (LoD)/quantification (LoQ) of biological and airborne measurements, and the between-individual variability. Ignoring both of these features in modelling leads to a loss of statistical power and potentially biased conclusions. The work carried out in this thesis allowed us to adapt the regression model to these two characteristics, in a Bayesian framework. The proposed approach is based on the modelling of airborne measurements using random effects models adapted for values below the LoD / LoQ, and on the simultaneous modelling of biological measurements, assumed to depend linearly on a logarithmic scale, on the airborne exposure, while taking into account between-subject variability. This work resulted in a scientific publication in a peer-reviewed journal. This methodology has been applied on beryllium and chromium occupational exposure datasets, after adaptation to the toxicokinetic characteristics of these two substances. It has thus been possible to propose a BLV for beryllium (0.06 μg / g creatinine). The analysis of chromium measurements in two different sectors of activity (occupational exposure to chromate paints, and occupational exposure in the electroplating sector) made it possible to show that urinary chromium depends mainly on airborne exposure to VI chromium, non-VI chromium having less impact. We were not able to show a relationship between the solubility of airborne VI chromium and urinary chromium. A BLV of 0.41 μg / g creatinine, close to the Biological Guidance Value (BGV) proposed by ANSES (0.54 μg / g creatinine), was estimated for occupational exposure to chromate paints, and a BLV of 1.85 μg/g creatinine was obtained for occupational exposure in the electrolytic chromium plating sector, which is consistent with the ANSES proposed BLV in this sector, i-e 1.8 μg / g creatinine
Dhingra, Manuj. "Compressor stability management." Diss., Available online, Georgia Institute of Technology, 2006, 2006. http://etd.gatech.edu/theses/available/etd-01102006-174943/.
Full textPrasad, J.V.R., Committee Chair ; Neumeier, Yedidia, Committee Member ; Seitzman, Jerry, Committee Member ; Sankar, Lakshmi, Committee Member ; Wadia, Aspi, Committee Member.
Sabek, Jad. "Combination of nanophotonic biosensors and light-assisted immobilization procedures for the detection of cardiac biomarkers." Doctoral thesis, Universitat Politècnica de València, 2019. http://hdl.handle.net/10251/124821.
Full text[CAT] L'atenció a la salut és un camp en què la detecció precoç de malalties està cobrant cada vegada més importància. Hui en dia, professionals i ciutadans demanen que les tècniques de diagnòstic siguin d'alta qualitat, tant per al sistema de sanitat privat com per al públic. Quan s'utilitzen tècniques de diagnòstic de manera inadequada, això pot comportar bastants conseqüències, com ara, un seriós perill sobre la salut i la sobrecàrrega tècnica i econòmica dels serveis de salut. Això és degut al fet que les tècniques de diagnòstic disponibles hui en dia són molt costoses, centralitzades en laboratoris i necessiten professionals altament qualificats per poder realitzar aquestes tasques, lo que comportaria a una demora en el temps que moltes vegades es vital pels malalts. És molt necessari, per tant, reflexionar sobre la necessitat i emergència de tals practiques preventives, especialment per a malalties d'alt risc com el càncer, l'Alzheimer o la primera causa de mort al món, les malalties cardiovasculars. En aquest context, l'objectiu principal del treball realitzat durant aquesta Tesi Doctoral és ajudar a superar aquests problemes mitjançant l'exploració de la possibilitat d'utilitzar tecnologia fotònica per al desenvolupament de sistemes d'anàlisis que puguin ser utilitzats per al diagnòstic i pronòstic de les malalties cardiovasculars. Aquest objectiu s'ha abordat mitjançant la combinació de la tecnologia nanofotònica, consistint en la nanofabricació de les estructures de detecció de PBG fotòniques que ofereix diversos beneficis, com una alta sensibilitat, una extrema reducció de mida i un procés de fabricació compatible amb el de la indústria microelectrònica, amb un mètode de biofuncionalització obtenint una capa de bio-reconeixement estable i selectiva mitjançant l'ús de la reacció TEC assistida per llum capaç de proporcionar unes capes de bioreconeixement extremadament fines amb una immobilització espacialment selectiva. preventives, especialment per a malalties d'alt risc com el càncer, l'Alzheimer o la primera causa de mort al món, les malalties cardiovasculars. En aquest context, l'objectiu principal del treball realitzat durant aquesta Tesi Doctoral és ajudar a superar aquests problemes mitjançant l'exploració de la possibilitat d'utilitzar tecnologia fotònica per al desenvolupament de sistemes d'anàlisis que puguin ser utilitzats per al diagnòstic i pronòstic de les malalties cardiovasculars. Aquest objectiu s'ha abordat mitjançant la combinació de la tecnologia nanofotònica, consistint en la nanofabricació de les estructures de detecció de PBG fotòniques que ofereix diversos beneficis, com una alta sensibilitat, una extrema reducció de mida i un procés de fabricació compatible amb el de la indústria microelectrònica, amb un mètode de biofuncionalització obtenint una capa de bio-reconeixement estable i selectiva mitjançant l'ús de la reacció TEC assistida per llum capaç de proporcionar unes capes de bioreconeixement extremadament fines amb una immobilització espacialment selectiva.
[EN] Healthcare is a field where the early detection of diseases is becoming more and more important. Nowadays, professionals and citizens demand high quality diagnosis techniques offered by both private and public health systems. When the application of diagnostic tests is not adequate, different consequences can be observed such as health hazard and technical and economic overload of health services. This is due to the fact that the diagnostic techniques available are expensive, centralized in laboratories and with the need for highly qualified professionals to carry out these tasks, what can fundamentally lead to delays in time, being critical for the patient's health. It is very necessary, therefore, to reflect on the need and emergency of such preventive practices, especially for high-risk diseases such as cancer, Alzheimer or the first cause of death in the world, the cardiovascular diseases. Within this context, the main objective of the work done during this PhD Thesis is to help on overcoming these problems by exploring the possibility of using photonic technology for the development of analysis devices which might be used for the early diagnosis and prognosis of cardiovascular diseases. This objective has been addressed by combining nanophotonic technology, by the nanofabrication of the photonic PBG sensing structures, which provides several benefits such as a high sensitivity, an extreme size reduction and a fabrication process being compatible with that from the microelectronics industry, with a light-assisted biofunctionalization method forming a stable and selective biorecognition layer using TEC reaction able to provide extremely thin biorecognition layers with a spatially-selective immobilization.
Sabek, J. (2019). Combination of nanophotonic biosensors and light-assisted immobilization procedures for the detection of cardiac biomarkers [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124821
TESIS
Badjatya, Vaibhav. "TUNABLE LASER INTERROGATION OF SURFACE PLASMON RESONANCE SENSORS." UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_theses/588.
Full textGilder, Jason R. "Computational methods for the objective review of forensic DNA testing results." Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1183999841.
Full textGursoy, Gonenc. "Neural Network Based Online Estimation Of Maneuvering Steady States And Control Limits." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612147/index.pdf.
Full textSomerse, Vernon Sydwill. "Mercaptobenzothiazole-on-Gold Biosensor Systems for Organophosphate and Carbamate Pesticide Compounds." Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_1006_1264535891.
Full textThis study firstly reports the development, characterisation, and application of thick-film acetylcholinesterase (AChE) biosensors based on a gold electrode modified with a mercaptobenzothiazole (MBT) self-assembled monolayer and either poly(omethoxyaniline) (POMA) or poly(2,5-dimethoxyaniline) (PDMA) in the presence of polystyrene(4-sulphonic acid) (PSSA). The Au/MBT/POMA-PSSA/AChE and Au/MBT/PDMA-PSSA/AChE biosensors were then applied to successfully detect standard organophosphorous and carbamate pesticides in a 0.1 M phosphate buffer, 0.1 M KCl (pH 7.2) solution. Secondly, it reports the construction of the Au/MBT/PANI/AChE/PVAc thick-film biosensor for the determination of certain organophosphate and carbamate pesticide solutions in selected aqueous organic solvent solutions.
Engström, Adam. "Metal mobility during metamorphism and formation of orogenic gold deposits: Insights from the Dalradian of Scotland." Thesis, Stockholms universitet, Institutionen för geologiska vetenskaper, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-92297.
Full textPipes, Latisha C. "Detection of Illicit Drug Use in Blood: A Validation Study of Solid Phase Extraction Coupled with Liquid Chromatography and Tandem Mass Spectrometry." Bowling Green State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1587613608312474.
Full textTrisiripisal, Phichet. "Image Approximation using Triangulation." Thesis, Virginia Tech, 2003. http://hdl.handle.net/10919/33337.
Full textMaster of Science
Skočovská, Katarína. "Detekce těžkých kovů v kapalinách metodou spektrometrie laserem buzeného plazmatu." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2015. http://www.nusl.cz/ntk/nusl-231994.
Full textRabus, David. "Résonateurs à ondes élastiques de volume à modes harmoniques élevés (HBARs) pour mesures gravimétriques : application à la détection de gaz." Thesis, Besançon, 2013. http://www.theses.fr/2013BESA2038/document.
Full textThe demand for compact and autonomous systems devoted to field detection of gaseous compounds is still persisting in arapidly changing international context (food-processing, sustainable development, security, and so on). The thesis reportedin this manuscript, supported by the Délégation Générale de l’Armement, develops new resonant sensor solutions basedon high overtone bulk acoustic waves (so-called HBARs) for chemical compound detection and more specifically explosivesubstances. These high compactness resonators are built using a transducer bound or deposited onto a resonant cavity,yielding a comb spectrum modulating its own frequency response. They are used generally as dipoles, but a quadrupolestructure allowing for transverse mode coupling has been particularly used for our developments. A theoretical study ofthe behaviour of these devices based on lithium niobate-on-quartz or qluminum nitride-on-silicon material stack has beenachieved to determine the gravimetric properties of these configurations accounting for their mode specificities. Variouscalibration techniques have been implemented to confirm the theoretical analysis and to define the most appropriate structurefor a given application. The produced results have been compared to those of a quartz guided-wave micro-balance toemphasize the strength (compactness, reduced chemical kinetics, multiphysics measurements) and weakness (gravimetricsensitivity requiring device thickness less than 100 μm) of our devices. An embedded signal processing electronics alsohas been developed to treat the information provided by our sensors, offering fast or accurate (millidegree range) detectionprotocols. The dedicated electronics aims at providing the flexibility needed to track multiple modes at variaous fixed frquencieswhile getting rid of the long sweep time of general purpose network analyzers. A eight-channel version of thissystem has been set to process several sensor in parallel or to monitor several modes of two HBAR sensors for effectivemuti-physics measurements in a reduced analysis domain (a few cubic mm). Phase noise is the limiting factor determiningthe detection limit. The system has been deployed for gas detection as well as for monitoring other physical parameters suchas temperature or viscosity under various experimental condition including fluid media
Ntshongontshi, Nomaphelo. "Molecularly imprinted polymer sensor systems for environmental estrogenic endocrine disrupting chemicals." University of the Western Cape, 2018. http://hdl.handle.net/11394/6241.
Full textThere is growing concern on endocrine disrupting compounds (EDCs). The presence of drugs in water supplies was first realized in Germany in the early 1990s when environmental scientists discovered clofibric acid. Clofibric acid has the ability to lower cholesterol in ground water below a water treatment plant. Endocrine disrupting compounds can be defined as those chemicals with the ability to alter daily functioning of the endocrine system in living organisms. There are numerous molecules that are regarded or referred to as EDCs such as but not limited to organochlorinated pesticides, industrial chemicals, plastics and plasticizers, fuels, estrogens and many other chemicals that are found in the environment or are in widespread use. 17?- estradiol is the principal estrogen found in mammals during reproductive years. Estriol is produced in large quantities during pregnancy. 17?-estradiol is the strongest, estriol the weakest. Estriol is water soluble, estrone and estradiol are not. Although estrogen is produced in women they are also at risk of over exposure to estrogen. Pesticides are extensively used today in agricultural settings to prevent and control pests. Various pesticides, including banned organochlorines (OCs) and modern non-persistent pesticides, have shown the ability to disrupt thyroid activity, disturbing the homeostasis of the thyroid system. Because these EDCs have adverse effects on health of both human and wildlife, it is imperative to develop viable costeffective analytical methods for the detection of these EDCs in complicated samples and at very low concentrations. Very high selectivity towards particular compounds is a very important property for the suitability of a detection method. This is because these compounds mostly coexist in complex matrices which makes the detection of a specific compound very challenging. It is paramount to develop highly sensitive and selective methods for the detection of these estrogens and phosphoric acid-based pesticides at trace levels.
2021-08-31
HUNTER, TINA D. "Gibbs Sampling and Expectation Maximization Methods for Estimation of Censored Values from Correlated Multivariate Distributions." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212157899.
Full textSchelin, Lina. "Spatial sampling and prediction." Doctoral thesis, Umeå universitet, Institutionen för matematik och matematisk statistik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-53286.
Full textHUANG, HE. "REDUCTION OF PERCHLORATE BY ZERO VALENT IRON." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1131047520.
Full textKunnil, Joseph. "Identification Studies of Bacillus Spores Using Fluorescence Spectroscopy." Thesis, University of Canterbury. Physics and Astronomy, 2005. http://hdl.handle.net/10092/1311.
Full textTrolise, Rodrigo Matias. "Desenvolvimento de metodologia para funcionalizar superfícies de ouro com biomoléculas. Construção de biosensor para detecção de citocromo c." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-12042011-135130/.
Full textIn this work we developed new strategies to functionalize gold surfaces based on the support of lipid bilayers on the surfaces of surface plasmon resonance imaging sensors (SPRi) and the construction of a biosensor for detection of cytochrome c. SPRi is an optical gravimetric real time technique. Through measurements of changes in refractive index (n) in close proximity to an interface, the adsorption and desorption of molecules can be measured. Initially we tested several strategies for finding a suitable medium that would adsorb on the gold surface and also support and stabilize a biotinylated phospholipid bilayer. Studies of FT-IR and SEM showed that chitosan induces the formation of an intact phospholipid bilayer, so that it reaches thickness values close to those expected, ~ 34.5 Å. Furthermore, we showed that this system has advantages in relation to other models, such as (poli-lisine/phospholipids) and (thiol hydrophobic / phospholipid). Using the chemical complex biotin/streptavidin anti cyt c antibody could be immobilized in the bilayer, keeping it away from the gold surface. The construction of the biosensor was accompanied with SPRi experiments. The limit of detection of cytochrome c was achieved from 10-11mol / L. A sensor built only with BSA and anti cyt c showed similar sensitivity. This sensitivity is about three orders of magnitude higher than the immunoblotting experiments commonly used for detection of cyt c. The main limitation of this biosensor, like in other immunoassays, is linked to the advantages and disadvantages of antibodies as analytical tools.
Mappa, Charlotte. "Exploration de nouveaux concepts pour les analyses quantitatives et fonctionnelles de microbiotes modèles d'intérêt dual." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT055.
Full textThe detection and identification of pathogenic microorganisms is a real public health issue for the food industry and the clinics or national interest as illustrated in the biodefense field. Thus, it is important to have identification and detection methods that are fast, sensitive and robust. This PhD thesis aims at contributing to the development of a rapid approach to identify microorganisms without any a priori by tandem mass spectrometry. This innovative approach, called phylopeptidomics, is based on the combination of peptidomics, i.e. large scale analysis of peptides derived from the enzymatic digestion of a biological sample, and the phylogeny of cellular organisms. After extraction of the proteins from the sample of interest, peptides are generated and analyzed by tandem mass spectrometry. The deconvolution of MS/MS signals using the "μOrg.ID" software developed in the laboratory enables the identification and quantification of organisms present in the sample according to the organisms indexed in generalist databases. The study of the proteome of Bacillus atrophaeus, a simulant agent of anthrax, in sporulated and vegetative form, has provided an illustration of a new method of identification of protein biomarkers, which allows determining the ratio between both forms. The limit of detection of phylopeptidomics in pure samples and equimolar mixtures was established with model bacteria of medical and environmental interests. The limit of detection of B. atrophaeus spores in the presence of 14 interfering matrices (food, environmental and others) has highlighted the advantages and limitations of the approach. Finally, a standardized artificial mixture of 24 organisms was developed in order to evaluate bioinformatics tools in metaproteomics
Shafiullah, Syed N. "On the role of correspondence noise in human visual motion perception. A systematic study on the role of correspondence noise affecting Dmax and Dmin, using random dot kinematograms: A psychophysical and modelling approach." Thesis, University of Bradford, 2008. http://hdl.handle.net/10454/4280.
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