Li, Gang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 102-108). / Abstracts in English and Chinese. / TABLE OF CONTENTS --- p.v / LIST OF FIGURES --- p.viii / LIST OF TABLES --- p.xi / ABBREVIATIONS --- p.xii / Chapter Chapter One --- Introduction / Chapter 1.1 --- Matrix-assisted Laser Desorption/Ionization (MALDI) --- p.2 / Chapter 1.1.1 --- Laser Desorption --- p.2 / Chapter 1.1.2 --- Matrix-assisted Laser Desorption/Ionization --- p.2 / Chapter 1.2 --- Time-of-flight Mass Spectrometry --- p.6 / Chapter 1.2.1 --- Linear Time-of-flight Mass Spectrometer --- p.6 / Chapter 1.2.2 --- Reflectron Time-of-flight Mass Spectrometer --- p.7 / Chapter 1.2.2.1 --- Linear-field Reflectron --- p.9 / Chapter 1.2.2.2 --- Nonlinear-field Reflectron --- p.12 / Chapter 1.3 --- Structural Analysis Using Time-of-flight Mass Spectrometer --- p.13 / Chapter 1.4 --- Project Objectives --- p.17 / Chapter Chapter Two --- Instrumentation and Experimental / Chapter 2.1 --- Instrumentation --- p.20 / Chapter 2.1.1 --- Laser system --- p.20 / Chapter 2.1.2 --- Flight Tube and Vacuum System --- p.20 / Chapter 2.1.3 --- Ion source --- p.22 / Chapter 2.1.4 --- Deflector and Time Ion Selector --- p.24 / Chapter 2.1.5 --- Two-stage Gridless Reflectron --- p.28 / Chapter 2.1.6 --- "Detectors, Digitizer and Computer System" --- p.28 / Chapter 2.2 --- Experimental --- p.31 / Chapter 2.2.1 --- Sample preparation --- p.32 / Chapter 2.2.2 --- PSD calibration --- p.32 / Chapter Chapter Three --- "Simulation Studies of Time Ion Selector, Collision cells and Curved-field Reflectron" / Chapter 3.1 --- Introduction --- p.35 / Chapter 3.2 --- Time Ion selector --- p.37 / Chapter 3.3 --- Collision cell --- p.46 / Chapter 3.3.1 --- Simulation of Collision Induced Dissociation (CID) Conditions --- p.46 / Chapter 3.3.2 --- Design and Performance Evaluation of Different Collision Cells --- p.48 / Chapter 3.4 --- Curved-field reflectron (CFR) --- p.58 / Chapter 3.4.1 --- Introduction --- p.58 / Chapter 3.4.2 --- Derivation of Analytical Equations --- p.58 / Chapter 3.4.3 --- Effect of Floating Potential of the Collision Cell --- p.65 / Chapter 3.4.4 --- Effect of R and θ Parameters --- p.65 / Chapter 3.4.5 --- Effect of Length of the Reflectron --- p.70 / Chapter 3.5 --- Conclusions --- p.73 / Chapter Chapter Four --- Construction and Performance Evaluation of Modified Time-of-flight Mass Spectrometer / Chapter 4.1 --- Benchmark Results for the Origin Reflectron Time-of-flight Mass Spectrometer --- p.75 / Chapter 4.2 --- Hardware Modifications of Reflectron Time-of-flight Mass Spectrometer --- p.75 / Chapter 4.2.1 --- Collision Cell --- p.75 / Chapter 4.2.2 --- Curved-field Reflectron --- p.79 / Chapter 4.3 --- Evaluation of the Curved-field Reflectron --- p.81 / Chapter 4.4 --- Evaluation of the field-shaped cylindrical collision cell --- p.85 / Chapter 4.5 --- Conclusions --- p.95 / Chapter Chapter Five --- Concluding Remarks / Chapter 5.1 --- Concluding Remarks --- p.100 / References --- p.101 / Appendix / Appendix 1 User program for time ion selection --- p.108 / Appendix 2 User program for gas collision --- p.111 / Appendix 3 MATHEMATICA program used in calculation for curved-fleld reflectron --- p.114

Isotachophoresis (ITP) coupled to capillary zone electrophoresis (CE) in a comprehensive manner was used to separate mixture components in both insufficient and sufficient concentrations without heart-cutting or splitting. Examples of comprehensive ITP-CE involving multiple CE injections of preconcentrated ITP zones are demonstrated. In the comprehensive arrangement, all of the sample in the first dimension (ITP) is subjected to analysis in the second dimension (CE), without significant sample loss or decrease in sample detectability resulting from removal of a portion of the sample. This is especially important for analytes at low concentrations which may form a single mixed zone instead of individual ITP zones. Direct online coupling of ITP to CE in this comprehensive arrangement involved the use of columns having different diameters with one directly inserted inside the other. A counterflow was applied when the isotachophoretic sample stack reached the bifurcation point. Large volume (10 µL) injections were made using an electrically-insulated commercial polymeric rotary valve injector for increased reproducibility compared to previous comprehensive ITP-CE studies, with ITP and CE retention time RSD values ranging from 2-5%. An ultraviolet (UV) detector positioned at the bifurcation point was used to determine the beginning of CE injection. Application of a splitting voltage at the bifurcation point showed no affect on analyte transfer into the CE column. By using multiple injections of the ITP band(s), CE column overloading was not observed. Online capillary isotachophoresis (ITP) and comprehensive isotachophoresis-capillary electrophoresis (ITP-CE) were also coupled with electrospray ionization (ESI)-orthogonal acceleration time-of-flight mass spectrometry (TOFMS). Separations were performed using 200 µm I.D. and 50 µM I.D. polyvinylalcohol (PVA)-coated fused silica capillaries for ITP and CE, respectively. Both ITP and ITP-CE were coupled to TOFMS for analysis of sufficient (10-5 M) and insufficient (10-6-10-7 M) concentrations of angiotensins in mixtures. ITP-TOFMS of a single mixed zone of five angiotensins (3 x 10-7 M) showed that ion suppression due to the co-elution of angiotensin III in the electrospray significantly reduced the ionization of other analytes. A practical solution to the detection difficulties for ITP mixed zones involved the insertion of a CE separation between the ITP and TOFMS for online preconcentration, separation, and identification in one system.

The observation, control and the maintenance of the physical condition of sows in acceptable levels are critical to maintain the animal welfare and production in appropriate standards. Lameness causes pain making locomotion difficult. However, lameness is a common disorder in sows that causes negative impacts in both welfare and production. Since the animals that demonstrate this problem, have a smaller number of born-alive piglets, fewer gestation per year and are removed from the herd at a younger age than the ideal. In addition, it is industry practice to limit feed sows to ensure that they remain at an ideal condition score. It is known that, during gestation, each sow should receive a different amount of food according to its body condition. Underweight animals have nutritional deficiency and lower number of piglets per litter. On the other hand, overweight sows have an abnormal development of mammary glands, reducing the amount of milk produced during lactation, causing economic losses. However, moving sows to group gestation makes it difficult to monitor condition score in gestating sows. Both the detection of lameness and the classification of body condition are currently assessed using subjective methods, which is time consuming and difficult to accurately complete. Therefore, the early recognition of animals that present physical condition outside the standards is important to prevent production losses caused by both the aggravation of the conditions presented and the impact on the animals\' welfare. The objective of this project is to obtain three characteristics (body condition score, mass and backfat thickness) through depth images, that proved to be effective on the acquisition of these features in other animals (boars and cows). The second objective is to develop a method for early detection of lameness using the kinematic approach, that has been generating good results and which difficulties have the potential to be reduced by using depth images instead of the method of reflective markers currently used. To predict body condition, a multiple linear regression was obtained using the minor axis of the ellipse fitted around sow\'s body, the width at shoulders, and the angle, of the last rib\'s curvature. To predict backfat, a multiple linear regression was performed using the height of last rib\'s curvature, the perimeter of sow\'s body, the major axis of the ellipse fitted around sow\'s body, the length from snout to rump, and the predicted body condition score. It was possible to obtain the body mass with a simple linear regression using the projected volume of the sows\' body. For lameness detection, three models presented the best accuracy (76.9%): linear discriminant analysis, fine 1-nearest neighbor, and weighted 10-nearest neighbors. The input variables used on the models were obtained from depth videos (number, time, and length of steps for each of the four regions analyzed - left and right shoulders and left and right hips; total walk time; and number of local maxima for head region). As a result of these studies, it has been demonstrated that a depth camera can be used to automate the weight, condition score, backfat thickness, and lameness acquisition/detection in gestating and lactating sows. / A observação, o controle e a manutenção das condições físicas de matrizes suínas em níveis aceitáveis são fundamentais para manter o bem-estar animal e a produção em padrões adequados. A claudicação causa dor e dificuldade de locomoção e, no entanto, é uma desordem comum em matrizes suínas que, além do impacto negativo no bem-estar, gera, também, grandes impactos na produção, uma vez que os animais que demonstram esse problema, apresentam um menor número de leitões nascidos vivos, menor número de partos por ano e são removidas do rebanho a uma idade mais jovem do que a ideal. Sabe-se, ainda, que, durante a gestação, cada matriz deve receber uma quantidade de ração diferenciada de acordo com sua condição corporal. Animais abaixo do peso apresentam deficiência nutricional e menor número de leitões nascidos por ninhada. Já as matrizes com excesso de peso apresentam um desenvolvimento anormal das glândulas mamárias, reduzindo a quantidade de leite produzida durante a lactação, acarretando em perdas econômicas. Tanto a detecção da claudicação quanto a classificação da condição corporal são feitos por meios subjetivos e dependentes da opinião pessoal do tratador, o que pode gerar divergências entre as classificações dadas por cada indivíduo. Destaca-se, portanto, a importância do reconhecimento precoce de animais que apresentam condições físicas fora dos padrões exigidos, visando a prevenção de perdas produtivas causadas tanto pelo agravamento das condições apresentadas quanto pelo grande impacto no bem-estar dos animais. Tendo-se isso em vista, o presente trabalho visou obter três características (escore de condição corporal, massa corporal e espessura de toucinho) por meio de imagens em profundidade, que se mostraram eficazes na obtenção dessas características em outros animais (suínos machos não- castrados e vacas leiteiras). Além disso, buscou-se desenvolver um método para a detecção precoce de claudicação em matrizes suínas, utilizando-se a abordagem da cinemática dos animais, que vem dando bons resultados e cujas dificuldades têm potencial para serem sanadas por meio do uso de imagens em profundidade em vez do método de marcadores reflexivos utilizado atualmente. Para predizer a condição corporal, uma regressão linear múltipla foi obtida usando o menor eixo da elipse ajustada ao redor do corpo da matriz suína, a largura dos ombros e o ângulo da curvatura da última costela. Para predizer a espessura de toucinho, foi realizada uma regressão linear múltipla usando a altura curvatura da última da costela, o perímetro do corpo da matriz, o maior eixo da elipse ajustada, o comprimento do focinho à cauda e o escore predito da condição corporal. Foi possível obter a massa corporal com uma regressão linear simples usando o volume projetado do corpo das matrizes. Para detecção de claudicação, três modelos apresentaram a melhor precisão (76,9%): análise discriminante linear, 1 vizinho mais próximo e 10 vizinhos mais próximos. As variáveis de entrada utilizadas nos modelos foram obtidas a partir de vídeos em profundidade (número, tempo e comprimento de passos para cada uma das quatro regiões analisadas-ombros esquerdo e direito e quadris esquerdo e direito; tempo total de caminhada e número de máximos locais para a região da cabeça). Como resultado desses estudos, observou-se que câmeras em profundidade podem ser utilizadas na automação de medidas de peso, condição corporal, espessura de toucinho e claudicação de matrizes suínas.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants and are mostly products of the incomplete combustion of organic material. PAHs are often found in environmental samples as a complex mixture of isomers. In addition, the same sources that produce complex PAH mixtures also produce other poorly characterized mixtures of organic compounds, commonly referred to as an unresolved complex mixture (UCM), that act as matrix interferences in the chromatographic analysis of samples. Conventional one-dimensional chromatographic techniques, such as gas chromatography coupled to mass spectrometry (GC/MS), are not sufficient for the analysis and quantitation of complex PAH mixtures present in environmental samples due to the high degree of overlap in compound vapor pressures, boiling points, and mass spectral fragmentation patterns. Therefore, the separation and quantitation of complex mixtures of individual PAH compounds in environmental samples requires high chromatographic resolution. Comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC��GC/ToF-MS) was used for this study. GC��GC/ToF-MS uses two different gas chromatographic columns, with different separation mechanisms, for the analysis of complex environmental samples. In theory, the peak capacity in GC��GC/ToF-MS is equivalent to the product of the individual peak capacities of each column used. However, in practice, this is rarely obtained because of the existing correlation between the two GC columns used. This dissertation is a compilation of three studies related to analytical method development for the identification and quantitation of complex PAH mixtures (including parent-PAHs, alkyl-PAHs, oxy-PAHs, nitro-PAHs, thio-PAHs, chloro-PAHs, bromo-PAHs and PAHs with molecular weight higher than 300 Da) that may be present in environmental samples using novel column combinations in GC��GC/ToF-MS. The use of a liquid crystal column (LC-50) in the first dimension, followed by a nano-stationary phase column (NSP-35) in the second dimension, was evaluated for the separation of a standard PAH mixture containing 97 different PAHs. Two standard reference materials purchased from NIST (NIST SRM1650b ��� Diesel Particulate Matter and NIST SRM1975 ��� Diesel Extract) were used, after extraction and cleanup, for method validation and comparison between the commonly used non-polar �� polar column combination and the LC-50 �� NSP-35 column combination with high orthogonality. As part of the method validation, an aliquot of NIST SRM1975 (Diesel extract), without sample cleanup was also analyzed for PAHs, showing that the LC-50 �� NSP-35 column combination was accurate (with an average absolute percent difference of approximately 30%) for the identification and quantitation of complex PAH mixtures in environmental samples, with reduced sample preparation prior to analysis. In addition, the LC-50 �� NSP-35 column combination was used for the analysis of PAHs sorbed to polystyrene pellets deployed in an urban bay area as passive water samplers because one-dimensional GC/MS was ineffective due to the presence of a strong unresolved complex mixture (UCM) and matrix interferences. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from Dec. 27, 2012 - June 27, 2013

Positron-Emission-Tomography (PET) is a modern imaging technique in nuclear medicine providing quantitative 3D distribution of a radioactive tracer substance in the human body. The gamma-detector is the first link in the chain of components that constitutes a PET. It converts incoming radiation into optical light pulses, which are detected by photo multiplier tubes. Here the light is converted into electric pulses, to be further processed by the acquisition electronics. Improving detector sensitivity and resolution is of great value in research and in clinical practice. The focus of this work is to improve the detector to give it time-of-flight (TOF) capabilities, in order to further improve sensitivity, which in turn leads to increased image quality, faster scan time and/or reduced dose exposure for the patient. Image quality has improved over the years, but losses in image quality have been reported for heavy patients, due to increased attenuation, and more dispersed counts over a larger volume. Instrumentation limits are still significant in heavy patient images, but the incorporation of TOF information promises to alleviate some of the limitations. In order to improve the timing resolution of the detector fast photo-multipliers and a novel scheme to extract the event timing trigger from a detector by using the summed dynode signal were investigated. When designing new PET detectors, it is important to have detailed understanding and control of the light sharing mechanisms in the crystal arrays. Therefore it was necessary to perform optical simulations and single crystal light output measurements to derive a model for an LSO block detector. Another way to improve the image quality is to use the depth-of-interaction (DOI) of the gamma ray within the detector. It is shown that a multi-layer phoswich detector comprised of LSO with different decay times and TOF capability, combines the benefits of TOF and DOI in one detector, maximizing the effective sensitivity gain. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 7: Submitted.

The neutron spectrometer TOFOR was installed at JET in 2005 for high-rate observation of neutrons from reactions between two deuterium (D) ions. Neutron spectrometry as a fusion plasma diagnostic technique is invoked to obtain information about the velocity states of fusion fuel ions. Based on neutron spectrometry data, conclusions can be drawn on the efficiency of plasma heating schemes as well as optimization of fuel ion confinement. The quality of TOFOR analysis is found to depend on how well the instrument response function is known; discriminator threshold levels, detector time alignment and electronics broadening are identified as crucial issues. About 19 percent of the neutrons observed with TOFOR have scattered off the JET vessel wall or other structures in the line-of-sight before reaching the instrument, as established through simulations and measurements. A method has been developed to take these neutrons into account in the analysis. TOFOR measurements of fast deuterium distributions are seen to agree with distributions deduced from NPA data, obtained based on an entirely different principle. This serves as validation of the modeling and analysis. Extraordinary statistics in the TOFOR measurements from JET pulses heated with 3rd harmonic RF heating on D beams allow for study of instabilities using neutron emission spectrometry. At ITER, similar studies should be possible on a more regular basis due to higher neutron rates. Observations of neutrons from Be+3He reactions in the TOFOR spectrum from D plasmas heated with fundamental RF tuned to minority 3He raise the question of beryllium neutrons at JET after installation of the ITER-like wall, and at ITER, with beryllium as the plasma facing component. This is especially important for the first few years of ITER operation, where the machine will not yet have been certified as a nuclear facility and should be run in zero-activation mode.

Polyyne molecules were produced as a result of the femtosecond laser irradiation of liquid acetone (CH3)2CO and alkane molecules hexane C6H14 and octane C8H18 using 800 nm, 100 fs duration pulses. These polyynes have been detected as a Raman band in irradiated liquid from 1800 to 2200 cm−1. Polyyne molecules generally detected as a Raman band in SERS experiment are C8H2, C10H2, C12H2 and C14H2. Two well established experimental techniques, time of flight mass spectrometry and surface enhanced Raman spectrometry were used to identify positively polyyne formation as a result of femtosecond laser irradiation of acetone and alkane liquids. Small polyynes C2H2, C4H2, and C6H2 were positively detected in the time of flight mass spectrometer TFMS, while longer polyynes from C6H2, C8H2, C10H2, C12H2 and C14H2 were detected by surface enhanced Raman spectroscopy SERS. Intensity capping occurs in a liquid due to filamentation, and the resulting intensity in a liquid is s 1013 W/cm2 during irradiation. This results in main process of ionization in the larger part of the laser focus as multiphoton ionization MPI. Focal volume increase in a liquid provides a larger volume where ions C+, C+2 and C2+are produced to initiate chemical reactions outside the laser focus. The current work established positively, that the longer polyyne formation does not occur by dehydrogenation of alkane molecules by only breaking the C-H bonds as was previously anticipated. It is proposed in this work that lengthening of polyyne chains occurs due to addition reaction of species of C+, C+2 and C2+ to double bonded species themselves produced as a result of the breaking down of the parent molecules in the laser focus. The carbon addition reactions occur outside the laser focus due to the close proximity of molecules in the liquid phase.

<p>Positron emission tomography (PET) is a nuclear medicine diagnostic imaging exam of metabolic processes in the body. Radiotracers, which consist of positron emitting radioisotopes and a molecular probe, are introduced into the body, emitted radiation is detected, and tomographic images are reconstructed. The primary clinical PET application is in oncology using a glucose analogue radiotracer, which is avidly taken up by some cancers.</p><p>It is well known that PET performance and image quality degrade as body size increases, and epidemiological studies over the past two decades show that the adult US population's body size has increased dramatically and continues to increase. Larger patients have more attenuating material that increases the number of emitted photons that are scattered or absorbed within the body. Thus, for a fixed amount of injected radioactivity and acquisition duration, the number of measured true coincidence events will decrease, and the background fractions will increase. Another size-related factor, independent of attenuation, is the volume throughout which the measured coincidence counts are distributed: for a fixed acquisition duration, as the body size increases, the counts are distributed over a larger area. This is true for both a fixed amount of radioactivity, where the concentration decreases as size increases, and a fixed concentration, where the amount radioactivity increases with size.</p><p>Time-of-flight (TOF) PET is a recently commercialized technology that allows the localization, with a certain degree of error, of a positron annihilation using timing differences in the detection of coincidence photons. Both heuristic and analytical evaluations predict that TOF PET will have improved performance and image quality compared to non-TOF PET, and this improvement increases as body size increases. The goal of this dissertation is to parameterize the image quality improvement of TOF PET compared to non-TOF PET as a function of body size. Currently, no standard for comparison exists.</p><p>Previous evaluations of TOF PET's improvement have been made with either computer-simulated data or acquired data using a few discrete phantom sizes. A phantom that represents a range of attenuating dimensions, that can have a varying radioactivity distribution, and that can have radioactive inserts positioned throughout its volume would facilitate characterizing PET system performance and image quality as a function of body size. A fillable, tapered phantom, was designed, simulated, and constructed. The phantom has an oval cross-section ranging from 38.5 &times; 49.5 cm to 6.8 &times; 17.8 cm, a length of 51.1 cm, a mass of 6 kg (empty), a mass of 42 kg (water filled), and 1.25-cm acrylic walls.</p><p>For this dissertation research, PET image quality was measured using multiple, small spheres with diameters near the spatial resolution of clinical whole-body PET systems. Measurements made on a small sphere, which typically include a small number of image voxels, are susceptible to fluctuations over the few voxels, so using multiple spheres improves the statistical power of the measurements that, in turn, reduces the influence of these fluctuations. These spheres were arranged in an array and mounted throughout the tapered phantom's volume to objectively measure image quality as a function of body size. Image quality is measured by placing regions of interest on images and calculating contrast recovery, background variability, and signal to noise ratio.</p><p>Image quality as a function of body size was parameterized for TOF compared to non-TOF PET using 46 1.0-cm spheres positioned in six different body sizes in a fillable, tapered phantom. When the TOF and non-TOF PET images were reconstructed for matched contrast, the square of the ratio of the images' signal-to-noise ratios for TOF to non-TOF PET was plotted as a function, <italic>f</italic>(<italic>D</italic>), of the radioactivity distribution size, <italic>D</italic>, in cm. A linear regression was fit to the data: <italic>f</italic>(<italic>D</italic>) = 0.108<italic>D</italic> - 1.36. This was compared to the ratio of <italic>D</italic> and the localization error, <italic>&sigma;_d</italic>, based on the system timing resolution, which is approximately 650 ps for the TOF PET system used for this research. With the image quality metrics used in this work, the ratio of TOF to non-TOF PET fits well to a linear relationship and is parallel to <italic>D/&sigma;_d</italic>. For <italic>D</italic> < 20 cm, there is no image quality improvement, but for radioactivity distributions <italic>D</italic> > 20 cm, TOF PET improves image quality over non-TOF PET. PET imaging's clinical use has increased over the past decade, and TOF PET's image quality improvement for large patients makes TOF an important new technology because the occurrence of obesity in the US adult population continues to increase.</p> / Dissertation

A method for the oxidation of lipoproteins in vitro was developed using the free radical initiator, 2,2?-azobis-(2-amidinopropane) dihydrochloride (AAPH). Following in vitro oxidation, the susceptibility to oxidation of the serum samples was studied using density gradient ultracentifugation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Shifts in mean buoyant density of the lipoprotein particles, specifically low density lipoprotein (LDL) and high density lipoprotein (HDL), were observed in the density profile following centrifugation. The degree of shift in the density proved to be proportional to the extent of oxidation. Changes in apolipoproteins were studied with MALDI-TOF-MS. Observed variations in the mass spectra include m/z shifts due to chemical modifications and change in isoform distributions. The oxidation procedure and analysis techniques were applied to a clinical application to study the effects of table grape consumption on lipoprotein susceptibility to oxidation. The main objective of the research, to show feasibility that these methods could be used in a clinical setting, was achieved.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI)is one of several proteomics technologies that can be used in biomarker discovery studies. Such studies often have the goal of finding protein markers that predict early onset of cancers such as cervical cancer. The reproducibility of SELDI has been shown to be an issue in the literature. There are numerous sources of error in a SELDI experiment starting with sample collection from patients to the signal processing steps used to estimate the protein mass and abundance values present in a sample. This dissertation is concerned with all aspects of signal processing related to SELDI's use in biomarker discovery projects. In chapter 2, we perform a comprehensive study of the most popular preprocessing algorithms available. Next, in chapter 3, we study the basic statistics of SELDI data acquisition. From here, we propose a quadratic variance measurement model for buffer+matrix only spectra. This model leads us to develop a modified Antoniadis-Sapatinas wavelet denoising algorithm that demonstrates superior performance when compared to MassSpecWavelet, one of the leading techniques for preprocessing SELDI data. In chapter 4, we show that the quadratic variance model 1) extends to real pooled cervical mucus QC data from a clinical study, 2) predicts behavior and reproducibility of peak heights, and 3) finds four times as many reproducible peaks as the vendor-supplied preprocessing programs. The quadratic variance measurement model for SELDI data is fundamental and promises to lead to improved techniques for analyzing the data from clinical studies using this instrument.