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Macromolecular interactions are essential for virtually all cellular functions including signal transduction processes, metabolic processes, regulation of gene expression and immune responses. This dissertation focuses on the characterization of two important macromolecular interactions involved in the relationship between Equine Infectious Anemia Virus (EIAV) and its host cell in horse: (1) the interaction between the EIAV Rev protein and its binding site, the Rev-responsive element (RRE) and (2) interactions between equine MHC class I molecules and epitope peptides derived from EIAV proteins. EIAV, one of the most divergent members of the lentivirus family, has a single-stranded RNA genome and carries several regulatory and structural proteins within its viral particle. Rev is an essential EIAV regulatory encoded protein that interacts with the viral RRE, a specific binding site in the viral mRNA. Using a combination of experimental and computational methods, the interactions between EIAV Rev and RRE were characterized in detail. EIAV Rev was shown to have a bipartite RNA binding domain contain two arginine rich motifs (ARMs). The RRE secondary structure was determined and specific structural motifs that act as cis-regulatory elements for EIAV Rev-RRE interaction were identified. Interestingly, a structural motif located in the high affinity Rev binding site is …

The search for the fundamental constituents of matter has been pursued and studied since the dawn of civilization. As early as the fourth century BCE, Democritus, expanding the teachings of Leucippus, proposed small, indivisible entities called atoms, interacting with each other to form the Universe. Democritus was convinced of this by observing the environment around him. He observed, for example, how a collection of tiny grains of sand can make out smooth beaches. Today, following the lead set by Democritus more than 2500 years ago, at the heart of particle physics is the hypothesis that everything we can observe in the Universe is made of a small number of fundamental particles interacting with each other. In contrast to Democritus, for the last hundred years we have been able to perform experiments that probe deeper and deeper into matter in the search for the fundamental particles of nature. Today's knowledge is encapsulated in the Standard Model of particle physics, a model describing the fundamental particles and their interactions. It is within this model that the work in this thesis is presented. This work attempts to add to the understanding of the Standard Model by measuring the relative branching fraction of the …

Optimal prediction is a general system reduction technique for large sets of differential equations. In this method, which was devised by Chorin, Hald, Kast, Kupferman, and Levy, a projection operator formalism is used to construct a smaller system of equations governing the dynamics of a subset of the original degrees of freedom. This reduced system consists of an effective Hamiltonian dynamics, augmented by an integral memory term and a random noise term. Molecular dynamics is a method for simulating large systems of interacting fluid particles. In this thesis, I construct a formalism for applying optimal prediction to molecular dynamics, producing reduced systems from which the properties of the original system can be recovered. These reduced systems require significantly less computational time than the original system. I initially consider first-order optimal prediction, in which the memory and noise terms are neglected. I construct a pair approximation to the renormalized potential, and ignore three-particle and higher interactions. This produces a reduced system that correctly reproduces static properties of the original system, such as energy and pressure, at low-to-moderate densities. However, it fails to capture dynamical quantities, such as autocorrelation functions. I next derive a short-memory approximation, in which the memory term is …

It is now widely accepted that the Standard Model assumption of massless neutrinos is wrong, due primarily to the observation of solar and atmospheric neutrino flavor oscillations by a small number of convincing experiments. The MINOS Far Detector, capable of observing both the outgoing lepton and associated showering products of a neutrino interaction, provides an excellent opportunity to independently search for an oscillation signature in atmospheric neutrinos. To this end, a MINOS data set from an 883 live day, 13.1 kt-yr exposure collected between July, 2003 and April, 2007 has been analyzed. 105 candidate charged current muon neutrino interactions were observed, with 120.5 {+-} 1.3 (statistical error only) expected in the absence of oscillation. A maximum likelihood analysis of the observed log(L/E) spectrum shows that the null oscillation hypothesis is excluded at over 96% confidence and that the best fit oscillation parameters are sin{sup 2} 2{theta}{sub 23} = 0.95{sub -0.32} and {Delta}m{sub 23}{sup 2} = 0.93{sub -0.44}{sup +3.94} x 10{sup -3} eV{sup 2}. This measurement of oscillation parameters is consistent with the best fit values from the Super-Kamiokande experiment at 68% confidence.

The phenomenon of flavour oscillations of neutrinos created in the atmosphere was first reported by the Super-Kamiokande collaboration in 1998 and since then has been confirmed by Soudan 2 and MACRO. The MINOS Far Detector is the first magnetized neutrino detector able to study atmospheric neutrino oscillations. Although it was designed to detect neutrinos from the NuMI beam, it provides a unique opportunity to measure the oscillation parameters for neutrinos and anti-neutrinos independently. The MINOS Far Detector was completed in August 2003 and since then has collected 2.52 kton-years of atmospheric data. Atmospheric neutrino interactions contained within the volume of the detector are separated from the dominant background from cosmic ray muons. Thirty seven events are selected with an estimated background contamination of less than 10%. Using the detector's magnetic field, 17 neutrino events and 6 anti-neutrino events are identified, 14 events have ambiguous charge. The neutrino oscillation parameters for {nu}{sub {mu}} and {bar {nu}}{sub {mu}} are studied using a maximum likelihood analysis. The measurement does not place constraining limits on the neutrino oscillation parameters due to the limited statistics of the data set analysed. However, this thesis represents the first observation of charge separated atmospheric neutrino interactions. It also …

The b quark fragmentation distribution has been measured, using data registered by the DELPHI experiment at the Z pole, in the years 1994-1995. The measurement made use of 176000 inclusively reconstructed B meson candidates. The errors of this measurement are dominated by systematic effects, the principal ones being related to the energy calibration. The distribution has been established in a nine bin histogram. Its mean value has been found to be <x{sub E}> = 0.704 {+-} 0.001(stat.) {+-} 0.008(syst.). Using this measurement, and other available analyses of the b-quark fragmentation distribution in e{sup +}e{sup -} collisions, the non-perturbative QCD component of the distribution has been extracted independently of any hadronic physics modeling. This distribution depends only on the way the perturbative QCD component has been defined. When the perturbative QCD component is taken from a parton shower Monte-Carlo, the non-perturbative QCD component is rather similar with those obtained from the Lund or Bowler models. When the perturbative QCD component is the result of an analytic NLL computation, the non-perturbative QCD component has to be extended in a non-physical region and thus cannot be described by any hadronic modeling. In the two examples, used to characterize these two situations, which are …

The sudden release of toxic contaminants that reach indoor spaces can be hazardousto building occupants. To respond effectively, the contaminant release must be quicklydetected and characterized to determine unobserved parameters, such as release locationand strength. Characterizing the release requires solving an inverse problem. Designinga robust real-time sensor system that solves the inverse problem is challenging becausethe fate and transport of contaminants is complex, sensor information is limited andimperfect, and real-time estimation is computationally constrained.This dissertation uses a system-level approach, based on a Bayes Monte Carloframework, to develop sensor-system design concepts and methods. I describe threeinvestigations that explore complex relationships among sensors, network architecture,interpretation algorithms, and system performance. The investigations use data obtainedfrom tracer gas experiments conducted in a real building. The influence of individual sensor characteristics on the sensor-system performance for binary-type contaminant sensors is analyzed. Performance tradeoffs among sensor accuracy, threshold level and response time are identified; these attributes could not be inferred without a system-level analysis. For example, more accurate but slower sensors are found to outperform less accurate but faster sensors. Secondly, I investigate how the sensor-system performance can be understood in terms of contaminant transport processes and the model representation that is used to solve the …

This thesis consists of two parts: In the first part we describe the Photomultiplier Tube (PMT) selection and testing processes for the Hadronic Forward (HF) calorimeter of the CMS, a Large Hadron Collier (LHC) experiment at CERN. We report the evaluation process of the candidate PMTs from three different manufacturers, the complete tests performed on the 2300 Hamamatsu PMTs which will be used in the HF calorimeter, and the details of the PMT Test Station that is in University of Iowa CMS Laboratories. In the second part we report the {Xi}{sub c}{sup +} lifetime measurement from SELEX, the charm hadro-production experiment at Fermilab. Based upon 301 {+-} 31 events from three di.erent decay channels, by using the binned maximum likelihood technique, we observe the lifetime of {Xi}{sub c}{sup +} as 427 {+-} 31 {+-} 13 fs.

Determining the composition of thin layers is increasingly important for a variety of industrial materials such as adhesives, coatings and microelectronics. Secondary ion mass spectrometry (SIMS), Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), glow discharge optical emission spectroscopy (GDOES), glow discharge mass spectrometry (GDMS), and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) are some of the techniques that are currently employed for the direct analysis of the sample surface. Although these techniques do not suffer from the contamination problems that often plague sample dissolution studies, they do require matrix matched standards for quantification. Often, these standards are not readily available. Despite the costs of clean hoods, Teflon pipette tips and bottles, and pure acids, partial sample dissolution is the primary method used in the semiconductor industry to quantify surface impurities. Specifically, vapor phase decomposition (VPD) coupled to ICP-MS or total reflection x-ray fluorescence (TXRF) provides elemental information from the top most surface layers at detection sensitivities in the 10{sup 7}-10{sup 10}atoms/cm{sup 2} range. The ability to quantify with standard solutions is a main advantage of these techniques. Li and Houk applied a VPD-like technique to steel. The signal ratio of trace element to matrix element was used for quantification. Although …

The MINOS Far Detector is a 5.4 kiloton (5.2 kt steel plus 0.2 kt scintillator plus aluminum skin) magnetized tracking calorimeter located 710 meters underground in the Soudan mine in Northern Minnesota. MINOS is the first large, deep underground detector with a magnetic field and thus capable of making measurements of the momentum and charge of cosmic ray muons. Despite encountering unexpected anomalies in distributions of the charge ratio (N{sub {mu}{sup +}}/N{sub {mu}{sup -}}) of cosmic muons, a method of canceling systematic errors is proposed and demonstrated. The result is R{sub eff} = 1.346 {+-} 0.002 (stat) {+-} 0.016 (syst) for the averaged charge ratio, and a result for a rising fit to slant depth of R(X) = 1.300 {+-} 0.008 (stat) {+-} 0.016 (syst) + (1.8 {+-} 0.3) x 10{sup -5} x X, valid over the range of slant depths from 2000 < X < 6000 MWE. This slant depth range corresponds to minimum surface muon energies between 750 GeV and 5 TeV.

Cross-sections are presented for 58 GeV {pi}, K, and p on a wide range of nuclear targets. These cross-sections are essential for determining the neutrino flux in measurements of neutrino cross-sections and oscillations. The E907 Main Injector Particle Production (MIPP) experiment at Fermilab is a fixed target experiment for measuring hadronic particle production using primary 120 GeV/c protons and secondary {pi}, K, and p beams. The particle identification is made by dE/dx in a time projection chamber, and by time-of-flight, differential Cherenkov and ring imaging Cherenkov detectors, which together cover a wide range of momentum from 0.1 GeV/c up to 120 GeV/c. MIPP targets span the periodic table, from hydrogen to uranium, including beryllium and carbon. The MIPP has collected {approx} 0.26 x 10{sup 6} events of 58 GeV/c secondary particles produced by protons from the main injector striking a carbon target.

The main focus of this dissertation is the design, development, and ground and microgravity validation of methods for monitoring drinking water quality on-board NASA spacecraft using clorimetric-solid phase extraction (C-SPE). The Introduction will overview the need for in-flight water quality analysis and will detail some of the challenges associated with operations in the absence of gravity. The ability of C-SPE methods to meet these challenges will then be discussed, followed by a literature review on existing applications of C-SPE and similar techniques. Finally, a brief discussion of diffuse reflectance spectroscopy theory, which provides a means for analyte identification and quantification in C-SPE analyses, is presented. Following the Introduction, four research chapters are presented as separate manuscripts. Chapter 1 reports the results from microgravity testing of existing C-SPE methods and procedures aboard NASA's C-9 microgravity simulator. Chapter 2 discusses the development of a C-SPE method for determining the total concentration of biocidal silver (i.e., in both dissolved and colloidal forms) in water samples. Chapter 3 presents the first application of the C-SPE technique to the determination of an organic analyte (i.e., formaldehyde). Chapter 4, which is a departure from the main focus of the thesis, details the results of an investigation …

The work presented herein describes a fundamental investigations of carbon as electrode material by using the pyrolysis of photoresist to create an optically transparent material. The development of these carbon-based optically transparent electrodes (C-OTEs) enables investigations of molecular interactions within the electrical double layer, processes that are central to a wide range of important phenomena, including the impact of changes in the surface charge density on adsorption. The electrochemical importance of carbon cannot be understated, having relevance to separations and detection by providing a wide potential window and low background current in addition to being low cost and light weight. The interactions that govern the processes at the carbon electrode surface has been studied extensively. A variety of publications from the laboratories of McCreery and Kinoshita provide in depth summaries about carbon and its many applications in electrochemistry. These studies reveal that defects, impurities, oxidation, and a variety of functional groups create adsorption sites on carbon surfaces with different characteristics. The interest in C-OTEs was sparked by the desire to study and understand the behavior of individual molecules at electrified interfaces. It draws on the earlier development of Electrochemically Modulated Liquid Chromatography (EMLC), which uses carbon as the stationary phase. …

Three major high performance quantum chemistry computational packages, NWChem, GAMESS and MPQC have been developed by different research efforts following different design patterns. The goal is to achieve interoperability among these packages by overcoming the challenges caused by the different communication patterns and software design of each of these packages. A chemistry algorithm is hard to develop as well as being a time consuming process; integration of large quantum chemistry packages will allow resource sharing and thus avoid reinvention of the wheel. Creating connections between these incompatible packages is the major motivation of the proposed work. This interoperability is achieved by bringing the benefits of Component Based Software Engineering through a plug-and-play component framework called Common Component Architecture (CCA). In this thesis, I present a strategy and process used for interfacing two widely used and important computational chemistry methodologies: Quantum Mechanics and Molecular Mechanics. To show the feasibility of the proposed approach the Tuning and Analysis Utility (TAU) has been coupled with NWChem code and its CCA components. Results show that the overhead is negligible when compared to the ease and potential of organizing and coping with large-scale software applications.

Ultra-sensitive native fluorescence detection of proteins with miniaturized one- and two-dimensional polyacrylamide gel electrophoresis was achieved with laser side-entry excitation, which provides both high excitation power and low background level. The detection limit for R-phycoerythrin protein spots in 1-D SDS-PAGE was as low as 15 fg, which corresponds to 40 thousand molecules only. The average detection limit of six standard native proteins was 5 pg per band and the dynamic range spanned more than 3 orders of magnitude. Approximately 150 protein spots from 30 ng of total Escherichia coli extraction were detected on a 0.8 cm x 1 cm gel in two-dimensional separation. Estrogen-DNA adducts as 4-OHE{sub 1}(E{sub 2})-1-N3Ade and 4-OHEI(E2)-2-NacCys were hypothesized as early risk assessment of prostate and breast cancers. Capillary electrophoresis, luminescence/absorption spectroscopy and LC-MS were used to characterize and detect these adducts. Monoclonal antibodies against each individual adduct were developed and used to enrich such compounds from urine samples of prostate and breast cancer patients as well as healthy people. Adduct 4-OHE{sub 1}-1-N3Ade was detected at much higher level in urine from subjects with prostate cancer patients compared to healthy males. The same adduct and 4-OHEI-2-NacCys were also detected at a much higher level in urine …

Generalized Parton Distributions (GPDs), introduced in the late 90s, provide a universal description of hadrons in terms of the underlying degrees of freedom of Quantum Chromodynamics: quarks and gluons. GPDs appear in a wide variety of hard exclusive reactions and the advent of high luminosity accelerator facilities has made the study of GPDs accessible to experiment. Deeply Virtual Compton Scattering (DVCS) is the golden process involving GPDs. The first dedicated DVCS experiment ran in the Hall A of Jefferson Lab in Fall 2004. An electromagnetic calorimeter and a plastic scintillator detector were constructed for this experiment, together with specific electronics and acquisition system. The experiment preparation, data taking and analysis are described in this document. Results on the absolute cross section difference for opposite beam helicities provide the first measurement of a linear combination of GPDs as a function of the momentum transfer to the nucleon.

Electromagnetic, thermal and structural analyses of radio-frequency (RF) cavities were performed as part of a developmental RF cavity program for muon cooling. RF cavities are necessary to provide longitudinal focusing of the muons and to compensate for their energy loss. Closing the cavity ends by electrically conducting windows reduces the power requirement and increases the on-axis electric field for a given maximum surface electric field. Many factors must be considered in the design of RF cavity windows. RF heating can cause the windows to deform in the axial direction of the cavity. The resulting thermal stresses in the window must be maintained below the yield stress of the window material. The out-of-plane deflection must be small enough so that the consequent frequency shift is tolerable. For example, for an 805 MHz cavity, the out-of-plane deflection must be kept below 25 microns to prevent the frequency of the cavity from shifting more than 10 kHz. In addition, the window design should yield smooth electric and magnetic fields, terminate field leakage beyond the window, and minimize beam scattering. In the present thesis, gridded-tube window designs were considered because of their high structural integrity. As a starting point in the analysis, a cylindrical …

This dissertation focused on using electrospray ionization mass spectrometry to study cluster ions and toxic metal ions in biology. In Chapter 2, it was shown that primary, secondary and quarternary amines exhibit different clustering characteristics under identical instrument conditions. Carbon chain length also played a role in cluster ion formation. In Chapters 3 and 4, the effects of solvent types/ratios and various instrumental parameters on cluster ion formation were examined. It was found that instrument interface design also plays a critical role in the cluster ion distribution seen in the mass spectrum. In Chapter 5, ESI-MS was used to investigate toxic metal binding to the [Gln{sup 11}]-amyloid {beta}-protein fragment (1-16). Pb and Cd bound stronger than Zn, even in the presence of excess Zn. Hg bound weaker than Zn. There are endless options for future work on cluster ions. Any molecule that is poorly ionized in positive ion mode can potentially show an increase in ionization efficiency if an appropriate anion is used to produce a net negative charge. It is possible that drug protein or drug/DNA complexes can also be stabilized by adding counter-ions. This would preserve the solution characteristics of the complex in the gas phase. Once in …

In a data sample of approximately 1.3 fb{sup -1} collected with the D0 detector between 2002 and 2006, the orbitally excited charm state D{sub s1}{sup {+-}}(2536)has been observed with a measured mass of 2535.7 {+-} 0.6(stat) {+-} 0.5(syst) MeV/c{sup 2} via the decay mode B{sub s}{sup 0} {yields} D{sub s1}{sup -}(2536){mu}{sup +}{nu}X followed by D{sub s1}{sup {+-}}(2536) {yields} D*{sup {+-}}K{sub S}{sup 0}. By normalizing to the known branching ratio Br({bar b} {yields} D*{sup -} {mu}{sup +}{nu}X) and to the number of reconstructed D* mesons with an associated identified muon, a first-ever measurement is made of the product branching ratio ({bar b} {yields} D{sub s1}{sup -}(2536){mu}{sup +}{nu}X) {center_dot} Br(D{sub s1}{sup -} {yields} D*{sup -}K{sub S}{sup 0}). Assuming that D{sub s1}{sup -}(2536) production in semileptonic decay is entirely from B{sub s}{sup 0}, an extraction of the semileptonic branching ratio Br(B{sub s}{sup 0} {yields} D{sub s1}{sup -}(2536){mu}{sup +}{nu}X) is made. Comparisons are made with theoretical expectations.

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By way of retaining the gauge invariance of the Standard Model (SM) and giving masses to the W{sup {+-}} and Z{sup 0} bosons and the fermions, the Higgs mechanism predicts the existence of a neutral scalar bosonic particle, whose mass is not exactly known. The Higgs boson is the only experimentally unconfirmed SM particle to date. This thesis documents a search for the Higgs boson in p{bar p} collisions at {radical}s = 1.96 TeV at the Tevatron, using 360 {+-} pb {sup -1} data collected by the Run II Collider Detector at Fermilab (CDF II), as part of the most important quest for contemporary particle physicists. The search was for a Higgs boson decaying to a pair of W{sup {+-}} bosons, where each W boson decays to an electron, a muon or a tau that further decays to an electron or a muon with associated neutrinos. Events with two charged leptons plus large missing energy were selected in data triggered on a high p{sub t} lepton and compared to the signal and backgrounds modeled using Monte Carlo and jet data. No signal-like excess was observed in data. Therefore, upper limits on the HWW production cross-section in the analyzed mass range …

Aptamers are short single-stranded nucleic acids that can bind to their targets with high specificity and high affinity. To study aptamer function and dynamics, the malachite green aptamer was chosen as a model. Malachite green (MG) bleaching, in which an OH- attacks the central carbon (C1) of MG, was inhibited in the presence of the malachite green aptamer (MGA). The inhibition of MG bleaching by MGA could be reversed by an antisense oligonucleotide (AS) complementary to the MGA binding pocket. Computational cavity analysis of the NMR structure of the MGA-MG complex predicted that the OH{sup -} is sterically excluded from the C1 of MG. The prediction was confirmed experimentally using variants of the MGA with changes in the MG binding pocket. This work shows that molecular reactivity can be reversibly regulated by an aptamer-AS pair based on steric hindrance. In addition to demonstrate that aptamers could control molecular reactivity, aptamer dynamics was studied with a strategy combining molecular dynamics (MD) simulation and experimental verification. MD simulation predicted that the MG binding pocket of the MGA is largely pre-organized and that binding of MG involves reorganization of the pocket and a simultaneous twisting of the MGA terminal stems around the pocket. …

The computing infrastructures of the modern high energy physics experiments need to address an unprecedented set of requirements. The collaborations consist of hundreds of members from dozens of institutions around the world and the computing power necessary to analyze the data produced surpasses already the capabilities of any single computing center. A software infrastructure capable of seamlessly integrating dozens of computing centers around the world, enabling computing for a large and dynamical group of users, is of fundamental importance for the production of scientific results. Such a computing infrastructure is called a computational grid. The SAM-Grid offers a solution to these problems for CDF and DZero, two of the largest high energy physics experiments in the world, running at Fermilab. The SAM-Grid integrates standard grid middleware, such as Condor-G and the Globus Toolkit, with software developed at Fermilab, organizing the system in three major components: data handling, job handling, and information management. This dissertation presents the challenges and the solutions provided in such a computing infrastructure.