New Statistical Algorithms for the Analysis of Mass Spectrometry Time-Of-Flight Mass Data with Applications in Clinical Diagnostics

Mass spectrometry (MS) based techniques have emerged as a standard forlarge-scale protein analysis. The ongoing progress in terms of more sensitive machines and improved data analysis algorithms led to a constant expansion of its fields of applications. Recently, MS was introduced into clinical proteomics with the prospect of early disease detection using proteomic pattern matching. Analyzing biological samples (e.g. blood) by mass spectrometry generates mass spectra that represent the components (molecules) contained in a sample as masses and their respective relative concentrations. In this work, we are interested in those components that are constant within a group of individuals but differ much between individuals of two distinct groups. These distinguishing components that dependent on a particular medical condition are generally called biomarkers. Since not all biomarkers found by the algorithms are of equal (discriminating) quality we are only interested in a small biomarker subset that - as a combination - can be used as a fingerprint for a disease. Once a fingerprint for a particular disease (or medical condition) is identified, it can be used in clinical diagnostics to classify unknown spectra. In this thesis we have developed new algorithms for automatic extraction of disease specific fingerprints from mass spectrometry data. Special emphasis has been put on designing highly sensitive methods with respect to signal detection. Thanks to our statistically based approach our methods are able to detect signals even below the noise level inherent in data acquired by common MS machines, such as hormones. To provide access to these new classes of algorithms to collaborating groups we have created a web-based analysis platform that provides all necessary interfaces for data transfer, data analysis and result inspection. To prove the platform's practical relevance it has been utilized in several clinical studies two of which are presented in this thesis. In these studies it could be shown that our platform is superior to commercial systems with respect to fingerprint identification. As an outcome of these studies several fingerprints for different cancer types (bladder, kidney, testicle, pancreas, colon and thyroid) have been detected and validated. The clinical partners in fact emphasize that these results would be impossible with a less sensitive analysis tool (such as the currently available systems). In addition to the issue of reliably finding and handling signals in noise we faced the problem to handle very large amounts of data, since an average dataset of an individual is about 2.5 Gigabytes in size and we have data of hundreds to thousands of persons. To cope with these large datasets, we developed a new framework for a heterogeneous (quasi) ad-hoc Grid - an infrastructure that allows to integrate thousands of computing resources (e.g. Desktop Computers, Computing Clusters or specialized hardware, such as IBM's Cell Processor in a Playstation 3)

Gravity anomaly detection: Apollo/Soyuz

The Goddard Apollo-Soyuz Geodynamics Experiment is described. It was performed to demonstrate the feasibility of tracking and recovering high frequency components of the earth's gravity field by utilizing a synchronous orbiting tracking station such as ATS-6. Gravity anomalies of 5 MGLS or larger having wavelengths of 300 to 1000 kilometers on the earth's surface are important for geologic studies of the upper layers of the earth's crust. Short wavelength Earth's gravity anomalies were detected from space. Two prime areas of data collection were selected for the experiment: (1) the center of the African continent and (2) the Indian Ocean Depression centered at 5% north latitude and 75% east longitude. Preliminary results show that the detectability objective of the experiment was met in both areas as well as at several additional anomalous areas around the globe. Gravity anomalies of the Karakoram and Himalayan mountain ranges, ocean trenches, as well as the Diamantina Depth, can be seen. Maps outlining the anomalies discovered are shown

Modularity revisited: A novel dynamics-based concept for decomposing complex networks

Finding modules (or clusters) in large, complex networks is a challenging task, in particular if one is not interested in a full decomposition of the whole network into modules. We consider modular networks that also contain nodes that do not belong to one of modules but to several or to none at all. A new method for analyzing such networks is presented. It is based on spectral analysis of random walks on modular networks. In contrast to other spectral clustering approaches, we use different transition rules of the random walk. This leads to much more prominent gaps in the spectrum of the adapted random walk and allows for easy identification of the network's modular structure, and also identifying the nodes belonging to these modules. We also give a characterization of that set of nodes that do not belong to any module, which we call transition region. Finally, by analyzing the transition region, we describe an algorithm that identifies so called hub-nodes inside the transition region that are important connections between modules or between a module and the rest of the network. The resulting algorithms scale linearly with network size (if the network connectivity is sparse) and thus can also be applied to very large networks

Soft Color Enhancement of the Production of J/psi's by Neutrinos

We calculate the production of J/psi mesons by neutrino-nucleon collisions in fixed target experiments. Soft color, often referred to as color evaporation effects, enhance production cross sections due to the contribution of color octet states. Though still small, J/\psi production may be observable in present and future experiments like NuTeV and muon colliders.Comment: 7 pages, Revtex, 4 postscript figures, uses epsfig.st

Supersymmetric Brane World Scenarios from Off-Shell Supergravity

Using N=2 off-shell supergravity in five dimensions, we supersymmetrize the brane world scenario of Randall and Sundrum. We extend their construction to include supersymmetric matter at the fixpoints.Comment: 15 pages, no figures, late

Spectral density of random graphs with topological constraints

The spectral density of random graphs with topological constraints is analysed using the replica method. We consider graph ensembles featuring generalised degree-degree correlations, as well as those with a community structure. In each case an exact solution is found for the spectral density in the form of consistency equations depending on the statistical properties of the graph ensemble in question. We highlight the effect of these topological constraints on the resulting spectral density.Comment: 24 pages, 6 figure

Electronic structure and the minimum conductance of a graphene layer on SiO2 from density-functional methods.

The effect of the SiO$_2$ substrate on a graphene film is investigated using realistic but computationally convenient energy-optimized models of the substrate supporting a layer of graphene. The electronic bands are calculated using density-functional methods for several model substrates. This provides an estimate of the substrate-charge effects on the behaviour of the bands near $E_F$, as well as a variation of the equilibrium distance of the graphene sheet. A model of a wavy graphene layer is examined as a possible candidate for understanding the nature of the minimally conducting states in graphene.Comment: 6 pages, 5 figure

Search for Point Sources of High Energy Neutrinos with AMANDA

This paper describes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector, an array of 302 photomultiplier tubes, used for the detection of Cherenkov light from upward traveling neutrino-induced muons, buried deep in ice at the South Pole. The absolute pointing accuracy and angular resolution were studied by using coincident events between the AMANDA detector and two independent telescopes on the surface, the GASP air Cherenkov telescope and the SPASE extensive air shower array. Using data collected from April to October of 1997 (130.1 days of livetime), a general survey of the northern hemisphere revealed no statistically significant excess of events from any direction. The sensitivity for a flux of muon neutrinos is based on the effective detection area for through-going muons. Averaged over the Northern sky, the effective detection area exceeds 10,000 m^2 for E_{mu} ~ 10 TeV. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the predicted performance of the detector. For a source with a differential energy spectrum proportional to E_{nu}^{-2} and declination larger than +40 degrees, we obtain E^2(dN_{nu}/dE) <= 10^{-6}GeVcm^{-2}s^{-1} for an energy threshold of 10 GeV.Comment: 46 pages, 22 figures, 4 tables, submitted to Ap.