Doctor of Philosophy

dissertationWe present a method for absolutely quantifying pharmacokinetic parameters in dynamic contrast-enhanced (DCE)-MRI. This method, known as alternating mini-mization with model (AMM), involves jointly estimating the arterial input function (AIF) and pharmacokinetic parameters from a characteristic set of measured tissue concentration curves. By blindly estimating the AIF, problems associated with AIF measurement in pharmacokinetic modeling, such as signal saturation, flow and partial volume eff ects, and small arterial lumens can be ignored. The blind estimation method described here introduces a novel functional form for the AIF, which serves to simplify the estimation process and reduce the deleterious e ffects of noise on the deconvolution process. Computer simulations were undertaken to assess the performance of the estimation process as a function of the input tissue curves. A con fidence metric for the estimation quality, based on a linear combination of the SNR and diversity of the input curves, is presented. This con fidence metric is then used to allow for localizing the region from which input curves are drawn. Local blood supply to any particular region can then be blindly estimated, along with some measure of con fidence for that estimation. Methods for evaluating the utility of the blind estimation algorithm on clinical data are presented, along with preliminary results on quantifying tissue parameters in soft-tissue sarcomas. The AMM method is applied to in vivo data from both cardiac perfusion and breast cancer scans. The cardiac scans were conducted using a dual-bolus protocol, which provides a measure of truth for the AIF. Twenty data sets were processed with this method, and pharmacokinetic parameter values derived from the blind AIF were compared with those derived from the dual-bolus measured AIF. For seventeen of the twenty datasets there were no statistically signifi cant differences in Ktrans estimates. The cardiac AMM method presented here provides a way to quantify perfusion of myocardial tissue with a single injection of contrast agent and without a special pulse sequence. The resulting parameters are similar to those given by the dual bolus method. The breast cancer scans were processed with the AMM method and the results were compared to an analysis done with the semiquantitative DCE-MRI scans. The e ffects of the temporal sampling rate of the data on the AMM method are examined. The ability of the AMM-derived parameters to distinguish benign and malignant tumors is compared to more conventional methods

Regulation of cargo transfer between ESCRT-0 and ESCRT-I complexes by flotillin-1 during endosomal sorting of ubiquitinated cargo

Ubiquitin-dependent sorting of membrane proteins in endosomes directs them to lysosomal degradation. In the case of receptors such as the epidermal growth factor receptor (EGFR), lysosomal degradation is important for the regulation of downstream signalling. Ubiquitinated proteins are recognised in endosomes by the endosomal sorting complexes required for transport (ESCRT) complexes, which sequentially interact with the ubiquitinated cargo. Although the role of each ESCRT complex in sorting is well established, it is not clear how the cargo is passed on from one ESCRT to the next. We here show that flotillin-1 is required for EGFR degradation, and that it interacts with the subunits of ESCRT-0 and -I complexes (hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) and Tsg101). Flotillin-1 is required for cargo recognition and sorting by ESCRT-0/Hrs and for its interaction with Tsg101. In addition, flotillin-1 is also required for the sorting of human immunodeficiency virus 1 Gag polyprotein, which mimics ESCRT-0 complex during viral assembly. We propose that flotillin-1 functions in cargo transfer between ESCRT-0 and -I complexes

In-situ probes for antenna array calibration

A novel calibration network for patch antennas is proposed. We introduce magnetically coupled in-situ probes, which excite the fundamental patch mode. In that way, finite array effects and mutual coupling can be detected, providing the opportunity for online calibration. The specific advantages of the approach are demonstrated for linearly polarized patch antennas. Measurement results of a single patch with the integrated probes agree with simulation. A two by two antenna array with in-situ probes is simulated to demonstrate the calibration accuracy in theory

Fault Models for Quantum Mechanical Switching Networks

The difference between faults and errors is that, unlike faults, errors can be corrected using control codes. In classical test and verification one develops a test set separating a correct circuit from a circuit containing any considered fault. Classical faults are modelled at the logical level by fault models that act on classical states. The stuck fault model, thought of as a lead connected to a power rail or to a ground, is most typically considered. A classical test set complete for the stuck fault model propagates both binary basis states, 0 and 1, through all nodes in a network and is known to detect many physical faults. A classical test set complete for the stuck fault model allows all circuit nodes to be completely tested and verifies the function of many gates. It is natural to ask if one may adapt any of the known classical methods to test quantum circuits. Of course, classical fault models do not capture all the logical failures found in quantum circuits. The first obstacle faced when using methods from classical test is developing a set of realistic quantum-logical fault models. Developing fault models to abstract the test problem away from the device level motivated our study. Several results are established. First, we describe typical modes of failure present in the physical design of quantum circuits. From this we develop fault models for quantum binary circuits that enable testing at the logical level. The application of these fault models is shown by adapting the classical test set generation technique known as constructing a fault table to generate quantum test sets. A test set developed using this method is shown to detect each of the considered faults.Comment: (almost) Forgotten rewrite from 200

Sources and budgets for CO and O-3 in the northeastern Pacific during the spring of 2001: Results from the PHOBEA-II Experiment

Abstract. Ground and airborne measurements of CO, ozone, and aerosols were obtained in th