Desensitisation and Potentiation of Platelet Inositol Phospholipid Hydrolysis

I attempted to clarify the role of receptor stimulated phosphoinositide hydrolysis in mediating the activity of a number of agonists whose putative mechanism of action was unknown or controversial. Phosphoinositide hydrolysis was routinely monitored by measuring the formation of [32P] phosphatidic acid (Ptd OH) in platelets prelabelled with [32P] orthophosphate. Ptd OH is the phosphorylated product of DAG, and the experimental conditions adopted allowed [32P] Ptd OH to obtain isotopic equilibrium with gamma-[32P] ATP such that changes in label reflect changes in Ptd OH content. In addition in some studies depletion of [32P] PIP2 was monitored. Cytosolic free calcium concentration was measured by Quin 2. In addition, I evaluated the role of various putative endogenous mediators of desensitisation on the stimulatory transduction process(es) and addressed the possible mechanism(s) whereby agonist-induced platelet reactivity could be potentiated

Real-time Voltage Stability Monitoring and Control for Load Areas: A Hybrid Approach

This dissertation proposes a hybrid approach for real-time monitoring and controlling voltage stability of a load area fed by N tie lines. This hybrid approach integrates both simulation-based and measurement-based approaches for voltage stability assessment (VSA). First, for measurement-based VSA (MBVSA), a new method is proposed for monitoring and control of load areas, which adopts an N+1 buses equivalent system so as to model and monitor individual tie lines of a load area compared to a traditional MBVSA method adopting a Thevenin equivalent. For each tie line, the new method solves the power transfer limit against voltage instability analytically as a function of all parameters of that equivalent, which is online identified from real-time synchronized measurements on boundary buses of the load area. Thus, this new MBVSA method can directly calculate the real-time power transfer limit on each tie line. Second, in order to assess the voltage stability margins under an n-1 contingency, based on the proposed MBVSA method, two sensitivity analyses have been performed, which are respectively for the parameter sensitivity of the equivalent system and the sensitivity of the tie line flow under an n-1 contingency. Third, the proposed MBVSA method implemented for both the real-time condition and potential n-1 contingencies is integrated with the simulation-based VSA approach to form a hybrid approach. The MBVSA method helps reduce the computation burden by eliminating the unimportant contingencies while the simulation-based method provides accurate information for specific “what if” scenarios such as stability limit and margin indices under n-1 contingency conditions. In addition, simulation using the model of the system can provide recommendations for preventive control if potential voltage instability is identified. This proposed hybrid VSA approach has been validated on the NPCC (Northeast Power Coordinating Council) Large-scale Test Bed (LTB) system developed by the CURENT (Center for Ultra-Wide-Area Resilient Electric Energy Transmission Networks), and also implemented on the CURENT Hardware Test Bed (HTB) system. The effectiveness of the MBVSA in real-time monitoring and closed-loop control against voltage instability has been validated

A statistical approach towards performance analysis of multimodal biometrics systems

Fueled by recent government mandates to deliver public functions by the use of biometrics, multimodal biometrics authentication has made rapid progress over the past a few years. Performance of multimodal biometrics systems plays a crucial role in government applications, including public security and forensic analysis. However, current performance analysis is conducted without considering the influence of noises, which may result in unreliable analytical results when noise levels change in practice. This thesis investigates the application of statistical methods in performance analysis of multimodal biometric systems. It develops an efficient and systematic approach to evaluate system performance in different situations of noise influences. Using this approach, 126 experiments are conducted with the BSSR1 dataset. The proposed approach helps to examine the performance of typical fusion methods that use different normalization and data partitioning techniques. Experiment results demonstrate that the Simple Sum fusion method working with the Min-Max normalization and Re-Substitution data partitioning yields the best overall performance in different noise conditions. In addition, further examination of the results reveals the need of systematic analysis of system performance as the performance of some fusion methods exhibits big variations when the level of noises changes and some fusion methods may produce very good performance in some application though normally unacceptable in others

Molecular tools in the diagnostic and epidemiology of infections caused by members of Mycobacterium avium Complex

Mycobacterium avium Complex (MAC) comprises microorganisms that affect a wide range of animals including humans. The most relevant are Mycobacterium avium subspecies hominissuis (Mah) with a high impact on public health affecting mainly immunocompromised individuals and Mycobacterium avium subspecies paratuberculosis (Map) causing paratuberculosis in animals with a high economic impact worldwide. In this work, we characterized 28 human and 67 porcine Mah isolates and evaluated the relationship among them by Multiple-Locus Variable number tandem repeat Analysis (MLVA). We concluded that Mah population presented a high genetic diversity and no correlations were inferred based on geographical origin, host or biological sample. For the first time in Portugal Map strains, from asymptomatic bovine faecal samples were isolated highlighting the need of more reliable and rapid diagnostic methods for Map direct detection. Therefore, we developed an IS900 nested real time PCR with high sensitivity and specificity associated with optimized DNA extraction methodologies for faecal and milk samples. We detected 83% of 155 faecal samples from goats, cattle and sheep, and 26% of 98 milk samples from cattle, positive for Map IS900 nested real time PCR. A novel SNPs (single nucleotide polymorphisms) assay to Map characterization based on a Whole Genome Sequencing analysis was developed to elucidate the genetic relationship between strains. Based on sequential detection of 14 SNPs and on a decision tree we were able to differentiate 14 phylogenetic groups with a higher discriminatory power compared to other typing methods. A pigmented Map strain was isolated and characterized evidencing for the first time to our knowledge the existence of pigmented Type C strains. With this work, we intended to improve the ante mortem direct molecular detection of Map, to conscientiously aware for the existence of Map animal infections widespread in Portugal and to contribute to the improvement of Map and Mah epidemiological studies

Detection of Johne\u27s disease in an Iowa (United States) dairy herd : comparisons of the milk ELISA, serum ELISA, Gamma-Interferon and fecal culture tests and the effect of a skin-test using a cell-free sonicate of Mycobacterium avium subsp. paratuberculosis (19698) on the production of Gamma-Interferon

Analysis using kappa returned a value of -0.116 indicated a very low percentage of agreement between the two testing means. With the SELISA being the regulatory US standard it is not recommended to use the MELISA for purposes of culling decisions. Results of the skin testing portion of the study indicates that inoculation of animals with 19698 MpS significantly increased production of [Gamma]-IFN in cattle declared to have positive (MpS-P) baseline [Gamma]-IFN responses for Johne\u27s disease. Peak production of [Gamma]-IFN occurred at 144 hr following skin testing and was statistically significant P = 0.0005 as compared to day 0. Levels of [Gamma]-IFN dropped on day 9, but remained at levels that were significantly higher than day 0 (P = 0.0325). Levels of [Gamma]-IFN again significantly increased on day 27 when compared to day 15 (P = 0.0362), and was significantly higher than day 0 (P = 0.0004). Further research is warranted to determine if the addition of skin testing to the [Gamma]-IFN assay could increase test sensitivity or durability.Cattle from the Iowa State University, Ames dairy herd were characterized for Johne\u27s disease using results from the milk ELISA (MELISA) (Dairy Lab Services; Dubuque, IA), serum ELISA (SELISA) (IDEXX Laboratories, Inc., Westbrook, ME), [Gamma]-IFN assay (CSL Limited Parkville Victoria Australia) and fecal culture. Using the results of the initial [Gamma]-IFN assay and the SELISA determination, all herd members were divided into four groups consisting of: a negative SELISA and [Gamma]-IFN, suspect [Gamma]-IFN, positive [Gamma]-IFN and SELISA positive individuals. The first three groups were enrolled in the skin testing trial and were randomly assigned within group to one of two treatments. This consisted of an injection of either 100[Mu]g (0.1m1) of a M. paratuberculosis strain 19698 cell free sonicate (19698 MpS) or 0.1 ml of 0.9% saline solution as an intradermal injection. Blood samples were obtained on days 0, 3, 6, 9, 15, and 27 days post-injection for [Gamma]-IFN assay, while skin lesion measurements were made on days 0, 3, 6 and 9. The MELISA test returned the greatest number of test positive individuals at 12.96%, The SELISA was 7.41% test positive, [Gamma]-IFN assay was 4.40%, and fecal culture yielded 0% positive. Further evaluation indicated the SELISA had a significantly lower age (37.2 vs. 50.5 and 48.3 months respectively) at positive test (P\u3e [T] = 0.0192) than did MELISA or [Gamma]-IFN. Due to the low number of fecal culture and [Gamma]-IFN positive individuals, and the significantly lower age at positive test it could be suspect that the SELISA had an inordinate number of false positive individuals. MELISA and SELISA results were compared using an XY plot. No common individuals were identified as test positive by both tests

Adaptive Optimal Control The Thinking Man's GPC

Exploring connections between adaptive control theory and practice, this book treats the techniques of linear quadratic optimal control and estimation (Kalman filtering), recursive identification, linear systems theory and robust arguments