published_or_final_version / Pathology / Master / Master of Medical Sciences

Background Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS). In Hong Kong, the prevalence rates of MS is 4.8/100,000. First line disease modifying agent (DMA) type 1 interferon β (IFN-β) is the most commonly use therapy for relapsing and remitting MS(RRMS). Depending on the administration type and route of IFN-β, up to 80% of patients develop harmless binding antibody (BAb),which binds to IFN molecules but not necessary interfere its bioactivity. When IFN-β therapy continues, maturation of BAb response can lead to the formation of high affinity neutralizing antibody (NAb). About 45% of MS patients develop NAb against IFN-β in one year of IFN-β treatment. NAb shows a loss of IFN-β clinical effect by increasing MRI activity and disease progression. As the clinical effect of NAb is lagging behind the initial appearance of NAb in the body, it is suggested to develop a NAb assay to predict treatment failure and advice switching therapy for patients when NAb is present. Aim The aim of this study was: I. To develop and evaluate a qPCR-based method for the measurement of NAb to IFN-β in MS patient. II. To establish the normal reference range of NAb in Chinese population. III. To seek the possibility of using anti-IFN-β BAb assay and in vivo MxA gene expression assay as a screening test for NAb IV. To compare the performance between MxA induction qPCR, ELISA, WB assay and luciferase IFN-β reporter gene assay Materials and methods23Chinese RRMS patients who treated with IFN-β-1a therapy for a minimum of12 months were recruited in this study. Serum and PBMC were collected12 hours after the IFN-β-1a injection. MxA, IFNAR1 and IFNAR2 mRNA from PBMC were tested byin vivo MxA gene expression assay. NAb containing serum was tested by anti-IFN-β BAb assay, IFN-β reporter gene assay, in vitro MxA induction WB, ELISA and qPCR assay. In addition, blood samples from 3 Chinese volunteers without any known autoimmune disease history were collected to evaluate the baseline of NAb titer and MxA expression. Result The experimental condition of MxA induction qPCR assay was optimized by using 2.5×105A549 cells plating density, 10% FCS concentration,5 hours IFN-β stimulation time and GAPDH normalization. Assay accuracy was validated by reference anti-IFN-β antibody. Starting from 2.5 TRU, linear relationship could be observed (r2= 0.9873). The lower limit of quantification (LLOQ) was 0.02 LU/mL, the upper limit of quantification (ULOQ) was 16LU/mL and the limit of detection (LOD) was 0.002 LU/mL. The reproducibility of the assay was measured, the intra-and inter-assay imprecision(%CV)for high value were 5.95% and 7.17% respectively, while the intra-and inter-assay impression were8.31% and 15.95%respectively.Results of the qPCR-based method were concurring with that of luciferase IFN-β reporter gene assay. The upper limit of the NAb reference range in Chinese population was 40.3 TRU (n=3, 95% CI = 31.7-48.8). The performance observed in MxA induction ELISA assay swas unsatisfactory. The correlation of anti-IFN-β BAb assay and in vivoMxA gene expression assay results with NAb status indicated both tests were sensitive enough for NAb screening. Conclusion A normal range of NAb titer in Chinese population was established in this study. Anti-IFN-β BAb assay and in vivo MxA gene expression assay were proved suitable for NAb screening. The performance of the developed MxA induction qPCR assay was superior to MxA induction ELISA, WB assay and comparable to luciferase IFN-β reporter gene assay. By using MxA induction qPCR assay, actual efficacy of IFN-β therapy could be measured and monitored. Any treatment failure could be predicted earlier. / published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

published_or_final_version / Electrical and Electronic Engineering / Master / Master of Philosophy

published_or_final_version / Electrical and Electronic Engineering / Master / Master of Philosophy

No description available.

No description available.

Systems biologists use interaction graphs to model the behaviour of biological systems at the molecular level. In an iterative process, such biologists observe the reactions of living cells under various experimental conditions, view the results in the context of the interaction graph, and then propose changes to the graph model. These graphs represent dynamic knowledge of the biological system being studied and evolve as new insight is gained from the experimental data. While numerous graph layout and drawing packages are available, these tools did not fully meet the needs of our immunologist collaborators. In this thesis, we describe the data display needs of these immunologists and translate these needs into visual encoding decisions. These decisions led us to create Cerebral, a system that uses a biologically guided graph layout and incorporates experimental data directly into the graph display. Our graph layout algorithm uses simulated annealing with constraints, optimized with a uniform grid to have an expected runtime of o(E/V). Small multiple views of different experimental conditions and a measurement-driven parallel coordinates view enable correlations between experimental conditions to be analyzed at the same time that the measurements are viewed in the graph context. This combination of coordinated views allows the biologist to view the data from many different perspectives simultaneously. To illustrate the typical analysis tasks performed, we analyze two datasets using Cerebral. Based on feedback from our collaborators, we conclude that Cerebral is a valuable tool for analyzing experimental data in the context of an interaction graph model.

The increasing demand on multimedia communication over wired and wireless networks imposes a continuous pressure on developing more robust coding schemes. Recently, joint source-channel coding with multiple description codes has become an attractive solution to ensure robust communication over noisy channels. In this thesis, we conduct analysis and design of multiple description codes for wired and wireless communication channels. First, a multiple description quantizer (MDQ) design method based on channel optimized quantization is developed. The proposed multiple channel optimized quantizer design scheme does not require index assignment and offers the benefit of resilience to both symbol and erasure errors. Low complexity MDQ is further explored and used to build a multiple description audio coder. Next, the advantages of employing multiple description coding over multiple-input multiple-output wireless channels are investigated. Information theoretical analysis is conducted and practical MDQ codes are designed. Finally, a new E-model based performance measure accounting for both rate-distortion performance and delay impairment is proposed to compare multiple description coding and layered coding for communication over packet networks. / Thesis (Ph.D, Electrical & Computer Engineering) -- Queen's University, 2007-09-28 15:07:27.322

Pryke, Lindsay, Dysart, and Dupuis (2004) investigated a novel method of lineup administration where participants made identifications from multiple lineups showing faces and bodies or playing recorded voices. Identifications from these multiple lineups was diagnostic of guilt; that is, the more lineups a person was selected from the more likely it was that the selected person was actually seen by the witness (as opposed to an innocent suspect; Pryke et al., 2004). The current studies expanded on this procedure and assessed how well the multiple lineup method works when each of the lineups for a target show faces of the same lineup members, with each lineup showing the members facing one of three angles. In Experiment 1, participants (n = 72) saw the targets in the same three views that were shown in the lineups and were asked to make lineup decisions for each of the three lineups. In Experiment 2, participants (n = 96) saw the targets in only one view, which did not always match the views seen in the lineups. Again, participants made lineup decisions for each of the three lineups. For both studies, when the data were collapsed across targets, the procedure was diagnostic in that more selections were associated with a higher probability of guilt (operationalized as being the previously seen target). However, the effectiveness of the procedure varied across targets such that in some cases multiple selections were no more diagnostic of guilt than single selections. Pryke et al., (2004) reported that multiple identifications were highly diagnostic of guilt but relatively rare. In the current studies, most participants made multiple identifications of the targets, probably because all of the lineups used photos of faces. Results for assessments of confidence-accuracy and advantages for certain lineup angles were generally mixed and often differed between the two studies. In all, the most pertinent assessments of utility (diagnosticity and percentage of participants making multiple identifications) showed promise for using multiple lineups of faces. / Thesis (Master, Psychology) -- Queen's University, 2009-10-01 16:22:03.154