Doctor of Philosophy

dissertationMagnetic Resonance Imaging (MRI) is one of the most important medical imaging technologies in use today. Unlike other imaging tools, such as X-ray imaging or computed tomography (CT), MRI is noninvasive and without ionizing radiation. A major limitation of MRI, however, is its relatively low imaging speed and low spatial-temporal resolution, as in the case of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). These hinder the clinical use of MRI. In this thesis, we aim to develop novel signal processing techniques to improve the imaging quality and reduce the imaging time of MRI. This thesis consists of two parts, corresponding to our work on parallel MRI and dynamic MRI, respectively. In the first part, we address an important problem in parallel MRI that the coil sensitivities functions are not known exactly and the estimation error often leads to artifacts in the reconstructed image. First, we develop a new framework based on multichannel blind deconvolution (MBD) to jointly estimate the image and the sensitivity functions. For fully sampled MRI, the proposed approach yields more uniform image reconstructions than that of the sum-of-squares (SOS) and other existing methods. Second, we extend this framework to undersampled parallel MRI and develop a new algorithm, termed Sparse BLIP, for blind iterative parallel image reconstruction using compressed sensing (CS). Sparse BLIP reconstructs both the sensitivity functions and the image simultaneously from the undersampled data, while enforcing the sparseness constraint in the image and sensitivities. Superior image constructions can be obtained by Sparse BLIP when compared to other state-of-the-art methods. In the second part of the thesis, we study highly accelerated DCE-MRI and provide a comparative study of the temporal constraint reconstruction (TCR) versus model-based reconstruction. We find that, at high reduction factors, the choice of baseline image greatly affects the convergence of TCR and the improved TCR algorithm with the proposed baseline initialization can achieve good performance without much loss of temporal or spatial resolution for a high reduction factor of 30. The model-based approach, on the other hand, performs inferior to TCR with even the best phase initialization

Preparation, characterization and application of a molecularly imprinted polymer for selective recognition of Sulpiride

A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio of sulpiride-ITA-EGDMA of 1:4:15 by single-factor experiments. The MIP showed good adsorption property with imprinting factor α of 5.36 and maximum adsorption capacity of 61.13 μmol/g, and was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and surface area analysis. With the structural analogs (amisulpride, tiapride, lidocaine and cisapride) and small molecules containing a mono-functional group (p-toluenesulfonamide, formamide and 1-methylpyrrolidine) as substrates, static adsorption, kinetic adsorption, and rebinding experiments were also performed to investigate the selective adsorption ability, kinetic characteristic, and recognition mechanism of the MIP. A serial study suggested that the highly selective recognition ability of the MIP mainly depended on binding sites provided by N-functional groups of amide and amine. Moreover, the MIP as solid-phase extractant was successfully applied to extraction of sulpiride from the mixed solution (consisted of p-toluenesulfonamide, sulfamethoxazole, sulfanilamide, p-nitroaniline, acetanilide and trimethoprim) and serum sample, and extraction recoveries ranged from 81.57% to 86.63%. The tentative tests of drug release in stimulated intestinal fluid (pH 6.8) demonstrated that the tablet with the MIP–sulpiride could obviously inhibit sulpiride release rate. Thus, ITA-based MIP is an efficient and promising alternative to solid-phase adsorbent for extraction of sulpiride and removal of interferences in biosample analysis, and could be used as a potential carrier for controlled drug releas

Genomic and transcriptomic analyses reveal distinct biological functions for cold shock proteins (<i>Vpa</i>CspA and <i>Vpa</i>CspD) in <i>Vibrio parahaemolyticus</i> CHN25 during low-temperature survival

Abstract Background Vibrio parahaemolyticus causes serious seafood-borne gastroenteritis and death in humans. Raw seafood is often subjected to post-harvest processing and low-temperature storage. To date, very little information is available regarding the biological functions of cold shock proteins (CSPs) in the low-temperature survival of the bacterium. In this study, we determined the complete genome sequence of V. parahaemolyticus CHN25 (serotype: O5:KUT). The two main CSP-encoding genes (VpacspA and VpacspD) were deleted from the bacterial genome, and comparative transcriptomic analysis between the mutant and wild-type strains was performed to dissect the possible molecular mechanisms that underlie low-temperature adaptation by V. parahaemolyticus. Results The 5,443,401-bp V. parahaemolyticus CHN25 genome (45.2% G + C) consisted of two circular chromosomes and three plasmids with 4,724 predicted protein-encoding genes. One dual-gene and two single-gene deletion mutants were generated for VpacspA and VpacspD by homologous recombination. The growth of the ΔVpacspA mutant was strongly inhibited at 10 °C, whereas the VpacspD gene deletion strongly stimulated bacterial growth at this low temperature compared with the wild-type strain. The complementary phenotypes were observed in the reverse mutants (ΔVpacspA-com, and ΔVpacspD-com). The transcriptome data revealed that 12.4% of the expressed genes in V. parahaemolyticus CHN25 were significantly altered in the ΔVpacspA mutant when it was grown at 10 °C. These included genes that were involved in amino acid degradation, secretion systems, sulphur metabolism and glycerophospholipid metabolism along with ATP-binding cassette transporters. However, a low temperature elicited significant expression changes for 10.0% of the genes in the ΔVpacspD mutant, including those involved in the phosphotransferase system and in the metabolism of nitrogen and amino acids. The major metabolic pathways that were altered by the dual-gene deletion mutant (ΔVpacspAD) radically differed from those that were altered by single-gene mutants. Comparison of the transcriptome profiles further revealed numerous differentially expressed genes that were shared among the three mutants and regulators that were specifically, coordinately or antagonistically modulated by VpaCspA and VpaCspD. Our data also revealed several possible molecular coping strategies for low-temperature adaptation by the bacterium. Conclusions This study is the first to describe the complete genome sequence of V. parahaemolyticus (serotype: O5:KUT). The gene deletions, complementary insertions, and comparative transcriptomics demonstrate that VpaCspA is a primary CSP in the bacterium, while VpaCspD functions as a growth inhibitor at 10 °C. These results have improved our understanding of the genetic basis for low-temperature survival by the most common seafood-borne pathogen worldwide

Genome Analyses of Icelandic Strains of Sulfolobus islandicus, Model Organisms for Genetic and Virus-Host Interaction Studies

The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad host range for exceptional crenarchaeal viruses and conjugative plasmids and was selected for studying their life cycles and host interactions. The genomes of strains REY15A and HVE10/4 are 2.5 and 2.7 Mb, respectively, and each genome carries a variable region of 0.5 to 0.7 Mb where major differences in gene content and gene order occur. These include gene clusters involved in specific metabolic pathways, multiple copies of VapBC antitoxin-toxin gene pairs, and in strain HVE10/4, a 50-kb region rich in glycosyl transferase genes. The variable region also contains most of the insertion sequence (IS) elements and high proportions of the orphan orfB elements and SMN1 miniature inverted-repeat transposable elements (MITEs), as well as the clustered regular interspaced short palindromic repeat (CRISPR)-based immune systems, which are complex and diverse in both strains, consistent with them having been mobilized both intra- and intercellularly. In contrast, the remainder of the genomes are highly conserved in their protein and RNA gene syntenies, closely resembling those of other S. islandicus and Sulfolobus solfataricus strains, and they exhibit only minor remnants of a few genetic elements, mainly conjugative plasmids, which have integrated at a few tRNA genes lacking introns. This provides a possible rationale for the presence of the introns

El Diario de Pontevedra : periódico liberal: Ano XXVIII Número 8146 - 1911 xullo 8

Circular maps of the V. parahaemolyticus CHN25 chromosomes. (a) and (b) represent the larger and smaller chromosomes of V. parahaemolyticus CHN25, respectively. Each circle in the grey lines, except for the two innermost circles, illustrates specific features on the plus (outer region) and minus (inner region) strands. The lines and boxes in the three outermost circles are coloured according to the COG categories. The circles indicate the following from the outside inwards: first circle, predicted protein-coding genes; second circle, classified essential genes, including cell division, replication, transcription, translation, and amino acid metabolism; third circle, tRNA genes and rRNA operons; fourth circle, GC-skew (values above zero are red, values below zero are blue); fifth circle, GC content. (TIF 22070 kb

Additional file 2: Figure S2. of Genomic and transcriptomic analyses reveal distinct biological functions for cold shock proteins (VpaCspA and VpaCspD) in Vibrio parahaemolyticus CHN25 during low-temperature survival

Circular maps of the V. parahaemolyticus CHN25 plasmids. (a)-(c): each circle in the grey lines, except for the two innermost circles, illustrates specific features on the plus (outer region) and minus (inner region) strands. Lines and boxes in the three outermost circles are coloured according to the COG categories. The circles indicate the following from the outside inwards: first circle, predicted protein-coding genes; second circle, GC-skew (values above zero in red, values below zero in blue); and third circle, GC content. (TIF 15096 kb