Indirect Detection of Axonal Architecture With Q-Space Imaging

Evaluating axon morphology would provide insights into connectivity, maturation, and disease pathology. Conventional diffusion MRI can provide metrics that are related to axon morphology, but cannot measure specific parameters such as mean axon diameter (MAD) and intracellular fraction (ICF). Q-space imaging (QSI) is an advanced diffusion MRI technique that may be able to provide more information on axon morphology. However, QSI has several limitations that affect its implementation and accuracy. The main objective of this dissertation was to address these limitations and to evaluate the potential of QSI to accurately assess axon morphology. First, a custom-built high-amplitude gradient coil was used to address the limitations in the maximum gradient amplitude available with commercial systems. Second, to understand the relationship between axon morphology and QSI, simulations were used to investigate the effects of the presence of both extracellular and intracellular signals (ECS and ICS) as well as variation in cell size and shape. Third, three QSI-based methods were designed provide specific measures of axon morphology which have not been reported before. The maximum amplitude of the custom gradient coil was 50 T/m that, for the first time, allowed for sub-micron displacement resolution while fulfilling the short gradient approximation. This enabled near-ideal QSI experiments to be performed. QSI experiments on excised mouse spinal cords showed good correlation with histology, but overestimated MAD. Simulations showed that axon morphology was the dominant effect on QSI and suggested that the presence of ECS and ICS signals may complicate interpretation. Three methods were designed to account for signal in ECS and ICS: two relied on a two-compartment model of the displacement probability density function and the echo attenuation at low q-values, and a third varied the gradient duration to differentiate diffusion in ECS from ICS. All three methods provided estimates of MAD and ICF that showed better agreement with histology than QSI. The methods were also evaluated implementation on a clinical scanner. This dissertation demonstrated the sensitivity of QSI to axon morphology and showed the feasibility of three methods to accurately estimate MAD and ICF. Further investigation is warranted to study future applications

The Expression of TNFα by Human Muscle: Relationship to Insulin Resistance

TNFα is overexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. Using RT-PCR, TNF was detected in human heart, in skeletal muscle from humans and rats, and in cultured human myocytes. Using competitive RT-PCR, TNF was quantitated in the muscle biopsy specimens from 15 subjects whose insulin sensitivity had been characterized using the glucose clamp technique. TNF expression in the insulin resistant subjects and the diabetic patients was fourfold higher than in the insulin sensitive subjects, and there was a significant inverse linear relationship between maximal glucose disposal rate and muscle TNF (r = -0.60, P \u3c 0.02). In nine subjects, muscle cells from vastus lateralis muscle biopsies were placed into tissue culture for 4 wk, and induced to differentiate into myotubes. TNF was secreted into the medium from these cells, and cells from diabetic patients expressed threefold more TNF than cells from nondiabetic subjects. Thus, TNF is expressed in human muscle, and is expressed at a higher level in the muscle tissue and in the cultured muscle cells from insulin resistant and diabetic subjects. These data suggest another mechanism by which TNF may play an important role in human insulin resistance

Enhancers of agrobacterium-mediated transformation of Tibouchina semidecandra selected on the basis of GFP expression

Genetic engineering is a powerful tool for the improvement of plant traits. Despite reported successes in the plant kingdom, this technology has barely scratched the surface of the Melastomataceae family. Limited studies have led to some optimisation of parameters known to affect the transformation efficiency of these plants. The major finding of this study was to optimise the presence of selected enhancers (e.g., monosaccharides (D-glucose, D-galactose and D-fructose), tyrosine, aluminium chloride and ascorbic acid) to improve the transformation efficiency of Tibouchina semidecandra. Agrobacterium tumefaciens strain LBA4404 harbouring the disarmed plasmid pCAMBIA1304 was used to transform shoots and nodes of T. semidecandra. Different concentrations of the transformation enhancers were tested by using GFP as a reporter. The results obtained were based on the percentage of GFP expression, which was observed 14 days post-transformation. A combination of 120 μM galactose and 100 μM tyrosine supplemented with 600 μM aluminium chloride in the presence of 15 mg/L ascorbic acid gave the highest percentage of positive transformants for T. semidecandra shoots. Whereas 60 μM galactose and 50 μM tyrosine with 200 μM aluminium chloride in the presence of 15 mg/L ascorbic acid was optimum for T. semidecandra nodes. The presence of the hptII transgene in the genomic DNA of putative T. semidecandra transformants was verified by PCR amplification with specific primers

Molecular Structure and Confining Environment of Sn Sites in Single-Site Chabazite Zeolites

Chabazite (CHA) molecular sieves, which are industrial catalysts for the selective reduction of nitrogen oxides and the conversion of methanol into olefins, are also ideal materials in catalysis research because their crystalline frameworks contain one unique tetrahedral-site. The presence of a single lattice site allows for more accurate descriptions of experimental data using theoretical models, and consequently for more precise structure-function relationships of active sites incorporated into framework positions. A direct hydrothermal synthesis route to prepare pure-silica chabazite molecular sieves substituted with framework Sn atoms (Sn-CHA) is developed, which is required to predominantly incorporate Sn within the crystalline lattice. Quantitative titra-tion with Lewis bases (NH3, CD3CN, pyridine) demonstrates that framework Sn atoms behave as Lewis acid sites, which catalyze intermolecular propionaldehyde reduction and ethanol oxidation, as well as glucose-fructose isomerization. Aqueous-phase glucose isomerization turnover rates on Sn-CHA are four orders-of-magnitude lower than on Sn-Beta zeolites, but similar to those on amorphous Sn-silicates. Further analysis of Sn-CHA by dynamic nuclear polarization enhanced solid-state nuclear magnetic reso-nance (DNP NMR) spectroscopy enables measurement of 119Sn NMR chemical shift anisotropy (CSA) of Sn sites. Comparison of experimentally determined CSA parameters to those computed on cluster models using density functional theory supports the pres-ence of closed sites (Sn-(OSi)4) and defect sites ((HO)-Sn-(OSi)3) adjacent to a framework Si vacancy), which respectively be-come hydrated hydrolyzed-open sites and defect sites when Sn-CHA is exposed to ambient conditions or aqueous solution. Kinetic and spectroscopic data show that large substrates (e.g., glucose) are converted only on Sn sites located within disordered mesopo-rous voids of Sn-CHA, which are selectively detected and quantified in IR and 15N and 119Sn DNP NMR spectra using pyridine titrants. This integrated experimental and theoretical approach allows precise description of the primary coordination and secondary confining environments of Sn active sites isolated in crystalline silica frameworks, and clearly establishes the role of confinement within microporous voids for aqueous-phase glucose isomerization catalysis

Cherenkov Telescopes as Optical Telescopes for Bright Sources: Today's Specialised Thirty Metre Telescopes?

Imaging Atmospheric Cherenkov Telescopes (IACTs) use large-aperture (~ 10 - 30 m) optical telescopes with arcminute angular resolution to detect TeV gamma-rays in the atmosphere. I show that IACTs are well-suited for optical observations of bright sources (V <= 8 - 10), because these sources are brighter than the sky background. Their advantages are especially great on rapid time-scales. Thus, IACTs are ideal for studying many phenomena optically, including transiting exoplanets and the brightest gamma-ray bursts. In principle, an IACT could achieve millimagnitude photometry of these objects with second-long exposures. I also consider the potential for optical spectroscopy with IACTs, finding that their poor angular resolution limits their usefulness for high spectral resolutions, unless complex instruments are developed. The high photon collection rate of IACTs is potentially useful for precise polarimetry. Finally, I briefly discuss the broader possibilities of extremely large, low resolution telescopes, including a 10" resolution telescope and spaceborne telescopes.Comment: 10 pages, 3 figures, accepted by MNRA

An investigation towards hostel space allocation problem with stochastic algorithms

This research presents the study of stochastic algorithms in one of the limited study in Space Allocation Problem. The domain involves the allocation of students into the available rooms which is known as Hostel Space Allocation Problem. The problem background of this domain which related with hard constraints and soft constraints are discussed and the formal mathematical models of constraints in Universiti Malaysia Sabah Labuan International Campus are presented. The construction of initial solution is handled by Constraint Programming algorithm. Two algorithms mainly Great Deluge with linear and non-linear decay rate and Simulated Annealing with linear reduction are proposed to improve the quality of solution. The experimental results show that Simulated Annealing with linear reduction temperature performs well in this domain

The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.

Background: It is frequently assumed that pre-invasive lesions are simpler precursors of cancer, and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments, and early detection methodologies. Methods: We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. Forty-eight samples from 16 patients were further examined using exome sequencing. Results: Evidence of a shared ancestor of both dysplasia and carcinoma was seen in all but one patient. One third of dysplasias showed independent copy number events. The remainder had a similar or simpler copy number pattern to the carcinoma. All dysplasias examined contained somatic mutations absent in the related carcinoma. Previously observed copy number changes and TP53 mutations were very frequently observed, and almost always shared between dysplasia and carcinoma. Other gene changes were more sporadic. Pathway analysis confirmed that each patient’s disease developed in a different way. Examining the numbers of shared mutations, and the rate of accumulation of mutations showed evidence that all samples contain a population of sub-clones, with little evidence of selective advantage of a subset of these. Conclusions: These findings suggest that most of the genomic changes driving oral cancer occur in the pre-cancerous state by way of gradual random accumulation rather than a dramatic single event

Notes on the mammals from Imbak Canyon Conservation Area

Primary forest sites for biodiversity conservation in Sabah are declining. Therefore, biodiversity surveys in areas where primary forests still exist are of paramount importance. Information derived from such studies are crucial in order to develop sound biodiversity conservation management plans. A brief camera trapping study of six days and nights in a localised area at the southern slopes of the Imbak Canyon Conservation Area in Sabah, supported by direct and indirect observations, revealed a rich mammal community in the surveyed areas. A total of 23 species of small to large-sized mammals from 6 orders and 13 families were recorded. Compared to an earlier study in the same area, the mammal species recorded in the present study included 14 species that are new records for Imbak Canyon. Clearly, Imbak Canyon is an important area for mammal conservation

Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging

Objective: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response. Methods: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. Results: Thirty-five participants completed, on average, 85 hours (IQR=70–100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen’s d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. Conclusions: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. Trial registration number: NCT02540889