Thesis (M. Sc.)--University of Hong Kong, 1978. / Typescript.

Besides age, inheritance of the apoE-E4 allele is the main risk factor for late-onset AD. To determine the role of apoE in amyloid deposition, we studied mice expressing both mutant human amyloid [beta]-protein precursor (APP) and presenilin 1 (PS1) that were either normal or knocked-out for apoE. By 7 months, amorphous A[beta] deposition developed equally in both lines, indicating that A[beta] alone is sufficient for deposition to occur. In contrast, filamentous amyloid deposition was catalyzed at least 3000 fold by apoE. Electron micrographs further illustrate the filamentous nature of these plaques. These results and other, behavioral, data indicate that the primary function of apoE in AD is to promote the polymerization of A[beta] into mature, neurotoxic, amyloid. ApoE is also synthesized in the liver and is crucial in cholesterol metabolism, for mice lacking apoE exhibit hypercholesterolemia. We investigated neuropathology in mice using an uncommon technique, parabiosis, to determine whether apoE in the peripheral circulation influences brain amyloid formation. This surgical procedure allows exchange of proteins via peripheral circulation. We show that plasma apoE is found in parabiosed PS/APP/apoE-KO mice, rescuing their hypercholesterolemia. Unexpectedly, amyloid deposition is reduced in parabiosed PS/APP/apoE-KO mice compared to PS/APP controls. ApoE in the periphery seems to slightly reduce amyloid burden, by likely promoting efflux of A[beta];from the brain. These findings reinforce that the mechanisms whereby apoE affects A[beta] metabolism are complex, and the modulation of peripheral apoE metabolism is not likely to impact AD neuropathology. Since cognitive stimulation is associated with lower risk of AD, we sought to investigate the preventative potential of environmental enrichment (EE) using our mouse model.

The character of the first galaxies at redshifts z [greater-than or equal to] 10 strongly depends on the star formation which takes place during their assembly. Conducting cosmological hydrodynamics simulations, we study how the radiative output and chemical enrichment from the first stars impacts the properties of the first galaxies. We find that the radiative feedback from the first stars suppresses the star formation rate at redshifts z [greater-than or equal to] 15 by a factor of only a few. In turn, this suggests that a large fraction of the first galaxies may form from gas which has already been enriched with the first heavy elements ejected by primordial supernovae. In order to characterize the properties of primordial dwarf galaxies, we carry out radiation hydrodynamics simulations which allow to determine how the luminosities in hydrogen and helium emission lines depend on the initial mass function of the stars in the galaxy. As well, we show that the chemical abundance patterns observed in metal-poor Galactic halo stars contain the signature of the first supernovae, and we use this data to indirectly probe the properties of the first stars. / text

Mercury (Hg) is a potent neurotoxin, has both natural and anthropogenic sources to the environment, and is globally dispersed. Humans have been using Hg since antiquity and continue its use in large quantities, mobilizing Hg from stable long-lived geologic reservoirs to actively cycling surface terrestrial and aquatic ecosystems. Human activities, such as mining and coal combustion, have perturbed the natural biogeochemical cycle of Hg. However, the distribution of natural versus anthropogenic Hg in the environment today and the extent of anthropogenic perturbation (i.e., enrichment) are uncertain. Previous model estimates of anthropogenic enrichment have been limited by a lack of information about historical emissions, examined only near-term effects, or have not accounted for the full coupling between biogeochemical reservoirs. Presented here is a framework that integrates recently available historical emission inventories and overcomes these barriers, providing an improved quantitative understanding of global Hg cycling. / Earth and Planetary Sciences

I investigate the chemical evolution of the Universe in a series of cosmological hydrodynamic simulations with the purpose of finding a self-consistent evolutionary scenario of galaxy formation able to reproduce key observables focusing on the enrichment of the intergalactic medium (IGM). The most successful models I run and analyze use the scalings of momentum-driven feedback whereby UV photons generated during the Main Sequence stage accelerate dust-driven winds while providing a significantly larger energy budget than from supernovae alone. The success of this outflow model relies on its ability to drive highly mass-loaded winds from small galactic haloes. These feedback relations, supported by observations of local starburst, are inserted into simulations at all epochs, reproducing observables including the C IV column density and linewidth distributions at z=6->1.5 and the O VI forest at z=0-0.5. Outflows at z>=5 propagate early nucleosynthetic products traced by C IV and lower ionization species into an otherwise metal-free IGM. Continual outflows at the peak ages of star formation (z=5->1.5) produce a non-evolving cosmic mass density of C IV despite continual enrichment increasing IGM metallicity by a factor of ten. The z=0-0.5 O VI forest is composed of weaker absorbers tracing photo-ionized diffuse IGM metals, sometimes injected by primordial galaxies, and stronger absorbers tracing recently injected metals, often unable to escape their parent haloes and sometimes collisionally ionized. Tracking the individual histories of metals in outflows shows the average outflow travels ~100 physical kpc and returns to galaxies on an average timescale of 1-2 Gyr; this result implies metals in superwinds do not remain in the IGM for a Hubble time and are more likely to rejoin galaxies. Metal absorbers aligned with Lyman-alpha are examined in detail, finding that the two often trace different phases of gas with the former tracing an inhomogeneous distribution of metals exhibiting turbulence imparted during the outflow phase dissipating on a Hubble timescale. I find this is the first model to self-consistently reproduce the wide range of IGM observables spanning the history of heavy metal production while being consistent with key galaxy observables. The link between star formation and galactic superwinds requires that a successful model of galaxy formation reproduces both the evolution of galaxies and the IGM.

We study specific aspects of the relationship between the stellar content and the intracluster media (ICM) of galaxy clusters. First, we attempt to solve the long-standing difficulty in explaining the highly enriched ICM by including a previously unaccounted for stellar component: the intracluster stars. To determine the relative contributions of galactic and intracluster stars to the enrichment of the intracluster medium (ICM), we present X-ray surface brightness, temperature, and Fe abundance profiles for a set of twelve galaxy clusters for which we have extensive optical photometry. Assuming a standard IMF and simple chemical evolution model scaled to match the present-day cluster early-type SN Ia rate, the stars in the brightest cluster galaxy (BCG) plus the intracluster stars (ICS) generate 31⁺¹¹₋₉%, on average, of the observed ICM Fe within r₅₀₀(∼ 0.6 times r₂₀₀, the virial radius). Because the ICS typically contribute 80% of the BCG+ICS Fe, we conclude that the ICS are significant, yet often neglected, contributors to the ICM Fe within r₅₀₀. However, the BCG+ICS fall short of producing all the Fe, so metal loss from stars in other cluster galaxies must also contribute. By combining the enrichment from intracluster and galactic stars, we can account for all the observed Fe. These models require a galactic metal loss fraction (0.84(−0.14)^(+0.11)) that, while large, is consistent with theoretical models of Fe mass not retained by galactic stars. The SN Ia rates, especially as a function of galaxy environment and redshift, remain a significant source of uncertainty in further constraining the metal loss fraction. Second, we study the effects of ram-pressure stripping on infalling galaxies using a warm molecular hydrogen (H₂) as a tracer by carrying out a Spitzer infrared spectrograph (IRS) survey of four galaxies with signatures of ram-pressure stripping. We have discovered two galaxies, ESO 137-001 and NGC 4522, with warm H₂ tails stretching 20 kpc and 4 kpc in length, respectively. In the case of ESO 137-001 where we measure a warm H₂ mass loss rate of ∼ 2 − 3 M⊙ yr⁻¹, we estimate that the galaxy will lose all of its gas in a single pass through the cluster core. Strong warm H₂ emission is detected in one other galaxy, CGCG 97-073, which a region within its tail that is mainly dominated by H₂ emission. The warm H₂ observed in these three galaxies share similar temperature and column density properties with warm H₂ masses ranging from 10⁶ − 10⁸ M⊙. From a comparison with the SINGS warm H₂ sample, our results indicate that these galaxies experiencing significant ram-pressure stripping show anomalously high warm H₂ emission that cannot be explained purely from star formation. This adds credence to the hypothesis that H₂ within these galaxies is being shock-heated from the interaction with the ICM. We also discover that stripping of warm and hot dust, as measured at 8 μm and 24 μm, is a common feature of the galaxies observed in our sample. In the case of NGC 4522, we capture the turbulent nature of the stripping process. We measure the star formation rates using published Hα and measured 24 μm luminosities for all of our galaxies and find that some of them have suppressed star formation rates compared to similar mass counterparts in the field. We find a possible association between Hα and warm H₂ emission in three of the four galaxies observed. We conclude that the variation of H₂ properties observed in our sample is likely due to the galaxies being in different stages of ram-pressure stripping. Finally, we report on our efforts to improve the performance of the Lochkeed Arizona Infrared Spectrometer (LAIRS), a near-IR, tunable filter imager. We have made significant progress in identifying the sources of key issues such as the a highly asymmetric line profile and the unstable performance of the servo controller at the MMT. Solutions have been implemented for these issues, such as a revised mounting strategy for the tunable filter plates and a completely new controller with higher bandwidth. Significant progress has been made towards resolving these issues, but a few issues remain before LAIRS meets all of its requirements.

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The chloride anion is known to be the most abundant salt ion in sea water. At the regions such as ODP Sites 1249 and 1250 the highly enriched chloride concentration is observed in a zone extended from near the sediment surface (~1 mbsf) to depths about 25 mbsf. Here, we designed the in-situ electric circuit system for measuring chloride concentration within reliable accuracy. In the cylindrical cell the 5-10 tubes having holes on the wall and electrodes were equipped around clay mixture. The open holes were made to regulate to a certain degree the interface area between methane gas and clay sample. As may be anticipated, the chloride concentration abnormally increased under fast rate condition for forming methane hydrate, but no noticeable concentration change was detected under relatively low rate. In fact, the present experiment seems to be a lot deficient to investigate the ion diffusion and moreover does not fully reflect the real deep-sea floor condition, but the meaningful results for describing the abnormal salinity enrichment might be drawn. The physical effects of chloride anions on surface morphologies of methane hydrate formed in the sediments were additionally examined with the Field Emission-Scanning Electronic Microscope (FE-SEM).

The DNA microarray biotechnology simultaneously monitors the expression of thousands of genes and aims to identify genes that are differently expressed under different conditions. From the statistical point of view, it can be restated as identify genes strongly associated with the response or covariant of interest. The Gene Set Enrichment Analysis (GSEA) method is one method which focuses the analysis at the functional related gene sets level instead of single genes. It helps biologists to interpret the DNA microarray data by their previous biological knowledge of the genes in a gene set. GSEA has been shown to efficiently identify gene sets containing known disease-related genes in the real experiments. Here we want to evaluate the statistical power of this method by simulation studies. The results show that the the power of GSEA is good enough to identify the gene sets highly associated with the response or covariant of interest.

The current study developed a paleolimnological approach to assess changes in diatom assemblages (class Bacillariophyceae) from present-day lake sediments in comparison to those deposited before significant human impact (ca. pre-1850) from 51 Halifax (Nova Scotia, Canada) region lakes in conjunction with a regional diatom-based transfer functions for pH and total phosphorus. All 51 lakes showed changes in diatom assemblages between the present-day and pre-industrial assemblages that was greater than would be expected (i.e. similarity between ‘top’ and ‘bottom’ samples was much less than the similarities within triplicate ‘top’ and ‘bottom’ samples). To help identify the most important environmental stressors impacting diatom assemblages in these lakes, diatom-based reconstructions of inferred changes in pH (DI-pH) and total phosphorus (DI-TP) that were greater than the Root Mean Squared Error (RMSE) of the respective inference models were reconstructed for each of the 51 lakes. For example, a decrease in DI-pH greater than the RMSE of the pH model would be a strong indication of recent acidification, whereas an increase in DI-TP greater than the RMSE of the model indicates nutrient enrichment. Based on this approach, 4% of the lakes are showing acidification-related trends occurring in lakes with low pre-industrial pH values and relatively undisturbed watersheds. Almost 14% of the study lakes have been impacted by nutrients and characterized by watershed development and high concentrations of TP. Approximately 4% of lakes showed oligotrophication and acidification. Diatom assemblages from almost 20% of the study lakes that were relatively unimpacted by the afore-listed environmental stressors show trends consistent with climate warming. These lakes show an increase in DI-pH greater than the RMSE of the inference model, and floristic changes typically showed a decrease in the relative abundance of Aulacoseira distans paralleled with increase in Cyclotella stelligera and other planktonic diatoms in the modern sediments. In addition, Diatoma tenue and Diploneis parma, diatoms tolerant of high conductivity, increased in 45% of the study lakes suggesting road salt as an additional stressor. This thesis provides a rapid paleolimnological-based technique to assess regional water-quality changes, and further demonstrates the complexity of ecological changes within freshwater resources. / Thesis (Master, Biology) -- Queen's University, 2009-09-10 15:18:07.01