Browsing by Subject "mechanism"

Now showing 1 - 4 of 4
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    Bacterial Response to Nanoparticles at the Molecular Level
    (2018-05) Qiu, Tian
    Nanotechnology has been an emerging field due to the promising properties of engineered nanomaterials, materials with at least one dimension less than 100 nanometers. With increasing application of NPs, the risk of these novel materials to environment requires thorough investigation to prevent negative impacts. NPs have enormous variety due to combinations of chemical compositions, sizes, shapes, structures and surface modifications. Building predictive models that link NP properties to biological outcomes is the key to proactive safer NP design. High-throughput toxicity screening and investigating toxicity mechanisms are the common two strategies building towards predictive models of nanotoxicity. These two strategies work together: high-throughput assays facilitate preliminary screening of potentially toxic materials for further mechanistic studies to discover biomarkers and molecular pathways of interest, which will in turn be validated on multiple materials and organisms with high-throughput screening. My thesis work combines both strategies to develop high-throughput screening assays and mechanistic understanding at different molecular levels of how an environmental bacterium, Shewanella oneidensis MR-1, responds to various NP exposures. In this work, Chapter 1 reviews recent advances in analytical nanotoxicology and identifies four key areas that would further bring the field to its maturity. Chapter 2 represents a comprehensive mechanistic study on bacteria responding to TiO2 NPs with UVA illumination. Chapter 3 uses gene expression to explore molecular response among two organisms at different trophic levels to positively and negatively charged gold NPs. Chapter 4 identifies that purification method can be one neglected source of apparent NP toxicity. A high-throughput bacterial viability assay that is free of NP interference is presented in Chapter 5. Finally, in Chapter 6, DNA damage is revealed as a toxicity mechanism for nanoscale complex metal oxide nanomaterials to bacteria.
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    Characterization of the cortical electrophysiological effects of motor thalamic DBS and assessment of a pharmacological model for essential tremor
    (2021-02) Bello, Edward
    Deep brain stimulation (DBS) of the cerebellar-receiving area of motor thalamus has proven to be a highly effective neurosurgical treatment for Essential tremor (ET). Previous clinical studies, however, have also indicated that the overall efficacy and efficiency of the therapy can vary from patient to patient and that the physiological rationale for this outcome variability is not well understood. Functional imaging studies have shown that the pathological state of ET and thalamic DBS treatment each exert a distributed effect on the motor control network including the primary motor cortex (M1). What this effect is on the neuronal level in M1 is not known. Through a series of electrophysiological experiments in a large preclinical animal model, we investigated first how neuronal spike rates and patterns in M1 change during thalamic DBS and second how such changes might explain the clinical observations that (1) higher frequency pulse trains for thalamic DBS are more effective in suppressing tremor and (2) electrode contacts at the ventral pole of motor thalamus are more efficient at reducing tremor. Higher frequency thalamic DBS resulted in a mild increase in the population averaged neuronal spike rate in M1, a significant decrease in population-averaged spike pattern entropy, and a strong increase in the proportion of neurons with phase-locked spike activity. In contrast, high-frequency DBS through electrodes at the ventral pole of motor thalamus at low current amplitudes (in comparison to electrodes within motor thalamus proper) was found to predominantly affect phase-locked spike activity but not spike rate and spike-pattern entropy. Together, these data suggest that M1 phase-locked spike activity may be a useful biomarker for future studies seeking to develop and assess new approaches for optimizing DBS therapy for action and postural tremors. Toward this goal, we also characterized and assessed the suitability of the alkaloid harmaline in generating a robust and consistent tremor in a large preclinical animal for future translational efforts developing technology to help individuals living with ET.
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    Oxygen Atom Transfer (OAT) Reactions Performed by Synthetic Nonheme Oxoiron(IV) Species Supported by Tetraaza-Macrocyclic Ligands.
    (2021-12) SHENG, YUAN
    Non-heme iron enzymes are of great importance in harvesting O2 to carry out versatile oxidation reactions such as the hydroxylation of aliphatic and aromatic substrates, olefin epoxidation, alkane halogenation and other vital biological transformations. The reactive oxoiron(IV) intermediate found in these non-heme iron enzymes has been synthesized separately in the absence of the enzyme active site and shown to mimic the enzymatic transformations. The focus of such applications relies heavily on the ability of these reactive oxoiron(IV) species to abstract H-atoms from organic substrates, despite the fact that enzymes typically perform two-electron oxidations of the substrates, such as oxygen atom transfer (OAT) reactions.This thesis explores three types of OAT reactions performed by different synthetic non-heme oxoiron(IV) complexes. It first complexes, demonstrating the different behaviors of the oxoiron(IV) moiety. Chapter 2 focuses on the exchange of the Fe(IV)=O moiety with water in non-heme systems as compared to their heme analogs. More importantly, Chapter 3 elucidates the general mechanism for the hydroxylation of a pendant aromatic ring by an oxoiron(IV) species to provide a complete reaction scheme. Lastly, Chapter 4 examines the ligand effects on perturbing the ability of an oxoiron(IV) species to transfer its oxygen atom, with the unexpected discovery of an FeIII-OH species performing disproportionation reactions.
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    Understanding Sensemaking in Undergraduate Science Classrooms
    (2020-08) Zhao, FangFang
    This three-paper dissertation explores sensemaking in undergraduate science classrooms. The first two studies explore the sensemaking of mathematical equations in science and the third study investigates students’ sensemaking of one scientific phenomenon. Together, these studies provide new resources for research and contribute to theory on the sensemaking of mathematical equations and scientific phenomena. In the first study, an extensive and systematic literature review was performed to identify possible types of sensemaking for mathematical equations in science. Relevant publications around sensemaking in both the science education and mathematics education literature were reviewed. The resulting Sci-Math Sensemaking Framework includes nine categories for different types of sensemaking, five in the mathematics dimension and four in the science dimension. This novel framework provides researchers with an analytical tool to explore sensemaking in the instruction of mathematical equations across the scientific disciplines. In the second study, the Sci-Math Sensemaking framework was used to understand the sensemaking opportunities provided by four undergraduate biology instructors teaching mathematical equations in the context of population growth. A multiple-case study was conducted with each instructor’s lesson(s) described and the different sensemaking opportunities identified. A comparison across instructors revealed that instructors provided different types of mathematics sensemaking and science sensemaking in their class, and they organized these different types of sensemaking opportunities in different ways. Instructors combined sensemaking across categories in the Sci-Math Sensemaking Framework in three different ways, two of which had not been previously identified in the literature. The third study investigated undergraduate biology students’ sensemaking of the scientific phenomenon of mutation. A qualitative analysis was performed on students’ written responses to open-ended questions on how mutations arise in animal populations. Although the questions should have elicited an explanation involving a biological process, many students responded with only a definition of mutation. It is suggested that instructional approaches should place greater emphasis on understanding the process-related features of mutation.