Electronic Theses and Dissertations

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Electronic theses and dissertations of masters and doctoral students submitted to the Graduate School.

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1.8 MeV proton response of thermally stabilized gallium nitride RF power transistors
(2017-11-07) McCurdy, Michael William Adelino; Ronald. D. Schrimpf; Daniel M. Fleetwood
Three commercially available GaN-based HEMT RF power devices were irradiated with 1.8 MeV protons in three operational modes. The operational modes were semi-on, fully-on and RF-on. The former two modes were low and manufacturer-specified quiescent levels of DC bias. The latter mode was at the manufacturer-specified quiescent DC bias with the test article under power RF operation. Thermoelectric cooling was used to minimize thermally induced parametric shifts. Electrical measurements such as ID-VG sweeps were conducted from which threshold voltage, VTH, and transconductance, gm, were calculated and plotted. RF parameters of interest were measured. S-parameter sweeps were conducted in the low power linear operational regime as well as gain measurements at a higher power level. Responses were plotted in terms of gain vs. frequency, gain vs. fluence and on Smith charts. One part type exhibited increased RF small signal gain with increasing fluence over all operational modes. The variety of responses seen indicate thorough testing of candidate devices should be performed to ensure the required level of operation for applications with high reliability requirements.
1/f noise and aging effects on MOS transistors
(2011-10-17) Danciu, Ioana; Daniel M. Fleetwood; W. Tim Holman
The 1/f noise magnitude of n-channel metal-oxide-semiconductor field effect transistors is found to decrease by up a factor of ~3 after 18 years of room-temperature aging. This decrease is largest in devices with high-temperature post-gate-oxidation nitrogen annealing, which increases the densities of O vacancies and strained Si-Si bonds near the silicon/silicon dioxide interface. Approximately 100 mV positive threshold voltage shifts are observed for all device types during aging; these are attributed to reactions with hydrogenous species (e.g., water vapor). The aging related changes in 1/f noise may well be caused by the relaxation of strained Si-Si bonds associated with O vacancies in the near-interfacial silicon dioxide layer.
13C metabolic flux analysis of industrial Chinese hamster ovary (CHO) cell cultures
(2018-11-26) McAtee Pereira, Allison Grace; Jamey D Young; John T Wilson; Matthew Lang; Robert Carnahan
Chinese hamster ovary (CHO) cells are the most commonly utilized host cell line for biomanufacturing monoclonal antibody (mAb) drugs and other therapeutic proteins. This dissertation describes the application of 13C metabolic flux analysis (MFA) to characterize CHO cell metabolism under various experimental conditions that are relevant to industrial bioprocesses. First, isotopically nonstationary (INST)-MFA was utilized to assess the metabolism of an industrial CHO cell line engineered to constitutively express PGC1α—a transcriptional co-activator previously reported to enhance mitochondrial metabolism in animal cells. Overexpression of PGC1α successfully increased specific productivity (qP) by a range of 2.6- to 5.2-fold over the parental cell line and increased overall carbon flux through the citric acid cycle (CAC). This finding is consistent with prior studies that have correlated increased CAC flux with elevated mAb productivity in CHO cell cultures. Next, we applied 13C MFA to industrial CHO cell cultures exposed to a novel proprietary growth medium designed to decrease excess ammonia production by roughly 40%. We determined that the low-ammonia-producing medium did not significantly alter central carbon metabolism of CHO cell cultures. Additionally, the presence of excess ammonia in the culture was determined to have no significant effect on metabolic phenotype. Therefore, it was concluded that nitrogen metabolism could be effectively manipulated through media redesign without significantly altering important bioenergetic fluxes. Next, a fed-batch 13C MFA study of CHO cells during stationary growth phase uncovered that anti-apoptotic gene expression increased glucose and lactate consumption rates and peak viable cell densities while reducing cell death rates. Because mAb productivities are typically highest when culture growth rate is minimal, attempts to prolong the stationary growth phase and enhance metabolism during this phase are important for maximizing overall product yields. Finally, the metabolism of a CHO cell clone producing a degraded mAb product was compared to a CHO cell clone producing the intact product. We hypothesized that an overactive oxidative pentose phosphate pathway (OPPP) was responsible for increased product degradation by fueling the thioredoxin system with NADPH, thus leading to disulfide bond reduction. However, the two CHO cell clones exhibited similar OPPP activities as quantified with 13C MFA. Therefore, we concluded that differences in OPPP activity were not responsible for the increase in product degradation. Overall, this dissertation details comprehensive metabolic studies of multiple industrial CHO cell lines providing actionable insights into further advances in biopharmaceuticals manufacturing.
13C metabolic flux analysis of recombinant Chinese hamster ovary (CHO) cell cultures
(2014-11-25) Templeton, Neil Andrew; Jamey D. Young; M. Douglas LeVan; Scott A. Guelcher; David L. Tabb
We have applied 13C metabolic flux analysis (13C MFA) to develop a system-wide understanding of the central carbon metabolism of Chinese hamster ovary (CHO) cells, the most widely used host for industrial production of monoclonal antibodies (mAbs) and other therapeutic proteins. First, we assessed dynamic changes in CHO metabolism during four different stages of a fed-batch culture to discover metabolic phenotypes that were associated with peak mAb productivity. While glycolytic metabolism dominated during the initial growth phase, enhanced oxidative metabolism involving increased citric acid cycle (CAC) flux and oxidative pentose phosphate pathway (oxPPP) activity prevailed during later phases when mAb production was highest. Next, we applied 13C MFA to examine CHO lines that had been engineered to express Bcl-2Δ, an engineered anti-apoptotic protein, to elucidate its impact on cell growth and metabolism. Not only was integrated viable cell density (IVCD) and culture longevity increased by Bcl-2Δ, but the intracellular fate of pyruvate was significantly altered over the entire course of a batch culture. More pyruvate was oxidized by mitochondrial CAC metabolism during the initial lactate-producing phase, and more lactate was consumed relative to glucose during the later lactate-consuming phase of culture. Finally, 13C MFA was applied to compare the metabolic phenotypes of nine different mAb secreting CHO lines, as well as three non-producing host lines. Among four clones that did not express Bcl-2Δ, a linear correlation was found between specific antibody productivity and total NADH production (an indicator of oxidative metabolism). Expression of Bcl-2Δ led to a general increase in NADH production that was accompanied by even greater specific mAb productivity. Overall, an in-depth quantification of CHO intracellular metabolism was accomplished by this dissertation, with multiple findings that are applicable to industrial antibody production.
161-Ho + IUdR: Optimized Photon Activation Therapy
(2010-05-17) Stephens, Bryan James; Marcus H. Mendenhall; Charles W. Coffey II; Richard F. Haglund Jr; Michael G. Stabin; Robert A. Weller
The radiosensitizing pharmaceutical iododeoxyuridine (IUdR) has been around since the 1950’s, but has never reached full efficacy due to a lack of practical activation radiation source in the suitable energy range. We have successfully created and characterized radioactive holmium as a solution to this dilemma. The spectrum consists primarily of dysprosium K x-rays of 45 and 52 keV from the decay of holmium-161; radiation just above the K-edge of iodine (33 keV) has been shown to be of optimal energy for photon activation therapy of this drug. This study compares survival of human colorectal cancer (HT-29) cells with and without exposure to IUdR and subsequent irradiation with Cs-137, 300 kVp x-rays, I-125 seeds, and radioactive holmium. In our analysis, we isolate mechanisms of dose enhancement from each other as well as from the mechanisms of radiosensitivity, and in doing so, extract information about fundamental physical processes of DNA breakage. Through this independent formalism and a phenomenological assay of cell survival, we make conclusions about the lethality of DNA dSBs that agree with the literature. Furthermore, we have developed an objective protocol to analyze sensitization effects that obviates an arbitrary choice of measurement criteria. Sensitization values from holmium irradiation reported here are by far the greatest given the uptake of our drug, even on a notably radioresistant cell line. Most importantly, since holmium is a feasible material for brachytherapy implants, the full efficacy of this combination therapy, which has gone unexploited for 60 years, can finally be realized. Our results suggest that in vivo studies and clinical trials of IUdR photon activation with holmium brachytherapy have the potential to save lives and therefore merit consideration.
2d coordinate space Hartree-Fock-Bogoliubov calculations for neutron-rich nuclei in the A~100 mass region
(2005-11-30) Blazkiewicz, Artur Robert; Volker E. Oberacker; Sait A. Umar; Thomas J. Weiler; S. Victoria Greene
We solve the Hartree-Fock-Bogoliubov (HFB) equations for deformed, axially symmetric even-even nuclei in coordinate space on a 2D lattice utilizing the Basis-Spline expansion method. Our 2D lattice HFB code is a highly optimized FORTRAN 95 program suitable for parallel supercomputers. We utilize a parallelization scheme for different angular momentum quantum numbers Ω and different isospins. Furthermore, we have reduced the size of the diagonalized Hamiltonian by applying a unitary transformation which decouples the HFB equations. The reduction of the size of the Hamiltonian matrix allows us to calculate even the heaviest systems such as U-238 at a reasonable computation time. Results are presented for the neutron-rich Zirconium and Krypton isotopes up to the two-neutron dripline. In particular, we calculate binding energies, two-neutron separation energies, normal densities and pairing densities, mean square radii, quadrupole moments, and pairing gaps. The results obtained for the Zr isotope chain agree remarkably well with the calculations by Stoitsov et al. In particular both codes agree on the dripline nucleus and predict the same shape change from prolate to spherical. The comparison of rms-radii and neutron densities show also the presence of a neutron skin in the neutron-rich Zr isotope chain. As in the case of Zirconium, we find in the Kr isotope chain a shape change from prolate into oblate deformation, which is reflected in the neutron and proton rms-radius as well. The results obtained for the chain of Kr isotopes confirm that the mass region of A~100 is an area of competition between various coexisting nuclear shapes. In particular we find several different coexisting shapes in three selected Kr nuclei. Such calculations are crucial for astrophysics.
3 Essays on Interventions that Intersect Health and Education
(2024-07-09) Shero, Mason; Heinrich, Carolyn J; Heinrich, Carolyn J
Health and education are fundamentally linked, with each significantly impacting and relying on the other. Scholars have recognized the potential to enhance health outcomes through educational interventions and the benefits of integrating health-focused initiatives within schools. Consequently, both the US federal government and state governments have invested in programs that bridge health and education sectors to address diverse issues. This dissertation examines health-focused interventions in educational settings to contribute to our understanding of the implementation and efficacy of these efforts. Chapter 1 leverages a 1-to-1 matched comparison design and logistic regression to examine the effects of one of the most widely used home visiting programs on birth outcomes and perinatal health behaviors. Chapter 2 maps the presence of school-based federal resources in Tennessee and uses linked, longitudinal health and education data to estimate the effects of these resources on student health and education outcomes. Chapter 3 analyzes semi-structured interviews with Tennessee Coordinated School Health Directors to understand student needs, school-based health-focused efforts, barriers to health across K-12 schools. Together, these chapters can inform policy and contribute toward state and federal government efforts to support health across a range of settings.
3D enantioselective descriptors for ligand-based computer-aided drug design
(2012-07-26) Sliwoski, Gregory Richard; Jens Meiler; Charles David Weaver; Vsevolod V Gurevich
A novel three dimensional stereoselective descriptor for use in ligand-based computer-aided drug design (CADD) is presented in this thesis. CADD is an important tool for drug discovery and ligand-based CADD involves the computational analysis and representation of known active compounds for the prediction of novel active compounds. Several approaches are available for ligand-based CADD including quantitative structure-activity relationship (QSAR) which seeks to describe molecules numerically using descriptors. Stereochemistry is an important determinant of a molecule’s biological activity but presents a challenge for QSAR applications. Presented is the novel 3D-QSAR descriptor termed “EMAS” (Enantio-selective Molecular ASymmetry) that is capable of distinguishing between enantiomers and describing stereochemistry in a physically meaningful way. The descriptor aims to measure the deviation from an overall symmetric shape of the molecule. EMAS showed good predictability when tested with a dataset of thirty-one steroids commonly used to benchmark stereochemistry descriptors (r2=0.89, q2= 0.78). Additionally, EMAS improved enrichment of 4.38 versus 3.94 without EMAS in a simulated virtual high-throughput screening (vHTS) for inhibitors and substrates of cytochrome P450.
3D Supervised Learning for CT Hematoma Segmentation via Transfer Learning from a 2D Trained Network
(2020-05-19) Wu, Zihao; Landman, Bennett
Supervised learning approaches are the most widely used models in medical image processing and tend to offer the highest level of accuracy when paired data and labels are available. However, manual labeling process is time-consuming and requires expert knowledge. Hence, the process of generating training data has become a severe bottleneck. Here, we explore feedback-driven augmentation of training data in the context of hematoma segmentation for computed tomography (CT) imaging of traumatic brain injury. Briefly, a previously published 2D patched-based segmentation model was trained on 33 manually labeled CT scans. This model was applied to 11477 scans from 4033 patients that were retrospectively acquired in deidentified from consecutive trauma patients. Each of the resulting 11477 predictions was visually inspected for quality assurance and manually scored as either (0) a good segmentation with hematoma (n=1199), (1) a reasonable quality segmentation with some errors (n=2475), (2) a failed segmentation (n=2340), (3) a good segmentation without hematoma (n=4995), or (4) invalid data. 2400 good segmentation scans with predicted masks were used a training data along with the original 33 patients to train a 3D model using 3D-Unet. The mean Dice Similarity Coefficient (DSC) obtained from the model was 0.729 on the same testing set as 2D Network. In summary, feedback of successful automated results presents an efficient manner to transfer a 2D model to 3D and increase robustness of supervised deep learning algorithms at substantially reduced manual effort (here in 35 hours for quality assurance versus an estimated 11477 hours for full tracing of 11477 scans).
3D-2D Representation Learning for Longitudinal Analysis Using Single-Slice CT Scans
(2024-07-16) Yu, Xin; Landman, Bennett A.; Landman, Bennett A.
Abdominal computed tomography (CT) offers high-resolution tissue maps that facilitate the quantification of body composition. The existing longitudinal CT dataset from the Baltimore Longitudinal Study of Aging (BLSA) enables us to explore the relationship between body composition and cognitive decline. To minimize radiation exposure, 2D axial scans are used instead of 3D volumetric scans, presenting several challenges. Notably, 2D scans lack the contextual information inherent in 3D data, complicating body composition segmentation. Furthermore, difficulties in consistently positioning cross-sectional scans mean that 2D slices may not always be taken at the same vertebral level, resulting in variability in the abdominal slices obtained from patients over different years. In this dissertation, we utilize existing 3D volumetric data for representation learning to mitigate the anatomical limitations present in single-slice data. We apply advanced deep learning techniques for segmentation and generation to address these challenges. Ultimately, we identify a potential underlying phenotype associated with cognitive decline using the derived body composition metrics, providing new insights into the connection between the body and the brain.
"A Battle of Books": The Westminster Conference of 1559 and the Rise of Disputative Literature
(2018-07-16) Ayris, Alexander Austin; Paul Lim; Peter Lake; Joel Harrington; Emily Nacol; Karl Gunther
This dissertation revitalizes and revisits the historical category of polemic by arguing for the existence of a distinct subgenre within polemic that was constructed as oral university-style disputation. It does by first analyzing the Westminster conference of 1559, the intellectual climate of late Renaissance England, and John Jewel’s subsequent ‘challenge sermon,’ which was the catalyst for the printed controversial works examined here. It then analyzes several of the print exchanges between Protestants and Catholics that were direct outgrowths of the Westminster conference and elucidates two distinct facets of disputative literature within them. The first of these is disputative methodology, or the use of sixteenth-century intellectual methods that accorded with oral disputation to construct their works. This is the primary defining characteristic of disputative literature, but it also reveals that late Renaissance authors were much more idiosyncratic and eclectic in their methods than previous scholarship has allowed for. The second is portrayals of moderation and, relatedly, denunciations of immoderation in the opponent. This is reflective of burgeoning social conventions in Elizabethan England that linked the social virtues of moderation and civility with intellectual credibility. In addition, this study highlights the rhetoric of abuse, or authors’ use of ad hominem, sarcasm, ridicule, and the like in these works. Elucidating vitriol in works expected to be academic and moderate reveals both the authors’ mindset that such language was justified in the name of religious truth, but also reveals that such rhetoric was neither new nor the sole property of early modern libel.
A Bayesian framework to integrate genomic annotations for identification of Autism risk genes
(2020-11-10) Ji, Ying; Tao, Ran
Autism spectrum disorder (ASD) is a group of complex neurodevelopment disorders with a strong genetic basis. Large scale sequencing studies have provided strong evidence for dozens of ASD risk genes. However, it is estimated that around 1000 genes contribute to ASD risk and it remains challenging to identify putative risk genes. To close the gap between the number of anticipated and known ASD genes, several computational approaches have been developed to prioritize ASD genes from biological annotations or functional network information. Yet, very few methods have attempted to integrate these two types of evidence together. In this paper, we present a Bayesian model-selection based approach that involves both biological annotations and functional network information. Unlike previous approaches, ours includes a more comprehensive set of evidence with known ASD genes of strong evidence from sequencing studies, to obtain predicted probability of ASD risk for each gene across the genome. We validated our prediction by testing candidate genes for 1) enrichment in independent gene lists from independent sequencing studies or experts’ curation and 2) enrichment of heritability from recent GWAS study. Leveraging the candidate genes identified in the study, we identified strong involvement of striatal medium spiny neurons and early developmental stages in ASD. It is our hope that this framework can provide an integrative approach to ASD gene discovery and contribute to advancing our understanding of the biology of ASD.
A Bayesian Model for Brain Network Functional Connectivity using PyMC3
(2018-07-22) Wang, Rui; Hakmook Kang; Qingxia Chen
Our brain network, as a complex integrative system, consists of many different regions. Each region has its own task and function and simultaneously shares structural and functional information. With the developed imaging techniques such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), researchers can investigate the underlying brain functions related to human behaviors and some diseases or disorders in the nervous system such as major depressive disorder (MDD). In this thesis, we developed a Bayesian hierarchical spatiotemporal model that combined fMRI and DTI data jointly to enhance the estimation of resting-state functional connectivity. Structural connectivity from DTI data was utilized to construct an informative prior for functional connectivity based on resting-state fMRI data through the Cholesky decomposition in a mixture model. The analysis took the advantages of probabilistic programming package as PyMC3 and next-generation Markov Chain Monte Carlo (MCMC) sampling algorithm as No-U-Turn Sampler (NUTS). The simulation study with this advanced algorithm, illustrated reduced mean squared errors (MSEs) of estimation. Furthermore, through a case study of MDD, we applied our model to examine how the estimated functional connectivity was associated with tasks of episodic memory, executive function, processing speed and working memory.
A behavioral study of emotional reactivity and emotion regulation in preschool-age children who stutter
(2011-08-08) Ntourou, Aikaterini; Edward G. Conture; Ellen M. Kelly; Ashmead H. Daniel; Tedra A. Walden
The purpose of this study was to experimentally investigate the behavioral correlates of emotional reactivity and emotion regulation and their relation to speech (dis)fluency in preschool-age children who do (CWS) and do not (CWNS) stutter during emotion-eliciting laboratory procedures. Participants (18 CWS, 14 boys; 18 CWNS, 14 boys) completed a neutral (“apples and leaves in a transparent box,” ALTB) and a frustrating (“attractive toy in a transparent box,” ATTB) task, both of which were followed by a narrative task. Dependent measures were emotional reactivity (positive affect, negative affect) and emotion regulation (self-speech, off-task) exhibited during the ALTB and the ATTB tasks, and percentage of stuttering-like disfluencies (SLDs) and percentage of other disfluencies (ODs) produced during the narratives. Results indicated that CWS, when compared to CWNS, exhibited more negative emotion and more self-speech. For CWS only, emotion regulation behaviors (i.e., off-task, self-speech) were predictive of stuttering-like disfluencies produced during the subsequent narrative tasks. Furthermore, for CWS there was no relation between emotional processes and other (i.e., non-stuttered) disfluencies, but for CWNS negative affect was related to other disfluencies. Findings from this study provide support for the notion that preschool-age CWS are more emotionally reactive than CWNS and that even though CWS seem to exhibit more self-speech regulatory behaviors than CWNS, these attempts might not be very effective in modulating their emotions. Furthermore, findings indicate that for preschool-age CWS, stuttering-like disfluencies, unlike non-stuttered disfluencies, are influenced by emotion regulatory processes, but results suggest a differential mechanism underlying the production of non-stuttered disfluencies by preschool-age CWS and CWNS. Overall, findings from this study support the notion that emotional processes are associated with childhood stuttering and likely contribute to the difficulties that at least some CWS have establishing normally fluent speech.
“A better understanding between the races”: Southern educational initiatives to improve race relations between World War I and World War II
(2013-04-18) Lipson, Steven Jay; Helmut Walser Smith; Gary Gerstle
From the 1920s to the 1940s, 350 colleges and more than 2,000 public schools throughout the South were using in their courses curricular materials designed to stress African-American achievements and point out the many injustices Southern blacks still endured. These efforts were initiated by the Commission on Interracial Cooperation (CIC), the dominant mouthpiece for white Southern liberal sentiment, and its Educational Director Robert Burns Eleazer. In contrast to those scholars who took a narrow view of the CIC’s mission and effectiveness, this paper will argue that the far-reaching educational work of the Commission demonstrates that the CIC undertook an ambitious campaign to fundamentally reshape Southern society. Through thorough but judicious marshalling of the latest scientific evidence on race relations, Eleazer produced curricular materials whose wide circulation in public schools and colleges across the South appeared to result in real and positive advancements in racial understanding among Southern students from the 1920s through at least the 1940s.
A Biochemical Characterization of the DNA Glycosylase DEMETER
(2014-06-25) Brooks, Sonja Claudia; Walter Chazin; Martin Egli; Carmelo Rizzo; Neil Osheroff; Brandt Eichman
The methylation state of DNA is important for gene expression, gene imprinting, X-chromosome inactivation, and transposon silencing in mammals and plants. DNA methylation is established by methyltransferases to mark a silenced gene in the form of 5-methylcytosine (5mC). The mechanism of 5mC removal in mammals remains poorly understood, but recent evidence indicates that DNA glycosylases, which function to remove toxic and mutagenic lesions to DNA, may also function in gene regulation by removing methylated cytosines. This dissertation includes a review of the structural mechanisms of DNA glycosylases, as the 3-dimensional structures of these enzymes have yielded significant insight into substrate specificity and function within the base excision repair (BER) pathway. In Arabidopsis thaliana, DEMETER (DME) is a 5mC DNA glycosylase that activates expression of the maternally imprinted MEDEA gene. Thus, DME has evolved what is normally a DNA repair function to remove the non-toxic 5mC. This dissertation focuses on a structure-function analysis of DME to understand the basis for this unique activity. DME contains a conserved iron-sulfur cluster-containing DNA glycosylase domain, as well as two flanking domains necessary for base excision activity but whose structures and functions are unknown. A homology model of DME constructed from EndoIII was used as a guide for mutational analysis of base excision and DNA binding to identify several residues important for DME activity. Recent literature indicates that removal of 5mC may proceed by removal of oxidation derivatives of 5mC by thymine DNA glycosylase. DME has reduced activity for 5-hydroxymethylcytosine, limited activity for 5-carboxyctyosine, and no activity for 5-formylcytosine. The Arabidopsis DME paralog, DML3, was also studied and compared to reports of the activity of DME paralog ROS1 in order to understand the rationale for high redundancy of 5mC excision in plants.
A biologically informed method for detecting associations with rare variants
(2013-12-05) Moore, Carrie Colleen Buchanan; Bingshan Li; Tricia Thornton-Wells; Dan Roden; William Bush; Marylyn Ritchie
Many recent studies have identified rare variants that contribute to common, complex disease. It is believed that rare variants likely have a larger effect size (compared to GWAS findings) and can act alone, in concert with other rare variants, or together with common variants. Multiple rare variants can potentially account for a portion of missing heritability in a given trait; therefore, binning or burden testing, may better account for genetic heterogeneity. BioBin, an innovative collapsing method developed in the Ritchie lab, utilizes a flexible repository of data assembled from multiple public databases. The novelty of BioBin lies in access to comprehensive knowledge-guided multi-level binning. BioBin can apply multiple levels of burden testing, including: functional regions, evolutionary conserved regions, genes, and/or pathways. BioBin does not include a specific statistical association test, since the application of statistical testing is dependent on data type and analysis in question. Therefore, the user has the flexibility to apply tests appropriately without constraint. BioBin has been tested in the context of extensive simulation studies, compared with multiple published statistical methods, and applied to the NHLBI GO Exome Sequencing Project for Cystic Fibrosis. BioBin is a very useful and flexible tool to analyze sequence data and can uncover novel associations with complex disease.
A biophysically based framework for examining phytoremediation strategies: optimization of uptake, transport and storage of cadmium in alpine pennycress (Thlaspi caerulescnes)
(2009-01-02) Takahashi, Maria; Dr. David Jon Furbish; Dr. James A. Clarke
This work consists of constructing a model that combines an understanding of physical transport processes and the biological mechanisms involved in the uptake, transport and sequestration of contaminants by a hyperaccumulator, alpine pennycress (Thlaspi caerulesciens), a non-accumulator, field pennycress (Thlaspi arvense), and a maize. Specifically, the model uses a Michaelis-Menten formulation to describe uptake, and transpiration-driven translocation into aboveground biomass. Model simulations indicate that, despite its small biomass and slow growth, the hyperaccumulator alpine pennycress is a reasonable choice for phytoextraction due to the fast uptake rate as well as high metal tolerance, specifically in the aboveground biomass. In contrast, the field pennycress, which has a similar small biomass, but can only tolerate cadmium at much lower levels and does not translocate cadmium into aboveground biomass, is not an ideal candidate for phytoextraction. Although maize has a much larger biomass, phytoextraction using maize requires chemical treatment that mobilizes cadmium into the surrounding environment, and it has negative features similar to those of the field pennycress. Further studies that account for diurnal and seasonal variations in moisture and radiation may be required; however, the relative performance between those three species is not expected to change.
A biphasic role for the voltage-gated sodium channel scn5Lab in cardiac development of zebrafish
(2013-06-17) Bennett, Jeffrey Scott; H. Scott Baldwin; Charles Hong; Al George; Doug Mortlock; Dan Roden
A BIPHASIC ROLE FOR THE VOLTAGE-GATED SODIUM CHANNEL SCN5LAB IN CARDIAC DEVELOPMENT OF ZEBRAFISH JEFFREY S. BENNETT Dissertation under direction of Professor Dan M. Roden, M.D. Voltage-gated sodium channels (VGSCs) play an important role in generation and propagation of action potentials in nervous and cardiac tissues. Less is known of a possible role for them in development of the heart. Homozygous deletion of the voltage-gated sodium channel Scn5a results in embryonic lethality and developmental defects in the mouse heart. Morpholino knockdown of the two cardiac VGSC isoforms in zebrafish, scn5Laa and scn5Lab, results in small dysmorphic ventricles and death by four days post-fertilization. Here, I examine a role for scn5Lab in multiple phases of cardiac development. I find that loss of scn5Lab results in impaired specification of pre-cardiac mesoderm, with specific loss of the cardiac transcription nkx2.5. Differentiation of myocardium from the second heart field is determined to be intact, genetically and morphologically. Further I find that proliferation of differentiated cardiomyocytes is absent in morpholino-injected embryos, an effect that appears to be independent of impaired cardiac function. Electrophysiologic studies suggest voltage-gated sodium channels are present, but not required for action potentials at this time. I conclude that scn5Lab has a biphasic role in cardiac development of zebrafish, likely independent of its role in sodium ion permeation
A Bitter Legacy: Coffee, Identity, and Cultural Memory in Nineteenth-Century Britain
(2019-07-30) Holliday, Sarah Elizabeth; Catherine A. Molineux; Arleen M. Tuchman; Lauren A. Benton; Chris Otter
The British coffeehouse has been the recipient of immense scholarly attention since Jürgen Habermas identified it as the paradigm of his public sphere, a space in which private and public interests intersected. But all of these histories end, somewhat abruptly, in the mid-eighteenth century. But coffee consumption never actually disappeared from British life, a fact that is supported by an abundance of evidence in the archives. In fact, British coffee consumption played a key role in nineteenth-century debates over British social and economic identity in the midst of an expanding empire. Expanding our view of British coffee culture to include the nineteenth century allows us to situate coffee in the context of Britain's empire as its contours evolved, and see how behaviors cultivated in and popularized by coffeehouses helped Britons negotiate their role in an increasingly interconnected world.

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