A Nano-sized Dose of Toxicology: Elucidating the Disconnect Between Nanomaterial Dosimetry and Biological Effects

Nanotechnologies continue to permeate a multitude of industries, with diverse applications ranging from pesticides to fuel additives. The unusual behavior of nanomaterials that drives their innovation also complicates the job of toxicologists tasked with assessing their potential environmental and public health impacts. This dissertation investigates the underlying reasons for uncertainty associated with the biological effects of nanomaterials. Chapter 2 and Chapter 3 focus on nanoparticles present in commercially available pesticide formulations and assess how particle size influences the environmental risk of a pesticide’s active ingredient. These studies reveal a size-specific effect on the toxicity of the nanoparticles despite normalized concentrations of active ingredient and highlight the potential for nanoparticles to mask the hydrophobic behavior of some chemicals. In Chapters 4 and 5, the focus shifts to soybeans and their microbiome as they respond to soils amended with cerium oxide nanoparticles. Utilizing metagenomic software to analyze large data sets and predict changes in ecological functionality, these companion chapters correlate plant growth with bacterial community structure and emphasize the atypical dose-response relationship of nanoparticles in terrestrial systems. Further, they address importance of acknowledging the difference between pristine and aged nanoparticle exposures. This body of work demonstrates the capacity for nanomaterials to confound toxicological assessment if the disconnect between nanomaterial dosimetry and biological response is not accounted for

Divergent Transcriptional Regulatory Logic at the Intersection of Tissue Growth and Developmental Patterning

The Yorkie/Yap transcriptional coactivator is a well-known regulator of cellular proliferation in both invertebrates and mammals. As a coactivator, Yorkie (Yki) lacks a DNA binding domain and must partner with sequence-specific DNA binding proteins in the nucleus to regulate gene expression; in Drosophila, the developmental regulators Scalloped (Sd) and Homothorax (Hth) are two such partners. To determine the range of target genes regulated by these three transcription factors, we performed genome-wide chromatin immunoprecipitation experiments for each factor in both the wing and eye-antenna imaginal discs. Strong, tissue-specific binding patterns are observed for Sd and Hth, while Yki binding is remarkably similar across both tissues. Binding events common to the eye and wing are also present for Sd and Hth; these are associated with genes regulating cell proliferation and “housekeeping” functions, and account for the majority of Yki binding. In contrast, tissue-specific binding events for Sd and Hth significantly overlap enhancers that are active in the given tissue, are enriched in Sd and Hth DNA binding sites, respectively, and are associated with genes that are consistent with each factor's previously established tissue-specific functions. Tissue-specific binding events are also significantly associated with Polycomb targeted chromatin domains. To provide mechanistic insights into tissue-specific regulation, we identify and characterize eye and wing enhancers of the Yki-targeted bantam microRNA gene and demonstrate that they are dependent on direct binding by Hth and Sd, respectively. Overall these results suggest that both Sd and Hth use distinct strategies – one shared between tissues and associated with Yki, the other tissue-specific, generally Yki-independent and associated with developmental patterning – to regulate distinct gene sets during development

Simultaneous Wavelength Translation and Amplitude Modulation of Single Photons from a Quantum Dot

Hybrid quantum information devices that combine disparate physical systems interacting through photons offer the promise of combining low-loss telecommunications wavelength transmission with high fidelity visible wavelength storage and manipulation. The realization of such systems requires control over the waveform of single photons to achieve spectral and temporal matching. Here, we experimentally demonstrate the simultaneous wavelength translation and amplitude modulation of single photons generated by a quantum dot emitting near 1300 nm with an exponentially-decaying waveform (lifetime $\approx$1.5 ns). Quasi-phase-matched sum-frequency generation with a pulsed 1550 nm laser creates single photons at 710 nm with a controlled amplitude modulation at 350 ps timescales.Comment: 5 pages, 4 figure

Yorkie Promotes Transcription by Recruiting a Histone Methyltransferase Complex

SummaryHippo signaling limits organ growth by inhibiting the transcriptional coactivator Yorkie. Despite the key role of Yorkie in both normal and oncogenic growth, the mechanism by which it activates transcription has not been defined. We report that Yorkie binding to chromatin correlates with histone H3K4 methylation and is sufficient to locally increase it. We show that Yorkie can recruit a histone methyltransferase complex through binding between WW domains of Yorkie and PPxY sequence motifs of NcoA6, a subunit of the Trithorax-related (Trr) methyltransferase complex. Cell culture and in vivo assays establish that this recruitment of NcoA6 contributes to Yorkie’s ability to activate transcription. Mammalian NcoA6, a subunit of Trr-homologous methyltransferase complexes, can similarly interact with Yorkie’s mammalian homolog YAP. Our results implicate direct recruitment of a histone methyltransferase complex as central to transcriptional activation by Yorkie, linking the control of cell proliferation by Hippo signaling to chromatin modification

Willow Creek, California Tourism Analysis

The primary objective of this study was to introduce and recommend different strategies for the city of Willow Creek, California to increase tourism post-Covid-19. After extensive research, the report outlines various opportunities that the Recreation 365 class, Tourism Industry Management, believe will help Willow Creek in their efforts to attract their target audience

Development and Application of a High-Resolution Thin-Film Probe

This paper documents the development, characterization, and application of a high-resolution thin-film magnetic-field probe. Probe diameter ranged from 5-μm to 100-μm. The 100-μm probe exhibits a 250-7μm improvement in spatial resolution compared to a conventional loop probe, measured at a height of 250 μm over differential traces with a 118-μm spacing. Electric field rejection was improved using shielding and using a 180-degree hybrid junction to separate common-mode (electric field) and differential-mode (primarily magnetic field) coupling. A network analyzer with narrow band filtering was used to detect the relatively weak signal from the probe and to allow detection of phase information. An application of the probe is demonstrated where the probe is used to identify the magnitude and phase of magnetic fields produced by currents in very closely-spaced IC package pins

The growth and hydrodynamic collapse of a protoplanet envelope

We have conducted three-dimensional self-gravitating radiation hydrodynamical models of gas accretion onto high mass cores (15-33 Earth masses) over hundreds of orbits. Of these models, one case accretes more than a third of a Jupiter mass of gas, before eventually undergoing a hydrodynamic collapse. This collapse causes the density near the core to increase by more than an order of magnitude, and the outer envelope to evolve into a circumplanetary disc. A small reduction in the mass within the Hill radius (R_H) accompanies this collapse as a shock propagates outwards. This collapse leads to a new hydrostatic equilibrium for the protoplanetary envelope, at which point 97 per cent of the mass contained within the Hill radius is within the inner 0.03 R_H which had previously contained less than 40 per cent. Following this collapse the protoplanet resumes accretion at its prior rate. The net flow of mass towards this dense protoplanet is predominantly from high latitudes, whilst at the outer edge of the circumplanetary disc there is net outflow of gas along the midplane. We also find a turnover of gas deep within the bound envelope that may be caused by the establishment of convection cells.Comment: 16 pages, 16 figures. Accepted for publication in MNRA

Determining the Composition of the Vacuum-Liquid Interface in Ionic-Liquid Mixtures

The vacuum-liquid interfaces of a number of ionic-liquid mixtures have been investigated using a combination of reactive-atom scattering with laser-induced fluorescence detection (RAS-LIF), selected surface tension measurements, and molecular dynamics (MD) simulations. The mixtures are based on the widespread 1-alkyl-3-methylimidazolium ([Cnmim]+) cation, including mixed cations which differ in chain length or chemical functionality with a common anion; and different anions for a common cation. RAS-LIF results imply that the surface compositions exhibit a general form of non-stoichiometric behaviour that mimics the well-known Henry’s and Raoult’s laws at low and high mole fraction, respectively. The Extended Langmuir model provides a moderately good single-parameter fit, but higher-order terms are required for an accurate description. The quantitative relationship between RAS-LIF and surface tension, which probes the surface composition only indirectly, is explored for mixtures of [C2mim]+ and [C12mim]+ with a common bis(trifluoromethylsulfonyl)imide ([NTf2]-) anion. Extended Langmuir model fits to surface tension data are broadly consistent with those to RAS-LIF; however, several other common approaches to extracting surface compositions from measured surface tensions result in much larger discrepancies. MD simulations suggest that RAS-LIF faithfully reports on the alkyl-chain exposure at the surface, which is only subtly modified by composition-dependent structural reorganisation

Reactive-Atom Scattering from Liquid Crystals at the Liquid-Vacuum Interface : [C12mim][BF4] and 4-Cyano-4′-Octylbiphenyl (8CB)

Two complementary approaches were used to study the liquid-vacuum interface of the liquid-crystalline ionic liquid 1-dodecyl-3-methylimidazolium tetrafluoroborate ([C12mim][BF4]) in the smectic A (SmA) and isotropic phases. O atoms with two distinct incident translational energies were scattered from the surface of [C12mim][BF4]. Angle-dependent time-of-flight distributions and OH yields, respectively, were recorded from high- and low-energy O atoms. There were no significant changes in the measurements using either approach, nor the properties derived from them, accompanying the transition from the SmA to the isotropic phase. This indicates that the surface structure of [C12mim][BF4] remains essentially unchanged across the phase boundary, implying that the bulk order and surface structure are not strongly correlated for this material. This effect is ascribed to the strong propensity for the outer surfaces of ionic liquids to be dominated by alkyl chains, over an underlying layer rich in anions and cation head groups, whether or not the bulk material is a liquid crystal. In a comparative study, the OH yield from the surface of the liquid crystal, 8CB, was found to be affected by the bulk order, showing a surprising step increase at the SmA-nematic transition temperature, whose origin is the subject of speculation