The contribution of multi-sensory aids to a meaningful art program.

Thesis (Ed.M.)--Boston Universit

Resolving singular forces in cavity flow: Multiscale modeling from atoms to millimeters

A multiscale approach for fluid flow is developed that retains an atomistic description in key regions. The method is applied to a classic problem where all scales contribute: The force on a moving wall bounding a fluid-filled cavity. Continuum equations predict an infinite force due to stress singularities. Following the stress over more than six decades in length in systems with characteristic scales of millimeters and milliseconds allows us to resolve the singularities and determine the force for the first time. The speedup over pure atomistic calculations is more than fourteen orders of magnitude. We find a universal dependence on the macroscopic Reynolds number, and large atomistic effects that depend on wall velocity and interactions.Comment: 4 pages,3 figure

Strong hydrodynamic drivers of coral reef fish biodiversity on submerged pinnacle coral reefs

Hydrodynamic processes are important in all marine environments and on coral reefs drive patterns of habitat zonation, community structure, and biodiversity. Abrupt geomorphological features like pinnacles and seamounts often possess distinct localized currents and these habitats are also often characterized by high abundance and biomass of fishes. However, differences in fish community structure between pinnacles and emergent reefs, and their key drivers are poorly understood. In this study, we compared fish communities among emergent fringing and offshore coral reefs, and submerged pinnacle reefs in Papua New Guinea. Submerged pinnacles possessed higher fish biomass, abundance, and species richness than both fringing and offshore emergent reefs. We collected in-situ current speed and temperature data over a full year at each reef and used random forest analysis to investigate the relative influence of hydrodynamics compared to other well-established drivers of reef fish biodiversity, including habitat and biogeographic factors. Environmental variables explained 70%, 52%, and 5% of variability in models for species richness, abundance and biomass respectively. In all models, average current speed, current speed variability, and reef area were consistently among the most influential variables. Models examining relationships between fish biodiversity metrics and current speed did not yield conclusive results but did highlight the association of distinct hydrodynamic regimes on pinnacles with high fish richness, abundance, and biomass. Our study highlights the strong influence of reef-scale hydrodynamics on fish biodiversity and demonstrates the ecological value of small, submerged coral reefs, which are globally numerous yet remain understudied in coral reef ecology

Contrasting hydrodynamic regimes of submerged pinnacle and emergent coral reefs

Hydrodynamics on coral reefs vary with depth, reef morphology and seascape position. Differences in hydrodynamic regimes strongly influence the structure and function of coral reef ecosystems. Submerged coral reefs on steep-sided, conical bathymetric features like seamounts experience enhanced water circulation as a result of interactions between currents and the abrupt physical structure. There may also be similar interactions between smaller pinnacles and regional water currents in offshore locations (crests > 10 m), while shallow reefs (crests <10 m) may be more subject to surface currents driven by wind, waves and tide. Here we tested whether coral pinnacles experienced stronger and more variable currents compared to emergent reefs at the same depth in both nearshore and offshore positions. Current speeds and temperature were monitored for 12 months at 11 reefs, representing the three different reef categories: submerged offshore pinnacles, emergent offshore reefs and emergent nearshore reefs. We found different patterns in current speeds and temperature among reef types throughout the year and between seasons. Submerged pinnacles exhibited stronger, more variable current speeds compared to both near and offshore emergent reefs. We found seasonal changes in current speeds for pinnacle and nearshore reefs but no variation in current strength on offshore reefs. Whilst instantaneous current directions did reflect the seascape position of individual sites, there was no difference in the directional variability of current speeds between reef types. Annual daily average temperatures at all reef types were not strongly seasonal, changing by less than 2 °C throughout the year. Daily temperature ranges at specific sites however, exhibited considerable variability (annual range of up to 6.5 °C), particularly amongst offshore emergent reefs which experienced the highest temperatures despite greater exposure to regional-scale circulation patterns. Additionally, we found a consistent mismatch between satellite sea surface temperatures and in-situ temperature data, which was on average 2 °C cooler throughout the annual study period. Our results suggest that distinct hydrodynamic processes occur on smaller submerged structures that are physically analogous to seamounts. Our findings highlight important nuances in environmental processes that occur on morphologically distinct coral reef habitats and these are likely to be important drivers for the community dynamics of organisms that inhabit these reefs

Light suppression of nitrate reductase activity in seedling and young plant tissues

Light is often reported to enhance plant nitrate reductase (NR) activity; we have identified a context in which light strongly suppresses NR activity. In vitro NR activity measurements of laboratory-grown seedlings showed strong suppression of nitrate-induced NR activity in cotyledon, hypocotyl, and root tissues of Ipomoea hederacea (L.) Jacquin; robust NR activity accumulated in nitrate-induced tissues in the dark, but was absent or significantly reduced in tissues exposed to light during the incubation. The suppressive mechanism appears to act at a point after nitrate perception; tissues pre-incubated with nitrate in the light were potentiated and developed NR activity more rapidly than nitrate-induced tissues not so pre-exposed. Suppression was affected by moderate to low light levels under full-spectrum light sources and by single-wavelength red, green, and blue sources. The suppression phenomenon persisted in early (first through fourth) leaves of glasshouse plants grown in soil, and in artificially rejuvenated cotyledons. Collectively these observations suggest a link between light perception and NR regulation that remains to be fully characterized

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

Protection of Hepatocytes from Cytotoxic T Cell Mediated Killing by Interferon-Alpha

&lt;p&gt;Background: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV) infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL) to recognise and kill hepatocytes under cytokine stimulation.&lt;/p&gt; &lt;p&gt;Methods/Principle Findings: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN-α treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-α stimulated hepatocyte lines were still able to present antigen and induce IFN-γ expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS-mediated apoptosis. In vitro stimulation with IFN-α, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor–proteinase inhibitor 9 (PI-9). PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection.&lt;/p&gt; &lt;p&gt;Conclusion/Significance: IFN-α induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections.&lt;/p&gt

Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity

The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no non-invasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc- maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here we show that tumor cell retention of a system xc--specific positron emission tomography radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment

The impact of BCG strains and repeat vaccinations on immunodiagnostic tests in Eurasian badgers (Meles meles)

Publication history: Accepted - 29 June 2022; Published online - 9July 2022.Bacille Calmette-Guerin (BCG) is a potential tool in the control of Mycobacterium bovis in European badgers (Meles meles). A five year Test and Vaccinate or Remove (TVR) research intervention project commenced in 2014 using two BCG strains (BCG Copenhagen 1331 (Years 1–3/ BadgerBCG) and BCG Sofia SL2222 (Years 4–5). Badgers were recaptured around 9 weeks after the Year 5 vaccination and then again a year later. The Dual-Path Platform (DPP) Vet TB assay was used to detect serological evidence of M. bovis infection. Of the 48 badgers, 47 had increased Line 1 readings (MPB83 antigen) between the Year 5 vaccination and subsequent recapture. The number of BCG Sofia vaccinations influenced whether a badger tested positive to the recapture DPP VetTB assay Line 1 (p < 0.001) while the number of BadgerBCG vaccinations did not significantly affect recapture Line 1 results (p = 0.59). Line 1 relative light units (RLU) were more pronounced in tests run with sera than whole blood. The results from an in_house MPB83 ELISA results indicated that the WB DPP VetTB assay may not detect lower MPB83 IgG levels as well as the serum DPP VetTB assay. Changes in interferon gamma assay (IFN-γ) results were seen in 2019 with significantly increased CFP-10 and PPDB readings. Unlike BadgerBCG, BCG Sofia induces an immune response to MPB83 (the immune dominant antigen in M. bovis badger infection) that then affects the use of immunodiagnostic tests. The use of the DPP VetTB assay in recaptured BCG Sofia vaccinated badgers within the same trapping season is precluded and caution should be used in badgers vaccinated with BCG Sofia in previous years. The results suggest that the DPP VetTB assay can be used with confidence in badgers vaccinated with BadgerBCG as a single or repeated doses.This work was funded by the Department of Agriculture, Environment and Rural Affairs, Northern Ireland (DAERA)

Towards Predictive Computational Models of Oncolytic Virus Therapy: Basis for Experimental Validation and Model Selection

Oncolytic viruses are viruses that specifically infect cancer cells and kill them, while leaving healthy cells largely intact. Their ability to spread through the tumor makes them an attractive therapy approach. While promising results have been observed in clinical trials, solid success remains elusive since we lack understanding of the basic principles that govern the dynamical interactions between the virus and the cancer. In this respect, computational models can help experimental research at optimizing treatment regimes. Although preliminary mathematical work has been performed, this suffers from the fact that individual models are largely arbitrary and based on biologically uncertain assumptions. Here, we present a general framework to study the dynamics of oncolytic viruses that is independent of uncertain and arbitrary mathematical formulations. We find two categories of dynamics, depending on the assumptions about spatial constraints that govern that spread of the virus from cell to cell. If infected cells are mixed among uninfected cells, there exists a viral replication rate threshold beyond which tumor control is the only outcome. On the other hand, if infected cells are clustered together (e.g. in a solid tumor), then we observe more complicated dynamics in which the outcome of therapy might go either way, depending on the initial number of cells and viruses. We fit our models to previously published experimental data and discuss aspects of model validation, selection, and experimental design. This framework can be used as a basis for model selection and validation in the context of future, more detailed experimental studies. It can further serve as the basis for future, more complex models that take into account other clinically relevant factors such as immune responses