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The sensing of pathogen infection and subsequent triggering of innate immunity are key to controlling zoonotic infections. Myxoma virus (MV) is a cytoplasmic DNA poxvirus that in nature infects only rabbits. Our previous studies have shown that MV infection of primary mouse cells is restricted by virus-induced type I interferon (IFN). However, little is known about the innate sensor(s) involved in activating signaling pathways leading to cellular defense responses in primary human immune cells. Here, we show that the complete restriction of MV infection in the primary human fibroblasts requires both tumor necrosis factor (TNF) and type I IFN. We also demonstrate that MV infection of primary human macrophages (pHMs) activates the cytoplasmic RNA sensor called retinoic acid inducible gene I (RIG-I), which coordinately induces the production of both TNF and type I IFN. Of note, RIG-I sensing of MV infection in pHMs initiates a sustained TNF induction through the sequential involvement of the downstream IFN-regulatory factors 3 and 7 (IRF3 and IRF7). Thus, RIG-I-mediated co-induction of TNF and type I IFN by virus-infected pHMs represents a novel innate defense mechanism to restrict viral infection in human cells. These results also reveal a new regulatory mechanism for TNF induction following viral infection.

Despite apartheid’s 1994 de jure abolition, contemporary university students in South Africa transgressively protest for ongoing, radical, de facto “decolonization” that they allege, and I agree, has not occurred. My thesis historicizes and analyzes the Rhodes Must Fall (RMF) and Open Stellenbosch (OS) protests at University of Cape Town (UCT) and Stellenbosch University (SU), respectively. I analyze how university students’ protests drive counter-hegemonic social movements locally, regionally, and potentially globally. I highlight marginalized students’ imagination and articulation of alternatives to global neoliberalism, which is transgressive and perceived as radical. I contextualize this case study of contemporary counter-hegemony in South Africa through a theoretical-conceptual approach, and a deep, colonial, historical approach. I present three critical premises: (1) neoliberalism is de-democratization and covert authoritarianism; (2) universities are potential sites of critical democratization; and (3) marginalized university students drive a radical, transgressive imagination of alternative worlds. I provide critical historical background to situate South Africa within Contemporary Globalization before chronicling the emergent themes of ongoing protests. Following my South Africa case study, I briefly compare RMF and OS to other university student protests around the globe, including California and Germany. I suggest that under Contemporary Globalization, apparently dissimilar social movements share much in common, including universities’ simultaneous assimilation into, and potential for resistance against, the new, covert authoritarianism and de-democratization of global neoliberalism.

Light emitting diodes (LEDs) are light sources of great technological importance because of their wide spectral tunability, long lifetimes, and potentially high energy efficiency. It is widely observed, however, that LEDs based on all relevant material platforms exhibit degraded internal quantum efficiency as the emission wavelength is shifted into the green part of the visible spectrum. Increasing device efficiency in this spectral region has therefore become the focus of intense research. In this work we study the use of plasmonic metallic nanostructures as a method for enhancing LED efficiency. Electromagnetic fields are known to exhibit resonances near metallic nanostructures originating from collective oscillations of the electron gas on the metal surface. Surface plasmon polaritons (SPPs) confined to the surface of a planar metal film, and localized surface plasmons (LSPs) confined to the surface of a nanostructure, feature unique optical properties such as large near optical fields and large modal densities. These spatial and spectral properties are highly dependent on the material and geometric properties of the nanostructure, allowing for extensive engineering of the plasmonic system to meet application needs. Plasmonic nanostructures are currently being studied for use in a wide range of applications such as waveguiding, bio-sensing, surface-enhanced spectroscopy, solid state light emission, and solar cells. Coupling into both SPP and LSP modes can enhance the spontaneous emission rate of a nearby radiating dipole, by virtue of their large associated local optical fields and high density of modes. Effective scattering of the excited plasmonic resonances into the radiation continuum can then lead to large enhancements in radiated field intensity. In this work, we have studied the application of various metallic nanostructures to nitride semiconductor light emitters to enhance their emission efficiency. Numerical investigations have been conducted to optimize nanostructure geometries, and experimental studies have demonstrated large enhancements in photoluminescence intensity and increased emitter recombination rates. These results indicate that LED emission efficiency can be strongly improved with properly engineered metallic nanostructures, which provides a promising new approach to further increase the performance of commercial devices.

The sensing of pathogen infection and subsequent triggering of innate immunity are key to controlling zoonotic infections. Myxoma virus (MV) is a cytoplasmic DNA poxvirus that in nature infects only rabbits. Our previous studies have shown that MV infection of primary mouse cells is restricted by virus-induced type I interferon (IFN). However, little is known about the innate sensor(s) involved in activating signaling pathways leading to cellular defense responses in primary human immune cells. Here, we show that the complete restriction of MV infection in the primary human fibroblasts requires both tumor necrosis factor (TNF) and type I IFN. We also demonstrate that MV infection of primary human macrophages (pHMs) activates the cytoplasmic RNA sensor called retinoic acid inducible gene I (RIG-I), which coordinately induces the production of both TNF and type I IFN. Of note, RIG-I sensing of MV infection in pHMs initiates a sustained TNF induction through the sequential involvement of the downstream IFN-regulatory factors 3 and 7 (IRF3 and IRF7). Thus, RIG-I-mediated co-induction of TNF and type I IFN by virus-infected pHMs represents a novel innate defense mechanism to restrict viral infection in human cells. These results also reveal a new regulatory mechanism for TNF induction following viral infection.

To investigate the validity and accuracy of tissue Doppler imaging (TDI) using a novel balloon phantom, validation of TDI myocardial velocity measurements has been carried out indirectly from conventional M-mode images. However it is not a true and independent gold standard. We described a new TDI validation method by using a specially developed left ventricular balloon model mounted in a water bath and constructed using two pear-shaped balloons. It was connected to a pulsatile flow pump at 8 stroke volumes (50–85 ml/beat). The displacement and velocity of the balloon walls were recorded simultaneously by video imaging and TDI on a GE-Vingmed System Five with a 5 MHz phased array probe at the highest frame rates available. Conventional M-mode and 2-D imaging verified that our balloon model mimicked the shape and wall motion of left ventricle. There was a good correlation and agreement between the maximum video excursion of the anterior and posterior walls of the phantom and the results of the temporal integration of digital distance data by TDI (Anterior wall: r=0. 97, SEE=0. 24 mm,x± s=0. 04±0. 24 mm; Posterior wall: r=0. 95, SEE = 0. 22 mm, −x±s−0. 03±0. 24 mm). Analysis of the velocity profile by the TDI method showed that the velocity at each measured point was correlated well with the velocity obtained from the video images (Anterior wall: r=0. 97, SEE = 0. 30 mm, −x±s= 0. 04±0. 28 mm; Posterior wall: r=0. 97, SEE = 0. 30 mm, −x±s = 0. 04 + 0. 28 mm). Our balloon model provided a new independent method for the validation of TDI data. This study demonstrated that the present TDI system is reliable for measuring wall motion distance and velocity.

A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.

This research examines a 58-year, 202 sequential issues, longitudinal published record of the Ontario Mathematics Gazette. The publication is oriented to K–12 teachers of mathematics in Ontario. A total of 3609 units of analysis were identified that led to 447 unique index categories. A chi-squared goodness of fit test found, within the limits of the test, that these categories arise continuously, independently, and at a steady rate. The frequency of occurrence in both absolute and relative terms showed a few trends, such as the shift of curriculum development away from teachers and toward research findings. A key finding was the absence of significant biases or short-term trends within the publication’s history. This speaks to the association being an independent voice, but the breadth of topics indicates it is an important support for teachers.

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones.Extra-intestinal pathogenic Escherichia coli cause urinary tract and bloodstream infections. Here, the authors show how mutations that disrupt the production of cellulose, a polysaccharide produced by many bacteria, drive enhanced virulence.

We recently reported two common filaggrin ( FLG ) null mutations that cause ichthyosis vulgaris 1 and predispose to eczema and secondary allergic diseases 2 . We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (χ 2 test: P = 2.12 × 10 −51 ; Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9–11.3), and homozygote OR = 151 (95% c.i. = 20–1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.