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In lung, thromboxane [A.sub.2] ([TXA.sub.2]) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and [TXA.sub.2] synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key roles in asthma and regulate the lung immune response to allergens. Herein, we found that [TXA.sub.2] reduces Th9 cell differentiation during allergic lung inflammation. Th9 cells were decreased approximately 2-fold and airway hyperresponsiveness was attenuated in lungs of allergic mice treated with [TXA.sub.2]. Naive [CD4.sup.+] T cell differentiation to Th9 cells and IL-9 production were inhibited dose-dependently by [TXA.sub.2] in vitro. TP receptor-deficient mice had an approximately 2-fold increase in numbers of Th9 cells in lungs in vivo after OVA exposure compared with wild-type mice. Naive [CD4.sup.+] T cells from TP- deficient mice exhibited increased Th9 cell differentiation and IL-9 production in vitro compared with [CD4.sup.+] T cells from wild-type mice. [TXA.sub.2] also suppressed Th2 and enhanced Treg differentiation both in vitro and in vivo. Thus, in contrast to its acute, proinflammatory effects, [TXA.sub.2] also has longer-lasting immunosuppressive effects that attenuate the Th9 differentiation that drives asthma progression. These findings may explain the paradoxical failure of anti-thromboxane therapies in the treatment of asthma., Introduction Development of allergic lung inflammation is a complex process involving both immune and inflammatory events. In the immune phase, allergens are taken up and processed by antigen-presenting cells such [...]

We report on the generation of high-power narrow-bandwidth terahertz (THz) pulses by cryogenic cooling of hand-made periodically poled lithium niobate (PPLN) wafer stacks. As a proof-of-concept, we cool stacks with up to 48 wafers down to 97 K and achieve few-percent bandwidths at a center frequency of 0.39 THz, with pulse energy up to 0.42 mJ and average power of 21 mW. Supported by modeling, we observe effective cooling of PPLN wafer stacks that not only reduces terahertz absorption but critically maintains the micrometer-scale inter-wafer gaps for optimal terahertz transmission. Our results unlock the potential for scaling these large-area sources to greater numbers of wafers to push both the energy and bandwidth beyond current capability, opening up possibilities in areas such as terahertz-driven particle acceleration, terahertz imaging, and control over material properties. [ABSTRACT FROM AUTHOR]

In lung, thromboxane A2 (TXA2) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and TXA2 synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key roles in asthma and regulate the lung immune response to allergens. Herein, we found that TXA2 reduces Th9 cell differentiation during allergic lung inflammation. Th9 cells were decreased approximately 2-fold and airway hyperresponsiveness was attenuated in lungs of allergic mice treated with TXA2. Naive CD4+ T cell differentiation to Th9 cells and IL-9 production were inhibited dose-dependently by TXA2 in vitro. TP receptor-deficient mice had an approximately 2-fold increase in numbers of Th9 cells in lungs in vivo after OVA exposure compared with wild-type mice. Naive CD4+ T cells from TP-deficient mice exhibited increased Th9 cell differentiation and IL-9 production in vitro compared with CD4+ T cells from wild-type mice. TXA2 also suppressed Th2 and enhanced Treg differentiation both in vitro and in vivo. Thus, in contrast to its acute, proinflammatory effects, TXA2 also has longer-lasting immunosuppressive effects that attenuate the Th9 differentiation that drives asthma progression. These findings may explain the paradoxical failure of anti-thromboxane therapies in the treatment of asthma. [ABSTRACT FROM AUTHOR]

Epoxyeicosatrienoic acids (EETs) have potent antiinflammatory properties. Hydrolysis of EETs by soluble epoxide hydrolase/ epoxide hydrolase 2 (sEH/EPHX2) to less active diols attenuates their antiinflammatory effects. Macrophage activation is critical to many inflammatory responses; however, the role of EETs and sEH in regulating macrophage function remains unknown. Lung bacterial clearance of Streptococcus pneumoniae was impaired in Ephx2-deficient ([Ephx2.sup.-/-]) mice and in mice treated with an sEH inhibitor. The EET receptor antagonist EEZE restored lung clearance of S. pneumoniae in Ephx2 /mice. [Ephx2.sup.-/-] mice had normal lung Il1b, Il6, and Tnfa expression levels and macrophage recruitment to the lungs during S. pneumoniae infection; however, Ephx2 disruption attenuated proinflammatory cytokine induction, Tlr2 and Pgylrp1 receptor upregulation, and Ras-related C3 botulinum toxin substrates 1 and 2 (Rac1/2) and cell division control protein 42 homolog (Cdc42) activation in PGN-stimulated macrophages. Consistent with these observations, [Ephx2.sup.-/-] macrophages displayed reduced phagocytosis of S. pneumoniae in vivo and in vitro. Heterologous overexpression of TLR2 and peptidoglycan recognition protein 1 (PGLYRP1) in [Ephx2.sup.-/-] macrophages restored macrophage activation and phagocytosis. Human macrophage function was similarly regulated by EETs. Together, these results demonstrate that EETs reduced macrophage activation and phagocytosis of S. pneumoniae through the downregulation of TLR2 and PGLYRP1 expression. Defining the role of EETs and sEH in macrophage function may lead to the development of new therapeutic approaches for bacterial diseases., Introduction Pneumonia is the leading cause of mortality in the United States Streptococcus pneumoniae and Klebsiella pneumoniae are the mosi frequently isolated bacterial pathogens in community-acquirec pneumonia (1). Together, these [...]

The promises of upward mobility and social transformation are intertwined with the story of higher education in South Africa. In the years leading up to and in sync with the democratic moment of 1994, multiple selection programmes and academic development projects engaged with questions of potential (e.g., Yeld 2007; Miller 1992) particularly in relation to the inequalities of apartheid schooling and implications for higher education. While access and success have been widened in the decades since, and participation rates are more demographically representative, #FMF and #RMF challenged the myth of meritocracy. In a disillusioning political present, higher education resembles a giant pyramid scheme in which the investment of many delivers results for only a “lucky” few, particularly the higher up the ladder one ascends (Bradbury 2022). This prioritisation of the privileged continues despite official labour surveys demonstrating that each step along the higher education degree path increases individual employment prospects and contributes to socioeconomic productivity. The focus of this article is on funding for postgraduate students who represent the intellectual future both within the academy and beyond, developing high level skills for the knowledge economy to solve the “wicked problems” of the 21st century. Inherited funding models reward individual excellence, treating students as isolated individuals, falsely assuming supportive middle class family networks and conceiving of study years as a temporal sequestration from communal responsibilities and projected future working life. In reality, the borders between home and campus, between studies and work, between (extended) childhood and adulthood, are far more porous. These funding models are unsustainable, irrational and unethical, and premised on “cruel optimism” (Berlant 2011) rather than the promise of radical forms of hope. The article presents some pragmatic possibilities for reimagining funding for postgraduate studies in South Africa in the present. It is however imperative that these responses attend to both the past and the future to create conditions of “freedom in security” (Manganyi 1973) in which individual and collective potential can be actualised for a more equal future. [ABSTRACT FROM AUTHOR]

Investigated the long-term academic effects of a first-year foundation course designed to enhance the academic performance of university students. Found that third-year academic performance is not simply a function of initial language and mathematics competence levels; those who improved performance in the foundation course tended to perform well as third-year students. (EV)

A study of 543 South African university freshmen examined testing issues in relation to use of English as a first or second language. Results suggest multiple-choice tests yield higher grades than essay tests for both native and nonnative speakers, performance on essay questions varies depending on type of question, and open-ended tutorial assessments are reasonable predictors of academic success. (Author/MSE)