Academic Resilience of Athletic Training Students During COVID-19 Pandemic

OBJECTIVE (1) To describe resilience in athletic training students enrolled in professional coursework during the spring 2020 semester, and (2) to determine the association between resilience and academic performance during the spring 2020 semester. MAIN OUTCOME MEASURESDescriptive statistics for GPA were calculated for Fall 2019, Spring 2020, cumulative Fall 2019, cumulative Spring 2020 (ie., current), change in cumulative GPA, and ARS-30 total score. The primary analysis was a Pearson correlation between change in cumulative GPA and ARS-30 total score. A secondary analysis was conducted to evaluate change in cumulative Fall 2019 and Spring 2020 GPA with a paired t-test. Cohen’s d effect size was calculated for the paired t-test. Alpha level was set at 0.05

Simulation of multistage compressor at off-design conditions

Computational fluid dynamics (CFD) has been widely used for compressor design, yet the prediction of performance and stage matching for multistage, high-speed machines remains challenging. This paper presents the authors' effort to improve the reliability of CFD in multistage compressor simulations. The endwall features (e.g., blade filet and shape of the platform edge) are meshed with minimal approximations. Turbulence models with linear and nonlinear eddy viscosity models are assessed. The nonlinear eddy viscosity model predicts a higher production of turbulent kinetic energy in the passages, especially close to the endwall region. This results in a more accurate prediction of the choked mass flow and the shape of total pressure profiles close to the hub. The nonlinear viscosity model generally shows an improvement on its linear counterparts based on the comparisons with the rig data. For geometrical details, truncated filet leads to thicker boundary layer on the filet and reduced mass flow and efficiency. Shroud cavities are found to be essential to predict the right blockage and the flow details close to the hub. At the part speed, the computations without the shroud cavities fail to predict the major flow features in the passage, and this leads to inaccurate predictions of mass flow and shapes of the compressor characteristic. The paper demonstrates that an accurate representation of the endwall geometry and an effective turbulence model, together with a good quality and sufficiently refined grid, result in a credible prediction of compressor matching and performance with steady-state mixing planes.</p

Simulation of multistage compressor at off-design conditions

Computational fluid dynamics (CFD) has been widely used for compressor design, yet the prediction of performance and stage matching for multistage, high-speed machines remains challenging. This paper presents the authors' effort to improve the reliability of CFD in multistage compressor simulations. The endwall features (e.g., blade filet and shape of the platform edge) are meshed with minimal approximations. Turbulence models with linear and nonlinear eddy viscosity models are assessed. The nonlinear eddy viscosity model predicts a higher production of turbulent kinetic energy in the passages, especially close to the endwall region. This results in a more accurate prediction of the choked mass flow and the shape of total pressure profiles close to the hub. The nonlinear viscosity model generally shows an improvement on its linear counterparts based on the comparisons with the rig data. For geometrical details, truncated filet leads to thicker boundary layer on the filet and reduced mass flow and efficiency. Shroud cavities are found to be essential to predict the right blockage and the flow details close to the hub. At the part speed, the computations without the shroud cavities fail to predict the major flow features in the passage, and this leads to inaccurate predictions of mass flow and shapes of the compressor characteristic. The paper demonstrates that an accurate representation of the endwall geometry and an effective turbulence model, together with a good quality and sufficiently refined grid, result in a credible prediction of compressor matching and performance with steady-state mixing planes

Regulatory T cells inhibit Fas ligand-induced innate and adaptive tumour immunity

CD4+CD25+ regulatory T cells (Treg) are known to influence T cell responses to tumours. Here we have explored the role of Treg in inhibiting not only adaptive, but also innate immune responses to tumours. To this end we used a Fas ligand (FasL)-expressing melanoma cell line in a mouse model. In this system, innate immunity is sufficient to reject the tumour. All mice depleted of Treg and challenged with FasL-expressing melanoma remained tumour-free. Investigation of the underlying cellular effector mechanisms revealed that depletion of Treg enhanced an NK cell response capable of tumour lysis. Furthermore, this initial innate immune response primed mice to make an effective adaptive immune response leading to complete rejection of challenge with the parental melanoma. Both antigen-specific antibody and CD4+ T cells were implicated in protection via adaptive immunity. We conclude that removal of Treg and vaccination with whole tumour cells expressing FasL activates multiple arms of the immune system, leading to efficient tumour rejection. These findings highlight a novel role for FasL in inducing innate immune responses that are normally inhibited by Treg and uncover an adjuvant effect of FasL that can be used to stimulate tumour immunity after depletion of Treg

Paracetamol reduces influenza-induced immunopathology in a mouse model of infection without compromising virus clearance or the generation of protective immunity

Background: Seasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies are of limited efficacy, and during a pandemic outbreak would only be available to a minority of the global population. Over-the-counter medicines are routinely taken by individuals suffering from influenza, but few studies have been conducted to determine their effectiveness in reducing pulmonary immunopathology or the influence they exert upon the generation of protective immunity. Methods: A mouse model of influenza infection was utilised to assess the efficacy of paracetamol (acetaminophen) in reducing influenza-induced pathology and to examine whether paracetamol affects generation of protective immunity. Results: Administration (intraperitoneal) of paracetamol significantly decreased the infiltration of inflammatory cells into the airway spaces, reduced pulmonary immunopathology associated with acute infection and improved the overall lung function of mice, without adversely affecting the induction of virus-specific adaptive responses. Mice treated with paracetamol exhibited an ability to resist a second infection with heterologous virus comparable with that of untreated mice. Conclusions: Our results demonstrate that paracetamol dramatically reduces the morbidity associated with influenza but does not compromise the development of adaptive immune responses. Overall, these data support the utility of paracetamol for reducing the clinical symptoms associated with influenza virus infection

The near-IR MbhM_{bh} - L and MbhM_{bh} - n relations

We present near-IR surface photometry (2D-profiling) for a sample of 29 nearby galaxies for which super-massive black hole (SMBH) masses are constrained. The data is derived from the UKIDSS-LASS survey representing a significant improvement in image quality and depth over previous studies based on 2MASS data. We derive the spheroid luminosity and spheroid S\'ersic index for each galaxy with GALFIT3 and use these data to construct SMBH mass -bulge luminosity ($M_{\rm bh}$--$L$) and SMBH - S\'ersic index ($M_{\rm bh}$--$n$) relations. The best fit K-band relation for elliptical and disk galaxies is $\log(M_{\rm bh}/M_{\odot})= -0.36(\pm 0.03) (M_{\rm K} + 18) + 6.17(\pm 0.16)$ with an intrinsic scatter of 0.4$^{+0.09}_{-0.06}$dex whilst for elliptical galaxies we find $\log(M_{\rm bh}/M_{\odot})= -0.42(\pm 0.06) (M_{\rm K} + 22) + 7.5(\pm 0.15)$ with an intrinsic scatter of 0.31$^{+0.087}_{-0.047}$dex. Our revised $M_{\rm bh}$--$L$ relation agrees closely with the previous near-IR constraint by \citet{tex:G07}. The lack of improvement in the intrinsic scatter in moving to higher quality near-IR data suggests that the SMBH relations are not currently limited by the quality of the imaging data but is either intrinsic or a result of uncertainty in the precise number of required components required in the profiling process. Contrary to expectation (see \citealt{tex:GD07a}) a relation between SMBH mass and the S\'ersic index was not found at near-IR wavelengths. This latter outcome is believed to be explained by the generic inconsistencies between 1D and 2D galaxy profiling which are currently under further investigation.Comment: 35 pages, 37 figures, MNRAS accepte

Progress in paleoclimate modeling

International audienceThis paper briefly surveys areas of paleoclimate modeling notable for recent progress. New ideas, including hypotheses giving a pivotal role to sea ice, have revitalized the low-order models used to simulate the time evolution of glacial cycles through the Pleistocene, a prohibitive length of time for comprehensive general circulation models (GCMs). In a recent breakthrough, however, GCMs have succeeded in simulating the onset of glaciations. This occurs at times (most recently, 115 kyr B.P.) when high northern latitudes are cold enough to maintain a snow cover and tropical latitudes are warm, enhancing the moisture source. More generally, the improvement in models has allowed simulations of key periods such as the Last Glacial Maximum and the mid-Holocene that compare more favorably and in more detail with paleoproxy data. These models now simulate ENSO cycles, and some of them have been shown to reproduce the reduction of ENSO activity observed in the early to middle Holocene. Modeling studies have demonstrated that the reduction is a response to the altered orbital configuration at that time. An urgent challenge for paleoclimate modeling is to explain and to simulate the abrupt changes observed during glacial epochs (i.e., Dansgaard-Oescher cycles, Heinrich events, and the Younger Dryas). Efforts have begun to simulate the last millennium. Over this time the forcing due to orbital variations is less important than the radiance changes due to volcanic eruptions and variations in solar output. Simulations of these natural variations test the models relied on for future climate change projections. They provide better estimates of the internal and naturally forced variability at centennial time scales, elucidating how unusual the recent global temperature trends are

The Immune Response to Melanoma Is Limited by Thymic Selection of Self-Antigens

The expression of melanoma-associated antigens (MAA) being limited to normal melanocytes and melanomas, MAAs are ideal targets for immunotherapy and melanoma vaccines. As MAAs are derived from self, immune responses to these may be limited by thymic tolerance. The extent to which self-tolerance prevents efficient immune responses to MAAs remains unknown. The autoimmune regulator (AIRE) controls the expression of tissue-specific self-antigens in thymic epithelial cells (TECs). The level of antigens expressed in the TECs determines the fate of auto-reactive thymocytes. Deficiency in AIRE leads in both humans (APECED patients) and mice to enlarged autoreactive immune repertoires. Here we show increased IgG levels to melanoma cells in APECED patients correlating with autoimmune skin features. Similarly, the enlarged T cell repertoire in AIRE−/− mice enables them to mount anti-MAA and anti-melanoma responses as shown by increased anti-melanoma antibodies, and enhanced CD4+ and MAA-specific CD8+ T cell responses after melanoma challenge. We show that thymic expression of gp100 is under the control of AIRE, leading to increased gp100-specific CD8+ T cell frequencies in AIRE−/− mice. TRP-2 (tyrosinase-related protein), on the other hand, is absent from TECs and consequently TRP-2 specific CD8+ T cells were found in both AIRE−/− and AIRE+/+ mice. This study emphasizes the importance of investigating thymic expression of self-antigens prior to their inclusion in vaccination and immunotherapy strategies

Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology

Balancing the generation of immune responses capable of controlling virus replication with those causing immunopathology is critical for the survival of the host and resolution of influenza-induced inflammation. Based on the capacity of interleukin-6 (IL-6) to govern both optimal T-cell responses and inflammatory resolution, we hypothesised that IL-6 plays an important role in maintaining this balance. Comparison of innate and adaptive immune responses in influenza-infected wild-type control and IL-6-deficient mice revealed striking differences in virus clearance, lung immunopathology and generation of heterosubtypic immunity. Mice lacking IL-6 displayed a profound defect in their ability to mount an anti-viral T-cell response. Failure to adequately control virus was further associated with an enhanced infiltration of inflammatory monocytes into the lung and an elevated production of the pro-inflammatory cytokines, IFN-α and TNF-α. These events were associated with severe lung damage, characterised by profound vascular leakage and death. Our data highlight an essential role for IL-6 in orchestrating anti-viral immunity through an ability to limit inflammation, promote protective adaptive immune responses and prevent fatal immunopathology

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design

The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ+) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4+CD25hiFoxp3+ regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth. This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Surprisingly, both immunogenic peptides and those recognised by Tregs clustered in the same HLA-DR transcending epitope-rich hotspots within the 5T4 protein. Similarly, regions of low Th1-cell immunogenicity also did not contain peptides capable of stimulating Tregs, further supporting the notion that Treg and Th1 cells recognise the same peptides. Understanding the rules which govern the balance of Th1 and Treg cells responding to a given peptide specificity is, therefore, of fundamental importance to designing strategies for manipulating the balance in favour of Th1 cells, and thus the most effective anti-cancer T cell responses