Advanced Ultrasonic Inspection of Thick-Section Composite Structures for In-Field Asset Maintenance

An investigation into the inspection capabilities of in-field advanced ultrasound detection for use on ultra-thick (20 to 100 mm) glass fibre-reinforced polyester composites is presented. Plates were manufactured using custom moulding techniques, such that delamination flaws were created at calibrated depths. The full matrix capture technique with an on-board total focussing method was used to detect flaws scanned by a 0.5 MHz linear array probe. Flaw through-thickness dimensions were altered to assess the threshold for crack face separation at which delaminations could be identified. Furthermore, part thickness and in-plane flaw dimensions were varied to identify the inspection capability limitations of advanced ultrasonics for thick composites. The results presented in this study demonstrate an inverse relationship between the ability to find delaminations and plate thicknesses, with inspections successful at depths up to 74 mm. When the delamination thickness exhibited surface-to-surface contact, the inspection capability was reduced to 35 mm. There was an exponential decay relationship between the accuracy of the flaw depth measurement and plate thickness, likely due to the necessity of low probe frequencies. The effective inspection depth was determined to be in the range of 1 to 20 times the wavelength. It is speculated that the accuracy of measurements could be improved using probes with novel coupling solutions, and detectors with optimised signal processing/filtration algorithms

Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers

Major histocompatibility complex (MHC) class II tetramers allow the direct visualization of antigen specific CD4+ T cells by flow cytometry. This method relies on the highly specific interaction between peptide loaded MHC and the corresponding T-cell receptor. While the affinity of a single MHC/peptide molecule is low, cross-linking MHC/peptide complexes with streptavidin increases the avidity of the interaction, enabling their use as staining reagents. Because of the relatively low frequencies of CD4+ T cells (~1 in 300,000 for a single specificity) this assay utilizes an in vitro amplification step to increase its threshold of detection. Mononuclear cells are purified from peripheral blood by Ficoll underlay. CD4+ cells are then separated by negative selection using biotinylated antibody cocktail and anti-biotin labeled magnetic beads. Using adherent cells from the CD4- cell fraction as antigen presenting cells, CD4+ T cells are expanded in media by adding an antigenic peptide and IL-2. The expanded cells are stained with the corresponding class II tetramer by incubating at 37 C for one hour and subsequently stained using surface antibodies such as anti-CD4, anti-CD3, and anti-CD25. After labeling, the cells can be directly analyzed by flow cytometry. The tetramer positive cells typically form a distinct population among the expanded CD4+ cells. Tetramer positive cells are usually CD25+ and often CD4 high. Because the level of background tetramer staining can vary, positive staining results should always be compared to the staining of the same cells with an irrelevant tetramer. Multiple variations of this basic assay are possible. Tetramer positive cells may be sorted for further phenotypic analysis, inclusion in ELISPOT or proliferation assays, or other secondary assays. Several groups have also demonstrated co-staining using tetramers and either anti-cytokine or anti-FoxP3 antibodies

Congruences modulo prime powers of Hecke eigenvalues in level 11

We continue the study of strong, weak, and $dc$-weak eigenforms introduced by Chen, Kiming, and Wiese. We completely determine all systems of Hecke eigenvalues of level $1$ modulo $128$, showing there are finitely many. This extends results of Hatada and can be considered as evidence for the more general conjecture formulated by the author together with Kiming and Wiese on finiteness of systems of Hecke eigenvalues modulo prime powers at any fixed level. We also discuss the finiteness of systems of Hecke eigenvalues of level $1$ modulo $9$, reducing the question to the finiteness of a single eigenvalue. Furthermore, we answer the question of comparing weak and $dc$-weak eigenforms and provide the first known examples of non-weak $dc$-weak eigenforms.Comment: 28 pages; Minor revisio

Consumption of Whole Cottonseed by White-Tailed Deer and Nontarget Species

Supplementing diets of white-tailed deer (Odocoileus virginianus) with pelleted rations is an increasingly common practice aimed at increasing deer antler size on rangelands in Texas. Feed loss to consumption by various nontarget species (e.g., raccoons [Procyon lotor] and feral pigs [Sus scrofa]) raises both ecological and economic concerns. Whole cottonseed is a feedstuff that may afford a more targeted supplemental feeding effort. Accordingly, we determined: (1) consumption rates of whole cottonseed by feral pigs and raccoons in captivity; and (2) species visitation at feed sites and preference for whole cottonseed relative to whole corn under field conditions. For experiments 1 and 2, we trapped subadult feral pigs and raccoons (n = 16 for each) and randomly assigned them to 4 feed treatments. We weighed and took blood to assess gossypol levels from both pigs and raccoons every 2 weeks for 2 months. Pigs were adept at sorting cottonseed from their feed ration in the laboratory trial. Raccoons consumed cottonseed only under severe dietary stress (i.e., diets reduced to 60% of maintenance requirements). To supplement laboratory findings we used motion-triggered video camera systems to monitor species visitation and feeding behaviors in the field. Video surveillance (125 hours of recorded events) of feeders supported our observations from laboratory trials that cottonseed was unpalatable to feral pigs and raccoons, whereas white-tailed deer consumed cottonseed readily. Given our results, we believe that whole cottonseed merits further consideration as a supplement for free-ranging deer

"It's Weird That it Knows What I Want": Usability and Interactions with Copilot for Novice Programmers

Recent developments in deep learning have resulted in code-generation models that produce source code from natural language and code-based prompts with high accuracy. This is likely to have profound effects in the classroom, where novices learning to code can now use free tools to automatically suggest solutions to programming exercises and assignments. However, little is currently known about how novices interact with these tools in practice. We present the first study that observes students at the introductory level using one such code auto-generating tool, Github Copilot, on a typical introductory programming (CS1) assignment. Through observations and interviews we explore student perceptions of the benefits and pitfalls of this technology for learning, present new observed interaction patterns, and discuss cognitive and metacognitive difficulties faced by students. We consider design implications of these findings, specifically in terms of how tools like Copilot can better support and scaffold the novice programming experience.Comment: 26 pages, 2 figures, TOCH

Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans.

Funder: National Institute for Health Research (NIHR)Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+ T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people

Seasonal weather and climate prediction over area burned in grasslands of northeast China

© 2020, The Author(s). Grassland fire dynamics are subject to myriad climatic, biological, and anthropogenic drivers, thresholds, and feedbacks and therefore do not conform to assumptions of statistical stationarity. The presence of non-stationarity in time series data leads to ambiguous results that can misinform regional-level fire management strategies. This study employs non-stationarity in time series data among multiple variables and multiple intensities using dynamic simulations of autoregressive distributed lag models to elucidate key drivers of climate and ecological change on burned grasslands in Xilingol, China. We used unit root methods to select appropriate estimation methods for further analysis. Using the model estimations, we developed scenarios emulating the effects of instantaneous changes (i.e., shocks) of some significant variables on climate and ecological change. Changes in mean monthly wind speed and maximum temperature produce complex responses on area burned, directly, and through feedback relationships. Our framework addresses interactions among multiple drivers to explain fire and ecosystem responses in grasslands, and how these may be understood and prioritized in different empirical contexts needed to formulate effective fire management policies

Downregulation of HLA-I by the molluscum contagiosum virus mc080 impacts NK-cell recognition and promotes CD8+ T-cell evasion.

Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of primary keratinocytes in the epidermis, MCV induces the proliferation of infected cells and this results in the production of wart-like growths. Full productive infection is observed only after the infected cells differentiate. During this prolonged replication cycle the virus must avoid elimination by the host immune system. We therefore sought to investigate the function of the two major histocompatibility complex class-I-related genes encoded by the MCV genes mc033 and mc080. Following insertion into a replication-deficient adenovirus vector, codon-optimized versions of mc033 and mc080 were expressed as endoglycosidase-sensitive glycoproteins that localized primarily in the endoplasmic reticulum. MC080, but not MC033, downregulated cell-surface expression of endogenous classical human leucocyte antigen (HLA) class I and non-classical HLA-E by a transporter associated with antigen processing (TAP)-independent mechanism. MC080 exhibited a capacity to inhibit or activate NK cells in autologous assays in a donor-specific manner. MC080 consistently inhibited antigen-specific T cells being activated by peptide-pulsed targets. We therefore propose that MC080 acts to promote evasion of HLA-I-restricted cytotoxic T cells

Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis

Objective Rheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-Associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA. Methods HLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-Associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry. Results We identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γexpression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN- 3-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity. Conclusions We significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.This study was funded by the following grants: Fondecyt 1181853, Fondef-IDeA ID15I10080; Fondef-IDeA ID15I20080, Fondef-IDeA ID18I10243, and REDES 180028, from ANID, Chile; and by Project RTI2018-097414-B-I00 from the Spanish Ministry of Science. Doctoral training of JM was supported by ANID-PFCHA/National Doctoral Scholarship 2018/No 21181538