953 research outputs found

    Frequency over function : raised levels of CD127low/- regulatory T cells in the tumour microenvironment compared with the periphery of head and neck cancer patients

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    Objective: Regulatory T cells (Tregs) are known to infiltrate the tumour microenvironment of many cancers, including head and neck malignancies, and are thought to contribute to the host's impaired anti-tumour immune response. However, their immunosuppressive function remains poorly understood within the tumour microenvironment and this study aimed to address this. Methods: The frequency and suppressive capacity of two CD4?CD127low/- Treg populations, separated on the basis of different levels of CD25 expression (CD25inter and CD25high), from the tumour/node microenvironment and peripheral circulation of newly-presenting head and neck squamous cell carcinoma patients (n=19), were assessed using multicolour flow cytometry. Results: The proportion of Tregs (CD4?CD25high/?interCD127low/-) in the tumour/node microenvironment was significantly elevated compared with the peripheral circulation (p<0.001) and similar percentages were present in both the primary tumour and metastatic lymph node. The percentage of suppression induced by Tregs isolated from tumour associated nodes on the proliferation of nodal effector T cells was similar to that of peripheral Tregs on peripheral effector T cells. However, when the suppressive activity of both nodal and peripheral Tregs was compared on the same peripheral effectors, peripheral Tregs suppressed proliferation to a greater extent. Conclusion: This work shows that the recruitment and percentages of tumour infiltrating Tregs are key factors in modulating the immune environment of head and neck tumours

    Development of an improved toughness hyperpure silica reflective heat shield

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    High purity three dimensionally woven silica-silica materials were evaluated for use as a tough reflective heat shield for planetary entry probes. A special weave design was selected to minimize light piping effects through the heat shield thickness. Various weave spacings were evaluated for densification efficiency with an 0.7 micron particle size high purity silica. Spectral hemispherical reflectance was measured from 0.2 to 2.5 microns at room temperature. Reflectance increases due to densification and purity of material were measured. Reflectance of 3D hyperpure silica was higher than 3D astroquartz silica for all wavelengths. Mechanical properties were measured in beam flexure and beam shear tests. Results indicated strengths lower than reported for slip cast fused silica. Low strengths were attributed to low densities achieved through vacuum impregnation

    High purity silica reflective heat shield development

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    Measurements were made of reflectance in the vacuum ultraviolet down to 0.15 micron. Scattering coefficients (S) and absorption coefficients (K) were also measured. These coefficients express the optical properties and are used directly in a thermodynamic analysis for sizing a heat shield. The effect of the thin silica melt layer formed during entry was also studied from the standpoint of trapped radiant energy

    Development, fabrication and test of a high purity silica heat shield

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    A highly reflective hyperpure ( 25 ppm ion impurities) slip cast fused silica heat shield material developed for planetary entry probes was successfully scaled up. Process development activities for slip casting large parts included green strength improvements, casting slip preparation, aggregate casting, strength, reflectance, and subscale fabrication. Successful fabrication of a one-half scale Saturn probe (shape and size) heat shield was accomplished while maintaining the silica high purity and reflectance through the scale-up process. However, stress analysis of this original aggregate slip cast material indicated a small margin of safety (MS. = +4%) using a factor of safety of 1.25. An alternate hyperpure material formulation to increase the strength and toughness for a greater safety margin was evaluated. The alternate material incorporates short hyperpure silica fibers into the casting slip. The best formulation evaluated has a 50% by weight fiber addition resulting in an 80% increase in flexural strength and a 170% increase in toughness over the original aggregate slip cast materials with comparable reflectance

    Validation and Improvement of the Beef Production Sub-index in Ireland for Beef Cattle

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    End of project reportThe objectives of the following study were to: a. Quantify the effect of sire genetic merit for BCI on: 1. feed intake, growth and carcass traits of progeny managed under bull or steer beef production systems. 2. live animal scores, carcass composition and plasma hormone and metabolite concentrations in their progeny. b. Compare the progeny of : 1. Late-maturing beef with dairy breeds and 2. Charolais (CH), Limousin (LM), Simmental (SM) and Belgian Blue (BB) sires bred to beef suckler dams, for feed intake, blood hormones and metabolites, live animal measurements, carcass traits and carcass value in bull and steer production systems

    Alcohol consumption in young adults: the role of multisensory imagery.

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    Accepted 19.11.2013Little is known about the subjective experience of alcohol desire and craving in young people. Descriptions of alcohol urges continue to be extensively used in the everyday lexicon of young, non-dependent drinkers. Elaborated Intrusion (EI) Theory contends that imagery is central to craving and desires, and predicts that alcohol-related imagery will be associated with greater frequency and amount of drinking. This study involved 1,535 age stratified 18- 25 year olds who completed an alcohol–related survey that included the Imagery scale of the Alcohol Craving Experience (ACE) questionnaire. Imagery items predicted 12-16% of the variance in concurrent alcohol consumption. Higher total Imagery subscale scores were linearly associated with greater drinking frequency and lower self-efficacy for moderate drinking. Interference with alcohol imagery may have promise as a preventive or early intervention target in young people

    ER stress in antigen‐presenting cells promotes NKT cell activation through endogenous neutral lipids

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    CD1d-restricted invariant natural killer T (iNKT) cells constitute a common glycolipid-reactive innate-like T-cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD1d-dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER) stress in APCs is a potent inducer of CD1d-dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol-requiring enzyme-1a (IRE1α) and protein kinase R-like ER kinase (PERK). Surprisingly, the neutral but not the polar lipids generated within APCs undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD1d-restricted iNKT cell responses through induction of distinct classes of neutral lipids
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