93 research outputs found

    The T Cell-mediated Response To A Syngeneic Tumour: Precytotoxic T Lymphocyte Frequency Measured By Limiting Dilution Assay

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    The T cell-mediated response to a syngeneic tumour has been studied using the DBA{dollar}\\{dollar} 2-P815X mouse tumour model. If one hopes to intervene to change (improve) the immune response of a cancer patient to their tumour, it is necessary to understand the role(s) of the cells involved in that response.;The potential magnitude of a cytotoxic T lymphocyte (CTL) response depends, in part, upon the precursor or pCTL frequency. A limiting dilution assay (LDA) has been developed and used to measure the frequency of pCTL\u27s in the animal both prior to tumour implantation and during the growth of the tumour. As well, it indicates whether or not suppressor cells, capable of down-regulating the immune response to the tumour, are present.;With the DBA{dollar}\\{dollar} 2-P815X syngeneic tumour model, there is an increase in pCTL frequency in the spleens of tumour-bearing mice two weeks after tumour implantation. Also, a correlation between pCTL frequency and tumour size, and between the presence of suppressor cells and tumour size, has been found. When pCTL frequencies are measured in normal animals, prior to tumour implantation, there is a correlation of that frequency with tumour progression after implantation. Higher frequencies correlate with smaller tumour sizes.;These results suggest that the frequency of precursors of cytotoxic T lymphocytes, specific for a syngeneic tumour, and the presence or absence of suppressor cells, may influence the growth of that tumour

    Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium

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    Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity

    Design process and simulation testing of a shape memory alloy actuated robotic microgripper

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    Microgrippers are commonly used for micromanipulation of micro-objects with dimensions from 1 to 100 µm and attain features of reliable accuracy, low cost, wide jaw aperture and variable applied force. This paper studies the design process, simulation, and testing of a microgripper which can manipulate and assemble a platinum resistance temperature probe, made from a 25 µm diameter platinum wire, a 20 mm diameter tinned copper wire, and a printed circuit board type connector. Various microgripper structures and actuator types were researched and reviewed to determine the most suitable design for the required micromanipulation task. Operation tests using SolidWorks and ANSYS software were conducted to test a parallelogram structure with flexible single-notch hinges. The best suited material was found to be Aluminium alloy 7075-T6 as it was capable of producing a large jaw tip displacement of 0.7 mm without exceeding its tensile yield strength limit. A shape memory alloy was chosen as a choice of actuator to close the microgripper jaws. To ensure a repeatably accurate datum point, the final microgripper consisted of a fixed arm and a flexible arm. An optimisation process using ANSYS studied the hinge thickness and radius dimensions of the microgripper which improved its deflection whilst reducing the experienced stress

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Regional Accommodation In Southeast Asia: A Study Of Attitudinal Compatibility And Distance

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    This dissertation is a study of dispositions and perceptions pertaining to increasing international interdependence. This study of attitudes as they may affect integration is not a study of integration per se. The single term accomodation is a reference to the attitudinal component of the larger integration process.--Preface
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