21 research outputs found

    Processing of aluminum-graphite particulate metal matrix composites by advanced shear technology

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    Copyright @ 2009 ASM International. This paper was published in Journal of Materials Engineering and Performance 18(9) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.To extend the possibilities of using aluminum/graphite composites as structural materials, a novel process is developed. The conventional methods often produce agglomerated structures exhibiting lower strength and ductility. To overcome the cohesive force of the agglomerates, a melt conditioned high-pressure die casting (MC-HPDC) process innovatively adapts the well-established, high-shear dispersive mixing action of a twin screw mechanism. The distribution of particles and properties of composites are quantitatively evaluated. The adopted rheo process significantly improved the distribution of the reinforcement in the matrix with a strong interfacial bond between the two. A good combination of improved ultimate tensile strength (UTS) and tensile elongation (e) is obtained compared with composites produced by conventional processes.EPSR

    Use of high-frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc-deficient mice

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    Objective: We used non-invasive high-frequency ultrasound (HFUS) imaging to investigate embryonic brain development in a mouse model for neural tube defects (NTDs) and non-ketotic hyperglycinemia (NKH). Method: Using HFUS, we imaged embryos carrying loss of function alleles of Gldc encoding glycine decarboxylase, a component of the glycine cleavage system in mitochondrial folate metabolism, which is known to be associated with cranial NTDs and NKH in humans. We serially examined the same litter during the second half of embryonic development and quantified cerebral structures. Genotype was confirmed using PCR. Histology was used to confirm ultrasound findings. Results: High-frequency ultrasound allowed in utero detection of two major brain abnormalities in Gldc-deficient mouse embryos, cranial NTDs (exencephaly) and ventriculomegaly (corresponding with the previous finding of post-natal hydrocephalus). Serial ultrasound allowed individual embryos to be analysed at successive gestational time points. From embryonic day 16.5 to 18.5, the lateral ventricle volume reduced in wild-type and heterozygous embryos but increased in homozygous Gldc-deficient embryos. Conclusion: Exencephaly and ventriculomegaly were detectable by HFUS in homozygous Gldc-deficient mouse embryos indicating this to be an effective tool to study CNS development. Longitudinal analysis of the same embryo allowed the prenatal onset and progression of ventricle enlargement in Gldc-deficient mice to be determined

    Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy.

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    Immunotherapy is revolutionizing cancer treatment but is often restricted by toxicities. What distinguishes adverse events from concomitant antitumor reactions is poorly understood. Here, using anti-CD40 treatment in mice as a model of T <sub>H</sub> 1-promoting immunotherapy, we showed that liver macrophages promoted local immune-related adverse events. Mechanistically, tissue-resident Kupffer cells mediated liver toxicity by sensing lymphocyte-derived IFN-γ and subsequently producing IL-12. Conversely, dendritic cells were dispensable for toxicity but drove tumor control. IL-12 and IFN-γ were not toxic themselves but prompted a neutrophil response that determined the severity of tissue damage. We observed activation of similar inflammatory pathways after anti-PD-1 and anti-CTLA-4 immunotherapies in mice and humans. These findings implicated macrophages and neutrophils as mediators and effectors of aberrant inflammation in T <sub>H</sub> 1-promoting immunotherapy, suggesting distinct mechanisms of toxicity and antitumor immunity

    Phospholipase D

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