13,032 research outputs found

    Extrapancreatic actions of incretin-based therapies on bone in diabetes mellitus

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    Diabetes mellitus is correlated with modifications in bone microarchitectural and mechanical strength, leading to increased bone fragility. The incretin hormones, with a classical effect to increase insulin secretion following food ingestion, are now postulated to have important direct effects on bone. As such, glucose-dependent insulinotropic polypeptide (GIP) has dual actions on bone cells; enhancing bone�forming activity of osteoblasts and suppressing bone resorption by osteoclasts. The sister incretin of GIP, glucagon-like peptide-1 (GLP-1), is also suspected to directly influence bone health in a beneficial manner, although mechanism are less clear at present. The physiological actions of incretins are attenuated by dipeptidyl peptidase (DPP-4) activity and it is speculated that introduction of DPP-4 inhibitor may also positively affect quality of the skeleton. As such, this thesis evaluates the potential beneficial effects of a DPP-4 resistant GIP analogue, namely [D-Ala2 ]GIP, on osteoblastic-derived, SaOS-2 cells, and also preliminary in vivo studies on the impact of genetic deficiencies of GIPRs and GLP-1Rs on bone mineral density and content. Further studies characterised the beneficial effects of incretin-based therapies on metabolic control, bone microstructure and bone mechanical integrity in animal models of pharmacologically-, genetically- and environmentally-induced diabetes. GIP and related stable analogue increased bone-forming biomarkers in SaOS-2 cells and importantly, [D-Ala2 ]GIP was shown to be more potent than native GIP. Knockout mouse studies revealed that both GIPR and GLP-1R signaling are important for optimum bone mass. All diabetic mouse models displayed reduced bone mass, altered bone micromorphology and impairment of bone mechanical strength, similar to the human situation, confirming their appropriateness. The incretin-based therapeutics, [D-Ala2 ]GIP and Liraglutide, in streptozotocin-diabetic significantly increased bone matrix properties, indicating recovery of bone strength at the tissue level. The beneficial effects of administration of [D-Ala2 ]GIP�oxyntomodulin on bone health in db/db mice were more prominent as the Oxm analogue did not only improve bone strength at tissue level, but also at whole-bone level. These modifications were independent of metabolic status. Twice-daily Exendin-4 therapy improved glycaemic control and increased work required to resist bone fracture in high-fat fed mice. It was also established that Sitagliptin had neutral effects on bone microstructure and mechanical strength in high-fat mice. In summary, these data demonstrate the negative impact of diabetes mellitus on normal skeleton development and bone quality. Moreover, this thesis highlights the growing potential of incretin-based therapies for ameliorating bone defects and improving the increased fragility fracture risk associated with diabete

    NASA technology utilization survey on composite materials

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    NASA and NASA-funded contractor contributions to the field of composite materials are surveyed. Existing and potential non-aerospace applications of the newer composite materials are emphasized. Economic factors for selection of a composite for a particular application are weight savings, performance (high strength, high elastic modulus, low coefficient of expansion, heat resistance, corrosion resistance,), longer service life, and reduced maintenance. Applications for composites in agriculture, chemical and petrochemical industries, construction, consumer goods, machinery, power generation and distribution, transportation, biomedicine, and safety are presented. With the continuing trend toward further cost reductions, composites warrant consideration in a wide range of non-aerospace applications. Composite materials discussed include filamentary reinforced materials, laminates, multiphase alloys, solid multiphase lubricants, and multiphase ceramics. New processes developed to aid in fabrication of composites are given

    Fractal Analysis of Cutting Force and Acoustic Emission Signals During CFRP Machining

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    AbstractCutting forces and acoustic emissions signals while machining Fiber Reinforced Plastics (FRP) depends strongly on the tool wear. Fractal analysis can be adapted to those signals to characterize their variations. This tool wear monitoring technique is presented herein for the carbon FRP (CFRP) orbital drilling. Fractal parameters, characterizing the signal complexity and ruggedness, are very efficient for machining quality estimation and to follow the tool wear evolution

    Tribological evaluation of composite materials made from a partially fluorinated polyimide

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    Preliminary tribological studies on a new polyimide formulated from the diamine 2,2-bis 4-(4-aminophenoxy) phenyl hexafluoropane (4-BDAF) indicates polyimides made from this diamine have excellent potential for high temperature applications. Two different polyimides were formulated from the diamine, and five different composites were formulated using one of the polyimides. Composites were made using 10 weight percent (w/o) graphite fluoride powder, 20 w/o PTFE powder, 30 w/o silver powder, or 50 w/o carbon fibers, both graphitic and nongraphitic types. The powder additions did not improve the tribological properties as much as the carbon fibers, and the graphitic fibers produced better results than did the nongraphitic fibers. Results also indicated that improved high temperature stability and tribological properties may be obtained with a polyimide made from the dianhydride pyromellitic acid (PMDA) rather than the dianhydride benzophenonetetracarboxylic acid (BTDA)
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