54 research outputs found
Synthesis and activity of a novel Autotaxin inhibitor-Icodextrin conjugate
© Copyright 2018 American Chemical Society. Autotaxin is an extracellular phospholipase D that catalyses the hydrolysis of lysophosphatidyl choline (LPC) to generate the bioactive lipid lysophosphatidic acid (LPA). Autotaxin has been implicated in many pathological processes relevant to cancer. Intraperitoneal administration of an autotaxin inhibitor may benefit patients with ovarian cancer, however low molecular mass compounds are known to be rapidly cleared from the peritoneal cavity. Icodextrin is a polymer that is already in clinical use because it is slowly eliminated from the peritoneal cavity. Herein we report conjugation of the autotaxin inhibitor HA-155 to icodextrin. The conjugate inhibits autotaxin activity (IC50 = 0.86 ± 0.13 μg mL-1) and reduces cell migration. Conjugation of the inhibitor increased its solubility, decreased its membrane permeability and improved its intraperitoneal retention in mice. These observations demonstrate the first application of icodextrin as a covalently-bonded drug delivery platform with potential use in the treatment of ovarian cancer
Resilience to loss and chronic grief: A prospective study from preloss to 18-months postloss.
Compensatory conviction in the face of personal uncertainty: Going to extremes and being oneself.
Plant Pest Impact Metric System (PPIMS): Framework and guidelines for a common set of metrics to classify and prioritise plant pests
Agricultural stakeholders need a common set of metrics to evaluate plant pest impacts to facilitate transparency and harmonisation of pest management and prioritisation across spatial scales and jurisdictions. We propose a classification system that articulates, defines and classifies the magnitude of impacts (historical, current or potential) of pest species (alien and native) in plant production systems. Metrics were identified and criteria defined through consideration of economic parameters, risk assessment standards and guidance tools, discussions with pest risk assessment practitioners and recent advances in environmental impact classification schemes. Twenty metrics were identified and assigned to one of four key metric types: spatiotemporal, market-driven, primary response and mid-to long-term response. Host crop value, Market access, Feasibility of management and Reversibility were identified as disruptor metrics, likely to influence overall classification by at least twice that of other metrics. Application of the system found it was able to classify well-known pests by importance, capturing changes in impact status as the management programme progressed for one pest, and how it was influenced by the geographic scale of assessment for another. Our work demonstrates the value of integrating plant protection science with invasion biology to derive a comprehensive measure of pest impact in agroecosystems that can be utilised by all plant biosecurity stakeholders
Options for Flight Testing Rocket-Based Combined-Cycle (RBCC) Engines
While NASA's current next-generation launch vehicle research has largely focused on advanced allrocket single-stage-to-orbit vehicles (i.e. the X-33 and it's RLV operational follow-on), some attention is being given to advanced propulsion concepts suitable for "next-generation-and-a-half" vehicles. Rocketbased combined-cycle (RBCC) engines combining rocket and airbreathing elements are one candidate concept. Preliminary RBCC engine development was undertaken by the United States in the 1960's. However, additional ground and flight research is required to bring the engine to technological maturity. This paper presents two options for flight testing early versions of the RBCC ejector scramjet engine. The first option mounts a single RBCC engine module to the X-34 air-launched technology testbed for test flights up to about Mach 6.4. The second option links RBCC engine testing to the simultaneous development of a small-payload (220 lb.) two-stage-to-orbit operational vehicle in the Banta..
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