Hormone-stimulated modulation of endocytic trafficking in osteoclasts

Copyright @ 2012 Stenbeck, Lawrence and Albert. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. This article has been made available through the Brunel Open Access Publishing Fund.A precise control of vesicular trafficking is crucial not only for osteoclastic bone resorption, but also for the crosstalk between osteoclasts and osteoblasts, which regulates bone homeostasis. In addition to the release of growth factors and modulators, such as glutamate, flux through the intracellular trafficking routes could also provide the osteoclast with a monitoring function of its resorption activity. To establish the signaling pathways regulating trafficking events in resorbing osteoclasts, we used the bone conserving hormone calcitonin, which has the unique property of inducing osteoclast quiescence. Calcitonin acts through the calcitonin receptor and activates multiple signaling pathways. By monitoring trafficking of a fluorescent low molecular weight probe in mature, bone resorbing osteoclasts we show for the first time that calcitonin blocks endocytosis from the ruffled border by phospholipase C (PLC) activation. Furthermore, we identify a requirement for polyunsaturated fatty acids in endocytic trafficking in osteoclasts. Inhibition of PLC prior to calcitonin treatment restores endocytosis to 75% of untreated rates. This effect is independent of protein kinase C activation and can be mimicked by an increase in intracellular calcium. We thus define an essential role for intracellular calcium levels in the maintenance of endocytosis in osteoclasts.Arthritis Research UK Grant (18197)

Financial statement fraud : capital market effects and ameliorating management actions

The purpose of this research is to examine the effects that financial statement fraud announcements and certain strategic actions have on the perceived validity of financial disclosures. This study posits that: (1) Financial statement fraud announcements damage the perceived validity of future financial disclosures, and (2) certain strategic actions performed subsequent to a fraud announcement improve the perceived validity of financial disclosures. The hypotheses are based upon the prior literature that uses the earnings response coefficient (ERC) to measure earnings quality. In a similar light, this study uses the ERC to measure the perceived validity of financial disclosures. Based on prior academic literature, anecdotal evidence, and data availability, the following four strategic actions were chosen for examination and are hypothesized to improve the ERC following a financial statement fraud announcement: change the external auditor, increase the percentage of outsiders comprising the board of directors, form an audit committee, and change upper management. The OLS regression results provide evidence that a financial statement fraud announcement is associated with a decrease in the ERC, and that the strategic actions of changing external auditor and increasing the percentage of outsiders comprising the board of directors following a fraud announcement improve the ERC. These results suggest that financial statement frauds reduce the perceived validity of future financial disclosures, and that the strategic actions of changing external auditor and increasing the percentage of outside directors help mitigate this reduction

Elm Farm Research Centre Bulletin 78

Regular newsletter and technical update

The development of a five-year budget for the San Joaquin Delta Community College District

The specific problem of this study was to develop a five-year budget for the San Joaquin Delta Community College District. The choice of a five-year budget was made by the administration after studying the advantages and disadvantages of. shorter and longer term budgets. A term of less than five years did not meet the objectives of the college for the building and educational programs. A ten-year budget would necessarily be less accurate, since the longer the projection, the more vague and theoretical it becomes. The purposes of this study were to: (1) review the literature pertaining to long-range budgeting, (2) examine the practices of long-range budgeting of other community college districts in California, (3) obtain data to be used in developing a long-range budget, (4) develop a continuing long-range budget for San Joaquin Delta·Community College District, and (5} make recommendations resulting from the study

The Potential of Synergistic Static, Dynamic and Speculative Loop Nest Optimizations for Automatic Parallelization

Research in automatic parallelization of loop-centric programs started with static analysis, then broadened its arsenal to include dynamic inspection-execution and speculative execution, the best results involving hybrid static-dynamic schemes. Beyond the detection of parallelism in a sequential program, scalable parallelization on many-core processors involves hard and interesting parallelism adaptation and mapping challenges. These challenges include tailoring data locality to the memory hierarchy, structuring independent tasks hierarchically to exploit multiple levels of parallelism, tuning the synchronization grain, balancing the execution load, decoupling the execution into thread-level pipelines, and leveraging heterogeneous hardware with specialized accelerators. The polyhedral framework allows to model, construct and apply very complex loop nest transformations addressing most of the parallelism adaptation and mapping challenges. But apart from hardware-specific, back-end oriented transformations (if-conversion, trace scheduling, value prediction), loop nest optimization has essentially ignored dynamic and speculative techniques. Research in polyhedral compilation recently reached a significant milestone towards the support of dynamic, data-dependent control flow. This opens a large avenue for blending dynamic analyses and speculative techniques with advanced loop nest optimizations. Selecting real-world examples from SPEC benchmarks and numerical kernels, we make a case for the design of synergistic static, dynamic and speculative loop transformation techniques. We also sketch the embedding of dynamic information, including speculative assumptions, in the heart of affine transformation search spaces