485 research outputs found

    Molecular analysis of placodal development in zebrafish

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    Vertebrates have evolved a unique way to sense their environment: placodallyderived sense organs. These sensory structures emerge from a crescent-shaped domain, the preplacodal domain, which surrounds the anterior neural plate and generates the paired sense organs as well as the cranial ganglia. For decades, embryologists have attempted to determine the tissue interactions required for induction of various placodal tissues. More recently, technological advances have allowed investigators to ask probing questions about the molecular nature of placodal development. In this dissertation I largely focus on development of the otic placode. I utilize loss-of-function techniques available in the zebrafish model system to demonstrate that two members of the fibroblast growth factors family of secreted ligands, Fgf3 and Fgf8, are redundantly required for otic placode induction. I go on to show that these factors are expressed in periotic tissues from the beginning of gastrulation. These findings are consistent with a model where Fgf3 and Fgf8 signal to preotic tissue to induce otic-specific gene expression. This model does not address other potential inducers in otic induction. A study using chick explant cultures suggests that a member of the Wnt family of secreted ligands also has a role in otic induction. I therefore test the relative roles of Wnt and Fgf in otic placode induction. The results demonstrate that Wnt functions primarily to correctly position the Fgf expression domain and that it is these Fgf factors which are directly received by future otic cells. Lastly, I examine the function of the muscle segment homeobox (msx) gene family expressed in the preplacodal domain. This study demonstrates that Msx proteins refine the boundary between the preplacodal domain and the neural plate. Further, msx genes function in the differentiation and survival of posterior placodal tissues (including the otic field), neural crest and dorsal neural cell types. Loss of Msx function results in precocious cell death and morphogenesis defects which may reflect perturbed BMP signaling

    Molecular analysis of placodal development in zebrafish

    Get PDF
    Vertebrates have evolved a unique way to sense their environment: placodallyderived sense organs. These sensory structures emerge from a crescent-shaped domain, the preplacodal domain, which surrounds the anterior neural plate and generates the paired sense organs as well as the cranial ganglia. For decades, embryologists have attempted to determine the tissue interactions required for induction of various placodal tissues. More recently, technological advances have allowed investigators to ask probing questions about the molecular nature of placodal development. In this dissertation I largely focus on development of the otic placode. I utilize loss-of-function techniques available in the zebrafish model system to demonstrate that two members of the fibroblast growth factors family of secreted ligands, Fgf3 and Fgf8, are redundantly required for otic placode induction. I go on to show that these factors are expressed in periotic tissues from the beginning of gastrulation. These findings are consistent with a model where Fgf3 and Fgf8 signal to preotic tissue to induce otic-specific gene expression. This model does not address other potential inducers in otic induction. A study using chick explant cultures suggests that a member of the Wnt family of secreted ligands also has a role in otic induction. I therefore test the relative roles of Wnt and Fgf in otic placode induction. The results demonstrate that Wnt functions primarily to correctly position the Fgf expression domain and that it is these Fgf factors which are directly received by future otic cells. Lastly, I examine the function of the muscle segment homeobox (msx) gene family expressed in the preplacodal domain. This study demonstrates that Msx proteins refine the boundary between the preplacodal domain and the neural plate. Further, msx genes function in the differentiation and survival of posterior placodal tissues (including the otic field), neural crest and dorsal neural cell types. Loss of Msx function results in precocious cell death and morphogenesis defects which may reflect perturbed BMP signaling

    Illustrating potential efficiency gains from using cost-effectiveness evidence to reallocate Medicare expenditures

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    This article is available open access through the publisher’s website at the linke below. Copyright @ 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).This article has been made available through the Brunel Open Access Publishing Fund.Objectives - The Centers for Medicare & Medicaid Services does not explicitly use cost-effectiveness information in national coverage determinations. The objective of this study was to illustrate potential efficiency gains from reallocating Medicare expenditures by using cost-effectiveness information, and the consequences for health gains among Medicare beneficiaries. Methods - We included national coverage determinations from 1999 through 2007. Estimates of cost-effectiveness were identified through a literature review. For coverage decisions with an associated cost-effectiveness estimate, we estimated utilization and size of the “unserved” eligible population by using a Medicare claims database (2007) and diagnostic and reimbursement codes. Technology costs originated from the cost-effectiveness literature or were estimated by using reimbursement codes. We illustrated potential aggregate health gains from increasing utilization of dominant interventions (i.e., cost saving and health increasing) and from reallocating expenditures by decreasing investment in cost-ineffective interventions and increasing investment in relatively cost-effective interventions. Results - Complete information was available for 36 interventions. Increasing investment in dominant interventions alone led to an increase of 270,000 quality-adjusted life-years (QALYs) and savings of $12.9 billion. Reallocation of a broader array of interventions yielded an additional 1.8 million QALYs, approximately 0.17 QALYs per affected Medicare beneficiary. Compared with the distribution of resources prior to reallocation, following reallocation a greater proportion was directed to oncology, diagnostic imaging/tests, and the most prevalent diseases. A smaller proportion of resources went to cardiology, treatments (including drugs, surgeries, and medical devices, as opposed to nontreatments such as preventive services), and the least prevalent diseases. Conclusions - Using cost-effectiveness information has the potential to increase the aggregate health of Medicare beneficiaries while maintaining existing spending levels.The Commonwealth Fun

    Numerical simulations of the Warm-Hot Intergalactic Medium

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    In this paper we review the current predictions of numerical simulations for the origin and observability of the warm hot intergalactic medium (WHIM), the diffuse gas that contains up to 50 per cent of the baryons at z~0. During structure formation, gravitational accretion shocks emerging from collapsing regions gradually heat the intergalactic medium (IGM) to temperatures in the range T~10^5-10^7 K. The WHIM is predicted to radiate most of its energy in the ultraviolet (UV) and X-ray bands and to contribute a significant fraction of the soft X-ray background emission. While O VI and C IV absorption systems arising in the cooler fraction of the WHIM with T~10^5-10^5.5 K are seen in FUSE and HST observations, models agree that current X-ray telescopes such as Chandra and XMM-Newton do not have enough sensitivity to detect the hotter WHIM. However, future missions such as Constellation-X and XEUS might be able to detect both emission lines and absorption systems from highly ionised atoms such as O VII, O VIII and Fe XVII.Comment: 18 pages, 5 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 14; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

    The birth of airplane stability theory

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    Airplane stability theory was born at the end of the XIX century and matured around 100 years ago, when airplanes were hardly controllable yet. The success and safety of flights in the pioneer years depended upon largely unknown stability and control characteristics. Understanding the modes of airplane motion has been of paramount importance for the development of aviation. The contributions made by a few scientists in the decades preceding and following the first flight by the Wright brothers set the concepts and equations that, with minor notation aspects, have remained almost unchanged till present day.Magraner Rullan, JP.; Martinez-Val, R. (2014). The birth of airplane stability theory. Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering. 228(9):1498-1506. doi:10.1177/0954410013494139S149815062289PERKINS, C. D. (1970). Development of airplane stability and control technology /1970 Von Karman Lecture/. Journal of Aircraft, 7(4), 290-301. doi:10.2514/3.44167Abzug, M. J., & Larrabee, E. E. (2002). Airplane Stability and Control, Second Edition. doi:10.1017/cbo9780511607141Graham, W. R. (1999). Asymptotic analysis of the classical aircraft stability equations. The Aeronautical Journal, 103(1020), 95-103. doi:10.1017/s0001924000027792Bryan, G. H., & Williams, W. E. (1904). The Longitudinal Stability of Aerial Gliders. Proceedings of the Royal Society of London, 73(488-496), 100-116. doi:10.1098/rspl.1904.0017Wegener, P. P. (1997). What Makes Airplanes Fly? doi:10.1007/978-1-4612-2254-5Pradeep, S., & Kamesh, S. (1999). Does the Phugoid Frequency Depend on Speed? Journal of Guidance, Control, and Dynamics, 22(2), 372-373. doi:10.2514/2.4391Phillips, W. F. (2000). Phugoid Approximation for Conventional Airplanes. Journal of Aircraft, 37(1), 30-36. doi:10.2514/2.2586Pamadi, B. N. (2004). Performance, Stability, Dynamics, and Control of Airplanes, Second Edition. doi:10.2514/4.862274Ananthkrishnan, N., & Ramadevi, P. (2002). Consistent Approximations to Aircraft Longitudinal Modes. Journal of Guidance, Control, and Dynamics, 25(4), 820-824. doi:10.2514/2.4952McRuer, D. T., Graham, D., & Ashkenas, I. (1990). Aircraft Dynamics and Automatic Control. doi:10.1515/978140085598

    'To live and die [for] Dixie': Irish civilians and the Confederate States of America

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    Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism
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