1,744 research outputs found

    Decision-support model to explore the feasibility of using translocation to restore a woodland caribou population in Pukaskwa National Park, Canada

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    The distribution and abundance of woodland caribou (Rangifer tarandus caribou) have declined dramatically in the past century. Without intervention the most southern population of caribou in eastern North America is expected to disappear within 20 years. Although translocations have reintroduced and reinforced some populations, approximately half of caribou translocation efforts fail. Translocations are resource intensive and risky, and multiple interrelated factors must be considered to assess their potential for success. Structured decision-making tools, such as Bayesian belief networks, provide objective methods to assess different wildlife management scenarios by identifying the key components and relationships in an ecosystem. They can also catalyze dialogue with stakeholders and provide a record of the complex thought processes used in reaching a decision. We developed a Bayesian belief network for a proposed translocation of woodland caribou into a national park on the northeastern coast of Lake Superior, Ontario, Canada. We tested scenarios with favourable (e.g., good physical condition of adult caribou) and unfavourable (e.g., high predator densities) conditions with low, medium, and high numbers of translocated caribou. Under the current conditions at Pukaskwa National Park, augmenting the caribou population is unlikely to recover the species unless wolf densities remain low (<5.5/1000 km2) or if more than 300 animals could be translocated

    Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics

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    Background and Purpose Clinical use of cinacalcet in hyperparathyroidism is complicated by its tendency to induce hypocalcaemia, arising partly from activation of calcium-sensing receptors (CaS receptors) in the thyroid and stimulation of calcitonin release. CaS receptor allosteric modulators that selectively bias signalling towards pathways that mediate desired effects [e.g. parathyroid hormone (PTH) suppression] rather than those mediating undesirable effects (e.g. elevated serum calcitonin), may offer better therapies. Experimental Approach We characterized the ligand-biased profile of novel calcimimetics in HEK293 cells stably expressing human CaS receptors, by monitoring intracellular calcium (Ca2+i) mobilization, inositol phosphate (IP)1 accumulation, ERK1/2 phosphorylation (pERK1/2) and receptor expression. Key Results Phenylalkylamine calcimimetics were biased towards allosteric modulation of Ca2+i mobilization and IP1 accumulation. S,R-calcimimetic B was biased only towards IP1 accumulation. R,R-calcimimetic B and AC-265347 were biased towards IP1 accumulation and pERK1/2. Nor-calcimimetic B was unbiased. In contrast to phenylalkylamines and calcimimetic B analogues, AC-265347 did not promote trafficking of a loss-of-expression, naturally occurring, CaS receptor mutation (G670E). Conclusions and Implications The ability of R,R-calcimimetic B and AC-265347 to bias signalling towards pERK1/2 and IP1 accumulation may explain their suppression of PTH levels in vivo at concentrations that have no effect on serum calcitonin levels. The demonstration that AC-265347 promotes CaS receptor receptor signalling, but not trafficking reveals a novel profile of ligand-biased modulation at CaS receptors The identification of allosteric modulators that bias CaS receptor signalling towards distinct intracellular pathways provides an opportunity to develop desirable biased signalling profiles in vivo for mediating selective physiological responses

    Expression, Purification, and Monitoring of Conformational Changes of hCB2 TMH67H8 in Different Membrane-Mimetic Lipid Mixtures Using Circular Dichroism and NMR Techniques

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    This work was intended to develop self-assembly lipids for incorporating G-protein coupled receptors (GPCRs) in order to improve the success rate for nuclear magnetic resonance spectroscopy (NMR) structural elucidation. We hereby report the expression and purification of uniformly 15N-labeled human cannabinoid receptor-2 domain in insect cell media. The domain was refolded by screening several membrane mimetic environments. Different q ratios of isotropic bicelles were screened for solubilizing transmembrane helix 6, 7 and 8 (TMH67H8). As the concentration of dimyristoylphosphocholine (DMPC) was increased such that the q ratio was between 0.16 and 0.42, there was less crowding in the cross peaks with increasing q ratio. In bicelles of q = 0.42, the maximum number of cross peaks were obtained and the cross peaks were uniformly dispersed. The receptor domain in bicelles beyond q = 0.42 resulted in peak crowding. These studies demonstrate that GPCRs folding especially in bicelles is protein-specific and requires the right mix of the longer chain and shorter chain lipids to provide the right environment for proper folding. These findings will allow further development of novel membrane mimetics to provide greater diversity of lipid mixtures than those currently being employed for GPCR stability and folding, which are critical for both X-ray and NMR studies of GPCRs

    Advancing coastal ocean modelling, analysis, and prediction for the US Integrated Ocean Observing System

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    Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here by permission of Taylor & Francis for personal use, not for redistribution. The definitive version was published in Journal of Operational Oceanography 10 (2017): 115-126, doi:10.1080/1755876X.2017.1322026.This paper outlines strategies that would advance coastal ocean modeling, analysis and prediction as a complement to the observing and data management activities of the coastal components of the U.S. Integrated Ocean Observing System (IOOSŸ) and the Global Ocean Observing System (GOOS). The views presented are the consensus of a group of U.S. based researchers with a cross-section of coastal oceanography and ocean modeling expertise and community representation drawn from Regional and U.S. Federal partners in IOOS. Priorities for research and development are suggested that would enhance the value of IOOS observations through model-based synthesis, deliver better model-based information products, and assist the design, evaluation and operation of the observing system itself. The proposed priorities are: model coupling, data assimilation, nearshore processes, cyberinfrastructure and model skill assessment, modeling for observing system design, evaluation and operation, ensemble prediction, and fast predictors. Approaches are suggested to accomplish substantial progress in a 3-8 year timeframe. In addition, the group proposes steps to promote collaboration between research and operations groups in Regional Associations, U.S. Federal Agencies, and the international ocean research community in general that would foster coordination on scientific and technical issues, and strengthen federal-academic partnerships benefiting IOOS stakeholders and end users.2018-05-2

    Geothermal reservoir engineering of HGP-A : a summary report of activities up to October 31, 1976. Technical report No. 19

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    The initial four holes were drilled in 1961 by the Hawaii Thermal Power Company. Recent measurements have shown that these temperatures have not change significantly. It is interesting to note that TTW #2 shows virtually a continuous increase in temperature with depth, with a sharp gradient from 253 to 262 feet. However, the well had caved in at around 361 feet, when a temperature of 97° was measured at this point in 1975. TTW #3 was measured to the bottom of the well. where a peak temperature of 93°C was measured at around 540 feet. A sharp positive gradient was measured from 460 feet to 540 feet, and a rather sharp negative gradient (not as steep as the positive gradient) from 540 feet to the bottom (Epp and Ha1unen, 1976).The history of geothermal well drilling in Hawaii is reviewed briefly. The following are discussed: the geophysical program, pre-drilling speculative models, geothermal reservoir engineering, the drilling program, the measurement activities, a preliminary reservoir analysis of HGP-A well, and future activities. (MHR)National Science Foundation Research Grant No. GI-38319Energy Research and Development Administration Research Grant No. E(04-3)-1093Department of Energy Contract Number: AC03-76ET2830

    The On-Orbit Performance of the Galaxy Evolution Explorer

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    We report the first year on-orbit performance results for the Galaxy Evolution Explorer (GALEX), a NASA Small Explorer that is performing a survey of the sky in two ultraviolet bands. The instrument comprises a 50 cm diameter modified Ritchey-Chretien telescope with a 1.25 degree field of view, selectable imaging and objective grism spectroscopic modes, and an innovative optical system with a thin-film multilayer dichroic beam splitter that enables simultaneous imaging by a pair of photon counting, microchannel plate, delay line readout detectors. Initial measurements demonstrate that GALEX is performing well, meeting its requirements for resolution, efficiency, astrometry, bandpass definition and survey sensitivity.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issu

    The Discovery of a Second Field Methane Brown Dwarf from Sloan Digital Sky Survey Commissioning Data

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    We report the discovery of a second field methane brown dwarf from the commissioning data of the Sloan Digital Sky Survey (SDSS). The object, SDSS J134646.45-003150.4 (SDSS 1346-00), was selected because of its very red color and stellar appearance. Its spectrum between 0.8-2.5 mic is dominated by strong absorption bands of H_2O and CH_4 and closely mimics those of Gliese 229B and SDSS 162414.37+002915.6 (SDSS 1624+00), two other known methane brown dwarfs. SDSS 1346-00 is approximately 1.5 mag fainter than Gliese 229B, suggesting that it lies about 11 pc from the sun. The ratio of flux at 2.1 mic to that at 1.27 mic is larger for SDSS 1346-00 than for Gliese 229B and SDSS 1624+00, which suggests that SDSS 1346-00 has a slightly higher effective temperature than the others. Based on a search area of 130 sq. deg. and a detection limit of z* = 19.8, we estimate a space density of 0.05 pc^-3 for methane brown dwarfs with T_eff ~ 1000 K in the 40 pc^3 volume of our search. This estimate is based on small-sample statistics and should be treated with appropriate caution.Comment: 9 pages, 3 figures, AASTeX, to appear in ApJ Letters, authors list update

    Ten Million Degree Gas in M 17 and the Rosette Nebula: X-ray Flows in Galactic H II Regions

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    We present the first high-spatial-resolution X-ray images of two high-mass star forming regions, the Omega Nebula (M 17) and the Rosette Nebula (NGC 2237--2246), obtained with the Chandra X-ray Observatory Advanced CCD Imaging Spectrometer (ACIS) instrument. The massive clusters powering these H II regions are resolved at the arcsecond level into >900 (M 17) and >300 (Rosette) stellar sources similar to those seen in closer young stellar clusters. However, we also detect soft diffuse X-ray emission on parsec scales that is spatially and spectrally distinct from the point source population. The diffuse emission has luminosity L_x ~ 3.4e33 ergs/s in M~17 with plasma energy components at kT ~0.13 and ~0.6 keV (1.5 and 7 MK), while in Rosette it has L_x \~6e32 ergs/s with plasma energy components at kT ~0.06 and ~0.8 keV (0.7 and 9 MK). This extended emission most likely arises from the fast O-star winds thermalized either by wind-wind collisions or by a termination shock against the surrounding media. We establish that only a small portion of the wind energy and mass appears in the observed diffuse X-ray plasma; in these blister H II regions, we suspect that most of it flows without cooling into the low-density interstellar medium. These data provide compelling observational evidence that strong wind shocks are present in H II regions.Comment: 35 pages, including 11 figures; to appear in ApJ, August 20, 2003. A version with high-resolution figures is available at ftp://ftp.astro.psu.edu/pub/townsley/diffuse.ps.g
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