299 research outputs found

    Seasonal and hydrological control of phytoplankton nutrient limitation in the lower Neuse River Estuary, North Carolina

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    The lower estuary experienced a general state of nitrogen limitation, with especially pronounced limitation during summer months, a period of high phytoplankton productivity. Bioassays conducted during spring months showed significantly greater stimulation of algal productivity with the addition of N and P than that found with N addition alone. This co-stimulation occurred during periods when surface-water dissolved inorganic N:dissolved inorganic P ratios were elevated above typical values of <5. Seasonal patterns in ambient nutrient concentrations revealed N maxima associated with spring, fall, and winter runoff events, with summer minima. Hydrologically driven N loading exerted a strong, year-round influence on primary production and nutrient limitation characteristics. High-flow events acted to oversaturate the upper estuarine nutrient filtering capacity, resulting in increased N delivery to the lower estuarine environment. The phytoplankton community responded to increased flow and nutrient loadings by increasing production and biomass levels, often very rapidly. Hydrologic factors influencing nitrogen loading (terrigenous runoff, point source inputs, and wet and dry atmospheric deposition) are key determinants of the trophic state of this estuary

    Glutamate carboxypeptidase activity in human skin biopsies as a pharmacodynamic marker for clinical studies

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    <p>Abstract</p> <p>Background</p> <p>Glutamate excitotoxicity is thought to be involved in the pathogenesis of neurodegenerative disease. One potential source of glutamate is N-acetyl-aspartyl-glutamate (NAAG) which is hydrolyzed to glutamate and N-acetyl-aspartate (NAA) in a reaction catalyzed by glutamate carboxypeptidase (GCP). As a result, GCP inhibition is thought to be beneficial for the treatment of neurodegenerative diseases where excess glutamate is presumed pathogenic. Both pharmacological and genetic inhibition of GCP has shown therapeutic utility in preclinical models and this has led to GCP inhibitors being pursued for the treatment of nervous system disorders in human clinical trials. Specifically, GCP inhibitors are currently being developed for peripheral neuropathy and neuropathic pain. The purpose of this study was to develop a pharmacodynamic (PD) marker assay to use in clinical development. The PD marker will determine the effect of GCP inhibitors on GCP enzymatic activity in human skin as measure of inhibition in peripheral nerve and help predict drug doses required to elicit pharmacologic responses.</p> <p>Methods</p> <p>GCP activity was first characterized in both human skin and rat paw pads. GCP activity was then monitored in both rodent paw pads and sciatic nerve from the same animals following peripheral administration of various doses of GCP inhibitor. Significant differences among measurements were determined using two-tailed distribution, equal variance student's t test.</p> <p>Results</p> <p>We describe for the first time, a direct and quantifiable assay to evaluate GCP enzymatic activity in human skin biopsy samples. In addition, we show that GCP activity in skin is responsive to pharmacological manipulation; GCP activity in rodent paws was inhibited in a dose response manner following peripheral administration of a potent and selective GCP inhibitor. Inhibition of GCP activity in rat paw pads was shown to correlate to inhibition of GCP activity in peripheral nerve.</p> <p>Conclusion</p> <p>Monitoring GCP activity in human skin after administration of GCP inhibitors could be readily used as PD marker in the clinical development of GCP inhibitors. Enzymatic activity provides a simple and direct measurement of GCP activity from tissue samples easily assessable in human subjects.</p

    Regulation of estuarine primary production by watershed rainfall and river flow

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    Enhanced phytoplankton production and algal blooms, symptoms of eutrophication, are frequently caused by elevated nutrient loading, usually as nitrogen, to coastal waters. This nitrogen is derived primarily from anthropogenic sources (urban, industrial, and agricultural) but is delivered to coastal waters through meteorological and hydrological means. We utilized a 4 yr monthly data set to investigate the effect of these upstream physical forces upon primary productivity of the Neuse River Estuary (North Carolina, USA), a large temperate coastal plain estuary. Our results indicate that the magnitude of estuarine primary production and the periodicity of algal blooms can be directly related to variations in upper watershed rainfall and its subsequent regulation of downstream river flow. Future changes in precipitation patterns for coastal regions may thus lead to substantial alterations in coastal primary productivity rates and patterns

    Imaging Molecular Structure through Femtosecond Photoelectron Diffraction on Aligned and Oriented Gas-Phase Molecules

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    This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray Free-Electron Laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laseraligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.Comment: 24 pages, 10 figures, Faraday Discussions 17

    Consistency checks of results from a Monte Carlo code intercomparison for emitted electron spectra and energy deposition around a single gold nanoparticle irradiated by X-rays

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    Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100 kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed

    Homogeneous Bubble Nucleation driven by local hot spots: a Molecular Dynamics Study

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    We report a Molecular Dynamics study of homogenous bubble nucleation in a Lennard-Jones fluid. The rate of bubble nucleation is estimated using forward-flux sampling (FFS). We find that cavitation starts with compact bubbles rather than with ramified structures as had been suggested by Shen and Debenedetti (J. Chem. Phys. 111:3581, 1999). Our estimate of the bubble-nucleation rate is higher than predicted on the basis of Classical Nucleation Theory (CNT). Our simulations show that local temperature fluctuations correlate strongly with subsequent bubble formation - this mechanism is not taken into account in CNT

    Chemical Kinetics and Photochemical Data for Use in Atmospheric Studies Evaluation Number 15

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    This is the fifteenth in a series of evaluated sets of rate constants and photochemical cross sections compiled by the NASA Panel for Data Evaluation. The data are used primarily to model stratospheric and upper tropospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena. Copies of this evaluation are available in electronic form and may be printed from the following Internet URL: http://jpldataeval.jpl.nasa.gov/

    Coulomb explosion imaging of small organic molecules at LCLS.

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    Fragmentation of small organic molecules by intense few-femtosecond X-ray free-electron laser pulses has been studied using Coulomb explosion imaging. By measuring kinetic energies and emission angles of the ionic fragments in coincidence, we disentangle different fragmentation pathways, for certain cases can reconstruct molecular geometry at the moment of explosion, and show how it depends on LCLS pulse duration

    towards time-resolved imaging of molecular structure

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    We demonstrate an experimental method to record snapshot diffraction images of polyatomic gas-phase molecules, which can, in a next step, be used to probe time-dependent changes in the molecular geometry during photochemical reactions with femtosecond temporal and angstrom spatial resolution. Adiabatically laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) molecules were imaged by diffraction of photoelectrons with kinetic energies between 31 and 62 eV, created from core ionization of the fluorine (1s) level by ≈80 fs x-ray free-electron-laser pulses. Comparison of the experimental photoelectron angular distributions with density functional theory calculations allows relating the diffraction images to the molecular structure
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