48 research outputs found

    Degradation of Riparian Leaves and the Recycling of Nutrients in a Stream Ecosystem

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    Leaves collected at 4 stations in the upper 5 km of Doe Run, Meade County, Kentucky, indicated an annual accumulation within the stream of 354 g/m2/year (17,700 kg). Leaves of sycamore (23.6%), red oak (21.7%), sugar maple (9.7%), beech (9.6%), white oak (7.1%), and hickory (6.0%) trees were most abundant, and leaves from 14 other kinds made up the remaining 22.3%. About a third of the annual leaf fall occurred during the last half of October and about two-thirds in the last 3 months of the year. Calorific equivalents for different kinds of leaves ranged from 3,789 cal/g dry weight for hickory to 4,417 cal/g for red oak. It is estimated that allochthonous leaf material made an annual contribution of about 70 million kcal of energy to the upper 5 km of Doe Run. Protein, carbohydrate, and lipid contents of leaves varied independently of seasons with average values of about 52, 79, and 32 mg/g dry weight, respectively. In leaves submersed in the stream experimentally, carbohydrates leached rapidly, lipids leached slowly, and there was an apparent increase in protein content. Indigenous amphipods preferred hickory, red elm, sugar maple, beech, red oak, and sycamore leaves as food in that order

    Characterization of the aquatic environment in Lake Mead near the proposed Spring Canyon pumped-storage project, and assessment of potential aquatic impacts

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    A pumped storage system consists of an upper reservoir and lower reservoir separated by an elevation difference. During low demand energy periods such as nights and weekends water is pumped from the lower to the upper reservoir using available energy from conventional steam electric power plants. During high energy demand periods, such as mornings and afternoons of weekdays, upper reservoir water is allowed to drop back down through the same system of water conduits and turbines, generating electricity to conveniently meet abrupt electrical energy requirements. The same water turbines thus act both as pumps and as conventional hydroelectric turbines. Because energy demands of electrical consumers vary considerably on a daily basis, the ability to economically store large amounts of energy during off - peak periods is of great advantage to utilities. Pumped-storage tends to stabilize a power generation and distribution system (Feickeisen 1979). Conventional steam electric power plants (fossil or nuclear fueled) operate more efficiently and have a longer life when they are run continuously rather than cycled to meet rapidly charging power demands. Pumped storage systems allow for a more continuous, efficient operation of base - load steam electric plants. Increasing populations in the Southwestern United States have resulted in increased peaking energy requirements. Following a decade of energy studies conducted by the Bureau of Reclamation and other Federal and non - Federal agencies, it was determined that pumped storage offered the best opportunity for meeting energy peaking needs while complementing large base-load steam electric plants. Some 200 potential pumped storage sites in Arizona, Nevada and southern California had been identified by 1982, and in \u27the same year, after an extensive screening process, the Bureau of Reclamation selected Spring Canyon as the preferred pumped storage site (USBR 1987). A total of 20 utility companies and power marketing agencies in Arizona, southern Nevada and southern California, are participating with the Bureau of Reclamation in a joint Spring Canyon Investigation that includes determination of potential environmental impacts, among other aspects. Contingent upon study findings, construction could begin in 1992 and be completed as early as 1997 (USBR 1987). The present study involves the aquatic environment of Lake Mead and addresses potential aquatic impacts of the Spring Canyon Pumped Storage Powerplant. The report is designed to aid the Bureau of Reclamation in development of a Draft Environmental Statement in 1988. The objectives were to evaluate the area of Lake Mead near the proposed pumped storage site (Virgin Canyon) and to predict the biological, hydrological and limnological conditions prevailing within Lake Mead and the Spring Canyon forebay (upper reservoir) once the project is operational. Items specifically considered include appraisal of existing conditions and impact assessment for the following: water temperature, water movements, dissolved oxygen, pH, conductivity and salinity, water transparency and light penetration, nutrients and chlorophyll, zooplankton, benthic macroinvertebrates, and fish (early life history stages and adults)

    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

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    BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.100213
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