Empirically Observed Distributions of Pharmacokinetic and Pharmacodynamic Variability in Humans—Implications for the Derivation of Single-Point Component Uncertainty Factors Providing Equivalent Protection as Existing Reference Doses

2016 ◽  
pp. 69-93 ◽  
Author(s):  
Dale Hattis ◽  
Meghan Keaney Lynch
Keyword(s):  
Single Point ◽  
Uncertainty Factors ◽  
Reference Doses

Fine-scale taxonomic and temporal variability in the energy density of invertebrate prey of juvenile Chinook salmon Oncorhynchus tshawytscha

2020 ◽  
Vol 655 ◽  
pp. 185-198
Author(s):  
J Weil ◽  
WDP Duguid ◽  
F Juanes
Keyword(s):  
Energy Density ◽  
Chinook Salmon ◽  
Temporal Variability ◽  
Energy Content ◽  
Single Point ◽  
Single Species ◽  
Fine Scale ◽  
Temporal Differences ◽  
Juvenile Chinook Salmon ◽  
Juvenile Chinook

Variation in the energy content of prey can drive the diet choice, growth and ultimate survival of consumers. In Pacific salmon species, obtaining sufficient energy for rapid growth during early marine residence is hypothesized to reduce the risk of size-selective mortality. In order to determine the energetic benefit of feeding choices for individuals, accurate estimates of energy density (ED) across prey groups are required. Frequently, a single species is assumed to be representative of a larger taxonomic group or related species. Further, single-point estimates are often assumed to be representative of a group across seasons, despite temporal variability. To test the validity of these practices, we sampled zooplankton prey of juvenile Chinook salmon to investigate fine-scale taxonomic and temporal differences in ED. Using a recently developed model to estimate the ED of organisms using percent ash-free dry weight, we compared energy content of several groups that are typically grouped together in growth studies. Decapod megalopae were more energy rich than zoeae and showed family-level variability in ED. Amphipods showed significant species-level variability in ED. Temporal differences were observed, but patterns were not consistent among groups. Bioenergetic model simulations showed that growth rate of juvenile Chinook salmon was almost identical when prey ED values were calculated on a fine scale or on a taxon-averaged coarse scale. However, single-species representative calculations of prey ED yielded highly variable output in growth depending on the representative species used. These results suggest that the latter approach may yield significantly biased results.

Risk and Regulation: Methylmercury Exposure and Fish Consumption

2010 ◽  
Vol 6 ◽  
Author(s):  
Jonathan M Gendzier
Keyword(s):  
Environmental Protection Agency ◽  
Fish Consumption ◽  
Government Regulation ◽  
Mercury Emissions ◽  
Methylmercury Exposure ◽  
Exposure Levels ◽  
Aquatic Food ◽  
Reference Doses ◽  
Fish And Shellfish ◽  
Global Cycle

Exposure to organic mercury (methylmercury) occurs almost universally due to ingestion via contaminated fish and shellfish tissue. Ultimate sources of mercury consist of air release by domestic industrial combustion, mining, and international mercury emissions transported via a global cycle. Deposition of mercury from air to surface waters results in methylation to organic methylmercury and bioaccumulation in the aquatic food web. Health effects from methylmercury exposure consist mainly of neurological and neurodevelopmental effects, with fetuses particularly sensitive. Thus regulation of methylmercury exposure has concentrated on acceptable exposure levels and reference doses aimed toward protecting developing fetuses. The risk of methylmercury exposure in humans is regulated largely by the federal government, especially by the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA). The EPA imposes limits on mercury emissions and seeks to research methylmercury levels in fish and humans. The EPA sets a reference dose for methylmercury exposure. The FDA conducts uses date on methylmercury levels in fish to advise consumers on how to make informed decisions regarding fish consumption. There are numerous shortcoming to government regulation of this issue. Further scientific research, improved implementation of available data and scientific conclusions, and improved public communication of risk would all lead to more effective treatment of the risk of methylmercury exposure via ingestion of fish and shellfish. This could include more effective monitoring systems of human and fish methylmercury levels, research into the process of bioaccumulation, and implementation of stricter fish labeling standards, as well as research into higher-risk subpopulations allowing for targeted standards and recommendations.

Mill Experiences with Single Point Kappa Analysers

2017 ◽  
Vol 71 (3) ◽  
pp. 289-293
Author(s):  
Yusuke Ishimoto
Keyword(s):  
Single Point

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Miho Yuasa ◽  
Yosuke Nishikawa ◽  
Genji Kurisu ◽  
Shinobu Itoh ◽  
...  
Keyword(s):  
Michael Addition ◽  
In Silico ◽  
Addition Reaction ◽  
Single Point ◽  
Point Mutations ◽  
Unsaturated Ketone ◽  
Michael Addition Reaction ◽  
Beta Barrel ◽  
Cupin Superfamily ◽  
Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

Optimal Duration of the Preincubation Phase in Enzyme Inhibition Experiments

2020 ◽  
Author(s):  
Petr Kuzmic
Keyword(s):  
Enzyme Inhibition ◽  
Dose Response ◽  
Enzyme Inhibitor ◽  
Single Point ◽  
Association Rate ◽  
Weakly Bound ◽  
Inhibitor Complex ◽  
Dissociation Equilibrium ◽  
Optimal Duration ◽  
Algebraic Formula

This report describes an algebraic formula to calculate the optimal duration of the pre-incubation phase in enzyme-inhibition experiments, based on the assumed range of expected values for the dissociation equilibrium constant of the enzyme–inhibitor complex and for the bimolecular association rate constant. Three typical experimental scenarios are treated, namely, (1) single-point primary screening at relatively high inhibitor concentrations; (2) dose-response secondary screening of relatively weakly bound inhibitors; (3) dose-response screening of tightly-bound inhibitors.

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