1,458 research outputs found

    Pb-Zn liquid metal diffusion

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    The Lead-Zinc binary equilibrium system is currently being investigated. Ground based studies of this system were performed to examine the possibility of obtaining a couple which, after diffusion, could be examined continuously along the diffusion axis by quantitative metallography to determine the extent of diffusion. The specimens were analyzed by X-ray fluorescence in the scanning electron microscope to provide exact information on the chemical composition gradient. Two diffusion experiments were run simultaneously in the multipurpose furnace, each in its own isothermal cavity. Two flight samples, two flight backup samples, and two flight space samples were generated

    Sex Differences in the Kinetic Profiles of d- and l- Methylphenidate in the Brains of Adult Rats

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    OBJECTIVE: Methylphenidate is commonly used in the treatment of Attention Deficit Hyperactivity Disorder and narcolepsy. Methylphenidate is administered as a racemic mixture of the d- and l- threo enantiomers; however, the d-enantiomer is primarily responsible for the pharmacologic activity. Previous studies of the behavioral effects of methylphenidate have highlighted sex differences in the responsiveness to the drug, namely an increased sensitivity of females to its stimulatory effects. These differences may be due to differences in the uptake, distribution, and elimination of methylphenidate from male and female brains. Therefore, we compared the pharmacokinetics of d- and l- threo methylphenidate in the brains of male and female rats. MATERIALS AND METHODS: Adult male and female Sprague-Dawley rats were injected with 5 mg/kg d, l- threo methylphenidate, and whole brains were collected at various time points following injection. We measured methylphenidate concentrations utilizing chiral high pressure liquid chromatography followed by mass spectrometry. RESULTS: Females exhibited consistently higher brain concentrations of both d- and l- methylphenidate and a slower clearance of methylphenidate from brain as compared to males, particularly with the active d-enantiomer. CONCLUSIONS: The increased sensitivity of females to methylphenidate may be partially explained by an increase in total brain exposure to the drug

    Marine Copepods, The Wildebeest of the Ocean

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    Copepods are amongst the most abundant animals on our planet. Who knew?! These small (typically 1–10 mm) crustaceans are found in all of the world’s oceans and play an important role in regulating Earth’s climate. Like wildebeest in the Serengeti graze on grasslands and are food for lions, herbivorous copepods represent a vital link in oceanic food chains between microscopic algae and higher predators, such as fish, birds, and whales. A group of copepods called Calanus are particularly important in the Northern Hemisphere. These tiny-but-mighty animals also share the wildebeest’s need to make a large annual migration—but in their case, they sink thousands of meters downwards to spend the winter in the deep, dark ocean. Understanding the lives of marine copepods, and how their populations will respond to climate change, is crucial for predicting the future health of the marine environment and how it helps our planet

    HIV-Specific Probabilistic Models of Protein Evolution

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    Comparative sequence analyses, including such fundamental bioinformatics techniques as similarity searching, sequence alignment and phylogenetic inference, have become a mainstay for researchers studying type 1 Human Immunodeficiency Virus (HIV-1) genome structure and evolution. Implicit in comparative analyses is an underlying model of evolution, and the chosen model can significantly affect the results. In general, evolutionary models describe the probabilities of replacing one amino acid character with another over a period of time. Most widely used evolutionary models for protein sequences have been derived from curated alignments of hundreds of proteins, usually based on mammalian genomes. It is unclear to what extent these empirical models are generalizable to a very different organism, such as HIV-1–the most extensively sequenced organism in existence. We developed a maximum likelihood model fitting procedure to a collection of HIV-1 alignments sampled from different viral genes, and inferred two empirical substitution models, suitable for describing between-and within-host evolution. Our procedure pools the information from multiple sequence alignments, and provided software implementation can be run efficiently in parallel on a computer cluster. We describe how the inferred substitution models can be used to generate scoring matrices suitable for alignment and similarity searches. Our models had a consistently superior fit relative to the best existing models and to parameter-rich data-driven models when benchmarked on independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid substitution that are unique to HIV, and that are not captured by the existing models. The scoring matrices derived from the models showed a marked difference from common amino-acid scoring matrices. The use of an appropriate evolutionary model recovered a known viral transmission history, whereas a poorly chosen model introduced phylogenetic error. We argue that our model derivation procedure is immediately applicable to other organisms with extensive sequence data available, such as Hepatitis C and Influenza A viruses

    CodonTest: Modeling Amino Acid Substitution Preferences in Coding Sequences

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    Codon models of evolution have facilitated the interpretation of selective forces operating on genomes. These models, however, assume a single rate of non-synonymous substitution irrespective of the nature of amino acids being exchanged. Recent developments have shown that models which allow for amino acid pairs to have independent rates of substitution offer improved fit over single rate models. However, these approaches have been limited by the necessity for large alignments in their estimation. An alternative approach is to assume that substitution rates between amino acid pairs can be subdivided into rate classes, dependent on the information content of the alignment. However, given the combinatorially large number of such models, an efficient model search strategy is needed. Here we develop a Genetic Algorithm (GA) method for the estimation of such models. A GA is used to assign amino acid substitution pairs to a series of rate classes, where is estimated from the alignment. Other parameters of the phylogenetic Markov model, including substitution rates, character frequencies and branch lengths are estimated using standard maximum likelihood optimization procedures. We apply the GA to empirical alignments and show improved model fit over existing models of codon evolution. Our results suggest that current models are poor approximations of protein evolution and thus gene and organism specific multi-rate models that incorporate amino acid substitution biases are preferred. We further anticipate that the clustering of amino acid substitution rates into classes will be biologically informative, such that genes with similar functions exhibit similar clustering, and hence this clustering will be useful for the evolutionary fingerprinting of genes
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