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- Nordgaard, Anders, 1962-, et al.
(författare)
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Prediction of the distribution of thepercentages of narcotic substances in drug seizures
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The percentage of the narcotic substance in a drug seizure may vary a lot depending on when and from whom the seizure was taken. Seizures from a typical consumer would in general show low percentages, while seizures from the early stages of a drug dealing chain would show higher percentages (these will be diluted). Historical records from the determination of the percentage of narcotic substance in seized drugs reveal that the mean percentage but also the variation of the percentage can differ between years. Some drugs show close to monotonic trends while others are more irregular in the temporal variation.Legal fact finders must have an up-to-date picture of what is an expected level of the percentage and what levels are to be treated as unusually low or unusually high. This is important for the determination of the sentences to be given in a drug case.In this work we treat the probability distribution of the percentage of a narcotic substance in a seizure from year to year as a time series of functions. The functions are probability density functions of beta distributions, which are successively updated with the use of point mass posteriors for the shape parameters. The predictive distribution for a new year is a weighted sum of beta distributions for the previous years where the weights are found from forward validation. We show that this method of prediction is more accurate than one that uses a predictive distribution built on a likelihood based on all previous years.
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- Tsai, Albert, et al.
(författare)
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The Impact of Aminoglycosides on the Dynamics of Translation Elongation
- 2013
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 3:2, s. 497-508
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Tidskriftsartikel (refereegranskat)abstract
- Inferring antibiotic mechanisms on translation through static structures has been challenging, as biological systems are highly dynamic. Dynamic single-molecule methods are also limited to few simultaneously measurable parameters. We have circumvented these limitations with a multifaceted approach to investigate three structurally distinct aminoglycosides that bind to the aminoacyl-transfer RNA site (A site) in the prokaryotic 30S ribosomal subunit: apramycin, paromomycin, and gentamicin. Using several single-molecule fluorescence measurements combined with structural and biochemical techniques, we observed distinct changes to translational dynamics for each aminoglycoside. While all three drugs effectively inhibit translation elongation, their actions are structurally and mechanistically distinct. Apramycin does not displace A1492 and A1493 at the decoding center, as demonstrated by a solution nuclear magnetic resonance structure, causing only limited miscoding; instead, it primarily blocks translocation. Paromomycin and gentamicin, which displace A1492 and A1493, cause significant miscoding, block intersubunit rotation, and inhibit translocation. Our results show the power of combined dynamics, structural, and biochemical approaches to elucidate the complex mechanisms underlying translation and its inhibition.
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