Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain

Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.status: publishe

Precision Measurement of 11Li moments: Influence of Halo Neutrons on the 9Li Core

The electric quadrupole moment and the magnetic moment of the 11Li halo nucleus have been measured with more than an order of magnitude higher precision than before, |Q| = 33.3(5)mb and mu=3.6712(3)mu_N, revealing a 8.8(1.5)% increase of the quadrupole moment relative to that of 9Li. This result is compared to various models that aim at describing the halo properties. In the shell model an increased quadrupole moment points to a significant occupation of the 1d orbits, whereas in a simple halo picture this can be explained by relating the quadrupole moments of the proton distribution to the charge radii. Advanced models so far fail to reproduce simultaneously the trends observed in the radii and quadrupole moments of the lithium isotopes.Comment: 4 pages, 4 figures, 1 tabl

Relativistic Beaming and the Intrinsic Properties of Extragalactic Radio Jets

Relations between the observed quantities for a beamed radio jet, apparent transverse speed and apparent luminosity (beta_app,L), and the intrinsic quantities, Lorentz factor and intrinsic luminosity (gamma,L_o), are investigated. The inversion from measured to intrinsic values is not unique, but approximate limits to gamma and L_o can be found using probability arguments. Roughly half the sources in a flux density--limited, beamed sample have a value of gamma close to the measured beta_app. The methods are applied to observations of 119 AGN jets made with the VLBA at 15 GHz during 1994-2002. The results strongly support the common relativistic beam model for an extragalactic radio jet. The (beta_app,L) data are closely bounded by a theoretical envelope, an aspect curve for gamma=32, L_o= 10^25 W/Hz. This gives limits to the maximum values of gamma and L_o in the sample: gamma_max about 32, and L_o,max ~ 10^26 W/Hz. No sources with both high beta_app and low L are observed. This is not the result of selection effects due to the observing limits, which are flux density S>0.5 Jy, and angular velocity mu<4 mas/yr. Many of the fastest quasars have a pattern Lorentz factor gamma_p close to that of the beam, gamma_b, but some of the slow quasars must have gamma_p<<gamma_b. Three of the 10 galaxies in the sample have a superluminal feature, with speeds up to beta_app about 6. The others are at most mildly relativistic. The galaxies are not off-axis versions of the powerful quasars, but Cygnus A might be an exception.Comment: 12 pages, 9 figures, 1 table, accepted for publication in the Astrophysical Journa

Twenty Years of Timing SS433

We present observations of the optical ``moving lines'' in spectra of the Galactic relativistic jet source SS433 spread over a twenty year baseline from 1979 to 1999. The red/blue-shifts of the lines reveal the apparent precession of the jet axis in SS433, and we present a new determination of the precession parameters based on these data. We investigate the amplitude and nature of time- and phase-dependent deviations from the kinematic model for the jet precession, including an upper limit on any precessional period derivative of $\dot P < 5 \times 10^{-5}$. We also dicuss the implications of these results for the origins of the relativistic jets in SS433.Comment: 21 pages, including 9 figures. To appear in the Astrophysical Journa

The properties of the gamma-ray blazars in the CJ-F VLBI sample

We present first results from the analysis of multi-epoch VLBI observations of the EGRET detected sources [9] in the CJ-F sample (Caltech Jodrell-Flat-spectrum, [10]). These objects form a subsample of 14 sources within the 293 AGN of the full CJ-F sample. 5 GHz VLBI snapshot observations of the CJ-F sources are continuously being performed in order to create a valid database for thorough statistical tests of pc-scale jet motion in AGN. All gamma-bright CJ-F AGN have been observed at least twice with the VLBA, which enables us to investigate jet component motions and paths. In particular, we concentrate on the analysis of those properties supposed to be essential for gamma-ray production, i.e., superluminal motion and bending. A paper discussing the possible relation between morphological changes and gamma-ray flaring/production is in preparation

TransCom N2O model inter-comparison - Part 2:Atmospheric inversion estimates of N2O emissions

This study examines N2O emission estimates from five different atmospheric inversion frameworks based on chemistry transport models (CTMs). The five frameworks differ in the choice of CTM, meteorological data, prior uncertainties and inversion method but use the same prior emissions and observation data set. The posterior modelled atmospheric N2O mole fractions are compared to observations to assess the performance of the inversions and to help diagnose problems in the modelled transport. Additionally, the mean emissions for 2006 to 2008 are compared in terms of the spatial distribution and seasonality. Overall, there is a good agreement among the inversions for the mean global total emission, which ranges from 16.1 to 18.7 TgN yr(-1) and is consistent with previous estimates. Ocean emissions represent between 31 and 38% of the global total compared to widely varying previous estimates of 24 to 38%. Emissions from the northern mid- to high latitudes are likely to be more important, with a consistent shift in emissions from the tropics and subtropics to the mid- to high latitudes in the Northern Hemisphere; the emission ratio for 0-30A degrees N to 30-90A degrees N ranges from 1.5 to 1.9 compared with 2.9 to 3.0 in previous estimates. The largest discrepancies across inversions are seen for the regions of South and East Asia and for tropical and South America owing to the poor observational constraint for these areas and to considerable differences in the modelled transport, especially inter-hemispheric exchange rates and tropical convective mixing. Estimates of the seasonal cycle in N2O emissions are also sensitive to errors in modelled stratosphere-to-troposphere transport in the tropics and southern extratropics. Overall, the results show a convergence in the global and regional emissions compared to previous independent studies

Integrating law, technology, and design : teaching data protection and privacy law in a digital age

Key Points The data protection lawyer of the future will be a key intermediary of innovation—or ‘transaction engineer’—who facilitates and coordinates new forms of business and other social relationships in rapidly evolving multi-disciplinary settings. The effective performance of this function requires legal professionals to develop a different mindset, along with new skills and capacities, specifically a better understanding of the underlying technologies and the value and techniques of legal design, as well as a knowledge of relevant data protection law. Transferable principles for teaching data protection law and privacy law in a digital age are identified. The article proposes a task-oriented, gamified, and sandbox approach to data protection education that delivers a more relevant student experience that cultivates meaningful capacities and skills that are more closely aligned with the needs and values of a digital age.©The Author(s) 2022. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.fi=vertaisarvioitu|en=peerReviewed

MX100, a new Escherichia coli tester strain for use in genotoxicity studies

The development of a new Escherichia coli tester strain for use in metabolic and mechanistic studies of genotoxins, strain MR2101/pKR11, has recently been reported. This strain, a derivative of the E.coli K12 laboratory strain AB1157, has sensitivity towards the detection of base-substitution mutagenesis, monitored by the reversion of arginine auxotrophy [argE3, (ochre)]. Besides arginine, MR2101/pKR11 is auxotrophic for histidine (hisG4), leucine (leuB6), proline (ΔproA) and threonine (thr-1). MX100 was developed to overcome the auxotrophy for four amino acids of MR2101/pKR11 which are non-essential for the mutagenic responsiveness of the strain. We restored the biosynthesis for these four amino acids in MR2101/pKR11, resulting in strain MX100. This strain showed an almost 2-fold increase in mutagenic activity relative to MR2101/pKR11 with a set of diagnostic mutagens (aflatoxin B1, benzo[α]pyrene, 4-nitroquinoline-1-oxide, 2,7-dimethyl-benz[a]anthracene and others) and was further characterized with other types of mutagens in which it showed sensitivity towards the detection of oxidative (H2O2, t-butyl-hydroperoxide, cumene-hydroperoxide, KO2) and carbonyl mutagens (methylglyoxal, malondialdehyde). As MX100 seems to have the right characteristics of a versatile genotoxicity tester strain and due to the extensive genetic and physiological knowledge of E.coli K12 in general and AB1157 in particular, we propose that MX100 could serve as mother strain for the development of specialized tester strains, of interest in studies of metabolism and/or mechanism of action of genotoxic carcinogens.publishersversionpublishe