Recombination is an important evolutionary force in bacteria, but it remains challenging to reconstruct the imports that occurred in the ancestry of a genomic sample. Here we present ClonalFrameML, ...which uses maximum likelihood inference to simultaneously detect recombination in bacterial genomes and account for it in phylogenetic reconstruction. ClonalFrameML can analyse hundreds of genomes in a matter of hours, and we demonstrate its usefulness on simulated and real datasets. We find evidence for recombination hotspots associated with mobile elements in Clostridium difficile ST6 and a previously undescribed 310kb chromosomal replacement in Staphylococcus aureus ST582. ClonalFrameML is freely available at http://clonalframeml.googlecode.com/.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Analysis of “big data” frequently involves statistical comparison of millions of competing hypotheses to discover hidden processes underlying observed patterns of data, for example, in the search for ...genetic determinants of disease in genome-wide association studies (GWAS). Controlling the familywise error rate (FWER) is considered the strongest protection against false positives but makes it difficult to reach the multiple testing-corrected significance threshold. Here, I introduce the harmonic mean p-value (HMP), which controls the FWER while greatly improving statistical power by combining dependent tests using generalized central limit theorem. I show that the HMP effortlessly combines information to detect statistically significant signals among groups of individually nonsignificant hypotheses in examples of a human GWAS for neuroticism and a joint human–pathogen GWAS for hepatitis C viral load. The HMP simultaneously tests all ways to group hypotheses, allowing the smallest groups of hypotheses that retain significance to be sought. The power of the HMP to detect significant hypothesis groups is greater than the power of the Benjamini–Hochberg procedure to detect significant hypotheses, although the latter only controls the weaker false discovery rate (FDR). The HMP has broad implications for the analysis of large datasets, because it enhances the potential for scientific discovery.
The ribosome is one of the main antibiotic targets in the bacterial cell. Crystal structures of naturally produced antibiotics and their semi-synthetic derivatives bound to ribosomal particles have ...provided unparalleled insight into their mechanisms of action, and they are also facilitating the design of more effective antibiotics for targeting multidrug-resistant bacteria. In this Review, I discuss the recent structural insights into the mechanism of action of ribosome-targeting antibiotics and the molecular mechanisms of bacterial resistance, in addition to the approaches that are being pursued for the production of improved drugs that inhibit bacterial protein synthesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We quantify how sensitive is migration by star scientists to changes in personal and business tax differentials across states. We uncover large, stable, and precisely estimated effects of personal ...and corporate taxes on star scientists' migration patterns. The long-run elasticity of mobility relative to taxes is 1.8 for personal income taxes, 1.9 for state corporate income tax, and — 1.7 for the investment tax credit. While there are many other factors that drive when innovative individuals and innovative companies decide to locate, there are enough firms and workers on the margin that state taxes matter.
Phosphagallenes (1 a/1 b) featuring double bonds between phosphorus and gallium were synthesized by reaction of (phosphanyl)phosphaketenes with the gallium carbenoid Ga(Nacnac) ...(Nacnac=HCC(Me)N(2,6‐i‐Pr2C6H3)2). The stability of these species is dependent on the saturation of the phosphanyl moiety. 1 a, which bears an unsaturated phosphanyl ring, rearranges in solution to yield a spirocyclic compound (2) which contains a P=P bond. The saturated variant 1 b is stable even at elevated temperatures. 1 b behaves as a frustrated Lewis pair capable of activation of H2 and forms a 1:1 adduct with CO2.
We describe the synthesis of compounds exhibiting gallium–phosphorus double bonds. The stability of these species is dependent on the saturation of the phosphanyl moiety, and the saturated variant behaves as a frustrated Lewis pair that is capable of activating H2 and forms a 1:1 adduct with CO2.
The incidence of osteoporotic pelvic fractures in elderly patient is rising. This brings an increasing burden on health and social care systems as these injuries often lead to prolonged hospital ...admissions, loss of independence, morbidity and mortality. Some centres now advocate stabilisation of these injuries to reduce pain, facilitate early mobilisation, decrease hospital stay and restore independence. A systematic review of the literature was planned to establish the evidence for this intervention.
A systematic review was performed according to PRISMA guidelines. A clinical librarian performed a search of the following databases: NHS Evidence, TRIP, the Cochrane Database of Systematic Reviews, MEDLINE and EMBASE. Seventeen eligible studies were identified with 766 patients.
The quality of evidence was poor with no good quality randomised trials. The majority of injuries were minimally displaced. Posterior ring injuries were most often stabilised with percutaneous screws which were sometimes augmented with void filler. A number of techniques were described for stabilisation of the anterior ring although fixation of the anterior ring was frequently not performed. There was consistent evidence from the included studies that operative intervention significantly improved pain. Complications were minimal but there were increased failure rates when a single unaugmented sacroiliac joint screw was used. The limited availability of non-operative comparators made it difficult to draw firm conclusions about the efficacy of surgical over non-surgical management in these patients.
Operative management of fragility fractures of the pelvis should be considered for patients failing a brief period of non-operative management, however prospective randomised trials need to be performed to provide improved evidence for this intervention. Surgeons should consider which fixation techniques for fragility fractures of the pelvis are robust enough to allow immediate weightbearing, whilst minimising operative morbidity and post-operative complications. PROSPERO Systematic Review ID: CRD42020171237.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Measuring news sentiment Shapiro, Adam Hale; Sudhof, Moritz; Wilson, Daniel J.
Journal of econometrics,
06/2022, Letnik:
228, Številka:
2
Journal Article
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This paper demonstrates state-of-the-art text sentiment analysis tools while developing a new time-series measure of economic sentiment derived from economic and financial newspaper articles from ...January 1980 to April 2015. We compare the predictive accuracy of a large set of sentiment analysis models using a sample of articles that have been rated by humans on a positivity/negativity scale. The results highlight the gains from combining existing lexicons and from accounting for negation. We also generate our own sentiment-scoring model, which includes a new lexicon built specifically to capture the sentiment in economic news articles. This model is shown to have better predictive accuracy than existing “off-the-shelf” models. Lastly, we provide two applications to the economic research on sentiment. First, we show that daily news sentiment is predictive of movements of survey-based measures of consumer sentiment. Second, motivated by Barsky and Sims (2012), we estimate the impulse responses of macroeconomic variables to sentiment shocks, finding that positive sentiment shocks increase consumption, output, and interest rates and dampen inflation.
Generation time varies widely across organisms and is an important factor in the life cycle, life history and evolution of organisms. Although the doubling time (DT) has been estimated for many ...bacteria in the laboratory, it is nearly impossible to directly measure it in the natural environment. However, an estimate can be obtained by measuring the rate at which bacteria accumulate mutations per year in the wild and the rate at which they mutate per generation in the laboratory. If we assume the mutation rate per generation is the same in the wild and in the laboratory, and that all mutations in the wild are neutral, an assumption that we show is not very important, then an estimate of the DT can be obtained by dividing the latter by the former. We estimate the DT for five species of bacteria for which we have both an accumulation and a mutation rate estimate. We also infer the distribution of DTs across all bacteria from the distribution of the accumulation and mutation rates. Both analyses suggest that DTs for bacteria in the wild are substantially greater than those in the laboratory, that they vary by orders of magnitude between different species of bacteria and that a substantial fraction of bacteria double very slowly in the wild.
The proliferation of R&D tax incentives among U.S. states in recent decades raises two questions: (i) Are these tax incentives effective in increasing in-state R&D? (ii) How much of any increase is ...due to R&D being drawn away from other states? This paper answers (i) "yes" and (ii) "nearly all." The paper estimates an augmented R&D factor demand model using state panel data from 1981 to 2004. I estimate that the long-run elasticity of in-state R&D with respect to the in-state user cost is about -2.5, while its elasticity with respect to out-of-state user costs is about +2.5, suggesting a zero-sum game among states.
•Nascent polypeptides within the ribosomal tunnel can stall translation.•Peptide mediated ribosome stalling is used to regulate translation.•Cryo-EM structures of stalled ribosomes reveal common and ...distincts mechanisms.
As the nascent polypeptide chain is being synthesized, it passes through a tunnel within the large ribosomal subunit. Interaction between the nascent polypeptide chain and the ribosomal tunnel can modulate the translation rate and induce translational stalling to regulate gene expression. In this article, we highlight recent structural insights into how the nascent polypeptide chain, either alone or in cooperation with co-factors, can interact with components of the ribosomal tunnel to regulate translation via inactivating the peptidyltransferase center of the ribosome and inducing ribosome stalling.
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