Clonal Interference, Multiple Mutations, and Adaptation in Large Asexual Populations

Two important problems affect the ability of asexual populations to accumulate beneficial mutations, and hence to adapt. First, clonal interference causes some beneficial mutations to be outcompeted by more-fit mutations which occur in the same genetic background. Second, multiple mutations occur in some individuals, so even mutations of large effect can be outcompeted unless they occur in a good genetic background which contains other beneficial mutations. In this paper, we use a Monte Carlo simulation to study how these two factors influence the adaptation of asexual populations. We find that the results depend qualitatively on the shape of the distribution of the effects of possible beneficial mutations. When this distribution falls off slower than exponentially, clonal interference alone reasonably describes which mutations dominate the adaptation, although it gives a misleading picture of the evolutionary dynamics. When the distribution falls off faster than exponentially, an analysis based on multiple mutations is more appropriate. Using our simulations, we are able to explore the limits of validity of both of these approaches, and we explore the complex dynamics in the regimes where neither are fully applicable.Comment: 24 pages, 5 figure

Electron transport properties of sub-3-nm diameter copper nanowires

Density functional theory and density functional tight-binding are applied to model electron transport in copper nanowires of approximately 1 nm and 3 nm diameters with varying crystal orientation and surface termination. The copper nanowires studied are found to be metallic irrespective of diameter, crystal orientation and/or surface termination. Electron transmission is highly dependent on crystal orientation and surface termination. Nanowires oriented along the [110] crystallographic axis consistently exhibit the highest electron transmission while surface oxidized nanowires show significantly reduced electron transmission compared to unterminated nanowires. Transmission per unit area is calculated in each case, for a given crystal orientation we find that this value decreases with diameter for unterminated nanowires but is largely unaffected by diameter in surface oxidized nanowires for the size regime considered. Transmission pathway plots show that transmission is larger at the surface of unterminated nanowires than inside the nanowire and that transmission at the nanowire surface is significantly reduced by surface oxidation. Finally, we present a simple model which explains the transport per unit area dependence on diameter based on transmission pathways results

Constraint fitting of experimental data with a jet quenching model embedded in a hydrodynamical bulk medium

21 pages, 11 eps figures. Experimental errors in figures 4-6 and minor misprints correctedInternational audienceWe present a global fit to single- and double-inclusive suppression data of high-p T particles in central Au+Au collisions at top RHIC energy. We also include in this analysis data on heavy quarks via their D and B meson semi-leptonic decays (i.e. non-photonic electrons). The analysis is based on the parton quenching weights for medium-induced gluon radiation computed in the BDMPS approximation then embedded in a hydrodynamical description of the bulk medium. Our results indicate that values of the transport coefficient more than four times larger than perturbative estimates are preferred by experimental data. This confirms previous calculations based on simpler implementations of the medium geometry or only the single-inclusive suppression. We also comment on the statistical compatibility of the heavy quark data within a radiative only energy loss scenario, and on the sensitivity of the results to nuclear modification of the parton distribution functions (PDFs) and to assumptions on the energy loss during times in the collision prior to the hydrodynamical behavior

Measurements of the Higgs boson inclusive and differential fiducial cross-sections in the diphoton decay channel with pp collisions at √s=13 TeV with the ATLAS detector

A measurement of inclusive and differential fiducial cross-sections for the production of the Higgs boson decaying into two photons is performed using 139 fb&minus;1 of proton-proton collision data recorded at = 13 TeV by the ATLAS experiment at the Large Hadron Collider. The inclusive cross-section times branching ratio, in a fiducial region closely matching the experimental selection, is measured to be 67 &plusmn; 6 fb, which is in agreement with the state-of-the-art Standard Model prediction of 64 &plusmn; 4 fb. Extrapolating this result to the full phase space and correcting for the branching ratio, the total cross-section for Higgs boson production is estimated to be 58 &plusmn; 6 pb. In addition, the cross-sections in four fiducial regions sensitive to various Higgs boson production modes and differential cross-sections as a function of either one or two of several observables are measured. All the measurements are found to be in agreement with the Standard Model predictions. The measured transverse momentum distribution of the Higgs boson is used as an indirect probe of the Yukawa coupling of the Higgs boson to the bottom and charm quarks. In addition, five differential cross-section measurements are used to constrain anomalous Higgs boson couplings to vector bosons in the Standard Model effective field theory framework.</p

Results from the Relativistic Heavy Ion Collider

We describe the current status of the heavy ion research program at the Relativistic Heavy Ion Collider (RHIC). The new suite of experiments and the collider energies have opened up new probes of the medium created in the collisions. Our review focuses on the experimental discoveries to date at RHIC and their interpretation in the light of our present theoretical understanding of the dynamics of relativistic heavy ion collisions and of the structure of strongly interacting matter at high energy density.Comment: 47 pages, 10 figures, submitted to Annual Review of Nuclear and Particle Science. The authors invite and appreciate feedback about possible errors and/or inconsistencies in the manuscrip

Demarcation of Sepsis-Induced Peripheral and Central Acidosis with pH (Low) Insertion Cycle Peptide

Acidosis is a key driver for many diseases, including cancer, sepsis, and stroke. The spatiotemporal dynamics of dysregulated pH across disease remain elusive, and current diagnostic strategies do not provide localization of pH alterations. We sought to explore if PET imaging using hydrophobic cyclic peptides that partition into the cellular membrane at low extracellular pH (denoted as pH [low] insertion cycles, or pHLIC) can permit accurate in vivo visualization of acidosis. Methods: Acid-sensitive cyclic peptide c[E4W5C] pHLIC was conjugated to bifunctional maleimide-NO2A and radiolabeled with 64Cu (half-life, 12.7 h). C57BL/6J mice were administered lipopolysaccharide (15 mg/kg) or saline (vehicle) and serially imaged with [64Cu]Cu-c[E4W5C] over 24 h. Ex vivo autoradiography was performed on resected brain slices and subsequently stained with cresyl violet to enable high-resolution spatial analysis of tracer accumulation. A non–pH-sensitive cell-penetrating control peptide (c[R4W5C]) was used to confirm specificity of [64Cu]Cu-c[E4W5C]. CD11b (macrophage/microglia) and TMEM119 (microglia) immunostaining was performed to correlate extent of neuroinflammation with [64Cu]Cu-c[E4W5C] PET signal. Results: [64Cu]Cu-c[E4W5C] radiochemical yield and purity were more than 95% and more than 99%, respectively, with molar activity of more than 0.925 MBq/nmol. Significantly increased [64Cu]Cu-c[E4W5C] uptake was observed in lipopolysaccharide-treated mice (vs. vehicle) within peripheral tissues, including blood, lungs, liver, and small intestines (P \u3c 0.001–0.05). Additionally, there was significantly increased [64Cu]Cu-c[E4W5C] uptake in the brains of lipopolysaccharide-treated animals. Autoradiography confirmed increased uptake in the cerebellum, cortex, hippocampus, striatum, and hypothalamus of lipopolysaccharide-treated mice (vs. vehicle). Immunohistochemical analysis revealed microglial or macrophage infiltration, suggesting activation in brain regions containing increased tracer uptake. [64Cu]Cu-c[R4W5C] demonstrated significantly reduced uptake in the brain and periphery of lipopolysaccharide mice compared with the acid-mediated [64Cu]Cu-c[E4W5C] tracer. Conclusion: Here, we demonstrate that a pH-sensitive PET tracer specifically detects acidosis in regions associated with sepsis-driven proinflammatory responses. This study suggests that [64Cu]Cu-pHLIC is a valuable tool to noninvasively assess acidosis associated with both central and peripheral innate immune activation

Quark-Gluon Plasma at RHIC and the LHC: Perfect Fluid too Perfect?

Relativistic heavy ion collisions have reached energies that enable the creation of a novel state of matter termed the quark-gluon plasma. Many observables point to a picture of the medium as rapidly equilibrating and expanding as a nearly inviscid fluid. In this article, we explore the evolution of experimental flow observables as a function of collision energy and attempt to reconcile the observed similarities across a broad energy regime in terms of the initial conditions and viscous hydrodynamics. If the initial spatial anisotropies are very similar for all collision energies from 39 GeV to 2.76 TeV, we find that viscous hydrodynamics might be consistent with the level of agreement for v2 of unidentified hadrons as a function of pT . However, we predict a strong collision energy dependence for the proton v2(pT). The results presented in this paper highlight the need for more systematic studies and a re-evaluation of previously stated sensitivities to the early time dynamics and properties of the medium.Comment: 11 pages, 9 figures, submitted to the New Journal of Physics focus issue "Strongly Correlated Quantum Fluids: From Ultracold Quantum Gases to QCD Plasmas

Le Forum, Vol. 43 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1099/thumbnail.jp

Agency, stewardship and the universal-family firm : a qualitative historical analysis

This paper introduces the idea of a non-kinship-based Universal-family firm, an organizational form we developed based on interpreting historical writings in their socio-economic context. We analyzed Luke’s gospel with an eye toward drawing implications for the stewardship-agency debate in the contemporary family business literature. Our paper makes contributions at two important levels. In addition to introducing and developing theory about the Universal-family firms, we also contribute to the methodological toolkit of family business scholars by providing a template for using historical documents to challenge, enhance and develop theory