Mutator Dynamics on a Smooth Evolutionary Landscape

We investigate a model of evolutionary dynamics on a smooth landscape which features a ``mutator'' allele whose effect is to increase the mutation rate. We show that the expected proportion of mutators far from equilibrium, when the fitness is steadily increasing in time, is governed solely by the transition rates into and out of the mutator state. This results is a much faster rate of fitness increase than would be the case without the mutator allele. Near the fitness equilibrium, however, the mutators are severely suppressed, due to the detrimental effects of a large mutation rate near the fitness maximum. We discuss the results of a recent experiment on natural selection of E. coli in the light of our model.Comment: 4 pages, 3 figure

Vector bundles on the projective line and finite domination of chain complexes

Finitely dominated chain complexes over a Laurent polynomial ring in one indeterminate are characterised by vanishing of their Novikov homology. We present an algebro-geometric approach to this result, based on extension of chain complexes to sheaves on the projective line. We also discuss the K-theoretical obstruction to extension.Comment: v1: 11 page

Influence of Hybridization on the Properties of the Spinless Falicov-Kimball Model

Without a hybridization between the localized f- and the conduction (c-) electron states the spinless Falicov-Kimball model (FKM) is exactly solvable in the limit of high spatial dimension, as first shown by Brandt and Mielsch. Here I show that at least for sufficiently small c-f-interaction this exact inhomogeneous ground state is also obtained in Hartree-Fock approximation. With hybridization the model is no longer exactly solvable, but the approximation yields that the inhomogeneous charge-density wave (CDW) ground state remains stable also for finite hybridization V smaller than a critical hybridization V_c, above which no inhomogeneous CDW solution but only a homogeneous solution is obtained. The spinless FKM does not allow for a ''ferroelectric'' ground state with a spontaneous polarization, i.e. there is no nonvanishing $$-expectation value in the limit of vanishing hybridization.Comment: 7 pages, 6 figure

Critical Innovations in the UK Peer-to-Peer (P2P) and Equity Alternative Finance Markets for Small Firm Growth

© The Author(s) 2016. The final, definitive version of this paper has been published in The International Journal of Entrepreneurship and Innovation by Sage Publications Ltd. All rights reserved. It is available at: https://doi.org/10.1177/1465750316655906This paper examines the disruptive nature of financial innovations available to small firms by the growing range of online platforms that have emerged in the UK since the financial crisis. It is unveiled that finance provided to small firms via such mechanisms is not identical to more traditional sources and its adoption therefore cannot be said to be simply a question of direct substitution based, for example, on a price comparison. These offer a series of important advantages over more traditional sources of early-stage capital for entrepreneurs seeking funding. Service innovations around security, flexibility of terms, speed of access and transparency of pricing are as important as price considerations for many users, as are innovations made possible by the way these online markets are structured and in particular in the way these innovative structures allow important types of risk to be dispersed and mitigated.Peer reviewedFinal Accepted Versio

EGIA–evolutionary optimisation of gene regulatory networks, an integrative approach

Quantitative modelling of gene regulatory networks (GRNs) is still limited by data issues such as noise and the restricted length of available time series, creating an under-determination problem. However, large amounts of other types of biological data and knowledge are available, such as knockout experiments, annotations and so on, and it has been postulated that integration of these can improve model quality. However, integration has not been fully explored, to date. Here, we present a novel integrative framework for different types of data that aims to enhance model inference. This is based on evolutionary computation and uses different types of knowledge to introduce a novel customised initialisation and mutation operator and complex evaluation criteria, used to distinguish between candidate models. Specifically, the algorithm uses information from (i) knockout experiments, (ii) annotations of transcription factors, (iii) binding site motifs (expressed as position weight matrices) and (iv) DNA sequence of gene promoters, to drive the algorithm towards more plausible network structures. Further, the evaluation basis is also extended to include structure information included in these additional data. This framework is applied to both synthetic and real gene expression data. Models obtained by data integration display both quantitative and qualitative improvement

Pedestrian, Crowd, and Evacuation Dynamics

This contribution describes efforts to model the behavior of individual pedestrians and their interactions in crowds, which generate certain kinds of self-organized patterns of motion. Moreover, this article focusses on the dynamics of crowds in panic or evacuation situations, methods to optimize building designs for egress, and factors potentially causing the breakdown of orderly motion.Comment: This is a review paper. For related work see http://www.soms.ethz.c

W18O49 Nanowires as Ultraviolet Photodetector

Photodetectors in a configuration of field effect transistor were fabricated based on individual W18O49 nanowires. Evaluation of electrical transport behavior indicates that the W18O49 nanowires are n-type semiconductors. The photodetectors show high sensitivity, stability and reversibility to ultraviolet (UV) light. A high photoconductive gain of 104 was obtained, and the photoconductivity is up to 60 nS upon exposure to 312 nm UV light with an intensity of 1.6 mW/cm2. Absorption of oxygen on the surface of W18O49 nanowires has a significant influence on the dark conductivity, and the ambient gas can remarkably change the conductivity of W18O49 nanowire. The results imply that W18O49 nanowires will be promising candidates for fabricating UV photodetectors

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis

Background & Aims Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC’s anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis. Methods Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC’s antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH) and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses. Results CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05). At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05), and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls). CVC treatment had no notable effect on body or liver/kidney weight. Conclusions CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC’s antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475)

Neural Mechanisms of Human Perceptual Learning: Electrophysiological Evidence for a Two-Stage Process

Artículo de publicación ISIBackground: Humans and other animals change the way they perceive the world due to experience. This process has been labeled as perceptual learning, and implies that adult nervous systems can adaptively modify the way in which they process sensory stimulation. However, the mechanisms by which the brain modifies this capacity have not been sufficiently analyzed. Methodology/Principal Findings: We studied the neural mechanisms of human perceptual learning by combining electroencephalographic (EEG) recordings of brain activity and the assessment of psychophysical performance during training in a visual search task. All participants improved their perceptual performance as reflected by an increase in sensitivity (d') and a decrease in reaction time. The EEG signal was acquired throughout the entire experiment revealing amplitude increments, specific and unspecific to the trained stimulus, in event-related potential (ERP) components N2pc and P3 respectively. P3 unspecific modification can be related to context or task-based learning, while N2pc may be reflecting a more specific attentional-related boosting of target detection. Moreover, bell and U-shaped profiles of oscillatory brain activity in gamma (30-60 Hz) and alpha (8-14 Hz) frequency bands may suggest the existence of two phases for learning acquisition, which can be understood as distinctive optimization mechanisms in stimulus processing.This research was supported by CONICYT doctoral grant to C.M.H. and by an ECOS-Sud/CONICYT grant C08S02 and FONDECYT 1090612 grant to D.C. and F.A