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

RETRACTED ARTICLE: The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination

Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds the RAG1 promoter and Erag enhancer to activate RAG1 and RAG2 transcription in pre-B cells. We employed BCL11A overexpression with recombination substrates in a cultured pre-B cell line as well as Cre recombinase-mediated Bcl11a(lox/lox) deletion in explanted murine pre-B cells to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination

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

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G1-phase lymphocytes

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G(1)-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G(1)-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G(1)-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G(1)-phase cells and suggest that there may be species-specific features to this activity

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

Clinical characteristics of vulnerable populations hospitalized and diagnosed with COVID-19 in Buenos Aires, Argentina

There is not in Argentina publications regarding the presentation of patients with COVID-19 requiring hospitalized and emergency care in vulnerable populations (lower incomes and less education tend at greater risk for poor health status and healthcare access), and it has few reports in developing countries. The objective is to determine whether in the care of vulnerable patients, to succeed against COVID-19, multiple public health tools and interventions will be needed to minimize morbidity and mortality. The study is a prospective cohort investigation of patients with lab-confirmed COVID-19, who required to any of the Health Centers response from April 8, 2020, to August 18, 2020. In Buenos Aires Metropolitan Area (AMBA), April 8, 2020 the virus was identified in patients hospitalized in the "Southeast Network" (SN), AMBA. SN covering an area of 661 square kilometers, with 1.8 million inhabitants residing in urban, and rural areas. A total of 14 health centers with different levels of care complexity provide care to patients in the region. The information of each patient with COVID-19 evaluated by SN, was incorporated in an Epidemiological Dashboard. The investigation was designed and reported with consideration of observational studies in epidemiology. We describe the hospitals presentation and care of persons who required SN response and were ultimately diagnosed with COVID-19. From April 8, 2020, to August 18, 2020, were included 1495 patients with lab-confirmed COVID-19 in SN. A total of 58% patients were men, and the mean age (SD) was 48.9 (15.59) years. Eighty one percent patients with pre-existing diseases, most frequent hypertension and diabetes, but hypertension, chronic lung disease, and cardiovascular disease presented higher risk. A total of 13% were hospitalized in Intensive Therapy Unit. The mortality of the cohort was 9.77%. Mortality was higher for patients aged 65 or more (OR 5.09), and for those had some pre-existing disease (OR 2.61). Our observations are consistent with reports demonstrating older persons, and those with comorbidities have the highest risk of mortality related to COVID-19. However, unlike other reports from developed or some developing countries, the mortality in our study is lower. This finding may be related to age of our cohort is younger than other published. Also, the health system was able to respond to the demand.Fil: Yacobitti, A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Otero, L.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Doldan Arrubarrena, V.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Arano, J.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Lage, S.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Silberman, M.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Zubieta, M.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Erbetta, I.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Danei, P.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Baeck, G.. Hospital Mi Pueblo; ArgentinaFil: Vallejos, V.. No especifíca;Fil: Cavalli, F.. No especifíca;Fil: Calderón, N.. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Di Gregorio, M.. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Hernandez, V.. Hospital Dr. Arturo Oñativia - Salta Capital.; ArgentinaFil: Bruno, D.. Hospital Dr. Arturo Oñativia - Salta Capital.; ArgentinaFil: Rodera, B.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Macherett, I.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Parisi, M.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Gallastegui, M.. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Paz, A.. Municipalidad de Quilmes (buenos Aires). Hospital Sub Zonal Materno Infantil Doctor Eduardo Oller.; ArgentinaFil: Bernardi, R.. No especifíca;Fil: Azcárate, S.. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Hraste, A.. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Caridi, Délida Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Boechi, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Salgado, P.. Universidad de Buenos Aires. Rectorado. Instituto de Investigaciones en Salud Pública; ArgentinaFil: Kochen, Sara Silvia. Gobierno de la Provincia de Buenos Aires. Hospital de Alta Complejidad Cuenca Alta Doctor Nestor Carlos Kirchner.; Argentina. Universidad Nacional Arturo Jauretche; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

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