The Effect of Mutators on Adaptability in Time-Varying Fitness Landscapes

This Letter studies the quasispecies dynamics of a population capable of genetic repair evolving on a time-dependent fitness landscape. We develop a model that considers an asexual population of single-stranded, conservatively replicating genomes, whose only source of genetic variation is due to copying errors during replication. We consider a time-dependent, single-fitness-peak landscape where the master sequence changes by a single point mutation every time $\tau$. We are able to analytically solve for the evolutionary dynamics of the population in the point-mutation limit. In particular, our model provides an analytical expression for the fraction of mutators in the dynamic fitness landscape that agrees well with results from stochastic simulations.Comment: 4 pages, 3 figure

ATC Trajectory Reconstruction for Automated Evaluation of Sensor and Tracker Performance

Currently most air traffic controller decisions are based on the information provided by the ground support tools provided by automation systems, based on a network of surveillance sensors and the associated tracker. To guarantee surveillance integrity, it is clear that performance assessments of the different elements of the surveillance system are necessary. Due to the evolution suffered by the surveillance processing chain in the recent past, its complexity has been increased by the integration of new sensor types (e.g., automatic dependent surveillance-broadcast [ADS-B], Mode S radars, and wide area multilateration [WAM]), data link applications, and networking technologies. With new sensors, there is a need for system-level performance evaluations as well as methods for establishing assessment at each component of the tracking evaluation.This work was funded by contract EUROCONTROL’s TRES, by the Spanish Ministry of Economy and Competitiveness under grants CICYT TEC2008-06732/TEC and CYCIT TEC2011-28626, and by the Government of Madrid under grant S2009/TIC-1485 (CONTEXTS).Publicad

TRES: Multiradar-Multisensor Data Processing assessment using Opportunity Traffic

In this paper we describe a new tool being currently developed by Eurocontrol for Air Traffic Control multiradarmultisensor data processing systems assessment. This tool, called TRES (Trajectory Reconstruction and Evaluation Suite), will become in a near future a replacement for some parts of current versions of SASS-C (Surveillance Analysis Support System for Centres) suite. The paper describes the overall architecture of the assessment system, and details the methods used in TRES for the calculation of reference trajectories, taking into account sensor detection characteristics, available information, sensor accuracies, biases, ... The whole system has been tested with real traffic and simulated data, some illustrative examples are presented at the end

Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice

Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators

Urban land planning: The role of a Master Plan in influencing local temperatures

Land use planning (LUP) is central for managing issues related to climatic variation in urban environments. However, Master Plans (MPs) usually do not include climatic aspects, and few studies have addressed climate change at the urban scale, especially in developing countries. This paper proposes a framework with ten categories for assessment of climatic variation in urban LUP. Each category comprises attributes that describe a complex of relationships in influencing local temperature variations. They are analyzed for the case of the Master Plan of Porto Alegre (MPPA), the Southernmost metropolis of Brazil. It is concluded that the MPPA is strongly grounded in climate-related land and zoning coordination, but exhibits weaknesses in building, cartographical and social aspects considered synergistically relevant for tackling problems related to urban climate variation. Furthermore, the MPPA does not contain provisions related to monitoring of local climate and greenhouse gases (GHG) emissions and it is ineffective for improving energy efficiency. Specific MPPA failures stemming from these weaknesses include: an increase of 21.79% in the city's urbanized area from 1986 to 2011 to accommodate a similar increase in population, with significant horizontal sprawl; average temperature rise of 0.392. °C from 1991-2000 to 2001-2010, with statistically significant increases in temperature found since 1931; significant vehicle traffic increases, especially since 2007. From these findings, it is possible to conclude that the MPPA does not offer answers to all the imbalances related to land use, and therefore gives insufficient support to tackle the issue of rising temperatures

Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer

Targeted Inhibition of CYP11A1 in Prostate CancerIn this single-arm, multicenter, combined phase 1 and phase 2 study, patients with metastatic prostate adenocarcinoma with progression on prior androgen receptor pathway inhibitors and taxane-based chemotherapy were treated with ODM-208. A decrease in prostate-specific antigen levels of 50% or more occurred in 16/42 (38.1%) and 24/45 (53.3%) in phase 1 and 2 respectively. Responses mainly occurred in patients with androgen receptor mutations. Adrenal insufficiency was the dose-limiting toxicity.</p

Human metabolic profiles are stably controlled by genetic and environmental variation

A comprehensive variation map of the human metabolome identifies genetic and stable-environmental sources as major drivers of metabolite concentrations. The data suggest that sample sizes of a few thousand are sufficient to detect metabolite biomarkers predictive of disease