Deleterious synonymous mutations hitchhike to high frequency in HIV-1 env evolution

Intrapatient HIV-1 evolution is dominated by selection on the protein level in the arms race with the adaptive immune system. When cytotoxic CD8+ T-cells or neutralizing antibodies target a new epitope, the virus often escapes via nonsynonymous mutations that impair recognition. Synonymous mutations do not affect this interplay and are often assumed to be neutral. We analyze longitudinal intrapatient data from the C2-V5 part of the envelope gene (env) and observe that synonymous derived alleles rarely fix even though they often reach high frequencies in the viral population. We find that synonymous mutations that disrupt base pairs in RNA stems flanking the variable loops of gp120 are more likely to be lost than other synonymous changes, hinting at a direct fitness effect of these stem-loop structures in the HIV-1 RNA. Computational modeling indicates that these synonymous mutations have a (Malthusian) selection coefficient of the order of -0.002 and that they are brought up to high frequency by hitchhiking on neighboring beneficial nonsynonymous alleles. The patterns of fixation of nonsynonymous mutations estimated from the longitudinal data and comparisons with computer models suggest that escape mutations in C2-V5 are only transiently beneficial, either because the immune system is catching up or because of competition between equivalent escapes

FFPopSim: An efficient forward simulation package for the evolution of large populations

The analysis of the evolutionary dynamics of a population with many polymorphic loci is challenging since a large number of possible genotypes needs to be tracked. In the absence of analytical solutions, forward computer simulations are an important tool in multi-locus population genetics. The run time of standard algorithms to simulate sexual populations increases as 8^L with the number L of loci, or with the square of the population size N. We have developed algorithms that allow to simulate large populations with a run-time that scales as 3^L. The algorithm is based on an analog of the Fast-Fourier Transform (FFT) and allows for arbitrary fitness functions (i.e. any epistasis) and genetic maps. The algorithm is implemented as a collection of C++ classes and a Python interface.Comment: available from: http://code.google.com/p/ffpopsi

On the expansion of finance and financialisation

In this paper we explore the role of finance in the recent crisis noting that its expansion, in a context of deregulation and globalisation, has boosted financial profits and capital accumulation, but at the cost of a growing systemic instability both in the leading capitalist economy, i.e. the USA, and at the international level. The expansion of finance tends to emerge in certain phases of capitalist development, in particular during periods of countries’ decline. At the same time, each phase has its peculiar aspects and, referring to the recent evolution, we focus on the phenomenon of financialisation, intended as an increasing involvement of economic agents in the working of financial markets.deregulation; renationalisation; capitalist accumulation; instability; inequality

A quasilinear differential inclusion for viscous and rate-independent damage systems in non-smooth domains

This paper focuses on rate-independent damage in elastic bodies. Since the driving energy is nonconvex, solutions may have jumps as a function of time, and in this situation it is known that the classical concept of energetic solutions for rate-independent systems may fail to accurately describe the behavior of the system at jumps. Therefore we resort to the (by now well-established) vanishing viscosity approach to rate-independent modeling, and approximate the model by its viscous regularization. In fact, the analysis of the latter PDE system presents remarkable difficulties, due to its highly nonlinear character. We tackle it by combining a variational approach to a class of abstract doubly nonlinear evolution equations, with careful regularity estimates tailored to this specific system, relying on a q-Laplacian type gradient regularization of the damage variable. Hence for the viscous problem we conclude the existence of weak solutions, satisfying a suitable energy-dissipation inequality that is the starting point for the vanishing viscosity analysis. The latter leads to the notion of (weak) parameterized solution to our rate-independent system, which encompasses the influence of viscosity in the description of the jump regime

Did Producer Hedging Opportunities in the Live Hog Contract Decline?

The paper assesses the usefulness of selective hedging strategies when combined with forecast techniques in the live hog contract. The use of routine futures and options hedging is not attractive relative to a cash-only strategy. However, forecasting and hedging can contribute to price risk management improvement for risk-averse producers. Consistent with previous research, the results indicate that the live hog contract continues to offer producers attractive pricing opportunities. The findings suggests that the success of the new lean value carcass contract may depend on its ability to attract trading volume from outside the traditional production sector.hedging, forecasting, risk management, live hog futures, lean hog futures