2,548 research outputs found
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
Using argumentation theory to identify the challenges of shared decision-making when the doctor and the patient have a difference of opinion
This paper aims to identify the challenges in the implementation of shared decision-making (SDM) when the doctor and the patient have a difference of opinion. It analyses the preconditions of the resolution of this difference of opinion by using an analytical and normative framework known in the field of argumentation theory as the ideal model of critical discussion. This analysis highlights the communication skills and attitudes that both doctors and patients must apply in a dispute resolution-oriented communication. Questions arise over the methods of empowerment of doctors and patients in these skills and attitudes as the preconditions of SDM. Overall, the paper highlights aspects in which research is needed to design appropriate programmes of training, education and support in order to equip doctors and patients with the means to successfully engage in shared decision-making
A multidisciplinary approach to evaluate the effectiveness of natural attenuation at a contaminated site
This study evaluates the natural attenuation of chlorinated hydrocarbons as remediation action in a contaminated site downtown the city of Parma (Italy). To achieve this goal, a combination of new investigation methods (bio-molecular analysis, compound specific isotope analysis, phytoscreening) has been proposed. The approach (named circular multi step) allows to: fully understand the phenomena that occur at the study site, design new investigation activities, and manage best practices. Consequently, each step of the approach improves the conceptual and numerical models with new knowledge. The activities carried out at the study site allowed to detect a contamination of perchloroethylene in a large part of the city of Parma and, of main importance, underneath a kindergarten. The results of the study did not show significant natural attenuation of chlorinated hydrocarbons and that the detected contamination could refer to the same unknown contaminant source. Furthermore, the innovative phytoscreening technique was applied to assess the presence of chlorinated hydrocarbons at the ground level. The plume spread was estimated through numerical modeling starting from potential contaminant sources. This study enhances the knowledge of groundwater flow and contamination in Parma and allows authorities to design new investigation/reclamation activities through management actions
Identification of groundwater contaminant source characteristics through artificial neural network
Erosive Wear Behavior of High-Chromium Cast Iron: Combined Effect of Erodent Powders and Destabilization Heat Treatments
High-chromium cast irons are frequently used in high-demanding applications, where low production costs and wear performance are key factors. The excellent abrasive resistance of these alloys results from the overall microstructural features, i.e., type, morphology, and distribution of hard primary and secondary carbides, along with the matrix constituents. Such a microstructure is the result of the chemical composition and solidification process, even though it could be further tuned by heat treatments. These latter are usually performed to destabilize the austenite and to induce the precipitation of secondary carbides. The present study investigates the combined effect of destabilization heat treatment route and erodent powder type on the erosive wear behavior of two commercial hypereutectic white cast irons. The as-received and the heat-treated materials were analyzed through optical and scanning electron microscopy, hardness tests, and X-ray diffraction to determine the relationship between microstructural variations and applied heat treatment. The erosive resistance was evaluated per the ASTM G76 standard in a purpose-built air blast test rig. Experiments were performed considering a raw meal powder, commonly used in cement factories, and Al2O3 as erodent powders. The adopted heat treatments were effective in increasing the overall hardness of the material, but this was not directly related to the erosion resistance. By contrast, the relative hardness ratio, i.e., erodent/target hardness, affects the erosion rate and different behaviors in relation to the softer/harder erodent particles were found
Milking procedures and milk ejection in Italian Brown cows
The aim of the study was to describe, on the basis of field data, the traits of milk flow curves of Italian Brown cows and to investigate some sources of variation. A total of 1,450 milk flow curves of the whole udder were collected in 81 Italian Brown dairy herds in Lombardy, Italy, using electronic mobile milk flow meters. Parity order and days in milk affected most milk flow traits. Milk flow curves showed some defects dependent on milking management practices: very long machine-on time, long duration of overmilking phase, high percentage of stripping and moderate percentage of bimodality
Parity Violation in Neutron Capture Reactions
In the last decade, the scattering of polarized neutrons on compound nucleus
resonances proved to be a powerful experimental technique for probing nuclear
parity violation. Longitudinal analyzing powers in neutron transmission
measurements on p-wave resonances in nuclei such as La and Th
were found to be as large as 10%. Here we examine the possibilities of carrying
out a parallel program to measure asymmetries in the ) reaction on
these same compound nuclear resonances. Symmetry-violating ) studies
can also show asymmetries as large as 10%, and have the advantage over
transmission experiments of allowing parity-odd asymmetries in several
different gamma-decay branches from the same resonance. Thus, studies of parity
violation in the reaction using high efficiency germanium
detectors at the Los Alamos Lujan facility, for example, could determine the
parity-odd nucleon-nucleon matrix elements in complex nuclei with high
accuracy. Additionally, simultaneous studies of the E1 and matrix
elements invol ved in these decays could be used to help constrain the
statistical theory of parity non-conservation in compound nuclei.Comment: 10 pages, 1 figur
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