464 research outputs found
Fluctuations of fitness distributions and the rate of Muller's ratchet
The accumulation of deleterious mutations is driven by rare fluctuations
which lead to the loss of all mutation free individuals, a process known as
Muller's ratchet. Even though Muller's ratchet is a paradigmatic process in
population genetics, a quantitative understanding of its rate is still lacking.
The difficulty lies in the nontrivial nature of fluctuations in the fitness
distribution which control the rate of extinction of the fittest genotype. We
address this problem using the simple but classic model of mutation selection
balance with deleterious mutations all having the same effect on fitness. We
show analytically how fluctuations among the fittest individuals propagate to
individuals of lower fitness and have a dramatically amplified effects on the
bulk of the population at a later time. If a reduction in the size of the
fittest class reduces the mean fitness only after a delay, selection opposing
this reduction is also delayed. This delayed restoring force speeds up Muller's
ratchet. We show how the delayed response can be accounted for using a path
integral formulation of the stochastic dynamics and provide an expression for
the rate of the ratchet that is accurate across a broad range of parameters.Comment: Genetics 201
Co-trimoxazole prophylaxis in HIV : the evidence
BibliographyHuman immunodeficiency virus (HIV) damages the body’s
immune system, making secondary (or opportunistic)
infections more common. Treatment and prevention of such
infections is integral to the management of patients with HIV
infection. Co-trimoxazole is a prophylactic treatment that has a
wide range of action against common bacteria, parasites, fungi
and yeasts. As part of a minimum care package, UNAIDS/
WHO recommends co-trimoxazole prophylaxis for HIVinfected
adults with symptomatic disease (WHO stage II, III
or IV), or asymptomatic individuals with CD4 counts ≤500
cells/ÎĽl, and for all HIV-positive pregnant women after the
first trimester.1 Co-trimoxazole is also recommended for use in
children with proven HIV infection and infants exposed to HIV
(from 4 - 6 weeks of age until infection with HIV is ruled out).2
The object of this report is to summarise the effects of
co-trimoxazole prophylaxis on morbidity and mortality among
HIV-infected individuals
Sharp transition towards shared vocabularies in multi-agent systems
What processes can explain how very large populations are able to converge on
the use of a particular word or grammatical construction without global
coordination? Answering this question helps to understand why new language
constructs usually propagate along an S-shaped curve with a rather sudden
transition towards global agreement. It also helps to analyze and design new
technologies that support or orchestrate self-organizing communication systems,
such as recent social tagging systems for the web. The article introduces and
studies a microscopic model of communicating autonomous agents performing
language games without any central control. We show that the system undergoes a
disorder/order transition, going trough a sharp symmetry breaking process to
reach a shared set of conventions. Before the transition, the system builds up
non-trivial scale-invariant correlations, for instance in the distribution of
competing synonyms, which display a Zipf-like law. These correlations make the
system ready for the transition towards shared conventions, which, observed on
the time-scale of collective behaviors, becomes sharper and sharper with system
size. This surprising result not only explains why human language can scale up
to very large populations but also suggests ways to optimize artificial
semiotic dynamics.Comment: 12 pages, 4 figure
Calibration of optimal execution of financial transactions in the presence of transient market impact
Trading large volumes of a financial asset in order driven markets requires
the use of algorithmic execution dividing the volume in many transactions in
order to minimize costs due to market impact. A proper design of an optimal
execution strategy strongly depends on a careful modeling of market impact,
i.e. how the price reacts to trades. In this paper we consider a recently
introduced market impact model (Bouchaud et al., 2004), which has the property
of describing both the volume and the temporal dependence of price change due
to trading. We show how this model can be used to describe price impact also in
aggregated trade time or in real time. We then solve analytically and calibrate
with real data the optimal execution problem both for risk neutral and for risk
averse investors and we derive an efficient frontier of optimal execution. When
we include spread costs the problem must be solved numerically and we show that
the introduction of such costs regularizes the solution.Comment: 31 pages, 8 figure
A variational method based on weighted graph states
In a recent article [Phys. Rev. Lett. 97 (2006), 107206], we have presented a
class of states which is suitable as a variational set to find ground states in
spin systems of arbitrary spatial dimension and with long-range entanglement.
Here, we continue the exposition of our technique, extend from spin 1/2 to
higher spins and use the boson Hubbard model as a non-trivial example to
demonstrate our scheme.Comment: 36 pages, 13 figure
Complementary methods for monitoring sugar beet aphids to improve risk management of virus yellows
Bistability in Apoptosis by Receptor Clustering
Apoptosis is a highly regulated cell death mechanism involved in many
physiological processes. A key component of extrinsically activated apoptosis
is the death receptor Fas, which, on binding to its cognate ligand FasL,
oligomerize to form the death-inducing signaling complex. Motivated by recent
experimental data, we propose a mathematical model of death ligand-receptor
dynamics where FasL acts as a clustering agent for Fas, which form locally
stable signaling platforms through proximity-induced receptor interactions.
Significantly, the model exhibits hysteresis, providing an upstream mechanism
for bistability and robustness. At low receptor concentrations, the bistability
is contingent on the trimerism of FasL. Moreover, irreversible bistability,
representing a committed cell death decision, emerges at high concentrations,
which may be achieved through receptor pre-association or localization onto
membrane lipid rafts. Thus, our model provides a novel theory for these
observed biological phenomena within the unified context of bistability.
Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our
model also suggests a mechanism by which cells may function as bistable
life/death switches independently of any such dynamics in their downstream
components. Our results highlight the role of death receptors in deciding cell
fate and add to the signal processing capabilities attributed to receptor
clustering.Comment: Accepted by PLoS Comput Bio
Colonyzer: automated quantification of micro-organism growth characteristics on solid agar
<p>Abstract</p> <p>Background</p> <p>High-throughput screens comparing growth rates of arrays of distinct micro-organism cultures on solid agar are useful, rapid methods of quantifying genetic interactions. Growth rate is an informative phenotype which can be estimated by measuring cell densities at one or more times after inoculation. Precise estimates can be made by inoculating cultures onto agar and capturing cell density frequently by plate-scanning or photography, especially throughout the exponential growth phase, and summarising growth with a simple dynamic model (e.g. the logistic growth model). In order to parametrize such a model, a robust image analysis tool capable of capturing a wide range of cell densities from plate photographs is required.</p> <p>Results</p> <p>Colonyzer is a collection of image analysis algorithms for automatic quantification of the size, granularity, colour and location of micro-organism cultures grown on solid agar. Colonyzer is uniquely sensitive to extremely low cell densities photographed after dilute liquid culture inoculation (spotting) due to image segmentation using a mixed Gaussian model for plate-wide thresholding based on pixel intensity. Colonyzer is robust to slight experimental imperfections and corrects for lighting gradients which would otherwise introduce spatial bias to cell density estimates without the need for imaging dummy plates. Colonyzer is general enough to quantify cultures growing in any rectangular array format, either growing after pinning with a dense inoculum or growing with the irregular morphology characteristic of spotted cultures. Colonyzer was developed using the open source packages: Python, RPy and the Python Imaging Library and its source code and documentation are available on SourceForge under GNU General Public License. Colonyzer is adaptable to suit specific requirements: e.g. automatic detection of cultures at irregular locations on streaked plates for robotic picking, or decreasing analysis time by disabling components such as lighting correction or colour measures.</p> <p>Conclusion</p> <p>Colonyzer can automatically quantify culture growth from large batches of captured images of microbial cultures grown during genome-wide scans over the wide range of cell densities observable after highly dilute liquid spot inoculation, as well as after more concentrated pinning inoculation. Colonyzer is open-source, allowing users to assess it, adapt it to particular research requirements and to contribute to its development.</p
Classical kinetic energy, quantum fluctuation terms and kinetic-energy functionals
We employ a recently formulated dequantization procedure to obtain an exact
expression for the kinetic energy which is applicable to all kinetic-energy
functionals. We express the kinetic energy of an N-electron system as the sum
of an N-electron classical kinetic energy and an N-electron purely quantum
kinetic energy arising from the quantum fluctuations that turn the classical
momentum into the quantum momentum. This leads to an interesting analogy with
Nelson's stochastic approach to quantum mechanics, which we use to conceptually
clarify the physical nature of part of the kinetic-energy functional in terms
of statistical fluctuations and in direct correspondence with Fisher
Information Theory. We show that the N-electron purely quantum kinetic energy
can be written as the sum of the (one-electron) Weizsacker term and an
(N-1)-electron kinetic correlation term. We further show that the Weizsacker
term results from local fluctuations while the kinetic correlation term results
from the nonlocal fluctuations. For one-electron orbitals (where kinetic
correlation is neglected) we obtain an exact (albeit impractical) expression
for the noninteracting kinetic energy as the sum of the classical kinetic
energy and the Weizsacker term. The classical kinetic energy is seen to be
explicitly dependent on the electron phase and this has implications for the
development of accurate orbital-free kinetic-energy functionals. Also, there is
a direct connection between the classical kinetic energy and the angular
momentum and, across a row of the periodic table, the classical kinetic energy
component of the noninteracting kinetic energy generally increases as Z
increases.Comment: 10 pages, 1 figure. To appear in Theor Chem Ac
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