A Driven Disordered Systems Approach to Biological Evolution in Changing Environments

Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organisms environment, and evolution in changing environments is still poorly understood. We study a particular model of antibiotic resistance evolution in bacteria where the antibiotic concentration is an environmental parameter and the fitness landscapes incorporate tradeoffs between adaptation to low and high antibiotic concentration. With evolutionary dynamics that follow fitness gradients, the evolution of the system under slowly changing antibiotic concentration resembles the athermal dynamics of disordered physical systems under external drives. Exploiting this resemblance, we show that our model can be described as a system with interacting hysteretic elements. As in the case of the driven disordered systems, adaptive evolution under antibiotic concentration cycling is found to exhibit hysteresis loops and memory formation. We derive a number of analytical results for quasistatic concentration changes. We also perform numerical simulations to study how these effects are modified under driving protocols in which the concentration is changed in discrete steps. Our approach provides a general framework for studying motifs of evolutionary dynamics in biological systems in a changing environment

Suppression of stimulated Brillouin scattering in optical fibers using a linearly chirped diode laser

The output of high power fiber amplifiers is typically limited by stimulated Brillouin scattering (SBS). An analysis of SBS with a chirped pump laser indicates that a chirp of 2.5 × 10^(15) Hz/s could raise, by an order of magnitude, the SBS threshold of a 20-m fiber. A diode laser with a constant output power and a linear chirp of 5 × 10^(15) Hz/s has been previously demonstrated. In a low-power proof-of-concept experiment, the threshold for SBS in a 6-km fiber is increased by a factor of 100 with a chirp of 5 × 10^(14) Hz/s. A linear chirp will enable straightforward coherent combination of multiple fiber amplifiers, with electronic compensation of path length differences on the order of 0.2 m

Quantum bath refrigeration towards absolute zero: unattainability principle challenged

A minimal model of a quantum refrigerator (QR), i.e. a periodically phase-flipped two-level system permanently coupled to a finite-capacity bath (cold bath) and an infinite heat dump (hot bath), is introduced and used to investigate the cooling of the cold bath towards the absolute zero (T=0). Remarkably, the temperature scaling of the cold-bath cooling rate reveals that it does not vanish as T->0 for certain realistic quantized baths, e.g. phonons in strongly disordered media (fractons) or quantized spin-waves in ferromagnets (magnons). This result challenges Nernst's third-law formulation known as the unattainability principle

Determining Pair Interactions from Structural Correlations

We examine metastable configurations of a two-dimensional system of interacting particles on a quenched random potential landscape and ask how the configurational pair correlation function is related to the particle interactions and the statistical properties of the potential landscape. Understanding this relation facilitates quantitative studies of magnetic flux line interactions in type II superconductors, using structural information available from Lorentz microscope images or Bitter decorations. Previous work by some of us supported the conjecture that the relationship between pair correlations and interactions in pinned flux line ensembles is analogous to the corresponding relationship in the theory of simple liquids. The present paper aims at a more thorough understanding of this relation. We report the results of numerical simulations and present a theory for the low density behavior of the pair correlation function which agrees well with our simulations and captures features observed in experiments. In particular, we find that the resulting description goes beyond the conjectured classical liquid type relation and we remark on the differences.Comment: 7 pages, 6 figures. See also http://rainbow.uchicago.edu/~grier

Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey

BACKGROUND: Biotinidase deficiency (BD) is an autosomal recessive inborn error of metabolism characterized by neurologic and cutaneous symptoms and can be detected by newborn screening. Newborn screening for BD was implemented in Turkey at the end of 2008. METHODS: In total, 203 patients who were identified among the infants detected by the newborn screening were later confirmed to have BD through measurement of serum biotinidase activity. We also performed BTD mutation analysis to characterize the genetic profile. RESULTS: Twenty-seven mutations were identified. The most commonly found variants were c.1330G>C (p.D444H), c.1595C>T (p.T532M), c.470G>A (p.R157H), and c.198_104delGCGGCTGinsTCC (p.C33Ffs ) with allele frequencies of 0.387, 0.175, 0.165 and 0.049, respectively. Three novel pathogenic and likely pathogenic variants were identified: p.W140* (c.419G>A), p.S319F (c.956C>T) and p.L69Hfs*24 (c.192_193insCATC). We also identified three mutations reported in just one patient in the past (p.V442Sfs*59 [c.1324delG], p.H447R [c.1340A>G] and p.198delV [c.592_594delGTC]). Although all of the patients were asymptomatic under the treatment of biotin, only one patient, who had the novel c.419G>A homozygous mutation became symptomatic during an episode of acute gastroenteritis with a presentation of ketosis and metabolic acidosis. Among the screened patients, 156 had partial and 47 had profound BD. CONCLUSIONS: We determined the mutation spectra of BD from the southeastern part of Turkey. The results of this study add three more mutations to the total number of mutations described as causing BD

Dynamics of Three Agent Games

We study the dynamics and resulting score distribution of three-agent games where after each competition a single agent wins and scores a point. A single competition is described by a triplet of numbers $p$, $t$ and $q$ denoting the probabilities that the team with the highest, middle or lowest accumulated score wins. We study the full family of solutions in the regime, where the number of agents and competitions is large, which can be regarded as a hydrodynamic limit. Depending on the parameter values $(p,q,t)$, we find six qualitatively different asymptotic score distributions and we also provide a qualitative understanding of these results. We checked our analytical results against numerical simulations of the microscopic model and find these to be in excellent agreement. The three agent game can be regarded as a social model where a player can be favored or disfavored for advancement, based on his/her accumulated score. It is also possible to decide the outcome of a three agent game through a mini tournament of two-a gent competitions among the participating players and it turns out that the resulting possible score distributions are a subset of those obtained for the general three agent-games. We discuss how one can add a steady and democratic decline rate to the model and present a simple geometric construction that allows one to write down the corresponding score evolution equations for $n$-agent games

The outcome of 41 Late-Diagnosed Turkish GA-1 Patients: A Candidate for the Turkish NBS

Background: Glutaric aciduria type 1(GA-1) is an inherited cerebral organic aciduria. Untreated patients with GA-1 have a risk of acute encephalopathic crises during the first 6 years of life. In so far as GA-1 desperately does not exist in Turkish newborn screening (NBS) program, most patients in our study were late-diagnosed. / Method: This study included 41 patients diagnosed with acylcarnitine profile, urinary organic acids, mutation analyses in the symptomatic period. We presented with clinical, neuroradiological, and molecular data of our 41 patients. / Results: The mean age at diagnosis was 14.8 13.9 (15 days to 72 months) and, high blood glutaconic acid, glutarylcarnitine and urinary glutaric acid (GA) levels in 41 patients were revealed. Seventeen different mutations in the glutaryl-CoA dehydrogenase gene were identified, five of which were novel. The patients, most of whom were late-diagnosed, had a poor neurological outcome. Treatment strategies made a little improvement in dystonia and the frequency of encephalopathic attacks. / Conclusion: All GA-1 patients in our study were severely affected since they were latediagnosed, while others show that GA-1 is a treatable metabolic disorder if it is diagnosed with NBS. This study provides an essential perspective of the severe impact on GA-1 patients unless it is diagnosed with NBS. We immediately advocate GA-1 to be included in the Turkish NBS

Analytical Solution of a Stochastic Content Based Network Model

We define and completely solve a content-based directed network whose nodes consist of random words and an adjacency rule involving perfect or approximate matches, for an alphabet with an arbitrary number of letters. The analytic expression for the out-degree distribution shows a crossover from a leading power law behavior to a log-periodic regime bounded by a different power law decay. The leading exponents in the two regions have a weak dependence on the mean word length, and an even weaker dependence on the alphabet size. The in-degree distribution, on the other hand, is much narrower and does not show scaling behavior. The results might be of interest for understanding the emergence of genomic interaction networks, which rely, to a large extent, on mechanisms based on sequence matching, and exhibit similar global features to those found here.Comment: 13 pages, 5 figures. Rewrote conclusions regarding the relevance to gene regulation networks, fixed minor errors and replaced fig. 4. Main body of paper (model and calculations) remains unchanged. Submitted for publicatio

String Matching and 1d Lattice Gases

We calculate the probability distributions for the number of occurrences $n$ of a given $l$ letter word in a random string of $k$ letters. Analytical expressions for the distribution are known for the asymptotic regimes (i) $k \gg r^l \gg 1$ (Gaussian) and $k,l \to \infty$ such that $k/r^l$ is finite (Compound Poisson). However, it is known that these distributions do now work well in the intermediate regime $k \gtrsim r^l \gtrsim 1$. We show that the problem of calculating the string matching probability can be cast into a determining the configurational partition function of a 1d lattice gas with interacting particles so that the matching probability becomes the grand-partition sum of the lattice gas, with the number of particles corresponding to the number of matches. We perform a virial expansion of the effective equation of state and obtain the probability distribution. Our result reproduces the behavior of the distribution in all regimes. We are also able to show analytically how the limiting distributions arise. Our analysis builds on the fact that the effective interactions between the particles consist of a relatively strong core of size $l$, the word length, followed by a weak, exponentially decaying tail. We find that the asymptotic regimes correspond to the case where the tail of the interactions can be neglected, while in the intermediate regime they need to be kept in the analysis. Our results are readily generalized to the case where the random strings are generated by more complicated stochastic processes such as a non-uniform letter probability distribution or Markov chains. We show that in these cases the tails of the effective interactions can be made even more dominant rendering thus the asymptotic approximations less accurate in such a regime.Comment: 44 pages and 8 figures. Major revision of previous version. The lattice gas analogy has been worked out in full, including virial expansion and equation of state. This constitutes the main part of the paper now. Connections with existing work is made and references should be up to date now. To be submitted for publicatio

Thermal Links for the Implementation of an Optical Refrigerator

Optical refrigeration has been demonstrated by several groups of researchers, but the cooling elements have not been thermally linked to realistic heat loads in ways that achieve the desired temperatures. The ideal thermal link will have minimal surface area, provide complete optical isolation for the load, and possess high thermal conductivity. We have designed thermal links that minimize the absorption of fluoresced photons by the heat load using multiple mirrors and geometric shapes including a hemisphere, a kinked waveguide, and a tapered waveguide. While total link performance is dependent on additional factors, we have observed net transmission of photons with the tapered link as low as 0.04%. Our optical tests have been performed with a surrogate source that operates at 625 nm and mimics the angular distribution of light emitted from the cooling element of the Los Alamos solid state optical refrigerator. We have confirmed the optical performance of our various link geometries with computer simulations using CODE V optical modeling software. In addition we have used the thermal modeling tool in COMSOL MULTIPHYSICS to investigate other heating factors that affect the thermal performance of the optical refrigerator. Assuming an ideal cooling element and a nonabsorptive dielectric trapping mirror, the three dominant heating factors are (1) absorption of fluoresced photons transmitted through the thermal link, (2) blackbody radiation from the surrounding environment, and (3) conductive heat transfer through mechanical supports. Modeling results show that a 1 cm3 load can be chilled to 107 K with a 100Wpump laser. We have used the simulated steady-state cooling temperatures of the heat load to compare link designs and system configurations