Solution of the Quasispecies Model for an Arbitrary Gene Network

In this paper, we study the equilibrium behavior of Eigen's quasispecies equations for an arbitrary gene network. We consider a genome consisting of $N$ genes, so that each gene sequence $\sigma$ may be written as $\sigma = \sigma_1 \sigma_2 ... \sigma_N$. We assume a single fitness peak (SFP) model for each gene, so that gene $i$ has some ``master'' sequence $\sigma_{i, 0}$ for which it is functioning. The fitness landscape is then determined by which genes in the genome are functioning, and which are not. The equilibrium behavior of this model may be solved in the limit of infinite sequence length. The central result is that, instead of a single error catastrophe, the model exhibits a series of localization to delocalization transitions, which we term an ``error cascade.'' As the mutation rate is increased, the selective advantage for maintaining functional copies of certain genes in the network disappears, and the population distribution delocalizes over the corresponding sequence spaces. The network goes through a series of such transitions, as more and more genes become inactivated, until eventually delocalization occurs over the entire genome space, resulting in a final error catastrophe. This model provides a criterion for determining the conditions under which certain genes in a genome will lose functionality due to genetic drift. It also provides insight into the response of gene networks to mutagens. In particular, it suggests an approach for determining the relative importance of various genes to the fitness of an organism, in a more accurate manner than the standard ``deletion set'' method. The results in this paper also have implications for mutational robustness and what C.O. Wilke termed ``survival of the flattest.''Comment: 29 pages, 5 figures, to be submitted to Physical Review

First model-independent Dalitz analysis of B0→DK∗0, D→K0Sπ+π− decay

We report a measurement of the amplitude ratio rS of B0 → D0K∗0 and B0 → D¯0K∗0 decays with a Dalitz analysis of D → K0 Sπ+π− decays, for the first time using a model-independent method. We set an upper limit rS \u3c 0.87 at the 68% confidence level, using the full data sample of 711 fb−1 corresponding to 772 × 106 BB¯ pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e+e− collider. This result is obtained from observables x− = +0.4+1.0+0.0 −0.6−0.1 ± 0.0, y− = −0.6+0.8+0.1 −1.0−0.0 ± 0.1, x+ = +0.1+0.7+0.0 −0.4−0.1 ± 0.1, and y+ = +0.3+0.5+0.0 −0.8−0.1 ± 0.1, where x± = rS cos(δS ± φ3), y± = rS sin(δS ± φ3), and φ3 (δS) is the weak (strong) phase difference between B0 → D0K∗0 and B0 → D¯0K∗0

Laboratory study on heterogeneous decomposition of methyl chloroform on various standard aluminosilica clay minerals as a potential tropospheric sink

International audienceMethyl chloroform (1,1,1-trichloroethane, CH3CCl3) was found to decompose heterogeneously on seven types of standard clay minerals (23 materials) in dry air at 313 K in the laboratory. All reactions proceeded through the elimination of HCl; CH3CCl3 was converted quantitatively to CH2=CCl2. The activities of the clay minerals were compared via their pseudo-first-order reaction rate constants (k1). A positive correlation was observed between the k1 value and the specific surface area (S) of clay minerals, where the S value was determined by means of the general Brunauer-Emmett-Teller (BET) equation. The k1 value was anti-correlated with the value of n, which was a parameter of the general BET equation and related to the average pore size of the clay minerals, and correlated with the water content that can be removed easily from the clay minerals. The reaction required no special pretreatment of clay minerals, such as heating at high temperatures; hence, the reaction can be expected to occur in the environment. Photoillumination by wavelengths present in the troposphere did not accelerate the decomposition of CH3CCl3, but it induced heterogeneous photodecomposition of CH2=CCl2. The temperature dependence of k1, the adsorption equilibrium coefficient of CH3CCl3 and CH2=CCl2, and the surface reaction rate constant of CH3CCl3 were determined for an illite sample. The k1 value increased with increasing temperature. The amount of CH3CCl3 adsorbed on the illite during the reaction was proportional to the partial pressure of CH3CCl3. The reaction was sensitive to relative humidity and the k1 value decreased with increasing relative humidity. However, the reaction was found to proceed at a relative humidity of 22% at 313 K, although the k1 value was about one-twentieth of the value in non-humidified air. The conditions required for the reaction may be present in major desert regions of the world. A simple estimation indicates that the possible heterogeneous decomposition of CH3CCl3 on the ground surface in arid regions is worth taking into consideration when inferring the tropospheric lifetime of CH3CCl3 and global OH concentration from the global budget concentration of CH3CCl3

I-V characteristics of single electron tunneling from symmetric and asymmetric double-barrier tunneling junctions

Copyright 2007 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Applied Physics Letters, 90(22), 223112, 2007 and may be found at http://dx.doi.org/10.1063/1.274525

Prednisone and azathioprine in patients with inflammatory cardiomyopathy: systematic review and meta-analysis

Aims: Chronic non-viral myocarditis, also called inflammatory cardiomyopathy, can be treated with immune suppression on tops of optimal medical therapy (OMT) for heart failure, using a combination of prednisolone and azathioprine (IPA). However, there has been inconsistency in the effects of immunosuppression treatment. This meta-analysis is the first to evaluate all available data of the effect of this treatment on left ventricular ejection fraction (LVEF) and the combined clinical endpoint of cardiovascular mortality and/or heart transplantation-free survival. Methods and results: All trials with using IPA vs. OMT in this syndrome were searched using OVID Medline and ClinicalTrials. gov, following the PRISMA guidelines. Missing data were retrieved after contacting the corresponding authors. All data was reviewed and analysed using and standard meta-analysis methods. A random effect model was used to pool the effect sizes. A total of four trials (three randomised controlled trials and one propensity-matched retrospective registry) including 369 patients were identified. IPA on top of OMT did not improve LVEF [mean difference 9.9% (95% confidence interval -1.8, 21.7)] with significant heterogeneity. When we limited our pooled estimate to the published studies only, significant LVEF improvement by IPA was observed [14% (1.4, 26.6)]. No cardiovascular mortality benefit was observed with the intervention [risk ratio 0.34 (0.08, 1.51)]. Conclusions: At the moment, there is insufficient evidence supporting functional and prognostic benefits of IPA added to OMT in virus negative inflammatory positive cardiomyopathy. Further adequate-powered well-designed prospective RCTs should be warranted to explore the potential effects of adding immunosuppressive therapy to OMT

Fabrication of nanoscale gaps using a combination of self-assembled molecular and electron beam lithographic techniques

Copyright 2006 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Applied Physics Letters, 88(22), 223111, 2006 and may be found at http://dx.doi.org/10.1063/1.220920