Error Propagation in the Hypercycle

We study analytically the steady-state regime of a network of n error-prone self-replicating templates forming an asymmetric hypercycle and its error tail. We show that the existence of a master template with a higher non-catalyzed self-replicative productivity, a, than the error tail ensures the stability of chains in which m<n-1 templates coexist with the master species. The stability of these chains against the error tail is guaranteed for catalytic coupling strengths (K) of order of a. We find that the hypercycle becomes more stable than the chains only for K of order of a2. Furthermore, we show that the minimal replication accuracy per template needed to maintain the hypercycle, the so-called error threshold, vanishes like sqrt(n/K) for large K and n<=4

Evolution of clonal populations approaching a fitness peak

Populations facing novel environments are expected to evolve through the accumulation of adaptive substitutions. The dynamics of adaptation depend on the fitness landscape and possibly on the genetic background on which new mutations arise. Here, we model the dynamics of adaptive evolution at the phenotypic and genotypic levels, focusing on a Fisherian landscape characterized by a single peak. We find that Fisher's geometrical model of adaptation, extended to allow for small random environmental variations, is able to explain several features made recently in experimentally evolved populations. Consistent with data on populations evolving under controlled conditions, the model predicts that mean population fitness increases rapidly when populations face novel environments and then achieves a dynamic plateau, the rate of molecular evolution is remarkably constant over long periods of evolution, mutators are expected to invade and patterns of epistasis vary along the adaptive walk. Negative epistasis is expected in the initial steps of adaptation but not at later steps, a prediction that remains to be tested. Furthermore, populations are expected to exhibit high levels of phenotypic diversity at all times during their evolution. This implies that populations are possibly able to adapt rapidly to novel abiotic environments.CAPES-IGC

Stabilization of Extra Dimensions and The Dimensionality of the Observed Space

We present a simple model for the late time stabilization of extra dimensions. The basic idea is that brane solutions wrapped around extra dimensions, which is allowed by string theory, will resist expansion due to their winding mode. The momentum modes in principle work in the opposite way. It is this interplay that leads to dynamical stabilization. We use the idea of democratic wrapping \cite{art5}-\cite{art6}, where in a given decimation of extra dimensions, all possible winding cases are considered. To simplify the study further we assumed a symmetric decimation in which the total number of extra dimensions is taken to be $Np$ where N can be called the order of the decimation. We also assumed that extra dimensions all have the topology of tori. We show that with these rather conservative assumptions, there exists solutions to the field equations in which the extra dimensions are stabilized and that the conditions do not depend on $p$. This fact means that there exists at least one solution to the asymmetric decimation case. If we denote the number of observed space dimensions (excluding time) by $m$, the condition for stabilization is $m\geq 3$ for pure Einstein gravity and $m\leq 3$ for dilaton gravity massaged by string theory parameters.Comment: Final versio

Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat

Ultrahigh Transmission Optical Nanofibers

We present a procedure for reproducibly fabricating ultrahigh transmission optical nanofibers (530 nm diameter and 84 mm stretch) with single-mode transmissions of 99.95 $\pm$ 0.02%, which represents a loss from tapering of 2.6 $\,\times \,$ 10$^{-5}$ dB/mm when normalized to the entire stretch. When controllably launching the next family of higher-order modes on a fiber with 195 mm stretch, we achieve a transmission of 97.8 $\pm$ 2.8%, which has a loss from tapering of 5.0 $\,\times \,$ 10$^{-4}$ dB/mm when normalized to the entire stretch. Our pulling and transfer procedures allow us to fabricate optical nanofibers that transmit more than 400 mW in high vacuum conditions. These results, published as parameters in our previous work, present an improvement of two orders of magnitude less loss for the fundamental mode and an increase in transmission of more than 300% for higher-order modes, when following the protocols detailed in this paper. We extract from the transmission during the pull, the only reported spectrogram of a fundamental mode launch that does not include excitation to asymmetric modes; in stark contrast to a pull in which our cleaning protocol is not followed. These results depend critically on the pre-pull cleanliness and when properly following our pulling protocols are in excellent agreement with simulations.Comment: 32 pages, 10 figures, accepted to AIP Advance

Mode decomposition and renormalization in semiclassical gravity

We compute the influence action for a system perturbatively coupled to a linear scalar field acting as the environment. Subtleties related to divergences that appear when summing over all the modes are made explicit and clarified. Being closely connected with models used in the literature, we show how to completely reconcile the results obtained in the context of stochastic semiclassical gravity when using mode decomposition with those obtained by other standard functional techniques.Comment: 4 pages, RevTeX, no figure

Intermodal Energy Transfer in a Tapered Optical Fiber: Optimizing Transmission

We present an experimental and theoretical study of the energy transfer between modes during the tapering process of an optical nanofiber through spectrogram analysis. The results allow optimization of the tapering process, and we measure transmission in excess of 99.95% for the fundamental mode. We quantify the adiabaticity condition through calculations and place an upper bound on the amount of energy transferred to other modes at each step of the tapering, giving practical limits to the tapering angle.Comment: 29 pages, 17 figure