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The intermediate evolution phase in case of truncated selection

Using methods of statistical physics, we present rigorous theoretical calculations of Eigen's quasispecies theory with the truncated fitness landscape which dramatically limits the available sequence space of a reproducing quasispecies. Depending on the mutation rates, we observe three phases, a selective one, an intermediate one with some residual order and a completely randomized phase. Our results are applicable for the general case of fitness landscape.Comment: 8 page

Quantifying Hopping and Jumping in Facilitated Diffusion of DNA-Binding Proteins

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A Compromise between Neutrino Masses and Collider Signatures in the Type-II Seesaw Model

A natural extension of the standard $SU(2)_{\rm L} \times U(1)_{\rm Y}$ gauge model to accommodate massive neutrinos is to introduce one Higgs triplet and three right-handed Majorana neutrinos, leading to a $6\times 6$ neutrino mass matrix which contains three $3\times 3$ sub-matrices $M_{\rm L}$, $M_{\rm D}$ and $M_{\rm R}$. We show that three light Majorana neutrinos (i.e., the mass eigenstates of $\nu_e$, $\nu_\mu$ and $\nu_\tau$) are exactly massless in this model, if and only if $M_{\rm L} = M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ exactly holds. This no-go theorem implies that small but non-vanishing neutrino masses may result from a significant but incomplete cancellation between $M_{\rm L}$ and $M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ terms in the Type-II seesaw formula, provided three right-handed Majorana neutrinos are of ${\cal O}(1)$ TeV and experimentally detectable at the LHC. We propose three simple Type-II seesaw scenarios with the $A_4 \times U(1)_{\rm X}$ flavor symmetry to interpret the observed neutrino mass spectrum and neutrino mixing pattern. Such a TeV-scale neutrino model can be tested in two complementary ways: (1) searching for possible collider signatures of lepton number violation induced by the right-handed Majorana neutrinos and doubly-charged Higgs particles; and (2) searching for possible consequences of unitarity violation of the $3\times 3$ neutrino mixing matrix in the future long-baseline neutrino oscillation experiments.Comment: RevTeX 19 pages, no figure

Large ESR forging ingots and their quality in production

ESR is known as an alternative step on the continuous improvement in single ingot production for heavyforgings. In the recent past a new state of the art ESR remelting system was installed with the possibility toproduce ingots in diameter from 1000mm for 45tons till 2000mm for 145tons. Consumable electrodes fromtraditional fabrication processes which consist of melting with electrical arc furnace, refining, degassingof the steel and bottom pouring will be used to produce one single heavy ingot with best cleanness withthe help of electrode exchange technique. This paper tells about the furnace characteristics and the efforts tobe made to ensure high quality level in material and furnace preparation as well as save automatic productionperformances during remelting and electrode exchange. Finally the results of ingots characterized by anelevated level of chemical homogeneity and internal quality such as to ensure the absence of defectgreater than 0.5mm AVG during the final inspection of the forged part from the ESR production will bepresented. The ESR process serves for the reproducible quality in heavy ingot making and tightens the limits inspecifications together with high material yield

The relationship between the error catastrophe, survival of the flattest, and natural selection

<p>Abstract</p> <p>Background</p> <p>The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.</p> <p>Results</p> <p>By means of a very simplified model, we show that the transition to an error catastrophe corresponds to a value of zero for the selective coefficient of the mutant phenotype with respect to the master phenotype, indicating that transition to the error catastrophe is in this case similar to the selection of a more robust species. This correspondence has been confirmed by considering a single-peak landscape in which sequences are grouped with respect to their Hamming distant from the master sequence. When the robustness of a classe is changed by modification of its quality factor, the distribution of the population changes in accordance with the new value of the robustness, although an error catastrophe can be detected at the same values as in the general case. When two quasispecies of different robustness competes with one another, the entry of one of them into error catastrophe causes displacement of the other, because of the greater robustness of the former. Previous works are explicitly reinterpreted in the light of the results obtained in this paper.</p> <p>Conclusions</p> <p>The main conclusion of this paper is that the entry into error catastrophe is a specific case of survival of the flattest acting on phenotypes that differ in the trade-off between replicative ability and mutational robustness. In fact, entry into error catastrophe occurs when the mutant phenotype acquires a selective advantage over the master phenotype. As both entry into error catastrophe and survival of the flattest are caused by natural selection when mutation rate is increased, we propose differentiating between them by the level of selection at which natural selection acts. So we propose to consider the transition to error catastrophe as a phenomenon of intra-quasispecies selection, and survival of the flattest as a phenomenon of inter-quasispecies selection.</p

PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH-/- cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localises with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH-/- cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis

Solution of the Crow-Kimura and Eigen models for alphabets of arbitrary size by Schwinger spin coherent states

To represent the evolution of nucleic acid and protein sequence, we express the parallel and Eigen models for molecular evolution in terms of a functional integral representation with an $h$-letter alphabet, lifting the two-state, purine/pyrimidine assumption often made in quasi-species theory. For arbitrary $h$ and a general mutation scheme, we obtain the solution of this model in terms of a maximum principle. Euler's theorem for homogeneous functions is used to derive this `thermodynamic' formulation of evolution. The general result for the parallel model reduces to known results for the purine/pyrimidine $h=2$ alphabet and the nucleic acid $h=4$ alphabet for the Kimura 3 ST mutation scheme. Examples are presented for the $h=4$ and $h=20$ cases. We derive the maximum principle for the Eigen model for general $h$. The general result for the Eigen model reduces to a known result for $h=2$. Examples are presented for the nucleic acid $h=4$ and the amino acid $h=20$ alphabet. An error catastrophe phase transition occurs in these models, and the order of the phase transition changes from second to first order for smooth fitness functions when the alphabet size is increased beyond two letters to the generic case. As examples, we analyze the general analytic solution for sharp peak, linear, quadratic, and quartic fitness functions.Comment: 50 pages, 8 figures, to appear in J. Stat. Phys; some typos fixe