Home Made Rugs

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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

Evidence for a diffusion-controlled mechanism for fluorescence blinking of colloidal quantum dots

Fluorescence blinking in nanocrystal quantum dots is known to exhibit power-law dynamics, and several different mechanisms have been proposed to explain this behavior. We have extended the measurement of quantum-dot blinking by characterizing fluctuations in the fluorescence of single dots over time scales from microseconds to seconds. The power spectral density of these fluctuations indicates a change in the power-law statistics that occurs at a time scale of several milliseconds, providing an important constraint on possible mechanisms for the blinking. In particular, the observations are consistent with the predictions of models wherein blinking is controlled by diffusion of the energies of electron or hole trap states

Molecular Evolution in Time Dependent Environments

The quasispecies theory is studied for dynamic replication landscapes. A meaningful asymptotic quasispecies is defined for periodic time dependencies. The quasispecies' composition is constantly changing over the oscillation period. The error threshold moves towards the position of the time averaged landscape for high oscillation frequencies and follows the landscape closely for low oscillation frequencies.Comment: 5 pages, 3 figures, Latex, uses Springer documentclass llncs.cl

First modulation of high-frequency polar mesospheric summer echoes by radio heating of the ionosphere

The first high-frequency (HF, 8 MHz) observations of the modulation of polar mesospheric summer echoes (PMSE) by artificial radio heating of the ionosphere are presented and compared to observations at 224 MHz and model predictions. The experiments were performed at the European Incoherent Scatter facility in northern Norway. It is shown that model results are in qualitative and partial quantitative agreement with the observations, supporting the prediction that with certain ranges of ice particle radii and concentration, PMSE at HF radar wavelengths can be enhanced by heating due to the dominance of dust charging over plasma diffusion

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

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

PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling

Centromeres provide a pivotal function for faithful chromosome segregation. They serve as a foundation for the assembly of the kinetochore complex and spindle connection, which is essential for chromosome biorientation. Cells lacking Polo-like kinase 1 (PLK1) activity suffer severe chromosome alignment defects, which is believed primarily due to unstable kinetochore-microtubule attachment. Here, we reveal a previously undescribed mechanism named ‘centromere disintegration’ that drives chromosome misalignment in PLK1-inactivated cells. We find that PLK1 inhibition does not necessarily compromise metaphase establishment, but instead its maintenance. We demonstrate that this is caused by unlawful unwinding of DNA by BLM helicase at a specific centromere domain underneath kinetochores. Under bipolar spindle pulling, the distorted centromeres are promptly decompacted into DNA threadlike molecules, leading to centromere rupture and whole-chromosome arm splitting. Consequently, chromosome alignment collapses. Our study unveils an unexpected role of PLK1 as a chromosome guardian to maintain centromere integrity for chromosome biorientation

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.Koronis Pharmaceutical