Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Utilization of the ART approach in a group of public oral health operators in South Africa: a 5-year longitudinal study

Contains fulltext : 80990.pdf (publisher's version ) (Open Access)BACKGROUND: A significant increase in the proportion of restorations to the number of tooth extractions was reported after the introduction of ART in an academic mobile dental service in South Africa. The changes were ascribed to its less threatening procedure. Based on these findings, ART was subsequently introduced into the public oral health service of Ekurhuleni district in the South African province of Gauteng. This article reports on the 5-year restorative treatment pattern of operators in the Ekurhuleni district, who adopted the ART approach into their daily dental practice. METHODS: Of the 21 trained operators, 11 had placed more than 10% of restorations using ART at year 1 and were evaluated after 5 years. Data, including number of restored and extracted teeth and type of restoration, were drawn from clinical records 4 months before, and up to 5 years after training. The restoration/extraction ratio (REX score) and the proportion of ART restorations to the total number of restorations were calculated. The paired sample t-test and linear regression analysis were applied. RESULTS: The mean percentage of ART restorations after 1 year was 24.0% (SE 7.2) and significantly increased annually to 42.7% (SE 9.2) after 5 years in permanent dentitions. In primary dentitions the mean percentage of ART restorations after 1 year was 80.6% (SE 4.9) and 72.6% (SE 8.8) after 5 years. The mean REX score before ART training was 0.08 (SE 0.03) and 0.07 (SE 0.04) for permanent and primary teeth, respectively and 0.11 (SE 0.03) and 0.17 (SE 0.05) after 5 years. CONCLUSION: Five years after training, ART had been used consistently in this selected group of operators as the predominant restorative treatment used for primary teeth and showed a significant annual increase in permanent teeth. However, this change had not resulted in an increase in the REX score in both dentitions

Quantum non-demolition measurement of a superconducting two-level system

In quantum mechanics, the process of measurement is a subtle interplay between extraction of information and disturbance of the state of the quantum system. A quantum non-demolition (QND) measurement minimizes this disturbance by using a particular system - detector interaction which preserves the eigenstates of a suitable operator of the quantum system. This leads to an ideal projective measurement. We present experiments in which we perform two consecutive measurements on a quantum two -level system, a superconducting flux qubit, by probing the hysteretic behaviour of a coupled nonlinear resonator. The large correlation between the results of the two measurements demonstrates the QND nature of the readout method. The fact that a QND measurement is possible for superconducting qubits strengthens the notion that these fabricated mesoscopic systems are to be regarded as fundamental quantum objects. Our results are also relevant for quantum information processing, where projective measurements are used for protocols like state preparation and error correction.Comment: 14 pages, 4 figure

Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum

BACKGROUND: Quantification of the metabolic network of an organism offers insights into possible ways of developing mutant strain for better productivity of an extracellular metabolite. The first step in this quantification is the enumeration of stoichiometries of all reactions occurring in a metabolic network. The structural details of the network in combination with experimentally observed accumulation rates of external metabolites can yield flux distribution at steady state. One such methodology for quantification is the use of elementary modes, which are minimal set of enzymes connecting external metabolites. Here, we have used a linear objective function subject to elementary modes as constraint to determine the fluxes in the metabolic network of Corynebacterium glutamicum. The feasible phenotypic space was evaluated at various combinations of oxygen and ammonia uptake rates. RESULTS: Quantification of the fluxes of the elementary modes in the metabolism of C. glutamicum was formulated as linear programming. The analysis demonstrated that the solution was dependent on the criteria of objective function when less than four accumulation rates of the external metabolites were considered. The analysis yielded feasible ranges of fluxes of elementary modes that satisfy the experimental accumulation rates. In C. glutamicum, the elementary modes relating to biomass synthesis through glycolysis and TCA cycle were predominantly operational in the initial growth phase. At a later time, the elementary modes contributing to lysine synthesis became active. The oxygen and ammonia uptake rates were shown to be bounded in the phenotypic space due to the stoichiometric constraint of the elementary modes. CONCLUSION: We have demonstrated the use of elementary modes and the linear programming to quantify a metabolic network. We have used the methodology to quantify the network of C. glutamicum, which evaluates the set of operational elementary modes at different phases of fermentation. The methodology was also used to determine the feasible solution space for a given set of substrate uptake rates under specific optimization criteria. Such an approach can be used to determine the optimality of the accumulation rates of any metabolite in a given network

Neutron Majorana mass from exotic instantons

We show how a Majorana mass for the Neutron could result from non-perturbative quantum gravity effects peculiar to string theory. In particular, "exotic instantons" in un-oriented string compactifications with D-branes extending the (supersymmetric) standard model could indirectly produce an effective operator delta{m} n^t n+h.c. In a specific model with an extra vector-like pair of `quarks', acquiring a large mass proportional to the string mass scale (exponentially suppressed by a function of the string moduli fields), delta{m} can turn out to be as low as 10^{-24}-10^{-25} eV. The induced neutron-antineutron oscillations could take place with a time scale tau_{n\bar{n}} > 10^8 s, that could be tested by the next generation of experiments. On the other hand, proton decay and FCNC's are automatically strongly suppressed and are compatible with the current experimental limits. Depending on the number of brane intersections, the model may also lead to the generation of Majorana masses for R-handed neutrini. Our proposal could also suggest neutron-neutralino or neutron-axino oscillations, with implications in UCN, Dark Matter Direct Detection, UHECR and Neutron-Antineutron oscillations. This suggests to improve the limits on neutron-antineutron oscillations, as a possible test of string theory and quantum gravity.Comment: 35 pages, 11 figures. More comments on neutron-neutralino mixin

Hidden SUSY at the LHC: the light higgsino-world scenario and the role of a lepton collider

While the SUSY flavor, CP and gravitino problems seem to favor a very heavy spectrum of matter scalars, fine-tuning in the electroweak sector prefers low values of superpotential mass \mu. In the limit of low \mu, the two lightest neutralinos and light chargino are higgsino-like. The light charginos and neutralinos may have large production cross sections at LHC, but since they are nearly mass degenerate, there is only small energy release in three-body sparticle decays. Possible dilepton and trilepton signatures are difficult to observe after mild cuts due to the very soft p_T spectrum of the final state isolated leptons. Thus, the higgsino-world scenario can easily elude standard SUSY searches at the LHC. It should motivate experimental searches to focus on dimuon and trimuon production at the very lowest p_T(\mu) values possible. If the neutralino relic abundance is enhanced via non-standard cosmological dark matter production, then there exist excellent prospects for direct or indirect detection of higgsino-like WIMPs. While the higgsino-world scenario may easily hide from LHC SUSY searches, a linear e^+e^- collider or a muon collider operating in the \sqrt{s}\sim 0.5-1 TeV range would be able to easily access the chargino and neutralino pair production reactions.Comment: 20 pages including 12 .eps figure

Neutralino versus axion/axino cold dark matter in the 19 parameter SUGRA model

We calculate the relic abundance of thermally produced neutralino cold dark matter in the general 19 parameter supergravity (SUGRA-19) model. A scan over GUT scale parameters reveals that models with a bino-like neutralino typically give rise to a dark matter density \Omega_{\tz_1}h^2\sim 1-1000, i.e. between 1 and 4 orders of magnitude higher than the measured value. Models with higgsino or wino cold dark matter can yield the correct relic density, but mainly for neutralino masses around 700-1300 GeV. Models with mixed bino-wino or bino-higgsino CDM, or models with dominant co-annihilation or A-resonance annihilation can yield the correct abundance, but such cases are extremely hard to generate using a general scan over GUT scale parameters; this is indicative of high fine-tuning of the relic abundance in these cases. Requiring that m_{\tz_1}\alt 500 GeV (as a rough naturalness requirement) gives rise to a minimal probably dip in parameter space at the measured CDM abundance. For comparison, we also scan over mSUGRA space with four free parameters. Finally, we investigate the Peccei-Quinn augmented MSSM with mixed axion/axino cold dark matter. In this case, the relic abundance agrees more naturally with the measured value. In light of our cumulative results, we conclude that future axion searches should probe much more broadly in axion mass, and deeper into the axion coupling.Comment: 23 pages including 17 .eps figure

Accretion of Planetary Material onto Host Stars

Accretion of planetary material onto host stars may occur throughout a star's life. Especially prone to accretion, extrasolar planets in short-period orbits, while relatively rare, constitute a significant fraction of the known population, and these planets are subject to dynamical and atmospheric influences that can drive significant mass loss. Theoretical models frame expectations regarding the rates and extent of this planetary accretion. For instance, tidal interactions between planets and stars may drive complete orbital decay during the main sequence. Many planets that survive their stars' main sequence lifetime will still be engulfed when the host stars become red giant stars. There is some observational evidence supporting these predictions, such as a dearth of close-in planets around fast stellar rotators, which is consistent with tidal spin-up and planet accretion. There remains no clear chemical evidence for pollution of the atmospheres of main sequence or red giant stars by planetary materials, but a wealth of evidence points to active accretion by white dwarfs. In this article, we review the current understanding of accretion of planetary material, from the pre- to the post-main sequence and beyond. The review begins with the astrophysical framework for that process and then considers accretion during various phases of a host star's life, during which the details of accretion vary, and the observational evidence for accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie

Loss of Dictyostelium HSPC300 causes a scar-like phenotype and loss of SCAR protein

<p>Abstract</p> <p>Background</p> <p>SCAR/WAVE proteins couple signalling to actin polymerization, and are thus fundamental to the formation of pseudopods and lamellipods. They are controlled as part of a five-membered complex that includes the tiny HSPC300 protein. It is not known why SCAR/WAVE is found in such a large assembly, but in <it>Dictyostelium </it>the four larger subunits have different, clearly delineated functions.</p> <p>Results</p> <p>We have generated <it>Dictyostelium </it>mutants in which the HSPC300 gene is disrupted. As has been seen in other regulatory complex mutants, SCAR is lost in these cells, apparently by a post-translational mechanism, though PIR121 levels do not change. HSPC300 knockouts resemble <it>scar </it>mutants in slow migration, roundness, and lack of large pseudopods. However <it>hspc300</it>-colonies on bacteria are larger and more similar to wild type, suggesting that some SCAR function can survive without HSPC300. We find no evidence for functions of HSPC300 outside the SCAR complex.</p> <p>Conclusion</p> <p>HSPC300 is essential for most SCAR complex functions. The phenotype of HSPC300 knockouts is most similar to mutants in <it>scar</it>, not the other members of the SCAR complex, suggesting that HSPC300 acts most directly on SCAR itself.</p

Sequential induction of auxin efflux and influx carriers regulates lateral root emergence

Peer reviewe