Parameter Estimation and Quantitative Parametric Linkage Analysis with GENEHUNTER-QMOD

Objective: We present a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations. Methods: The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method. Results: The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions. Conclusion: With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads. Copyright (C) 2012 S. Karger AG, Base

Regulation by Gonadal Steroids of Estrogen and Progesterone Receptors Along the Reproductive Tract in Female Lambs

The regulation of estrogen and progesterone receptor (ER, PR) expression by estradiol (E2) and progesterone (P4) in the oviduct, uterus and cervix of female lambs was studied. The animals received three intramuscular injections of E2, P4 or vehicle with an interval of 24 h and they were slaugthered 24 h after the third injection. Determinations of ER and PR were performed by binding assays and mRNAs of ERα and PR by solution hybridization. High levels of ER and PR in both cervix and oviduct were found in the female lamb, differing from other mammalian species. No significant effects by either E2 or P4 treatment on ER and PR levels in the cervix and oviduct could be observed. E2 treatment increased the mRNA levels of ERa and PR more than 3-fold in the cervix, while P4 treatment increased the mRNA levels of ERa and PR in the uterus. The results show differential effects of gonadal steroids on sex steroid receptor expression along the reproductive tract in female lambs, suggesting that steroid target tissues can modulate responses to the same circulating levels of steroid hormones

Ant colony optimisation and local search for bin-packing and cutting stock problems

The Bin Packing Problem and the Cutting Stock Problem are two related classes of NP-hard combinatorial optimization problems. Exact solution methods can only be used for very small instances, so for real-world problems, we have to rely on heuristic methods. In recent years, researchers have started to apply evolutionary approaches to these problems, including Genetic Algorithms and Evolutionary Programming. In the work presented here, we used an ant colony optimization (ACO) approach to solve both Bin Packing and Cutting Stock Problems. We present a pure ACO approach, as well as an ACO approach augmented with a simple but very effective local search algorithm. It is shown that the pure ACO approach can compete with existing evolutionary methods, whereas the hybrid approach can outperform the best-known hybrid evolutionary solution methods for certain problem classes. The hybrid ACO approach is also shown to require different parameter values from the pure ACO approach and to give a more robust performance across different problems with a single set of parameter values. The local search algorithm is also run with random restarts and shown to perform significantly worse than when combined with ACO

Mean-Payoff Optimization in Continuous-Time Markov Chains with Parametric Alarms

Continuous-time Markov chains with alarms (ACTMCs) allow for alarm events that can be non-exponentially distributed. Within parametric ACTMCs, the parameters of alarm-event distributions are not given explicitly and can be subject of parameter synthesis. An algorithm solving the $\varepsilon$-optimal parameter synthesis problem for parametric ACTMCs with long-run average optimization objectives is presented. Our approach is based on reduction of the problem to finding long-run average optimal strategies in semi-Markov decision processes (semi-MDPs) and sufficient discretization of parameter (i.e., action) space. Since the set of actions in the discretized semi-MDP can be very large, a straightforward approach based on explicit action-space construction fails to solve even simple instances of the problem. The presented algorithm uses an enhanced policy iteration on symbolic representations of the action space. The soundness of the algorithm is established for parametric ACTMCs with alarm-event distributions satisfying four mild assumptions that are shown to hold for uniform, Dirac and Weibull distributions in particular, but are satisfied for many other distributions as well. An experimental implementation shows that the symbolic technique substantially improves the efficiency of the synthesis algorithm and allows to solve instances of realistic size.Comment: This article is a full version of a paper accepted to the Conference on Quantitative Evaluation of SysTems (QEST) 201

Conclusive quantum steering with superconducting transition edge sensors

Quantum steering allows two parties to verify shared entanglement even if one measurement device is untrusted. A conclusive demonstration of steering through the violation of a steering inequality is of considerable fundamental interest and opens up applications in quantum communication. To date all experimental tests with single photon states have relied on post-selection, allowing untrusted devices to cheat by hiding unfavourable events in losses. Here we close this "detection loophole" by combining a highly efficient source of entangled photon pairs with superconducting transition edge sensors. We achieve an unprecedented ~62% conditional detection efficiency of entangled photons and violate a steering inequality with the minimal number of measurement settings by 48 standard deviations. Our results provide a clear path to practical applications of steering and to a photonic loophole-free Bell test.Comment: Preprint of 7 pages, 3 figures; the definitive version is published in Nature Communications, see below. Also, see related experimental work by A. J. Bennet et al., arXiv:1111.0739 and B. Wittmann et al., arXiv:1111.076

5d quivers and their AdS(6) duals

We consider an infinite class of 5d supersymmetric gauge theories involving products of symplectic and unitary groups that arise from D4-branes at orbifold singularities in Type I' string theory. The theories are argued to be dual to warped AdS(6)x S4/Zn backgrounds in massive Type IIA supergravity. In particular, this demonstrates the existence of supersymmetric 5d fixed points of quiver type. We analyze the spectrum of gauge fields and charged states in the supergravity dual, and find a precise agreement with the symmetries and charged operators in the quiver theories. We also comment on other brane objects in the supergravity dual and their interpretation in the field theories.Comment: 29 pages, 15 figure

Causarum Investigatio and the Two Bell's Theorems of John Bell

"Bell's theorem" can refer to two different theorems that John Bell proved, the first in 1964 and the second in 1976. His 1964 theorem is the incompatibility of quantum phenomena with the joint assumptions of Locality and Predetermination. His 1976 theorem is their incompatibility with the single property of Local Causality. This is contrary to Bell's own later assertions, that his 1964 theorem began with the assumption of Local Causality, even if not by that name. Although the two Bell's theorems are logically equivalent, their assumptions are not. Hence, the earlier and later theorems suggest quite different conclusions, embraced by operationalists and realists, respectively. The key issue is whether Locality or Local Causality is the appropriate notion emanating from Relativistic Causality, and this rests on one's basic notion of causation. For operationalists the appropriate notion is what is here called the Principle of Agent-Causation, while for realists it is Reichenbach's Principle of common cause. By breaking down the latter into even more basic Postulates, it is possible to obtain a version of Bell's theorem in which each camp could reject one assumption, happy that the remaining assumptions reflect its weltanschauung. Formulating Bell's theorem in terms of causation is fruitful not just for attempting to reconcile the two camps, but also for better describing the ontology of different quantum interpretations and for more deeply understanding the implications of Bell's marvellous work.Comment: 24 pages. Prepared for proceedings of the "Quantum [Un]speakables II" conference (Vienna, 2014), to be published by Springe

Fake Superpotential for Large and Small Extremal Black Holes

We consider the fist order, gradient-flow, description of the scalar fields coupled to spherically symmetric, asymptotically flat black holes in extended supergravities. Using the identification of the fake superpotential with Hamilton's characteristic function we clarify some of its general properties, showing in particular (besides reviewing the issue of its duality invariance) that W has the properties of a Liapunov's function, which implies that its extrema (associated with the horizon of extremal black holes) are asymptotically stable equilibrium points of the corresponding first order dynamical system (in the sense of Liapunov). Moreover, we show that the fake superpotential W has, along the entire radial flow, the same flat directions which exist at the attractor point. This allows to study properties of the ADM mass also for small black holes where in fact W has no critical points at finite distance in moduli space. In particular the W function for small non-BPS black holes can always be computed analytically, unlike for the large black-hole case.Comment: 30 pages, LaTeX source. Discussion on the radial evolution of the scalar fields, in relation to the symmetries of the W-function, extended. Table 1 added. Typos correcte

Controllability and controller-observer design for a class of linear time-varying systems

“The final publication is available at Springer via http://dx.doi.org/10.1007/s10852-012-9212-6"In this paper a class of linear time-varying control systems is considered. The time variation consists of a scalar time-varying coefficient multiplying the state matrix of an otherwise time-invariant system. Under very weak assumptions of this coefficient, we show that the controllability can be assessed by an algebraic rank condition, Kalman canonical decomposition is possible, and we give a method for designing a linear state-feedback controller and Luenberger observer

THE EFFECT OF LABELING INTENSITY, ESTIMATED BY REAL-TIME CONFOCAL LASER SCANNING MICROSCOPY, ON FLOW CYTOMETRIC APPEARANCE AND IDENTIFICATION OF IMMUNOCHEMICALLY LABELED MARINE DINOFLAGELLATES

Two different fluorescein isothiocyanate (FITC) conjugates were used to analyze the effect of labeling intensity on the flow cytometric appearance of marine dinoflagellates labeled with antibodies that specifically recognized the outer cell wall. Location of the labeling was revealed by epifluorescence and real-time confocal laser scanning microscopy using an anti-rabbit IgG/FITC-conjugated secondary antiserum. Flow cytometric measurements showed that cells of Prorocentrum species labeled this way could not always be distinguished from unlabeled cells. The labeling intensity increased several times when a biotinylated anti-rabbit IgG secondary antiserum was used in combination with a streptavidin/FITC conjugate. Flow cytometry indicated that the labeling intensity had increased 50%, which resulted in an improved separation of clusters of labeled and unlabeled cells.</p