QuickXsort: Efficient Sorting with n log n - 1.399n +o(n) Comparisons on Average

In this paper we generalize the idea of QuickHeapsort leading to the notion of QuickXsort. Given some external sorting algorithm X, QuickXsort yields an internal sorting algorithm if X satisfies certain natural conditions. With QuickWeakHeapsort and QuickMergesort we present two examples for the QuickXsort-construction. Both are efficient algorithms that incur approximately n log n - 1.26n +o(n) comparisons on the average. A worst case of n log n + O(n) comparisons can be achieved without significantly affecting the average case. Furthermore, we describe an implementation of MergeInsertion for small n. Taking MergeInsertion as a base case for QuickMergesort, we establish a worst-case efficient sorting algorithm calling for n log n - 1.3999n + o(n) comparisons on average. QuickMergesort with constant size base cases shows the best performance on practical inputs: when sorting integers it is slower by only 15% to STL-Introsort

LARES/WEBER-SAT and the equivalence principle

It has often been claimed that the proposed Earth artificial satellite LARES/WEBER-SAT-whose primary goal is, in fact, the measurement of the general relativistic Lense-Thirring effect at a some percent level-would allow to greatly improve, among (many) other things, the present-day (10^-13) level of accuracy in testing the equivalence principle as well. Recent claims point towards even two orders of magnitude better, i.e. 10^-15. In this note we show that such a goal is, in fact, unattainable by many orders of magnitude being, instead, the achievable level of the order of 10^-9.Comment: LaTex, 4 pages, no figures, no tables, 26 references. Proofs corrections included. To appear in EPL (Europhysics Letters

Human X chromosome inactivation and reactivation: implications for cell reprogramming and disease

X chromosome inactivation (XCI) is an exemplar of epigenetic regulation that is set up as pluripotent cells differentiate. Once established, XCI is stably propagated, but can be reversed in vivo or by pluripotent reprogramming in vitro. Although reprogramming provides a useful model for inactive X (Xi) reactivation in mouse, the relative instability and heterogeneity of human ESCs and iPSCs, hampers comparable progress in human. Here we review studies aimed at reactivating the human Xi using different reprogramming strategies. We outline our recent results using mouse ESCs to reprogram female human fibroblasts by cell-cell fusion. We show that pluripotent reprogramming induces widespread and rapid chromatin remodelling in which the human Xi loses XIST and H3K27m3 enrichment and selected Xi genes become reactivated, ahead of mitotic division. Using RNA sequencing to map the extent of human Xi reactivation, and chromatin modifying drugs to potentiate reactivation, we outline how this approach could be used to better design strategies to reexpress human X-linked loci. As cell fusion induces the expression of human pluripotency genes that represent both the 'primed' and 'naïve' states, this approach may also offer a fresh opportunity to segregate human pluripotent states with distinct Xi expression profiles, using single-cell-based approaches

Changing a semantics: opportunism or courage?

The generalized models for higher-order logics introduced by Leon Henkin, and their multiple offspring over the years, have become a standard tool in many areas of logic. Even so, discussion has persisted about their technical status, and perhaps even their conceptual legitimacy. This paper gives a systematic view of generalized model techniques, discusses what they mean in mathematical and philosophical terms, and presents a few technical themes and results about their role in algebraic representation, calibrating provability, lowering complexity, understanding fixed-point logics, and achieving set-theoretic absoluteness. We also show how thinking about Henkin's approach to semantics of logical systems in this generality can yield new results, dispelling the impression of adhocness. This paper is dedicated to Leon Henkin, a deep logician who has changed the way we all work, while also being an always open, modest, and encouraging colleague and friend.Comment: 27 pages. To appear in: The life and work of Leon Henkin: Essays on his contributions (Studies in Universal Logic) eds: Manzano, M., Sain, I. and Alonso, E., 201

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Performance of the Main Dipole Magnet Circuits of the LHC during Commissioning

During hardware commissioning of the Large Hadron Collider (LHC), 8 main dipole circuits are tested at 1.9 K and up to their nominal current. Each dipole circuit contains 154 magnets of 15 m length, and has a total stored energy of up to 1.3 GJ. All magnets are wound from Nb-Ti superconducting Rutherford cables, and contain heaters to quickly force the transition to the normal conducting state in case of a quench, and hence reduce the hot spot temperature. In this paper the performance of the first three of these circuits is presented, focussing on quench detection, heater performance, operation of the cold bypass diodes, and magnet-to-magnet quench propagation. The results as measured on the entire circuits will be compared to the test results obtained during the reception tests of the individual magnets

Performance of the Superconducting Corrector Magnet Circuits during the Commissioning of the LHC

The LHC is a complex machine requiring more than 7400 superconducting corrector magnets distributed along a circumference of 26.7 km. These magnets are powered in 1446 different electrical circuits at currents ranging from 60 A up to 600 A. Among the corrector circuits the 600 A corrector magnets form the most diverse and differentiated group. All together, about 60000 high current connections had to be made. A fault in a circuit or one of the superconducting connections would have severe consequences for the accelerator operation. All magnets are wound from various types of Nb-Ti superconducting strands, and many contain parallel protection resistors to by-pass the current still flowing in the other magnets of the same circuit when they quench. In this paper the performance of these magnet circuits is presented, focussing on the quench behaviour of the magnets. Quench detection and the performance of the electrical interconnects will be dealt with. The results as measured on the entire circuits are compared to the test results obtained at the reception of the individual magnets

Long-Term Effects of the Periconception Period on Embryo Epigenetic Profile and Phenotype: The Role of Stress and How This Effect Is Mediated

Stress represents an unavoidable aspect of human life, and pathologies associated with dysregulation of stress mechanisms - particularly psychiatric disorders - represent a significant global health problem. While it has long been observed that levels of stress experienced in the periconception period may greatly affect the offspring's risk of psychiatric disorders, the mechanisms underlying these associations are not yet comprehensively understood. In order to address this question, this chapter will take a 'top-down' approach, by first defining stress and associated concepts, before exploring the mechanistic basis of the stress response in the form of the hypothalamic-pituitary-adrenal (HPA) axis, and how dysregulation of the HPA axis can impede our mental and physical health, primarily via imbalances in glucocorticoids (GCs) and their corresponding receptors (GRs) in the brain. The current extent of knowledge pertaining to the impact of stress on developmental programming and epigenetic inheritance is then extensively discussed, including the role of chromatin remodelling associated with specific HPA axis-related genes and the possible role of regulatory RNAs as messengers of environmental stress both in the intrauterine environment and across the germ line. Furthering our understanding of the role of stress on embryonic development is crucial if we are to increase our predictive power of disease risk and devise-effective treatments and intervention strategies

Genome-scale bacterial transcriptional regulatory networks: reconstruction and integrated analysis with metabolic models

Advances in sequencing technology are resulting in the rapid emergence of large numbers of complete genome sequences. High throughput annotation and metabolic modeling of these genomes is now a reality. The high throughput reconstruction and analysis of genome-scale transcriptional regulatory networks represents the next frontier in microbial bioinformatics. The fruition of this next frontier will depend upon the integration of numerous data sources relating to mechanisms, components, and behavior of the transcriptional regulatory machinery, as well as the integration of the regulatory machinery into genome-scale cellular models. Here we review existing repositories for different types of transcriptional regulatory data, including expression data, transcription factor data, and binding site locations, and we explore how these data are being used for the reconstruction of new regulatory networks. From template network based methods to de novo reverse engineering from expression data, we discuss how regulatory networks can be reconstructed and integrated with metabolic models to improve model predictions and performance. Finally, we explore the impact these integrated models can have in simulating phenotypes, optimizing the production of compounds of interest or paving the way to a whole-cell model.J.P.F. acknowledges funding from [SFRH/BD/70824/2010] of the FCT (Portuguese Foundation for Science and Technology) PhD program. The work was supported in part by the ERDF—European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness), National Funds through the FCT within projects [FCOMP-01-0124-FEDER015079] (ToMEGIM—Computational Tools for Metabolic Engineering using Genome-scale Integrated Models) and FCOMP-01-0124-FEDER009707 (HeliSysBio—molecular Systems Biology in Helicobacter pylori), the U.S. Department of Energy under contract [DE-ACO2-06CH11357] and the National Science Foundation under [0850546]