Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq).

Next-generation sequencing has enabled the genome-wide identification of human DNA replication origins. However, different approaches to mapping replication origins, namely (i) sequencing isolated small nascent DNA strands (SNS-seq); (ii) sequencing replication bubbles (bubble-seq) and (iii) sequencing Okazaki fragments (OK-seq), show only limited concordance. To address this controversy, we describe here an independent high-resolution origin mapping technique that we call initiation site sequencing (ini-seq). In this approach, newly replicated DNA is directly labelled with digoxigenin-dUTP near the sites of its initiation in a cell-free system. The labelled DNA is then immunoprecipitated and genomic locations are determined by DNA sequencing. Using this technique we identify >25,000 discrete origin sites at sub-kilobase resolution on the human genome, with high concordance between biological replicates. Most activated origins identified by ini-seq are found at transcriptional start sites and contain G-quadruplex (G4) motifs. They tend to cluster in early-replicating domains, providing a correlation between early replication timing and local density of activated origins. Origins identified by ini-seq show highest concordance with sites identified by SNS-seq, followed by OK-seq and bubble-seq. Furthermore, germline origins identified by positive nucleotide distribution skew jumps overlap with origins identified by ini-seq and OK-seq more frequently and more specifically than do sites identified by either SNS-seq or bubble-seq.Francis Crick Institute, which receives its core funding from Cancer Research UK [FC001-157]; Medical Research Council [FC001-157]; Wellcome Trust [FC001-157]; National Institute for Health Research; Biotechnology and Biological Sciences Research Council [BB/K013378/1]This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/nar/gkw76

The GEO600 squeezed light source

The next upgrade of the GEO600 gravitational wave detector is scheduled for 2010 and will, in particular, involve the implementation of squeezed light. The required non-classical light source is assembled on a 1.5m^2 breadboard and includes a full coherent control system and a diagnostic balanced homodyne detector. Here, we present the first experimental characterization of this setup as well as a detailed description of its optical layout. A squeezed quantum noise of up to 9dB below the shot-noise level was observed in the detection band between 10Hz and 10kHz. We also present an analysis of the optical loss in our experiment and provide an estimation of the possible non-classical sensitivity improvement of the future squeezed light enhanced GEO600 detector.Comment: 8 pages, 4 figure

Phase shift experiments identifying Kramers doublets in a chaotic superconducting microwave billiard of threefold symmetry

The spectral properties of a two-dimensional microwave billiard showing threefold symmetry have been studied with a new experimental technique. This method is based on the behavior of the eigenmodes under variation of a phase shift between two input channels, which strongly depends on the symmetries of the eigenfunctions. Thereby a complete set of 108 Kramers doublets has been identified by a simple and purely experimental method. This set clearly shows Gaussian unitary ensemble statistics, although the system is time-reversal invariant.Comment: RevTex 4, 5 figure

First Experimental Evidence for Chaos-Assisted Tunneling in a Microwave Annular Billiard

We report on first experimental signatures for chaos-assisted tunneling in a two-dimensional annular billiard. Measurements of microwave spectra from a superconducting cavity with high frequency resolution are combined with electromagnetic field distributions experimentally determined from a normal conducting twin cavity with high spatial resolution to resolve eigenmodes with properly identified quantum numbers. Distributions of so-called quasi-doublet splittings serve as basic observables for the tunneling between whispering gallery type modes localized to congruent, but distinct tori which are coupled weakly to irregular eigenstates associated with the chaotic region in phase space.Comment: 5 pages RevTex, 5 low-resolution figures (high-resolution figures: http://linac.ikp.physik.tu-darmstadt.de/heiko/chaospub.html, to be published in Phys. Rev. Let

GEO 600 and the GEO-HF upgrade program: successes and challenges

The German-British laser-interferometric gravitational wave detector GEO 600 is in its 14th year of operation since its first lock in 2001. After GEO 600 participated in science runs with other first-generation detectors, a program known as GEO-HF began in 2009. The goal was to improve the detector sensitivity at high frequencies, around 1 kHz and above, with technologically advanced yet minimally invasive upgrades. Simultaneously, the detector would record science quality data in between commissioning activities. As of early 2014, all of the planned upgrades have been carried out and sensitivity improvements of up to a factor of four at the high-frequency end of the observation band have been achieved. Besides science data collection, an experimental program is ongoing with the goal to further improve the sensitivity and evaluate future detector technologies. We summarize the results of the GEO-HF program to date and discuss its successes and challenges

Experimental Test of a Trace Formula for a Chaotic Three Dimensional Microwave Cavity

We have measured resonance spectra in a superconducting microwave cavity with the shape of a three-dimensional generalized Bunimovich stadium billiard and analyzed their spectral fluctuation properties. The experimental length spectrum exhibits contributions from periodic orbits of non-generic modes and from unstable periodic orbit of the underlying classical system. It is well reproduced by our theoretical calculations based on the trace formula derived by Balian and Duplantier for chaotic electromagnetic cavities.Comment: 4 pages, 5 figures (reduced quality

Design of a speed meter interferometer proof-of-principle experiment

The second generation of large scale interferometric gravitational wave detectors will be limited by quantum noise over a wide frequency range in their detection band. Further sensitivity improvements for future upgrades or new detectors beyond the second generation motivate the development of measurement schemes to mitigate the impact of quantum noise in these instruments. Two strands of development are being pursued to reach this goal, focusing both on modifications of the well-established Michelson detector configuration and development of different detector topologies. In this paper, we present the design of the world's first Sagnac speed meter interferometer which is currently being constructed at the University of Glasgow. With this proof-of-principle experiment we aim to demonstrate the theoretically predicted lower quantum noise in a Sagnac interferometer compared to an equivalent Michelson interferometer, to qualify Sagnac speed meters for further research towards an implementation in a future generation large scale gravitational wave detector, such as the planned Einstein Telescope observatory.Comment: Revised version: 16 pages, 6 figure

Modeling Complex Nuclear Spectra - Regularity versus Chaos

A statistical analysis of the spectrum of two particle - two hole doorway states in a finite nucleus is performed. On the unperturbed mean-field level sizable attractive correlations are present in such a spectrum. Including particle-hole rescattering effects via the residual interaction introduces repulsive dynamical correlations which generate the fluctuation properties characteristic of the Gaussian Orthogonal Ensemble. This signals that the underlying dynamics becomes chaotic. This feature turns out to be independent of the detailed form of the residual interaction and hence reflects the generic nature of the fluctuations studied.Comment: 8 pages of text (LATEX), figures (not included, available from the authors), Feb 9