A phylogeny-based sampling strategy and power calculator informs genome-wide associations study design for microbial pathogens

Whole genome sequencing is increasingly used to study phenotypic variation among infectious pathogens and to evaluate their relative transmissibility, virulence, and immunogenicity. To date, relatively little has been published on how and how many pathogen strains should be selected for studies associating phenotype and genotype. There are specific challenges when identifying genetic associations in bacteria which often comprise highly structured populations. Here we consider general methodological questions related to sampling and analysis focusing on clonal to moderately recombining pathogens. We propose that a matched sampling scheme constitutes an efficient study design, and provide a power calculator based on phylogenetic convergence. We demonstrate this approach by applying it to genomic datasets for two microbial pathogens: Mycobacterium tuberculosis and Campylobacter species. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0101-7) contains supplementary material, which is available to authorized users

Spin-dependent Bohm trajectories associated with an electronic transition in hydrogen

The Bohm causal theory of quantum mechanics with spin-dependence is used to determine electron trajectories when a hydrogen atom is subjected to (semi-classical) radiation. The transition between the 1s ground state and the 2p0 state is examined. It is found that transitions can be identified along Bohm trajectories. The trajectories lie on invariant hyperboloid surfaces of revolution in R^3. The energy along the trajectories is also discussed in relation to the hydrogen energy eigenvalues.Comment: 18 pages, 8 figure

Complementarity of direct detection experiments in search of light Dark Matter

Dark Matter experiments searching for Weakly interacting massive particles (WIMPs) primarily use nuclear recoils (NRs) in their attempt to detect WIMPs. Migdal-induced electronic recoils (ERs) provide additional sensitivity to light Dark Matter with $\mathcal{O}(\text{GeV}/c^2)$ masses. In this work, we use Bayesian inference to find the parameter space where future detectors like XENONnT and SuperCDMS SNOLAB will be able to detect WIMP Dark Matter through NRs, Migdal-induced ERs or a combination thereof. We identify regions where each detector is best at constraining the Dark Matter mass and spin independent cross-section and infer where two or more detection configurations are complementary to constraining these Dark Matter parameters through a combined analysis.Comment: 19 pages, 7 figure

Implications of Lorentz covariance for the guidance equation in two-slit quantum interference

It is known that Lorentz covariance fixes uniquely the current and the associated guidance law in the trajectory interpretation of quantum mechanics for spin particles. In the non-relativistic domain this implies a guidance law for the electron which differs by an additional spin-dependent term from that originally proposed by de Broglie and Bohm. In this paper we explore some of the implications of the modified guidance law. We bring out a property of mutual dependence in the particle coordinates that arises in product states, and show that the quantum potential has scalar and vector components which implies the particle is subject to a Lorentz-like force. The conditions for the classical limit and the limit of negligible spin are given, and the empirical sufficiency of the model is demonstrated. We then present a series of calculations of the trajectories based on two-dimensional Gaussian wave packets which illustrate how the additional spin-dependent term plays a significant role in structuring both the individual trajectories and the ensemble. The single packet corresponds to quantum inertial motion. The distinct features encountered when the wavefunction is a product or a superposition are explored, and the trajectories that model the two-slit experiment are given. The latter paths exhibit several new characteristics compared with the original de Broglie-Bohm ones, such as crossing of the axis of symmetry.Comment: 27 pages including 6 pages of figure

Transmission analysis of a large tuberculosis outbreak in London:a mathematical modelling study using genomic data

Outbreaks of tuberculosis (TB) - such as the large isoniazid-resistant outbreak centred on London, UK, which originated in 1995 - provide excellent opportunities to model transmission of this devastating disease. Transmission chains for TB are notoriously difficult to ascertain, but mathematical modelling approaches, combined with whole-genome sequencing data, have strong potential to contribute to transmission analyses. Using such data, we aimed to reconstruct transmission histories for the outbreak using a Bayesian approach, and to use machine-learning techniques with patient-level data to identify the key covariates associated with transmission. By using our transmission reconstruction method that accounts for phylogenetic uncertainty, we are able to identify 21 transmission events with reasonable confidence, 9 of which have zero SNP distance, and a maximum distance of 3. Patient age, alcohol abuse and history of homelessness were found to be the most important predictors of being credible TB transmitters

Method of plant tissue culture and regeneration

Plants may be regenerated from stomatal cells or protoplasts of such cells. Prior to regeneration the cells or protoplasts may be genetically transformed by the introduction of hereditary material most preferably by a DNA construct which is free of genes which specify resistance to antibiotics. The regeneration step may include callus formation on a hormone-free medium. The method is particularly suitable for sugar beet

GridPix application to dual phase TPC

GridPix is a gas-filled detector with an aluminium mesh stretched 50 μm above the Timepix CMOS pixel chip. This defines a high electric field where gas amplification occurs. A feasibility study is ongoing at Nikhef for the application of the GridPix technology as a charge sensitive device in a dual phase noble gas Time Projection Chamber (TPC), within the framework of the DARWIN design study for next generation dark matter experiments. The smallness of the device and well defined materials allow for high radio-purity and low outgassing. The high granularity of a pixel readout and the high detection efficiency of single electrons of GridPix bring benefits especially in terms of energy resolution for small energy deposits. This feature is interesting also for the measurement of the scintillation yield and the ionisation yield of noble liquids. The accurate measurements of such quantities have a direct impact on the data interpretation of dark matter experiments. The application in dual phase argon or xenon TPCs implies several technological challenges, such as the survival of the device at cryogenic temperature as well as the operation in a pure noble gas atmosphere without discharges. We describe here the recent developments of the project

Timing performance of the Timepix4 front-end

A characterisation of the Timepix4 pixel front-end with a strong focus on timing performance is presented. Externally generated test pulses were used to probe the per-pixel time-to-digital converter (TDC) and measure the time-bin sizes by precisely controlling the test-pulse arrival time in steps of 10 ps. The results indicate that the TDC can achieve a time resolution of 60 ps, provided that a calibration is performed to compensate for frequency variation in the voltage controlled oscillators of the pixel TDCs. The internal clock distribution system of Timepix4 was used to control the arrival time of internally generated analog test pulses in steps of about 20 ps. The analog test pulse mechanism injects a controlled amount of charge directly into the analog front-end (AFE) of the pixel, and was used to measure the time resolution as a function of signal charge, independently of the TDC. It was shown that for the default configuration, the AFE time resolution in the hole-collecting mode is limited to 105 ps. However, this can be improved up to about 60 ps by increasing the preamplifier bias-current at the cost of increased power dissipation. For the electron-collecting mode, an AFE time resolution of 47 ps was measured for a bare Timepix4 device at a signal charge of 21 ke. It was observed that additional input capacitance from a bonded sensor reduces this figure to 62 ps

Timing measurements with a 3D silicon sensor on Timepix3 in a 180 GeV/<i>c</i> hadron beam

Test beam measurements have been carried out with a 3D sensor on a Timepix3 ASIC and the time measurements are presented. The measurements are compared to those of a thin planar sensor on Timepix3. It is shown that for a perpendicularly incident beam the time resolution of both detectors is dominated by the Timepix3 front-end. The 3D detector is dominated by the time-to-digital conversion whereas the analog front-end jitter also gives a significant contribution for the thin planar detector. The 3D detector reaches an overall time resolution of 567 ± 6 ps compared to 683 ± 8 ps for the thin planar detector. For a grazing angle beam, however, the thin planar detector achieves a better time resolution because it has a lower pixel capacitance, and therefore suffers less from jitter in the analog front-end for the low charge signals that mainly occur in this type of measurement. Finally, it is also shown that the 3D and thin planar detector can achieve time resolutions for large clusters of about 100 ps and 250 ps, respectively, by combining many single hit measurements