Phase-slip induced dissipation in an atomic Bose-Hubbard system

Phase slips play a primary role in dissipation across a wide spectrum of bosonic systems, from determining the critical velocity of superfluid helium to generating resistance in thin superconducting wires. This subject has also inspired much technological interest, largely motivated by applications involving nanoscale superconducting circuit elements, e.g., standards based on quantum phase-slip junctions. While phase slips caused by thermal fluctuations at high temperatures are well understood, controversy remains over the role of phase slips in small-scale superconductors. In solids, problems such as uncontrolled noise sources and disorder complicate the study and application of phase slips. Here we show that phase slips can lead to dissipation for a clean and well-characterized Bose-Hubbard (BH) system by experimentally studying transport using ultra-cold atoms trapped in an optical lattice. In contrast to previous work, we explore a low velocity regime described by the 3D BH model which is not affected by instabilities, and we measure the effect of temperature on the dissipation strength. We show that the damping rate of atomic motion-the analogue of electrical resistance in a solid-in the confining parabolic potential fits well to a model that includes finite damping at zero temperature. The low-temperature behaviour is consistent with the theory of quantum tunnelling of phase slips, while at higher temperatures a cross-over consistent with the transition to thermal activation of phase slips is evident. Motion-induced features reminiscent of vortices and vortex rings associated with phase slips are also observed in time-of-flight imaging.Comment: published in Nature 453, 76 (2008

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

In Scotland, a national HPV immunisation programme began in 2008 for 12-13 year olds, with a catch-up campaign from 2008-2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.  We analysed colposcopy data from a cohort of women born between 1988-1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012.  By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1) (RR 0.71, 95% CI 0.58 to 0.87, p=0.0008), CIN 2 (RR 0.5, 95% CI 0.4, 0.63, p<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58, p< 0.0001) for women who received 3 doses of vaccine compared with unvaccinated women.  To our knowledge, this is one of the first studies to show a reduction of low and high grade cervical intraepithelial neoplasia associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake

Histological evidence for a supraspinous ligament in sauropod dinosaurs

Supraspinous ossified rods have been reported in the sacra of some derived sauropod dinosaurs. Although different hypotheses have been proposed to explain the origin ofthis structure, histological evidence has never been provided to support or reject any of them. In order to establish its origin, we analyse and characterize the microstructure of thesupraspinous rod of two sauropod dinosaurs from the Upper Cretaceous of Argentina. The supraspinous ossified rod is almost entirely formed by dense Haversian bone. Remains ofprimary bone consist entirely of an avascular tissue composed of two types of fibre-like structures, which are coarse and longitudinally (parallel to the main axis of the element) oriented. These structures are differentiated on the basis of their optical properties under polarized light. Very thin fibrous strands are also observed in some regions. These small fibres are all oriented parallel to one another but perpendicular to the element main axis. Histological features of the primary bone tissue indicate that the sacral supraspinous rod corresponds to an ossified supraspinous ligament. The formation of this structure appears to have been a non-pathological metaplastic ossification, possibly induced by the continuous tensile forces applied to the element.Fil: Cerda, Ignacio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia ; ArgentinaFil: Ibiricu, Lucio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentin

Retaining young people in a longitudinal sexual health survey: a trial of strategies to maintain participation

Background: There is an increasing trend towards lower participation in questionnaire surveys. This reduces representativeness, increases costs and introduces particular challenges to longitudinal surveys, as researchers have to use complex statistical techniques which attempt to address attrition. This paper describes a trial of incentives to retain longitudinal survey cohorts from ages 16 to 20, to question them on the sensitive topic of sexual health.Methods: A longitudinal survey was conducted with 8,430 eligible pupils from two sequential year groups from 25 Scottish schools. Wave 1 (14 years) and Wave 2 (16 years) were conducted largely within schools. For Wave 3 (18 years), when everyone had left school, the sample was split into 4 groups that were balanced across predictors of survey participation: 1) no incentive; 2) chance of winning one of twenty-five vouchers worth 20; pound 3) chance of winning one 500 pound voucher; 4) a definite reward of a 10 pound voucher sent on receipt of their completed questionnaire. Outcomes were participation at Wave 3 and two years later at Wave 4. Analysis used logistic regression and adjusted for clustering at school level.Results: The only condition that had a significant and beneficial impact for pupils was to offer a definite reward for participation (Group 4). Forty-one percent of Group 4 participated in Wave 3 versus 27% or less for Groups 1 to 3. At Wave 4, 35% of Group 4 took part versus 25% or less for the other groups. Similarly, 22% of Group 4 participated in all four Waves of the longitudinal study, whereas for the other three groups it was 16% or less that participated in full.Conclusions: The best strategy for retaining all groups of pupils and one that improved retention at both age 18 and age 20 was to offer a definite reward for participation. This is expensive, however, given the many benefits of retaining a longitudinal sample, we recommend inclusion of this as a research cost for cohort and other repeat-contact studies

Neurotrophic requirements of human motor neurons defined using amplified and purified stem-cell derived cultures

Neurotrophic requirements of human motor neurons defined using amplified and purified stem-cell derived culturesHuman motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK) inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC(50) 1-2 pM). The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.This work was funded by Project A.L.S., P2ALS and NYSTEM grant number CO24415. The work of N.J.L. was supported by the Portuguese Foundation for Science and Technology SFRH/BD/33421/2008 and the Luso-American Development Foundation. B.J.-K. was supported by the National Institute of Neurological Disorders and Stroke (NINDS). L.R. was supported by the Swedish Brain Foundation/Hjarnfonden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Undular tidal bores: Effect of channel constriction and bridge piers

A tidal bore may occur in a macro-tidal estuary when the tidal range exceeds 4.5-6 m and the estuary bathymetry amplifies the tidal wave. Its upstream propagation induces a strong mixing of the estuarine waters. The propagation of undular tidal bores was investigated herein to study the effect of bridge piers on the bore propagation and characteristics. Both the tidal bore profile and the turbulence generated by the bore were recorded. The free-surface undulation profiles exhibited a quasi-periodic shape, and the potential energy of the undulations represented up to 30% of the potential energy of the tidal bore. The presence of the channel constriction had a major impact on the free-surface properties. The undular tidal bore lost nearly one third of its potential energy per surface area as it propagated through the channel constriction. The detailed instantaneous velocity measurements showed a marked effect of the tidal bore passage suggesting the upstream advection of energetic events and vorticity "clouds" behind the bore front in both channel configurations: prismatic and with constriction. The turbulence patches were linked to some secondary motions and the proposed mechanisms were consistent with some field observations in the Daly River tidal bore. The findings emphasise the strong mixing induced by the tidal bore processes, and the impact of bridge structures on the phenomenon. © 2010 Springer Science+Business Media B.V

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well

FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis

Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci) to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ

Aptamers for respiratory syncytial virus detection.

The identification of the infectious agents is pivotal for appropriate care of patients with viral diseases. Current viral diagnostics rely on selective detection of viral nucleic acid or protein components. In general, detection of proteins rather than nucleic acids is technically more suitable for rapid tests. However, protein-based virus identification methods depend on antibodies limiting the practical applicability of these approaches. Aptamers rival antibodies in target selectivity and binding affinity, and excel in terms of robustness and cost of synthesis. Although aptamers have been generated for virus identification in laboratory settings, their introduction into routine virus diagnostics has not been realized, yet. Here, we demonstrate that the rationally designed SELEX protocol can be applied on whole virus to select aptamers, which can potentially be applied for viral diagnostics. This approach does not require purified virus protein or complicated virus purification. The presented data also illustrate that corroborating the functionality of aptamers with various approaches is essential to pinpoint the most appropriate aptamer amongst the panel of candidates obtained by the selection. Our protocol yielded aptamers capable of detecting respiratory syncytial virus (RSV), an important pathogen causing severe disease especially in young infants, at clinically relevant concentrations in complex matrices