Parametric coupling between macroscopic quantum resonators

Time-dependent linear coupling between macroscopic quantum resonator modes generates both a parametric amplification also known as a {}"squeezing operation" and a beam splitter operation, analogous to quantum optical systems. These operations, when applied properly, can robustly generate entanglement and squeezing for the quantum resonator modes. Here, we present such coupling schemes between a nanomechanical resonator and a superconducting electrical resonator using applied microwave voltages as well as between two superconducting lumped-element electrical resonators using a r.f. SQUID-mediated tunable coupler. By calculating the logarithmic negativity of the partially transposed density matrix, we quantitatively study the entanglement generated at finite temperatures. We also show that characterization of the nanomechanical resonator state after the quantum operations can be achieved by detecting the electrical resonator only. Thus, one of the electrical resonator modes can act as a probe to measure the entanglement of the coupled systems and the degree of squeezing for the other resonator mode.Comment: 15 pages, 4 figures, submitte

Holographic multiverse and the measure problem

We discuss the duality, conjectured in earlier work, between the wave function of the multiverse and a 3D Euclidean theory on the future boundary of spacetime. In particular, we discuss the choice of the boundary metric and the relation between the UV cutoff scale xi on the boundary and the hypersurfaces Sigma on which the wave function is defined in the bulk. We propose that in the limit of xi going to 0 these hypersurfaces should be used as cutoff surfaces in the multiverse measure. Furthermore, we argue that in the inflating regions of spacetime with a slowly varying Hubble rate H the hypersurfaces Sigma are surfaces of constant comoving apparent horizon (CAH). Finally, we introduce a measure prescription (called CAH+) which appears to have no pathological features and coincides with the constant CAH cutoff in regions of slowly varying H.Comment: A minor change: the discussion of unitarity on p.9 is clarifie

Spectroscopy of Blue Stragglers and Turnoff Stars in M67 (NGC 2682)

We have analyzed high-resolution spectra of relatively cool blue stragglers and main sequence turnoff stars in the old open cluster M67 (NGC 2682). We attempt to identify blue stragglers whose spectra are least contaminated by binary effects (contamination by a binary companion or absorption by circumstellar material). These ``best'' stragglers have metallicities ([Fe/H] = -0.05) and abundance ratios of the blue stragglers are not significantly different from those of the turnoff stars. Based on arguments from hydrodynamical models of stellar collisions, we assert that the current upper limits for the lithium abundances of all blue stragglers observed in M67 (by us and others) are consistent with no mixing during the formation process, assuming pre-main sequence and main sequence depletion patterns observed for M67 main sequence stars. We discuss composition signatures that could more definitively distinguish between blue straggler formation mechanisms in open cluster stars. We confirm the spectroscopic detection of a binary companion to the straggler S 1082. From our spectra, we measure a projected rotational speed of 90+/-20 km/sec for the secondary, and find that its radial velocity varies with a peak-to-peak amplitude of ~ 25 km/sec. Because the radial velocities do not vary with a period corresponding to the partial eclipses in the system, we believe this system is currently undergoing mass transfer. In addition we present evidence that S 984 is a true blue straggler (and not an unresolved pair). If this can be proven, our detection of lithium may indicate a collisional origin.Comment: 20 pages, 4 figures, to appear in October 2000 A

Pattern selection in the absolutely unstable regime as a nonlinear eigenvalue problem: Taylor vortices in axial flow

A unique pattern selection in the absolutely unstable regime of a driven, nonlinear, open-flow system is analyzed: The spatiotemporal structures of rotationally symmetric vortices that propagate downstream in the annulus of the rotating Taylor-Couette system due to an externally imposed axial through-flow are investigated for two different axial boundary conditions at the in- and outlet. Unlike the stationary patterns in systems without through-flow the spatiotemporal structures of propagating vortices are independent of parameter history, initial conditions, and system's length. They do, however, depend on the axial boundary conditions, the driving rate of the inner cylinder and the through-flow rate. Our analysis of the amplitude equation shows that the pattern selection can be described by a nonlinear eigenvalue problem with the frequency being the eigenvalue. Approaching the border between absolute and convective instability the eigenvalue problem becomes effectively linear and the selection mechanism approaches that one of linear front propagation. PACS:47.54.+r,47.20.Ky,47.32.-y,47.20.FtComment: 15 pages (LateX-file), 8 figures (Postscript

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women

STUDY QUESTION: Can additional genetic variants for circulating anti-Müllerian hormone (AMH) levels be identified through a genome-wide association study (GWAS) meta-analysis including a large sample of premenopausal women? SUMMARY ANSWER: We identified four loci associated with AMH levels at P < 5 × 10(−8): the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 and CDCA7. WHAT IS KNOWN ALREADY: AMH is expressed by antral stage ovarian follicles in women, and variation in age-specific circulating AMH levels has been associated with disease outcomes. However, the physiological mechanisms underlying these AMH-disease associations are largely unknown. STUDY DESIGN, SIZE, DURATION: We performed a GWAS meta-analysis in which we combined summary statistics of a previous AMH GWAS with GWAS data from 3705 additional women from three different cohorts. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, we included data from 7049 premenopausal female participants of European ancestry. The median age of study participants ranged from 15.3 to 48 years across cohorts. Circulating AMH levels were measured in either serum or plasma samples using different ELISA assays. Study-specific analyses were adjusted for age at blood collection and population stratification, and summary statistics were meta-analysed using a standard error-weighted approach. Subsequently, we functionally annotated GWAS variants that reached genome-wide significance (P < 5 × 10(−8)). We also performed a gene-based GWAS, pathway analysis and linkage disequilibrium score regression and Mendelian randomization (MR) analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We identified four loci associated with AMH levels at P < 5 × 10(−8): the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 and CDCA7. The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among single nucleotide polymorphisms for AMH levels and for age at menopause (r(g) = 0.82, FDR = 0.003). Exploratory two-sample MR analyses did not support causal effects of AMH on breast cancer or polycystic ovary syndrome risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. LARGE SCALE DATA: The full AMH GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/). LIMITATIONS, REASONS FOR CAUTION: Whilst this study doubled the sample size of the most recent GWAS, the statistical power is still relatively low. As a result, we may still lack power to identify more genetic variants for AMH and to determine causal effects of AMH on, for example, breast cancer. Also, follow-up studies are needed to investigate whether the signal for the AMH gene is caused by reduced AMH detection by certain assays instead of actual lower circulating AMH levels. WIDER IMPLICATIONS OF THE FINDINGS: Genes mapped to the MCM8, TEX41 and CDCA7 loci are involved in the cell cycle and processes such as DNA replication and apoptosis. The mechanism underlying their associations with AMH may affect the size of the ovarian follicle pool. Altogether, our results provide more insight into the biology of AMH and, accordingly, the biological processes involved in ovarian ageing. STUDY FUNDING/COMPETING INTEREST(S): Nurses’ Health Study and Nurses’ Health Study II were supported by research grants from the National Institutes of Health (CA172726, CA186107, CA50385, CA87969, CA49449, CA67262, CA178949). The UK Medical Research Council and Wellcome (217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the listed authors, who will serve as guarantors for the contents of this article. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). Funding for the collection of genotype and phenotype data used here was provided by the British Heart Foundation (SP/07/008/24066), Wellcome (WT092830M and WT08806) and UK Medical Research Council (G1001357). M.C.B., A.L.G.S. and D.A.L. work in a unit that is funded by the University of Bristol and UK Medical Research Council (MC_UU_00011/6). M.C.B.’s contribution to this work was funded by a UK Medical Research Council Skills Development Fellowship (MR/P014054/1) and D.A.L. is a National Institute of Health Research Senior Investigator (NF-0616-10102). A.L.G.S. was supported by the study of Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases (H2020-SC1-2019-Single-Stage-RTD, project ID 874739). The Doetinchem Cohort Study was financially supported by the Ministry of Health, Welfare and Sports of the Netherlands. The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Ansh Labs performed the AMH measurements for the Doetinchem Cohort Study free of charge. Ansh Labs was not involved in the data analysis, interpretation or reporting, nor was it financially involved in any aspect of the study. R.M.G.V. was funded by the Honours Track of MSc Epidemiology, University Medical Center Utrecht with a grant from the Netherlands Organization for Scientific Research (NWO) (022.005.021). The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) (U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The SWAN Genomic Analyses and SWAN Legacy have grant support from the NIA (U01AG017719). The Generations Study was funded by Breast Cancer Now and the Institute of Cancer Research (ICR). The ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent official views of the funders. The Sister Study was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (Z01-ES044005 to D.P.S.); the AMH assays were supported by the Avon Foundation (02-2012-065 to H.B. Nichols and D.P.S.). The breast cancer genome-wide association analyses were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie, de la Science et de l’Innovation du Québec’ through Genome Québec and grant PSR-SIIRI-701, The National Institutes of Health (U19 CA148065, X01HG007492), Cancer Research UK (C1287/A10118, C1287/A16563, C1287/A10710) and The European Union (HEALTH-F2-2009-223175 and H2020 633784 and 634935). All studies and funders are listed in Michailidou et al. (Nature, 2017). F.J.M.B. has received fees and grant support from Merck Serono and Ferring BV. D.A.L. has received financial support from several national and international government and charitable funders as well as from Medtronic Ltd and Roche Diagnostics for research that is unrelated to this study. N.S. is scientific consultant for Ansh Laboratories. The other authors declare no competing interests

Boldness by habituation and social interactions: a model

Most studies of animal personality attribute personality to genetic traits. But a recent study by Magnhagen and Staffan (Behav Ecol Sociobiol 57:295–303, 2005) on young perch in small groups showed that boldness, a central personality trait, is also shaped by social interactions and by previous experience. The authors measured boldness by recording the duration that an individual spent near a predator and the speed with which it fed there. They found that duration near the predator increased over time and was higher the higher the average boldness of other group members. In addition, the feeding rate of shy individuals was reduced if other members of the same group were bold. The authors supposed that these behavioral dynamics were caused by genetic differences, social interactions, and habituation to the predator. However, they did not quantify exactly how this could happen. In the present study, we therefore use an agent-based model to investigate whether these three factors may explain the empirical findings. We choose an agent-based model because this type of model is especially suited to study the relation between behavior at an individual level and behavioral dynamics at a group level. In our model, individuals were either hiding in vegetation or feeding near a predator, whereby their behavior was affected by habituation and by two social mechanisms: social facilitation to approach the predator and competition over food. We show that even if we start the model with identical individuals, these three mechanisms were sufficient to reproduce the behavioral dynamics of the empirical study, including the consistent differences among individuals. Moreover, if we start the model with individuals that already differ in boldness, the behavioral dynamics produced remained the same. Our results indicate the importance of previous experience and social interactions when studying animal personality empirically

Convection in Binary Fluid Mixtures. II. Localized Traveling Waves. (Physical Review E, in press)

Nonlinear, spatially localized structures of traveling convection rolls are investigated in quantitative detail as a function of Rayleigh number for two different Soret coupling strengths (separation ratios) with Lewis and Prandtl numbers characterizing ethanol-water mixtures. A finite-difference method was used to solve the full hydrodynamic field equations numerically. Structure and dynamics of these localized traveling waves (LTW) are dominated by the concentration field. Like in the spatially extended convective states ( cf. accompanying paper), the Soret-induced concentration variations strongly influence, via density changes, the buoyancy forces that drive convection. The spatio-temporal properties of this feed-back mechanism, involving boundary layers and concentration plumes, show that LTW's are strongly nonlinear states. Light intensity distributions are determined that can be observed in side-view shadowgraphs. Detailed analyses of all fields are made using colour-coded isoplots, among others. In the frame comoving with their drift velocity, LTW's display a nontrivial spatio-temporal symmetry consisting of time-translation by half an oscillation period combined with vertical reflection through the horizontal midplane of the layer. A time-averaged concentration current is driven by a phase difference between the waves of concentration and vertical velocity in the bulk of the LTW state. The associated large-scale concentration redistribution stabilizes the LTW and controls its drift velocity into the quiescent fluid by generating a buoyancy-reducing concentration "barrier" ahead of the leading LTW front. The selection of the width of the LTW's is investigated and comparisons with experiments are presented.Comment: 18 pages and 6 figures as uuencoded Postscript file (using uufiles) 1 color figure as uuencoded Postscript file, a high resolution version of the color figure (about 10MB) can be requested from [email protected] or [email protected].: (Barten)present address: PSI, CH-5232 Villigen PSI, Switzerlan

Exposure to aircraft and road traffic noise and associations with heart disease and stroke in six European countries: a cross-sectional study

This work was supported by the Economic and Social Research Council (grant ES/F038763/1) with additional funding from the European Network for Noise and Health (ENNAH, EU FP7 grant number 226442)

Directed adenovirus evolution using engineered mutator viral polymerases

Adenoviruses (Ads) are the most frequently used viruses for oncolytic and gene therapy purposes. Most Ad-based vectors have been generated through rational design. Although this led to significant vector improvements, it is often hampered by an insufficient understanding of Ad’s intricate functions and interactions. Here, to evade this issue, we adopted a novel, mutator Ad polymerase-based, ‘accelerated-evolution’ approach that can serve as general method to generate or optimize adenoviral vectors. First, we site specifically substituted Ad polymerase residues located in either the nucleotide binding pocket or the exonuclease domain. This yielded several polymerase mutants that, while fully supportive of viral replication, increased Ad’s intrinsic mutation rate. Mutator activities of these mutants were revealed by performing deep sequencing on pools of replicated viruses. The strongest identified mutators carried replacements of residues implicated in ssDNA binding at the exonuclease active site. Next, we exploited these mutators to generate the genetic diversity required for directed Ad evolution. Using this new forward genetics approach, we isolated viral mutants with improved cytolytic activity. These mutants revealed a common mutation in a splice acceptor site preceding the gene for the adenovirus death protein (ADP). Accordingly, the isolated viruses showed high and untimely expression of ADP, correlating with a severe deregulation of E3 transcript splicing