Experimental test of higher-order Laguerre–Gauss modes in the 10 m Glasgow prototype interferometer

Brownian noise of dielectric mirror coatings is expected to be one of the limiting noise sources, at the peak sensitivity, of next generation ground based interferometric gravitational wave (GW) detectors. The use of higher-order Laguerre–Gauss (LG) beams has been suggested to reduce the effect of coating thermal noise in future generations of gravitational wave detectors. In this paper we describe the first test of interferometry with higher-order LG beams in an environment similar to a full-scale gravitational wave detector. We compare the interferometric performance of higher-order LG modes and the fundamental mode beams, injected into a 10 m long suspended cavity that features a finesse of 612, a value chosen to be typical of future gravitational wave detectors. We found that the expected mode degeneracy of the injected LG3, 3 beam was resolved into a multiple peak structure, and that the cavity length control signal featured several nearby zero crossings. The break up of the mode degeneracy is due to an astigmatism (defined as |Rcy − Rcx|) of 5.25 ± 0.5 cm on one of our cavity mirrors with a radius of curvature (Rc) of 15 m. This observation agrees well with numerical simulations developed with the FINESSE software. We also report on how these higher-order mode beams respond to the misalignment and mode mismatch present in our 10 m cavity. In general we found the LG3, 3 beam to be considerably more susceptible to astigmatism and mode mismatch than a conventional fundamental mode beam. Therefore the potential application of higher-order Laguerre–Gauss beams in future gravitational wave detectors will impose much more stringent requirements on both mode matching and mirror astigmatism

On the degree of scale invariance of inflationary perturbations

Many, if not most, inflationary models predict the power-law index of the spectrum of density perturbations is close to one, though not precisely equal to one, |n-1| \sim O(0.1), implying that the spectrum of density perturbations is nearly, but not exactly, scale invariant. Some models allow n to be significantly less than one (n \sim 0.7); a spectral index significantly greater than one is more difficult to achieve. We show that n \approx 1 is a consequence of the slow-roll conditions for inflation and ``naturalness,'' and thus is a generic prediction of inflation. We discuss what is required to deviate significantly from scale invariance, and then show, by explicit construction, the existence of smooth potentials that satisfy all the conditions for successful inflation and give $n$ as large as 2.Comment: 7 pages, 2 figures, submitted to Phys. Rev.

Cosmic Microwave Background Anisotropy with Cosine-Type Quintessence

We study the Cosmic Microwave Background (CMB) anisotropies produced by cosine-type quintessence models. In our analysis, effects of the adiabatic and isocurvature fluctuations are both taken into account. For purely adiabatic fluctuations with scale invariant spectrum, we obtain a stringent constraint on the model parameters using the CMB data from COBE, BOOMERanG and MAXIMA. Furthermore, it is shown that isocurvature fluctuations have significant effects on the CMB angular power spectrum at low multipoles in some parameter space, which may be detectable in future satellite experiments. Such a signal may be used to test the cosine-type quintessence models.Comment: 21 pages, 9 figure

Sociological variety and the transmission efficiency of Mycobacterium tuberculosis: a secondary analysis of qualitative and quantitative data from 15 communities in Zambia

Objectives: Selected Zambian communities formed part of a cluster randomised trial: the Zambia and South Africa TB and AIDS Reduction study (ZAMSTAR). There was wide variability in the prevalence of Mycobacterium tuberculosis infection and tuberculosis (TB) disease across these communities. We sought to clarify whether specific communities could have been more/less vulnerable to M. tuberculosis transmission as a result of sociological variety relevant to transmission efficiency. Design: We conducted a mixed methods secondary analysis using existing data sets. First, we analysed qualitative data to categorise and synthesise patterns of socio-spatial engagement across communities. Second, we compared emergent sociological variables with a measure of transmission efficiency: the ratio of the annual risk of infection to TB prevalence. Setting: ZAMSTAR communities in urban and peri-urban Zambia, spanning five provinces. Participants Fifteen communities, each served by a health facility offering TB treatment to a population of at least 25 000. TB notification rates were at least 400 per 100 000 per annum and HIV seroprevalence was estimated to be high. Results: Crowding, movement, livelihoods and participation in recreational activity differed across communities. Based on 12 socio-spatial indicators, communities were qualitatively classified as more/less spatially crowded and as more/less socially ‘open’ to contact with others, with implications for the presumptive risk of M. tuberculosis transmission. For example, watching video shows in poorly ventilated structures posed a presumptive risk in more socially open communities, while outdoor farming and/or fishing were particularly widespread in communities with lower transmission measures. Conclusions: A dual dynamic of ‘social permeability’ and crowding appeared relevant to disparities in M. tuberculosis transmission efficiency. To reduce transmission, certain socio-spatial aspects could be adjusted (eg, increasing ventilation on transport), while more structural aspects are less malleable (eg, reliance on public transport). We recommend integrating community level typologies with genome sequencing techniques to further explore the significance of ‘social permeability’. Trial registration number: ISRCTN36729271

Paraspeckle subnuclear bodies depend on dynamic heterodimerisation of DBHS RNA-binding proteins via their structured domains

RNA-binding proteins of the DBHS (Drosophila Behavior Human Splicing) family, NONO, SFPQ, and PSPC1 have numerous roles in genome stability and transcriptional and posttranscriptional regulation. Critical to DBHS activity is their recruitment to distinct subnuclear locations, for example, paraspeckle condensates, where DBHS proteins bind to the long noncoding RNA NEAT1 in the first essential step in paraspeckle formation. To carry out their diverse roles, DBHS proteins form homodimers and heterodimers, but how this dimerization influences DBHS localization and function is unknown. Here, we present an inducible GFP-NONO stable cell line and use it for live-cell 3D-structured illumination microscopy, revealing paraspeckles with dynamic, twisted elongated structures. Using siRNA knockdowns, we show these labeled paraspeckles consist of GFP-NONO/endogenous SFPQ dimers and that GFP-NONO localization to paraspeckles depends on endogenous SFPQ. Using purified proteins, we confirm that partner swapping between NONO and SFPQ occurs readily in vitro. Crystallographic analysis of the NONOSFPQ heterodimer reveals conformational differences to the other DBHS dimer structures, which may contribute to partner preference, RNA specificity, and subnuclear localization. Thus overall, our study suggests heterodimer partner availability is crucial for NONO subnuclear distribution and helps explain the complexity of both DBHS protein and paraspeckle dynamics through imaging and structural approaches.Pei Wen Lee, Andrew C. Marshall, Gavin J. Knott, Simon Kobelke, Luciano Martelotto, Ellie Cho, Paul J. McMillan, Mihwa Lee, Charles S. Bond, and Archa H. Fo

Hubble expansion and structure formation in the "running FLRW model" of the cosmic evolution

A new class of FLRW cosmological models with time-evolving fundamental parameters should emerge naturally from a description of the expansion of the universe based on the first principles of quantum field theory and string theory. Within this general paradigm, one expects that both the gravitational Newton's coupling, G, and the cosmological term, Lambda, should not be strictly constant but appear rather as smooth functions of the Hubble rate. This scenario ("running FLRW model") predicts, in a natural way, the existence of dynamical dark energy without invoking the participation of extraneous scalar fields. In this paper, we perform a detailed study of these models in the light of the latest cosmological data, which serves to illustrate the phenomenological viability of the new dark energy paradigm as a serious alternative to the traditional scalar field approaches. By performing a joint likelihood analysis of the recent SNIa data, the CMB shift parameter, and the BAOs traced by the Sloan Digital Sky Survey, we put tight constraints on the main cosmological parameters. Furthermore, we derive the theoretically predicted dark-matter halo mass function and the corresponding redshift distribution of cluster-size halos for the "running" models studied. Despite the fact that these models closely reproduce the standard LCDM Hubble expansion, their normalization of the perturbation's power-spectrum varies, imposing, in many cases, a significantly different cluster-size halo redshift distribution. This fact indicates that it should be relatively easy to distinguish between the "running" models and the LCDM cosmology using realistic future X-ray and Sunyaev-Zeldovich cluster surveys.Comment: Version published in JCAP 08 (2011) 007: 1+41 pages, 6 Figures, 1 Table. Typos corrected. Extended discussion on the computation of the linearly extrapolated density threshold above which structures collapse in time-varying vacuum models. One appendix, a few references and one figure adde

Linking NHS data for pediatric pharmacovigilance: Results of a Delphi survey

Background: Adverse drug events are a major cause of patient safety incidents. Current systems of pharmacovigilance under-report adverse drug reactions (ADRs), especially in children, leading to delays in their identification. This is of particular concern, as children especially have an increased vulnerability toADRs. Objectives: The objective was to seek consensus among healthcare professionals (HCPs) about barriers and facilitators to the linkage of routinely collected health data for pediatric pharmacovigilance in Scotland. Methods: A Delphi survey was conducted with a random sample of HCPs including nurses, pharmacists and doctors, working in primary or secondary care, in Scotland. Participants were identified from sampling frames of the target professionals such as an NHS workforce list for general practitioners and recruited by postal invitation. A total of 819 HCPs were invited to take part. Those agreeing to participate were given the option of completing the questionnaires online or as hard copy. Reminders were sent twice at a fortnightly interval. Questions content included description of professional role as well as testing for the willingness to support the proposed project and was informed by the Theoretical Domains Framework of Behavior Change (TDF) and earlier qualitative work. Three Delphi rounds were administered, including a first round for item generation. Results: 121 of those invited agreed to take part (15%). The first round of the Delphi study included 21 open questions and generated over a 1000 individual statements from 61 participants that returned the questionnaires (50.4%). These were rationalized to 149 items for the second round in which participants rated their views on the importance (or not) of each item on a 9-point Likert scale (strongly disagree - strongly agree). After the third round, there was consensus on items that focused on professional standards, and practical requirements, overall there was support for data linkage and a multi-professional approach. Conclusions: It would be acceptable to stakeholders to introduce a data linkage system for pharmacovigilance as long as identified concerns are addressed. Concerns included adherence to current professional, legal and ethical standards, as well resolving practical issues

Constraints from Inflation on Scalar-Tensor Gravity Theories

We show how observations of the perturbation spectra produced during inflation may be used to constrain the parameters of general scalar-tensor theories of gravity, which include both an inflaton and dilaton field. An interesting feature of these models is the possibility that the curvature perturbations on super-horizon scales may not be constant due to non-adiabatic perturbations of the two fields. Within a given model, the tilt and relative amplitude of the scalar and tensor perturbation spectra gives constraints on the parameters of the gravity theory, which may be comparable with those from primordial nucleosynthesis and post-Newtonian experiments.Comment: LaTeX (with RevTex) 19 pages, 8 uuencoded figures appended, also available on WWW via http://star.maps.susx.ac.uk/index.htm

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major

Background The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip. Objectives In this study, co-crystallography experiments with recombinant B. pseudomallei Mip (BpMip) protein and Mip inhibitors, biochemical analysis and computational modelling were used to predict the efficacy of lead compounds for broad-spectrum activity against other pathogens. Methods Binding activity of three lead compounds targeting BpMip was verified using surface plasmon resonance spectroscopy. The determination of crystal structures of BpMip in complex with these compounds, together with molecular modelling and in vitro assays, was used to determine whether the compounds have broad-spectrum antimicrobial activity against pathogens. Results Of the three lead small-molecule compounds, two were effective in inhibiting the PPIase activity of Mip proteins from Neisseria meningitidis, Klebsiella pneumoniae and Leishmania major. The compounds also reduced the intracellular burden of these pathogens using in vitro cell infection assays. Conclusions These results indicate that Mip is a novel antivirulence target that can be inhibited using small-molecule compounds that prove to be promising broad-spectrum drug candidates in vitro. Further optimization of compounds is required for in vivo evaluation and future clinical applications