164 research outputs found

    Tumbleweeds and airborne gravitational noise sources for LIGO

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    Gravitational-wave detectors are sensitive not only to astrophysical gravitational waves, but also to the fluctuating Newtonian gravitational forces of moving masses in the ground and air around the detector. This paper studies the gravitational effects of density perturbations in the atmosphere, and from massive airborne objects near the detector. These effects were previously considered by Saulson; in this paper I revisit these phenomena, considering transient atmospheric shocks, and the effects of sound waves or objects colliding with the ground or buildings around the test masses. I also consider temperature perturbations advected past the detector as a source of gravitational noise. I find that the gravitational noise background is below the expected noise floor even of advanced interferometric detectors, although only by an order of magnitude for temperature perturbations carried along turbulent streamlines. I also find that transient shockwaves in the atmosphere could potentially produce large spurious signals, with signal-to-noise ratios in the hundreds in an advanced interferometric detector. These signals could be vetoed by means of acoustic sensors outside of the buildings. Massive wind-borne objects such as tumbleweeds could also produce gravitational signals with signal-to-noise ratios in the hundreds if they collide with the interferometer buildings, so it may be necessary to build fences preventing such objects from approaching within about 30m of the test masses.Comment: 15 pages, 10 PostScript figures, uses REVTeX4.cls and epsfig.st

    Tropospheric Phase Calibration in Millimeter Interferometry

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    We review millimeter interferometric phase variations caused by variations in the precipitable water vapor content of the troposphere, and we discuss techniques proposed to correct for these variations. We present observations with the Very Large Array at 22 GHz and 43 GHz designed to test these techniques. We find that both the Fast Switching and Paired Array calibration techniques are effective at reducing tropospheric phase noise for radio interferometers. In both cases, the residual rms phase fluctuations after correction are independent of baseline length for b > b_{eff}. These techniques allow for diffraction limited imaging of faint sources on arbitrarily long baselines at mm wavelengths. We consider the technique of tropospheric phase correction using a measurement of the precipitable water vapor content of the troposphere via a radiometric measurement of the brightness temperature of the atmosphere. Required sensitivities range from 20 mK at 90 GHz to 1 K at 185 GHz for the MMA, and 120 mK for the VLA at 22 GHz. The minimum gain stability requirement is 200 at 185 GHz at the MMA assuming that the astronomical receivers are used for radiometry. This increases to 2000 for an uncooled system. The stability requirement is 450 for the cooled system at the VLA at 22 GHz. To perform absolute radiometric phase corrections also requires knowledge of the tropospheric parameters and models to an accuracy of a few percent. It may be possible to perform an `empirically calibrated' radiometric phase correction, in which the relationship between fluctuations in brightness temperature differences with fluctuations in interferometric phases is calibrated by observing a celestial calibrator at regular intervals.Comment: AAS LATEX preprint format. to appear in Radio Science 199

    A New Strategy for Deep Wide-Field High Resolution Optical Imaging

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    We propose a new strategy for obtaining enhanced resolution (FWHM = 0.12 arcsec) deep optical images over a wide field of view. As is well known, this type of image quality can be obtained in principle simply by fast guiding on a small (D = 1.5m) telescope at a good site, but only for target objects which lie within a limited angular distance of a suitably bright guide star. For high altitude turbulence this 'isokinetic angle' is approximately 1 arcminute. With a 1 degree field say one would need to track and correct the motions of thousands of isokinetic patches, yet there are typically too few sufficiently bright guide stars to provide the necessary guiding information. Our proposed solution to these problems has two novel features. The first is to use orthogonal transfer charge-coupled device (OTCCD) technology to effectively implement a wide field 'rubber focal plane' detector composed of an array of cells which can be guided independently. The second is to combine measured motions of a set of guide stars made with an array of telescopes to provide the extra information needed to fully determine the deflection field. We discuss the performance, feasibility and design constraints on a system which would provide the collecting area equivalent to a single 9m telescope, a 1 degree square field and 0.12 arcsec FWHM image quality.Comment: 46 pages, 22 figures, submitted to PASP, a version with higher resolution images and other supplementary material can be found at http://www.ifa.hawaii.edu/~kaiser/wfhr

    The Impact of Atmospheric Fluctuations on Degree-scale Imaging of the Cosmic Microwave Background

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    Fluctuations in the brightness of the Earth's atmosphere originating from water vapor are an important source of noise for ground-based instruments attempting to measure anisotropy in the Cosmic Microwave Background. This paper presents a model for the atmospheric fluctuations and derives simple expressions to predict the contribution of the atmosphere to experimental measurements. Data from the South Pole and from the Atacama Desert in Chile, two of the driest places on Earth, are used to assess the level of fluctuations at each site.Comment: 29 pages, 7 figures, 1 table, appears in The Astrophysical Journa

    Formulation of hydrophobic peptides for skin delivery via coated microneedles

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    Microneedles (MNs) have been investigated as a minimally-invasive delivery technology for a range of active pharmaceutical ingredients (APIs). Various formulations and methods for coating the surface of MNs with therapeutics have been proposed and exemplified, predominantly for hydrophilic drugs and particulates. The development of effective MN delivery formulations for hydrophobic drugs is more challenging with dosing restrictions and the use of organic solvents impacting on both the bioactivity and the kinetics of drug release. In this study we propose a novel formulation that is suitable for MN coating of hydrophobic auto-antigen peptides currently being investigated for antigen specific immunotherapy (ASI) of type 1 diabetes. The formulation, comprising three co-solvents (water, 2-methyl-2-butanol and acetic acid) and polyvinylalcohol 2000 (PVA2000) can dissolve both hydrophilic and hydrophobic peptide auto-antigens at relatively high, and clinically relevant, concentrations (25 mg/ml or 12.5 mg/ml). The drug:excipient ratio is restricted to 10:1 w/w to maximise dose whilst ensuring that the dry-coated payload does not significantly impact on MN skin penetration performance. The coating formulation and process does not adversely affect the biological activity of the peptide. The delivery efficiency of the coated peptide into skin is influenced by a number of parameters. Electropolishing the metal MN surface increases delivery efficiency from 2.0 ± 1.0% to 59.9 ± 6.7%. An increased mass of peptide formulation per needle, from 0.37 μg to 2 μg peptide dose, resulted in a thicker coating and a 20% reduction in the efficiency of skin delivery. Other important performance parameters for coated MNs include the role of excipients in assisting dissolution from the MNs, the intrinsic hydrophobicity of the peptide and the species of skin model used in laboratory studies. This study therefore both exemplifies the potential of a novel formulation for coating hydrophobic and hydrophilic peptides onto MN devices and provides new insight into the factors that influence delivery efficiency from coated MNs. Importantly, the results provide guidance for identifying critical attributes of the formulation, coating process and delivery device, that confer reproducible and effective delivery from coated MNs, and thus contribute to the requirements of the regulators appraising these devices

    Observing Conditions at Mt.Graham: VATT UBVR Sky Surface Brightness and Seeing Measurements from 1999 through 2003

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    We present measurements of sky surface brightness and seeing on Mt.Graham obtained at the Vatican Advanced Technology Telescope (VATT) during 16 observing runs between April 1999 and December 2003. We show that the sky surface brightness is significantly darker during photometric conditions, and can be highly variable over the course of a single observing run as well as from one run to the next, regardless of photometricity. In our photometric observations we find an average low-airmass (sec z < 1.2) sky surface brightness of 22.00, 22.53, 21.49, and 20.88 mag arcsec^-2 in U, B, V, and R, respectively. The darkest run (02/00 in U and 02/01 in BVR) had an average sky surface brightness of 22.38, 22.86, 21.72, and 21.19 mag arcsec^-2 in U, B, V, and R, respectively. With these results we show that under the best conditions, Mt. Graham can compete with the darkest sites in Hawaii and Chile, thanks in part to the strict dark-sky ordinances in place in Tucson and Safford. We expect the sky over Mt. Graham to be even darker than our 1999--2003 results during solar minimum (2006--2007). We find a significant improvement of about 0.45 arcsec in our measured stellar FWHM after improvements to the telescope were made in Summer and Fall 2001. Stellar FWHM values are highly variable, with median R-band focus FWHM values in each observing run ranging from 0.97 arcsec to 2.15 arcsec. Significantly sub-arcsecond seeing was occasionally achieved with values as low as 0.65 arcsec FWHM in R. There may possibly still be a significant telescope contribution to the seeing at the VATT, but nearby trees as high as the dome are currently the dominant factor.Comment: 22 pages, 11 figures, to appear in PAS

    Editorial

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    Models and methods to characterise levonorgestrel release from intradermally administered contraceptives

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    Microneedle (MN)-based technologies have been proposed as a means to facilitate minimally invasive sustained delivery of long-acting hormonal contraceptives into the skin. Intradermal administration is a new route of delivery for these contraceptives and therefore no established laboratory methods or experimental models are available to predict dermal drug release and pharmacokinetics from candidate MN formulations. This study evaluates an in vitro release (IVR) medium and a medium supplemented with ex vivo human skin homogenate (SH) as potential laboratory models to investigate the dermal release characteristics of one such hormonal contraceptive that is being tested for MN delivery, levonorgestrel (LNG), and provides details of an accompanying novel two-step liquid–liquid drug extraction procedure and sensitive reversed-phase HPLC–UV assay. The extraction efficiency of LNG was 91.7 ± 3.06% from IVR medium and 84.6 ± 1.6% from the medium supplemented with SH. The HPLC–UV methodology had a limit of quantification of 0.005 µg/mL and linearity between 0.005 and 25 µg/mL. Extraction and detection methods for LNG were exemplified in both models using the well-characterised, commercially available sustained-release implant (Jadelle®). Sustained LNG release from the implant was detected in both media over 28 days. This study reports for the first time the use of biologically relevant release models and a rapid, reliable and sensitive methodology to determine release characteristics of LNG from intradermally administered long-acting drug delivery systems

    Hydrodynamic gene delivery in human skin using a hollow microneedle device

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    Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50 μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery
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