Dielectric response of a polar fluid trapped in a spherical nanocavity

We present extensive Molecular Dynamics simulation results for the structure, static and dynamical response of a droplet of 1000 soft spheres carrying extended dipoles and confined to spherical cavities of radii $R=2.5$, 3, and 4 nm embedded in a dielectric continuum of permittivity $\epsilon' \geq 1$. The polarisation of the external medium by the charge distribution inside the cavity is accounted for by appropriate image charges. We focus on the influence of the external permittivity $\epsilon'$ on the static and dynamic properties of the confined fluid. The density profile and local orientational order parameter of the dipoles turn out to be remarkably insensitive to $\epsilon'$. Permittivity profiles $\epsilon(r)$ inside the spherical cavity are calculated from a generalised Kirkwood formula. These profiles oscillate in phase with the density profiles and go to a ``bulk'' value $\epsilon_b$ away from the confining surface; $\epsilon_b$ is only weakly dependent on $\epsilon'$, except for $\epsilon' = 1$ (vacuum), and is strongly reduced compared to the permittivity of a uniform (bulk) fluid under comparable thermodynamic conditions. The dynamic relaxation of the total dipole moment of the sample is found to be strongly dependent on $\epsilon'$, and to exhibit oscillatory behaviour when $\epsilon'=1$; the relaxation is an order of magnitude faster than in the bulk. The complex frequency-dependent permittivity $\epsilon(\omega)$ is sensitive to $\epsilon'$ at low frequencies, and the zero frequency limit $\epsilon(\omega=0)$ is systematically lower than the ``bulk'' value $\epsilon_b$ of the static primitivity.Comment: 12 pages including 17 figure

IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination

We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection.This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR), the Australian Centre for Hepatitis and HIV Virology EOI grant 2010/12 (CR&RJ), and Bill and Melinda Gates Foundation GCE Phase I grant OPP1015149 (CR)

Reduced Interleukin-4 Receptor α Expression on CD8+ T Cells Correlates with Higher Quality Anti-Viral Immunity

With the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα) was significantly down-regulated on anti-viral CD8(+) T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT) mice with vaccinia virus (VV) or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6) were required to increase IL-4Rα expression on CD8(+) T cells, but not interferon (IFN)-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+) T cells was a feature of poor quality anti-viral CD8(+) T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α) in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+) T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+) T cell immunity. Our findings have important implications in understanding anti-viral CD8(+) T cell immunity and designing effective vaccines against chronic viral infections.This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR) and the Australian Centre for Hepatitis and HIV Virology EOI grant 2010 (CR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Improved Constraints on Isotropic Shift and Anisotropies of the Speed of Light using Rotating Cryogenic Sapphire Oscillators

We demonstrate that Michelson-Morley tests, which detect direction-dependent anisotropies in the speed of light, can also be used to place limits upon isotropic deviations of the vacuum speed of light from $c$, as described by the photon sector Standard Model Extension (SME) parameter $\tilde{\kappa}_{tr}$. A shift in the speed of light that is isotropic in one inertial frame implies anisotropic shifts in others. Using observer Lorentz covariance, we derive the time-dependent variations in the relative resonance frequencies of a pair of electromagnetic resonators that would be generated by such a shift in the rest frame of the Sun. A new analysis of a recent experimental test of relativity using this result constrains $\tilde{\kappa}_{tr}$ with a precision of $7.4\times10^{-9}$. This represents the first constraint on $\tilde{\kappa}_{tr}$ by a Michelson-Morley experiment and the first analysis of a single experiment to simultaneously set limits on all nine non-birefringent terms in the photon sector of the SME

The properties of extragalactic radio sources selected at 20 GHz

We present some first results on the variability, polarization and general properties of radio sources selected in a blind survey at 20 GHz, the highest frequency at which a sensitive radio survey has been carried out over a large area of sky. Sources with flux densities above 100 mJy in the AT20G Pilot Survey at declination -60 to -70 were observed at up to three epochs during 2002-4, including near-simultaneous measurements at 5, 8 and 18 GHz in 2003. Of the 173 sources detected, 65% are candidate QSOs, BL Lac objects or blazars, 20% galaxies and 15% faint (b > 22 mag) optical objects or blank fields. On a 1-2 year timescale, the general level of variability at 20 GHz appears to be low. For the 108 sources with good-quality measurements in both 2003 and 2004, the median variability index at 20 GHz was 6.9% and only five sources varied by more than 30% in flux density. Most sources in our sample show low levels of linear polarization (typically 1-5%), with a median fractional polarization of 2.3% at 20 GHz. There is a trend for fainter sources to show higher fractional polarization. At least 40% of sources selected at 20GHz have strong spectral curvature over the frequency range 1-20 GHz. We use a radio `two-colour diagram' to characterize the radio spectra of our sample, and confirm that the radio-source population at 20 GHz (which is also the foreground point-source population for CMB anisotropy experiments like WMAP and Planck) cannot be reliably predicted by extrapolating the results of surveys at lower frequencies. As a result, direct selection at 20 GHz appears to be a more efficient way of identifying 90 GHz phase calibrators for ALMA than the currently-proposed technique of extrapolation from all-sky surveys at 1-5 GHz.Comment: 14-page paper plus 5-page data table. Replaced with published versio

Mining oral history collections using music information retrieval methods

Recent work at the Sussex Humanities Lab, a digital humanities research program at the University of Sussex, has sought to address an identified gap in the provision and use of audio feature analysis for spoken word collections. Traditionally, oral history methodologies and practices have placed emphasis on working with transcribed textual surrogates, rather than the digital audio files created during the interview process. This provides a pragmatic access to the basic semantic content, but obviates access to other potentially meaningful aural information; our work addresses the potential for methods to explore this extra-semantic information, by working with the audio directly. Audio analysis tools, such as those developed within the established field of Music Information Retrieval (MIR), provide this opportunity. This paper describes the application of audio analysis techniques and methods to spoken word collections. We demonstrate an approach using freely available audio and data analysis tools, which have been explored and evaluated in two workshops. We hope to inspire new forms of content analysis which complement semantic analysis with investigation into the more nuanced properties carried in audio signals

The extragalactic radio-source population at 95 GHz

We have used the Australia Telescope Compact Array (ATCA) at 95GHz to carry out continuum observations of 130 extragalactic radio sources selected from the Australia Telescope 20GHz (AT20G) survey. Over 90% of these sources are detected at 95 GHz, and we use a triple-correlation method to measure simultaneous 20 and 95 GHz flux densities. We show that the ATCA can measure 95GHz flux densities to ~10% accuracy in a few minutes for sources above ~50mJy. The median 20-95GHz spectral index does not vary significantly with flux density for extragalactic sources with S20>150 mJy. This allows us to estimate the extragalactic radio source counts at 95GHz by combining our observed 20-95GHz spectral-index distribution with the accurate 20GHz source counts measured in the AT20G survey. The resulting 95GHz source counts down to 80 mJy are significantly lower than those found by several previous studies. The main reason is that most radio sources with flat or rising spectra in the frequency range 5-20GHz show a spectral turnover between 20 and 95 GHz. As a result, there are fewer 95GHz sources (by almost a factor of two at 0.1 Jy) than would be predicted on the basis of extrapolation from the source populations seen in lower-frequency surveys. We also derive the predicted confusion noise in CMB surveys at 95GHz and find a value 20-30% lower than previous estimates. The 95GHz source population at the flux levels probed by this study is dominated by QSOs with a median redshift z~1. We find a correlation between optical magnitude and 95GHz flux density which suggests that many of the brightest 95 GHz sources are relativistically beamed, with both the optical and millimetre continuum significantly brightened by Doppler boosting.Comment: Replaced with final version (MNRAS, in press), 15 pages plus two landscape data table

Predictors of early and late mortality following open extent IV thoracoabdominal aortic aneurysm repair in a large contemporary single-center experience

ObjectiveThe primary purpose of this study was to examine outcomes following open repair of extent IV thoracoabdominal aortic aneurysms (TAAAs) at a single university hospital. As a secondary aim, comparison was made to patients who underwent open abdominal aortic aneurysm (AAA) repair with supraceliac clamping but without left renal artery bypass to assess the effect of left renal artery bypass on outcomes.MethodsPatients undergoing open extent IV TAAA repair from 1998 to 2008 were identified (n = 108). Primary outcomes were 30-day and long-term survival. Secondary outcomes were major complication, renal failure, and postoperative change in renal function. A second analysis was performed, comparing patients undergoing extent IV TAAA repair with patients undergoing AAA repair with supraceliac clamping but without left renal artery bypass (n = 50).ResultsEighty-three men (76.9%) and 25 women (23.1%), with a mean age of 72.9 years, underwent open extent IV TAAA repair. Nine patients (8.3%) were ruptured. Mean aneurysm maximal diameter was 6.5 ± 1.3 cm. Supraceliac and left renal ischemic times were 22.9 ± 9.3 and 40.6 ± 16.2 minutes, respectively. Six patients (5.6%) died at 30 days. The only predictor of 30-day mortality was decreased preoperative estimated glomerular filtration rate (eGFR) (P = .044 by multivariate analysis; and P = .011 by univariate analysis). One-year and 5-year survival rates were 87% and 50%, respectively. Patients with a history of cerebrovascular disease (P = .001) and postoperative renal insufficiency (P = .034) had increased long-term mortality by log-rank test. Twenty-five (25.3%) patients sustained a postoperative decrease in renal function, while 19 (19.2%) patients had an improvement in renal function. There was no difference in 30-day mortality (5.6% vs 6.0%; P = 1.000), 5-year survival (50% vs 48%; P = .886), major complications (37.0% vs 38.0%; P = 1.000), renal failure (6.1% vs 0%; P = .215), or postoperative change in renal function, in patients undergoing extent IV TAAA repair vs AAA repair with supraceliac clamping but without left renal artery bypass.ConclusionsOpen extent IV TAAA repair can be performed with low morbidity and mortality rates. The performance of left renal artery bypass does not appear to contribute to the morbidity and mortality of extent IV TAAA repair. While decreased preoperative eGFR appears to increase the risk of 30-day mortality, a history of cerebrovascular disease and postoperative renal insufficiency appear to increase the risk of long-term mortality. Finally, open extent IV TAAA repair not uncommonly improves renal function

Radio Observations of the Hubble Deep Field South region: I. Survey Description and Initial Results

This paper is the first of a series describing the results of the Australia Telescope Hubble Deep Field South (ATHDFS) radio survey. The survey was conducted at four wavelengths - 20, 11, 6, and 3 cm, over a 4-year period, and achieves an rms sensitivity of about 10 microJy at each wavelength. We describe the observations and data reduction processes, and present data on radio sources close to the centre of the HDF-S. We discuss in detail the properties of a subset of these sources. The sources include both starburst galaxies and galaxies powered by an active galactic nucleus, and range in redshift from 0.1 to 2.2. Some of them are characterised by unusually high radio-to-optical luminosities, presumably caused by dust extinction.Comment: Accepted by AJ. 32 pages, 4 tables, 3 figures. PDF with full-resolution figures is on http://www.atnf.csiro.au/people/rnorris/N197.pd

The permeability of SPION over an artificial three-layer membrane is enhanced by external magnetic field

BACKGROUND: Sensorineural hearing loss, a subset of all clinical hearing loss, may be correctable through the use of gene therapy. We are testing a delivery system of therapeutics through a 3 cell-layer round window membrane model (RWM model) that may provide an entry of drugs or genes to the inner ear. We designed an in vitro RWM model similar to the RWM (will be referred to throughout the paper as RWM model) to determine the feasibility of using superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPION) for targeted delivery of therapeutics to the inner ear. The RWM model is a 3 cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix and fibroblasts seeded in between. Dextran encapsulated nanoparticle clusters 130 nm in diameter were pulled through the RWM model using permanent magnets with flux density 0.410 Tesla at the pole face. The SIS membranes were harvested at day 7 and then fixed in 4% paraformaldehyde. Transmission electron microscopy and fluorescence spectrophotometry were used to verify transepithelial transport of the SPION across the cell-culture model. Histological sections were examined for evidence of SPION toxicity, as well to generate a timeline of the position of the SPION at different times. SPION also were added to cells in culture to assess in vitro toxicity. RESULTS: Transepithelial electrical resistance measurements confirmed epithelial confluence, as SPION crossed a membrane consisting of three co-cultured layers of cells, under the influence of a magnetic field. Micrographs showed SPION distributed throughout the membrane model, in between cell layers, and sometimes on the surface of cells. TEM verified that the SPION were pulled through the membrane into the culture well below. Fluorescence spectrophotometry quantified the number of SPION that went through the SIS membrane. SPION showed no toxicity to cells in culture. CONCLUSION: A three-cell layer model of the human round window membrane has been constructed. SPION have been magnetically transported through this model, allowing quantitative evaluation of prospective targeted drug or gene delivery through the RWM. Putative in vivo carrier superparamagnetic nanoparticles may be evaluated using this model