The radius and mass of the subgiant star bet Hyi from interferometry and asteroseismology

We have used the Sydney University Stellar Interferometer (SUSI) to measure the angular diameter of beta Hydri. This star is a nearby G2 subgiant whose mean density was recently measured with high precision using asteroseismology. We determine the radius and effective temperature of the star to be 1.814+/-0.017 R_sun (0.9%) and 5872+/-44 K (0.7%) respectively. By combining this value with the mean density, as estimated from asteroseismology, we make a direct estimate of the stellar mass. We find a value of 1.07+/-0.03 M_sun (2.8%), which agrees with published estimates based on fitting in the H-R diagram, but has much higher precision. These results place valuable constraints on theoretical models of beta Hyi and its oscillation frequencies.Comment: 3 figures, 3 tables, to appear in MNRAS Letter

Characterization of hexabundles: Initial results

New multi-core imaging fibre bundles -- hexabundles -- being developed at the University of Sydney will provide simultaneous integral field spectroscopy for hundreds of celestial sources across a wide angular field. These are a natural progression from the use of single fibres in existing galaxy surveys. Hexabundles will allow us to address fundamental questions in astronomy without the biases introduced by a fixed entrance aperture. We have begun to consider instrument concepts that exploit hundreds of hexabundles over the widest possible field of view. To this end, we have compared the performance of a 61-core fully-fused hexabundle and 5 lightly-fused bundles with 7 cores each. All fibres in the bundles have 100 micron cores. In the fully-fused bundle, the cores are distorted from a circular shape in order to achieve a higher fill fraction. The lightly-fused bundles have circular cores and five different cladding thicknesses which affect the fill fraction. We compare the optical performance of all 6 bundles and find that the advantage of smaller interstitial holes (higher fill fraction) is outweighed by the increase in modal coupling, cross-talk and the poor optical performance caused by the deformation of the fibre cores. Uniformly high throughput and low cross-talk are essential for imaging faint astronomical targets with sufficient resolution to disentangle the dynamical structure. Devices already under development will have between 100 and 200 lightly-fused cores, although larger formats are feasible. The light-weight packaging of hexabundles is sufficiently flexible to allow existing robotic positioners to make use of them.Comment: Accepted for publication in MNRAS. See also a complimentary paper on the development of hexabundles - Bland-Hawthorn et al. 2011, Optics Express, vol. 19, p. 2649 (http://www.opticsinfobase.org/abstract.cfm?URI=oe-19-3-2649

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

Orbital parameters, masses and distance to Beta Centauri determined with the Sydney University Stellar Interferometer and high resolution spectroscopy

The bright southern binary star beta Centauri (HR 5267) has been observed with the Sydney University Stellar Interferometer (SUSI) and spectroscopically with the ESO CAT and Swiss Euler telescopes at La Silla. The interferometric observations have confirmed the binary nature of the primary component and have enabled the determination of the orbital parameters of the system. At the observing wavelength of 442 nm the two components of the binary system have a magnitude difference of 0.15. The combination of interferometric and spectroscopic data gives the following results: orbital period 357 days, semi-major axis 25.30 mas, inclination 67.4 degrees, eccentricity 0.821, distance 102.3 pc, primary and secondary masses M1 = M2 = 9.1 solar masses and absolute visual magnitudes of the primary and secondary M1V = -3.85 and M2V = -3.70. The high accuracy of the results offers a fruitful starting point for future asteroseismic modelling of the pulsating binary components.Comment: 10 pages, 4 figures. Accepted for publication in MNRA

Nestor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background - Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results - Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions - Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease

hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

The maintenance of genome stability is an essential cellular process to prevent the development of diseases including cancer. hSSB1 (NABP2/ OBFC2A) is a critical component of the DNA damage response where it participates in the repair of double-strand DNA breaks and in base excision repair of oxidized guanine residues (8-oxoguanine) by aiding the localization of the human 8-oxoguanine glycosylase (hOGG1) to damaged DNA. Here we demonstrate that following oxidative stress, hSSB1 is stabilized as an oligomer which is required for hSSB1 to function in the removal of 8-oxoguanine. Monomeric hSSB1 shows a decreased affinity for oxidized DNA resulting in a cellular 8-oxoguanine-repair defect and in the absence of ATM signaling initiation. While hSSB1 oligomerization is important for the removal of 8-oxoguanine from the genome, it is not required for the repair of double-strand DNA-breaks by homologous recombination. These findings demonstrate a novel hSSB1 regulatory mechanism for the repair of damaged DNA.Publisher PDFPeer reviewe

Single-Agent Versus Combination Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer and a Performance Status of 2: Prognostic Factors and Treatment Selection Based on Two Large Randomized Clinical Trials

Purpose:Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2.Patients and Methods:Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy.Results:Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival times were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0–2 risk factors had similar outcomes independent of treatment, whereas patients with 3–4 factors had a nonsignificant improvement in median survival with combination chemotherapy.Conclusion:Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy

Suppression of the near-infrared OH night sky lines with fibre Bragg gratings - first results

The background noise between 1 and 1.8 microns in ground-based instruments is dominated by atmospheric emission from hydroxyl molecules. We have built and commissioned a new instrument, GNOSIS, which suppresses 103 OH doublets between 1.47 - 1.7 microns by a factor of ~1000 with a resolving power of ~10,000. We present the first results from the commissioning of GNOSIS using the IRIS2 spectrograph at the AAT. The combined throughput of the GNOSIS fore-optics, grating unit and relay optics is ~36 per cent, but this could be improved to ~46 per cent with a more optimal design. We measure strong suppression of the OH lines, confirming that OH suppression with fibre Bragg gratings will be a powerful technology for low resolution spectroscopy. The integrated OH suppressed background between 1.5 and 1.7 microns is reduced by a factor of 9 compared to a control spectrum using the same system without suppression. The potential of low resolution OH suppressed spectroscopy is illustrated with example observations. The GNOSIS background is dominated by detector dark current below 1.67 microns and by thermal emission above 1.67 microns. After subtracting these we detect an unidentified residual interline component of ~ 860 +/ 210 ph/s/m^2/micron/arcsec^2. This component is equally bright in the suppressed and control spectra. We have investigated the possible source of the interline component, but were unable to discriminate between a possible instrumental artifact and intrinsic atmospheric emission. Resolving the source of this emission is crucial for the design of fully optimised OH suppression spectrographs. The next generation OH suppression spectrograph will be focussed on resolving the source of the interline component, taking advantage of better optimisation for a FBG feed. We quantify the necessary improvements for an optimal OH suppressing fibre spectrograph design.Comment: Accepted for publication in MNRAS. 15 pages, 18 figure

A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks

BACKGROUND Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort®, AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication. METHODS We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort® vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better. RESULTS Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort®. For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort® vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either "a little better" or "much better" on the 5-point Likert scale, with none reporting "no change" or getting worse. CONCLUSION This study suggests that there is no statistical difference between using Symbicort® vs. nebulized salbutamol as the reliever for the first 15 min post-intervention

αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Background and Aims The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions. Methods αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology