Structure and physical properties of GexAsySe1−x−y glasses with the same mean coordination number of 2.5

We have prepared and analyzed five different compositions of GexAsySe1−x−yglasses that have the same mean coordination number (MCN) of 2.5 in order to understand whether MCN or chemical composition has the dominant effect on the physical properties of the glass. Density measurements showed a maximum for the chemically stoichiometric Ge12.5As25Se62.5 sample and suggested that some rearrangement of the atoms was occurring as one atom substituted for another. The measurements of Tg, however, showed that the glasses had almost same glass transition temperature and suggested that the glassnetwork connectivity did not change much with composition. Although Raman scattering and x-ray photoelectron spectra of the glasses indicate that the percentage of the different structural units changes with the composition, there was no evidence of the existence of structural units that could change the overall connectivity of the glassnetwork. Therefore, we concluded that glasses with same MCN but different composition have similar glassnetwork connectivity, and that chemical composition has only a secondary effect on the physical properties of the glasses.This research was partly supported by the Australian Research Council through its Centres of Excellence and Discovery DP110102753 programs

Supercontinuum generation in dispersion engineered highly nonlinear (y=10/W/m) As2S3 chalcogenide planar waveguide

We demonstrate supercontinuum generation in a highly nonlinear As2S3 chalcogenide planar waveguide which is dispersion engineered to have anomalous dispersion at near-infrared wavelengths. This waveguide is 60 mm long with a cross-section of 2 μm by 870 nm, resulting in a nonlinear parameter of 10 /W/m and a dispersion of +29 ps/nm/km. Using pulses with a width of 610 fs and peak power of 68 W, we generate supercontinuum with a 30 dB bandwidth of 750 nm, in good agreement with theory

COVID-19 managed on respiratory wards and intensive care units: Results from the national COVID-19 outcome report in Wales from March 2020 to December 2021

Background: A COVID-19 hospital guideline was implemented across all 18 acute hospitals in Wales in March 2020, promoting ward management of COVID pneumonitis and data collected across the first 3 Waves of the pandemic (Wave 1 March 1st 2020 to November 1st 2020, Wave 2 November 2st 2020 to February 21st 2021 and Wave 3 June 1st 2021 to December 14th 2021). The aim of this paper is to compare outcomes for patients by admission setting and type of ventilatory support given, with a particular focus on CPAP therapy. Methods: This is a retrospective observational study of those aged over 18 admitted to hospital with community acquired COVID-19 between March 2020 and December 2021. The outcome of interest was in-hospital mortality. Univariate logistic regression models were used to compare crude outcomes across the waves. Multivariable logistic regression models were used to assess outcomes by different settings and treatments after adjusting for Wave, age, sex, co-morbidity and deprivation. Results: Of the 7,803 records collected, 5,887 (75.4%) met the inclusion criteria. Analysis of those cases identified statistically significant outcome improvements across the waves for all patients combined (Waves 1 to 3: 31.5% to 18.8%, p<0.01), all ward patients (28.9% to 17.7%, p<0.01), and all ICU patients (44.3% to 32.2%, p = 0.03). Sub group analyses identified outcome improvements in ward patients without any oxygen therapy (Waves 1 to 3: 22.2% to 12.7%, p<0.01), with oxygen therapy only (34.0% to 12.9%, p<0.01) and with CPAP only (63.5% to 39.2%, p<0.01). The outcome improvements for ICU patients receiving CPAP only (35.7% to 24.6%, p = 0.31) or invasive ventilation (61.6% to 54.6%, p = 0.43) were not statistically significant though the numbers being admitted to ICU were small. The logistic regression models identified important age and comorbidity effects on outcomes. The multivariable model that took these into account suggested no statistically significantly greater risk of death for those receiving CPAP on the ward compared to those receiving CPAP in ICU (OR 0.89, 95% CI: 0.49 to 1.60). Conclusions: There were successive reductions in mortality in inpatients over the three Waves reflecting new treatments and better management of complications. Mortality for those requiring CPAP was similar in respiratory wards and ICUs after adjusting for differences in their respective patient populations

Correlation functions for the three state superintegrable chiral Potts spin chain of finite lengths

We compute the correlation functions of the three state superintegrable chiral Potts spin chain for chains of length 3,4,5. From these results we present conjectures for the form of the nearest neighbor correlation function.Comment: 10 pages; references update

Dispersion engineered As2S3 planar waveguides for broadband four-wave mixing based wavelength conversion of 40 Gb/s signals

We demonstrate broadband wavelength conversion of a 40 Gb/s return-to-zero signal using four-wave-mixing (FWM) in a dispersion engineered chalcogenide glass waveguide. The 6 cm long planar rib waveguide 2 μm wide was fabricated in a 0.87 μm thick film etched 350nm deep to correspond to a design where waveguide dispersion offsets the material leading to near-zero dispersion in the C-band and broadband phase matched FWM. The reduced dimensions also enhance the nonlinear coefficient to 9800 W-1km-1 at 1550 nm enabling broadband conversion in a shorter device. In this work, we demonstrate 80 nm wavelength conversions with 1.65 dB of power penalty at a bit-error rate of 10-9. Spectral measurements and simulations indicate extended broadband operation is possible

Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy

The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated ARW741L/C mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of ARW741L highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, ARW741L transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients

All optical wavelength conversion via cross phase modulation in chalcogenide glass rib waveguides

We demonstrate all-optical wavelength conversion in a 5 cm As2S3 chalcogenide glass rib waveguide with 5.4 ps pulses over a wavelength range of 10 nm near 1550 nm. We present frequency resolved optical gating (FROG) measurements that show good converted pulse integrity in terms of amplitude and phase in the frequency and time domains. The short interaction length ensures that dispersion induced walkoff does not hinder the conversion range of the device

The Extragalactic Distance Scale Key Project XXVII. A Derivation of the Hubble Constant Using the Fundamental Plane and Dn-Sigma Relations in Leo I, Virgo, and Fornax

Using published photometry and spectroscopy, we construct the fundamental plane and D_n-Sigma relations in Leo I, Virgo and Fornax. The published Cepheid P-L relations to spirals in these clusters fixes the relation between angular size and metric distance for both the fundamental plane and D_n-Sigma relations. Using the locally calibrated fundamental plane, we infer distances to a sample of clusters with a mean redshift of cz \approx 6000 \kms, and derive a value of H_0=78+- 5+- 9 km/s/Mpc (random, systematic) for the local expansion rate. This value includes a correction for depth effects in the Cepheid distances to the nearby clusters, which decreased the deduced value of the expansion rate by 5% +- 5%. If one further adopts the metallicity correction to the Cepheid PL relation, as derived by the Key Project, the value of the Hubble constant would decrease by a further 6%+- 4%. These two sources of systematic error, when combined with a +- 6% error due to the uncertainty in the distance to the Large Magellanic Cloud, a +- 4% error due to uncertainties in the WFPC2 calibration, and several small sources of uncertainty in the fundamental plane analysis, combine to yield a total systematic uncertainty of +- 11%. We find that the values obtained using either the CMB, or a flow-field model, for the reference frame of the distant clusters, agree to within 1%. The Dn-Sigma relation also produces similar results, as expected from the correlated nature of the two scaling relations. A complete discussion of the sources of random and systematic error in this determination of the Hubble constant is also given, in order to facilitate comparison with the other secondary indicators being used by the Key Project.Comment: 21 pages, 3 figures, Accepted for publication in Ap

Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer

The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells. In contrast, when the AKT inhibitor AZD7328 was applied to patient-derived prostate cultures that retained expression of PTEN, activation of a compensatory Ras/MEK/ERK pathway was observed. Moreover, whilst autophagy was induced following treatment with AZD7328, cell viability was less affected in the patient-derived cultures than in cell lines. Surprisingly, treatment with a combination of both AZD7328 and two separate MEK1/2 inhibitors further enhanced phosphorylation of ERK1/2 in primary prostate cultures. However, it also induced irreversible growth arrest and senescence.Ex vivo treatment of a patient-derived xenograft (PDX) of prostate cancer with a combination of AZD7328 and the mTOR inhibitor KU-0063794, significantly reduced tumour frequency upon re-engraftment of tumour cells.The results demonstrate that single agent targeting of the PI3K/AKT/mTOR pathway triggers activation of the Ras/MEK/ERK compensatory pathway in near-patient samples. Therefore, blockade of one pathway is insufficient to treat prostate cancer in man