Photochemical-dynamical models of externally FUV irradiated protoplanetary discs

There is growing theoretical and observational evidence that protoplanetary disc evolution may be significantly affected by the canonical levels of far ultraviolet (FUV) radiation found in a star forming environment, leading to substantial stripping of material from the disc outer edge even in the absence of nearby massive stars. In this paper we perform the first full radiation hydrodynamic simulations of the flow from the outer rim of protoplanetary discs externally irradiated by such intermediate strength FUV fields, including direct modelling of the photon dominated region (PDR) which is required to accurately compute the thermal properties. We find excellent agreement between our models and the semi–analytic models of Facchini et al. (2016) for the profile of the flow itself, as well as the mass loss rate and location of their “critical radius”. This both validates their results (which differed significantly from prior semi–analytic estimates) and our new numerical method, the latter of which can now be applied to elements of the problem that the semi–analytic approaches are incapable of modelling. We also obtain the composition of the flow, but given the simple geometry of our models we can only hint at some diagnostics for future observations of externally irradiated discs at this stage. We also discuss the potential for these models as benchmarks for future photochemical–dynamical codes

Characterisation of a human bilirubin UDP-glucuronosyltransferase stably expressed in hamster lung fibroblast cell cultures

AbstractA cDNA encoding a human bilirubin UDP-glucuronosyltransferase has been isolated and stably expressed in Chinese hamster V79 lung fibroblast cell line. Western blotting of cell homogenates with anti-UGT antibody revealed a highly expressed protein of approx. 55.5 kDa in size. The expressed enzyme specifically catalysed the formation of bilirubin mono- and diglucuronides, and also catalysed the glucuronidation of two phenolic compounds, which are good substrates for other human UGT isoenzymes, at low rates

High Spatial Resolution X-Ray Spectroscopy of the IC443 Pulsar Wind Nebula and Environs

Deep Chandra ACIS observations of the region around the putative pulsar, CXOU J061705.3+222127, in the supernova remnant IC443 reveal an ~5$^{\prime\prime}$-radius ring-like structure surrounding the pulsar and a jet-like feature oriented roughly north-south across the ring and through the pulsar's location at 06$^{\rm h}$17$^{\rm m}$5.200$^{\rm s}$ +22$^{\circ}$21$^{\prime}$27.52$^{\prime\prime}$ (J2000.0 coordinates). The observations further confirm that (1) the spectrum and flux of the central object are consistent with a rotation-powered pulsar, (2) the non-thermal spectrum and morphology of the surrounding nebula are consistent with a pulsar wind and, (3) the spectrum at greater distances is consistent with thermal emission from the supernova remnant. The cometary shape of the nebula, suggesting motion towards the southwest, appears to be subsonic: There is no evidence either spectrally or morphologically for a bow shock or contact discontinuity; the nearly circular ring is not distorted by motion through the ambient medium; and the shape near the apex of the nebula is narrow. Comparing this observation with previous observations of the same target, we set a 99% confidence upper limit to the proper motion of CXOU J061705.3+222127 to be less than 44 mas/yr (310 km/s for a distance of 1.5 kpc), with the best-fit (but not statistically significant) projected direction toward the west.Comment: Accepted for publication in the Astrophysical Journa

Cytotoxicity of Triorganophosphinegold(I) Complexes of Thiobenzoate

The preparation and characterization of two triorganophosphinegold(I) complexes containing the anion derived from thiobenzoic acid are described. The cytotoxicity of these complexes has been investigated along with that of triphenylphosphinegold(I) mercaptopurinate, a known anti-tumor compound, against a variety of human cell lines. The complexes showed moderate to high cytotoxicity (ID50 250 – 2500 ng/ml)

Core Outcome Set-STAndards for Development: The COS-STAD recommendations

Background The use of core outcome sets (COS) ensures that researchers measure and report those outcomes that are most likely to be relevant to users of their research. Several hundred COS projects have been systematically identified to date, but there has been no formal quality assessment of these studies. The Core Outcome Set-STAndards for Development (COS-STAD) project aimed to identify minimum standards for the design of a COS study agreed upon by an international group, while other specific guidance exists for the final reporting of COS development studies (Core Outcome Set-STAndards for Reporting [COS-STAR]). Methods and findings An international group of experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives produced the COS-STAD recommendations to help improve the quality of COS development and support the assessment of whether a COS had been developed using a reasonable approach. An open survey of experts generated an initial list of items, which was refined by a 2-round Delphi survey involving nearly 250 participants representing key stakeholder groups. Participants assigned importance ratings for each item using a 1–9 scale. Consensus that an item should be included in the set of minimum standards was defined as at least 70% of the voting participants from each stakeholder group providing a score between 7 and 9. The Delphi survey was followed by a consensus discussion with the study management group representing multiple stakeholder groups. COS-STAD contains 11 minimum standards that are the minimum design recommendations for all COS development projects. The recommendations focus on 3 key domains: the scope, the stakeholders, and the consensus process. Conclusions The COS-STAD project has established 11 minimum standards to be followed by COS developers when planning their projects and by users when deciding whether a COS has been developed using reasonable methods

The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in non-dialysis chronic kidney disease : a systematic review

Objective: People with nondialysis-dependent chronic kidney disease (CKD) and renal transplant recipients (RTRs) have compromised physical function and reduced physical activity (PA) levels. Whilst established in healthy older adults and other chronic diseases, this association remains underexplored in CKD. We aimed to review the existing research investigating poor physical function and PA with clinical outcome in nondialysis CKD. Data sources: Electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials) were searched until December 2017 for cohort studies reporting objective or subjective measures of PA and physical function and the associations with adverse clinical outcomes and all-cause mortality in patients with nondialysis CKD stages 1–5 and RTRs. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42016039060). Review methods: Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare and Research Quality (AHRQ) standards. Results: A total of 29 studies were included; 12 reporting on physical function and 17 on PA. Only eight studies were conducted with RTRs. The majority were classified as ‘good’ according to the AHRQ standards. Although not appropriate for meta-analysis due to variance in the outcome measures reported, a coherent pattern was seen with higher mortality rates or prevalence of adverse clinical events associated with lower PA and physical function levels, irrespective of the measurement tool used. Sources of bias included incomplete description of participant flow through the study and over reliance on self-report measures. Conclusions: In nondialysis CKD, survival rates correlate with greater PA and physical function levels. Further trials are required to investigate causality and the effectiveness of physical function and PA interventions in improving outcomes. Future work should identify standard assessment protocols for PA and physical function

The Gemini NICI Planet-Finding Campaign

Our team is carrying out a multi-year observing program to directly image and characterize young extrasolar planets using the Near-Infrared Coronagraphic Imager (NICI) on the Gemini-South 8.1-meter telescope. NICI is the first instrument on a large telescope designed from the outset for high-contrast imaging, comprising a high-performance curvature adaptive optics system with a simultaneous dual-channel coronagraphic imager. Combined with state-of-the-art observing methods and data processing, NICI typically achieves ~2 magnitudes better contrast compared to previous ground-based or space-based programs, at separations inside of ~2 arcsec. In preparation for the Campaign, we carried out efforts to identify previously unrecognized young stars, to rigorously construct our observing strategy, and to optimize the combination of angular and spectral differential imaging. The Planet-Finding Campaign is in its second year, with first-epoch imaging of 174 stars already obtained out of a total sample of 300 stars. We describe the Campaign's goals, design, implementation, performance, and preliminary results. The NICI Campaign represents the largest and most sensitive imaging survey to date for massive (~1 Mjup) planets around other stars. Upon completion, the Campaign will establish the best measurements to date on the properties of young gas-giant planets at ~5-10 AU separations. Finally, Campaign discoveries will be well-suited to long-term orbital monitoring and detailed spectrophotometric followup with next-generation planet-finding instruments.Comment: Proceedings of the SPIE, vol 7736 (Advances in Adaptive Optics, San Diego, CA, June 2010 meeting), in pres

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

Twelve weeks of supervised exercise improves self-reported symptom burden and fatigue in chronic kidney disease : a secondary analysis of the ‘ExTra CKD’ trial

Background Chronic kidney disease (CKD) patients experience a high symptom burden including fatigue, sleep difficulties, muscle weakness and pain. These symptoms reduce levels of physical function (PF) and activity, and contribute to poor health-related quality of life (HRQoL). Despite the gathering evidence of positive physiological changes following exercise in CKD, there is limited evidence on its effect on self-reported symptom burden, fatigue, HRQoL and physical activity. Methods Thirty-six patients [mean ± SD 61.6 ± 11.8 years, 22 (61%) females, estimated glomerular filtration rate: 25.5 ± 7.8 mL/min/1.73 m2] not requiring renal replacement therapy underwent 12 weeks (3 times/week) of supervised aerobic exercise (AE), or a combination (CE) of AE plus resistance training. Outcomes included self-reported symptom burden, fatigue, HRQoL and physical activity. Results Exercise reduced the total number of symptoms reported by 17% and had favourable effects on fatigue in both groups. AE reduced the frequency of ‘itching’, ‘impotence’ and ‘shortness of breath’ symptoms, and the intrusiveness for symptoms of ‘sleep disturbance’, ‘loss of muscular strength/power’, ‘muscle spasm/stiffness’ and ‘restless legs’. The addition of resistance exercise in the CE group saw a reduction in ‘loss of muscular strength/power’. No changes were seen in subjective PF or physical activity levels. AE increased self-efficacy for physical activity. Conclusions Supervised exercise had favourable effects on symptom frequency and intrusiveness, including substantial improvements in fatigue. Although the intervention did not improve self-reported physical activity levels, AE increased patients’ self-efficacy for physical activity. These favourable changes in self-reported outcomes support the important role of exercise in CKD