The massive star population of Cygnus OB2

We have compiled a significantly updated and comprehensive census of massive stars in the nearby Cygnus OB2 association by gathering and homogenizing data from across the literature. The census contains 169 primary OB stars, including 52 O-type stars and 3 Wolf–Rayet stars. Spectral types and photometry are used to place the stars in a Hertzsprung–Russell diagram, which is compared to both non-rotating and rotating stellar evolution models, from which stellar masses and ages are calculated. The star formation history and mass function of the association are assessed, and both are found to be heavily influenced by the evolution of the most massive stars to their end states. We find that the mass function of the most massive stars is consistent with a ‘universal’ power-law slope of Γ = 1.3.Peer reviewedFinal Accepted Versio

Massive stars in the hinterland of the young cluster, Westerlund 2

Accepted for publication in MNRAS, 13 July 2018. 16 pages, plus one-page table in an appendix.An unsettled question concerning the formation and distribution of massive stars is whether they must be born in massive clusters and, if found in less dense environments, whether they must have migrated there. With the advent of wide-area digital photometric surveys, it is now possible to identify massive stars away from prominent Galactic clusters without bias. In this study we consider 40 candidate OB stars found in the field around the young massive cluster, Westerlund 2, by Mohr-Smith et al.: these are located inside a box of 1.5 × 1.5 deg 2 and are selected on the basis of their extinctions and K magnitudes.We present VLT/X-shooter spectra of two of the hottest O stars, respectively 11 and 22 arcmin from the centre of Westerlund 2. They are confirmed as O4V stars, with stellar masses likely to be in excess of 40 M ·. Their radial velocities relative to the non-binary reference object, MSP 182, in Westerlund 2 are -29.4 ± 1.7 and -14.4 ± 2.2 km s -1, respectively. Using Gaia DR2 proper motions we find that between 8 and 11 early O/WR stars in the studied region (including the two VLT targets, plus WR 20c and WR 20aa) could have been ejected fromWesterlund 2 in the last one million years. This represents an efficiency of massive-star ejection of up to ~ 25 per cent. On sky, the positions of these stars and their proper motions show a near N-S alignment. We discuss the possibility that these results are a consequence of prior sub-cluster merging combining with dynamical ejection.Peer reviewe

Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements

Label-free biosensor technology based on dynamic mass redistribution (DMR) of cellular constituents promises to translate GPCR signaling into complex optical 'fingerprints' in real time in living cells. Here we present a strategy to map cellular mechanisms that define label-free responses, and we compare DMR technology with traditional second-messenger assays that are currently the state of the art in GPCR drug discovery. The holistic nature of DMR measurements enabled us to (i) probe GPCR functionality along all four G-protein signaling pathways, something presently beyond reach of most other assay platforms; (ii) dissect complex GPCR signaling patterns even in primary human cells with unprecedented accuracy; (iii) define heterotrimeric G proteins as triggers for the complex optical fingerprints; and (iv) disclose previously undetected features of GPCR behavior. Our results suggest that DMR technology will have a substantial impact on systems biology and systems pharmacology as well as for the discovery of drugs with novel mechanisms

Promoting interactive skills and mind-mindedness among early childcare professionals:Study protocol for a randomized wait-list controlled trial comparing the Circle of Security approach with care as usual in center-based childcare (the SECURE project)

Background: In countries where the majority of young children are enrolled in professional childcare, the childcare setting constitutes an important part of children’s caregiving environment. Research consistently shows that particularly the quality of the daily interactions and relationship between young children and their professional caregivers have long-term efects on a range of developmental child outcomes. Therefore, professional caregivers’ capacity for establishing high quality interactions with the children in their care is an important target of intervention. Methods: A prospective, parallel, cluster-randomized wait-list controlled trial is used to test the efcacy of the attachment- and mentalization theory informed Circle of Security (COS) approach adapted to the childcare setting (COSClassroom) on caregiver interactive skills and mind-mindedness. Participants are professional caregivers of children aged 0–2.9 years working in center-based childcare in Denmark. Approximately 31 childcare centers, corresponding to an estimated 113 caregivers, are expected to participate. The primary outcome is caregiver Sensitive responsiveness measured with the Caregiver Interactive Profle Scales (CIP-scales). Secondary outcomes include caregiver Mind-mindedness, the fve remaining CIP-scales (Respect for autonomy, Structure and limit setting, Verbal communication, Developmental stimulation, and Fostering positive peer interactions), and caregivers’ resources to cope with work-related stress. Data on structural factors (e.g., staf stability, caregiver-child ratio, and level of pre-service education), caregiver attachment style, acceptability and feasibility of the COS-C together with qualitative data on how the participants experience the COS-C is additionally collected to investigate moderating and confounding efects. Discussion: Examining the efectiveness of the COS-C in center-based childcare contributes to the knowledge of evidence-based intervention programs and can potentially improve the caregiver quality early childcare

MicroRNA Function in Human Diseases

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease

MicroRNA Function in Human Diseases

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease

Reddening-free Q indices to identify Be star candidates

Astronomical databases currently provide high-volume spectroscopic and photometric data. While spectroscopic data is better suited to the analysis of many astronomical objects, photometric data is relatively easier to obtain due to shorter telescope usage time. Therefore, there is a growing need to use photometric information to automatically identify objects for further detailed studies, specially H{\alpha} emission line stars such as Be stars. Photometric color-color diagrams (CCDs) are commonly used to identify this kind of objects. However, their identification in CCDs is further complicated by the reddening effect caused by both the circumstellar and interstellar gas. This effect prevents the generalization of candidate identification systems. Therefore, in this work we evaluate the use of neural networks to identify Be star candidates from a set of OB-type stars. The networks are trained using a labeled subset of the VPHAS+ and 2MASS databases, with filters u, g, r, H{\alpha}, i, J, H, and K. In order to avoid the reddening effect, we propose and evaluate the use of reddening-free Q indices to enhance the generalization of the model to other databases and objects. To test the validity of the approach, we manually labeled a subset of the database, and use it to evaluate candidate identification models. We also labeled an independent dataset for cross dataset evaluation. We evaluate the recall of the models at a 99% precision level on both test sets. Our results show that the proposed features provide a significant improvement over the original filter magnitudes.Comment: 14 pages, 4 figures, Accepted for inclusion in the JCC-BD&ET 2020 minutes book, which will be published in the Springer series CCIS - Communications in Computer and Information Scienc

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

FoxO3 increases miR-34a to cause palmitate-induced cholangiocyte lipoapoptosis.

Nonalcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate (PA) showed increased caspase 3/7 activity and increased levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3, demonstrating cholangiocyte lipoapoptosis. Interestingly, treatment with PA significantly increased the levels of microRNA miR-34a, a pro-apoptotic microRNA known to be elevated in NASH. PA induction of miR-34a was abolished in cholangiocytes transduced with forkhead family of transcription factor class O (FoxO)3 shRNA, demonstrating that FoxO3 activation is upstream of miR-34a and suggesting that FoxO3 is a novel transcriptional regulator of miR-34a. Further, anti-miR-34a protected cholangiocytes from PA-induced lipoapoptosis. Direct and indirect targets of miR-34a, such as SIRT1, receptor tyrosine kinase (MET), Kruppel-like factor 4, fibroblast growth factor receptor (FGFR)1, and FGFR4, were all decreased in PA-treated cholangiocytes. SIRT1 and MET were partially rescued by a miR-34a antagonist. Cholangiocyte apoptosis and miR-34a were dramatically increased in the liver of mice with early histologic features of NASH. Our study provides evidence for the pro-apoptotic role of miR-34a in PA-induced cholangiocyte lipoapoptosis in culture and in the liver