Serendipitous XMM-Newton discovery of a cluster of galaxies at z=0.28

We report the discovery of a galaxy cluster serendipitously detected as an extended X-ray source in an offset observation of the group NGC 5044. The cluster redshift, z=0.281, determined from the optical spectrum of the brightest cluster galaxy, agrees with that inferred from the X-ray spectrum using the Fe K alpha complex of the hot ICM (z=0.27 +/- 0.01). Based on the 50 ks XMM observation, we find that within a radius of 383 kpc the cluster has an unabsorbed X-ray flux, f_X (0.5-2 keV) = 3.34 (+0.08, -0.13) x 10^{-13} erg/cm^2/s, a bolometric X-ray luminosity, L_X = 2.21 (+0.34, -0.19) x 10^{44} erg/s, kT = 3.57 +/- 0.12 keV, and metallicity, 0.60 +/- 0.09 solar. The cluster obeys the scaling relations for L_X and T observed at intermediate redshift. The mass derived from an isothermal NFW model fit is, M_vir = 3.89 +/- 0.35 x 10^{14} solar masses, with a concentration parameter, c = 6.7 +/- 0.4, consistent with the range of values expected in the concordance cosmological model for relaxed clusters. The optical properties suggest this could be a ``fossil cluster''.Comment: 5 pages, 4 colour figures, accepted for publication in Ap

Evaluating complex mine ventilation operational changes through simulations

Increasing the profitability of the mining industry is contingent on its ability to improve operational efficiency. Mine ventilation networks typically represent 25-50% of a mine’s energy consumption and, therefore, exhibits scope for optimisation. Ventilation networks comprise numerous complex integrated airways, branches and ventilation fans. The most effective way to optimise and evaluate them is computer-aided simulations. However, no framework exists to clarify exactly how operational changes in ventilation networks should be evaluated. In this study, a scalable method was developed, implemented and analysed. The case study validation resulted in satisfying key performance indicators of both service delivery and operational energy costs, thereby increasing operational efficiency. The significance of the novel method is that it allows for improved operational decisions on mine ventilation networks. The value of the method was illustrated by the adoption of the method by the case study mining personnel to form the new norm of their procedures and standards

Assessing adolescents' critical health literacy: How is trust in government leadership associated with knowledge of COVID-19?

This study explored relations between COVID-19 news source, trust in COVID-19 information source, and COVID-19 health literacy in 194 STEM-oriented adolescents and young adults from the US and the UK. Analyses suggest that adolescents use both traditional news (e.g., TV or newspapers) and social media news to acquire information about COVID-19 and have average levels of COVID-19 health literacy. Hierarchical linear regression analyses suggest that the association between traditional news media and COVID-19 health literacy depends on participants' level of trust in their government leader. For youth in both the US and the UK who used traditional media for information about COVID-19 and who have higher trust in their respective government leader (i.e., former US President Donald Trump and UK Prime Minister Boris Johnson) had lower COVID-19 health literacy. Results highlight how youth are learning about the pandemic and the importance of not only considering their information source, but also their levels of trust in their government leaders

Discovery and Optimization of Pyrrolopyrimidine Derivatives as Selective Disruptors of the Perinucleolar Compartment, a Marker of Tumor Progression toward Metastasis

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, Copyright © 2022 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jmedchem.2c00204.The perinucleolar compartment (PNC) is a dynamic subnuclear body found at the periphery of the nucleolus. The PNC is enriched with RNA transcripts and RNA-binding proteins, reflecting different states of genome organization. PNC prevalence positively correlates with cancer progression and metastatic capacity, making it a useful marker for metastatic cancer progression. A high-throughput, high-content assay was developed to identify novel small molecules that selectively reduce PNC prevalence in cancer cells. We identified and further optimized a pyrrolopyrimidine series able to reduce PNC prevalence in PC3M cancer cells at submicromolar concentrations without affecting cell viability. Structure–activity relationship exploration of the structural elements necessary for activity resulted in the discovery of several potent compounds. Analysis of in vitro drug-like properties led to the discovery of the bioavailable analogue, metarrestin, which has shown potent antimetastatic activity with improved survival in rodent models and is currently being evaluated in a first-in-human phase 1 clinical trial

Stratospheric aerosol - Observations, processes, and impact on climate

Interest in stratospheric aerosol and its role in climate have increased over the last decade due to the observed increase in stratospheric aerosol since 2000 and the potential for changes in the sulfur cycle induced by climate change. This review provides an overview about the advances in stratospheric aerosol research since the last comprehensive assessment of stratospheric aerosol was published in 2006. A crucial development since 2006 is the substantial improvement in the agreement between in situ and space-based inferences of stratospheric aerosol properties during volcanically quiescent periods. Furthermore, new measurement systems and techniques, both in situ and space based, have been developed for measuring physical aerosol properties with greater accuracy and for characterizing aerosol composition. However, these changes induce challenges to constructing a long-term stratospheric aerosol climatology. Currently, changes in stratospheric aerosol levels less than 20% cannot be confidently quantified. The volcanic signals tend to mask any nonvolcanically driven change, making them difficult to understand. While the role of carbonyl sulfide as a substantial and relatively constant source of stratospheric sulfur has been confirmed by new observations and model simulations, large uncertainties remain with respect to the contribution from anthropogenic sulfur dioxide emissions. New evidence has been provided that stratospheric aerosol can also contain small amounts of nonsulfate matter such as black carbon and organics. Chemistry-climate models have substantially increased in quantity and sophistication. In many models the implementation of stratospheric aerosol processes is coupled to radiation and/or stratospheric chemistry modules to account for relevant feedback processes

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade >/= 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC