Enantioselective synthesis of (+)-petromyroxol, enabled by rhodium-catalyzed denitrogenation and rearrangement of a 1-sulfonyl-1,2,3-triazole

Petromyroxol is a non-racemic mixture of enantiomeric oxylipids isolated from water conditioned with larval sea lamprey. The (+)-antipode exhibits interesting biological properties but only 1 mg was isolated from >100000 L of water. Recently, transition metal-catalyzed denitrogenation of 1-sulfonyl-1,2,3-triazoles has emerged as a powerful strategy for the synthesis of value-added products, including efficient diastereocontrolled construction of tetrahydrofurans. This methodology enabled the rapid development of the first synthesis of (+)-petromyroxol in 9 steps and 20% overall yield from a readily accessible starting material

Rhodium(II)-catalyzed stereocontrolled synthesis of 2-tetrasubstituted saturated heterocycles from 1-Sulfonyl-1,2,3-triazoles

Rhodium(II) acetate catalyzes the denitrogenative transformation of 4-substituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ethers and thioethers to onium ylides that undergo [2,3]-sigmatropic rearrangement to give 2-tetrasubstituted heterocycles with high yield and diastereoselectivity

Stereodefined synthesis of cyclic amidines by domino 1,7-H shift and 6π electrocyclisation

Unsaturated N2-sulfonyl amidines are transformed into valuable N-heterocyclic products when heated with BF2OTf. Mechanism studies suggest a domino 1,7-H shift, activating a C–H bond, followed by electrocylisation that results in stereodefined cyclic amidines

Rhodium(II)-catalyzed stereocontrolled synthesis of dihydrofuran-3-imines from 1-Tosyl-1,2,3-triazoles

Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to give substituted dihydrofuran-3-imines in high yield and diastereoselectivity

Guidelines for Modeling and Reporting Health Effects of Climate Change Mitigation Actions.

BACKGROUND: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers. OBJECTIVE: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions. METHODS: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies. RESULTS: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting. DISCUSSION: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can inform evidence-based decision making and practice. https://doi.org/10.1289/EHP6745

Future Ocean Observations to Connect Climate, Fisheries and Marine Ecosystems

Advances in ocean observing technologies and modeling provide the capacity to revolutionize the management of living marine resources. While traditional fisheries management approaches like single-species stock assessments are still common, a global effort is underway to adopt ecosystem-based fisheries management (EBFM) approaches. These approaches consider changes in the physical environment and interactions between ecosystem elements, including human uses, holistically. For example, integrated ecosystem assessments aim to synthesize a suite of observations (physical, biological, socioeconomic) and modeling platforms [ocean circulation models, ecological models, short-term forecasts, management strategy evaluations (MSEs)] to assess the current status and recent and future trends of ecosystem components. This information provides guidance for better management strategies. A common thread in EBFM approaches is the need for high-quality observations of ocean conditions, at scales that resolve critical physical-biological processes and are timely for management needs. Here we explore options for a future observing system that meets the needs of EBFM by (i) identifying observing needs for different user groups, (ii) reviewing relevant datasets and existing technologies, (iii) showcasing regional case studies, and (iv) recommending observational approaches required to implement EBFM. We recommend linking ocean observing within the context of Global Ocean Observing System (GOOS) and other regional ocean observing efforts with fisheries observations, new forecasting methods, and capacity development, in a comprehensive ocean observing framework

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Increased Cycling Cell Numbers and Stem Cell Associated Proteins as Potential Biomarkers for High Grade Human Papillomavirus+ve Pre-Neoplastic Cervical Disease

High risk (oncogenic) human papillomavirus (HPV) infection causes cervical cancer. Infections are common but most clear naturally. Persistent infection can progress to cancer. Pre-neoplastic disease (cervical intraepithelial neoplasia/CIN) is classified by histology (CIN1-3) according to severity. Cervical abnormalities are screened for by cytology and/or detection of high risk HPV but both methods are imperfect for prediction of which women need treatment. There is a need to understand the host virus interactions that lead to different disease outcomes and to develop biomarker tests for accurate triage of infected women. As cancer is increasingly presumed to develop from proliferative, tumour initiating, cancer stem cells (CSCs), and as other oncogenic viruses induce stem cell associated gene expression, we evaluated whether presence of mRNA (detected by qRT-PCR) or proteins (detected by flow cytometry and antibody based proteomic microarray) from stem cell associated genes and/or increased cell proliferation (detected by flow cytometry) could be detected in well-characterised, routinely collected cervical samples from high risk HPV+ve women. Both cytology and histology results were available for most samples with moderate to high grade abnormality. We found that stem cell associated proteins including human chorionic gonadotropin, the oncogene TP63 and the transcription factor SOX2 were upregulated in samples from women with CIN3 and that the stem cell related, cell surface, protein podocalyxin was detectable on cells in samples from a subset of women with CIN3. SOX2, TP63 and human gonadotrophin mRNAs were upregulated in high grade disease. Immunohistochemistry showed that SOX2 and TP63 proteins clearly delineated tumour cells in invasive squamous cervical cancer. Samples from women with CIN3 showed increased proliferating cells. We believe that these markers may be of use to develop triage tests for women with high grade cervical abnormality to distinguish those who may progress to cancer from those who may be treated more conservatively