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This study reports the first example of using a dual catalytic system with copper(II) acetate and 2-hydroxynicotinaldehyde to achieve transient C(sp2)–H sulfonylation of benzylamines with sulfinate salts via a dynamically formed imine directing group. Manganese(IV) oxide was identified as an effective oxidant and base. Computational DFT investigations suggest that the TDG lowers the energy barrier for an acetate-mediated, turnover limiting C–H activation step and subsequent combination of the cupracycle with a RSO2 radical.

Directed C–H functionalization is a powerful means to functionalize otherwise unreactive C‒H bonds, for which aminoquinoline amides provide a powerful and frequently used directing group. Saturated N-heterocycles are crucial motifs in medicinal chemistry. However, the C–H functionalization of N-heterocycles has posed considerable chal-lenges, often giving incomplete conversions. On unsymmetrical substrates, poorly understood regio- and stereoselectivity considerations have prevented more forcing conditions and further limited yields. Here we present a combined experimental and computational study on the regio- and stereoselective C4 arylation of pyrrolidines and piperidines with C3 aminoquinoline amide directing groups. Detailed mechanistic experiments are presented including deuteration, kinetics investigations, and isolation of palladacycles. The palladacycle formation is reversible and proceeds preferentially at C4, though activation of both C–H bonds at C4, cis and trans to the directing group, occurs equally. The cis-selectivity results from strain in the trans-palladacycle (ΔΔGtrans-cis ~6 kcal∙mol–1), that is retained in subsequent transition states. Hence, the oxidative addition step is stereodetermining. However, the turnover-limiting step for the catalytic cycle is reductive elimination, and reduced rates and yields were observed with electron poor aryl iodides. Importantly, kinetics experiments reveal a rapid loss of active Pd catalyst, likely due to the build-up of iodide, and a role for K2CO3/PivOH in catalyst turnover. Finally, we present the discovery of an improved 4-dimethylamine-8-aminoquinoline directing group (DMAQ). This removable auxiliary achieves >2x rate acceleration, generally im-proved yields, as well as improved cis-selectivity, by promoting reductive elimination. A broad reaction scope of aryl iodides is demonstrated, including the late-stage functionalization of drug compounds which is enabled by the use of only one equivalent of functionalized iodides.

Oxetanes and azetidines continue to draw significant interest in medicinal chemistry, as small, polar and non-planar motifs. Oxetanes also represent interesting surrogates for carbonyl-containing functional groups. Here we report a synthesis of 3,3- disubstituted oxetane- and azetidine-ethers, with comparisons made to the ester functional group. The tertiary benzylic alcohols of the 4-membered rings are selectively activated using Brønsted acid catalysis and reacted with simple alcohols to form the ethers and maintain the oxetane ring intact. This approach avoids the use of strong bases and halide alkylating agents and allows alcohol libraries to be leveraged. Oxetane ethers demonstrate excellent chemical stability across a range of conditions and an improved stability vis-à-vis analogous esters under basic and reducing conditions.

This technical report is a short investigation into how Rust couldbe used for a scientific application in a HPC system. A computational fluid dynamics model of fluid flow into and out of a box was developed in Rust and compared to the same algorithm implementedin C and Fortran. These simulations were performed for both serial and parallelised versions over a variety of problem sizes. The report discusses the results of these simulations and the implications for using Rust as a tool for scientific programming in HPC.

SUMMARY Vertical fluid-escape structures observed in seismic reflection data represent an important class of potentially active fluid flow pathways. An understanding of the mechanism of fluid flow in these types of structures is needed to assess the risk of natural gas venting from potential subsurface carbon dioxide storage operations. The Scanner Pockmark Complex is a 22 m deep, 900 × 450 m seabed depression in the North Sea, which actively vents methane, and is underlain by a seismic chimney structure with horizontal dimensions of ∼300 × 600 m. Gas accumulation is evidenced by the presence of bright reflectors at the top of this seismic chimney, at a depth of ∼50 m below the seabed. Here, we analyse seismic anisotropy in these shallow sediments using shear wave splitting observed on ocean bottom seismographs (OBS). Anisotropy varies spatially, with a strength of ∼1–4 per cent, on several OBS located in and around the pockmark complex. By correlating these observations with calculated subsurface P- and S-wave velocities, we show that there is anisotropy present throughout the sediments through which the chimney passes, which are interpreted as relating to syn- and post-depositional glaciomarine processes. However, within the chimney itself the orientation of the fast direction is different to that outside the chimney and the degree of anisotropy is lower. We attribute this difference as indicating that the anisotropy observed within the chimney is associated with the formation and continued presence of the gas migration system, which overprints the background depositional anisotropy.

Made available in DSpace on 2022-04-28T19:29:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 Medical Research Council Canada National Institute for Health Research Objectives: To develop consensus definitions for the core outcome set for pre-eclampsia. Study design: Potential definitions for individual core outcomes were identified across four formal definition development initiatives, nine national and international guidelines, 12 Cochrane systematic reviews, and 79 randomised trials. Eighty-six definitions were entered into the consensus development meeting. Ten healthcare professionals and three researchers, including six participants who had experience of conducting research in low- and middle-income countries, participated in the consensus development process. The final core outcome set was approved by an international steering group. Results: Consensus definitions were developed for all core outcomes. When considering stroke, pulmonary oedema, acute kidney injury, raised liver enzymes, low platelets, birth weight, and neonatal seizures, consensus definitions were developed specifically for low- and middle-income countries because of the limited availability of diagnostic interventions including computerised tomography, chest x-ray, laboratory tests, equipment, and electroencephalogram monitoring. Conclusions: Consensus on measurements for the pre-eclampsia core outcome set will help to ensure consistency across future randomised trials and systematic reviews. Such standardization should make research evidence more accessible and facilitate the translation of research into clinical practice. Video abstract can be available at: www.dropbox.com/s/ftrgvrfu0u9glqd/6.%20Standardising%20definitions%20in%20teh%20pre-eclampsia%20core%20outcome%20set%3A%20a%20consensus%20development%20study.mp4?dl=0. Nuffield Department of Primary Care Health Sciences University of Oxford Institute for Women’s Health University College London Department of Women and Children’s Health School of Life Course Sciences King’s College London Department of Obstetrics and Gynecology Amsterdam UMC Academic Medical Center Academic Neonatal Medicine Imperial College London Department of Renal Medicine St George Hospital and University of New South Wales Department of Obstetrics and Gynaecology Feinberg School of Medicine Northwestern University Health Services Research Unit Nuffield Department of Population Health University of Oxford Cedars-Sinai Medical Center London North West University Healthcare NHS Trust Women’s Health Care Research Group Department of Obstetrics and Gynaecology Monash University Department of Obstetrics and Gynaecology University of Adelaide Women’s Health Research Unit Barts and The London School of Medicine and Dentistry School of Health and Related Research University of Sheffield MRC North West Hub for Trials Methodology Research Department of Biostatistics University of Liverpool Centro Rosarino de Estudios Perinatales Chelsea and Westminster Hospital NHS Foundation Trust Babcock University Ailem Academic Counselling KU Leuven Universidad Nacional de Colombia Northwell Health University of Oxford Université de Montréal University of Montreal Hospital Centre Ondokuz Mayıs University Prince Sultan Military Medical City Postgraduate Institute of Medical Education and Research King's Fertility Fetal Medicine Research Institute University Hospital Limerick Drexel University University of Aberdeen University of Groningen University of Auckland Haaglanden Medisch Centrum Nottingham University Medical School Utrecht University King Edward Memorial Hospital for Women Imperial College Healthcare NHS Trust Jean-Verdier Hospital Downland Practice University of Campinas Université Lyon University of North Carolina School of Medicine South Ural State Medical University Stellenbosch University Irish Neonatal Health Alliance University of Rzeszow Royal Brisbane and Women’s Hospital Nottingham University Hospitals NHS Trust University Hospitals of Leicester North Bristol NHS Trust University of Nottingham Soroka University Medical Center Ben Gurion University of the Negev St George’s University Hospitals NHS Foundation Trust Hospitalsenhed Midt University of Glasgow Amsterdam Universitair Medische Centra All India Institute of Medical Sciences Patna Luton and Dunstable University Hospital Khyber Medical University Institution of Medical Sciences Midwife Mid Essex Hospitals NHS Trust University of Oulu University of Michigan Bastyr University Irish Nurses and Midwives Organisation University of Toronto Barts Health NHS Trust University Hospitals Plymouth NHS Trust Burnet Institute Aga Khan University Medical University of Graz Homerton University Hospital NHS Foundation Trust Mount Royal University Université de Paris Royal Surrey County Hospital University Hospital Southampton NHS Foundation Trust University of Washington School of Nursing Evelina London Children's Hospital Neonatal Unit University of Sydney University of Leicester Academic Hospital of Udine NHS Borders Weill Cornell Medical College University of Dundee University of Edinburgh South Australian Health and Medical Research Institute University of Sheffield Monash University and Monash Health United Lincolnshire Hospitals NHS Trust University of Kwa Zulu-Natal Beatrix Hospital Keele University Government Medical College Institut Catala de la Salut. IdiapJgol University College London National Center for Child Health and Development Basavatarakam Indo-American Cancer Hospital and Research Institute Axon Anaesthesia Associates Pennine Acute Hospitals NHS Trust St George's University of London Norfolk and Norwich University Hospital Jichi Medical University School of Medicine São Paulo State University National Institute of Public Health University of Kyrenia King Edward Memorial Hospital Amsterdam University Centres University of British Columbia Chulalongkorn University University of Brescia University Of British Columbia University of Montreal Women's Clinic of Tartu University Hospital Universidade Federal de São Paulo Université de Sherbrooke University Hospital of Wales University of Iowa King's College London Westmead Hospital Princess Royal Maternity Leipzig University Centre Hospitalier Public du Cotentin Lewisham and Greenwich NHS Trust Juntendo University Faculty of Medicine Western Sydney University National Institute of Health Research University of Washington Baylor College of Medicine Capelle aan den Ijssel Sanatorio Anchorena Oxford University Hospitals NHS Foundation Trust University of Leeds Institute of Medical Sciences UPMC Magee Womens Hospital Penn Medicine Princeton Health University of North Carolina at Chapel Hill São Paulo State University