A Photoredox Coupling Reaction of Benzylboronic Esters and Carbonyl Compounds in Batch and Flow.

Mild cross-coupling reaction between benzylboronic esters with carbonyl compounds and some imines was achieved under visible-light-induced iridium-catalyzed photoredox conditions. Functional group tolerance was demonstrated by 51 examples, including 13 heterocyclic compounds. Gram-scale reaction was realized through the use of computer-controlled continuous flow photoreactors.Uniqsis Ltd and Mark Ladlow for the generous loan 236 of a Photosyn reactor. Y.C. thanks Pfizer for funding the 237 postdoctoral fellowship. The authors also gratefully acknowl- 238 edge financial support from H2020-FETOPEN-2016-2017 239 program of European commission (S.V.L.; grant agreement 240 no.: 737266-ONE FLOW)

Visible-Light-Mediated Annulation of Electron-Rich Alkenes and Nitrogen-Centered Radicals from N-Sulfonylallylamines: Construction of Chloromethylated Pyrrolidine Derivatives.

A visible-light-mediated annulation of N-sulfonylallylamines and olefins is reported. Rapid access to highly functionalized chloromethylated pyrrolidines can be achieved using mild conditions for the generation of nitrogen-centered radicals. Both a transition-metal-based catalyst and an organic dye can be used as photosensitizers with 0.5 mol % loading. The reaction was found to be applicable to a large variety of electron-rich and electron-neutral olefins.This work was supported by a postdoctoral fellowship from Pfizer (L.C. and A.G.) and the EPSRC Grants EP/K009494/1 and EP/M004120/1 (S.V.L.)

Photoredox generation of sulfonyl radicals and coupling with electron deficient olefins

Various sulfone tetrazoles were activated via iridium photoredox catalysis in the presence of DMAP to give dialkyl sulfones. The presumed sulfone radical intermediates were trapped by a range of electron deficient olefins in generally good to excel-lent yields.Pfizer for funding the postdoctoral fellowship. COST Action CA18133 ERNEST for funding short term scientific mission (STSM). American Chemical Society through the Arthur C. Cope Fund (award to SVL). H2020-FETOPEN-2016-2017 programe of European commission (SVL; grant agreement number: 737266-ONE FLOW

Capacity fade in nickel cadmium and nickel hydrogen cells

Research and operational experience with capacity fade in nickel cadmium and nickel hydrogen cells are summarized in outline form. The theoretical causes of capacity fade are reviewed and the role of cell storage, positive electrodes, and cobalt additives are addressed. Three examples of observed capacity fade are discussed: INTELSAT 5, INTELSAT 6, and an Explorer platform. Finally, prevention and recovery methods are addressed and the current status of Eagle Picher/Hughes research is discussed

Contrasting changes in palatability following senescence of the lichenized fungi Lobaria pulmonaria and L. scrobiculata

Epiphytic lichens can contribute significantly to ecosystem nutrient input because they efficiently accumulate atmospheric mineral nutrients and, in the case of cyanolichens, also fix nitrogen. The rate at which carbon and other nutrients gained by lichens enters the ecosystem is determined by lichen litter decomposability and by invertebrate consumption of lichen litter. In turn, these processes are driven by the secondary compounds present in senesced lichens. Therefore, we explored how lichen palatability and concentrations of secondary compounds change with tissue senescence for Lobaria pulmonaria, a green algal lichen with cyanobacterial cephalodia, and L. scrobiculata, a cyanobacterial lichen. During senescence both lichens lost 38-48% of their stictic acid chemosyndrome, while m-scrobiculin and usnic acid in L. scrobiculata remained unchanged. Snails preferred senesced rather than fresh L. pulmonaria, while senesced L. scrobiculata were avoided. This provides evidence that species with labile secondary compounds will have higher turnover rates, through consumption and decomposition, than those producing more stable secondary compounds

Three-component assembly of multiply-substituted homoallylic alcohols and amines using a flow chemistry photoreactor

Oxadiazolines are bench-stable diazo precursors, which are activated under UV radiation in the presence of vinylboronic acids and aldehydes to enable a one-step three-component assembly of densely-functionalized homoallylic alcohols. Sub-stitution on all positions of the homoallylic alcohol product were achieved with high functional group tolerance. No catalyst or other additive was required to effect the reaction which proceeds at 20 ℃ over 40 minutes. Imines and indoles were also incorporated, giving access to homoallylic amines

Copper-catalyzed synthesis of masked (hetero)aryl sulfinates

Catalysis using substoichiometric copper facilitates the synthesis of masked (hetero)aryl sulfinates under mild, base-free conditions from aryl iodides and the commercial sulfonylation reagent sodium 1-methyl 3-sulfinopropanoate (SMOPS). The development of a tert-butyl ester variant of the SMOPS reagent allowed the use of aryl bromide substrates. The sulfones thus generated can be unmasked and functionalized in situ to form a variety of sulfonyl-containing functional groups

Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: Positioning of a highly mobile antigenic loop

Data from cryo-electron microscopy and X-ray crystallography have been combined to study the interactions of foot-and-mouth disease virus serotype C (FMDV-C) with a strongly neutralizing monoclonal antibody (mAb) SD6. The mAb SD6 binds to the long flexible GH-loop of viral protein 1 (VP1) which also binds to an integrin receptor. The structure of the virus-Fab complex was determined to 30 Å resolution using cryo-electron microscopy and image analysis. The known structure of FMDV-C, and of the SD6 Fab co-crystallized with a synthetic peptide corresponding to the GH-loop of VP1, were fitted to the cryo-electron microscope density map. The SD6 Fab is seen to project almost radially from the viral surface in an orientation which is only compatible with monovalent binding of the mAb. Even taking into account the mAb hinge and elbow flexibility, it is not possible to model bivalent binding without severely distorting the Fabs. The bound GH-loop is essentially in what has previously been termed the 'up' position in the best fit Fab orientation. The SD6 Fab interacts almost exclusively with the GH-loop of VP1, making very few other contacts with the viral capsid. The position and orientation of the SD6 Fab bound to FMDV-C is in accord with previous immunogenic data.Peer Reviewe

Is telephone health coaching a useful population health strategy for supporting older people with multimorbidity? : An evaluation of reach, effectiveness and cost-effectiveness using a 'trial within a cohort'

BACKGROUND: Innovative ways of delivering care are needed to improve outcomes for older people with multimorbidity. Health coaching involves 'a regular series of phone calls between patient and health professional to provide support and encouragement to promote healthy behaviours'. This intervention is promising, but evidence is insufficient to support a wider role in multimorbidity care. We evaluated health coaching in older people with multimorbidity. METHODS: We used the innovative 'Trials within Cohorts' design. A cohort was recruited, and a trial was conducted using a 'patient-centred' consent model. A randomly selected group within the cohort were offered the intervention and were analysed as the intervention group whether they accepted the offer or not. The intervention sought to improve the skills of patients with multimorbidity to deal with a range of long-term conditions, through health coaching, social prescribing and low-intensity support for low mood. RESULTS: We recruited 4377 older people, and 1306 met the eligibility criteria (two or more long-term conditions and moderate 'patient activation'). We selected 504 for health coaching, and 41% consented. More than 80% of consenters received the defined 'dose' of 4+ sessions. In an intention-to-treat analysis, those selected for health coaching did not improve on any outcome (patient activation, quality of life, depression or self-care) compared to usual care. We examined health care utilisation using hospital administrative and self-report data. Patients selected for health coaching demonstrated lower levels of emergency care use, but an increase in the use of planned services and higher overall costs, as well as a quality-adjusted life year (QALY) gain. The incremental cost per QALY was £8049, with a 70-79% probability of being cost-effective at conventional levels of willingness to pay. CONCLUSIONS: Health coaching did not lead to significant benefits on the primary measures of patient-reported outcome. This is likely related to relatively low levels of uptake amongst those selected for the intervention. Demonstrating effectiveness in this design is challenging, as it estimates the effect of being selected for treatment, regardless of whether treatment is adopted. We argue that the treatment effect estimated is appropriate for health coaching, a proactive model relevant to many patients in the community, not just those seeking care. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ( ISRCTN12286422 )