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1. Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355

Author

Kepplinger, Bernhard, Mardiana, Lina, Cowell, Joseph, Morton-Laing, Stephanie, Dashti, Yousef, Wills, Corinne, Marrs, Emma C. L., Perry, John D., Gray, Joe, Goodfellow, Michael, Errington, Jeff, Probert, Michael R., Clegg, William, Bogaerts, Jonathan, Herrebout, Wouter, Allenby, Nick E. E., and Hall, Michael J.

Published
2022
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4. How can we achieve a sustainable nuclear fuel cycle?

Author

Harwood, Laurence M., Afsar, Ashfaq, Babra, Jasraj Singh, Bond, Gary, Burk, Jaanus, Choi, Sang June, Cowell, Joseph, Davis, Frederick, Distler, Petr, Eccles, Harry, Edwards, Chad, Geist, Andreas, Hodson, Mark E., Hopkins, Iain, Hudson, Michael, Holdsworth, Alistair, Jang, Geungseok, Jang, Jiseon, John, Jan, Lee, Dae Sung, Lee, Kyung Jin, Lee, Taek Seung, Lewis, Frank, Mohan, Saaed, Ogden, Mark, Pepper, Sarah, Selfe, Zoe, Shaw, Elizabeth, Sharrad, Clint, Smith, Chris, Song, Jong Soon, Tamm, Kaldo, Westwood, James, Whitehead, Roger, Whittle, Karl, Harwood, Laurence M., Afsar, Ashfaq, Babra, Jasraj Singh, Bond, Gary, Burk, Jaanus, Choi, Sang June, Cowell, Joseph, Davis, Frederick, Distler, Petr, Eccles, Harry, Edwards, Chad, Geist, Andreas, Hodson, Mark E., Hopkins, Iain, Hudson, Michael, Holdsworth, Alistair, Jang, Geungseok, Jang, Jiseon, John, Jan, Lee, Dae Sung, Lee, Kyung Jin, Lee, Taek Seung, Lewis, Frank, Mohan, Saaed, Ogden, Mark, Pepper, Sarah, Selfe, Zoe, Shaw, Elizabeth, Sharrad, Clint, Smith, Chris, Song, Jong Soon, Tamm, Kaldo, Westwood, James, Whitehead, Roger, and Whittle, Karl

Abstract

Dealing with spent nuclear fuel is key if nuclear fission is to be used more widely going forward. Nuclear power is close to carbon neutral, but spent nuclear fuel has a storage lifetime of ~300,000 years. Reprocessing spent nuclear fuel is carried out on large scale using the PUREX “Plutonium Uranium Reduction and Extraction” process. The spent nuclear fuel is reduced to 15% of its original weight and the separated uranium and plutonium reused as “Mixed Oxide Fuel”. In the civil sector, this was carried out by the UK at Sellafield (now curtailed) and continues in France at La Hague. A plant in Rokashamura in Japan has been mothballed after the Fukushima accident. The residual waste must be stored for ~9,000 years with most of the remaining radiotoxicity due to traces of the minor actinides, neptunium, americium and curium, constituting just 0.1% of the original spent fuel. Separation of these minor actinides from the chemically very similar lanthanides (rare earths) in the last 15% of waste remaining after PUREX is the key step for future reprocessing. If separated, the minor actinides can be used as fuel in the next generation of nuclear reactors and converted into benign products, but lanthanides will cause the fission process to shut down if introduced into the reactor pile as they absorb neutrons efficiently. Removing the minor actinides from post PUREX waste will mean that the final residue need only be stored for 300 years. The highly challenging separation of the chemically very similar minor actinides from the lanthanides has been achieved using nitrogen-bearing organic ligands developed at Reading University. This can lead to significantly improved handling of spent nuclear fuels and means that waste nuclear fuel need not be a long-term storage liability but a source of yet more clean power.

Published
2024

6. Diels-Alder/ene reactions of 3-vinyl-1H-indoles : rapid synthesis of unsaturated carbazoles and pyradazino[3,4-b]indoles

Author

Cowell, Joseph

Subjects
615.7
Abstract

Unsaturated carbazole frameworks are found in several important naturally occurring and synthetic biologically active compounds. We envisaged synthesising compounds of this type using an intermolecular Diels-Alder reaction between 3-vinyl-1H-indole and a dienophile, followed by an intermolecular ene reaction between the resultant Diels-Alder adduct (6) and an enophile. This route was tested using tosyl protected 3-vinyl-1H-indole (4) and N-methylmaleimide (5) in a Diels- Alder reaction, followed by ene reactions with a range of enophiles to give unsaturated carbazoles (7) in yields of 50-60% over the two steps. Through utilisation of Soos’s organo-catalyst3, we have been able to control the Diels-Alder reaction between 3-vinyl-1H-indole (8) and N-methylmaleimide (5), to form the Diels-Alder adduct (9) with high enantiomeric excess. The subsequent stereospecific ene reaction then gives unsaturated carbazoles (10) in >96% ee. We then developed a sequential “one-pot” Diels-Alder / ene methodology with an Nprotected 3-vinyl-1H-indole (11), a dienophile and an enophile to make unsaturated carbazoles and pyridazino[3,4-b]indoles (13). This methodological approach gave increased overall yields and reduced purification steps. When Cbz N-protected 3-vinyl-1H-indoles were used the Diels-Alder / ene products (14) could then be deprotected through a PtO2 catalysed hydrogenation reaction to give molecules (15). Several of the synthesised compounds (15) showed moderate biological activity against Escherichia coli, Staphylococcus aureus and Schizosaccharomyces pombe. Compounds (15) are also moderate (μM) inhibitors of several important kinases, including Chk2, Aurora B, Src and JAK2, which are potential targets for cancer treatment.

Published
2014

10. Discovery, Isolation, Heterologous Expression and Mode of Action Studies of the Antibiotic Polyketide Tatiomicin from Amycolatopsis sp. DEM30355

Author

Kepplinger, Bernhard, primary, Mardiana, Lina, additional, Cowell, Joseph, additional, Morton-Laing, Stephanie, additional, Wills, Corinne, additional, Dashti, Yousef, additional, Marrs, Emma, additional, Perry, John, additional, Grey, Joe, additional, Goodfellow, Michael, additional, Errington, Jeff, additional, Probert, Michael, additional, Clegg, Bill, additional, Bogaerts, Jonathan, additional, Herrebout, Wouter, additional, Allenby, Nick E. E., additional, and Hall, Michael, additional

Published
2022
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12. Discovery of the Antibiotic Polyketide Tatiomicin via a Genomics Guided Analysis of Amycolatopsis sp. DEM30355

Author

Kepplinger, Bernhard, primary, Cowell, Joseph, primary, Morton-Laing, Stephanie, primary, Wills, Corinne, primary, Marrs, Emma, primary, Perry, John, primary, Grey, Joe, primary, Goodfellow, Michael, primary, Errington, Jeff, primary, Probert, Michael, primary, Clegg, Bill, primary, Bogaerts, Jonathan, primary, Herrebout, Wouter, primary, Allenby, Nick E. E., primary, and Hall, Michael, primary

Published
2020
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13. Head-to-head comparison of DFO* and DFO chelators: selection of the best candidate for clinical 89Zr-immuno-PET

Author

Chomet, Marion, primary, Schreurs, Maxime, additional, Bolijn, Maria J., additional, Verlaan, Mariska, additional, Beaino, Wissam, additional, Brown, Kari, additional, Poot, Alex J., additional, Windhorst, Albert D., additional, Gill, Herman, additional, Marik, Jan, additional, Williams, Simon, additional, Cowell, Joseph, additional, Gasser, Gilles, additional, Mindt, Thomas L., additional, van Dongen, Guus A. M. S, additional, and Vugts, Danielle J., additional

Published
2020
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20. Cobalt and nickel uptake by silica-based extractants.

Author

Pepper, Sarah E., Whittle, Karl R., Harwood, Laurence M., Cowell, Joseph, Lee, Taek Seung, and Ogden, Mark D.

Subjects
COBALT, NICKEL, SILICA, ION exchange resins, LANGMUIR isotherms
Abstract

The pKas of ethyl/butyl phosphonate silica (EBP-Si) have been determined, and the removal of cobalt and nickel from solution was investigated as a function of various parameters and compared with those of Purolite S950. pH uptake experiments suggested a combination of ion exchange and acid dissociation of the surface occurring. Isotherm data, fitted using the Langmuir and Dubinin-Radushkevich (D-R) models, indicated that stronger complexes formed with S950 than with EBP-Si. Kinetic data, fitted using a pseudo-second-order model, suggested that the rate-determining process is the reaction of metal ions with the chelating functionality of the resin. Uptake by EBP-Si is two to three times faster than that on S950. [ABSTRACT FROM AUTHOR]

Published
2018
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23. Synthesis of Novel BTPhen-Functionalized Silica-Coated Magnetic Nanoparticles for Separating Trivalent Actinides and Lanthanides.

Author

Afsara, Ashfaq, Cowell, Joseph, Distler, Petr, Harwood, Laurence M., John, Jan, and Westwood, James

Subjects
*SILICA, *MAGNETIC nanoparticles, *NANOSTRUCTURED materials synthesis, *SEPARATION (Technology)
Abstract

Bis-(1,2,4-triazin-3-yl)-1,10-phenanthroline (BTPhen) functionalized magnetic nanoparticles (MNPs), which selectively extract Am(III) over europium(III) from 0.1 M HNO3 with fast kinetics and a separation factor of 30 have been synthesized. These MNPs also show a small but significant selectivity for Am(III) over Cm(III) with a separation factor of around 3 in 0.1 M HNO3. We report also the synthesis of these BTPhen and related ligands via an improved synthetic route bypassing the problematic benzylic oxidation with stoichiometric SeO2. [ABSTRACT FROM AUTHOR]

Published
2017
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26. ART OF PSYCHOTIC PERSONS: A RESTRAINT-ACTIVITY INDEX AND ITS RELATION TO DIAGNOSIS

Author

SCHUBE, PURCELL G. and COWELL, JOSEPH G.

Abstract

Art expression in a normal person tends to show a balance between activity and restraint in the mental state. This is adequately demonstrated in the paintings of such artists as Sargent, Raphael, Reynolds and Rembrandt. In the drawings of a psychotic person, on the other hand, there is definite evidence of a dominance of either activity or restraint. In many such productions this can be observed immediately; in others it must be sought in situations in which the restraint or activity is concealed or overshadowed by other material. Investigation of this material, moreover, appears to reveal a definite correlation not only between certain types of psychoses and artistic productions but also between the activity or restraint exhibited in a series of productions by a patient and the course of the patient's mental illness. In the division of creative therapy at this hospital we have been investigating these factors for several

Published
1939
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27. An LC/MS/MS method for stable isotope dilution studies of β-carotene bioavailability, bioconversion, and vitamin A status in humans

Author

G A Taylor, Georg Lietz, Joseph Cowell, John E. Hesketh, Alan V. Boddy, Anthony Oxley, Michael J. Hall, Philip Berry, Oxley, Anthony, Berry, Philip, Taylor, Gordon, Cowell, Joseph, Hall, Michael J, Hesketh, John, Lietz, Georg, and Boddy, Alan V

Subjects
Adult, Male, Biochemistry & Molecular Biology, Time Factors, Adolescent, medicine.medical_treatment, β-carotene 15,15′-monooxygenase, Biological Availability, Atmospheric-pressure chemical ionization, QD415-436, retinol metabolism, Retinyl acetate, Isotope dilution, Biochemistry, Young Adult, chemistry.chemical_compound, Endocrinology, Isotopes, Retinyl palmitate, tandem mass spectrometry, Methods, medicine, Humans, Vitamin A, Biotransformation, Chromatography, Carotene, Retinol, Cell Biology, Middle Aged, beta Carotene, Bioavailability, Retinol binding protein, chemistry, retinyl esters, Female, carotenoid metabolism, Chromatography, Liquid
Abstract

Isotope dilution is currently the most accurate technique in humans to determine vitamin A status and bioavailability/bioconversion of provitamin A carotenoids such as beta-carotene. However, limits of MS detection, coupled with extensive isolation procedures, have hindered investigations of physiologically-relevant doses of stable isotopes in large intervention trials. Here, a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) analytical method was developed to study the plasma response from coadministered oral doses of 2 mg [C-13(10)]beta-carotene and 1 mg [C-13(10)]retinyl acetate in human subjects over a 2 week period. A reverse phase C-18 column and binary mobile phase solvent system separated beta-carotene, retinol, retinyl acetate, retinyl linoleate, retinyl palmitate/retinyl oleate, and retinyl stearate within a 7 min run time. Selected reaction monitoring of analytes was performed under atmospheric pressure chemical ionization in positive mode at m/z 537 -> 321 and m/z 269 -> 93 for respective [C-12]beta-carotene and [C-12]retinoids; m/z 547 -> 330 and m/z 274 -> 98 for [C-13(10)]beta-carotene and [C-13(5)] cleavage products; and m/z 279 -> 100 for metabolites of [C-13(10)]retinyl acetate. A single one-phase solvent extraction, with no saponification or purification steps, left retinyl esters intact for determination of intestinally-derived retinol in chylomicrons versus retinol from the liver bound to retinol binding protein. Coadministration of [C-13(10)]retinyl acetate with [C-13(10)]beta-carotene not only acts as a reference dose for inter-individual variations in absorption and chylomicron clearance rates, but also allows for simultaneous determination of an individual's vitamin A status. Refereed/Peer-reviewed

Published
2014

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