Neuroprotective effects of phenolic antioxidant tBHQ associate with inhibition of FoxO3a nuclear translocation and activity

The Forkhead transcription factor, FoxO3a induces genomic death responses in neurones following translocation from the cytosol to the nucleus. Nuclear translocation of FoxO3a is triggered by trophic factor withdrawal, oxidative stress and the stimulation of extrasynaptic NMDA receptors. Receptor activation of phosphatidylinositol 3-kinase (PI3K) – Akt signalling pathways retains FoxO3a in the cytoplasm thereby inhibiting the transcriptional activation of death promoting genes. We hypothesised that phenolic antioxidants such as tert-Butylhydroquinone (tBHQ), which is known to stimulate PI3K-Akt signalling, would inhibit FoxO3a translocation and activity. Treatment of cultured cortical neurones with NMDA increased the nuclear localisation of FoxO3a, reduced the phosphorylation of FoxO3a, increased caspase activity and upregulated Fas ligand expression. In contrast the phenolic antioxidant tBHQ caused retention of FoxO3a in the cytosol coincident with enhanced PI3K- dependent phosphorylation of FoxO3a. tBHQ-induced nuclear exclusion of FoxO3a was associated with reduced FoxO-mediated transcriptional activity. Exposure of neurones to tBHQ inhibited NMDA-induced nuclear translocation of FoxO3a prevented NMDA-induced upregulation of FoxO-mediated transcriptional activity, blocked caspase activation and protected neurones from NMDA-induced excitotoxic death. Collectively, these data suggest that phenolic antioxidants such as tBHQ oppose stress-induced activation of FoxO3a and therefore have potential neuroprotective utility in neurodegeneration.

Nuclear fuel cycles: interfaces with the environment

The waste materials generated in the nuclear fuel cycle are very varied,ranging from the tailings arising from mining and processing uranium ore, depleted uranium in a range of chemical forms, to a range of process wastes of differing activities and properties. Indeed, the wastes generated are intimately linked to the options selected in operating the nuclear fuel cycle, most obviously to the management of spent fuel. An open fuel cycle implies the disposal of highly radioactive spent fuel, whereas a closed fuel cycle generates a complex array of waste streams. On the other hand, a closed fuel cycle offers options for waste management, for example reduction in highly active waste volume, decreased radiotoxicity, and removal of fissile material. Many technological options have been proposed or explored, and each brings its own particular mix of wastes and environmental challenges.

Use of soft heterocyclic N‑donor ligands to separate actinides and lanthanides

The removal of the most long-lived radiotoxic elements from used nuclear fuel, minor actinides, is foreseen as an essential step toward increasing the public acceptance of nuclear energy as a key component of a low-carbon energy future. Once removed from the remaining used fuel, these elements can be used as fuel in their own right in fast reactors or converted into shorter-lived or stable elements by transmutation prior to geological disposal. The SANEX process is proposed to carry out this selective separation by solvent extraction. Recent efforts to develop reagents capable of separating the radioactive minor actinides from lanthanides as part of a future strategy for the management and reprocessing of used nuclear fuel are reviewed. The current strategies for the reprocessing of PUREX raffinate are summarized, and some guiding principles for the design of actinide-selective reagents are defined. The development and testing of different classes of solvent extraction reagent are then summarized, covering some of the earliest ligand designs right through to the current reagents of choice, bis(1,2,4-triazine) ligands. Finally, we summarize research aimed at developing a fundamental understanding of the underlying reasons for the excellent extraction capabilities and high actinide/lanthanide selectivities shown by this class of ligands and our recent efforts to immobilize these reagents onto solid phases.

The Bomb: Nuclear Weapons in their Historical, Strategic and Ethical Context

This book examines to what extent the invention and first use of nuclear weapons was a turning point in the history of warfare and strategy(to what extent was it a mere continuation or perfection of air power strategy? Were the casualty numbers really unprecedented?), the ethics of war (was this form of war against civilians unprecedented?), and it asks whether it was an expression of total war or did it create total war

Nuclear Mentalities? Strategies and Beliefs in Britain, France and the FRG

This is volume II of my two-volume study of the nuclear strategies/strategy preferences of Britain, France and West Germany in the Cold War. It shows that the great variable is the mentalities, culture, and particular interpretations of particular historical experiences of these three countries. These mental frameworks are reconstructed, in the tradition of the French Annales/Mentalite schools (that in turn is rooted in anthropology) by looking at a very large nunber of public texts in the context of the public discourse about nuclear strategy in each country.

NATO, Britain, France and the FRG: Nuclear Strategies and Forces for Europe, 1949-2000

This is vol. I of my two-volume study of the nuclear strategies/strategy preferences of NATO collectively, and individually of Britain, France, and West Germany in the Cold War. It shows that NATO strategy was a fragile compromise, and that these three countries, all within range of Soviet medium/intermediate range nuclear missiles and thus with less geostrategic difference than in previous military threat contexts, had wildly divergent strategies/preferences which cannot be explained merely by geography. It raises the question of what made them so different, addressed in Volume II "Nuclear Mentalities" (q.v.)

‘Victory in a Nuclear War? A Comparison of NATO and WTO War Aims and Strategies’

Given the danger of the unbearable catastrophe of nuclear war, NATO in the mid-1950s abandoned any war aim of achieving victory in an all-out war with the Soviet Union or the Warsaw Treaty Organisation. Instead, it adopted the war aim of a cease-fire or war termination. By contrast, the WTO clung on to the war aim of victory - expressed even in terms of the survival of slightly more Soviet citizens than NATO citizens, after unprecedented losses of life in nuclear exchanges - until the mid-1980s when under Gorbachev the concept of victory in nuclear war was abandoned.

Beliefs, cultures, proliferation and use of nuclear weapons

This article demonstrates the centrality of mentality, culture, beliefs and historical lessons for nuclear prolifertion. Using the historical casestudies of Britain, France, and West Germany, it encourages researchers to look at the mentality/culture of potential proliferators rather than apply a culture-less "Realist" IR theory approach that assumes that desicion-makers the world over think like Bismarck.

‘What Price Solidarity? Nuclear Dependence in NATO, 1949-1967’

Archive-based study of the dependence of NATO member states on the USA as nuclear guarantor, and the problems this entailed.

‘European strategists and European identity in the nuclear age’

European writers on strategy (in French: strategistes, as opposed to practitioners, stratèges) developed their thoughts on the best strategies and postures of nuclear deterrence against their own beliefs in the identities of their own countries - were they seen as "Europesn" or as "nation-states" who must under no condition surrender their sovereignty?

‘Containing Uncertainty: Options for British Nuclear Strategy’

If Britain wants to stem the tide of nuclear proliferation, it must continue to assume "the nuclear man's burden" and guarantee the security of non-nuclear allies, as it did in the Cold War.

Syntheses, characterization and X-ray crystal structures of a mono- and a penta-nuclear nickel(II) complex with oximato Schiff base ligands

A mononuclear octahedral nickel(II) complex [Ni(HL(1))(2)](SCN)(2) (1) and an unusual penta-nuclear complex [{(NiL(2))(mu-SCN)}(4)Ni(NCS)(2)]center dot 2CH(3)CN (2) where HL(1) = 3-(2-aminoethylimino)butan-2-one oxime and HL(2) = 3-(hydroxyimino)butan-2-ylidene)amino)propylimino)butan-2-one oxime have been prepared and characterized by X-ray crystallography. The mono-condensed ligand, HL(1), was prepared by the 1:1 condensation of the 1,2-diaminoethane with diacetylmonoxime in methanol under high dilution. Complex 1 is found to be a mer isomer and the amine hydrogen atoms are involved in extensive hydrogen bonding with the thiocyanate anions. The dicondensed ligand, HL(2), was prepared by the 1:2 condensation of the 1,3-diaminopropane with diacetylmonoxime in methanol. The central nickel(II) in 2 is coordinated by six nitrogen atoms of six thiocyanate groups, four of which utilize their sulphur atoms to connect four NiL2 moieties to form a penta-nuclear complex and it is unique in the sense that this is the first thiocyanato bridged penta-nuclear nickel(II) compound with Schiff base ligands.

Azide monoliths as convenient flow reactors for efficient Curtius rearrangement reactions

The preparation and use of an azide-containing monolithic reactor is described for use in a flow chemistry device and in particular for conducting Curtius rearrangement reactions via acid chloride inputs.