The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries

Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury

Interpretative and predictive modelling of Joint European Torus collisionality scans

Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as □(→┬E ) X □(→┬B ) shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges

Trapping with gaseous methanol the C7H7+ daughter ions from the decay of tritiated toluenes

Labeled daughter ions from the decay of selectively multitritiated toluenes were trapped with MeOH(g) at different pressures. The ions from C6X5Me (X = H, T) yield tritiated Me tolyl ethers, while those from PhCX3 yield exclusively tritiated benzyl Me ether. The primary decay ions retain their cyclic structure, without collapsing to the tropylium ion, at least during the time (10-9 to 10-7 s) required for their trapping by the gaseous nucleophile

Gas-phase acylation reactions. Formation of free benzoyl cations in the gas phase

The β-decay of benzene-1,4-t2 in a large excess of CO(g) contg. EtOH or C6H6 gave 4.9% PhOEt and 95.1% PhCO2Et, and 96.9% Ph2 and 3.1% PhCO2H, resp. The results substantiate the intermediacy of PhCO+ which shows high substance discrimination forming PhOEt and PhCO2Et with EtOH, an n-type base, but no corresponding ethers or esters with C6H6, a π-type base

Structure and reactivity of C7H7+ ions from the decay of tritiated toluenes. 1. Reactions of free tolyl ions with methanol in the gas and liquid phases

Labeled tolyl cations from the decay of ring-multitritiated toluene have been allowed to react with methanol in the liq. and the gas phases, at pressures ranging from 6 to 100 torr, yielding Me tolyl ethers as the major products, without appreciable formation of benzyl Me ether. The isomeric compn. of the products from the gaseous systems depends on the pressure, the percentage of o-tolyl ether increasing at the expense of the para isomer as the methanol pressure is reduced. The results show that the three tolyl ions exist as distinct species in the dil. gas state. When formed in a sufficiently excited state, as from the β decay of a 3H atom in toluene, they undergo appreciable interconversion, without detectable isomerization to the benzyl cation, at least within the pressure range accessible to the decay technique

Aromatic substitution by free benzyl cations from the nuclear decay of multi-tritiated toluene. Competitive benzylation of benzene and toluene in the gas phase and in solution.

Benzyl cations, free of counter ions, have been generated from the nuclear decay of tritium atoms contained exclusively in the side-chain of multi-labelled toluene and allowed to react in competition experiments with benzene and toluene. The aromatic substitution was studied in both the gaseous and liquid phase, employing pure aromatics or aromatics dissolved in n-hexane, carbon tetrachloride and nitromethane as the reaction medium. In the gaseous systems, at 20 Torr total pressure, High meta substitution of toluene indicates extensive isomerization of the excited intermediates, while the increase of the kT/kB value in the Presence of NH3 suggests that selective transalkylation competes with proton transfer to ammonia from the benzyl cation adducts with benzene, but not with toluene. High positional and low substrate selectivities were measured in solution, the decrease in kT/kB (from 2·8 to 1·7) in the different solvents being accompanied by an increase in the o/2p ratio. Competition experiments between benzene and methanol indicate that the reaction is not diffusion controlled. The influence of the reaction medium on the substrate selectivity is explained by postulating the formation of a cation–solvent adduct, where the solvent molecule undergoes displacement by the substrate. Positional selectivity would be controlled in a subsequent step

GAS-PHASE HETEROAROMATIC SUBSTITUTION .11. ELECTRON-TRANSFER MECHANISM IN THE GAS-PHASE ACYLATION OF SIMPLE 5-MEMBERED HETEROARENES

The results of a study of the gas-phase reactions of unsaturated carbocations, such as the CH3CO' ion from y-radiolysis of CH3F/C0 mixtures, and the C6H4TCO+ ion from the P-decay of 1,4-ditritiobenzene in the presence of CO, with pyrrole, N-methylpyrrole, furan, and thiophene, are reported. In all systems investigated, acylated heteroarenes represent the predominant reaction products, accompanied by the methylated derivatives in the CH3F/C0 radiolytic mixtures, and by the phenylated ones in the 1,4-ditritiobenzene/CO decay samples. All substrates investigated are found to undergo predominant a substitution by both acetyl (88.6-98.4% (pyrrole); 90.8-98.7% (N-methylpyrrole); 97.2-98.9% (furan); 94.9-98.6% (thiophene)) and benzoyl cations (92.6-96.5% (pyrrole)) under all conditions. The predominant formation of the a-acylated pyrroles from both reactants (>88%), whose relative yields appear unaffected within the temperature interval from 303 to 383 K, indicates, in agreement with ancillary FT-ICR mass spectrometric evidence, that gas-phase acylation reactions toward simple five-membered heteroarenes proceed via a two-step substitution mechanism, involving a quasi-resonant single-electron transfer (SET) step followed by recombination of the ensuing radical - radical ion pair. By virtue of this entropy-favored mechanism, gaseous electrophiles with relatively high SCF STO-3G calculated LUMO energies such as CH3CO' and C6H4TCO' are effectively oriented toward the "soft" C, sites of the selected heteroarenes, at variance with Klopman's Charge and Frontier Orbital Control predictions. The behavior of gaseous acylating reactants toward simple heteroarenes is discussed and compared with that of other gaseous electrophiles, whose reactivity appears instead in qualitative agreement with Klopman's model

Gas-phase heteroaromatic substitutions. 5. Gas-phase protonation of five-membered heteroaromatic rings by hydro-t-helium(1+)-3He (3HeT+) ions. A model reaction for a theoretical approach to heteroaromatic reactivity

The reactions of the powerful Broensted acid, the 3HeT+ ion from the β decay of mol. tritium, with gaseous pyrrole, N-methylpyrrole, furan, and thiophene are reported. The tritiated heteroarom. substrate is the major product, and it is accompanied in the case of furan by very minor amts. (ca. 3%) of tritiated crotonaldehyde. The nature and the yields of the products and their intramol. tritium distribution suggest that the gas-phase protonation reaction on simple five-membered heteroaroms. is regulated by factors related to the electrostatic interactions established within the encounter pair. A close correspondence exists between the gas-phase protonation results and recent theor. and exptl. evidence concerning related substitution processes