As a result of transcriptional editing, Ebola virus (EBOV) produces multiple soluble products from its glycoprotein gene, the primary product of which is the secreted glycoprotein (sGP), in addition to the membrane-bound viral spike protein GP1,2. A lack of leukocyte infiltration is observed during EBOV infection, which is thought to allow virus replication to proceed unchecked and thus represents a significant role in the immunopathology of the disease. Currently the only know function of sGP is that it has an anti-inflammatory effect on endothelial cells treated with TNF-α, an effect that has been hypothesized to interfere with recruitment or extravasation of leukocytes. To better characterize this anti-inflammatory function, a link between sGP structure and function was sought. Mass spectrometry (MS) analysis of recombinant sGP demonstrated that it is a parallel-orientated disulphide-linked homodimer that contains Cys53-C53’ and Cys306-C306’ intermolecular disulphide bonds. In addition to being glycosylated with complex N-glycans, sGP also contained a novel post-translation modification, termed C-mannosylation. C-mannosylation was not required for the anti-inflammatory function of sGP; however, glycine mutations at amino acids 53 and 306 resulted in the complete loss of the anti-inflammatory effect on TNF-α treated endothelial cells. Thus, a specific structure mediated by intermolecular disulphide bonds is required for the proposed anti-inflammatory function of sGP, suggesting that this effect is the result of a specific interaction. The spike protein GP1,2, also contains C-mannosylation motifs. MS analysis of GP1,2 indicated that GP1 was C-mannosylated, while two adjacent motifs in the membrane proximal region (MPER) of GP2 were not. The infectious virus-like particle (iVLP) assay, a system for investigating virus particle assembly and entry, was utilized to determine the functional importance of these conserved tryptophans. Elimination of the C-mannosylation motif, which resides in an external loop region of GP1, increased reporter activity, suggesting that particle entry is enhanced and this region may interact with the cell surface despite being outside of the receptor binding site. Decreased reporter activity was observed for all MPER mutants, with multiple MPER tryptophan mutations resulting in decreased GP1,2 incorporation. These data place the MPER tryptophan residues in an important role for glycoprotein incorporation and particle entry. Given the tryptophan content and location is similar to the MPER of HIV gp41, where these residues are required for glycoprotein incorporation and fusion, the MPER of EBOV GP2 may function similarly.

The just war tradition has largely consisted of dialogues, approaches, and frameworks dominated by the conceptual primacy of the individual. While such focus upon the individual is appropriate for many battlefield contexts, it is by no means exhaustive. My aim is to demonstrate that in addition to battlefield harms amenable to traditional individually-oriented approaches, there exists another set of unique battlefield harms problematic for such individualistic approaches and thus warranting a structural account instead. I will conclude that in order for Just War Theory to be fully adequate, it must both recognize the unique set of battlefield harms caused by structures as well as account for them by means of a notion of structural responsibility. / Graduate

No description available.

When a fire reaches the point of flashover the hot gases inside the burning room ignite resulting in furnace-like conditions. Thereafter, the building frame experiences temperatures sufficient to compromise its structural integrity. Physical and mathematical models help to predict when this will happen. This thesis looks at both the thermal and structural aspects of modelling a frame exposed to a post-flashover fire. The temperatures in the frame are calculated by solving a 2D heat conduction equation over the cross-section of each beam. The solution procedure uses the finite element method with automatic mesh generation/adaption based on the Delaunay triangulation process and the recovered heat flux. With the Euler-Bernoulli assumption that the cross-section of a beam remains plane and perpendicular to the neutral line and that strains are small, an error estimator, based on the work of Bank and Weiser [9], has been derived for finite element solutions to small-deformation, thermoelastic and thermoplastic frame problems. The estimator has been shown to be consistent for all finite element solutions and asymptotically exact when the solution involves appropriate higher degree polynomials. The asymptotic exactness is shown to be closely related to superconvergence properties of the approximate solution in these cases. Specifically, with coupled bending and compression, it is necessary to use quadratic approximations, instead of linear, for the compression and twisting terms to get a global O(h2) rate of convergence in the energy norm, some superconvergence properties and asymptotic exactness with the error estimator.

A cryogenically pumped, windowless gas target has been used to study the radiative alpha-capture reaction on ¹⁶O and ¹²C targets, giving information on the electromagnetic decay properties of various unbound states in ²⁰Ne and ¹⁶O. Several states in ²⁰Ne have been observed in this reaction for the first time. The first five unit-isospin, natural parity states in ²⁰Ne have been observed. The isospin assignment of the 11.27 MeV (1^-)) state has been made definite by the observation of a strong Ml decay to the 8.85 MeV (1^-)state, and the analogue of the 1.97 MeV state in ²⁰F has been identified with the ²⁰Ne state at 12.25 MeV. Angular distribution measurements have shown the spin of this state to be 3^-), and the total width has been shown to be less than 1 keV, contradicting previous reports. The 12.22 MeV (2⁺)state has been resolved clearly as an individual resonance for the first time. The electromagnetic transition rates for the lower T=l states in ²⁰Ne are compared with shell model calculations. Five zero-isospin capture resonances in ²⁰Ne have been studied, the gamma-decay of the 8.70 MeV (1^-), 9.11 MeV (3^-) and 11.92 MeV (4⁺) states being observed for the first time. A remeasurement has been made of the enhanced E2 decay strength of the 8⁺ member of the ground state rotational band, giving ^ω=l31 ^±18 meV, in agreement with a previous less accurate value. This result is compared with shell model calculations. A study of the capture reaction on ¹²C has been performed in the beam energy range 5.22 MeV < Eα < 9.53 MeV. No new capture resonances have been found but the known inelastic resonances have been seen. The 11.10 MeV (4⁺) state has been studied and the strength for the decay to the 6.13 MeV (3^-) state has been shown to be only half of a previous result. The 12.05 MeV (0⁺) state has not been observed, but a limit has been placed on its strength.

The synchrotron emissivity distribution of the Milky Way Galaxy has been modelled from the 408 MHz allsky survey of Haslam et al.(1982) after separation of its thermal component with the help of IRAS 60 micron emission(Broadbent et al 1989). We have refined the spiral arm pattern in the inner part of the Galaxy by including a bar at the Galactic centre and an updated the Galactic distance scale and obtained fitted free parameters. At 408 MHz, there is very little absorption in the interstellar medium and the line of sight distribution of synchrotron emissivity was inferred mainly from its presumed relationship to the other tracers of spiral structure via these fitted free parameters. At lower frequencies, the absorption of synchrotron emission due to thermal electrons becomes significant and can give direct information of the nonthermal distribution along the line of sight. We have modelled the distribution of thermal electrons according to our synchrotron arm model and an alternative model based on pulsar dispersion measures using the Galactic rotation curve and the surveys of the distribution of Hl66a emission We have then used our synchrotron model applied at lower frequencies including the absorption to compare with the surveys of Dwarakanath et al.(l990) at 34.5 MHz and Jones and Finlay(l974) at 29.9 MHz. The result confirms that the absorption model of the synchrotron emissivity in the Galactic plane is broadly correct and illustrates the potentials of the absorption technique. However we were not able to distinguish the two models of ionised hydrogen spiral structure. To do this, recombination line surveys with improved frequency resolution are required. Using a new value of the cosmic ray gradient in the Galaxy from diffuse gamma-ray emission we obtain the separate variation of magnetic field and cosmic ray electron density. We give the global properties of the thermal and nonthermal emission that our model implies.

Amidines [RNC(R')NR, I] and their complexes of the nickel group metals have been studied. Accurate mass spectrometry applied to (R'=H, R=Ph; R'=CH(_3), R=Ph; R'=Ph=R) have given detailed fragmentation patterns which form the basis for the interpretation of related amidines. Differences in skeletal fragmentation patterns were noted between formamidines and acetamidines/benzamidines, (^1)H, (^13)C and (^19)F n.m.r. and mass spectroscopy of lithioamidines indicate a bidentate symmetrically bonded amidine. The reactions of amidines [RN(X)C(R^)NR] X=H, Li) with compounds of the nickel group metals, results in a wide variety of complexes; their nature depending on the amidine substituents, the metal and the synthetic route used. Complexes with N,N'chelate, or't/20-metallated, and bridging groups were prepared and characterised together with complexes containing new N,N'chelate and bridging groups, resulting from nucleophilic attack of an amidine at a coordinated nitrile. The reactions of M(PhCN)(_2)C1(_2) (M=Pd, Pt) and anhydrous NiC1(_2) with lithioamidines result in yellow Pt(Am)(_2), where Am = RNC(R')NR, red Pd(_2)(Am)(_4) and dark green Ni(_2)(Am)(_4) complexes. The platinum complexes are monomeric for the acetamidine (R'=CH(_3)), and benzamidine (R(_6)H(_5)) ligands, though for palladium the benzamidine complexes are dimeric. The nickel complexes are dimeric for the acetamidine,and benzamidine ligands. Spectroscopic studies indicate that the amidino-groups adopt a carboxylate type mode of bonding through the two nitrogen atoms, and the structure of one of the complexes, bis, N,N'diphenylbenzamicline-platinum(II) has been characterised by X-ray crystallography. The structure showed a monomeric PtN(_4) square planar unit. N.m.r. ((^19)F and (^13)C) studies have indicated fluxionality when M=Pd, R'=C(_6)H(_5), R=C(_6)H(_4)-F-p. With K(_2)MCl(_4)(M=Pd, Pt) and NiC1(_2), N,N'diarylamidines form polymeric ortho-metallated complexes, N,N' diarylformamidines and acetamidines form six-membered rings, benzamidines five-membered. Treatment of Pt(PhCN)(_2)C1(_2) with HN(Li)(C(_6)H(_5))NH results in nucleophilic attack at the nitrile and formation of Pt[HNC(C(_6)H(_5))NC(C(_6)H(_5))NH](_2). A similar reaction occurred with Pd(PhCN)(_2)C1(_2) and HNLiC(C(_4)(_9))NH.

No description available.

No description available.

No description available.