The geometric and electronic structures of MoO3 and MoO2 have been calculated using the generalized gradient approximation to density functional theory. The calculated cross-section weighted densities of states are compared with high-resolution X-ray photoemission spectra. There is very good agreement between the calculated structures and those determined previously by X-ray diffraction and between the computed densities of states and the present photoemission measurements. MoO2 is shown to be a metallic material, as is found experimentally, but the Fermi level sits in a distinct trough in the density of states. Satellite peaks found in core photoemission spectra of MoO2 are shown to derive from final state screening effects in this narrow band metallic material.

Shiga toxin-producing Escherichia coli O157 are important enteropathogens causing outbreaks of haemorrhagic colitis and haemolytic uraemic syndrome. Strains of E. coli belonging to other serogroups also produce Shiga toxins but are less frequently isolated from cases of diarrhoeal illness despite humans having greater exposure to these organisms in food and the environment. It is generally considered that E. coli O157 is more virulent than these other Shiga toxin-producing E. coli. The question of which factors make toxigenic E. coli O157 more virulent is unanswered. In this review the various virulence properties of E. coli O157 and their incidence in non-O157 Shiga toxin-producing E. coli are described. The most important factors for E. coli O157 are the production of Shiga toxin 2 and the adhesin intimin.The role of some of the other virulence factors, such as enterohaemolysin, a serine protease (EspP) and a catalase/peroxidase (Katp), in infection may be low. Uncharacterized virulence properties such as a clostridial-like toxin and haemoglobin uptake require further study and it is likely that other virulence properties remain to be discovered.

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 μg/mLgreater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals.antifungal drug | Aspergillus fumigatus | mechanism of action | dihydroorotate dehydrogenase

High-resolution core-and valence-level photoemission spectra of Nb-doped TiO 2 ceramics (Ti 1Ϫx Nb x O 2 with 0.01ϽxϽ0.8) have been measured using monochromatic x-ray excitation. Nb doping produces a welldefined photoemission peak in the bulk band gap of rutile, whose intensity increases with increasing doping level. Core-level spectroscopy shows that the Nb is incorporated within the rutile lattice at low doping levels mainly as Nb͑V͒ and that the gap state is associated with Ti͑III͒ ions. This conclusion is reinforced by variable energy photoemission measurements on Ti 0.9 Nb 0.1 O 2 in the vicinity of the Ti 3p and Nb 4p core thresholds. The photoemission resonance profile for the gap states reaches half maximum intensity at the same energy as found for oxygen-deficient TiO 2Ϫx but is shifted from the resonance profile for the Nb 4d states of NbO 2 . STM images on Nb-doped TiO 2 ͑110͒ are considered in relation to the spectroscopic measurements. Nb dopant atoms are imaged as ''bright spot'' clusters, implying delocalization of charge from Nb onto neighboring Ti ions. The experimental x-ray photoelectron spectroscopy data are compared with density-of-states profiles derived from local-density approximation calculations on pure and Nb-doped TiO 2 clusters. These calculations show that Nb doping of TiO 2 introduces new states of mixed Nb 4d -Ti 3d character above the O 2p valence band of the host material. In addition, there is increased x-ray photoemission intensity across the O 2p valence band owing to strong Nb 4d/O 2p hybridization and a cross section for ionization of Nb 4d states that is an order of magnitude larger than that for O 2p or Ti 3d states.