Spectrum of antibacterial activity and mode of action of a novel tris-stilbene bacteriostatic compound

The spectrum of activity and mode of action of a novel antibacterial agent, 135C, was investigated using a range of microbiological and genomic approaches. Compound 135C was active against Gram-positive bacteria with MICs for Staphylococcus aureus ranging from 0.12–0.5 μg/ml. It was largely inactive against Gram-negative bacteria. The compound showed bacteriostatic activity in time-kill studies and did not elicit bacterial cell leakage or cell lysis. Checkerboard assays showed no synergy or antagonism when 135C was combined with a range of other antibacterials. Multi-step serial passage of four S. aureus isolates with increasing concentrations of 135C showed that resistance developed rapidly and was stable after drug-free passages. Minor differences in the fitness of 135C-resistant strains and parent wildtypes were evident by growth curves, but 135C-resistant strains did not show cross-resistance to other antibacterial agents. Genomic comparison of resistant and wildtype parent strains showed changes in genes encoding cell wall teichoic acids. 135C shows promising activity against Gram-positive bacteria but is currently limited by the rapid resistance development. Further studies are required to investigate the effects on cell wall teichoic acids and to determine whether the issue of resistance development can be overcome

Effect of vitamin D3 supplementation on Staphylococcus aureus nasal carriage: a randomized, double-blind, placebo-controlled trial in healthy adults

AbstractObservational studies have reported an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and Staphylococcus aureus nasal carriage; however, clinical trials of vitamin D supplementation are lacking. To assess the effect of vitamin D3 supplementation on persistent S. aureus nasal carriage we conducted a randomized, double-blind, placebo-controlled trial among 322 healthy adults. Participants were given an oral dose of either 200 000 IU vitamin D3 for each of 2 months, followed by 100 000 IU monthly or placebo in an identical dosing regimen, for a total of 18 months. Nasal swabs for S. aureus culture and serum for 25OHD measurement were obtained at baseline, 6, 12 and 18 months of study. The mean baseline concentration of 25OHD was 72 nM (SD 22 nM). Vitamin D3 supplementation increased 25OHD levels which were maintained at >120 nM throughout the study. Nasal colonization by S. aureus was found in 31% of participants at baseline. Persistent carriage, defined as those that had positive S. aureus nasal cultures for all post-baseline swabs, occurred in 20% of the participants but vitamin D3 supplementation was not associated with a reduction in persistent carriage (OR = 1.39, 95% CI 0.63–3.06). Risk factor analysis showed that only gender was significantly associated with carriage, where women were less likely to be carriers than men (relative risk 0.83, 95% CI 0.54–0.99). Serum 25OHD concentrations were not associated with the risk of carriage. In conclusion, monthly administration of 100 000 IU of vitamin D3 did not reduce persistent S. aureus nasal carriage

Non-Fermi liquid behavior from two-dimensional antiferromagnetic fluctuations: a renormalization-group and large-N analysis

We analyze the Hertz-Moriya-Millis theory of an antiferromagnetic quantum critical point, in the marginal case of two dimensions (d=2,z=2). Up to next-to-leading order in the number of components (N) of the field, we find that logarithmic corrections do not lead to an enhancement of the Landau damping. This is in agreement with a renormalization-group analysis, for arbitrary N. Hence, the logarithmic effects are unable to account for the behavior reportedly observed in inelastic neutron scattering experiments on CeCu_{6-x}Au_x. We also examine the extended dynamical mean-field treatment (local approximation) of this theory, and find that only subdominant corrections to the Landau damping are obtained within this approximation, in contrast to recent claims.Comment: 15 pages, 8 figure

Statistics of Coulomb blockade peak spacings for a partially open dot

We show that randomness of the electron wave functions in a quantum dot contributes to the fluctuations of the positions of the conductance peaks. This contribution grows with the conductance of the junctions connecting the dot to the leads. It becomes comparable with the fluctuations coming from the randomness of the single particle spectrum in the dot while the Coulomb blockade peaks are still well-defined. In addition, the fluctuations of the peak spacings are correlated with the fluctuations of the conductance peak heights.Comment: 13 pages, 1 figur

A weakly stable algorithm for general Toeplitz systems

We show that a fast algorithm for the QR factorization of a Toeplitz or Hankel matrix A is weakly stable in the sense that R^T.R is close to A^T.A. Thus, when the algorithm is used to solve the semi-normal equations R^T.Rx = A^Tb, we obtain a weakly stable method for the solution of a nonsingular Toeplitz or Hankel linear system Ax = b. The algorithm also applies to the solution of the full-rank Toeplitz or Hankel least squares problem.Comment: 17 pages. An old Technical Report with postscript added. For further details, see http://wwwmaths.anu.edu.au/~brent/pub/pub143.htm

Quantum dots in magnetic fields: thermal response of broken symmetry phases

We investigate the thermal properties of circular semiconductor quantum dots in high magnetic fields using finite temperature Hartree-Fock techniques. We demonstrate that for a given magnetic field strength quantum dots undergo various shape phase transitions as a function of temperature, and we outline possible observable consequences.Comment: In Press, Phys. Rev. B (2001

Virus shapes and buckling transitions in spherical shells

We show that the icosahedral packings of protein capsomeres proposed by Caspar and Klug for spherical viruses become unstable to faceting for sufficiently large virus size, in analogy with the buckling instability of disclinations in two-dimensional crystals. Our model, based on the nonlinear physics of thin elastic shells, produces excellent one parameter fits in real space to the full three-dimensional shape of large spherical viruses. The faceted shape depends only on the dimensionless Foppl-von Karman number \gamma=YR^2/\kappa, where Y is the two-dimensional Young's modulus of the protein shell, \kappa is its bending rigidity and R is the mean virus radius. The shape can be parameterized more quantitatively in terms of a spherical harmonic expansion. We also investigate elastic shell theory for extremely large \gamma, 10^3 < \gamma < 10^8, and find results applicable to icosahedral shapes of large vesicles studied with freeze fracture and electron microscopy.Comment: 11 pages, 12 figure

Bailing Out the Milky Way: Variation in the Properties of Massive Dwarfs Among Galaxy-Sized Systems

Recent kinematical constraints on the internal densities of the Milky Way's dwarf satellites have revealed a discrepancy with the subhalo populations of simulated Galaxy-scale halos in the standard CDM model of hierarchical structure formation. This has been dubbed the "too big to fail" problem, with reference to the improbability of large and invisible companions existing in the Galactic environment. In this paper, we argue that both the Milky Way observations and simulated subhalos are consistent with the predictions of the standard model for structure formation. Specifically, we show that there is significant variation in the properties of subhalos among distinct host halos of fixed mass and suggest that this can reasonably account for the deficit of dense satellites in the Milky Way. We exploit well-tested analytic techniques to predict the properties in a large sample of distinct host halos with a variety of masses spanning the range expected of the Galactic halo. The analytic model produces subhalo populations consistent with both Via Lactea II and Aquarius, and our results suggest that natural variation in subhalo properties suffices to explain the discrepancy between Milky Way satellite kinematics and these numerical simulations. At least ~10% of Milky Way-sized halos host subhalo populations for which there is no "too big to fail" problem, even when the host halo mass is as large as M_host = 10^12.2 h^-1 M_sun. Follow-up studies consisting of high-resolution simulations of a large number of Milky Way-sized hosts are necessary to confirm our predictions. In the absence of such efforts, the "too big to fail" problem does not appear to be a significant challenge to the standard model of hierarchical formation. [abridged]Comment: 12 pages, 3 figures; accepted by JCAP. Replaced with published versio

Reach in and reach out : the story of the MSc in pipeline engineering at Newcastle University

This paper presents an unusual case of university-industry interaction whereby a group of small businesses came together to persuade a university to establish an MSc in Pipeline Engineering. We identify that the course contributed to regional development in four ways. Firstly, it provided graduates for local industry. Secondly, it linked local firms with pipeline engineers world wide and raised the region's profile within that network. Thirdly, it strengthened the research base of the university through the recruitment of pipeline engineers from industry and fourthly, it facilitated the possibility of joint research between the university and local firms. We question whether this model is transferable to other industry sectors/universities. We conclude that this outreach activity has been shaped by the 'reach-in' to the university of the local business community and propose a revised model of university interaction with regional industry. Traditionally universities have been seen as 'reaching out' to regional industry and the collaborations have been viewed as being instigated by the university and often research-based. Our revised model proposes an alternative mechanism whereby collaborations can be instigated by industry and through a teaching-route