A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection

Background: Polymicrobial infections represent a great challenge for the clarification of disease etiology and the development of comprehensive diagnostic or therapeutic tools, particularly for fastidious and difficult-to-cultivate bacteria. Using bovine digital dermatitis (DD) as a disease model, we introduce a novel strategy to study the pathogenesis of complex infections. Results: The strategy combines meta-transcriptomics with high-density peptide-microarray technology to screen for in vivo-expressed microbial genes and the host antibody response at the site of infection. Bacterial expression patterns supported the assumption that treponemes were the major DD pathogens but also indicated the active involvement of other phyla (primarily Bacteroidetes). Bacterial genes involved in chemotaxis, flagellar synthesis and protection against oxidative and acidic stress were among the major factors defining the disease. Conclusions: The extraordinary diversity observed in bacterial expression, antigens and host antibody responses between individual cows pointed toward microbial variability as a hallmark of DD. Persistence of infection and DD reinfection in the same individual is common; thus, high microbial diversity may undermine the host's capacity to mount an efficient immune response and maintain immunological memory towards DD. The common antigenic markers identified here using a high-density peptide microarray address this issue and may be useful for future preventive measures against DD.Fil: Marcatili, Paolo. Technical University of Denmark; DinamarcaFil: Nielsen, Martin W.. Technical University of Denmark; DinamarcaFil: Sicheritz Ponten, Thomas. Technical University of Denmark; DinamarcaFil: Jensen, Tim K.. Technical University of Denmark; DinamarcaFil: Schafer Nielsen, Claus. Schafer-N ApS; DinamarcaFil: Boye, Mette. Hospital of Southern Jutland; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Klitgaard, Kirstine. Technical University of Denmark; Dinamarc

Manifestly supersymmetric M-theory

In this paper, the low-energy effective dynamics of M-theory, eleven-dimensional supergravity, is taken off-shell in a manifestly supersymmetric formulation. We show that a previously proposed relaxation of the superspace torsion constraints does indeed accommodate a current supermultiplet which lifts the equations of motion corresponding to the ordinary second order derivative supergravity lagrangian. Whether the auxiliary fields obtained this way can be used to construct an off-shell lagrangian is not yet known. We comment on the relation and application of this completely general formalism to higher-derivative (R^4) corrections. Some details of the calculation are saved for a later publication.Comment: 13 pages, plain tex. v2: minor changes, one ref. adde

A variational description of the quantum phase transition in the sub-Ohmic spin-boson model

The sub-ohmic spin-boson model is known to possess a novel quantum phase transition at zero temperature between a localised and delocalised phase. We present here an analytical theory based on a variational ansatz for the ground state, which describes a continuous localization transition with mean-field exponents for $0<s<0.5$. Our results for the critical properties show good quantitiative agreement with previous numerical results, and we present a detailed description of all the spin observables as the system passes through the transition. Analysing the ansatz itself, we give an intuitive microscopic description of the transition in terms of the changing correlations between the system and bath, and show that it is always accompanied by a divergence of the low-frequency boson occupations. The possible relevance of this divergence for some numerical approaches to this problem is discussed and illustrated by looking at the ground state obtained using density matrix renormalisation group methods

Immunosuppressants and risk of Parkinson disease

We performed a population-based case-control study of United States Medicare beneficiaries age 60-90 in 2009 with prescription data (48,295 incident Parkinson disease cases and 52,324 controls) to examine the risk of Parkinson disease in relation to use of immunosuppressants. Inosine monophosphate dehydrogenase inhibitors (relative risk = 0.64; 95% confidence interval 0.51-0.79) and corticosteroids (relative risk = 0.80; 95% confidence interval 0.77-0.83) were both associated with a lower risk of Parkinson disease. Inverse associations for both remained after applying a 12-month exposure lag. Overall, this study provides evidence that use of corticosteroids and inosine monophosphate dehydrogenase inhibitors might lower the risk of Parkinson disease

Generalised 11-dimensional supergravity

The low-energy effective dynamics of M-theory, eleven-dimensional supergravity, is taken off-shell in a manifestly supersymmetric superspace formulation. We show that a previously proposed relaxation of the torsion constraints can indeed accomodate a current supermultiplet. We comment on the relation and application of this completely general formalism to higher-derivative (R^4) corrections. This talk was presented by Bengt EW Nilsson at the Triangle Meeting 2000 ``Non-perturbative Methods in Field and String Theory'', NORDITA, Copenhagen, June 19-22, 2000, and by Martin Cederwall at the International Conference ``Quantization, Gauge Theory and Strings'' in memory of Efim Fradkin, Moscow, June 5-10, 2000

Holographic Noncommutativity

We examine noncommutative Yang-Mills and open string theories using magnetically and electrically deformed supergravity duals. The duals are near horizon regions of Dp-brane bound state solutions which are obtained by using O(p+1,p+1) transformations of Dp-branes. The action of the T-duality group implies that the noncommutativity parameter is constant along holographic RG-flows. The moduli of the noncommutative theory, i.e., the open string metric and coupling constant, as well as the zero-force condition are shown to be invariant under the O(p+1,p+1) transformation, i.e., deformation independent. We find sufficient conditions, including zero force and constant dilaton in the ISO(3,1)-invariant D3 brane solution, for exact S-duality between noncommutative Yang-Mills and open string theories. These results are used to construct noncommutative field and string theories with N=1 supersymmetry from the T^(1,1) and Pilch-Warner solutions. The latter has a non-trivial zero-force condition due to the warping.Comment: latex, 40 pp. v2: minor changes, one ref. added. v3: corrections in eqs. 27 and 7

Climate Change Is Likely to Increase the Development Rate of Anthelmintic Resistance in Equine Cyathostomins in New Zealand

Climate change is likely to influence livestock production by increasing the prevalence of diseases, including parasites. The traditional practice of controlling nematodes in livestock by the application of anthelmintics is, however, increasingly compromised by the development of resistance to these drugs in parasite populations. This study used a previously developed simulation model of the entire equine cyathostomin lifecycle to investigate the effect a changing climate would have on the development of anthelmintic resistance. Climate data from six General Circulation Models based on four different Representative Concentration Pathways was available for three New Zealand locations. These projections were used to estimate the time resistance will take to develop in the middle (2040–49) and by the end (2090–99) of the century in relation to current (2006–15) conditions under two treatment scenarios of either two or six yearly whole-herd anthelmintic treatments. To facilitate comparison, a scenario without any treatments was included as a baseline. In addition, the size of the infective and parasitic stage nematode population during the third simulation year were estimated. The development of resistance varied between locations, time periods and anthelmintic treatment strategies. In general, the simulations indicated a more rapid development of resistance under future climates coinciding with an increase in the numbers of infective larvae on pasture and encysted parasitic stages. This was especially obvious when climate changes resulted in a longer period suitable for development of free-living parasite stages. A longer period suitable for larval development resulted in an increase in the average size of the parasite population with a larger contribution from eggs passed by resistant worms surviving the anthelmintic treatments. It is projected that climate change will decrease the ability to control livestock parasites by means of anthelmintic treatments and non-drug related strategies will become increasingly important for sustainable parasite control

Simulating Hamiltonians in Quantum Networks: Efficient Schemes and Complexity Bounds

We address the problem of simulating pair-interaction Hamiltonians in n node quantum networks where the subsystems have arbitrary, possibly different, dimensions. We show that any pair-interaction can be used to simulate any other by applying sequences of appropriate local control sequences. Efficient schemes for decoupling and time reversal can be constructed from orthogonal arrays. Conditions on time optimal simulation are formulated in terms of spectral majorization of matrices characterizing the coupling parameters. Moreover, we consider a specific system of n harmonic oscillators with bilinear interaction. In this case, decoupling can efficiently be achieved using the combinatorial concept of difference schemes. For this type of interactions we present optimal schemes for inversion.Comment: 19 pages, LaTeX2

Influence of static electric fields on an optical ion trap

We recently reported on a proof-of-principle experiment demonstrating optical trapping of an ion in a single-beam dipole trap superimposed by a static electric potential [Nat. Photonics 4, 772--775 (2010)]. Here, we first discuss the experimental procedures focussing on the influence and consequences of the static electric potential. These potentials can easily prevent successful optical trapping, if their configuration is not chosen carefully. Afterwards, we analyse the dipole trap experiments with different analytic models, in which different approximations are applied. According to these models the experimental results agree with recoil heating as the relevant heating effect. In addition, a Monte-Carlo simulation has been developed to refine the analysis. It reveals a large impact of the static electric potential on the dipole trap experiments in general. While it supports the results of the analytic models for the parameters used in the experiments, the analytic models cease their validity for significantly different parameters. Finally, we propose technical improvements for future realizations of experiments with optically trapped ions.Comment: 16 pages, 16 figure