Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.

In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.

Design considerations for a micro aerial vehicle aerodynamic characterization facility at the University of Florida research and engineering education facility

This paper describes the design considerations for a proposed aerodynamic characterization facility (ACF) for micro aerial vehicles (MAVs). This is a collaborative effort between the Air Force Research Laboratory Munitions Directorate (AFRL/MN) and the University of Florida Research and Engineering Education Facility (UF/REEF). The ACF is expected to provide a capability for the characterization of the aerodynamic performance of future MAVs. This includes the ability to gather the data necessary to devise control strategies as well as the potential to investigate aerodynamic 'problem areas' or specific failings. Since it is likely that future MAVs will incorporate advanced control strategies, the facility must enable researchers to critically assess such novel methods. Furthermore, the aerodynamic issues should not be seen (and tested) in isolation, but rather the facility should be able to also provide information on structural responses (such as aeroelasticity) as well as integration issues (say, thrust integration or sensor integration). Therefore the mission for the proposed facility ranges form fairly basic investigations of individual technical issues encountered by MAVs (for example an evaluation of wing shapes or control effectiveness) all the way to testing a fully integrated vehicle in a flight configuration for performance evaluation throughout the mission envelope.

Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Growth and shape control of disks by bending and extension

Differential growth of thin elastic bodies furnishes a surprisingly simple explanation of the complex and intriguing shapes of many biological systems, such as plant leaves and organs. Similarly, inelastic strains induced by thermal effects or active materials in layered plates are extensively used to control the curvature of thin engineering structures. Such behaviour inspires us to distinguish and to compare two possible modes of differential growth not normally compared to each other, in order to reveal the full range of out-of-plane shapes of an initially flat disk. The first growth mode, frequently employed by engineers, is characterised by direct bending strains through the thickness, and the second mode, mainly apparent in biological systems, is driven by extensional strains of the middle surface. When each mode is considered separately, it is shown that buckling is common to both modes, leading to bistable shapes: growth from bending strains results in a double-curvature limit at buckling, followed by almost developable deformation in which the Gaussian curvature at buckling is conserved; during extensional growth, out-of-plane distortions occur only when the buckling condition is reached, and the Gaussian curvature continues to increase. When both growth modes are present, it is shown that, generally, larger displacements are obtained under in-plane growth when the disk is relatively thick and growth strains are small, and vice versa. It is also shown that shapes can be mono-, bi-, tri- or neutrally stable, depending on the growth strain levels and the material properties: furthermore, it is shown that certain combinations of growth modes result in a free, or natural, response in which the doubly curved shape of disk exactly matches the imposed strains. Such diverse behaviour, in general, may help to realise more effective actuation schemes for engineering structures. © 2012 Elsevier Ltd. All rights reserved.