Clearance of ESKAPE Pathogens from Blood Using Bacterially Activated Macrophage Membrane-Coated Silicon Nanowires

Extracorporeal devices to cleanse blood from infecting bacteria are based upon bacterial capture to surfaces, but the current generation of capture devices has variable and inconclusive therapeutic efficacy. Here, a microfluidic device equipped with a Si capture surface with a highly periodic nanowired structure is designed. Nanowired Si surfaces are coated with macrophage membranes to benefit from the natural blood compatibility and ligand–receptor binding of macrophages. When macrophages are activated by uptake of Staphylococcus aureus or Escherichia coli, zeta potentials of activated macrophage membrane coatings become less negative than those of nonactivated ones, stimulating nonspecific bacterial capture. In addition, Toll-like receptors in bacterially activated membrane coatings on nanowired surfaces that are absent in nonactivated membrane coatings contribute to specific bacterial capture. These two factors, together with the maintenance of fluidity in activated membrane coatings, cause broad spectrum, high capture efficiencies of all six ESKAPE member pathogens, considered most threatening to human health. Surfaces with such broad-spectrum capture efficiencies have not been previously described, but are clinically most relevant because blood cleansing should start as soon as possible after a septic patient becomes symptomatic, when the causative bacterial strain is still unknown.     

Bioinspired Double‐Dynamic‐Bond Crosslinked Bioadhesive Enables Post‐Wound Closure Care

Most existing bioadhesives, even those showing superiority in wound closure effectiveness, do not assist in the post‐wound closure process. A bioinspired, in situ formed, double‐dynamic‐bond crosslinked hydrogel bioadhesive that is capable of efficiently closing open wounds and enabling post‐wound closure care is reported. Catechol‐modified ε‐poly‐l ‐lysine and oxidized dextran are employed as natural polymer backbones and they are in situ crosslinked using Schiff's base dynamic bond and catechol? Fe coordinate dynamic bond through a process inspired by that used to cure marine mussel glue, forming a hydrogel bioadhesive. The unique double‐dynamic‐bond crosslinked structure endows the bioadhesive with higher mechanical and adhesive strength while retaining quick dissociation and good self‐healing capacities. Accordingly, the bioadhesive can exhibit multiple desirable functions, such as dissolution on demand, repeatable adhesiveness, adhesive and mechanical strength sufficient for wound closure, injectability, and good biocompatibility (DREAMING). After efficiently closing skin incisions, the bioadhesive can be facilely removed or repeatedly close the reopened wounds, thus enabling post‐wound closure care. On the basis of favorable functions in wound closure and the ability to enable post‐wound closure care, the bioadhesive demonstrates great potential in dealing with skin wounds.     

Tumor Microenvironment‐Tailored Weakly Cell‐Interacted Extracellular Delivery Platform Enables Precise Antibody Release and Function

Precise delivery of extracellularly functional protein drugs is limited by the drawback in that the protective carrier often causes undesirable cellular uptake of these therapeutic agents. Here, the design of a weakly cell‐interacted, nanosized, environment‐responsive vehicle (WINNER) with rational phosphorylcholine (PC) surface filling ratios capable of precise extracellular delivery of therapeutic agents for enhanced tumor suppression is reported. Highly hydrophilic zwitterionic PC and enzyme‐responsive peptides are engineered into the functional shell of WINNER which reasonably covers the inner protein. It is demonstrated that rationally controlled PC surface filling ratios (50.5–58.3%) are necessary for weakening interactions between the cell and WINNER whilst providing enough sites on WINNER for enzyme recognition. Consequently, WINNER (50.5–58.3%) can protect inner cargos from cellular uptake and undergo enzymatic degradation, resulting in precise extracellular release of inner protein, such as therapeutic monoclonal antibody (mAb). After intravenous administration, therapeutic mAb nimotuzumab‐loaded WINNER (51.2%) shows highest in vivo antitumor activity compared with free nimotuzumab or nimotuzumab‐loaded PC‐free nanocarrier in a lung adenocarcinoma xenograft tumor animal model. This work presents a simple and flexible approach to design precise extracellular delivery platform which can uncage the therapeutic power of extracellular targeting therapeutic agents.     

The Role of Plant Rapidly Induced Responses in Asymmetric Interspecific Interactions Among Insect Herbivores

The role of induced responses of tomato, Lycopersicon esculentum, in interspecific interactions between two polyphagous herbivores, the silverleaf whitefly, Bemisia argentifolii (WF), and the vegetable leafminer, Liriomyza trifolii (LM), was characterized in laboratory and field experiments. Feeding by LMs and WFs induced local and systemic production of putative defensive proteins, i.e., chitinases, peroxidases, -1,3-glucanases, and lysozymes. The magnitude of the induction for each defensive protein varied between species. Unlike WFs, LMs caused a 33% local reduction in total foliar protein content. In a whole-plant choice experiment, adult LM feeding, oviposition, and larval survival were reduced by 47.7%, 30.7%, and 26.5%, respectively, for the WF-infested host compared with the controls. Early WF infestations also had negative systemic (plant-mediated) effects on LMs. Adult LMs preferred leaves from control plants to leaves of plants that had been previously infested with WFs; no reciprocal effect of LMs on WFs were found. Feeding by Helicoverpa zea larvae, which has been shown previously to affect LM performance, had no effect on WF survival and development. LM natural population dynamics were monitored on WF-preinfested and control plants in a field experiment. WF-infested plants were less suitable for LM development with an overall 41% reduction in LM population density. These results demonstrate asymmetric direct and plant-mediated interspecific interactions between generalist herbivores feeding simultaneously on the same host. Possible mechanisms by which WFs overcome plant defenses are suggested. This ability may also contribute to WF success that makes them a major pest worldwide. The study supports the idea that over an evolutionary time scale, herbivores sharing the same host plant will automatically compete.     

M out of n inspected systems subject to shocks in random environment

Consider a parallel redundant system, consisting n components, that is subject to shocks. The shocks cause the components to fail with certain probabilities. Shocks arrival rate and components’ failure probabilities may depend on an external Markovian environment. We consider warm and cold stand-by systems. Systems’ failures are silent. The system is maintained through inspection and repair/replacement. We propose several state-dependent maintenance policies and derive system availability and cost function.     

Hybrid systems: from verification to falsification by combining motion planning and discrete search

We propose HyDICE, Hybrid Discrete Continuous Exploration, a multi-layered approach for hybrid-system falsification that combines motion planning with discrete search and discovers safety violations by computing witness trajectories to unsafe states. The discrete search uses discrete transitions and a state-space decomposition to guide the motion planner during the search for witness trajectories. Experiments on a nonlinear hybrid robotic system with over one million modes and experiments with an aircraft conflict-resolution protocol with high-dimensional continuous state spaces demonstrate the effectiveness of HyDICE. Comparisons to related work show computational speedups of up to two orders of magnitude. Work supported in part by NSF CNS 0615328 (EP, LK, MV), NSF 0713623 (EP, LK), a Sloan Fellowship (LK), and NSF CCF 0613889 (MV). Equipment supported by NSF CNS 0454333 and NSF CNS 0421109 in partnership with Rice, AMD, and Cray. A preliminary version of this work was published in the Proceedings of the 19th International Conference on Computer Aided Verification (CAV 2007). Lecture Notes in Computer Science, eds. W. Damm and H. Hermanns, vol. 4590, pp. 468–481. This work contains substantial improvements to the overall computational method introduced in the preliminary work and new experiments that were not included in the preliminary work.     

Electric Control on the Nanoscale Using Tubular Image States

We discuss the use of Tubular Image States (TIS) of electrons in the vicinity of nanotubes as a new vehicle for controlling and optically addressing nanoscale devices. We show that the stability of the TIS arises from the interplay between the attractive image potentials and the repulsive centrifugal potentials arising from the rotation of the electron about the cylindrically shaped nanotubes. We discuss the theory and some of the potential applications of TIS, and, in particular, the trapping of a single electron by a quadrupole made up of four nanotubes in the so-called “nano-Paul trap” configuration.     

Chemical sensing materials based on electrically‐conductive immiscible polymer blends

Two families of electrically‐conductive immiscible polymer blends were studied as liquid sensing materials for an homologous series of alcohols. The systems studied include: multiphase matrices [containing carbon black (CB)] consisting of either polypropylene or high‐impact polystyrene as the major phase and thermoplastic polyurethane as the minor dispersed phase; and polyaniline (PANI) dispersed within a polystyrene matrix. Extruded filaments, produced by a capillary rheometer at various shear‐rate levels were used in the sensing experiments. The electrical resistance of these filaments was selectively sensitive to the various alcohols. Moreover, the responses displayed by these filaments are reproducible and reversible. The sensing behaviour of these blends is determined by the nature of the blend components, the blend composition and the processing conditions. An attempt is made to identify the dominant mechanisms controlling the sensing process in CB‐containing immiscible polymer blends and PANI‐containing blends. In addition, the sensing performances of these blends are compared in the light of their sensing mechanisms. Copyright © 2005 Society of Chemical Industry     

Spatiotemporal patterns in models of cross-flow reactors

We review the behavior of stationary and moving spatially periodic patterns in a simple cross-flow fixed-bed reactor with a first-order exothermic reaction subject to the Danckwert’s boundary conditions and realistically high Le and Pe. Spatiotemporal patterns emerge due to the interaction of concentration and temperature balances, much like dynamic patterns in a CSTR. Moving waves emerge in an unbounded system, but they transform into stationary spatially inhomogeneous patterns in a bounded system above certain Pe threshold. The critical parameters of this threshold are derived analytically. A weakly nonlinear analysis is used in order to derive the governing amplitude equation.

The spatial behavior in the bounded system with Pe →∞ is analogous to the temporal behavior of the simple thermokinetic CSTR problem and the behavior of the distributed system is classified according to that of the lumped one. Both regular kinetics and oscillatory one (with reversible catalytic activity) are considered. Suggestions for experimental realization of these phenomena are discussed.     

Agent-based project scheduling

Agent technology offers a new way of thinking about many of the classic problems in operations research. Among these are problems such as project scheduling subject to resource constraints. In this paper, we develop and experimentally evaluate eight agent-based algorithms for solving the multimode, resource-constrained project scheduling problem. Our algorithms differ in the priority rules used to control agent access to resources. We apply our approach to a 51-activity project originally published by Maroto and Tormos [1]. We solve the problem using two types of agent-based systems: (i) a system of simple, reactive agents that we call basic agents; and (ii) a system of more complex, deliberative agents that we call enhanced agents. Of the eight priority rules tested, we find that priority based on shortest processing time performs best in terms of schedule quality when applied by basic agents while the priority based on earliest due date performs best when applied by enhanced agents. In comparing agents across priority rules, we find that enhanced agents generate much better schedules (with makespans up to 66% shorter in some cases) and require only slightly more computation time.