G. W. Young

In vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria

OBJECTIVES Silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. Here, the bactericidal activity of four silver carbene complexes (SCCs) with different formulations, including nanoparticles (NPs) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections. METHODS MIC, MBC and multidose experiments were conducted against a broad range of bacteria and fungi. Time-release and cytotoxicity studies of the compounds were also carried out. Free SCCs and SCC NPs were tested against a panel of medically important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MRAB), Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae. RESULTS All four SCCs demonstrated strong efficacy in concentration ranges of 0.5-90 mg/L. Clinical bacterial isolates with high inherent resistance to purified compounds were more effectively treated either with an NP formulation of these compounds or by repeated dosing. Overall, the compounds were active against highly resistant bacterial strains, such as MRSA and MRAB, and were active against the biodefence pathogens Bacillus anthracis and Yersinia pestis. All of the medically important bacterial strains tested play a role in many different infectious diseases. CONCLUSIONS The four SCCs described here, including their development as NP therapies, show great promise for treating a wide variety of bacterial and fungal pathogens that are not easily killed by routine antimicrobial agents.

Anisotropic interface kinetics and tilted cells in unidirectional solidification

Abstract We derive a nonlinear evolution equation governing the cellular structure of a binary alloy having small segregation coefficient, including the effects of anisotropic interface kinetics. This equation, applicable to long-wave instabilities of a planar interface, describes the spatial pattern of the growing disturbances. The presence of anisotropy causes the cells to grow at an angle to the normal of the planar front. This transition to a cellular morphology is shown to be a subcritical instability.

Steady-state thermal-solutal diffusion in a float zone

Abstract A model is presented for a float zone established in a thin vertical sheet. In a coordinate system translating with the heater, the equations describing the steady, two-dimensional diffusion of solute in the melt, and diffusion of heat in the feed material and the product crystal are discussed. Heat transfer between the system (melt, feed and product) and the surrounding environment (including the heating source) is assumed to take place via both convection and radiation. Given the translation velocity, the heater and the ambient temperature profiles, and material properties, asymptotic solutions for the temperature and concentration profiles and the melting, solidifying and melt/gas interfacial shapes are developed in the limit of small aspect ratio (zone half-width/length). Results of a parametric investigation are presented and compared to both numerical and experimental observations. The physical mechanisms involved in the formation of the zone configuration are discussed for both the pure and binary systems of Si and GeGa, respectively.

Surface tension driven heat, mass, and momentum transport in a two-dimensional float-zone

Abstract A model is presented for a float zone established in a thin vertical sheet. In a coordinate system translating with the heater, equations describing the steady, two-dimensional transport of momentum, heat and solute in the melt, and diffusion of heat in the feed material and the product crystal are discussed. Heat transfer between the system (melt, feed and product) and the surrounding environment (including the heating source) is assumed to take place via radiation. Given the translation velocity, the heater and the ambient temperature profiles, and material properties, asymptotic solutions for the temperature, concentration, and melt flow profiles and the melting, solidifying and melt/gas interfacial shapes are developed in the limit of small aspect ratio (zone half-width/length) and weak surface tension driven flows. We find that convective heat transport leads to melt back of the solidification front near the edges. Further, lateral solute segregation is due to both convective effects and curved solidification fronts. Increasing the flow or increasing the velocity of solidification leads to increased lateral solute segregation in melts that are not well mixed. Finally, flat solidification fronts may not yield flat concentration profiles.

An asymptotic model of the mold region in a continuous steel caster

A model is developed to simulate the solidification of the steel shell in the mold region of the continuous casting process. Conduction-dominated temperature fields in the mold, mold flux, steel shell, and molten steel regions are determined through the development of an evolution equation for the solidifying front. This equation is derived in the limit of small aspect ratio, mold width to height, using asymptotic methods. These results are coupled with a lubrication-theory model for the mold flux region. This model assumes a temperature-dependent viscosity for the mold flux and allows for solidification of the flux at temperatures below a critical value. System response to changing casting speeds, superheat, mold wall temperatures, and mold flux properties is investigated.

Nanoparticle Deposition onto Biofilms

We develop a mathematical model of nanoparticles depositing onto and penetrating into a biofilm grown in a parallel-plate flow cell. We carry out deposition experiments in a flow cell to support the modeling. The modeling and the experiments are motivated by the potential use of polymer nanoparticles as part of a treatment strategy for killing biofilms infecting the deep passages in the lungs. In the experiments and model, a fluid carrying polymer nanoparticles is injected into a parallel-plate flow cell in which a biofilm has grown over the bottom plate. The model consists of a system of transport equations describing the deposition and diffusion of nanoparticles. Standard asymptotic techniques that exploit the aspect ratio of the flow cell are applied to reduce the model to two coupled partial differential equations. We perform numerical simulations using the reduced model. We compare the experimental observations with the simulation results to estimate the nanoparticle sticking coefficient and the diffusion coefficient of the nanoparticles in the biofilm. The distributions of nanoparticles through the thickness of the biofilm are consistent with diffusive transport, and uniform distributions through the thickness are achieved in about four hours. Nanoparticle deposition does not appear to be strongly influenced by the flow rate in the cell for the low flow rates considered.

Comparison of Asymptotic Solutions of a Phase-Field Model to a Sharp-Interface Model

A one-dimensional directional solidification problem is considered for the purpose of analyzing the relationship between the solution resulting from a phase-field model to that from a sharp-interface model. The solidification problem is posed within a finite domain, rather than an infinite extent, as in classical Stefan problems. An asymptotic analysis based upon a small Stefan number is performed on the sharp-interface model. In the phase-field case, the small Stefan number expansion is coupled with a small interface-thickness boundary layer expansion. This approach enables us to develop analytical solutions to the phase-field model. The results show agreement at leading order between the two models for the location of the solidification front and the temperature profiles in the solid and liquid phases. However, due to the nonzero interface thickness in the phase-field model, corrections to the sharp-interface location and temperature profiles develop. These corrections result from the conduction of late...

Modeling the time-dependent growth of single-crystal fibers

A model is developed to simulate time-dependent behavior in laser-heated miniature pedestal growth (LHPG) of single-crystal fibers. This process is meniscus controlled since the diameter of the growing fiber changes in response to variations between the equilibrium and the instantaneous contact angle at the melt/solidifying-solid interface. One of the operational problems associated with the LHPG technique is controlling diameter fluctuations in the growing fiber due to process perturbations. Smooth source feed and fiber pull rates, steady laser-heat input, and suppression of mechanical vibrations are necessary to achieve a constant fiber diameter. We derive a system of time-dependent, one-dimensional equations of motion and heat transfer as the leading order equations in an asymptotic expansion based upon the melt slenderness ratio (fiber radius/melt height). This system is solved numerically to predict the thermal profiles, mean positions of the melting and solidifying fronts, melt/gas interface, melt volume, and fiber diameter. System response to perturbations in the pull rates, thermal environment, and gravitational field is investigated.

Development of the Pseudomonas aeruginosa mushroom morphology and cavity formation by iron-starvation: a mathematical modeling study.

We present a mathematical model of mushroom-like architecture and cavity formation in Pseudomonas aeruginosa biofilms. We demonstrate that a proposed disparity in internal friction between the stalk and cap extracellular polymeric substances (EPS) leads to spatial variation in volumetric expansion sufficient to produce the mushroom morphology. The capability of diffusible signals to induce the formation of a fluid-filled cavity within the cap is then investigated. We assume that conversion of bacteria to the planktonic state within the cap occurs in response to the accumulation or depletion of some signal molecule. We (a) show that neither simple nutrient starvation nor signal production by one or more subpopulations of bacteria is sufficient to trigger localized cavity formation. We then (b) demonstrate various hypothetical scenarios that could result in localized cavity formation. Finally, we (c) model iron availability as a detachment signal and show simulation results demonstrating cavity formation by iron starvation. We conclude that iron availability is a plausible mechanism by which fluid-filled cavities form in the cap region of mushroom-like structures.

Development of experimental techniques and an analytical model for aluminum nitriding

The rates of diffusion of nitrogen into aluminum and the subsequent formation of aluminum nitride are unclear. By matching experimental data to analytical models one can gain a better understanding of the diffusion process for nitrogen into aluminum and formation of aluminum nitride. We combine novel experimental and modeling approaches to achieve this goal. We develop a technique for in situ measurement of nitrogen deposition using a microbalance and present a simple reaction diffusion equation to simulate the diffusion of nitrogen into aluminum and subsequent precipitation into aluminum nitride. A mixed boundary condition formulation is presented to account for the initial influx of nitrogen at the surface until a saturation level is reached. We curve fit the derived model equations to the experimental data and determine the system diffusion coefficient and reaction rate constant.