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The insertion of a stent in diseased arteries is a common endovascular procedure that can be compromised by the development of short- and long-term inflammatory responses leading to restenosis and thrombosis, respectively. While treatment with drugs, either systemic or localized, has decreased the incidence of restenosis and thrombosis these complications persist and are associated with a high mortality in those that present with stent thrombosis. We reasoned that if stents could be made to undergo accelerated endothelialization in the deployed region, then such an approach would further decrease the occurrence of stent thrombosis and restenosis thereby improving clinical outcomes. Toward that objective, the first step necessitated efficient capture of progenitor stem cells, which eventually would become the new endothelium. To achieve this objective, we engineered intrinsic ferromagnetism within nonmagnetizable, biodegradable magnesium (Mg) bare metal stents. Mg stents were coated with biodegradable polylactide (PLA) polymer embedding magnetizable iron-platinum (FePt) alloy nanoparticles, nanomagnetic particles, nMags, which increased the surface area and hence magnetization of the stent. nMags uniformly distributed on stents enabled capture, under flow, up to 50 mL/min, of systemically injected iron-oxide-labeled (IO-labeled) progenitor stem cells. Critical parameters enhancing capture efficiency were optimized, and we demonstrated the generality of the approach by showing that nMag-coated stents can capture different cell types. Our work is a potential paradigm shift in engineering stents because implants are rendered as tissue in the body, and this "natural stealthiness" reduces or eliminates issues associated with pro-inflammatory immune responses postimplantation.

Malcolm Dole's pioneering work using electrospray ionization to produce gas phase ions of molecules `too large to be vaporized by conventional means' formed the inspiration for work begun in John Fenn's laboratory at Yale in the 1980s. By the end of the decade, it revolutionized mass spectrometrists' approach to large molecule analysis. Key to Fenn's success was the introduction of counter-current flow drying gas that enhanced droplet evaporation and prevented solvent from condensing on the ions during rapid cooling that accompanies expansion into vacuum. For this work in `making molecular elephants fly,' John Fenn was awarded the 2002 Nobel Prize in Chemistry.

This numerical analysis examines early-stage Interlukin-2 (IL-2) capture in large populations of secreting T helper (Th) and absorbing T regulatory (Treg) cells in an attempt to provide rational guidelines for when diffusive interactions can affect the Th autocrine cycle, as reflected in capture times. Autocrine and paracrine capture is calculated over a wide range of conditions: the mix of cells in a population; cell size and spacing; antigen activated IL-2 secretion and Th receptor expression rates; receptor dissociation constant; and number of resting Treg receptors. Correlations for quickly estimating IL-2 capture over these conditions are provided. This study suggests that a typical Treg can scavenge a significant amount of IL-2 without affecting autocrine capture by the Th. As a result, Treg influence on autocrine capture is shorter-ranged than previously reported. It is conjectured that high early-stage paracrine relative to autocrine capture leads to faster receptor enhancement for a Treg than a Th. The resulting enhancement time gap is considerably longer and, thus, diffusive suppression more likely, for a weakly- as opposed to strongly-activated Th. The methodology can be extended to later-stage capture to confirm this conjecture and to diffusive interactions in other cell-type populations.

Polymeric nanoparticles (nano-paAPCs) modified with T-cell antigens and encapsulating immunostimulatory or immunoinhibitory factors may act as artificial antigen-presenting cells to circulating immune cells, improving the selective delivery of encapsulated drug or cytokine to antigen-specific T-cells. Paracrine delivery of encapsulated agents from these nanoparticles to adjacent cells facilitate sustained delivery lowering the overall administered dose, thus enhancing the overall drug efficacy while reducing toxicity of pleiotropic factors. Little is known mathematically regarding the local concentration of released agent that accumulates around a nanoparticle that is near or embeds in a cell. These concentration fields are calculated here in an attempt to understand paracrine efficacy of these nano-paAPC systems. The significant factor accumulation that can occur if the particles were to embed in the cell membrane may explain observed experimental data regarding enhanced T-cell activation and nanoparticle-mediated improvement in the drug delivery process to non-internalizing cellular targets. (C) 2015 Elsevier Inc. All rights reserved.

Paracrine transfer of chemical factors between two interacting cells is a fundamental biological signaling process that can mediate cell differentiation, proliferation or even cell death. A hallmark geometrical feature of such interactions is deformation due to the flattening of membranes at the interface, referred to here as the synaptic gap. Of particular interest here is the accumulation of synaptic factor during the early stages of cell activation when one cell (REC) does not have sufficient surface receptors to absorb/adsorb the factor emitted by the other (EMC). Since factor accumulation has been conjectured to play an important role in cell activation, as in any reactive system, whether chemical or biological, an estimate of concentrations is essential for understanding the process. The purpose of this work is to provide just such an estimate by taking an engineering approach to this biological problem. In this regard, instead of providing a comprehensive “model” for paracrine delivery, the analysis is a solution of the quasi-steady diffusion equation in and around the interacting cells as a function of the degree of deformation and the kinetics of emission. Using a singularity method, it is found that, depending on the emission rate, cell deformation can lead to synaptic factor concentrations that are more than an order of magnitude higher than cells that retain a spherical shape. Analytical expressions for the radial variation of factor concentration within the gap are also derived. These analytical expressions, however, only provide the concentration difference between the synaptic axis and edge points but are nevertheless useful for estimating synaptic behavior and for validation of the computational method. The results also highlight the importance of deformation on paracrine signaling and indicate a mechanism by which cells can increase the range and function of transmitted factor by geometric alteration of the interface. While T cell activation is of primary interest, the analysis is cast in general terms so it can be applied to other non-absorbing RECs.

The diffusive transfer, or paracrine delivery, of chemical factors during the interaction of an emitting cell and a receiving cell is a ubiquitous cellular process that facilitates information exchange between the cells and/or to bystander cells. In the cellular immune response this exchange governs the magnitude and breadth of killing of cellular targets, inflammation or tolerance. Paracrine delivery is examined here by solving the steady-state diffusion equation for the concentration field surrounding two intensely interacting, equi-sized cells on which surface kinetics limits the rates of factor emission and absorption. These chemical factors may be cytokines, such as Interlukins and Interferons, but the results are presented in a generic form so as to be applicable to any chemical factor and/or cell-type interaction. In addition to providing overall transfer rates and transfer efficiencies, the results also indicate that when the receiving cell is naïve, with few factor receptors on its surface, there may be a significant accumulation of factor in the synaptic region between the cells with a consequent release of factor to the medium where it can signal bystander cells. This factor accumulation may play a critical role in activating a naïve receiving cell. As the receiving cell activates and becomes more absorbent, the factor accumulation diminishes, as does potential bystander signaling.

Artificial antigen-presenting cells (aAPCs) are an emerging technology to induce therapeutic cellular immunity without the need for autologous antigen-presenting cells (APCs). To fully replace natural APCs, an optimized aAPC must present antigen (signal 1), provide costimulation (signal 2), and release cytokine (signal 3). Here we demonstrate that the spatial and temporal characteristics of paracrine release of IL-2 from biodegradable polymer aAPCs (now termed paAPCs) can significantly alter the balance in the activation and proliferation of CD8+ and CD4+ T cells. Paracrine delivery of IL-2 upon T cell contact with paAPCs induces significant IL-2 accumulation in the synaptic contact region. This accumulation increases CD25 (the inducible IL-2 Rα chain) on responding T cells and increases proliferation of CD8+ T cells in vitro to levels 10 times that observed with equivalent amounts of bulk IL-2. These CD8+ T cell responses critically depend upon close contact of T cells and the paAPCs and require sustained release of low levels of IL-2. The same conditions promote activation-induced cell death in CD4+ T cells. These findings provide insight into the response of T cell subsets to paracrine IL-2.

We consider here the effects of gas-phase turbulence on the evaporation dynamics of a polydispersed dilute fuel spray in an adiabatic well-stirred reactor (WSR) supplied with hot compressed air. Turbulence increases the time-averaged rate of heat diffusion-controlled droplet evaporation but the augmentation factor is droplet size-dependent because of droplet inertia and evaporative drag reduction. Consequently, each droplet in a spray population will not be characterized by the same rate of area change even in the same time-averaged environment. When these physical phenomena are convoluted with the residence time distribution characterizing a WSR (simulating, say, the primary zone of an aircraft gas turbine combustor), we predict the resulting fraction evaporated, evaporation rate-controlled combustion “intensity”, and corresponding exit droplet size distributions (DSD).

An entrainment parameter, based on the ratio of the characteristic particle lifetime to the stopping time of a non-volatile particle, is shown to be a more rational choice than the Stokes number for describing the dynamic response of a volatile spherical particle suddenly immersed in a steady flow field.

A model is presented which shows that the energy required to emit small singly charged and large multiply charged (protein) solvated ions from electrospray droplets can be considerably lower than those predicted by earlier models. By allowing the droplet surface to distort in reaction to the emerging ion, a more nuanced picture of the ion emission mechanism appears, one that covers the range from pure ion evaporation (PIE) for small ions to what may be termed activated pseudo-Rayleigh ion release (PRIR), a mechanism that yields charge states nearly indistinguishable from the charge residue model (CRM), for large ions. Predictions based on this model are qualitatively consistent with many experimentally observed trends.

A miniaturized version of an isopotential nano-differential mobility analyzer (DMA) [Labowsky, M., & Fernández de la Mora, J. (2006). Novel ion mobility analyzers and filters. Journal of Aerosol Science, 37, 340–362] has been tested experimentally and simulated by means of the commercial code COMSOL® to take into account Brownian diffusion. Compared with the prototype tested by [Martínez-Lozano, P., & Fernández de la Mora, J. (2006). Resolution improvements of a nano-DMA operating transonically. Journal of Aerosol Science, 37, 500–512.] this model is half the size and weights 920g. Resolution, defined as the inverse of the relative full width at half height (FWHH), has been improved by a 50%, attaining a maximum resolution of 75 operating at a Reynolds number (Re) of ∼47,000, measuring ions of equivalent mobility diameter ∼1nm. The maximum diameter theoretically measurable by this DMA is 15nm. The predictions of the numerical simulations are in reasonable agreement with experiments with respect to resolution and the device constant, which provides an estimation of the measurable size range. The model suggests future approaches to improve resolution and to extend the measurable size range.

Motivated by the insights it can provide, we revisit the classical problem of liquid fuel-fed idealized steady-flow combustors. New quadrature-based results are presented for the theoretical combustion intensity and corresponding efficiency for well-stirred adiabatic vessels fed with a prescribed polydispersed spray. Each droplet of the spray is assumed to evaporate according to a non-quasi-steady (non-QS) gas-phase energy/mass diffusion-controlled rate for the pseudo-single-component fuel. As a byproduct, we calculate the complete droplet size distribution (DSD) function exiting the chamber, of interest for the design of downstream components. We explicitly assume that the volumetric rate of chemical energy release in such “primary” combustion chambers is controlled by the liquid fuel physical vaporization process (with negligible lags due to propellant droplet heat-up or vapor-phase ignition). In this instructive asymptotic limit, two decisive non-dimensional parameters are shown to be: (1) a vaporization Damköhler number (defined by the ratio of the mean residence time of the chemically reacting vapor mixture in the combustion space, to the reference value of the vaporization lifetime of a droplet with the injector-Sauter-mean diameter, and (2) a single dimensionless non-QS parameter. Illustrative numerical results for a kerosene-like fuel burning in air at pressures up to 24atm are displayed for the case of a log-normal feedstream DSD with a range of spreads. Our results reveal the existence of an optimum vaporization Damköhler number which maximizes the combustion intensity—with maximum intensities, occurring well before nearly complete fuel evaporation, being quite sensitive to the non-QS parameter at high pressures. These deliberately idealized mathematical model results, spanning more than a 1000 combinations of operational parameters, set instructive bounds to the achievable performance of “real” spray combustors. Even without tractable enhancements (see Section 5.2), this approach can be used to economically map the sensitivity of spray combustor performance to a large number of important design and control parameters.

Various novel mobility analyzer (MA) designs useful for the separation of gas phase ions and charged particles according to their electrical mobilities are discussed. Traditional differential mobility analyzer (DMA) designs have mostly been restricted to two-elements (electrodes) of either parallel or coaxial cylindrical geometries, with the inlet and the outlet on different elements, between which is maintained a large voltage difference. Calculations of the performance of several MA designs free from some such restrictions are presented in the case of potential flows. They include, for example, devices in which (i) the inlet and outlet are on the same element; (ii) the inlet and outlet are at the same voltage (“isopotential devices”); (iii) more than two-elements exist; (iv) a fair fraction of the sheath gas flow passes through one of the elements; (v) all ions within a finite mobility range originating at an inlet point are focused on the outlet (mobility focusing). These latter devices may be more properly described as “Ion Filters” because only ions within a tunable mobility range can reach the outlet. By restricting the “bandwidth” through additional elements or auxiliary sheath gas flow suction/injection, these filters can be used as high resolution DMAs. Isopotential aspiration counters have been used previously as atmospheric ion counters.

A novel isopotential differential mobility analyzer (DMA) concept described by Labowsky and Fernández de la Mora [(2006). Novel ion mobility analyzers and filters. Journal of Aerosol Science, 37, 340–362.] is tested experimentally. Its aerosol inlet and outlet lines are grounded, while the electric field is created with a metallic grid electrode that also acts as a laminarization screen. A minimum gas suction qo is required at the outlet for aerosol to be sampled, so that qo at optimal operation conditions tends to exceed the aerosol inlet flow rate qi. A resolving power of 50 (full peak width at half height FWHH=2%) is demonstrated for ions with mobility diameter of 1.44nm when operating at sheath flow Qs up to 2300l/min, with qi/Qs=0.6% and qo/Qs=2%. Remarkably, this high resolution is achieved with a very modest area ratio of 1.27 between the laminarization section and the aerosol inlet section. The lack of voltage jumps anywhere in the aerosol path is an effective means to eliminate electrophoretic losses of nanoparticles, particularly when several DMAs are operated in tandem.