Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model

<p>Abstract</p> <p>Background</p> <p>Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated.</p> <p>Methods</p> <p>SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells), human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4⁺T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array.</p> <p>Results</p> <p>SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake) and led to a decreased secretion of pro-inflammatory cytokines.</p> <p>Conclusion</p> <p>These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.</p

Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration

It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.8 nm nanoparticles with opposite surface charges by intra-oesophageal instillation into healthy adult female rats. The quantitative amount of the particles in organs, tissues and excrements was measured after 24 h by gamma-spectroscopy. The highest accumulation in secondary organs was mostly found for 1.4 nm particles; the negatively charged particles were accumulated mostly more than positively charged particles. Importantly, 18 nm particles show a higher accumulation in brain and heart compared to other sized particles. No general rule accumulation can be made so far. Therefore, specialized drug delivery systems via the oral route have to be individually designed, depending on the respective target organ

Efficient convexity and domination algorithms for fine- and medium-grain hypercube computers

This paper gives hypercube algorithms for some simple problems involving geometric properties of sets of points. The properties considered emphasize aspects of convexity and domination. Efficient algorithms are given for both fine- and medium-grain hypercube computers, including a discussion of implementation, running times and results on an Intel iPSC hypercube, as well as theoretical results. For both serial and parallel computers, sorting plays an important role in geometric algorithms for determining simple properties, often being the dominant component of the running time. Since the time required to sort data on a hypercube computer is still not fully understood, the running times of some of our algorithms for unsorted data are not completely determined. For both the fine- and medium-grain models, we show that faster expected-case running time algorithms are possible for point sets generated randomly. Our algorithms are developed for sets of planar points, with several of them extending to sets of points in spaces of higher dimension.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41352/1/453_2005_Article_BF01758751.pd

Computing convexity properties of images on a pyramid computer

We present efficient parallel algorithms for using a pyramid computer to determine convexity properties of digitized black/white pictures and labeled figures. Algorithms are presented for deciding convexity, identifying extreme points of convex hulls, and using extreme points in a variety of fashions. For a pyramid computer with a base of n simple processing elements arranged in an n 1/2 × n 1/2 square, the running times of the algorithms range from Θ(log n ) to find the extreme points of a convex figure in a digitized picture, to Θ( n 1/6 ) to find the diameter of a labeled figure, Θ( n 1/4 log n ) to find the extreme points of every figure in a digitized picture, to Θ( n 1/2 ) to find the extreme points of every labeled set of processing elements. Our results show that the pyramid computer can be used to obtain efficient solutions to nontrivial problems in image analysis. We also show the sensitivity of efficient pyramid-computer algorithms to the rate at which essential data can be compressed. Finally, we show that a wide variety of techniques are needed to make full and efficient use of the pyramid architecture.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41351/1/453_2005_Article_BF01759066.pd

A Study of Quantum-classical Dynamics in the Mapping Basis

Solving quantum dynamics is an exponentially difficult problem. Thus, an exact numerical solution is inaccessible for any condensed matter system. A promising approach is to divide the system into a quantum subsystem containing degrees of freedom which are of greater interest or those which have more profound quantum character (e.g., have smaller mass) and a classical bath containing the rest of the system. Imposing such a partition and treating the bath classically results in quantum-classical dynamics. The quantum-classical Liouville equation is a general equation in the Hilbert space of quantum degrees of freedom while it resides in the phase space of the classical degrees of freedom. Any numerical solution to this equation requires representation of the quantum subsystem in some basis. Solutions to this equation have been already proposed in the subsystem, adiabatic and force bases, each with its own cons and pros. In this work, the quantum-classical equations of motion are cast in the subsystem basis and subsequently mapped to a number of fictitious harmonic oscillators. The result is quantum-classical dynamics in the mapping basis which treats both quantum and classical degrees of freedom on the same footing, i.e., in phase space. Neglecting a portion of the back reaction of the quantum-subsystem to classical bath results in an expression for the time evolution of an operator (density matrix) equal to its Poisson bracket with the Hamiltonian. This equation can be solved in terms of characteristics to provide a computationally tractable method for calculating quantum-classical dynamical properties. The expressions for expectation values and correlation functions in this formalism are derived. Calculations on spin-boson system, barrier crossing models---the so called Tully models---and the Fenna-Mathews-Olson pigments show very good agreement between the results of this method and numerical solutions to the Schrödinger equation.Ph

An ethnography of political leaders in Afghanistan

This study consisted of qualitative interviews with six Afghan political leaders who served as cabinet members in the Afghan government prior to the Soviet invasion. The study sought to report the political conditions in Afghanistan based on the direct experiences and the reflections of these leaders whose titles and names remain anonymous.The data were collected and analyzed using a modified version of Spradley's Developmental Research Sequence Writing methodology. The data included field notes gathered from numerous interviews, casual conversations, tape recording, library research and documents provided by the informants.The rivalries that prevented political unity during the war of resistance have exacerbated the quest for power now that the common enemy, the Soviet Union and Afghan-Marxist regimes, has disappeared from the scene. No credible social or political within the country to initiate and promote political reconciliation. Each group appears to be attempting a unilateral solution to the national crisis. The great majority of Afghans are not only left out of the political process, but are also held hostage to the confrontation between competing groups whose political and military strategies is the elimination, or at best exclusion, of other competing groups. Dangerously, none of the powerful group's adversaries has given up the idea of war as the institution or nationally acceptable leadership is available instrument of political settlement. Among political leaders there is still much in Afghan political culture that is basically hostile to open and competitive politics.Department of Educational LeadershipThesis (D. Ed.