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The pathophysiology of sickle cell disease is complicated by the multiscale processes that link the molecular genotype to the organismal phenotype: hemoglobin polymerization occurring in milliseconds, microscopic cellular sickling in a few seconds or less [Eaton WA, Hofrichter J (1990) Adv Protein Chem 40:63-279], and macroscopic vessel occlusion over a time scale of minutes, the last of which is necessary for a crisis [Bunn HF (1997) N Engl J Med 337:762-769]. Using a minimal but robust artificial microfluidic environment, we show that it is possible to evoke, control, and inhibit the collective vasoocclusive or jamming event in sickle cell disease. We use a combination of geometric, physical, chemical, and biological means to quantify the phase space for the onset of a jamming event, as well as its dissolution, and find that oxygen-dependent sickle hemoglobin polymerization and melting alone are sufficient to recreate jamming and rescue. We further show that a key source of the heterogeneity in occlusion arises from the slow collective jamming of a confined, flowing suspension of soft cells that change their morphology and rheology relatively quickly. Finally, we quantify and investigate the effects of small-molecule inhibitors of polymerization and therapeutic red blood cell exchange on this dynamical process. Our experimental study integrates the dynamics of collective processes associated with occlusion at the molecular, polymer, cellular, and tissue level; lays the foundation for a quantitative understanding of the rate-limiting processes; and provides a potential tool for optimizing and individualizing treatment, and identifying new therapies. blood flow | jamming | microfluidics

The incorporation of monolayers of cultured hepatocytes into an extracorporeal perfusion system has become a promising approach for the development of a temporary bioartificial liver (BAL) support system. In this paper we present a numerical investigation of the oxygen tension, shear stress, and pressure drop in a bioreactor for a BAL composed of plasma-perfused chambers containing monolayers of porcine hepatocytes. The chambers consist of microfabricated parallel disks with center-to-edge radial flow. The oxygen uptake rate (OUR), measured in vitro for porcine hepatocytes, was curve-fitted using Michaelis-Menten kinetics for simulation of the oxygen concentration profile. The effect of different parameters that may influence the oxygen transport inside the chambers, such as the plasma flow rate, the chamber height, the initial oxygen tension in the perfused plasma, the OUR, and Km was investigated. We found that both the plasma flow rate and the initial oxygen tension may have an important effect upon oxygen transport. Increasing the flow rate and/or the inlet oxygen tension resulted in improved oxygen transport to cells in the radial-flow microchannels, and allowed significantly greater diameter reactor without oxygen limitation to the hepatocytes. In the range investigated in this paper (10 [[micro]meter] < H < 100 [[micro]meter]), and for a constant plasma flow rate, the chamber height, H, had a negligible effect on the oxygen transport to hepatocytes. On the contrary, it strongly affected the mechanical stress on the cells that is also crucial for the successful design of the BAL reactors. A twofold decrease in chamber height from 50 to 25 [[micro]meter] produced approximately a fivefold increase in maximal shear stress at the inlet of the reactor from 2 to 10 dyn/[cm.sup.2]. Further decrease in chamber height resulted in shear stress values that are physiologically unrealistic. Therefore, the channel height needs to be carefully chosen in a BAL design to avoid deleterious hydrodynamic effects on hepatocytes.

An analysis of magnetoconductivity of polycrystalline Bi2Sr2Ca(1-x)Y(x)Cu2O(8 + delta) in magnetic fields of 4 T shows an insignificant value for the Maki-Thompson-Zeeman contribution (Delta-sigma-MTZ) and the phase braking time. Increase in Y implantation increases the phase breaking time, but has no effect on the Delta-sigma-MTZ value, the absence of which makes confirmation of the Thompson correction impossible.

Abstract: From resistivity specific heat (measured at and 9T) and thermoelectric power measurements on La1−xPrxSr2Mn2O7, , we find the electronic and the thermal transport in these materials to be predominantly two-dimensional. The localization especially at low temperatures increases with Pr concentration. For , the relative proportion of CE-phase grows with , and becomes unstable for between 120&#60;T&#60;160K. [Copyright &y& Elsevier]

Abstract: The paramagnetic susceptibility measured on La1−x Y x Sr2−y Ca y Mn2O7 (x, y or z=0, 0.03 and 0.1) manganites does not obey the Curie–Weiss law. The Curie constant exceeds the expected values by more than order of magnitude. Based on strong disorder we have compared the experimental data with predictions based on Griffith''s singularity model. We find that this model allows for consistent interpretation of the data in contrary to a model assumes that magnetic polarons make contribution akin to cluster to susceptibility. In particular the values of Curie constant agree excellently with those theoretically expected, whereas the magnetic polarons model is less satisfactory. [Copyright &y& Elsevier]