A Monolayer of Primary Colonic Epithelium Generated on a Scaffold with a Gradient of Stiffness for Drug Transport Studies

Animal models are frequently used for in vitro physiologic and drug transport studies of the colon, but there exists significant pressure to improve assay throughput as well as to achieve tighter control of experimental variables than can be achieved with animals. Thus, development of a primary in vitro colonic epithelium cultured as high resistance with transport protein expression and functional behavior similar to that of a native colonic would be of enormous value for pharmaceutical research. A collagen scaffold, in which the degree of collagen cross-linking was present as a gradient, was developed to support the proliferation of primary colonic cells. The gradient of cross-linking created a gradient in stiffness across the scaffold, enabling the scaffold to resist deformation by cells. mRNA expression and quantitative proteomic mass spectrometry of cells growing on these surfaces as a monolayer suggested that the transporters present were similar to those in vivo. Confluent monolayers acted as a barrier to small molecules so that drug transport studies were readily performed. Transport function was evaluated using atenolol (a substrate for passive paracellular transport), propranolol (a substrate for passive transcellular transport), rhodamine 123 (Rh123, a substrate for P-glycoprotein), and riboflavin (a substrate for solute carrier transporters). Atenolol was poorly transported with an apparent permeability (Papp) of < 5 × 10-7 cm s-1, while propranolol demonstrated a Papp of 9.69 × 10-6 cm s-1. Rh123 was transported in a luminal direction (Papp,efflux/Papp,influx = 7) and was blocked by verapamil, a known inhibitor of P-glycoprotein. Riboflavin was transported in a basal direction, and saturation of the transporter was observed at high riboflavin concentrations as occurs in vivo. It is anticipated that this platform of primary colonic epithelium will find utility in drug development and physiological studies, since the tissue possesses high integrity and active transporters and metabolism similar to that in vivo

Comparison of Strangeness Production between A+A and p+p Reactions from 2 to 160 AGeV

The measured K$^+/\pi^+$ ratios from heavy-ion reactions are compared with the K$^+/\pi^+$ ratios from p+p reactions over the energy range 2-160 AGeV. The K/$\pi$ enhancement in heavy-ion reactions is largest at the lower energies, consistent with strangeness production in secondary scattering becoming relatively more important than initial collisions near the kaon production threshold. The enhancement decreases steadily from 4 to 160 AGeV, suggesting that the same enhancement mechanism of hadronic rescattering and decay of strings may be applicable over this full energy range. Based on existing data, the mid-rapidity K$^+/\pi^+$ ratio is predicted to be $0.27\pm0.05$ for the forthcoming Pb+Pb reactions at 40 AGeV/c.Comment: 14 pages, 4 figures, submitted to Phys. Rev.

Two-band second moment model and an interatomic potential for caesium

A semi-empirical formalism is presented for deriving interatomic potentials for materials such as caesium or cerium which exhibit volume collapse phase transitions. It is based on the Finnis-Sinclair second moment tight binding approach, but incorporates two independent bands on each atom. The potential is cast in a form suitable for large-scale molecular dynamics, the computational cost being the evaluation of short ranged pair potentials. Parameters for a model potential for caesium are derived and tested

Familial influences on sustained attention and inhibition in preschoolers

Background: In this study several aspects of attention were studied in 237 nearly 6-year-old twin pairs. Specifically, the ability to sustain attention and inhibition were investigated using a computerized test battery (Amsterdam Neuropsychological Tasks). Furthermore, the Teacher's Report Form (TRF) was filled out by the teacher of the child and the attention subscale of this questionnaire was analyzed. Methods: The variance in performance on the different tasks of the test battery and the score on the attention scale of the TRF were decomposed into a contribution of the additive effects of many genes (A), environmental effects that are shared by twins (C) and unique environmental influences not shared by twins (E) by using data from MZ and DZ twins. Results: The genetic model fitting results showed an effect of A and E for the attention scale of the TRF, and for some of the inhibition and sustained attention measures. For most of the attention variables, however, it was not possible to decide between a model with A and E or a model with C and E. Time-on-task effects on reaction time or number of errors and the delay after making an error did not show familial resemblances. A remarkable finding was that the heritability of the attention scale of the TRF was found to be higher than the heritability of indices that can be considered to be more direct measures of attention, such as mean tempo in the sustained attention task and response speed in the Go-NoGo task. Conclusion: In preschoolers, familial resemblances on sustained attention and inhibition were observed. © Association for Child Psychology and Psychiatry, 2004

On non-local variational problems with lack of compactness related to non-linear optics

We give a simple proof of existence of solutions of the dispersion manage- ment and diffraction management equations for zero average dispersion, respectively diffraction. These solutions are found as maximizers of non-linear and non-local vari- ational problems which are invariant under a large non-compact group. Our proof of existence of maximizer is rather direct and avoids the use of Lions' concentration compactness argument or Ekeland's variational principle.Comment: 30 page

Theory of spin-polarized bipolar transport in magnetic p-n junctions

The interplay between spin and charge transport in electrically and magnetically inhomogeneous semiconductor systems is investigated theoretically. In particular, the theory of spin-polarized bipolar transport in magnetic p-n junctions is formulated, generalizing the classic Shockley model. The theory assumes that in the depletion layer the nonequilibrium chemical potentials of spin up and spin down carriers are constant and carrier recombination and spin relaxation are inhibited. Under the general conditions of an applied bias and externally injected (source) spin, the model formulates analytically carrier and spin transport in magnetic p-n junctions at low bias. The evaluation of the carrier and spin densities at the depletion layer establishes the necessary boundary conditions for solving the diffusive transport equations in the bulk regions separately, thus greatly simplifying the problem. The carrier and spin density and current profiles in the bulk regions are calculated and the I-V characteristics of the junction are obtained. It is demonstrated that spin injection through the depletion layer of a magnetic p-n junction is not possible unless nonequilibrium spin accumulates in the bulk regions--either by external spin injection or by the application of a large bias. Implications of the theory for majority spin injection across the depletion layer, minority spin pumping and spin amplification, giant magnetoresistance, spin-voltaic effect, biasing electrode spin injection, and magnetic drift in the bulk regions are discussed in details, and illustrated using the example of a GaAs based magnetic p-n junction.Comment: 36 pages, 11 figures, 2 table

Resummation of the Divergent Perturbation Series for a Hydrogen Atom in an Electric Field

We consider the resummation of the perturbation series describing the energy displacement of a hydrogenic bound state in an electric field (known as the Stark effect or the LoSurdo-Stark effect), which constitutes a divergent formal power series in the electric field strength. The perturbation series exhibits a rich singularity structure in the Borel plane. Resummation methods are presented which appear to lead to consistent results even in problematic cases where isolated singularities or branch cuts are present on the positive and negative real axis in the Borel plane. Two resummation prescriptions are compared: (i) a variant of the Borel-Pade resummation method, with an additional improvement due to utilization of the leading renormalon poles (for a comprehensive discussion of renormalons see [M. Beneke, Phys. Rep. vol. 317, p. 1 (1999)]), and (ii) a contour-improved combination of the Borel method with an analytic continuation by conformal mapping, and Pade approximations in the conformal variable. The singularity structure in the case of the LoSurdo-Stark effect in the complex Borel plane is shown to be similar to (divergent) perturbative expansions in quantum chromodynamics.Comment: 14 pages, RevTeX, 3 tables, 1 figure; numerical accuracy of results enhanced; one section and one appendix added and some minor changes and additions; to appear in phys. rev.

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc