A versatile high-permittivity phantom for EIT.

Phantoms are frequently used in medical imaging systems to test hardware, reconstruction algorithms, and the interpretation of data. This report describes and characterizes the use of powdered graphite as a means of adding a significant reactive component or permittivity to useful phantom media for electrical impedance imaging. The phantom materials produced have usable complex admittivity at the electrical impedance tomography (EIT) frequencies from a few kilohertz to 1 MHz, as measured by our EIT system (ACT4) and by a commercial bioimpedance analyzer (BIS 4000, Xitron). We have also studied a commercial ultrasound coupling gel, which is highly electrically conductive and semisolid but that permits objects to move within it. The mixture of agar-graphite and gel-graphite, increases in permittivity and conductivity are proportional to the graphite concentration. We also report the use of a porous polymer membrane to simulate skin. A thin layer of this membrane increased resistance and the characteristic frequency of the phantoms, providing a promising candidate to simulate the effect of skin and the layered structure of a breast or other anatomical structure. The graphite also provides a realistic level of "speckle" in ultrasound images of the phantom, which may be useful in developing dual-mode imaging systems with ultrasound and the EIT.

Potent, orally active corticotropin-releasing factor receptor-1 antagonists containing a tricyclic pyrrolopyridine or pyrazolopyridine core.

Two new classes of tricyclic-based corticotropin-releasing factor (CRF(1)) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based molecules 19g and 22a, respectively, were discovered that potently bind the recombinant CRF(1) receptor (K(i) = 3.5, 2.9 nM) and inhibit adrenocorticotropic hormone (ACTH) release from rat pituitary cell culture (IC(50) = 14, 6.8 nM). These compounds show good oral bioavailabity (F = 24%, 7.0%) and serum half-lives in rats (t(1/2) = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] = 0.27, 0.52) but tend toward large volumes of distribution (V(D) = 38, 44 L kg(-1)) and rapid clearances (CL = 70, 43 mL min(-1) kg(-1)). When given orally, both the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg(-1) doses.

A new approach to stereospecific synthesis of P-chiral phosphorothioates. Preparation of diastereomeric dithymidyl-(3'-5') phosphorothioates.

A new method for stereospecific synthesis of P-chiral phosphorothioates based on intramolecular nucleophile catalysis was developed.

Self-Assembling Sieves.

A modular strategy has been applied to synthesize large, porous, self-assembling capsules. The coupling of tricyclic building blocks incorporating glycoluril hydrogen-bonding units and derivatives of triethylbenzene produces monomers which readily form homo- and heterodimeric assemblies (calculated structure is shown). Large guests can be trapped while small solvent molecules flow freely through the pores of the capsules.