A stereotypic,transplantable liver tissue-culture system

A method of coculturing adult rat hepatic parenchymal cells (PC) and stromal cells in a three-dimensional framework of nylon filtration screens or biodegradable polymer meshes was developed in our laboratory. Rat liver stroma, which includes vascular and bile duct endothelial cells, fat-storing cells, fibroblasts, and Kupffer cells, were isolated by gradient centrifugation afterin situ liver perfusion and expanded in monolayer culture prior to seeding onto nylon screens or bioresorbable polyglycolic acid (PGA) polymers oriented into a felt-like construct. A second inoculum of freshly isolated PC was applied after the stromal cells became established. Histological analyses revealed that PC proliferation occurred until all available space for expansion within the template was exhausted. These cells retained their rounded morphology, and after 4–5 wk 7–9 “layers” of PC filled the 140-μm deep template. Dioxin-inducible cytochrome P450 activity was detected for up to 58 d in culture, and albumin, fibrinogen, transferrin, and soluble fibronectin were detected in the medium by enzyme-linked immunosorbent assay (ELISA) for 48 d in vitro. Immunohistochemical analysis of sections through the cultures confirmed the presence of these proteins as well as cytokeratin at the cellular level; the extracellular matrix stained for both collagen type III and laminin. Long-term PC proliferation and function were enhanced by the presence of stromal cells as well as by a meshwork template whose geometry allows the interaction of PC with stroma and matrix on several different planes. To permit transplantation, co-cultures of hepatic PC and stromal cells were established on PGA felt constructs instead of nylon screens. After 24 d in vitro, these constructs were grafted into sites in the mesentery, omentum, and sub-cutaneous tissues of adult Long-Evans rats. The growth of hepatocytes after 30 din situ was evident by histological analysis; grafts of co-cultures regenerated a liver-like architecture consisting of sinusoids and putative biliary structures. In addition, PC at these extrahepatic graft sites were positive for albumin, transferrin, and fibrinogen synthesis by immunohistochemistry. Graft survival was enhanced when recipients were subjected to 40% hepatectomy. Hepatic PC:stromal cell cocultures may prove useful in the restoration of liver function either by direct transplantation using PGA or similar templates, or as extracorporeal devices, using nylon screens.     

Asymptotic mass degeneracies in conformal field theories

By applying a method of Hardy and Ramanujan to characters of rational conformal field theories, we find an asymptotic expansion for degeneracy of states in the limit of large mass which isexact for strings propagating in more than two uncompactified space-time dimensions. Moreover we explore how the rationality of the conformal theory is reflected in the degeneracy of states. We also consider the one loop partition function for strings, restricted to physical states, for arbitrary (irrational) conformal theories, and obtain an asymptotic expansion for it in the limit that the torus degenerates. This expansion depends only on the spectrum of (physical and unphysical) relevant operators in the theory. We see how rationality is consistent with the smoothness of mass degeneracies as a function of moduli.     

Geometry of N = 1 dualities in four dimensions

We discuss how N = 1 dualities in four dimensions are geometrically realized by wrapping D-branes about 3-cycles of Calabi-Yau threefolds. In this setup the N = 1 dualities for SU, SO and USp gauge groups with fundamental fields get mapped to statements about the monodromy and relations among 3-cycles of Calabi-Yau threefolds. The connection between the theory and its dual requires passing through configurations which are T-dual to the well-known phenomenon of decay of BPS states in N = 2 field theories in four dimensions. We compare our approach to recent works based on configurations of D-branes in the presence of NS 5-branes and give simple classical geometric derivations of various exotic dynamics involving D-branes ending on NS branes.     

Large N Duality, Lagrangian Cycles, and Algebraic Knots

We consider knot invariants in the context of large N transitions of topological strings. In particular we consider aspects of Lagrangian cycles associated to knots in the conifold geometry. We show how these can be explicitly constructed in the case of algebraic knots. We use this explicit construction to explain a recent conjecture relating study of stable pairs on algebraic curves with HOMFLY polynomials. Furthermore, for torus knots, using the explicit construction of the Lagrangian cycle, we also give a direct A-model computation and recover the HOMFLY polynomial for this case.     

On classification ofN=2 supersymmetric theories

We find a relation between the spectrum of solitons of massiveN=2 quantum field theories ind=2 and the scaling dimensions of chiral fields at the conformal point. The condition that the scaling dimensions be real imposes restrictions on the soliton numbers and leads to a classification program for symmetricN=2 conformal theories and their massive deformations in terms of a suitable generalization of Dynkin diagrams (which coincides with the A-D-E Dynkin diagrams for minimal models). The Landau-Ginzburg theories are a proper subset of this classification. In the particular case of LG theories we relate the soliton numbers with intersection of vanishing cycles of the corresponding singularity; the relation between soliton numbers and the scaling dimensions in this particular case is a well known application of Picard-Lefschetz theory.     

Global anomalies on orbifolds

Communicated by A. Jaffe