Angiotensin II (Ang II) has been implicated in the development of progressive glomerulosclerosis, but the precise mechanism of this effect remains unclear. In an experimental model, we have shown previously that TGF-,6 plays a key role in glomerulosclerosis by stimulating extracellular matrix protein synthesis, increasing matrix protein receptors, and altering protease /protease-inhibitor balance, thereby inhibiting matrix degradation. We hypothesized that Ang II contributes to glomerulosclerosis through induction of TGF-fl. Ang 6 blocked the Ang II-induced increases in matrix protein expression. Continuous in vivo administration of Ang II to normal rats for 7 d resulted in 70% increases in glomerular mRNA for both TGF-ft and collagen type I. These results indicate that Ang II induces mesangial cell synthesis of matrix proteins and show that these effects are mediated by Ang II induction of 6 expression. This mechanism may well contribute to glomerulosclerosis in vivo. (J. Clin. Invest. 1994. 93:2431-2437
A proof-theoretic characterization of logical languages that form suitable bases for Prolog-like programming languages is provided. This characterization is based on the principle that the declarative meaning of a logic program, provided by provability in a logical system, should coincide with its operational meaning, provided by interpreting logical connectives as simple and fixed search instructions. The operational semantics is formalized by the identification of a class of cut-free sequent proofs called uniform proofs. A uniform proof is one that can be found by a goal-directed search that respects the interpretation of the logical connectives as search instructions. The concept of a uniform proof is used to define the notion of an abstract logic programming language, and it is shown that first-order and higherorder Horn clauses with classical provability are examples of such a language. Horn clauses are then generalized to hereditary Harrop formulas and it is shown that first-order and higher-order versions of this new class of formulas are also abstract logic programming languages if the inference rules are those of either intuitionistic or minimal logic. The programming language significance of the various generalizations to first-order Horn clauses is briefly discussed.
Whole-mount in situ hybridization (WISH) is a powerful tool for visualizing gene expression patterns in specific cell and tissue types. Each model organism presents its own unique set of challenges for achieving robust and reproducible staining with cellular resolution. Here, we describe a formaldehyde-based WISH method for the freshwater planarian Schmidtea mediterranea developed by systematically comparing and optimizing techniques for fixation, permeabilization, hybridization, and postprocessing. The new method gives robust, high-resolution labeling in fine anatomical detail, allows co-labeling with fluorescent probes, and is sufficiently sensitive to resolve the expression pattern of a microRNA in planarians. Our WISH methodology not only provides significant advancements over current protocols that make it a valuable asset for the planarian community, but should also find wide applicability in WISH methods used in other systems. Developmental Dynamics 238:443-450, 2009.
A focused proof system provides a normal form to cut-free proofs in which the application of invertible and non-invertible inference rules is structured. Within linear logic, the focused proof system of Andreoli provides an elegant and comprehensive normal form for cut-free proofs. Within intuitionistic and classical logics, there are various different proof systems in the literature that exhibit focusing behavior. These focused proof systems have been applied to both the proof search and the proof normalization approaches to computation. We present a new, focused proof system for intuitionistic logic, called LJF, and show how other intuitionistic proof systems can be mapped into the new system by inserting logical connectives that prematurely stop focusing. We also use LJF to design a focused proof system LKF for classical logic. Our approach to the design and analysis of these systems is based on the completeness of focusing in linear logic and on the notion of polarity that appears in Girard's LC and LU proof systems.
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