Refusing to Endorse. A must Explanation for Pejoratives.

In her analysis of pejoratives, Eva Picardi rejects a too sharp separation between descriptive and expressive content. I reconstruct some of her arguments, endorsing Eva’s criticism of Williamson’s analysis of Dummett and developing a suggestion by Manuel Garcia Carpintero on a speech act analysis of pejoratives. Eva’s main concern is accounting for our instinctive refusal to endorse an assertion containing pejoratives because it suggests a picture of reality we do not share. Her stance might be further developed claiming that uses of pejoratives not only suggest, but also promote a wrong picture of reality. Our refusal to endorse implies rejecting not only a wrong picture of reality but also a call for participation to what that picture promotes

The development of low temperature curing adhesives

An approach for the development of a practical low temperature (293 K-311 K/68 F-100 F) curing adhesive system based on a family of amide/ester resins was studied and demonstrated. The work was conducted on resin optimization and adhesive compounding studies. An improved preparative method was demonstrated which involved the reaction of an amine-alcohol precursor, in a DMF solution with acid chloride. Experimental studies indicated that an adhesive formulation containing aluminum powder provided the best performance when used in conjunction with a commercial primer

The Causes of Early Implant Bone Loss: Myth or Science?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141921/1/jper0322.pd

Bicyclic imidazolium inhibitors of Gli transcription factor activity

Gli transcription factors within the Hedgehog (Hh) signaling pathway direct key events in mammalian development and promote a number of human cancers. Current therapies for Gli‐driven tumors target Smoothened (SMO), a G protein‐coupled receptor‐like protein that functions upstream in the Hh pathway. Although these drugs can have remarkable clinical efficacy, mutations in SMO and downstream Hh pathway components frequently lead to chemoresistance. In principle, therapies that act at the level of Gli proteins, through direct or indirect mechanisms, would be more efficacious. We therefore conducted a screen of 325,120 compounds for their ability to block the constitutive Gli activity induced by loss of Suppressor of Fused (SUFU), a scaffolding protein that directly inhibits Gli function. Our studies reveal a family of bicyclic imidazolium derivatives that can inhibit Gli‐dependent transcription without affecting the ciliary trafficking or proteolytic processing of these transcription factors. We anticipate that these chemical antagonists will be valuable tools for investigating the mechanisms of Gli regulation and developing new strategies for targeting Gli‐driven cancers

Heat-stable enterotoxin receptor/guanylyl cyclase C is an oligomer consisting of functionally distinct subunits, which are non-covalently linked in the intestine

Guanylyl cyclase (GC) C is a heat-stable enterotoxin (STa) receptor with a monomeric M(r) of approximately 140,000. We calculated from its hydrodynamic parameters that an active GC-C complex has a M(r) of 393,000, suggesting that GC-C is a trimer under native conditions. Both trimeric and dimeric GC-C complexes were detected by 125I-STa binding and SDS-polyacrylamide gel electrophoresis under non-reducing conditions. The GC activity and STa binding from intestinal brush border membranes comigrated in gel filtration and velocity sedimentation with recombinant GC-C. However, 125I-STa cross-linking demonstrated that STa receptors with molecular masses of 52 and 74 kDa are non-covalently attached to GC in the intestine. Radiation inactivation revealed different functional sizes for basal GC activity, STa-stimulated GC activity, and STa binding (59, 210-240, and 32-52 kDa, respectively). At low radiation doses, basal GC activity was stimulated, suggesting that GC-C is inhibited by a relatively large, probably internal structure. These results suggest that STa may activate GC-C by promoting monomer-monomer interaction (internal "dimerization") within a homotrimeric GC-C complex, and that GC-C is proteolytically modified in the brush border membrane but retains its function