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A new class of selective FXIIIa inhibitors with a bicyclic [1,2,4]-thiadiazole pharmacophore is described. At 160 μM, compound 8 caused 50% reduction in fibrin γ-chain cross-linking and suppressed the polymerization of α chains in platelet-depleted human plasma clots. Fibrinolysis rates in response to tissue plasminogen activator were directly proportional to the concentration of 8 in plasma at the time of clotting.

In recent years the trend in combinatorial library design has shifted to include target class focusing along with diversity and drug-likeness criteria. In this manuscript we review the computational tools available for target class library design and highlight the areas where they have proven useful in our work. The protein kinase family is used to illustrated structure-based target class focused library design, and the G-protein coupled receptor (GPCR) family is used to illustrate ligand-based target class focused library design. Most of the tools discussed are those designed for libraries targeted to a single protein and are simply applied “bruteforce” to a large number of targets within the family. The tools that have proven to be the most useful in our work are those that can extract trends from the computational data such as docking and clustering or data mining large amounts of structure activity or high throughput screening data. Finally, areas where improvements are needed in the computational tools available for target class focusing are highlighted. These areas include tools to extract the relevant patterns from all available information for a family of targets, tools to efficiently apply models for all targets in the family rather than just a small subset, mining tools to extract the relevant information from the computational absorption, distribution, metabolism, excretion and toxicity (ADMET) and targeting data, and tools to allow interactive exploration of the virtual space around a library to facilitate the selection of the library that best suits the needs of the design team.

More than sixty years ago, in his preface to Carl Russell Fish's excellent Guide to the Materials for American History in Roman and Other Archives, the General Editor, J. Franklin Jameson, wrote as follows.In any series of guides to the materials for American history in foreign archives, the Roman archives deserve a prominent position and early treatment. Two reasons justify this statement. In the first place, although the documents in those archives relate primarily to ecclesiastical affairs, yet religious history constantly deserves the attention of the student of civil as well as of ecclesiastical history, and the influence of the Catholic Church and the scope of its operations can never be appropriately defined within confessional limits. In the second place, of all the great national archives of Europe there are none that have been so little exploited for purposes of American history as those of Rome and Italy.Although these words were written decades ago, it still remains true that too little use is made of such archival materials, and not only by American historians. One of the microfilm additions to the collections at Saint Louis University includes precisely this type of material in a collection that runs to about 250,000 manuscript pages from the Archive of the Sacred Congregation de Propaganda Fide (for the propagation of the faith). The congregation was definitively established by Gregory XV (1621-1623) in his constitution Inscrutabiliof June 22, 1622, although there had been some discussion about the formation of such a congregation for almost fifty years. This brief note description will be oriented toward the African materials only, but a general description of the indexes is necessary that the Africanist may be able to use them.

Leakage tests have been run over a wide range of pressure ratios and clearances for several types of seals. The results of tests of labyrinth seals show some important differences compared to previous theory. The discharge coefficient of a single seal has been found to jump from 0.62 to 0.78 when a second seal is added downstream. This effect depends on the clearance, pitch, and the pressure ratio across the seal. This phenomena has not been considered in past theories which assumed fixed seal discharge coefficients independent of the seal position and its pressure ratio in the Labyrinth. The test results are presented in a form which is easier to use than those based on the more complicated previous theory.