Abstract: Methods for rapidly generating large rationally designed libraries of structurally-diverse small molecular weight compounds using a multicombinatorial approach.

Abstract: The present invention relates to a novel class of compounds which are IMPDH inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Abstract: This disclosure relates to novel antibodies specific to the recently discovered receptor to human interleukin 12 (IL-12R). The antibodies to IL-12R, most preferably, the monoclonal antibodies to that protein, are useful in determining the status of the human immune system and as diagnostic reagents or potential therapeutic reagents for conditions involving imbalances in IL-12 levels or cell types sensitive to IL-12 activation.Further aspects of the disclosure relate to methods of producing and purifying such novel antibodies and hybridoma cell lines capable of their production. Another aspect of the disclosure relates to an immunoprecipitation assay for the detection of solubilized IL-12R which employs, in a preferred embodiment, monoclonal antibodies to the receptor of the present invention covalently bound to Protein G-Sepharose resin.

Abstract: Disclosed is an improvement to the method of determining the concentration of a hemoglobin adduct in a blood sample by the steps of assaying the blood sample for the total amount of hemoglobin, assaying the blood sample for the hemoglobin adduct, and dividing the hemoglobin adduct concentration by the total hemoglobin concentration. The improvement involves normalizing the measurement of the hemoglobin adduct to the total amount of hemoglobin in the blood sample.

Abstract: The present invention provides for novel reagents whose fluorescence increases in the presence of particular proteases. The reagents comprise a characteristically folded peptide backbone each end of which is conjugated to a fluorophore. When the folded peptide is cleaved, as by digestion with a protease, the fluorophores provide a high intensity fluorescent signal at a visible wavelength. Because of their high fluorescence signal in the visible wavelengths, these protease indicators are particularly well suited for detection of protease activity in biological samples, in particular in frozen tissue sections. Thus this invention also provides for methods of detecting protease activity in situ in frozen sections.

Abstract: The present invention relates, inter alia, to methodologies for the synthesis, screening and characterization of organometallic compounds and catalysts (e.g., homogeneous catalysts). The methods of the present invention provide for the combinatorial synthesis, screening and characterization of libraries of supported and unsupported organometallic compounds and catalysts (e.g., homogeneous catalysts). The methods of the present invention can be applied to the preparation and screening of large numbers of organometallic compounds which can be used not only as catalysts (e.g., homogeneous catalysts), but also as additives and therapeutic agents.

Abstract: This invention includes methods for analyzing data generated by various solid-state NMR experiments, including rotational echo double resonance (REDOR), transferred echo double resonance (TEDOR), dipolar recoupling at the magic angle (DRAMA), dipolar recoupling with a windowless sequence (DRAWS), and melding of spin-locking and DRAMA (MELODRAMA). The methods are based alternately on a new analytical transform or the maximum entropy method and their multi-dimensional extensions. They permit simultaneous, multiple distance measurements of high accuracy and precision, even from nuclei with identical chemical shifts. By providing high quality easily obtained distance measurement from disordered solid state materials, this invention also improves drug discovery and design through fast determination of structures of pharmaceutical lead compounds, drug molecules, or their targets.

Abstract: A chemical synthesis apparatus (20) for building chemical compounds includes a head assembly (21) having an array of nozzles (22) with each nozzle or plurality of nozzles coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) in a longitudinal X-direction for deposition of liquid reagent (24) into selected reaction wells (26). A plurality of independently controllable sliders (100) move nozzle columns (41) in a lateral Y-direction for deposition of liquid reagent (24) into selected reaction wells (26). A first sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A plurality of second sliding seals (120) is positioned between head assembly (21) and sliders (100).

Abstract: An insulated structure is formed by injection of a foamed thermal-insulating material created by foaming into a space between a plastic board and metal plate with a disposition of copper pipes. A non-halogenated organophosphorus compound having a molecular weight over 150 as an additive with an OH group as a functional group is mixed with the raw materials of the foamed thermal-insulating material including polyol, a foam stabilizer, a catalyst, a foaming agent having at least one component of hydrocarbon, and an organic polyisocyanates. By adding a non-halogenated organophosphorus compound, which has a molecular weight over 150 as an additive with an OH group as a functional group, the burning rate of the foamed thermal-insulating material becomes the same as that of the foamed thermal-insulating material which uses CFC11 as a foaming agent.

Abstract: The present invention provides for systems and methods that utilize automated and integratable workstations for identifying chemicals having useful activity. The present invention is also directed to chemical entities and information (e.g., chemical or biological activities of chemicals) generated or discovered by operation of workstations of the present invention. The present invention includes automated workstations that are programmably controlled to minimize processing times at each workstation and that can be integrated to minimize the processing time of the liquid samples from the start to finish of the process.

Abstract: Combinatorial chemical libraries of the Formula [S]-C(O)-L'-Z containing dihyroxy amides and hydroxyphosphonate amides are disclosed, in which [S] represents a solid support and -L'-Z is a linker/ligand residue. In these libraries, Z is ##STR1## and Y is --P(O)(OR.sup.6)(OR.sup.7), --CH(OH)--COR.sup.8, --CH.sub.2 CH.dbd.CH.sub.2 --CH.sub.2 CH(OH)CH.sub.2 OH, --CH.sub.2 CHO, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 OC(O)NHR.sup.26, --CH.sub.2 CH.sub.2 NR.sup.27 R.sup.28, or ##STR2## The combinatorial libraries are optionally encoded with tags. The use of these libraries in assays to discover biologically active compounds is also disclosed.

Abstract: Combinatorial chemical libraries of Formula I ##STR1## and methods for their preparation are disclosed. The libraries allow one to screen large numbers of compounds for a desired biological activity with relative ease. The libraries may be tagged or untagged. In preferred libraries, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. The use of the libraries to discover biologically active compounds is also disclosed.

Abstract: The invention provides a non-enzymatic method for the release of cells which have been positively selected from a heterogeneous cell suspension by antibody-mediated binding to beads or other solid support. The method entails forming within the cell suspension a complex comprising the solid support linked to a primary antibody, which in turn is specifically bound to a cell surface antigen on the target cells. The complex is separated from the cell suspension, and then contacted with a specific peptide which binds to the primary antibody, displacing the antibody from the cell surface antigen, thereby releasing the target cell from the complex. The invention also provides methods for positive/negative cell selection wherein target cells having a first antigen are selected from a heterogeneous cell suspension containing undesired cells having a second antigen.

Abstract: The invention provides methods for screening libraries of complexes for compounds having a desired property, especially, the capacity to agonize, bind to, or antagonize a cellular receptor. The complexes in such libraries comprise a compound under test, a tag recording at least one step in synthesis of the compound, and a tether susceptible to modification by a reporter molecule. Modification of the tether is used to signify that a complex contains a compound having a desired property. The tag can be decoded to reveal at least one step in the synthesis of such a compound.

Abstract: This invention provides a method for preparing molecules that bind to a preselected receptor, whereby the receptor itself acts as an agent for either joining two ligand fragments to form a composite, tight binding ligand, or selects a composite ligand from a mixture in solution where ligand fragments are being joined and unjoined reversibly under equilibrium conditions.

Abstract: A fluid injector for use with a burner having at least a pair of concentric tubes which conduct at least two different fluids via inner and outer passageways to a discharge tip. The passageways having different linear fluid velocity rates which causes the issuing discharge flow of the fluids to constrict causing mixing and combining of the fluids for introducing to a combustion chamber. Protection of the injector from thermal melting or burning is provided by location of the injector within the coils of a feed preheater constituting a heat exchanger.

Abstract: An apparatus is provided for detecting the pressure of a fluid. The device includes a device for detecting the pressure of a fluid comprising (a) a housing; (b) a first conduit disposed within the housing, having an open inlet end, and an outlet end; (c) a second conduit disposed within the housing having an inlet end and an open outlet end; and (d) a pressure detector disposed within the housing in abutment with the outlet end of the first conduit and the inlet end of the second conduit, such that the pressure detector is in direct operative contact with a fluid flowing within the first and second conduits. Typically, the pressure detector is a pressure transducer. Preferably, the pressure transducer is located within the body, such that the first conduit is disposed at an angle with respect to the pressure sensitive surface of the transducer, the angle being between about 50.degree. and about 75.degree., most preferably between about 65.degree. and about 70.degree..

Abstract: The present invention provides a method of control in thickness of the biaxially oriented film of a plastic material to be extruded via an extrusion port gap adjustable by adjustment of a plurality of die bolts provided on an automatic T-die. A position corresponding to the die bolt is set on the film biaxially oriented so that a thickness of the film at the above position is measured to find a deviation of the measured thickness from a reference thickness predetermined to thereby carry out a feed-back control of the adjustment of the die bolt in accordance with the deviation. It is important for the present invention that the feed-back control in the adjustment of the die bolt is carried out with reference to partial side-drawing rates different in a width direction of a sheet to be drawn prior to formation of the film, where the partial sidedrawing rates are determined for parts aligned in the width direction of the film.

Abstract: Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.

Abstract: The present invention relates to novel tricyclic tetrahydroquinoline compounds of the following formula, libraries containing such compounds, and to the generation of such combinatorial libraries composed of such compounds: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, n, and Y have the meanings provided.