Abstract: The use of protection schemes and solid phase synthesis reactions to generate molecules of core structure M, which have a plurality of moieties, each of which can be individually deprotected or subsequently derivatized are provided. In one process, M is a multifunctional low molecular weight compound, such as a saccharide, aminosugar, deoxysugar, nucleoside, nucleotide, coenzyme, amino acid, lipid, steroid, vitamin, hormone, alkaloid, or small molecule drug. In another process, M is an oligomeric compound, such as an oligosaccharide, oligonucleotide, peptide or protein.

Abstract: The invention relates to a method for quantitatively analyzing tumor cells in a body fluid. According to the inventive method, the test sample to be examined is first subjected to a method for accumulating or depleting tumor cells, and a reaction is carried out on the accumulated or depleted tumor cells. During the reaction, the mRNA which codes for the catalytic subunit of the telomerase is specifically amplified, and afterwards, the quantity of amplified nucleic acid is quantitatively analyzed. The invention also relates to test kits suited for the invented method.

Abstract: Processes and kits for immobilizing a high density of nucleic acids on an insoluble surface, which are particularly useful for mass spectrometric detection of nucleic acids, are disclosed. Arrays containing the immobilized nucleic acids and use of the immobilized nucleic acids in a variety of solid phase nucleic acid chemistry applications, including nucleic acid synthesis (chemical and enzymatic), hybridization and/or extension, and sequencing, are provided. Serial and parallel dispensing tools that can deliver defined volumes of fluid to generate multi-element arrays of sample material on a substrate surface are further provided. Tools provided herein can include an assembly of vesicle elements, or pins, wherein each of the pins can include a narrow interior chamber suitable for holding nanoliter volumes of fluid. Methods for dispensing tools that can be employed to generate multi-element arrays of sample material on a substrate surface are also provided.

Abstract: Matrix assisted laser desorption/ionization (MALDI) is performed in a manner that thermalizes large analyte ions in a plume of desorbed material for spectroscopic analysis. The thermalized ions have a low or zero mean velocity and are presented at a well-defined instant in time, reducing artifacts and sharpening the spectral peaks. In one embodiment the light is delivered to a matrix or sample holder having a cover, baffle or compartment. The baffle or compartment impedes or contains a plume of desorbed material and the analyte undergoes collisions to lower its mean velocity and directionality. Thus “thermalized” the analyte ions are passed to a mass analysis instrument.

Abstract: Double stranded DNAs, expression vectors and methods for their use are provided in which the intracellular expression of the double stranded DNAs is used to alter the phenotype of a target cell so that the function of a target nucleic acid that includes a nucleotide sequence encoding a motif of interest can be determined using a combinatorial ribozyme library. The members of the library are catalytic RNAs that disrupt the expression of the transcription product of the target nucleic acid. Disruption of transcription product expression results in an altered cell phenotype which is used to determine the function of the target nucleic acid. The specific phenotype or response may be associated with normal cellular processes, or it may contribute to the generation of pathogenesis involved in disease development. The compositions find use in high-throughput screens to assign gene functions.

Abstract: A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

Abstract: Methods for preparing cell lines that contain artificial chromosomes, methods for preparation of artificial chromosomes, methods for purification of artificial chromosomes, methods for targeted insertion of heterologous DNA into artificial chromosomes, and methods for delivery of the chromosomes to selected cells and tissues are provided. Also provided are cell lines for use in the methods, and cell lines and chromosomes produced by the methods. In particular, satellite artificial chromosomes that, except for inserted heterologous DNA, are substantially composed of heteroaromatic are provided. Methods for use of the artificial chromosomes, including for gene therapy, production of gene products and production of transgenic plants and animals are also provided.

Abstract: Methods for detecting receptivity of mammalian endometrium to embryo implantation comprising obtaining a sample of the endometrium, contacting the endometrium with a monoclonal antibody for &bgr;3 and detecting &bgr;3 in the endometrium. The invention also provides for methods of diagnosing infertility in a mammal and methods of detecting the window of embryo implantation in endometrium. Methods of in vitro fertilization, methods of preventing embryo implantation and a method of monitoring endometrial maturation are also within the scope of the present invention. The present invention is also directed to contraceptives. Diagnostic kits useful in the practice of the methods of the invention are also provided.

Abstract: Fully automated modular analytical systems with integrated instrumentation for analysis of biopolymer samples, such as nucleic acids, proteins, peptides and carbohydrates, are provided. Analytical methods of detection and analysis, such as mass spectrometry, radiolabeling, mass tags, chemical tags and fluorescence chemiluminescence, are integrated with robotic technology and automated chemical reaction systems to provide a high-throughput, accurate Automated Process Line (APL).

Abstract: Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

Abstract: Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

Abstract: Compounds, compositions and methods for modulating the activity of nuclear receptors are provided. In particular, heterocyclic compounds are provided for modulating the activity of farnesoid X receptor (FXR), liver X receptor (LXR) and/or orphan nuclear receptors. In certain embodiments, the compounds are thiazolidinone derivatives.

Abstract: Thienyl-, furyl-, pyrrolyl- and phenylsulfonamides, formulations of pharmaceutically-acceptable derivatives thereof and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides, N-(isoxazolyl)pyrrolylsulfonamides and N-(isoxazolyl)phenylsulfonamides, formulations thereof and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or pharmaceutically acceptable derivatives thereof that inhibit the activity of endothelin are also provided.

Abstract: Thienylsulfonamides and their pharmaceutically acceptable derivatives, pharmaceutical compositions, articles of manufacture, combinations, lyophilized powders and methods for the treatment of endothelin diseases using these formulations and sulfonamides are provided. A process of preparing an alkali metal salt of a hydrophobic sulfonamide is provided. The process includes the step of dissolving a free sulfonamide in an organic solvent in the presence of a saturated alkali metal salt solution and recovering the formed sulfonamide salt from the organic phase.

Abstract: Methods are provided for developing medical diagnostic tests using decision-support systems, such as neural networks. Patient data or information, typically patient history or clinical data, are analyzed by the decision-support systems to identify important or relevant variables and decision-support systems are trained on the patient data. Patient data are augmented by biochemical test data, or results, where available, to refine performance. The resulting decision-support systems are employed to evaluate specific observation values and test results, to guide the development of biochemical or other diagnostic tests, too assess a course of treatment, to identify new diagnostic tests and disease markers, to identify useful therapies, and to provide the decision-support functionality for the test.

Abstract: Compounds and pharmaceutical compositions useful as plasminogen activator inhibitor (PAI) antagonists are provided. In particular, methods of antagonizing PAI with substituted and unsubstituted aryl and heteroaryl ethers and thioethers, benzils, benzyl ethers, benzoate esters, sulfones and benzophenones are provided.

Abstract: Oil-in-water emulsion formulations contain both free fluorouracil and fluorouracil impregnated in porous microparticles. The formulations are suitable for topical administration, and are useful for the treatment of solar keratoses, actinic keratoses, and superficial basal cell carcinomas.

Abstract: Methods and kits that use nucleotide analogs to confer increased accuracy and improved resolution in the analysis and sequencing of oligonucleotide mixtures are provided.

Abstract: An eyecup shield for use during ocular examinations. The eyecup shield is formed from a cylindrical member having a proximal end with an opening, a distal end with an opening, and a wall. The wall is substantially rigid and has one or more access ports which are sized to receive a finger.

Abstract: Using nonvolatile, releasable, mass-labels, the present invention provides for the synthesis and use of mass-labeled compounds to specifically interact with biomolecular targets. Following binding of the mass-labeled compounds to the target molecule, the unique mass-label can be analyzed using mass spectrometry to identify and characterize the target molecule. In one embodiment of the invention, a mass-labeled oligonucleotide probe is used to identify a specific gene sequence. A myriad of mass-labeled compounds may be produced for use in a wide variety of interactions such as oligonucleotide-oligonucleotide hybridization, polynucleotide-polynucleotide interactions, enzyme-substrate or substrate analog/intermediate interactions, polypeptide-nucleic acid interactions, protein-ligand interactions, receptor-ligand interactions, polypeptide-metal interactions, nucleic acid-metal interactions or antigen-antibody interactions.