Abstract: A method and apparatus for the physico-chemical encoding of a collection of beaded resin (“beads”) to determine the chemical identity of bead-anchored compounds by in-situ interrogation of individual beads. The present invention provides method and apparatus to implement color-coding strategies in applications and including the ultrahigh-throughput screening of bead-based combinatorial compounds libraries as well as multiplexed diagnostic and environmental testing and other biochemical assays.

Abstract: Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19–23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3? ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.

Abstract: The use in a ribosome display system for selection of a specific binding pair member (e.g. antibody molecule) able to bind a complementary specific binding pair member (e.g. antigen) of encapsidating specific binding member/ribosome complexes in a viral coat, optionally in combination with incorporation of an Midvariant RNA template and optionally one or more other improvements selected from: a glycine-serine tether, protein disulphide isomerase, protein disulphide isomerase in combination with oxidized and reduced glutathione at a ratio of between 1:1 and 10:1, addition of oxidized and reduced glutathione at a ratio of between 1:1 and 10:1 after 30 minutes of in vitro translation; blocking with heparin during selection.

Abstract: A diazaphosphacycle may be synthesized by reacting a phosphine with a diimine and optionally one or more equivalents of an acid halide, a sulfonyl halide, a phosphoryl halide, or an acid anhydride in the substantial absence of O2 to form the diazaphosphacycle. The phosphine has the formula R1—PH2 where R1 is a substituted or unsubstituted aryl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cycloalkyl group, or a substituted or unsubstituted ferrocenyl group.

Abstract: A NMR method to verify the presence of organic molecular compounds consisting of repetitive occurring individual structures is presented. The method comprises the steps of assigning structure codes to the selected compounds, in accordance with the respective starting compounds used, measuring multi-dimensional NMR spectra from at least some of the compounds, uniquely assigning signal groups of NMR spectra to the individual structures, checking the NMR spectra of the compounds for the presence of all assigned signal groups, and characterizing a particular compound as being TRUE if the check of its particular combination of structures yields the result that the signal groups of structures contained in its total code had been observed. The method permits rapid and accurate verification of the presence of compounds having repetitive structures such as those produced in combinatorial chemistry.

Abstract: Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19–23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3? ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.

Abstract: A method and system for high-throughput screening of multiphase reactions are provided. In an exemplary embodiment the method includes the steps of sequentially loading a plurality of discrete combinations of reactants into a longitudinal reaction zone; reacting each of the combinations as it passes through the reaction zone to provide a continuously or an incrementally varying reaction product; and sequentially discharging the reaction product of each of combination from the reaction zone as reaction of each combination is completed.

Abstract: The present invention relates to the tumor-specific expression of heterologous polynucleotides, particularly genes encoding cytotoxic products, under the control of transcriptional regulatory sequences. Particularly preferred transcriptional regulatory sequences comprise H19, IGF-1 and IGF-2 P4 transcriptional regulatory sequences, and variants thereof. The present invention also provides expression constructs and methods of administering such expression constructs. The compositions and methods of the invention are useful for the treatment of proliferative disorders, particularly cancer.

Abstract: Antisense oligonucleotide sequences which enable the measurement of the distribution and structure of antisense oligonucleotide drugs in the body, with lapse of time, and a method of detecting these sequences are provided. The antisense chains have a natural or non-natural nucleotide or peptide nucleic acid as a structural unit in which carbon atoms and nitrogen atoms are substituted by 13C and 15N, respectively, and the antisense chains can be detected by nuclear magnetic resonance spectroscopy (NMR) such as 15N—1H or 13C—1H hetero nuclear multiple quantum coherence spectroscopy.

Abstract: The present invention relates to nucleic acid molecules such as ribozymes, DNAzymes, and antisense which modulate the synthesis, expression and/or stability of an mRNA encoding one or more receptors of vascular endothelial growth factor, such as flt-1 and KDR. Nucleic acid molecules and methods for the inhibition of angiogenesis and treatment of cancer and ocular diseases are provided, optionally in conjunction with other therapeutic agents.

Abstract: The present invention relates to methods for the diagnosis, evaluation and treatment of metastatic diseases using metastatic sequences, such as caveolin, to target metastatic cells. According to the methods of the present invention, certain cancers, including metastatic prostate cancer, may be treated by therapies which suppress expression of the caveolin gene. The present invention relates to biological technologies designed to block the activity of caveolin or the function of caveolae, including vector delivery of antisense caveolin sequences, the use of anti-caveolin antibodies, the use of promoters, and other approaches targeting the expression of caveolin.

Abstract: The object of this invention is to provide a method by which to form molecule recognizing films on sensor electrodes efficiently, within a short period, uniformly and in a high quality state. Another object of this invention is to provide a method by which to accurately introduce a vast number of biological samples for evaluation to the plural minute sensor electrode dots within a short period and efficiently. In order to form organic thin films on electrodes, a solution of a material for the organic thin film is accurately printed via an ink-jet onto the surface of microelectrodes as required, thereby producing a high density array of microelectrodes. Further, a solution of a sample substance or a liquid substance to be sensed is ejected into air via an ink-jet nozzle to fall to the surface of organic thin membranes on the microelectrodes so that the sample is evaluated.

Abstract: The present invention relates to a human CTGF-2 polypeptide and DNA (RNA) encoding such polypeptide. Also provided is a procedure for producing such polypeptide by recombinant techniques and antibodies and antagonist/inhibitors against such polypeptide. Also provided are methods of using the polypeptide therapeutically for stimulating angiogenesis enhancing the repair of connective and support tissue, promoting the attachment, fixation and stabilization of tissue implants and enhancing wound healing. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed.

Abstract: Oligonucleotides capable of modifying or inhibiting in vivo or in vitro expression of a target gene wherein the oligonucleotide has an antisense sequence, at least one secondary structure, and optionally a supplementary nucleotide sequence located at one and/or both ends of the antisense sequence and wherein the secondary structure disintegrates upon attachment of the oligonucleotide to a target nucleic acid; a pharmaceutical composition containing such an oligonucleotide as an active ingredient; and a method of treatment using such an oligonucleotide.

Abstract: Two previously undescribed human cdc25 genes, designated cdc25 A and cdc25 B, which have been shown to have an endogenous tyrosine phosphatase activity that can be specifically activated by B-type cyclin, in the complete absence of cdc2 are described. As a result of this work, new approaches to regulating the cell cycle in eukaryotic cells and, particularly, to regulating the activity of tyrosine specific phosphatases which play a key role in the cell cycle are available. Applicant's invention relates to methods of regulating the cell cycle and, specifically, to regulating activation of cdc2-kinase, through alteration of the activity and/or levels of tyrosine phosphatases or through alteration of the interaction of components of MPF. More specifically, the invention relates to inhibiting transcription or translation of mammalian CDC25A genes using oligonucleotides.

Abstract: A library of candidate target binding fragments (CTBF's) each CTBF being a small organic molecule and having a linkable functional group (LFG) or blocked form thereof (BLFG), wherein the LFG or BLFG contains a linking group (LG), the LG being a disulfide group.

Abstract: The present invention provides a library of viral vectors, wherein each member comprises a first heterologous DNA encoding a first gene product and a second heterologous DNA encoding a second gene product. The first heterologous DNA is common to each member of the library, while the second heterologous DNA varies between members of the library. The present invention additionally provides a method of constructing a library of viral vectors. The method comprises carrying out homologous recombination between a first DNA molecule and a second DNA molecule to form a pool of intermediate viral vector genomes. One or more linear third DNA molecules are ligated into the pool of intermediate viral genomes to produce a library of viral vector genomes. Alternatively, homologous recombination between linear DNA molecules and recipient DNA molecules produces a library of viral vector genomes. The library of viral vector genomes is converted into a library of viral vectors.

Abstract: The present invention provides novel methods for ligand discovery. The inventive methods rely on a process termed “tethering” where potential ligands are covalently bonded or “tethered” to a target and subsequently identified.

Abstract: A high throughput, on-line, pulsed ultrafiltration-mass spectrometric method has been developed to determine whether a compound has predetermined characteristics that would make it suitable for a specific purpose, e.g. drug development. The method is useful to generate, identify, and quantify metabolites of compounds formed by drug metabolizing enzymes such as cytochrome P450, UDP-glucuronyltransferases, and glutathione transferases. The method is useful for rapid screening of drugs or other compounds to determine the extent of their metabolism and to characterize their primary metabolites. If reactive and potentially toxic metabolites are formed during, e.g. cytochrome P450 oxidation, the metabolites can be reacted with glutathione and then detected on-line using mass spectrometry in a rapid assay to assess the potential for toxicity. In addition, the method is useful for the determination of bioavailability, absorption and cell permeability of compounds.

Abstract: Polymeric brush substrates and methods for their preparation are provided. Methods are also provided for preparing macromolecular arrays on such polymeric brush substrates. Using polymeric brush substrates allows control over functional site density as well as wettability and porosity of the substrate. These polymeric brushes are useful in solid-phase synthesis of arrays of peptides, polynucleotides or small organic molecules.