Abstract: The present invention relates to a pharmaceutical composition for the prevention and treatment for ?-amyloid (A?) accumulation in brain comprising GCP-II (Glutamate carboxypeptidase-II) as an active ingredient, a composition for screening method of the same. GCP-II of the present invention not only degrades A? monomer and oligomer but also degrades soluble A? and insoluble A?, particularly aggregated A?, so that it can prevent the accumulation of A? in brain or reduce the accumulation, making it an excellent candidate for the therapeutic agent for Alzheimer's disease and Down's syndrome.

Abstract: The present invention is directed to methods for readily propagating somatic liver stem cells. The methods comprise enhancing guanine nucleotide (GNP) biosynthesis, thereby expanding guanine nucleotide pools. This in turn conditionally suppresses asymmetric cell kinetics in the explanted cells. The methods of the invention include pharmacological methods and genetic methods. For example, the resulting cultured somatic liver stem cells can be used for a variety of applications including cell replacement therapies, gene therapies, drug discovery applications, and tissue engineering applications, such as the generation of artificial liver.

Abstract: In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. The invention provides means and methods reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.

Abstract: The present invention provides stabilized, high affinity nucleic acid ligands to PSMA. Methods for the identification and preparation of novel, stable, high affinity ligands to PSMA using the SELEX™ method with 2?-O-methyl substituted nucleic acids, and cell surface SELEX™ are described herein. Also included are methods and compositions for the treatment and diagnosis of disease characterized by PSMA expression, using the described nucleic acid ligands.

Abstract: Compositions and methods are provided for treatment of diseases involving unwanted neovascularization (NV). The invention provides treatments that control NV through selective inhibition of pro-angiogenic biochemical pathways, including inhibition of the VEGF pathway gene expression and inhibition localized at pathological NV tissues. Tissue targeted nanoparticle compositions comprising polymer conjugates and nucleic acid molecules that induce RNA interference (RNAi) are provided. The nanoparticle compositions of the invention can be used alone or in combination with other therapeutic agents such as VEGF pathway antagonists. The compositions and methods can be used for the treatment of NV diseases such as cancer, ocular disease, arthritis, and inflammatory diseases.

Abstract: Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rationale design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes.

Abstract: Human individuals at increased risk for vascular pathology are identified by determining whether the individuals' genome comprises a Notch1 allele predetermined to be associated with an increased risk for vascular pathology. Notch1 alleles are identified as being associated with increased risk for vascular pathology by detecting the presence of a same Notch allele in a plurality of persons with increased risk for vascular pathology.

Abstract: A structure and method for forming single-stranded DNA segments/single-wall carbon nanotube complexes and a method of preparing single-stranded DNA segments. The method for forming single-stranded DNA segments/single-wall carbon nanotube complexes including: attaching single-stranded DNA segments to single-wall carbon nanotubes to form single-stranded DNA segment/single-wall carbon nanotube complexes, each of the single-stranded DNA segments having a same length of greater than 2,000 bases.

Abstract: The described method provides, methods, and kits to produce, identify, catalog and classify a comprehensive collection of nucleic acid targets produced from a nucleic acid sample. The method, referred to as Cataloging and Classification of Sequence Tags, involves generating a set of target nucleic acid fragments; coupling the target nucleic acid fragments to a nucleic acid bridge comprising, for example, two or more primer binding sites and two recognition sites for cleavage at a site offset from the recognition site to the fragment's end; and cleaving the fragments to generate chimeric nucleic acids of known length. The nucleic acid bridge is thus disposed between the two nucleic acid fragments in the chimeric nucleic acid. The resulting duplex nucleic acids comprise a set of sequence tags (i.e., by amplification using universal primers), comprising an addressable portion, a target nucleic portion and a portion of the nucleic acid bridge.

Abstract: An gene was identified as a RA disease susceptibility gene on Human Chromosome 8, the gene coding a protein that has an amino acid sequence shown in SEQ. ID NO. 1 and that has such mutation that glycine is inserted as a 269th amino acid in the sequence. Moreover, it was found that mutation of the gene and the protein relate to onset of RA. Achieved is a method of evaluating with high accuracy the onset or onset possibility of RA by using the mutation.

Abstract: This invention provides method and apparatus for performing chemical and biochemical reactions in solution using in situ generated photo-products as reagent or co-reagent. In particular, the present invention provides methods and devices for generating a photogenerated reaction in solution on a substrate comprising generating a light beam using an optical device system comprising a light source and a computer-controlled spatial optical modulator comprising a digital micromirror device and using the spatial optical modulator to direct light to fluidly isolated reaction sites under conditions such that a photogenerated reaction takes place. The method and apparatus of the present invention have applications in parallel synthesis of molecular sequence arrays on solid surfaces.

Abstract: Compounds which are 3-aminoindazole derivatives or pharmaceutically acceptable salts thereof, together with pharmaceutical compositions comprising them are disclosed; these compounds or compositions are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, cell proliferative disorders, Alzheimer's disease, viral infections, auto-immune diseases and neurodegenerative disorders.

Abstract: The present invention relates to solid phase or solution phase combinatorial libraries of autoinducer analogs. The present invention also relates to autoinducer agonists and antagonists. In addition, the present invention relates to methods for identifying autoinducer agonists and antagonists, as well as methods for regulating the activity of an autoinducer receptor, regulating biofilm formation, regulating growth or virulence of an organism in a subject, inhibiting the quorum sensing mechanism of an organism, and treating an infection in a subject caused by an organism possessing a quorum sensing mechanism which use the autoinducer analogs of the present invention.

Abstract: This invention provides method and apparatus for performing chemical and biochemical reactions in solution using in situ generated photo-products as reagent or co-reagent. In some embodiments, the present invention provides methods and devices for generating one or more selected multimers at specific reaction sites on a substrate comprising contacting the substrate with a liquid solution comprising photo-reagent precursors, isolating the reaction sites, selectively irradiating the reaction sites with a digital micromirror device, and contacting the substrate with monomers. The method and apparatus of the present invention have applications in parallel synthesis of molecular sequence arrays on solid surfaces.

Abstract: A glycopeptide of the formula A1-A2-A3-A4-A5-A6-A7, in which each dash represents a covalent bond; wherein A1 comprises a modified or unmodified ?-amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of A2 to A7 comprises a modified or unmodified ?-amino acid residue, whereby (i) A1 is linked to an amino group on A2, (ii) each of A2, A4 and A6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) A7 bears a terminal carboxyl, ester, amide, or N-substituted amide group; and wherein one or more of A1 to A7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues, at least one of the sugar residues bearing one or more substituents of the formula YXR, N+(R1)=CR2R3, N=PR1R2R3, N+R1R2R3 or P+R1R2R3 in which Y is a singl

Abstract: Methods for treating gestational diabetes which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that lower blood glucose levels.

Abstract: The aim of the invention is to investigate the bonding of substances to target molecules. This is achieved by means of a densely packed device wherein various target molecules are bonded in a large number of sample areas. Cross-contamination and evaporation need to be minimized. The active surface of the sample areas have to be maximized. The inventive solution resides in the use of carrier plates, containing densely packed capillary structures and having a very large inner surface despite small outer dimensions. 1000 times more molecules can be bonded than on a flat outer surface of a comparable size. Cross contamination is avoided by the lack of cross links between the capillaries. Evaporation is minimized by a small outer surface. After the inner surface of the capillaries has been silanized, peptides and peptidomimetics are synthesized in a locally targeted manner.

Abstract: The present invention provides catalytic RNA molecules having cis or trans aminoacylation activity. The catalytic RNA molecules having cis aminoacylation activity comprise a catalytic domain and an aminoacylation domain. The catalytic RNA molecules having trans aminoacylation activity only have the catalytic domain. A method is provided for constructing and screening of these molecules. These molecules are suitable for aminoacylating tRNA-like molecules with specific amino acids.

Abstract: Disclosed is a method of transdifferentiating an epidermal basal cell into a cell having one or more morphological, physiological and/or immunological features of a neural progenitor, neuronal, or glial cell by culturing a proliferating epidermal basal cell population derived from the skin of a mammalian subject; exposing the epidermal basal cell(s) to an antagonist of bone morphogenetic protein (BMP), such as fetuin, noggin, chordin, gremlin, or follistatin; and growing the cell(s) in the presence of at least one antisense oligonucleotide comprising a segment of a human MSX1 gene and/or a segment of a human HES1 gene, or homologous non-human counterpart of either of these. Also disclosed is a transdifferentiated cell of epidermal origin and cell cultures derived therefrom.

Abstract: A novel nucleic acid construct for delivery of antisense targeting sequences is provided. The construct includes intact stem loop structures and an antisense nucleic acid. Optionally, a ribozyme nucleic acid is included in the construct. The construct is useful for inhibition of selected genes in a cell. This allele-specific targeting is also useful in combination with replacement gene therapy.