Abstract: Methods for identifying genetic sequences useful as genomic equivalent markers for organisms are described. The method involves determining the ratio of the absolute number of copies of wild type and mutant amplicons in a number of samples from organisms heterozygous for the mutation. After establishing the number of copies of a particular genetic sequence per genome, the sequence may be used as a measure of the number of genomes per sample, in order to normalize the analysis of another target sequence to abundance per cell. By way of example, the CCR5 gene was shown to be present at 2 copies per genome, and used to measure the number of copies per cell of HIV-1 provirions, human herpesvirus-8, and &agr; deletion circles, a measure of recent thymic emigrants for assessing immune reconstitution.

Abstract: A method of increasing the sensitivity and efficiency of MALDI-MS analysis of an oligosaccharide which comprises derivatization, prior to analysis by MALDI-MS, of said oligosaccharide by efficient ligation to a basic aminooxyacetylpeptide by oxime formation reaction to result in the formation of a glycoconjugate.

Abstract: A detailed three dimensional structure for a bacterial core RNA polymerase is provided. Crystals of the bacterial core RNA polymerase are also included in the invention. The present invention further provides procedures for identifying agents that can inhibit bacterial proliferation through the use of rational drug design predicated on the crystals and crystallographic data disclosed.

Abstract: Methods and compositions for the prevention and/or treatment of cardiovascular diseases, the methods comprising administering to individuals in need thereof, an effective amount of a non-steroidal anti-inflammatory drug alone or in combination with other conventional therapies to induce apoptosis, reduce proliferation, induce quiescence, inhibit cell migration, or influence cell differentiation of the cells in the vascular wall and or/induce hypolipidemia.

Abstract: The present invention provides a vertebrate translation initiation factor (eIF-4AIII), that plays a role in the differentiation of an embryonic cell to an epideimal cell. This translation initiation factor interacts with BMP-4 in a positive regulatory loop. The nucleic acid and amino acid sequences are also disclosed. Also disclosed are methods of using the translation initiation factor, nucleic acids encoding the same, and corresponding antibodies and the like.

Abstract: Methods are described for the preparation of quantities of preselected polynucleotide sequences in purified form. The method is independent of length or sequence, and can be used to prepare multi-milligram quantities of, for example, single length, isotope-enriched duplex DNA following a single-step chromatographic purification of the desired product. The method of the present invention allows for preparative scale synthesis of DNA yielding a single product length. The application of the method to NMR spectroscopy of DNA provides the opportunity to identify biologically relevant interactions between polynucleotide sequences and other macromolecules, and assist in the identification and development of agents having therapeutic utility as a consequence of the promotion or antagonism of these interactions.

Abstract: The present invention describes a novel polypeptide, and methods of its use in effective thrombolytic therapy in the treatment of coronary and pulmonary thrombosis. Its use is also disclosed in vaccines to abrogate a streptococcal infection. Pharmaceutical compositions containing the novel polypeptide are included. One particular form of the novel polypeptide is streptococcal surface enolase (SEN), a specific binding protein for human plasmin and/or human plasminogen on group A streptococci that displays classical &agr;-enolase activity, i.e., it can catalyze the dehydration of D-glycerate-2-phosphate to phosphoenolpyruvate. In addition, SEN impedes the inhibition of the fibrinolytic activity of plasmin by &agr;2-antiplasmin and can bind plasminogen without preventing streptokinase from cleaving this plasmin precursor.

Abstract: Novel imidazolium compounds of the formula wherein A represents the atomic group necessary to form a heteroaromatic ring, which may be optionally substituted by one or more R substituents selected from the group consisting of aryl, heteroaryl, lower alkyl, hydroxy, halide, or carboxy substitutents; B is an optional substituent which represents the atomic group necessary to form a heteroaromatic ring or a double or triple carbon-nitrogen bond, which may optionally be substituted by one or more R′ substituents selected from the group consisting of aryl, heteroaryl, lower alkyl, hydroxy, halide, or carboxy substitutents; C is an optional substituent which represents the atomic group necessary to form an aromatic or heteroaromatic ring, which may optionally be substituted by one or more R″″ substituents selected from the group consisting of aryl, heteroaryl, lower alkyl, hydroxy, halide, or carboxy substituents; R″ and R′″ are each independently a lower alk

Abstract: The present invention relates to a promoter functional in plant cells and plasmid that can regulate efficient expression of a gene of interest in plant cells. The promoter comprises a G-Box element, which enhances expression of an operably linked gene of interest in plants or plant cells. A further object of the invention is the plasmid pGbox10 or pGbox11, as well as plants or plant cells transformed with said plasmid.

Abstract: The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which treat nervous system disease, and a method of treating such disease.

Abstract: The present invention provides methods for determining the relative orientation of the individual components of a macromolecule in solution with respect to the global molecular coordinate frame of the macromolecule. The present invention further provides methods for applying this structural information, including for rational drug design.

Abstract: The invention relates to the use of adeno-associated virus vectors for the transfer of genes to the heart and vasculature. The vector preferably contains a gene encoding a protein which improves heart and vascular function during heart failure. In a specific embodiment, the vector is introduced into the heart and vasculature via a catheter, with the aid of fluoroscopy. The method and vectors for use therein provide for safe and stable gene expression of the transferred genes.

Abstract: The present invention provides a crystal of the core portion of the STAT protein in dimeric form with an 18-mer duplex DNA that contains a binding site for the STAT-dimer. The crystal is of sufficient quality to perform X-ray crystallographic studies. Methods of preparing the crystals are include in the invention. The present invention further discloses the three-dimensional structure of the crystal. The present invention also provides methods of using the structural information in drug discovery and drug development.

Abstract: A method of efficiently sequencing multiple exons from complex genomic DNAs is disclosed. The methodology includes the use of bacterial and bacteriophage-derived artificial chromosomes (BBPACs) in novel gene trapping protocols. Targeted gene trapping by homologous recombination, and random gene trapping with the use of a transposon system are exemplified. Included in the invention are methods of preparing a gene map from BBPAC contigs, the resulting gene maps, methods of constructing a cDNA library from BBPAC contigs, and the resulting cDNA libraries.

Abstract: The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit, or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections.

Abstract: The invention discloses a fluorescent bead that can be used for determining the temperature and/or metabolic state of a single cell contained in a cell/tissue sample. The fluorescent bead contains at least one temperature-sensitive fluorophore. The invention also includes methods of monitoring cellular metabolism and methods of diagnosing abnormal metabolism of a cell.

Abstract: A method of efficiently sequencing multiple exons from complex genomic DNAs is disclosed. The methodology includes the use of bacterial and bacteriophage-derived artificial chromosomes (BBPACs) in novel gene trapping protocols. Targeted gene trapping by homologous recombination, and random gene trapping with the use of a transposon system are exemplified. Included in the invention are methods of preparing a gene map from BBPAC contigs, the resulting gene maps, methods of constructing a cDNA library from BBPAC contigs, and the resulting cDNA libraries.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of body weight, and to diagnostic and therapeutic uses of such modulators. In its broadest aspect, the present invention relates to nucleotide sequences corresponding to the murine and human OB gene, and two isoforms thereof, and proteins expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight and that have been postulated to play a critical role in the regulation of body weight and adiposity. The present invention further provides nucleic acid molecules for use as molecular probes or as primers for polymerase chain reaction (PCR) amplification. In further aspects, the present invention provides cloning vectors and mammalian expression vectors comprising the nucleic acid molecules of the invention.

Abstract: A detailed three-dimensional structure for the complex formed between Ras and the Son of sevenless (Sos) protein is provided. Crystals of this complex are also included in the invention. The present invention further provides procedures for identifying agents that can inhibit tumor proliferation through the use of rational drug design predicated on the crystals and crystallographic data disclosed.

Abstract: The present invention relates to methods for inhibiting protein aging. Accordingly, methods are disclosed for treating an animal to inhibit the formation of advanced glycosylation end products of target proteins with the animal by adminstering a pharmaceutical composition comprising an agent capable of reacting with the carbonyl moiety of the early glycosylation product, whereby the subsequent cross-linking of the early glycosylation product is inhibited. Agents of the present invention comprise aminoguanidine, its pharmaceutically acceptable salts, and mixtures thereof.