Abstract: A microbial strain which converts anthracycline metabolites into non-natural anthracycline antibiotics is described. A process for converting anthracycline metabolites into anthracycline antibiotics using a microbial strain is also described.

Abstract: The present invention relates to a process for preparing an extract from ivy leaves which includes the active ingredient hederacoside C and ?-hederin, and to extracts prepared by this process. According to this there is initially provision of a first, ?-hederin-rich extract and subsequently provision of a second, hederacoside C-rich extract. In a last step, the two extracts are blended to give an extract which has an adjusted hederacoside C content and an adjusted ?-hederin content.

Abstract: The present invention relates to a biotransformation process, effected by means of selected microbial strains, for the preparation of 3-O-glycosyl derivatives of colchicinoid compounds.

Abstract: The present invention provides novel systems for sequencing nucleic acid molecules using dNTPs that are 3? end labeled with cleavable tags that block further extension and uniquely identify the bases to which they are attached. Removal of the tags liberates the 3? ends of the extension products for further extension. In related embodiments, oligonucleotides containing sequence-related cleavable tags are employed in a ligation reaction to determine the sequence of a particular DNA sample.

Abstract: Disclosed is a transformant prepared by introducing a ketoreductase gene involved in the biosynthesis of L-epivancosamine into an actinobacterium originally capable of producing daunorubicin. Also disclosed is a process of efficiently producing a non-natural daunorubicin derivative using the transformant. The transformant is capable of efficiently producing a non-natural daunorubicin derivative such as epidaunorubicin.

Abstract: The invention relates to ginsenoside glycosidases which hydrolyzes ginsenosides having higher contents in ginsengs so as to prepare rare ginsenosides with high physioloigical activity. Said ginsenoside glycosidases are derived from microorganism cultures, ginseng plants, almonds, wheat brans, malts and animal livers etc., and are categoried to four types depending on their capability of hydrolyzing the sugar moieties of ginsenosides, namely, ginsenoside glycosidase I, ginsenoside glycosidase II, ginsenoside glycosidase III and ginsenoside-?-rhamnosidase. The invention also relates to the uses of the ginsenoside glycosidases in preparing rare ginsenosides.

Abstract: Sweeteners on the basis of a simultaneously transglucosylated sweet glycoside mixture of Stevia rebaudiana Bertoni are prepared. The transglucosylation was developed in the presence of starch under the action of cyclodextrin glucanotransferase. The remaining maltodextrins are transformed to the fructose-terminated oligosaccharides by the addition of sucrose. The sweeteners are purified to not less than 98% content of sweet glycosides and derivatives. The preparations are almost non-caloric, non-cariogenic, non-bitter, non-lingering sweeteners, which may be advantageously applied in foods, beverages, cosmetics and milk products.

Abstract: The invention refers to a microbial strain, which produces anthracycline metabolites at a titre of at least 0.5 g/l fermentation broth.

Abstract: The present invention provides compounds characterized by the formula (I), where each of the substituent radicals is described in the specification. The invention also describes the use of said compounds in the treatment of various diseases, including: cancer or tumoral processes in general, Paget's disease, hypercalcaemia, hypercalciuria and neurological diseases (inter alia, Parkinson's, Alzheimer's, Huntington's).

Abstract: The invention relates to a method for cleaving cervimycin esters. An object of the invention to convert in a simple manner the cervimycin esters which are less active but formed in larger quantity into the highly active cervimycin K that occurs as a minor component in the preparation by fermentation, is achieved by preparing unesterified cervimycins from cervimycin esters with di- or monomethylated malonic acids, by ester cleavage effected by at least one esterolytic enzyme at temperatures of 20° C. to 75° C. and a pH of pH 5.0 to 10.0, preferably pH 6.0 to 9.0.

Abstract: A titanylphthalocyanine crystal having an X-ray diffraction spectrum having plural diffraction peaks and a primary particle diameter not greater than 0.2 ?m, wherein a maximum diffraction peak is observed at a Bragg (2?) angle of 27.2±0.2°; main peaks are observed at 9.4°, 9.6° and 24.0°; and a minimum diffraction peak is observed at 7.3°; and preferably no diffraction peak is observed at an angle greater than 7.3° and less than 9.4° when a specific X-ray of CuK? having a wavelength of 1.542 ? irradiates the titanylphthalocyanine crystal.

Abstract: A display device and a display panel driving method, in which a matrix panel includes pixel portions each have a series circuit of a bistable element and a light emitting element, every time one scan line is specified in order in accordance with an input image signal, a driving line corresponding to at least one pixel portion to be driven to emit light on the one scan line is specified in accordance with the input image signal, a first predetermined voltage lower than a turn-off threshold voltage is applied between the one scan line and the specified driving line, and thereafter a second predetermined voltage higher than a turn-on threshold voltage is applied therebetween.

Abstract: The present invention provides novel systems for sequencing nucleic acid molecules using dNTPs that are 3′ end labeled with cleavable tags that block further extension and uniquely identify the bases to which they are attached. Removal of the tags liberates the 3′ ends of the extension products for further extension. In related embodiments, oligonucleotides containing sequence-related cleavable tags are employed in a ligation reaction to determine the sequence of a particular DNA sample.

Abstract: The present invention relates to a process for the production of monoglycosidated flavonoids by enzymatic hydrolysis of rutinosides, in which the enzymatic hydrolysis is carried out using an enzyme immobilized on a support. This process can avoid high enzyme costs whilst at the same time a high degree of automation, combined with high space-time yields is achieved.

Abstract: This invention provides nucleic acid sequences and characterization of the gene cluster responsible for the biosynthesis of the enediyne C-1027 (produced by Streptomyces globisporus). Methods are provided for the biosynthesis of enediynes, enediyne analogs and other biological molecules. This invention also provides enediyne and enediyne analogs biosynthesized by manipulation of the C-1027 gene pathway.

Abstract: The present invention provides arrays having associated modified oligonucleotides that selectively bind to DNA or RNA, methods of making such arrays, assays for using such arrays, and the like. In one embodiment, the arrays of the invention exhibit an increased binding affinity with complementary nucleic acids, and in particular with complementary RNA. In another embodiment, the associated nucleic acids of the array of the invention exhibit substantial acid resistance, allowing the arrays to be treated with low pH solutions. In another embodiment, the modified associated nucleic acids of the array of the invention exhibit substantial resistance to nuclease degradation.

Abstract: Cell-free systems which effect the production of polyketides employing modular polyketide synthases are described. Libraries of new and/or known polyketides may also be produced in cell-free systems employing aromatic PKS, modular PKS or both.

Abstract: This invention relates to the isolation of a novel putative efflux gene from Pseudomonas mendocina. The putative efflux gene is useful for probing an organism's efflux system to gain an understanding of the mechanisms of solvent tolerance. The invention further provides a Pseudomonas mendocina strain deficient in this gene. This strain is unable to grow in the presence of chloramphenicol and, compared to the wildtype strain, grows slowly in the presence of high concentrations of PHBA.

Abstract: The present invention relates to novel hybrid anthracyclines generated by cloning of fused genes in a mutated Streptomyces galilaeus strain DSM 11638. Said strain was obtained by mutagenization of the S. galilaeus wild type (ATCC 31615). The aglycone moieties of the compounds obtained are modified alkavinones, caused by the gene products introduces into the mutant, and the sugar moieties are those derived from the host strain, i.e. rhodosamine-2-deoxyfucose-2-deoxyfucose or 2-deoxyfucose-2-deoxyfucose-2-deoxyfucose, or the disaccharide or monosaccharide forms of these.

Abstract: The present invention is directed to a process for improving daunorubicin and doxorubicin production by means of a recombinant microorganism in which a gene of daunorubicin metabolism is mutated. The mutated gene is preferably dnrU and/or dnrX.

Abstract: An anthracycline glycoside of formula I wherein R is one of the two following residues: or a pharmaceutically acceptable salt thereof.

Abstract: Isozyme-specific agonists or activators of .epsilon.PKC are disclosed. The agonists include peptides corresponding to the region of .epsilon.PKC between about amino acids 85 and 92. Also disclosed are therapeutic methods employing such .epsilon.PKC-specific agonists to induce preconditioning and thereby reduce injury due to subsequent ischemia, as well as methods for screening test compounds for .epsilon.PKC-selective agonist properties.

Abstract: The present invention encompasses polypeptides that comprise a chemokine receptor binding sequence and are useful in determining the affinity of a compound for a chemokine receptor. Substitution of one of the amino acids of the C-terminal region of the polypeptide with a cysteine enables the polypeptide to be detectably labelled without loss of receptor binding activity and without the problems inherent in radioiodine labelling. Methods for use of the polypeptides in competitive binding assays are also disclosed.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders.

Abstract: A (1.fwdarw.3)-.beta.-D-glucan binding protein obtainable by affinity chromatography or gel filtration of an extract of horseshoe crab amoebocytes and having a molecular weight of about 580 kDa, as determined by gel filtration under non-reducing conditions, and about 170 kDa, as determined by SDS-PAGE under reducing conditions, is provided.An antibody which selectively recognizes the protein is also provided. Methods for detecting or removing (1.fwdarw.3)-.beta.-D-glucan in or from a sample using the protein and antibody are disclosed.

Abstract: The invention relates in part to methods and compositions for identifying the presence, measuring the amount, stabilizing, and facilitating recovery of troponin complexes or individual troponin isoforms in a sample.

Abstract: DNA sequences encoding a novel human intercellular adhesion molecule polypeptide (designated "ICAM-R") and variants thereof are disclosed along with methods and materials for production of the same by recombinant procedures. Binding molecules specific for ICAM-R and variants thereof are also disclosed as useful in both the isolation of ICAM-R from natural cellular sources and the modulation of ligand/receptor binding biological activities of ICAM-R.

Abstract: The present invention relates to a method for biotinylating a desired subset of a larger population of proteins, wherein the subset of proteins is first selectively bound to a solid phase, thereby separating it from undesired proteins of the population, and then, still bound to solid phase, it is biotinylated. Unreacted biotin may then be washed from the solid phase, and the biotinylated protein may be uncoupled from the solid phase.

Abstract: The invention relates to a method for carrying out heterogeneous immunoassays, in particular to a method for separating a coated solid phase from a liquid phase by means of precipitation and subsequent centrifugation, with a detectable activity remaining in the liquid phase.

Abstract: Fluorescent dyes possess reactive linkers for conjugating to nucleic acids, carbohydrates and peptides. The conjugates fluoresce in the visible and UV spectrum and have an excellent solvochromatic response as compared to other fluorescence or chromatic labels. The conjugates are stable but also have medium sensitive. The fluorescent dyes have little triplet state formation and are not photoreactive, making them an excellent substance for biological investigations. Uses for the dyes include protein labeling, DNA labeling, single molecule spectroscopy and fluorescence. A synthesis of the dyes is disclosed. Methods of use include the detection of carbohydrate-protein interactions.

Abstract: The invention concerns a method for the determination of an analyte in a sample liquid wherein the sample liquid is incubated with (a) a first receptor which binds to a first epitope that is only present once on the analyte and is immobilized on a particulate carrier material and (b) a second receptor which binds to a second epitope on the analyte and has at least two binding sites for the second epitope, the first epitope being different from the second epitope and the analyte is determined by means of the binding to both receptors.

Abstract: The invention relates to a method for protecting sensory hair cells of the inner ear from damage caused by ototoxic drugs, in particular, aminoglycoside antibiotics, by administering to a vertebrate a growth factor, or mixture thereof. Additionally, the method protects against loss of sensory hair cells as a result of aging. In particular, the growth factor is an insulin-like growth factor or platelet-derived growth factor. The invention also relates to a method for detecting protection against an ototoxic drug on sensory hair cells of an inner ear of a vertebrate by a growth factor or biologically active fragment.

Abstract: A high-affinity salicylic acid-binding protein (SABP2) derivable from tobacco and Arabidopsis is disclosed. The tobacco protein has a molecular weight of approximately 25 kDa and reversibly binds SA with an apparent K.sub.d of approximately 90 nM and a B.sub.max of 10 fmol/mg protein. The SABP2 of the invention may be used to identify analogues of SA. Analogues so identified may be used in plants to augment disease-resistance response pathways or other SA-sensitive processes in which SA plays a role. Possible examples include flowering and alternative respiration. The SABP2 of the invention may also be used to identify and clone a gene or cDNA that encodes it, which then may be used to generate transgenic plants having altered SABP2 levels.

Abstract: The present invention relates to methods useful for identifying compounds capable of specifically controlling CD40 regulation of JNK or p38 activity useful for inhibiting immunoglobulin heavy chain class switching, cytokine production and activation of cells involved in an inflammatory response. The present invention also includes kits to perform such assays and methods to control disease related to such responses.

Abstract: The present invention provides substantially purified nucleic acid molecules encoding Bax inhibitor protein-1 (BI-1; SEQ ID NO: 1) or Bax inhibitor protein-2 (BI-2; SEQ ID NO: 4), nucleic acid molecules complementary thereto (SEQ ID NO: 2 and SEQ ID NO: 5, respectively), portions of such nucleic acid molecules, vectors containing the nucleic acid molecules, and host cells containing the vectors. The invention also provides methods of using such nucleic acid molecules to identify the presence of a nucleic acid molecule encoding a Bax inhibitor protein in a sample or to increase or decrease the level of expression of a Bax inhibitor protein in a cell. In addition, the invention provides substantially purified BI-1 (SEQ ID NO: 3) and BI-2 (SEQ ID NO: 6) polypeptides, portions of such polypeptides, and antibodies specific for BI-1 or BI-2.

Abstract: Therapeutical and diagnostic agents for amyloidosis comprise molecules that inhibit the binding of serum amyloid P component to amyloid fibrils or analogues or homologues of the amyloid binding site on serum amyloid P component. The resolution of the complete three dimensional structure of serum amyloid P component enables inhibitors, binding site analogues and homologues to be designed by computer-aided molecular modelling.

Abstract: The invention relates to a diagnostic test for the detection and identification of Mycobacterium species in biological specimens of human and animal origin. The test is based on the immunological detection of one or more antigens originating from Mycobacterium. To enable the detection of an antibody-antigen reaction, the antibodies specific for these antigens can be labelled with an enzyme or fluorescent dye or attached to latex particles or any other suitable label. The diagnostic test may be in a form of ELISA and may or may not require concentration of the Mycobacterium antigens prior to the actual test.

Abstract: The invention relates to an improved method for the manufacture of magnetically responsive particles, also called ferrofluids. The improved method involves a heat treatment step, which may occur at various times during the preparation of the materials, including during subdivision of the magnetic starting material, during the addion of a coating material, after formation of a magnetically responsive particle, or some combination thereof. The materials formed by such a process have numerous advantages over materials formed by other processes, including enhanced salt stability, increased coating uptake, and increased binding capacity. These ferrofluids have applications in a variety of preparative and diagnostic techniques, including immunoassay, cell separations, toxicity testing, food testing, environmental analysis, and MRI.

Abstract: Screening of the autoantibodies and autoantigens which are specific to Sjogren's syndrome, particularly primary Sjogren's syndrome, and provision of a prophylactic and therapeutic drug for Sjogren's syndrome, particularly primary Sjogren's syndrome, and a highly sensitive diagnostic agent for Sjogren's syndrome. The .alpha.-fodrin or .alpha.-fodrin fragment of the invention is an antigen to the autoantibodies specifically found in Sjogren's syndrome and this autoantigen finds application as a prophylactic and therapeutic drug for autoimmune diseases, particularly Sjogren's syndrome, or a diagnostic agent for such diseases.

Abstract: A purified polypeptide which provides for initial binding of sperm to oocyte investments and has an active amino acid sequence of SEQ ID NO:12 (Cys-Gln-Ser-Leu-Gln-Glu-Tyr-Leu-Ala-Glu-Gln-Asn-Gln-Arg-Gln-Leu-Glu-Ser-A sn-Lys-Ile-Pro-Glu-Val-Asp-Leu-Ala-Arg-Val-Val-Ala-Pro-Phe-Met-Ser-Asn-Ile- Pro-Leu-Leu-Leu-Tyr-Pro-Gln-Asp-Arg-Pro-Arg-Ser-Gln-Pro-Gln-Pro-Lys-Ala-Asn -Glu-Asp-Val-Cys); or SEQ ID NO:13 (Cys-Glu-Ser-Leu-Gln-Lys-His-Leu-Ala-Glu-Leu-Asn-His-Gln-Lys-Gln-Leu-Glu-S er-Asn-Lys-Ile-Pro-Glu-Leu-Asp-Met-Thr-Glu-Val-Val-Ala-Pro-Phe-Met-Ala-Asn- Ile-Pro-Leu-Leu-Leu-Tyr-Pro-Gln-Asp-Gly-Pro-Arg-Ser-Lys-Pro-Gln-Pro-Lys-Asp -Asn-Gly-Asp-Val-Cys); or the shorter but biologically active SEQ ID NO:1 and SEQ ID NO:9 (Tyr-Pro-Gln-Asp-Arg-X-Arg-Ser-Gln-Pro-Gln-Pro-Lys-Ala-Asn, where X is Thr or Pro).

Abstract: Chitinase fungal diagnostic reagents comprising a chitinase conjugate comprising a chitinase enzyme and a label, the label selected from among a flourescent or a radioactive compound, an enzyme and a dye, the said chitinase fungal diagnostic reagent comprises a substantially pure aqueous solution of said chitinase conjugate; kits for detecting a fungal cell wall glucosamine compound in a biological specimen comprising the chitinase fungal diagnostic reagent and a filter capable of collecting the fungal cell wall glucosamine compound; and methods for detecting a fungal cell wall glucosamine compound in a biological specimen.

Abstract: Methods and compositions related to the identification of compounds that block neurotransmitter release are disclosed. Using the methods of the present invention, candidate compounds may be screened for the ability to bind to presynaptic calcium channels such that the docking of presynaptic vesicles to presynaptic calcium channels will be inhibited. The present invention also discloses peptides useful in the screening methods.

Abstract: The present invention relates to novel mammalian amino acid transporter proteins and the genes that encode such proteins. The invention is directed toward the isolation, characterization and pharmacological use of a human amino acid transporter protein termed EAAT4 and genes encoding such a transporter. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to this transporter gene. Also provided are recombinant expression constructs capable of expressing this amino acid transporter gene in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the human amino acid transporter protein encoded therein. The invention also provides methods for screening in vitro compounds having transport-modulating properties using preparations of transporter proteins from such cultures of cells transformed with recombinant expression constructs.

Abstract: A method of producing analgesia in nociceptive and neuropathic pain is disclosed. The method includes administering to a subject an omega conopeptide which is characterized by its ability to (a) inhibit electrically stimulated contraction of the guinea pig ileum, and (b) bind selectively to omega conopeptide MVIIA binding sites present in neuronal tissue. Also disclosed are novel omega conotoxin peptides effective in producing analgesia.

Abstract: The invention provides a method for diagnosing in a subject a neoplastic condition which comprises (a) obtaining from the subject a sample of a biological fluid; and (b) detecting the presence in the sample of a mutant p53 polypeptide encoded by an activated p53 oncogene, the presence of the mutant p53 polypeptide in the sample indicating that the subject has the neoplastic condition.

Abstract: The present invention provides seeds for cultivation of a new variety of Stevia rebaudiana Bertoni, the new variety, a sweetening obtained from dried leaves of the new variety and a process for production of the sweetening.

Abstract: The subject invention concerns novel means for adsorption of materials from fluids. In a specific example, polymer substrates are modified with dendrimers to facilitate attachment of multiple ligands held at a distance from the surface of the substrate.

Abstract: The present invention relates to novel mammalian amino acid transporter proteins and the genes that encode such proteins. The invention is directed toward the isolation, characterization and pharmacological use of the human amino acid transporter proteins EAAT1, EAAT2, EAAT3 and ASCT1. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to each of these transporter genes. Also provided are recombinant expression constructs capable of expressing each of the amino acid transporter genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the human amino acid transporter proteins encoded therein. The invention also provides methods for screening in vitro compounds having transport-modulating properties using preparations of transporter proteins from such cultures of cells transformed with recombinant expression constructs.

Abstract: The present invention provides methods and reagents for assessing lipoprotein metabolism. The methods provided are applicable for use on multiple samples in a clinical laboratory, thus obviating the need for sophisticated instrumentation, such as flow cytometry. Selected cell types in a test sample are uniformly labelled with a detectable reporter substance, so that they may later be enumerated. Pre-determined lipoprotein receptors associated with the cells of interest are labelled with a receptor-selective marker, thereby to determine the number of lipoprotein receptors per cell in the test sample. Selected cells of interest are conveniently separated from the test sample by binding thereto a specific binding substance attached to a solid support. The specific binding substance binds specifically with a characteristic determinant of the cell subset of interest. The remainder of the test sample may be washed away or discarded.

Abstract: The present invention is directed to screening for an agent that inhibits mononuclear phagocyte-plaque component complex formation (hereinafter "complex formation"). The methods include the steps of contacting a mononuclear phagocyte with a plaque component to stimulate complex formation and adding an agent suspected of inhibiting complex formation, measuring complex formation, and comparing complex formation to a measured control, wherein the reduction of complex formation compared to the control results in detection of an agent that inhibits complex formation. The mononuclear phagocytes may be from mammalian brain. The plaque component may be coupled to a solid support.