34th week of 2008 patent applcation highlights part 38 |
Patent application number | Title | Published |
20080199843 | Bioartificial Heart Tissue Graft And Method For The Production Therefor - The invention relates to a method for producing a bioartificial heart tissue graft, which leads to excellent biomechanical properties on the product and guarantees a high cell freedom with optimal preservation of the matrix. During the method, biological cells of a heart tissue preparation, particularly a heart valve or a heart vessel adhering in and/or to an extracellular matrix, are removed in-vitro. The method comprises that following steps carried out in this sequence: a) providing the heart tissue preparation of natural origin; b) removing cells, which are located in the tissue, from the extracellular matrix with the aid of an acellularization solution consisting of an aqueous solution of at least one strong anionic detergent and at least containing sodium deoxycholate; c) osmotically treating the tissue with distilled or deionized water, and; d) treating the tissue with a physiological saline solution with continuous flow or exchanging of the rinsing solution three times. | 2008-08-21 |
20080199844 | Solution for the storage and perfusion or organs awaiting transplantation - A storage solution to maintain and perfuse organs awaiting transplantation comprising (a) an isotonic balanced solution comprising a physiologically acceptable amount of potassium, mono acidic phosphate, biacidic phosphate, chloride, sodium and bicarbonate ions; (b) 50-250 mM glucose; (c) 0.2-20 mM of an alkanoyl L-carnitine or a physiologically acceptable salt thereof; (d) 1-100 mM of L-carnitine or a physiologically acceptable salt thereof; (e) water is described. The storage solution can also include other components such as anti-oxidants and/or chelating agents. | 2008-08-21 |
20080199845 | Compositions and Methods for Prolonging Survival of Platelets - The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis. | 2008-08-21 |
20080199846 | Poultry semen extender - A medium for preserving and extending the viable useful life of poultry (e.g., turkey) semen, in vitro, is provided. Semen is preserved without loss of fertility for up to about 24 hours in the medium. The medium contains di-potassium phosphate, sodium glutamate, fructose, sodium acetate, mono-potassium phosphate, potassium citrate, magnesium chloride, N-tris hydroxymethyl methyl-2-aminoethane sulfonic acid, phosphatidylcholine, and zinc, and optionally sialic acid, carnitine, serine ethanolamine phosphodiesterase, or mixtures thereof. A method for extending the fertility of poultry (e.g., turkey) semen for up to about 24 hours when held in vitro at about 5° to about 10° C., involving mixing poultry (e.g., turkey) semen containing live spermatozoa with an aqueous medium containing di-potassium phosphate, sodium glutamate, fructose, sodium acetate, mono-potassium phosphate, potassium citrate, magnesium chloride, N-tris hydroxymethyl methyl-2-aminoethane sulfonic acid, phosphatidylcholine, and zinc, and optionally at least one of sialic acid, carnitine, serine ethanolamine phosphodiesterase, or mixtures thereof. | 2008-08-21 |
20080199847 | Method for Predicting the Metabolism of Drug in Human Liver and Liver Function - The invention provides a method for precisely predicting the metabolism of a drug in human liver and the effect of the drug on liver function. The invention provides a method for predicting a metabolite of a test substance produced in human liver and functions of the liver, wherein the method includes administering a test substance to a nonhuman chimeric animal and a non-chimeric animal of the same species, wherein the chimeric animal intracorporeally carries a population of human-origin hepatocytes having proliferation potential and in which the hepatocyte, population substantially functions as the liver of the chimeric animal, and wherein these animals are protected from the attack by a human complement produced by the hepatocytes; and analyzing and comparing metabolites from the chimeric animal and the non-chimeric animal. | 2008-08-21 |
20080199848 | Method For Determining the Concentration of Asymmetric Dimethylarginine (Adma) - The invention relates to a method for determining the concentration of asymmetric dimethylarginine (ADMA) simultaneously with arginine and with symmetric dimethylarginine (SDMA) in biological samples by means of HPLC-MS-MS. The sample preparation consists exclusively of adding a solution of isotope-labeled internal standards ( | 2008-08-21 |
20080199849 | Method of Deriving Progenitor Cell Line - We disclose a method comprising: (a) providing an embryonic stem (ES) cell; and (b) establishing a progenitor cell line from the embryonic stem cell; in which the progenitor cell line is selected based on its ability to self-renew. Preferably, the method selects against somatic cells based on their inability to self-renew. Preferably, the progenitor cell line is derived or established in the absence of co-culture, preferably in the absence of feeder cells, which preferably selects against embryonic stem cells. Optionally, the method comprises (d) deriving a differentiated cell from the progenitor cell line. | 2008-08-21 |
20080199850 | Egfr Dependent Modulation of Chemokine Expression and Influence on Therapy and Diagnosis of Tumors and Side Effects Thereof - The invention relates to diagnosis and therapy of tumors utilizinging the epidermal growth factor (EGFR) by means of chemical inhibitors or monoclonal antibodies. The invention relates also to skin irritations, preferably skin rash, in conjunction and associated with the treatment of tumor cells that utilize EGF receptor with anti-cancer agents. The invention is also directed to methods of predicting the efficiency of a tumor therapy/tumor response in a patient based on the treatment with EGFR inhibitors, especially anti-EGFR antibodies. The invention further relates to a method of determining the optimum dose of an anti-cancer agent in EGFR related tumor therapy. | 2008-08-21 |
20080199851 | METHODS AND COMPOSITIONS FOR ANALYTE DETECTION - The present invention is directed to methods and apparatus for detection of one or more analytes. Analytes include agents or components of infectious agents such as pathogenic virus, as well as enzymes, proteins and biomarkers. | 2008-08-21 |
20080199852 | Detection method for human pappilomavirus (HPV) and its application in cervical cancer - Embodiments of the invention provide methods, assays, and kits for detecting HPV infection and HPV associated epithelial cell abnormalities, most notably those associated with pre-malignant and malignant epithelial cell lesions. Detection of HPV DNAs, genomes, and/or oncoproteins by nucleic acid hybridization assays and immunological assays can be used in early clinical screening for HPV infection and diagnosis for cervical cancer. The polypeptides, recombinant proteins, antibodies, nucleic acids, and various detection methods thereof are particularly useful for diagnosing carcinomas of the uterine cervix and those at risk of developing cervical cancer. | 2008-08-21 |
20080199853 | Methods and Compositions for Diagnosis and Monitoring Auto Immune and Chronic Inflammatory Diseases - Methods of diagnosing or monitoring auto immune and chronic inflammatory diseases, particularly systemic lupus erythematosis and rheumatoid arthritis, in a patient by detecting the expression level of one or more genes in a patient, are described. Diagnostic oligonucleotides for diagnosing or monitoring auto immune and chronic inflammatory diseases, particularly systemic lupus erythematosis and rheumatoid arthritis and kits or systems containing the same are also described. | 2008-08-21 |
20080199854 | Methods and compositions for identifying RNA-binding proteins - The present invention includes compositions, methods and kits for the identification of a polypeptide that binds to a predetermined RNA sequence. The invention comprises, in part, a photoreactive moiety to aid in identification of such a polypeptide. | 2008-08-21 |
20080199855 | Identification And Characterization Of A Subset of Glioblastomas Sensitive To Treatment With Imatinib - The present invention relates to methods for in vitro diagnosing a cell proliferative disease in a mammal, for predicting the behaviour of a mammal having a cell proliferative disease in response to a medical treatment using at least one PDGF receptor antagonist, and for selecting a mammal having a cell proliferative disease and predicted to be responsive to a medical treatment using at least one PDGF receptor antagonist, by using given genetic markers. | 2008-08-21 |
20080199856 | Probe for Diagnosis of Marfan Syndrome and a Method for Screening Using the Probe - The purpose of this invention is to provide a probe for diagnosis of Marfan syndrome, which enables early diagnosis of Marfan syndrome, and to provide a method for screening using said probe. The invention is a probe for a Marfan Syndrome characterized by using a nucleic acid comprising following (a) or (b);
| 2008-08-21 |
20080199857 | METHOD OF INCREASING SPECIFICITY OF NUCLEIC ACID HYBRIDIZATION USING ZWITTERIONIC COMPOUND - A method of increasing the specificity of nucleic acid hybridization, comprising hybridizing nucleic acid in a solution containing a zwitterionic compound selected from the group consisting of 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS), 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS), 3-(cyclohexylamino)-2-hydroxy-1-propane sulfonate (CAPSO), and 2-(cyclohexylamino)ethane sulfonate (CHES) is provided. The method allows a reduction in the yield of non-specific amplification products in multiplex PCRs while maintaining the yield of target amplification products. | 2008-08-21 |
20080199858 | Method for Detecting Estrogen-Like Chemicals by Plant | 2008-08-21 |
20080199859 | Identification Marker Responsive to Interferon Therapy for Renal Cell Cancer - The present invention provides an identification marker responsive to IFN therapy for renal cell cancer and a means of detecting the same. Namely, a method which comprises preparing a genomic DNA of a human gene or a complementary strand thereof from a specimen of a patient with renal cell cancer, analyzing the DNA sequence of the genomic DNA or the complementary strand thereof to determine the gene polymorphism of the human gene, and evaluating the tumor-suppression effect of IFN therapy on renal cell cancer by using the polymorphism as an indicator. | 2008-08-21 |
20080199860 | VARIANTS OF THE ALPHA 1 SUBUNIT OF HUMAN AMPK - Variants of the α subunit of AMPK, nucleic acids encoding such variants, and methods for their use are provided. | 2008-08-21 |
20080199861 | Real-time microarray apparatus and methods related thereto - Embodiments of the invention relate to a real-time microarray apparatus comprising an upper substrate, a lower substrate, a buffer positioned between the upper and lower substrate, a microarray positioned on either the upper substrate or the lower substrate, a heater positioned near the microarray, a pump positioned near the buffer and microarray and an imaging sensor positioned near the microarray. | 2008-08-21 |
20080199862 | Active biochip for nucleic acid analysis - Embodiments of the invention relate to an active biochip for nucleic acid analysis. The biochip comprises an inlet for introducing a nucleic acid sample, fluid channels, valves in contact with the fluid channels and pumps in contact with the fluid channels and adapted to generate a carrier gas or move a buffer through a portion of the fluid channels. The biochip also includes one or more hydroxyapatite columns for separating a portion of the nucleic acid sample, buffer reservoirs in contact with the fluid channels and positioned near the pumps, air exits, a waste reservoir and a nucleic acid analysis region. | 2008-08-21 |
20080199863 | PROBES AND METHODS FOR DETECTION OF PATHOGENS AND ANTIBIOTIC RESISTANCE - Described are probes and methods for detecting pathogens and antibiotic resistance of a specimen. The method comprises contacting the specimen with a growth medium; and lysing the specimen to release nucleic acid molecules from the specimen. The lysate of the specimen is contacted with a capture probe immobilized on a substrate, wherein the capture probe comprises an oligonucleotide that specifically hybridizes with a first target nucleic acid sequence region of ribosomal RNA. The lysate is in contact with a detector probe that comprises a detectably labeled oligonucleotide that specifically hybridizes with a second target nucleic acid sequence region of ribosomal RNA. The presence or absence of labeled oligonucleotide complexed with the substrate is determined. Detection of labeled oligonucleotide complexed with the substrate is indicative of the presence of pathogen. Performing the method in the presence and absence of an antibiotic permits detection of antibiotic resistance. | 2008-08-21 |
20080199864 | METHODS FOR CELL SCREENING OF COMPOUNDS CAPABLE OF MODULATING THE ACTIVITY OF UBIQUITIN-LIGASE SCF COMPLEXES AND THEIR USES - The invention concerns methods for cell screening of agents capable of modulating the activity of SCF.sup.Met30 complexes comprising the following steps: (i) contacting the product to be tested with a modified yeast strain, including (a) a hybrid sequence comprising a sequence coding for a Met4 protein, in its wild or mutated form, fused in phase with at least a sequence coding for an appropriate marker, said hybrid sequence being expressed under the control of a promoter, active in the yeast and optionally (b) a reporter transcriptional system, consisting of a reporter gene placed under the control of an appropriate operating sequence or an appropriate yeast promoter, (ii) adding methionine and (iii) determining the level of expression and stability of the expressed protein from the hybrid sequence, and their uses. The invention also concerns plasmids and yeast strains capable of being used in said methods. | 2008-08-21 |
20080199865 | Methods for Detecting and Treating the Early Onset of Aging-Related Conditions - Certain aspects of the invention relate to methods for determining a subject's susceptibility to the early onset or progression of aging-related conditions. In certain aspects the invention relates to accessing the genotype of a subject with respect to an allele of IL-1 pattern 1, pattern 2 and/or pattern 3. In other aspects, the invention relates to methods for selecting a therapeutic regimen, identifying age-related biomarkers, monitoring the progress of age-related conditions and identifying therapeutics for delaying or diminishing the onset of aging-related conditions. | 2008-08-21 |
20080199866 | SNP DETECTION AND OTHER METHODS FOR CHARACTERIZING AND TREATING BIPOLAR DISORDER AND OTHER AILMENTS - The present application relates to the use of SNPs and differential exon expression to characterize, diagnose or treat bipolar disorder and other mental illnesses, such as major depressive disorder and schizophrenia. | 2008-08-21 |
20080199867 | MULTIPLE MODE MULTIPLEX REACTION QUENCHING METHOD - Methods for balancing multiplexed PCR reactions are provided which exploit differences in primer and amplicon Tms. The methods may be controlled by a computer process. Also provided are articles of manufacture useful in such methods and compositions containing primers and probes useful in such methods. | 2008-08-21 |
20080199868 | Massive parallel method for decoding DNA and RNA - This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap the —OH group at the 3′-position of the deoxyribose. | 2008-08-21 |
20080199869 | Novel mycobacterium tuberculosis protein composition - proteins and protein compositions that are components of a desaturase complex are provided. The | 2008-08-21 |
20080199870 | COMPOSITIONS AND METHODS FOR THE IDENTIFICATION OF INHIBITORS OF PROTEIN SYNTHESIS - Compositions and methods for identifying inhibitors of RNA-target molecule interactions are provided as well as identifying inhibitors that block the role of tRNA in protein synthesis. The methods involve forming a mixture comprising a tRNA fragment molecule containing a modified nucleotide, a target molecule capable of binding to the tRNA fragment, and a test compound. The mixture is incubated under conditions that allow binding of the tRNA and the target molecule in the absence of the test compound. Assays can then be performed that detect whether or not the test compound inhibits the binding of the tRNA molecule and the target molecule. High throughput assays are also provided. | 2008-08-21 |
20080199871 | Systems and methods of analyzing nucleic acid polymers and related components - Systems and methods of identifying, sequencing and/or detecting nucleic acid polymers, as well as related components (e.g., substrates, software and the like) are disclosed. | 2008-08-21 |
20080199872 | Method and Kit for Analyzing a Target Nucleic Acid Sequence - This invention discloses methods for determining the presence of a target nucleic acid sequence using oligonucleotides that cooperate in a nucleic acid processing reaction to produce a detectable signal. In some embodiments, the methods also facilitate quantification of a target nucleic acid sequence. The present invention further discloses kits that can be used to conduct the methods of the present invention. | 2008-08-21 |
20080199873 | Companion diagnostic assays for cancer therapy - Methods for identifying cancer patients eligible to receive Bcl-2 family inhibitor therapy and for monitoring patient response to Bcl-2 family inhibitor therapy comprise assessment of the expression levels of the biomarker combinations set out in TABLES 1, 2, 3, 4, 5 or 6 in a patient tissue sample. The methods of the invention allow more effective identification of patients to receive Bcl-2 family inhibitor therapy and of determination of patient response to the therapy. | 2008-08-21 |
20080199874 | CONTROLLABLE STRAND SCISSION OF MINI CIRCLE DNA - The invention provides methods and compositions for the controlled termination of polymerase mediated primer extension reactions. The methods and compositions of the invention are broadly useful, and in a preferred aspect can be used in identifying sequence elements of template nucleic acids. Control of termination not only provides temporal control over termination, but, when used in conjunction with optically confined reaction regions, also spatially controls such termination. | 2008-08-21 |
20080199875 | UNSYMMETRICAL CYANINE DIMER COMPOUNDS AND THEIR APPLICATION - Embodiments of the present invention provide methods and nucleic acid reporter molecules for the detection of nucleic acid in a sample. The nucleic acid reporter molecule comprises two unsymmetrical cyanine monomer moieties, which may be the same or different, that are covalently attached by a linker comprising at least one aromatic, heteroaromatic, cyclic or heterocyclic moiety comprising 3-20 non-hydrogen atoms selected from the group consisting of O, N, S, P and C. The linker may be rigid, relatively flexible or some degree thereof. The unsymmetrical cyanine monomer moieties comprise a substituted or unsubstituted benzazolium moiety and a substituted or unsubstituted pyridinium or quinolinium moiety that is connected by a methine bridge that is monomethine, trimethine or pentamethine. The linkers form the cyanine dimer compounds by attaching to the pyridinium or quinolinium moiety of the monomer moieties. The present nucleic acid reporter molecules find utility in forming a nucleic acid-reporter molecule complex and detecting the nucleic acid. In particular, present nucleic acid reporter molecules with a rigid linker and monomer moieties with a monomethine bridge find utility in detecting RNA in the presence of DNA. | 2008-08-21 |
20080199876 | Method of Detection of Alterations in MSH5 - We have now discovered that mammals have a DNA gene analogous to that existing in bacteria. MSH5 defects or alterations in this mismatch repair pathway in a mammal, such as a human can be diagnostic of a predisposition to cancer, and prognostic for a particular cancer. We have discovered and sequenced MSH5 in this in a number of mammals, including humans. This gene can be used in assays, to express gene product, for drug screens, and therapeutically. | 2008-08-21 |
20080199877 | OLIGONUCLEOTIDE PROBES FOR DETECTING ENTEROBACTERIACEAE AND QUINOLONE-RESISTANT ENTEROBACTERIACEAE - Oligonucleotide probes for detecting Enterobacteriaceae species. Unique gyrA coding regions permit the development of probes specific for eight different species: | 2008-08-21 |
20080199878 | DETECTION, IDENTIFICATION AND DIFFERENTIATION OF EUBACTERIAL TAXA USING A HYBRIDIZATION ASSAY - The present invention relates to a method for the specific detection and/or identification of | 2008-08-21 |
20080199879 | Method of Assaying Alzheimer's Disease and Diagnostic Reagent - The present invention is intended to devise a process of measuring β-amyloid in a biological sample such as blood and to apply the process to diagnosis of Alzheimer's disease. | 2008-08-21 |
20080199880 | SPIN ARRAY METHOD - An improvement in heterogeneous immunoassays to significantly reduce assay time, from as much as 50% up to 90% of what used to be typical assay times. The improvement involves rotating the captured substrate during incubation times for antigen capture and during incubation times for sample labeling. | 2008-08-21 |
20080199881 | MN Gene and Protein - Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter, and which vectors preferably further encode a cytokine. The MN gene promoter is characterized, and the binding site for a repressor of MN transcription is disclosed. | 2008-08-21 |
20080199882 | METHOD FOR DETECTION OF BIOMARKERS FOR EXPOSURE TO STACHYBOTRYS - A method of determining exposure of an individual to a macrocyclic trichothecene comprises isolating a sample of at least a portion of a naturally occurring protein from an individual, and detecting a reaction of the sample with a macrocyclic trichothecene. The macrocyclic trichothecene may be a product of | 2008-08-21 |
20080199883 | Schizophrenia Related Gene and Protein - The invention relates to polynucleotides of the PAPAP gene, polypeptides encoded by the PAPAP gene, and antibodies directed specifically against such polypeptides. The invention also concerns methods for the treatment or diagnosis of schizophrenia, bipolar disorder or related CNS disorder. The invention also concerns the interaction of PAPAP with schizophrenia candidate gene g34872. | 2008-08-21 |
20080199884 | Method For Measuring Protozoan Oocyst and Detecting Reagent - The present invention provides a method for measuring oocyst of protozoa, such as | 2008-08-21 |
20080199885 | Overexpression of mammaglobin B in ovarian and endometrial tumors - a new diagnostic and therapeutic marker - The invention involves the discovery that the mammaglobin B gene is the single most overexpressed gene in primary ovarian serous papillary cancer over normal ovarian epithelium among over 14,000 genes tested. It is expressed over 800-fold higher in primary ovarian tumors than normal ovarian epithelium. Mammaglobin B gene expression was detected in endometrioid, mucinous, undifferentiated, serous papillary, clear cell, and mixed histology ovarian tumors. The protein can be found in blood and ascites fluid, and a simple blood test for the presence of mammaglobin B protein can provide early detection of ovarian and other cancers. The invention provides a method of screening for cancer involving detecting mammaglobin B in a fluid sample. | 2008-08-21 |
20080199886 | IGF BINDING PROTEINS - IGFBP-3 fusion proteins are provided that are useful, for example, in cell-based assays, as IGF antagonists, and in mapping IGF-I and IGF-II binding sites on other molecules such as wild-type IGFBP-3 and IGF agonist peptides identified by phage display. Methods for making such fusion proteins are also provided. | 2008-08-21 |
20080199887 | COMPOUNDS AND METHODS FOR USE IN DETECTING GABAPENTIN - Compounds and methods for use in detecting gabapentin in a sample suspected of containing gabapentin are disclosed. Gabapentin derivatives are used to produce gabapentin conjugates. A gabapentin-immunogenic carrier conjugate may be used as an immunogen for the preparation of an anti-gabapentin antibody. A gabapentin-detectable label may be used in a signal producing system in gabapentin assays. | 2008-08-21 |
20080199888 | Non-endogenous, constitutively activated versions of human G protein coupled receptor: FSHR - The invention disclosed in this patent document relates to transmembrane receptors, particularly to a human G protein-coupled receptor, more particularly to a follicle stimulating hormone receptor (FSHR), and most particularly to mutated (non-endogenous) versions of the human FSHR for evidence of constitutive activity. | 2008-08-21 |
20080199889 | Human orphan G protein-coupled receptors - The invention disclosed in this patent document relates to transmembrane receptors, more particularly to endogenous, human orphan G protein-coupled receptors. | 2008-08-21 |
20080199890 | Methods of Determining Cellular Chemosensitivity - The present invention provides methods of determining cell sensitivity to a therapeutic agent. | 2008-08-21 |
20080199891 | Reagents and Methods For Use In Cancer Diagnosis, Classification and Therapy - Methods and reagents for classifying tumors and for identifying new tumor classes and subclasses. Methods for correlating tumor class or subclass with therapeutic regimen or outcome, for identifying appropriate (new or known) therapies for particular classes or subclasses, and for predicting outcomes based on class or subclass. New therapeutic agents and methods for the treatment of cancer. | 2008-08-21 |
20080199892 | Process for Screening Glycoform-Specific Antibodies - The present invention relates to the use of the assessment of the binding between—antibodies elicited against a first glycoprotein, and—at least one glycoform of a second glycoprotein, said second glycoprotein being itself a glycoform of the first protein, wherein said glycoform of the second glycoprotein is selected from a group of glycoforms of the second glycoprotein, each glycoform of said group corresponding to a determined glycosylation state defined by a determined sialylation state, and/or a determined branching state, and/or a determined fucosylation state, provided that said glycosylation state is not uniquely defined by a substantially unsialylated state, for the screening of glycoform specific antibodies directed against a given glycoform of the second glycoprotein. | 2008-08-21 |
20080199893 | Medical Biosensor By Means of Which Biological Liquids are Analyzed - Medical biosensor by means of which biological liquids are analyzed, having at least three layers; a functional layer to which a contact adhesive strip, adhesive on both sided, is applied, and a structural film applied to the contact adhesive strip. | 2008-08-21 |
20080199894 | DEVICE AND METHOD FOR AUTOMATIC DATA ACQUISITION AND/OR DETECTION - Methods and system for providing diabetes management including automatic time acquisition protocol and expiration date detection are provided. | 2008-08-21 |
20080199895 | Highly purified and stabilized Na,K-ATPase isoforms and methods of producing same - A composition of matter comprising active Na,K-ATPase is disclosed, each Na,K-ATPase comprising an α and β subunit, the Na,K-ATPase being at least 85% purified. Methods of purifying same and uses thereof are also disclosed. | 2008-08-21 |
20080199896 | Diagnosis and Treatment of Diseases Arising from Defects in the Tuberous Sclerosis Pathway - The present invention relates to compositions and methods for identifying abnormalities in TSC signaling pathways. In particular, the present invention relates to methods of diagnosing and treating disorders such as tuberous sclerosis, which are caused by mutations in the TSC genes. The present invention further relates to methods and compositions for treating cancers mediated by TSC signaling disorders. | 2008-08-21 |
20080199897 | CLASS II HISTONE DEACETYLASE WHOLE CELL ENZYME ASSAY - The invention relates to enzymatic assays and substrates for Class II histone deacetylases. More particularly, the invention relates to such assays and substrates utilizing whole cells, extracts of such whole cells, extracts of sub-cellular compartments of such whole cells, or bodily fluids. | 2008-08-21 |
20080199898 | COMPOSITIONS FOR THE DETECTION OF ENZYME ACTIVITY IN BIOLOGICAL SAMPLES AND METHODS OF USE THEREOF - The present invention provides for novel reagents whose fluorescence increases in the presence of particular proteases. The reagents comprise a characteristically folded peptide backbone conjugated to two fluorophores such that the fluorophores are located opposite sides of a cleavage site. When the folded peptide is cleaved, as by digestion with a protease, the fluorophores provide a high intensity fluorescent signal at a visible wavelength. Because of their high specificity and their high fluorescence signal in the visible wavelengths, these protease indicators are particularly well suited for detection of protease activity in biological samples, in particular in frozen tissue sections. Thus this invention also provides for methods of detecting protease activity in situ in frozen sections. | 2008-08-21 |
20080199899 | Method For Screening Modulators of Mitochondrial Functioning and New Modulators Obtained - The invention relates to a method for screening modulators of mitochondrial function comprising adding a compound to be tested in a purified, isolated mitochondria preparation and simultaneously using fluorimetric analysis of mitochondrial morphology, and especially real-time fluorimetric analysis, combining analysis of morphometric parameters (SSC/FSC parameters) with analysis of membrane integrity by dye fluorescence. Application to the obtention of peptides which induce mitochondrial membrane permeabilization. | 2008-08-21 |
20080199900 | Disposable Device For One Or More Introductions, Treatment And Sampling Of Biological Material From At Least One Of The Separation Phases Present Within The Device, Under Sterility Conditions and Constant Pressure - A disposable device ( | 2008-08-21 |
20080199901 | METHOD OF MONITORING MICROBIOLOGICAL ACTIVITY IN PROCESS STREAMS - An apparatus and method for monitoring microbiological activity in a process stream by measuring dissolved oxygen is disclosed. Bulk microbiological activity and surface associated biological activity are measured using this apparatus and method. | 2008-08-21 |
20080199902 | Biosensor For Determining The Biochemical Oxygen Demand (Bod) By Respirometry - A removable cartridge that contains an adjustable number of capsules inside of which there are adjustable masses of immobilized microorganisms, allowing the design of a simple, portable apparatus and the use of a reactor with less priming time. A circulating pump injects maintenance water into the reactor, and the used maintenance water is pumped out to a disposal location or device by the same pump. An air pump injects air into the maintenance liquid and the excess air is released through an airflow outlet. A dissolved oxygen sensor is used to take several measurements of the dissolved oxygen content of the sample water, and various formulas are used to analyze the results. Reactors of this type can be stored in cold allowing the replacement of the operating reactor easily. | 2008-08-21 |
20080199903 | Biological indicator - A biological indicator for monitoring the effectiveness of a sterilizing, disinfecting, etc., compound or condition is disclosed which comprises a substrate having a surface layer containing functional groups thereon desirably free of silicone linking groups. The functional groups are desirably in the form of a monolayer of a uniformed distribution and of a selected quantity. Various types of microorganisms such as spores and/or etiological agents are covalently bonded to the surface layer functional groups through a crosslinking reagent and thus form a uniform number and distribution of the microorganisms and/or etiological agents. After being subjected to sterilization or other similar treatment, etc., along with various articles such as instruments, the indicator can be cultivated to determine the effectiveness of the sterilization, disinfection, etc. process. | 2008-08-21 |
20080199904 | Apparatus and method for detecting and identifying microorganisms - The present invention is an apparatus for detecting the presence, quantity and identity of one or more microorganisms in a sample and a method for using the same. The apparatus is composed of one or more chambers and a sensing element for sensing microorganisms. In particular embodiments, the sensing element is an array of chemoresponsive dyes deposited on a substrate in a predetermined pattern combination, wherein the combination of the dyes have a distinct and direct spectroscopic, transmission, or reflectance response to distinct analytes produced by the microorganism which is indicative of the presence, quantity and identity of the microorganism. | 2008-08-21 |
20080199905 | Catalytic Domains Of Beta(1,4)-Galactosyltransferase I Having Altered Metal Ion Specificity - Disclosed are mutants of galactosyltransferases that can catalyze formation of oligosaccharides in the presence of magnesium; mutants of galactosyltransferases having altered donor and acceptor specificity which can catalyze formation of oligosaccharides in the presence of magnesium; methods and compositions that can be used to synthesize oligosaccharides; methods for increasing the immunogenicity of an antigen; and methods to stabilize platelets. | 2008-08-21 |
20080199906 | Optimized Nucleotide Sequences Encoding Sgp 130 - Described are codon optimized sgp130 encoding nucleic acid molecules as well as a method for the highly efficient recombinant production of sgp130 in mammalian cells or bacteria using a nucleic acid molecule of the invention. | 2008-08-21 |
20080199907 | Method For Preparing a Target Protein Using the Shsps - The present invention relates to a method for separating and purifying a target protein, a method for preparing a target protein, and a method for bioconversion by a whole cell enzyme or a partially purified enzyme. According to the present invention, when the sHSPs are added in cultivation, separation and purification processes for preparing a target protein, the target protein can be obtained at high yields by preventing the loss of protein by proteases. Also, when sIISPs are added in a reaction process using a whole cell enzyme or a partially purified enzyme, the yield of bioconversion using enzyme can be increased by preventing the loss of enzyme by proteases. | 2008-08-21 |
20080199908 | Production Of Cellulase - The invention relates to a process of producing cellulase in a host cell, comprising cultivating said host cell capable of producing cellulase under conditions conducive for production of cellulase, wherein pre-treated ligno-cellulosic material is added to induce cellulase production. The invention also relates to use of pre-treated ligno-cellulosic material as inducer or carbon source in cellulase production processes. | 2008-08-21 |
20080199909 | Methods for Expression and Purification of Recombinant Human Growth Hormone - The present invention relates generally to the production, purification, and isolation of human growth hormone (hGH). More particularly, the invention relates to the production, purification, and isolation of substantially purified hGH from recombinant host cells or culture medium including, for example, yeast, insect, mammalian and bacterial host cells. The process of the present invention is also useful for purification of hGH linked to polymers or other molecules. | 2008-08-21 |
20080199910 | Production of recombinant insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) in transgenic monocots - Two important human proteins, insulin growth factor I (IGF-I) and insulin growth factor binding protein 3 (IGFBP-3) have been produced in monocots. The recombinantly produced proteins exhibit the known activities of the native forms. | 2008-08-21 |
20080199911 | VP1 OF FOOT-AND-MOUTH DISEASE VIRUS - A pure, water-soluble polypeptide containing one or more monomers of a VP1 protein of a foot-and-mouth disease virus; or a pure, water-insoluble polypeptide comprising two or more monomers of a VP1 protein of a foot-and-mouth disease virus. Also disclosed are a vaccine containing the polypeptide, a method of producing the polypeptide, and a method of inducing an immune response in a subject by administering to the subject an effective amount of the polypeptide. | 2008-08-21 |
20080199912 | Methods for Obtaining Optically Active Epoxides and Diols from 2,3-Disubstituted and 2,3-Trisubstituted Epoxides - The invention provides yeast strains, and polypeptides encoded by genes of such yeast strains, that have enantiospecific internal epoxide hydrolase activity. The invention also features nucleic acid molecules encoding such polypeptides, vectors containing such nucleic acid molecules, and cells containing such vectors. Also embraced by the invention are methods for obtaining optically active internal epoxides and corresponding optically active internal diols. | 2008-08-21 |
20080199913 | Production of Recombinant Il-18 Binding Protein - The invention relates to a process for the production of IL-18 binding protein (IL-18BP), and to a composition comprising IL-18BP characterized by a specific glycosylation pattern. | 2008-08-21 |
20080199914 | Modified Alginates, Methods of Production and Use - Process for preparing a modified alginate polymers are disclosed. The processes comprise the steps of covalently attaching a modifying moiety to one or more unmodified monomeric subunits of an alginate polymer; and changing one or more unmodified mannuronic (M) monomeric subunits of the alginate polymer to one or more unmodified guluronic (G) monomeric sub-units by an enzymatic epimerization reaction performed in any order. Processes for preparing alginate gels, fiber, and compositions are also disclosed. Modified alginates in which only M monomeric subunits are modified, and alginate gels, fibers and compositions comprising the same, are disclosed. | 2008-08-21 |
20080199915 | Methods and Kits For Mass Production Of Dsrna - The invention relates to methods and kits for propagating target nucleic acid in the form of double stranded RNA. This invention relates in particular to a method for mass production of dsRNA. The method comprises that a target nucleic acid is provided in a form replicable by an RNA-dependent RNA polymerase in a living cell, said replicable form of the target nucleic acid is contacted with said polymerase under conditions sufficient for template-directed RNA synthesis, wherein one of the reaction products is necessarily double-stranded (ds) RNA and said dsRNA products are recovered in a sufficiently pure form. The dsRNA products can be used in various applications, for example in gene silencing. | 2008-08-21 |
20080199916 | Multiplex targeted amplification using flap nuclease - Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5′ or 3′ flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are hybridized to dU probes so that 5′ and 3′ flaps are generated. The flaps are cleaved using 5′ or 3′ flap endonucleases or 3′ to 5′ exonucleases. The target sequences are then ligated to common primers, the dU probes digested and the ligated targets amplified. | 2008-08-21 |
20080199917 | Means and methods for producing adenovirus vectors - The invention relates to methods and means for producing adenoviral vectors on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenoviral vector and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products provided by the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell. | 2008-08-21 |
20080199918 | Starch Process - The present invention relates to a process for enzymatic hydrolysis of granular starch into a soluble starch hydrolysate at a temperature below the initial gelatinization temperature of said granular starch | 2008-08-21 |
20080199919 | METHOD FOR PRODUCING L-LYSINE OR L-ARGININE BY USING METHANOL ASSIMILATING BACTERIUM - A DNA encoding a variant of a protein having a loop region and six hydrophobic helixes which is involved in excretion of L-lysine to outside of a cell is described, wherein the DNA encodes a mutant protein which does not contain the loop region that is present in the wild-type protein. The mutant protein facilitates excretion of L-lysine, L-arginine, or both to the outside of the cell of a methanol assimilating bacterium when the DNA is introduced into the bacterium. Specifically, lysE | 2008-08-21 |
20080199920 | S-Adenosylmethionine-6-N-Lysine-Methyltransferase From Neurospora Crassa, A Gene Encoding The Same, A Vector And Host Cell Containing The Same, And Method For Producing Trimethyllysine Using The Host Cell - Provided is S-adenosylmethionine-6-N-lysine-methyl-transferase obtained from Neνrospora | 2008-08-21 |
20080199921 | PROCESS FOR PRODUCING GLUTAMATE DERIVATIVES - The present invention relates to a process for producing efficiently glutamic acid derivatives (including salts thereof) such as monatin by converting a substituted α-keto acid of formula (1) into a glutamic acid derivative of formula (2) in the presence of an enzyme catalyzing conversion of the same. | 2008-08-21 |
20080199922 | Chemoenzymatic Process for the Synthesis of Escitalopram - A process is described for the preparation of escitalopram and the pharmaceutically acceptable salts thereof starting from 5-cyanophthalide by a process which provides an enantioselective enzymatic deacylation reaction of a complex of the formula (IV) where R represents a C | 2008-08-21 |
20080199923 | Process for the Heterotrophic Production of Microbial Products with High Concentrations of Omega-3 Highly Unsaturated Fatty Acids - Disclosed is a process for growing the microflora | 2008-08-21 |
20080199924 | Production of Degummed Fatty Acid Alkyl Esters - The present invention relates to a method for producing fatty acid alkyl esters, such as fatty acid methyl esters (FAME) and fatty acid ethyl esters with a low level of impurities such as phospholipids. The method of the invention is simplified by combining two process steps into one single process step and is therefore economically cheaper The method includes mixing water, alcohol, triglyceride and/or free fatty acids a lipolytic enzyme and a phospholipase. Subsequently the aqueous phase, which contains glycerine, residual enzyme and most of the hydrolyzed phospholipids, is separated from the non-aqueous phase, whereby the content of phospholipids in the non-aqueous phase is reduced. | 2008-08-21 |
20080199925 | Method For Producing an Aqueous Polymer Dispersion - A process for preparing an aqueous polymer dispersion, in which, in an aqueous medium, in a first reaction stage, a hydroxycarboxylic acid compound is reacted in the presence of an enzyme and of a dispersant, and also, if appropriate, of a low water solubility organic solvent and/or of an ethylenically unsaturated monomer, to give a polyester, and thereafter, in the presence of the polyester, in a second reaction stage, an ethylenically unsaturated monomer is free-radically polymerized. | 2008-08-21 |
20080199926 | Methods and Organisms for Growth-Coupled Production of 3-Hydroxypropionic Acid - The invention provides a non-naturally occurring microorganism having one or more gene disruptions, the one or more gene disruptions occurring in genes encoding an enzyme obligatory coupling 3-hydroxypropionic acid production to growth of the microorganism when the gene disruption reduces an activity of the enzyme, whereby the one or more gene disruptions confers stable growth-coupled production of 3-hydroxypropionic acid onto the non-naturally occurring microorganism. Also provided is a non-naturally occurring microorganism comprising a set of metabolic modifications obligatory coupling 3-hydroxypropionic acid production to growth of the microorganism, the set of metabolic modifications having disruption of one or more genes including: (a) the set of genes selected from: (1) adhE, ldhA, pta-ackA; (2) adhE, ldhA, frdABCD; (3) adhE, ldhA, frdABCD, ptsG; (4) adhE, ldhA, frdABCD, pntAB; (5) adhE, ldhA, fumA, fumB, fumC; (6) adhE, ldhA, fumA, fumB, fumC, pntAB; (7) pflAB, ldhA, or (8) adhE, ldhA, pgi in a microorganism utilizing an anaerobic β-alanine 3-HP precursor pathway; (b) the set of genes selected from: (1) tpi, zwf; (2) tpi, ybhE; (3) tpi, gnd; (4) fpb, gapA; (5) pgi, edd, or (6) pgi, eda in a microorganism utilizing an aerobic glycerol 3-HP precursor pathway; (c) the set of genes selected from: (1) eno; (2) yibO; (3) eno, atpH, or other atp subunit, or (4) yibO, atpH, or other atp subunit, in a microorganism utilizing a glycerate 3-HP precursor pathway, or an ortholog thereof, wherein the microorganism exhibits stable growth-coupled production of 3-hydroxypropionic acid. The disruptions can be complete gene disruptions and the non-naturally occurring organisms can include a variety of prokaryotic or eukaryotic microorganisms. A method of producing a non-naturally occurring microorganism having stable growth-coupled production of 3-hydroxypropionic acid is further provided. The method includes: (a) identifying in silico a set of metabolic modifications requiring 3-hydroxypropionic acid production during exponential growth, and (b) genetically modifying a microorganism to contain the set of metabolic modifications requiring 3-hydroxypropionic acid production. | 2008-08-21 |
20080199927 | Aspergillus Kawachi Acid-Stable Alpha Amylase and Applications in Granular Starch Hydrolysis - The present invention relates to a method for producing an end product and particularly an alcohol which comprises contacting a granular starch substrate with an acid-stable alpha amylase (asAA) having granular starch hydrolyzing (GSH) activity and a glucoamylase (GA) in a fermentation step which also comprises ethanologenic microorganisms at a temperature between about 25 to 65° C. and producing an end-product. | 2008-08-21 |
20080199928 | Producing Hydrogen By Heterologous Expression Of A Type II Nad (P)H Deshydrogenase In Chlamydomonas - The invention concerns the use of a type II NAD(P)H dehydrogenase (NDH-II), or of a polynucleotide encoding said NDH-II, to increase the capacity of a green algae to produce hydrogen. Said polynucleotide is in particular useful for transforming said green algae, so as to improve its hydrogen production. | 2008-08-21 |
20080199929 | Method and System For Collecting Cells Following Laser Microdissection - A method of collecting target regions from a target object is described. The method in one embodiment comprises mounting a negatively-charged membrane on a first side of a substrate, mounting a target object on the membrane, positioning a collection material adjacent to the target object, and passing a laser beam from a second side of the substrate, through the substrate, the membrane, and the target object, to dissect target regions from the prepared tissue section, whereby the dissected target regions adhere to the collection material. In another embodiment, the present invention is a system for collecting target regions from a target object. In one embodiment, the system comprises a substrate having a first side and a second side, a negatively-charged membrane adhered to the first side of the substrate, and a collection material mountable adjacent to the membrane. In another embodiment, the system further comprises an inverted microscope, a stage for holding the substrate over the microscope, a generator operable to generate a laser beam to pass through the substrate from the second side and to dissect target regions from a target object mounted on the membrane, whereby the dissected target regions adhere to the collection material. In the preferred embodiments, the target objects are tissues and the target regions are cells. | 2008-08-21 |
20080199930 | METHOD AND APPARATUS FOR THE RAPID DISRUPTION OF CELLS OR VIRUSES USING MICRO BEADS AND LASER - A method and apparatus for rapid disruption of cells or viruses using beads and a laser are provided. According to the method and apparatus for rapid disruption of cells or viruses using beads and a laser, cell lysis within 40 seconds is possible, the apparatus can be miniaturized using a laser diode, a DNA purification step can be directly performed after a disruption of cells or viruses, and a solution containing DNA can be transferred to a subsequent step after cell debris and beads to which inhibitors of a subsequent reaction are attached are removed with an electromagnet. In addition, by means of the cell lysis chip, an evaporation problem is solved, vibrations can be efficiently transferred to cells through magnetic beads, a microfluidics problem on a rough surface is solved by hydrophobically treating the inner surface of the chip, and the cell lysis chip can be applied to LOC. | 2008-08-21 |
20080199931 | POLYNUCLEOTIDE ENCODING AN INTRACELLULAR ESTRADIOL BINDING PROTEIN - Described herein is a novel intracellular estradiol binding protein (“IEBP”), as well as a polynucleotide encoding this protein and various cells and cell lines producing and/or overexpressing it. IEBP is believed to play a role in the modulation of estrogen signaling and in the physiological resistance to the same. Abnormally elevated or decreased levels of IEBP may thus be a component of the etiology of diseases generally correlated with estrogen signaling, such as, by way of example, breast cancer and osteoporosis. Various embodiments of the present invention are believed to provide important tools for developing treatments for these conditions, such as, for example, by providing means for screening therapeutic compounds and identifying a genetic target for therapy. | 2008-08-21 |
20080199932 | Active surface coupled polymerases - Active surface coupled polymerases, surfaces that include such polymerases, and methods of making and using surface-attached polymerases are provided. | 2008-08-21 |
20080199933 | Amine Oxidase Inhibitors - A therapeutic agent for selectively inhibiting amine oxidases associated diseases and conditions in humans includes at least one compound selected from the group consisting of propargylamines, polypropargylamines, homopropargylamines, 4-substituted-2-butynylamines, 2- and 3-halloallylamines, pyrroline derivatives, cycloalkenyl branched primary amines, propargyl diamines, homopropargyl amines and diamines, allenyl amines and diamines, chloroallyl diamines, lysyne analogues, β-haloamines, RF-substituted amines, RC | 2008-08-21 |
20080199934 | Functional peptide fiber, production method thereof and method for recovering peptide chains - This invention provides a functional peptide fiber which comprises a plurality of peptide structure units each containing at least one peptide chain, wherein peptide chains contained in each adjacent peptide structure units do not form peptide bond but are structured into a fibrous form by taking a β-sheet structure, and wherein at least one of the plurality of peptide structure units contains a peptide chain having a functional material connected thereto. Also disclosed are a method for producing the functional peptide fiber and a method for recovering peptide chains from the functional peptide fiber. | 2008-08-21 |
20080199935 | Compositions and methods utilizing DNA polymerases - The invention features a novel isolated Family B DNA polymerase, a | 2008-08-21 |
20080199936 | FEN Endonucleases - The present invention provides novel cleavage agents and polymerases for the cleavage and modification of nucleic acid. The cleavage agents and polymerases find use, for example, for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. In some embodiments, the 5′ nuclease activity of a variety of enzymes is used to cleave a target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. | 2008-08-21 |
20080199937 | Reagent Composition and Methods of Using and Forming the Same - A reagent composition containing GDH-PQQ as an enzyme-co-factor and screen-printed on working and counter electrodes of electrochemical biosensors, maintains activity of the enzyme reagents by proper selection of components. A preferred composition includes hydrophilic polymers, amorphous untreated silica, buffers, surfactants, and a mediator For example, the biosensor is useful in the amperometric determination of glucose. | 2008-08-21 |
20080199938 | Novel Cellulase Resistant to Surfactant - Disclosed is a novel cellulose having an amino acid sequence in which the 162nd and/or 166th amino acid residues in the amino acid sequence of cellulose NCE5 are substituted. Further, a polynucleotide encoding the novel cellulose, an expression vector containing the polynucleotide, a host cell transformed with the expression vector, and a cellulose preparation and a washing composition containing the cellulose are disclosed. The cellulose of the present invention is resistant to surfactants, and maintains a high activity even under alkaline conditions. | 2008-08-21 |
20080199939 | Adenoviral Vectors and Uses Thereof - The present invention relates to recombinant adenoviral vectors based on adenoviruses that encounter pre-existing immunity in a minority of the human population and which harbour a chimeric capsid. The chimeric capsid comprises fiber proteins that have at least the knob domain of a human adenovirus that binds to the Coxsackievirus and Adenovirus Receptor (CAR) and a hexon protein from an adenovirus serotype that encounters pre-existing immunity in a low percentage of the human population. | 2008-08-21 |
20080199940 | Farnesyl dibenzodiazepinone and processes for its production - This invention relates to a novel farnesylated dibenzodiazepinone, named ECO-04601, its pharmaceutically acceptable salts and derivatives, and to methods for obtaining such compounds. One method of obtaining the ECO-04601 compound is by cultivation of a novel strain of | 2008-08-21 |
20080199941 | FUSOBACTERIUM POLYPEPTIDES AND METHODS OF USE - The present invention provides isolated polypeptides isolatable from a | 2008-08-21 |
20080199942 | Method of engineering a cytidine monophosphate-sialic acid synthetic pathway in fungi and yeast - The present invention provides methods for generating CMP-sialic acid in a non-human host which lacks endogenous CMP-Sialic by providing the host with enzymes involved in CMP-sialic acid synthesis from a bacterial, mammalian or hybrid CMP-sialic acid biosynthetic pathway. Novel fungal hosts expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided. | 2008-08-21 |