Abstract: The present invention relates to advanced glycosylation endproducts, and particularly to the use of novel cyclopentenone aminoreductones, 3-alkylamino-2 -hydroxy-4-hydroxymethyl-2-cyclopenten-1-ones. Such AGEs can be used in various diagnostic and therapeutic methods.

Abstract: A method of determining the glycosylated fraction of a protein in a sample includes the steps of examining the sample to determine the total quantity of protein in the sample (READ 1), removing the glycosylated fraction of the protein, and then reexamining the sample to measure the glycosylated fraction of the protein (READ 2). The glycosylated fraction of the protein may then be calculated by the formula (READ 1-READ 2)/READ .times.100. The glycosylated fraction of the protein is removed by inserting a cartridge containing a binder into the sample, or by urging the sample through a cartridge containing a binder. Both of the cartridge assemblies preferably include a flow through body, a support material disposed in the body, and a binder material attached to the support wherein the binder has an affinity for the glycosylated fraction of the protein.

Abstract: Method of detecting chronic exposure of an organism to a stressor, and for evaluating biological damage due to chronic exposure to sublethal levels of stressors and kits for carrying out the method are disclosed. The methods comprise: (a) sampling at least one organism in order to determine whether it has been chronically exposed to a sublethal concentration of one or more stressors in its environment, under sampling conditions that do not induce any additional heat shock protein (hsp) response in the organism; (b) obtaining a sample of cells or secretions of said organism, suspected of having elevated levels of heat shock proteins and solubilizing the heat shock proteins in the sample; and (c) measuring the concentration of a heat shock protein in said sample.

Abstract: This invention discloses a population of cells which have been preserved in non-frozen hydrated form, and which have been chemically treated in a manner that renders them metabolically inert and free of proteolytic enzyme activity, but without significantly altering the cell surface proteins that are of interest in flow cytometry. The absence of alteration of the surface proteins is indicated by the ability of the surface proteins to bind to monoclonal antibodies that bind to untreated proteins of the same type, with approximately the same affinity as proteins on untreated cells. The preserved cells and their surface antigens are stable for at least a month when stored at 4.degree. C. in buffered saline solution. These cell preparations are useful as quality control (QC) reagents for processes such as calibrating and standardizing flow cytometry equipment, and for use as "unknown" test samples for QC testing programs, or as patient specimens for archival storage and subsequent retrospective analysis.

Abstract: Lipid is determined quantitatively by treating a sample with a surfactant in an aqueous medium to obtain a liquid sample dispersion, then reacting the dispersion with a reagent containing cupric ion and bicinchoninic acid, and measuring a colored state developed by complex formation of bicinchoninic acid with cuprous ion formed from cupric ion in the presence of lipid. This method can be effectively applied to determination of amphiphilic lipid having a tendency of gathering in an aqueous medium. Further, two different species interfering with each other in quantitative determination thereof are determined respectively by conducting two different determination methods on the same sample followed by calculation using the values obtained.

Abstract: A cyanide-free lytic reagent composition and method for measuring the total hemoglobin concentration in a blood sample, for counting the number of leukocytes and for deferential counting of three leukocyte subpopulations including lymphocytes, monocytes, and granulocytes are described. The cyanide-free lytic reagent composition includes a hemolytic surfactant chosen from quaternary ammonium salts, pyridinium salts, organic phosphate esters, and alkyl sulfonates to lyse erythrocytes and release hemoglobin, and an organic ligand chosen from triazole and its derivatives, tetrazole and its derivatives, alkaline metal salts of oxonic acid, melamine, aniline-2-sulfonic acid, quinaldic acid, 2-amino-1,3,4-thiadiazole, triazine and its derivatives, urazole, DL-pipecolinic acid. isonicotinamide, anthranilonitrile, 6-aza-2-thiothymine, adenine, 3-(2-thienyl)acrylic acid, benzoic acid and alkali metal and ammonium salts of benzoic acid, and pyrazine and its derivatives to form a stable chromogen with hemoglobin.

Abstract: The invention relates to a composition comprising among others a fibrinopeptide A releasing compound. Furthermore the invention relates to the use of the composition as calibrator in plasma containing fibrinogen. A test kit comprising the said composition and a method to determine soluble fibrin also belong to the invention.

Abstract: The invention relates to a plasma which can be used as a calibrator in coagulation tests which detect the degradation of factor V by activated protein C, to the preparation of such a plasma and to its use.

Abstract: A process for the elimination of labile glycohaemoglobin from a sample comprises adding to the sample a reagent comprising a temperature dependent buffer having a pH/temperature coefficient of -0.011 or less, and a method for measuring the concentration of stable glycohaemoglobin in sample containing stable and labile glycohaemoglobin fractions.

Abstract: Provided is a method of preparing dye-based reference materials useful for calibrating or qualifying instrument systems that are diagnostic spectroscopically for hemoglobin and CO-ox fractions. The dye-based reference materials are non-proteinaceous and may be interpreted by CO-oximeter instrument systems as providing a spectrum substantially equivalent to the spectrum of blood, particularly with regard to hemoglobin and hemoglobin CO-ox fractions. Dye-based reference materials may be formulated to provide CO-ox fractions approximating those seen in a clinical setting, including normal physiological CO-ox fractions. The dye-based reference materials may be combined with other ingredients thus making the materials useful as references for pH and blood gas instruments and/or electrolyte instruments in addition to CO-oximeter instrument systems.

Abstract: In high volume laboratory analysis of patient medical specimens, control materials are inserted at periodical intervals (e.g. once per eight hours) and analyzed. If the results of the analysis deviate from the mean according to statistical rules, the run of analyses prior to the insertion of control materials has in the past been rejected, often causing a substantial loss of results because the control materials were not inserted sufficiently frequently. According to the invention the patient mean of a test is determined, and when the mean deviates from the predetermined mean by more than a selected amount, this determination is used, not to reject the run, but rather to trigger insertion and analysis of control materials. If the analysis of control materials shows that the run is in control, the analyses made prior thereto are reported and the run is resumed. If the control material analysis shows that the run is out of control, then the prior analyses are rejected.

Abstract: The present invention relates to a method for stimulating hematopoiesis in a mammal comprising administration of a therapeutically effective amount of a hemoglobin, including recombinant hemoglobin, and methods for treating cytopenias. These cytopenias include anemia, thrombocytopenia, lymphopenia, neutropenia and the like. The stimulation of hematopoiesis can occur both in vivo and ex vivo, as in the treatment of cytopenias associated with disease states, in cell culture or ex vivo expansion of bone marrow cells.

Abstract: Detectably labelled annexines and compositions thereof are disclosed. Also disclosed are methods for diagnosing a disruption or activation of the hemostatic system or a prothrombotic state in an individual suspected of having a hemostatic disorder, by contacting the blood of said individual with an annexine, and detecting whether an annexine-platelet complex is formed.

Abstract: A nutrient medium comprising amino acids and other substrates used by mammalian or insect cells in protein synthesis that are either double-labeled with .sup.2 H and .sup.13 C or triple-labeled with .sup.2 H, .sup.13 C and .sup.15 N is disclosed. The invention is also directed to a method for producing the nutrient medium.

Abstract: The invention is a rapid, continuous test for glycated hemoglobin using a non-equilibrium affinity binding method. Agarose beads derivatized with 3-aminophenylboronic acid specifically bind glycated hemoglobin. This solid phase is incorporated into a sample processor card, modified to mix and to separate the test solution from the solid phase prior to absorbance readings. Two absorbance readings are made on the test solution, one immediately after mixing the reagent/diluent with the specimen, and one after a significant amount of binding has occurred. A linear correlation between total glycated hemoglobin and hemoglobin A.sub.1c permits standardization and reporting of units equivalent to % hemoglobin A.sub.1c. Stable glycated hemoglobin solutions for use as standards in the assay, and a method for preparing the standards are also disclosed.

Abstract: A method for stabilizing the functional activity of annexins in a biological fluid sample is provided.

Abstract: The present invention relates to immunoglobulin-binding artificial proteins (repetitively linked-proteins) which result when either one of or several numbers of the IgG-binding domains in protein A molecule is defined as a unit, and repetitive multiple links are made thereof. These repetitive proteins exhibit a superior ability for IgG purification to naturally occurring protein A, and the mixture of these repetitive proteins may be used as excellent molecular weight markers.

Abstract: The present invention is directed to the assay and purification of proteins, and particularly to the non-radioactive assay and purification of protein kinases, phosphatases and protease by incubating the enzyme with a substrate modified peptide to form a product modified peptide under conditions where the enzyme is active. The product modified peptide and substrate modified peptide are then separated, and the product modified peptide is measured. The present invention is also directed to kits and bioreagents for performing the assays.

Abstract: A reference solution for calibrating and monitoring blood gas instrumentation that has a shelf line of two years or greater is disclosed. The solution is contained in a closed container having a gas or gas mixture that is inert to the reference solution and comprises an aqueous mixture containing a hemoglobin, a source of bicarbonate ions and an organic buffer. The solution optionally contains a methemoglobin reducing system, reference concentrations of selected electrolytes, a polyphosphate compound and antibiotics. The ampule is subsequently opened and the solution is equilibrated with a gas mixture having components which provide gasses in a physiological range to the solution. The solution is characterized by exhibiting properties similar to fresh blood subsequent to equilibration.

Abstract: The invention relates to a composition for stabilizing proteins for long term dry storage and superior recovery of their native protein structure for extended reconstituted stability at 2.degree.-8.degree. C. The composition comprises: 1) a defibrinated sodium-free blood plasma, 2) a glass-forming sugar, 3) a serum albumin and/or a gelatin, and 4) a potassium salt. In another aspect, the present invention relates to a method for stabilizing a protein for long term dry storage using the above mentioned composition.

Abstract: A hematology control product comprising leukocyte analogs is described. The analogs comprise red blood cells which simulate at least two physical properties of human leukocytes. A method for making leukocyte analogs from blood cells having desired physical properties is also described. The process comprises expanding the cell volume, changing the hemoglobin content of the cell and fixing the cell. Generally, the monocyte and lymphocyte analogs leak hemoglobin from the cell while the eosinophil analog has the hemoglobin precipitated in the cell. A further method is described to use the control product to determine whether an automatic instrument is operating within manufacturer's specification.

Abstract: A method for preparing a solventless protein standard is disclosed in which a solventless dye indicator and a predetermined amount of solventless protein are placed in an appropriate receptacle such as the well of a multiwell plate. This results in a solventless protein standard in which the solventless protein and the solventless dye are contained within the same receptacle. When an appropriate solvent is added to the receptacle, the protein and dye react together to produce a color change which is detectable, and which can be used as a standard for a protein assay using that dye. Also claimed is the solventless protein assay standard produced by the process.

Abstract: The invention concerns peptides which have a partial sequence of lipoprotein (a) as well as their use for the purification of antibodies by means of affinity chromatography, as an immunogen for the production of antibodies and as a standard in an immunological test or as a competitive hapten in an agglutination test.

Abstract: There is described a positive calibrator/control composition for use in assays for the detection of antibodies to infectious disease agents. The composition includes a composite antibody of a nonspecific IgM immunoglobulin moiety covalently linked to a specific, non-IgM antibody moiety. Also described is an assay method which utilizes the positive calibrator or control composition.

Abstract: Appendicitis can be detected in human beings suspected of having appendicitis by determining a threshold level of 10 mg/liter of .sigma.-hydroxyhippuric acid in the urine of such humans. This threshold level can be determined by qualitative, semiquantitative, or quantitative methods including HPLC (high pressure liquid chromatography), TLC (thin layer chromatography), radioimmunoassay, colorimetric tests, NMR (nuclear magnetic resonance), mass spectrometry, electrophoresis, monoclonal antibody tests, and enzymatic tests. The absence of appendicitis can be established by the presence of .sigma.-hydroxyhippuric acid in concentrations less than about 10 mg/liter in a urine sample.

Abstract: Disclosed is a serum free control reagent formulation useful for the determination of a pre-selected analyte. The formulation involves an aqueous solution of a predetermined amount of the analyte together with a polymerized quaternary salt of di- or mono- allyl, di- or tri- alkyl ammonium characterized by the formulae: ##STR1## where R is straight or branched chain alkyl of 1 to 4 carbon atoms, n is a number of at least 9 and .theta. represents a counteranion. The formulation typically contains a buffer to maintain its pH at a level of about 7.5 and a preservative.

Abstract: An eliminating agent used for the measurement of the amount of glycosylated hemoglobins in a blood sample is provided. The eliminating agent comprises condensed phosphoric acids and/or the salts thereof as the main ingredient, wherein the agent eliminates labile glycosylated hemoglobin A.sub.1c into non-glycosylated hemoglobin and glucose. There is also provided a reagent comprising the eliminating agent and a hemolysis agent, which is used for the measurement of the amount of glycosylated hemoglobins; and an eluent comprising the eliminating agent, which is used for the separation of glycosylated hemoglobins in blood samples by ion-exchange chromatography to measure the amount of the glycosylated hemoglobins. A method for measuring the amount of glycosylated hemoglobin A.sub.1c in a blood sample involves the use of the eliminating agent, the reagent comprising the eliminating agent and the hemolysis agent, and/or the eluent.

Abstract: The present invention relates to a biosynthetic cerebrospinal fluid control and method of use. Additionally, this invention relates to the isolation and purification of stable liquid human prealbumin, a component in the biosynthetic cerebrospinal fluid control.

Abstract: Disclosed is an improvement to the assay for protein in urine involving the use of a molybdate or tungstate salt and an indicator dye which forms a complex with molybdate or tungstate whose absorption band is shifted in the presence of protein. The improvement involves the use of an ionizable phosphate containing compound characterized by the formula: ##STR1## to reduce background interference caused by constituents normally present in urine.

Abstract: This invention primarily is directed to a hematology reference control solution, the three separate white cell control portions thereof consisting of three types of fixed red cells of determined size distribution for checking the operation of a particle analyzing instrument, including its predetermined lower and upper threshold settings for each class or subclass of leukocytes.For preparing a human granulocyte analogue, nurse shark erythrocytes are altered and fixed in a chilled solution to simulate in number, size and distribution the granulocytes in human whole blood.

Abstract: A hematology control product comprising leukocyte analogs is described. The analogs comprise red blood cells which simulate at least two physical properties of human leukocytes. A method for making leukocyte analogs from blood cells having desired physical properties is also described. The process comprises expanding the cell volume, changing the hemoglobin content of the cell and fixing the cell. Generally, the monocyte and lymphocyte analogs leak hemoglobin from the cell while the eosinophil analog has the hemoglobin precipitated in the cell. A further method is described to use the control product to determine whether an automatic instrument is operating within manufacturer's specification.

Abstract: A stable reference solution for calibrating and monitoring blood gas instrumentation is disclosed. The solution comprises an aqueous mixture containing a hemoglobin solution derived from a mammalian source which comprises at least about 95% reduced hemoglobin. The solution additionally contains a bicarbonate buffer and a metal catalyzed methemoglobin reducing system and an organic buffer. To provide a control element having a variety of properties similar to fresh, whole, human blood, the reference solution is stored in a sealed ampule under an inert atmosphere containing CO.sub.2 until just prior to use. The ampule is subsequently opened and the solution is equilibrated with a gas mixture having components which provide gasses in a physiological range to the solution. The solution is characterized by exhibiting properties similar to fresh blood subsequent to equilibration and an extended storage life prior to equilibration.

Abstract: A stable reference solution for calibrating and monitoring blood gas instrumentation is disclosed. The solution comprises an aqueous mixture containing a hemoglobin solution derived from a mammalian source which comprises at least about 95% reduced hemoglobin. The solution additionally contains a metal catalyzed methemoglobin reducing system, reference concentrations of selected electrolytes and an organic buffer. To provide a control element having a variety of properties similar to fresh, whole, human blood, the reference solution is stored in a sealed ampule under an inert atmosphere containing CO.sub.2 until just prior to use. The ampule is subsequently opened and the solution is equilibrated with a gas mixture having components which provide gasses in a physiological range to the solution. The solution is characterized by exhibiting properties similar to fresh blood subsequent to equilibration and an extended storage life prior to equilibration.

Abstract: An eliminating agent used for the measurement of the amount of glycosylated hemoglobins in a blood sample is provided. The eliminating agent comprises condensed phosphoric acids and/or the salts thereof as the main ingredient, wherein the agent eliminates labile glycosylated hemoglobin A.sub.1c into non-glycosylated hemoglobin and glucose. There is also provided a reagent comprising the eliminating agent and a hemolysis agent, which is used for the measurement of the amount of glycosylated hemoglobins; and an eluent comprising the eliminating agent, which is used for the separation of glycosylated hemoglobins in blood samples by ion-exchange chromatography to measure the amount of the glycosylated hemoglobins. A method for measuring the amount of glycosylated hemoglobin A.sub.1c in a blood sample involves the use of the eliminating agent, the reagent comprising the eliminating agent and the hemolysis agent, and/or the eluent.

Abstract: A stabilized prolactin calibrator is disclosed. The calibrator has a pH from about 5.5 to about 9.0, and contains prolactin in a 0.01 M to 0.2 M matrix of tris-(hydroxymethyl)aminomethane which additionally contains about 0.3 to 4 percent of bovine serum albumin, about 0.05 to 0.2 percent of sodium azide and from about 0.01 to about 0.2 mole/liter NaCl.

Abstract: Disclosed herein is a method of labelling a sugar at its reducing end by using 1-(p-methoxyphenyl)-3-methyl-5-pyrazolone, thereby analyzing said sugar with high sensitivity, and to a kit to be used for sugar labelling by this method.

Abstract: This invention provides a primary standard and/or secondary standards for assay for glycated proteins in samples such as blood. The primary standard is composed of a polymer or copolymer of an amino acid, such as lysine, serine or those listed on table 37 (pages 100-110 of the second edition of Organic Chemistry by Robert Morris and Robert Nielson-Boyd) glycated with a known amount of glucose, preferably .sup.14 C glucose or .sup.3 H glucose, and free of unbound glucose. The preferred secondary standards are composed of glycated native protein per se, or a mixture of a glycated native protein and native protein that has been standardized against a primary standard to give the actual glycated protein value. These primary standards and secondary standards may be packaged and sold as a kit that contains a primary standard and/or a secondary standard and the reagents needed to perform the glycated protein assay.

Abstract: The present invention provides a process for the determination of fructosamine in body fluids using as a standard, a solution which contains a peptide or protein, the amino acid units of which consist of at least 25% of lysine and/or ornithine and is present in glycosylated form.The present invention also provides a standard solution for the determination of fructosamine containing a peptide or protein, the amino acid unit content of which consists of at least 25% lysine and/or ornithine and is present in glycosylated form, and a method of calibrating such a standard solution.

Abstract: Human tumor associated Thomsen-Friedenreich (TF) antigen is purified from adenocarcinoma conditioned media, adenocarcinoma cell detergent extracts or plural effusion fluid by affinity chromatography using an insolubilized TF-specific monoclonal antibody, MAb 49H.8. The TF antigen is a glycoprotein characterized by a non-cryptic Gal .beta.(1.fwdarw.3) GalNAc epitope, a molecular weight in excess of 1,000,000 daltons, and extractability with perchloric acid, the epitope being sensitive to alkali and periodate but resistant to acid. A heterologous sandwich immunoassay has been developed for human TF antigen using a monoclonal antibody as the catcher and labelled peanut agglutinin as the probe. Since human TF antigen is shed by tumor cells, a positive determination of the TF antigen in a patient sample indicates the presence of cancer.

Abstract: For the determination of fructosamine in body fluids a solution containing fructosamine and albumin is used as the standard solution for calibration which standard solution is essentially free of glucose and which has a pH between 5.0 and 6.0 and contains at least 10 mmol/l buffer.

Abstract: A stable reference solution for calibrating and monitoring blood gas instrumentation is disclosed. The solution comprises an aqueous mixture containing a hemoglobin solution derived from a mammalian source which comprises at least about 95% reduced hemoglobin. The solution additionally contains a bicarbonate buffer and a metal catalyzed methemoglobin reducing system and an organic buffer. To provide a control element having a variety of properties similar to fresh, whole, human blood, the reference solution is stored in a sealed ampule under an inert atmosphere containing CO.sub.2 until just prior to use. The ampule is subsequently opened and the solution is equilibrated with a gas mixture having components which provide gasses in a physiological range to the solution. The solution is characterized by exhibiting properties similar to fresh blood subsequent to equilibration and an extended storage life prior to equilibration.

Abstract: The invention relates to a solution for controlling the performance of the ionic exchange chromatography column of HPLC apparatuses, and more particularly of the AUTO A1C HA 8110-8111 apparatus with a MICROPEARL S-F-W-A1C column, said solution being made up of a lyophilic hemolysate comprising hemoglobin, monobasic potassium phosphate, dibasic potassium phosphate, .alpha.-D-ribose, guanine, cytosine, thymine and uracil, and a solvent, for restoring the lyophilic hemolysate, comprising a nonionic surface active agent such as TRITON X-100, a bacteriostatic agent, such as for instance sodium azide, and water, and it also relates to a process for the production of said solution.

Abstract: A liquid control standard for the use in the quality assurance of blood analysis instrumentation systems is disclosed. The liquid control standard is able to act as a control standard for blood gas instrumentation systems measuring pH, pCO.sub.2 and pO.sub.2 of blood, as a liquid control standard for ion selective electrode instrumentation systems for the measuring of electrolytes such as ionized calcium and total calcium as well as Na, K and Li ions in the blood and, optionally, as a control standard for a co-oximeter measuring the amount of total hemoglobin present in the blood and the relative amounts of other hemoglobin fractions present in the blood.

Abstract: A stable human serum based control for the assay of Total LD and CK and their isoenzymes. This control may be lyophilized and reconstituted and still provide the same enzyme activity prior to lyophilization, for seven (7) days after reconstitution, if stored in the dark at or about 2.degree.0 to 8.degree. C. No thiol compounds other than the amount normally used to purify CK isoenzymes are found in this highly stable control.

Abstract: A liquid control standard for the use in the qualilty assurance of blood analysis instrumentation systems is disclosed. The liquid control standard is able to act as a control standard for blood gas instrumentation systems measuring pH, pCO.sub.2 and pO.sub.2 of blood, as a liquid control standard for ion selective electrode instrumentation systems for the measuring of electrolytes such as ionized calcium and total calcium as well as Na, K and Li ions in the blood and, optionally, as a control standard for a co-oximeter measuring the amount of total hemoglobin present in the blood and the relative amounts of other hemoglobin fractions present in the blood.

Abstract: A method for calibrating an instrument for using that instrument to obtain at least one light-related signal from particles under analysis comprises directing an incident beam of light at calibration particles having one or more known characteristics related to the particles expected to be analyzed. Both a light signal and a noise signal from the calibration particles are detected. A measurement is made of the ratio of the detected light signal to the detected noise signal, and that measurement is reported. The measured ratio is then compared to a predetermined ratio which represents a threshold for minimum instrument performance. This method further includes adjusting, if the predetermined ratio has not been attained, the operation of the instrument, while the calibration particles are within the incident beam of light, until the measured ratio reaches the predetermined ratio whereby the instrument is calibrated for subsequently obtaining the light signal from particles to be analyzed.

Abstract: Disclosed herein is a composition useful for stabilizing diagnostic reagent which functions to react with a specimen to determine the presence or absence of a biological condition comprising about 0.01 to 35 parts by weight protein or peptide and either (A) about 1 to 90 parts by weight of a saccharide polyol selected from the group consisting of corn syrup and dextrose and optionally up to about 25 parts by weight of a pyrrol, or (B) about 1 to 90 parts by weight of a saccharide polyol and about 0.01 to 25 parts by weight of a pyrrol. Also disclosed is a method of stabilizing such diagnostic reagents comprising using the stabilizing composition, and a diagnositc device comprising a non-absorbent base carrying at least one deposition area in which is carried the evaporative residue of such diagnostic reagent and the stabilizing composition.

Abstract: A method and reagent useful therein are cyanide-free and capable of providing a rapid indication, e.g., less than 30 seconds, of total hemoglobin in a blood sample, so as to fine particular application in automated hematological instrumentation. The novel reagent comprises an ionic surfactant, a pH of at least about 11.3 and is free of ionic cyanide. The ionic surfactant itself can impart the required pH or a strong base independent of such surfactant may be included.

Abstract: This invention discloses a multiple control standard for the use in the quality assurance of blood analysis instrumentation systems. The liquid control standard is able to act as a control standard for blood gas instrumentation systems measuring pH, pCO2 and pO.sub.2 of blood, as a control standard for a co-oximeter measuring the amount of total hemoglobin present in the blood and the relative amounts of other hemoglobin fractions present in the blood, and as a liquid control standard for ion selective electrode instrumentation systems for the measuring of electrolytes such as Na, K, Li and Ca ions in the blood.

Abstract: Inclusion in a blood sample of an isomer of glucose which is capable of replacing glucose in blood cell metabolism ensures accuracy of glucose assay.