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The invention relates to liquid compositions for use with hair removal devices comprising a silicone polyether block copolymer comprising from 1% to 50%, by weight of polyethylene oxide, from 20% to 90% by weight of polypropylene oxide and from 1% to 20%, by weight of silicone for improved lubrication.

1. A composition dispensing hair removal device, said device comprising a composition comprising from about 0.1% to about 60% by weight of a silicone polyether block copolymer wherein said silicone polyether block copolymer comprises from about 1 to about 50%, by weight of polyethylene oxide, from about 20% to about 90% by weight of polypropylene oxide and from about 1% to about 20%, by weight of silicone. 2. The device according to claim 1, wherein said silicone polyether block copolymer comprises from about 1% to about 30%, by weight of polyethylene oxide, from about 20% to about 80% by weight of polypropylene oxide and from about 1 to about 20%, by weight of silicone. 3. The device according to claim 1, wherein said silicone polyether block copolymer comprises from about 15% by weight of silicone. 4. The device according to claim 1, wherein said silicone polyether block copolymer has a molecular weight of from about 10000 to about 19000. 5. The device according to claim 1, wherein said silicone polyether block copolymer has a molecular weight of from about 10000 to about 15000. 6. The device according to claim 1, wherein said silicone polyether block copolymer has a ratio of polyethylene oxide to polypropylene oxide of from about 2.0 to about 0.1. 7. The device according to claim 6, wherein said silicone polyether block copolymer has a ratio of polyethylene oxide to polypropylene oxide of from about 0.6 to 0.25. 8. The device according to claim 1, wherein said composition further comprises from about 0.1% to about 8% by weight of a water soluble polymer and preferably wherein the ratio of said water soluble polymer to said silicone block copolymer is from about 1:5 to about 5:1. 9. The device according to claim 8, wherein said water soluble polymer is selected from polyethylene oxide, polyvinyl pyrrolidone, polyacrylamide, polyhydroxymethacrylate, polyvinyl imidazoline, polyethylene glycol, polyvinyl alcohol, polyhydroxyethymethacrylate, guars, celluloses, modified celluloses and mixtures thereof. 10. The device according to claim 5, wherein said water soluble polymer is polyethylene oxide having an average molecular weight of at least about 300000. 11. The device according to claim 10, wherein said polyethylene oxide has an average molecular weight of from about 1 million to about 5 million. 12. The device according to claim 1, wherein said composition further comprising from about 0.1% to about 8%, by weight of the lubricating material of a copolymer of polyethylene oxide and polypropylene oxide. 13. The device according to claim 1 wherein said composition comprises from about 0.1% to about 5% of a thickening agent and at least about 30% by weight of water. 14. The device according to claim 1, wherein said device comprises a handle connected to a hair removal head, wherein said handle comprises a cavity for housing said composition disposed within said handle and an actuator adapted to displace said composition from said cavity to a fluid dispensing member. 15. The device according to claim 10, wherein said fluid dispensing member comprises an elongated contact region forming at least one dispensing orifice. 16. The device according to claim 11, wherein said elongate elastomeric contact region forms a one way valve, preferably selected from a flap valve, a slit valve, a duckbill valve and a combination thereof. 17. A personal care composition comprising from about 40% to about 95% by weight of water, about 1% to about 6% by weight of a volatile post foaming agent and from about 0.1% to about 60% by weight of silicone polyether block copolymer wherein said silicone polyether block copolymer comprises at comprises from about 1 to about 50%, by weight of polyethylene oxide, from about 20% to about 90% by weight of polypropylene oxide and from about 1 to about 20%, by weight of silicone.

The invention relates to liquid compositions for use with hair removal devices comprising a silicone polyether block copolymer comprising from 1% to 50%, by weight of polyethylene oxide, from 20% to 90% by weight of polypropylene oxide and from 1% to 20%, by weight of silicone for improved lubrication.1. A composition dispensing hair removal device, said device comprising a composition comprising from about 0.1% to about 60% by weight of a silicone polyether block copolymer wherein said silicone polyether block copolymer comprises from about 1 to about 50%, by weight of polyethylene oxide, from about 20% to about 90% by weight of polypropylene oxide and from about 1% to about 20%, by weight of silicone. 2. The device according to claim 1, wherein said silicone polyether block copolymer comprises from about 1% to about 30%, by weight of polyethylene oxide, from about 20% to about 80% by weight of polypropylene oxide and from about 1 to about 20%, by weight of silicone. 3. The device according to claim 1, wherein said silicone polyether block copolymer comprises from about 15% by weight of silicone. 4. The device according to claim 1, wherein said silicone polyether block copolymer has a molecular weight of from about 10000 to about 19000. 5. The device according to claim 1, wherein said silicone polyether block copolymer has a molecular weight of from about 10000 to about 15000. 6. The device according to claim 1, wherein said silicone polyether block copolymer has a ratio of polyethylene oxide to polypropylene oxide of from about 2.0 to about 0.1. 7. The device according to claim 6, wherein said silicone polyether block copolymer has a ratio of polyethylene oxide to polypropylene oxide of from about 0.6 to 0.25. 8. The device according to claim 1, wherein said composition further comprises from about 0.1% to about 8% by weight of a water soluble polymer and preferably wherein the ratio of said water soluble polymer to said silicone block copolymer is from about 1:5 to about 5:1. 9. The device according to claim 8, wherein said water soluble polymer is selected from polyethylene oxide, polyvinyl pyrrolidone, polyacrylamide, polyhydroxymethacrylate, polyvinyl imidazoline, polyethylene glycol, polyvinyl alcohol, polyhydroxyethymethacrylate, guars, celluloses, modified celluloses and mixtures thereof. 10. The device according to claim 5, wherein said water soluble polymer is polyethylene oxide having an average molecular weight of at least about 300000. 11. The device according to claim 10, wherein said polyethylene oxide has an average molecular weight of from about 1 million to about 5 million. 12. The device according to claim 1, wherein said composition further comprising from about 0.1% to about 8%, by weight of the lubricating material of a copolymer of polyethylene oxide and polypropylene oxide. 13. The device according to claim 1 wherein said composition comprises from about 0.1% to about 5% of a thickening agent and at least about 30% by weight of water. 14. The device according to claim 1, wherein said device comprises a handle connected to a hair removal head, wherein said handle comprises a cavity for housing said composition disposed within said handle and an actuator adapted to displace said composition from said cavity to a fluid dispensing member. 15. The device according to claim 10, wherein said fluid dispensing member comprises an elongated contact region forming at least one dispensing orifice. 16. The device according to claim 11, wherein said elongate elastomeric contact region forms a one way valve, preferably selected from a flap valve, a slit valve, a duckbill valve and a combination thereof. 17. A personal care composition comprising from about 40% to about 95% by weight of water, about 1% to about 6% by weight of a volatile post foaming agent and from about 0.1% to about 60% by weight of silicone polyether block copolymer wherein said silicone polyether block copolymer comprises at comprises from about 1 to about 50%, by weight of polyethylene oxide, from about 20% to about 90% by weight of polypropylene oxide and from about 1 to about 20%, by weight of silicone.

A method for in vivo, ex vivo and in vitro regeneration of cartilage and collagen. In vivo, ex vivo and in vitro regeneration and de novo formation of articular cartilage and collagen by intermittently applied hydrostatic pressure. The application of external interval loading consisting of repeated periods of applied hydrostatic pressure followed and interrupted by periods of recovery. The application of the intermittent hydrostatic pressure at physiological levels 5-10 MPA for an interval of 4 hours followed by a recovery period up to about 20 hours, said pressure applied to the cartilage cells in vitro, explants of cartilage ex vivo and in vivo to cartilage that remains intact within to joint space of diarthrotic joints. The interval loading results in the selective inhibition of matrix degrading enzymes, pro-inflammatory cytokines and chemokines that attract inflammatory cells into the joint cavity and in selective decrease of gene expression of growth factors that are inhibitory to type II collagen expression.

1. A method of treating diseased, aged or injured osteoarthritic cartilage using pressure treated chondrocytes, said chondrocytes releasing a lowered level, when compared to non-treated osteoarthritic chondrocytes, of at least one protein selected from the group consisting of: (i) matrix metalloproteinase-2 (MMP-2); (ii) interleukin-6 (IL-6); and (iii) macrophage chemottractant protein-1 (MCP-1); wherein said regenerated levels of aggrecan in pressure treated osteoarthritic chondrocytes are increased to levels between 4 and 7%, wet weight, when compared to pathological levels between 0.1% and 1%, wet weight, of non-treated osteoarthritic chondrocytes; and wherein said regenerated levels of collagen type II in pressure treated osteoarthritic chondrocytes are increased to levels between 10% and 20%, wet weight, when compared to pathological levels between 1% and 10%, wet weight, of non-treated osteoarthritic chondrocytes. 2. The pressure treated osteoarthritic chondrocytes of claim 1 which are human osteoarthritic chondrocytes. 3. The pressure treated osteoarthritic chondrocytes of claim 2 in a culture medium. 4. The pressure treated osteoarthritic chondrocytes of claim 1 having a lowered level of MMP-2. 5. The pressure treated osteoarthritic chondrocytes of claim 1 having a lowered level of MMP-2, IL-6, and MCP-1. 6. The pressure treated osteoarthritic chondrocytes of claim 2 having a lowered level of MMP-2. 7. The pressure treated osteoarthritic chondrocytes of claim 2 having a lowered level of MMP-2, IL-6, and MCP-1. 8. The pressure treated osteoarthritic chondrocytes of claim 3 having a lowered level of MMP-2. 9. The pressure treated osteoarthritic chondrocytes of claim 3 having a lowered level of MMP-2, IL-6, and MCP-1. 10. The pressure treated osteoarthritic chondrocytes of claim 1 further releasing an increased level of FGF (fibroblast growth factor) when compared to osteoarthritic chondrocytes not treated with pressure. 11. A preparation of pressure treated osteoarthritic chondrocytes isolated from a diseased, aged or injured osteoarthritic cartilage, having increased production of: aggrecan from levels of between 0.1% and 1%, wet weight, of osteoarthritic chondrocytes not treated with pressure, to regenerated levels of aggrecan between 4% and 7%, wet weight; and type II collagen from levels of between 1% and 10%, wet weight, of osteoarthritic chondrocytes not treated with pressure, to regenerated levels of between 10 and 20%, wet weight. 12. The pressure treated osteoarthritic chondrocytes of claim 11 wherein said regeneration and pressure treatment is performed under intermittently applied hydrostatic pressure of between about 0.5 MPa and about 30 MPa, applied at a frequency of about 0.1 Hz to about 10 Hz, for a period of about 1 to about 8 hours, followed with a constant atmospheric pressure applied for a period of about 16 to 23 hours, wherein said period of hydrostatic pressure and said period of constant atmospheric pressure are repeated for about 4 to about 100 days. 13. The pressure treated osteoarthritic chondrocytes of claim 11 wherein, before pressure treatment, levels of between 0.1% and 1%, wet weight, of aggrecan and levels of between 1% and 10%, wet weight, of type II collagen are measured in injured, diseased or aged metabolically inactive osteoarthritic chondrocytes isolated from a diseased, aged or injured osteoarthritic cartilage before pressure treatment and wherein said levels of between 4% and 7%, wet weight, of aggrecan and levels of between 10% and 20%, wet weight, of type II collagen are regenerated levels measured in said regenerated and said pressure activated chondrocytes after the regeneration and pressure treatment. 14. The pressure treated osteoarthritic chondrocytes of claim 13 wherein said injured, degenerated or aged metabolically inactive osteoarthritic chondrocytes are submitted to said regeneration and pressure treatment for a number of repetitions and such a period of time that is needed for said levels of aggrecan or Type II collagen to reach said regenerated levels. 15. The pressure treated osteoarthritic chondrocytes of claim 12 wherein said intermittently applied hydrostatic pressure is between about 1 MPa and about 20 MPa and is applied at a frequency of about 1 Hz. 16. The pressure treated osteoarthritic chondrocytes of claim 15 wherein said intermittently applied hydrostatic pressure is between about 5 MPa and about 10 MPa, applied at a frequency of about 1 Hz. 17. The pressure treated osteoarthritic chondrocytes of claim 14 wherein said intermittently applied hydrostatic pressure is applied for a period of about 4 hours and is followed with a period of about 20 hours of constant atmospheric pressure and wherein said period of hydrostatic pressure and said period of constant atmospheric pressure are repeated for about 7 to about 30 days. 18. The pressure treated osteoarthritic chondrocytes of claim 11 wherein said chondrocytes are human osteoarthritic chondrocytes. 19. The pressure treated osteoarthritic chondrocytes of claim 18 wherein said chondrocytes are autologous.

A method for in vivo, ex vivo and in vitro regeneration of cartilage and collagen. In vivo, ex vivo and in vitro regeneration and de novo formation of articular cartilage and collagen by intermittently applied hydrostatic pressure. The application of external interval loading consisting of repeated periods of applied hydrostatic pressure followed and interrupted by periods of recovery. The application of the intermittent hydrostatic pressure at physiological levels 5-10 MPA for an interval of 4 hours followed by a recovery period up to about 20 hours, said pressure applied to the cartilage cells in vitro, explants of cartilage ex vivo and in vivo to cartilage that remains intact within to joint space of diarthrotic joints. The interval loading results in the selective inhibition of matrix degrading enzymes, pro-inflammatory cytokines and chemokines that attract inflammatory cells into the joint cavity and in selective decrease of gene expression of growth factors that are inhibitory to type II collagen expression.1. A method of treating diseased, aged or injured osteoarthritic cartilage using pressure treated chondrocytes, said chondrocytes releasing a lowered level, when compared to non-treated osteoarthritic chondrocytes, of at least one protein selected from the group consisting of: (i) matrix metalloproteinase-2 (MMP-2); (ii) interleukin-6 (IL-6); and (iii) macrophage chemottractant protein-1 (MCP-1); wherein said regenerated levels of aggrecan in pressure treated osteoarthritic chondrocytes are increased to levels between 4 and 7%, wet weight, when compared to pathological levels between 0.1% and 1%, wet weight, of non-treated osteoarthritic chondrocytes; and wherein said regenerated levels of collagen type II in pressure treated osteoarthritic chondrocytes are increased to levels between 10% and 20%, wet weight, when compared to pathological levels between 1% and 10%, wet weight, of non-treated osteoarthritic chondrocytes. 2. The pressure treated osteoarthritic chondrocytes of claim 1 which are human osteoarthritic chondrocytes. 3. The pressure treated osteoarthritic chondrocytes of claim 2 in a culture medium. 4. The pressure treated osteoarthritic chondrocytes of claim 1 having a lowered level of MMP-2. 5. The pressure treated osteoarthritic chondrocytes of claim 1 having a lowered level of MMP-2, IL-6, and MCP-1. 6. The pressure treated osteoarthritic chondrocytes of claim 2 having a lowered level of MMP-2. 7. The pressure treated osteoarthritic chondrocytes of claim 2 having a lowered level of MMP-2, IL-6, and MCP-1. 8. The pressure treated osteoarthritic chondrocytes of claim 3 having a lowered level of MMP-2. 9. The pressure treated osteoarthritic chondrocytes of claim 3 having a lowered level of MMP-2, IL-6, and MCP-1. 10. The pressure treated osteoarthritic chondrocytes of claim 1 further releasing an increased level of FGF (fibroblast growth factor) when compared to osteoarthritic chondrocytes not treated with pressure. 11. A preparation of pressure treated osteoarthritic chondrocytes isolated from a diseased, aged or injured osteoarthritic cartilage, having increased production of: aggrecan from levels of between 0.1% and 1%, wet weight, of osteoarthritic chondrocytes not treated with pressure, to regenerated levels of aggrecan between 4% and 7%, wet weight; and type II collagen from levels of between 1% and 10%, wet weight, of osteoarthritic chondrocytes not treated with pressure, to regenerated levels of between 10 and 20%, wet weight. 12. The pressure treated osteoarthritic chondrocytes of claim 11 wherein said regeneration and pressure treatment is performed under intermittently applied hydrostatic pressure of between about 0.5 MPa and about 30 MPa, applied at a frequency of about 0.1 Hz to about 10 Hz, for a period of about 1 to about 8 hours, followed with a constant atmospheric pressure applied for a period of about 16 to 23 hours, wherein said period of hydrostatic pressure and said period of constant atmospheric pressure are repeated for about 4 to about 100 days. 13. The pressure treated osteoarthritic chondrocytes of claim 11 wherein, before pressure treatment, levels of between 0.1% and 1%, wet weight, of aggrecan and levels of between 1% and 10%, wet weight, of type II collagen are measured in injured, diseased or aged metabolically inactive osteoarthritic chondrocytes isolated from a diseased, aged or injured osteoarthritic cartilage before pressure treatment and wherein said levels of between 4% and 7%, wet weight, of aggrecan and levels of between 10% and 20%, wet weight, of type II collagen are regenerated levels measured in said regenerated and said pressure activated chondrocytes after the regeneration and pressure treatment. 14. The pressure treated osteoarthritic chondrocytes of claim 13 wherein said injured, degenerated or aged metabolically inactive osteoarthritic chondrocytes are submitted to said regeneration and pressure treatment for a number of repetitions and such a period of time that is needed for said levels of aggrecan or Type II collagen to reach said regenerated levels. 15. The pressure treated osteoarthritic chondrocytes of claim 12 wherein said intermittently applied hydrostatic pressure is between about 1 MPa and about 20 MPa and is applied at a frequency of about 1 Hz. 16. The pressure treated osteoarthritic chondrocytes of claim 15 wherein said intermittently applied hydrostatic pressure is between about 5 MPa and about 10 MPa, applied at a frequency of about 1 Hz. 17. The pressure treated osteoarthritic chondrocytes of claim 14 wherein said intermittently applied hydrostatic pressure is applied for a period of about 4 hours and is followed with a period of about 20 hours of constant atmospheric pressure and wherein said period of hydrostatic pressure and said period of constant atmospheric pressure are repeated for about 7 to about 30 days. 18. The pressure treated osteoarthritic chondrocytes of claim 11 wherein said chondrocytes are human osteoarthritic chondrocytes. 19. The pressure treated osteoarthritic chondrocytes of claim 18 wherein said chondrocytes are autologous.

Methods and compositions are provided for the treatment and diagnosis of diseases related to hyperglycemic conditions, including diabetes, insulin resistance, and the like. Genetic polymorphisms are shown to be associated with disease susceptibility, and their detection is used in the diagnosis of a predisposition to these conditions. The corresponding proteins are useful as targets for therapeutic intervention.

1. A method of treating or preventing the onset of type 2 diabetes in an individual, the method comprising: administering to said individual an inhibitor of CD44. 2. The method of claim 1, wherein the CD44 is expressed on adipose tissue macrophages or adipocytes. 3. The method of claim 1, wherein said inhibitor inhibits CD44 binding to one or more cognate ligands. 4. The method of claim 3, wherein the ligand is osteopontin. 5. The method of claim 3, wherein the ligand is hyaluronic acid. 6. The method of claim 3, wherein the inhibitor is an antibody or fragment thereof. 7. The method of claim 3, wherein the inhibitor is an analog of a CD44 ligand. 8. The method of claim 1, wherein the inhibitor reduces expression of CD44. 9. The method of claim 8, wherein the inhibitor is an antisense oligonucleotide. 10. The method of claim 8, wherein the inhibitor is an RNAi nucleic acid. 11. The method of claim 1 wherein the inhibitor reduces CD44 signaling activity. 12. A method of diagnosing a susceptibility to type 2 diabetes mellitus (T2D) in an individual, comprising determining the presence or absence of a polymorphic allele in a biological sample from said individual, wherein the at least polymorphic allele genetically linked to one or more of CD44, SPP1 and HDC loci, and wherein presence of the allele is indicative of a susceptibility to type 2 diabetes mellitus. 13. The method of claim 12, wherein the polymorphic allele comprises a single nucleotide polymorphism. 14. The method of claim 13, wherein the single nucleotide polymorphism is within an intron or exon of the CD44, SPP1 or HDC loci. 15. The method of claim 13, wherein the single nucleotide polymorphism is within a regulatory region associated with the CD44, SPP1 or HDC loci. 16. The method of claim 14, wherein the SNP is selected from the polymorphisms set forth in SEQ ID NO:1-12. 17. The method of claim 12, further comprising treating said individual with the method set forth in any one of claims 1-11. 18. The method of claim 12, wherein the increased susceptibility is characterized by a relative risk (RR) or odds ratio (OR) of at least 1.2. 19. The method of claim 12, wherein said biological sample is a genetic sample. 20. The method of claim 19, wherein the genetic sample comprises mRNA or a cDNA derived therefrom. 21. A method of diagnosing insulin resistance in an individual, comprising quantitating serum levels of CD44 in said individual. 22. A kit for assessing susceptibility to type 2 diabetes mellitus in an individual, the kit comprising reagents for selectively determining the presence or absence of at least one polymorphic allele in a biological sample from said individual, wherein the polymorphic allele is selected from the polymorphisms set forth in SEQ ID NO:1-12, and wherein the presence of the at least one SNP indicates susceptibility to type 2 diabetes. 23. The kit according to claim 22, comprising probes that specifically bind to at least one sequence set forth in SEQ ID NO:1-12. 24. The kit according to claim 22, further comprising reagents for selectively determining the presence or absence of additional polymorphic alleles associated with a predisposition to type 2 diabetes. 25. The kit according to claim 23, comprising an array of probes that selectively bind to polymorphic alleles associated with a susceptibility to type 2 diabetes.

Methods and compositions are provided for the treatment and diagnosis of diseases related to hyperglycemic conditions, including diabetes, insulin resistance, and the like. Genetic polymorphisms are shown to be associated with disease susceptibility, and their detection is used in the diagnosis of a predisposition to these conditions. The corresponding proteins are useful as targets for therapeutic intervention.1. A method of treating or preventing the onset of type 2 diabetes in an individual, the method comprising: administering to said individual an inhibitor of CD44. 2. The method of claim 1, wherein the CD44 is expressed on adipose tissue macrophages or adipocytes. 3. The method of claim 1, wherein said inhibitor inhibits CD44 binding to one or more cognate ligands. 4. The method of claim 3, wherein the ligand is osteopontin. 5. The method of claim 3, wherein the ligand is hyaluronic acid. 6. The method of claim 3, wherein the inhibitor is an antibody or fragment thereof. 7. The method of claim 3, wherein the inhibitor is an analog of a CD44 ligand. 8. The method of claim 1, wherein the inhibitor reduces expression of CD44. 9. The method of claim 8, wherein the inhibitor is an antisense oligonucleotide. 10. The method of claim 8, wherein the inhibitor is an RNAi nucleic acid. 11. The method of claim 1 wherein the inhibitor reduces CD44 signaling activity. 12. A method of diagnosing a susceptibility to type 2 diabetes mellitus (T2D) in an individual, comprising determining the presence or absence of a polymorphic allele in a biological sample from said individual, wherein the at least polymorphic allele genetically linked to one or more of CD44, SPP1 and HDC loci, and wherein presence of the allele is indicative of a susceptibility to type 2 diabetes mellitus. 13. The method of claim 12, wherein the polymorphic allele comprises a single nucleotide polymorphism. 14. The method of claim 13, wherein the single nucleotide polymorphism is within an intron or exon of the CD44, SPP1 or HDC loci. 15. The method of claim 13, wherein the single nucleotide polymorphism is within a regulatory region associated with the CD44, SPP1 or HDC loci. 16. The method of claim 14, wherein the SNP is selected from the polymorphisms set forth in SEQ ID NO:1-12. 17. The method of claim 12, further comprising treating said individual with the method set forth in any one of claims 1-11. 18. The method of claim 12, wherein the increased susceptibility is characterized by a relative risk (RR) or odds ratio (OR) of at least 1.2. 19. The method of claim 12, wherein said biological sample is a genetic sample. 20. The method of claim 19, wherein the genetic sample comprises mRNA or a cDNA derived therefrom. 21. A method of diagnosing insulin resistance in an individual, comprising quantitating serum levels of CD44 in said individual. 22. A kit for assessing susceptibility to type 2 diabetes mellitus in an individual, the kit comprising reagents for selectively determining the presence or absence of at least one polymorphic allele in a biological sample from said individual, wherein the polymorphic allele is selected from the polymorphisms set forth in SEQ ID NO:1-12, and wherein the presence of the at least one SNP indicates susceptibility to type 2 diabetes. 23. The kit according to claim 22, comprising probes that specifically bind to at least one sequence set forth in SEQ ID NO:1-12. 24. The kit according to claim 22, further comprising reagents for selectively determining the presence or absence of additional polymorphic alleles associated with a predisposition to type 2 diabetes. 25. The kit according to claim 23, comprising an array of probes that selectively bind to polymorphic alleles associated with a susceptibility to type 2 diabetes.

The present invention for the first time discloses a novel small molecular weight enamel matrix polypeptide which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ ID NO: 1 (MPLPPHPGHP GYINFSYEVL TPLKWYQNMI RHPYTSYGYE PMGGWLHHQI IPWSQQTPQ SHA) (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof. The present invention further discloses a pharmaceutical composition consisting of an enamel matrix polypeptide which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ ID NO: 1, a homologue, analogue, or a pharmaceutically acceptable salt thereof, and a suitable pharmaceutical carrier, which further can consist of one or more enamel matrix polypeptides selected from the group of enamel matrix polypeptides which correspond to: a. SEQ ID NO: 2, b. SEQ ID NO: 3 and c. SEQ ID NO: 4.

1. An enamel matrix polypeptide which is at least 80%, such ac 90% identical to the amino acid sequence as shown in SEQ ID NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, and which stimulates the tissue formation phase of a wound healing process. 2. A pharmaceutical composition comprising an enamel matrix polypeptide according to claim 1, and a suitable pharmaceutical carrier 3. A pharmaceutical composition according to claim 2, further comprising one or more enamel matrix polypeptides selected from the group of enamel matrix polypeptides which correspond to: a. SEQ ID NO: 2 (TRAP43), b. SEQ ID NO: 3 (TRAP45), and c. SEQ ID NO: 4 (LRAP56), which stimulates the tissue formation phase of a wound healing process 4. A pharmaceutical composition comprising an acid-extraction of enamel proteins and/or polypeptides derived from developing mammalian tooth buds, which is at least 2× enriched in an enamel matrix polypeptide, which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ ID NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, which stimulates the tissue formation phase of a wound healing process. 5. A pharmaceutical composition comprising an enamel matrix polypeptide which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ 10 NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, which stimulates the tissue formation phase of a wound healing process, which composition consists of all isolated enamel polypeptides and/or proteins with a molecular weight (M.W.)<7 kDa, derivable from a defined amount of developing mammal tooth buds, and a suitable pharmaceutical carrier. 6. A process for producing an enamel matrix polypeptide which is at least 80% identical to the amino acid sequence as shown in SEQ 10 NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, which stimulates the tissue formation phase of wound healing process, comprising: a. Isolating the enamel proteins present in a defined amount of developing animal tooth buds, and b. Removing any protein with a molecular weight (M.W.) >8 kDa from said isolate. 7. A process according to claim 6, wherein the enamel polypeptides are isolated from human, porcine, bovine, rat, mouse and/or sheep developing tooth buds. 8. A pharmaceutical composition comprising proteins with a molecular weight (M.W.) >7 kDa, wherein said composition is produced according to the process of claim 6. 9. A pharmaceutical composition according to claim 2, comprising at least one of said enamel polypeptides produced by synthesis in vitro. 10. A pharmaceutical composition according to claim 2, comprising at least one of said enamel polypeptides that is a purified recombinant polypeptide fragment. 11. A pharmaceutical composition according to claim 2, wherein at least one of said enamel polypeptides is synthetically and/or chemically altered. 12. A pharmaceutical composition according to claim 2, comprising at least one of said enamel polypeptides produces by synthesis in vivo. 13. A pharmaceutical composition according to claim 9, wherein the pharmaceutically acceptable carrier is selected from the group consisting of PGA and PEG. 14. A pharmaceutical composition according to claim 2, further comprising EMO. 15. (canceled) 16. A method of accelerating onset of wound healing comprising administering an enamel matrix polypeptide according to claim 1 to a subject suffering from a wound, in an amount sufficient to accelerate onset of wound healing. 17. A method of accelerating wound healing, comprising administering an enamel matrix polypeptide according to claim 1 to a subject suffering from a wound in an amount sufficient to accelerate wound healing. 18. A method of treating an inflammatory condition, comprising administering a therapeutically effective amount of an enamel matrix polypeptide according to claim 1 to a subject suffering from an inflammatory condition. 19. A method of promoting periodontal soft tissue generation, comprising administering, to a subject in need of such treatment, an enamel matrix polypeptide according to any claim 1 in an amount sufficient to promote periodontal soft tissue regeneration 20. A method of stimulating angiogenesis, comprising administering an enamel matrix polypeptide to a subject in an amount sufficient to generate angiogenesis. 21. (canceled) 22. (canceled)

The present invention for the first time discloses a novel small molecular weight enamel matrix polypeptide which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ ID NO: 1 (MPLPPHPGHP GYINFSYEVL TPLKWYQNMI RHPYTSYGYE PMGGWLHHQI IPWSQQTPQ SHA) (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof. The present invention further discloses a pharmaceutical composition consisting of an enamel matrix polypeptide which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ ID NO: 1, a homologue, analogue, or a pharmaceutically acceptable salt thereof, and a suitable pharmaceutical carrier, which further can consist of one or more enamel matrix polypeptides selected from the group of enamel matrix polypeptides which correspond to: a. SEQ ID NO: 2, b. SEQ ID NO: 3 and c. SEQ ID NO: 4.1. An enamel matrix polypeptide which is at least 80%, such ac 90% identical to the amino acid sequence as shown in SEQ ID NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, and which stimulates the tissue formation phase of a wound healing process. 2. A pharmaceutical composition comprising an enamel matrix polypeptide according to claim 1, and a suitable pharmaceutical carrier 3. A pharmaceutical composition according to claim 2, further comprising one or more enamel matrix polypeptides selected from the group of enamel matrix polypeptides which correspond to: a. SEQ ID NO: 2 (TRAP43), b. SEQ ID NO: 3 (TRAP45), and c. SEQ ID NO: 4 (LRAP56), which stimulates the tissue formation phase of a wound healing process 4. A pharmaceutical composition comprising an acid-extraction of enamel proteins and/or polypeptides derived from developing mammalian tooth buds, which is at least 2× enriched in an enamel matrix polypeptide, which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ ID NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, which stimulates the tissue formation phase of a wound healing process. 5. A pharmaceutical composition comprising an enamel matrix polypeptide which is at least 80%, such as 90% identical to the amino acid sequence as shown in SEQ 10 NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, which stimulates the tissue formation phase of a wound healing process, which composition consists of all isolated enamel polypeptides and/or proteins with a molecular weight (M.W.)<7 kDa, derivable from a defined amount of developing mammal tooth buds, and a suitable pharmaceutical carrier. 6. A process for producing an enamel matrix polypeptide which is at least 80% identical to the amino acid sequence as shown in SEQ 10 NO: 1 (TRAP63), a homologue, analogue, or a pharmaceutically acceptable salt thereof, which stimulates the tissue formation phase of wound healing process, comprising: a. Isolating the enamel proteins present in a defined amount of developing animal tooth buds, and b. Removing any protein with a molecular weight (M.W.) >8 kDa from said isolate. 7. A process according to claim 6, wherein the enamel polypeptides are isolated from human, porcine, bovine, rat, mouse and/or sheep developing tooth buds. 8. A pharmaceutical composition comprising proteins with a molecular weight (M.W.) >7 kDa, wherein said composition is produced according to the process of claim 6. 9. A pharmaceutical composition according to claim 2, comprising at least one of said enamel polypeptides produced by synthesis in vitro. 10. A pharmaceutical composition according to claim 2, comprising at least one of said enamel polypeptides that is a purified recombinant polypeptide fragment. 11. A pharmaceutical composition according to claim 2, wherein at least one of said enamel polypeptides is synthetically and/or chemically altered. 12. A pharmaceutical composition according to claim 2, comprising at least one of said enamel polypeptides produces by synthesis in vivo. 13. A pharmaceutical composition according to claim 9, wherein the pharmaceutically acceptable carrier is selected from the group consisting of PGA and PEG. 14. A pharmaceutical composition according to claim 2, further comprising EMO. 15. (canceled) 16. A method of accelerating onset of wound healing comprising administering an enamel matrix polypeptide according to claim 1 to a subject suffering from a wound, in an amount sufficient to accelerate onset of wound healing. 17. A method of accelerating wound healing, comprising administering an enamel matrix polypeptide according to claim 1 to a subject suffering from a wound in an amount sufficient to accelerate wound healing. 18. A method of treating an inflammatory condition, comprising administering a therapeutically effective amount of an enamel matrix polypeptide according to claim 1 to a subject suffering from an inflammatory condition. 19. A method of promoting periodontal soft tissue generation, comprising administering, to a subject in need of such treatment, an enamel matrix polypeptide according to any claim 1 in an amount sufficient to promote periodontal soft tissue regeneration 20. A method of stimulating angiogenesis, comprising administering an enamel matrix polypeptide to a subject in an amount sufficient to generate angiogenesis. 21. (canceled) 22. (canceled)

The present invention relates to methods for evaluating and/or predicting the outcome of a clinical condition, such as cancer, metastasis, AIDS, autism, Alzheimer's, and/or Parkinson's disorder. The methods can also be used to monitor and track changes in a patient's DNA and/or RNA during and following a clinical treatment regime. The methods may also be used to evaluate protein and/or metabolite levels that correlate with such clinical conditions. The methods are also of use to ascertain the probability outcome for a patient's particular prognosis.

1. A computer-based genomic sequence analysis system comprising: a memory storing at least two genomic sequence datasets including: a tumor sequence dataset comprising genomic sequence strings of a tumor tissue sample of a patient; and a matched normal dataset comprising genomic sequence strings of a normal tissue sample of the same patient; and a sequence analysis engine coupled with the memory and configured to: simultaneously and synchronously read a tumor sequence string from the tumor sequence dataset and a matched normal sequence string from the matched normal sequence dataset; wherein the tumor sequence string is incrementally synchronized with the matched normal sequence string based on a given genomic position; identify a genomic alteration associated with the given genomic position according to a probability derived from reads of the tumor sequence string and of the matched normal sequence string; and store the genomic alteration in a device memory. 2. The system of claim 1, wherein the genomic alteration comprises a genomic variant. 3. The system of claim 2, wherein the genomic variant comprises a somatic variant. 4. The system of claim 2, wherein the genomic variant comprises a germline variant. 5. The system of claim 1, wherein the genomic alteration comprises a single nucleotide polymorphism. 6. The system of claim 1, wherein the genomic alteration comprises an alteration selected from the group consisting of: an allele-specific copy number, a loss of heterozygosity, a structural rearrangement, a chromosomal fusion, and a breakpoint. 7. The system of claim 1, wherein the tumor sequence dataset comprises a tumor BAM file. 8. The system of claim 1, wherein the matched normal dataset comprises a normal BAM file. 9. The system of claim 1, wherein the at least two dataset comprises more than two datasets. 10. The system of claim 9, wherein the more than two datasets comprises related sequencing datasets. 11. The system of claim 9, wherein the more than two datasets include at least one relapse dataset. 12. The system of claim 1, wherein sequence analysis engine is further configured to simultaneously read and synchronize a third dataset with the tumor dataset and matched normal dataset. 13. The system of claim 1, further comprising a genome browser configured to display the genomic alteration in relation to the tumor sequence dataset and the matched normal sequence dataset. 14. The system of claim 1, wherein the memory is configured to store the at least two sequencing data sets as files within a file system. 15. The system of claim 1 wherein identification of a genomic alteration uses pile-ups of the genomic reads that overlap every common genomic location between the tumor sequence strings and the normal sequence strings. 16. The system of claim 1 wherein the given genomic positions for the tumor sequence strings and the normal sequence strings is based on a reference genome. 17. The system of claim 1 wherein the probability is determined by maximizing joint likelihood of both tumor and germline genotypes. 18. The system of claim 17 wherein maximizing the joint likelihood includes deriving a probability from patient data as defined by P(D g ,D t ,G g ,G t |α,r)=P(D g |G g)P(G g |r)P(D t |G g ,G t,α)P(G t |G g)  (1) P(D 1 g,D 1 t,G 1 g,G 1 t┤|α,r)=P(D 1 g┤|G 1 g)P(G 1 g┤|r)P(D 1 t┤|G 1 g,G 1 t,α)P(G 1 t┤|G 1 g)  (2) where r is an observed reference allele, α is a fraction of normal contamination, where tumor and germline genotypes are defined by Gt=(t1, t2) and Gg=(g1,g2), where t1, t2, g1, g2ε{A, T, C, G}, and where tumor and germline sequence data are defined as a set of reads Dt={dt 1, dt 2 . . . , dt n} and Dg={dg 1,dg 2 . . . , dg n}, respectively, with the observed bases dt i, dg iε{A, T, C, G}. 19. The system of claim 18 wherein a probability of germline alleles given a germline genotype is modeled as a multinomial over four nucleotides: P  ( D g | G g ) = n ! n A !  n T !  n G !  n C !  ∏ i n   P  ( d g i | G g ) , where n is the total number of germline reads at the genomic position and nA, nG, nC, nt are reads supporting each observed allele, and a probability of tumor alleles given a tumor genotype is modeled as a multinomial over four nucleotides: P  ( D t | D t , G g , α ) = n ! n A !  n T !  n G !  n C !  ∏ i n   P  ( d t i | G t , G g , α ) , where n is the total number of germline reads at the genomic position and nA, nG, nC, nt are patient data reads supporting each observed allele.

The present invention relates to methods for evaluating and/or predicting the outcome of a clinical condition, such as cancer, metastasis, AIDS, autism, Alzheimer's, and/or Parkinson's disorder. The methods can also be used to monitor and track changes in a patient's DNA and/or RNA during and following a clinical treatment regime. The methods may also be used to evaluate protein and/or metabolite levels that correlate with such clinical conditions. The methods are also of use to ascertain the probability outcome for a patient's particular prognosis.1. A computer-based genomic sequence analysis system comprising: a memory storing at least two genomic sequence datasets including: a tumor sequence dataset comprising genomic sequence strings of a tumor tissue sample of a patient; and a matched normal dataset comprising genomic sequence strings of a normal tissue sample of the same patient; and a sequence analysis engine coupled with the memory and configured to: simultaneously and synchronously read a tumor sequence string from the tumor sequence dataset and a matched normal sequence string from the matched normal sequence dataset; wherein the tumor sequence string is incrementally synchronized with the matched normal sequence string based on a given genomic position; identify a genomic alteration associated with the given genomic position according to a probability derived from reads of the tumor sequence string and of the matched normal sequence string; and store the genomic alteration in a device memory. 2. The system of claim 1, wherein the genomic alteration comprises a genomic variant. 3. The system of claim 2, wherein the genomic variant comprises a somatic variant. 4. The system of claim 2, wherein the genomic variant comprises a germline variant. 5. The system of claim 1, wherein the genomic alteration comprises a single nucleotide polymorphism. 6. The system of claim 1, wherein the genomic alteration comprises an alteration selected from the group consisting of: an allele-specific copy number, a loss of heterozygosity, a structural rearrangement, a chromosomal fusion, and a breakpoint. 7. The system of claim 1, wherein the tumor sequence dataset comprises a tumor BAM file. 8. The system of claim 1, wherein the matched normal dataset comprises a normal BAM file. 9. The system of claim 1, wherein the at least two dataset comprises more than two datasets. 10. The system of claim 9, wherein the more than two datasets comprises related sequencing datasets. 11. The system of claim 9, wherein the more than two datasets include at least one relapse dataset. 12. The system of claim 1, wherein sequence analysis engine is further configured to simultaneously read and synchronize a third dataset with the tumor dataset and matched normal dataset. 13. The system of claim 1, further comprising a genome browser configured to display the genomic alteration in relation to the tumor sequence dataset and the matched normal sequence dataset. 14. The system of claim 1, wherein the memory is configured to store the at least two sequencing data sets as files within a file system. 15. The system of claim 1 wherein identification of a genomic alteration uses pile-ups of the genomic reads that overlap every common genomic location between the tumor sequence strings and the normal sequence strings. 16. The system of claim 1 wherein the given genomic positions for the tumor sequence strings and the normal sequence strings is based on a reference genome. 17. The system of claim 1 wherein the probability is determined by maximizing joint likelihood of both tumor and germline genotypes. 18. The system of claim 17 wherein maximizing the joint likelihood includes deriving a probability from patient data as defined by P(D g ,D t ,G g ,G t |α,r)=P(D g |G g)P(G g |r)P(D t |G g ,G t,α)P(G t |G g)  (1) P(D 1 g,D 1 t,G 1 g,G 1 t┤|α,r)=P(D 1 g┤|G 1 g)P(G 1 g┤|r)P(D 1 t┤|G 1 g,G 1 t,α)P(G 1 t┤|G 1 g)  (2) where r is an observed reference allele, α is a fraction of normal contamination, where tumor and germline genotypes are defined by Gt=(t1, t2) and Gg=(g1,g2), where t1, t2, g1, g2ε{A, T, C, G}, and where tumor and germline sequence data are defined as a set of reads Dt={dt 1, dt 2 . . . , dt n} and Dg={dg 1,dg 2 . . . , dg n}, respectively, with the observed bases dt i, dg iε{A, T, C, G}. 19. The system of claim 18 wherein a probability of germline alleles given a germline genotype is modeled as a multinomial over four nucleotides: P  ( D g | G g ) = n ! n A !  n T !  n G !  n C !  ∏ i n   P  ( d g i | G g ) , where n is the total number of germline reads at the genomic position and nA, nG, nC, nt are reads supporting each observed allele, and a probability of tumor alleles given a tumor genotype is modeled as a multinomial over four nucleotides: P  ( D t | D t , G g , α ) = n ! n A !  n T !  n G !  n C !  ∏ i n   P  ( d t i | G t , G g , α ) , where n is the total number of germline reads at the genomic position and nA, nG, nC, nt are patient data reads supporting each observed allele.

The present invention relates to a microorganism having a reduced fatty acid degradation capacity and expressing a recombinant alkane oxidase, a method for oxidizing an alkyl, comprising a contacting the alkyl with an aqueous solution comprising the inventive cell.

1. A microorganism having a reduced fatty acid degradation capacity and expressing a recombinant alkane oxidase. 2. The microorganism according to claim 1, wherein the expressed recombinant alkane oxidase is selected from the group consisting of a rubredoxin-dependent alkane oxidase, a cytochrome P450 enzyme, a xylene monooxygenase, a methane monooxygenase, and variants thereof. 3. The microorganism according to claim 1, wherein the fatty acid degradation capacity is reduced due to deletion of a gene encoding an enzyme selected from the group consisting of a fatty acid importer, a fatty acid-CoA ligase, an acyl-CoA dehydrogenase, a 2,4-dienoyl-CoA reductase, an enoyl-CoA hydratase and a 3-ketoacyl-CoA thiolase. 4. The microorganism according to claim 1, wherein the microorganism is a prokaryotic or a lower eukaryotic cell. 5. The microorganism according to claim 1, wherein the microorganism expresses a recombinant alcohol dehydrogenase. 6. The microorganism according to claim 1, wherein the microorganism expresses a recombinant transaminase. 7. The microorganism according to claim 6, wherein the microorganism expresses a recombinant amino acid dehydrogenase. 8. A method for oxidizing an alkyl, comprising a) contacting the alkyl with an aqueous solution comprising the microorganism according to claim 1. 9. The method according to claim 8, further comprising b) contacting the aqueous solution from a) with a water-immiscible organic solvent. 10. The method according to claim 9, wherein b) is carried out following completion of the alkyl oxidation. 11. (canceled) 12. The method according to claim 8, wherein the alkyl is a compound represented by the formula H—(CH2)x—R, wherein x is 1 to 30, and R is any chemical group. 13. The method according to claim 8, wherein the alkyl is a linear alkane. 14. The method according to claim 9, wherein the water-immiscible organic solvent is a water-immiscible fatty acid or fatty acid ester. 15. The microorganism according to claim 1, wherein the microorganism is a bacterial cell. 16. The microorganism according to claim 1, wherein the microorganism is E. coli. 17. The microorganism according to claim 7, wherein the recombinant amino acid dehydrogenase is an alanine dehydrogenase.

The present invention relates to a microorganism having a reduced fatty acid degradation capacity and expressing a recombinant alkane oxidase, a method for oxidizing an alkyl, comprising a contacting the alkyl with an aqueous solution comprising the inventive cell.1. A microorganism having a reduced fatty acid degradation capacity and expressing a recombinant alkane oxidase. 2. The microorganism according to claim 1, wherein the expressed recombinant alkane oxidase is selected from the group consisting of a rubredoxin-dependent alkane oxidase, a cytochrome P450 enzyme, a xylene monooxygenase, a methane monooxygenase, and variants thereof. 3. The microorganism according to claim 1, wherein the fatty acid degradation capacity is reduced due to deletion of a gene encoding an enzyme selected from the group consisting of a fatty acid importer, a fatty acid-CoA ligase, an acyl-CoA dehydrogenase, a 2,4-dienoyl-CoA reductase, an enoyl-CoA hydratase and a 3-ketoacyl-CoA thiolase. 4. The microorganism according to claim 1, wherein the microorganism is a prokaryotic or a lower eukaryotic cell. 5. The microorganism according to claim 1, wherein the microorganism expresses a recombinant alcohol dehydrogenase. 6. The microorganism according to claim 1, wherein the microorganism expresses a recombinant transaminase. 7. The microorganism according to claim 6, wherein the microorganism expresses a recombinant amino acid dehydrogenase. 8. A method for oxidizing an alkyl, comprising a) contacting the alkyl with an aqueous solution comprising the microorganism according to claim 1. 9. The method according to claim 8, further comprising b) contacting the aqueous solution from a) with a water-immiscible organic solvent. 10. The method according to claim 9, wherein b) is carried out following completion of the alkyl oxidation. 11. (canceled) 12. The method according to claim 8, wherein the alkyl is a compound represented by the formula H—(CH2)x—R, wherein x is 1 to 30, and R is any chemical group. 13. The method according to claim 8, wherein the alkyl is a linear alkane. 14. The method according to claim 9, wherein the water-immiscible organic solvent is a water-immiscible fatty acid or fatty acid ester. 15. The microorganism according to claim 1, wherein the microorganism is a bacterial cell. 16. The microorganism according to claim 1, wherein the microorganism is E. coli. 17. The microorganism according to claim 7, wherein the recombinant amino acid dehydrogenase is an alanine dehydrogenase.

Compositions containing one or more metal phosphites and prohexadione calcium are suitable for providing micronutrients for plant health and growth regulation when applied to agricultural crops.

1. A method of treating agricultural crops, comprising: applying a composition to a crop, wherein the composition comprises prohexadione calcium and one or more metal phosphites in aqueous solution; wherein the one or more metal phosphites are selected from the group consisting of zinc phosphite, manganese phosphite, magnesium phosphite, calcium phosphite, iron phosphite and copper phosphite. 2. The method of claim 1, wherein applying the composition comprises applying the composition at a rate to provide an amount of prohexadione calcium that is efficacious for growth regulation of the crop. 3. The method of claim 1, wherein applying the composition comprises applying an aqueous solution comprising 0.02-6.0 lbs of one or more of the metal phosphites, measured on a metal basis, for every 1.0 lb of prohexadione calcium. 4. The method of claim 1, wherein applying the composition comprises applying an aqueous solution comprising 1.0-4.0 lbs of calcium as calcium phosphite for every 1.0 lb of prohexadione calcium. 5. The method of claim 1, wherein applying the composition comprises applying the composition to provide 0.2-3.0 lbs/acre of prohexadione calcium and 0.01-1.5 lbs/acre of one or more of the metal phosphites, measured on a metal basis. 6. The method of claim 1, wherein applying the composition comprises applying the composition using a broadcast application method. 7. The method of claim 6, wherein the broadcast method of application is selected from the group consisting of boom spray and air blaster. 8. The method of claim 1, wherein applying the composition comprises applying the composition comprising prohexadione calcium, one or more metal phosphites and one or more additional components selected from the group consisting of dyes, stabilizers, buffers, conditioners, surfactants, preservatives, organic materials, fertilizers other than metal phosphites, plant growth regulators other than prohexadione calcium, herbicides, fungicides and insecticides, in aqueous solution. 9. The method of claim 1, wherein applying the composition comprises applying the composition to apple trees. 10. A composition for treatment of agricultural crops, comprising: prohexadione calcium; and one or more metal phosphites; wherein the one or more metal phosphites are selected from the group consisting of zinc phosphite, manganese phosphite, magnesium phosphite, calcium phosphite, iron phosphite and copper phosphite. 11. The composition of claim 10, wherein the composition is an aqueous solution comprising 1-10% by weight of one or more of the metal phosphites, measured on a metal basis, and 1-25% by weight of prohexadione calcium. 12. The composition of claim 10, wherein at least one of the metal phosphites is calcium phosphite. 13. The composition of claim 10, wherein the composition is a free-flowing solids composition comprising 1-97% by weight of one or more of the metal phosphites by total weight, and 3-99% by weight of prohexadione calcium. 14. The composition of claim 13, wherein at least one of the metal phosphites is calcium phosphite. 15. The composition of claim 13, wherein the free-flowing solids composition is granular. 16. The composition of claim 13, further comprising one or more additional components selected from the group consisting of flow agents, fillers and desiccants. 17. The composition of claim 10, wherein the composition comprises 0.02-6.0 lbs of one or more of the metal phosphites, measured on a metal basis, for every 1.0 lb of prohexadione calcium. 18. The composition of claim 17, wherein the composition comprises 1.0-4.0 lbs of calcium as calcium phosphite for every 1.0 lb of prohexadione calcium. 19. A composition for treatment of agricultural crops, comprising: prohexadione calcium; and calcium phosphite. 20. The composition of claim 19, wherein the composition is an aqueous solution comprising 1-10% by weight of calcium as calcium phosphite and 1-25% by weight of prohexadione calcium. 21. The composition of claim 19, wherein the composition is a free-flowing solids composition comprising 2-40% by weight of calcium phosphite, and 3-40% by weight of prohexadione calcium. 22. The composition of claim 19, wherein the composition comprises 0.02-6.0 lbs of calcium as calcium phosphite for every 1.0 lb of prohexadione calcium. 23. The composition of claim 19, further comprising one or more metal phosphites selected from the group consisting of zinc phosphite, manganese phosphite, magnesium phosphite, iron phosphite and copper phosphite. 24. The composition of claim 19, further comprising one or more additional components selected from the group consisting of flow agents, fillers, desiccants, dyes, stabilizers, buffers, conditioners, surfactants, preservatives, organic materials, fertilizers other than metal phosphites, plant growth regulators other than prohexadione calcium, herbicides, fungicides and insecticides.

Compositions containing one or more metal phosphites and prohexadione calcium are suitable for providing micronutrients for plant health and growth regulation when applied to agricultural crops.1. A method of treating agricultural crops, comprising: applying a composition to a crop, wherein the composition comprises prohexadione calcium and one or more metal phosphites in aqueous solution; wherein the one or more metal phosphites are selected from the group consisting of zinc phosphite, manganese phosphite, magnesium phosphite, calcium phosphite, iron phosphite and copper phosphite. 2. The method of claim 1, wherein applying the composition comprises applying the composition at a rate to provide an amount of prohexadione calcium that is efficacious for growth regulation of the crop. 3. The method of claim 1, wherein applying the composition comprises applying an aqueous solution comprising 0.02-6.0 lbs of one or more of the metal phosphites, measured on a metal basis, for every 1.0 lb of prohexadione calcium. 4. The method of claim 1, wherein applying the composition comprises applying an aqueous solution comprising 1.0-4.0 lbs of calcium as calcium phosphite for every 1.0 lb of prohexadione calcium. 5. The method of claim 1, wherein applying the composition comprises applying the composition to provide 0.2-3.0 lbs/acre of prohexadione calcium and 0.01-1.5 lbs/acre of one or more of the metal phosphites, measured on a metal basis. 6. The method of claim 1, wherein applying the composition comprises applying the composition using a broadcast application method. 7. The method of claim 6, wherein the broadcast method of application is selected from the group consisting of boom spray and air blaster. 8. The method of claim 1, wherein applying the composition comprises applying the composition comprising prohexadione calcium, one or more metal phosphites and one or more additional components selected from the group consisting of dyes, stabilizers, buffers, conditioners, surfactants, preservatives, organic materials, fertilizers other than metal phosphites, plant growth regulators other than prohexadione calcium, herbicides, fungicides and insecticides, in aqueous solution. 9. The method of claim 1, wherein applying the composition comprises applying the composition to apple trees. 10. A composition for treatment of agricultural crops, comprising: prohexadione calcium; and one or more metal phosphites; wherein the one or more metal phosphites are selected from the group consisting of zinc phosphite, manganese phosphite, magnesium phosphite, calcium phosphite, iron phosphite and copper phosphite. 11. The composition of claim 10, wherein the composition is an aqueous solution comprising 1-10% by weight of one or more of the metal phosphites, measured on a metal basis, and 1-25% by weight of prohexadione calcium. 12. The composition of claim 10, wherein at least one of the metal phosphites is calcium phosphite. 13. The composition of claim 10, wherein the composition is a free-flowing solids composition comprising 1-97% by weight of one or more of the metal phosphites by total weight, and 3-99% by weight of prohexadione calcium. 14. The composition of claim 13, wherein at least one of the metal phosphites is calcium phosphite. 15. The composition of claim 13, wherein the free-flowing solids composition is granular. 16. The composition of claim 13, further comprising one or more additional components selected from the group consisting of flow agents, fillers and desiccants. 17. The composition of claim 10, wherein the composition comprises 0.02-6.0 lbs of one or more of the metal phosphites, measured on a metal basis, for every 1.0 lb of prohexadione calcium. 18. The composition of claim 17, wherein the composition comprises 1.0-4.0 lbs of calcium as calcium phosphite for every 1.0 lb of prohexadione calcium. 19. A composition for treatment of agricultural crops, comprising: prohexadione calcium; and calcium phosphite. 20. The composition of claim 19, wherein the composition is an aqueous solution comprising 1-10% by weight of calcium as calcium phosphite and 1-25% by weight of prohexadione calcium. 21. The composition of claim 19, wherein the composition is a free-flowing solids composition comprising 2-40% by weight of calcium phosphite, and 3-40% by weight of prohexadione calcium. 22. The composition of claim 19, wherein the composition comprises 0.02-6.0 lbs of calcium as calcium phosphite for every 1.0 lb of prohexadione calcium. 23. The composition of claim 19, further comprising one or more metal phosphites selected from the group consisting of zinc phosphite, manganese phosphite, magnesium phosphite, iron phosphite and copper phosphite. 24. The composition of claim 19, further comprising one or more additional components selected from the group consisting of flow agents, fillers, desiccants, dyes, stabilizers, buffers, conditioners, surfactants, preservatives, organic materials, fertilizers other than metal phosphites, plant growth regulators other than prohexadione calcium, herbicides, fungicides and insecticides.

A composition for detecting hepatitis B virus cccDNA includes an upstream primer having the DNA sequence set forth in SEQ ID NO. 1, a downstream primer having the DNA sequence set forth in SEQ ID NO. 2, and a TaqMan probe having the DNA sequence set forth in SEQ ID NO. 3. A qualitative and absolute quantification kit for detecting hepatitis C virus cccDNA includes an extraction agent for HBV DNA; an ATP-Dependent DNase; an upstream primer having DNA sequence set forth in SEQ ID NO. 1; a downstream primer having DNA sequence set forth in SEQ ID NO. 2; a TaqMan probe having DNA sequence set forth in SEQ ID NO. 3; EvaGreen fluorescent dyes; a PCR DNA polymerase; and a digital PCR DNA polymerase.

1. A composition for detecting hepatitis B virus cccDNA, comprising an upstream primer having the DNA sequence set forth in SEQ ID NO. 1, a downstream primer having the DNA sequence set forth in SEQ ID NO. 2, and a TaqMan probe having the DNA sequence set forth in SEQ ID NO. 3. 2. A qualitative and absolute quantification kit for detecting hepatitis B virus cccDNA comprising an extraction agent for HBV DNA; an ATP-Dependent DNase; an upstream primer having DNA sequence set forth in SEQ ID NO. 1; a downstream primer having DNA sequence set forth in SEQ ID NO. 2; a TaqMan probe having DNA sequence set forth in SEQ ID NO. 3; EvaGreen fluorescent dyes; a PCR DNA polymerase; and a digital PCR DNA polymerase. 3. The qualitative and absolute quantification kit for detecting hepatitis C virus cccDNA of claim 1, wherein the extraction agent for HBV DNA includes a cell lysate, a Tris saturated phenol, a mixture of phenol:chloroform:isoamyl alcohol=25:24:1, anhydrous ethanol, 75% ethanol, and TE buffer.

A composition for detecting hepatitis B virus cccDNA includes an upstream primer having the DNA sequence set forth in SEQ ID NO. 1, a downstream primer having the DNA sequence set forth in SEQ ID NO. 2, and a TaqMan probe having the DNA sequence set forth in SEQ ID NO. 3. A qualitative and absolute quantification kit for detecting hepatitis C virus cccDNA includes an extraction agent for HBV DNA; an ATP-Dependent DNase; an upstream primer having DNA sequence set forth in SEQ ID NO. 1; a downstream primer having DNA sequence set forth in SEQ ID NO. 2; a TaqMan probe having DNA sequence set forth in SEQ ID NO. 3; EvaGreen fluorescent dyes; a PCR DNA polymerase; and a digital PCR DNA polymerase.1. A composition for detecting hepatitis B virus cccDNA, comprising an upstream primer having the DNA sequence set forth in SEQ ID NO. 1, a downstream primer having the DNA sequence set forth in SEQ ID NO. 2, and a TaqMan probe having the DNA sequence set forth in SEQ ID NO. 3. 2. A qualitative and absolute quantification kit for detecting hepatitis B virus cccDNA comprising an extraction agent for HBV DNA; an ATP-Dependent DNase; an upstream primer having DNA sequence set forth in SEQ ID NO. 1; a downstream primer having DNA sequence set forth in SEQ ID NO. 2; a TaqMan probe having DNA sequence set forth in SEQ ID NO. 3; EvaGreen fluorescent dyes; a PCR DNA polymerase; and a digital PCR DNA polymerase. 3. The qualitative and absolute quantification kit for detecting hepatitis C virus cccDNA of claim 1, wherein the extraction agent for HBV DNA includes a cell lysate, a Tris saturated phenol, a mixture of phenol:chloroform:isoamyl alcohol=25:24:1, anhydrous ethanol, 75% ethanol, and TE buffer.

The disclosure provides an oral composition for reducing serum cholesterol, serum lipids, body fat, or atherogenic index or for prophylaxis or treatment of atherosclerosis, cardiovascular or cerebrovascular diseases, comprising a highly bsh active bacteria, isolate or supernatant thereof; wherein the highly bsh active bacteria degrades >50 μmol glycodeoxycholic acid (GDCA)/gram/hour and >2 μmol taurodeoxycholic acid (TDCA)/gram/hour when measured over 1 hour and 5 hours, respectively, or degrades >65 μmol GDCA/g/hr and >7 μmol TDCA/g/hr when measured over 30 minutes.

1. An oral composition comprising a highly bsh active bacteria, isolate or supernatant thereof; wherein the highly bsh active bacteria degrades >50 μmol GDCA/gram/hour and >2 μmol TDCA/gram/hour when measured over 1 hour and 5 hours, respectively; or >65 μmol GDCA/g/hr and >7 μmol TDCA/g/hr when measured over 30 minutes. 2. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >300 μmol GDCA/g/hr and >40 μmol TDCA/g/hr when measured over 30 minutes. 3. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >2000 μmol GDCA/g/hr and >500 μmol TDCA/g/hr when measured over 30 minutes. 4. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >15000 μmol GDCA/g/hr and >2000 μmol TDCA/g/hr when measured over 30 minutes. 5. The oral composition of claim 1, wherein the bacteria is Lactobacillus, Bifidobacteria, Pediococcus, Streptococcus, Enterococcus, or Leuconostoc. 6. The oral composition of claim 5, wherein the Lactobacillus reuteri is Lactobacillus reuteri (NCIMB 701359), Lactobacillus reuteri (NCIMB 701089), Lactobacillus reuteri (ATCC 55148), Lactobacillus reuteri (ATCC 23272), Lactobacillus reuteri (NCIMB 702655), Lactobacillus reuteri (LMG 18238), Lactobacillus reuteri (CCUG 32271), Lactobacillus reuteri (CCUG 32305), Lactobacillus reuteri (CCUG 37470), Lactobacillus reuteri (CCUG 44001) or Lactobacillus reuteri (CCUG 44144). 7. The oral composition of claim 1, wherein the concentration of bacteria is 106-1012 CFU/gram. 8. The oral composition of claim 1, wherein the highly bsh active bacteria are grown under fermentation conditions comprising a carbon source, a nitrogen source, a pH of 4-7 and a harvest time of 6 to 24 hours. 9. The oral composition of claim 8, further comprising a reducing agent. 10. The oral composition of claim 1, wherein the bacteria are immobilized in a polymer or are encapsulated in polymeric semi permeable microcapsules or nanocapsules. 11. The oral composition of claim 1, wherein the composition is lyophilized, heat dried, spray dried, prepared wet, or flash frozen in a cryoprotectant solution. 12. The oral composition of claim 11, wherein the composition is lyophilized with lyoprotectants comprising (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin and 0.05 to 0.33% yeast extract, (c) 0.05 to 10% inulin, (d) 0.2 to 10% maltodextrin and 0.01 to 0.1% cysteine or (e) 0.05 to 10% inulin and 0.01 to 0.1% cysteine. 13. The oral composition of claim 11, wherein the composition is stored in liquid, wherein the liquid storage conditions comprise a final preservative solution comprising 2.5-10% growth media, 50-99.99% yogurt or other fermented milk, 50-99.99% culture supernatant or 5% MRS solution. 14. The oral composition of claim 11, wherein the cryoprotectant solution comprises a final concentration of (a) 0.2-10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose or fructose, (e) 0.5M lactose, (f) 0.5M maltose, (g) 50-99.99% spent media, (h) 0.2-10% maltodextrin and 0.01 to 0.1% cysteine or (i) 0.05% to 10% inulin and 0.01 to 0.1% cysteine. 15. The oral composition of claim 1, wherein the composition further comprises a triglyceride lowering agent, an agent for increasing HDL or limiting HDL decrease, a cholesterol lowering agent, an agent for preserving bsh activity, an agent for modulating adipokines or hormones of obesity, a hypoglycemic agent, a therapeutic for reducing the pro-inflammatory cytokines IL-1α/β, IL-2, IL-15, IL-3, IL-6, IL-8, IL-12, IL-17, IFN-gamma, TNF-alpha, or for increasing the level of the anti-inflammatory cytokines IL-1ra, IL-9, IL-10, IL-11, vitamin B12, conjugated linoleic acid (CLA), reuterin or reutericyclin. 16. A method for lowering serum cholesterol of an animal comprising administering the oral composition of claim 1 to the animal in need thereof. 17. The method of claim 16, for reducing atherosclerotic risk factors of the animal, wherein the atherosclerotic risk factors are selected from serum homocystine, fibrinogen, C-reactive protein, lipoprotein(a), uric acid, matrix metallopeptidase 9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1) or its antigen, tissue plasminogen activator (tPA), TNF alpha, IL-6, P-selectin, monocyte chemotactic protein-1 (MCP-1), soluble CD40 ligand (sCD40L), inter-cellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), adiponectin, leptin, lipoprotein-associated phospholipase A, and insulin. 18. A method for reducing the atherogenic index of an animal comprising administering the oral composition of claim 1 to the animal in need thereof, wherein atherogenic index (AI) is calculated by at least one of the following equations: AI=Log(Triglycerides/HDL-C) or AI=TC-HDL-C/HDL-C. 19. A method for increasing or limiting the reduction of serum high density lipoproteins (HDL-C) of an animal, for decreasing serum triglycerides of the animal, or for producing and delivering vitamin B12, conjugated linoleic acid (CLA), reuterin or reutericyclin to the animal, comprising administering the oral composition of claim 1 to the animal in need thereof. 20. A method for prophylaxis or treatment of atherosclerosis or a degenerative disorder caused by atherosclerosis in an animal, for lowering total body fat or treating obesity or pre-obesity in an animal, for prophylaxis or treatment of metabolic disease or disorder in an animal or for prophylaxis or treatment of a liver disease or disorder associated with high serum or hepatic lipid and triglyceride concentrations, hepatic inflammation, non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, liver steatosis, liver fibrosis, abnormally high serum ALT, AST, GGT, or Alk-P levels, Epstein-Barr virus, hepatitis, autoimmune hepatitis, hepatic granulomatus disease, cholangitis, hepatocellular cancer, cholangiocarcinoma or metabolic liver disease in an animal, comprising administering the oral composition of claim 1 to the animal in need thereof. 21. A process for preparing a highly bsh active bacteria comprising growing bsh-producing bacteria in media comprising a carbon source, a nitrogen source, and a pH of 4 to 7 and harvesting the bacteria after 6 to 24 hours. 22. The process of claim 21, wherein the media further comprises a reducing agent 23. The process of claim 21, further comprising lyophilizing the free or microencapsulated bacteria with lyoprotectants, wherein the lyoprotectants comprise (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin and 0.05 to 0.33% yeast extract, (c) 0.05 to 10% inulin, (d) 0.2 to 10% maltodextrin and 0.01 to 0.1% cysteine or (e) 0.05 to 10% inulin and 0.01 to 0.1% cysteine. 24. The process of claim 21, further comprising storing the highly bsh active free or microencapsulated bacteria under liquid storage conditions, wherein the liquid storage conditions comprises a final preservative solution comprising 2.5-10% growth media, 50-99.99% yogurt or other fermented milk, 50-99.99% culture supernatant or 5% MRS solution. 25. The process of claim 21, further comprising flash freezing the composition in cryoprotectant solution at less than −80 Degrees Celsius, wherein the cryoprotectant solution comprises a final concentration of (a) 0.2-10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose or fructose, (e) 0.5M lactose, (f) 0.5M maltose, (g) 50-99.99% spent media, (h) 0.2-10% maltodextrin and 0.01 to 0.1% cysteine or (i) 0.05 to 10% inulin and 0.01 to 0.1% cysteine.

The disclosure provides an oral composition for reducing serum cholesterol, serum lipids, body fat, or atherogenic index or for prophylaxis or treatment of atherosclerosis, cardiovascular or cerebrovascular diseases, comprising a highly bsh active bacteria, isolate or supernatant thereof; wherein the highly bsh active bacteria degrades >50 μmol glycodeoxycholic acid (GDCA)/gram/hour and >2 μmol taurodeoxycholic acid (TDCA)/gram/hour when measured over 1 hour and 5 hours, respectively, or degrades >65 μmol GDCA/g/hr and >7 μmol TDCA/g/hr when measured over 30 minutes.1. An oral composition comprising a highly bsh active bacteria, isolate or supernatant thereof; wherein the highly bsh active bacteria degrades >50 μmol GDCA/gram/hour and >2 μmol TDCA/gram/hour when measured over 1 hour and 5 hours, respectively; or >65 μmol GDCA/g/hr and >7 μmol TDCA/g/hr when measured over 30 minutes. 2. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >300 μmol GDCA/g/hr and >40 μmol TDCA/g/hr when measured over 30 minutes. 3. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >2000 μmol GDCA/g/hr and >500 μmol TDCA/g/hr when measured over 30 minutes. 4. The oral composition of claim 1, wherein the highly bsh active bacteria degrades >15000 μmol GDCA/g/hr and >2000 μmol TDCA/g/hr when measured over 30 minutes. 5. The oral composition of claim 1, wherein the bacteria is Lactobacillus, Bifidobacteria, Pediococcus, Streptococcus, Enterococcus, or Leuconostoc. 6. The oral composition of claim 5, wherein the Lactobacillus reuteri is Lactobacillus reuteri (NCIMB 701359), Lactobacillus reuteri (NCIMB 701089), Lactobacillus reuteri (ATCC 55148), Lactobacillus reuteri (ATCC 23272), Lactobacillus reuteri (NCIMB 702655), Lactobacillus reuteri (LMG 18238), Lactobacillus reuteri (CCUG 32271), Lactobacillus reuteri (CCUG 32305), Lactobacillus reuteri (CCUG 37470), Lactobacillus reuteri (CCUG 44001) or Lactobacillus reuteri (CCUG 44144). 7. The oral composition of claim 1, wherein the concentration of bacteria is 106-1012 CFU/gram. 8. The oral composition of claim 1, wherein the highly bsh active bacteria are grown under fermentation conditions comprising a carbon source, a nitrogen source, a pH of 4-7 and a harvest time of 6 to 24 hours. 9. The oral composition of claim 8, further comprising a reducing agent. 10. The oral composition of claim 1, wherein the bacteria are immobilized in a polymer or are encapsulated in polymeric semi permeable microcapsules or nanocapsules. 11. The oral composition of claim 1, wherein the composition is lyophilized, heat dried, spray dried, prepared wet, or flash frozen in a cryoprotectant solution. 12. The oral composition of claim 11, wherein the composition is lyophilized with lyoprotectants comprising (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin and 0.05 to 0.33% yeast extract, (c) 0.05 to 10% inulin, (d) 0.2 to 10% maltodextrin and 0.01 to 0.1% cysteine or (e) 0.05 to 10% inulin and 0.01 to 0.1% cysteine. 13. The oral composition of claim 11, wherein the composition is stored in liquid, wherein the liquid storage conditions comprise a final preservative solution comprising 2.5-10% growth media, 50-99.99% yogurt or other fermented milk, 50-99.99% culture supernatant or 5% MRS solution. 14. The oral composition of claim 11, wherein the cryoprotectant solution comprises a final concentration of (a) 0.2-10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose or fructose, (e) 0.5M lactose, (f) 0.5M maltose, (g) 50-99.99% spent media, (h) 0.2-10% maltodextrin and 0.01 to 0.1% cysteine or (i) 0.05% to 10% inulin and 0.01 to 0.1% cysteine. 15. The oral composition of claim 1, wherein the composition further comprises a triglyceride lowering agent, an agent for increasing HDL or limiting HDL decrease, a cholesterol lowering agent, an agent for preserving bsh activity, an agent for modulating adipokines or hormones of obesity, a hypoglycemic agent, a therapeutic for reducing the pro-inflammatory cytokines IL-1α/β, IL-2, IL-15, IL-3, IL-6, IL-8, IL-12, IL-17, IFN-gamma, TNF-alpha, or for increasing the level of the anti-inflammatory cytokines IL-1ra, IL-9, IL-10, IL-11, vitamin B12, conjugated linoleic acid (CLA), reuterin or reutericyclin. 16. A method for lowering serum cholesterol of an animal comprising administering the oral composition of claim 1 to the animal in need thereof. 17. The method of claim 16, for reducing atherosclerotic risk factors of the animal, wherein the atherosclerotic risk factors are selected from serum homocystine, fibrinogen, C-reactive protein, lipoprotein(a), uric acid, matrix metallopeptidase 9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1) or its antigen, tissue plasminogen activator (tPA), TNF alpha, IL-6, P-selectin, monocyte chemotactic protein-1 (MCP-1), soluble CD40 ligand (sCD40L), inter-cellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), adiponectin, leptin, lipoprotein-associated phospholipase A, and insulin. 18. A method for reducing the atherogenic index of an animal comprising administering the oral composition of claim 1 to the animal in need thereof, wherein atherogenic index (AI) is calculated by at least one of the following equations: AI=Log(Triglycerides/HDL-C) or AI=TC-HDL-C/HDL-C. 19. A method for increasing or limiting the reduction of serum high density lipoproteins (HDL-C) of an animal, for decreasing serum triglycerides of the animal, or for producing and delivering vitamin B12, conjugated linoleic acid (CLA), reuterin or reutericyclin to the animal, comprising administering the oral composition of claim 1 to the animal in need thereof. 20. A method for prophylaxis or treatment of atherosclerosis or a degenerative disorder caused by atherosclerosis in an animal, for lowering total body fat or treating obesity or pre-obesity in an animal, for prophylaxis or treatment of metabolic disease or disorder in an animal or for prophylaxis or treatment of a liver disease or disorder associated with high serum or hepatic lipid and triglyceride concentrations, hepatic inflammation, non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, liver steatosis, liver fibrosis, abnormally high serum ALT, AST, GGT, or Alk-P levels, Epstein-Barr virus, hepatitis, autoimmune hepatitis, hepatic granulomatus disease, cholangitis, hepatocellular cancer, cholangiocarcinoma or metabolic liver disease in an animal, comprising administering the oral composition of claim 1 to the animal in need thereof. 21. A process for preparing a highly bsh active bacteria comprising growing bsh-producing bacteria in media comprising a carbon source, a nitrogen source, and a pH of 4 to 7 and harvesting the bacteria after 6 to 24 hours. 22. The process of claim 21, wherein the media further comprises a reducing agent 23. The process of claim 21, further comprising lyophilizing the free or microencapsulated bacteria with lyoprotectants, wherein the lyoprotectants comprise (a) 0.2 to 10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin and 0.05 to 0.33% yeast extract, (c) 0.05 to 10% inulin, (d) 0.2 to 10% maltodextrin and 0.01 to 0.1% cysteine or (e) 0.05 to 10% inulin and 0.01 to 0.1% cysteine. 24. The process of claim 21, further comprising storing the highly bsh active free or microencapsulated bacteria under liquid storage conditions, wherein the liquid storage conditions comprises a final preservative solution comprising 2.5-10% growth media, 50-99.99% yogurt or other fermented milk, 50-99.99% culture supernatant or 5% MRS solution. 25. The process of claim 21, further comprising flash freezing the composition in cryoprotectant solution at less than −80 Degrees Celsius, wherein the cryoprotectant solution comprises a final concentration of (a) 0.2-10% maltodextrin and 0.05 to 0.33% yeast extract, (b) 0.05 to 10% inulin, (c) 0.5M Trehalose, (d) 0.5M sucrose or fructose, (e) 0.5M lactose, (f) 0.5M maltose, (g) 50-99.99% spent media, (h) 0.2-10% maltodextrin and 0.01 to 0.1% cysteine or (i) 0.05 to 10% inulin and 0.01 to 0.1% cysteine.

We describe herein a cell-based multiplexing technique called detectable cell barcoding (DCB). In DCB, each individual sample is labeled with a different DCB signature that distinguishes each sample by one or both of detected intensity or type of detection characteristic. The samples are then combined and analyzed for a detectable characteristic of interest (e.g., presence of an analyte). By employing multiple distinct DCB labels at varying concentrations, one can perform multiplex analyses on up to hundreds or thousands (or more) of cell samples in a single reaction tube. DCB reduces reagent consumption by factors of 100-fold or more, significantly reduces data acquisition times and allows for stringent control sample analysis.

1-21. (canceled) 22. A kit comprising at least one detectable cell barcode (DCB) label in a form that is optimized to DCB label multiple cell samples according the method of claim 1, wherein said at least one DCB label is pre-measured into aliquots, wherein each of said aliquots comprises a different amount of said at least one DCB label that will distinguishably DCB mark starting cell samples in a multiplex DCB assay. 23. The kit of claim 22, wherein said at least one DCB label comprises a cell binding moiety. 24. The kit of claim 23, wherein said cell binding moiety is selected from one or both of a covalent cell binding moiety and a non-covalent cell binding moiety. 25. The kit of claim 22, wherein said at least one DCB label is in a liquid composition. 26. The kit of claim 22, wherein said at least one DCB label is in a dry composition. 27. (canceled) 28. (canceled) 29. The kit of claim 22, wherein said aliquots are provided in a multi-well strip or multi-well plate. 30. The kit of claim 22, wherein said kit comprises multiple distinct DCB labels. 31. The kit of claim 22, wherein said kit further comprises reagents for performing a DCB assay, wherein said reagents are selected form one or more of from the group consisting of: buffers for reconstitution and/or dilution of said at least one DCB label, buffers for labeling cell samples with said at least one DCB label, wash buffers, DCB labeling control cells, DCB labeling control beads, fluorescent beads for flow cytometer calibration, one or more detectable binding agents specific for detection of a cellular characteristic of interest, analyte detection control reagents, and combinations thereof. 32. The kit of claim 31, wherein said one or more detectable binding agents comprises an analyte-specific antibody. 33. The kit of claim 32, wherein said analyte is a specific isoform of a protein. 34. The kit of claim 31, wherein said analyte detection control reagents comprises one or more of: a non-specific isotype control antibody, a positive analyte control sample, a negative analyte control sample, and combinations thereof. 35. The kit of claim 22, wherein said DCB label comprises a fluorescent dye. 36. The kit of claim 22, wherein said DCB label comprises a mass label. 37. The kit of claim 24 wherein said covalent cell binding moiety is selected from the group consisting of: amine-reactive groups, thiol-reactive groups, hydroxyl reactive groups, aldehyde-reactive groups, isothiocyanate groups, amino groups, haloacetyl groups, maleimides, succinimidyl esters, thiols, aldehydes, hydrazides, azides, sulfonyl halides, and combinations thereof. 38. The kit of claim 30, wherein each of said multiple distinct DCB labels can be distinguished from one another based on fluorescence emission wavelength, fluorescence polarization, fluorescence lifetime, light scatter, mass, molecular mass, or combinations thereof. 39. The kit of claim 31, wherein said one or more detectable binding agents comprises a DNA binding agent. 40. The kit of claim 31, wherein said one or more detectable binding agents comprises a detectable catalytic activity. 41. The kit of claim 33, wherein said specific isoform is the phosphorylated isoform of a protein. 42. The kit of claim 30, wherein said aliquots comprise ready-made combinations of said multiple distinct DCB labels that will distinguishably DCB mark starting cell samples in a multiplex DCB assay. 43. The kit of claim 22, wherein said DCB label is pre-measured into three or more aliquots.

We describe herein a cell-based multiplexing technique called detectable cell barcoding (DCB). In DCB, each individual sample is labeled with a different DCB signature that distinguishes each sample by one or both of detected intensity or type of detection characteristic. The samples are then combined and analyzed for a detectable characteristic of interest (e.g., presence of an analyte). By employing multiple distinct DCB labels at varying concentrations, one can perform multiplex analyses on up to hundreds or thousands (or more) of cell samples in a single reaction tube. DCB reduces reagent consumption by factors of 100-fold or more, significantly reduces data acquisition times and allows for stringent control sample analysis.1-21. (canceled) 22. A kit comprising at least one detectable cell barcode (DCB) label in a form that is optimized to DCB label multiple cell samples according the method of claim 1, wherein said at least one DCB label is pre-measured into aliquots, wherein each of said aliquots comprises a different amount of said at least one DCB label that will distinguishably DCB mark starting cell samples in a multiplex DCB assay. 23. The kit of claim 22, wherein said at least one DCB label comprises a cell binding moiety. 24. The kit of claim 23, wherein said cell binding moiety is selected from one or both of a covalent cell binding moiety and a non-covalent cell binding moiety. 25. The kit of claim 22, wherein said at least one DCB label is in a liquid composition. 26. The kit of claim 22, wherein said at least one DCB label is in a dry composition. 27. (canceled) 28. (canceled) 29. The kit of claim 22, wherein said aliquots are provided in a multi-well strip or multi-well plate. 30. The kit of claim 22, wherein said kit comprises multiple distinct DCB labels. 31. The kit of claim 22, wherein said kit further comprises reagents for performing a DCB assay, wherein said reagents are selected form one or more of from the group consisting of: buffers for reconstitution and/or dilution of said at least one DCB label, buffers for labeling cell samples with said at least one DCB label, wash buffers, DCB labeling control cells, DCB labeling control beads, fluorescent beads for flow cytometer calibration, one or more detectable binding agents specific for detection of a cellular characteristic of interest, analyte detection control reagents, and combinations thereof. 32. The kit of claim 31, wherein said one or more detectable binding agents comprises an analyte-specific antibody. 33. The kit of claim 32, wherein said analyte is a specific isoform of a protein. 34. The kit of claim 31, wherein said analyte detection control reagents comprises one or more of: a non-specific isotype control antibody, a positive analyte control sample, a negative analyte control sample, and combinations thereof. 35. The kit of claim 22, wherein said DCB label comprises a fluorescent dye. 36. The kit of claim 22, wherein said DCB label comprises a mass label. 37. The kit of claim 24 wherein said covalent cell binding moiety is selected from the group consisting of: amine-reactive groups, thiol-reactive groups, hydroxyl reactive groups, aldehyde-reactive groups, isothiocyanate groups, amino groups, haloacetyl groups, maleimides, succinimidyl esters, thiols, aldehydes, hydrazides, azides, sulfonyl halides, and combinations thereof. 38. The kit of claim 30, wherein each of said multiple distinct DCB labels can be distinguished from one another based on fluorescence emission wavelength, fluorescence polarization, fluorescence lifetime, light scatter, mass, molecular mass, or combinations thereof. 39. The kit of claim 31, wherein said one or more detectable binding agents comprises a DNA binding agent. 40. The kit of claim 31, wherein said one or more detectable binding agents comprises a detectable catalytic activity. 41. The kit of claim 33, wherein said specific isoform is the phosphorylated isoform of a protein. 42. The kit of claim 30, wherein said aliquots comprise ready-made combinations of said multiple distinct DCB labels that will distinguishably DCB mark starting cell samples in a multiplex DCB assay. 43. The kit of claim 22, wherein said DCB label is pre-measured into three or more aliquots.

An olfaction processor (OLP) ( 100 ) that generates RAW data ( 35 ) including content data ( 139 d ) relating to chemical substances is provided. The OLP ( 100 ) includes a generator ( 130 ) that generates the RAW data ( 35 ). The chemical substances include at least one of compounds, molecules, and elements. The generator ( 130 ) includes a conversion unit ( 131 ) that converts intensity variations, which show detected chemical substances included in data from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data ( 139 d ) by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances.

1. A system including a generator that generates first data including content data relating to chemical substances, wherein the chemical substances include at least one of compounds, molecules, and elements, and the generator comprises a conversion unit that converts intensity variations showing detected chemical substances included in data from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances. 2. The system according to claim 1, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and the conversion unit converts the intensity variations showing detected chemical substances to intensity variations of frequencies included in any of the sub-bands. 3. The system according to claim 2, wherein the content data is data for transmitting information for analyzing odors and/or information that relates to odors, and the plurality of groups includes groups divided according to functional groups. 4. The system according to claim 3, wherein the plurality of groups further includes an inorganic group and an unclassified group. 5. The system according to claim 3, further comprising sensors that obtain environmental information including at least temperature and humidity, and the generator comprises a supplementary information adding unit that obtains the environmental information of when the first data is generated and includes the environmental information in the first data as the environmental information of when the first data was generated. 6. The system according to claim 3, wherein the at least one sensor includes left and right sensors with different detection characteristics relating to direction, and the conversion unit includes a function that maps left and right intensity variations showing detected chemical substances included in data from the left and right sensors onto left and right frequency spaces respectively. 7. The system according to claim 1, further comprising a convertor converting the first data to data on a time region. 8. The system according to claim 7, further comprising an interface that outputs the data on a time region using images and/or sounds. 9. The system according to claim 7, further comprising an interface for recording the data on a time region and/or transferring the data on a time region to the outside. 10. The system according to claim 1, further comprising a compression apparatus that generates compressed data produced by compressing the first data. 11. The system according to claim 10, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and in the first data, intensity variations showing detected chemical substances have been converted to intensity variations of frequencies included in any of the sub-bands, and the compression apparatus includes a compression control unit that changes compression conditions according to the sub-band. 12. The system according to claim 11, wherein the content data is data for transmitting information for analyzing odors and/or information that relates to odors, and the plurality of groups includes groups divided according to functional groups, and the compression control unit reduces a data amount of the compressed data by deleting sub-bands assigned to groups not related to odors out of the plurality of groups or increasing a compression ratio by using an irreversible compression method. 13. The system according to claim 10, further comprising an interface for recording the compressed data and/or transferring the compressed data to the outside. 14. The system according to claim 1, further comprising: a capture unit that generates static data from the first data; and a recognition apparatus that recognizes a specified substance based on the static data. 15. The system according to claim 14, further comprising: a library including a plurality of patterns for recognition where chemical substances included in a plurality of substances have been mapped onto the frequency space, and a recognition engine that refers to the library, carries out pattern recognition on the static data, and outputs substances that have been recognized. 16. The system according to claim 15, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and in the first data, intensity variations showing detected chemical substances have been converted to intensity variations of frequencies included in any of the sub-bands, and the recognition engine carries out pattern recognition in sub-band units. 17. The system according to claim 14, further comprising a communication interface for communication with the outside, wherein the recognition apparatus outputs the static data or data for carrying out pattern recognition on the static data via the communication interface and obtains information relating to a recognized substance. 18. The system according to claim 14, further comprising an interface for carrying out a specified action that depends on a recognized substance. 19. The system according to claim 1, wherein the at least one sensor includes a spectrometry-type sensor whose sensitivity, resolution, and/or selectivity is controlled according to setting conditions, and the system further comprises a preprocessor that sets the setting conditions at preliminary detection conditions that scan a wider range using the spectrometry-type sensor, carries out preliminary analysis based on results of preliminary detection, and changes the setting conditions based on substances analyzed by the preliminary analysis. 20. The system according to claim 19, wherein the preprocessor periodically sets the preliminary detection conditions and carries out the preliminary analysis. 21. The system according to claim 1, wherein the at least one sensor includes a plurality of sensors of different types, and the conversion unit includes a function that maps intensity variations showing detected chemical substances included in data from respective sensors in the plurality of sensors onto the frequency space together. 22. The system according to claim 1, further comprising a reproduction apparatus for supplying a device driver with odor data based on the content data of the first data, wherein the device driver includes a function that converts the odor data to a combination of a plurality of odor sources that are used in an odor generating apparatus. 23. The system according to claim 22, further comprising sensors that obtain environmental information including at least temperature and humidity, wherein the first data includes the environmental information of when the first data was generated, and the reproduction apparatus includes a first compensation unit that obtains environmental information for a time of reproduction from the sensors that obtain environmental information, compares the obtained environmental information with the environmental information of when the first data was generated, and converts the content data of the first data to odor data suited to the obtained environmental information. 24. The system according to claim 22, wherein the reproduction apparatus includes a second compensation unit that obtains information relating to chemical substances during reproduction based on intensity variations showing detected chemical substances included in data from the at least one sensor, compares the obtained information with the content data of the first data, and converts the content data of the first data to the odor data suited to the obtained information relating to chemical substances. 25. The system according to claim 22, wherein the reproduction apparatus includes a reconstruction unit that converts the content data of the first data to the odor data based on characteristics of the human sense of smell. 26. The system according to claim 1, further comprising at least one chip in which circuits including at least the generator are integrated. 27. A system comprising: an interface that receives first data including content data where intensity variations showing chemical substances, which include at least one of compounds, molecules, and elements, have been mapped onto a frequency space where a plurality of frequencies have been respectively assigned to specified chemical substances; and a reproduction apparatus that supplies odor data based on the content data of the first data to a device driver, wherein the device driver includes a function that converts the odor data to a combination of a plurality of odor sources that are used in an odor generating apparatus. 28. The system according to claim 27, further comprising an interface that obtains environmental information at a time of reproduction that includes at least temperature and humidity from sensors that obtain environmental information, wherein the first data includes environmental information of when the first data was generated, and the reproduction apparatus includes a first compensation unit that obtains environmental information for a time of reproduction from the sensor, compares the obtained environmental information with the environmental information of when the first data was generated, and converts the content data of the first data to odor data suited to the obtained environmental information. 29. The system according to claim 27, further comprising an interface that obtains information, which relates to chemical substances at a time of reproduction and includes intensity variations showing chemical substances at a time of reproduction, from a sensor detecting an amount that changes according to presence of the chemical substances, wherein the reproduction apparatus includes a second compensation unit that obtains the information relating to chemical substances at the time of reproduction, compares the obtained information with the content data of the first data, and converts the first data to odor data suited to the obtained information relating to chemical substances. 30. The system according to claim 27, wherein the reproduction apparatus includes a reconstruction unit that converts the first data to the odor data based on characteristics of the human sense of smell. 31. The system according to claim 27, wherein the system is integrated into at least one chip. 32. A method of generating first data including content data relating to chemical substances, wherein the chemical substances include at least one of compounds, molecules, and elements, the method comprising converting intensity variations showing detected chemical substances included in data obtained from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances. 33. The method according to claim 32, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and the step of converting includes converting the intensity variations showing detected chemical substances to intensity variations of frequencies included in any of the sub-bands. 34. The method according to claim 32, further comprising obtaining environmental information of when the first data is generated from sensors that obtain environmental information including at least temperature and humidity and including the obtained environmental information in the first data as environmental information of when the first data was generated. 35. The method according to claim 32, wherein the at least one sensor includes left and right sensors with different detection characteristics relating to direction, and the converting includes mapping intensity variations showing detected chemical substances included in the data from the left and right sensors onto left and right frequency spaces respectively. 36. The method according to claim 32, further comprising converting the first data to second data on a time region. 37. The method according to claim 32, further comprising generating compressed data produced by compressing the first data. 38. The method according to claim 32, wherein the at least one sensor includes a spectrometry-type sensor whose sensitivity, resolution, and/or selectivity is controlled according to setting conditions, and the method further comprises setting the setting conditions at preliminary detection conditions that scan a wider range using the spectrometry-type sensor, carrying out preliminary analysis based on results of preliminary detection, and changing the setting conditions based on substances analyzed by the preliminary analysis. 39. The method according to claim 32, wherein the at least one sensor includes a plurality of sensors of different types, and the converting includes mapping intensity variations showing the detected chemical substances included in data from respective sensors in the plurality of sensors onto the frequency space together. 40. A method of testing, investigating, or diagnosing, comprising: a method according to claim 32; a step of capturing static data from the first data; and a step of recognizing a specified substance based on the static data. 41. A method of generating odors, comprising: receiving first data including content data produced by mapping intensity variations showing chemical substances including at least one of compounds, molecules, and elements onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances; supplying odor data to a device driver based on the content data of the first data; and converting, by the device driver, the odor data to a combination of a plurality of odor sources that are used in an odor generating apparatus. 42. The method according to claim 41, further comprising obtaining, from sensors, environmental information at a time of reproduction that includes at least one of temperature and humidity; and comparing the obtained environmental information at the time of reproduction to environmental information of when the first data was generated and converting the content data of the first data to odor data suited to the obtained environmental information at a time of reproduction. 43. The method according to claim 41, further comprising obtaining information, which relates to chemical substances at a time of reproduction and includes intensity variations showing chemical substances at the time of reproduction, from a sensor detecting an amount that changes according to presence of a chemical substance; and comparing the obtained information related to chemical substances at the time of reproduction to the content data of the first data and converting the first data to odor data suited to the obtained information related to chemical substances at the time of reproduction. 44. The method according to claim 41, further comprising converting the content data of the first data to the odor data based on characteristics of the human sense of smell. 45. A program for causing a computer to function as an apparatus that generates first data including content data relating to chemical substances, wherein the chemical substances include at least one of compounds, molecules, and elements, and the apparatus that generates comprises a conversion unit that converts intensity variations showing detected chemical substances included in data from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances.

An olfaction processor (OLP) ( 100 ) that generates RAW data ( 35 ) including content data ( 139 d ) relating to chemical substances is provided. The OLP ( 100 ) includes a generator ( 130 ) that generates the RAW data ( 35 ). The chemical substances include at least one of compounds, molecules, and elements. The generator ( 130 ) includes a conversion unit ( 131 ) that converts intensity variations, which show detected chemical substances included in data from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data ( 139 d ) by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances.1. A system including a generator that generates first data including content data relating to chemical substances, wherein the chemical substances include at least one of compounds, molecules, and elements, and the generator comprises a conversion unit that converts intensity variations showing detected chemical substances included in data from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances. 2. The system according to claim 1, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and the conversion unit converts the intensity variations showing detected chemical substances to intensity variations of frequencies included in any of the sub-bands. 3. The system according to claim 2, wherein the content data is data for transmitting information for analyzing odors and/or information that relates to odors, and the plurality of groups includes groups divided according to functional groups. 4. The system according to claim 3, wherein the plurality of groups further includes an inorganic group and an unclassified group. 5. The system according to claim 3, further comprising sensors that obtain environmental information including at least temperature and humidity, and the generator comprises a supplementary information adding unit that obtains the environmental information of when the first data is generated and includes the environmental information in the first data as the environmental information of when the first data was generated. 6. The system according to claim 3, wherein the at least one sensor includes left and right sensors with different detection characteristics relating to direction, and the conversion unit includes a function that maps left and right intensity variations showing detected chemical substances included in data from the left and right sensors onto left and right frequency spaces respectively. 7. The system according to claim 1, further comprising a convertor converting the first data to data on a time region. 8. The system according to claim 7, further comprising an interface that outputs the data on a time region using images and/or sounds. 9. The system according to claim 7, further comprising an interface for recording the data on a time region and/or transferring the data on a time region to the outside. 10. The system according to claim 1, further comprising a compression apparatus that generates compressed data produced by compressing the first data. 11. The system according to claim 10, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and in the first data, intensity variations showing detected chemical substances have been converted to intensity variations of frequencies included in any of the sub-bands, and the compression apparatus includes a compression control unit that changes compression conditions according to the sub-band. 12. The system according to claim 11, wherein the content data is data for transmitting information for analyzing odors and/or information that relates to odors, and the plurality of groups includes groups divided according to functional groups, and the compression control unit reduces a data amount of the compressed data by deleting sub-bands assigned to groups not related to odors out of the plurality of groups or increasing a compression ratio by using an irreversible compression method. 13. The system according to claim 10, further comprising an interface for recording the compressed data and/or transferring the compressed data to the outside. 14. The system according to claim 1, further comprising: a capture unit that generates static data from the first data; and a recognition apparatus that recognizes a specified substance based on the static data. 15. The system according to claim 14, further comprising: a library including a plurality of patterns for recognition where chemical substances included in a plurality of substances have been mapped onto the frequency space, and a recognition engine that refers to the library, carries out pattern recognition on the static data, and outputs substances that have been recognized. 16. The system according to claim 15, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and in the first data, intensity variations showing detected chemical substances have been converted to intensity variations of frequencies included in any of the sub-bands, and the recognition engine carries out pattern recognition in sub-band units. 17. The system according to claim 14, further comprising a communication interface for communication with the outside, wherein the recognition apparatus outputs the static data or data for carrying out pattern recognition on the static data via the communication interface and obtains information relating to a recognized substance. 18. The system according to claim 14, further comprising an interface for carrying out a specified action that depends on a recognized substance. 19. The system according to claim 1, wherein the at least one sensor includes a spectrometry-type sensor whose sensitivity, resolution, and/or selectivity is controlled according to setting conditions, and the system further comprises a preprocessor that sets the setting conditions at preliminary detection conditions that scan a wider range using the spectrometry-type sensor, carries out preliminary analysis based on results of preliminary detection, and changes the setting conditions based on substances analyzed by the preliminary analysis. 20. The system according to claim 19, wherein the preprocessor periodically sets the preliminary detection conditions and carries out the preliminary analysis. 21. The system according to claim 1, wherein the at least one sensor includes a plurality of sensors of different types, and the conversion unit includes a function that maps intensity variations showing detected chemical substances included in data from respective sensors in the plurality of sensors onto the frequency space together. 22. The system according to claim 1, further comprising a reproduction apparatus for supplying a device driver with odor data based on the content data of the first data, wherein the device driver includes a function that converts the odor data to a combination of a plurality of odor sources that are used in an odor generating apparatus. 23. The system according to claim 22, further comprising sensors that obtain environmental information including at least temperature and humidity, wherein the first data includes the environmental information of when the first data was generated, and the reproduction apparatus includes a first compensation unit that obtains environmental information for a time of reproduction from the sensors that obtain environmental information, compares the obtained environmental information with the environmental information of when the first data was generated, and converts the content data of the first data to odor data suited to the obtained environmental information. 24. The system according to claim 22, wherein the reproduction apparatus includes a second compensation unit that obtains information relating to chemical substances during reproduction based on intensity variations showing detected chemical substances included in data from the at least one sensor, compares the obtained information with the content data of the first data, and converts the content data of the first data to the odor data suited to the obtained information relating to chemical substances. 25. The system according to claim 22, wherein the reproduction apparatus includes a reconstruction unit that converts the content data of the first data to the odor data based on characteristics of the human sense of smell. 26. The system according to claim 1, further comprising at least one chip in which circuits including at least the generator are integrated. 27. A system comprising: an interface that receives first data including content data where intensity variations showing chemical substances, which include at least one of compounds, molecules, and elements, have been mapped onto a frequency space where a plurality of frequencies have been respectively assigned to specified chemical substances; and a reproduction apparatus that supplies odor data based on the content data of the first data to a device driver, wherein the device driver includes a function that converts the odor data to a combination of a plurality of odor sources that are used in an odor generating apparatus. 28. The system according to claim 27, further comprising an interface that obtains environmental information at a time of reproduction that includes at least temperature and humidity from sensors that obtain environmental information, wherein the first data includes environmental information of when the first data was generated, and the reproduction apparatus includes a first compensation unit that obtains environmental information for a time of reproduction from the sensor, compares the obtained environmental information with the environmental information of when the first data was generated, and converts the content data of the first data to odor data suited to the obtained environmental information. 29. The system according to claim 27, further comprising an interface that obtains information, which relates to chemical substances at a time of reproduction and includes intensity variations showing chemical substances at a time of reproduction, from a sensor detecting an amount that changes according to presence of the chemical substances, wherein the reproduction apparatus includes a second compensation unit that obtains the information relating to chemical substances at the time of reproduction, compares the obtained information with the content data of the first data, and converts the first data to odor data suited to the obtained information relating to chemical substances. 30. The system according to claim 27, wherein the reproduction apparatus includes a reconstruction unit that converts the first data to the odor data based on characteristics of the human sense of smell. 31. The system according to claim 27, wherein the system is integrated into at least one chip. 32. A method of generating first data including content data relating to chemical substances, wherein the chemical substances include at least one of compounds, molecules, and elements, the method comprising converting intensity variations showing detected chemical substances included in data obtained from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances. 33. The method according to claim 32, wherein the plurality of chemical substances are divided into a plurality of groups and a plurality of sub-bands are assigned respectively to the plurality of groups, and the step of converting includes converting the intensity variations showing detected chemical substances to intensity variations of frequencies included in any of the sub-bands. 34. The method according to claim 32, further comprising obtaining environmental information of when the first data is generated from sensors that obtain environmental information including at least temperature and humidity and including the obtained environmental information in the first data as environmental information of when the first data was generated. 35. The method according to claim 32, wherein the at least one sensor includes left and right sensors with different detection characteristics relating to direction, and the converting includes mapping intensity variations showing detected chemical substances included in the data from the left and right sensors onto left and right frequency spaces respectively. 36. The method according to claim 32, further comprising converting the first data to second data on a time region. 37. The method according to claim 32, further comprising generating compressed data produced by compressing the first data. 38. The method according to claim 32, wherein the at least one sensor includes a spectrometry-type sensor whose sensitivity, resolution, and/or selectivity is controlled according to setting conditions, and the method further comprises setting the setting conditions at preliminary detection conditions that scan a wider range using the spectrometry-type sensor, carrying out preliminary analysis based on results of preliminary detection, and changing the setting conditions based on substances analyzed by the preliminary analysis. 39. The method according to claim 32, wherein the at least one sensor includes a plurality of sensors of different types, and the converting includes mapping intensity variations showing the detected chemical substances included in data from respective sensors in the plurality of sensors onto the frequency space together. 40. A method of testing, investigating, or diagnosing, comprising: a method according to claim 32; a step of capturing static data from the first data; and a step of recognizing a specified substance based on the static data. 41. A method of generating odors, comprising: receiving first data including content data produced by mapping intensity variations showing chemical substances including at least one of compounds, molecules, and elements onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances; supplying odor data to a device driver based on the content data of the first data; and converting, by the device driver, the odor data to a combination of a plurality of odor sources that are used in an odor generating apparatus. 42. The method according to claim 41, further comprising obtaining, from sensors, environmental information at a time of reproduction that includes at least one of temperature and humidity; and comparing the obtained environmental information at the time of reproduction to environmental information of when the first data was generated and converting the content data of the first data to odor data suited to the obtained environmental information at a time of reproduction. 43. The method according to claim 41, further comprising obtaining information, which relates to chemical substances at a time of reproduction and includes intensity variations showing chemical substances at the time of reproduction, from a sensor detecting an amount that changes according to presence of a chemical substance; and comparing the obtained information related to chemical substances at the time of reproduction to the content data of the first data and converting the first data to odor data suited to the obtained information related to chemical substances at the time of reproduction. 44. The method according to claim 41, further comprising converting the content data of the first data to the odor data based on characteristics of the human sense of smell. 45. A program for causing a computer to function as an apparatus that generates first data including content data relating to chemical substances, wherein the chemical substances include at least one of compounds, molecules, and elements, and the apparatus that generates comprises a conversion unit that converts intensity variations showing detected chemical substances included in data from at least one sensor that detects an amount that changes due to presence of at least one of the chemical substances, to the content data by mapping onto a frequency space where a plurality of frequencies have been respectively assigned to a plurality of specified chemical substances.

Semen and sperm cell processing and preservation systems, and methods of producing a mammal and methods of producing mammalian embryos are disclosed. The present invention is directed to sperm cell preservation, fertilization, and insemination, maintaining or enhancing sperm quality and addressing one or more sperm cell characteristics, such as viability, motility, functionality, fertilization rates, and pregnancy rates. Further, sperm cell characteristics may be addressed within the context of various collection, handling, separation, storage, transportation, usage, fertilization, or insemination techniques.

1-53. (canceled) 54. A method of producing a non-human mammalian embryo comprising: obtaining cryopreserved sperm cells; thawing the cryopreserved sperm cells; sorting the thawed sperm cells; cryopreserving the sorted sperm cells; thawing the twice cryopreserved sperm cells; fertilizing at least one egg with the thawed, twice cryopreserved sperm cells; and producing a non-human mammalian embryo. 55. The method of claim 54, further comprising the step of producing a non-human mammal from the at least one fertilized egg. 56. The method of claim 54, further comprising the step of inseminating at least one female of a species of the non-human mammal said thawed, twice cryopreserved sperm cells. 57. The method of claim 54, wherein the step of inseminating a female comprises inseminating a superovulated female with the thawed, twice cryopreserved sperm cells. 58. The method of claim 54, wherein the step of fertilizing further comprises fertilizing the at least one egg in vitro. 59. The method of claim 54, further comprising the step of transferring the at least one fertilized egg to a recipient female. 60. The method of claim 54, further comprising the step of obtaining at least one egg of a superovulated female of a species of the mammal and wherein the step of fertilizing includes fertilizing the at least one egg in vitro. 61. The method of claim 60, wherein the step of fertilizing the at least one egg in vitro further comprises fertilizing more than one egg in vitro. 62. The method of claim 60, further comprising the step of transferring the at least one fertilized egg to a recipient female. 63. The method of claim 54, further comprising the step of establishing at least one sperm sample from the sperm cells. 64. The method of claim 63, wherein the step of establishing at least one sperm sample further comprises establishing at least one sperm sample of the thawed sperm cells, and in that the second cryopreserving step includes cryopreserving the at least one sperm sample. 65. The method of claim 63, wherein the step of establishing at least one sperm sample further comprises establishing a sample of the sperm cells capable of fertilizing at least one egg of the female non-human mammal. 66. The method of claim 63, wherein the step of establishing at least one sperm sample further comprises establishing a sample of the sperm cells capable of fertilizing at least one egg of a superovulating female non-human mammal. 67. The method claim of 63, wherein the step of establishing at least one sperm sample further comprises establishing a sample of the sperm cells capable of fertilization in vitro of at least one egg. 68. The method of claim 63, further comprising the step of producing an offspring from the sperm sample. 69. The method of claim 54, further comprising the step of fertilizing a plurality of eggs of a female non-human mammal. 70. The method of claim 54, further comprising the step of producing at least one animal of a pre-selected sex from the cryopreserved processed sperm cells. 71. The method of claim 54, wherein the twice cryopreserved sperm cells have a pre-selected sex. 72. The method of claim 54, wherein the twice cryopreserved sperm cells include a sperm sample selected from the group consisting of: a straw, a pellet, an insemination dose, and a prepared sperm sample.

Semen and sperm cell processing and preservation systems, and methods of producing a mammal and methods of producing mammalian embryos are disclosed. The present invention is directed to sperm cell preservation, fertilization, and insemination, maintaining or enhancing sperm quality and addressing one or more sperm cell characteristics, such as viability, motility, functionality, fertilization rates, and pregnancy rates. Further, sperm cell characteristics may be addressed within the context of various collection, handling, separation, storage, transportation, usage, fertilization, or insemination techniques.1-53. (canceled) 54. A method of producing a non-human mammalian embryo comprising: obtaining cryopreserved sperm cells; thawing the cryopreserved sperm cells; sorting the thawed sperm cells; cryopreserving the sorted sperm cells; thawing the twice cryopreserved sperm cells; fertilizing at least one egg with the thawed, twice cryopreserved sperm cells; and producing a non-human mammalian embryo. 55. The method of claim 54, further comprising the step of producing a non-human mammal from the at least one fertilized egg. 56. The method of claim 54, further comprising the step of inseminating at least one female of a species of the non-human mammal said thawed, twice cryopreserved sperm cells. 57. The method of claim 54, wherein the step of inseminating a female comprises inseminating a superovulated female with the thawed, twice cryopreserved sperm cells. 58. The method of claim 54, wherein the step of fertilizing further comprises fertilizing the at least one egg in vitro. 59. The method of claim 54, further comprising the step of transferring the at least one fertilized egg to a recipient female. 60. The method of claim 54, further comprising the step of obtaining at least one egg of a superovulated female of a species of the mammal and wherein the step of fertilizing includes fertilizing the at least one egg in vitro. 61. The method of claim 60, wherein the step of fertilizing the at least one egg in vitro further comprises fertilizing more than one egg in vitro. 62. The method of claim 60, further comprising the step of transferring the at least one fertilized egg to a recipient female. 63. The method of claim 54, further comprising the step of establishing at least one sperm sample from the sperm cells. 64. The method of claim 63, wherein the step of establishing at least one sperm sample further comprises establishing at least one sperm sample of the thawed sperm cells, and in that the second cryopreserving step includes cryopreserving the at least one sperm sample. 65. The method of claim 63, wherein the step of establishing at least one sperm sample further comprises establishing a sample of the sperm cells capable of fertilizing at least one egg of the female non-human mammal. 66. The method of claim 63, wherein the step of establishing at least one sperm sample further comprises establishing a sample of the sperm cells capable of fertilizing at least one egg of a superovulating female non-human mammal. 67. The method claim of 63, wherein the step of establishing at least one sperm sample further comprises establishing a sample of the sperm cells capable of fertilization in vitro of at least one egg. 68. The method of claim 63, further comprising the step of producing an offspring from the sperm sample. 69. The method of claim 54, further comprising the step of fertilizing a plurality of eggs of a female non-human mammal. 70. The method of claim 54, further comprising the step of producing at least one animal of a pre-selected sex from the cryopreserved processed sperm cells. 71. The method of claim 54, wherein the twice cryopreserved sperm cells have a pre-selected sex. 72. The method of claim 54, wherein the twice cryopreserved sperm cells include a sperm sample selected from the group consisting of: a straw, a pellet, an insemination dose, and a prepared sperm sample.

Compositions and methods for reducing susceptibility to infectious disease in bees using RNA interference technology, and more particularly, prevention and treatment of viral infections in honeybees such as Israel acute paralysis virus (IAPV) by feeding of pathogen-specific dsRNA. Further, multiple-pathogen specific dsRNA is disclosed.

1. A method for increasing the tolerance of a honeybee to a disease caused by a bee pathogen, comprising feeding the bee an effective amount of a bee-ingestible composition comprising a double stranded ribonucleic acid (dsRNA) comprising an RNA sequence capable of hybridizing to an mRNA transcript encoding a polypeptide or a RNA target sequence of at least one bee pathogen, thereby increasing the tolerance of the honeybee to the disease. 2. The method of claim 1, wherein the at least one bee pathogen is selected from the group consisting of: Acute Bee Paralysis Virus (ABPV), Kashmir Bee Virus (KBV), Sacbrood virus (SBV), Black queen cell virus (BQCV), Kakugo virus (KV), Deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). 3. The method of claim 1, wherein the dsRNA comprises an RNA sequence that is capable of hybridizing to an mRNA transcript encoding a polypeptide or a RNA target sequence of two or more bee pathogens. 4. The method of claim 1, wherein the isolated dsRNA comprises an RNA sequence that is complementary to a nucleic acid comprising a nucleotide sequence as set forth in SEQ ID NOs: 24, 47, 49, 50 or 51. 5. The method of claim 1, wherein the dsRNA is selected from the group consisting of siRNA, shRNA and miRNA. 6. The method of claim 1, wherein the bee-ingestible composition is in solid form. 7. The method of claim 1, wherein the bee-ingestible composition is in liquid form. 8. The method of claim 1, wherein the bee-ingestible composition comprises a protein. 9. The method of claim 1, wherein the honeybee is a member of a colony, and wherein providing the bee-ingestible composition to the honeybee increases the tolerance of the colony to the disease. 10. A bee-ingestible composition comprising a double stranded ribonucleic acid (dsRNA) comprising an RNA sequence complementary to a nucleic acid comprising a nucleotide sequence that is highly homologous to a nucleotide sequence of at least one bee virus. 11. The bee-ingestible composition of claim 10, wherein the at least one bee virus is selected from the group consisting of: Acute Bee Paralysis Virus (ABPV), Kashmir Bee Virus (KBV), Sacbrood virus (SBV), Black queen cell virus (BQCV), Kakugo virus (KV), Deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). 12. The bee-ingestible composition of claim 10, wherein the dsRNA comprises an RNA sequence that is complementary to a nucleotide sequence that is highly homologous to a nucleotide sequence of two or more bee viruses. 13. The bee-ingestible composition of claim 10, wherein the dsRNA comprises an RNA sequence that is complementary to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 24, 47, 49, 50 and 51. 14. The bee-ingestible composition of claim 10, wherein the composition is in solid form. 15. The bee-ingestible composition of claim 10, wherein said composition is in liquid form. 16. The bee-ingestible composition of claim 10, wherein the composition comprises a protein. 17. The bee-ingestible composition of claim 10, wherein the composition comprises a carbohydrate or sugar supplement. 18. The bee-ingestible composition of claim 10, wherein the dsRNA is selected from the group consisting of siRNA, shRNA and miRNA. 19. A nucleic acid construct comprising a promoter operably linked to a nucleic acid encoding the dsRNA of claim 10. 20. The nucleic acid construct of claim 19, wherein the dsRNA comprises an RNA sequence that is complementary to SEQ ID NO: 24.

Compositions and methods for reducing susceptibility to infectious disease in bees using RNA interference technology, and more particularly, prevention and treatment of viral infections in honeybees such as Israel acute paralysis virus (IAPV) by feeding of pathogen-specific dsRNA. Further, multiple-pathogen specific dsRNA is disclosed.1. A method for increasing the tolerance of a honeybee to a disease caused by a bee pathogen, comprising feeding the bee an effective amount of a bee-ingestible composition comprising a double stranded ribonucleic acid (dsRNA) comprising an RNA sequence capable of hybridizing to an mRNA transcript encoding a polypeptide or a RNA target sequence of at least one bee pathogen, thereby increasing the tolerance of the honeybee to the disease. 2. The method of claim 1, wherein the at least one bee pathogen is selected from the group consisting of: Acute Bee Paralysis Virus (ABPV), Kashmir Bee Virus (KBV), Sacbrood virus (SBV), Black queen cell virus (BQCV), Kakugo virus (KV), Deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). 3. The method of claim 1, wherein the dsRNA comprises an RNA sequence that is capable of hybridizing to an mRNA transcript encoding a polypeptide or a RNA target sequence of two or more bee pathogens. 4. The method of claim 1, wherein the isolated dsRNA comprises an RNA sequence that is complementary to a nucleic acid comprising a nucleotide sequence as set forth in SEQ ID NOs: 24, 47, 49, 50 or 51. 5. The method of claim 1, wherein the dsRNA is selected from the group consisting of siRNA, shRNA and miRNA. 6. The method of claim 1, wherein the bee-ingestible composition is in solid form. 7. The method of claim 1, wherein the bee-ingestible composition is in liquid form. 8. The method of claim 1, wherein the bee-ingestible composition comprises a protein. 9. The method of claim 1, wherein the honeybee is a member of a colony, and wherein providing the bee-ingestible composition to the honeybee increases the tolerance of the colony to the disease. 10. A bee-ingestible composition comprising a double stranded ribonucleic acid (dsRNA) comprising an RNA sequence complementary to a nucleic acid comprising a nucleotide sequence that is highly homologous to a nucleotide sequence of at least one bee virus. 11. The bee-ingestible composition of claim 10, wherein the at least one bee virus is selected from the group consisting of: Acute Bee Paralysis Virus (ABPV), Kashmir Bee Virus (KBV), Sacbrood virus (SBV), Black queen cell virus (BQCV), Kakugo virus (KV), Deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). 12. The bee-ingestible composition of claim 10, wherein the dsRNA comprises an RNA sequence that is complementary to a nucleotide sequence that is highly homologous to a nucleotide sequence of two or more bee viruses. 13. The bee-ingestible composition of claim 10, wherein the dsRNA comprises an RNA sequence that is complementary to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 24, 47, 49, 50 and 51. 14. The bee-ingestible composition of claim 10, wherein the composition is in solid form. 15. The bee-ingestible composition of claim 10, wherein said composition is in liquid form. 16. The bee-ingestible composition of claim 10, wherein the composition comprises a protein. 17. The bee-ingestible composition of claim 10, wherein the composition comprises a carbohydrate or sugar supplement. 18. The bee-ingestible composition of claim 10, wherein the dsRNA is selected from the group consisting of siRNA, shRNA and miRNA. 19. A nucleic acid construct comprising a promoter operably linked to a nucleic acid encoding the dsRNA of claim 10. 20. The nucleic acid construct of claim 19, wherein the dsRNA comprises an RNA sequence that is complementary to SEQ ID NO: 24.

Novel compositions including bepotastine besilate are provided such as sorbitol-free compositions, compositions including at least about 0.008% w/v benzalkonium chloride, and compositions including hydroxypropylmethyl cellulose E15 LV.

1-58. (canceled) 59. A method of treating at least one of rhinitis, mucosal inflammation associated with rhinitis, sinusitis, rhinosinusitis, and symptoms associated with rhinitis, mucosal inflammation associated with rhinitis, sinusitis, and/or rhinosinusitis in a patient in need of such treatment, the method comprising nasally administering a pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine at a concentration ranging from 0.5% w/v to 8.00% w/v in aqueous solution to the patient in need thereof, in a dose regimen effective to treat at least one of rhinitis, mucosal inflammation associated with rhinitis, sinusitis, rhinosinusitis, and symptoms associated with rhinitis, mucosal inflammation associated with rhinitis, sinusitis, and/or rhinosinusitis. 60. The method of claim 59 wherein bepotastine in the composition administered is at a concentration ranging from 2.00% w/v to 4.00% w/v and administration is from 1 time a day to 4 times a day. 61. The method of claim 59 wherein bepotastine in the composition administered is at a concentration of either 3.00% w/v or 4.00% w/v and administration is either 1 time a day or is at more than 12 hour intervals. 62. The method of claim 59 wherein the dose regimen is effective to treat allergic rhinitis. 63. The method of claim 59 wherein the composition administered comprises dibasic sodium phosphate heptahydrate at a concentration of 0.10% w/v to 1.00% w/v; sodium chloride at a concentration of 0.9% w/v with 0.5% bepotastine, 0.4% w/v with 2.00%-3.00% bepotastine, 0.3% w/v with 4.00% bepotastine, 0.2% w/v with 6.00% bepotastine, 0.1% w/v with 8.00% bepotastine; edetate disodium at a concentration of 0.005% w/v to 0.100% w/v; benzalkonium chloride at a concentration of 0.002% w/v to 0.200% w/v; and one of either: a blend of microcrystalline cellulose and carboxymethyl cellulose (AVICEL®) at a concentration of 0.5% w/v to 2.5% w/v and polyoxyethylene (20) sorbitan monooleate (polysorbate 80) at a concentration of 0.005% w/v to 0.050% w/v, or HPMC E15 LV at a concentration of 0.01% w/v to 1.00% w/v, citric acid monohydrate at a concentration of 0.10% w/v to 1.00% w/v, and a taste-making agent at a concentration of 0.01% w/v to 1.00% w/v. 64. The method of claim 59 wherein the composition administered comprises dibasic sodium phosphate heptahydrate at a concentration of 0.70% w/v, sodium chloride at a concentration of 0.30% w/v, edetate disodium at a concentration of 0.020% w/v, benzalkonium chloride at a concentration of 0.020% w/v, and one of either: AVICEL® at a concentration of 2.00% w/v and polysorbate 80 at a concentration of 0.015% w/v, or HPMC at a concentration of 0.10% w/v, citric acid monohydrate at a concentration of 0.10% w/v, and sucralose at a concentration of 0.10% w/v. 65. The method of claim 59 wherein the pharmaceutically acceptable salt of bepotastine is besilate. 66. The method of claim 63 wherein AVICEL® is AVICEL® CL-611. 67. The method of claim 63 wherein HPMC is HPMC E15 LV.

Novel compositions including bepotastine besilate are provided such as sorbitol-free compositions, compositions including at least about 0.008% w/v benzalkonium chloride, and compositions including hydroxypropylmethyl cellulose E15 LV.1-58. (canceled) 59. A method of treating at least one of rhinitis, mucosal inflammation associated with rhinitis, sinusitis, rhinosinusitis, and symptoms associated with rhinitis, mucosal inflammation associated with rhinitis, sinusitis, and/or rhinosinusitis in a patient in need of such treatment, the method comprising nasally administering a pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine at a concentration ranging from 0.5% w/v to 8.00% w/v in aqueous solution to the patient in need thereof, in a dose regimen effective to treat at least one of rhinitis, mucosal inflammation associated with rhinitis, sinusitis, rhinosinusitis, and symptoms associated with rhinitis, mucosal inflammation associated with rhinitis, sinusitis, and/or rhinosinusitis. 60. The method of claim 59 wherein bepotastine in the composition administered is at a concentration ranging from 2.00% w/v to 4.00% w/v and administration is from 1 time a day to 4 times a day. 61. The method of claim 59 wherein bepotastine in the composition administered is at a concentration of either 3.00% w/v or 4.00% w/v and administration is either 1 time a day or is at more than 12 hour intervals. 62. The method of claim 59 wherein the dose regimen is effective to treat allergic rhinitis. 63. The method of claim 59 wherein the composition administered comprises dibasic sodium phosphate heptahydrate at a concentration of 0.10% w/v to 1.00% w/v; sodium chloride at a concentration of 0.9% w/v with 0.5% bepotastine, 0.4% w/v with 2.00%-3.00% bepotastine, 0.3% w/v with 4.00% bepotastine, 0.2% w/v with 6.00% bepotastine, 0.1% w/v with 8.00% bepotastine; edetate disodium at a concentration of 0.005% w/v to 0.100% w/v; benzalkonium chloride at a concentration of 0.002% w/v to 0.200% w/v; and one of either: a blend of microcrystalline cellulose and carboxymethyl cellulose (AVICEL®) at a concentration of 0.5% w/v to 2.5% w/v and polyoxyethylene (20) sorbitan monooleate (polysorbate 80) at a concentration of 0.005% w/v to 0.050% w/v, or HPMC E15 LV at a concentration of 0.01% w/v to 1.00% w/v, citric acid monohydrate at a concentration of 0.10% w/v to 1.00% w/v, and a taste-making agent at a concentration of 0.01% w/v to 1.00% w/v. 64. The method of claim 59 wherein the composition administered comprises dibasic sodium phosphate heptahydrate at a concentration of 0.70% w/v, sodium chloride at a concentration of 0.30% w/v, edetate disodium at a concentration of 0.020% w/v, benzalkonium chloride at a concentration of 0.020% w/v, and one of either: AVICEL® at a concentration of 2.00% w/v and polysorbate 80 at a concentration of 0.015% w/v, or HPMC at a concentration of 0.10% w/v, citric acid monohydrate at a concentration of 0.10% w/v, and sucralose at a concentration of 0.10% w/v. 65. The method of claim 59 wherein the pharmaceutically acceptable salt of bepotastine is besilate. 66. The method of claim 63 wherein AVICEL® is AVICEL® CL-611. 67. The method of claim 63 wherein HPMC is HPMC E15 LV.

A tag database establishment section converts, based on information such as an amino acid sequence of an identified peptide and m/z of a peak, a sequence tag indicating a partial sequence and information related to the tag into a database and creates a tag database. When MS2 spectrum information is obtained by measuring a target peptide, a sequence tag acquisition section executes, on the tag database, a search based on coincidence of the m/z of the peak and the like and extracts a sequence tag with high reliability. A peptide identification section performs, based on an amino acid sequence of the sequence tag, m/z of a precursor ion, and the like, a search by a sequence tag search method taking into account a post-translational modification or a variation and identifies a peptide.

1. A mass spectrometric data analyzing apparatus that identifies, based on MSn spectrum data collected by executing an MSn analysis (n is an integer equal to or larger than 2) on a test sample, a target peptide in the test sample, the mass spectrometric data analyzing apparatus comprising: a) a tag database establishment section for establishing a sequence tag database in advance obtaining, from an amino acid sequence of a known peptide and MSn spectrum information, a sequence tag, which is a partial amino acid sequence, and spectrum peak information corresponding to the sequence tag; b) a sequence tag acquisition section for acquiring a sequence tag of the target peptide by collating peak information extracted from a measured MSn spectrum obtained for the test sample with information in the sequence tag database; and c) a peptide identification section for identifying a peptide by performing a database search in the sequence tag database or in a protein database using, as search conditions, the sequence tag for the target peptide obtained by the sequence tag acquisition section and mass of a precursor ion deriving from the target peptide. 2. The mass spectrometric data analyzing apparatus according to claim 1, wherein the tag database establishment section stores information indicating that an amino acid sequence of a sequence tag is subjected to a post-translational modification or a variation in association with the sequence tag when an amino acid sequence of a sequence tag is subjected to a post-translational modification or variation. 3. The mass spectrometric data analyzing apparatus according to claim 1, wherein the peptide identification section performs a database search with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database. 4. The mass spectrometric data analyzing apparatus according to claim 2, wherein the peptide identification section performs a database search with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database. 5. The mass spectrometric data analyzing apparatus according to claim 3, wherein the peptide identification section distinguishes, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and the peptide identification section performs, when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search after correcting the amino acid sequence of the sequence tag to be subjected to a post-translational modification or a variation equivalent to the difference. 6. The mass spectrometric data analyzing apparatus according to claim 4, wherein the peptide identification section distinguishes, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and the peptide identification section performs, when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search after correcting the amino acid sequence of the sequence tag to be subjected to a post-translational modification or a variation equivalent to the difference. 7. A mass spectrometric data analyzing method for identifying, based on MSn spectrum data collected by executing an MSn analysis (n is an integer equal to or larger than 2) on a test sample, a target peptide in the test sample, the mass spectrometric data analyzing method comprising: a) a tag database establishment step for establishing a sequence tag database in advance by obtaining, from an amino acid sequence of a known peptide and MSn spectrum information, a sequence tag, which is a partial amino acid sequence, and spectrum peak information corresponding to the sequence tag; b) a sequence tag acquisition step for acquiring a sequence tag of the target peptide by collating peak information extracted from a measured MSn spectrum obtained for the test sample with information in the sequence tag database; and c) a peptide identification step for identifying a peptide by performing a database search in the sequence tag database or in a protein database using, as search conditions, the sequence tag for the target peptide obtained in the sequence tag acquisition step and mass of a precursor ion deriving from the target peptide. 8. The mass spectrometric data analyzing method according to claim 7, wherein, in the tag database establishment step, when an amino acid sequence of a sequence tag is subjected to a post-translational modification or a variation, information indicating to that effect is stored in association with the sequence tag. 9. The mass spectrometric data analyzing method according to claim 7, wherein, in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, a database search is performed with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to the difference. 10. The mass spectrometric data analyzing method according to claim 8, wherein, in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, a database search is performed with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to the difference. 11. The mass spectrometric data analyzing method according to claim 9, wherein in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, it is distinguished whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search is performed after the amino acid sequence of the sequence tag is corrected to be subjected to a post-translational modification or a variation equivalent to the difference. 12. The mass spectrometric data analyzing method according to claim 10, wherein in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, it is distinguished whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search is performed after the amino acid sequence of the sequence tag is corrected to be subjected to a post-translational modification or a variation equivalent to the difference.

A tag database establishment section converts, based on information such as an amino acid sequence of an identified peptide and m/z of a peak, a sequence tag indicating a partial sequence and information related to the tag into a database and creates a tag database. When MS2 spectrum information is obtained by measuring a target peptide, a sequence tag acquisition section executes, on the tag database, a search based on coincidence of the m/z of the peak and the like and extracts a sequence tag with high reliability. A peptide identification section performs, based on an amino acid sequence of the sequence tag, m/z of a precursor ion, and the like, a search by a sequence tag search method taking into account a post-translational modification or a variation and identifies a peptide.1. A mass spectrometric data analyzing apparatus that identifies, based on MSn spectrum data collected by executing an MSn analysis (n is an integer equal to or larger than 2) on a test sample, a target peptide in the test sample, the mass spectrometric data analyzing apparatus comprising: a) a tag database establishment section for establishing a sequence tag database in advance obtaining, from an amino acid sequence of a known peptide and MSn spectrum information, a sequence tag, which is a partial amino acid sequence, and spectrum peak information corresponding to the sequence tag; b) a sequence tag acquisition section for acquiring a sequence tag of the target peptide by collating peak information extracted from a measured MSn spectrum obtained for the test sample with information in the sequence tag database; and c) a peptide identification section for identifying a peptide by performing a database search in the sequence tag database or in a protein database using, as search conditions, the sequence tag for the target peptide obtained by the sequence tag acquisition section and mass of a precursor ion deriving from the target peptide. 2. The mass spectrometric data analyzing apparatus according to claim 1, wherein the tag database establishment section stores information indicating that an amino acid sequence of a sequence tag is subjected to a post-translational modification or a variation in association with the sequence tag when an amino acid sequence of a sequence tag is subjected to a post-translational modification or variation. 3. The mass spectrometric data analyzing apparatus according to claim 1, wherein the peptide identification section performs a database search with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database. 4. The mass spectrometric data analyzing apparatus according to claim 2, wherein the peptide identification section performs a database search with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the sequence tag database. 5. The mass spectrometric data analyzing apparatus according to claim 3, wherein the peptide identification section distinguishes, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and the peptide identification section performs, when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search after correcting the amino acid sequence of the sequence tag to be subjected to a post-translational modification or a variation equivalent to the difference. 6. The mass spectrometric data analyzing apparatus according to claim 4, wherein the peptide identification section distinguishes, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and the peptide identification section performs, when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search after correcting the amino acid sequence of the sequence tag to be subjected to a post-translational modification or a variation equivalent to the difference. 7. A mass spectrometric data analyzing method for identifying, based on MSn spectrum data collected by executing an MSn analysis (n is an integer equal to or larger than 2) on a test sample, a target peptide in the test sample, the mass spectrometric data analyzing method comprising: a) a tag database establishment step for establishing a sequence tag database in advance by obtaining, from an amino acid sequence of a known peptide and MSn spectrum information, a sequence tag, which is a partial amino acid sequence, and spectrum peak information corresponding to the sequence tag; b) a sequence tag acquisition step for acquiring a sequence tag of the target peptide by collating peak information extracted from a measured MSn spectrum obtained for the test sample with information in the sequence tag database; and c) a peptide identification step for identifying a peptide by performing a database search in the sequence tag database or in a protein database using, as search conditions, the sequence tag for the target peptide obtained in the sequence tag acquisition step and mass of a precursor ion deriving from the target peptide. 8. The mass spectrometric data analyzing method according to claim 7, wherein, in the tag database establishment step, when an amino acid sequence of a sequence tag is subjected to a post-translational modification or a variation, information indicating to that effect is stored in association with the sequence tag. 9. The mass spectrometric data analyzing method according to claim 7, wherein, in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, a database search is performed with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to the difference. 10. The mass spectrometric data analyzing method according to claim 8, wherein, in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, a database search is performed with an additional condition that a peptide is subjected to a post-translational modification or a variation equivalent to the difference. 11. The mass spectrometric data analyzing method according to claim 9, wherein in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, it is distinguished whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search is performed after the amino acid sequence of the sequence tag is corrected to be subjected to a post-translational modification or a variation equivalent to the difference. 12. The mass spectrometric data analyzing method according to claim 10, wherein in the peptide identification step, when there is a difference between mass of a precursor ion deriving from the target peptide and mass of a precursor ion stored in the tag database, it is distinguished whether the difference is present in an amino acid sequence portion corresponding to the sequence tag, and when the difference is present in the amino acid sequence portion corresponding to the sequence tag, the database search is performed after the amino acid sequence of the sequence tag is corrected to be subjected to a post-translational modification or a variation equivalent to the difference.

The present invention provides liposomes that are useful for delivery of bioactive agents such as therapeutics. Among others, the liposomes of the invention are capable of delivering their payload at sites of increased secretory phospholipase A2 (sPLA2) activity, because phospholipase A2 (PLA2) will hydrolyse lipids of the liposome. Thus, the liposomes of the invention may e.g. be used in relation to cancer therapy. Another aspect of the invention is a liposomal formulation comprising the liposome of the invention. Still another aspect is a method of producing a liposomal formulation of the invention.

1. A liposome comprising between 25% and 45% (mol/mol) of an anionic lipid, less than 1% cholesterol (mol/mol) and a therapeutic agent selected from the group consisting of small molecule antitumour agents, antibiotics, antifungals, and anti-inflammatory agents wherein the liposome has been exposed to a divalent cation at a concentration between 0.1 mM and 1 mM. 2. The liposome of claim 1, wherein the anionic lipid is selected from a group consisting of PI (phosphatidyl inositol), PS (phosphatidyl serine), DPG (bisphosphatidyl glycerol), PA (phosphatidic acid), PEOH (phosphatidyl alcohol), and PG (phosphatidyl glycerol). 3. The liposome of claim 2, wherein the anionic lipid is phosphatidyl glycerol. 4. The liposome of claim 1, further comprising a hydrophilic polymer selected from the group of PEG [poly(ethylene glycol)], PAcM [poly(N-acryloylmorpholine)], PVP [poly(vinylpyrrolidone)], PLA [poly(lactide)], PG [poly(glycolide)], POZO [poly(2-methyl-2-oxazoline)], PVA [poly(vinyl alcohol)], HPMC (hydroxypropylmethylcellulose), PEO [poly(ethylene oxide)], chitosan [poly(D-glucosamine)], PAA [poly(aminoacid)], polyHEMA [Poly(2-hydroxyethylmethacrylate)] and co-polymers thereof. 5. The liposome of claim 4, wherein the polymer is PEG with a molecular weight between 100 Da and 10 kDa. 6. The liposome of claim 4, wherein polymer is conjugated to the head group of phosphatidyl ethanolamine. 7. The liposome of claim 6, wherein the amount of polymer-conjugated lipid is between 2.5% and 7.5% (mol/mol). 8. The liposome of claim 1, further comprising an uncharged phospholipid selected from the group consisting of PC (phosphatidyl choline) and PE (phosphatidylethanolamine). 9. The liposome of claim 1, comprising no cholesterol. 10. The liposome of claim 1, wherein the alkyl chains of the lipids are C18 saturated chains. 11. The liposome of claim 1, wherein the therapeutic agent is a small molecule antitumour agent selected from the group consisting of anthracyclin derivatives, cisplatin, oxaliplatin, carboplatin, doxorubicin, paclitaxel, 5-fluoruracil, exisulind, cis-retinoic acid, suldinac sulphide, methotrexate, bleomycin and vincristine. 12. The liposome of claim 11, wherein the therapeutic agent is oxaliplatin or cisplatin. 13. The liposome of claim 1, wherein the liposome is a Large Unilamellar Vesicle (LUV). 14. The liposome of claim 13, wherein the liposome has a diameter between 80 and 120 nm. 15. The liposome of claim 1, wherein at least one of the lipids in the liposome is a substrate for sPLA2. 16. A liposome of any of claim 1, further comprising between 0.1 mM and 1 mM of a divalent cation. 17. The liposome of claim 16, wherein the divalent cation is Ca2+. 18. The liposome formulation comprising liposomes according to claim 17. 19. The liposome formulation of claim 18, wherein the Poly Dispersity Index is 0.20 or less. 20. A method for the preparation of a liposomal formulation according to claim 18 comprising the steps of: a. preparing a lipid mixture by dissolving selected lipids in an organic solvent b. hydrating the product of step a) with an aqueous hydration solvent so as to form liposomes; and c. removing the organic solvent of step a) either before addition of the aqueous hydration solvent or after the addition of the aqueous hydration solvent. 21. The method of claim 20, wherein organic solvent is removed before addition of hydration solvent. 22. The method of claim 20 further comprising a step of sonicating the liposomal formulation to produce liposomes of a certain size. 23. The method of claim 20, wherein the hydration solvent comprises a divalent cation at a concentration between 0.1 mM and 1 mM. 24. The method of claim 20 further comprising a step of changing the exterior water phase to another exterior water phase comprising a divalent cation at a concentration 0.1 mM and 1 mM. 25. The method of claim 20, wherein the divalent cation is Ca2+.

The present invention provides liposomes that are useful for delivery of bioactive agents such as therapeutics. Among others, the liposomes of the invention are capable of delivering their payload at sites of increased secretory phospholipase A2 (sPLA2) activity, because phospholipase A2 (PLA2) will hydrolyse lipids of the liposome. Thus, the liposomes of the invention may e.g. be used in relation to cancer therapy. Another aspect of the invention is a liposomal formulation comprising the liposome of the invention. Still another aspect is a method of producing a liposomal formulation of the invention.1. A liposome comprising between 25% and 45% (mol/mol) of an anionic lipid, less than 1% cholesterol (mol/mol) and a therapeutic agent selected from the group consisting of small molecule antitumour agents, antibiotics, antifungals, and anti-inflammatory agents wherein the liposome has been exposed to a divalent cation at a concentration between 0.1 mM and 1 mM. 2. The liposome of claim 1, wherein the anionic lipid is selected from a group consisting of PI (phosphatidyl inositol), PS (phosphatidyl serine), DPG (bisphosphatidyl glycerol), PA (phosphatidic acid), PEOH (phosphatidyl alcohol), and PG (phosphatidyl glycerol). 3. The liposome of claim 2, wherein the anionic lipid is phosphatidyl glycerol. 4. The liposome of claim 1, further comprising a hydrophilic polymer selected from the group of PEG [poly(ethylene glycol)], PAcM [poly(N-acryloylmorpholine)], PVP [poly(vinylpyrrolidone)], PLA [poly(lactide)], PG [poly(glycolide)], POZO [poly(2-methyl-2-oxazoline)], PVA [poly(vinyl alcohol)], HPMC (hydroxypropylmethylcellulose), PEO [poly(ethylene oxide)], chitosan [poly(D-glucosamine)], PAA [poly(aminoacid)], polyHEMA [Poly(2-hydroxyethylmethacrylate)] and co-polymers thereof. 5. The liposome of claim 4, wherein the polymer is PEG with a molecular weight between 100 Da and 10 kDa. 6. The liposome of claim 4, wherein polymer is conjugated to the head group of phosphatidyl ethanolamine. 7. The liposome of claim 6, wherein the amount of polymer-conjugated lipid is between 2.5% and 7.5% (mol/mol). 8. The liposome of claim 1, further comprising an uncharged phospholipid selected from the group consisting of PC (phosphatidyl choline) and PE (phosphatidylethanolamine). 9. The liposome of claim 1, comprising no cholesterol. 10. The liposome of claim 1, wherein the alkyl chains of the lipids are C18 saturated chains. 11. The liposome of claim 1, wherein the therapeutic agent is a small molecule antitumour agent selected from the group consisting of anthracyclin derivatives, cisplatin, oxaliplatin, carboplatin, doxorubicin, paclitaxel, 5-fluoruracil, exisulind, cis-retinoic acid, suldinac sulphide, methotrexate, bleomycin and vincristine. 12. The liposome of claim 11, wherein the therapeutic agent is oxaliplatin or cisplatin. 13. The liposome of claim 1, wherein the liposome is a Large Unilamellar Vesicle (LUV). 14. The liposome of claim 13, wherein the liposome has a diameter between 80 and 120 nm. 15. The liposome of claim 1, wherein at least one of the lipids in the liposome is a substrate for sPLA2. 16. A liposome of any of claim 1, further comprising between 0.1 mM and 1 mM of a divalent cation. 17. The liposome of claim 16, wherein the divalent cation is Ca2+. 18. The liposome formulation comprising liposomes according to claim 17. 19. The liposome formulation of claim 18, wherein the Poly Dispersity Index is 0.20 or less. 20. A method for the preparation of a liposomal formulation according to claim 18 comprising the steps of: a. preparing a lipid mixture by dissolving selected lipids in an organic solvent b. hydrating the product of step a) with an aqueous hydration solvent so as to form liposomes; and c. removing the organic solvent of step a) either before addition of the aqueous hydration solvent or after the addition of the aqueous hydration solvent. 21. The method of claim 20, wherein organic solvent is removed before addition of hydration solvent. 22. The method of claim 20 further comprising a step of sonicating the liposomal formulation to produce liposomes of a certain size. 23. The method of claim 20, wherein the hydration solvent comprises a divalent cation at a concentration between 0.1 mM and 1 mM. 24. The method of claim 20 further comprising a step of changing the exterior water phase to another exterior water phase comprising a divalent cation at a concentration 0.1 mM and 1 mM. 25. The method of claim 20, wherein the divalent cation is Ca2+.

The invention relates to the combination of a sulforaphane precursor, an enzyme capable of converting the sulforaphane precursor to sulforaphane, an enzyme potentiator, and a milk thistle extract or powder. The invention also relates to the combination of a sulforaphane or a derivative thereof and a milk thistle extract or powder. The invention also relates to the combination of a broccoli extract or powder and a milk thistle extract or powder. The invention provides compositions and methods relating to these combinations.

1-14. (canceled) 15. An orally administrable composition comprising a broccoli extract or powder and a milk thistle extract or powder. 16. The orally administrable composition of claim 15, wherein the broccoli extract or powder comprises glucoraphanin in an amount of about 1 to about 75% w/w. 17. The orally administrable composition of claim 15, wherein the broccoli extract or powder comprises myrosinase. 18. The orally administrable composition of claim 15, further comprising an enzyme potentiator. 19. The orally administrable composition of claim 15, wherein the enzyme potentiator comprises ascorbic acid. 20. The orally administrable composition of claim 15, wherein the composition comprises an enteric-coated dosage form. 21. The orally administrable composition of claim 15, comprising a milk thistle extract comprising silymarin. 22. The orally administrable composition of claim 15, comprising a milk thistle extract comprising silibinin. 23. The orally administrable composition of claim 15, further comprising one or more additional components selected from the group consisting of: quercetin, an aminosugar, a glycosaminoglycan, avocado/soybean unsaponifiable, a vitamin, coffee fruit, magnesium, silymarin, proanthocyanidins, ursolic acid, curcumin, phytosterols, phytostanols, and S-adenosylmethionine (SAMe). 24. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of, a disease or condition associated with the liver, prostate, brain, lung, kidneys, colon, breast, esophagus, pancreas, or ovaries in a subject in need thereof, comprising administering to the subject the orally administrable composition of claim 15. 25. A method of increasing glutathione levels in a subject, comprising administering to the subject in need thereof the orally administrable composition of claim 15. 26. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of a non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to the subject in need thereof the orally administrable composition of claim 15. 27. An orally administrable composition comprising sulforaphane or a derivative thereof and a milk thistle extract or powder. 28. The orally administrable composition of claim 27, comprising a milk thistle extract comprising silymarin. 29. The orally administrable composition of claim 27, comprising a milk thistle extract comprising silibinin. 30. The orally administrable composition of claim 27, further comprising one or more additional components selected from the group consisting of: quercetin, an aminosugar, a glycosaminoglycan, avocado/soybean unsaponifiable, a vitamin, coffee fruit, magnesium, silymarin, proanthocyanidins, ursolic acid, curcumin, phytosterols, and phytostanols. 31. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of, a disease or condition associated with the liver, prostate, brain, lung, kidneys, colon, breast, esophagus, pancreas, or ovaries in a subject in need thereof, comprising administering to the subject the orally administrable composition of claim 27. 32. A method of increasing glutathione levels in a subject, comprising administering to the subject in need thereof the orally administrable composition of claim 27. 33. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of a non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to the subject in need thereof the orally administrable composition of claim 27.

The invention relates to the combination of a sulforaphane precursor, an enzyme capable of converting the sulforaphane precursor to sulforaphane, an enzyme potentiator, and a milk thistle extract or powder. The invention also relates to the combination of a sulforaphane or a derivative thereof and a milk thistle extract or powder. The invention also relates to the combination of a broccoli extract or powder and a milk thistle extract or powder. The invention provides compositions and methods relating to these combinations.1-14. (canceled) 15. An orally administrable composition comprising a broccoli extract or powder and a milk thistle extract or powder. 16. The orally administrable composition of claim 15, wherein the broccoli extract or powder comprises glucoraphanin in an amount of about 1 to about 75% w/w. 17. The orally administrable composition of claim 15, wherein the broccoli extract or powder comprises myrosinase. 18. The orally administrable composition of claim 15, further comprising an enzyme potentiator. 19. The orally administrable composition of claim 15, wherein the enzyme potentiator comprises ascorbic acid. 20. The orally administrable composition of claim 15, wherein the composition comprises an enteric-coated dosage form. 21. The orally administrable composition of claim 15, comprising a milk thistle extract comprising silymarin. 22. The orally administrable composition of claim 15, comprising a milk thistle extract comprising silibinin. 23. The orally administrable composition of claim 15, further comprising one or more additional components selected from the group consisting of: quercetin, an aminosugar, a glycosaminoglycan, avocado/soybean unsaponifiable, a vitamin, coffee fruit, magnesium, silymarin, proanthocyanidins, ursolic acid, curcumin, phytosterols, phytostanols, and S-adenosylmethionine (SAMe). 24. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of, a disease or condition associated with the liver, prostate, brain, lung, kidneys, colon, breast, esophagus, pancreas, or ovaries in a subject in need thereof, comprising administering to the subject the orally administrable composition of claim 15. 25. A method of increasing glutathione levels in a subject, comprising administering to the subject in need thereof the orally administrable composition of claim 15. 26. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of a non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to the subject in need thereof the orally administrable composition of claim 15. 27. An orally administrable composition comprising sulforaphane or a derivative thereof and a milk thistle extract or powder. 28. The orally administrable composition of claim 27, comprising a milk thistle extract comprising silymarin. 29. The orally administrable composition of claim 27, comprising a milk thistle extract comprising silibinin. 30. The orally administrable composition of claim 27, further comprising one or more additional components selected from the group consisting of: quercetin, an aminosugar, a glycosaminoglycan, avocado/soybean unsaponifiable, a vitamin, coffee fruit, magnesium, silymarin, proanthocyanidins, ursolic acid, curcumin, phytosterols, and phytostanols. 31. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of, a disease or condition associated with the liver, prostate, brain, lung, kidneys, colon, breast, esophagus, pancreas, or ovaries in a subject in need thereof, comprising administering to the subject the orally administrable composition of claim 27. 32. A method of increasing glutathione levels in a subject, comprising administering to the subject in need thereof the orally administrable composition of claim 27. 33. A method of treating, preventing, reducing the occurrence of, decreasing the symptoms associated with, and/or reducing secondary recurrences of a non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to the subject in need thereof the orally administrable composition of claim 27.