Abstract: The present invention relates to compounds of formula I, wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, —CH2—C3-6-cycloalkyl, or bridged C3-5-cycloalkyl, optionally substituted by one, two or three substituents, selected from halogen, lower alkyl or lower alkyl substituted by halogen; R2 is hydrogen, halogen, lower alkoxy, lower alkyl substituted by halogen or lower alkoxy substituted by halogen; R3 is a five membered heteroaryl group, selected from wherein R6 is hydrogen or lower alkyl; R7 is halogen or lower alkyl; R8 is hydrogen or lower alkyl; R9 is hydrogen or lower alkyl; R4 is lower alkyl or lower alkyl substituted by hydroxy; R5/R5? is independently from each other hydrogen or lower alkyl; ( )n- is —CH2— or —CH2CH2— for n being 1 or 2; X is CH or N; or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers and/or optical isomers and/or stereoisomers thereof.

Abstract: The present invention relates to a compound of formula I wherein R1 is phenyl, lower alkyl, C3-6-cycloalkyl, —CH2—C3-6-cycloalkyl or bridged C4-6-cycloalkyl, substituted by one, two or three halogen atoms, or by lower alkyl or lower alkyl substituted by halogen; R2 is a five or six membered heteroaryl group, selected from wherein R6 is hydrogen, lower alkyl, halogen or lower alkoxy; and R7 is hydrogen, lower alkoxy or halogen; R3 is lower alkyl or lower alkyl substituted by hydroxy: R4 is hydrogen or lower alkyl; R5 is hydrogen or lower alkyl; n is 1 or 2; -( )n- is —CH2— or —CH2CH2— for n being 1 or 2; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

Abstract: The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R1?, R2, R2?, R3, R4, R4? and R5 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are LMP7 inhibitors and may be useful in treating associated inflammatory diseases and disorders such as, for example, rheumatoid arthritis, lupus and irritable bowel disease.

Abstract: Methods for enhancing opsonophagocytosis of a pathogen of interest are disclosed. The disclosed methods include administering to a subject an isolated P4 peptide, which includes the amino acid sequence set forth as SEQ ID NO: 1 and optionally an isolated opsonic antibody or a fragment thereof that specifically binds to an antigen present on the surface of the pathogen of interest. In some examples isolated complement protein or a fragment thereof (for example, a C3a, C3b, iC3b, C3d, C4b, or C5a fragment of a complement protein) is also administered. Compositions containing isolated P4 peptide and one or more isolated opsonic antibodies or a fragment thereof that specifically binds to an antigen present on the surface of a pathogen of interest are also disclosed. In some examples, the compositions also include isolated complement protein or fragment thereof, such as one or more of C3a, C3b, iC3b, C3d, C4b, or C5a.

Abstract: Methods for enhancing opsonophagocytosis of a pathogen of interest are disclosed. The disclosed methods include administering to a subject an isolated P4 peptide, which includes the amino acid sequence set forth as SEQ ID NO: 1 and optionally an isolated opsonic antibody or a fragment thereof that specifically binds to an antigen present on the surface of the pathogen of interest. In some examples isolated complement protein or a fragment thereof (for example, a C3a, C3b, iC3b, C3d, C4b, or C5a fragment of a complement protein) is also administered. Compositions containing isolated P4 peptide and one or more isolated opsonic antibodies or a fragment thereof that specifically binds to an antigen present of the surface of a pathogen of interest are also disclosed. In some examples, the compositions also include isolated complement protein or fragment thereof, such as one or more of C3a, C3b, iC3b, C3d, C4b, or C5a.

Abstract: Compounds having the formula I wherein A, R1, R2, R3, R4a, R4b, R4c, R5, R6, R7a, R7b, Ar1, Rc, Rd, Re, Rf, X, n and p are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

Abstract: Methods for enhancing opsonophagocytosis of a pathogen of interest are disclosed. The disclosed methods include administering to a subject an isolated P4 peptide, which including the amino acid sequence set forth as SEQ ID NO: 1 and optionally an isolated opsonic antibody or a fragment thereof that specifically binds to an antigen present of the surface of the pathogen of interest. In some examples isolated complement protein or a fragment thereof (for example, a C3a, C3b, iC3b, C3d, C4b, or C5a fragment of a complement protein) is also administering. Compositions contain isolated P4 peptide and one or more isolated opsonic antibodies or a fragment thereof that specifically binds to an antigen present of the surface of a pathogen of interest are also disclosed. In some examples, the compositions also isolated complement protein or fragment thereof, such as one or more of C3a, C3b, iC3b, C3d, C4b, or C5a.

Abstract: Provided is a P4 peptide, which contains functional epitopes of the PsaA protein of Streptococcus pneumoniae, and related methods and compositions. P4 peptide mimetics having a conformational structure identical or similar to the conformation of P4 (e.g., SEQ ID NO: 1 and SEQ ID NO:2) are provided. An antibody that specifically binds to the epitope defined by the disclosed peptides is provided. A P4-specific antibody is PsaA-specific since P4 defines an epitope specific for PsaA. Immunogenic compositions comprising the peptide of SEQ ID NO: 1 and a pharmaceutical carrier or the peptide of SEQ ID NO:2 and a pharmaceutical carrier are also provided. Methods of using the peptides and antibodies of the invention are provided.

Abstract: Compounds having the formula I wherein A, R1, R2, R3, R4a, R4b, R4c, R5, R6, R7a, R7b, Ar1, Rc, Rd, Re, Rf, X, n and p are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

Abstract: This application discloses a multivalent opsonophagocytosis assay that does not rely on counting of bacterial colonies to determine bacteria viability following opsonophagocytosis. Instead, the method uses a metabolic colorimetric indicator to determine if viable bacteria are present. Also disclosed are arrays that can be used to determine the viability of bacteria following opsonophagocytosis.

Abstract: This application discloses a multivalent opsonophagocytosis assay that does not rely on counting of bacterial colonies to determine bacteria viability following opsonophagocytosis. Instead, the method uses a metabolic colorimetric indicator to determine if viable bacteria are present. Also disclosed are arrays that can be used to determine the viability of bacteria following opsonophagocytosis.

Abstract: Provided is a P4 peptide, which contains functional epitopes of the PsaA protein of Streptococcus pneumoniae, and related methods and compositions. A peptide that comprises the amino acid sequence defined in SEQ ID NO:1 (an example of the P4 peptide) is provided. Also provided is a peptide comprising the amino acid sequence defined as VPSLFVDSSVDDRPMKTVSQDTNIPIYAQIFTDS (SEQ ID NO:2). P4 peptide mimetics having a conformational structure identical or similar to the conformation of P4 (e.g., SEQ ID NO: 1 and SEQ ID NO:2) are provided. An antibody that specifically binds to the epitope defined by the disclosed peptides is provided. For example, the antibody can specifically bind to a peptide comprising the sequence set forth in SEQ ID NO: 1 and having the conformation defined by the peptide consisting of SEQ ID NO: 1. An antibody that specifically binds to a peptide comprising the sequence set forth in SEQ ID NO:2 and having the conformation defined by the peptide consisting of SEQ ID NO:2 is also provided.

Abstract: This application discloses a multivalent opsonophagocytosis assay that does not rely on counting of bacterial colonies to determine bacteria viability following opsonophagocytosis. Instead, the method uses a metabolic colorimetric indicator to determine if viable bacteria are present. Also disclosed are arrays that can be used to determine the viability of bacteria following opsonophagocytosis.

Abstract: Protein markers of toxicity and efficacy for antilipemic drugs are determined. Methods and reagents are disclosed for determining whether a patient receiving an antilipemic drug, especially a statin or HMGCoA reductase inhibiting drug, is experiencing drug efficacy and/or toxicity. Individual susceptibility is also determined prior to treatment. Also, drug discovery of similar acting candidates and their likelihood of being toxic or effective is determined by analysis of all proteins in a sample simultaneously by 2-dimensional gel electrophoresis.

Abstract: Methods and compositions comprising immunoassays for the detection of functional antibodies and the analysis of vaccine efficacy are described. In particular, the present invention provides opsonophagocytic assays. The assays are useful for the rapid and simultaneous detection of multiple different functional antibodies. In preferred embodiments, the assays include fluorescent labels of multiple colors and/or intensities.

Abstract: Protein disease markers for obesity, osteoporosis, diabetes, osteoarthritis and hypertension are disclosed. These markers are not inherited or of genetic origin as they were not found in identical twins of the affected individual. Methods and uses for diagnostic, therapeutic and drug discovery are disclosed.