The present invention relates to fusion proteins which are capable of binding to phosphatidylserine comprising a phosphatidylserene binding ligand and a modified O6-alkylguanine-DNA alkyltransferase which is capable of autoconjugation to an O6-benzylguanine-modified label, the fusion proteins being capable of binding to phosphatidylserine on the surface of a cell undergoing apoptosis. The invention also relates to recombinant polypeptide precursors of the fusion proteins which comprise a secretion leader sequence, purification tag, protease cleavage site and the fusion protein. Also included in the scope of the invention are nucleic acids encoding the recombinant polypeptide precursor, vectors comprising the nucleic acids, host cells comprising the vectors, methods of production of the fusion proteins, kits and assays for detecting apoptosis.

According to one embodiment, a vector set includes a first vector and a second vector. The first vector includes a transposase target sequence, a first promoter sequence ligated to downstream of the transposase target sequence, and a first reporter gene ligated to downstream of the first promoter sequence. The second vector includes a 5′-side transposase recognition sequence, a 3′-side transposase recognition sequence, and a first enhancer sequence arranged therebetween.

Provided herein are methods of determining NAT acetylation status of a subject with a 3,4-DAP-sensitive disease, methods of selecting a dose of 3,4-DAP or a pharmaceuticaliy acceptable salt thereof adjusted to a subject's acetylation status, methods of administering 3,4-diaminopyridine or a pharmaceutically acceptable salt thereof to a patient in need thereof, and methods of treating 3,4-DAP sensitive diseases.

Provided herein are methods of determining NAT acetylation status of a subject with a 3,4-DAP-sensitive disease, methods of selecting a dose of 3,4-DAP or a pharmaceuticaliy acceptable salt thereof adjusted to a subject's acetylation status, methods of administering 3,4-diaminopyridine or a pharmaceutically acceptable salt thereof to a patient in need thereof, and methods of treating 3,4-DAP sensitive diseases.

An immobilized enzymatic reactor can include a wall defining a chamber having an inlet and an outlet; a solid stationary phase covalently linked to an enzyme and disposed within the chamber; and a pressure modulator in a fluid communication with the chamber and adapted to support continuous flow of a liquid sample comprising a polymer analyte through the inlet, over the solid stationary phase, and out of the outlet under a pressure between about 2,500 and 35,000 psi. In one example, the solid stationary phase includes inorganic/organic hybrid particles in an ultra performance liquid chromatography system, the enzyme is a protease, and the polymer analyte is a polypeptide. The immobilized enzymatic reactor can prepare an analyte for applications such as for hydrogen deuterium exchange mass spectrometry.

An immobilized enzymatic reactor can include a wall defining a chamber having an inlet and an outlet; a solid stationary phase covalently linked to an enzyme and disposed within the chamber; and a pressure modulator in a fluid communication with the chamber and adapted to support continuous flow of a liquid sample comprising a polymer analyte through the inlet, over the solid stationary phase, and out of the outlet under a pressure between about 2,500 and 35,000 psi. In one example, the solid stationary phase includes inorganic/organic hybrid particles in an ultra performance liquid chromatography system, the enzyme is a protease, and the polymer analyte is a polypeptide. The immobilized enzymatic reactor can prepare an analyte for applications such as for hydrogen deuterium exchange mass spectrometry.

In one embodiment, an object of the present invention is to provide a liquid cycling luminescence reagent excellent in stability. In one embodiment, the present invention provides a liquid composition for measuring ATP and AMP and/or ADP in a sample after storage of the liquid composition, wherein (i) the liquid composition comprises luciferase, luciferin, an enzyme that catalyzes a reaction that produces ATP from AMP, a substrate of the enzyme that catalyzes a reaction that produces ATP from AMP, and a cofactor, or when at least one of these components is not contained in the liquid composition, the component that is not contained in the liquid composition is added to the liquid composition before or during measurement, and (ii) the relative luminescence level of the liquid composition during storage is 5500 RLU or less, and the relative level of luminescence is a value determined by subtracting a control value from a measurement value.

In one embodiment, an object of the present invention is to provide a liquid cycling luminescence reagent excellent in stability. In one embodiment, the present invention provides a liquid composition for measuring ATP and AMP and/or ADP in a sample after storage of the liquid composition, wherein (i) the liquid composition comprises luciferase, luciferin, an enzyme that catalyzes a reaction that produces ATP from AMP, a substrate of the enzyme that catalyzes a reaction that produces ATP from AMP, and a cofactor, or when at least one of these components is not contained in the liquid composition, the component that is not contained in the liquid composition is added to the liquid composition before or during measurement, and (ii) the relative luminescence level of the liquid composition during storage is 5500 RLU or less, and the relative level of luminescence is a value determined by subtracting a control value from a measurement value.

As a result of dedicated studies, the present inventors succeeded in discovering, for the first time, that fibrogenesis could be suppressed at the physiological tissue level by inhibiting sulfation at position 4 or 6 of GalNAc, which is a sugar that constitutes sugar chains. Furthermore, the present inventors conducted studies using various disease model animals, and as a result, successfully demonstrated that inhibitors of sulfation at position 4 or 6 of GalNAc had therapeutic effects on diseases caused by tissue fibrogenesis (tissue fibrogenic disorders).

As a result of dedicated studies, the present inventors succeeded in discovering, for the first time, that fibrogenesis could be suppressed at the physiological tissue level by inhibiting sulfation at position 4 or 6 of GalNAc, which is a sugar that constitutes sugar chains. Furthermore, the present inventors conducted studies using various disease model animals, and as a result, successfully demonstrated that inhibitors of sulfation at position 4 or 6 of GalNAc had therapeutic effects on diseases caused by tissue fibrogenesis (tissue fibrogenic disorders).