Abstract: Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.

Abstract: Provided is a method of assaying for an analyte, including combining a test sample having the analyte, with a calibration sample having at least two different aliquots of the analyte, each aliquot having a different known quantity of the analyte. The test sample and each aliquot are differentially labeled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry. The method further includes determining by mass spectrometry the quantity of analyte in the test sample and in each aliquot, and calibrating the quantity of analyte in the test sample against known and determined quantities of analytes in the aliquots.

Abstract: The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl)carbonyl]indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof; and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.

Abstract: The present invention provides a method for labelling one or more analytes in a sample, the method comprising: a) contacting the sample with one or more bifunctional linker reagents having the general formula Re1-L1-Re2, wherein Re1 is a first reactive group, L1 is a linker moiety and Re2 is a second reactive group, wherein Re1 reacts with an analyte to form a modified analyte; and b) contacting the sample with one or more mass labels, wherein Re2 of the bifunctional linker attached to the analyte reacts with a mass label to form a labelled analyte, wherein each mass label is relatable to an analyte by mass spectrometry.

Abstract: The present invention relates to a set of two or more mass labels. Each mass label comprises: X-L-M-Re; X is a reporter moiety having exact mass; L is a bond cleavable by collision in a mass spectrometer; M is a mass modifier; Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte. Each mass label in the set has the same integer mass; wherein the set comprises two or more subsets of mass labels, each subset comprising one or more mass labels; wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets; each mass label is distinguishable by mass spectrometry.

Abstract: Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.

Abstract: The present invention provides 2-Methyl-amino-3-[(4-fluorophenyl)carbonyl]indolizine-1-carboxamide of formula (I) or a pharmaceutically acceptable salt thereof; and its therapeutic uses in the treatment of neurodegenerative disorders, in particular tauopathies and most preferably in the treatment of Alzheimer's disease.

Abstract: The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.

Abstract: Provided is a method of assaying for an analyte, including combining a test sample having the analyte, with a calibration sample having at least two different aliquots of the analyte, each aliquot having a different known quantity of the analyte. The test sample and each aliquot are differentially labeled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry. The method further includes determining by mass spectrometry the quantity of analyte in the test sample and in each aliquot, and calibrating the quantity of analyte in the test sample against known and determined quantities of analytes in the aliquots.

Abstract: The present invention provides a method for labelling one or more analytes in a sample, the method comprising: a) contacting the sample with one or more bifunctional linker reagents having the general formula Re1-L1-Re2, wherein Re1 is a first reactive group, L1 is a linker moiety and Re2 is a second reactive group, wherein Re1 reacts with an analyte to form a modified analyte; and b) contacting the sample with one or more mass labels, wherein Re2 of the bifunctional linker attached to the analyte reacts with a mass label to form a labelled analyte, wherein each mass label is relatable to an analyte by mass spectrometry.

Abstract: The present invention provides set of two or more mass labels, wherein each mass label in the set has the same integer mass as every other label in the set, and each mass label in the set has an exact mass which is different to the mass of all other mass labels in the set such that all the mass labels in the set are distinguishable from each other by mass spectrometry.

Abstract: A reactive mass label for labelling a biological molecule for detection by mass spectrometry, which label comprises a reactive functionality for labelling thiol groups or carbonyl groups. Also provided is a reactive mass label for labelling a biological molecule for detection by mass spectrometry, wherein the mass label comprises the following structure: X-L-M-S—Re wherein X is a mass marker moiety, L is a cleavable linker, M is a mass normalization moiety, S is a mass series modifying group comprising the following group: wherein J is C?O, K is NH, and n is 2 or J and K are both CH2 and n is 1, and wherein m is at least 1; and Re is a reactive functionality for attaching the mass label to a biological molecule.

Abstract: Provided is a method of assaying for an analyte, including combining a test sample having the analyte, with a calibration sample having at least two different aliquots of the analyte, each aliquot having a different known quantity of the analyte. The test sample and each aliquot are differentially labeled with one or more isobaric mass labels each with a mass spectrometrically distinct mass marker group, such that the test sample and each aliquot of the calibration sample can be distinguished by mass spectrometry. The method further includes determining by mass spectrometry the quantity of analyte in the test sample and in each aliquot, and calibrating the quantity of analyte in the test sample against known and determined quantities of analytes in the aliquots.

Abstract: A mass label for labelling and detecting a biological molecule by mass spectroscopy, which label comprises the following structure: X-L-M wherein X is a mass marker moiety comprising the following group: formula (I), wherein the cyclic unit is aromatic or aliphatic and comprises from 0-3 double bonds independently between any two adjacent atoms; each Z is independently N, N(R1), C(R1), CO, CO(R1), C(R1)2, O or S; X is N, C or C(R1); each R1 is independently H, a substituted or unsubstituted straight or branched C1-C6 alkyl group, a substituted or unsubstituted aliphatic cyclic group, a substituted or unsubstituted aromatic group or a substituted or unsubstituted heterocyclic group; and y is an integer from 0-10, L is a cleavable linker comprising an amide bond and M is a mass normalization moiety.

Abstract: A reactive mass label for labelling a biological molecule for detection by mass spectrometry includes the following structure: X-L-M-S-Re, wherein X is a mass marker moiety, L is a cleavable linker, M is a mass normalization moiety, and S is a mass series modifying group including the following group: wherein J is C?O, K is NH, and n is 2 or J and K are both CH2 and n is 1, m is at least 1; and Re is a reactive functionality for attaching the reactive mass label to a biological molecule.

Abstract: The invention concerns in vitro proteomic analysis of cells to determine the sensitizing potential (including allergic potential) of compounds on said cells. Several protein markers are provided that allow assays to be performed to determine whether a chemical has a sensitizing potential of contact sensitizers.

Abstract: The invention concerns in vitro proteomic analysis of cells to determine the sensitizing potential (including allergic potential) of compounds on said cells. Several protein markers are provided that allow assays to be performed to determine whether a chemical has a sensitizing potential of contact and/or respiratory sensitizers.

Abstract: Provided is a method for characterizing a molecule by mass spectrometry, which molecule comprises one or more free amino groups, which method comprises: (a) reacting one or more free amino groups in the molecule with a mass tag reagent comprising a reactive functionality capable of reacting with an amino group, and a tertiary amino group linked to the reactive functionality; and (b) characterizing the molecule by mass spectrometry.

Abstract: An optical system for imaging an object is provided that is in particular embodied as binocular field glasses, as monocular field glasses, as a spotting scope or as a telescope. The optical system comprises at least one first objective, at least one first image stabilizing unit, and at least one first eyepiece. As seen from the first objective in the direction of the first eyepiece, the first objective is arranged first along a first optical axis in a first housing, followed by the first image stabilizing unit and then the first eyepiece. The first image stabilizing unit is mounted in a cardan-joint fashion in the first housing, rotatably about a first hinge point, wherein the first hinge point is arranged between the first objective and the first eyepiece. Furthermore, the optical system comprises at least one first drive unit for contactless driving of the first image stabilizing unit.

Abstract: A reactive mass label for labelling a biological molecule for detection by mass spectrometry, which label comprises a reactive functionality for labelling thiol groups or carbonyl groups. Also provided is a reactive mass label for labelling a biological molecule for detection by mass spectrometry, wherein the mass label comprises the following structure: X-L-M-S-Re wherein X is a mass marker moiety, L is a cleavable linker, M is a mass normalization moiety, S is a mass series modifying group comprising the following group: wherein J is C?O, K is NH, and n is 2 or J and K are both CH2 and n is 1, and wherein m is at least 1; and Re is a reactive functionality for attaching the mass label to a biological molecule.