Abstract: Methods and systems for separating and/or quantifying peptides using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicant's teachings, the methods and systems can provide for the separation of one or more peptides, for example, peptides that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), by complexing the peptides with a metal cation (e.g., Ca2+) prior to DMS. In some aspects, the present teachings can prevent proton stripping from ionized peptides that can occur in DMS to prevent unintended and/or undesirable alterations to the peptide's charge state distribution.

Abstract: The present invention relates to novel methods for detection of the presence or absence of particulate matter in an opaque fluid, novel methods for inspection of an opaque fluid for the presence or absence of particulate matter therein, and use of such methods in the manufacture of an opaque fluid. Methods comprise clarifying the fluid to enable detection of the presence or absence of particulate matter therein or to enable inspection of the opaque fluid for the presence or absence of particulate matter therein.

Abstract: The present invention relates to compounds of formula (I): and salts thereof, wherein: R1-R4 have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of BRG1, BRM and/or PB1. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various BRG1-mediated disorders, BRM-mediated disorders and/or PB1-mediated disorders.

Abstract: Provided herein are compounds of formula I: and salts thereof and compositions and uses thereof. The compounds are useful as inhibitors of LSD1. Also included are pharmaceutical compositions comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various LSD1-mediated disorders.

Abstract: The present invention relates to compounds of formula (I): and to salts thereof, wherein R1, R2, and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

Abstract: The present invention relates to compounds of formula (I): and to salts thereof, wherein R1, R2, and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

Abstract: The present invention relates to compounds of formula (I): and to salts thereof, wherein R1, R2, Rc, and Rd have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

Abstract: The present invention relates to methods for treating PCAF mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein R1, R3-R6, X, and each Re have any of the values defined in the specification. Also included are novel compounds of formula (I) and salts thereof, as well as pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to compounds of formula (I): and to salts thereof, wherein A has any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

Abstract: The present invention relates to methods for treating PCAF and GCN5 mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein ring A, R1, R3, R4, R5, and each Re have any of the values defined in the specification. Also included are novel compounds of Formula (I) and salts thereof, as well as pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: Methods and systems for separating and/or quantifying peptides using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicant's teachings, the methods and systems can provide for the separation of one or more peptides, for example, peptides that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), by complexing the peptides with a metal cation (e.g., Ca2+) prior to DMS. In some aspects, the present teachings can prevent proton stripping from ionized peptides that can occur in DMS to prevent unintended and/or undesirable alterations to the peptide's charge state distribution.

Abstract: Methods and systems for processing fluids utilizing a digital microfluidic device and transferring droplets from the digital microfluidic device to a downstream analyzer are described herein. Methods and systems in accordance with the present teachings can allow for the withdrawal of fluid from a digital microfluidic device, and can in some aspects enable the integration of a digital microfluidic device as a direct, in-line sample processing platform from which a droplet can be transferred to a downstream analyzer.

Abstract: The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Abstract: The present invention relates to compounds formula (I): and to salts thereof, wherein R1-R4 and A have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of histone demethylases, such as KDM5. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Abstract: A method for analyzing a sample that contains a plurality of lipid isomers is described that involves forming one or more lipid metal ion adducts and transporting the one or more lipid metal ion adducts through a differential mobility spectrometer to cause separation of the one or more lipid metal ion adducts from each other. The lipid isomers can be chosen, for example, from fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids. Particular examples include phosphatidylcholine regioisomers such as 1-palmatoyl-2-oleoyl-sn-phosphatidylcholine (POPC) and 1-oleoyl-2-palmatoyl-sn-phosphatidylcholine and triacylglycerols containing palmetic and oleic acid groups. The metal chosen can include a cationization reagent that contains sodium, potassium, silver or lithium.

Abstract: An apparatus, system and method of providing that allow for the generation of reagent ions within an inner region of a mass spectrometer for use in ion-ion reactions such as PTRs and ETD using a reagent ion generator. The location where these reagent ions are generated can be as close as possible to the point of action, or the reaction zone where the reagent ion and analyte ions will interact via ion-ion reactions to cause, e.g., PTRs and/or ETD.

Abstract: An electrospray ion source method and system is provided for detecting emitter failure comprising a liquid chromatography column suitable for chromatographic separation of a sample. The column can have an inlet for receiving the sample; and an outlet for ejecting the sample. A make-up flow channel is provided for introducing make-up flow of liquid to the sample post-column, wherein the make-up flow normalizes the spray current. An electrospray ionization source is provided having one or more electrospray ionization emitter nozzles for receiving the make-up flow containing sample. A power supply can provide a voltage to the one or more emitter nozzles, and a measurement device can measure and monitor the spray current.

Abstract: A method for analyzing a sample that contains a plurality of lipid isomers is described that involves forming one or more lipid metal ion adducts and transporting the one or more lipid metal ion adducts through a Mix of POPC+OPPC differential mobility spectrometer to cause separation of the one or more lipid metal ion adducts from each other. The lipid isomers can be chosen, for example, from fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, polyketides, sterol lipids, and prenol lipids. Particular examples include phosphatidylcholine regioisomers such as 1-palmatoyl-2-oleoyl-sn-phosphatidylcholine (POPC) and 1-oleoyl-2-palmatoyl-sn-phosphatidylcholine and triacylglycerols containg palmetic and oleic acid groups. The metal chosen can include a cationization reagent that contains sodium, potassium, silver or lithium.

Abstract: Methods and systems for performing mass spectrometry of analytes labeled with isobaric tags are provided herein. In accordance with various aspects of the applicants' teachings, the methods and systems can enable enhanced discrimination between an analyte of interest and one or more interfering species when using isobaric tagging techniques.

Abstract: The present invention provides isoxazoline FAAH inhibitors of the formula (I): or pharmaceutically acceptable forms thereof, wherein each of G, Ra, Rb, Rc, and Rd are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient. The present invention also provides methods for treating an FAAH-mediated condition comprising administering a therapeutically effective amount of a compound of formula (I), or pharmaceutically acceptable form thereof, to a subject in need thereof.