Abstract: 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, or a pharmaceutically acceptable salt, amorphous form, polymorph form, or pharmaceutical composition (including solid formulations or liquid formulations) thereof and the use thereof for treating diseases and disorders which can be treated with a RET kinase inhibitor, such as RET-associated diseases and disorders, e.g., proliferative disorders such as cancers, including hematological cancers and solid tumors, and gastrointestinal disorders such as IBS are disclosed.

Abstract: A re-useable partitioning seal used storage containers creates a virtually airtight chambers, to preserve products therein. A disc or differently shaped layer, with flat top and bottom surfaces, is configured to fit against the interior surface of a storage container. A thin, flexible perimeter forming a gasket around the layer, and a handle attached to the layer without fissure or cavity, thereby providing and a single piece, inexpensive re-useable partitioning seal.

Abstract: An apparatus includes a processor with first and second input ports and a memory operably coupled to the processor. The processor can detect streams of media samples at the input ports and determine, in response to the detection of the streams of media samples, a capture start time. The processor can also capture a first frame of a first stream of media samples beginning at the capture start time, and a first frame of a second stream of media samples beginning at a first time subsequent to the capture start time. The processor can also calculate a relative offset time based on the capture start time, the first time, and a rate associated with the second stream of media samples, and store, in the memory, an indication of an association between the captured first frame of the second stream of media samples and the relative offset time.

Abstract: A liquid formulation of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Abstract: 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, or a pharmaceutically acceptable salt, amorphous form, polymorph form, or pharmaceutical composition (including solid formulations or liquid formulations) thereof and the use thereof for treating diseases and disorders which can be treated with a RET kinase inhibitor, such as RET-associated diseases and disorders, e.g., proliferative disorders such as cancers, including hematological cancers and solid tumors, and gastrointestinal disorders such as IBS are disclosed.

Abstract: An apparatus includes a processor with first and second input ports and a memory operably coupled to the processor. The processor can detect streams of media samples at the input ports and determine, in response to the detection of the streams of media samples, a capture start time. The processor can also capture a first frame of a first stream of media samples beginning at the capture start time, and a first frame of a second stream of media samples beginning at a first time subsequent to the capture start time. The processor can also calculate a relative offset time based on the capture start time, the first time, and a rate associated with the second stream of media samples, and store, in the memory, an indication of an association between the captured first frame of the second stream of media samples and the relative offset time.

Abstract: A liquid formulation of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Abstract: An apparatus includes a processor with first and second input ports and a memory operably coupled to the processor. The processor can detect streams of media samples at the input ports and determine, in response to the detection of the streams of media samples, a capture start time. The processor can also capture a first frame of a first stream of media samples beginning at the capture start time, and a first frame of a second stream of media samples beginning at a first time subsequent to the capture start time. The processor can also calculate a relative offset time based on the capture start time, the first time, and a rate associated with the second stream of media samples, and store, in the memory, an indication of an association between the captured first frame of the second stream of media samples and the relative offset time.

Abstract: Systems, methods, and apparatus for treating a molten metal are provided. A metal treatment system, comprising: a wire feeding subsystem; and a cored wire; wherein the wire feeding subsystem feeds the cored wire into a metal bath at a controlled wire feed rate, and wherein the metal bath comprises a molten metal; wherein the cored wire comprises: a consumable outer sheath having a tubular cross section; and a core fill material coupled to an inner surface of the outer sheath, wherein the core fill material comprises a refining agent for refining the molten metal; and wherein the refining agent reacts with the molten metal, thereby causing an impurity to be removable from the metal bath.

Abstract: The present invention provides metformin-containing dental materials that can be widely applied in a variety of dental applications. The metformin-containing dental materials of the invention include metformin-containing dental primers, metformin-containing dental adhesives, metformin-containing dental resins, metformin-containing dental composites, metformin-containing dental bonding systems and the like, as well as metformin-containing dental cements, metformin-containing dental sealants, metformin-containing dental bases and metformin-containing dental liners.

Abstract: 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile, or a pharmaceutically acceptable salt, amorphous form, polymorph form, or pharmaceutical composition (including solid formulations or liquid formulations) thereof and the use thereof for treating diseases and disorders which can be treated with a RET kinase inhibitor, such as RET-associated diseases and disorders, e.g., proliferative disorders such as cancers, including hematological cancers and solid tumors, and gastrointestinal disorders such as IBS are disclosed.

Abstract: A liquid formulation of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Abstract: Process for preparing (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3-ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (formula 11) to (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R)-2-hydroxysuccinate (formula 10) by treating (R)—N—((R)-1-(2,5-difluorophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (formula 19) with an acid and a reducing agent.

Abstract: A liquid formulation of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Abstract: An apparatus includes a processor with first and second input ports and a memory operably coupled to the processor. The processor can detect streams of media samples at the input ports and determine, in response to the detection of the streams of media samples, a capture start time. The processor can also capture a first frame of a first stream of media samples beginning at the capture start time, and a first frame of a second stream of media samples beginning at a first time subsequent to the capture start time. The processor can also calculate a relative offset time based on the capture start time, the first time, and a rate associated with the second stream of media samples, and store, in the memory, an indication of an association between the captured first frame of the second stream of media samples and the relative offset time.

Abstract: A light assembly, comprising: a base; at least one electromagnetic radiation source mounted on the base; a cover located over the base, the cover being transparent to the electromagnetic radiation produced by the electromagnetic radiation source; and at least one photo detector, optically Isolated from the at least one electromagnetic radiation source, the at least one photo detector being configured to receive electromagnetic radiation conveyed by the cover.

Abstract: The invention provides chimeric capture probes immobilizable via an L-nucleic acid tail that can bind to a complementary L-nucleic acid in an immobilized probe. The capture probes are useful for capturing a target nucleic acid from a sample. The L-nucleic acid in the tail of the capture probe bind to the complementary L-nucleic acid in the immobilized probe with similar affinity as would otherwise equivalent D-nucleic acids. However, the L-nucleic acid of the capture probe tail and immobilized probes do not form stable duplexes with D-nucleic acids present in the in the sample containing the target nucleic acid. Binding of nucleic acids in the sample directly to immobilized probe or to the tail of the capture probe is reduced or eliminated increasing the sensitivity and/or specificity of the assay.

Abstract: The invention provides chimeric capture probes immobilizable via an L-nucleic acid tail that can bind to a complementary L-nucleic acid in an immobilized probe. The capture probes are useful for capturing a target nucleic acid from a sample. The L-nucleic acid in the tail of the capture probe bind to the complementary L-nucleic acid in the immobilized probe with similar affinity as would otherwise equivalent D-nucleic acids. However, the L-nucleic acid of the capture probe tail and immobilized probes do not form stable duplexes with D-nucleic acids present in the sample containing the target nucleic acid. Binding of nucleic acids in the sample directly to immobilized probe or to the tail of the capture probe is reduced or eliminated increasing the sensitivity and/or specificity of the assay.

Abstract: A liquid formulation of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.

Abstract: A light assembly, comprising: a base; at least one electromagnetic radiation source mounted on the base; a cover located over the base, the cover being transparent to the electromagnetic radiation produced by the electromagnetic radiation source; and at least one photo detector, optically Isolated from the at least one electromagnetic radiation source, the at least one photo detector being configured to receive electromagnetic radiation conveyed by the cover.