Abstract: The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R1, R2, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: A computer-implemented method for motion compensation of medical imaging data includes estimating, via a processor, non-periodic motion of a myocardium of a heart due to respiration and/or other body movements throughout a positron emission tomography (PET) scan based on list-mode emission data acquired during the PET scan of the heart of a subject. The method also includes performing, via the processor, event-by-event motion-corrected list-mode reconstruction on the list-mode emission data to generate cardiac images with the non-periodic motion removed.

Abstract: The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R1, R2, Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drug conjugates, and the resulting antibody drug conjugates made with components having heteroaryl sulfone-based conjugation handles.

Abstract: The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R1, R2, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Abstract: The present disclosure relates to an amperometric sensor for measuring free chlorine, which sensor comprises: an elongate body with a tip, wherein the circumferential surface of the body constitutes a counter electrode; a reference electrode having a silver/silverchloride electrode surface arranged on the tip of the elongate body; and a working electrode having a gold electrode surface arranged on the tip of the elongate body wherein the gold electrode surface is composed out of a string of electrically connected, spaced apart surface parts.

Abstract: Parenteral delivery of a beneficial agent using an auto-injector configured for reduction of forces acting on a primary container for the beneficial agent during activation of the auto-injector. The primary container may be disposed within a pressure chamber of the auto-injector such that an increased pressure within the pressure chamber during activation is applied to a stopper of the primary container and an external surface of a sidewall of the primary container. In turn, a pressure differential between a containment volume of the primary container and the pressure chamber may be reduced or eliminated. In turn, forces acing on the primary container in response to the pressure increase in the pressure container may be reduced or eliminated. Configurations are also provided for improved relative movement between a stopper and a sidewall of the primary container for more reliable injection.

Abstract: The present invention provides, in part, compounds of Formula I, or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: (R1)a, (R2)b, (R3)c, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R1, R2, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R1, R2, Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drig conjugates, and the resulting antibody drig conjugates made with components having heteroaryl sulfone-based conjugation handles.

Abstract: The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylam ides and analogues thereof, having the structure: or a pharmaceutically acceptable salt thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Abstract: Methods and systems for estimating a symbol timing error for an offset quadrature phase shift keying (O-QPSK) modulated signal. The method includes: receiving a plurality of complex samples representing an O-QPSK modulated signal, wherein if the O-QPSK modulated signal is sampled on time each of the plurality of samples has substantially no imaginary component; generating an early error metric and a late error metric for each sample, the early error metric based on the imaginary component for the sample and a sign of a real component of a previous sample and the late error metric based on the imaginary component for the sample and a sign of a real component of a next sample; generating a combined early error metric based on the early error metrics for the plurality of samples; generating a combined late metric based on the late error metrics for the plurality of samples; and generating an estimate of the symbol timing error based on the combined early error metric and the combined late metric.

Abstract: The present invention provides, in part, compounds of Formula I, or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: (R1)a, (R2)b, (R3)c, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.

Abstract: The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides, and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Abstract: The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R1, R2, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: R1, R2, L, A, and E are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder.

Abstract: Methods and systems for estimating a symbol timing error for an offset quadrature phase shift keying (O-QPSK) modulated signal. The method includes: receiving a plurality of complex samples representing an O-QPSK modulated signal, wherein if the O-QPSK modulated signal is sampled on time each of the plurality of samples has substantially no imaginary component; generating an early error metric and a late error metric for each sample, the early error metric based on the imaginary component for the sample and a sign of a real component of a previous sample and the late error metric based on the imaginary component for the sample and a sign of a real component of a next sample; generating a combined early error metric based on the early error metrics for the plurality of samples; generating a combined late metric based on the late error metrics for the plurality of samples; and generating an estimate of the symbol timing error based on the combined early error metric and the combined late metric.

Abstract: The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.

Abstract: The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, traumatic brain injury, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.