Abstract:
The present invention provides compounds of Formula (I) and (II): wherein R1, R2, R4, R5, R6, X and n are as defined herein, and wherein R3 is hydrogen or a sulfur protecting group. Compounds of Formula (I) and (II), wherein R3 is hydrogen, may be useful in methods for detecting a reactive metabolite in a sample, e.g., wherein the metabolite is generated from the metabolism of a test compound, and wherein the metabolite and the compound of Formula (I) or (II) react to form a detectable adduct, e.g., detectable by mass spectrometry.
Abstract:
Aspect of the disclosure relate to methods of assessing a bioreactor culture that involve determining a culture parameter of the manufacturing-scale bioreactor culture using a model that relates a Raman spectrum to the culture parameter. Related bioreactor system are also provided.
Abstract:
Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; R4 is absent, heteroarylene, arylene, C1-3 alkylene, or R4 and R3 taken together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring; R5 is absent, C(O)NR51, NR52 or O; R6 is C2-10 alkylene or alkenylene, wherein one or two of the carbon atoms in the alkylene chain is optionally replaced by an O, S, SO, SO2 or NR61, and wherein two of the carbon atoms in the alkylene chain are optionally connected by a two or three carbon atom alkylene chain to form a 5- to 7-membered ring; R7 is absent, NR71 or O. The compounds are IRAK4 inhibitors useful for the treatment of inflammatory diseases.
Abstract:
Various embodiments of medical detector systems as well as their methods of operation are disclosed. In one embodiment, one or more detectors are coupled to wearable structures for detecting at least a first tracer within a body portion. In another embodiment, one or more detectors are coupled to a wearable structure, where the detector corresponds to a CMOS chip that directly detects a first radioactive tracer.
Abstract:
Systems, devices, and methods for the delivery of gas bubbles to liquids are generally described. The devices can include a primary conduit (102) comprising a plurality of openings (104) fluidically connecting an internal flow pathway (106) of the primary conduit to an environment outside the primary conduit. The devices may also include, in some instances, a secondary conduit (114) located at least partially within the primary conduit, the secondary conduit configured to redistribute the pressure of the gas delivered to the openings of the primary conduit, and comprising a plurality of openings (116) fluidically connecting an internal flow pathway (118) of the secondary conduit to a portion of the internal flow pathway (106) of the primary conduit outside the secondary conduit. Certain of the gas delivery systems and methods described herein are capable of delivering gas at relatively uniform linear flow velocities across multiple gas outlet openings. Certain embodiments are related to inventive configurations (e.g., spacings and/or sizing) of gas outlet openings in one or more conduits of the gas delivery device (e.g., the primary conduit and/or, when present, the secondary conduit). In addition, some embodiments are related to inventive arrangements for joining a gas delivery device is to a vessel, which may be part of for example, a reactor such as a bioreactor. Certain embodiments are related to the orientation of the gas delivery device and/or its components (e.g., during operation).
Abstract:
In one aspect, the disclosure provides neutralizing antibodies against JCV and methods for the treatment of PML. In some embodiments, aspects of the invention relate to an isolated JC-vims neutralizing monoclonal antibody against JCV capsid protein VPI (JCV-VP1). In some embodiments, the antibody suppresses infectivity of the JC-vims. In some embodiments, the antibody binds the sialic acid binding pocket of JCV-VP1.
Abstract:
Endogenous LINGO-1 is a negative regulator for neuronal survival, axon regeneration, oligodendrocyte differentiation and myelination. Molecules that block endogenous LINGO-1 function, such anti-LINGO-1 antibodies can be used as therapeutics for the treatment of neuron and oligodendrocyte dysfunction. The present invention provides antibodies specific for LINGO-1, and methods of using such antibodies as antagonists of endogenous LINGO-1 function. The invention further provides specific hybridoma and phage library-derived monoclonal antibodies, nucleic acids encoding these antibodies, and vectors and host cells comprising these antibodies. The invention further provides methods of promoting oligodendrocyte survival and myelination in a vertebrate, comprising administering to a vertebrate in need of such treatment an effective amount of an anti-LINGO-1 antibody
Abstract:
Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.
Abstract:
Methods of improving the efficiency of production of a protein product of interest in mammalian cell culture are presented. In particular, the methods result in an increase in the quantity of a protein product produced, or decreases protein product production time in a manufacturing-scale bioreactor cell culture. The disclosed methods comprise: (a) culturing the N-1 bioreactor culture to high viable cell densities; and (b) seeding the production bioreactor culture at high viable cell seeding densities.
Abstract:
The invention is directed to methods of purifying a chimeric protein comprising subjecting the chimeric protein to a factor VIII-specific affinity chromatography, and subjecting the chimeric protein to an AEX chromatography; wherein the chimeric protein comprises a factor VIII protein or a fragment thereof. The chimeric protein purified by the present methods shows improved factor VIII activity.