Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are inhibitors of Nav1.8 channel activity and may be useful in the treatment, prevention, management, amelioration, control and suppression of diseases mediated by Nav1.8 channel activity. The compounds of the present invention may be useful in the treatment, prevention or management of pain disorders, cough disorders, acute itch disorders, and chronic itch disorders.

Abstract: Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.

Abstract: Described are antibody peptide conjugates (APCs) comprising an antibody conjugated to a peptide analog of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have agonist activity at the glucagon (GCG) receptor and the glucagon-like peptide 1 (GLP-1) receptor and the use of such APCs for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

Abstract: A system and method are disclosed for segmenting a set of two-dimensional CT slices corresponding to a lesion. In an embodiment, for each of at least a subset of the set of CT slices, the system inputs the CT slice into a plurality of branches of a trained segmentation block. Each branch of the segmentation block includes a convolutional neural network (CNN) with filters at a different scale, and produces a plurality of levels of output. The system generates, for each CT slice in the subset, feature maps for each level of output. The system generates a segmentation of each CT slice in the subset based on the feature maps of each level of output. The system aggregates the segmentations of each slice in the subset to generate a three-dimensional segmentation of the lesion. The system provides data representing the three-dimensional segmentation for display.

Abstract: The present invention is directed to certain 2-aminoquinzaoline derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R3, R4, X1, and X2 are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

Abstract: The present invention provides methods of treating malaria comprising administration of an N3-substituted iminopyrimidinone of Formula (I) or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the variables R1, R2, R3, R4, R5, A, B, L, m, and n are as defined herein. The invention also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin V activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.

Abstract: The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions:

Abstract: The present invention provides capsular polysaccharides from Streptococcus pneumoniae serotypes identified using NMR. The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additional Streptococcus pneumoniae serotypes.

Abstract: The present invention provides capsular polysaccharides from Streptococcus pneumoniae serotypes identified using NMR. The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additional Streptococcus pneumoniae serotypes.

Abstract: The present invention provides capsular polysaccharides from Streptococcus pneumoniae serotypes identified using NMR. The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additional Streptococcus pneumoniae serotypes.

Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

Abstract: Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.

Abstract: The present invention relates to efficient processes useful in the preparation of fluorinated nucleosides, such as (O—{[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl}O,O-dihydrogen phosphorothioate, also known as 2?-(S)-fluoro-thio-adenosine monophosphate or 2?-F-thio-AMP. Such fluorinated nucleosides may be useful as a biologically active compound and or as an intermediate for the synthesis of more complex biologically active compounds. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

Abstract: The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

Abstract: A microwave vacuum dryer includes a loading chamber and a first vacuum pump in communication with the loading chamber, a first door separating the loading chamber from an external environment, a drying chamber adjacent the loading chamber, a second vacuum pump in communication with the drying chamber, and a condenser in communication with the drying chamber, a second door separating the loading chamber and the drying chamber, an unloading chamber adjacent the drying chamber and a third vacuum pump in communication with the unloading chamber, a third door separating the drying chamber from the unloading chamber, a fourth door separating the unloading chamber from the external environment, and a microwave chamber having a plurality of magnetrons, the microwave chamber positioned on a different plane from the loading and unloading chambers and adjacent the drying chamber.

Abstract: Novel compounds of the structural formula I, and the pharmaceutically acceptable salts thereof, are inhibitors of TarO and may be useful in the prevention, treatment and suppression of diseases mediated by TarO, such as bacterial infections, including gram negative bacterial infections and gram positive bacterial infections such as MRSA and MRSE, alone or in combination with a ?-lactam antibiotic.

Abstract: The present invention relates to stable formulations of a cytomegalovirus (CMV) comprising for example, a genetically modified CMV that is conditionally replication defective, a buffer, alkali or alkaline salt, a sugar, a cellulose derivative and optionally a polyol.

Abstract: The invention is related to multivalent immunogenic compositions comprising more than one S. pneumoniae polysaccharide protein conjugates, wherein each of the conjugates comprises a polysaccharide from an S. pneumoniae serotype conjugated to a carrier protein, wherein the serotypes of S. pneumoniae are as defined herein. In some embodiments, at least one of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. In further embodiments, each of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. Also provided are methods for inducing a protective immune response in a human patient comprising administering the multivalent immunogenic compositions of the invention to the patient. The multivalent immunogenic compositions are useful for providing protection against S. pneumoniae infection and/or pneumococcal diseases caused by S. pneumoniae.

Abstract: An injecting device includes a reservoir for containing a medicament, a needle in communication with the reservoir and configured to deliver the medicament to a patient’s body, at least two electrodes spaced apart from one another and disposed on opposing sides of the needle, and a capacitance-to-digital converter circuit configured to generate a signal and measure capacitance between the at least two electrodes.

Abstract: Disclosed herein are novel processes for preparing IL-2 conjugates with one or more water-soluble polymers. In one embodiment, the IL-2 conjugate comprises five poly(ethylene glycol) polymers each of which is covalently attached to the IL-2 moiety via a releasable linkage to an amino group of the IL-2 moiety.