The Broad Institute, Inc.

The General Hospital Corporation

Massachusetts Institute of Technology

Dana-Farber-Cancer Institute Inc.

The University of Texas System

Gas Technology Institute

Samsung Electronics Co., Ltd.

University of Pa.

The General Hospital Corporation D/b/a Massachusetts General Hospital

Michael C Lewis

Edward Holson

Florence Fevrier Wagner

Jennifer Q Pan

Michel Weiwer

Stephen J Haggarty

Yan-Ling Zhang

Benito Munoz

Joshua A Bishop

Sivaraman Dandapani

Partha Pratim Nag

Michelle Palmer

Kimberly Stegmaier

Andrew Germain

Qihong Xu

Versha Banerji

Edward Scolnick

Raymond C Zowarka

Siddharth B Pratap

Tracey Lynn Petryshen

Bridget K Wagner

Hsing-Pang Liu

Clay Hearn

Charles Penney

Michael Worthington

Luka Dordevic

Jason Stair

Anthony Lindsay

Morten Lundh

Ahsan Habib Chowdhury

Brian M Millar

Jim L Upshaw

John M Fedor

Daniel Fass

Florence Fevrier

Josh Ketterman

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.

Dopamine D2 receptor ligands

The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3α or GSK3β) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.

Kinase inhibitors and methods of use thereof

A linear motor compressor including a compressor housing and a cylinder housing having a plurality of opposing compression chambers. A piston freely reciprocates within the cylinder housing using a linear electric motor. A piston position feedback control system provides adaptive current output as a function of position feedback and/or velocity feedback from the piston and/or the electric motor, to directly power and control the electric motor, wherein the piston reciprocates without assistance from a mechanical spring or other equivalent centering force.

Free piston linear motor compressor and associated systems of operation

The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X, X, X, X, X, W, W, W, and Ware as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting &#x3b2;-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals.

Inhibitors of histone deacetylase

The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3&#x3b1; or GSK3&#x3b2;) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer. 

The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0-arrestin pathway and/or on the cAMP pathway.

A linear motor compressor including a compressor housing and a cylinder housing having a plurality of opposing compression chambers. A piston freely reciprocates within the cylinder housing using a linear electric motor.

The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X, X, X, X, X, W, W, W, and Ware as described. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting &#x3b2;-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals. 

According to one aspect, a method may include receiving a circuit model that includes a clock mesh that controls each of a plurality of logic circuits by inputting a respective clock signal to an end-point of each logic circuit. The method may include providing an incremental latency adjustment to the circuit model by determining one or more end-points that are candidates for adjustment of a respective end-point's clock skew schedule. And, for each end-point that is associated with a negative front slack, adjusting a clock skew schedule of an end-point by a quantized amount. Further, for each end-point that is associated with a negative back-slack, adjusting the clock skew schedule of an end-point that is associated by a quantized amount. The method may also include repeating, the step of providing an incremental timing update. The method may include performing a timing evaluation upon the circuit model.

Efficient skew scheduling methodology for performance and low power of a clock-mesh implementation

Aspects of this invention are related, at least in part, to the use of chemical compounds able to inhibit GSK-3 and/or to stabilize &#x3b2;-catenin and formulations thereof. Some aspects of this invention relate to compositions comprising such compounds. Some aspects of the invention provide methods of using such compounds and/or compositions in the treatment of subjects having a neurological disease and/or psychiatric disorder. Some aspects of this invention provide methods of using ruboxistaurin, enzastaurin, sunitinib, midostaurin, lestaurtinib, 7-hydroxystaurosporine, and/or Chir99021 in the treatment of subjects having a neurological disease and/or psychiatric disorder. In some embodiments, compounds are administered in combination with Lithium.

Uses of chemicals to modulate GSK-3 signaling for treatment of bipolar disorder and other brain disorders

Aspects described herein relate to an electromagnetic seismic vibrator (EMSV) architecture that provide wide frequency range operation, ground force application with high fidelity, and low environmental impact. The EMSV architecture can include a base member that can support a force coil and mitigate electrical heating due, at least in part, to spurious currents. The EMSV architecture can include means for restricting movement of a reaction member included in the EMSV architecture relative to the base member. Such means can permit mitigation of damage of the EMSV architecture in scenarios in which control of the EMSV architecture may fail.

Electromagnetic seismic vibrator architecture

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Dedham, MA, United States of America

Michael C Lewis