Abstract: A method of treating cancer in a subject in need thereof, comprising administering to the subject a first amount of a compound of the HAT inhibitor of the following formula: wherein R is chosen from coenzyme A, (CH2)2NHCO(CH2)2NHCOR2; (CH2)2NHCOR3; (CH2)2NHCO(CH2)2NHCOR4; R1 is H, NH2, NH, N, and R1 can optionally cyclize with at least one other X2 to form a C3-8 membered ring containing C, O, S, or N; R2 is chosen from alkyl, cycloalkyl, aryl, heteroaryl; R3 is chosen from an alkyl, cycloalkyl, aryl, heteroaryl; R4 is chosen from CH(OH)C(CH3)2CH2)OCOR2; X1 is chosen from H or can cyclize with one other X2 or R1 to form a C3-8 membered ring containing C, O, S, or N; and X2 is chosen from C, N, NH, and can optionally cyclize with at least one other X2 or R1 to form a C3-8 membered ring containing C, O, S, or N; or a pharmaceutically acceptable salt or hydrate thereof, thereby treating the cancer.

Abstract: Pyrazolopyridine, pyrazolopyrazine, pyrazolopyrimidine, pyrazolothiophene and pyrazolothiazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction.

Abstract: The present invention relates to a system and apparatus for implementing a method for identifying tube parameters of a curved tube of an active cannula for operating on a target in a patient. The method includes the step (a) of acquiring a model of the patient anatomy including the target. The method also includes the step (b) of selecting a set of parameters characterizing a curved tube. The method also includes the step (c) of computing a workspace for an active cannula having the selected curved tube parameters. The method also includes the step (d) of comparing the workspace to the anatomical model to determine the degree to which an active cannula having the selected curved tube parameters covers the target. The method also includes the step (e) of repeating steps (b) through (d) through a defined number of curved tube parameter sets. The method also includes the step (f) of identifying the curved tube parameters that provide an active cannula with an optimal degree of target coverage.

Abstract: Disclosed are fluorescent indicators and methods for detecting the activity of an ion channel or transporter in a cell. The indicators and methods may be used to measure influx or efflux of thallium through an ion channel or a transporter.

Abstract: A device includes a first member (120) and a second member (122) disposed in series along a longitudinal axis. The device also includes links coupling first joints (124, 126) of the first member to second joints of the second member (128, 130). The first and second members and the links arranged to define a planar parallelogram linkage. The devices also include a resilient element (142) disposed between the first member and the second member, the first member and the second member preloaded against the resilient element. The first member and the second member are preloaded to provide an arrangement of the first and the second joints in which a motion of the first joints with respect to the second joints is constrained to a direction substantially parallel to the longitudinal axis. The devices further include a sensor (140) for generating a signal indicating a separation between the first member and the second member.

Abstract: In one aspect, the invention relates to novel bicyclic oxazole and thiazole compounds which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions; and methods for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: In one aspect, the invention relates to substituted benzylspiroindolin-2-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The invention regards the modulation of TGF-? activity by administering to a subject an antibody that binds to TGF-?, thereby increasing bone growth, bone formation, bone mass and bone strength. The antibody acts to increase osteoblast number and function while at the same time decreasing osteoclast number and function. Such drugs are useful in the treatment of diseases or disorders such as osteoporosis, Paget's disease, metastatic bone cancer, myeloma bone disease, bone fractures, etc.

Abstract: The present invention provides small molecule activators of GIRK potassium channels and methods for use thereof.

Abstract: In one aspect, the invention relates to substituted 1H-pyrazolo[3?,4?:4,5]thieno[2,3-b]pyridin-3-amine analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: In one aspect, the invention relates to substituted pyrazolo[3?,4?:4,5]thieno[2,3-c]pyridazine-3-amine analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention relates to compositions and methods for treating diseases associated with dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, steatohepatitis, atherosclerosis, obesity, hyperglycemia, metabolic syndrome, and related aspects of and conditions associated with metabolic syndrome. The compositions and methods disclosed herein are useful for regulating the lipid balance (lipid homeostasis) in a subject. Compositions and methods including a Nuclear Transport Modifier may be administered to a subject to modulate the transport of transcription factors, mediated by nuclear import adaptors, into the nucleus of a cell resulting in a decrease in cholesterol and triglyceride levels in the blood and liver, a decrease in atherosclerotic lesion size, a decrease in body weight and in hyperglycemia, a reduction of fatty liver inflammation, and an improvement in liver function.

Abstract: Certain aspects of the present disclosure are directed to a method of applying infrared neural stimulation (INS) to the central nervous system (CNS) of a target. The methods includes applying a pulsed infrared laser at a stimulation site in the CNS; and evoking responses from a region of interest of the CNS that is at or adjacent to the stimulation site by the pulsed infrared laser. In the method, the pulsed infrared laser penetrates a predetermined penetration depth of the stimulation site. Certain aspects of the present disclosure are directed to an apparatus for applying INS to the CNS of a target. The apparatus includes a generator generating a pulsed infrared laser, which penetrates a predetermined penetration depth of a stimulation site to evoke a response from the CNS, and an optical medium adapted for delivering the pulsed infrared laser at the stimulation site of the CNS.

Abstract: Systems and methods for processing magnetic resonance imaging (MRI) data are provided. A method includes receiving MRI data comprising a plurality of k-space points and deriving a plurality of image data sets based on the MRI data, each of the plurality of MRI image sets obtained by zeroing a different one of the plurality of k-space points. The method further includes computing image space metric values for each of the plurality of image data sets and adjusting a portion of the MRI data associated with ones of the image space metric values that fail to meet a threshold value to yield adjusted MRI data.

Abstract: The presently-disclosed subject matter relates to compounds of the formula: and methods for use thereof. The presently-disclosed subject matter relates methods of selectively differentiating a stem cell, and methods of screening for compounds useful for enhancing terminal differentiation of committed cardiac progenitor cells.

Abstract: Methods for the control of an exoskeleton comprising at least one powered joint associated with lower limbs of a user and control systems therefrom are provided. A method includes estimating a configuration of a body of the user associated with the exoskeleton with respect to a gravity vector and computing a first control torque for the at least one powered joint that at least partially compensates gravitational dynamics of the user based on the configuration. The method further includes calculating a gravitational energy gradient for the at least one powered joint, attenuating the first control torque based at least on the gravitational energy gradient to yield a second control torque, and applying a final control torque at the at least one powered joint, the final control torque based, at least in part, on the second control torque.

Abstract: In one aspect, the invention relates to substituted 1-benzylindolin-2-one analog compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: In one aspect, the invention relates to substituted bicyclic alkoxy pyrazole analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention, in one aspect, relates to a system for stimulating neural tissue of a living subject. The system comprises an energy source capable of generating optical energy, a connector having a first end and a second end capable of transmitting optical energy, and a probe operably coupled to the second end of the connector and having an end portion for delivering optical energy to a target neural tissue. In one embodiment, the energy source comprises a tunable laser.