Abstract: The present invention is directed to promoter sequences and promoter control elements, polynucleotide constructs comprising the promoters and control elements, and methods of identifying the promoters, control elements, or fragments thereof. The invention further relates to the use of the present promoters or promoter control elements to modulate transcript levels.

Abstract: Certain substituted urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: A method of manufacturing and using micro assembler systems are described. A method of manufacturing includes disposing a first plurality of electrodes above a first zone of the substrate, wherein the first plurality of electrodes has a first range of spacing. The method further includes disposing a second plurality of electrodes above a second zone of the substrate, wherein the second plurality of electrodes has a second range of spacing that is less than the first range of spacing. A method of using micro assembler systems includes disposing a mobile particle at least partially submersed in an assembly medium above a substrate, a first plurality of electrodes and a second plurality of electrodes. The method further includes conducting a field through individual electrodes of the first plurality of electrodes and the second plurality of electrodes to generate electrophoretic forces or dielectrophoretic forces on the mobile particle.

Abstract: An electrode array including a substrate. The electrode array includes a first plurality of electrodes disposed above a first zone of the substrate, wherein the first plurality of electrodes has a first range of spacing. The electrode array further includes a second plurality of electrodes disposed above a second zone of the substrate, wherein the second plurality of electrodes has a second range of spacing that is less than the first range of spacing.

Abstract: Provided are compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X and m are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.

Abstract: A native tensor processor calculates tensor contractions using a sum of outer products. In one implementation, the native tensor processor preferably is implemented as a single integrated circuit and includes an input buffer and a contraction engine. The input buffer buffers tensor elements retrieved from off-chip and transmits the elements to the contraction engine as needed. The contraction engine calculates the tensor contraction by executing calculations from an equivalent matrix multiplications, as if the tensors were unfolded into matrices, but avoiding the overhead of expressly unfolding the tensors. The contraction engine includes a plurality of outer product units that calculate matrix mutiplications by a sum of outer products. By using outer products, the equivalent matrix multiplications can be partitioned into smaller matrix multiplications, each of which is localized with respect to which tensor elements are required.

Abstract: Certain substituted urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: A computer-implemented method for automatically pausing advertisements based on user attention includes rendering a digital video to a user, in response to the user initiating the digital video through a web multimedia player. The computer-implemented method also includes streaming an advertisement to the user once the user begins to watch the digital video and monitoring the user attention as the user watches the advertisement. The user attention is monitored based on keystrokes and mouse movements. Further, the computer-implemented method includes detecting one or more changes in the user attention. Furthermore, the computer-implemented method includes pausing the advertisement automatically at instance of detecting the one or more changes. Moreover, the computer-implemented method includes detecting the one or more changes that directs the user attention to the paused advertisement and resuming streaming of the advertisement.

Abstract: Provided are a computer program product, system, and method for generating data structure to maintain error and connection information on components and use the data structure to determine an error correction operation. For each of a plurality of first level components in enclosures connected to second level components, errors at the first level component and a connection between the first level component to one of the second level components are determined and error variables are set to indicate whether an error was reported at the first level component. A data structure is generated indicating connections among the first level components and the second level components. The error variable values and the data structure are used to determine an error correction operation with respect to at least one of the first level component and the connected second level component.

Abstract: The present invention relates to the treatment of Pin1-associated disorders (e.g., disorders characterized by elevated Pin1 activity) with arsenic trioxide, optionally in combination with a retinoic acid compound. Pin1-associated disorders may include, for example, proliferative disorders (e.g., cancers), inflammatory conditions, and autoimmune disorders associated with aberrant levels of Pin1 activity.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations.

Abstract: A microassembler system includes an alignment surface, a two-dimensional array of electrodes adjacent the alignment surface, a sensor network arranged adjacent the array of electrodes, and a control computer electrically connected to the array of electrodes and the sensor network, the control computer to receive signals from the sensor network indicating a position of at least one chiplet and to actuate the electrodes to change the position of the chiplet based upon the signals. A method of assembling chiplets includes receiving, at one of an array of control logic units, a signal from a control computer identifying an assembly location in a block of an assembly template at which a chiplet is to be located, using a sensor to determine a chiplet location of a nearest chiplet, and generating, using electrodes corresponding to the control logic unit, a traveling wave pattern to translate and orient the nearest chiplet to the location.

Abstract: The system and method described below allow for real-time control over positioning of a micro-object. A movement of at least one micro-object suspended in a medium can be induced by a generation of one or more forces by electrodes proximate to the micro-object. Prior to inducing the movement, a simulation is used to develop a model describing a parameter of an interaction between each of the electrodes and the micro-object. A function describing the forces generated by an electrode and an extent of the movement induced due to the forces is generated using the model. The function is used to design closed loop policy control scheme for moving the micro-object towards a desired position. The position of the micro-object is tracked and taken into account when generating control signals in the scheme.

Abstract: The present invention features methods and compositions for the generation and use of conformation-specific antibodies or fragments thereof.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: There is provided an alignment system and method for use in an ultrashort pulse duration laser-based Fiber Bragg Grating (FBG) writing system, the alignment system comprising: clamps configured to hold a coated optical fiber in a position perpendicular to a beam path of an ultrashort pulse duration laser-based FBG writing station; an optical detector; and a control system with an input from the optical detector and an output to adjust parameters of an optical source and the FBG writing station adjust a distance between the optical fiber and an optical source of the writing station based on luminescence generated in a core of the optical fiber as indicated in a signal received at the input from the optical detector.

Abstract: Provided are compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X and m are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.

Abstract: The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of treating a proliferative disorder characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering an ATRA-related compound. The invention also features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering an ATRA-related compound in combination with another therapeutic compound.