Abstract: The present invention relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with HDAC6, having a Formula I: where R, L, X1, X2, X3, X4, Y1, Y2, Y3, and Y4 are described herein.

Abstract: The present invention relates to inhibitors of histone deacetylases, in particular HDAC8, that are useful for the treatment of cancer and other diseases and disorders, as well as the synthesis and applications of said inhibitors.

Abstract: A microneedle injection and infusion apparatus, and a method of using same. The apparatus can include a housing, a microneedle array holder for holding a microneedle array, and a shuttle that holds a cartridge (e.g., that contains an active agent). The microneedle array holder can be movable between a retracted position and an extended position. The shuttle can be movable between a first position in which the cartridge is not in fluid communication with a fluid path and a second position in which the cartridge is in fluid communication with the fluid path. The apparatus can further include an actuator movable between a first position and a second position. The method can include moving the actuator to its second position to allow the shuttle to move toward its second position, wherein movement of the shuttle toward its second position allows the microneedle array holder to move to its extended position.

Abstract: The present invention relates in general to polymer-bioactive agent conjugates for delivering a bioactive agent to a subject. The polymer-bioactive agent conjugates contain triazole moieties in the polymer backbone and a bioactive moiety selected from quinolones, NSAIDs and mixtures thereof. The present invention also relates to methods for preparing the polymer conjugates using click cycloaddition chemical reactions, to monomer-bioactive agent conjugates suitable for preparing the polymer conjugates, and to pharmaceutical products comprising the polymer conjugates for the post-surgical care to treat or prevent infections, provide analgesia and treat inflammation.

Abstract: A container is provided. The container includes a body, a first plug, and a second plug. The body has a first end, a second end, and a bypass with a length L disposed between the ends. The first and second plugs are slideably disposed in the body and define a first compartment. A second compartment is in the body between the second plug and the second end. The second plug has a first edge; a second edge; and a plurality of primary conduits, each primary conduit extending from first openings in the side wall to second openings in the bottom surface. The bottom surface does not define a plane oriented substantially orthogonal to the longitudinal axis. A distance D extends longitudinally from the first edge to the second edge. A distance E extends longitudinally from the first edge to the first opening. D?L and E<L.

Abstract: A microneedle injection and infusion apparatus, and a method of using same. The apparatus can include a housing, a microneedle array holder for holding a microneedle array, and a shuttle that holds a cartridge (e.g., that contains an active agent). The microneedle array holder can be movable between a retracted position and an extended position. The shuttle can be movable between a first position in which the cartridge is not in fluid communication with a fluid path and a second position in which the cartridge is in fluid communication with the fluid path. The apparatus can further include an actuator movable between a first position and a second position. The method can include moving the actuator to its second position to allow the shuttle to move toward its second position, wherein movement of the shuttle toward its second position allows the microneedle array holder to move to its extended position.

Abstract: A microneedle injection apparatus comprising an inverted actuator. The apparatus can include a housing having a base and a cavity, and a microneedle array holder configured to hold a microneedle array within the cavity of the housing. The microneedle array holder can be movable between a retracted position, and an extended position. The apparatus can further include an actuator movable with respect to the housing and the microneedle array holder between a first position and a second position to cause the microneedle array holder to move from the retracted position to the extended position. At least a portion of the actuator can be located on a skin-facing side of the apparatus (e.g., adjacent the base of the housing) and can be configured to be moved from the first position to the second position in response to the apparatus being pressed toward the skin surface.

Abstract: A programmable integrated circuit with lookup table circuitry is provided. The lookup table (LUT) circuitry may be formed using multiplexers. A multiplexer in the lookup table circuitry may be implemented using only tristate inverting circuits. Each tristate inverting circuit may include a first set of n-channel and p-channel transistors that receive a static control bit from a memory element and a second set of n-channel and p-channel transistors that receive true and complementary versions of a user signal. The first and second sets of transistors may be coupled in series between a positive power supply terminal and a ground power supply terminal. A LUT multiplexer implemented in this way need not include separate transmission gates at the output of each tristate inverting circuit and may exhibit minimal subthreshold leakage.

Abstract: An FPGA includes a number of logic elements in a core fabric. Each logic element includes a number of registers and each register includes a registered circuit path and a combinatorial circuit path. The registered and combinatorial circuit paths are in parallel. Each register includes a DFT circuit path that comprises an input in the registered circuit path and an output in the registered circuit path. The DFT circuit path is not in series with the registered circuit path and is not in series with the combinatorial circuit path. Each register includes a CE time-borrowing circuit path. Each the CE time-borrowing circuit path includes an input in the registered circuit path and an output that is coupled to the input of the registered circuit path. The CE time-borrowing circuit path is not in series with the registered circuit path and is not in series with the combinatorial circuit path.

Abstract: The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.

Abstract: A drug-polymer conjugate, which is a copolymer of at least one monomer of formula (I): (I) where: X may be the same or different at each occurrence and represents a terminal functional group comprising an alkyne or an azide; Q is independently selected at each occurrence and may be present or absent and when present, represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon, optionally substituted aryl and optionally substituted heteroaryl; D is a releasable drug selected from prostaglandins, ?-blockers and mixtures thereof; L is a linker group group; and at least one co-monomer of Formula III III J represents a linking functional group, n is 2 to 8, preferably 3 to 8; Y comprises a polyether of formula (ORa)m wherein Ra is independently ethylene, propylene and butylene and m is from 1 to 300 (preferably 2 to 300) and the polyether is in chain with one or more groups which are preferably selected from one or more of optionally substituted straight or branched Ci to

Abstract: A polymer-prostaglandin conjugate comprising: a polymer backbone comprising a plurality of moieties of formula (I): where: T represents a triazole moiety; Q is independently selected at each occurrence and may be present or absent and when present represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon; D is selected from prostaglandins; and L is a group of formula (II) wherein R5 is selected from hydrogen and C1 to C6 alkyl; (R) indicates the end of the group bonded to the R group; and (D) indicates the end of the group attached to the group D.

Abstract: The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract: The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases.

Abstract: In an example, a method includes capturing one or more friction ridge images of a finger at an instance in time, the one or more friction ridge images including a plurality of perspectives of the finger. The method also includes determining, from the one or more friction ridge images, a rolled fingerprint representation of the finger, the rolled fingerprint representation comprising data from the plurality of perspectives, and outputting the rolled fingerprint representation.

Abstract: An article comprising at least one microneedle is provided. The article can comprises a first side and a second side opposite the first side. The first side comprises a central cavity portion and a platform portion, with at least one microneedle extending therefrom, wherein the platform portion is not coplanar with the central cavity portion. The platform portion substantially surrounds the central cavity portion. The at least one microneedle comprises a body comprising an outer surface; a base segment having a base and a first shape; a tip segment having a tip and a second shape, wherein the second shape is distinct from the first shape; a transition plane that delineates the base segment and the tip segment; and a central axis. Methods of using the article are also provided.

Abstract: The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I: where R, L, X1, X2, X3, X4, Y1, Y2, Y3, and Y4 are described herein.

Abstract: The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I: where R, L, X1, X2, X3, X4, Y1, Y2, Y3, and Y4 are described herein.

Abstract: The present invention relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with HDAC6, having a Formula I: where R, L, X1, X2, X3, X4, Y1, Y2, Y3, and Y4 are described herein.

Abstract: The present invention is directed to inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.