Abstract: Sublingual formulations containing an opioid, preferably, fentanyl or a pharmaceutically acceptable salt or ester thereof, naloxone or a pharmaceutically acceptable salt or ester thereof, and a terpene; as well as methods of treating pain by administering the formulations of the invention to a patient in need thereof.

Abstract: An input circuit for detecting low voltage analog signals in an electrically noisy environment receives the analog input signal at an input terminal. The analog input signal is compared to a variable reference signal at a comparator circuit. An active hysteresis circuit provides feedback to the comparator. In a first operating mode, the active hysteresis circuit may be disabled or be configured to output a constant voltage. In a second operating mode, the active hysteresis circuit may be enabled or configured to output a varying level of voltage. The output of the feedback circuit is summed with the variable reference signal and supplied as the input signal to the comparator, such that signal against which the analog input signal is compared is a general constant value in the first operating mode and varies with respect to time in the second operating mode.

Abstract: An input circuit for detecting low voltage analog signals in an electrically noisy environment receives the analog input signal at an input terminal. The analog input signal is compared to a variable reference signal at a comparator circuit. An active hysteresis circuit provides feedback to the comparator. In a first operating mode, the active hysteresis circuit may be disabled or be configured to output a constant voltage. In a second operating mode, the active hysteresis circuit may be enabled or configured to output a varying level of voltage. The output of the feedback circuit is summed with the variable reference signal and supplied as the input signal to the comparator, such that signal against which the analog input signal is compared is a general constant value in the first operating mode and varies with respect to time in the second operating mode.

Abstract: The present disclosure relates to stimulators of soluble guanylate cyclase (sGC), pharmaceutical formulations comprising them and their uses thereof, alone or in combination with one or more additional agents, for treating various diseases, wherein an increase in the concentration of nitric oxide (NO) or an increase in the concentration of cyclic Guanosine Monophosphate (cGMP), or both, or an upregulation of the NO pathway is desirable.

Abstract: The present patent application discloses at least the compounds according to Formula I? shown below, or pharmaceutically acceptable salts thereof, wherein ring D, ring A, ring E, JB, n, JD, J, X, Z, Z1, RC1, RC2, Y, R9, o and W are as defined herein.

Abstract: Compounds of Formulae I? and I are described, which are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds are also useful for treating, preventing or managing various disorders that are herein disclosed.

Abstract: Conjugates of an active agent such as DM1 attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker, have been designed. Methods of administering the conjugates to a subject in need thereof are provided, for example, to treat or prevent cancer.

Abstract: An industrial control I/O module for interfacing with industrial control equipment, such as sensors and actuators, can be configured to dynamically provide differing resistances in each channel as may be required for reliably achieving particular modes of operation in the channel. Providing differing resistances in such channels flexibly allows different modes in the channel to provide universal I/O capability. Modes of operation could include, for example, digital output, digital input, analog output, analog input and the like, in the same channel, but at different times. In one aspect, a processor or voltage divider can be used to control an amplifier, with feedback, driving a transistor in a channel to dynamically adjust resistance in the channel by selectively biasing the transistor to achieve a resistance in the channel suitable for the selected mode.

Abstract: Conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to an HSP90 targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The invention provides compositions and methods for regulating thermogenesis and muscle inflammation through modulation of Metrnl and/or Metrn activity and/or expression. Also provided are methods for preventing or treating metabolic disorders and muscle inflammation disorders in a subject through modulation of Metrnl and/or Metrn activity and/or expression. Further provided are methods for identifying compounds that are capable of treating metabolic disorders and muscle inflammation disorders by modulating Metrnl and/or Metrn activity and/or expression.

Abstract: Nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker have been designed. Such nanoparticles and microparticles can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

Abstract: An industrial control I/O module for interfacing with industrial control equipment, such as sensors and actuators, can be configured to dynamically provide differing resistances in each channel as may be required for reliably achieving particular modes of operation in the channel. Providing differing resistances in such channels flexibly allows different modes in the channel to provide universal I/O capability. Modes of operation could include, for example, digital output, digital input, analog output, analog input and the like, in the same channel, but at different times. In one aspect, a processor or voltage divider can be used to control an amplifier, with feedback, driving a transistor in a channel to dynamically adjust resistance in the channel by selectively biasing the transistor to achieve a resistance in the channel suitable for the selected mode.

Abstract: A method for automated control of a drilling operation of a blast hole drilling machine using a down-the-hole drill bit mounted on a drill string is disclosed. The method may include: receiving input data from a user input including information of the drill bit, drill string weight, and desired hole settings; receiving a command from the user to initiate an automatic down-the-hole operation; identifying a location of the down-the-hole drill bit; and using the received input data and based on the location of the down-the-hole drill bit, automatically initiating the steps of: collaring a hole; drilling the hole; and retracting the drill when the hole is drilled.

Abstract: A novel SH-SAW biosensor capable of non-invasive and touch-free detection of cancer cell viability and growth or proliferation in two-dimensional (2D) and three-dimensional (3D) cell cultures as well as stem cell regeneration as it pertains to cancer cell biology and anti-cancer drug development is presented. The biosensor includes two pairs of resonators including interdigital transducers reflecting fingers to quantify mass loading by the cells in suspension as well as within a tumoroid culture platform. The biosensor can be part of a perfused 3PNS-tumoroid system that is amenable to real-time non-invasive monitoring of the cell proliferation, viability, and multiplexed detection of key physiologic and clinical biomarkers.

Abstract: Compounds of Formulae I? and I are described, which are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds are also useful for treating, preventing or managing various disorders that are herein disclosed.

Abstract: Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

Abstract: Nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker have been designed. Such nanoparticles and microparticles can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.

Abstract: Conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to an HSP90 targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.

Abstract: Conjugates of an active agent attached to a targeting moiety, such as an HSP90 binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.