Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.

Abstract: The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, Z, J, M, and R1 to R8 are defined herein, these compounds are effective in treating conditions associated with dysregulation of the RAS/RAF/MEK/ERK pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: A method of making glass is disclosed in which a flue gas that comprises water vapor is exhausted from a submerged combustion melter that is operated to discharge combustion products into a glass melt that results from the combustion of a mixture of hydrogen gas and an oxidant gas. Heat may be recovered from the exhausted flue gas to heat batch feedstock material fed to the melter, or water vapor in the exhausted flue gas may be condensed and returned to the melter for cooling purposes, or both. A glass-melting system is also disclosed that includes a submerged combustion melter, a batch feedstock material preheater in fluid communication with the submerged combustion melter and configured to heat batch feedstock material, a condenser in fluid communication with the batch feedstock material preheater, and a cooling water reservoir in fluid communication with the condenser and the submerged combustion melter.

Abstract: Provided herein are methods of detecting or determining aging and/or oxidative damage in tissue, including placental tissue, skin, kidney and brain tissue. One embodiment provides a method for detecting or determining aging in body tissue, comprising measuring one or more markers of aldehyde oxidase 1 (AOX1) expression or activity in a biological sample, wherein the level of AOX1 expression or activity, or of the one or more markers, is indicative of aging in the tissue. Also provided herein are methods of treating a disease or condition associated with ageing or oxidative damage in one or more cells or tissues, comprising administering to a subject in need thereof an inhibitor of AOX1.

Abstract: A drive unit for driving an acceleration electrode of a mass spectrometer is disclosed. The drive unit includes a power converter comprising a switching element and pulsing circuitry that can form output pulses suitable for driving an acceleration electrode of a mass spectrometer. The drive unit also includes a controller that is configured to synchronise operation of the switching element with the pulsing circuitry.

Abstract: Systems for determining a phase of a device coupled to an electrical distribution system. The system includes a number of gateway devices configured to transmit a synchronization signal. The gateway device receives a node response message from a first node device that includes a duration value indicating a time between a receipt of the transmitted synchronization signal and a detected zero crossing. The gateway device compares the duration value against duration values received from node devices with a known phase connection and determines a phase of the first node device based on the comparison.

Abstract: A system for determining a phase of a power supply coupled to a metering device. The system includes a collection device in electronic communication with a metering device connected to a power distribution network and having a memory and one or more electronic processors. The electronic processors are configured to receive a first beacon signal and measure a phasor in response to receiving the first beacon signal. The phasor is stored in the memory along with an identification value associated with the device that transmitted the first beacon signal and a first time. The electronic processors receive a second beacon signal, and extract data from the request message. The electronic processors determine whether the extracted time matches the first time and based on determining that the extracted time matches the first time stored in the memory, calculate a phase by comparing the reference phasor data to the stored phasor.

Abstract: Presented herein are techniques for adapting settings/operations of a remote microphone device associated with an auditory prosthesis based on a desired/preferred listening direction of a recipient of the auditory prosthesis. More specifically, an auditory prosthesis worn by a recipient and a remote microphone device, which are configured to wirelessly communicate with one another, are both positioned in the same spatial area. At least one of a recipient-specified (e.g., recipient-preferred) region of interest within the spatial area, or a recipient-specified listening direction, is determined. Based on a determined relative positioning (e.g., location and orientation) of the remote microphone device and the auditory prosthesis, operation of the remote microphone device is dynamically adapted so that the remote microphone device can focus on (e.g., have increased sensitivity to) sounds originating from the recipient-specified region of interest/listening direction.

Abstract: A fiber blend containing: (a) a cellulose acetate (CA) staple fibers having a denier per filament (DPF) of 3.0 or less; and (b) structural staple fibers having a dpf of 6.0 or more; and (c) optionally binder fibers. The fiber blend can be made into nonwoven webs for heat-bonding and subsequent use as thermal insulation in, e.g., outerwear, bedding, etc. The fiber blend can now contain sustainably derived fibers, optionally biodegradable, that provide good thermal insulation clo values and loft even after multiple wash cycles along with good short term compression recovery.

Abstract: Systems for determining a phase of a device coupled to an electrical distribution system. The system includes a number of gateway devices configured to transmit a synchronization signal. The gateway device receives a node response message from a first node device that includes a duration value indicating a time between a receipt of the transmitted synchronization signal and a detected zero crossing. The gateway device compares the duration value against duration values received from node devices with a known phase connection and determines a phase of the first node device based on the comparison.

Abstract: A system for determining a phase of a power supply coupled to a metering device. The system includes a collection device in electronic communication with a metering device connected to a power distribution network and having a memory and one or more electronic processors. The electronic processors are configured to receive a first beacon signal and measure a phasor in response to receiving the first beacon signal. The phasor is stored in the memory along with an identification value associated with the device that transmitted the first beacon signal and a first time. The electronic processors receive a second beacon signal, and extract data from the request message. The electronic processors determine whether the extracted time matches the first time and based on determining that the extracted time matches the first time stored in the memory, calculate a phase by comparing the reference phasor data to the stored phasor.

Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.

Abstract: Presented herein are techniques for adapting settings/operations of a remote microphone device associated with an auditory prosthesis based on a desired/preferred listening direction of a recipient of the auditory prosthesis. More specifically, an auditory prosthesis worn by a recipient and a remote microphone device, which are configured to wirelessly communicate with one another, are both positioned in the same spatial area. At least one of a recipient-specified (e.g., recipient-preferred) region of interest within the spatial area, or a recipient-specified listening direction, is determined. Based on a determined relative positioning (e.g., location and orientation) of the remote microphone device and the auditory prosthesis, operation of the remote microphone device is dynamically adapted so that the remote microphone device can focus on (e.g., have increased sensitivity to) sounds originating from the recipient-specified region of interest/listening direction.

Abstract: Disclosed herein are immunogenic compositions for producing immediate and sustained immunity to infectious viral and bacteriological pathogens. A univalent immunogenic composition is disclosed comprising an isolated antigen and a polynucleotide formulated into a nanoparticle or liposome. Furthermore, multivalent immunogenic compositions are disclosed comprising multiple univalent immunogenic compositions. Also disclosed, are methods of inducing protective or therapeutic immune responses in individuals comprising administering one or more univalent immunogenic compositions.

Abstract: The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, Z, J, M, and R1 to R8 are defined herein, these compounds are effective in treating conditions associated with dysregulation of the RAS/RAF/MEK/ERK pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: Provided herein are methods of amplifying and detecting biothreat pathogens in complex samples (e.g., blood), as well as related panels and compositions (e.g., systems, cartridges, and kits).

Abstract: Provided herein are methods of amplifying and detecting pathogens and drug resistance markers (e.g., antibiotic resistance genes) in complex samples (e.g., blood), as well as related panels and compositions (e.g., primers, probes, magnetic particles, systems, cartridges, and kits). The methods, panels, and compositions can be used for comprehensive detection of pathogens and drug resistance markers for patient identification, patient selection, optimization of therapies, and antimicrobial stewardship.

Abstract: Provided herein are methods of detecting and sequencing target nucleic acids in complex samples (e.g., blood), as well as related panels and compositions (e.g., systems, cartridges, and kits).

Abstract: A modular solution mining method may include the steps of: providing an injection wellbore, the injection wellbore including a horizontal injection portion, in which the horizontal injection portion includes a toe end and heel end; providing a production wellbore, in which the production wellbore includes a horizontal production portion that is proximate to the toe end; injecting a solvent into the horizontal injection portion; generating a turbulent solvent flow proximate to the toe end to generate a mineral solution and an initial cavern proximate to the horizontal production portion; and motivating the mineral solution from the initial cavern, into the horizontal production portion, and to a surface location. Optionally, the method may include the step of repositioning the turbulent solvent flow to be closer to heel ends to generate mineral solution and subsequent caverns further from horizontal production wellbore.

Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.