Abstract: Improved processes for rationally-designing and producing biomolecules are disclosed herein. More specifically, disclosed processes comprise the steps of (i) selecting at least one biomolecule suitable for modification; (ii) obtaining at least one structure of the at least one biomolecule; (iii) simulating the molecular dynamics of the at least one structure to generate dynamic information about at least one position within the at least one structure; (iv) using the dynamic information to calculate a score for the at least one position; (v) comparing the score with at least one reference score to identify at least one target position within the biomolecule suitable for modification; and (vi) modifying the at least one target position.

Abstract: Small molecule inhibitors of salt inducible kinases (SIKs) are provided. In particular, compounds of formula (II) and compounds of formula (III), and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof are provided. Also provided are pharmaceutical compositions containing the compounds, methods of preparing the compounds, and methods of using the compounds for inhibiting SIKs, such as SIK1 and SIK2, and methods of treating diseases mediated by SIKs.

Abstract: An instrument includes a fluidic cartridge having a body comprising a malleable material and a layer comprising a deformable material bonded to a surface of the body that seals one or more fluidic channels that communicate with one or more valve bodies formed in a surface of the body. The valve can be closed by applying pressure to the deformable material sufficient to close off a fluidic channel in the body. A cartridge interface is configured to engage the cartridge.

Abstract: A steering shaft assembly includes a shaft having a first end region including a nose, a male spline region coupleable with a female spline region of a clamp yoke, a ring flag seat adjacent said nose, and a first ring flag locating feature between said ring flag seat and said male spline region. The steering shaft assembly also includes a ring flag having an annular band seated on said ring flag seat, a flag extending axially from said annular band in a first direction beyond said first end and radially outwardly from said annular band, and a second ring flag locating feature extending axially from said annular band in a second direction opposite said first direction, said second ring flag locating feature interacting with said first ring flag locating feature to orient said ring flag in a predetermined rotational orientation relative to said shaft.

Abstract: Printable high-strength alloys, including aluminum alloys can be produced in an additive manufacturing process. Such alloys can include aluminum-silver (“Al—Ag”) alloys that are produced by a laser melting process using a powder bed fusion. The results of the process and the characteristics of the produced alloy can be determined by controlling at least an energy beam power, an energy beam speed, and/or an energy beam size. The operational parameters can be controlled with high precision to produce a printable, high-strength aluminum alloy.

Abstract: Provided are a computer program product, system, and method for a data set connection manager having a plurality of data sets to represent one data set. A request is processed to open a connection to a data set having members, wherein the connection is used to perform read and write requests to the members in the data set. In response to establishing the connection, establishing for the connection a primary data set having all the members; a secondary data set to which updated members in the primary data set are written; and a pending delete data set to pending delete members comprising members that are updated.

Abstract: A method for hardware management of DMA transfer commands includes accessing, by a first DMA engine, a DMA transfer command and determining a first portion of a data transfer requested by the DMA transfer command. Transfer of a first portion of the data transfer by the first DMA engine is initiated based at least in part on the DMA transfer command. Similarly, a second portion of the data transfer by a second DMA engine is initiated based at least in part on the DMA transfer command. After transferring the first portion and the second portion of the data transfer, an indication is generated that signals completion of the data transfer requested by the DMA transfer command.

Abstract: Systems and methods are presented that automatically construct a directed acyclic graph (DAG) workflow used to control and manage algorithms on multiple, disparate, cloud-based development and deployment platforms. DAG workflows are comprised of a set of simplified, fixed time-affecting linear pathways (STALPs). Algorithms are constructed using no-code/low-code methods that are then automatically decomposed into a set of markup or scripting language time-affecting linear pathways (M-S TALPs). Prediction polynomials that approximate advanced time and space complexity functions are created using M-S TALPs and are used for M-S TALP identification, optimization, efficiency, and performance enhancement on selected computing platforms.

Abstract: Systems and methods are provided for assembling a section of a fuselage of an aircraft. The method includes pulsing a half barrel section of the fuselage along a track in a process direction, utilizing an indexing feature associated with the half barrel section to determine a desired contour for a portion of the half barrel section, and enforcing the desired contour onto the half barrel section using components that enforce an inner mold line and components that enforce an outer mold line when the half barrel section is out of tolerance from the desired contour.

Abstract: A hybrid electrofusion processor selectively operating on either battery power or AC power.

Abstract: An emergency dispatch system configured to allow first responders to efficiently utilize video-based systems using static images of a space and to understand a physical layout of the space. The system includes a dispatch processing hub linked via a communications network with client devices. The system further includes data storage storing a static image of a monitored space from a supplemental camera and video of the monitored space from video sources. A map interface generator is provided that is configured for generating a map-based interface for display upon a display device of the client devices. The map-based interface provides access to the static image and to the video. The hub functions to serve the map-based interface to the client devices. The dispatch processing hub responds to user input selecting the static image by providing a view, e.g., a 360-degree view, of the monitored space based on the static image.

Abstract: Devices, systems and methods are provided for low-power and high-sampling rate of analog signals received from sensors transported by host devices. The devices, systems and methods may be adapted to utilize GPS and PPS signals for synchronization with digitized signals generated based on the sampling of the analog signals that are simultaneously received and processed by multiple channels. Synchronized data packets may be recorded by the disclosed data acquisition systems, and may be further transmitted to host devices and remote devices.

Abstract: The present invention provides agents and compositions for modulating expression (e.g., enhanced or reduced expression) of a hepatocyte nuclear factor 4 alpha (HNF4?) gene by targeting an HNF4? expression control region and methods of use thereof for treating an HNF4? associated disorder, e.g., cirrhosis.

Abstract: Methods, devices and systems for evaluating olfactory function are configured to: electronically estimate a user-specific odorant detection threshold sensitivity threshold using at least one target stimulus odorant delivered to a nose of a user; flowably deliver a plurality of different target stimulus odorants to the nose of the user with defined concentrations of the different target stimulus odorants based, at least in part, on the estimated user-specific odorant detection sensitivity threshold; and evaluate olfactory function of the user based on the user's response to the delivered different target stimulus odorants.

Abstract: The present disclosure relates to the use of 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea or 1-(5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-bromo-2-fluorophenyl)-3-phenylurea, or a pharmaceutically acceptable salt thereof, in combination with a MAPKAP kinase inhibitor for the treatment of cancers, including c-KIT-mediated cancers, such as GIST.

Abstract: A system for selecting a sensitivity level for adjusting an intensity setting for therapy provided to a patient includes one or more processors and one or more processors coupled to the memory. The one or more processors are configured to receive an indication of an input to adjust an intensity setting related to the therapy provided to the patient and determine a sensitivity level for adjustment of the intensity setting based on an efficacy of the therapy provided to the patient. The one or more processors are further configured to determine an updated intensity level for the intensity setting based on the sensitivity level and the input to adjust the intensity setting and output an instruction to cause a medical device to provide the therapy at the updated intensity level.

Abstract: Systems and methods are provided for installing ribs and/or spars to a wing panel while a contour is enforced. Methods include suspending a wing panel beneath a shuttle that enforces the contour, advancing the wing panel through work stations via the shuttle, and installing a rib or a spar (or another wing panel) at a work station, while the contour is enforced. Other methods include locating a wing panel beneath a shuttle, coupling adjustable-length pogos to the wing panel at locations distinct from those corresponding with an installation location, e.g. for a rib or a spar, and controlling the length of the pogos to enforce a contour to the wing panel. Some systems include a track, work stations disposed along the track, and a shuttle to advance along the track and convey a wing panel to each of the work stations while enforcing a contour onto the wing panel.

Abstract: Small molecule inhibitors of salt inducible kinases (SIKs) are provided. In particular, compounds of formula (I), and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof are provided. Also provided are pharmaceutical compositions containing the compounds, methods of preparing the compounds, and methods of using the compounds for inhibiting SIKs, such as SIK1 and SIK2, and methods of treating diseases mediated by SIKs.

Abstract: Systems and methods are provided for assembling a wing. Methods include suspending an upper wing panel of an aircraft beneath a shuttle, translating a rib to a position it, and placing the rib into contact with, then affixing the rib to, the upper wing panel, while suspended. Some methods include installing ribs and spars to the upper wing panel, and joining a lower wing panel to the ribs and spars, while the upper wing panel is suspended. Some methods involve joining ribs to spars (e.g., all, or some) to produce a support structure that is then affixed to the upper wing panel. Systems include a shuttle that suspends an upper wing panel, and a cart that includes supports to hold a rib, a chassis to translate the rib to a position beneath the upper wing panel, and a lifting apparatus to lift the rib into contact with the upper wing panel.

Abstract: Systems and methods are provided for assembling a structure. The systems and method including micro pulsing a structure along a track in a process direction by less than a length of the structure. The structure is indexed to one or more work stations by mating indexing features in a manufacturing excess of the structure to complementary features at the work stations. The work stations would the perform work on the structure at the work stations while the structure is indexed to the work stations. Iteratively repeating the micro pulsing and indexing and working upon the structure until it is ready to advance to the next assembly process.