Abstract: Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

Abstract: The present invention provides a method for multiproduct resin reuse (MRR) utilizing ionic exchange chromatography columns. The methods of the invention outline the cleaning steps necessary for reuse as well as the analytical processes used in determining product carryover from production of one product to the next. The invention outlines a successful MRR strategy that can be utilized not just in lab-scale studies, but in a GMP manufacturing setting.

Abstract: The invention provides methods of detecting transthyretin (TTR) using a capture antibody and a reporter antibody. The capture antibody binds preferentially to misfolded TTR over native tetrameric form of TTR. The capture antibody binds to an epitope within amino acid residues 89-97 or TTR or to an epitope within amino acid residues 101-109 of TTR. 9D5 and 18C5 are examples of suitable capture antibodies. The methods can be used for diagnosing diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis) and for monitoring the efficacy of TTR therapies, among other applications.

Abstract: The present disclosure provides engineered proline hydroxylase polypeptides for the production of hydroxylated compounds, polynucleotides encoding the engineered proline hydroxylases, host cells capable of expressing the engineered proline hydroxylases, and methods of using the engineered proline hydroxylases to prepare compounds useful in the production of active pharmaceutical agents.

Abstract: This dual-compartment liver co-culture system exposes target microtissue to metabolites, allowing for evaluating toxicity using a standard multi-well plate for high throughput analysis. Discovery scientists can rapidly select lead compounds with desirable metabolic profiles, while safety scientists can determine the safety of drugs, pesticides, and environmental chemicals. This platform is allometrically scalable, so it can mimic the natural size differences between healthy organs and, with the liver, produce sufficient quantities of metabolites. The device is simple to use and designed for immediate in vitro pathology assessment using confocal microscopy, transcriptomics, and proteomics.

Abstract: Genetically modified microorganisms that have the ability to convert carbon substrates into chemical products such as isobutanol are disclosed. For example, genetically modified methanotrophs that are capable of generating isobutanol at high titers from a methane source are disclosed. Methods of making these genetically modified microorganisms and methods of using them are also disclosed.

Abstract: The present disclosure relates to antibodies and antibody conjugates, for instance antibody drug conjugates, with binding specificity for receptor tyrosine kinase orphan receptor 1 (ROR1) and its isoforms and homologs, and compositions comprising the antibodies or antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibodies and antibody conjugates and compositions thereof as well as methods of using the antibodies and antibody conjugates and compositions thereof, such as in therapeutic and diagnostic methods.

Abstract: Systems and methods for detecting roadway lane boundaries are disclosed herein. One embodiment receives image data of a portion of a roadway; receives historical vehicle trajectory data for the portion of the roadway; generates, from the historical vehicle trajectory data, a heatmap indicating, for a given pixel in the heatmap, an extent to which the given pixel coincides spatially with vehicle trajectories in the historical vehicle trajectory data; and projects the heatmap onto the image data to generate a composite image that is used in training a neural network to detect roadway lane boundaries, the projected heatmap acting as supervisory data. The trained neural network is deployed in a vehicle to generate and save map data including detected roadway lane boundaries for use by other vehicles or to control operation of the vehicle itself based, at least in part, on roadway lane boundaries detected by the trained neural network.

Abstract: The disclosure relates to compositions and methods for altering, e.g., enhancing, the expression of GCase proteins, whether in vitro and/or in vivo. Such compositions include delivery of an adeno-associated viral (AAV) particle. The compositions and methods of the present disclosure are useful in the treatment of subjects diagnosed with, or suspected of having Parkinson Disease or related condition resulting from a deficiency in the quantity and/or function of GBA gene product or associated with decreased expression or protein levels of GCase protein.

Abstract: The present disclosure relates to RNAi agents, for example, double stranded RNAi agents, able to inhibit HIF-2 alpha (EPAS1) gene expression. Also disclosed are pharmaceutical compositions that include HIF-2 alpha RNAi agents and methods of use thereof. The HIF-2 alpha RNAi agents disclosed herein may be linked or conjugated to targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-3 and alpha-v-beta-5 integrins) and pharmacokinetic (PK) enhancers, to facilitate the delivery to cells and tissues, including to clear cell renal cell carcinoma (ccRCC) cells and tumors. Delivery of compositions comprising the HIF-2 alpha RNAi agents in vivo provides for inhibition of HIF-2 alpha gene expression. The HIF-2 alpha RNAi agents can be used in methods of treatment of various diseases and disorders, including ccRCC.

Abstract: A structural reinforcement for an article including a carrier (10) that includes: (i) a mass of polymeric material (12) having an outer surface; and (ii) at least one fibrous composite insert (14) or overlay (960) having an outer surface and including at least one elongated fiber arrangement (e.g., having a plurality of ordered fibers). The fibrous insert (14) or overlay (960) is envisioned to adjoin the mass of the polymeric material in a predetermined location for carrying a predetermined load that is subjected upon the predetermined location (thereby effectively providing localized reinforcement to that predetermined location). The fibrous insert (14) or overlay (960) and the mass of polymeric material (12) are of compatible materials, structures or both, for allowing the fibrous insert or overlay to be at least partially joined to the mass of the polymeric material. Disposed upon at least a portion of the carrier (10) may be a mass of activatable material (126).

Abstract: Techniques and systems for testing, evaluating and/or otherwise assessing the operation of vehicles are discussed herein. Some aspects relate to a system and method which may receive, at a first computer system, vehicle data derived from a vehicle data logging system, and may receive a playback time associated with a portion of the vehicle data. A sharable data structure may be generated which identifies the vehicle data and the playback time. The sharable data structure may be transmitted to a second computer system, wherein the sharable data structure allows the second computer system to retrieve the vehicle data.

Abstract: A profile or article formed from a moisture- and/or thermo-curable elastomeric polymer composition including: (A) at least one ethylene-olefinic monomer-silane polymer; wherein the polymer has an olefinic monomer content of from 5 weight percent to 50 weight percent and a silane content of from 0.1 weight percent to 2.5 weight percent; and wherein the polymer has a melt index of from 0.1 gram/10 minutes to 10.0 grams/10; and (B) at least one silanol condensation catalyst; a shaped article made from the above elastomeric polymer composition; and a method of making a shaped article using the above elastomeric polymer composition.

Abstract: Wheat variety designated KS Big Bow is disclosed. The variety is a hard white winter wheat that is white seeded and is well adapted for the semi-arid regions in western Kansas and surrounding states. Plants and seeds of wheat variety KS Big Bow, methods for producing a wheat plant produced by crossing the variety KS Big Bow with another wheat plant, and hybrid wheat seeds and plants produced by crossing the variety KS Big Bow with another wheat line or plant, and the creation of variants by backcrossing, mutagenesis or transformation of variety KS Big Bow are disclosed. Methods for producing other wheat varieties or breeding lines derived from wheat variety KS Big Bow and to wheat varieties or breeding lines produced by those methods are also provided.

Abstract: The disclosure provides compositions and methods for the preparation, manufacture and use of an adeno-associated virus (AAV) particle for the vectorized delivery of an antibody molecule that binds to tau.

Abstract: A computer-implemented method, a computer system and a computer program product add a mapped holographic projection to a screen sharing session. The method includes transmitting a screen image from a presenter computing device to a participant computing device. The method also includes capturing a body movement image of the presenter using a camera. The method further includes identifying a gesture in the body movement image and mapping the gesture to the screen image. In addition, the method includes generating a holographic projection of a mapped gesture of the presenter. Lastly, the method includes displaying the holographic projection at the participant computing device in front of the screen image.

Abstract: The present disclosure relates to antibodies and antibody conjugates, for instance antibody drug conjugates, with binding specificity for receptor tyrosine kinase orphan receptor 1 (ROR1) and its isoforms and homologs, and compositions comprising the antibodies or antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibodies and antibody conjugates and compositions thereof as well as methods of using the antibodies and antibody conjugates and compositions thereof, such as in therapeutic and diagnostic methods.

Abstract: The present application provides materials and methods for treating hemoglobinopathies. More specifically, the application provides methods for producing progenitor cells that are genetically modified via genome editing to increase the production of fetal hemoglobin (HbF), as well as modified progenitor cells (including, for example, CD34+ human hematopoietic stem cells) producing increased levels of HbF, and methods of using such cells for treating hemoglobinopathies such as sickle cell anemia and ?-thalassemia.

Abstract: The present application provides materials and methods for treating a patient with Alpha-1 antitrypsin deficiency (AATD) both ex vivo and in vivo. In addition, the present application provides materials and methods for editing the SERPINA1 gene in a cell by genome editing.

Abstract: Systems and methods for map simulation testing are provided. A method includes receiving, by a computer-implemented system, information associated with an operational design domain (ODD); generating, by the computer-implemented system based at least in part on the information associated with the ODD, a plurality of map test cases for a map representative of a geographical area in the ODD, where each map test case of the plurality of map test cases includes one of a plurality of paths in the geographical area; evaluating a vehicle planning process in navigating through one or more of the plurality of paths corresponding to one or more of the plurality of map test cases; and determining a metric for the map based on the evaluating.