Abstract: Disclosed are compositions and related methods of recapitulating bone marrow stroma using scaffold materials (e.g., a porous alginate hydrogel scaffold) containing one or more cellular differentiation factors, and one or more growth factors. Such methods and compositions promote the formation of an ectopic nodule or site that can improve transplanted cell engraftment and selectively drive the development of lymphocytes and the reconstitution of the adaptive immunity after hematopoietic stem cell transplant.

Abstract: Storage media are provided. A substrate has an array of addressable locations thereon, each addressable location adapted to be physically associated with a collection of molecules, each collection comprising at least a first subcollection of molecules and a second subcollection of molecules. The molecules in the collection are selected from a set of unambiguously identifiable molecules, the set comprising at least a first subset of molecules and a second subset of molecules. Each molecule in the first subset is identifiable by a first physical property, and each molecule in the second subset is identifiable by a second physical property, different from the first physical property. Each molecule in the set is uniquely associated with a predetermined position in a numerical value, wherein the presence of the molecule in the collection indicates a predetermined digit at the associated position and the absence of said molecule in the collection indicates a zero at said associated position.

Abstract: This disclosure is generally directed to methods for obtaining sequence information at nucleotide resolution with spatial information directly from chromosome(s) in situ.

Abstract: The present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. In some aspects, the systems comprise a first and second prime editor complex, wherein each of the first and second prime editor complexes comprises (1) a prime editor comprising (i) a nucleic acid programmable DNA binding protein (napDNAbp), and (ii) a polypeptide having an RNA-dependent DNA polymerase activity; and (2) a pegRNA comprising a spacer sequence, gRNA core, a DNA synthesis template, and a primer binding site, wherein the DNA synthesis template encodes a desired DNA sequence or a complement thereof, wherein the desired DNA sequence and the complement thereof form a duplex comprising an edited portion which integrates into the target site to be edited. In some aspects, the systems comprise a first, second, third, and fourth prime editor complex, each comprising a prime editor and a PEgRNA.

Abstract: Methods and compositions for diagnosing the presence of a cancer cell in an individual are provided. Methods and compositions for identifying a tumor-specific signature in an individual having cancer are also provided. Methods and compositions for diagnosing the presence of an infectious agent in an individual and/or for identifying an infectious agent-specific signature in an infected individual are provided. Methods and compositions for diagnosing the presence of a disease in an individual are also provided. Methods and compositions for identifying a disease-specific signature in an individual having the disease are also provided.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: Provided herein, in some embodiments, are compositions and methods for proximity detection of molecular targets.

Abstract: Embodiments of various aspects described herein relate to methods, kits, and cell culture media for generation of podocytes from pluripotent stem (PS) cells, as well as cells produced by the same, and methods of use.

Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

Abstract: Provided herein, in some embodiments, are recombinant viral genomes comprising an inhibitory oligonucleotide that reduces inflammation for use, for example, in gene therapy.

Abstract: A method of generating uniform large-scale optical focus arrays (LOT As) with a phase spatial light modulator (SLM) includes identifying and removing undesired phase rotation in the iterative Fourier transform algorithm (IFTA), thereby producing computer-generated holograms of highly uniform LOT As using a reduced number of iterations as compared to a weighted Gerchberg-Saxton algorithm. The method also enables a faster compensation of optical system-induced LOT A intensity inhomogeneity than the conventional IFTA.

Abstract: Provided herein are antibody drug conjugates of Formula (I): G-R7(I) and pharmaceutically acceptable salts thereof, wherein G is a molecular payload; and R7 is -L-A-B, wherein L is a linking group, A is a conjugating group, and B is an antibody or antibody fragment. Also provided are methods of preparing the antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the antibody drug conjugates (e.g., compounds of Formula (III), novel trioxacarcins without an antibody conjugated thereto), pharmaceutical compositions thereof, and methods of their use and treatment.

Abstract: Methods of analyzing nucleic acids of a cell are provided.

Abstract: Described herein are methods for providing an in vitro intestinal model system, e.g., using primary cells instead of cell lines and/or cancerous cells.

Abstract: An optical device for aberration correction (e.g., chromatic aberration correction) is disclosed. The optical device includes an optical component (e.g., a spherical lens) and a metasurface optically coupled to the optical component. The metasurface includes a plurality of nanostructures that define a phase profile. The phase profile corrects an aberration (e.g., chromatic aberration) caused by the optical component. The resulting optical device becomes diffraction-limited (e.g., for the visible spectrum) with the metasurface.

Abstract: Microfluidic devices for sterilizing fluids using pulsed electric fields are disclosed. In some embodiments, a device may include first and second electrode layers and a spacer layer positioned between the electrode layers. The spacer layer may define one or more fluid channels extending between the electrode layers. A power supply may be coupled to the electrode layers and configured to supply voltage pulses to the electrode layers to generate electric field pulses within the fluid channels. In some embodiments, the electrode layers may be textured such that the electric fields generated in the fluid channels are non-uniform.

Abstract: The present disclosure provides methods for identifying cells in an image. An apparatus for identifying cells in an image is also provided by the present disclosure. Further provided herein is a non-transitory computer-readable storage medium for performing the methods disclosed herein. Methods of diagnosing a disease or disorder and of treating a disease or disorder in a subject using the methods disclosed are also provided herein.

Abstract: Provided herein, in some embodiments, are engineered nucleic acid targeting vectors that include a sequence of interest flanked by homology arms, each homology arm comprising a sequence homologous to a sequence in a safe harbor site in the human genome in any one of the following loci: 1q31, 3p24, 7q35, and Xq21. Also provided herein are methods of using and compositions the comprising engineered nucleic acid targeting vectors.

Abstract: The present disclosure provides an optical component, which may be a metasurface grating, including (a) a substrate; and (b) an array of subwavelength-spaced phase-shifting elements, which are tessellated on the substrate to produce, when illuminated with a polarized incident light, a diffracted light beam with a distinct polarization state for each of a finite number of diffraction orders, wherein the finite number is 2 or more.

Abstract: In one aspect, the present disclosure provides a nozzle for a 3D printing system. The nozzle may include a flowpath with a material inlet and a material outlet. The nozzle may further include a valve in fluid communication with the flowpath between the material inlet and the material outlet, where the valve includes a closed state and an open state, where in the closed state the valve obstructs the flowpath between the material inlet and the material outlet, and where in the open state the material inlet is in fluid communication with the material outlet. The nozzle may further include a compensator in fluid communication with the flowpath, where the compensator includes a contracted state associated with the open state of the valve and an expanded state associated with the closed state of the valve.