Abstract: The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells. In some aspects, cells may be analyzed, e.g., imaged, to determine their phenotype, and their genotypes may be determined by exposing the cells to nucleic acid probes, e.g., as in smFISH. MERFISH, FISH, in situ hybridization, or other suitable techniques. In some cases, the cells may be exposed to a nucleic acid comprising an identification portion, which may be used to distinguish the cells from each other. In some embodiments, the cells may be exposed to a nucleic acid comprising an expression portion, e.g. a gene, or coding region for a non-translated RNA, etc., that when expressed, produces a protein, RNA, DNA, or the like that may alter the phenotype of the cell or the variable nucleic acid sequence can consist of promoters, gene regulatory elements, transcription factor binding sites, Cas9 guide RNA coding regions, etc. that otherwise alter the phenotype of the cell.

Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA to treat Hutchin-son-Gilford progeria syndrome (HOPS). The disclosure also provides fusion proteins, guide RNAs and compositions comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA, for example in a LNA gene. In some embodiments, adenosine deaminases provided herein are used to correct a C1824T mutation in LMNA. In some embodiments, the methods and compositions provided herein are used to treat Hutchinson-Gilford progeria syndrome (HGPS).

Abstract: A first fluidic solution having a first ionic concentration is provided in a first fluidic reservoir in direct fluidic connection with a nanopore. A second fluidic solution, having a second ionic concentration, is provided in a second fluidic reservoir disposed in fluidic connection with the nanopore through a fluidic passage having at least one fluidic section in which the section length is greater than the section width. The electrical potential local to the fluidic passage is measured, and the resistance of both the fluidic passage the nanopore are determined based on the fluidic passage electrical potential. The fluidic passage resistance is compared with the nanopore resistance and at least one of the first and second ionic concentrations is adjusted based on the comparison. The measuring, determining, comparing, and adjusting steps are conducted until the fluidic passage resistance is between about 0.1 times and about 10 times the nanopore resistance.

Abstract: A display system includes an optical device configured according to constructive interference for a plurality of wavelengths at a focal length. The display system includes a fiber. The display system includes a controller configured to scan the fiber using a Lissajous scanning method to generate a display. The display can be disposed within a focal plane of the optical device. The controller is configured to modulate light intensity from the fiber. The controller can be configured to form a display image that passes through the optical device. The display system can include an optical combiner configured to reflect the display image from the optical device and form a virtual image. The optical device can be configured to magnify a display image from the display and form a virtual image.

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

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

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.