Abstract: Provided herein, in some aspects, are methods of imaging molecules without a microscope or other specialized equipment, referred to herein as “microscope-free imaging (MFI).” Herein, “molecular instruments” (e.g., DNA-based and protein-based molecules) are used, instead of microscopes, in a “bottom-up” approach for inspecting molecular targets.

Abstract: The present invention provides triazolone compounds of general formula (I): in which R1, R2, R3, R4, and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and prophylaxis of diseases, in particular hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

Abstract: The present disclosure is generally directed to systems and methods for retrieving cells from a continuous culture microfluidic device. In some aspects, a system that allows for selective extraction of one or more cells of interest from an arbitrary population of cells using a high-throughput negative cell selection technique is disclosed herein. For example, the system may comprise a microfluidic device comprising a plurality of cell growth trenches configured to contain cells and a patterned light source capable of selectively killing unwanted cells contained within the device. Coupled with time-lapse imaging, one or more cells of interest within the device may, in some aspects, be identified and extracted with a relatively high extraction efficiency, e.g., at least 99.9% of cells of interest may be extracted from the plurality of cells. In addition, some aspects of the disclosure are directed to methods for using such a system.

Abstract: A sensing probe may be formed of a diamond material comprising one or more spin defects that are configured to emit fluorescent light and are located no more than 50 nm from a sensing surface of the sensing probe. The sensing probe may include an optical outcoupling structure formed by the diamond material and configured to optically guide the fluorescent light toward an output end of the optical outcoupling structure. An optical detector may detect the fluorescent light that is emitted from the spin defects and that exits through the output end of the optical outcoupling structure after being optically guided therethrough. A mounting system may hold the sensing probe and control a distance between the sensing surface of the sensing probe and a surface of a sample while permitting relative motion between the sensing surface and the sample surface.

Abstract: The present invention provides novel compounds (e.g., compounds of Formulae (I), (II), (III), (IV)) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or pharmaceutically acceptable salts thereof, optionally in a pharmaceutically acceptable carrier, and a medical uses thereof.

Abstract: A method of fabricating a visible spectrum optical component includes: providing a substrate; forming a resist layer over a surface of the substrate; patterning the resist layer to form a patterned resist layer defining openings exposing portions of the surface of the substrate; performing deposition to form a dielectric film over the patterned resist layer and over the exposed portions of the surface of the substrate, wherein a top surface of the dielectric film is above a top surface of the patterned resist layer; removing a top portion of the dielectric film to expose the top surface of the patterned resist layer and top surfaces of dielectric units within the openings of the patterned resist layer; and removing the patterned resist layer to retain the dielectric units over the substrate.

Abstract: Provided are new nickel./zirconium-mediated coupling reactions useful in the synthesis of ketone-containing compounds, e.g., halichondrin natural products and related molecules. A feature of the present disclosure is the use of a nickel(I) catalyst in tandem with a nickel (II) catalyst in the Ni/Zr-mediated coupling reactions. Without wishing to be bound by any particular theory, the nickel (I) catalyst selectively activates the electrophilic coupling partner (i.e., the compound of Formula (A)), and the nickel(ll) catalyst selectively activates the nucleophilic coupling partner (i.e., a thioester of Formula (B)). This dual catalyst system leads to improved coupling efficiency and eliminates the need for a large excess of one of the coupling partners (i.e., a compound of Formula (A) or (B)).

Abstract: The technology described herein is directed to methods for detection of microbes and microbe components. In some embodiments of any of the aspects, the methods comprise methods of microbe isolation, sample preparation, mass spectrometry, or analysis. In some embodiments of any of the aspects, such methods can be applied to detect at least one microbe or at least one microbial component in a sample, including not limited to a patient sample, an animal model sample, an environmental sample, or a non-biological sample.

Abstract: The disclosure provides modified pegRNAs comprising one or more appended nucleotide structural motifs which increase the editing efficiency during prime editing, increase half-life in vivo, and increase lifespan in a cell. Modifications include, but are not limited to, an aptamer (e.g., prequeosim-1 riboswitch aptamer or “evopreQi-1”) or a variant thereof, a pseudoknot (the MMLV viral genome pseudoknot or “Mpknot-1”) or a variant thereof, a tRNA (e.g., the modified tRNA used by MMLV as a primer for reverse transcription) or a variant thereof, or a G-quadruplex or a variant thereof. The disclosure further provides prime editor complexes comprising the modified pegRNAs and having improved characteristics and/or performance, including stability, improved cellular lifespan, and improved editing efficiency.

Abstract: Described herein are methods inducing the uptake of an agent by a cell. Aspects of the invention relate to physically compressing the cell to induce perturbations (e.g., holes) in the cell membrane or wall. An agent is taken up by the cell through induced perturbations.

Abstract: The present disclosure relates to a microfluidic devices and methods for culturing bone marrow cells. Aspects include methods of preparing microfluidic devices and culturing bone marrow cells with the microfluidic devices. In some aspects, a method includes providing a microfluidic device having an upper chamber, a lower chamber, and a porous membrane separating the upper chamber from the lower chamber. The method further includes seeding walls of the lower chamber and a bottom surface of the membrane with endothelial cells. The method further includes providing a matrix within the upper chamber. The matrix includes fibrin gel and bone marrow cells. The method further includes filling or perfusing the upper chamber with a media.

Abstract: Kerr and electro-optic frequency comb generation in integrated lithium niobate devices is provided. In various embodiments, a microring resonator comprising lithium niobate is disposed on a thermal oxide substrate. The microring resonator has inner and outer edges. Electrodes are positioned along the inner and outer edges of the microring resonator. The electrodes are adapted to modulate the refractive index of the microring. A pump laser is optically coupled to the microring resonator. The microring resonator is adapted to emit an electro-optical frequency comb when receiving a pump mode from the pump laser and when the electrodes are driven at a frequency equal to a free-spectral-range of the microring resonator.

Abstract: A method for detecting oncogenic growth and viability, and/or degree of cellular transformation and/or identifying an agent that inhibits cellular transformation is disclosed. The method including: providing a cellular sample, such as a sample of cells obtained from a subject or a cell line; culturing the cellular sample in low attachment conditions; and detecting growth and7or cell viability of the sample, wherein increased growth relative and/or viability relative to a control or control level indicative of basal growth and/or viability indicates cellular transformation. In some embodiments, the method includes introducing a n expression vector into cells of the cellular sample, wherein the expression vector comprises a gene product expression sequence being tested for transformation ability. In some embodiments the cellular sample is contacted with a test agent and growth and/or cell viability of the sample is determined to determine if the agent inhibits transformation.

Abstract: Described herein are engineered microbe-targeting molecules, microbe-targeting articles, kits comprising the same, and uses thereof. Such microbe-targeting molecules, microbe-targeting articles, or the kits comprising the same can not only bind or capture of a microbe or microbial matter thereof, but they also have improved capability (e g, enhanced sensitivity or signal intensity) of detecting a microbe or microbial matter. Thus, the microbe-targeting molecules, microbe-targeting articles, and/or the kit described herein can be used in various applications, e.g., but not limited to assays for detection of a microbe or microbial matter, diagnostic and/or therapeutic agents for diagnosis and/or treatment of an infection caused by microbes in a subject or any environmental surface, and/or devices for removal of a microbe or microbial matter from a fluid.

Abstract: This application provides for methods of treatment for IBD, especially in subjects who have R. gnavus species or R. gnavus group IBD strains as a component of their microbiome. The application also provides for methods of diagnosing IBD, as well as kits for use in the claimed methods.

Abstract: A microfluidic device is directed to sustaining a complex microbial community in direct and indirect contact with living human intestinal cells in vitro. The device includes a first microchannel having cultured cells of a human intestinal epithelium and microbiota, the first microchannel further having a first level of oxygen. The device further includes a second microchannel having cultured cells of a vascular endothelium, the second microchannel further having a second level of oxygen. The device also includes a membrane located at an interface region between the first microchannel and the second microchannel, the membrane being composed of an oxygen-permeable material or further having pores via which oxygen flows between the first microchannel and the second microchannel to form a physiologically-relevant oxygen gradient.

Abstract: Provided are fast relaxing hydrogels that are useful for regulating cell behavior and enhancing tissue regeneration, e.g., bone regeneration.

Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of nucleic acid programmable DNA binding proteins (napDNAbp), e.g., Cpf1 or variants thereof, and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a napDNAbp (e.g., CasX, CasY, Cpf1, C2c1, C2c2, C2C3, and Argonaute) and nucleic acid editing proteins or domains, are provided.

Abstract: The technology described herein is directed to compositions and methods for determining provenance of an item, a non-limiting example being a food item. In one aspect described herein is an engineered microorganism comprising at least one genetic barcode element, essential gene mutations, and/or germination gene mutations. In another aspect described herein is a method of determining the provenance of an item comprising contacting the item with an engineered microorganism and later detecting the genetic barcode element to determine the provenance of the item. In another aspect, described herein is a method of determining the path of an item or individual across a surface.

Abstract: Systems and methods are provided for characterizing shuttle capture events in a nanopore sensor. The method first collects time-dependent current blockage signatures for at least one bias voltage. The method then identifies each signature as corresponding to a permanent or transient event. The method then generates a protein dynamics landscape (PDL) for the transient event signatures. The PDL comprises a set of histograms of nanopore current data and characterizes current through the nanopore during shuttle capture events. The method can then comprise identifying an entrance level blockage value based on the permanent event signatures. Permanent event captures can be determined by time duration which is larger than a certain threshold time value. Applying a voltage between the fluidic chambers above a threshold voltage level can be used to control that the vast majority of events are permanent.