The invention provides flow batteries and methods of using flow batteries that reduce loss of capacity. The loss of capacity may be mitigated by electrically oxidizing an organic species in the negolyte.
A compact laser-steering end effector includes a frame, at least two active mirrors, and a pair of actuators. The frame has a greatest dimension in a plane orthogonal to a longitudinal axis of no more than 13 mm, and the mirrors are mounted proximate to the distal end of the frame. The actuators are mounted to the frame and configured to respectively change the tilt of the active mirrors relative to the frame. A pathway is provided through the frame to deliver a laser beam to the mirrors, and wherein the mirrors are positioned and configurable via the actuators to reflect the laser beam off of each mirror en route to an external target.
A61B 18/20 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Articles and devices comprising fluorinated polymers, as well as methods of preparing fluorinated polymers, are generally described. In some cases, such fluorinated elastomers can be used for sensing neural activity, e.g., by encapsulating electronic circuits, or other applications. Furthermore, according to certain embodiments, polymers can, surprisingly, be directly deposited onto layers comprising low molecular weight fluorinated polymers, e.g., without swelling in the presence of certain solvents. Some embodiments are generally directed to devices and methods for treating fluorinated polymers and subsequently depositing material onto the treated fluorinated polymers. This may allow the fabrication and patterning of multilayered articles comprising fluorinated elastomers.
B32B 27/08 - Layered products essentially comprising synthetic resin as the main or only constituent of a layer next to another layer of a specific substance of synthetic resin of a different kind
Some aspects of this disclosure provide methods for phage-assisted continuous evolution (PACE) of proteases. Some aspects of this invention provide methods for evaluating and selecting protease inhibitors based on the likelihood of the emergence of resistant proteases as determined by the protease PACE methods provided herein. Some aspects of this disclosure provide strategies, methods, and reagents for protease PACE, including fusion proteins for translating a desired protease activity into a selective advantage for phage particles encoding a protease exhibiting such an activity and improved mutagenesis-promoting expression constructs. Evolved proteases that recognize target cleavage sites which differ from their canonical cleavage site are also provided herein.
Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy.
The disclosure provides a method for detecting a target analyte in a biological sample including contacting the sample with one or more probe sets each comprising a primary probe and a linker, contacting the sample with an initiator sequence, contacting the sample with a plurality of fluorescent DNA hairpins, wherein the probe binds the target molecule, the linker connects the probe to the initiator sequence, and wherein the initiator sequence nucleates with the cognate hairpin and triggers self-assembly of tethered fluorescent amplification polymers, and detecting the target molecule by measuring fluorescent signal of the sample.
Disclosed herein are GDF11 variant polypeptides. Also disclosed herein are methods for increasing GDF11 protein levels in a subject by administering a GDF11 variant polypeptide.
The present invention provides a new type of alpha-helix nucleating cross-link (“staple”) formed by olefin metathesis of a proline derivative with an alkenyl side chain and another amino acid derivative with an alkenyl side chain. The proline derivatives as described herein have been found to be strong nucleators of alpha-helix formation. The invention also provides moieties for shielding the free amide N—H's at the N-terminus of an alpha-helix, thereby further stabilizing the helix. The proline derivatives, precursors prior to cross-linking, and the cross-linked peptides are provided as well as methods of using and preparing these compounds and peptides.
C07K 7/56 - Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
C07D 207/16 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07K 1/113 - General processes for the preparation of peptides by chemical modification of precursor peptides without change of the primary structure
10.
Metasurface Optical Components for Altering Incident Light
Multi-wavelength light is directed to an optic including a substrate and metasurface optical components deposited on a surface of the substrate. The metasurface optical components comprise a pattern of silicon dielectric resonators with nonperiodic gap distances between adjacent dielectric resonators. Incident light directed to the metasurface optical components is scattered and phase-shifted by the configuration of the gap distances and the widths and thicknesses of the dielectric resonators. Each dielectric resonator has a rectangular cross-section such that a first phase shift is imparted for a transverse-electric (TE) component of the incident light and a second phase shift is imparted for a transverse-magnetic (TM) component of the incident light.
H01Q 15/10 - Refracting or diffracting devices, e.g. lens, prism comprising three-dimensional array of impedance discontinuities, e.g. holes in conductive surfaces or conductive discs forming artificial dielectric
The technology described herein is directed to compositions comprising antibodies and antibody reagent that binds specifically to Mfsd2A and method of using such compositions, e.g., to increase blood-brain barrier permeability in therapeutic methods.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The technology described herein is directed to engineered chemoautotrophic bacteria and methods of producing triacylglycerides. Also described herein are systems or bioreactors comprising said engineered bacteria.
Forced expression of a handful of transcription factors (TFs) can induce conversion between cell identities; however, the extent to which TFs can alter cell identity has not been systematic ally assessed. Here, we assembled a “human TFome,” a comprehensive expression library of 1,578 human TF clones with fall coverage of the major TF families. By systematically screening the human TFome, we identified many individual TFs that induce loss of human-induced-pluripotent-stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression pantiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
The present invention generally relates to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells or tissues. In one aspect, a sample is exposed to a plurality of nucleic acid probes that are determined within the sample. In some cases, however, background fluorescence or off-target binding may make it more difficult to determine properly bound nucleic acid probes. Accordingly, other components of the samples that may be contributing to the background, such as proteins, lipids, and/or other non-targets, may be “cleared” from the sample to improve determination. However, in certain embodiments, nucleic acids or other desired targets may be prevented from also being cleared, e.g., using polymers or gels within the sample. Other aspects are generally directed to compositions or kits involving such systems, methods of using such systems, or the like.
Provided herein are systems, compositions, and methods of introducing protective and/or loss-of-function variants of CCR5 and CCR2. Variants may be introduced using a CRISPR/Cas9-based nucleobase editor or other guide nucleotide sequence-programmable DNA binding protein domain-based fusion protein described herein. Further provided herein are compositions and methods of preventing and treating conditions related to HIV infection and progression as well as to AIDS.
The embodiments of the invention described herein relate to systems and methods for culturing and/or maintaining intestinal cells, tissues and/or organoids in vitro. The cells, tissues and/or organoids cultured according to the methods and systems described herein can mimic or reproduce natural intestinal epithelial structures and behavior as well as support co-culture of intestinal microflora.
INTERCONNECTION LAYER STRUCTURES INCLUDING TWO-DIMENSIONAL (2D) MATERIAL, ELECTRONIC DEVICES INCLUDING INTERCONNECTION LAYER STRUCTURES, AND ELECTRONIC APPARATUSES INCLUDING ELECTRONIC DEVICES
An interconnection layer structure including a two-dimensional (2D) material, an electronic device including the interconnection layer structure, and an electronic apparatus including the electronic device are disclosed. The interconnection layer structure may include a first interconnection layer, and a work function modulation layer directly on one surface of the first interconnection layer. The first interconnection layer may include a metal layer, and the work function modulation layer may be a two-dimensional (2D) material layer that includes ruthenium (Ru).
H01L 23/532 - Arrangements for conducting electric current within the device in operation from one component to another including external interconnections consisting of a multilayer structure of conductive and insulating layers inseparably formed on the semiconductor body characterised by the materials
H01L 23/528 - Layout of the interconnection structure
A semiconductor device may include a two-dimensional (2D) material having a semiconductor characteristic, a conductive layer on a first surface of the 2D material layer, and an alignment adjusting layer on a second surface of the 2D material layer. The second surface may be different from the first surface. The alignment adjusting layer may adjust an energy-band alignment between the 2D material layer and the conductive layer.
H01L 21/02 - Manufacture or treatment of semiconductor devices or of parts thereof
H01L 29/24 - Semiconductor bodies characterised by the materials of which they are formed including, apart from doping materials or other impurities, only inorganic semiconductor materials not provided for in groups , , or
The present invention provides vaccine compositions and methods of producing such compositions. Other embodiments of the invention include methods of treating a pathogen infection, methods of vaccinating a subject against a pathogen infection, and methods for treating an antibiotic-resistance bacterial infection in a subject in need thereof. In further embodiments, the invention includes methods of decreasing the level of a pathogen in a subject having a pathogen infection, methods of increasing the surviving rate of a subject having a pathogen infection, methods of reducing the level of pain associated with a pathogen infection, and methods of reducing the level of distress associated with a pathogen infection in a subject in need thereof. Novel scaffold compositions and opsonin-bound or lectin-bound pathogen compositions, and uses thereof, are also provided herein.
Described herein are compositions and methods of CRISPR effector system mediated detection of targets, including, but not limited to viral targets. Also described herein are devices and kits for carrying out the CRISPR effector system mediated nucleic acid detection assays.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
Described herein are compositions and methods for generating a viable cell that expresses at least one or more woolly mammoth genes. Also described herein are compositions and methods for generating an embryo, blastula, oocyte, or non-human organism that expresses one or more woolly mammoth genes.
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.
B33Y 30/00 - ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING - Details thereof or accessories therefor
B33Y 40/00 - Auxiliary operations or equipment, e.g. for material handling
24.
SC-BETA CELLS AND COMPOSITIONS AND METHODS FOR GENERATING THE SAME
Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy.
An optical component can include a substrate. The optical component can include a metasurface disposed on the substrate. The metasurface can include one or more linearly birefringent elements. A spatially-varying Jones matrix and a far-field of the metasurface can define a transfer function of the metasurface configured to generate a controlled response in the far-field according to polarization of light incident on the metasurface.
A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
Methods, systems, compositions and strategies for the delivery of RNA into cells in vivo, ex vivo, or in vitro via ARMMs are provided. In some aspects, ARMMs containing fusion proteins of ARRDC1 fused to an RNA binding protein or an RNA binding protein fused to a WW domain are provided. In some aspects, ARMMs containing binding RNAs associated with cargo RNAs are provided. In other aspects, cargo RNAs associated with a binding RNA, such as a TAR element, are loaded into ARMMs via ARRDC1 fusion proteins containing an RNA binding protein, such as trans-activator of transcription (Tat) protein.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
31.
ORGANOMIMETIC DEVICES AND METHODS OF USE AND MANUFACTURING THEREOF
An organomimetic device includes a microfluidic device that can be used to culture cells in its microfluidic channels. The organomimetic device can be part of dynamic system that can apply mechanical forces to the cells by modulating the microfluidic device and the flow of fluid through the microfluidic channels. The membrane in the organomimetic device can be modulated mechanically via pneumatic means and/or mechanical means. The organomimetic device can be manufactured by the fabrication of individual components separately, for example, as individual layers that can be subsequently laminated together.
The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.
The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).
Disclosed herein are 3-D neural tissue structures or “brain organoids” created from human pluripotent cells (e.g., stem cells) differentiated into neuronal cell types that include cortical and subcortical neuronal subtypes along with sensory cells. Also disclosed herein are methods for the in vitro generation of 3-D neural tissue structures capable of sensory perception, methods for generating a “brain organoid-machine interface” (BOMI), and methods for screening of molecular, cellular and network-level defects associated with complex mental diseases through use of patient-derived induced pluripotent stem cells.
Systems and methods for producing and using a body having a first structure defining a first chamber, a second structure defining a second chamber, a membrane located at an interface region between the first chamber and the second chamber to separate the first chamber from the second chamber. The first chamber comprises a first permeable matrix disposed therein and the first permeable matrix comprises at least one or a plurality of lumens each extending therethrough, which is optionally lined with at least one layer of cells. The second chamber can comprise cells cultured therein. The systems and methods described herein can be used for various applications, including, e.g., growth and/or differentiation of primary cells, and/or simulation of a microenvironment in living tissues and/or organs (to model physiology or disease states, and/or to identify therapeutic agents). The systems and methods can also permit co-cultures of two or more different cell types.
The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a DNA-targeting Cpf1 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. The present disclosure relates to engineered programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert trigger hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. The circuits and systems disclosed herein leverage an ability to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.
G06K 19/02 - Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the selection of materials, e.g. to avoid wear during transport through the machine
G06K 19/00 - Record carriers for use with machines and with at least a part designed to carry digital markings
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.
G02B 13/14 - Optical objectives specially designed for the purposes specified below for use with infrared or ultraviolet radiation
C23C 16/04 - Coating on selected surface areas, e.g. using masks
C23C 16/455 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition (CVD) processes characterised by the method of coating characterised by the method used for introducing gases into the reaction chamber or for modifying gas flows in the reaction chamber
G02B 1/00 - Optical elements characterised by the material of which they are made; Optical coatings for optical elements
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
G03F 7/40 - Treatment after imagewise removal, e.g. baking
H01L 31/02 - SEMICONDUCTOR DEVICES NOT COVERED BY CLASS - Details thereof - Details
41.
METHODS FOR MULTI-FOCAL IMAGING FOR MOLECULAR PROFILING
The present disclosure generally relates to systems and methods for multi-focal imaging, for example, for determining nucleic acids in cells or other samples. In some cases, multiple focal planes may simultaneously be determined, e.g., by using a plurality of detectors, such as a plurality of cameras, which image the same sample, but at least some of which are focused on different focal planes within the sample. Thus, the sample may be imaged in 3 dimensions, e.g., without sample refocusing. In certain cases, this may improve the resolution of imaging, in space and/or time. Various embodiments can be used to increase imaging throughput and/or resolution in image-based approaches, e.g., for single-cell molecular profiling such as multiplexed error robust fluorescence in situ hybridization (MERFISH), or for other applications.
The invention relates to the synthetic functionalization of an anthraquinone molecule that is substituted with at least one hydroxyl or amino group. In some aspects of the invention a mixture containing said anthraquinone starting material, an aldehyde, a base, an optional solvent, and an optional catalyst is reacted with hydrogen and then with an oxidant. In other aspects of the invention the synthetic functionalization of the anthraquinone molecule takes place electrochemically rather than chemically, through the use of a divided electrolytic cell.
Modified viral genomes are able to reduce induction of inflammatory and immune antiviral responses. This manifests itself in reduced NF-kB activity, increased viral transduction rates, and increased expression of transgenes. Viral genomes are modified by incorporating one or more oligonucleotide sequences which are able to bind to TLR9 but not induce activation of it. The oligonucleotide sequences may be synthetic, bacterial, human, or from any other source.
Articles and devices comprising fluorinated elastomers, as well as methods of preparing fluorinated elastomers, are generally described. In some cases, such fluorinated elastomers can be used for sensing neural activity, e.g., by encapsulating electronic circuits, or other applications. Furthermore, according to certain embodiments, polymers can, surprisingly, be directly deposited onto layers comprising low molecular weight fluorinated elastomers, e.g., without swelling in the presence of certain solvents. Some embodiments are generally directed to devices and methods for treating fluorinated elastomers and subsequently depositing material onto the treated fluorinated elastomers. This may allow the fabrication and patterning of multilayered articles comprising fluorinated elastomers.
C08L 27/12 - Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment containing fluorine atoms
A61B 5/294 - Bioelectric electrodes therefor specially adapted for particular uses for nerve conduction study [NCS]
A61B 5/388 - Nerve conduction study, e.g. detecting action potential of peripheral nerves
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.
G01N 24/10 - Investigating or analysing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using electron paramagnetic resonance
G01R 33/032 - Measuring direction or magnitude of magnetic fields or magnetic flux using magneto-optic devices, e.g. Faraday
G01Q 60/54 - Probes, their manufacture or their related instrumentation, e.g. holders
G01R 33/12 - Measuring magnetic properties of articles or specimens of solids or fluids
G01R 33/60 - Arrangements or instruments for measuring magnetic variables involving magnetic resonance using electron paramagnetic resonance
The present disclosure relates to compositions and methods for detecting nucleic acid sequences (e.g., coding and non-coding RNAs; nuclear/genomic DNA; mtDNA; pathogen nucleic acids, etc.) in a tissue sample, specifically providing improved matrices and matrix-employing methods for performance of nucleic acid capture and amplification in a tissue sample in situ and/or in a manner that retains spatial location information for captured nucleic acids (including nucleic acid-associated macromolecules).
The present disclosure provides fusion proteins comprising a nanobody and a split glycosyl hydrolase enzyme. Also provided herein are split glycosyl hydrolase enzymes and fusion proteins comprising such enzymes. Further provided herein are polynucleotides, vectors, and cells. The present disclosure also provides methods of deglycosylating a protein and methods of studying the effects of glycosylation on protein function in cells. Also provided herein are methods of treating diseases.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
49.
BATTERIES WITH SOLID STATE ELECTROLYTE MULTILAYERS
The invention provides rechargeable solid state batteries with multilayers of solid state electrolytes. The rechargeable solid state batteries disclosed herein are advantageous as they provide improved battery cycling performance combined with excellent power and energy density.
H01M 10/0525 - Rocking-chair batteries, i.e. batteries with lithium insertion or intercalation in both electrodes; Lithium-ion batteries
H01M 10/0585 - Construction or manufacture of accumulators having only flat construction elements, i.e. flat positive electrodes, flat negative electrodes and flat separators
H01M 10/04 - Construction or manufacture in general
50.
BARCODING SYSTEMS AND METHODS FOR GENE SEQUENCING AND OTHER APPLICATIONS
The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets or other compartments, for instance, arising from a cell. In one set of embodiments, particles may be prepared containing oligonucleotides that can be used to determine target nucleic acids, e.g., attached to the surface of the particles. The oligonucleotides may include “barcodes” or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together or removed from the droplets. Certain embodiments of the invention are generally directed to systems and methods for attaching additional or arbitrary sequences to the nucleic acids within microfluidic droplets or other compartments, e.g., recognition sequences that can be used to selectively determine or amplify a desired sequence suspected of being present within a droplet. Such systems may be useful, for example, for selective amplification in various applications, such as high-throughput sequencing applications.
Some aspects of this disclosure provide compositions, 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 capable of inducing a cytosine (C) to guanine (G) change in a nucleic acid (e.g., genomic DNA) are provided. In some embodiments, fusion proteins of a nucleic acid programmable DNA binding protein (e.g., Cas9) and nucleic acid editing proteins or protein domains, e.g., deaminase domains, polymerase domains, and/or base excision enzymes 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 nucleic acid programmable DNA binding protein (e.g., Cas9), and nucleic acid editing proteins or domains, are provided.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/90 - Stable introduction of foreign DNA into chromosome
The technology described herein is directed to pharmaceutical compositions comprising at least one Scg2 neuropeptide, as well as cell culture media or kits comprising such Scg2 neuropeptides. Also described herein are nucleic acids, vectors, or viral vectors encoding at least one Scg2 neuropeptide. In further aspects, described herein are methods of treating a memory-associated disorder, a learning disability, a neurodegenerative disease or disorder, or epilepsy with a pharmaceutical composition, nucleic acid, vector, or viral vector as described herein. In further aspects, described herein are detection methods of memory-associated analytes, such as Scg2 neuropeptides.
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
54.
CHOLESTEROL REDUCING COMPOSITIONS AND METHODS OF USE THEREOF
Microbes expressing cholesterol oxidoreductase (COR) proteins, methods of engineering the microbes expressing COR proteins, compositions and methods of using the microbes are provided.
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 9/00 - Medicinal preparations characterised by special physical form
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
C12N 9/04 - Oxidoreductases (1.), e.g. luciferase acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
C12Q 1/26 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
Provided herein are compositions and methods comprising engineered microorganisms and their use for locally degrading an antibiotic in the gastrointestinal tract to prevent or limit death of beneficial flora.
Topological qubits are provided in a quantum spin liquid. In various embodiments, a device is provided comprising a two-dimensional array of particles, each particle disposed at a vertex of a ruby lattice having a parameter ρ greater than
Topological qubits are provided in a quantum spin liquid. In various embodiments, a device is provided comprising a two-dimensional array of particles, each particle disposed at a vertex of a ruby lattice having a parameter ρ greater than
1
2
;
Topological qubits are provided in a quantum spin liquid. In various embodiments, a device is provided comprising a two-dimensional array of particles, each particle disposed at a vertex of a ruby lattice having a parameter ρ greater than
1
2
;
each particle having a first state and an excited state; each particle that belongs to at least three unit cells of the ruby lattice having a blockade radius, when in the excited state, sufficient to blockade each of at least six nearest neighboring particles in the ruby lattice from transitioning from its first state to its excited state, and wherein the array has at least one outer edge configured to be in a first boundary condition.
The present disclosure, at least in part, provides a dual-AAV vector system and compositions thereof for expression full-length PCDH15 in target cells. The present disclosure also provides the method of using the dual rAAV system for delivering full-length PCDH15 to a target cell (e.g., inner cells or cells in the eye) for treating deafness and/or blindness (e.g., Usher syndrome 1F).
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Disclosed herein are methods and systems for correlating continuous physiological processes (e.g., electrophysiological activity) and biomolecular processes (e.g., gene expression) in cells within a tissue. Also disclosed herein are methods for preparing a tissue for continuous electrophysiological recording. Further disclosed herein are systems comprising nanoelectronic devices within cells in a tissue, wherein each nanoelectronic device comprises a unique electronic barcode. The methods and systems described herein comprise any tissue with electrical activity (e.g., brain tissue, heart tissue, nervous system tissue, muscle tissue, pancreas tissue, or gastrointestinal tract tissue). Additionally disclosed herein are methods for disease modeling, methods for discovering a target for treating a disease, and methods for drug screening.
Human-derived virus-like particles (heVLPs), comprising a membrane comprising a phospholipid bilayer with one or more HERV-derived envelope proteins on the external side; one or more HERV-derived GAG proteins in the heVLP core, and a cargo molecule, e.g., a biomolecule and/or chemical cargo molecule, disposed in the core of the heVLP on the inside of the membrane, wherein the heVLP does not comprise a gag protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome, and methods of use thereof for delivery of the cargo molecule to cells.
The inventions provided herein relate to detection reagents, compositions, methods, and kits comprising the detection reagents for use in detection, identification, and/or quantification of analytes in a sample. Such detection reagents and methods described herein allow multiplexing of many more labeled species in the same procedure than conventional methods, in which multiplexing is limited by the number of available and practically usable colors.
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
G01N 33/569 - Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
Described herein are tough gel compositions that comprise an interpenetrating networks (IPN) hydrogel. The IPN hydrogel comprises a first polymer network (covalently crosslinked) and a second polymer network (ionically crosslinked), at least one therapeutic agent, and a clay material. The tough gel compositions may further include an adhesive polymer layer attached to the IPN hydrogel. Methods of use of these compositions, such as for extended release drug delivery, are also described.
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
A61K 47/18 - Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
A61K 47/12 - Carboxylic acids; Salts or anhydrides thereof
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
The invention features a method of treating a disease or disorder in a subject, the method comprising administering a therapeutically effective amount of a 5′-tiRNA to treat the disease or disorder in the subject.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
64.
ENGINEERED HUMAN-ENDOGENOUS VIRUS-LIKE PARTICLES AND METHODS OF USE THEREOF FOR DELIVERY TO CELLS
Human-derived virus-like particles (heVLPs), comprising a membrane comprising a phospholipid bilayer with one or more HERV-derived envelope proteins on the external side; one or more HERV-derived GAG proteins in the heVLP core, and a cargo molecule, e.g., a biomolecule and/or chemical cargo molecule, disposed in the core of the heVLP on the inside of the membrane, wherein the heVLP does not comprise a gag protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome, and methods of use thereof for delivery of the cargo molecule to cells.
The disclosure relates to compositions and methods for treating a disease or condition associated with a TDP-pathology or a decline in TDP-43 functionality in neuronal cells in a subject, and for identifying candidate agents to suppress or prevent inclusion of an abortive or altered STMN2 RNA sequence.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
66.
ENGINEERED HUMAN-ENDOGENOUS VIRUS-LIKE PARTICLES AND METHODS OF USE THEREOF FOR DELIVERY TO CELLS
Human-derived virus-like particles (heVLPs), comprising a membrane comprising a phospholipid bilayer with one or more HERV-derived envelope proteins on the external side; one or more HERV-derived GAG proteins in the heVLP core, and a cargo molecule, e.g., a biomolecule and/or chemical cargo molecule, disposed in the core of the heVLP on the inside of the membrane, wherein the heVLP does not comprise a gag protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome, and methods of use thereof for delivery of the cargo molecule to cells.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
67.
APPLICATIONS, METHODS, AND TOOLS FOR DEVELOPMENT, RAPID PREPARATION AND DEPOSITION OF A NANOCOMPOSITE COATING ON SURFACES FOR DIAGNOSTIC DEVICES INCLUDING ELECTROCHEMICAL SENSORS
Method for making a coating on a surface of a substrate are described herein. The methods include applying a mixture to a surface of a substrate while maintaining the substrate at an elevated temperature. The mixture includes a particulate material and a proteinaceous material.
The present disclosure is directed to methods of screening for pathological mechanisms in neurodevelopmental and neuropsychological disorders using brain organoids. The present disclosure is also directed to methods of screening agents using the brain organoids.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
69.
Complex Human Gut Microbiome Cultured In An Anaerobic Human Gut-On-A-Chip
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.
Methods making and using genomically recoded cells or organisms are provided including genomically recoded cells or organisms that lack the ability to translate a foreign nucleic acid sequence into a polypeptide that may be toxic to the genomically recoded cell or organism.
A testing device includes an elongated member and a tube assembly. The tube assembly has a first end and a second end. The tube assembly is configured to receive the elongated member at the second end. The tube assembly includes a plurality of chambers, including a first chamber and a second chamber. The first chamber and the second chamber are separated by a membrane. The tube assembly further includes a spring positioned at the second end of the tube assembly. The tube assembly further includes a spring retainer configured to prevent the spring from decompressing when in a locked position and permit the spring to decompress when in an unlocked position.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
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.
The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and medical uses thereof.
The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and medical uses thereof.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
75.
VARIANT TXNIP COMPOSITIONS AND METHODS OF USE THEREOF FOR THE TREATMENT OF DEGENERATIVE OCULAR DISEASES
The present invention provides compositions, e.g., pharmaceutical compositions, which include a recombinant adeno-associated viral (AAV) expression construct, AAV vectors, AAV particles, and methods of treating a subject having a degenerative ocular disorder, e.g., retinitis pigmentosa.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
Disclosed herein are methods, systems, compositions and strategies for the creation and use WW-domain-Activated Extracellular Vesicles, or WAEVs. These WAEVs can be harnessed to deliver and present viral or bacterial antigens useful for vaccine development; to display homing molecules for targeted delivery of therapeutic molecules to specific cells or tissues; and for packaging and delivery of therapeutic molecules via interactions with the WW domains.
A method of controlling macroscopic properties of a metamaterial includes 3D printing a lattice structure comprising interconnected struts, where each strut comprises one or more printed filaments. Each printed filament comprises an active material or a passive material, and the active material has a modulus with a higher stimulus dependence than that of the passive material. The printed filaments comprising the active material are disposed at predetermined regions of the lattice structure. After 3D printing, the lattice structure is exposed to a stimulus, and the predetermined regions comprising the active material soften or stiffen. Thus, the macroscopic properties of the lattice structure may be controlled.
B29C 64/118 - Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using filamentary material being melted, e.g. fused deposition modelling [FDM]
B33Y 70/00 - Materials specially adapted for additive manufacturing
B33Y 80/00 - Products made by additive manufacturing
A device, comprising at least one monochromatic light source configured to generate a first optical trap; an ensemble of particles disposed in the first optical trap, each particle of the ensemble of particles being excitable to a first Rydberg state and a second Rydberg state, the second Rydberg state having a blockade radius, each particle of the ensemble of particles being within the blockade radius of each other and within the blockade radius of an atomic qubit, the atomic qubit being a particle that is excitable to the second Rydberg state, the ensemble of particles having a first transmissivity at a first wavelength when neither any particle of the ensemble of particles nor the atomic qubit is in the second Rydberg state, the ensemble of particles having a second transmissivity at the first wavelength when the atomic qubit is in the second Rydberg state, the second transmissivity being lower than the first transmissivity; and a second monochromatic light source configured to drive each particle of the ensemble of particles into the first Rydberg state; a probe light source configured to direct a probe beam having the first wavelength to the ensemble of particles; and a photosensor configured to determine the state of the atomic qubit.
Disclosed herein are methods, systems, compositions and strategies for the creation and use WW-domain-Activated Extracellular Vesicles, or WAEVs for presenting SARS-CoV-2 antigen domains, for example the SARS-CoV-2 M protein, the SARS-CoV-2 E protein, or the SARS-CoV-2 S protein. These WAEVs can be harnessed to deliver and present SARS-CoV-2 antigens useful for vaccine development.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
80.
WW-DOMAIN-ACTIVATED EXTRACELLULAR VESICLES TARGETING HIV
Disclosed herein are methods, systems, compositions and strategies for the creation and use WW-domain-Activated Extracellular Vesicles (WAEVs) for presenting HIV antigen domains. These WAEVs can be harnessed to deliver and present HIV antigens useful for vaccine development. Specifically, the disclosure provides a fusion protein comprising: (a) a WW-containing domain; (b) a transmembrane domain; and (c) an extracellular domain, wherein the extracellular domain is an HIV antigen domain. Further provided are sequences of each domain as well as methods of producing and using the fusion protein.
To increase the gas solubility of polar liquids, the invention leverages coordination chemistry, nanoscience, and porous materials design to create porous liquids, e.g., aqueous solutions, containing a high density of networks of dry pores—which will feature dramatically higher capacities for dissolved gases than conventional polar liquids.
B01J 20/22 - Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
B01J 20/28 - Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
Disclosed herein are viscoelastic conductive composite. The viscoelastic conductive composite includes a viscoelastic conductive material; and a conductive filler. The viscoelastic conductive material has a viscoelastic property that matches the viscoelastic property of a tissue.
H01B 1/12 - Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances organic substances
H01B 1/18 - Conductive material dispersed in non-conductive inorganic material the conductive material comprising carbon-silicon compounds, carbon, or silicon
C08L 33/26 - Homopolymers or copolymers of acrylamide or methacrylamide
C08B 37/00 - Preparation of polysaccharides not provided for in groups ; Derivatives thereof
83.
METHODS AND COMPOSITIONS FOR PRIME EDITING NUCLEOTIDE SEQUENCES
Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.
This disclosure presents methods for vapor deposition of metal halides involving exposure of substrates to vapors of organometallic copper complexes with halosilane vapors. The methods described herein are advantageous for the production of transparent hole conducting layers, e.g., for perovskite solar cells.
C23C 16/455 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition (CVD) processes characterised by the method of coating characterised by the method used for introducing gases into the reaction chamber or for modifying gas flows in the reaction chamber
C23C 16/30 - Deposition of compounds, mixtures or solid solutions, e.g. borides, carbides, nitrides
85.
METHODS FOR REGULATING BLOOD-CENTRAL NERVOUS SYSTEM (BLOOD-CNS) BARRIER AND USES THEREOF
The present disclosure, at least in part, provides methods for regulating Blood-Central Nervous System (blood-CNS) barrier permeability (e.g., increasing or decreasing Blood-CNS barrier permeability) by regulating signaling between pericyte derived vitronectin and integrin expressed on CNS endothelial cells (e.g., integrin α5). In some aspects, the present disclosure also provides a Blood-Central Nervous System (blood-CNS) barrier model comprising CNS endothelial cells and vitronectin or a plurality of cells secreting vitronectin, and methods for producing the same.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61P 43/00 - Drugs for specific purposes, not provided for in groups
The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.
Provided herein is a replication-defective oncolytic herpes simplex virus 1 (HSV-1) recombinant virus, comprising within its genome: a coding sequence encoding a fusion protein.
The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
90.
SYSTEMS AND METHODS FOR RETRIEVING CELLS FROM A CONTINUOUS CULTURE MICROFLUIDIC DEVICE
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.
UNITED KINGDOM RESEARCH AND INNOVATION (United Kingdom)
Inventor
Griffiths, Andrew David
Weitz, David A.
Link, Darren Roy
Ahn, Keunho
Bibette, Jerome
Abstract
The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalising two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets; wherein one or both of steps (a) and (b) is performed under microfluidic control; preferably electronic microfluidic control The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalised into the microcapsules.
C40B 40/08 - Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B82Y 10/00 - Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
B82Y 30/00 - Nanotechnology for materials or surface science, e.g. nanocomposites
C07K 1/04 - General processes for the preparation of peptides on carriers
C40B 40/10 - Libraries containing peptides or polypeptides, or derivatives thereof
B01F 25/433 - Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
B01F 33/302 - Micromixers the materials to be mixed flowing in the form of droplets
B01F 33/3031 - Micromixers using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
B01J 13/02 - Making microcapsules or microballoons
92.
2,4,5-TRISUBSTITUTED 1,2,4-TRIAZOLONES USEFUL AS INHIBITORS OF DHODH
The present invention provides triazolone compounds of general formula (I):
The present invention provides triazolone compounds of general formula (I):
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.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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.
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)).
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.
An organ-on-a-chip microfluidic device is disclosed that mimics a human lymph node and/or human lymphoid tissue. The device can include cells from human blood and lymphatic tissue, include an extracellular matrix for the development of immune system components, and provide for the perfusion of fluids and solids resembling blood and lymphatic fluid within micrometer sized channels.
The present invention relates to a shear-activated nanotherapeutic (SA-NT) for use in treating stroke by increasing blood supply to the brain via collateral vessels, wherein the SA-NT comprises an aggregate comprising a plurality of nanoparticles, the aggregate further comprising one or more vasodilating agents or pharmaceutically acceptable salts thereof; wherein the aggregate is configured to disaggregate above a predetermined shear stress.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
A61K 31/21 - Esters, e.g. nitroglycerine, selenocyanates
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
98.
INTRACELLULAR DELIVERY USING MICROFLUIDICS-ASSISTED CELL SCREENING (MACS)
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.
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.
The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.
patents
