Dynamically reconfigurable architectures for quantum information and simulation are provided. A plurality of neutral atoms is provided. Each neutral atom is disposed in a corresponding optical trap. Each of the plurality of neutral atoms is prepared in a mF = 0 clock state. A pair of neutral atoms of the plurality of neutral atoms is entangled by directing a laser pulse thereto. The laser pulse is configured to transition the pair of neutral atoms through a Rydberg state. The optical trap corresponding to at least one neutral atom of the pair is adiabatically moved, thereby moving one atom of the pair relative to the other atom of the pair without destroying entanglement of the pair.
A device for modulating an amplitude of a light beam, comprising a coherent light source configured to generate a phase -modulated beam having a plurality of frequency components; and a dispersive optical element. The dispersive optical element has a group delay dispersion and is configured to receive the phase-modulated beam, to introduce an optical phase shift to each of the plurality of the frequency components, so that the values of the optical phase shift vary non-linearly with frequency according to the group delay dispersion, and to recombine the plurality of frequency components, thereby generating an amplitude -modulated beam.
G06N 10/20 - Models of quantum computing, e.g. quantum circuits or universal quantum computers
H04B 10/2519 - Arrangements specific to fibre transmission for the reduction or elimination of distortion or dispersion due to chromatic dispersion using Bragg gratings
G06N 10/40 - Physical realisations or architectures of quantum processors or components for manipulating qubits, e.g. qubit coupling or qubit control
G02F 1/11 - Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour based on acousto-optical elements, e.g. using variable diffraction by sound or like mechanical waves
G02F 1/1335 - Structural association of cells with optical devices, e.g. polarisers or reflectors
The invention provides ultrasensitive methods for detection and quantification of target analytes in samples. The methods can be multiplexed to allow simultaneous detection and quantification of multiple target analytes. The methods can achieve an attomolar limit of detection. The invention also provides related compositions and kits.
Provided herein are genetically encoded voltage indicator (GEVI) variants (e.g., QuasArba, QuasArbb) of Archaerhodopsin 3 useful for applications, such as optical measurement of membrane potential. Described herein are also polynucleotides encoding the variants, nucleic acid constructs, vectors (e.g., expression vectors), cells comprising the polynucleotides, nucleic acid constructs, and vectors, and cells comprising the polypeptides; and methods of using the variants.
C07K 14/215 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Halobacteriaceae (F)
7.
SYSTEMS AND METHODS FOR CONTROLLING FLUID FLOW BETWEEN MULTIPLE CHAMBERS OF A TESTING DEVICE
A device for performing an assay includes a housing, an elongated member, and a vent. The housing has a first end and a second end. The housing defines a first opening at the first end, a first chamber, and a second chamber. The first chamber is fluidly connected to (i) the second chamber, and (ii) an exterior of the housing via the first opening. The elongated member is configured to be received through the first opening such that the elongated member is least partially disposed within the first chamber. The vent is configured to aid in controlling flow of a fluid from the first chamber of the housing to the second chamber of the housing.
The technology described herein is directed to systems and methods for producing a bioproduct from microorganisms such as bacteria. The system can comprise a growth phase and a production phase, that can occur in the same or different bioreactor chambers; the growth phase can use using gas fermentation or mixotrophic fermentation, and the production phase can use gas fermentation, mixotrophic fermentation, or organic carbon fermentation. In one example, the system can comprise at least one primary reactor chamber using gas fermentation or mixotrophic fermentation and at least one secondary reactor chamber using gas fermentation, mixotrophic fermentation, or organic carbon fermentation. Such systems can use bacteria that are capable of both autotrophy and heterotrophy and capable of switching between autotrophy and heterotrophy.
C12P 1/04 - Preparation of compounds or compositions, not provided for in groups , by using microorganisms or enzymes; General processes for the preparation of compounds or compositions by using microorganisms or enzymes by using bacteria
The present disclosure provides compositions and methods for prime editing with improved editing efficiency and/or reduced indel formation with modified prime editors and prime editor fusion proteins. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure.
Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.
The present disclosure provides compounds of Formula (I) and (II), which may be R0CK2 inhibitors. The present disclosure also provides pharmaceutical compositions and kits comprising the compounds, and methods of treating or preventing diseases and disorders associated with R0CK2 (e.g., fibrotic disease, autoimmune disease, inflammatory-fibrotic condition, inflammatory condition, edema, ophthalmic disease, cardiovascular disease, central nervous system disorder, cancer) by administering to a subject in need thereof the compounds or pharmaceutical compositions.
C07D 401/14 - 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 three or more hetero rings
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/4162 - 1,2-Diazoles condensed with heterocyclic ring systems
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/429 - Thiazoles condensed with heterocyclic ring systems
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/538 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
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
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
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
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 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The present disclosure provides adenine base editors (ABEs) that have context specificity, i.e., a preference for a pyrimidine positioned 5' of the target adenosine, or preference for a purine positioned 5' of the target adenosine. In addition, methods for targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising the ABEs. Also provided are vectors useful for the generation and delivery of the ABEs, including vector systems for engineering the ABEs through directed evolution. Cells containing such vectors and ABEs are also provided. Further provided are methods of treatment and uses comprising administering the ABEs.
Error detection in a quantum computer is provided. The quantum computer includes a plurality of qubits encoding a plurality of data qudits and an ancilla qudit. The qubits encoding the plurality of data qudits are arranged into a grouping wherein the qubits encoding each of the plurality of data qudits are within an interaction distance of an interacting state of the qubits encoding the ancilla qudit. A leakage error of a first data qudit of the plurality of data qudits into the interacting state is detected by detecting a state of the ancilla qudit. Error correction in the quantum computer is also provided. Quantum states of the plurality of qudits are selected such that angular momentum selection rules prohibit mixing between the selected quantum states during a leakage error of one of the plurality of qudits into a noninteracting state. The leakage error is corrected by optical pumping of the noninteracting state, the optical pumping preserving coherence of the selected quantum states in the absence of the leakage error.
Provided herein are polymeric particles and compositions (i.e., "backpacks") that can adhere to cells and provide delivery of payload agents to those cells, and/or direct therapeutic activity of those cells.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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
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 31/4745 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 49/18 - Nuclear magnetic resonance (NMR) contrast preparations; Magnetic resonance imaging (MRI) contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
15.
SYSTEM AND PROCESS FOR ANTHRAQUINONE FUNCTIONALIZATION
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.
C07C 51/377 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by hydrogenolysis of functional groups
RNA editing tools for use in systems designed to measure RNA in vivo and manipulate specific cell types are disclosed herein. An RNA sensor system comprising a) a single-stranded RNA (ssRNA) sensor comprising a stop codon and a payload; optionally wherein the ssRNA sensor further comprises a normalizing gene; and b) an adenosine deaminase acting on RNA (ADAR) deaminase; wherein the sensor is capable of binding to a ssRNA target to form a double-stranded RNA (dsRNA) duplex that becomes a substrate for the ADAR deaminase; wherein the substrate comprises a mispairing within the stop codon; and wherein the mispairing is editable by the ADAR deaminase, which editing can effectively remove the stop codon so as to enable translation and expression of the payload. A method of quantifying ribonucleic acid (RNA) levels using the RNA sensor system is also disclosed.
The present disclosure generally relates to sugar reduction in foods and, in some aspects, to enzyme-polymer conjugated particles for food and other applications. Certain aspects of the disclosure are directed to compositions for reducing sugar content and/or producing dietary fiber within food products during or after consumption (e.g., in a subject's gastrointestinal (Gl) tract), while maintaining the sweetness and flavor of the sugar in food products upon consumption (e.g., in a subject's mouth). For example, in one set of embodiments, a composition may comprise a particle comprising an enzyme capable of converting a sugar into a relatively non-digestible form (e.g., a polymer), optionally an inhibitor that reversibly inhibits the enzyme from converting the sugar, and optionally an additive capable of associating with the inhibitor. The composition may be used for in situ conversion of sugars upon exposure to an environment condition (e.g., pH and/or temperature) in the Gl tract.
Disclosed herein are methods for generating mature cardiomyocytes and compositions including mature cardiomyocytes. Also disclosed herein are methods for enhancing maturation of quiescent cardiomyocytes and compositions including mature quiescent cardiomyocytes.
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 27/06 - Layered products essentially comprising synthetic resin as the main or only constituent of a layer next to another layer of a specific substance
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.
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.
H01M 8/06 - Combination of fuel cells with means for production of reactants or for treatment of residues
H01M 10/0564 - Accumulators with non-aqueous electrolyte characterised by the materials used as electrolytes, e.g. mixed inorganic/organic electrolytes the electrolyte being constituted of organic materials only
23.
ENGINEERED BACTERIA AND METHODS OF PRODUCING TRIACYLGLYCERIDES
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.
The present disclosure provides compositions and methods for prime editing with improved editing efficiency and/or reduced indel formation by inhibiting the DNA mismatch repair path way while conducting prime editing of a target site. Accordingly, the present disclosure provides a method for editing a nucleic acid molecule by prime editing that involves contacting a nucleic acid molecule with a prime editor, a pegRNA, and an inhibitor of the DNA mismatch repair pathway, thereby installing one or more modifications to the nucleic acid molecule at a target site with increased editing efficiency and/or lower indel formation. The present disclosure further provides polynucleotides for editing a DNA target site by prime editing comprising a nucleic acid sequence encoding a napDNAbp, a polymerase, and an inhibitor of the DNA mismatch repair pathway, wherein the napDNAbp and polymerase is capable in the presence of a pegRNA of installing one or more modifications in the DNA target site with increased editing efficiency and/or lower indel formation. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure. The present disclosure also provides compositions and methods for prime editing with improved editing efficiency and/or reduced indel formation with modified prime editor fusion proteins. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure.
The present invention relates to methods of characterizing cell-free DNA (cfDNA), detecting cancer, detecting the eradication of cancer, and determining a probability distribution of haplotypes. The methods use the data from genomic sequences from CpG Islands (CGI) methylated in the genome of extraembryonic ectoderm (ExE) to determine a proportion of fully methylated haplotypes in order to characterize the cfDNA sample and detect certain cancers.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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 ? greater than AA; 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.
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.
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.
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.
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 10/0585 - Construction or manufacture of accumulators having only flat construction elements, i.e. flat positive electrodes, flat negative electrodes and flat separators
31.
WW-DOMAIN-ACTIVATED EXTRACELLULAR VESICLES TARGETING HIV
BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA (USA)
Inventor
Lu, Quan
Xiang, Shi-Hua
Abstract
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.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C07K 1/00 - General processes for the preparation of peptides
C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12P 21/06 - Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
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.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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 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.
OXFORD UNIVERSITY INNOVATION LIMITED (United Kingdom)
PRESIDENT AND FELLOWS OF HARVARD COLLEGE (USA)
Inventor
Beard, Daniel
Ingber, Donald
Uzun, Oktay
Bobe, Frank
Abstract
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.
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. The disclosure also provides methods of editing a genome using the prime editor complexes with modified pegRNAs, and to nucleotide sequences and expression vectors encoding said prime editors and modified pegRNAs, and to cells, kits, and pharmaceutical compositions comprising the improved prime editor complexes.
Provided herein are methods of treating cancer in an individual that has failed an anti- PD1/PD-L1 therapy, comprising selecting an individual that has failed a prior anti-PD1/PD- L1 therapy; and administering to the individual a first agent that blocks or disrupts PD-L2, RGMb, or a combination thereof, and a second agent that blocks or disrupts PD-L1, PD-1 or a combination thereof. Also provided herein are kits and therapeutic compositions for use in the methods described herein.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
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
The present disclosure, at least in part, relates to compositions (e.g., isolated nucleic acid and rAAVs) and methods for treating Non-syndromic hearing loss and deafness (DFNB1) by delivering gap junction beta 2 (GJB2) protein to inner ear cells that normally express GJB2 (e.g., fibrocytes and supporting cells of the organ of Corti and nearby regions). The isolated nucleic acid of the present disclosure comprises an expression cassette, wherein the expression cassette comprises a gap junction beta 2 (GJB2) gene regulatory element (GRE) (e.g., GJB2 enhancers, GJB2 promoters, GJB2 5' UTR, and/or GJB2 3' UTR), and a nucleotide sequence encoding a GJB2 protein.
Aspects of the disclosure relate to compositions and methods for treating hereditary hearing loss and/or vision loss, for example, due to Usher syndrome, Type 3A. In some embodiments, the disclosure provides a recombinant adeno-associated virus comprising: (i) an AAV-S capsid protein, and (ii) an isolated nucleic acid comprising a transgene (e.g., a transgene for expressing a clarin-1 protein). The present disclosure also provides methods of treating hereditary hearing loss and/or vision loss (e.g., Usher Syndrome, Type 3A) using the same.
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/015 - Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
The present invention relates to a homogeneous, time resolved, Förster resonance energy transfer (TR-FRET)-based method for detection of SARS-CoV-2, SARS CoV-1, and MERS-CoV antibodies in a patient fluid sample.
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
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
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH (USA)
PRESIDENT AND FELLOWS OF HARVARD COLLEGE (USA)
Inventor
Oklu, Rahmi
Albadawi, Hassan
Mitragotri, Samir
Abstract
This document relates to methods and materials for tissue ablation. For example, methods for using a composition including one or more ionic liquids (e.g., a composition including a LATTE solution) for tissue ablation are provided. In some cases, a composition including one or more ionic liquids (e.g., a composition including a LATTE solution) can be used to ablate tumor tissue within a mammal having cancer (e.g., to treat the mammal).
Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
Enhanced virus-like particles (eVLPs), comprising a membrane comprising a phospholipid bilayer with one or more virally-derived glycoproteins on the external side; and a cargo disposed in the core of the eVLP on the inside of the membrane, wherein the eVLP does not comprise an exogenous gag/pol protein, and methods of use thereof for delivery of the cargo to cells.
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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
The technology described herein is directed to an anterior nares swab that is automation compatible. In one aspect, the swab comprises a cap, a threaded portion, a neck, and a sample collection head. The cap can be integrally and/or monolithically formed with any one or more of the threaded portion, the neck, and the sample collection head; or can be removably coupled to any one or more of the threaded portion, the neck, and the sample collection head. In additional aspects, described herein are kits comprising said swabs and methods of using said swabs.
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
A61J 1/05 - Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
A device for performing an assay comprises a tube, a cap, an insert, and a reaction container. The tube includes a lateral flow strip disposed therein. The cap is coupled to the tube and includes a hollow interior defined at least partially therethrough. The insert is configured to be at least partially received within the hollow interior of the cap. The reaction container includes a cavity configured to store one or more fluids therein, and is rotatably coupled to the cap such that rotation of the cap relative to the reaction container causes (i) mixing of the one or more fluids and (ii) at least a portion of the mixed fluids to be delivered from the reaction container to the lateral flow strip via the insert.
Disclosed herein are semiconductor devices to provide a CMOS -compatible, wafer- scale, multi-well platform that can be used for biomedical or other applications, and methods to operate the same. In some embodiments, circuitry is provided underneath a multiple-well array to electrically interface with electrodes in the wells. To interface with electrodes in a large array, circuitry may be fabricated on a single silicon (Si) wafer having a dimension that is at least the same or larger than that of the multiple-well array. According to one aspect of the present disclosure, standard CMOS fabrication process such as those known to be used in a standard semiconductor foundry may be used without expensive customization for complex fabrication procedures. This may help the production cost to be lowered in some cases.
Disclosed herein are small molecules that inhibit apoptosis and promote autophagy through the TRADD pathway, and their use for treatment of neurodegenerative diseases. Methods of preparing these small molecules and medicinal efficacy are described.
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
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
47.
APPARATUSES FOR CELL MAPPING VIA IMPEDANCE MEASUREMENTS AND METHODS TO OPERATE THE SAME
Disclosed herein are an apparatus for electrically assessing and/or manipulating cells. One aspect is directed to electrically mapping cells on the surface of the semiconductor substrate via cross-electrode impedance measurements. Further according to some aspects, the electrode array allows for spatially addressable electrical stimulation and/or recording of electrical signals in real-time using the CMOS circuitry. Some of these aspects are directed to using an electrode array to perform cell patterning through electrochemical gas generation, and extracellular electrochemical mapping.
Disclosed herein are an apparatus for electrically assessing and/or manipulating cells. One aspect is directed to electrically mapping cells on the surface of the semiconductor substrate via cross-electrode impedance measurements. Further according to some aspects, the electrode array allows for spatially addressable electrical stimulation and/or recording of electrical signals in real-time using the CMOS circuitry. Some of these aspects are directed to using an electrode array to perform cell patterning through electrochemical gas generation, and extracellular electrochemical mapping.
The present disclosure provides genetic constructs comprising a recombinant internal ribosome entry site (IRES), which may be used as riboswitches to modulate translation of an operably-mRNA sequence encoding a protein of interest. In other aspects, the disclosure provides recombinant cells, methods, kits and systems that utilize the same, e.g., to provide a platform for modulating the expression of essentially any protein of interest in a eukaryotic cell.
The present invention provides methods, compositions and kits for assembling an enzyme-deoxyribonucleic acid (DNA) complex for use in preparing a double stranded DNA molecule comprising one or more loci of interest for determining the methylation status of the one or more loci of interest therein.
The present disclosure provides genetic constructs comprising a recombinant internal ribosome entry site (IRES), which may be used as riboswitches to modulate translation of an operably- mRNA sequence encoding a protein of interest in a plant. In other aspects, the disclosure provides recombinant plant cells, methods, kits and systems that utilize the same, e.g., to provide a platform for modulating the expression of essentially any protein of interest in a plant cell.
Methods, systems, compositions and strategies for the use of ARMM-mediated delivery of molecules (e.g., biological molecules, small molecules, proteins, and nucleic acids (e.g., DNA, RNA), DNA plasmids shRNA, mRNA) to cells of the nervous system (e.g., central nervous system and peripheral nervous system).
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
53.
LIVING CELLS ENGINEERED WITH POLYPHENOL-FUNCTIONALIZED BIOLOGICALLY ACTIVE NANOCOMPLEXES
Described herein are functionalizing nanocomplexes comprising one or more polyphenol molecules; and one or more biomolecules. Further described herein are functionalized cells comprising one or more of the nanocomplexes. In some embodiments, the biomolecules can be therapeutic agents and the functionalized cells can be administered to patients to provide improved delivery (e.g., dosing and specificity) of the therapeutic agent.
A61K 47/50 - 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
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 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
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. Also provided herein are methods for simultaneously editing both strands of a double- stranded DNA sequence at a target site to be edited. Further provided herein are pharmaceutical compositions, polynucleotides, vectors, cells, and kits.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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
C12N 15/90 - Stable introduction of foreign DNA into chromosome
The present invention provides novel recombinant relaxin-2 compositions and methods for making the same. Also disclosed herein are methods of treating relaxin-2-associated disorders or diseases using the compositions of the invention.
Described in several exemplary embodiments are compositions including a targeting moiety effective to target a central nervous system cell and formulations thereof. In certain embodiments, the targeting moiety is composed of a n-mer motif, P motif, or both. Also described in certain example embodiments are vector systems configured to generate polypeptides containing the one or more targeting moieties. Also described herein are methods of generating a targeting moiety effective to target a central nervous system cell and using the compositions containing the targeting moieties described herein, such as to deliver a cargo to a subject and/or treat a central nervous system disease, disorder, or system thereof.
The technology described herein is directed to a swab for sample collection. In one aspect, the swab comprises a sample collection head, which comprises a plurality of spaced annular rings. In one embodiment, the swab further comprises a tapered neck and a handle. In one embodiment, the swab is injection-molded using polypropylene. In other aspects, described herein are swabs comprising a water-soluble or biodegradable material. In additional aspects, described herein are kits comprising said swabs and methods of using said swabs.
The technology described herein is directed to methods, kits, compositions, devices, and systems for detecting a target nucleic acid, such as a viral RNA. In one aspect, described herein are methods of detecting the target nucleic acid. In other aspects, described herein are compositions, kits, devices, and systems suitable to practice the methods described herein to detect the target nucleic acid.
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
59.
METHODS AND COMPOSITIONS FOR RESTORING STMN2 LEVELS
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.
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
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
60.
METHODS AND SYSTEMS FOR SELECTING PARAMETERS TO APPROXIMATE DESIRED PROPERTIES OF STRUCTURAL COLOR
Exemplary embodiments relate to techniques for determining structural color from parameters of an array of nanoparticles. The techniques include inputting structural and optical parameters and performing a probabilistic simulation to determine the structural color. An evolutionary optimization may be performed to determine parameters of the array of nanoparticles according to desired properties of structural color. The evolutionary optimization may employ the probabilistic simulation and further adjust one or more parameters of the array to approximate the desired properties of the structural color. Based on applying the probabilistic simulation, the technique may generate an output describing a value, or a range of values, for the one or more parameters of the array of nanoparticles that are selected to approximate the desired properties of the structural color.
B01J 13/00 - Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
G06F 30/25 - Design optimisation, verification or simulation using particle-based methods
The technology described herein is directed to engineered chemoautotrophic bacteria and methods of producing sustainable biomolecules. In several aspects, described herein are engineered bacteria and corresponding methods, compositions, and systems for the production of products such as polyhydroxyalkanoates (PHA), sugar feedstocks, and lipochitooligosaccharide (LCO) fertilizers.
The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in mitochondrial DNA (mtDNA) with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Casp) and double-stranded DNA deaminase that is capable of being delivered to the mitochondria and carrying out precise installation of nucleotide changes in the mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but also may be used for base editing of any double- stranded target DNA.
A system includes a quantum computer, and a computing node configured to: receive a description of a probability distribution, determine a first Hamiltonian having a ground state encoding the probability distribution, determine a second Hamiltonian, the second Hamiltonian being continuously transformable into the first Hamiltonian via a path through at least one quantum phase transition, and provide instructions to the quantum computer to: initialize a quantum system according to a ground state of the second Hamiltonian, and evolve the quantum system from the ground state of the second Hamiltonian to the ground state of the first Hamiltonian according to the path through the at least one quantum phase transition. The computing node is further configured to receive from the quantum computer a measurement on the quantum system, thereby obtaining a sample from the probability distribution.
Provided herein are methods for promoting biostasis or preservation of a cell, tissue or organ during cancer treatment or for transplantation comprising contacting the cell, tissue or organ with an agonist of the ?-opioid receptor, SNC-80, an or Donepezil. Further provided herein is a method of treating a hematological neoplastic disease.
The present invention generally relates to genomics. Some embodiments are directed to imaging the 3D organization of the genome, or part of the genome, with high throughput in the sequence space. Some embodiments are directed to imaging the 3D organization of the genome, or part of the genome, in the context of transcriptional activity and nuclear structures. In addition, certain embodiments are directed to chromatin structures, 3D chromatin organizations, trans-chromosomal interactions and chromatin-nuclear-structure interactions as well as their relationship with transcription, etc. In addition, various embodiments are directed to imaging methods that allow mapping of the 3D organization of the genome, or part of the genome, in the context of nuclear structures and transcriptional activity. Some embodiments are directed to massively multiplexed fluorescence in situ hybridization methods for imaging chromatin loci and/or nascent RNA transcripts at the chromosome or genome scale.
Provided herein are compositions, kits, and methods for nucleic acid barcoding. The barcode compositions provided herein can be used to linearly, combinatorially, or spatially barcode a plurality of targets in a sample. Also provided herein is a device for use in a barcoding method provided herein comprising a light source and a sample holder.
Methods, apparatus, systems, and methods are described that relate to microneedle-assisted aptamer-based electrochemical sensing for label-free, continuous real-time monitoring of biomarkers in a biofluid. One example device for electrochemical monitoring of one or more analytes in a biofluid includes a substrate and at least two microneedles coupled to the substrate. Each microneedle in the at least two microneedles includes a protruded needle structure and an electrode probe structure. The electrode probe structure of a first microneedle in the at least two microneedles includes an aptamer sequence which is specific for a first analyte and the electrode probe structure of the first microneedle is operable as a working electrode for detection of the first analyte using a first electrochemical detection technique.
Methods are provided for treating osteoarthritis by administering ?Klotho protein and sTGF?-R2 protein to a site within a mammal exhibiting symptoms of osteoarthritis, such as a knee joint. The ?Klotho protein and the sTGF?-R2 protein are both present at the osteoarthritic site.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
The technology described herein is directed to compositions, sets, and methods for analyzing, detecting, and/or visualizing target molecules. In one aspect, described herein are sets of readout molecules to determine the identity of at least one oligonucleotide tag hybridized to at least one target molecule. In another aspect, described herein are methods of detecting said oligonucleotide tags bound to at least one target molecules using said set of readout molecules.
The present disclosure generally relates to methods for multi-focal imaging for determining nucleic acids in cells or other samples. A sample is exposed to a plurality of nucleic acid probes. For each of the nucleic acid probes, imaginges of the sample are captured using at least 2 detectors focused on different focal planes within the sample. Multiple focal planes may simultaneously be determined, e.g., by using 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 binding, abundance and/or spatial distribution of the nucleic acid probes within the sample is determined using the captured images.
Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and/or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein.
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A61K 47/50 - 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
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
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
C07K 14/015 - Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
Disclosed herein are minimal arrestin domain containing protein 1 (ARRDC1 ) constructs, which drive the formation of ARRDC1 -mediated microvesicles (ARMMs). These vesicles can be harnessed to package and deliver a variety of molecular cargos such as small molecules, nucleic acids, and proteins. An example of such cargo is the genome editor Cas9.
C12N 15/62 - DNA sequences coding for fusion proteins
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
74.
MODIFIED BACTERIAL RETROELEMENT WITH ENHANCED DNA PRODUCTION
THE J. DAVID GLADSTONE INSTITUTES, A TESTAMENTARY TRUST ESTABLISHED UNDER THE WILL OF J. DAVID GLADSTONE (USA)
PRESIDENT AND FELLOWS OF HARVARD COLLEGE (USA)
Inventor
Shipman, Seth
Abstract
Engineered retrons, modified to enhance production of multicopy single-stranded DNA (msDNA), are provided. In addition, vector systems encoding such engineered retrons and methods of using engineered retrons and vector systems encoding them in various applications such as CRISPR/Cas-mediated genome editing, recombineering, cellular barcoding, and molecular recording are also disclosed.
Described herein are methods of generating engineered viral capsid variants. Also described herein are engineered viral capsid variants, engineered viral particles and formulations and cells thereof. Also described herein are vector systems containing an engineered viral capsid polynucleotide and uses thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/005 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
The technology described herein is directed to methods, systems, and compositions for analyzing, detecting, and/or visualizing target molecules. Described herein are compositions and systems comprising oligonucleotide tags comprising barcoded cassettes. Also described herein are methods for analyzing target molecules, the method comprising contacting a sample with at least one oligonucleotide tag, contacting the sample with at least two readout molecules, and detecting the relative spatial order of the readout molecules.
A device includes a grouping of N qubits, where N is equal to two or more, and a coherent light source configured to, given selected values for a set of parameters of at least a first and a second laser pulse, the parameters selected from a relative phase shift, a laser frequency, a laser intensity, and a pulse duration: apply at least the first and second laser pulses to all qubits within the grouping of N qubits, thereby coupling a non-interacting quantum state |1> to an interacting excited state |r), such that each qubit that begins in quantum state |1) returns to the state |1) upon completion of the at least first and second laser pulses, and such that qubits in the grouping are mutually blockaded.
A microfluidic device comprises a cell flow layer and a control layer. The cell flow layer includes a growth channel, a collection channel, a plurality of bridge channels connecting the growth channel and the collection channel, a plurality of bridge valve portions, and a plurality of cell growth trenches coupled to the growth channel. The growth channel includes an inlet valve portion and an outlet valve portion controlling flow into and out of the growth channel. The collection channel includes an inlet valve portion and an outlet valve controlling flow into and out of the collection channel. The bridge valve portions control flow between the growth channel and the collection channel. The control layer includes a fist control channel actuating the bridge valve portions and a second control channel actuating the inlet valve portions and the outlet valve portions of the growth channel and the collection channel.
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
G01N 35/02 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
G01N 35/04 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations - Details of the conveyor system
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
79.
COMPOSITIONS AND SYNERGISTIC METHODS FOR TREATING INFECTIONS
The present invention relates to compositions and methods for treating microbial infections in subjects, in particular methods of administering a gelsolin agent and an antimicrobial agent to produce a synergistic therapeutic effect against a microbial infection in a subject. The present invention also relates to methods for treating viral infections in subjects, including methods that include delay ed-dosing methods and/or synergistic methods.
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.
Provided herein are erythrocytes with polymeric particles (i.e., "backpacks") adhered that provide delivery of payload therapeutic agents to subjects administered these cells.
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Provided herein is a differentiation agent that consists essentially of SOX9 for the production of oligodendrocyte progenitor cells (OPCs) from pluripotent stem cells (PSCs). Also provided herein are methods of producing the PSCs and methods of using the PSCs to produce OPCs and oligodendrocytes.
A system for optically modulating a plurality of optical channels includes a power delivery module adapted to convert a coherent light beam into a plurality of optical channels, at least one optical modulator, optically coupled to the power delivery module, the at least one optical modulator adapted to optically modulate each of the plurality of the optical channels, and a vacuum chamber having a trapping plane therein, the vacuum chamber adapted to generate an addressable array of trapped particles at the trapping plane, wherein each of the plurality of optical channels is optically coupled to at least one of the trapped particles of the addressable array.
G02F 1/00 - Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics
G06N 10/40 - Physical realisations or architectures of quantum processors or components for manipulating qubits, e.g. qubit coupling or qubit control
G02B 6/28 - Optical coupling means having data bus means, i.e. plural waveguides interconnected and providing an inherently bidirectional system by mixing and splitting signals
G02B 6/293 - Optical coupling means having data bus means, i.e. plural waveguides interconnected and providing an inherently bidirectional system by mixing and splitting signals with wavelength selective means
Described herein are methods and compositions related to inhibiting bile salt hydrolase (BSH) and uses thereof. Provided herein is a method for treating a metabolic disorder (e.g., diabetes, obesity), gastrointestinal disease (e.g., a gastrointestinal infection; inflammatory bowel disease (IBD); appendicitis; Crohn's disease (CD); ulcerative colitis (UC); gastritis; enteritis; esophagitis; pancreatitis; diabetes; hepatitis; liver diseases (e.g., Non-alcoholic Fatty Liver Disease (NAFLD); non-alcoholic steatohepatitis (NASH); hepatitis A; hepatitis B; hepatitis C; autoimmune hepatitis; and cirrhosis of the liver) gastroesophageal reflux disease (GERD); celiac disease; diverticulitis; food intolerance; ulcer; infectious colitis; irritable bowel syndrome; leaky gut; and cancer), cancer (e.g., cancer of the digestive system, liver cancer), or an inflammatory disease (e.g., Crohn's disease, inflammatory bowel disease, ulcerative colitis, pancreatitis, hepatitis, appendicitis, gastritis, diverticulitis, celiac disease, food intolerance, enteritis, ulcer, gastroesophageal reflux disease (GERD), psoriatic arthritis, psoriasis, and rheumatoid arthritis) in a subject in need thereof comprising administering to a subject a compound of Formulae (I) -(XVIII).
C07J 9/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
A61K 31/047 - Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells, e.g., to build genotype-phenotype corresponse for high-throughput screening. In some cases, the cells may be manipulated, e.g., using CRISPR or other techniques. In certain embodiments, nucleic acids may be introduced to the cell, e.g., using a lentivirus. The nucleic acids may contain a guide portion comprising a DNA or RNA recognition sequence, a reporter portion, and an identification portion comprising one or more read sequences. The guide portion may be used to alter the phenotype of the cells, e.g., using a sequence, e.g., an sgRNA sequence, that can be targeted using CRISPR or other techniques, and in some cases, the phenotype of the cells may be determined using various imaging approaches. The identification portion may be determined using MERFISH or other suitable techniques. In addition, in some cases, association or colocalization between determination of the reporter and the read sequences may substantially improve decoding accuracy, e.g., due to lowered misidentification of background signals. Other aspects are generally directed to compositions or devices for use in such methods, kits for use in such methods, or the like.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
87.
ENGINEERED ADENO-ASSOCIATED (AAV) VECTORS FOR TRANSGENE EXPRESSION
Engineered AAV vectors for transgene expression, e.g., in the CNS, PNS, inner ear, heart, or retina, and methods of use thereof. Also provided are methods for discovering new engineered AAV vectors that mediate transgene expression in desired cell types.
The present disclosure provides compositions and methods 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 nucleotide change can include a single- nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides 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 homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incoporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the intallation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.
The present disclosure provides new prime editor guide RNAs for prime editing, constructs for prime editing, and methods for using same. In addition, the present disclosure provides compositions and methods 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 (e.g., insertion or deletion). The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides 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 prime editor RNA (PEgRNA). The prime editor guide RNA comprises an extension arm that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to an endogenous DNA sequence, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule.
Described herein are methods and compositions related to the modulation of progranulin expression or activity in the brain for the treatment of neurodegenerative diseases.
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
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
Provided herein are methods and compositions for treating cancer or a tumor in a subject by administering to the subject a first agent that disrupts the interaction between PD-L2/RGMb and a second agent that disrupts the interaction between PD-1/PD-L1. The subject may have dysbiosis and/or be nonresponsive to immune checkpoint therapy.
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
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.
Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein have modulated expression of one or more MHC-I and MHC-II human leukocyte antigens and one or more tolerogenic factors.
Provided are therapeutic virus vectors, particularly, recombinant adeno-associated virus (rAAV) vectors, designed to contain an enhancer sequence that specifically restricts expression of an effector gene (e.g., an SCN1A-encoding polynucleotide, Gq-DREADD-encoding polynucleotide, or PSAM-encoding polynucleotide) contained in the vector to PV-expressing GABAergic interneuron or to neuron cell populations in the brain. The rAAV vectors, compositions and methods thereof are useful for treating subjects afflicted with neuropathologies, seizures, pharmacologically-intractable forms of epilepsy including Dravet syndrome (DS), a form of infantile epilepsy associated with severe seizures, cognitive impairment and premature death, as the cause of DS involves loss of function of a sodium channel encoded by the SCN1A gene. The described vectors restore expression of effector genes to the appropriate interneuron or neuron cell populations with specificity and sensitivity, advantageously to address the root cause of the disease by restoring the excitation-inhibition balance by means of gene-therapy (with SCN1A) or pharmacogenetics.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Systems and methods for focused direction deposition of a micron or nanometer dimension polymeric fiber and materials of such fibers are described herein. Systems and methods employ one or more gas flows to entrain and deflect fibers produced by a rotary jet spinning system forming a focused fiber stream. Some embodiments enable control of alignment and distribution of the fibers with a relatively high fiber throughput.
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 restore expression of a normal full-length or protein coding STMN2 RNA.
The present invention generally relates to systems and methods for imaging or determining nucleic acids in cells or other samples. In some cases, the transcriptome of a cell may be determined. Certain embodiments are generally directed to determining nucleic acids and other targets in a sample at relatively high resolutions. For instance, nucleic acid probes may be applied to sample, and binding of the nucleic acid probes to a target may be amplified using primary and secondary amplifier nucleic acids. In some cases, there is a maximum number of amplifier nucleic acids that can be bound to a target, e.g., the binding is saturatable, and cannot grow indefinitely, even in the presence of abundant reagents. This may be advantageous, for example, for controlling the brightness of each binding event, controlling the size of the amplified regions (e.g., during imaging), and/or for limiting the degree of amplification noise (i.e. the final variation in amplified signal from molecule to molecule), etc. In addition, in some embodiments, the primary and/or secondary amplifier nucleic acids may be formed from only 3 of the 4 naturally-occurring nucleotides, which may result in less secondary structure, faster binding rates, etc. These properties can in some cases facilitate the rapid design of multiple orthogonal amplification sequences, allowing the extension of such an approach to many distinct molecular targets.
A structural lattice includes a rectangular base defined by four periphery beams, and two non-diagonal beams that divide the rectangular base in four quadrants. The structural lattice further includes a diagonal reinforcement strut system overlaid on the rectangular base and having at least two intersecting sets of diagonal beams forming an open-and-closed cell architecture.
B21D 47/00 - Making rigid structural elements or units, e.g. honeycomb structures
B32B 3/12 - Layered products essentially comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar form; Layered products essentially having particular features of form characterised by a discontinuous layer, i.e. apertured or formed of separate pieces of material characterised by a layer of regularly-arranged cells whether integral or formed individually or by conjunction of separate strips, e.g. honeycomb structure
E04C 3/04 - Joists; Girders, trusses, or truss-like structures, e.g. prefabricated; Lintels; Transoms of metal
E04C 5/06 - Reinforcing elements of metal, e.g. with non-structural coatings of high bending resistance, i.e. of essentially three-dimensional extent, e.g. lattice girders
The invention provides rechargeable batteries including a solid state electrolyte (SSE) containing an alkali metal disposed between two electrodes. The batteries are volumetrically constrained imparting increased stability under voltage cycling conditions, e.g., through microstructure mechanical constriction on the solid state electrolyte and the electrolyte-electrode interface. These batteries of the invention are advantageous as they may be all-solid-state batteries, e.g., no liquid electrolytes are necessary, and can achieve higher voltages with minimal electrolyte degradation.
H01M 4/13 - Electrodes for accumulators with non-aqueous electrolyte, e.g. for lithium-accumulators; Processes of manufacture thereof
H01M 4/131 - Electrodes based on mixed oxides or hydroxides, or on mixtures of oxides or hydroxides, e.g. LiCoOx
H01M 4/485 - Selection of substances as active materials, active masses, active liquids of inorganic oxides or hydroxides of mixed oxides or hydroxides for inserting or intercalating light metals, e.g. LiTi2O4 or LiTi2OxFy
H01M 4/525 - Selection of substances as active materials, active masses, active liquids of inorganic oxides or hydroxides of nickel, cobalt or iron of mixed oxides or hydroxides containing iron, cobalt or nickel for inserting or intercalating light metals, e.g. LiNiO2, LiCoO2 or LiCoOxFy
H01M 10/05 - Accumulators with non-aqueous electrolyte
Provided are 13-membered macrolides for the treatment of infectious diseases. The 13- membered macrolides described herein are azaketolides. Also provided are methods for preparing the 13-membered macrolides, pharmaceutical compositions comprising the 13- membered macrolides, and methods of treating infectious diseases, and in particular, disease resulting from Gram negative bacteria using the disclosed macrolides.
C07H 17/08 - Hetero rings containing eight or more ring members, e.g. erythromycins
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
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