Embodiments of the present disclosure provide composition and methods for recording an iterative nucleic acid editing event. The compositions and methods described herein comprise a first active target domain, comprising an editable recording sequence configured to hybridize with a first prime editing guide RNA (pegRNA) and one or more inactive truncated target domains comprising a non-editable sequence configured to not hybridize with the pegRNA, wherein the first pegRNA edits the first active target domain, wherein the pegRNA edit shifts the position of the recoding sequence from the editable sequence to the non-editable sequence, thereby changing the editable sequence to a non-editable sequence and the inactive truncated target domain to a second active target domain comprising a second recoding sequence configured to hybridize with a second pegRNA.
Disclosed herein are -sheet polypeptide multimers, comprising two or more monomeric -sheet polypeptides that are covalently linked. In various embodiments, the multimer comprises a dimer, trimer, tetramer, pentamer, or hexamer, or wherein the multimer comprises a dimer. Also disclosed are compositions and medical devices comprising -sheets, and their use for treating and diagnosing amyloid diseases or amyloid-associated diseases.
A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A61L 31/16 - Biologically active materials, e.g. therapeutic substances
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 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
3.
SYNERGISTIC MICROBIAL STRAINS FOR INCREASING THE ACTIVITY OF NITROGEN-FIXING MICROORGANISMS
Embodiments of the present disclosure provide methods and compositions for increasing the nitrogen (N) fixation of diazotrophs or acquisition of N for a plant in need thereof. Embodiments of the methods and compositions comprise at least one live endophyte strain, wherein the live endophyte strain is isolated from one or more plants grown in a nutrient-limited and/or water-stressed environment. In some embodiments, the endophyte strain can be administered to a plant, wherein the endophyte strain synergistically increases the nitrogen fixation of the diazotrophic strain associated with the plant. In other embodiments, the diazotrophic strain is not associated with a plant. Embodiments of the present disclosure have broad application to reduce fertilizer requirements, increase plant carbon sequestration, increase production of hydrogen gas for use as an energy source or in chemical industries and to increase growth of industrial microbial strains, reducing the need for ammonium or nitrates in fermenters.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermen
Systems and methods to remove carbon from liquids such as seawater and other natural waters are described. The systems and methods utilize photoactive compounds to alter the pH of a fluid, drawing carbon out of the liquid and channeling it into a secondary environment. The carbon can be captured and sequestered or used in the formation of a product.
B01D 53/22 - Separation of gases or vapours; Recovering vapours of volatile solvents from gases; Chemical or biological purification of waste gases, e.g. engine exhaust gases, smoke, fumes, flue gases or aerosols by diffusion
A continuous reactor and method for destroying contaminants, such as perfluoroalkyl and/or polyfluoroalkyl substances in various feedstocks. Liquid byproducts are continuously hydrolyzed in an aqueous alkaline solution to achieve greater than 99.99% destruction of the contaminants. Continuous hydrolysis achieves a greater conversion efficiency as compared to batch reactions and has a wide application of contaminated feedstocks.
B01D 53/04 - Separation of gases or vapours; Recovering vapours of volatile solvents from gases; Chemical or biological purification of waste gases, e.g. engine exhaust gases, smoke, fumes, flue gases or aerosols by adsorption, e.g. preparative gas chromatography with stationary adsorbents
F25J 3/02 - Processes or apparatus for separating the constituents of gaseous mixtures involving the use of liquefaction or solidification by rectification, i.e. by continuous interchange of heat and material between a vapour stream and a liquid stream
6.
MODULAR KINETICALLY-CONTROLLED FUNCTIONAL RNA CONSTRUCTS AND RELATED COMPOSITIONS, SYSTEMS, AND METHODS
Disclosed are kinetically-controlled RNA biosensor constructs and related, nucleic acids, vectors, cells, systems and methods useful for detecting ligands of interest. Also disclosed are computer implemented methods for designing kinetically-controlled biosensors, guide RNA molecules, and/or target promoter sequences, and constructs produced thereby. Exemplary embodiments include scRNAs and expression cassettes incorporating synthetic promoters for implementation of CRISPRa.
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
Provided herein are compositions and methods comprising mutated coronavirus "S" spike proteins or receptor binding domains thereof that have an increased expression level, yield and stability compared to its corresponding native or wild-type coronavirus spike protein under the same expression, culture or storage conditions. These mutated spike proteins can be used for generating a protein-based vaccine against one or more coronaviruses.
Apparatuses and methods for measuring total blood volume with ultrasound are disclosed. In one embodiment, a system for monitoring a blood volume of a patient includes an ultrasound transmitter configured for emitting an ultrasound toward a target blood vessel of the patient; and an ultrasound receiver configured for receiving the ultrasound reflected from the target blood vessel of the patient. The system also includes, a controller configured for: determining an expanded state of the blood vessel based on the ultrasound reflected from the target blood vessel; determining a collapsed stated of the blood vessel based on the ultrasound reflected from the target blood vessel; and determining the blood volume of the patient based on the ratio of the collapsed stated and the expanded stated of the blood vessel.
A61B 5/02 - Measuring pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography; Heart catheters for measuring blood pressure
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
CANCER RESEARCH TECHNOLOGY LIMITED (United Kingdom)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD (United Kingdom)
THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (United Kingdom)
UNIVERSITY OF WASHINGTON (USA)
THE UNITED STATES GOVERNMENT REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
Inventor
Islam, Md. Saiful
Tumber, Anthony
Schofield, Christopher
Paschalis, Alec
Welti, Jonathan
Sharp, Adam
De Bono, Johann
Plymate, Stephen
Abstract
The invention relates to methods for treating prostate cancer by targeting the generation of splice variants of the androgen receptor. In one aspect, this can be achieved by targeting JMJD6 to reduce the production of androgen receptor splice variants. The invention finds particular use in the treatment of prostate cancer that is resistant to conventional androgen therapy.
The present disclosure is directed to polypeptides capable of cleaving gluten proteins, e.g., gliadins, nucleic acid molecules encoding the same, pharmaceutical compositions comprising the same, and methods of use thereof for treating celiac sprue disease and/or non-celiac gluten sensitivity (NCGS).
Disclosed herein are embodiments of a hydrothermal reactor, such as a downflow hydrothermal reactor and methods of using the same. Also disclosed herein are system embodiments comprising the hydrothermal reactor. Method embodiments disclosed herein facilitate determining operation parameters for the hydrothermal reactor that give rise to efficient feedstock conversion to products while maintaining integrity of the reactor (e.g., avoiding corrosion) and providing safe operating conditions. The disclosed reactor and system embodiments facilitate situations where small scale and/or remote destruction of feedstocks (e.g., chemical warfare agents and/or environmental toxins) is needed.
B01J 8/00 - Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
B01J 19/26 - Nozzle-type reactors, i.e. the distribution of the initial reactants within the reactor is effected by their introduction or injection through nozzles
B01J 37/10 - Heat treatment in the presence of water, e.g. steam
B09B 3/00 - Destroying solid waste or transforming solid waste into something useful or harmless
C02F 1/72 - Treatment of water, waste water, or sewage by oxidation
F23G 5/02 - Methods or apparatus, e.g. incinerators, specially adapted for combustion of waste or low-grade fuels including pretreatment
F23G 5/24 - Methods or apparatus, e.g. incinerators, specially adapted for combustion of waste or low-grade fuels with combustion in a vertical, substantially cylindrical, combustion chamber
The present disclosure provides transferring receptor binding polypeptides of the general formula H1-H2-E1-H3-E2-E3-H4, wherein H1, H2, H3, and H4 each independently comprise an alpha, helical domain of between 11-20 amino acids in length; E1, E2, and E3 each independently comprise a beta sheet of 5 amino acids in length; and optional amino acid linkers between domains.
The present disclosure relates generally to a method of blocking, attenuating, or limiting the development of one or more vasomotor symptoms (VMS) in a patient who has cancer, has had cancer, or has an increased risk for cancer by administering a NK antagonist.
Polypeptide inhibitors of SARS-CoV-2 are disclosed comprising an amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-17, 19-21, 23-34 and 100-101, and their use for treating and limiting development of SARS-CoV-2 infection.
Kits, methods, polypeptides, systems, and non-transitory, machine-readable storage media for detecting a nucleic acid in a sample are described. In an embodiment, the kit comprises a loop primer nucleic acid molecule configured for loop-mediated isothermal amplification (LAMP), the loop primer nucleic acid molecule comprising: a targeting sequence complementary to a target portion of a target nucleic acid sequence; and an adapter sequence; a displacement nucleic acid probe comprising: a fluorophore adapter sequence; and the adapter sequence; and a fluorophore adapter complement nucleic acid molecule complementary to the fluorophore adapter sequence, wherein the fluorophore adapter sequence or the fluorophore adapter complement nucleic acid molecule is coupled to a fluorophore. In an embodiment, the system comprises a thermal subsystem for heating a sample disposed therein, and an optical subsystem for optically excited the sample and detecting light emitted from the sample.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
The present disclosure provides human 1L-23R (WL-23R) binding polypeptides, conditionally maximally active SilL~23R binding proteins, multimers thereof, and methods for using the polypeptides and binding proteins for therapeutic use.
Polypeptides are disclosed comprising an (Fc) binding domain, a helical polypeptide monomer, and an oligomer domain, polymers thereof, and uses thereof.
C07K 14/32 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Bacillus (G)
C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
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
Antibody particles are disclosed comprising polypeptides comprising an (Fc) binding domain, a helical polypeptide monomer, and an oligomer domain, and either Tie2 antibodies or dimers, or tumor necrosis factor receptor superfamily antibodies, and uses thereof.
C07K 14/32 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Bacillus (G)
C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
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
19.
MODULAR AND GENERALIZABLE BIOSENSOR PLATFORM BASED ON DE NOVO DESIGNED PROTEIN SWITCHES
The disclosure provides cage proteins comprising a helical bundle, wherein the cage protein comprises a structural region and a latch region, wherein the latch region comprises one or more target binding polypeptide, wherein the cage protein further comprises a first reporter protein domain, wherein the first reporter protein domain undergoes a detectable change in reporting activity when bound to a second split reporter protein domain, and wherein the structural region interacts with the latch region to prevent solution access to the one or more target binding polypeptide.
UNITED STATES GOVERNMENT AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (USA)
UNIVERSITY OF WASHINGTON (USA)
Inventor
Baker, Jeremy D.
Kraemer, Brian C.
Uhrich, Rikki L.
Stovas, Timothy J.
Saxton, Aleen D.
Abstract
Described herein are compositions and methods for treating Alzheimer's disease, a tauopathy disorder or dementia. The compositions include mammalian suppressor of taupathy 2 (MSUT2) inhibitors. The methods include steps for identifying candidate compositions capable of inhibiting RNA binding proteins to poly(A) RNA and detecting RNA polyadenylation of poly(A) RNA. The methods include reducing accumulation of phosphorylated and aggregated human tau.
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
The invention relates to the in vivo transduction of hematopoietic stem and progenitor cells (HSPCs) in a subject, such as a human subject, and to the treatment of subjects suffering from various pathologies, such as blood diseases, metabolic disorders, cancers, and autoimmune diseases, among others.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
The current disclosure provides recombinant adenoviral vectors and adenoviral genomes that can accommodate or that contain a large transposon payload, for instance a transposon payload of up to 40 kb. The adenoviral vectors and genomes can deliver the large transposon payload into a target genome, for instance for gene therapy.
THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL (USA)
UNIVERSITY OF WASHINGTON (USA)
Inventor
Allbritton, Nancy L.
Wang, Yuli
Sims, Christopher E.
Villegas Novoa, Cecilia
Abstract
Provided are new strategies, methods and systems, described herein as vasoactive intestinal peptide (VlP)-assisted air-liquid-interface (ALI) culture, to significantly increase the number of enteroendocrine (EEC) and enterochromaffin (EC) cells over the traditional submerged culture, while at the same time maintaining a high barrier integrity of monolayers. The new strategies, methods and systems overcome the limitations of the existing EEC enrichment methods by maintaining high cell viability and barrier integrity and without requiring complicated procedures of cocultures or genetic engineering/induction. The created EEC-enriched, contiguous monolayer platform acts as a robust analytical tool to enable functional studies of hormone secretion from EEC cells with high signal background ratio and repeatability.
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
C12M 1/00 - Apparatus for enzymology or microbiology
C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
C12M 3/04 - Tissue, human, animal or plant cell, or virus culture apparatus with means providing thin layers
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
King, Neil P.
Ellis, Daniel
Kanekiyo, Masaru
Lederhofer, Julia
Graham, Barney S.
Abstract
The disclosure provides non-naturally occurring mutant neuraminidase (NA) polypeptides that improve expression and/or modifies the open/closed tetramerie conformational state of the NA polypeptide, and uses thereof.
Disclosed herein are polypeptides comprising an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-84, 138-146, and 167-184, nanoparticles thereof, related nanoparticle compositions, and their use to treat or limit development of an infection.
Described herein are methods and compositions related to treating and preventing an engraftment arrhythmia with an effective amount of amiodarone and ivabradine. Also described herein is a method of cardiomyocyte transplant, the method comprises: administering in vitro-differentiated cardiomyocytes to cardiac tissue of a subject in need thereof; and administering to the subject an amount of amiodarone and an amount of ivabradine effective to reduce engraftment arrhythmia in the subject.
Disclosed herein arc ?-barrel polypeptides including self-complementing multipartite ?-barrel polypeptides and circularly permuted ?-barrel polypeptides and methods for their design and use in mediating real-time monitoring of polypeptide-polypeptide association and dissociation events.
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.
Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the sequencing library includes nucleic acids that represent the chromatin accessibility from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. In another embodiment, the present disclosure provides methods for characterizing rare events in isolated cells and nuclei.
Alpha(v) beta (6) integrin (avb6) binding polypeptides are disclosed herein, and their use in treating and detecting tumors, and their use in treating pulmonary fibrosis.
Chromophores with large hyperpolarizabilities, films with electro-optic activity comprising the chromophores, and electro-optic devices comprising the chromophores are disclosed.
C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
C07D 307/30 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 409/08 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
The disclosure provides compositions and methods for delivering a payload to cells or tissues that express GLUT4. In some embodiments, the compositions comprise an antibody, or fragment or derivative thereof, that specifically binds to glucose transporter 4 ("GLUT4") protein, and a therapeutic payload conjugated thereto. In some exemplary embodiments, the compositions are useful for methods of treating a disease or condition in a subject with a genetic mutation in a gene encoding dystrophin protein, wherein the payload comprises a nucleic acid encoding a functional dystrophin protein or functional fragment thereof to ameliorate aspects of the disease.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
33.
RECOMBINANT AD35 VECTORS AND RELATED GENE THERAPY IMPROVEMENTS
The present disclosure provides, among other things, helper-dependent adenoviral serotype 35 (Ad35) vectors. In various embodiments, helper-dependent Ad35 vectors can be used to deliver a therapeutic payload to a subject in need thereof. Exemplary payloads can encode replacement proteins, antibodies, CARs, TCRs, small RNAs, and genome editing systems. In certain embodiments, a helper-dependent Ad35 vector is engineered for integration of a payload into a host cell genome. The present disclosure further includes methods of gene therapy that include administration of a helper-dependent Ad35 vector to a subject in need thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C12N 15/90 - Stable introduction of foreign DNA into chromosome
34.
CROSSLINKABLE NONLINEAR-OPTICAL CHROMOPHORE SYSTEM
Crosslinked films having electro-optic activity, compositions and compounds for making the films, methods for making the films, and devices that include the films are disclosed.
Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive ("off") state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co/localized when bound to their targets, components of such protein switches, and their use.
Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (''off'') state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use.
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
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
Described herein are methods and compositions related to methods of improving survival and engraftment of human cells differentiated in vitro, and uses thereof.
Zwitterionic carboxybetaine copolymers and their use in coatings to impart non-fouling and functionality to surfaces, particularly surfaces of blood-contacting medical devices.
C09D 133/00 - Coating compositions based on 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 only one carboxyl radical, or of salts, a; Coating compositions based on derivatives of such polymers
40.
HIGH-THROUGHPUT SINGLE-NUCLEI AND SINGLE-CELL LIBRARIES AND METHODS OF MAKING AND OF USING
Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the method includes nuclear or cellular hashing which permits increased sample throughput and increased doublet detection at high collision rates. In one embodiment, the method includes normalization hashing which aids in estimating and removing technical noise in cell to cell variation and increases sensitivity and specificity.
Disclosed herein are methods of editing a gene in a cell that involve contacting the cell with a replication fork modulator, as well as edited cells and their methods of use.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
42.
INDOOR AIR POLLUTANT DEGRADATION BY GENETICALLY MODIFIED PLANTS
A genetically modified houseplant capable of reducing levels of volatile organic carcinogenic compounds, such as formaldehyde, benzene, and chloroform, in the indoor air in urban homes of developed countries is disclosed. The plant expresses a detoxifying transgene, mammalian cytochrome P450 2e, and has shown sufficient detoxifying activity against benzene and chloroform. Air purifying biofilters utilizing the plants and methods of their use are also disclosed.
Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
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
44.
DE NOVO DESIGN OF PROTEIN SWITCHES FOR TUNABLE CONTROL OF PROTEIN DEGRADATION
Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypeptides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix
The present disclosure provides danoprevir/NS3a complex reader (DNCR) and grazoprevir/NS3a complex readers (GNCR) polypeptides, fusion proteins, and combinations and their use.
Conditionally active receptor agonists that, when activated, bind to IL-2 receptor ß?c heterodimer (IL-2Rß?c), 1L-4 receptor a?cheterodimer (IL-4Ra?c), or IL-13 receptor a subunit (IL~13 Ra) are disclosed, as are components of the conditionally active receptor agonists and methods for using the conditionally active receptor agonists.
Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.
Kits and methods for enriching target nucleic acid sequences, such as nucleic acid molecules including the target nucleic acid sequence, and kits and methods for depleting target nucleic acid sequences, such as nucleic acid molecules including the target nucleic acid sequences. In an embodiment, the methods for enriching target nucleic acid sequences include selectively degrading single- stranded sample nucleic acid molecules, such as those that do not include the target nucleic acid sequences. In an embodiment, the methods for depleting target nucleic acid sequences include selectively degrading double- stranded sample nucleic acid molecules, such as those including the target nucleic acid sequence.
Disclosed herein are methods for identifying a ubiquitin ligase agonist, and the methods include (a) contacting a ubiquitin ligase with a candidate agonist and a neo-substrate; and (b) determining whether the candidate agonist is effective to result in binding the ubiquitin ligase to the neo-substrate, wherein binding of the ubiquitin substrate to the neo- substrate identifies the candidate agonist as a ubiquitin ligase agonist.
Compositions and method for reducing the concentration of uremic toxins in the body of a patient suffering from some degree of kidney failure are disclosed. The methods can be used to delay the need for conventional dialysis treatment or as an adjunct therapy to reduce the frequency of dialysis sessions, and in some instances, as an alternative to such dialysis sessions.
Apparatus and method for photo-chemical oxidation are disclosed herein. In one embodiment, a dialysis fluid regeneration system includes: a nanostructured anode; a source of light configured to illuminate the anode; and a cathode that is oxygen permeable.
Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive ("off") state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain, components of such protein switches, and their use.
C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
A61K 47/66 - 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 the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
C07K 14/435 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNOR UNIVERSITY (USA)
Inventor
Yu, Shawn
Ulge, Umut
Baker, David
Garcia, Kenan Christopher
Spangler, Jamie
Walkey, Carl
Quijano Rubio, Alfredo
Jude, Kevin
Weitzner, Brian
Silva Manzano, Daniel Adriano
Castellanos, Javier
Marcos, Enrique
Abstract
De novo designed polypeptides that bind to IL-2 receptor ß? c heterodimer (IL- 2Rß? c), IL-4 receptor a? cheterodimer (IL-4Ra? c), or IL-13 receptor a subunit (IL-13Ra) are disclosed, as are methods for using and designing the polypeptides.
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
G16B 50/00 - ICT programming tools or database systems specially adapted for bioinformatics
This disclosure relates to compounds that target microtubules, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases. More particularly, this disclosure relates to modified carbazole compounds and pharmaceutical compositions thereof, methods of targeting microtubules with these compounds, and methods of treating diseases affected by microtubule disruption.
C07D 401/06 - 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 carbon chain containing only aliphatic carbon atoms
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
C07D 209/86 - Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the sequencing library includes nucleic acids that represent the whole transcriptomes from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. Also provided herein are compositions, such as compositions that include the nucleic acids having three index sequences.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
57.
METHOD FOR IMPROVING MUSCLE FORCE OR PHYSICAL FUNCTION
The present invention relates to a method for improving a muscle force and a physical function, comprising combined use of an ingestion of a composition comprising one or more components selected from the group consisting of astaxanthin and its ester and a physical exercise.
Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the methods include linear amplification of the nucleic acids. In one embodiment, the sequencing library includes whole genome nucleic acids from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. Also provided herein are compositions, such as compositions that include the nucleic acids having three index sequences.
Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the methods include linear amplification of the nucleic acids. In one embodiment, the sequencing library includes whole genome nucleic acids from the plurality of single cells. In one embodiment, the nucleic acids include three index sequences. Also provided herein are compositions, such as compositions that include the nucleic acids having three index sequences
The disclosure features compositions and methods for the treatment of disorders associated with improper ribonucleic acid (RNA) splicing, including disorders characterized by nuclear retention of RNA transcripts containing aberrantly expanded repeat regions that bind and sequester splicing factor proteins. Disclosed herein are interfering RNA constructs that suppress the expression of RNA transcripts containing expanded repeat regions, as well as viral vectors, such as adeno-associated viral vectors, encoding such interfering RNA molecules. For example, the disclosure features interfering RNA molecules, such as siRNA, miRNA, and shRNA constructs, that anneal to dystrophia myotonica protein kinase (DMPK) RNA transcripts and attenuate the expression of DMPK RNA containing expanded CUG trinucleotide repeats. Using the compositions and methods described herein, a patient having an RNA dominance disorder, such as a human patient having myotonic dystrophy, among other conditions described herein, may be administered an interfering RNA construct or vector containing the same so as to reduce the occurrence of spliceopathy in the patient, thereby treating an underlying etiology of the disease.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
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
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
The present disclosure relates to methods, systems, and devices for performing analyses of biological nanoparticles. More specifically, the present disclosure relates to methods, systems, and devices for performing single biological nanoparticle size determination on a sample while the biological nanoparticle is in transit through a microfluidic chip. In other aspects, the present disclosure relates to methods, systems, and devices for selectively capturing biological nanoparticles on a coated planar surface, the capturing being facilitated by centrifugation.
The present disclosure provides nanostructures and nanostructure-based vaccines. Some nanostructures of the present disclosure display antigens capable of eliciting immune responses to infectious agents such as bacteria, viruses, and pathogens. Some vaccines of the present disclosure are useful for preventing or decreasing the severity of infection with an infectious agent, including, for example and without limitation, lyme disease, pertussis, herpes virus, orthomyxovirus, paramyxovirus, pneumovirus, filovirus, flavivirus, reovirus, retrovirus, meningococcus, or malaria. The antigens may be attached to the core of the nanostructure either non-covalently or covalently, including as a fusion protein or by other means disclosed herein. Multimeric antigens may optionally be displayed along a symmetry axis of the nanostructure. Also provided are proteins and nucleic acid molecules encoding such proteins, vaccine compositions, and methods of administration.
Nanoporous selective sol-gel ceramic membranes, selective-membrane structures, and related methods are described. Representative ceramic selective membranes include ion-conductive membranes (e.g., proton-conducting membranes) and gas selective membranes. Representative uses for the membranes include incorporation into fuel cells and redox flow batteries (RFB) as ion-conducting membranes.
B01D 69/00 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
B01D 71/00 - Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
Methods of uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs and/or cDNAs.
Provided herein is a crystalline form of a mesylate salt of (4R,75)-2-(3-(4- chlorophenyOureido)- 9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3- carboxamide, or solvate thereof wherein the mesylate salt has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 7.6 2-Theta, 10.6 2-Theta, 15.0 2-Theta, 16.0 2- Theta, 16.8 2-Theta, 17.7 2-Theta, 21.9 2-Theta, and 22.5 2-Theta. Further there are provided pharmaceutical compositions comprising the crystalline form and uses thereof.
A61K 31/439 - 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 the ring forming part of a bridged ring system, e.g. quinuclidine
The present disclosure provides binding proteins, such as TCRs, that specifically bind various tumor associated antigens (including human BRAFV600E epitope), cells expressing such antigen specific binding proteins, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells express BRAFV600E, such as in cancer.
An example plasma confinement system includes an inner electrode having a rounded first end that is disposed on a longitudinal axis of the plasma confinement system and an outer electrode that at least partially surrounds the inner electrode. The outer electrode includes a solid conductive shell and an electrically conductive material disposed on the solid conductive shell and on the longitudinal axis of the plasma confinement system. The electrically conductive material has a melting point within a range of 170 °C to 800 °C at 1 atmosphere of pressure. Related plasma confinement systems and methods are also disclosed herein.
G21B 1/05 - Thermonuclear fusion reactors with magnetic or electric plasma confinement
H05H 1/16 - Arrangements for confining plasma by electric or magnetic fields; Arrangements for heating plasma using applied electric and magnetic fields
INSTITUTE FOR RESEARCH IN BIOMEDICINE (Switzerland)
Inventor
King, Neil P.
Baker, David
Nickerson, Brooke
Stewart, Lance Joseph
Perez, Laurent
Lanzavecchia, Antonio
Marcandalli, Jessica
Abstract
Disclosed herein are nanostructures and their use, where the nanostructures include (a) a plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides; (b) a plurality of second assemblies, each second assembly comprising a plurality of identical second polypeptides, wherein the second polypeptide differs from the first polypeptide; wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form a nanostructures; and wherein the nanostructure displays multiple copies of one or more paramyxovirus and/or pneumovirus F proteins or antigenic fragments thereof, on an exterior of the nanostructure.
The present technology relates generally to methods and compositions for targeted nucleic acid sequence enrichment, as well as uses of such enrichment for error-corrected nucleic acid sequencing applications. In some embodiments, highly accurate, error corrected and massively parallel sequencing of nucleic acid material is possible using a combination of uniquely labeled strands in a double-stranded nucleic acid complex in such a way that each strand can be informatically related to its complementary strand, but also distinguished from it following sequencing of each strand or an amplified product derived therefrom. In various embodiments, this information can be used for the purpose of error correction of the determined sequence.
An example method includes directing gas, via one or more first valves, from within an inner electrode to an acceleration region between the inner electrode and an outer electrode that substantially surrounds the inner electrode, directing gas, via two or more second valves, from outside the outer electrode to the acceleration region, and applying, via a power supply, a voltage between the inner electrode and the outer electrode, thereby converting at least a portion of the directed gas into a plasma saving a substantially annular cross section, the plasma flowing axially within the acceleration region toward a first end of the inner electrode and a first end of the outer electrode and, thereafter, establishing a Z-pinch plasma that flows between the first end of the outer electrode and the first end of the inner electrode. Related plasma confinement systems and methods are also disclosed herein.
The instant disclosure provides biomarkers and methods for identifying subjects at risk of developing cytokine release syndrome (CRS), neurotoxicity, or both after adoptive immunotherapy to guide preemptive intervention, modified therapy, or the like. For example, adverse event biomarkers may be measured in a subject before pre-conditioning chemotherapy, before immunotherapy (e.g., adoptive immunotherapy infusion comprising a chimeric antigen receptor (CAR) modified T cell), or shortly after pre-conditioning chemotherapy and/or immunotherapy. Exemplary biomarkers include temperature, cytokine levels and endothelial activation biomarkers, such as angiopoietin 2, von Willebrand factor (vWF), ratio of angiopoietin 2 to angiopoietin 1, and ratio of ADAMTS13 to vWF. Also provided are methods of treating subjects identified as at risk of developing cytokine release syndrome (CRS), neurotoxicity, or both to minimize such potential adverse events.
The present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.
Eyeglasses are disclosed that include eyeglass frames and a pair of ophthalmic lenses mounted in the frames. The lenses include a dot pattern distributed across each lens, the dot pattern including an array of dots spaced apart by a distance of 1 mm or less, each dot having a maximum dimension of 0.3 mm or less, the dot pattern including a clear aperture free of dots having a maximum dimension of more than 1 mm, the clear aperture being aligned with a viewing axis of a wearer of the pair of eyeglasses.
The present disclosure provides organic-inorganic hybrid polymer particles, which have desirable surface chemistry and optical properties that make them particularly suitable for biological and optical applications. The present disclosure also provides methods of making organic-inorganic hybrid polymer particles. The present disclosure also provides methods of using the organic-inorganic hybrid polymer particles for biological and optical applications.
The present disclosure provides nanoparticle transducers and methods of use thereof for the detection of analyte concentrations in a fluid. Nanoparticle transducers can comprise a nanoparticle, such as a Pdot, coupled to an enzyme that catalyzes a reaction with the analyte. The nanoparticle transducers further comprise chromophores that emit fluorescence that varies as a function of the concentration of one of the elements of the reaction. The nanoparticle transducer thus changes fluorescence as the analyte concentration changes, transforming analyte concentration values into fluorescence intensities. The measurement of these intensities provides a measurement of the analyte concentration. The nanoparticle transducers are biocompatible, allowing for use in vivo, for the monitoring of analyte blood concentrations such as blood glucose concentrations.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
B82Y 15/00 - Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
C09K 11/02 - Use of particular materials as binders, particle coatings or suspension media therefor
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12N 9/00 - Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
C12N 11/00 - Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
C12Q 1/54 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.
The present invention relates to the use of at least one biomarker for predicting the severity of a disease caused by the infection of an individual with an influenza virus, wherein said biomarker is selected in a group comprising (i) the alpha diversity value of the microbiome present in a respiratory sample of said individual and (ii) the microbiome profile of the said respiratory sample.
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
UNIVERSITY OF WASHINGTON (USA)
Inventor
Garcia, Kenan Christopher
Sockolosky, Jonathan
Baker, David
King, Chris
Abstract
Engineered orthogonal cytokine receptor/ligand pairs, and methods of use thereof, are provided. Specifically, the disclosure provides a system for selective activation of a receptor in a cell, the system comprising: (a) an orthogonal receptor, which does not bind to its native ligand; and (b) an orthogonal cytokine, which (i) does not bind to its native receptor and (ii) binds to and activates the orthogonal receptor. Further disclosed are methods of using an engineered cell population for treating disorders.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 5/071 - Vertebrate cells or tissues, e.g. human cells or tissues
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
80.
A SYSTEM AND METHOD FOR DIRECT-SAMPLE EXTREMELY WIDE BAND TRANSCEIVER
Systems and methods for direct sample, extremely wideband transceivers are disclosed. An example transceiver includes an antenna, an N bit analog to digital converter a digital signal processor, a digital to analog converter, and an adder. The N bit ADC receives a wideband RF input signal from the antenna, where the input signal includes weak signals and a strong signal, oversamples the input signal and provides a digital sample signal. The digital signal processor generates a digital cancelation signal from the digital sample signal, where the digital cancellation signal is generated using M bits, M greater than N. The DAC provides an analog cancellation signal based on the digital cancellation signal, and the adder provides a residual analog signal from the addition of the input signal and the analog cancellation signal, where the strong signal is at least reduced in the residual analog signal due to the analog cancellation signal.
H04B 1/38 - Transceivers, i.e. devices in which transmitter and receiver form a structural unit and in which at least one part is used for functions of transmitting and receiving
Polypeptides, and methods for their use, are disclosed that have an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO: 1, are provided, wherein (a) the polypeptide degrades a PFQPQLPY (SEQ ID NO: 140) peptide and/or a PFPQPQQPF (SEQ ID NO: 68) at pH 4; (b) residue 467 is Ser, residue 267 is Glu, and residue 271 is Asp; and (c) the polypeptide comprises an amino acid change from SEQ ID NO: 1 at one or more residues selected from the group consisting of 221, 262E, 268, 269, 270, 319A, 320, 354E/Q/R/Y, 358S/Q/T, 368F/Q, 399, 402, 406, 424, 449, 461, 463, 105, 171, 172, 173, 174, and 456.
An expression vector capable of disrupting the silencing of cell cycle genes in adult cells, such as adult cardiac myocytes and other quiescent cells in terminally differentiated tissues, comprising: (a) a nucleic acid sequence encoding lysine-specific demethylase 4D (KDM4D); (b) a promoter that induces or effects overexpression of KDM4D, wherein the promoter is operably linked to the nucleic acid sequence; and (c) a regulatory element that inducibly represses the overexpression of KDM4D. The vector can be administered to a subject in a method for inducing tissue-specific hyperplasia in a mammal, including cardiomyocyte proliferation. The method provides for regenerative therapy, including improving cardiac function after myocardial infarct and other forms of cardiac damage.
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
A protective helmet comprises an inner layer and an outer layer separated from the inner layer by a space. An interface layer is positioned in the space between the inner layer and the outer layer and includes an impact absorbing material that non-linearly deforms in response to an incident force on the protective helmet. For example, the impact absorbing material includes multiple filaments each having an end proximate to the inner layer and another end proximate to the outer layer interface, with the filaments configured to non- linearly deform in response to an incident force on the helmet.
Methods and compositions are provided for intravitreally delivering a polynucleotide to cone photoreceptors. Aspects of the methods include injecting a recombinant adeno-associated virus comprising a polynucleotide of interest into the vitreous of the eye. These methods and compositions find particular use in treating ocular disorders associated with cone dysfunction and/or death.
Methods and reagents for determining a subject's predisposition for refractive error based on the presence of opsin gene exon 3 splicing defects are provided. In one aspect, the invention provides methods for determining a subject's predisposition for refractive error comprising: (a) testing a biological sample obtained from the subject to determine exon 3 splicing defects in one or more opsin gene; and (b) correlating the exon 3 splicing defects in the one or more opsin gene with a predisposition for refractive error.
Compounds of Formula (I) and use of the compounds for preventing or treating sensory hair cell death in an individual, wherein the sensory hair cell death is associated with exposure to an ototoxic agent. Z is a single bond. Ri is aryl or heteroaryl, optionally substituted with R4. R2 is H, Ci-Colkyl, Ci-C6alkyl- 0R8, C1-C6alkylC3-C8cycloalkyl, C1-C6alkylC2-C7heterocycloalkyl, Ci-Colkyl- CO2R8, optionally substituted Ci-Colkylaryl, or optionally substituted Ci-Colkylheteroaryl. R3 and R6 are each H. Each R4 is independently F, CI, Br, I, -CN, -NO2, -CF3, -0R9, -0CF3, -NR8R9, - C(0)Rio, -0O2R9, -C(0)NR8R9, -N(R8)C(0)Rio, -N(R8)CO2R10, -NHS(0)2Rio, -S(0)2NR8R9, Ci-Colkyl, C3-C8cycloalkyl, C1- C8heteroalkyl, C1-C8haloalkyl, C2-C7heterocycloalkyl, aryl, or heteroaryl. R6 is H or Ci-Colkyl. R8 is H or Ci-Colkyl. R9 is H, Ci-Colkyl, C3-C8cycloalkyl, C2-C7heterocycloalkyl, aryl, heteroaryl, Ci-Colkylaryl, or Ci-Colkylheteroaryl. Rio is Ci-Colkyl, C3-C8cycloalkyl, C2- C7heterocycloalkyl, aryl, heteroaryl, Ci- Colkylaryl, or Ci-Colkylheteroaryl. Rii is H, Ci-Colkyl, Ci-C8haloalkyl, C3- C8cycloalkyl, C2- C7heterocycloalkyl, aryl, heteroaryl, Ci-ColkylC3-C8cycloalkyl, Ci-Colkylaryl, or Ci-Colkylheteroaryl. Ri2 is H, Ci-Colkyl, Ci-C8haloalkyl, C3-C8cycloalkyl, C2-C7heterocycloalkyl, aryl, heteroaryl, Ci- C6alkylC3-C8cycloalkyl, Ci-Colkylaryl, or Ci-Colkylheteroaryl; or Ril and Ri2 together with nitrogen form an optionally substituted C2-C7heterocycloalkyl ring. Ri3 and Ri4 are each H.
A61K 31/4743 - Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having sulfur as a ring hetero atom
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
The present disclosure is directed to compositions and methods for inhibiting either Toxoplasma gondii (T. gondii) calcium dependent protein kinases (TgCDPKs) or Cryptosporidium parvum (C. parvum) and Cryptosporidium hominus (C. hominus) calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the Formula (I), wherein the variables X, Y, Z, R1, and R3 are defined herein.
Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.
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
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A baffled ram accelerator system includes a ram accelerator tube with an inner surface and an outer surface and a plurality of baffles disposed on the inner surface. The plurality of baffles forms a sequential series of propellant chambers along the longitudinal axis of the ram accelerator tube. An accelerator gun is also disposed on an input end of the ram accelerator tube, and the accelerator gun is positioned to fire a projectile into the ram accelerator tube.
F41A 1/02 - Hypervelocity missile propulsion using successive means for increasing the propulsive force, e.g. using successively initiated propellant charges arranged along the barrel length; Multistage missile propulsion
A baffled ram accelerator system includes a ram accelerator tube with an inner surface and an outer surface and a plurality of baffles disposed on the inner surface. The plurality of baffles forms a sequential series of propellant chambers along the longitudinal axis of the ram accelerator tube. An accelerator gun is also disposed on an input end of the ram accelerator tube, and the accelerator gun is positioned to fire a projectile into the ram accelerator tube.
F41A 1/02 - Hypervelocity missile propulsion using successive means for increasing the propulsive force, e.g. using successively initiated propellant charges arranged along the barrel length; Multistage missile propulsion
B64G 1/40 - Arrangements or adaptations of propulsion systems
B64G 5/00 - Ground equipment for vehicles, e.g. starting towers, fuelling arrangements
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
Inventor
Garcia, Kenan Christopher
Baker, David
Janda, Claudia Yvonne
Dang, Luke
Moody, James Daniel
Abstract
Wnt signaling agonist compositions and methods for their use are provided. Wnt signaling agonists of the invention comprise a frizzled binding moiety, which is fused or conjugated to an LRP5 or LRP6 binding moiety.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.
A wireless power transfer system (100) includes a transmitter (110) configured to transmit power to a receiver ( 120), for example, through coupled resonators (111,121). The transmitter receives feedback from the receiver, and uses the feedback to control the power transmission, to control a parameter at the receiver, for example, a rectified voltage output by the receiver. The feedback to the transmitter may be provided, for example, by an out-of-band radio system ( 117, 126) between the transmitter and receiver, by a reflection coefficient at the transmitter (116), and/or by an encoded modulation of power in the receiver, for example, in an impedance matching module (121). The transmitter may control the transmitted power, for example, by controlling a transmitter signal generator voltage (VSIG), a transmitter gate driver voltage (VGD), a transmitter amplifier voltage (VpA), and/or an impedance setting in a transmitter impedance matching module (111).
H02J 50/12 - Circuit arrangements or systems for wireless supply or distribution of electric power using inductive coupling of the resonant type
H02J 50/80 - Circuit arrangements or systems for wireless supply or distribution of electric power involving the exchange of data, concerning supply or distribution of electric power, between transmitting devices and receiving devices
94.
METHODS OF DETERMINING TISSUES AND/OR CELL TYPES GIVING RISE TO CELL-FREE DNA, AND METHODS OF IDENTIFYING A DISEASE OR DISORDER USING SAME
The present disclosure provides methods of determining one or more tissues and/or cell-types contributing to cell-free DNA ("cfDNA") in a biological sample of a subject. In some embodiments, the present disclosure provides a method of identifying a disease or disorder in a subject as a function of one or more determined more tissues and/or cell-types contributing to cfDNA in a biological sample from the subject.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
C40B 20/00 - Methods specially adapted for identifying library members
C40B 50/06 - Biochemical methods, e.g. using enzymes or whole viable microorganisms
95.
PRODUCTION OF ENGINEERED T-CELLS BY SLEEPING BEAUTY TRANSPOSON COUPLED WITH METHOTREXATE SELECTION
SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE) (USA)
UNIVERSITY OF WASHINGTON (USA)
Inventor
Jensen, Michael C.
Pun, Suzie
Kacherovsky, Nataly
Abstract
Aspects of the invention described herein include methods of treating, inhibiting, ameliorating and/or eliminating a virus or cancer cells in a subject utilizing genetically engineered human T-cells having receptors for a molecule presented by the virus or the cancer cells, wherein the genetically engineered T cells are isolated utilizing a two-stage MTX selection that employs increasing concentrations of MTX.
The present disclosure provides a polynucleotide cassette for enhanced expression of a transgene in cone cells of a mammalian retina, comprising (a) a promoter region consisting of a truncated M-opsin promoter having a sequence identity of 85% or more over its full length to SEQ ID NO: 80 or a functional fragment thereof (b) a coding sequence operatively linked to the promoter region and (c) a polyadenylation site operatively linked to the coding sequence.
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
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 15/08 - Cells resulting from interspecies fusion
INSITU, INC. (A SUBSIDIARY OF THE BOEING COMPANY) (USA)
UNIVERSITY OF WASHINGTON (USA)
Inventor
Arbeit, Amy C.
Lum, Christopher W.
Abstract
A method of planning a flight path for a search can include receiving, by a control system, an indication of a search area boundary; receiving, by the control system, an indication of a selected search pattern; determining, by the control system, a flight path based on the search area boundary and the selected search pattern; and transmitting one or more indications of the flight path to an unmanned aerial vehicle.
Substrates are provided that include compounds suitable for detecting the activity of an enzyme such as a lysosomal storage enzyme where the substrates include: a sugar moiety; a linker moiety allowing the conjugation of sugar moiety with the remaining structure of the substrate; and two or more fatty acid chains or derivatives thereof at least one of which is sufficiently structured to provide improved solubility in aqueous or organic solvent systems. Also provided are methods for using substrates for detecting enzymatic activity using the inventive substrates.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
99.
CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit Rl -encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Alternatively, viral vector(s) having the Rl and R2-encoding construct(s) are administered to the mammal directly. Overexpression of Rl and R2 subunits leads to formation of the RR complex, which in turn generates dATP. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q-substituted, I61Q-substituted, or L57Q-substituted cTnC variant. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing Rl and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes.
Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.
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
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