Abstract

A wearable robotic device, called linear exoskeleton, is provided. The linear exoskeleton applies active assistance to reduce the knee contact forces during walking. The objective of the exoskeleton is to reduce knee contact force by using a motor to apply forces between a strap on the thigh and the ground. The force applied is controllable. The exoskeleton itself has a linear actuator type design, with a carriage that slides along a carbon pole.

IPC Classes  ?

• A61F 2/70 - Operating or control means electrical
• A61H 3/00 - Appliances for aiding patients or disabled persons to walk about
• A63B 23/035 - Exercising apparatus specially adapted for particular parts of the body for limbs, i.e. upper or lower limbs, e.g. simultaneously
• B25J 9/00 - Programme-controlled manipulators

Abstract

In exemplary methods, diamond is grown al low-temperature (e g., under 600° C or under 400° C) is grown. In one aspect, the method includes controlling growth of the diamond, during the diamond growth, by a gas chemistry that abates sp2 carbon formation and enhances diamond grain sizes in both lateral and vertical directions in the diamond while mitigating new diamond grains from forming on top of each other. As another aspect, the low-temperature diamond is grown on a wafer including one or more Si-based semiconductor devices adjacent and sufficiently close to a hot spot in a channel region of the semiconductor device(s) to cause, during operation of the semiconductor device(s), heat to be drawn from multiple sides of the hot spot, without undermining performance during operation of the semiconductor device(s).

Abstract

The present invention provides modified oligo(dT) primers containing at least one deliberate mismatch within the dT span of the primer which provides improved stability and replicability of the resulting cDNA molecules. In the context of RNA sequencing applications, incorporation of the modified oligo(dT) primers results in fewer sequence reads lost to PCR artifacts and easier detection of the end position of each sequence read.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6841 - In situ hybridisation

Abstract

Provided herein is a method that involves lysing cells that have a fusion between a first gene and a second gene at an end of an electrophoresis gel, applying a voltage potential to the gel to intact genomic DNA at one end of the gel, digesting the trapped genomic DNA using two or more pairs of RNA-guided endonucleases to release segments, electrophoresing the segments, eluting the segments into different fractions and analyzing the sequences nucleic acid collected in the fractions to identify a fraction that contains the segments of the first and second genes and a fraction that contains the segment of the gene fusion.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• G01N 27/447 - Systems using electrophoresis
• C12N 15/62 - DNA sequences coding for fusion proteins
• C12N 15/09 - Recombinant DNA-technology

Abstract

The present invention provides a set of robust, genetic-based assays to screen for common abnormalities that occur in cultured cells utilizing a digital PCR (dPCR) platform.

IPC Classes  ?

• C12Q 1/686 - Polymerase chain reaction [PCR]

Abstract

222, and methane. The gas recovered from an off-gas collection system is beneficially used, such as for energy recovery while minimizing greenhouse gas emissions.

IPC Classes  ?

• C02F 3/12 - Activated sludge processes
• B01D 53/62 - Carbon oxides

Abstract

Organoid culture and image-processing methods and systems are described. Such methods and systems provide the ability for high-throughput characterization of a variety of phenotypes at single-organoid resolution.

IPC Classes  ?

• C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
• C12N 5/07 - Animal cells or tissues

Abstract

Methods are provided for the classification, diagnosis, and/or prognosis of an individual who has PD or is suspected to have PD. The method comprises obtaining one or more biological samples from an individual who has or is suspected to have PD, quantifying the amount of one or more PD related polypeptides in the one or more biological samples, and integrating the results of the quantifying step with the age and sex of the individual from whom the biological sample was obtained from to generate a metric that indicates if that individual has PD wherein the integration is performed by a computer comprising software components for data analysis as a program of instructions executable by the computer.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
• A61P 25/16 - Anti-Parkinson drugs
• C12N 9/88 - Lyases (4.)
• G01N 33/53 - Immunoassay; Biospecific binding assay; Materials therefor
• G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid

Abstract

The present invention provides methods and related compositions for producing a sequencing ready DNA library in as few as three steps by combining adapter ligation, degradation, fill-in, and amplification of adapter-DNA fragments into a single reaction.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay

Abstract

inter aliainter alia, a copolymer, cell penetrating complexes, compositions and methods for the delivery of therapeutic, including small interfering RNA-based therapeutic agents, into a cell and related methods for treating cancer, including breast cancer and triple-negative breast cancer.

IPC Classes  ?

• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 47/59 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes

Abstract

Methods, systems, and devices, including computer programs encoded on a computer storage medium are provided for optimizing neurostimulation therapy for treatment of neurological and neurodegenerative diseases. Joint dynamic causal modeling and biophysics modeling are used for optimization of the stimulation targets and parameters. In particular, methods of performing neuromodulation to suppress b-band oscillations in the brain of a subject are provided.

Abstract

Methods, systems, and devices, including computer programs encoded on a computer storage medium are provided for optimizing neurostimulation therapy for treatment of neurological and neurodegenerative diseases. In particular, an algorithm is used to provide a predicted regional pathological density map of neuropathology and predict locations of future spreading. Neurostimulation therapy parameters including the location, strength, and frequency of neurostimulation can be adjusted accordingly to treat neuropathology and reduce aggregation and spreading.

IPC Classes  ?

• 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
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• G16H 30/00 - ICT specially adapted for the handling or processing of medical images

Abstract

Compositions, methods, and kits are provided for diagnosing vitreoretinal diseases and age-related pathologies. In particular, aqueous humor biomarkers have been identified that correlate with biological aging and age-related pathologies and morbidity. The use of such biomarkers may allow earlier intervention in treatment of aging-related diseases. In addition, methods of using aqueous humor biomarkers for prognosis, diagnosis, and monitoring treatment of vitreoretinal diseases are also provided.

Abstract

Provided herein are methods for screening edited genomic sequences for their effect on expression of a target gene, and for designing a target sequence edit for introducing to a target sequence of a nucleic acid molecule. Also provided are compositions and cells including the edited sequences, and methods for their use in preventing or treating a disease.

IPC Classes  ?

• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Abstract

A Purcell enhanced metamaterial scintillator structure comprises a conducting structure and a dielectric structure disposed adjacent to the conducting structure. The dielectric structure comprises a structure of scintillating nanoparticles.

IPC Classes  ?

• G01T 1/202 - Measuring radiation intensity with scintillation detectors the detector being a crystal
• B82Y 20/00 - Nanooptics, e.g. quantum optics or photonic crystals
• C09K 11/66 - Luminescent, e.g. electroluminescent, chemiluminescent, materials containing inorganic luminescent materials containing germanium, tin or lead

Abstract

The present disclosure provides methods of treating an individual for a muco-obstructive, the methods including: administering to the individual a b-adrenergic agonist or an adenylate cyclase activator, in combination with a cholinergic agonist to treat the individual for the muco-obstructive disorder.

IPC Classes  ?

• A61P 11/08 - Bronchodilators
• A61K 31/06 - Phenols the aromatic ring being substituted by nitro groups
• A61K 31/14 - Quaternary ammonium compounds, e.g. edrophonium, choline
• A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

An independent control method of actuators in for example an everting robot or a soft everting robot is provided. The robot has distributed thereto or therewith multiple actuators which steer the robot. Energy is supplied from a single energy line to each of the multiple actuators. This energy enables force and displacement for each of the multiple actuators. Energy from the single energy line to each of the multiple actuators is controlled by a single control line. The single energy line and the single control line can be pneumatic sources or electric sources. The method allows for controlling greater than two actuators with at most two supply lines instead of one supply line per actuator. Reduction of the number of supply lines and complexity of subsystems provides numerous advantages in terms of cost, size, stiffness, friction, amount of material used, ease for tip mounts as well as mobility.

IPC Classes  ?

• B25J 18/02 - Arms extensible
• B25J 18/06 - Arms flexible
• B25J 9/06 - Programme-controlled manipulators characterised by multi-articulated arms
• B25J 9/14 - Programme-controlled manipulators characterised by positioning means for manipulator elements fluid
• D06G 3/04 - Turning inside-out flexible tubular or other hollow articles pneumatically
• F01B 19/04 - Positive-displacement machines or engines of flexible-wall type with tubular flexible members

Abstract

Methods of treating a subject for a cellular proliferative disease, e.g., a cancer, are provided. Aspects of the methods include: administering to the subject an agent that modulates DSIF complex activity, e.g., activity of a DSIF complex made up of a SPT4 and SPT5 protein, such as a DSIF complex made up of Supt4h and Supt5h, in a manner sufficient to treat the subject for the cellular proliferative disease. Also provided are compositions for practicing the methods.

IPC Classes  ?

• 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 35/00 - Antineoplastic agents
• C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum

Abstract

Embodiments herein describe systems and methods to generate a risk score for an individual to develop postoperative neurocognitive disorder (POND). Various embodiments obtain multi-omics data from an individual, such as genomics, transcriptomics, and proteomics. In certain embodiments, a machine learning algorithm is used to generate the risk score based on the multi-omics data. In further embodiments, clinical data is further used in the determination of the risk score.

IPC Classes  ?

• G06N 20/20 - Ensemble learning
• G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• 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
• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers

Abstract

A method for assessing fatigue of a subject is provided. The method includes providing a device comprising a first electrode, a second electrode, and a circuit operably coupled to the first and second electrodes, the first and second electrodes configured to detect an electrical activity associated with an eye blink of a subject, and the circuit is configured to process a signal from the first electrode and the second electrode; determining a blink event based on the electrical activity; and assessing a degree of fatigue of the subject, based on the blink event. A headset including circuitry, such as a processor and a memory storing instructions to cause the headset to perform the above method are also provided. Also provided are systems and kits that include the devices. The methods, devices, headsets, systems and kits find use in a variety of different applications.

IPC Classes  ?

• A61B 5/11 - Measuring movement of the entire body or parts thereof, e.g. head or hand tremor or mobility of a limb
• A61B 5/16 - Devices for psychotechnics; Testing reaction times
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• A61B 5/18 - Devices for psychotechnics; Testing reaction times for vehicle drivers

Abstract

Provided herein are retroviral vector systems useful for producing universal pseudotyped retroviruses for cell and gene therapies. The vector systems include an envelope plasmid and a packaging plasmid, where at least one of these plasmids encodes a binding moiety that directly binds a target cell through a cell binding domain, or that indirectly binds a target cell through an antibody binding domain. Also provided are related retrovirus-packaging cells, retroviruses, virus-like particles, and methods for their production and use in preventing or treating a disease.

IPC Classes  ?

• C12N 15/867 - Retroviral vectors
• A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links

Abstract

Provided herein are compositions and methods for modifying T cells.

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Abstract

Provided are fusion proteins including an amino acid sequence of an ectodomain of Spike protein of a coronavirus, such as SARS-CoV-2, joined to an amino acid sequence of a ferritin subunit polypeptide. Nanoparticles including such fusion proteins, with surface-exposed trimers of the ectodomain of the Spike protein of the coronavirus, are also provided. Also provided are nucleic acids and vectors encoding the fusion proteins, cells containing such nucleic acid and vectors, immunogenic compositions including the fusion proteins, the nanoparticles, or the vectors, as well as corresponding methods and kits.

IPC Classes  ?

• C07K 14/165 - Coronaviridae, e.g. avian infectious bronchitis virus
• A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

Methods for treating a neuropsychiatric disorder by administering an iboga alkaloid and a cardioprotective agent in conjunction with analysis of brain image data is described. Also described are methods to improve brain health and to slow or reverse brain aging by disorder by administering an iboga alkaloid and a cardioprotective agent, where analysis of brain image data is used to monitor and/or evaluate treatment effectiveness.

IPC Classes  ?

• A61P 25/00 - Drugs for disorders of the nervous system
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 31/435 - 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
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 9/06 - Antiarrhythmics
• A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
• 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

Abstract

Provided are nucleic acids encoding kinase-modulated bioluminescent indicator (KiMBI) polypeptides. In certain embodiments, a nuclei acid of the present disclosure encodes a KiMBI polypeptide comprising a first bioluminescent enzyme fragment, a phospho-binding domain, a 5 second bioluminescent enzyme fragment capable of forming an active bioluminescent enzyme with the first fragment via enzyme fragment complementation, and a kinase substrate bound by the phospho-binding domain when phosphorylated. KiMBI polypeptide may be fused to one or more fluorescent proteins, e.g., which exhibit resonance energy transfer (RET). Also provided are KiMBI polypeptides encoded by the nucleic acids of the present disclosure. Cells that express 10 a KiMBI polypeptide are also provided, as are non-human animals comprising such cells. Also provided are methods of assessing activity of a kinase of interest in a non-huma animal, and methods of assessing a test agent for the ability to inhibit a kinase of interest in a non-human animal.

IPC Classes  ?

• G01N 21/76 - Chemiluminescence; Bioluminescence
• C12Q 1/66 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving luciferase
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• 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
• C12N 9/12 - Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)

Abstract

Compositions comprising an iboga alkaloid and a cardioprotective agent are provided. Use of the compositions in treating neuropsychiatric disorders are described, where the cardioprotective agent is administered before, during and/or after the iboga alkaloid.

IPC Classes  ?

• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61K 31/13 - Amines, e.g. amantadine
• A61K 31/135 - Amines, e.g. amantadine having aromatic rings, e.g. methadone
• 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 36/185 - Magnoliopsida (dicotyledons)
• A61K 31/33 - Heterocyclic compounds

Abstract

Laser feedback stabilization combined with isolation is provided in an integrated approach. The main element is a high quality factor resonator that acts as a circulator under high optical power due to the Kerr nonlinearity. This resonator can then be coupled to a laser or optical gain media to provide isolation and combined with a feedback path to stabilize the lasing mode.

IPC Classes  ?

• H01S 3/13 - Stabilisation of laser output parameters, e.g. frequency or amplitude
• H01S 3/08 - Construction or shape of optical resonators or components thereof
• G02F 1/35 - Non-linear optics
• H03G 3/12 - Manually-operated control in untuned amplifiers having semiconductor devices incorporating negative feedback

Abstract

The present disclosure provides methods for treating a disease or disorder or enhancing phagocytosis of a target cell. The methods comprise administering or contacting an immune cell with an inhibitor of paired immunoglobulin-like type 2 receptor-alpha (PILRA).

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents
• 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

Abstract

The present embodiments relate generally to stable cycling of metallic lithium under high current densities and realistic cell conditions based on a flower-like nanostructured hard carbon host (CF). In embodiments, CF is both intercalated with lithium ions and plated with lithium metal to render a hybrid lithium-ion/lithium-metal anode capacity. The hybrid cells showed >99% CE up to 12 mA/cm2(4 mAh/cm2) and >99.5% CE up to 16 mA/cm2(2.5 mAh/cm2) with commercial carbonate electrolyte. The stability of the hybrid anodes was attributed to uniform lithium plating morphology and fast ion diffusion pathways enabled by the open-pore nanostructures of CF. Moreover, the CF||NMC811 hybrid cells (2 mAh/cm2) showed excellent performance (~70% capacity retention after 200 cycles, 100% SOC, room temperature) at 10 mA/cm2 current densities (<20 min charging for 100% SOC), while demonstrating ~4 times anode specific capacity and much better cyclic stability compared to graphite] |NMC lithium-ion cells at such current.

IPC Classes  ?

• H01M 10/052 - Li-accumulators
• H01M 10/058 - Construction or manufacture
• H01M 4/13 - Electrodes for accumulators with non-aqueous electrolyte, e.g. for lithium-accumulators; Processes of manufacture thereof
• H01M 4/139 - Processes of manufacture
• H01M 4/36 - Selection of substances as active materials, active masses, active liquids
• H01M 4/62 - Selection of inactive substances as ingredients for active masses, e.g. binders, fillers
• H01M 4/02 - Electrodes composed of, or comprising, active material

Abstract

in vivo ex vivo ex vivo delivery of a molecular cargo into endo-lysosomal compartments of LRP1-expressing cells. A molecular cargo of interest is linked to a substrate or inhibitor for recognition and transport via human transglutaminase 2 (TG2).

IPC Classes  ?

• A61K 38/45 - Transferases (2)
• A61K 38/43 - Enzymes; Proenzymes; Derivatives thereof
• C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
• 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
• C12N 9/48 - Hydrolases (3.) acting on peptide bonds, e.g. thromboplastin, leucine aminopeptidase (3.4)
• C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin

Abstract

A salt-philic solvent-phobic (SP2) polymer coating on a lithium anode, sodium anode, or a silicon anode selectively transports salt over solvent and is configured to promote salt-derived SEI formation on the anode. The SP2 coating can include a polymer backbone, a first side chain comprising a first moiety having salt affinity, and a second side chain comprising a second moiety immiscible with polar aprotic solvents.

IPC Classes  ?

• C09D 7/20 - Diluents or solvents
• C09D 201/00 - Coating compositions based on unspecified macromolecular compounds
• C08G 77/04 - Polysiloxanes
• C08F 220/06 - Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
• H01M 4/62 - Selection of inactive substances as ingredients for active masses, e.g. binders, fillers
• H01M 4/134 - Electrodes based on metals, Si or alloys
• H01M 10/052 - Li-accumulators
• H01M 4/02 - Electrodes composed of, or comprising, active material

Abstract

Methods and systems are presented for using optical parametric amplifiers in various ways that enhance a native quadratic coupling strength so that a photonic component of interest can be measured or otherwise observed without demolishing the component of interest at a system output. For example such components may include a number of signal Bogoliubov excitations, a pump modular quadrature, or a signal quadrature squared.

IPC Classes  ?

• G06N 10/40 - Physical realisations or architectures of quantum processors or components for manipulating qubits, e.g. qubit coupling or qubit control
• G02F 1/35 - Non-linear optics
• G06N 10/20 - Models of quantum computing, e.g. quantum circuits or universal quantum computers
• B82Y 10/00 - Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• G06N 10/60 - Quantum algorithms, e.g. based on quantum optimisation, or quantum Fourier or Hadamard transforms
• G06N 10/80 - Quantum programming, e.g. interfaces, languages or software-development kits for creating or handling programs capable of running on quantum computers; Platforms for simulating or accessing quantum computers, e.g. cloud-based quantum computing

Abstract

Provided are methods of assessing an enzyme for plastic-degrading activity. In certain embodiments, the methods comprise contacting a plastic with the enzyme under conditions suitable for plastic-degrading enzyme activity, and assessing for degradation of the plastic by the enzyme. Also provided are plastic-degrading enzymes and methods of using the same. As a non-limiting example, the plastic-degrading enzymes are polyester-degrading enzymes. As an example, polylactic acid (PLA)-degrading enzymes and methods of using the same. As another example, polyethylene terephthalate (PET)-degrading enzymes and methods of using the same.

IPC Classes  ?

• C12N 15/52 - Genes encoding for enzymes or proenzymes
• C08J 11/10 - Recovery or working-up of waste materials of polymers by chemically breaking down the molecular chains of polymers or breaking of crosslinks, e.g. devulcanisation
• C12N 9/18 - Carboxylic ester hydrolases

Abstract

Compositions and methods are provided for preventing or treating obesity and/or overweight, and managing body weight. Compositions comprise partial agonists of the leptin receptor (lepr), including variant leptin polypeptides, which partial agonists elicit sub-maximal signaling at saturating ligand concentrations, and bias the response to STAT3 signaling. Human leptin protein variants, for example leptin modified to increase affinity at site 2 binding site(s) and decrease binding at site 3 binding site(s), preferentially suppress phosphorylation of SHP2, ERK, and STAT1 relative to STAT3, resulting in a biased signal that selectively activates pathways associated with satiety, with decreased activation of pathways associated with leptin resistance. The variant proteins find use in the suppression of appetite, and can provide for therapeutic weight loss.

IPC Classes  ?

• A61K 38/22 - Hormones
• C07K 14/57 - IFN-gamma
• A61P 3/04 - Anorexiants; Antiobesity agents
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Abstract

Ballistic microscopy - a completely new approach to " image" a cell utili zing particle bombardment, is described. These are ballistic micro and nano particles that travel through a cell at ballistic speed and capture a pico or femto-liter of cellular content and bring it out for analysis without harming the cell. This enables a new approach to omics-based imaging where millions of these particles are bombarded on cells with resolved space and time and captured to process using well known omics techniques including proteomics (mass spec ) or sequencing - while keeping the spatial and temporal resolution. This work provides - for the first time - a way to resolve atomic details of live cells without any labels.

IPC Classes  ?

• A61K 51/12 - Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• C12N 5/04 - Plant cells or tissues
• C12N 5/07 - Animal cells or tissues
• G01N 33/483 - Physical analysis of biological material
• G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals

Abstract

Compositions, methods, and kits are provided for treating infections and cancer with metallic nanoclusters. In particular, metallic nanoclusters having a size of less than 10 nm that are conjugated to adenosine triphosphate (ATP) or an analogue thereof can be used to eradicate a cell in a growth arrest phase such as infectious bacterial or fungal cells. Such nanoclusters can also induce endoplasmic reticulum stress and inhibit growth of cancerous cells. Additionally, such metallic nanoclusters can be used to inhibit a purinergic P2X7 receptor and FtsH protease.

IPC Classes  ?

• 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

Abstract

Compositions and methods for treating a cardiomyopathy, such as dilated cardiomyopathy (DCM) are provided. Embodiments of the present disclosure provide compositions having a bisphosphonate compound, wherein the compound acts as a structure-based corrector therapeutic by targeting a genetic mutation associated with familial DCM.

IPC Classes  ?

• A61K 31/66 - Phosphorus compounds
• A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61K 9/14 - Particulate form, e.g. powders
• 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

Abstract

The present disclosure provides a versatile and multi-functional platform for transcriptome regulation using the RNA-guided, RNA-targeting activity of type VI-D CRISPR effectors with RNA-guided RNA endonuclease activity combined with guide arrays that express a plurality of guide RNAs. The system can be used to perform quantitative, reversible, and massively-multiplexed gene knockdown in primary human T cells and to perform multiplexed suppression of exhaustion-associated genes in T cells. The system can be used to enhance the anti-tumor activity of dysfunctional CAR T cells.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

Provided are nucleic acids encoding chimeric cytokine receptors (CCRs) capable of signaling in the absence of their cognate cytokines. In some embodiments, provided are one or more nucleic acids encoding a first subunit of a chimeric cytokine receptor and a second subunit of the chimeric cytokine receptor. The first subunit comprises a first heterologous dimerization domain and a first cytokine receptor intracellular signaling domain (ICD). The second subunit comprises a second heterologous dimerization domain cognate for the first heterologous dimerization domain, and a second cytokine receptor ICD. The CCRs find use in a variety of contexts, including but not limited to, increasing the persistence of therapeutic cells. Accordingly, also provided are methods of administering a cell-based therapy, the methods comprising administering therapeutic cells (e.g., CAR-T cells, etc.) expressing the CCRs to a subject in need thereof.

IPC Classes  ?

• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Abstract

A system described herein can perform lightweight data compression that optimizes an embedded database for high-performance throughput, low memory usage, and fast query/response times. The embedded compression and decompression can be performed without libraries or branches, so as to define library-free and branch-free compression with highly predictable runtime behavior for lifecycle data management.

IPC Classes  ?

• H03M 7/30 - Compression; Expansion; Suppression of unnecessary data, e.g. redundancy reduction

Abstract

in vivoin vivo plasmid assembly, donor recruitment, and retron donor DNA generation. Each editing system improves edit outcomes at different sites in different ways. The integration of all three systems results in substantially improved editing at all sites measured and in multiple distinct assays, enabling effective editing of structural variant prone regions and saturation editing across entire genomic loci.

IPC Classes  ?

• C12N 15/75 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Bacillus
• A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links

Abstract

Described herein is a CRISPR guide and retron donor expressed separately to mediate genome editing by homology-directed repair. The split system works more efficiently than previous approaches employing retron-gRNA fusions, demonstrating that recruitment of the retron to the target site by Cas9 is not essential for retron-based editing and that retron and guide functionality can be enhanced when expressed via distinct promoters and RNA processing elements. More efficient editing was achieved with a mutant Cas9 nickase than with the fully active Cas9 nuclease in mammalian cells, avoiding the toxicity and error-prone repair pathways triggered by double-strand breaks which are of major concern for therapeutic applications.

IPC Classes  ?

• C12N 15/90 - Stable introduction of foreign DNA into chromosome
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof

Abstract

Provided are multi-omic methods of analyzing samples. In some embodiments, the methods comprise receiving a blood microsample from a subject, and extracting proteins, lipids and metabolites from the blood microsample. Such methods further comprise acquiring proteomics data, lipidomics data, and metabolomics data from the extracted proteins, lipids and metabolites, respectively, and analyzing the proteomics data, lipidomics data, and metabolomics data. The methods may be performed on time-stamped serial blood microsamples acquired by the subject. In certain embodiments, the methods comprise receiving wearable data, dietary intake data, and/or medication intake data which in turn may be correlated with each other and/or the multi-omics data to identify actionable correlations (e.g., causal relationships) upon which diagnostics and/or recommendations to the subject may be based. Also provided are methods of generating lagged correlations between first time series data and second time series data.

IPC Classes  ?

• 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
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G01N 33/92 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol
• G01N 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals

Abstract

Compositions and methods are provided for increasing proliferation of hematopoietic stem cells (HSC), and increasing HSC capacity for self-renewal. It is shown herein that overexpression of the protein TCL1A in HSC allows the cells to expand in absolute number to a greater number than unmodified cells, and to maintain stem cell surface markers in culture in media supplemented with cytokines.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C12N 5/0789 - Stem cells; Multipotent progenitor cells
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• A61K 35/545 - Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells

Abstract

The present disclosure provides a method for ligand induced ADAR (adenosine deaminase acting on RNA) mediated expression of an RNA coding sequence, the method comprising contacting a ligand with a cell associated LIDAR meditated expression system comprising: 1) an output RNA, 2) a stem loop binding protein and 3) an RNA editing protein; to express the RNA coding sequence. The present disclosure also provides compositions and kits for practicing the methods disclosed herein.

IPC Classes  ?

• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 9/78 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5)

Abstract

A non-human animal comprising chimeric microglia and methods of performing blastocyst microglia complementation to produce such a non-human chimeric animal are disclosed. In particular, the disclosed methods can be used to produce a non-human animal model carrying microglia mutations of interest for gene validation and therapeutic screening.

IPC Classes  ?

• A01K 67/027 - New breeds of vertebrates
• C07K 14/71 - Receptors; Cell surface antigens; Cell surface determinants for growth regulators
• C12N 5/079 - Neural cells
• C12Q 1/6851 - Quantitative amplification
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 9/22 - Ribonucleases

Abstract

in vitroin vitroin vitro culture is assessed for a level of one or more HHV-6 analytes by quantitative nucleic acid sequencing. The present disclosure further provides non-transitory computer-readable media and computer devices that find use in practicing the methods of the present disclosure.

IPC Classes  ?

• C12Q 1/6851 - Quantitative amplification
• A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
• C12Q 1/6869 - Methods for sequencing
• G16B 30/10 - Sequence alignment; Homology search
• G16B 30/20 - Sequence assembly
• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage

Abstract

Systems and methods for decoding speech from neural activity in accordance with embodiments of the invention are illustrated. One embodiment includes a brain-computer interface for decoding intended speech including a microelectrode array, a processor communicatively coupled to the microelectrode array, and a memory, the memory containing a speech decoding application that configures the processor to: receive neural signals from a user's brain recorded by a microelectrode array, where the neural signals comprise action potential spikes, bin the received action potential spikes by time, provide the bins to a recurrent neural network (RNN) to receive a likely phoneme at the time of each provided bin, generate an estimated intended speech using a phoneme decoder provided with the likely phonemes, where the phoneme decoder comprises a language model formatted as a weighted finite-state transducer, and vocalize the estimated intended speech using a loudspeaker communicatively coupled to the brain-computer interface.

IPC Classes  ?

• G10L 15/24 - Speech recognition using non-acoustical features
• G10L 13/02 - Methods for producing synthetic speech; Speech synthesisers
• G10L 15/14 - Speech classification or search using statistical models, e.g. Hidden Markov Models [HMM]
• G10L 25/63 - Speech or voice analysis techniques not restricted to a single one of groups specially adapted for particular use for comparison or discrimination for estimating an emotional state
• G10L 15/22 - Procedures used during a speech recognition process, e.g. man-machine dialog
• A61F 4/00 - Methods or devices enabling patients or disabled persons to operate an apparatus or a device not forming part of the body

Abstract

Systems and methods for cancer screening are provided. The system and methods can utilize cell-free DNA (cfDNA) to identify one or more cfDNA features. The cfDNA features can include sequence variant data features, base modification data features, and cfDNA molecule fragment length data features. A trained machine-learning model can utilize cfDNA features to determine whether an individual has a cancer.

IPC Classes  ?

• 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
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations

Abstract

Compositions and methods are provided for preventing or treating obesity and/or overweight, and managing body weight. It is shown herein that a peptide that is proteolytically cleaved from the parent protein BRINP2 is effective in reducing food intake and obesity in a mammal. The peptide is referred to herein as BRINP2-related peptide (BRP).

IPC Classes  ?

• A61K 38/08 - Peptides having 5 to 11 amino acids
• A61P 3/04 - Anorexiants; Antiobesity agents
• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids

Abstract

Provided are methods of producing a cyclobutane compound. In some embodiments, the methods include contacting an un-activated diene with a copper(II) catalyst under conditions so that the un-activated diene undergoes a [2+2] cycloaddition to produce the cyclobutane compound.

IPC Classes  ?

• C07C 13/02 - Monocyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
• C07C 13/06 - Monocyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with a four-membered ring
• C07C 23/06 - Monocyclic halogenated hydrocarbons with a four-membered ring
• C07B 61/00 - Other general methods

Abstract

Systems and methods for transcranial ultrasound stimulation that mimics the excitatory and inhibitory effects of various transcranial magnetic stimulation protocols in accordance with embodiments of the invention are illustrated. In many embodiments, low intensity focused ultrasound (LIFU) is directed at a target brain region, the LIFU has a fundamental frequency between 250-750 KHz, a spatial peak, temporal average intensity between 0.5- 5 W/cm2, and a pulse repetition frequency between 2.5Hz-7.5Hz, and the LIFU is delivered in an intermittent theta burst pattern over at least one session lasting between 1 minutes and 30 minutes, during which several neurostimulation trains are delivered, each neurostimulation train separated by an interval of no neurostimulation lasting between 0 and 480 seconds, where each train includes bursts lasting 10-30 milliseconds which are repeated every 100-300 milliseconds for a total of 40-120 seconds, and where a duty cycle for each train is between 5% and 15%

IPC Classes  ?

• A61N 7/00 - Ultrasound therapy

Abstract

Annuloplasty devices are provided for implantation around a tricuspid valve to avoid placement over a septal leaflet of the valve and/or avoid suture placement adjacent the septal leaflet. In one example, the device includes a "C" shaped body that includes spaced apart ends to provide a gap to avoid placement over the septal leaflet. Alternatively, a flexible portion may be connected, to the ends of the "C" shaped body for placement over the septal region. In another example, the device includes an enclosed band including a contoured bridge configured to sit over the septal leaflet, e.g., to avoid unnecessary leaflet abrasion and/or conform to the septal wall and aorta.

IPC Classes  ?

• A61F 2/24 - Heart valves

Abstract

Adjustable mitral annuloplasty rings are disclosed that include a body including an anterior segment with a hub and first and second curved lateral segments extending from opposite ends of the anterior segment. In one example, the body terminates at tips of the lateral segments generally opposite the anterior segment to define a "C" shape. Alternatively, the body includes a posterior segment extending between ends of the lateral segments opposite the anterior segment to define a "D" shape. One or more channels are provided around a perimeter of the body, e.g., through the segments and communicating with openings in the hub, and a filament is received in the channels such that the filament extends around the perimeter of the body and ends of the filament exit the openings in the hub such that the ends may be tensioned to cause constriction of one or more of the segments of the body.

IPC Classes  ?

• A61F 2/24 - Heart valves

Abstract

BALF2 BALF2 BALF2 BALF2 gene simultaneously in a single assay. In addition, methods are provided for identifying individuals at high risk of developing nasopharyngeal carcinoma who are in need of further screening and treatment.

IPC Classes  ?

• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/686 - Polymerase chain reaction [PCR]
• 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

Abstract

The present invention relates to polygenic nucleic acid constructs comprising nucleotide sequences encoding Mycobacterium tuberculosis antigens and to mRNA vaccine constructs transcribed or obtained therefrom. Also provided are lipid nanoparticles including the mRNA vaccine constructs and vaccine compositions comprising the constructs described. The constructs, lipid nanoparticles containing them, and vaccine compositions described may be useful in methods for eliciting a protective immune response against Mycobacterium tuberculosis in a subject.

IPC Classes  ?

• A61K 39/04 - Mycobacterium, e.g. Mycobacterium tuberculosis

Abstract

Supported catalyst systems comprise a bimodal nanoporous support, the support comprising: a plurality of porous bodies connected by interconnecting structures, wherein the porous bodies have primary pores throughout their structures, the primary pores defined by a first average pore diameter; and wherein the spaces between the interconnected porous bodies define secondary pores having a second average pore diameter; and catalyst deposits (e.g., comprising Pt) within the primary pores. The first average pore diameter is less than or equal to 20 nm, and the second average pore diameter is greater than 20 nm. The supported catalyst system further comprises an ionomer deposited onto the supported catalyst system, wherein the ionomer is localized to the secondary pores and the exterior surfaces of the porous bodies and interconnecting stmctures but does not enter the primary pores or contact the catalyst deposits inside the primary pores.

IPC Classes  ?

• H01M 4/90 - Selection of catalytic material
• H01M 4/92 - Metals of platinum group
• H01M 8/1004 - Fuel cells with solid electrolytes characterised by membrane-electrode assemblies [MEA]
• B01J 35/10 - Solids characterised by their surface properties or porosity
• B01J 37/02 - Impregnation, coating or precipitation
• B01J 23/42 - Platinum
• B01J 21/18 - Carbon
• H01M 8/10 - Fuel cells with solid electrolytes

Abstract

Systems and methods for unsupervised calibration of brain-computer interfaces (BCIs) in accordance with embodiments of the invention are illustrated. One embodiment includes a closed-loop recalibrating (BCI) including a neural signal recorder configured to record brain activity, and a decoder, including a processor, and a memory, where the memory contains a neural decoder model, an inference model, and a decoder application that configures the processor to obtain a neural signal from the neural signal recorder, translate the neural signal into a command for an interface device communicatively coupled to the decoder, using the neural decoder model, infer an intended target of a user based on the command using the inference model, annotate the neural signal with the inferred intended target, and retrain the neural decoder model using the annotated neural signal as training data.

IPC Classes  ?

• G06F 3/01 - Input arrangements or combined input and output arrangements for interaction between user and computer
• G06N 5/04 - Inference or reasoning models
• G06N 20/00 - Machine learning
• A61B 5/375 - Electroencephalography [EEG] using biofeedback
• G06N 20/10 - Machine learning using kernel methods, e.g. support vector machines [SVM]
• A61F 2/68 - Operating or control means

Abstract

Methods of treating a metabolic disorder in a subject are provided. Aspects of the method include enhancing extracellular Carboxylesterase 2 (CES2) activity in the subject in order to treat the subject for the metabolic disorder. Also provided are compositions for use in practicing the methods.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
• C12Q 1/44 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving esterase

Abstract

Tunable optical metasurfaces for amplitude and phase control of light are provided based on electrochemical tuning of the thickness of a polymer spacer between metal structures. The resulting Fabry-Perot and/or plasmon resonances are thereby made tunable, with a figure of merit that can greatly exceed the figure of merit for electrochromic tuning. This operating principle can be generali zed to provide optical sensing of various environmental parameters such as humidity, pressure etc.

IPC Classes  ?

• G01N 21/41 - Refractivity; Phase-affecting properties, e.g. optical path length
• G01N 21/552 - Attenuated total reflection
• G02B 26/06 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the phase of light
• G02F 1/01 - 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
• G01S 7/481 - Constructional features, e.g. arrangements of optical elements
• H01L 31/0232 - Optical elements or arrangements associated with the device
• H01M 4/137 - Electrodes based on electro-active polymers

Abstract

Provided herein are minimally invasive compositions, methods, systems, kits and uses for biomarkers derived from the plasma proteome that identify, predict, and monitor organ health, aging, dysfunction and disease in humans. Said methods comprise a) obtaining a sample from said subject; b) measuring the concentrations of two or more proteins from said organ in said sample from said subject wherein said concentrations of said two or more proteins provides a biological age of said organ in health and/or disease; and c) comparing said biological age of said organ to a chronological age of said subject, wherein a gap between said biological age of said organ and said chronological age of said subject identifies accelerated and slowed aging of said organ.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• G01N 33/48 - Biological material, e.g. blood, urine; Haemocytometers
• G01N 33/53 - Immunoassay; Biospecific binding assay; Materials therefor

Abstract

The present disclosure provides compositions including a polyacrylamide-based copolymer, one or more preservatives, and insulin or an analog thereof. Also provided are methods of using the insulin compositions, including methods of administering the compositions to a human subject in need thereof.

IPC Classes  ?

• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 47/08 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen
• A61K 47/10 - Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
• A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
• C08F 12/00 - 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 an aromatic carbocyclic ring
• A61K 38/28 - Insulins

Abstract

Non-plant cells that produce tetrahydropapaverine (THP) via an engineered THP-biosynthetic pathway are provided. In embodiments of the invention, the engineered THP-biosynthetic pathway is a norreticuline mediated pathway. Also provided are methods of producing THP using the cells, as well as methods of producing papaverine, e.g., via oxidation of THP, as well as other produces from THP, e.g., atracurium and cisatracurium.

IPC Classes  ?

• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
• C12N 1/16 - Yeasts; Culture media therefor

Abstract

Engineered tunable chimeric receptor/ligand pairs, and methods of use thereof, are provided.

IPC Classes  ?

• C07K 14/715 - Receptors; Cell surface antigens; Cell surface determinants for interferons
• C07K 14/71 - Receptors; Cell surface antigens; Cell surface determinants for growth regulators
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• A61P 35/00 - Antineoplastic agents
• C12N 15/62 - DNA sequences coding for fusion proteins
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells

Abstract

Systems and methods for fabricating a metal core truss panel with seamlessly embedded features in accordance with embodiments of the invention are illustrated. One embodiment includes a method of treatment for major depressive disorder including obtaining functional imaging data of a patient's brain, identifying disordered lagged correlations between different brain regions using the functional imaging data, identifying a first region of a dorsolateral prefrontal cortex most strongly anti-correlated with an anterior cingulate cortex, identifying a second region of the dorsolateral prefrontal cortex abnormally receiving signals from the anterior cingulate cortex, generating a neurostimulation target as the overlap between the first region and the second region, and applying neurostimulation to the target using a neurostimulation device.

IPC Classes  ?

• A61N 2/00 - Magnetotherapy
• G06T 7/11 - Region-based segmentation
• A61N 1/36 - Applying electric currents by contact electrodes alternating or intermittent currents for stimulation, e.g. heart pace-makers
• A61B 5/383 - Somatosensory stimuli, e.g. electric stimulation
• A61N 1/05 - Electrodes for implantation or insertion into the body, e.g. heart electrode
• A61N 1/18 - Applying electric currents by contact electrodes
• G16H 20/70 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mental therapies, e.g. psychological therapy or autogenous training
• 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

Abstract

Methods and compositions are provided for the treatment of glaucoma and other optic neuropathies by administering an effective dose of an HDAC4 coding sequence or protein.

IPC Classes  ?

• A61P 27/06 - Antiglaucoma agents or miotics
• A61P 27/02 - Ophthalmic agents
• A61K 9/00 - Medicinal preparations characterised by special physical form

Abstract

Methods are provided for targeting cells for depletion, including without limitation tumor cells such as solid tumor cells, in a regimen comprising contacting the tumor and immune effector cells with an effective dose of an anti-MSDC agent that reduces the abundance, immunosuppressive activity, or tumor recruitment of CXCR2+ granulocytic-myeloid derived suppressor cells, for example, an inhibitor of CXCR2; in combination with an effective dose of an inhibitor of CD47/SIRPα signaling.

IPC Classes  ?

• A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• A61P 35/04 - Antineoplastic agents specific for metastasis
• A61P 35/00 - Antineoplastic agents
• 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

Abstract

in vitroin vitro changes in the phenotype and function of the cells.

IPC Classes  ?

• A01N 1/02 - Preservation of living parts
• A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
• A61K 35/17 - Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells

Abstract

Provided are methods of manufacturing cells. The methods comprise expanding cells in the presence of inosine, and harvesting the cells after expansion. In certain embodiments, the cells are genetically modified. For example, the cells may be genetically modified to express an engineered receptor, non-limiting examples of which are chimeric antigen receptors (CARs), engineered T cell receptors (TCRs), and the like. According to some embodiments, the cells are immune cells, e.g., T cells or natural killer cells. Also provided are populations of cells manufactured according to the methods of the present disclosure. Also provided are methods comprising administering an effective amount of a population of cells manufactured according to the methods of the present disclosure to a subject in need thereof. In certain embodiments, the subject has cancer, and the cells express an engineered receptor that binds to a tumor antigen on the surface of cells of the cancer.

IPC Classes  ?

• C12P 19/32 - Nucleotides having a condensed ring system containing a six-membered ring having two nitrogen atoms in the same-ring, e.g. purine nucleotides, nicotineamide-adenine dinucleotide
• A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
• C12N 5/02 - Propagation of single cells or cells in suspension; Maintenance thereof; Culture media therefor
• C12N 5/0783 - T cells; NK cells; Progenitors of T or NK cells
• C12P 19/40 - Nucleosides having a condensed ring system containing a six-membered ring having two nitrogen atoms in the same ring, e.g. purine nucleosides

Abstract

Provided are methods of genetically modifying cells. In certain embodiments, the methods comprise modifying a coding region of a mitochondrial gene of the cell. According to some embodiments, the modification results in increased translation of a messenger RNA (mRNA) encoded by the mitochondrial gene by increasing the affinity of a codon-anti-codon interaction during translation of the mRNA as compared to the affinity of the codon-anti-codon interaction prior to the modifying. In certain embodiments, the modification results in decreased translation of an mRNA encoded by the mitochondrial gene by decreasing the affinity of a codon-anti-codon interaction during translation of the mRNA as compared to the affinity of the codon-anti-codon interaction prior to the modifying. Also provided are populations of the genetically modified cells, compositions comprising such populations, and methods of administering the compositions to a subject as a cell-based therapy.

IPC Classes  ?

• C12N 15/09 - Recombinant DNA-technology
• 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 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression

Abstract

A library of copolymers for use as broad-spectrum antibiotics is provided where each copolymer includes three distinct acrylamide-based monomers: (1) a cationic monomer to attract the polymer selectively to bacterial surfaces; (2) a hydrophilic carrier monomer to impart water solubility; and (3) a hydrophobic dopant monomer. Methods and compositions comprising the copolymer are useful as effective antimicrobials.

IPC Classes  ?

• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
• C08F 220/36 - Esters containing nitrogen containing oxygen in addition to the carboxy oxygen
• C08F 220/54 - Amides
• C09D 133/26 - Homopolymers or copolymers of acrylamide or methacrylamide
• C08L 33/26 - Homopolymers or copolymers of acrylamide or methacrylamide
• A61L 33/06 - Use of macromolecular materials

Abstract

Devices, systems, and methods for performing ablation are provided, e.g., for performing pulsed field ablation (PFA) for treating atrial fibrillation (AF). In one example, the systems may be used to create lesions similar to the Cox Maze lesion set using minimally invasive methods, e.g., creating endocardial and epicardial lesions sets using one or more ablation devices introduced into a patient's body.

IPC Classes  ?

• A61B 18/14 - Probes or electrodes therefor
• A61B 18/00 - Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
• A61B 17/00 - Surgical instruments, devices or methods, e.g. tourniquets

Abstract

There is a tremendous need for advanced human model systems to screen new immunomodulatory candidates in an economical and robust manner, which is addressed by the present disclosure. Compositions and methods are provided for in vitro immune organoid cultures that can be adapted to large screening assays for flexible downstream immunological readout.

IPC Classes  ?

• C12N 5/078 - Cells from blood or from the immune system
• C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
• C12Q 1/6869 - Methods for sequencing

Abstract

Systems and methods for assessment of sequence and molecule diversity are provided. In the realm of nucleic acids, sequencing results can be analyzed for diversity without alignment of sequencing reads to a reference sequence. The sequencing reads are utilized within a statistical framework to identify sequence anchors and sequence targets. The diversity among the sequence targets can be assessed for each sequence anchor.

IPC Classes  ?

• G16B 30/10 - Sequence alignment; Homology search
• G16B 30/20 - Sequence assembly
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 5/20 - Probabilistic models

Abstract

Among various examples, one is directed to identifying one or more particular photocathode semiconductor structures via a computer-based method. The method includes calculating, for each of a plurality of semiconductor materials and via a database characterizing electronic band structures of respective semiconductor materials corresponding to the plurality of semiconductor materials, an intrinsic emittance score (e g., using an optimistic selection of a work function) as a predictive screening metric for whether the semiconductor material may exhibit low intrinsic emittance. A subset of the semiconductor materials may be selected, wherein each of the semiconductor materials in the subset satisfies screening criteria based on the intrinsic emittance score, and photocathode brightness properties of said one or more of the semiconductor materials in the subset are characterized, thereby identifying certain semiconductor materials in the subset of the semiconductor materials with desirable photocathode brightness properties.

IPC Classes  ?

• G06F 30/32 - Circuit design at the digital level
• H01L 33/00 - SEMICONDUCTOR DEVICES NOT COVERED BY CLASS - Details thereof

Abstract

The present disclosure provides a method of producing a non-human mammalian animal model comprising human neural tissue, the method comprising introducing a first human neural organoid into a central nervous system location of a newborn non-human mammal; and allowing the newborn non-human mammal to mature to produce the non-human mammalian animal model comprising human neural tissue. The present disclosure provides a method of modeling a neuropsychiatric disorder. The present disclosure also provides a method of determining the effectiveness of a candidate agent on a neuropsychiatric disorder. The present disclosure provides a method for altering the behavior of a mammal. Also provided are non-human mammalian animal models comprising human neural tissue.

IPC Classes  ?

• C12N 5/0793 - Neurons
• A61N 5/06 - Radiation therapy using light
• C12N 5/0735 - Embryonic stem cells; Embryonic germ cells
• C12N 15/90 - Stable introduction of foreign DNA into chromosome

Abstract

We provide a method for optical convolution based on frequency synthetic dimensions using a single optical ring resonator undergoing dynamic modulations. The convolution is achieved using the scattering matrix of such a modulated system with discrete frequency input matching the free spectral range of the ring resonator. We use both a phase modulator and an amplitude modulator to obtain both unitary and non-unitary scattering matrices, analogous to non- Hermitian physics in synthetic dimensions.

IPC Classes  ?

• H04B 10/54 - Intensity modulation
• H04B 10/548 - Phase or frequency modulation
• G06N 3/0464 - Convolutional networks [CNN, ConvNet]
• G06N 3/067 - Physical realisation, i.e. hardware implementation of neural networks, neurons or parts of neurons using optical means

Abstract

Compositions and methods are provided for determining immunogenic dsRNA level in an individual, based on the individual's genotype. This information is useful for disease stratification, and for selecting appropriate therapeutic intervention, including, for example inhibition of MDA5, inhibition of type 1 interferon signaling, and the like. In some embodiments a tissue specific subset of immunogenic dsRNAs are analyzed, where the tissue is associated with an immune-related disease of interest.

IPC Classes  ?

• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G01N 33/564 - Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation

Abstract

xx contact is then protected with a passivation structure. Such contacts have various device applications, such as forming Schottky diodes and acting as a gate in a transistor or 2D electron gas structure.

IPC Classes  ?

• H01L 21/04 - Manufacture or treatment of semiconductor devices or of parts thereof the devices having at least one potential-jump barrier or surface barrier, e.g. PN junction, depletion layer, carrier concentration layer
• H01L 29/24 - Semiconductor bodies characterised by the materials of which they are formed including, apart from doping materials or other impurities, only inorganic semiconductor materials not provided for in groups , ,  or
• H01L 29/66 - Types of semiconductor device
• H01L 29/778 - Field-effect transistors with two-dimensional charge carrier gas channel, e.g. HEMT

Abstract

The present disclosure is directed, in part, to saxiphilin proteins, nucleic acids encoding the same, compositions comprising the same, kits comprising the same, and methods of detecting toxin in samples and for diagnosing a subject as contaminated with a toxin. In some embodiments, the toxin is saxitoxin or derivatives of the same.

IPC Classes  ?

• G01N 33/53 - Immunoassay; Biospecific binding assay; Materials therefor
• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants

Abstract

Compositions and methods for ultrasound-induced light generation in the brain (e.g, for use in optogenetic methods) are provided. Mechanoluminescent nanoparticles and liposomes are provided. In some aspects, biocompatible and biodegradable liposomes comprising a sonosensitizer (e.g., IR780) and a chemiluminescent compound (e.g., L012) are provided and can be used, e.g., in combination with focused ultrasound (FUS) to generate light in the brain. Related in vivo and therapeutic methods are also provided.

IPC Classes  ?

• A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
• A61K 9/51 - Nanocapsules
• A61K 31/765 - Polymers containing oxygen
• A61K 47/10 - Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones

Abstract

The present disclosure is directed to compounds and compositions for treating PSP such as, for example, therapeutically effective amount of a saxiphilin. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61P 39/02 - Antidotes
• C07K 14/46 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates

Abstract

Adjustable aortic annuloplasty rings are disclosed for constricting a valve annulus, comprising an annular body sized for positioning around an exterior of the valve annulus, the annular body comprising a compliant uni-body driven by a Bowden cable constriction mechanism to adjust an inner diameter of the device.

IPC Classes  ?

• A61F 2/24 - Heart valves

Abstract

Design of transparent mesh counter electrodes for use in dynamic window articles capable of reversible metal electrodeposition (RME). Such an RME window may include a transparent conductive electrode, an electrolyte in contact with the electrode, where the electrolyte includes metal cations that can be reversibly electrodeposited onto the electrode, and a mesh counter electrode. The mesh counter electrode includes an electrochemically inert core with a thin metal coating thereover. The thin metal coating can be of the material that is involved in electrodeposition (e.g., a combination of copper and bismuth). The mesh counter electrode is substantially transparent (e.g., transparency of at least about 70%). Such a mesh counter electrode can provide a high capacity (1.5 C/cm2) that provides good durability over numerous tinting and bleaching cycles, with minimal change in coloration efficiency, reflection profile, and electrodeposition metal concentration (e.g., [Cu2+]) in the electrolyte.

IPC Classes  ?

• G02F 1/153 - Constructional details
• G02F 1/155 - Electrodes
• G02F 1/1506 - 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 an electrochromic effect based on electrodeposition, e.g. electrolytic deposition of an inorganic material on or close to an electrode
• G02F 1/1514 - 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 an electrochromic effect characterised by the electrochromic material, e.g. by the electrodeposited material
• E06B 9/24 - Screens or other constructions affording protection against light, especially against sunshine; Similar screens for privacy or appearance
• G02F 1/163 - Operation of electrochromic cells, e.g. electrodeposition cells; Circuit arrangements therefor

Abstract

Eyelets or grommets are provided for reinforcing tissue and/or sutures. Devices and methods for delivering such eyelets or grommets are also provided. In one example, the device includes an elongate shaft comprising a. proximal end and a distal end sized for introduction into a subject's body; a first jaw on the distal end carrying eyelet material; and a second jaw on the distal end carrying needles such that tissue may be positioned between the jaws, and the second jaw may be actuated to penetrate the tissue and pass the eyelet material through the tissue.

IPC Classes  ?

• A61B 17/04 - Surgical instruments, devices or methods, e.g. tourniquets for closing wounds, or holding wounds closed, e.g. surgical staples; Accessories for use therewith for suturing wounds; Holders or packages for needles or suture materials

Abstract

The disclosure provides methods for detecting a molecule of tumor DNA (tDNA) in a sample of cell-free DNA (cfDNA). In certain embodiments, cfDNA is sequenced using a single molecule sequencing to obtain a methylation profile of a sequence read. Such methylation profile is compared to a reference methylation profile from a cancer cell and/or a non-cancer cell to identify the sequence read as being from a molecule of tDNA. Further embodiments provide estimating the number of molecules of tDNA in the sample of cfDNA and, to determine as a tumor load of the cfDNA, the proportion of the number of molecules of tDNA to the total number of molecules of cfDNA in the sample. Such tumor load can be used to monitor cancer progression in a subject or efficacy of a cancer therapy administered to a subject.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• 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
• G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
• G16B 40/20 - Supervised data analysis
• 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

Abstract

A system for providing a repeated therapy to an internal organ within a patient comprises a marker configured to be affixed to an exterior of the patient; and an energy device having an energy treatment portion and having a fastener configured to permit securing of the energy device to an exterior of the patient, the energy device further including a mating surface to couple the marker and the energy device, such that when the marker is affixed to the exterior of the patient the energy device can be coupled to the marker allowing for automatic alignment of the energy treatment portion to the internal organ from the exterior of the patient.

IPC Classes  ?

• A61N 7/00 - Ultrasound therapy
• A61B 8/08 - Detecting organic movements or changes, e.g. tumours, cysts, swellings

Abstract

Provided herein are nanoparticles including a TLR agonist, a saponin, a phospholipid, and a sterol. The composition of the nanoparticles is modularly tunable and can be configured such that the nanoparticles are particularly useful as adjuvants for enhancing a variety of potent and durable immunogenic responses. Also provided are adjuvant compositions and immunogenic compositions including the nanoparticles, and methods for using these compositions to induce an immunogenic response and treat or prevent a disease.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 9/00 - Medicinal preparations characterised by special physical form
• 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 47/55 - 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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/61 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
• C07D 471/04 - Ortho-condensed systems
• A61P 37/00 - Drugs for immunological or allergic disorders

Abstract

Polyacrylamide-based copolymers act as stabilizing excipients in formulations of antibody biopharmaceutical agents without interacting directly with the antibody or altering its pharmacokinetic properties. The polyacrylamide-based copolymers confer a substantial stability benefit to high concentration compositions of a variety of antibodies by precluding adsorption of the antibody to the interfaces of the composition, preventing undesirable aggregation events and maintaining the binding activity of the antibody. Such antibody compositions are useful in methods of administering the composition to a subject.

IPC Classes  ?

• A61K 9/107 - Emulsions
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
• A61K 9/08 - Solutions
• 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
• A61P 31/18 - Antivirals for RNA viruses for HIV

Abstract

There is provided herein a copolymer comprising a ligand moiety that binds to a cell surface receptor, one or two lipophilic polymer blocks and a poly(alpha aminoester) block for the delivery of therapeutic, diagnostic and imaging agents, including small molecules therapeutic agents and nucleic acids, into a cell.

IPC Classes  ?

• A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
• A61K 47/55 - 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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• A61K 47/59 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• A61P 35/00 - Antineoplastic agents
• A61P 37/00 - Drugs for immunological or allergic disorders

Abstract

Methods and systems for applying passive haptic stimulation to the muscles to stimulate afferent receptors in the muscles to treat neurological dysfunction. The muscle haptic stimulation provides modulation and retraining to treat one or more neurological dysfunctions, such as hypertonia (including spastic hypertonia), loss of motor control, and/or impaired sensation. A wearable muscle haptic stimulation system is used to apply muscle haptic stimulation for a treatment session (e.g., 3 hours daily, or 30 minutes as needed), and repeating the treatment session over a treatment period (e.g., a week, several weeks, months, etc.) in order to retrain new neurological connections thereby providing long term improvement in the neurological dysfunction.

IPC Classes  ?

• A61H 1/02 - Stretching or bending apparatus for exercising

Abstract

Compositions, methods, and kits are provided for screening for candidate agents that inhibit formation of integrin-mediated curved adhesions. Screening assays may further include determining the effectiveness of candidate agents in reducing cell adhesion, proliferation, cell spreading, migration, or survival of cells and screening candidate agents for efficacy in treating disorders associated with integrin-mediated formation of curved adhesions.

IPC Classes  ?

• C07K 14/705 - Receptors; Cell surface antigens; Cell surface determinants
• G01N 33/52 - Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper
• 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
• C07K 14/78 - Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin (CIG)

Abstract

Compositions and methods are provided for determining the presence of early-stage osteoarthritis (OA) in an individual by single cell profiling of a blood sample. Through use of machine learning, it is shown that immune cell features associated with OA are present and detectable in the early stages of OA and can be utilized for early detection of the disease.

IPC Classes  ?

• G01N 33/564 - Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease
• G01N 15/14 - Electro-optical investigation
• 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
• 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

Abstract

The present disclosure provides methods and compositions for genetically modifying hematopoietic stem and progenitor cells (HSPCs), in particular by replacing the HBA1 or HBA2 locus in the HSPCs with a transgene encoding a therapeutic protein.

IPC Classes  ?

• A61K 35/14 - Blood; Artificial blood
• C12N 5/0797 - Stem cells; Progenitor cells
• C12N 5/078 - Cells from blood or from the immune system
• 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
• A61K 38/36 - Blood coagulation or fibrinolysis factors
• A61K 35/545 - Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells

Abstract

The disclosure provides compositions and methods for introducing two or more genetic modifications into the genome of a host cell or organism. The compositions comprise retron guide RNA cassettes that can be used to introduce a first genetic modification, such as a genetic variant, at a first target locus and a second genetic modification, such as a unique barcode sequence, at a second target locus. The methods allow tracking of the first genetic modification by detecting the presence of the barcode sequence or a protein encoded by the barcode sequence. The methods can be used to track multiple genetic variants introduced into a host cell by detecting the presence of multiple unique barcode sequences, without having to detect the vector sequences used to transform the host cell.

IPC Classes  ?

• C12N 15/90 - Stable introduction of foreign DNA into chromosome
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• C12N 15/81 - Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts

Abstract

Methods and compositions for treating obesity, obesity-related diseases, fatty liver and fatty liver associated diseases are provided. Aspects of the methods include administering to a subject in need thereof an effective amount of an anti-CD24 agent to treat the subject. Also provided are compositions for use in practicing embodiments of the methods.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
• A61P 3/04 - Anorexiants; Antiobesity agents

Abstract

Methods for identifying, isolating and enriching neural stem and progenitor cells (NSPC) such as ventricular radial glia, outer radial glia, astrocytes, pre-oligodendrocyte precursor cells, oligodendrocyte precursor cells, oligodendrocytes, early excitatory neurons, late excitatory neurons, bipotent glial progenitors, and inhibitory neurons are provided. These methods find use in transplantation, to eliminate specific cell subsets, for experimental evaluation, as a source of lineage and cell-specific products, and the like, for example for use in treating human disorders of the central nervous system (CNS).

IPC Classes  ?

• C12N 5/0797 - Stem cells; Progenitor cells
• A61K 35/30 - Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• G01N 15/14 - Electro-optical investigation
• G01N 33/533 - Production of labelled immunochemicals with fluorescent label
• C12N 5/0793 - Neurons

Abstract

Methods and compositions for treating fatty liver and viral infections are provided. Aspects of the methods includes administering to a subject in need thereof an effective amount of a KxL motif binding agent, e.g., A27, to treat the subject. Also provided are compositions for use in practicing embodiments of the methods.

IPC Classes  ?

• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
• 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 31/33 - Heterocyclic compounds

Abstract

Processes to spatially align single cells to yield a specimen map with single cell resolution are provided. Methods can perform spatial omics on a specimen to yield spatial omics data. The spatial omics data can be used in combination with single cell omics data to assign single cells to spatial coordinates to yield a resolved specimen map.

IPC Classes  ?

• G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
• C12N 9/22 - Ribonucleases
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/11 - DNA or RNA fragments; Modified forms thereof
• G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
• C12Q 1/6841 - In situ hybridisation
• G16B 40/20 - Supervised data analysis
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

Systems and methods for ultraviolet light emission are provided. Generally, amphiphilic vesicles contain an organic core. The organic core can incorporate organic compounds for performing triplet-triplet annihilation upconversion for emitting ultraviolet light. Accordingly, input light is impinged upon the amphiphilic vesicle, resulting in upconversion of the input light photons into UV light photons.

IPC Classes  ?

• G01J 1/42 - Photometry, e.g. photographic exposure meter using electric radiation detectors
• F21L 4/02 - Electric lighting devices with self-contained electric batteries or cells characterised by provision of two or more light sources
• B05D 3/06 - Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by exposure to radiation