Abstract: The present disclosure provides methods and compositions for genetically modifying hematopoietic stem and progenitor cells (HSPCs), in particular by replacing the HBB locus in the HSPCs with a transgene encoding alpha globin.

Abstract: Edited cell chimerism is currently one of the greatest bottlenecks to clinical efficacy of gene therapies for the hemoglobinopathies. For example, it is difficult to go from low hematopoietic stem cell (HSC) edited cell chimerism in the bone marrow to high edited red blood cell (RBC) chimerism in the bloodstream. The present disclosure provides methods and compositions for genetically modifying hematopoietic stem and progenitor cells (HSPCs), in particular by creating HSPCs that express truncated forms of the EPO.receptor (tEPOR).

Abstract: The present disclosure provides methods and compositions for genetically modifying hematopoietic stem and progenitor cells (HSPCs), in particular by correcting a JAK2V617F mutation in the HSPCs.

Abstract: A wearable rapid pulse confirmation (RPC) device is designed to be worn by a living subject, and includes a Doppler array comprising at least one piezoelectric ultrasonic transducer, configured to detect a change in blood velocity in a blood vessel; a screen; a loud speaker; and a band or adhesive configured to hold the wearable RPC device in proximity to a body surface of the living subject. The Doppler array is configured to detect a change in blood velocity, pulse rate, pulse strength, or a combination thereof in a blood vessel; and to provide feedback through the screen and the loudspeaker. The Doppler array may include multiple types of piezoelectric ultrasonic transducers, including low frequency piezoelectric ultrasonic transducers having a working frequency ranging from 2 MHz to <6 MHz; medium frequency piezoelectric ultrasonic transducers having a working frequency of 6 MHz to 10 MHz; and high frequency piezoelectric ultrasonic transducers having a working frequency of 10 MHz to 18 MHz.

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.

Abstract: The disclosure provide methods and compositions that use gene editing or gene therapy to treat alpha thalassemia major. The gene editing may be performed ex vivo in fetal cells or cells obtained after birth to improve production of globin, with those cells then delivered to the fetus. In other embodiments, gene editing reagents are delivered to the fetus or the patient after birth in vivo to edit genes of the alpha-globin cluster and improve globin production. Gene editing system such as CRISPR, TALENs, or ZFNs are used to increase production of alpha, zeta, or theta globin and/or to decrease production of gamma globin. Globin production may be improved by inserting a copy of globin gene or mutating a globin gene to change its expression. Any of the gene editing strategies may be performed in conjunction with delivering to a fetus or patient after birth a therapeutic blood transfusion. Exemplary patients after birth are patients no older than one year of age.

Abstract: A wearable rapid pulse confirmation (RPC) device is designed to be worn by a living subject, and includes a Doppler array comprising at least one piezoelectric ultrasonic transducer, configured to detect a change in blood velocity in a blood vessel; a screen; a loud speaker; and a band or adhesive configured to hold the wearable RPC device in proximity to a body surface of the living subject. The Doppler array is configured to detect a change in blood velocity, pulse rate, pulse strength, or a combination thereof in a blood vessel; and to provide feedback through the screen and the loudspeaker. The Doppler array may include multiple types of piezoelectric ultrasonic transducers, including low frequency piezoelectric ultrasonic transducers having a working frequency ranging from 2 MHz to <6 MHz; medium frequency piezoelectric ultrasonic transducers having a working frequency of 6 MHz to 10 MHz; and high frequency piezoelectric ultrasonic transducers having a working frequency of 10 MHz to 18 MHz.

Abstract: Software, such as malware, may be classified using phylogenetic techniques. An evolutionary history of a representative set of software programs may be reconstructed to generate a reference phylogeny. Dynamic traces of the representative software programs may be obtained. The dynamic traces may include time-ordered sequences of execution commands extracted from running software binaries. Metrics may be developed using the dynamic traces. One or more unknown software programs may then be classified against the reference phylogeny using the metrics developed using the dynamic traces of the representative set of software programs.

Abstract: A process for producing products from biomass comprising fermenting biomass to produce a first product stream comprising carboxylic acid salts; acidifying at least one of the first product stream and a second product stream to produce a third product stream comprising acids; extracting such acids from the third product stream with a solvent; separating the extracting solvent from the acids to produce the separated extracting solvent and a fourth product stream comprising acids; and processing the fourth product stream to produce a fifth product stream.

Abstract: A musical instrument indicator apparatus for aiding at least one user in learning to play at least one musical instrument, the musical instrument indicator apparatus includes: at least one user indicator device configured for attachment to at least one component of the at least one musical instrument and further configured to indicate when the at least one component of the at least one musical instrument should be used by the at least one user; and at least one controller configured to control indication from the at least one user indicator device.

Abstract: According to one embodiment of the invention, an engine system comprises a housing, an outer gerotor, an inner gerotor, a tip inlet port, a face inlet port, and a tip outlet port. The housing has a first sidewall, a second sidewall, a first endwall, and a second endwall. The outer gerotor is at least partially disposed in the housing and at least partially defines an outer gerotor chamber. The inner gerotor is at least partially disposed within the outer gerotor chamber. The tip inlet port is formed in the first sidewall and allows fluid to enter the outer gerotor chamber. The face inlet port is formed in the first endwall and allows fluid to enter the outer gerotor chamber. The tip outlet port is formed in the second sidewall and allows fluid to exit the outer gerotor chamber.

Abstract: According to one embodiment of the invention, an engine system comprises a housing, an outer gerotor, an inner gerotor, a tip inlet port, a face inlet port, and a tip outlet port. The housing has a first sidewall, a second sidewall, a first endwall, and a second endwall. The outer gerotor is at least partially disposed in the housing and at least partially defines an outer gerotor chamber. The inner gerotor is at least partially disposed within the outer gerotor chamber. The tip inlet port is formed in the first sidewall and allows fluid to enter the outer gerotor chamber. The face inlet port is formed in the first endwall and allows fluid to enter the outer gerotor chamber. The tip outlet port is formed in the second sidewall and allows fluid to exit the outer gerotor chamber.

Abstract: A process for producing products from biomass comprising fermenting biomass to produce a first product stream comprising carboxylic acid salts; acidifying at least one of the first product stream and a second product stream to produce a third product stream comprising acids; extracting such acids from the third product stream with a solvent; separating the extracting solvent from the acids to produce the separated extracting solvent and a fourth product stream comprising acids; and processing the fourth product stream to produce a fifth product stream.

Abstract: Methods and apparatus, including computer products, for generating a natural language expression in response to a query. A computer-implemented method of generating a natural language expression in response to a query, includes generating a text frame from the query, and processing the text frame in conjunction with a grammar and one or more logic configuration files applied recursively to the text frame to generate the natural language expression from the query, the logic configuration files including functions that can pass arguments.

Abstract: A method of maintaining a collection of data includes extracting text from the collection of data, the text corresponding to keys and values, generating a feature lexicon from the extracted text, generating a language lexicon from the extracted text and generating configuration files corresponding to the extracted text.

Abstract: A method of producing hydrocarbons from biomass that includes converting at least a portion of the biomass into a first product having at least one of a carboxylic acid, a ketone, an ammonium carboxylate salt, and combinations thereof; converting at least a portion of the first product into an alcohol; reacting at least some of the alcohol in an oligomerization reactor as part of a process that produces an oligomerization product.

Abstract: A method of database aliasing is provided. A method for aliasing a collection of data includes extracting names and associated terms from the collection of data, generating normalized text from the names and associated terms, parsing the normalized text in conjunction with a grammar to produce meaning fragments and mapping the meaning fragments to a collection of concepts.

Abstract: A method of producing alcohols, hydrocarbons, or both from biomass, the method including converting biomass into a carboxylic acid; reacting the carboxylic acid with an olefin to produce an ester; and hydrogenolyzing the ester to produce alcohol. The steps of reacting the carboxylic acid with an olefin to produce an ester, and hydrogenolyzing the ester to produce an alcohol, may both be carried out in the same reactor.

Abstract: A method of producing alcohols, hydrocarbons, or both from biomass, the method including converting biomass into a carboxylic acid; reacting the carboxylic acid with an olefin to produce an ester; and hydrogenolyzing the ester to produce alcohol. The steps of reacting the carboxylic acid with an olefin to produce an ester, and hydrogenolyzing the ester to produce an alcohol, may both be carried out in the same reactor.

Abstract: A method of producing hydrocarbons from biomass that includes converting at least a portion of the biomass into a first product having at least one of a carboxylic acid, a ketone, an ammonium carboxylate salt, and combinations thereof; converting at least a portion of the first product into an alcohol; reacting at least some of the alcohol in an oligomerization reactor as part of a process that produces an oligomerization product.