Abstract: The present invention relates to a pharmaceutical composition for preventing or treating neonatal hypoxic ischemic encephalopathy (HIE), comprising thrombin-treated stem cells or exosomes derived therefrom as an active ingredient, and a method for producing the same. According to the present invention, the thrombin-treated stem cell or the exosome derived therefrom has an increased expression of growth factors, immunoregulatory factors, antioxidation factors, or regeneration factors compared to a group not treated with thrombin and also enhances a neuronal apoptosis inhibitory effect, and thus has an advantage in that the therapeutic effect thereof on neonatal hypoxic ischemic encephalopathy (HIE) is excellent.

Abstract: In this application, the provided are: a Down syndrome rat model characterized in that a rat gene homologous to at least one gene present on a human chromosome 21 or fragment thereof is a trisomy and is transmittable to progeny; or a Down syndrome rat model characterized in that it comprises a human chromosome 21 or fragment thereof, or an exogenous rat chromosome or fragment thereof on which a rat gene homologous to the human chromosome 21 or fragment thereof is present, wherein at least one gene on the human chromosome 21 or fragment thereof or on the exogenous rat chromosome or fragment thereof is added to endogenous rat genes homologous to the at least gene so as to become a trisomy and to be transmittable to progeny: and a method for producing the Down syndrome rat model.

Abstract: Methods, systems, compositions and strategies for the delivery of WW domain-containing fusion proteins into cells in vivo, ex vivo, or in vitro via ARMMs are provided. Methods, systems, compositions and strategies for the delivery of Cas9 proteins and/or Cas9 variants into cells in vivo, ex vivo, or in vitro via fusion to ARMM associated proteins (e.g., ARRDC1 or TSG101) are also provided.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The disclosure provides methods for generating an optimized nucleotide sequence encoding an engineered influenza structural protein and the optimized nucleotide sequences obtained therefrom. The optimized nucleotide sequences can be used in a reverse genetics system to facilitate the rescue of infectious influenza virus containing the engineered structural proteins and/or enhance viral titers. Also provided are methods of preparing an influenza vaccine composition using the optimized nucleotide sequences, as well as methods of inducing an immune response using the influenza vaccine composition.

Abstract: The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Abstract: A hanging drop device is provided in the present disclosure. The hanging drop device includes a hanging drop box and a negative pressure module. The hanging drop box includes a plate and a cover. The cover is coupled with the plate to jointly delimit a pressure chamber. The cover includes an upper surface and a bottom surface, a plurality of wells are recessed from the upper surface, and each of the wells is communicated with the pressure chamber through a hole. The negative pressure module is communicated with the pressure chamber. Each of the wells is for containing a liquid, the negative pressure module is for generating a negative pressure in the pressure chamber, so as to drive the liquid in each of the wells to pass through the hole, and the liquid forms a hanging drop hanging from the bottom surface of the cover.

Abstract: Automatic load-balancing techniques in a network device are used to select, from a multipath group, a path to assign to a flow based on observed state attributes such as path state(s), device state(s), port state(s), or queue state(s) of the paths. A mapping of the path previously assigned to a flow or group of flows (e.g., on account of having then been optimal in view of the observed state attributes) is maintained, for example, in a table. So long as the flow(s) are active and the path is still valid, the mapped path is selected for subsequent data units belonging to the flow(s), which may, among other effects, avoid or reduce packet re-ordering. However, if the flow(s) go idle, or if the mapped path fails, a new optimal path may be assigned to the flow(s) from the multipath group.

Abstract: The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and/or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and/or CIITA or by using nucleic acid molecules which inhibit the expression of B2M and/or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism.

Abstract: Presented herein are technologies and methods for improved production of AAV vectors.

Abstract: The invention provides isolated primate cells preferably human cells that comprise a genetically engineered disruption in a beta-2 microglobulin (B2M) gene, which results in deficiency in MHC class I expression and function. Also provided are the method of using the cells for transplantation and treating a disease condition.

Abstract: The present invention relates to a preparation comprising Epstein-Barr virus-like particles (EB-VLPs), said EB-VLPs being essentially free of Epstein Barr virus (EBV) DNA, wherein said EB-VLPs comprise a vaccination polypeptide comprising at least one peptide of an EBV tegument polypeptide and at least one immunogenic peptide; and to polynucleotides, host cells, and methods related thereto.

Abstract: A cell culture device includes a holding member including a main body cylindrical portion extending in a cylindrical shape in an axial direction and a holding portion provided at an axially intermediate portion of the main body cylindrical portion and holding a culture membrane; and a first cylindrical member detachably mounted on one axial side with respect to the holding member, extending in a cylindrical shape in the axial direction, and protruding from one axial end of the holding member toward the one axial side when being mounted to the holding member. Also included is a second cylindrical member detachably mounted on another axial side with respect to the holding member, extending in a cylindrical shape in the axial direction, and protruding from another axial end of the holding member toward the other axial side when being mounted to the holding member.

Abstract: The invention provides a microfluidic device comprising at least one cell culture chamber, the at least one cell culture chamber being connected to at least two openings, the device being configured to supply at least one physiologically active substance from at least one of the openings to the at least one cell culture chamber in such a manner as to form a concentration gradient or concentration gradients in the at least one chamber when cells and a hydrogel are introduced into the at least one cell culture chamber to culture the cells in a 3D-gel medium.

Abstract: The present application relates to methods of producing a protein in fucosylated and afucosylated forms at a predetermined ratio.

Abstract: Provided herein are, inter alia, methods of treating red blood cell disorders and cancer using anti-miR126 compounds. The methods include administering phosphorothioated CpG oligodeoxynucleotides conjugated to an anti-miR126 nucleic acid sequence to treat red blood cell disorders. Other methods provided herein include administering phosphorothioated CpG oligodeoxynucleotides conjugated to an anti-miR126 nucleic acid sequence and a tyrosine kinase inhibitor to treat cancer.

Abstract: Methods of, treatments using, and devices for restoring the regenerative capability for mesenchymal stem cells and isolating and expanding a small subpopulation of less defective mesenchymal stem cells from the bone marrow stromal cells of people with decreased quality and/or quantity of mesenchymal stem cells, such as elderly people.

Abstract: An article comprising: a planar base having a first surface and an opposing second surface and an outer peripheral edge, wherein the second surface includes an area comprising a plurality of protuberances and configured to attach and maintain orientation of a frozen tissue specimen block; and a removable lid having a first side and a second side, wherein the first side defines a continuous planar surface and the second side defines a recessed portion configured to cover a frozen tissue specimen block and an outer rim configured to engage with the outer peripheral edge of the base, wherein the outer rim does not form part of the recessed portion, wherein the area of the base and the recessed portion of the lid are aligned.

Abstract: The present disclosure provides polypeptides that inhibit activity of a CRISPR/Cas effector polypeptide, nucleic acids encoding the polypeptides, and systems comprising the polypeptides and/or nucleic acids encoding the polypeptides. The present disclosure provides methods of inhibiting activity of a CRISRP/Cas effector polypeptide.

Abstract: The present invention relates to a method of identifying epigenetic reprogramming. Identifying epigenetic reprogramming comprises detecting large organized heterochromatin lysine (K)-9 modified domains (LOCKs) and large DNA hypomethylated blocks in a sample containing DNA from a subject having cancer, for example, PDAC.

Abstract: A method of obtaining a pancreatic multipotent or unipotent cell including providing a cell of a first type which is not a pancreatic multipotent or unipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pancreatic multipotent or unipotent gene regulator in the cell of a first type, to a level at which the at least one pancreatic multipotent or unipotent gene regulator is capable of driving transformation of the cell of a first type into the pancreatic multipotent or unipotent cell; and placing or maintaining the cell in a pancreatic cell culture medium and maintaining intracellular levels of the at least one pancreatic multipotent or unipotent gene regulator for a sufficient period of time to allow a pancreatic multipotent or unipotent cell to be obtained.

Abstract: The present invention relates, in part, to blood-brain barrier-like tissues that comprise engineered E40RF1+ endothelial cells, and to various compositions and methods useful for making and using such blood-brain barrier-like tissues—both in vitro and in vivo.

Abstract: Disclosed herein, are decoy peptides or polypeptides capable of neutralizing and/or inhibiting the binding of anti-Ro antibodies to a hERG potassium channel extracellular pore region, and pharmaceutical compositions containing the decoy peptides or polypeptides and methods of use.

Abstract: A therapeutic agent and method of administering the therapeutic agent for the treatment of tumors and/or cancers of a subject, the therapeutic agent comprising a first pharmaceutical composition comprising a first active ingredient in a first druggable vehicle, wherein the first active ingredient comprises a nucleic acid encoding a labelling polypeptide comprising one or more antigenic epitope peptides and/or encoding a MHC protein; a second pharmaceutical composition comprising a second active ingredient in a second druggable vehicle, wherein the second active ingredient comprises immune cells purified from peripheral blood or from tumor tissue and are cultured in vitro; wherein the nucleic acid when administered to the subject as part of the pharmaceutical composition causes the tumor cells and/or cancer cells of the subject to express the one or more antigenic epitope peptides to elicit an immune response of the immune cells.

Abstract: Described are methods of using a lipase for hydrolysis and esterification. In a first method of producing a medium chain fatty acid by hydrolysis, the method comprises providing a polypeptide with at least 90% degree of identity to SEQ ID No. 3, and contacting the polypeptide with a medium chain fatty acid ester and water to produce the medium chain fatty acid. In a second method of forming an ester, the method comprises providing a polypeptide with at least 90% degree of identity to SEQ ID No. 3; and contacting the polypeptide with a long chain fatty acid, an alcohol, and water to form the ester of the long chain fatty acid and the alcohol.

Abstract: A vitrification device for gametes or embryos, wherein, the vitrification straw comprises: a loading rod, wherein the loading rod is a metal rod; a loading strip, wherein, the loading strip is connected with one end of the loading rod. According to the present invention, the loading rod is arranged as metal rod, which avoids embrittlement fracture caused by sudden temperature change when the loading rod is taken out of liquid nitrogen, moreover, the ice crystals that form on gametes or embryos when the loading rod floats out of the surface of liquid nitrogen, affecting the safety of gametes or embryos, the metal material used by this invention can increase the weight of the loading rod, preventing it from floating up in the liquid nitrogen, hence improve safety of gametes or embryos.

Abstract: The disclosed method provides a novel approach of generating antigen-specific Immunological Memory in a subject which consists primarily of extracting and purifying monocytes, naive T and B lymphocytes from a subject and educating said lymphocytes against a pathogen in vitro until a population of antigen-specific memory lymphocytes are generated with a memory against an infectious agent. Said memory lymphocytes are administered to a subject in a solution which consist primarily of blood plasma derived from said subject. In embodiments, one will see a vaccine approach wherein said vaccine excludes the inoculation of attenuated or killed whole pathogens, where inoculation of said vaccine does not illicit an immune response upon inoculation, and where said vaccine excludes chemicals such as thimerosal, formaldehyde, and aluminum which is all shunned by anti-vaccinators.

Abstract: The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.

Abstract: The invention provides Epstein-Barr Virus antigen polynucleotides, polypeptides and vectors; as well as immunogenic compositions comprising the same. It includes the use of Epstein-Barr Virus antigen constructs to produce vaccines for treating and preventing Epstein-Barr Virus infections and Epstein-Barr Virus-associated diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus.

Abstract: Provided herein are methods for identifying expression of SDHA, MIF, and or monosomy 3 or disomy 3 status in sample to identify the sample as high-risk melanoma and/or the sensitivity to oxidative phosphorylation inhibitors. Also provided herein are methods for treating monosomy 3 uveal melanoma by administering a SDHA inhibitor in combination with an oxidative phosphorylation inhibitor.

Abstract: Disclosed herein are methods, cells, engineered microorganisms, and kits for increased production of a nucleic acid molecule that comprises an unnatural nucleotide.

Abstract: The present disclosure discloses methods for purifying antibodies providing an air overlay or headspace to single-use storage bags containing the antibody during purification. In specific embodiments, the application relates to purification of antibodies to human TIGIT (T cell immunoreceptor with Ig and ITIM domains), such as antibody 22G2, which decrease unwanted disulfide bond reduction. The application further provides depth filtration at lower throughput and/or flux, which also minimizes unwanted disulfide bond reduction.

Abstract: The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.

Abstract: The present invention relates to the use of cannabidivarin (CBDV) in the treatment of autism spectrum disorder (ASD) and ASD-associated disorders such as Fragile X syndrome (FXS); Rett syndrome (RS); or Angelman syndrome (AS). In a further embodiment the invention relates to the use of CBDV in the treatment of schizophrenia. CBDV has been shown to be particularly effective in improving cognitive dysfunction in rodent models of ASD, FXS, RS, AS and schizophrenia. The CBDV is preferably substantially pure. It may take the form of a highly purified extract of cannabis such that the CBDV is present at greater than 95% of the total extract (w/w) and the other components of the extract are characterised. Alternatively, the CBDV is synthetically produced.

Abstract: Provided herein are conjugated oligonucleotides that are characterized by efficient and specific tissue distribution.

Abstract: This disclosure provides fluidic devices and methods for performing a bioassay, for example bioassays performed on zebrafish. The disclosure provides various fluidic devices for performing a bioassay that include a sample chamber in fluid communication with an air valve; and a bioassay channel that can include a first bioassay region, for example for studying zebrafish in early stages of development and a second bioassay region, for studying zebrafish in later stages of development. The first bioassay region and second bioassay region can be defined using pillars, such as a first and second array of pillars. The fluidic device can have additional structures that are provided herein. Also provided herein are sample loading manifold devices for loading zebrafish embryos into fluidic devices and reagent delivery manifold devices for delivering reagents to fluidic devices. Furthermore, methods using any or all of the devices are provided.

Abstract: Methods, systems, compositions and strategies for the delivery of RNA into cells in vivo, ex vivo, or in vitro via ARMMs are provided. In some aspects, ARMMs containing fusion proteins of ARRDC1 fused to an RNA binding protein or an RNA binding protein fused to a WW domain are provided. In some aspects, ARMMs containing binding RNAs associated with cargo RNAs are provided. In other aspects, cargo RNAs associated with a binding RNA, such as a TAR element, are loaded into ARMMs via ARRDC1 fusion proteins containing an RNA binding protein, such as trans-activator of transcription (Tat) protein.

Abstract: Compositions and methods are related to utilizing glycine and N-acetylcysteine for a variety of medical conditions related to reduced levels of glycine, N-acetylcysteine, and/or glutathione, for example, muscle loss such as sarcopenia, HIV infection and other infections, organ damage such as those from diabetes and insulin resistance and diabetic nephropathy, cardiac function and failure such as preventing or improving heart failure, fatty liver, cancer prevention, and other conditions.

Abstract: The present disclosure relates to genetically modified animals and cells with humanized heavy chain immunoglobulin locus and/or humanized light chain immunoglobulin locus.

Abstract: Described is a method for the preparation of a gelatin hydrolysate having a decreased endotoxin content, comprising the steps of incubating a solution of gelatin of gelatin hydrolysate at a temperature of 70-125° C. at a pH of 3.5 or less for a time period of at least 15 minutes, and recovering the gelatin hydrolysate. Further a gelatin hydrolysate thus obtained is described.

Abstract: The present invention may provide a pharmaceutical composition for preventing or treating skin diseases, a cosmetic composition for preventing or improving skin diseases, and a stem cell therapeutic agent, which comprise an induced pluripotent stem cell-derived mesenchymal stem cell (iMSC), a culture thereof, or an exosome isolated from an iMSC or iMSC culture as active ingredients. When the composition of the present invention, etc. is used, it is possible to provide a composition for improving, preventing or treating skin diseases and a stem cell therapeutic agent which have an improved immunomodulating function over conventional mesenchymal stem cells.

Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.

Abstract: This disclosure provides methods for producing a sample of subcellular organelles, particularly nuclei, from a tissue. In some embodiments, this disclosure provides a method of processing a tissue sample involves performing enzymatic/chemical disruption of tissue in a chamber to produce disrupted tissue comprising released cells and/or nuclei and debris; separating the released cells and/or nuclei from the debris therein; and moving the released cells and/or nuclei. In some instances, the method comprises mechanical disruption of the tissue sample.

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: A neural network is trained using transfer learning to analyze medical image data, including 2D, 3D, and 4D images and models. Where the target medical image data is associated with a species or problem class for which there is not sufficient labeled data available for training, the system may create enhanced training datasets by selecting labeled data from other species, and/or labeled data from different problem classes. During training and analysis, image data is chunked into portions that are small enough to obfuscate the species source, while being large enough to preserve meaningful context related to the problem class (e.g., the image portion is small enough that it can't be determined whether it is from a human or canine, but abnormal liver tissues are still identifiable). A trained checkpoint may then be used to provide automated analysis and heat mapping of input images via a cloud platform or other application.

Abstract: The present disclosure provides a method for designing a set of guide RNAs for hybridizing a genomic region of interest. The present disclosure further provides methods of editing at least one genomic region of interest with at least one set of guide RNAs.

Abstract: Disclosed are enhanced umbilical cord-derived adhesive stem cells, a preparation method therefor, and a use thereof. The enhanced umbilical cord-derived adhesive stem cells have an anti-inflammatory effect, a blood vessel regeneration effect, or a nerve regeneration effect, thereby being usable in a pharmaceutical composition or a cell therapeutic agent for treating or preventing various diseases.

Abstract: The present invention provides several non-naturally occurring sulfotransferase enzymes that have been engineered to react with aryl sulfate compounds as sulfo group donors, instead of the natural substrate 3?-phosphoadenosine 5?-phosphosulfate (PAPS), and with heparosan-based polysaccharides, particularly heparan sulfate, as sulfo group acceptors. Each of the engineered sulfotransferase enzymes have a biological activity characterized by the position within the heparosan-based polysaccharide that receives the sulfo group, including glucosaminyl N-sulfotransferase activity, hexuronyl 2-O sulfotransferase activity, glucosaminyl 6-O sulfotransferase activity, or glucosaminyl 3-O sulfotransferase activity. Methods of using the engineered sulfotransferases to produce sulfated heparosan-based polysaccharides, including polysaccharides having anticoagulant activity, are also provided.

Abstract: Provided herein are methods for treating cancer, comprising administering to a subject having cancer a therapeutically effective amount of an anti-GITR antibody alone or together with an anti-PD-1 or anti-PD-L1 antibody.

Abstract: Technologies and implementations for a system and method for determining a force applied to a cell or tissue culture is disclosed. The system and method may include an elastic element mounted in or suitable for mounting in a culture chamber. The elastic element may be adapted to be coupled with the cell or the tissue culture such that a force applied to the cell or the tissue culture leads to a deflection of the elastic element against a restoring force. A magnetic field sensor may be mounted outside said culture chamber. The magnetic field sensor may be adapted to detect a change of magnetic field attributable to a corresponding movement of a magnetic element upon deflection.