Abstract: The present disclosure provides systems and methods for determining effects of genetic variants on selection of polyadenylation sites (PAS) during polyadenylation processes. In an aspect, the present disclosure provides a polyadenylation code, a computational model that can predict alternative polyadenylation patterns from transcript sequences. A score can be calculated that describes or corresponds to the strength of a PAS, or the efficiency in which it is recognized by the 3?-end processing machinery. The polyadenylation model may be used, for example, to assess the effects of anti-sense oligonucleotides to alter transcript abundance. As another example, the polyadenylation model may be used to scan the 3?-UTR of a human genome to find potential PAS.

Abstract: A method of growing primary human epithelial cells, in particular human epithelial cells using a basal formula containing individual (a) amino acids, (b) vitamins, (c) trace elements, and (d) other organics such as linoleic acid. The basal medium may be a mixture of amino acids, vitamins, and salts that constitute the basic media that is used to culture epithelial cells over a number of population doublings, e.g., over at least one week, while maintaining a normal phenotype and exerting low stress on the cultured cells, and maintaining lineage heterogeneity.

Abstract: A bench top incubator is described. The bench top incubator includes a multiple temperature sensors and control systems so as to provide independent data logs of temperature data from each of the multiple temperature sensors. The incubator is relatively simple and small in design and can be conveniently located to carry out temperature processing of biological samples such as fixed cells and tissues, biological fluids, and so forth.

Abstract: This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.

Abstract: The invention provides compositions, methods and treatment regimens for treating cancer comprising periodic subcutaneous administration of the fusion protein of SEQ ID NO:1 to a cancer patient resulting in enhanced activation of CD8+ T-cells with minimal effects on regulatory T cell (Treg) expansion and providing enhanced anti-tumor efficacy while also mitigating T cell inactivation/exhaustion.

Abstract: A collection pipette that collects a microscopic object includes a first tube part, a second tube part connected to an end of the first tube part, and a third tube part connected to the other end of the first tube part. The longitudinal direction of the third tube part intersects with the longitudinal direction of the first tube part, and is parallel to the longitudinal direction of the second tube part. For example, the length in the longitudinal direction of the third tube part is shorter than the length in the longitudinal direction of the first tube part.

Abstract: Disclosed are methods for delivering a therapeutic or diagnostic agent to the cytosol of a cell in a subject. The disclosed methods generally include administering to the subject an effective amount of a lipid nanoparticle comprising the therapeutic or diagnostic agent and an effective amount of a membrane-destabilizing polymer. Also disclosed are related compositions and delivery systems.

Abstract: Disclosed herein are antisense oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA at the 5?-end of UBE3A-AS, which is downstream of SNORD115-45 snoRNA. Also disclosed are pharmaceutical compositions and methods for treatment of Angelman syndrome.

Abstract: The present invention provides a hollow fiber membrane module which makes it possible to concentrate incubated platelets by efficiently removing water from an incubated platelet suspension liquid containing incubated platelets while suppressing deterioration of the function of the incubated platelets. The present invention provides an incubated platelet concentration module in which a plurality of hollow fiber membranes each having pores with an average pore diameter of 2 ?m or less on a surface of the hollow fiber membrane are packed in a casing having at least one inlet for supplying an incubated platelet suspension liquid before concentration into the hollow fiber membranes, wherein a value (X/Y1) obtained by dividing a total cross-sectional area (X) of the plurality of hollow fiber membranes by a total cross-sectional area (Y1) of the least one inlet is 4.0 or less.

Abstract: The present invention relates to the field of dental care, e.g., with toothpaste, tooth gel, mouth-wash, mouth spray or oral care foam. In particular, it provides an anti-inflammatory and senolytic dental care product with tooth whitening characteristics. The dental care product comprises calcium phosphate particles of a specific size, the self-assembling peptide P11-4 or oligopeptide 104 of SEQ ID NO: 1, an extract of a plant of the genus Rhododendron, preferably, an alpine rose or Alpenrose such as Rhododendron ferrugineum or Rhododendron hirsutum, and an extract of a plant of the genus Leontopodium, such as Leontopodium nivale, which is also called Edelweiss. The dental care product may further comprise an extract of a plant of the genus Eleutherococcus, such as Eleutherococcus senticosus, which is also designated Siberian ginseng or Acanthopanax senticosus.

Abstract: Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester-moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels/nanofibrils form, and screening the collected secretome.

Abstract: The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR or EGFR expression and methods of using these splice-switching oligonucleotides to treat cancer.

Abstract: Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a “bandaid-like” covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue.

Abstract: An antisense oligonucleotide capable of preventing or reducing exon 80 inclusion into a human COL7A1 mRNA, and methods for preventing or reducing exon 80 inclusion into a human COL7A1 mRNA.

Abstract: Provided are a unimolecular nanoparticle, a composition thereof, and methods of use thereof, and includes 1) a dendritic polymer having a molecular weight of about 500-120,000 Da and terminating in hydroxyl, amino or carboxylic acid groups; 2) cationic polymers attached to at least a majority of the terminating groups of the dendritic polymer via a pH-sensitive linker, wherein each cationic polymer comprises a polymeric backbone attached to cationic functional groups and to weakly basic groups by disulfide bonds, wherein the molar ratio of cationic functional groups to weakly basic groups ranges from 1:1-5:1, and has a molecular weight from about 1,000-5,000 Da; and 3) poly(ethylene glycol) attached to a plurality of cationic polymers and having a terminal group selected from a targeting ligand, OH, O-alkyl, NH2, biotin, or a dye, wherein the terminal group of at least one poly(ethylene glycol) is having a molecular weight of about 1,000-15,000 Da.

Abstract: Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.

Abstract: The present disclosure relates to RNAi constructs with improved cellular uptake characteristics and methods of use of these compounds for silencing expression of long coding RNAs (IncRNAs).

Abstract: The invention relates to new identified mutations in the epidermal growth factor receptor gene, leading to amino acidic changes which highly correlate with the resistance to a therapy regimen comprising cetuximab. The invention includes peptide sequences and primers to detect the mutations, as well as kits for predicting the response of a subject to a therapy regime comprising cetuximab. In particular, the invention is useful in the therapy regimen applicable to metastasic colorectal cancer.

Abstract: An object of the present invention is to provide a medium that comprises fewer protein components and enables the maintenance of pluripotent stem cells in an undifferentiated state. The culture medium for pluripotent stem cells comprises a GSK3? inhibitor (A) and a DYRK inhibitor (B).

Abstract: Method for targeted alteration of a duplex acceptor DNA sequence in a plant cell protoplast, comprising combining the duplex acceptor DNA sequence with a donor mutagenic nucleobase, wherein the duplex acceptor DNA sequence contains a first DNA sequence and a second DNA sequence which is the complement of the first DNA sequence and wherein the donor mutagenic nucleobase comprises at least one mismatch with respect to the duplex acceptor DNA sequence to be altered, preferably with respect to the first DNA sequence, wherein the method further comprises a step of introducing the donor mutagenic nucleobase into the cell protoplasts using polyethylene glycol (PEG) mediated transformation and the use of PEG protoplast transformation for enhancing the rate of targeted mutagenesis.

Abstract: The present invention relates to a method of inhibiting p-glycoprotein (P-gp) expression in a cell. The method involves contacting a cell expressing P-gp with a composition comprising an effective amount of an A2A adenosine receptor (A2A AR) agonist to inhibit P-gp expression in the cell. Methods of enhancing the bioavailability of a chemotherapeutic in a subject having multi-drug resistant (MDR) cancer and methods of increasing P-gp-mediated efflux in a cell are also disclosed.

Abstract: Provided herein is a method of making an aligned ECM scaffold useful in refractive correction of the eye and repair of the cornea. Methods of use of the scaffold as well as a scaffold construct are provided.

Abstract: Method for reprogramming differentiated cells into lineage restricted progenitor cells is provided. The method may include contacting differentiated cells with inhibitors of tyrosine phosphatases and apoptosis to de-differentiate differentiated cells into lineage restricted progenitor cells.

Abstract: An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.

Abstract: This present invention discloses an antisense oligonucleotide for splicing adjustment of mutant dopa decarboxylase gene which is complementary to SEQ ID NO: 1. This antisense oligonucleotide can modulate alternative splicing site of mutant dopa decarboxylase gene. It is helpful to research and develop drug to treat AADC deficiency symptom. This present invention also discloses a method to use said antisense oligonucleotide in vitro.

Abstract: A method for preparing exosomes or exosome-like vesicles packaged with a nucleic acid of interest is provided. In certain embodiments, the method may comprise: introducing into an exosome-producing cell a nucleic acid construct comprising the nucleic acid sequence of interest incorporated in a pre-miR-451 structural mimic, and allowing the cell to produce exosomes. Nucleic acid constructs, compositions, and uses thereof are also provided.

Abstract: The invention relates to methods of altering expression of a genomic locus of interest or specifically targeting a genomic locus of interest in an animal cell, which may involve contacting the genomic locus with a non-naturally occurring or engineered composition that includes a deoxyribonucleic acid (DNA) binding polypeptide having a N-terminal capping region, a DNA binding domain comprising at least five or more Transcription activator-like effector (TALE) monomers and at least one or more half-monomers specifically ordered to target the genomic locus of interest, and a C-terminal capping region, wherein the polypeptide includes at least one or more effector domains, and wherein the polypeptide is encoded by and translated from a codon optimized nucleic acid molecule so that the polypeptide preferentially binds to the DNA of the genomic locus.

Abstract: Methods and compositions for modulating the activities of connexins are provided, including, for example, for use in post-surgical, trauma, or tissue engineering applications. These compounds and methods can be used therapeutically, for example, to reduce the severity of adverse effects associated diseases and disorders where localized disruption in direct cell-cell communication is desirable.

Abstract: The disclosure relates generally to neurodegenerative disorders and more specifically to a group of presenilin/G-protein/c-src binding polypeptides and methods of use for modulating signaling and progression of Alzheimer's disease.

Abstract: A hierarchy of endothelial colony forming cells (EPCs) was identified from mammalian cord blood, umbilical vein and aorta. A newly isolated cell named high proliferative potential—endothelial colony forming cell (HPP-ECFC) was isolated and characterized. Single cell assays were developed that test the proliferative and clonogenic potential of endothelial cells derived from cord blood, or from HUVECs and HAECs. EPCs were found to reside in vessel walls. Use of a feeder layer of cells derived from high proliferative potential-endothelial colony forming cells (HPP-ECPCS) from human umbilical cord blood, stimulates growth and survival of repopulating hematopoietic stem and progenitor cells. Stimulation of growth and survival was determined by increased numbers of progenitor cells in in vitro cultures and increased levels of human cell engraftment in the NOD/SCID immunodeficient mouse transplant system.

Abstract: Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

Abstract: The invention provides engineered RNA precursors that when expressed in a cell are processed by the cell to produce targeted small interfering RNAs (siRNAs) that selectively silence targeted genes (by cleaving specific mRNAs) using the cell's own RNA interference (RNAi) pathway. By introducing nucleic acid molecules that encode these engineered RNA precursors into cells in vivo with appropriate regulatory sequences, expression of the engineered RNA precursors can be selectively controlled both temporally and spatially, i.e., at particular times and/or in particular tissues, organs, or cells.

Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Abstract: MicroRNA-30 is identified as being dysregulated in adipose tissue macrophages during obesity and can be used in treatment of disease in which adipose tissue macrophage polarization dysregulation plays a part. Increased concentration of microRNA-30, e.g., via pharmaceutical delivery, can decrease the polarization of macrophages, and in particular adipose tissue macrophages, to inflammatory M1 phenotype and can decrease expression of pro-inflammatory cytokines. One or more members of the miR-30 family can be utilized in the methods. Methods can be beneficial in treatment of a large number of inflammatory diseases including obesity, diabetes, cancer, autoimmune, etc.

Abstract: The invention relates to compositions of vault complexes for use as delivery agents for hydrophobic and/or aqueous insoluble therapeutic compounds. In one aspect, provided herein is a vault complex comprising a modified major vault protein (MVP), wherein the modified major vault protein comprises a fusion peptide, wherein said fusion peptide is fused to the N-terminus of the major vault protein, and wherein said peptide provides enhanced sequestering of a hydrophobic and/or aqueous insoluble therapeutic compound within the vault complex.

Abstract: The present invention relates generally to the field of tissue engineering and in particular to the production of tissue films or cell matrices, which can be used as a living tissue substitute or an artificial tissue construct in tissue repair or replacement.

Abstract: The present invention relates to a method for treating a Leber congenital amaurosis in a patient harbouring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c.2991+1655 A>G CEP290 mRNA.

Abstract: The invention provides a method of treating a vascular condition within a subject comprising administering a therapeutic agent to said subject that is capable of modulating the expression levels of a long non-coding RNA (IncRNA) selected from the group consisting of lncRNA2, lncRNA4, lncRNA5, lncRNA6, ncRNA7 and ncRNA8 as defined in FIG. 39.

Abstract: Provided herein are isolated populations of kidney cells harvested from differentiated cells of the kidney, wherein the cells have been expanded in vitro. The kidney cells preferably produce erythropoietin (EPO). The kidney cells may also be selected based upon EPO production. Methods of producing an isolated population of EPO producing cells are also provided, and methods of treating a kidney disease resulting in decreased EPO production in a patient in need thereof are provided, including administering the population to the patient, whereby the cells express EPO in vivo in an oxygen tension-dependent manner.

Abstract: Methods and compositions are provided for modulating, e.g., reducing, viral coding sequence expression in mammals and mammalian cells. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is introduced into a target cell, e.g., by being administered to a mammal that includes the target cell, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

Abstract: The instant disclosure features single-stranded RNA molecules comprising one or more internal, non-nucleotide spacers. A non-nucleotide spacer covalently links nucleotide portions of the molecule. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism and, thus, represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.

Abstract: Androgen receptor-based vaccines for eliciting an immune reaction in vivo against cells expressing androgen receptor are disclosed. The vaccines are useful in the treatment of prostate cancer. Also disclosed are methods for inducing immune reaction to androgen receptor or treating prostate cancer in a mammal, using the vaccines and pharmaceutical compositions comprising the vaccines.

Abstract: This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.

Abstract: Provided are a therapeutic and/or prophylactic agent for a lung disease and a method for screening for the therapeutic and/or prophylactic agent. Provided are a therapeutic and/or prophylactic agent for a lung disease comprising an Arid5A inhibitor as an active ingredient and a method for screening for the therapeutic and/or prophylactic agent.

Abstract: Compounds useful as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Abstract: Aspects of the present disclosure include methods that include co-culturing a cell and a microparticle that includes a capture ligand, in a culture medium under conditions in which a biomarker produced by the cell is bound by the capture ligand. Such methods may further include detecting (e.g., by flow or mass cytometry) complexes that include the microparticle, the capture ligand, the biomarker, and a detection reagent. The methods may further include determining the proportion or number of cells among a heterogeneous cell population that produced the biomarker and/or the level of biomarker secreted by such cells. Compositions, systems and kits are also provided.

Abstract: Embodiments of the present disclosure include particles, methods of making particles, methods of delivering an active agent using the particle, and the like.

Abstract: Systems and methods for generating a mask for automated assessment of embryo quality are disclosed herein. The method for generating a mask for automated assessment of embryo quality can include receiving an image, including a plurality of pixels, of a human embryo from an imaging system. A pixel can be selected and features of the selected pixel can be determined by generating a plurality of random boxes of random sizes and at random locations about the selected pixel. The selected pixel can be identified as one of: inside of a mask area; and outside of the mask area based on the determined features.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Alpha-L-Iduronidase (IDUA), in particular, by targeting natural antisense polynucleotides of Alpha-L-Iduronidase (IDUA). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of IDUA.

Abstract: This invention provides compositions for use in distributing active agents for treating a malignant tumor in a subject. The compositions contain RNAi molecules targeted to a human GST-?, along with RNAi molecules targeted to a human p21, and a pharmaceutically acceptable carrier. The carrier can include nanoparticles composed of an ionizable lipid, a structural lipid, one or more stabilizer lipids, and a lipid for reducing immunogenicity of the nanoparticles. This invention further provides methods for preventing or treating a malignant tumor by administering a therapeutically effective amount of an RNAi composition.