Abstract: The present invention relates to CNP prodrugs in which the carrier is covalently and reversibly attached to the ring moiety of a CNP moiety, to pharmaceutical compositions comprising such CNP prodrugs, to their uses and to methods of treating diseases that can be treated with the CNP prodrugs of the present invention.

Abstract: A sheet aligning mechanism includes first and second conveyance mechanisms disposed on first and second sides of a sheet conveyance path, respectively. A nip is formed between the first and second conveyance mechanisms. The first conveyance mechanism includes a first roller, a second roller, and a first conveyance belt wound around the first and second rollers. The first and second rollers are configured to rotate in a first direction along a sheet conveying direction for sheet conveyance, and stop rotation or rotate in a second direction opposite to the first direction for sheet alignment. The first conveyance belt includes an extended region between the first and second rollers in an extending direction inclined with respect to the sheet conveying direction, such that a width of the sheet conveyance path becomes narrower towards the nip in the sheet conveying direction.

Abstract: This invention concerns an integrated microfluidic system that utilizes microfluidic chip technology to receive a patient sample including cells, expand the cells, reprogram the expanded cells and then store the reprogrammed cells in a microfluidic chip. These microfluidic chips with stored reprogrammed cells may then be used in scenarios of genetic differentiation into specific cell types. Overall this system and workflow is suitable as a hospital based device that will allow the generation of iPSCs from every patient for downstream diagnostic or therapeutic use.

Abstract: The invention provides for compositions and methods for identifying and validating modulators of cell fate, such as such as maintenance, cell specification, cell determination, induction of stem cell fate, cell differentiation, cell dedifferentiation, and cell trans-differentiation. The invention relates to reporter nucleic acid constructs, host cells comprising such constructs, and methods using such cells and constructs. The invention relates to methods for making cells comprising one or more reporter nucleic acid constructs using fluorogenic oligonucleotides. The methods relate to high throughput screens.

Abstract: Methods for de-differentiating or altering the life-span of desired “recipient” cells, e.g., human somatic cells, by the introduction of cytoplasm from a more primitive, less differentiated cell type, e.g., oocyte or blastomere are provided. These methods can be used to produce embryonic stem cells and to increase the efficiency of gene therapy by allowing for desired cells to be subjected to multiple genetic modifications without becoming senescent. Such cytoplasm may be fractionated and/or subjected to subtractive hybridization and the active materials (sufficient for de-differentiation) identified and produced by recombinant methods.

Abstract: Devices, systems, and methods for continuous cell culture and other reactions are generally described. In some embodiments, chambers (e.g., cell growth chambers) including at least a portion of a wall formed of a flexible member are provided. A retaining structure can be incorporated outside and proximate to the chamber such that when liquid is added to the chamber, the flexible member is consistently and predictably deformed, and a consistent volume of liquid is added. The flexible member can be formed of, in some embodiments, a gas-permeable medium. In some embodiments, reaction chambers can be arranged in a fluidic loop, and a bypass channel can be used to introduce and/or extract fluid from the loop without affecting loop operation.

Abstract: The present invention provides a method for improving pancreatic function in a subject in need thereof, the method comprising administering to the subject STRO-1+ cells and/or progeny cells thereof and/or soluble factors derived therefrom. The method of the invention is useful for treating and/or preventing and/or delaying the onset or progression of a disorder resulting from or associated with pancreatic dysfunction, e.g., resulting from abnormal endocrine or exocrine function of the pancreas.

Abstract: The present invention relates to a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1). The two polypeptides can be should preferentially be expressed at a ratio between 3:1 and 15:1, such as between 3:1 and 7:1. The invention is useful in the treatment of catecholamine deficient disorders, such as dopamine deficient disorders including but not limited to Parkinson's Disease. Moreover, the present invention provides a method to deliver the vector construct in order to limit the increased production of the catecholamine to the cells in need thereof.

Abstract: A method for suppressing an immune response is provided. The method involves administration of isolated lymphoid tissue-derived suppressive stromal cells (LSSC) to a subject in need of such treatment in an amount effective to suppress the immune response in the subject. The invention also involves a method to isolate LSSC by digesting lymphoid tissue fragments using a combination of an enzyme mix and agitation and then collecting the LSSC. Pharmaceutical preparations comprising LSSC are also provided.

Abstract: An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms.

Abstract: Methods are described for the delivery of one or more small interfering RNAs (siRNAs) to a eukaryotic cell using a bacterium. Methods are also described for using this bacterium to regulate gene expression in eukaryotic cells using RNA interference, and methods for treating an inflammatory disease or disorder. The bacterium includes one or more siRNAs or one or more DNA molecules encoding one or more siRNAs. Vectors are also described for use with the bacteria of the invention for causing RNA interference in eukaryotic cells.

Abstract: Disclosed are methods of gene delivery using capsid-modified recombinant adeno-associated viral (rAAV) vectors. Exemplary methods are provided employing vectors that have altered affinity for heparin or heparin sulfate, as well as vectors, expression systems, and rAAV virions that lack functional VP2 protein expression, but are nevertheless, fully virulent. Also provided by the invention are methods employing the rAAV vector-based compositions, virus particles, host cells, and pharmaceutical formulations in the expression of selected therapeutic proteins, polypeptides, peptides, antisense oligonucleotides and/or ribozymes in selected mammals, including organs, tissues, and human host cells.

Abstract: The invention provides an isolated H3 equine influenza A virus, as well as methods of preparing and using the virus, and genes or proteins thereof.

Abstract: The present invention relates to a novel method for expanding mesenchymal stem cells (MSCs) in low-density and hypoxic condition as compared to normal air conditions traditionally used in cell culture. The present method provides rapid and efficient expansion of human MSCs without losing cellular proliferation and stem cell properties, including increase in proliferation, decrease in senescence, and increase in differentiation potential both in vitro and in vivo. The expanded MSCs by the present method may maintain normal karyotyping, and will not form tumor when transplanted into mammal.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing one or more proteins under the control of a gene expression modulation, system in the presence of activating ligand and uses for therapeutic purposes in animals. The vector may be provided to treat or prevent disease.

Abstract: A family of novel feline bitter taste receptors, referred to as feline TAS2R (fTAS2R), are disclosed herein. Isolated polynucleotides encoding the novel feline bitter taste receptors and chimeric polypeptides are also disclosed, as are expression vectors and host cells for expression of the novel feline bitter taste receptors. Methods of identifying compounds that bind to the novel feline bitter taste receptors and modulate their activity are disclosed.

Abstract: The present invention is concerned with nuclease fusion proteins and various uses thereof. Specifically, it relates to a polynucleotide encoding a polypeptide comprising (i) a first module comprising at least a first DNA binding domain derived from a homing endonuclease, (ii) a linker, and (iii) a second module comprising at least a second DNA binding domain and a cleavage domain derived from a restriction endonuclease, wherein said polypeptide functionally interacts only with DNA comprising a DNA recognition site for the first DNA binding domain and a DNA recognition site for the second DNA binding domain, and wherein said cleavage domain cleaves DNA within a specific DNA cleavage site upon binding of the polypeptide. Further contemplated are a vector and a non-human transgenic organism comprising said polynucleotide as well as a polypeptide encoded by the polynucleotide of the invention.

Abstract: Described are methods for determining the permissiveness of a cell for a virus that is a member of the family Arteriviridae or Coronaviridae or Asfarviridae, in particular, for Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). Further described are methods and compositions related to the generation of host cells permissive for a virus that is a member of the family Arteriviridae or Coronaviridae or Asfarviridae, in particular, for PRRSV. Methods of utilzing the cells thus identified or thus generated, in preparing a culture of a virus that is a member of the family Arteriviridae or Coronaviridae or Asfarviridae, as well as the use of the virus for the purpose of vaccine production or diagnosis, are also described.

Abstract: Provided is a method of dedifferentiating somatic cells using embryonic stem cell-derived microvesicles. Particularly, a method of preparing induced pluripotent stem cells by treating a composition including embryonic stem cell-derived microvesicles to the somatic cells. According to the method of preparing induced pluripotent stem cells, the dedifferentiation of the somatic cells may be efficiently performed without side effects using the embryonic stem cell-derived microvesicles, and moreover, the method is expected to be very useful in developing a cell therapy product having immunocompatibilities by individuals.

Abstract: The present invention relates to the field of biotechnology or genetic engineering. More specifically, the present invention relates to a multiple inducible gene regulation system that functions within cells to simultaneously control the quantitative expression of multiple genes.

Abstract: A transgenic cat with a phenotype characterized by the substantial absence of the major cat allergen, Fel d I. The phenotype is conferred in the transgenic cat by disrupting the coding sequence of the target gene with a specialized construct. The phenotype of the transgenic cat is transmissible to its offspring.

Abstract: Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

Abstract: Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

Abstract: This disclosure relates to vectors, isolated cells, compositions, and methods for the treatment of critical limb ischemia and associated disorders. One aspect of the disclosure relates to a vector comprising a nucleic acid encoding a 165A isoform VEGF protein and a promoter that regulates expression of the nucleic acid encoding the VEGF.

Abstract: Methods for producing compositions of decellularized extracellular matrix (DM) tissue culture are described. The compositions can be used for coating supports such as tissue culture substrates, osteogenic gels, and medical devices.

Abstract: Pharmaceutical compositions and methods for inhibiting cell growth, modulating function of PCNA, treating prostate cancer, and enhancing PCNA trimer formation are disclosed.

Abstract: Generally, compositions and methods for handling processed sperm populations including samples that are freshly collected, transported as fresh samples, as well as samples that are frozen and thawed, those sorted into one or more subpopulations, and those that are otherwise processed or handled that impose trauma on the sperm cell. Such trauma can reduce the motility, fertility, viability and overall integrity of the sperm and reduce the sperm's ability to fertilize an egg, grow into a healthy embryo and produce a healthy offspring. The novel compounds described can be added to the sperm cell sample to reduce the traumatic effects of physical stress during mild as well as extensive sperm cell processing, methods of using the compounds in standard sperm processing procedures, the end products made from these methods including sperm and embryos, as well as methods of using those end products in assisted reproductive biology techniques in animals.

Abstract: Two vIRF4 (Kaposi's-sarcoma-associated-herpesvirus vIRF4) peptides, vif1, corresponding to aa202-216 of vIRF4, and vif2, corresponding to aa220-236 of vIRF4, are potent and selective HAUSP antagonists. The vif1 and vif2 peptides robustly suppress HAUSP DUB enzymatic activity, ultimately leading to p53-mediated anti-cancer activity. The vif1 and vif2 peptides, along with their homologues, are useful in treating cancer through regulation of p53 activity in a cancer cell. Also disclosed is the crystalline structure of vIRF4-HAUSP TRAF domain complex. The structure is useful in computer aided drug design for identifying an agent that interacts with and inhibits HAUSP, resulting in p53 medicated cell cycle arrest of cancer cells.

Abstract: This invention relates to a cell comprising a reporter gene under control of an ARIA gene promoter, the cell being used for searching for an agent for prevention or treatment of diseases attributed to reduced insulin sensitivity, for searching for an obesity-controlling substance, or for searching for an obesity-inducing substance.

Abstract: Disclosed herein are flowable tissue matrix compositions comprising small pieces of partially or completely decellularized tissue suspended in a gelatinized tissue or gelatin gel comprising partially or completely decellularized tissue or synthetic gelatin. The flowable tissue matrix compositions can contain factors that promote or enhance native cell migration, proliferation, and/or revascularization after implantation into a subject. Also disclosed are methods of making and using the flowable tissue matrix compositions. The compositions can be implanted into a tissue in need of repair, regeneration, healing, treatment, and/or alteration, and can promote or enhance native cell migration, proliferation, and/or revascularization.

Abstract: The application discloses peptides capable of preventing or treating fungal disease, including fungal allergy disease.

Abstract: An in vitro system for generating sequence, and thus structural, diversity in proteins is described. The system can be constructed using appropriately selected nucleic acid molecules that encode regions of a selected protein or proteins and recombination signal sequences (RSS). The selected protein(s) can be, for example, immunoglobulin (Ig) V, D, J and/or C regions, regions of a non-immunoglobulin (non-Ig) protein, or a combination of Ig regions and non-Ig regions. Assembly of such appropriately selected components and their introduction into suitable recombination-competent host cells allows for recombination between the RSS sequences and introduction of sequence and structural diversity into the protein(s).

Abstract: The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.

Abstract: The present invention relates to compositions and methods for the handling of processed sperm including samples that are freshly collected, those transported as fresh samples, samples that are frozen and thawed, those sorted into one or more subpopulations, and those that are otherwise processed or handled that impose trauma on the cell. Trauma can reduce the motility, fertility, viability and overall integrity of the sperm and reduce the ability to fertilize, produce an embryo and a healthy offspring. The present invention relates to novel compounds that can be added to the sperm cell sample to reduce the traumatic effects of physical stress during mild as well as extensive sperm cell processing, methods of using the compounds in standard sperm processing procedures, the end products made from these methods including sperm and embryos, as well as methods of using those end products in assisted reproductive biology techniques in animals.

Abstract: Methods for preparing a variety of cell (e.g., hepatocyte) preparations and preparations so prepared are described. Uses of such preparations are described. In one embodiment, centrifugal elutriation is used to separate hepatocytes with preferred characteristics. Such hepatocyte preparations may be used for cryopreservation, multiple cryopreservations, in vitro assays, plating and other methods for which preparations of hepatocytes are useful.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a Group H nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: Methods for de-differentiating or altering the life-span of desired “recipient” cells, e.g., human somatic cells, by the introduction of cytoplasm from a more primitive, less differentiated cell type, e.g., oocyte or blastomere are provided. These methods can be used to produce embryonic stem cells and to increase the efficiency of gene therapy by allowing for desired cells to be subjected to multiple genetic modifications without becoming senescent. Such cytoplasm may be fractionated and/or subjected to subtractive hybridization and the active materials (sufficient for de-differentiation) identified and produced by recombinant methods.

Abstract: This invention provides a crystalline recombinant interferon (rSIFN-co (SEQ ID NO: 1)) having (i) the same amino acid sequence as that of human consensus interferon, and (ii) altered three-dimensional structure as compared to IFN-?2b. The interferon of the present invention exhibits enhanced biological activities. The present invention also provides a structure model of said interferon useful for drug screening and/or drug design and the mimetic of said interferon.

Abstract: Disclosed herein is a method of producing multipotent cells, comprising, activating ALK2 of isolated endothelial cells in a serum starved environment, to thereby produce isolated multipotent cells. Activation can be following a threshold period of serum starvation. Activating ALK2 is by contacting the isolated endothelial cells with TGF?-2 and/or BMP4. The isolated endothelial cells may be human, such as primary vascular, primary microvascular endothelial cells, primary human umbilical vein endothelial cells (HUVEC) or primary human cutaneous microvascular endothelial cells (HCMEC). The activation of ALK2 significantly decreases expression of VE-cadherein of the cells and/or significantly increases expression of one or more of STRO-1, FSP-1, ?-SMA, N-cadherin, fibronectin (FN1), Snail (SNAI1), Slug (SNAI2), ZEB-1, SIP-1, LEF-1, Twist, CD10, CD13, CD44, CD73, CD90, CD120A, and CD124.

Abstract: The present invention discloses a method for modulating the quality of a selected phenotype that is displayed by an organism or part thereof and that results from the expression of a polypeptide-encoding polynucleotide by replacing at least one codon of that polynucleotide with a synonymous codon that has a higher or lower preference of usage by the organism or part thereof to produce the selected phenotype than the codon it replaces. The present invention is also directed to the use of a codon-modified polynucleotide so constructed for modulating the quality of a selected phenotype displayed by an organism or part thereof.

Abstract: The invention provides compositions for making erythroid progenitor cells that comprise in vitro-activated bone marrow mesenchymal stem cells and embryoid bodies (EBs) or pluripotent stem cells, and methods for making and using them, including ameliorating (e.g., preventing or treating) anemia and/or stimulating erythropoiesis. In one embodiment, the invention provides methods of increasing propensity of committed stem cell differentiation towards the erythroid lineage.

Abstract: The present invention relates to isolated organ-specific feline endothelial cells. Specifically, the present invention relates to established organ-specific feline endothelial cells. The present invention also relates to organ-specific feline endothelial cells derived from micro- and macro-vascularisation. The present invention also relates to methods for screening molecules, for studying pathologies and for producing pathogens using same.

Abstract: An apparatus and method to maintain pH within a range conducive for cell growth in a bicarbonate-containing cell culture system without the addition of base. The method relies on the gas transfer characteristics of the bioreactor system to modulate the CO2 transfer to and from the cell culture such that the pH of the cell culture can be maintained within a desired range.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic plants and animals.

Abstract: The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).

Abstract: This invention provides new combinatorial approaches for the biosynthesis and screening of cyclic peptides inside living cells. These novel approaches are useful for finding biologically relevant molecules, e.g., those able to inhibit the cytotoxicity of Anthrax Edema Factor. Key to this ‘living combinatorial’ approach is the use of a living cell as a micro-chemical factory for both synthesis and screening of potential inhibitors for a given molecular recognition event.

Abstract: Biological surfactants connected to surfaces of silicone-based materials are provided. Compositions of electrolytes and a biological surfactant are also provided. Methods for increasing the surface wettability of a silicone-based material by contacting the silicone-based material with a biological surfactant, methods for increasing evaporation from a silicone-based material by contacting a surface of the silicone-based material with a biological surfactant, methods for increasing levels of interleukin-8 during inflammation by contacting a cell with a biological surfactant, and methods for decreasing expression of a biological surfactant by contacting a cell with an siRNA are further provided.

Abstract: The invention relates to the use of an active collagen matrix for culturing mammalian cells and the use of the active collagen matrix and cells for the treatment of disease.

Abstract: The invention provides for compositions and methods for identifying and validating modulators of cell fate, such as such as maintenance, cell specification, cell determination, induction of stem cell fate, cell differentiation, cell dedifferentiation, and cell trans-differentiation. The invention relates to reporter nucleic acid constructs, host cells comprising such constructs, and methods using such cells and constructs. The invention relates to methods for making cells comprising one or more reporter nucleic acid constructs using fluorogenic oligonucleotides. The methods relate to high throughput screens.