Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

The present application relates to compositions and methods for genome editing in cells by homology-independent mechanisms, in particular for genome editing in cells that lack the machinery necessary for repair by homology-dependent mechanisms.

The present invention provides: a composition for reconstituting human skin tissue having hair follicles, the composition characterized by containing human epidermal cells and human dermal cells, the human dermal cells containing cell groups of human hair papilla derived from non-embryos via spheroid formation; and a human skin tissue model animal to which said composition is applied. The invention also provides a method for producing said composition and animal.

Immune-based approaches to treat and prevent skin cancer by boosting T cell immunity against commensal HPVs present on skin. Thus, provided herein are compositions comprising: (i) a plurality of antigenic peptides each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses, (ii) a plurality of live or live attenuated commensal human papilloma viruses, (iii) a plurality of antigenic proteins from commensal human papilloma viruses, preferably in virus-like particles, and/or (iv) a plurality of nucleic acids encoding (a) a plurality of antigenic peptides, each comprising a sequence of 9-30 amino acids derived from proteins from commensal human papilloma viruses or (b) a plurality of antigenic proteins from commensal human papilloma viruses; and optionally a T cell adjuvant that increases T cell response to the antigenic peptides.

A catalyst support comprising at least 95% silicon carbide, having surface areas of ≤10 m.sup.2/g and pore volumes of ≤1 cc/g. A method of producing a catalyst support, the method including mixing SiC particles of 0.1-20 microns, SiO.sub.2 and carbonaceous materials to form an extrusion, under inert atmospheres, heating the extrusion at temperatures of greater than 1400° C., and removing residual carbon from the heated support under temperatures below 1000° C. A catalyst on a carrier, comprising a carrier support having at least about 95% SiC, with a silver solution impregnated thereon comprising silver oxide, ethylenediamine, oxalic acid, monoethanolamine and cesium hydroxide. A process for oxidation reactions (e.g., for the production of ethylene oxide, or oxidation reactions using propane or methane), or for endothermic reactions (e.g., dehydrogenation of paraffins, of ethyl benzene, or cracking and hydrocracking hydrocarbons).

The present invention relates to the use of an embryonated egg model grafted with tumour cells to investigate anti-cancer effectiveness or to screen immunotherapeutic molecules, in the absence of immune effector cells other than those in the grafted egg.

A genetically reprogrammed, biologically active and metabolically active cell, tissue, and/or an organ comprising live cells that vascularize after xenotransplantation, wherein the genetically reprogrammed, biologically active and metabolically active cell, tissue, and/or an organ has been obtained from a non-wild type, biologically engineered porcine comprising a nuclear genome that has been reprogrammed to replace a plurality of nucleotides in a plurality of exon regions of a major histocompatibility complex of a wild-type porcine with a plurality of synthesized nucleotides from a human captured reference sequence, wherein the nuclear genome has wild-type porcine intron regions from a wild-type porcine and has been reprogrammed at exon regions.

The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdc.sup.scid IL2re.sup.tmlWjl/SzJ (NSG), NOD.Cg-Rag1.sup.tm1Mom Il2rg.sup.tmlWjl/SzJ (NRG) and NOD.Cg-Prkdc.sup.scid Il2rg.sup.tm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.

The present invention provides peptidic TGF-β antagonists capable of inhibiting TGF-β signaling and disrupting the biochemical events that promote fibrosis and the epithelial-mesenchymal transition. The peptidic TGF-β antagonist may contain from 11 to 28 amino acid residues (for instance, may consist of from 12 to 16 amino acid residues) and may have the following structure (II):
NH.sub.2′ETWIWLDTNMG-Xaa.sub.1-Y′COOH  (II)
wherein Xaa.sub.1 is any amino acid and Y is a peptide having from 0 to 9 amino acids. The peptidic TGF-β antagonists can advantageously be used for the prevention, treatment, and/or alleviation of the symptoms of a condition associated with an increase in TGF-β activity, including fibrosis (such as fibrosis of the skin, liver, lungs, and heart, among others) and cancer (including various carcinomas, such as squamous cell carcinoma, sarcomas, and metastatic cancers).

Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.