Abstract: The present invention provides compositions and methods for utilizing a large capacity cloning vector (e.g., BAC) to carry a large exogenous genomic DNA (about 10-300 kb) flanked by a proximal and distal regions (10 kb) to efficiently insert into the genome of a cell in a CRISPR/Cas9-stimulated homologous recombination. Methods and compositions for microinjecting a large human gene into a mouse zygote to prepare a genetically modified mouse are also provided.

Abstract: The present disclosure is directed to chemically-stable and pharmaceutically acceptable sildenafil oral spray formulations for the treatment of diseases such as pulmonary arterial hypertension and/or SSRI-induced sexual dysfunction, wherein the oral spray formulation has a pH of about 1.5 to less than 3.0. The present disclosure is also directed to methods for treating diseases such as pulmonary arterial hypertension and/or SSRI-induced sexual dysfunction.

Abstract: The present disclosure is directed to chemically-stable and pharmaceutically acceptable sildenafil oral spray formulations for the treatment of diseases such as pulmonary arterial hypertension and/or SSRI-induced sexual dysfunction, wherein the oral spray formulation has a pH of about 1.5 to less than 3.0. The present disclosure is also directed to methods for treating diseases such as pulmonary arterial hypertension and/or SSRI-induced sexual dysfunction.

Abstract: The present disclosure is directed to chemically-stable and pharmaceutically-acceptable sildenafil oral spray formulations for the treatment of male erectile dysfunction, wherein the oral spray formulation has a pH of about 1.5 to less than 3.0. The present disclosure is also directed to methods for treating male erectile dysfunction.

Abstract: Compositions of zolpidem, and methods for their manufacture and use for treating insomnia. The compositions are formulated as oral sprays for transmucosal absorption of zolpidem. The methods of treatment in some cases involve night-time dosing administration to achieve therapeutic zolpidem blood levels within 20 minutes or less, tapering off to less than 20 ng/ml within less than five hours, in some cases less than four hours, post dosing.

Abstract: Compositions of zolpidem, and methods for their manufacture and use for treating insomnia. The compositions are formulated as oral sprays for transmucosal absorption of zolpidem. The methods of treatment in some cases involve night-time dosing administration to achieve therapeutic zolpidem blood levels within 20 minutes or less, tapering off to less than 20 ng/ml within less than five hours, in some cases less than four hours, post dosing.

Abstract: A method for producing a single-clad or multiple-clad product includes providing a welded assembly comprising a cladding material disposed on a substrate material. Both the substrate material and the cladding material are individually selected alloys. At least a first edge of the cladding material of the welded assembly does not extend to a first edge of the substrate material and thereby provides a margin between the first edges. A material that is an alloy having hot strength greater than the cladding material is within the margin and adjacent the first edge of the cladding material. The welded assembly is hot rolled to provide a hot rolled band, and the material within the margin inhibits the cladding material from spreading beyond the edge of the substrate material during the hot rolling. In certain embodiments of the methods, the substrate material is stainless steel and the cladding material is nickel or a nickel alloy.