Abstract: Methods and compositions for enhancing viral gene transfer, such as lentiviral gene transfer, and improving the efficacy of gene delivery to cells such as primitive hematopoietic cells, are described. These methods and compositions are based on the use of pyrimido[4,5-b]indole derivatives. Cell-based compositions and methods useful for therapeutic indications amenable to treatment with gene therapies, including hematopoietic stem cell therapies, are also described.

Abstract: The invention provides methods, uses, kits and compositions comprising a therapeutically effective amount of the microRNA miR-223 for treating myelogenous leukemia in a subject in need of such treatment. The invention further comprises methods encompassing the use of miR-223 for promoting the differentiation of a leukemia stem cell that is resistant to a differentiating agent, and a method of screening for candidate compounds capable of treating a myeloid leukemia by comparison of the therapeutic activity of the candidate compound with the therapeutic activity of miR-233.

Abstract: The present invention relates to a stem cell expansion factor, and to a method for enhancing hematopoietic stem cell expansion by direct delivery of a protein in the cell and which protein is able to cross cell membrane. The method comprises directly delivering in a HSC an amino acid sequence having the activity of a peptide encoded by a Hoxb4 nucleotide sequence. Once delivered, the amino acid sequence is functionally active in the hematopoietic stem cell and enhances expansion thereof. The amino acid sequence may is a HOXB4 or HOXA4 protein.

Abstract: A polypeptide, the amino acid sequence of which comprises a sequence as set forth in SEQ ID NO:2, including at least one mutation within the degron domain of the polypeptide encompassed between positions 1 and 35 of the sequence, wherein said at least one mutation reduces the susceptibility of the polypeptide to ubiquitin-proteasome degradation.

Abstract: The invention provides methods, uses, kits and compositions comprising a therapeutically effective amount of the microRNA miR-223 for treating myelogenous leukemia in a subject in need of such treatment. The invention further comprises methods encompassing the use of miR-223 for promoting the differentiation of a leukemia stem cell that is resistant to a differentiating agent, and a method of screening for candidate compounds capable of treating a myeloid leukemia by comparison of the therapeutic activity of the candidate compound with the therapeutic activity of miR-233.

Abstract: The present invention relates to a stem cell expansion factor, and to a method for enhancing hematopoietic stem cell expansion by direct delivery of a protein in the cell and which protein is able to cross cell membrane. The method comprises directly delivering in a HSC an amino acid sequence having the activity of a peptide encoded by a Hoxb4 nucleotide sequence. Once delivered, the amino acid sequence is functionally active in the hematopoietic stem cell and enhances expansion thereof. The amino acid sequence may is a HOXB4 or HOXA4 protein.

Abstract: A polypeptide, the amino acid sequence of which comprises a sequence as set forth in SEQ ID NO:2, including at least one mutation within the degron domain of the polypeptide encompassed between positions 1 and 35 of the sequence, wherein said at least one mutation reduces the susceptibility of the polypeptide to ubiquitin-proteasome degradation.

Abstract: Nucleic acid constructs encoding homeobox-nucleoporin fusions are disclosed, compositions comprising same, and methods which provide enhanced expansion of stem cells. In particular, an isolated nucleic acid construct encoding a NUP98-HOX fusion is provided, which when introduced into hemopoietic stem cells provides enhanced expansion of these cells. Methods of expanding stem cells in vivo or ex vivo and methods of treatment using the stem cells are also described.

Abstract: The present invention relates to a stem cell expansion factor comprising a blocker which reduces expression level of at least one gene normally limiting HOX-induced expansion of stem cells, whereby reducing expression level of said gene enhances expansion of stem cells containing a HOX peptide. The present invention also relates to a composition for enhancing expansion of stem cells comprising an amino acid sequence having the activity of a HOX peptide, wherein said peptide being able to cross a cell membrane, and a blocker which reduces expression level of at least one gene normally limiting HOX-induced expansion of stem cells, whereby reducing expression level of said gene in the presence of a HOX peptide enhances expansion of stem cells. The preferred HOX peptide is HOXB4 and the preferred gene is PBX.

Abstract: An electron beam physical vapor deposition (EBPVD) apparatus for producing a coating material (e.g., a ceramic thermal barrier coating) on an article. The EBPVD apparatus generally includes a coating chamber that is operable at elevated temperatures and subatmospheric pressures. An electron beam gun projects an electron beam into the coating chamber through an aperture in a wall of the chamber and onto a coating material within a coating region defined within the chamber, causing the coating material to melt and evaporate. An article is supported within the coating chamber so that vapors of the coating material deposit on the article. The operation of the EBPVD apparatus is enhanced by the inclusion within the coating chamber of a second chamber that encloses the aperture so as to separate the aperture from the coating region. The second chamber is maintained at a pressure lower than the coating region.

Abstract: An electron beam physical vapor deposition (EBPVD) apparatus and a method for using the apparatus to produce a coating material (e.g., a ceramic thermal barrier coating) on an article. The EBPVD apparatus generally includes a coating chamber that is operable at elevated temperatures and subatmospheric pressures. An electron beam gun projects an electron beam into the coating chamber and onto a coating material within the chamber, causing the coating material to melt and evaporate. An article is supported within the coating chamber so that vapors of the coating material deposit on the article. The operation of the EBPVD apparatus is enhanced by the inclusion or adaptation of one or more mechanical and/or process modifications, including those necessary or beneficial when operating the apparatus at coating pressures above 0.010 mbar.

Abstract: The present invention relates to a stem cell expansion factor, and to a method for enhancing hematopoietic stem cell expansion by direct delivery of a protein in the cell and which protein is able to cross cell membrane. The method comprises directly delivering in a HSC an amino acid sequence having the activity of a peptide encoded by a Hoxb4 nucleotide sequence. Once delivered, the amino acid sequence is functionally active in the hematopoietic stem cell and enhances expansion thereof. The amino acid sequence may is a HOXB4 or HOXA4 protein.

Abstract: The present invention relates to a stem cell expansion factor, and to a method for enhancing hematopoietic stem cell expansion by direct delivery of a protein in the cell and which protein is able to cross cell membrane. The method comprises directly delivering in a HSC an amino acid sequence having the activity of a peptide encoded by a Hoxb4 nucleotide sequence. Once delivered, the amino acid sequence is functionally active in the hematopoietic stem cell and enhances expansion thereof. The amino acid sequence may consist of a HOXB4 protein.

Abstract: An electron beam physical vapor deposition (EBPVD) apparatus and a method for using the apparatus to produce a coating material (e.g., a ceramic thermal barrier coating) on an article. The EBPVD apparatus generally includes a coating chamber that is operable at elevated temperatures and subatmospheric pressures. An electron beam gun projects an electron beam into the coating chamber and onto a coating material within the chamber, causing the coating material to melt and evaporate. An article is supported within the coating chamber so that vapors of the coating material deposit on the article. The operation of the EBPVD apparatus is enhanced by the inclusion or adaptation of one or more mechanical and/or process modifications, including those necessary or beneficial when operating the apparatus at coating pressures above 0.010 mbar.

Abstract: The present invention relates to a hematopoietic stem cell expansion factor, and to a method for enhancing hematopoietic stem cell expansion by direct delivery of a protein in the cell. The method comprises directly delivering in a HSC an amino acid sequence having the activity of a peptide encoded by a Hoxb4 nucleotide sequence. Once delivered, the amino acid sequence is functionally active in the hematopoietic stem cell and enhances expansion thereof. The amino acid sequence may consist of a HOXB4 peptide.

Abstract: Stem cells transduced with HOXB4 exhibit enhanced in vitro and in vivo ability for self-regeneration and generate higher-numbers of tranplantable pluripotent hematopoietic stem cells relative to control and nonmanipulated cells.

Abstract: A method of marking a cell involving introducing into the cell a nucleotide sequence encoding a cell surface protein and having substantial homology to the nucleotide sequence encoding CD24, and expressing the cell surface protein on the cell.