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 present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

Abstract: The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

Abstract: The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

Abstract: The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

Abstract: Radiation may be delivered in a number of segments shaped by a multi-leaf collimator. The collimator may be at different angles of rotation for the different segments. A method for planning radiation treatment involves obtaining an optimized set of collimator configurations by a direct aperture optimization method that takes into account collimator rotation. In some embodiments, area constraints are applied to the optimization. Methods according to embodiments of the invention can generate efficient treatment plans.

Abstract: The invention provides methods, kits, and compositions comprising novel mutant loxP sites. Such sites are particularly useful for procedures requiring multiple site-specific recombination reactions, including deletions or insertions of multiple genes or other sequences in the same organism, staged insertions or deletions of genes of the same organism at different times, assembly of large polynucleotide constructs by serial site-specific recombination, and the like. In one aspect, compositions of the invention includes particular mutant spacer oligonucleotides of loxP recombination elements, the recombination elements themselves, and pairs of non-promiscuous mutant loxP sites.

Abstract: The invention provides methods and compositions for loading an agent, such as econazole, onto a liposome for parental delivery. The loading of the agent into a liposome comprises combining the agent with a micelle-forming compound to form a micelle including the agent, where the agent is releasable from the micelle-forming compound, and adding the micelle to the liposome, where the micelle combines with the liposome such that the agent is loaded into the liposome to form a loaded liposome. The methods are suitable for the loading of poorly soluble agents onto liposome.

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 invention relates to the formation of multivalent antibody constructs for testing and therapeutic purposes. In one embodiment the constructs consist of antibodies or antibody fragments conjugated to liposomes. The constructs are employed in a cell-based in vitro assay for comparing the therapeutic activity of antibodies or antibody fragments in multivalent form to the same antibodies or fragments in bivalent, free form. The assay is useful for identifying antibodies having potential in vivo activity. Selected antibodies may then be tested in an animal model of a disease state, such as cancer or an autoimmune disorder. Co-delivery of antibodies and chemotherapeutics may also be investigated. In accordance with the invention, a significant enhancement in the activity of antibodies such as trastuzumab and rituximab was observed when these antibodies were presented in the multivalent liposomal form.

Abstract: Surface roughness measurements are made by illuminating a surface with coherent light to generate a speckle pattern and studying characteristics of the speckle pattern. The disclosed techniques may be applied to measuring the surface roughness of skin or other biological surfaces. Skin roughness information may be used in the diagnosis of conditions such as malignant melanoma. Methods and apparatus for measuring the coherence length of optical sources involve extracting information about speckle patterns resulting when light from the optical sources interacts with a surface having a known roughness.

Abstract: An optical computed-tomography microscope for three-dimensional (3-D) imaging employs tomographic reconstruction for image acquisition. The microscope has an optical scanner to vary an angle at which a light beam passes through a specimen. A method for limited-angle computed-tomography reconstruction applies a transform to produce an image from a number of projections. The image is iteratively feedback-corrected.

Abstract: A method and system for controlling the spatial distribution of radiation produced by a radiation device having a multi-leaf collimator can generate arbitrary intensity-modulated radiation fields. The methods control both angles and leaf configuration of the multi-leaf collimator for each of multiple sub-fields. The leaf positions, collimator angles, and individual sub-field contributions may be derived by optimization techniques.

Abstract: Methods and apparatus for generating multispectral images of tissue. The multispectral images may be used as a diagnostic tool for conditions such as cervical cancer detection and diagnosis. Primary radiation is produced with an illumination source. The primary radiation is filtered to select a first wavelength and a first polarization. Tissue is illuminated with the filtered primary radiation to generate secondary radiation, which is filtered to select a second wavelength and a second polarization. The filtered secondary radiation is collected with a detector, and a plurality of multispectral images of the tissue is generated according to different combinations of first and second wavelengths and first and second polarization with an analysis unit in operable relation with the detector. Apparatus utilizing the invention include endoscopes and colposcopes.

Abstract: A method of radiotherapy includes irradiating a treatment volume containing a high atomic number contrast medium with a photon beam characterized by a peak energy of at least 1 MeV and a mean energy in excess of 250 keV. The irradiation may be provided by a beam from a linear accelerator operating without a flattening filter. The linear accelerator may have multiple modes including one or more modes for operating with a flattening filter and one or modes for operating without a flattening filter.