Abstract: The present disclosure provides constructs that comprise (a) a TNF-related apoptosis-inducing ligand (TRAIL) trimer comprising three consecutive extracellular TRAIL domains fused together in a head-to-tail configuration; (b) an epitope binding agent, and (c) optionally one or more additional components, wherein the epitope binding agent competitively inhibits binding of P4-TR3 or HN1-TR3 to cell surface human mesothelin. Constructs of the present disclosure induce apoptosis in cells expressing human mesothelin and a death receptor (DR4 or DR5) on the cell's surface.

Abstract: The present disclosure provides constructs that comprise (a) a TNF-related apoptosis-inducing ligand (TRAIL) trimer comprising three consecutive extracellular TRAIL domains fused together in a head-to-tail configuration; (b) an epitope binding agent, and (c) optionally one or more additional components, wherein the epitope binding agent competitively inhibits binding of P4-TR3 or HN1-TR3 to cell surface human mesothelin. Constructs of the present disclosure induce apoptosis in cells expressing human mesothelin and a death receptor (DR4 or DR5) on the cell's surface.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

Abstract: Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic. acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.

Abstract: Pharmaceutical compounds, pharmaceutical compositions and methods of treatment are disclosed, wherein a compound comprises a targeting moiety which, in free form, binds a cell receptor with a dissociation constant Kd of less than about 10?7 M, and a pharmaceutically active moiety, wherein the targeting moiety is other than an oligopeptide, a polypeptide, a peptidomimetic, a protein or a protein domain, and wherein the targeting moiety and the pharmaceutically active moiety are covalently attached. In some aspects, the targeting moiety binds a sigma-2 receptor with high affinity and high specificity, and the pharmaceutically active moiety is a pro-apoptotic peptide moiety. Methods of cancer treatment are disclosed comprising administering a disclosed pharmaceutical compound to a subject in need of thereof. The treatments selectively induce apoptosis in cancer cells. These methods can further comprise co-administration of radiation therapy and/or an additional chemotherapeutic agent.

Abstract: Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. In some configurations, a modification such as the addition of a functional domain can be stoichiometrically controlled. In some configurations, a modification can be inconsequential with regard to the bioactivity of TRAIL. In various embodiments, a TR3, including a modified TR3, can be a cancer-selective drug.

Abstract: Pharmaceutical compounds, pharmaceutical compositions and methods of treatment are disclosed, wherein a compound comprises a targeting moiety which, in free form, binds a cell receptor with a dissociation constant Kd of less than about 10?7 M, and a pharmaceutically active moiety, wherein the targeting moiety is other than an oligopeptide, a polypeptide, a peptidomimetic, a protein or a protein domain, and wherein the targeting moiety and the pharmaceutically active moiety are covalently attached. In some aspects, the targeting moiety binds a sigma-2 receptor with high affinity and high specificity, and the pharmaceutically active moiety is a pro-apoptotic peptide moiety. Methods of cancer treatment are disclosed comprising administering a disclosed pharmaceutical compound to a subject in need of thereof. The treatments selectively induce apoptosis in cancer cells. These methods can further comprise co-administration of radiation therapy and/or an additional chemotherapeutic agent.

Abstract: A nuclear camera (10) includes a plurality of detector heads (12) which have collimators (14) for fixing the trajectory along which radiation is receivable. A rotating gantry (22) rotates the detector heads around the subject collecting less than 360° of data, e.g., 204° of data. A zero-filling processor (50) generates zero-filled projection views such that the actually collected projection views and the zero-filled projection views span 360°. A smoothing processor (56) smooths an interface between the zero-filled and actually collected projection views. The zero-filled and smoothed views are Fourier transformed (60) into frequency space, filtered with a stationary deconvolution function (62), and Fourier transformed (64) back into real space. The resolution recovered projection data sets in real space are reconstructed by a reconstruction processor (68) into a three-dimensional image representation for storage in an image memory (70).

Abstract: A fluid ejector includes a fluid channel having a resistive heater and terminating in a nozzle, a common bus formed transverse to the fluid channel and between the resistive heater and the nozzle, a connection line laterally adjacent to the fluid channel, and a connection structure for electrically connecting the common bus with the resistive heater and the connection line, the connection structure including a first set of one or more layers for electrical connection and a second set of one or more layers for covering the common bus and connection line. The first set of one or more layers includes a doped polysilicon layer on or overlaid by an optional tantalum-silicide layer. The second set of one or more layers includes a nitride layer on or overlaid by a tantalum layer.

Abstract: A nuclear camera (10) includes a plurality of detector heads (12) which have collimators (14) for fixing the trajectory along which radiation is receivable. A rotating gantry (22) rotates the detector heads around the subject collecting less than 360° of data, e.g., 204° of data. A zero-filling processor (50) generates zero-filled projection views such that the actually collected projection views and the zero-filled projection views span 360°. A smoothing processor (56) smooths an interface between the zero-filled and actually collected projection views. The zero-tilled and smoothed views are Fourier transformed (60) into frequency space, filtered with a stationary deconvolution function (62), and Fourier transformed (64) back into real space. The resolution recovered projection data sets in real space are reconstructed by a reconstruction processor (68) into a three-dimensional image representation for storage in an image memory (70).

Abstract: A method and Apparatus for protection of semiconductor micromechanical devices that use circuits with dynamic logic addressing is disclosed. In one exemplary embodiment of the invention, a fail-safe circuit is provided for an ink jet print head integrated circuit which prevents a catastrophic consequence of the dynamic logic addressed integrated circuit losing its charge.

Abstract: A fluid ejector includes a fluid channel having a resistive heater and terminating in a nozzle, a common bus formed transverse to the fluid channel and between the resistive heater and the nozzle, a connection line laterally adjacent to the fluid channel, and a connection structure for electrically connecting the common bus with the reistive heater and the connection line, the connection structure including a first set of one or more layers for electrical connection and a second set of one or more layers for covering the common bus and connection line. The first set of one or more layers includes a doped polysilicon layer on or overlaid by an optional tantalum-silicide layer. The second set of one or more layers includes a nitride layer on or overlaid by a tantalum layer.

Abstract: A method and Apparatus for protection of semiconductor micromechanical devices that use circuits with dynamic logic addressing is disclosed. In one exemplary embodiment of the invention, a fail-safe circuit is provided for an ink jet print head integrated circuit which prevents a catastrophic consequence of the dynamic logic addressed integrated circuit losing its charge.

Abstract: Printing systems and methods that reduce inter-color bleeding between dark and light colored inks without losing productivity of a color ink jet printer by distributing the printing of a total amount of black ink required in a single swath over multiple passes while each of the color inks required for the same swath is printed in a single pass. For example, the print method may print a single swath by printing portions of the slow dry black ink in three passes while printing each of the fast dry color inks in single passes.

Abstract: A method of ML-EM image reconstruction is provided for use in connection with a diagnostic imaging apparatus (10) that generates projection data. The method includes collecting projection data, including measured emission projection data and measured transmission projection data. Optionally, the measured transmission projection data is truncated. An initial emission map and attenuation map are assumed. The emission map and the attenuation map are iteratively updated. With each iteration, the emission map is recalculated by taking a previous emission map and adjusting it based upon: (i) the measured emission projection data; (ii) a reprojection of the previous emission map which is carried out with a multi-dimensional projection model; and, (iii) a reprojection of the attenuation map.