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Calumet, MI, United States

Fabre C.,Dana-Farber Cancer Institute | Mimura N.,Dana-Farber Cancer Institute | Bobb K.,Profectus Biosciences, Inc. | Kong S.-Y.,Dana-Farber Cancer Institute | And 13 more authors.
Clinical Cancer Research | Year: 2012

Purpose: NF-κB transcription factor plays a key role in the pathogenesis of multiple myeloma in the context of the bone marrow microenvironment. Both canonical and noncanonical pathways contribute to total NF-κB activity. Recent studies have shown a critical role for the noncanonical pathway: selective inhibitors of the canonical pathway present a limited activity, mutations of the noncanonical pathway are frequent, and bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-κB activity. Experimental Design: Multiple myeloma cell lines, primary patient cells, and the human multiple myeloma xenograft murine model were used to examine the biologic impact of dual inhibition of both canonical and noncanonical NF-κB pathways. Results: We show that PBS-1086 induces potent cytotoxicity in multiple myeloma cells but not in peripheral blood mononuclear cells. PBS-1086 overcomes the proliferative and antiapoptotic effects of the bone marrow milieu, associated with inhibition of NF-κB activity. Moreover, PBS-1086 strongly enhances the cytotoxicity of bortezomib in bortezomib-resistant multiple myeloma cell lines and patient multiple myeloma cells. PBS-1086 also inhibits osteoclastogenesis through an inhibition of RANK ligand (RANKL)-induced NF-κB activation. Finally, in a xenograft model of human multiple myeloma in the bone marrow milieu, PBS-1086 shows significant in vivo anti-multiple myeloma activity and prolongs host survival, associated with apoptosis and inhibition of both NF-κB pathways in tumor cells. Conclusions: Our data show that PBS-1086 is a promising dual inhibitor of the canonical and noncanonical NF-κB pathways. Our preclinical study therefore provides the framework for clinical evaluation of PBS-1086 in combination with bortezomib for the treatment of multiple myeloma and related bone lesions. ©2012 AACR.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2014

This Small Business Innovation Research (SBIR) Phase I project will develop a metal matrix composite concrete cutting diamond blade. This project has the potential to address a distinct need in a $2 billion domestic market. The technology for cutting concrete hasn't changed in over 20 years and the industry continues to deal with the same issues: blade overheat and warping, slow cutting speeds, multiple blade compositions, loud cutting and blade "sing", and short blade life. The proposed technology addresses each of these issues; it will be commercialized by working with industry partners to insure a faster transition of developed technology from lab concept to industrial application. These partnerships will result in a product line that will permit new domestic manufacturing operations (a majority of current blades are imported) and a reduced environmental impact (harmful byproducts are a result of today's blade manufacturing processes). The 200% increase in blade life and faster cutting operations enabled by this technology will reduce overall operating costs for users. Finally, the aluminum-diamond metal matrix composite (MMC) technology to be utilized will find utility in additional applications, such as stone polishing, stone quarries, and wear and thermal management applications. The proposed aluminum MMC diamond blade will have significantly better thermal properties and longer life span compared to conventional blades. Conventional concrete blades have diamond particles embedded in segments within an iron (Fe)-cobalt (Co) matrix. The Fe-Co matrix hardness has to be changed for different concrete aggregate to enable effective cutting. When mismatched, the blade will overheat and warp, becoming unusable. The proposed diamond MMC blade material has high thermal conductivity that rapidly draws the heat from the cutting zone, thereby avoiding these issues, while increasing the life of the blade. The cast MMC blade will include MMC diamond-containing segments attached to an MMC hub which can be tailored for stiffness, noise mitigation, and optimized thermal properties. The Phase I project will focus on design and development including 1) an optimized segment composition, 2) geometry of the segments and the hub, and 3) an MMC casting process optimized for blade efficiency and life. Finally, field testing will be conducted to verify and optimize blade performance. Process scale-up will follow to meet specific product requirements as required by end users of the technology.


Grant
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase I | Award Amount: 120.00K | Year: 2010

Presently, the Army experiences numerous problems with existing manufacturing processes for the metal encapsulation of ceramic tiles within the current inventory of armor solutions. REL, Inc. will address the specific problems of directly casting the encapsulated ceramic structure to net/near net shape and the high cost of ceramic tile finishing practices currently required for existing ceramic panel designs through the identification and implementation of a new manufacturing process. This process will allow the ceramic tiles to remain unfinished before encapsulation, thereby eliminating the need for close tolerances and greatly reducing manufacturing costs while increasing the quality and consistency of the end product. Ultimately, this will result in the availability of more systems through the establishment of a new industry standard that will provide the required legacy and future platform for an innovative integrate and materials process for the survivability of the Warfighter.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 150.00K | Year: 2014

This Small Business Innovation Research (SBIR) Phase I project will develop a metal matrix composite concrete cutting diamond blade. This project has the potential to address a distinct need in a $2 billion domestic market. The technology for cutting concrete hasnt changed in over 20 years and the industry continues to deal with the same issues: blade overheat and warping, slow cutting speeds, multiple blade compositions, loud cutting and blade sing, and short blade life. The proposed technology addresses each of these issues; it will be commercialized by working with industry partners to insure a faster transition of developed technology from lab concept to industrial application. These partnerships will result in a product line that will permit new domestic manufacturing operations (a majority of current blades are imported) and a reduced environmental impact (harmful byproducts are a result of todays blade manufacturing processes). The 200% increase in blade life and faster cutting operations enabled by this technology will reduce overall operating costs for users. Finally, the aluminum-diamond metal matrix composite (MMC) technology to be utilized will find utility in additional applications, such as stone polishing, stone quarries, and wear and thermal management applications.

The proposed aluminum MMC diamond blade will have significantly better thermal properties and longer life span compared to conventional blades. Conventional concrete blades have diamond particles embedded in segments within an iron (Fe)-cobalt (Co) matrix. The Fe-Co matrix hardness has to be changed for different concrete aggregate to enable effective cutting. When mismatched, the blade will overheat and warp, becoming unusable. The proposed diamond MMC blade material has high thermal conductivity that rapidly draws the heat from the cutting zone, thereby avoiding these issues, while increasing the life of the blade. The cast MMC blade will include MMC diamond-containing segments attached to an MMC hub which can be tailored for stiffness, noise mitigation, and optimized thermal properties. The Phase I project will focus on design and development including 1) an optimized segment composition, 2) geometry of the segments and the hub, and 3) an MMC casting process optimized for blade efficiency and life. Finally, field testing will be conducted to verify and optimize blade performance. Process scale-up will follow to meet specific product requirements as required by end users of the technology.


Patent
REL Inc | Date: 2015-11-06

Some embodiments provide methods and systems for casting articles. One example of a method includes providing and positioning a thermal blanket within a mold cavity and then introducing a molten material into the mold cavity and into contact with the thermal blanket. The method allows the molten material to remain in a molten state during a dwell time that extends from the introduction of the molten material at least until the mold cavity is filled. In another example, a method of using a thermal blanket includes keeping a molten material in a molten state during a dwell time extending from first introduction of the molten material until pressurization. Systems including a variety of mold types, one or more thermal blankets, and in some cases preforms and/or inserts are also provided. Also described is a novel thermal blanket and method of manufacturing the same.

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