77 research outputs found

    Superflywheel energy storage system

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    A windpowered system using the superflywheel configuration for energy storage is considered. Basic elements of superflywheels are thin rods assembled in pregrooved hub lamina so that they fan out in radial orientation. Adjacent layers of hub lamina are assembled 90 degree in rotation to each other so as to form a circular brush configuration. Thus stress concentrations and rod failure are minimized and realistic failure containment for a high performance flywheel is obtained

    Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

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    Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

    CEBPA-mutated leukemia is sensitive to genetic and pharmacological targeting of the MLL1 complex

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    The gene encoding the transcription factor C/EBP alpha is mutated in 10-15% of acute myeloid leukemia (AML) patients. N-terminal CEBPA mutations cause ablation of full-length C/EBP alpha without affecting the expression of a shorter oncogenic isoform, termed p30. The mechanistic basis of p30-induced leukemogenesis is incompletely understood. Here, we demonstrate that the MLL1 histone-methyltransferase complex represents a critical actionable vulnerability in CEBPA-mutated AML. Oncogenic C/EBP alpha p30 and MLL1 show global co-localization on chromatin and p30 exhibits robust physical interaction with the MLL1 complex. CRISPR/Cas9-mediated mutagenesis of MLL1 results in proliferation arrest and myeloid differentiation in C/EBP alpha p30-expressing cells. In line, CEBPA-mutated hematopoietic progenitor cells are hypersensitive to pharmacological targeting of the MLL1 complex. Inhibitor treatment impairs proliferation and restores myeloid differentiation potential in mouse and human AML cells with CEBPA mutations. Finally, we identify the transcription factor GATA2 as a direct critical target of the p30-MLL1 interaction. Altogether, we show that C/EBP alpha p30 requires the MLL1 complex to regulate oncogenic gene expression and that CEBPA-mutated AML is hypersensitive to perturbation of the MLL1 complex. These findings identify the MLL1 complex as a potential therapeutic target in AML with CEBPA mutations

    Low-cost flywheel demonstration program. Final report, 1 October 1977-31 December 1979

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    The Applied Physics Laboratory/Department of Energy Low Cost Flywheel Demonstration Program was initiated on 1 October 1977 and was successfully concluded on 31 December 1979. The total cost of this program was 355,190.Allprimaryobjectivesweresuccessfullyachievedasfollows:demonstrationofafullsize,1kWhflywheelhavinganestimatedcostinlargevolumeproductionofapproximately355,190. All primary objectives were successfully achieved as follows: demonstration of a full-size, 1-kWh flywheel having an estimated cost in large-volume production of approximately 50/kWh; development of a ball-bearing system having losses comparable to the losses in a totally magnetic suspension system; successful and repeated demonstration of the low-cost flywheel in a complete flywheel energy-storage system based on the use of ordinary house voltage and frequency; and application of the experience gained in the hardware program to project the system design into a complete, full-scale, 30-kWh home-type flywheel energy-storage system
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