1,723,705 research outputs found
Union Pacific (UP) 9006
No full textA photograph postcard showing Union Pacific (UP) 9006, 4-12-2, on freight extra, Laramie, WY
BAY 43-9006 inhibition of oncogenic RET mutants.
No full textWe examined BAY 43-9006 activity against oncogenic RET in vitro and in cellular RET signaling in oncogenic RET-transfected NIH3T3 fibroblasts by using immunocomplex kinase assays and immunoblotting with phospho-specific antibodies. The effects of BAY 43-9006 on proliferation of human TPC1 and TT thyroid carcinoma cells, which harbor spontaneous oncogenic RET alleles, and on RAT1 fibroblasts transformed with oncogenic RET mutants, including mutants that are resistant to other chemotherapeutic agents, were determined using growth curves and flow cytometry. Growth of TT cell-derived xenograft tumors in athymic mice treated orally with BAY 43-9006 or with vehicle was measured. All statistical tests were two-sided. BAY 43-9006 inhibited oncogenic RET kinase activity at half-maximal inhibitory concentrations (IC50s) of 50 nM or less in NIH3T3 cells. It also arrested the growth of NIH3T3 and RAT1 fibroblasts transformed by oncogenic RET and of thyroid carcinoma cells that harbor spontaneous oncogenic RET alleles. Moreover, BAY 43-9006 inhibited the growth of cells carrying RET V804L (IC50 = 110 nM, 95% confidence interval [CI] = 88 to 133 nM) or RET V804M (IC50 = 147 nM, 95% CI = 123 nM to 170 nM), both mutants that are resistant to anilinoquinazolines and pyrazolopyrimidines. After 3 weeks of oral treatment with BAY 43-9006 (60 mg/kg/day), the volume of TT cell xenografts (n = 7) was reduced from 72.5 to 44 mm3 (difference = 28.5 mm3, 95% CI = 7 mm3 to 50 mm3), whereas in vehicle-treated mice (n = 7), mean tumor volume increased to 408 mm3 (difference = 320 mm3, 95% CI = 180 mm3 to 460 mm3; untreated versus treated, P =.02). This inhibition paralleled a decrease in RET phosphorylation. BAY 43-9006 is a powerful inhibitor of the RET kinase. Its potential as a therapeutic tool for RET-positive thyroid tumors, including those expressing V804 mutations merits study
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Can a Family Farm Benefit from Section 9006?
No full textSection 9006 of the 2002 U.S. Farm Bill provides grants and guaranteed loans for rural renewable energy and energy efficiency projects. This fact sheet describes how the Tjaden family of Iowa pursued Section 9006 funding in pursuit of a wind turbine for their family farm
Preconditioning and iterative solution of symmetric indefinite linear systems arising from interior point methods for linear programming
No full text10.1007/s10589-006-9006-8Computational Optimization and Applications362-3221-247CPPP
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Avoiding the Haircut: Potential Ways to Enhance the Value of theUSDA's Section 9006 Program
Full text linkSection 9006 of Title IX of The Farm Security and Rural Investment Act of 2002 (the '2002 Farm Bill') established the Renewable Energy Systems and Energy Efficiency Improvements Program (the 'Section 9006 program'). Administered by the United States Department of Agriculture (USDA), the Section 9006 program provides grants, loan guarantees, and - perhaps in the future - direct loans to farmers, ranchers, and rural small businesses for assistance with purchasing renewable energy systems and making energy efficiency improvements. In the three rounds of Section 9006 funding to date (FY03-FY05), roughly 40% of all grant dollars in aggregate have been awarded to 'large' (defined as > 100 kW) wind projects. Such projects are also typically eligible for the Federal Production Tax Credit (PTC) codified in Section 45 of the US tax code. Because the PTC provides a significant amount of value to a wind project, most 'large wind' applicants to the Section 9006 program have also tried to take advantage of the PTC. Through what are known as 'anti-double-dipping' or, more colloquially, 'haircut' provisions, however, the size of the PTC is reduced if a project receives certain other forms of governmental support. Specifically, Section 45(b)(3) of the US tax code reduces the size of the PTC in proportion to the aggregate amount of government grants, tax-exempt or subsidized financing, or other Federal tax credits that a project receives over time, relative to its overall capital cost (with the proportion not to exceed 50%). The legislative and regulatory history surrounding the PTC's haircut provisions suggests that grants and direct loans (but not loan guarantees) provided under the Section 9006 program will cause a PTC haircut. Focusing exclusively on 'large wind' projects, this report demonstrates that the magnitude of the haircut can be significant: Section 9006 grants lose between 11% and 46% of their face value (depending on the wind project's capital cost and capacity factor) to PTC haircuts. And because Section 9006 grants are most likely considered taxable income, an additional 20%-37% (depending on tax bracket) is lost to income tax payments on the grant. In combination, depending on the specific combination of tax bracket, capital cost, and capacity factor that pertain to a given wind project, the percentage of a Section 9006 grant lost to both income tax payments and the PTC haircut can range from 31% to 83% of the dollar value of the grant. Our base-case scenario falls in the middle of that range, at a combined loss of 58% (37% due to income tax payments, and 21% due to PTC haircut). Add to this the transaction costs of applying for a Section 9006 grant, as well as the possibility of an unsuccessful application, and some might be left with relatively little motivation to apply
Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin
No full textAbstract Background Targeted inhibition of protein kinases is now acknowledged as an effective approach for cancer therapy. However, targeted therapies probably have limited success because cancer cells have alternate pathways for survival and proliferation thereby avoiding inhibition. We tested the hypothesis that combination of targeted agents would be more effective than single agents in arresting melanoma cell proliferation. Methods We evaluated whether BAY43-9006, an inhibitor of the B-Raf kinase, and rapamycin, an inhibitor of the mTOR kinase, would inhibit serum-stimulated proliferation of human melanoma cell lines, either alone or in combination. Proliferation was measured by quantitating melanoma cell numbers with a luciferase for ATP. Phosphorylation of proteins downstream of targeted kinase(s) was assayed by immunoblots. Statistical significance was determined with the Student-T test. Isobologram analysis was performed to distinguish additive versus synergistic effects of combinations of drugs. Results Serum-stimulated proliferation of multiple human melanoma cell lines was inhibited by BAY43-9006 and by rapamycin. Melanoma cells containing the B-Raf mutation V599E were more sensitive than cells with wild-type B-raf to 10 nM doses of both BAY43-9006 and rapamycin. Regardless of B-Raf mutational status, the combination of low dose rapamycin and BAY43-9006 synergistically inhibited melanoma cell proliferation. As expected, rapamycin inhibited the phosphorylation of mTOR substrates, p70S6K and 4EBP1, and BAY43-9006 inhibited phosphorylation of ERK, which is dependent on B-Raf activity. We also observed unexpected rapamycin inhibition of the phosphorylation of ERK, as well as BAY43-9006 inhibition of the phosphorylation of mTOR substrates, p70S6K and 4EBP1. Conclusion There was synergistic inhibition of melanoma cell proliferation by the combination of rapamycin and BAY 43-9006, and unexpected inhibition of two signaling pathways by agents thought to target only one of those pathways. These results indicate that combinations of inhibitors of mTOR and of the B-raf signaling pathways may be more effective as a treatment for melanoma than use of either agent alone.</p
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