Materials/manufacturing support element for the Advanced Turbine Systems Program

In 1993, DOE initiated a program to develop advanced gas turbines for power generation in utility and industrial applications. A materials/manufacturing plan was developed in several stages with input from gas turbine manufacturers, materials suppliers, universities, and government laboratories. This plan was developed by a small advanced materials and turbine technology team over a 6-month period. The technology plan calls for initiation of several high priority projects in FY 1995. The technical program for the materials/manufacturing element focuses on generic materials issues, components, and manufacturing processes. Categories include coatings and process development, turbine airfoil development, ceramics adaptation, directional solidification and single crystal airfoils manufactoring technology, materials characterization, catalytic combustor materials, and technology information exchange

ATS materials support

The technology based portion of the Advanced Turbine System Program (ATS) contains several subelements which address generic technology issues for land-base gas turbine systems. One subelement is the Materials/Manufacturing Technology Program which is coordinated by DOE-Oak Ridge Operations and Oak Ridge National laboratory (ORNL) for the Department of Energy. The work in this subelement is being performed predominantly by industry with assistance from national laboratories and universities. Projects in this subelement are aimed toward hastening the incorporation of new materials and components in gas turbines. The materials manufacturing subelement was developed with input from gas turbine manufacturers, material suppliers, government laboratories and universities. Work is currently ongoing on thermal barrier coatings (TBCs), the scale-up of single-crystal airfoil manufacturing technologies, materials characterization and technology information exchange. Westinghouse Power Generation and Pratt and Whitney each have material programs to develop dependable TBCs that enable increased turbine inlet temperatures while maintaining airfoil substrate temperatures at levels to meet the ATS life goals. Howmet and PCC Airfoils each have projects to extend the capability of single-crystal complex-cored airfoil technology to larger sizes so that higher turbine inlet temperatures can be attained in land-based turbines in a cost-effective manner. Materials characterization tasks are ongoing on TBCs in support of the industrial projects. In addition, a project on long-term testing of ceramics and ceramic-matrix composites for gas turbines is being conducted in support of programs at Solar Turbines, Allison Engines, and Westinghouse Power Generation

Tensile Creep and Creep-Recovery Behavior of a SiC-Fiber Si 3 N 4 -Matrix Composite

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65802/1/j.1151-2916.1993.tb03753.x.pd

Checkpoint Signaling, Base Excision Repair, and PARP Promote Survival of Colon Cancer Cells Treated with 5-Fluorodeoxyuridine but Not 5-Fluorouracil

The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor

B7-H4 Treatment of T Cells Inhibits ERK, JNK, p38, and AKT Activation

B7-H4 is a newly identified B7 homolog that plays an important role in maintaining T-cell homeostasis by inhibiting T-cell proliferation and lymphokine-secretion. In this study, we investigated the signal transduction pathways inhibited by B7-H4 engagement in mouse T cells. We found that treatment of CD3+ T cells with a B7-H4.Ig fusion protein inhibits anti-CD3 elicited T-cell receptor (TCR)/CD28 signaling events, including phosphorylation of the MAP kinases, ERK, p38, and JNK. B7-H4.Ig treatment also inhibited the phosphorylation of AKT kinase and impaired its kinase activity as assessed by the phosphorylation of its endogenous substrate GSK-3. Expression of IL-2 is also reduced by B7-H4. In contrast, the phosphorylation state of the TCR proximal tyrosine kinases ZAP70 and lymphocyte-specific protein tyrosine kinase (LCK) are not affected by B7-H4 ligation. These results indicate that B7-H4 inhibits T-cell proliferation and IL-2 production through interfering with activation of ERK, JNK, and AKT, but not of ZAP70 or LCK

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells