Odin, Lord of the Dead: Religious Legitimization for Social and Political Change in Late Iron Age and Early Medieval Scandinavia

Recently, scholars of pre-Christian religions in Scandinavia have argued against a unified pantheon with Odin at its head. Instead, scholars have argued that religious beliefs in pre-Christian Scandinavia should be understood as a body of interrelated beliefs that varied by region, social class, and environmental setting. Significant cults within pre-Christian Scandinavia include those of Thor, Freyr, Odin, and a cult of the dead. Acknowledging that various religious beliefs coexisted leads to the question of how they interacted with each other. The cult of Odin has often been considered a cult of royalty and elites. Scholars have argued that Odin\u27s various aspects were tools for legitimizing rule. Significantly, Odin was not the god of the farmers, who may have favored a cult of the dead. By using the religious ruler ideology framework outlined by Sundqvist, this thesis argues that the followers of a cult of Odin benefited from Odin\u27s perceived power over the dead because those followers existed in a society which used the dead to establish social and political standing. Using textual and archaeological evidence, I first establish how pre-Christian Scandinavians used the dead to create social and political power through óðal rights. I then use Icelandic sagas to show that overpowering the dead was a theme in the transfer of inheritance and power. Finally, I show how Odin and Odinic figures were shown overpowering the dead before gaining social and political standing. This thesis concludes that Odin\u27s power over the dead was an aspect of religious legitimization for his cult. Critically, this thesis adds to the historiography by examining how different pre-Christian religions in Scandinavia interacted with one another

National Educators' Workshop: Update 95. Standard Experiments in Engineering Materials Science and Technology

This document contains a collection of experiments presented and demonstrated at the National Educators' Workshop: Update 95. The experiments related to the nature and properties of engineering materials and provided information to assist in teaching about materials in the education community

The Role of Checkpoint Kinase 1 in Sensitivity to Topoisomerase I Poisons

Agents that target topoisomerase I are widely utilized to treat human cancer. Previous studies have indicated that both the ataxia telangiectasia mutated (ATM)/ checkpoint kinase (Chk) 2 and ATM- and Rad 3-related (ATR)/Chk1 checkpoint pathways are activated after treatment with these agents. The relative contributions of these two pathways to survival of cells after treatment with topoisomerase I poisons are currently unknown. To address this issue, we assessed the roles of ATR, Chk1, ATM, and Chk2 in cells treated with the topoisomerase I poisons camptothecin and 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan. Colony forming assays demonstrated that down-regulation of ATR or Chk1 sensitized cells to SN-38 and camptothecin. In contrast, ATM and Chk2 had minimal effect of sensitivity to SN-38 or camptothecin. Additional experiments demonstrated that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin, which down-regulates Chk1, also sensitized a variety of human carcinoma cell lines to SN-38. Collectively, these results show that the ATR/Chk1 pathway plays a predominant role in the response to topoisomerase I inhibitors in carcinoma cells and identify a potential approach for enhancing the efficacy of these drugs

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

dUTPase inhibition augments replication defects of 5-Fluorouracil

The antimetabolite 5-Fluorouracil (5-FU) is used in the treatment of various forms of cancer and has a complex mode of action. Despite 6 decades in clinical application the contribution of 5-FdUTP and dUTP [(5-F)dUTP] and 5-FUTP misincorporation into DNA and RNA respectively, for 5-FU-induced toxicity is still under debate. This study investigates DNA replication defects induced by 5-FU treatment and how (5-F)dUTP accumulation contributes to this effect. We reveal that 5-FU treatment leads to extensive problems in DNA replication fork progression, causing accumulation of cells in S-phase, DNA damage and ultimately cell death. Interestingly, these effects can be reinforced by either depletion or inhibition of the deoxyuridine triphosphatase (dUTPase, also known as DUT), highlighting the importance of (5-F)dUTP accumulation for cytotoxicity. With this study, we not only extend the current understanding of the mechanism of action of 5-FU, but also contribute to the characterization of dUTPase inhibitors. We demonstrate that pharmacological inhibition of dUTPase is a promising approach that may improve the efficacy of 5-FU treatment in the clinic

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline <i>BRCA1/2</i> mutated patients with advanced ovarian cancer

Background The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib.Results 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib.Methods We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib.Conclusion PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity

Recruitment of Slp-76 to the Membrane and Glycolipid-Enriched Membrane Microdomains Replaces the Requirement for Linker for Activation of T Cells in T Cell Receptor Signaling

Two hematopoietic-specific adapters, src homology 2 domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) and linker for activation of T cells (LAT), are critical for T cell development and T cell receptor (TCR) signaling. Several studies have suggested that SLP-76 and LAT function coordinately to promote downstream signaling. In support of this hypothesis, we find that a fraction of SLP-76 localizes to glycolipid-enriched membrane microdomains (GEMs) after TCR stimulation. This recruitment of SLP-76 requires amino acids 224–244. The functional consequences of targeting SLP-76 to GEMs for TCR signaling are demonstrated using a LAT/SLP-76 chimeric protein. Expression of this construct reconstitutes TCR-inducted phospholipase Cγ1 phosphorylation, extracellular signal–regulated kinase activation, and nuclear factor of activated T cells (NFAT) promoter activity in LAT-deficient Jurkat T cells (J.CaM2). Mutation of the chimeric construct precluding its recruitment to GEMs diminishes but does not eliminate its ability to support TCR signaling. Expression of a chimera that lacks SLP-76 amino acids 224–244 restores NFAT promoter activity, suggesting that if localized, SLP-76 does not require an association with Gads to promote T cell activation. In contrast, mutation of the protein tyrosine kinase phosphorylation sites of SLP-76 in the context of the LAT/SLP-76 chimera abolishes reconstitution of TCR function. Collectively, these experiments show that optimal TCR signaling relies on the compartmentalization of SLP-76 and that one critical function of LAT is to bring SLP-76 and its associated proteins to the membrane

RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network

The DNA damage–activated E3 ubiquitin ligase RAD18 promotes repair of interstrand DNA cross-links by ubiquitylating PCNA and recruiting FANCL to chromatin