Savage in limbo a study in lighting design

Designing the elements of a theatrical production is a unique and often experimental process. This process changes from show to show, and it can be difficult for a viewer to differentiate mistakes from design choices without a background in lighting. That is why it is important to take a look at the design process step by step. Two goals I strove for when designing Savage In Limbo were, how the director\u27s concept blended with a design and if the integrity of the designer\u27s vision was evident on stage. To explore these goals, script analysis and consideration of the director\u27s vision are two very important processes. Additionally, an exploration of the design process will better describe the growth and personal achievements of the design. This thesis will show the process of the lighting design for The University of Central Florida\u27s 2011 production of John Patrick Shanley\u27s Savage In Limbo. The project will highlight the design achievements and the goals explained previously, and create a formal dialogue on this specific design in order to provide insight into the process. When analyzing the design it was important that I assessed the process as well as the product by looking at whether the design met the expectations of the script and audience. This thesis will also explore how my past experiences, education and current skill level have prepared me for this design process in order to create a guideline for others interested in the development of knowledge needed for design

Alien Registration- Haines, Kenneth G. (Mars Hill, Aroostook County)

https://digitalmaine.com/alien_docs/33915/thumbnail.jp

Laser Welding of Complex Phase and Dual Phase Advanced High Strength Steels - The Effects that Welding has on Microstructure and Formability

To assist in the successful applications of tailor-welded assemblies made from advanced high strength steel (AHSS), there needs to be a thorough understanding of how laser welding process parameters influences the weld cross-section profile, mechanical properties, global formability and local formability performance of the base metal. This study investigates microstructure formability correlation of fiber laser welds of an un-coated complex phase (CP) AHSS and a hot dipped galvannealed (HDGA) dual phase (DP) AHSS. Both steels were developed to have a minimum tensile strength of 980 MPa, a minimum yield strength of 590 MPa and a minimum total elongation of 12% in the material’s transverse direction - 90° to the material’s rolling direction. Tensile tests, limiting dome height (LDH) tests, bi-axial stretch tests, forming-strain analyses, and hole expansion tests (HET) were used to compare base metal (BM) samples to laser welded samples. The LDH and bi-axial stretch tests showed that, for both materials, the global formability of the welded samples was lower than that of the base metal. For the CP 980 steel, observations during global formability were correlated to the martensitic dominant regions within the weld’s heat affected zone (HAZ). The welds resisted strain during forming, forcing the surrounding material to accommodate for the restriction. The failure propagated through the path which had the highest about of strain. For the CP steel, this path was through the BM, perpendicular to the welds. Hole expansion tests (HET) showed that the welds significantly decreased the local formability of the BM. Failure during HET initiated in, and propagated along, the weld HAZ. This was correlated to the microstructures created in the HAZ which were more sensitive to edge stretch failure as compared to the microstructure of the BM. For the DP 980 steel, observations during global formability tests were correlated to the larger soft region within the weld’s HAZ. During forming, strain localized in this zone and caused the material to fail. The failure propagated along the length of the weld which was the path containing the highest about of strain. HET showed that the welds only slightly decreased the local formability of the BM. The failure during HET initiated, and propagated, in the BM rather than the weld. This was correlated to the microstructures created in the HAZ which were less sensitive to edge stretch failure as compared to the microstructure of the BM

Nitrosative stress induces DNA strand breaks but not caspase mediated apoptosis in a lung cancer cell line

BACKGROUND: Key steps crucial to the process of tumor progression are genomic instability and escape from apoptosis. Nitric oxide and its interrelated reactive intermediates (collectively denoted as NO(X)) have been implicated in DNA damage and mutational events leading to cancer development, while also being implicated in the inhibition of apoptosis through S-nitrosation of key apoptotic enzymes. The purpose of this study was to explore the interrelationship between NO(X)-mediated DNA strand breaks (DSBs) and apoptosis in cultured tumor cell lines. METHODS: Two well-characterized cell lines were exposed to increasing concentrations of exogenous NO(X )via donor compounds. Production of NO(X )was quantified by the Greiss reaction and spectrophotometery, and confirmed by nitrotyrosine immunostaining. DSBs were measured by the alkaline single-cell gel electrophoresis assay (the COMET assay), and correlated with cell viability by the MTT assay. Apoptosis was analyzed both by TUNEL staining and Annexin V/propidium iodine FACS. Finally, caspase enzymatic activity was measured using an in-vitro fluorogenic caspase assay. RESULTS: Increases in DNA strand breaks in our tumor cells, but not in control fibroblasts, correlated with the concentration as well as rate of release of exogenously administered NO(X). This increase in DSBs did not correlate with an increase in cell death or apoptosis in our tumor cell line. Finally, this lack of apoptosis was found to correlate with inhibition of caspase activity upon exposure to thiol- but not NONOate-based NO(X )donor compounds. CONCLUSIONS: Genotoxicity appears to be highly interrelated with both the concentration and kinetic delivery of NO(X). Moreover, alterations in cell apoptosis can be seen as a consequence of the explicit mechanisms of NO(X )delivery. These findings lend credence to the hypothesis that NO(X )may play an important role in tumor progression, and underscores potential pitfalls which should be considered when developing NO(X)-based chemotherapeutic agents

Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues

The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators of integrin αvβ3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution of phospho (p)FAK, pPyk2, pSrc, pPaxillin and pPLCγ in the synovial tissue (ST) from patients with RA, osteoarthritis (OA) and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB MΦs) treated with tumor necrosis factor-α (TNFα) or interleukin-1β (IL1β). RA and OA STs showed a greater percentage of pFAK on lining cells and MΦs compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNFα or IL1β stimulation. Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MΦs. pPyk2 was expressed on RA ST fibrobasts but not in MΦs at baseline, however it was upregulated upon TNFα or IL1β activation in both cell types. pSrc was expressed in RA ST fibroblasts and MΦs at baseline and was further increased by TNFα or IL1β stimulation. pPaxillin and pPLCγ were upregulated in RA versus OA and ND lining cells and sublining MΦs. Activation of the FAK family signaling cascade on RA and OA lining cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway may be beneficial in RA

ADAM‐10 is overexpressed in rheumatoid arthritis synovial tissue and mediates angiogenesis

Objective To examine the expression of ADAM‐10 in rheumatoid arthritis (RA) synovial tissue (ST) and the role it plays in angiogenesis. Methods ADAM‐10 expression was determined using immunohistology, Western blotting, and quantitative polymerase chain reaction. In order to examine the role of ADAM‐10 in angiogenesis, we performed in vitro Matrigel tube formation and chemotaxis assays using human microvascular endothelial cells (HMVECs) transfected with control or ADAM‐10 small interfering RNA (siRNA). To determine whether ADAM‐10 plays a role in angiogenesis in the context of RA, we performed Matrigel assays using a coculture system of HMVECs and RA synovial fibroblasts. Results Endothelial cells and lining cells within RA ST expressed high levels of ADAM‐10 compared with cells within osteoarthritis ST and normal ST. ADAM‐10 expression was significantly elevated at the protein and messenger RNA levels in HMVECs and RA synovial fibroblasts stimulated with proinflammatory mediators compared with unstimulated cells. ADAM‐10 siRNA–treated HMVECs had decreased endothelial cell tube formation and migration compared with control siRNA–treated HMVECs. In addition, ADAM‐10 siRNA–treated HMVECs from the RA synovial fibroblast coculture system had decreased endothelial cell tube formation compared with control siRNA–treated HMVECs. Conclusion These data show that ADAM‐10 is overexpressed in RA and suggest that ADAM‐10 may play a role in RA angiogenesis. ADAM‐10 may be a potential therapeutic target in inflammatory angiogenic diseases such as RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94711/1/37755_ftp.pd

Using elemental chemostratigraphy on Mid-Late Frasnian platform-top successions from the Lennard Shelf outcrops, Canning Basin, Western Australia.

High-resolution chronostratigraphic correlation using elemental chemostratigraphy in platform carbonates is typically difficult to achieve. Here, elemental chemostratigraphy is used to correlate between two platform-top, carbonate-dominated field sections from the narrow Lennard Shelf that existed on the NE margin of the Canning Basin, Western Australia, during the mid–late Frasnian. The correlation, constrained by magnetic polarity reversals and physical ground truthing, is based on recognition of distinctive cyclical ‘‘stacking patterns’’ defined by changes in concentrations of the trace element zirconium (Zr). Zr concentrations are controlled by the amount of the heavy mineral zircon in the sediments, which is derived from a terrigenous source and is diagenetically very stable. The stacking patterns in the lower part of the study sections display gradually upward-increasing values of Zr to a maximum, followed by an almost immediate fall to a minimum. In the upper part of the study interval, the cycles are more symmetrical, with both gradually increasing and decreasing portions. The point at which the change in Zr stacking pattern occurs in the two sections is synchronous and occurs in association with a supersequence maximum flooding surface. The correlation based on maximum and minimum Zr values throughout the two sections is demonstrated to be chronostratigraphic by comparison with correlations based upon paleomagnetism and physical ground truthing. When element ratios commonly used as provenance and paleoclimate proxies are plotted, the variations between closely spaced samples are greater than any systematic variations throughout the study intervals. Therefore, no isochemical chemozones can be defined, implying that during deposition of the study intervals, there were no long-lived changes in sediment provenance or paleoclimate that the elemental chemistry can detect. The work presented here shows that the standard approach of defining isochemical chemozones for chemostratigraphic correlation is not always appropriate. However, an approach using cyclical changes in elemental variables for chemostratigraphic correlation between two closely spaced sections is chronostratigraphically valid. The greater challenge is in application of the same approach to more widely spaced sections, potentially in different facies of a carbonate setting

Macrophage migration inhibitory factor: a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destruction of bone and cartilage, which is mediated, in part, by synovial fibroblasts. Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes responsible for matrix degradation. Macrophage migration inhibitory factor (MIF) is a cytokine that induces the production of a large number of proinflammatory molecules and has an important role in the pathogenesis of RA by promoting inflammation and angiogenesis. In the present study, we determined the role of MIF in RA synovial fibroblast MMP production and the underlying signaling mechanisms. We found that MIF induces RA synovial fibroblast MMP-2 expression in a time-dependent and concentration-dependent manner. To elucidate the role of MIF in MMP-2 production, we produced zymosan-induced arthritis (ZIA) in MIF gene-deficient and wild-type mice. We found that MMP-2 protein levels were significantly decreased in MIF gene-deficient compared with wild-type mice joint homogenates. The expression of MMP-2 in ZIA was evaluated by immunohistochemistry (IHC). IHC revealed that MMP-2 is highly expressed in wild-type compared with MIF gene-deficient mice ZIA joints. Interestingly, synovial lining cells, endothelial cells, and sublining nonlymphoid mononuclear cells expressed MMP-2 in the ZIA synovium. Consistent with these results, in methylated BSA (mBSA) antigen-induced arthritis (AIA), a model of RA, enhanced MMP-2 expression was also observed in wild-type compared with MIF gene-deficient mice joints. To elucidate the signaling mechanisms in MIF-induced MMP-2 upregulation, RA synovial fibroblasts were stimulated with MIF in the presence of signaling inhibitors. We found that MIF-induced RA synovial fibroblast MMP-2 upregulation required the protein kinase C (PKC), c-jun N-terminal kinase (JNK), and Src signaling pathways. We studied the expression of MMP-2 in the presence of PKC isoform-specific inhibitors and found that the PKCδ inhibitor rottlerin inhibits MIF-induced RA synovial fibroblast MMP-2 production. Consistent with these results, MIF induced phosphorylation of JNK, PKCδ, and c-jun. These results indicate a potential novel role for MIF in tissue destruction in RA