Deformable bearing seat

A deformable bearing seat is described for seating a bearing assembly in a housing. The seat includes a seating surface in the housing having a first predetermined spheroidal contour when the housing is in an undeformed mode. The seating surface is deformable to a second predetermined spherically contoured surface when the housing is in a deformed mode. The seat is particularly adaptable for application to a rotating blade and mounting ring assembly in a gas turbine engine

Tissue Targets, Molecular Mechanisms and Health Effects of Bisphenolic Chemicals in Zebrafish

Bisphenol A (BPA) is a chemical incorporated in plastics and resins used for food and beverage containers that has been shown to have estrogenic activity. The fact that BPA possess this activity should not be surprising as it was originally explored for use as a pharmaceutical estrogen. Exposure to BPA has been associated with adverse reproductive and developmental effects in wildlife and laboratory animal models. There are also associations between exposure in humans and adverse health effects, although some of these findings are controversial. The mechanism(s) of action of BPA are well researched, however there is no definitive explanation for the frequently reported discrepancies between in vitro and in vivo studies. Metabolic activation of BPA in vivo has been suggested as a possible reason for this discrepancy in estrogenic potency. As public awareness of the possible health effects of BPA increases manufacturers have increasingly started to use replacement chemicals as monomers in materials that can be labelled as BPA-free. However there is still little information on the estrogenic potency of these structurally similar bisphenol chemicals or how they may affect health outcomes, as observed with BPA. The studies conducted in this thesis therefore aimed to investigate the tissue targets, molecular mechanisms and health effects of BPA, its related chemicals Bisphenol S (BPS), Bisphenol F (BPF) and Bisphenol AF (BPAF) and the BPA metabolite 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP). For this work, a novel ERE transgenic (ERE-TG) zebrafish, that expresses green fluorescent protein (GFP) in response to activation of ERE was employed. These fish can be applied to identify body targets of environmental estrogens in real time with high sensitivity and specificity. BPA, BPF, BPS and BPAF were shown to all preferentially target the heart in ERE-TG zebrafish and GFP induction occurred first in the heart out of the different responding body tissues. The response to BPA was shown to be dependent on the classical estrogen receptor (ER) signalling pathway. However concentrations necessary to induce this response varied for the different bisphenols, with the rank order of potency of BPAF>BPA=BPF>BPS. Bioconcentration factors of the bisphenols were 4.5, 17.8, 5.3 and 0.067 for exposures to 1000 µg BPA/l, 1000 µg BPF/l, 100 µg BPAF/l and 50000 µg BPS/l respectively. These data indicate bioavailability is an important consideration in the differing estrogenic potencies of the different bisphenols. The toxicities of the different bisphenols on early life stage zebrafish followed a similar rank potency order as for the estrogenic activity (BPAF>BPA>BPF>BPS). Specific morphological abnormalities were observed for the different bisphenolic chemical treatments in the toxicity assessments, possibly suggesting that they may act through different ways in inducing their toxic effects. It is recognised that the toxicities for the bisphenolic chemicals were observed at concentrations several orders of magnitude higher than those measured in most aquatic environments and thus the threat they pose to wildlife health might be considered as relatively low, except in circumstances where short but high exposures may occur from accidental release into the environment. The BPA metabolite MBP was found to be up to 1000-fold more potent than the parent compound as an estrogen in ERE-TG fish. The heart was a key target tissue for MBP, as observed for the other bisphenolic compounds. The atrioventricular valves and bulbus arteriosus were identified as the primary targets within the heart. MBP was not measured in zebrafish embryos exposed to BPA and whether this is produced as a metabolite in zebrafish is still not known. Morpholino knockdown of specific ER subtypes indicated that esr1 is a major pathway for the estrogenic response to BPA in the heart during early life stages of zebrafish. Video capture and analysis was used to assess the cardiovascular health of zebrafish exposed to BPA and it was found that at very high exposure concentrations (2500 µg/l) BPA could induce an unstable atrial:ventricular beat ration in 5 dpf larvae and reduced heart beat rate in 14 dpf. In the final study of this thesis transcriptomic profiling was conducted on hearts extracted from 96 hpf ERE-TG zebrafish larvae exposed to BPA. The findings demonstrated that BPA, at an exposure concentration of 150 µg/l caused a down-regulation of a number of genes associated with ion transport and cell-to-cell communication, functions that are essential in maintaining a regular and consistent heart rate. These effect mechanisms may help to explain the effects on the heart seen at the higher BPA exposure concentrations in the previous chapter, although this would need more extensive work to draw any such associations with good confidence Overall, the findings presented in this thesis have provided a body of evidence to show that all of the bisphenolic chemicals tested possess estrogenic activity and as such have the potential for health effects in wildlife and also to humans. It is also the case however that currently in most ambient environments concentrations of these bisphenolic chemicals are far below those that could induce adverse health outcomes. The work in this thesis re-enforces the importance of understanding metabolic activation of chemicals in vivo. It furthermore illustrates the power of transgenic fish and an integrated approach for gaining greater insight into potential health effects of chemicals.NER

I Am Legend

This is a review of I Am Legend (2007)

Stratigraphy and paleontology of the Eagle Ford formation of north and central Texas

Dissertation (Ph.D.)--University of Kansas, Geology, 1931

Common Threads among Different Forms of Charismatic Leadership

The following paper examines the role of charismatic leadership across religious, political, and business leadership in order to come to terms with charisma, what is often described as an intangible quality. The term itself is derived from a Greek term indicating divine favor, a notion that scholars have increasingly tried to move away from, or ignore, but from a systematic analysis of ways in which charisma manifests, the authors hope to bring the subject into a more defined relief

High Yield Expression of Recombinant Human Proteins with the Transient Transfection of HEK293 Cells in Suspension

The art of producing recombinant proteins with complex post-translational modifications represents a major challenge for studies of structure and function. The rapid establishment and high recovery from transiently-transfected mammalian cell lines addresses this barrier and is an effective means of expressing proteins that are naturally channeled through the ER and Golgi-mediated secretory pathway. Here is one protocol for protein expression using the human HEK293F and HEK293S cell lines transfected with a mammalian expression vector designed for high protein yields. The applicability of this system is demonstrated using three representative glycoproteins that expressed with yields between 95-120 mg of purified protein recovered per liter of culture. These proteins are the human FcγRIIIa and the rat α2-6 sialyltransferase, ST6GalI, both expressed with an N-terminal GFP fusion, as well as the unmodified human immunoglobulin G1 Fc. This robust system utilizes a serum-free medium that is adaptable for expression of isotopically enriched proteins and carbohydrates for structural studies using mass spectrometry and nuclear magnetic resonance spectroscopy. Furthermore, the composition of the N-glycan can be tuned by adding a small molecule to prevent certain glycan modifications in a manner that does not reduce yield

Researching the Ends of Identity: Birth and Death on Social Media

This paper argues that expanding the scope of social media studies to examine birth and early life at one end, and death and memorialisation at the other, demonstrates that social media is never just about an individual, but also the way individuals are always already joined together as families, groups, communities and more. Mapping these ends of identity also reveals more of the nuances of everyday social media use and its impact

Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol A and Its Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish Embryo-Larvae

This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this recordBisphenol A (BPA), a chemical incorporated into plastics and resins, has estrogenic activity and is associated with adverse health effects in humans and wildlife. Similarly structured BPA analogues are widely used but far less is known about their potential toxicity or estrogenic activity in vivo. We undertook the first comprehensive analysis on the toxicity and teratogenic effects of the bisphenols BPA, BPS, BPF, and BPAF in zebrafish embryo-larvae and an assessment on their estrogenic mechanisms in an estrogen-responsive transgenic fish Tg(ERE:Gal4ff)(UAS:GFP). The rank order for toxicity was BPAF > BPA > BPF > BPS. Developmental deformities for larval exposures included cardiac edema, spinal malformation, and craniofacial deformities and there were distinct differences in the effects and potencies between the different bisphenol chemicals. These effects, however, occurred only at concentrations between 1.0 and 200 mg/L which exceed those in most environments. All bisphenol compounds induced estrogenic responses in Tg(ERE:Gal4ff)(UAS:GFP) zebrafish that were inhibited by coexposure with ICI 182 780, demonstrating an estrogen receptor dependent mechanism. Target tissues included the heart, liver, somite muscle, fins, and corpuscles of Stannius. The rank order for estrogenicity was BPAF > BPA = BPF > BPS. Bioconcentration factors were 4.5, 17.8, 5.3, and 0.067 for exposure concentrations of 1.0, 1.0, 0.10, and 50 mg/L for BPA, BPF, BPAF, and BPS, respectively. We thus show that these BPA alternatives induce similar toxic and estrogenic effects to BPA and that BPAF is more potent than BPA, further highlighting health concerns regarding the use of BPA alternatives.Natural Environment Research Council (NERC

Project Final Report: Ubiquitous Computing and Monitoring System (UCoMS) for Discovery and Management of Energy Resources

The UCoMS research cluster has spearheaded three research areas since August 2004, including wireless and sensor networks, Grid computing, and petroleum applications. The primary goals of UCoMS research are three-fold: (1) creating new knowledge to push forward the technology forefronts on pertinent research on the computing and monitoring aspects of energy resource management, (2) developing and disseminating software codes and toolkits for the research community and the public, and (3) establishing system prototypes and testbeds for evaluating innovative techniques and methods. Substantial progress and diverse accomplishment have been made by research investigators in their respective areas of expertise cooperatively on such topics as sensors and sensor networks, wireless communication and systems, computational Grids, particularly relevant to petroleum applications