Developing Character in the Nineteenth-Century Novel.

This dissertation examines the intersection between narratological theories of character and moral understandings of character development in the nineteenth-century novel. Focusing on British and French Bildungsromane, which take character-building as their central conflict, I demonstrate how the novel’s presentation of moral character is inextricable from the construction of character as a narrative form. This interpenetration between morality and form becomes manifest in character’s multiple meanings: “character” denotes both a quality one possesses (e.g. “Joe has an unsavory character”) and a constitutive element of narrative (along with story, point-of-view, etc.). My broadest goal is to make character a more fundamental concern within narratology, a discipline which tends to privilege the temporal (i.e. plot-centered) aspects of narrative texts. I analyze represented thought—that is, the techniques through which narratives depict the mental lives of characters—to contest the critical assumption that nineteenth-century Bildungsromane figure character development as a portrait of increasing psychological “depth.” Moreover, where scholars frequently note the Bildungsroman’s celebration of its protagonist’s transformative growth, I demonstrate how Bildungsromane resist aligning morality with interior change, either by illustrating the losses that attend maturation or by endorsing stasis as a moral value. Chapter One argues that development in Dickens’s David Copperfield and Charlotte Brontë’s Jane Eyre requires numerous characters to be “sacrificed” from the narrative; the protagonists’ alleged fulfillment relies less on increasing depth than on formal techniques of diminishment. Chapter Two considers how Eliot’s The Mill on the Floss and Staël’s Corinne figure development not as transformation but as a resistance to change that that can only resolve itself through the protagonist’s death. The next two chapters analyze how the voice of a third-person narrator affects developmental paradigms: Chapter Three examines the phenomenon of indecision in Trollope’s Palliser novels, illustrating how the narrator’s valorization of his characters’ refusal to choose endorses a model of development that diverges from conventions of transformative epiphany previously associated with novelistic maturation. Chapter Four contends that Gissing’s Born in Exile and Flaubert’s Sentimental Education estrange the narrators from protagonists who develop surface qualities rather than inner consciences; both novels thus satirize the representation of psychological depth.Ph.D.English Language & LiteratureUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60743/1/cbgiorda_1.pd

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Structure and magnetic properties of two new lanthanide complexes with the 1-((E)-2-pyridinylmethylidene)semicarbazone ligand

Two novel semicarbazone-lanthanide(III) complexes were prepared and structurally characterized as [Ln (Hscpy)2 (NO3)2]NO3·MeOH (Ln = Gd and Tb; Hscpy = 1-((E)-2-pyridinylmethylidene)semicarbazone). The 4f metal ions experience deca-coordination geometry. Each molecular formula contains two neutral Hscpy molecules in the keto form coordinated through two nitrogen atoms and one oxygen atom, while two nitrate ligands are both coordinated in a chelate mode. The 1 + charge of the cation-complex is balanced by a nitrate anion. Extensive intermolecular hydrogen bonds are formed through the methanol solvate molecule, which acts both as a donor and an acceptor molecule. The chemical composition of the compounds was confirmed by high resolution mass spectra (ESI-MS); peaks at m/z = 122.07 and 148.05, assigned to the fragments C6H8N3+ and C7H6N3O+, respectively, are in agreement with the coordination of Hscpy. Alternating current magnetic susceptibility analysis was performed in the 10–10000 Hz range, and the terbium-complex showed slow relaxation of the magnetization when immersed in a static magnetic field of 1 kOe and 1.5 kOe, with an activation barrier to the relaxation (21.9(4) cm−1) among the highest found for ten-coordinated Tb(III) complexes. This behavior of slow relaxation of the magnetization is relevant as a memory effect regarding the development of Single Molecule Magnets (SMM)

Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as Caarv1/Caarv1 cells expressing the full-length zinc-binding domain mutants, Caarv1C3S and Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of Caarv1/Caarv1, Caarrv1AHD, Caarv1C3S, and Caarv1C28S cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution

In vitro synergisms obtained by amphotericin B and voriconazole associated with non-antifungal agents against Fusarium spp

AbstractFusarium spp is an opportunistic fungal pathogen responsible for causing invasive hyalohyphomycosis in immunocompromised patients. Due to its susceptibility pattern with a remarkable resistance to antifungal agents the treatment failures and mortality rates are high. To overcome this situation, combination therapy may be considered which must be subjected to in vitro tests.In vitro activities of amphotericin B, itraconazole, and voriconazole associated with azithromycin, ciprofloxacin, fluvastatin, ibuprofen, metronidazole, and also the combination of amphotericin B plus rifampin against 23 strains of Fusarium spp. through the checkerboard technique based on M38-A2 [Clinical and Laboratory Standards Institute (2008). Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. (CLSI document M38-A2) (ISBN 1-56238-668-9). Wayne, PA: CLSI] were evaluated.The best synergistic interactions with amphotericin B were with ibuprofen (43.5%) (FICI [fractional inhibitory concentration index] range = 0.25–2). Combinations with voriconazole showed synergism, mainly with ciprofloxacin (30.4%) (FICI range = 0.25–3) and metronidazole (30.4%) (FICI range = 0.1–4); however, all the combinations with itraconazole were indifferent. In general, antagonistic interactions were not registered.Our results showed that in vitro synergisms obtained by some combinations studied deserve attention since they were better than those showed by the antimycotic

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Digital energy visualisations in the workplace: the e-Genie tool

Building management systems are designed for energy managers; there are few energy feedback systems designed to engage staff. A tool, known as e-Genie, was developed to engage workplace occupants with energy data and support them to take action to reduce energy use. Building on research insights within the field, e-Genie’s novel approach encourages users to make plans to meet energy saving goals, supports discussion, and considers social energy behaviours (e.g. discussing energy issues, taking part in campaigns) as well as individual actions. A field based study of e-Genie indicated that visualisations of energy data were engaging and that the discussion ‘Pinboard’ was particularly popular. Pre- and post survey (N = 77) evaluation of users indicated that people were significantly more concerned about energy issues and reported engaging more in social energy behaviour after ~two weeks of e-Genie being installed. Concurrently, objective measures of electricity use decreased over the same period, and continued decreasing over subsequent weeks. Indications are that occupant facing energy feedback visualisations can be successful in reducing energy use in the workplace; furthermore supporting social energy behaviour in the workplace is likely to be a useful direction for promoting action