American callings : humanitarian selfhood in American literature from Reconstruction to the American century

textIn "American Callings" I argue that late-nineteenth and early-twentieth-century American literature dealing with cross-cultural humanitarianism contains a strand that sought to rectify the potentially oppressive shortcomings of humanitarian practice. The authors whose work I examine--novelists William Dean Howells and Albion Tourgeé, reformer Jane Addams, humorist George Ade, and memoirists Mary Fee and George Freer--grappled in their writing with two reciprocal questions. First, they meditated on how humanitarianism shapes, changes, and constitutes the self. Second, they theorized how increased self-awareness and self-criticism might help the humanitarian actor avoid the pitfalls of humanitarian practice that critics, in their time and ours, have seized upon. "American Callings" thus challenges three critiques that have been instrumental to American literary studies for decades: critiques of sentimental humanitarianism's complicity in projects of cultural domination, realism's investment in the status quo, and reform's role in maintaining social discipline through surveillance. The dissertation disputes the prevalent assertion that literature dealing with cross-cultural humanitarianism constitutes a sentimental, imperialistic, and ultimately violent discourse. I accomplish this by looking to instances of what Gregory Eiselein (1996) has called "eccentric" reform, efforts articulated from within a culture but in opposition to certain aspects of it. Drawing on narratives of what I call "humanitarian selfhood" in three historical contexts--industrializing urban centers in the North, the South during Reconstruction, and the Philippines during the U.S. occupation--"American Callings" traces an "eccentric" literary genealogy, one that offers up the humanitarian dynamic as a heuristic wherein the humanitarian agent arrives at a new kind of self-understanding by way of wrestling with the questions raised by service to others. The literature written by and about these humanitarians, I suggest, then provides an opportunity for readers to be transformed, as well.Englis

Role of suppressor of cytokine signaling 3 in colorectal cancer

Patients with inflammatory bowel diseases (IBD) have an increased lifetime risk of developing colorectal cancer (CRC). Suppressors of cytokine signaling (SOCS) are intracellular proteins that provide negative feedback on pro-inflammatory cytokine signaling. SOCS3 silencing in intestinal epithelial cells has previously been shown to promote tumorigenesis in the azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model of inflammation-associated CRC. Mechanisms associated with this effect were increased activation of signal transducer and activator of transcription 3 (STAT3) and NF[kappa]B, and increased expression of TNF[alpha] receptor 2 (TNFR2). TNFR2 is increased in IBD and CRC, but how this receptor is regulated remains undefined. Studies in this dissertation tested the hypothesis that TNFR2 is induced by STAT3 and/or NF[kappa]B pathways, that SOCS3 limits TNFR2 expression, and that SOCS3 is a tumor suppressor in both sporadic and inflammation-associated cancer. Colon cancer cell lines were treated with IL-6 and TNF[alpha] in the presence of STAT3 or NF[kappa]B inhibitors. STAT3 inhibition dramatically decreased cytokine-induction of TNFR2, implicating STAT3 as a critical mediator of TNFR2 induction. SOCS3 limited cytokine-induction of TNFR2, as well as STAT3 binding to consensus sequences within the TNFR2 promoter. SOCS3 also limited TNFR2-mediated proliferation and anchorage-independent growth of colon cancer cells. Together these findings support the concept that SOCS3 exerts a tumor suppressor role in part by limiting the growth-promoting abilities of TNFR2. To test the whether low SOCS3 expression predicts risk of early stage CRC, biopsies of normal mucosa from colonoscopy patients with and without adenomas were assayed for SOCS3 mRNA. No significant difference in SOCS3 mRNA was observed in normal mucosa of patients with and without adenoma. Thus SOCS3 silencing in normal mucosa does not predict adenoma risk. To test whether SOCS3 normally limits tumorigenesis in sporadic CRC, mice with IEC-SOCS3 silencing were subjected to the AOM model of spontaneous, non-inflammatory CRC. Mice with SOCS3 silencing exhibited a 75% increase in colon tumor incidence. Collectively, these data indicate that SOCS3 normally modulates multiple pro-tumorigenic pathways that contribute to both inflammation-associated and sporadic CRC

Sporadic cerebral small vessel disease and cognitive abilities

Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, contributing to multiple neurological disorders ranging from stroke, to mild cognitive impairment and dementia. However, despite a huge number of studies on the subject, we have a limited understanding of how SVD affects cognitive ability. This thesis aims to address this knowledge gap, by examining domain-specific cognitive abilities in a range of clinical and non-clinical presentations of SVD. In the introductory chapters of this thesis I will discuss what is meant by the term cerebral small vessel disease (SVD), describing key radiological features of SVD and its varied clinical and non-clinical presentations. However, before considering the current consensus on how SVD impacts different domains of cognitive ability, I will first consider what happens to these abilities in the context healthy cognitive ageing. Finally, I will consider the current consensus on the pattern of cognitive changes that occur in SVD and will examine the vast and often conflicting evidence that underpins this. To gain a comprehensive overview of the published literature examining cognitive abilities in SVD, Chapter 4 presents a systematic review and meta-analysis of 69 studies presenting cognitive data for at least one cohort with SVD (n=3679) and one comparison control group without SVD (n=3229). Results indicated that relative to controls, cohorts with SVD performed more poorly on cognitive tests in all of the cognitive domains examined. Meta-regression analyses suggested that fewer years of education in the SVD vs. control groups accounted for a proportion of the differences in their test scores in some cognitive domains. Further meta-regression analyses suggested that cohorts with SVD-related cognitive impairment or dementia performed more poorly on tests in certain cognitive domains than cohorts with stroke or non-clinical presentations of SVD. Overall, however, SVD cohorts performed more poorly than controls on cognitive tests in all domains, regardless of their SVD presentation. Chapters 5 and 6 focus more closely on the key radiological markers of SVD and their associations with cognitive test scores using data from the Lothian Birth Cohort 1936 (LBC1936): a cohort of relatively healthy, community-dwelling, older individuals. To increase the fidelity with which SVD is typically measured, I combined computational volumes and visually-rated MRI markers of SVD to construct a variable representing the total MRI-visible burden of SVD. The study in Chapter 5 presents the results of cross-sectional associations between this latent SVD variable and latent variables of processing speed, verbal memory and visuospatial ability, within a structural equation modelling framework (SEM; n=540; mean age 72.6±0.7 years). Age, sex, vascular risk, depression status, and age-11 IQ were included as covariates. The latent SVD variable was negatively associated with all cognitive factors, in line with the results of the systematic review and meta-analysis. However, after accounting for the shared variance between the different cognitive domains (a construct described as general cognitive ability, which previous studies have not accounted for), only the association between the latent SVD variable and processing speed remained significant. This suggests that SVD’s association with slowed processing speed is not driven by, but is independent of its association with poorer general cognitive ability. In Chapter 6 this work is developed further by exploring associations between the latent SVD variable and decline in the same latent cognitive factors over a period of 9 years, from the age of around 73 to 82, again in the LBC1936. This was carried out using latent growth curve modelling within a SEM framework. Age, sex, vascular risk, and age-11 IQ were included as covariates. Results indicated that the latent SVD variable was associated with greater decline in general cognitive ability and processing speed. However, after accounting for the covariance between tests of processing speed and general cognitive ability, only the association between greater SVD burden and decline in general cognitive ability remained significant. Whereas the results of Chapter 5 suggested that SVD burden at age 73 may have specific and independent effects on processing speed measured at the same age, the results of our longitudinal analyses suggest that SVD burden at age 73 associates with declining processing speed due to SVD’s overarching association with general cognitive decline. In the final chapter of this thesis, I summarise the findings of these three studies, discuss their limitations, and make recommendations for future research

Detection limits of organic compounds achievable with intense, short-pulse lasers

Many organic molecules have strong absorption bands which can be accessed by ultraviolet short pulse lasers to produce efficient ionization. This resonant multiphoton ionization scheme has already been exploited as an ionization source in time-of-flight mass spectrometers used for environmental trace analysis. In the present work we quantify the ultimate potential of this technique by measuring absolute ion yields produced from the interaction of 267 nm femtosecond laser pulses with the organic molecules indole and toluene, and gases Xe, N2 and O2. Using multiphoton ionization cross sections extracted from these results, we show that the laser pulse parameters required for real-time detection of aromatic molecules at concentrations of one part per trillion in air and a limit of detection of a few attomoles are achievable with presently available commercial laser systems. The potential applications for the analysis of human breath, blood and tissue samples are discussed

What features epitomize cohesion: development of a preliminary measure

Presently, no consensus has been reached with regards to measuring workplace cohesion. Cohesion measures often allude to abstract concepts rather than tangible features, therefore this study identified the tangible features and specific practices that epitomize cohesive workgroups. Specifically, 28 individuals were interviewed and asked to reflect upon two workgroups in which they had been employed before, only one of which was cohesive. Participants identified tangible features, practices, or characteristics that typified each of these workgroups. Content analysis uncovered 14 features of cohesion, such as shared emotional events in the past, friendly and welcoming greetings, and a feeling of pride when other people in the team excel on some task. A provisional measure of cohesion was then distilled from these items

Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation

Ribonucleotides represent a threat to DNA genome stability and transmission. Two types of Ribonuclease H (RNase H) excise ribonucleotides when they form part of the DNA strand, or hydrolyse RNA when it base-pairs with DNA in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast survives the absence of both enzymes. RNase H1 loss is tolerated by the parasite Trypanosoma brucei but no work has examined the function of RNase H2. Here we show that loss of T. brucei RNase H2 (TbRH2A) leads to growth and cell cycle arrest that is concomitant with accumulation of nuclear damage at sites of RNA polymerase (Pol) II transcription initiation, revealing a novel and critical role for RNase H2. Differential gene expression analysis reveals limited overall changes in RNA levels for RNA Pol II genes after TbRH2A loss, but increased perturbation of nucleotide metabolic genes. Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol I transcription sites, also leading to altered gene expression. Thus, we demonstrate separation of function between two nuclear T. brucei RNase H enzymes during RNA Pol II transcription, but overlap in function during RNA Pol I-mediated gene expression during host immune evasion