Corrupting Cooks: Domestic Service and Expertise in Eighteenth-Century France

In this dissertation I argue that a new type of cook emerged during the eighteenth century: a "taste professional" who articulated a sophisticated policy of fashion and health, known as la cuisine moderne, in order to advance cooking's status. By proposing ever-accelerating cycles of culinary change, these domestic servants drove the consumer revolution at the most basic intersection of gustatory and metaphorical taste. Capitalizing on the Enlightenment's concern for bodily and material happiness, cooks claimed to be medical practitioners, placing them at odds with those who argued that cooks lacked the requisite authority to practice a science of the kitchen. By appealing to public opinion in their effort to secure recognition as taste and health experts, however, cooks forced doctors to debate with them on implicitly equal terms. Cooks were singularly unqualified assume these roles. They worked primarily as domestic servants, including both men and women in their ranks and lacking formal certifying and training institutions. Contemporaries responded to the incongruity of cooks' scientific claims by vilifying them in a wide range of visual and textual media. I contend that the vitriolic response to la cuisine moderne grew out of the perception that cooks destabilized social and cultural order. I conclude that cooks' explicit assertion of modernity worked against them, since servants ultimately could not be modern. Thisdissertation thus revises our understanding of the limits of modernity as a successful rhetorical strategy. I organize my analysis along three axes: practices, discourse, and representations. I open with an archive-based study of the spatial and material constraints faced by cooks and the strategies they deployed to structure their occupation. Next I explore the claims made by cooks as new taste experts: here I utilize printed cookbooks not just as indicators of dining practices but rather to propose a novel discursive space where cooks asserted revolutionary expertise. Finally I analyze the contemporary response to cooks' selfstyled authority. Paintings, engravings, plays, verse, and medical treatises consistently portrayed cooks as both physiological and moral dangers that threatened to corrupt the body, the household, and indeed even society.Ph.D.PhilosophyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/98985/1/takats.pd

Application of novel solid phase extraction-NMR protocols for metabolic profiling of human urine

Metabolite identification and annotation procedures are necessary for the discovery of biomarkers indicative of phenotypes or disease states, but these processes can be bottlenecked by the sheer complexity of biofluids containing thousands of different compounds. Here we describe low-cost novel SPE-NMR protocols utilising different cartridges and conditions, on both natural and artificial urine mixtures, which produce unique retention profiles useful for metabolic profiling. We find that different SPE methods applied to biofluids such as urine can be used to selectively retain metabolites based on compound taxonomy or other key functional groups, reducing peak overlap through concentration and fractionation of unknowns and hence promising greater control over the metabolite annotation/identification process

BASIS: High-performance bioinformatics platform for processing of large-scale mass spectrometry imaging data in chemically augmented histology

Mass Spectrometry Imaging (MSI) holds significant promise in augmenting digital histopathologic analysis by generating highly robust big data about the metabolic, lipidomic and proteomic molecular content of the samples. In the process, a vast quantity of unrefined data, that can amount to several hundred gigabytes per tissue section, is produced. Managing, analysing and interpreting this data is a significant challenge and represents a major barrier to the translational application of MSI. Existing data analysis solutions for MSI rely on a set of heterogeneous bioinformatics packages that are not scalable for the reproducible processing of large-scale (hundreds to thousands) biological sample sets. Here, we present a computational platform (pyBASIS) capable of optimized and scalable processing of MSI data for improved information recovery and comparative analysis across tissue specimens using machine learning and related pattern recognition approaches. The proposed solution also provides a means of seamlessly integrating experimental laboratory data with downstream bioinformatics interpretation/analyses, resulting in a truly integrated system for translational MSI

Type IIb Supernova SN 2011dh: Spectra and Photometry from the Ultraviolet to the Near-Infrared

We report spectroscopic and photometric observations of the Type IIb SN 2011dh obtained between 4 and 34 days after the estimated date of explosion (May 31.5 UT). The data cover a wide wavelength range from 2,000 Angstroms in the UV to 2.4 microns in the NIR. Optical spectra provide line profiles and velocity measurements of HI, HeI, CaII and FeII that trace the composition and kinematics of the SN. NIR spectra show that helium is present in the atmosphere as early as 11 days after the explosion. A UV spectrum obtained with the STIS reveals that the UV flux for SN 2011dh is low compared to other SN IIb. The HI and HeI velocities in SN 2011dh are separated by about 4,000 km/s at all phases. We estimate that the H-shell of SN 2011dh is about 8 times less massive than the shell of SN 1993J and about 3 times more massive than the shell of SN 2008ax. Light curves (LC) for twelve passbands are presented. The maximum bolometric luminosity of $1.8 \pm 0.2 \times 10^{42}$ erg s$^{-1}$ occurred about 22 days after the explosion. NIR emission provides more than 30% of the total bolometric flux at the beginning of our observations and increases to nearly 50% of the total by day 34. The UV produces 16% of the total flux on day 4, 5% on day 9 and 1% on day 34. We compare the bolometric light curves of SN 2011dh, SN 2008ax and SN 1993J. The LC are very different for the first twelve days after the explosions but all three SN IIb display similar peak luminosities, times of peak, decline rates and colors after maximum. This suggests that the progenitors of these SN IIb may have had similar compositions and masses but they exploded inside hydrogen shells that that have a wide range of masses. The detailed observations presented here will help evaluate theoretical models for this supernova and lead to a better understanding of SN IIb.Comment: 23 pages, 14 figures, 9 tables, accepted by Ap

De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis

Development and Application of Ultra-Performance Liquid Chromatography-TOF MS for Precision Large Scale Urinary Metabolic Phenotyping

To better understand the molecular mechanisms underpinning physiological variation in human populations, metabolic phenotyping approaches are increasingly being applied to studies involving hundreds and thousands of biofluid samples. Hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) has become a fundamental tool for this purpose. However, the seemingly inevitable need to analyze large studies in multiple analytical batches for UPLC-MS analysis poses a challenge to data quality which has been recognized in the field. Herein, we describe in detail a fit-for-purpose UPLC-MS platform, method set, and sample analysis workflow, capable of sustained analysis on an industrial scale and allowing batch-free operation for large studies. Using complementary reversed-phase chromatography (RPC) and hydrophilic interaction liquid chromatography (HILIC) together with high resolution orthogonal acceleration time-of-flight mass spectrometry (oaTOF-MS), exceptional measurement precision is exemplified with independent epidemiological sample sets of approximately 650 and 1000 participant samples. Evaluation of molecular reference targets in repeated injections of pooled quality control (QC) samples distributed throughout each experiment demonstrates a mean retention time relative standard deviation (RSD) of <0.3% across all assays in both studies and a mean peak area RSD of <15% in the raw data. To more globally assess the quality of the profiling data, untargeted feature extraction was performed followed by data filtration according to feature intensity response to QC sample dilution. Analysis of the remaining features within the repeated QC sample measurements demonstrated median peak area RSD values of <20% for the RPC assays and <25% for the HILIC assays. These values represent the quality of the raw data, as no normalization or feature-specific intensity correction was applied. While the data in each experiment was acquired in a single continuous batch, instances of minor time-dependent intensity drift were observed, highlighting the utility of data correction techniques despite reducing the dependency on them for generating high quality data. These results demonstrate that the platform and methodology presented herein is fit-for-use in large scale metabolic phenotyping studies, challenging the assertion that such screening is inherently limited by batch effects. Details of the pipeline used to generate high quality raw data and mitigate the need for batch correction are provided

Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma.

Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients' breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis