Evacuation decisions in a chemical air pollution incident: cross sectional survey.

OBJECTIVE: To compare the health outcomes in sheltered and evacuated populations after a chemical incident in a plastics factory. DESIGN: Cross sectional survey. SETTING: Urban area in southwest England. PARTICIPANTS: 1750 residents from the area exposed to the chemical smoke, of which 472 were evacuated and the remaining 1278 were advised to shelter indoors. MAIN OUTCOME MEASURE: Number of adverse health symptoms. A case was defined by the presence of four or more symptoms. MAIN RESULTS: 1096 residents (63%; 299 evacuated, 797 sheltered) provided data for analyses. The mean symptom score and proportion of cases were higher in evacuated people than in the sheltered population (evacuated: symptom score 1.9, cases 19.7% (n = 59); sheltered: symptom score 1.0, cases 9.5% (n = 76); P < 0.001 for both). The difference between the two groups attenuated markedly at the end of two weeks from the start of the incident. The two main modifiable risk factors for the odds of becoming a case were evacuation (odds ratio 2.5, 95% confidence interval 1.7 to 3.8) and direct exposure to smoke for more than two hours on the first day of the incident (2.0, 1.7 to 2.3). The distance of residence from the factory or level of exposure before intervention (first six hours) had little effect on the odds of a person becoming a case. CONCLUSIONS: Sheltering may have been a better protective action than evacuation in this chemical incident, which is consistent with the prevailing expert view. Although this study has limitations, it is based on a real event. Evacuations carry their own risks and resource implications; increased awareness may help to reduce unnecessary evacuations in the future

Understanding, normativity, and scientific practice

Understanding, Normativity, and Scientific Practice Harry Lewendon-Evans PhD Thesis Department of Philosophy Durham University 2018 Recent work in epistemology and philosophy of science has argued that understanding is an important cognitive achievement that philosophers should seek to address for its own sake. This thesis outlines and defends a new account of scientific understanding that analyses the concept of understanding in terms of the concept of normativity. The central claim is that to understand means to grasp something in the light of norms. The thesis is divided into two parts: Part I (chapters one to three) addresses the question of the agency of understanding and Part II (chapters four to five) focuses on the vehicles of scientific understanding. Chapter One begins with an account of understanding drawn from the work of Martin Heidegger, which presents understanding as a practical, normative capacity for making sense of entities. Chapter Two builds on Robert Brandom’s normative inferentialism to argue that conceptual understanding is grounded in inferential rules embedded within norm-governed, social practices. Chapter Three argues that normativity should be located in the intersubjective nature of social practices. The chapters in Part II draw on and extend the account of understanding developed in Part I by focusing on how models and explanations function within scientific practice to facilitate scientific understanding. Chapter Four investigates the nature of model-based understanding. It defends the claim that constructing and using models enables a form of conceptual articulation which facilitates scientific understanding by rendering scientific phenomena intelligible. Chapter Five considers the connection between understanding and explanation through the role of explanatory discourse in scientific practice. I argue that the function of explanations is to sculpt and make explicit the norms of intelligibility required for scientific understanding. This thesis concludes that scientific understanding is an inherently norm-governed phenomenon that is unintelligible without reference to the normative dimension of our social and scientific practices

Studies on the 5-enolpyruvylshikimate 3-phosphate synthase of Escherichia coli

1. A method for the purification of EPSP synthase of E. coli K12 has been developed. The purification procedure consisted of ammonium sulphate fractionation, ion-exchange chromatography and hydrophobic chromatography. The final step involved substrate elution from a phosphocellulose column. EPSP synthase was purified 843-fold and in 22% yield over the (NH4)2SO4 fraction. 2. E. coli EPSP synthase has been shown to be a monomeric enzyme. The subunit Mr was estimated to be 49,000 by SDS PAGE, and native Mr values of 42,000 and 55,000 were determined by gel filtration. Kinetic parameters for E. coli EPSP synthase are reported. The enzyme was inhibited by the herbicide glyphosate, inhibition was competitive with respect to phosphoenolpyruvate. 3. EPSP synthase has also been purified from an overproducing strain, E. coli AB2829/pKD501. The overproduced enzyme was purified 50-fold and in 30% yield over the crude extract fraction. EPSP synthase can be purified in milligram quantities from the overproducing strain. 4. The overproduced enzyme has been shown to be identical in its physical and kinetic properties to EPSP synthase purified from E. coli K12. The amino acid composition and N-terminal amino acid sequence of E. coli EPSP synthase are reported. 5. Chemical modification of EPSP synthase by 3-bromopyruvate has been examined. Although substrate protection against inactivation was observed, bromopyruvate did not appear to be an/ an active-site-directed reagent for E. coli EPSP synthase. 6. Phosphoserine aminotransferase has been purified from the overproducing strain, E. coli AB2829/pKD501. The purification procedure was similar to that developed for EPSP synthase; (NH4)2SO4 fractionation, ion-exchange chromatography and hydrophobic chromatography. The final step was ion-exchange chromatography on a mono-Q column. PSAT was purified approximately 7-fold over the crude extract fraction. 7. The subunit Mr of E. coli PSAT has been shown to be 39,000 and this enzyme appeared to be dimeric. The amino acid composition and N-terminal amino acid sequence of PSAT are reported. Some kinetic properties of this enzyme are also described

Electrophysiological differentiation of the effects of stress and accent on lexical integration in highly fluent bilinguals

Individuals who acquire a second language (L2) after infancy often retain features of their native language (L1) accent. Cross-language priming studies have shown negative effects of L1 accent on L2 comprehension, but the role of specific speech features, such as lexical stress, is mostly unknown. Here, we investigate whether lexical stress and accent differently modulate semantic processing and cross-language lexical activation in WelshEnglish bilinguals, given that English and Welsh differ substantially in terms of stress realisation. In an L2 cross-modal priming paradigm, we manipulated the stress pattern and accent of spoken primes, whilst participants made semantic relatedness judgments on visual word targets. Event-related brain potentials revealed a main effect of stress on target integration, such that stimuli with stress patterns compatible with either the L1 or L2 required less processing effort than stimuli with stress incompatible with both Welsh and English. An independent cross-language phonological overlap manipulation revealed an interaction between accent and L1 access. Interestingly, although it increased processing effort, incorrect stress did not significantly modulate semantic priming effects or covert access to L1 phonological representations. Our results are consistent with the concept of language-specific stress templates, and suggest that accent and lexical stress affect speech comprehension mechanisms differentially.(VLID)4898090Version of recor

Isoxazole-derived amino acids are bromodomain-binding acetyl-lysine mimics: incorporation into histone H4 peptides and histone H3

A range of isoxazole-containing amino acids was synthesized, which displace acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazolecontaining peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3

Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3.

A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3.Pfizer Neusentis for studentship suppor