127 research outputs found
Improvement in inner retinal function in glaucoma in response to nicotinamide (Vitamin B3) supplementation: a crossover randomized clinical trial
No full textAbstract #3493Flora Hui, Jessica Tang, Pete Williams, Myra McGuinness, Xavier Hadoux, Robert James Casson, Michael Coote, Ian Trounce, Keith R Martin, Peter van Wijngaarden, Jonathan Guy Crowsto
Determination of the molecular and physiological basis of citric acid tolerance in spoilage yeast
No full textThe ability of yeasts to grow and adapt under extreme environmental conditions including within the presence of weak organic acid preservatives has led to substantial economic losses through manufactured food and beverage spoilage. The food industry has employed the use of various weak organic acids such as sorbic, benzoic and acetic acid as preservatives to help prevent spoilage by yeasts and moulds. The mechanisms by which S. cerevisiae is able to adapt to these weak organic acids have been extensively studied. A lesser studied weak organic acid preservative is citric acid. The aim of this study was to gain further information on the mechanisms of citric acid adaptation and through this identify potential targets for new preservation strategies.
Current knowledge indicates the involvement of the HOG pathway in citric acid adaptation. A citric acid sensitivity screen from a previous study also isolated a SR protein kinase Sky1p, involved in polyamine metabolism, which has been connected with other crucial cellular processes including modulation of ion homeostasis and osmotic shock.
In this study we have undertaken a systematic screen for genes that confer increased sensitivity to citric acid paying particular attention to those involved in polyamine metabolism and those known to encode proteins which have evidence of interactions with Sky1p. Many of the deletion strains tested exhibited hypersensitivity to citric acid including Δsky1. Protein-protein interaction maps for Sky1p highlighted an interesting secondary interacting protein Nmd5p, an importin crucial for the nuclear localization of Hog1p. This information suggested there may be the possibility of linkage between Sky1p and Hog1p and their roles in citric acid tolerance, perhaps through Nmd5p. This provided an incentive to perform a range of experiments to test this theory.
Proteomic and phosphoproteomic analyses were carried out to study protein expression and phosphorylation changes in response to citric acid stress. Comparative proteomic analyses for Δsky1, Δhog1 and BY4741a with and without citric acid identified four instances of analogous protein expression responses in both Δsky1 and Δhog1, suggesting functional overlap upon exposure to citric acid.
Epistasis studies of Δhog1Δsky1 suggested that the two protein kinases do not function on the same pathway. However, overexpression analyses did suggest some functional interaction between Hog1p and Sky1p in mediating citric acid resistance since overexpression of Sky1p in Δhog1 resulted in partial rescue of growth. Further supporting evidence for some functional interaction or linkage was provided by Hog1p phosphorylation and localisation studies. Δsky1 exhibited dual phosphorylation of Hog1p in the absence of citric acid stress; implying that loss of SKY1 results in dual phosphorylation of Hog1p by either prompting phosphorylation or perhaps by interfering with dephosphorylation of Hog1p. Localisation studies of Hog1p proved that like osmotic stress, citric acid stress results in nuclear translocation of Hog1p and deletion of SKY1 seemed to interfere with this localisation to some extent.
In light of the results attained in this study we believe we have evidence to propose a novel role for Sky1p in mediating resistance to citric acid and that there is also substantial evidence to suggest that Sky1p shares some functional redundancy and perhaps functional linkage with Hog1p in citric acid adaptation
The grand imperial Bible [electronic resource] : By the Revd. Wm. Luke Phillips, late of Lembroke College Oxford.
No full textFinal leaf = 23Y.The titlepage to vol.1 is engraved.The titlepage to vol.2 has the imprint: London: printed for the author, and sold by J. Coote, 1766.The Apocrypha is in the list of books but has separate register and a titlepage bearing the imprint: London: printed for J. Coote, 1766.The N.T. has a separate titlepage bearing the same imprint.Sometimes found with engravings including maps.Vol.1 contains a 4-page list of subscribers.Electronic reproduction.English Short Title Catalog,Reproduction of original from British Library
What's the Point of Authors?
No full textIn this paper, I want to start to untangle some of the philosophical issues associated with our practices of ascribing authorship for collaborative work, with an eye to formulating better guidelines for authorship.
I will focus on the following questions:
1. What epistemic, social, and ethical functions are played by our practices of ascribing authorship for academic papers?
2. What ways of ascribing authorship would best address these functions? Can any one way of ascribing authorship address all of the functions?
I hope to make three contributions. First, I hope to build on established debates about authorship to offer a general framework for assessing practices of assigning authorship. Secondly, to argue that the different functions of authorship are incoherent, making different predictions about who should be an author. Thirdly, I will argue that this incoherence points in the direction of replacing the role of an author with a number of different roles which address the different functions. In the final section I will set out a proposal that does just this, which I will call the no author account of authorship
Wanderings, south and east : with 2 maps and 47 wood engravings executed under the direction of Edward Whymper, from sketches by the author, native drawings, etc.
No full textDeepfakes and the epistemic apocalypse
No full text[Author note: There is a video explainer of this paper on youtube at the new work in philosophy channel (search for surname+deepfakes).]
It is widely thought that deepfake videos are a significant and unprecedented threat to our epistemic practices. In some writing about deepfakes, manipulated videos appear as the harbingers of an unprecedented _epistemic apocalypse_. In this paper I want to take a critical look at some of the more catastrophic predictions about deepfake videos. I will argue for three claims: (1) that once we recognise the role of social norms in the epistemology of recordings, deepfakes are much less concerning, (2) that the history of photographic manipulation reveals some important precedents, correcting claims about the novelty of deepfakes, and (3) that proposed solutions to deepfakes have been overly focused on technological interventions. My overall goal is not so much to argue that deepfakes are not a problem, but to argue that behind concerns around deepfakes lie a more general class of social problems about the organisation of our epistemic practices
Mechanistic Investigations into the Palladium-Catalyzed Decarboxylative Allylic Alkylation of Ketone Enolates Using the PHOX Ligand Architecture
No full textPalladium-catalyzed asymmetric allylic alkylation has become a large and important field for chemical synthesis. Many methodologies in this field offer mild conditions under which challenging and important molecular features can be reliably synthesized, including chiral all-carbon quaternary stereocenters. As a result, palladium- catalyzed asymmetric allylic alkylation has found significant use in total synthesis, and growing use in industry. While the general process of palladium-catalyzed asymmetric allylic alkylation has been studied for decades, there have been a number of recent modifications and developments, such as asymmetric versions of decarboxylative allylic alkylation procedures that are not yet well understood. The development of future implementations and improvements to palladium-catalyzed asymmetric allylic alkylation and related methodologies is expected to be facilitated by a better understanding of these more recent developments, and thus further mechanistic investigation is warranted.
Reported herein is a set of investigations into the palladium-catalyzed decarboxylative asymmetric allylic alkylation of ketone enolates using the PHOX ligand architecture. By monitoring the reaction via 31P NMR, a series of previously unidentified key intermediates is discovered. Two representatives of these key intermediates are isolated and characterized. The solution behavior of these species under reaction-like conditions is studied along with a few novel and related complexes. The role of these intermediates and their impact on the behavior of the reaction and product formation is discussed. Previously confounding experimentally observed behavior for this methodology is rationalized via the properties elucidated for these discovered intermediates.</p
Haemolytic and cytotoxic activities of the Tween 80-extracted putative haemolysin of Pasteurella multocida B:2
No full textThe objective of this study was to investigate the haemolytic and cytotoxic activity of Pasteurella multocida B:2 strains, originally from cases of haemorrhagic septicaemia in cattle. All six P. multocida B:2 strains were non-haemolytic on sheep blood agar (SBA) and horse blood agar (HBA) when grown aerobically and on SBA anaerobically but they were haemolytic on HBA when grown anaerobically. No haemolytic activity against horse red blood cells was detected in culture supernates from aerobically or anaerobically grown cultures and only very weak haemolytic activity was obtained in supernates or pellet fractions from sonicated cells. However, after repeated extraction of sonicated cells with Tween 80, haemolytic activity was found in various cell fractions, both Tween-soluble and -insoluble. The Tween-extracted putative haemolysin and other bacterial fractions were also cytotoxic for mouse macrophage-like J774.2 cells. Further characterisation of the putative haemolysin revealed it to be a heat-labile, non-pore-forming protein of molecular weight >10ákDa whose activity was completely destroyed by trypsin and greatly reduced with protease and proteinase K treatment. Congo red also reduced the haemolytic activity. Non-denaturing gel-electrophoresis and RBC agar overlay revealed clear haemolytic zones but suggested that Tween was bound to some component of the P. multocida B:2 fractions and was responsible, to some extent, for the haemolytic activity observed. However, the effect of heat and other reagents on the Tween-extracted fractions and the lack of haemolytic activity in different Tween-extracted cell fractions of organisms other than P. multocida suggested that some proteinaceous component of the organism could indeed act as a haemolysin. This putative haemolysin may be one of the virulence attributes of P. multocida, but its characterisation and role in pathogenesis require further stud
Specific PCR primers from the 16S-23S rRNA spacer region for the rapid detection and identification of Actinobacillus seminis
No full textDeepfakes and the epistemic apocalypse
No full text[Author note: There is a video explainer of this paper on youtube at the new work in philosophy channel (search for surname+deepfakes).]
It is widely thought that deepfake videos are a significant and unprecedented threat to our epistemic practices. In some writing about deepfakes, manipulated videos appear as the harbingers of an unprecedented _epistemic apocalypse_. In this paper I want to take a critical look at some of the more catastrophic predictions about deepfake videos. I will argue for three claims: (1) that once we recognise the role of social norms in the epistemology of recordings, deepfakes are much less concerning, (2) that the history of photographic manipulation reveals some important precedents, correcting claims about the novelty of deepfakes, and (3) that proposed solutions to deepfakes have been overly focused on technological interventions. My overall goal is not so much to argue that deepfakes are not a problem, but to argue that behind concerns around deepfakes lie a more general class of social problems about the organisation of our epistemic practices
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