1,901 research outputs found
Supplemental Material2 - Supplemental material for The National Institute for Health Research Critical Care Research Priority Setting Survey 2018
No full textSupplemental material, Supplemental Material2 for The National Institute for Health Research Critical Care Research Priority Setting Survey 2018 by Kate C Tatham, Daniel F McAuley, Mark Borthwick, Neil G Henderson, Gemma Bashevoy and Stephen J Brett in Journal of the Intensive Care Society</p
Supplemental Material1 - Supplemental material for The National Institute for Health Research Critical Care Research Priority Setting Survey 2018
No full textSupplemental material, Supplemental Material1 for The National Institute for Health Research Critical Care Research Priority Setting Survey 2018 by Kate C Tatham, Daniel F McAuley, Mark Borthwick, Neil G Henderson, Gemma Bashevoy and Stephen J Brett in Journal of the Intensive Care Society</p
Supplemental Material3 - Supplemental material for The National Institute for Health Research Critical Care Research Priority Setting Survey 2018
No full textSupplemental material, Supplemental Material3 for The National Institute for Health Research Critical Care Research Priority Setting Survey 2018 by Kate C Tatham, Daniel F McAuley, Mark Borthwick, Neil G Henderson, Gemma Bashevoy and Stephen J Brett in Journal of the Intensive Care Society</p
Narrative support for technical documents: Formalising Rhetorical Structure Theory
No full textBusiness Process Re-engineering (BPR) is an area that requires a lot of technical documents and an important feature of a well-written document is a coherent narrative. Even though computer software has helped authors in many other aspects of writing, support for document narratives is almost non-existent. Therefore, we introduce CANS (Computer-Aided Narrative Support), a tool that uses Rhetorical Structure Theory to enhance the narrative of a document. From this narrative, the tool generates questions to prompt the author for the content of the document. CANS also allows the author to explore alternative narratives for a document. A catalogue of predefined narrative structures for popular types of documents is provided too. Our tool is still in its rudimentary stages but sufficiently complete to be demonstrated
Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo
No full textPhosphatidylcholine (PC) synthesis by the direct cytidine diphosphate choline (CDP-choline) pathway in rat liver generates predominantly mono- and di-unsaturated molecular species, while polyunsaturated PC species are synthesized largely by the phosphatidylethanolamine-N-methyltransferase (PEMT) pathway. Although altered PC synthesis has been suggested to contribute to development of hepatocarcinoma and nonalcoholic steatohepatitis, analysis of the specificity of hepatic PC metabolism in human patients has been limited by the lack of sensitive and safe methodologies. Here we incorporated a deuterated methyl-d9-labled choline chloride, to quantify biosynthesis fluxes through both of the PC synthetic pathways in vivo in human volunteers and compared these fluxes with those in mice. Rates and molecular specificities of label incorporated into mouse liver and plasma PC were very similar and strongly suggest that label incorporation into human plasma PC can provide a direct measure of hepatic PC synthesis in human subjects. Importantly, we demonstrate for the first time that the PEMT pathway in human liver is selective for polyunsaturated PC species, especially those containing docosahexaenoic acid. Finally, we present a multiple isotopomer distribution analysis approach, based on transfer of deuterated methyl groups to S-adenosylmethionine and subsequent sequential methylations of PE, to quantify absolute flux rates through the PEMT pathway that are applicable to studies of liver dysfunction in clinical studies. <br/
Analysis of lung surfactant phosphatidylcholine metabolism in transgenic mice using stable isotopes
No full textStable isotope labelling of lipid precursors coupled with mass spectrometry-based lipidomic analyses and determination of isotope enrichment in substrate, intermediate and product pools provide the parameters needed to determine absolute flux rates through lipid pathways in vivo. Here, as an illustration of the power of such analyses we investigated lung phosphatidylcholine (PC) synthesis in Surfactant Protein-D (SP-D) null mice. These animals develop emphysema, foamy alveolar macrophages and an alveolar lipoproteinosis with increasing age. We used the incorporation of methyl-9-[2H] choline chloride coupled with ESI-MS/MS to quantify absolute rates of lung surfactant PC synthesis and secretion in an SP-D-/? mouse model, together with an analysis of the molecular specificity of lung PC synthesis. PC synthetic rates were comparable in control (0.52 ?moles/lung/h) and SP-D-/? (0.69 ?moles/lung/h) mice, as were rates of surfactant PC secretion (29.8 and 30.6 nmoles/lung/h respectively). Increased lung PC in the SP-D-/? mouse was due to impaired catabolism, with a rate of accumulation of 0.057 ?moles/lung/h. The relatively low rates of surfactant PC secretion compared with total lung PC synthesis were compatible with a suggested ABCA1-mediated basolateral lipid efflux from alveolar type II epithelial cells. Finally, PC molecular species analysis suggested that a proportion of newly-synthesised PC is secreted rapidly into the lung air spaces in both control and SP-D-/? mice before significant PC acyl remodelling occurs<br/
Fluorescence lifetime imaging with distance and ranging for biomedical endoscopic applications
No full textEndoscopic cameras play a vital role in medical diagnostics as they provide a minimally invasive way to image inside the body. Conventional cameras, however, are reliant on the use of white light which does not offer any additional diagnostic information over cues from colour and intensity.
Fluorescence lifetime imaging (FLIm) is a technique that can enhance endoscopy by providing differentiation between tissue types without the need
for biomarkers. This could be particularly valuable, for example, in the identification of cancerous tissue margins pre-intervention.
Time resolved arrays which incorporate single photon avalanche diodes (SPADs) are a prime candidate for FLIm as they offer very fast and precise
measurements of individual photon arrival times. In addition, they are able to obtain high speed images, even in low light conditions such as typically
observed in FLIm of endogenous fluorophores in the human body.
Another time resolved technique enabled by SPADs is time of flight (ToF) imaging which allows the distance to a target to be determined. ToF based
distance mapping could provide crucial depth perception which FLIm images inherently lack. In the case of endoscopic imaging, this allows for greater
camera and instrument control which in turn mitigates the risk of tissue damage during surgical procedures.
This research presents a combined fluorescence lifetime imaging with distance and ranging (FLImDAR) technique, realised through the use of SPAD
arrays. The FLImDAR modality has strong applications in clinical endoscopic imaging and thus is the focus of this research. Similar previous studies have
investigated depth measurements using deep tissue fluorescence which requires the addition of fluorescent dyes. This work, however, targets surface
auto-fluorescence.
Firstly, a computational model is used to examine and refine various algorithms which can be implemented to perform FLImDAR. This model is
used to decide the final FLImDAR technique, as well as investigate the impact of signal noise. Next, FLImDAR is demonstrated experimentally using
fluorescent polymer targets. Three SPAD sensors (MegaFrame, Quanticam and Endocam) are tested for compatibility with the FLImDAR modality, each
showcasing different strengths and limitations. To further prove FLImDAR’s ability to perform in low photon level auto-fluorescent applications, ovine and cancerous human pulmonary targets are imaged. The final part of this study regards performing FLImDAR with a miniaturised imaging system. The SPAD sensor, Endocam, is characterised prior to integration into a handheld camera. Using the handheld camera, FLIm videos of ovine tissue are captured as well as long exposure FLImDAR images.
With further advances in detectors, sensor architecture and photon budgets, this research indicates the significant performance improvements that will enable practical clinical application of the FLImDAR technique
Powerful regulatory systems and post-transcriptional gene silencing resist increases in cellulose content in cell walls of barley
No full textBACKGROUND: The ability to increase cellulose content and improve the stem strength of cereals could have beneficial applications in stem lodging and producing crops with higher cellulose content for biofuel feedstocks. Here, such potential is explored in the commercially important crop barley through the manipulation of cellulose synthase genes (CesA). RESULTS: Barley plants transformed with primary cell wall (PCW) and secondary cell wall (SCW) barley cellulose synthase (HvCesA) cDNAs driven by the CaMV 35S promoter, were analysed for growth and morphology, transcript levels, cellulose content, stem strength, tissue morphology and crystalline cellulose distribution. Transcript levels of the PCW HvCesA transgenes were much lower than expected and silencing of both the endogenous CesA genes and introduced transgenes was often observed. These plants showed no aberrant phenotypes. Although attempts to over-express the SCW HvCesA genes also resulted in silencing of the transgenes and endogenous SCW HvCesA genes, aberrant phenotypes were sometimes observed. These included brittle nodes and, with the 35S:HvCesA4 construct, a more severe dwarfing phenotype, where xylem cells were irregular in shape and partially collapsed. Reductions in cellulose content were also observed in the dwarf plants and transmission electron microscopy showed a significant decrease in cell wall thickness. However, there were no increases in overall crystalline cellulose content or stem strength in the CesA over-expression transgenic plants, despite the use of a powerful constitutive promoter. CONCLUSIONS: The results indicate that the cellulose biosynthetic pathway is tightly regulated, that individual CesA proteins may play different roles in the synthase complex, and that the sensitivity to CesA gene manipulation observed here suggests that in planta engineering of cellulose levels is likely to require more sophisticated strategies.Hwei-Ting Tan, Neil J Shirley, Rohan R Singh, Marilyn Henderson, Kanwarpal S Dhugga, Gwenda M Mayo, Geoffrey B Fincher, and Rachel A Burto
Physiological concentration of calcium inhibits elastase-induced cleavage of a functional recombinant fragment of surfactant protein D
No full textSurfactant protein D (SP-D) plays an important role in lung host defence. SP-D levels have been shown to be depleted in cystic fibrosis (CF) patients. A recombinant fragment of the human SP-D (rfhSP-D) which consist of a hydrophobic neck and a CRD has been shown to be active in vivo and partially reverses the symptoms of the SP-D deficiency in the lungs when administered to SP-D knock-out mice. In this paper we studied the in vitro effect of different proteolytic enzymes commonly found in CF patients lungs, such as neutrophil elastase, cathepsin G and protease 3 as well as Pseudomonas elastase, on rfhSP-D. It was also shown that cleavage was inhibited by physiological concentration of calcium. When Western blot was compared with ELISA, we show that an anti-SP-D ELISA is a not a reliable assay of functional SP-D levels since non-functional fragments of SP-D are also detected. Thus, ELISA cannot be used as a reliable "diagnostic" tool for SP-D deficiency. Finally, we observe that SP-D is not cleaved in control patients but is degraded in about half the samples from cystic fibrosis patients, indicating that degradation of endogenous SP-D, by enzymes present in CF bronchioalveolar lavage fluid (BALF), may lead to deficiency of the protein as seen in CF and therefore rfhSP-D may be a useful future therapy
Henderson the Rain King : The Comic Form and the Style of Saul Bellow
No full textiii, 42 p.Quoting Leslie Fiedler, the author asserts that the modern novel has turned "from mythology to psychology from a body of communal story to the mind of the individual," and as a result, he concludes, the comic novel is a rarity. In this tradition, the six novels of Saul Bellow focus on the psychological development of one central character. However, the author asserts, one of Bellow's novels, Henderson the Rain King, stands above the rest because of the introduction of comic elements to the author's style of writing
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