A study of the of ytterbium disilicates undergoing water vapour corrosion for environmental barrier coating applications

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The style and timing of the last deglaciation of Wester Ross, Northwest Scotland

The climate of the Wester Ross region of NW Scotland is particularly sensitive to fluctuations in the strength and latitude of the North Atlantic Gulf Stream. This was particularly apparent during the last deglaciation (14.7-12.9 ka), when overall climatic amelioration was interrupted by periods of cooling, the most significant being a 1.2 ka return to glacial conditions during the Younger Dryas (12.9-11.5 ka). Glacial readvances during these cooling episodes left behind numerous geomorphological features, which have been mapped and interpreted through a variety of methods, including fieldwork observations, aerial photography and digital elevation models, to form a detailed reconstruction of the style and timing of deglaciation. These methods were augmented by the study of 3D digital models, produced by combining 5cm resolution, Light Detection and Ranging (LiDAR) scans with colour photography, leading to the production of a detailed geomorphological map of a cirque formation in Torridon, Wester Ross, which was covered by an ice-sheet at the Last Glacial Maximum, and experienced localised ice flow during subsequent deglaciation and readvances. Six statistically comparable cosmogenic 10Be bedrock exposure ages give a Younger Dryas age for sites in Torridon and Applecross (Wester Ross), and have also been used to constrain the vertical extent of these ice fields. Reconstructions of these ice bodies revealed that the Torridon ice field (mean ELA, 482m) covered ~100km2, over twice the surface area covered by the Applecross ice field (~43km2). This could have resulted from the survival of ice in Torridon prior to the onset of the Younger Dryas cooling, and is tentativelty supported by pre-Younger Dryas cosmogenic 10Be exposure ages from this study and previous studies, which imply that ice existed close to the Wester Ross coastline and within central Torridon between 14-13ka. The Applecross ice field mean ELA (361m) was lowered by the presence of independent glaciers, which formed in low-lying troughs as snow was efficiently transferred to the NE by prevailing SW winds. Using empirical values from a global dataset, average annual Younger Dryas palaeoprecipitation values for the Torridon and Applecross ELAs are 2010 ± 266 and 2312 ± 534 mm a-1 respectively, suggesting a wetter climate than today. Palaeoprecipitation calculated using equations based on a climate model of NW Scotland, yield lower values between 1005 ± 67 mm a-1 and 1758 ± 118 mm a-1 for the Torridon ELA and 1205 ± 233 mm a-1 to 2109 ± 407 mm a-1 for the Applecross ELA, perhaps a more reliable estimate which reflect enhanced continentaility, promoted by the formation of sea ice on the NE Atlantic seaboard during the Younger Dryas.Despite the rapid warming observed in palaeotemperature proxies, studies of glacial geomorphology and basal shear stress suggest that initial deglaciation was slow, oscillatory and warm-based, leading to the formation of prominent retreat moraines in the lower valleys. This prolonged transition can be related to the northward migration of sea ice and the gradual reintroduction of a Gulf Stream-dominated maritime climate. Ice remaining in the central area down-wasted in-situ as the regional ELA increased, creating hummocky landscape. Finally, cosmogenic 10Be exposure ages indicate that glaciers (probably characerised by a polythermal regime) retreated into the high north-facing corries at approximately 11.8ka, depositing a series of flutes.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Generative Design in Minecraft (GDMC), Settlement Generation Competition

This paper introduces the settlement generation competition for Minecraft, the first part of the Generative Design in Minecraft challenge. The settlement generation competition is about creating Artificial Intelligence (AI) agents that can produce functional, aesthetically appealing and believable settlements adapted to a given Minecraft map - ideally at a level that can compete with human created designs. The aim of the competition is to advance procedural content generation for games, especially in overcoming the challenges of adaptive and holistic PCG. The paper introduces the technical details of the challenge, but mostly focuses on what challenges this competition provides and why they are scientifically relevant.Comment: 10 pages, 5 figures, Part of the Foundations of Digital Games 2018 proceedings, as part of the workshop on Procedural Content Generatio

Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study

Rationale Mechanistic target of rapamycin inhibitors reduce loss of lung function in lymphangioleiomyomatosis (LAM), although their benefit varies between individuals. We examined lung function response and side effects to rapamycin in a national cohort. Methods Subjects were receiving rapamycin for progressive lung disease. Clinical evaluation, detailed phenotyping, serial lung function, rapamycin and safety monitoring were performed according to a clinical protocol. Lung function change, measured as FEV1 slope (ΔFEV1), was reported for those treated for 1 year or longer. Results Rapamycin was associated with improved ΔFEV1 in 21 individuals where pretreatment data were available (p<0.0001). In 47 treated for a mean duration of 35.8 months, mean ΔFEV1 was +11 (SD 75) mL/year, although it varied from +254 to −148 mL/year. The quartile with the highest positive ΔFEV1 had greater pretreatment FEV1 (p=0.02) and shorter disease durations (p=0.02) than the lowest quartile. Serum rapamycin level was positively associated with side effects (p=0.02) but not ΔFEV1 over 1 year. Within the first month of therapy, apthous ulcers, nausea and diarrhoea were associated with higher rapamycin levels. Acne, oedema and menstrual irregularities tended to increase over the first year of therapy. At the end of observation, the prevalence of side effects was 5% or less. Conclusions Rapamycin reduces lung function loss in LAM, although in some, ΔFEV1 continues to fall at an accelerated rate. Poor response to rapamycin was associated with lower pretreatment lung function and longer disease duration but not serum level. Early intervention with low-dose rapamycin may preserve lung function and reduce side effects

Reverse transcriptase drug resistance mutations in HIV-1 subtype C infected patients on ART in Karonga District, Malawi

<p>Abstract</p> <p>Background</p> <p>Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme.</p> <p>Results</p> <p>Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically.</p> <p>Conclusion</p> <p>Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge</p

Antimicrobial Properties of Vertically Aligned Nano-Tubular Copper

In this work, the antimicrobial properties of vertically aligned nano-tubular Cu arrays (NT-Cu) fabricated via a template-based electrodeposition approach were investigated. The NT-Cu display good bactericidal activity against S.aureus and bacteriostatic properties against E.coli, S.sonnei, S.enterica and C.albicans. In contrast, Cu-foil electrodeposited from the same solution shows low biological activity against the same microorganisms. The antimicrobial activity of NT-Cu depends on both the type of microorganism and exposure time. After 6 hours of exposure, over 99.99% (log red = 4.43) of S.aureus population was inactivated, whereas, for E.coli, S.sonnei, S.enterica and C.albicans it was 97.8, 94.2, 89.9, and 90.3%, respectively

Thickness dependence of the stability of the charge-ordered state in Pr0.5_{0.5}Ca0.5_{0.5}MnO3_{3} thin films

Thin films of the charge-ordered (CO) compound Pr$_{0.5}$Ca$_{0.5}$MnO$_{3}$ have been deposited onto (100)-oriented SrTiO$_{3}$ substrates using the Pulsed Laser Deposition technique. Magnetization and transport properties are measured when the thickness of the film is varied. While the thinner films do not exhibit any temperature induced insulator-metal transition under an applied magnetic field up to 9T, for thickness larger than 1100\UNICODE{0xc5} a 5T magnetic field is sufficient to melt the CO state. For this latest film, we have measured the temperature-field phase diagram. Compared to the bulk material, it indicates that the robustness of the CO state in thin films is strongly depending on the strains and the thickness. We proposed an explanation based on the distortion of the cell of the film.Comment: 9 pages, 6 figures, submitted to Phys. Rev.

The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis

Background: Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM. Methods: 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM (Nottingham, UK). 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the NHLBI LAM Registry (USA). Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control sera using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and SNPs in GC encoding Vitamin D Binding Protein (VTDB) genotyped. Results: Proteomic analysis showed VTDB was 2.6 fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A containing haplotypes at rs7041/4588 (p=0.014 and 0.008 respectively). Conclusions: The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant free survival in LAM

Protein with negative surface charge distribution, Bnr1, shows characteristics of aDNA‐mimic protein andmay be involved in the adaptation of Burkholderia cenocepacia

Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate survival in the host. Burkholderia cenocepacia, a Gram-negative bacterium with a large genome of ∼8 Mb that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages. We previously identified an immunoreactive acidic protein encoded on replicon 3, BCAS0292. Deletion of the BCAS0292 gene significantly altered the abundance of 979 proteins by 1.5-fold or more; 19 proteins became undetectable while 545 proteins showed ≥1.5-fold reduced abundance, suggesting the BCAS0292 protein is a global regulator. Moreover, the ∆BCAS0292 mutant showed a range of pleiotropic effects: virulence and host-cell attachment were reduced, antibiotic susceptibility was altered, and biofilm formation enhanced. Its growth and survival were impaired in 6% oxygen. In silico prediction of its three-dimensional structure revealed BCAS0292 presents a dimeric β-structure with a negative surface charge. The ΔBCAS0292 mutant displayed altered DNA supercoiling, implicated in global regulation of gene expression. Three proteins were identified in pull-downs with FLAG-tagged BCAS0292, including the Histone H1-like protein, HctB, which is recognized as a global transcriptional regulator. We propose that BCAS0292 protein, which we have named Burkholderia negatively surface-charged regulatory protein 1 (Bnr1), acts as a DNA-mimic and binds to DNA-binding proteins, altering DNA topology and regulating the expression of multiple genes, thereby enabling the adaptation of B. cenocepacia to highly diverse environments