A cellular automaton model of crystalline cellulose hydrolysis by cellulases

<p>Abstract</p> <p>Background</p> <p>Cellulose from plant biomass is an abundant, renewable material which could be a major feedstock for low emissions transport fuels such as cellulosic ethanol. Cellulase enzymes that break down cellulose into fermentable sugars are composed of different types - cellobiohydrolases I and II, endoglucanase and β-glucosidase - with separate functions. They form a complex interacting network between themselves, soluble hydrolysis product molecules, solution and solid phase substrates and inhibitors. There have been many models proposed for enzymatic saccharification however none have yet employed a cellular automaton approach, which allows important phenomena, such as enzyme crowding on the surface of solid substrates, denaturation and substrate inhibition, to be considered in the model.</p> <p>Results</p> <p>The Cellulase 4D model was developed <it>de novo </it>taking into account the size and composition of the substrate and surface-acting enzymes were ascribed behaviors based on their movements, catalytic activities and rates, affinity for, and potential for crowding of, the cellulose surface, substrates and inhibitors, and denaturation rates. A basic case modeled on literature-derived parameters obtained from <it>Trichoderma reesei </it>cellulases resulted in cellulose hydrolysis curves that closely matched curves obtained from published experimental data. Scenarios were tested in the model, which included variation of enzyme loadings, adsorption strengths of surface acting enzymes and reaction periods, and the effect on saccharide production over time was assessed. The model simulations indicated an optimal enzyme loading of between 0.5 and 2 of the base case concentrations where a balance was obtained between enzyme crowding on the cellulose crystal, and that the affinities of enzymes for the cellulose surface had a large effect on cellulose hydrolysis. In addition, improvements to the cellobiohydrolase I activity period substantially improved overall glucose production.</p> <p>Conclusions</p> <p>Cellulase 4D simulates the enzymatic hydrolysis of cellulose to glucose by surface and solution phase-acting enzymes and accounts for complex phenomena that have previously not been included in cellulose hydrolysis models. The model is intended as a tool for industry, researchers and educators alike to explore options for enzyme engineering and process development and to test hypotheses regarding cellulase mechanisms.</p

Regionalisation and the rescaling of agro-food governance: case study evidence from two English regions

Copyright © 2012 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Political Geography, 2012, Vol. 31 Issue 2, pp. 83 – 93 DOI: 10.1016/j.polgeo.2011.10.007Some researchers detected a new-found subsidiarity in rural policy after England’s 2001 Foot and Mouth Disease epidemic, with regional and sub-regional institutions working together to implement an economic recovery strategy. While such research began to link debates on the new regionalism and the re-scaling of agro-food governance, its conception of the latter focused too narrowly on the ‘turn to quality’, thereby overlooking other important aspects of food relocalisation. Based on interviews conducted in England’s South West and West Midlands regions, this paper examines whether the attitudes of key actors from regional and sub-regional governance institutions provided a sound basis for partnership working on the food relocalisation policies recommended in the Government’s Strategy for Sustainable Farming and Food. It finds different attitudes on the part of regional and sub-regional actors, with the former favouring regional foods and the latter local foods. Despite scepticism from both groups about the ability of the England Rural Development Programme (2000-2006) to promote food relocalisation, grants were awarded to both regional and local food entrepreneurs, suggesting that the programme contributed more to food relocalisation than previously thought

A Quantitative Analysis of Published Skull Base Endoscopy Literature

Objectives Skull base endoscopy allows for minimal access approaches to the sinonasal contents and cranial base. Advances in endoscopic technique and applications have been published rapidly in recent decades. Setting: We utilized an Internet-based scholarly database (Web of Science, Thomson Reuters) to query broad-based phrases regarding skull base endoscopy literature. Participants: All skull base endoscopy publications. Main Outcome Measures: Standard bibliometrics outcomes. Results: We identified 4,082 relevant skull base endoscopy English-language articles published between 1973 and 2014. The 50 top-cited publications (n = 51, due to articles with equal citation counts) ranged in citation count from 397 to 88. Most of the articles were clinical case series or technique descriptions. Most (96% [49/51])were published in journals specific to either neurosurgery or otolaryngology. Conclusions: A relatively small number of institutions and individuals have published a large amount of the literature. Most of the publications consisted of case series and technical advances, with a lack of randomized trials

Artists on the edge of the world : An integrated approach to the study of Magdalenian engraved stone plaquettes from Jersey (Channel Islands)

The Upper Palaeolithic is characterised by the appearance of iconographic expressions most often depicting animals, including anthropomorphic forms, and geometric signs. The Late Upper Palaeolithic Magdalenian saw a flourishing of such depictions, encompassing cave art, engraving of stone, bone and antler blanks and decoration of tools and weapons. Though Magdalenian settlement exists as far northwest as Britain, there is a limited range of art known from this region, possibly associated with only fleeting occupation of Britain during this period. Stone plaquettes, flat fragments of stone engraved on at least one surface, have been found in large quantities at numerous sites spanning the temporal and geographical spread of the Magdalenian, but they have been absent so far from the archaeological record of the British Isles. Between 2015 and 2018, ten fragments of stone plaquettes extensively engraved with abstract designs were uncovered at the Magdalenian site of Les Varines, Jersey, Channel Islands. In this paper, we report detailed analyses of these finds, which provide new evidence for technologies of abstract mark-making, and their significance within the lives of people on the edge of the Magdalenian world. These engraved stone fragments represent important, rare evidence of artistic expression in what is the far northern and western range of the Magdalenian and add new insight to the wider significance of dynamic practices of artistic expression during the Upper Palaeolithic

Targeting Survivin with YM155 (Sepantronium Bromide): A novel therapeutic strategy for paediatric acute myeloid leukaemia

Despite aggressive chemotherapy, approximately one-third of children with acute myeloid leukaemia(AML) relapse. More effective treatments are urgently needed. Survivin is an inhibitor-of-apoptosis protein with key roles in regulating cell division, proliferation and apoptosis. Furthermore, high expression of Survivin has been associated with poor clinical outcome in AML. The Survivin suppressant YM155 (Sepantronium Bromide) has pre-clinical activity against a range of solid cancers and leukemias, although data in AML is limited. Therefore, we undertook a comprehensive pre-clinical evaluation of YM155 in paediatric AML. YM155 potently inhibited cell viability in a diverse panel of AML cell lines. All paediatric cell lines were particularly sensitive, with a median IC50 of 0.038 mu M. Cell cycle analyses demonstrated concentration-dependent increases in a sub-G1 population with YM155 treatment, suggestive of apoptosis that was subsequently confirmed by an increase in annexin-V positivity. YM155-mediated apoptosis was confirmed across a panel of 8 diagnostic bone marrow samples from children with AML. Consistent with the proposed mechanism of action, YM155 treatment was associated with down-regulation of Survivin mRNA and protein expression and induction of DNA damage

Dietary long-chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats.

Short-term consumption of a high-fat diet impairs exercise capacity in both rats and humans, and increases expression of the mitochondrial uncoupling protein, UCP3, in rodent cardiac and skeletal muscle via activation of the transcription factor, peroxisome proliferator-activated receptor α (PPARα). Unlike long-chain fatty acids however, medium-chain fatty acids do not activate PPARα and do not increase muscle UCP3 expression. We therefore investigated exercise performance and cardiac mitochondrial function in rats fed a chow diet (7.5% kcal from fat), a long-chain triglyceride (LCT) rich diet (46% kcal from LCTs) or a medium-chain triglyceride (MCT) rich diet (46% kcal from MCTs). Rats fed the LCT-rich diet for 15 days ran 55% less far than they did at baseline, whereas rats fed the chow or MCT-rich diets neither improved nor worsened in their exercise capacities. Moreover, consumption of an LCT-rich diet increased cardiac UCP3 expression by 35% and decreased oxidative phosphorylation efficiency, whereas consumption of the MCT-rich diet altered neither UCP3 expression nor oxidative phosphorylation efficiency. Our results suggest that the negative effects of short-term high-fat feeding on exercise performance are predominantly mediated by long-chain rather than medium-chain fatty acids, possibly via PPARα-dependent upregulation of UCP3.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Multiply-connected Bose-Einstein condensed alkali gases: Current-carrying states and their decay

The ability to support metastable current-carrying states in multiply-connected settings is one of the prime signatures of superfluidity. Such states are investigated theoretically for the case of trapped Bose condensed alkali gases, particularly with regard to the rate at which they decay via thermal fluctuations. The lifetimes of metastable currents can be either longer or shorter than experimental time-scales. A scheme for the experimental detection of metastable states is sketched.Comment: 4 pages, including 1 figure (REVTEX

Rater Reliability of the Hardy Classification for Pituitary Adenomas in the Magnetic Resonance Imaging Era

Objectives The Hardy classification is used to classify pituitary tumors for clinical and research purposes. The scale was developed using lateral skull radiographs and encephalograms, and its reliability has not been evaluated in the magnetic resonance imaging (MRI) era. Design Fifty preoperative MRI scans of biopsy-proven pituitary adenomas using the sellar invasion and suprasellar extension components of the Hardy scale were reviewed. Setting This study was a cohort study set at a single institution. Participants There were six independent raters. Main Outcome Measures The main outcome measures of this study were interrater reliability, intrarater reliability, and percent agreement. Results Overall interrater reliability of both Hardy subscales on MRI was strong. However, reliability of the intermediate scores was weak, and percent agreement among raters was poor (12-16%) using the full scales. Dichotomizing the scale into clinically useful groups maintained strong interrater reliability for the sellar invasion scale and increased the percent agreement for both scales. Conclusion This study raises important questions about the reliability of the original Hardy classification. Editing the measure to a clinically relevant dichotomous scale simplifies the rating process and may be useful for preoperative tumor characterization in the MRI era. Future research studies should use the dichotomized Hardy scale (sellar invasion Grades 0-III versus Grade IV, suprasellar extension Types 0-C versus Type D)

The potential for aquaculture to reduce poverty and control schistosomiasis in Côte d’Ivoire (Ivory Coast) during an era of climate change : a systematic review

This work was supported by the Natural Environment Research Council (NERC) via the Belmont Forum: Climate and Health under grant # NE/T013710/1. CLW and GADL were partially supported by US National Science Foundation (NSF) project ICER-2024383. GADL was also partially supported by NSF DEB—2011179.The development of water management infrastructures, such as dams and canals, are important components of society’s response to feed a growing human population and to fight climate change. Yet, these changes in land use can also increase the transmission risk for waterborne diseases. Transmission risk associated with artificial reservoirs has been extensively documented for schistosomiasis, a parasitic disease of poverty that infects more than 240 million people worldwide. Over 90% of these cases are in sub-Saharan Africa, a region that is being steadily reshaped by climate change. Controlling the parasite’s obligate intermediate host snail is key to reducing transmission of this disease. Using commercial aquaculture to farm marketable species which predate upon these snails in vulnerable regions can have multiple positive effects, including the improved socioeconomic and nutritional health of surrounding communities. Here the authors assessed the viability of using the aquaculture of snail predators to simultaneously control schistosomiasis infection rates while alleviating economic and/or nutritional poverty in endemic regions of sub-Saharan Africa. A PRISMA-based 6-step systematic methodology was used to explore the primary literature using the case study of Côte d’Ivoire and two native species of snail predator to make evidence-based conclusions on the viability of this method for controlling schistosomiasis. This detailed thematic examination of the literature concluded that using specific approaches and species, aquaculture could be effective in reducing economic poverty and chronic malnourishment along with high levels of schistosomiasis infection. More current species-specific aquaculture data and consumer survey data are, however, needed to determine the economic and logistical effectiveness of farming native snail predators in-country. These and other opportunities for future research are highlighted.Publisher PDFPeer reviewe