123 research outputs found

    Methodology for evaluating the safety level of current accepted design solutions for limiting fire spread between buildings

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    External fire spread between buildings is internationally considered as a major concern for buildings in dense urban environments. While design guidelines differ between countries, the fundamental methods currently used for limiting the risk of fire spread between buildings are generally limited to specifying the minimum required separation distance for a given unprotected façade area, or conversely, limiting the maximum allowable unprotected façade area for a given separation distance. The safety level associated with the current design guidelines is however unknown, making the implementation of innovative, safer and more cost-effective design solutions difficult. In order to assess the safety target implicitly incorporated in currently accepted design solutions, a methodology is developed for evaluating the annual probability of reaching unacceptable radiation intensities at the opposite façade. As a case study, the methodology is applied to a design which is in agreement with the current UK requirements specified in BR 187. This case study exposes inconsistencies in the current design guidelines, indicating the need for developing explicit safety targets

    A pathway-driven predictive model of tramadol pharmacogenetics

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    Predicting metabolizer phenotype (MP) is typically performed using data from a single gene. Cytochrome p450 family 2 subfamily D polypeptide 6 (CYP2D6) is considered the primary gene for predicting MP in reference to approximately 30% of marketed drugs and endogenous toxins. CYP2D6 predictions have proven clinically effective but also have well-documented inaccuracies due to relatively high genotype-phenotype discordance in certain populations. Herein, a pathway-driven predictive model employs genetic data from uridine diphosphate glucuronosyltransferase, family 1, polypeptide B7 (UGT2B7), adenosine triphosphate (ATP)-binding cassette, subfamily B, number 1 (ABCB1), opioid receptor mu 1 (OPRM1), and catechol-O-methyltransferase (COMT) to predict the tramadol to primary metabolite ratio (T:M1) and the resulting toxicologically inferred MP (t-MP). These data were then combined with CYP2D6 data to evaluate performance of a fully combinatorial model relative to CYP2D6 alone. These data identify UGT2B7 as a potentially significant explanatory marker for T:M1 variability in a population of tramadol-exposed individuals of Finnish ancestry. Supervised machine learning and feature selection were used to demonstrate that a set of 16 loci from 5 genes can predict t-MP with over 90% accuracy, depending on t-MP category and algorithm, which was significantly greater than predictions made by CYP2D6 alone.Peer reviewe

    Effect of site of lactate infusion on regional lactate exchange in pigs

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    Background The rate of extra-hepatic lactate production and the route of influx of lactate to the liver may influence both hepatic and extra-hepatic lactate exchange. We assessed the dose-response of hepatic and extra-hepatic lactate exchange during portal and central venous lactate infusion. Methods Eighteen pigs randomly received either portal (n=5) or central venous (n=7) lactate infusion or saline (n=6). Sodium lactate was infused at 33, 66, 99, and 133 µmol kg−1 min−1 for 20 min each. Systemic and regional abdominal blood flows and plasma lactate were measured at 20 min intervals until 1 h post-infusion, and regional lactate exchange was calculated (area under lactate uptake-time curve). Results Total hepatic lactate uptake [median (95% confidence interval)] during the experimental protocol (140 min) was higher during portal [8198 (5487-12 798) µmol kg−1] than during central venous lactate infusion [4530 (3903-5514) µmol kg−1, P<0.05]. At a similar hepatic lactate delivery (∼400 µmol kg−1 min−1), hepatic lactate uptake [mean and standard deviation (sd)] was higher during portal [118 (sd 55) µmol kg−1 min−1] than during central venous lactate infusion [44 (12) µmol kg−1 min−1, P<0.05]. Time courses of arterial lactate concentrations and lactate uptake at other measured regions were similar in both groups. Conclusions Higher hepatic lactate uptake during portal compared with central venous lactate infusion at a similar total hepatic lactate influx underlines the role of portal vein lactate concentration in total hepatic lactate uptake capacity. Arterial lactate concentration does not depend on the site of lactate infusion. At higher arterial lactate concentrations, all regions participated in lactate uptak

    Evolutionary conservation and post-translational control of S-adenosyl-L-homocysteine hydrolase in land plants

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    Trans-methylation reactions are intrinsic to cellular metabolism in all living organisms. In land plants, a range of substrate-specific methyltransferases catalyze the methylation of DNA, RNA, proteins, cell wall components and numerous species-specific metabolites, thereby providing means for growth and acclimation in various terrestrial habitats. Trans-methylation reactions consume vast amounts of S-adenosyl-L-methionine (SAM) as a methyl donor in several cellular compartments. The inhibitory reaction by-product, S-adenosyl-L-homocysteine (SAH), is continuously removed by SAH hydrolase (SAHH), which essentially maintains trans-methylation reactions in all living cells. Here we report on the evolutionary conservation and post-translational control of SAHH in land plants. We provide evidence suggesting that SAHH forms oligomeric protein complexes in phylogenetically divergent land plants and that the predominant protein complex is composed by a tetramer of the enzyme. Analysis of light-stress-induced adjustments of SAHH inArabidopsis thalianaandPhyscomitrella patensfurther suggests that regulatory actions may take place on the levels of protein complex formation and phosphorylation of this metabolically central enzyme. Collectively, these data suggest that plant adaptation to terrestrial environments involved evolution of regulatory mechanisms that adjust the trans-methylation machinery in response to environmental cues

    The influence of learner characteristics on degree and type of participation in a CSCL environment

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    Computer-Supported Collaborative Learning (CSCL) is often presented as a promising learning method. However, it is also facing some new challenges. Apart from answering the question of whether or not working with CSCL generates satisfying learning outcomes, it is important to determine whether or not all participants profit from collaboration, with the computer as a means of communication. This paper describes the implementation and effects of an experimental program in 5 classes with a total of 120 students in elementary education who, in groups of four, engaged in Knowledge Forum discussion tasks on the subject of healthy eating. The study explores whether or not differences occur in the participation of students who differ in gender, sociocultural background and ability, and whether or not computer skills, computer attitudes, comprehensive reading scores and popularity with classmates are related to student participation. Students’ participation in this CSCL environment appears to be dependent on a number of learner characteristics. Girls contribute more words to the discussions than boys do and are more dependent on their computer skills in this production. Students who are good at comprehensive reading also contribute more words. Popularity among classmates appears to influence the degree of participation further. We also found indications that students with immigrant parents write fewer contributions than those whose parents are not immigrants

    Recombinant family 3 carbohydrate-binding module as a new additive for enhanced enzymatic saccharification of whole slurry from autohydrolyzed eucalyptus globulus wood

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    By-products resulting from lignocellulosics pretreatment affect the digestibility of resulting whole slurries, but this can be minimized by additives supplementation. In this work, a family 3 carbohydrate-binding module (CBM3), recombinantly produced from Escherichia coli, was used as additive in the enzymatic hydrolysis of the whole slurry from autohydrolyzed Eucalyptus globulus wood (EGW). At the higher dosage used (30 mg/gsolids), CBM3 led to an increase in glucose yield from 75 to 89%. A similar result was obtained for bovine serum albumin (BSA) (11% increase), which has a well-documented additive effect. CBM3 had no effect on the non-productive binding of enzymes, since it could not bind to EGW lignin, while it rapidly bound to cellulose, as shown by fluorescence microscopy. CBM3 is a valid additive for enhanced lignocellulosic saccharification and a valuable alternative to costly additives (e.g. polyethylene glycol) as it can be affordably produced from heterologous bacterium, thus contributing to more cost-efficient biomass valorization bioprocesses.This work was developed under the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte. The research leading to the reported results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the project MultiBiorefinery (POCI-01–0145-FEDER-016403) and through grants to C. Oliveira (SFRH/BPD/110640/2015) and D. Gomes (SFRH/BD/88623/2012).info:eu-repo/semantics/publishedVersio

    Assessing the potential for sea-based macroalgae cultivation and its application for nutrient removal in the Baltic Sea

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    Marine eutrophication is a pervasive and growing threat to global sustainability. Macroalgal cultivation is a promising circular economy solution to achieve nutrient reduction and food security. However, the location of production hotspots is not well known. In this paper the production potential of macroalgae of high commercial value was predicted across the Baltic Sea region. In addition, the nutrient limitation within and adjacent to macroalgal farms was investigated to suggest optimal site-specific configuration of farms. The production potential of Saccharina latissima was largely driven by salinity and the highest production yields are expected in the westernmost Baltic Sea areas where salinity is >23. The direct and interactive effects of light availability, temperature, salinity and nutrient concentrations regulated the predicted changes in the production of Ulva intestinalis and Fucus vesiculosus. The western and southern Baltic Sea exhibited the highest farming potential for these species, with promising areas also in the eastern Baltic Sea. Macroalgal farming did not induce significant nutrient limitation. The expected spatial propagation of nutrient limitation caused by macroalgal farming was less than 100–250 m. Higher propagation distances were found in areas of low nutrient and low water exchange (e.g. offshore areas in the Baltic Proper) and smaller distances in areas of high nutrient and high water exchange (e.g. western Baltic Sea and Gulf of Riga). The generated maps provide the most sought-after input to support blue growth initiatives that foster the sustainable development of macroalgal cultivation and reduction of in situ nutrient loads in the Baltic Sea.</p
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