Growing Graphs with Hyperedge Replacement Graph Grammars

Discovering the underlying structures present in large real world graphs is a fundamental scientific problem. In this paper we show that a graph's clique tree can be used to extract a hyperedge replacement grammar. If we store an ordering from the extraction process, the extracted graph grammar is guaranteed to generate an isomorphic copy of the original graph. Or, a stochastic application of the graph grammar rules can be used to quickly create random graphs. In experiments on large real world networks, we show that random graphs, generated from extracted graph grammars, exhibit a wide range of properties that are very similar to the original graphs. In addition to graph properties like degree or eigenvector centrality, what a graph "looks like" ultimately depends on small details in local graph substructures that are difficult to define at a global level. We show that our generative graph model is able to preserve these local substructures when generating new graphs and performs well on new and difficult tests of model robustness.Comment: 18 pages, 19 figures, accepted to CIKM 2016 in Indianapolis, I

Building Information Modelling (BIM) value realisation framework for asset owners

The paper is presenting a value realisation framework for asset owners based on an exploratory study. The study is descriptive in nature and adopting a qualitative approach towards data collection. The paper adopts the viewpoint of BIM business value measurement considering that; (i) if the process is better as a result of BIM-based processes, then it is different in some relevant way; (ii) if it is different in some relevant way as a result of certain BIM properties or characteristics, then the change is observable; (iii) if the change is observ-able because of certain direct BIM benefits, then it is countable; (iv) if it is countable using defined measurement metrics, then it is measurable; (v) if it is measurable using established measurement techniques, an organisation can value each unit and therefore, realise the benefits of BIM. The specific contribution of paper is to improve asset owners’ understanding of BIM-business value measurement techniques and approaches

Improving lipid recovery from Scenedesmus wet biomass by surfactant-assisted disruption

Citation: Lai, Y. S., De Francesco, F., Aguinaga, A., Parameswaran, P., & Rittmann, B. E. (2016). Improving lipid recovery from Scenedesmus wet biomass by surfactant-assisted disruption. Green Chemistry, 18(5), 1319-1326. doi:10.1039/c5gc02159fMicroalgae-derived lipids are good sources of biofuel, but extracting them involves high cost, energy expenditure, and environmental risk. Surfactant treatment to disrupt Scenedesmus biomass was evaluated as a means to make solvent extraction more efficient. Surfactant treatment increased the recovery of fatty acid methyl ester (FAME) by as much as 16-fold vs. untreated biomass using isopropanol extraction, and nearly 100% FAME recovery was possible without any Folch solvent, which is toxic and expensive. Surfactant treatment caused cell disruption and morphological changes to the cell membrane, as documented by transmission electron microscopy and flow cytometry. Surfactant treatment made it possible to extract wet biomass at room temperature, which avoids the expense and energy cost associated with heating and drying of biomass during the extraction process. The best FAME recovery was obtained from high-lipid biomass treated with Myristyltrimethylammonium bromide (MTAB)- and 3-(decyldimethylammonio)-propanesulfonate inner salt (3_DAPS)-surfactants using a mixed solvent (hexane : isopropanol = 1 : 1, v/v) vortexed for just 1 min; this was as much as 160-fold higher than untreated biomass. The critical micelle concentration of the surfactants played a major role in dictating extraction performance, but the growth stage of the biomass had an even larger impact on how well the surfactants disrupted the cells and improved lipid extraction. Surfactant treatment had minimal impact on extracted-FAME profiles and, consequently, fuel-feedstock quality. This work shows that surfactant treatment is a promising strategy for more efficient, sustainable, and economical extraction of fuel feedstock from microalgae

D. Andrés Piquer, su vida y sus escritos : discurso

Copia Digital. España : Ministerio de Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2022- L

Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs.

OBJECTIVES: Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. METHODS: The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. RESULTS: All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. CONCLUSIONS: TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes

Currently, biased agonism is at the center stage of drug development approaches. We analyzed effects of a battery of cannabinoids plus/minus cannabidiol (CBD) in four functional parameters (cAMP levels, phosphorylation of extracellular signal–regulated kinases (ERK1/2), β-arrestin recruitment and label-free/DMR) in HEK-293T cells expressing cannabinoid receptors, CB or CB, or CB-CB heteroreceptor complexes. In all cases two natural agonists plus two selective synthetic agonists were used. Furthermore, the effect of cannabidiol, at a dose (100 nM) that does not allow significant binding to the orthosteric center of either receptor, was measured. From the huge amount of generated data, we would like to highlight that the two psychotropic molecules (Δ-tetrahydrocannabinol/THC and CP-55940) showed similar bias in CBR and that the bias of THC was particularly relevant toward MAPK pathway. Furthermore, THC did not activate the G protein coupled to CBR. Interestingly, the biased agonism was reduced when assays were performed in cells expressing the two receptors, thus suggesting that the heteromer allows less functional selectivity. In terms of cannabidiol action, the phytocannabinoid altered the functional responses, likely by allosteric means, and modified potency, agonist IC/EC values and biased agonism in qualitative and/or quantitative different ways depending on the agonist. The effect of cannabidiol on anandamide actions on both cannabinoid receptors was particularly noteworthy as was significantly different from that of other compounds. Results are a compendium of data on biased agonism on cannabinoid receptors in the absence and presence of cannabidiol. In addition, for the first time, GPCR biased agonism is characterized in an heteromeric context.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (Ref. no. BFU2015-64405-R and SAF2017-84117-R; they may include FEDER funds) and by grant 201413-30 from: Fundació la Marató de TV3Peer Reviewe

Acute Toxicity and Determination of the Active Constituents of Aqueous Extract of Uncaria tomentosa

Uncaria tomentosa is a medicinal plant used in folk medicine by Amazon tribes. In this study the constituents of aqueous extract of U. tomentosa bark were quantified by chromatographic technique and its lethal concentration 50 (48 h) in Hyphessobrycon eques was determined. The chromatography showed high levels of oxindole alkaloids, quinovic acid glycosides, and low molecular weight polyphenols. The CL50 48 h was 1816 mg/L. Fish showed behavior changes at concentrations above 2000 mg/L, accompanied by a significant decrease of dissolved oxygen. At the highest concentration 100% mortality was observed attributed to oxygen reduction by the amount of oxindole alkaloids, polyphenols accumulation of the extract in the gills, and the interaction of these compounds with dopamine. In conclusion, the aqueous extract of U. tomentosa did not alter the chemical components and it was shown that U. tomentosa has low toxicity to H. eques; therefore, it can be used safely in this species