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A flexible Integrated Bayesian Multi-model Uncertainty Estimation Framework (IBMUEF) is presented to simultaneously quantify conceptual model structure, input and parameter uncertainty of a groundwater flow model. In this fully Bayesian framework, the DiffeRential Evolution Adaptive Metropolis (DREAM) algorithm with a novel likelihood function is combined with Bayesian Model Averaging (BMA). Four alternative conceptual models, representing different geological representations of an overexploited aquifer, have been developed. The uncertainty of the input of the model is represented by multipliers. A novel likelihood function based on a new heteroscedastic error model is included to extend the applicability of the framework. The results of the study confirm that neglecting conceptual model structure uncertainty results in unreliable prediction. Consideration of both model structure and input uncertainty are important to obtain confident parameter sets and better model predictions. This study shows that the IBMUEF provides more reliable model predictions and accurate uncertainty bounds. • Full Bayesian multi-model approach to quantify uncertainty of MODFLOW model. • Simultaneously quantifies model structure, input and parameter uncertainty. • DREAM with a novel likelihood function is combined with BMA. • Neglecting conceptual model uncertainty results in unreliable prediction. • Results in more reliable model predictions and accurate uncertainty bounds. [ABSTRACT FROM AUTHOR]

This article presents a low-rank decomposition algorithm based on subsampling of matrix entries. The proposed algorithm first computes rank-revealing decompositions of submatrices with a blocked adaptive cross approximation (BACA) algorithm, and then applies a hierarchical merge operation via truncated singular value decompositions (H-BACA). The proposed algorithm significantly improves the convergence of the baseline ACA algorithm and achieves reduced computational complexity compared to the traditional decompositions such as rank-revealing QR. Numerical results demonstrate the efficiency, accuracy, and parallel scalability of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Sparse solvers provide essential functionality for a wide variety of scientific applications. Highly parallel sparse solvers are essential for continuing advances in high-fidelity, multi-physics and multiscale simulations, especially as we target exascale platforms. This paper describes the challenges, strategies and progress of the US Department of Energy Exascale Computing project towards providing sparse solvers for exascale computing platforms. We address the demands of systems with thousands of high-performance node devices where exposing concurrency, hiding latency and creating alternative algorithms become essential. The efforts described here are works in progress, highlighting current success and upcoming challenges. [ABSTRACT FROM AUTHOR]

It is still unclear which outcome measures should be used in future clinical trials of adult patients with Becker Muscular Dystrophy (BMD) because of the paucity of studies and its heterogeneous progression. We evaluated a wide range of clinical and magnetic resonance imaging (MRI) outcome measures in 21 adults with BMD and 21 age- and sex-matched controls at baseline and after 9 and 18 months of follow-up. We used 6-point Dixon imaging with semi-automated 3D muscle segmentation to measure proton density fat fraction (PDFF) in all entire leg muscles (n=17 in thighs, n=10 in lower legs). In patients, PDFF increased significantly over 9 months in 14/17 thigh muscles, with a mean overall increase of 1.3±1.1% (p<0.001). This increase was significantly higher than that in controls (p=0.018), who increased 0.6±0.6% (p<0.001). Data of 18-months follow-up and lower leg PDFF are currently still under analysis. The north star ambulatory assessment (NSAA; -1.3 points, p=0.013), 32-point motor function measurement (MFM-32; -1.3%, p=0.017) and activity limitations scale (ActivLim; -0.3 logits, p=0.018) deteriorated significantly over 9 months. In the subgroup of patients with abnormal thigh muscle MRI findings, Biodex® isometric dynamometry measurement of peak torque decreased significantly in the quadriceps muscle group (-2.64 Nm, p=0.030), but not in the hamstrings. In all patients, the six-minute walk distance, 10-meter walk test, time to rise from floor test, time to climb 4 stairs test, timed up and go test, and Medical Research Council sum scores (150 and 60-points) did not change significantly over 9 months. All clinical outcome measures correlated strongly to total thigh PDFF at baseline. We conclude that analyzing PDFF in entire thigh muscles is a highly sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, even after 9 months of follow-up. The NSAA, MFM-32 and ActivLim could also be used as outcome measures in future clinical trials. [ABSTRACT FROM AUTHOR]

This study outlines the effect of citric acid leaching on the quality and stability of fast pyrolysis bio-oils from sugarcane bagasse (SCB) and sugarcane trash (SCT). The quality of bio-oil was probed by GC-MS analysis, elemental composition, higher heating value, water and solids content, pH, dynamic viscosity and stability (ageing). Pyrolysis was performed at 500 °C in a fully controlled, continuously operated plant with a biomass throughput of ca. 300 g.hr−1. While citric acid leaching causes a decrease of the average bio-oil yield with 5%, it does not lead to a bio-oil with improved fuel-related properties. However, the bio-oil composition became more advantageous in light of its biorefining. Indeed, citric acid leaching led to an increased levoglucosan concentration – a promising platform chemical – of 17% for SCB and of to 35% for SCT (based on relative abundance in GC-MS). In tandem, the concentration of carboxylic acids and phenols in the bio-oil decreased after citric acid leaching, which is beneficial for downstream purification of levoglucosan. Regarding the non-condensable gases, CO and CO 2 represented between 88% and 91% by weight of the total non-condensable gases produced in pyrolysis. Therefore, the results of this study demonstrate that optimized biomass demineralization pretreatment with citric acid could produce bio-oil at high yield and rich in high-value chemical compounds like levoglucosan. Biomass demineralization pretreatment however, does not result in bio-oil with improved quality for fuel purposes, nor does it necessarily lead to bio-oil having higher stability. • Mild pretreatment with CA is effective in ash removal in sugarcane residues. • CA pretreated feedstock has higher bio-oil yields on pretreated feedstock basis. • Fresh/aged trash derived bio-oils have lower viscosity than bagasse derived bio-oils. • CA pretreatment holds no major benefit for bio-oil composition in terms of fuel use. • Major increase in anhydrosugar content after mild CA pretreatment of sugarcane residues. [ABSTRACT FROM AUTHOR]

Over recent years, pyrolysis has grown into a mature technology with added value for producing soil improvers. Further innovations of this technology lie in developing tailor-made products from specific feedstocks (or mixtures thereof) in combination with adjusted mixing ratio-temperature regimes. In this context, co-pyrolysis of pig manure (PM) and the invasive plant Japanese knotweed (JK) at different mixture ratios (w/w) of 3:1 (P3J1), 1:1 (P1J1), and 1:3 (P1J3) and varying temperatures (400–700 °C) was studied to address the low carbon properties and heavy metals (HMs) risks of manure-derive biochars and beneficially ameliorate the bio-invasion situation by creating value from the plant biomass. Co-pyrolysis of PM with JK increased by nearly 1.5 folds the fixed carbon contents in the combined feedstock biochars obtained at 600 °C compared with PM-derived biochar alone, and all combined feedstock biochars met the requirements for soil improvement and carbon sequestration. The total HMs in PM biochars were significantly reduced by adding JK. The combined feedstock biochar P1J1 generated at 600 °C was the most effective in transforming Cu and Zn into more stable forms, accordingly reducing the associated environmental risk of heavy metal leaching from the biochar. In addition, the accumulation of macronutrients can be an added benefit of the co-pyrolysis process, and P1J1-600 was also the biochar that retained the most nutrients (P, Ca, Mg, and K). [Display omitted] • Japanese knotweed addition improved the aromaticity of pig manure-derived biochar. • Co-pyrolysis reduced total Cu and Zn compared to pig manure-derived biochar. • Cu and Zn transformed to stable forms reduce the environmental risk of the biochar. • Co-pyrolysis retained higher nutrients than Japanese knotweed-derived biochar alone. • A 1:1 ratio of pig manure to Japanese knotweed at 600 °C was the optimal condition. [ABSTRACT FROM AUTHOR]

Drug discovery is usually focused on a single protein target; in this process, existing compounds that bind to related proteins are often ignored. We describe ProBiS plugin, extension of our earlier ProBiS-ligands approach, which for a given protein structure allows prediction of its binding sites and, for each binding site, the ligands from similar binding sites in the Protein Data Bank. We developed a new database of precalculated binding site comparisons of about 290000 proteins to allow fast prediction of binding sites in existing proteins. The plugin enables advanced viewing of predicted binding sites, ligands' poses, and their interactions in three-dimensional graphics. Using the InhA query protein, an enoyl reductase enzyme in the Mycobacterium tuberculosis fatty acid biosynthesis pathway, we predicted its possible ligands and assessed their inhibitory activity experimentally. This resulted in three previously unrecognized inhibitors with novel scaffolds, demonstrating the plugin's utility in the early drug discovery process. [ABSTRACT FROM AUTHOR]

Limb-Girdle Muscular Dystrophy autosomal recessive type 12 (LGMDR12) is a rare hereditary muscle disease for which outcome measures are lacking. We evaluated intramuscular fat fraction as an outcome measure to track disease progression, to determine if this could be useful in future clinical trials to evaluate potential therapies. We prospectively performed a 6-point Dixon MRI of the thighs in 24 genetically confirmed, adult LGMDR12 patients and 24 age- and sex-matched healthy controls at baseline and after 1 and 2 years. The most affected muscles were the semimembranosus, biceps femoris long head and adductor magnus, respectively, and there was generally an increase in proton density fat fraction (PDFF) with increasing age and disease duration. Patients with intermediate stage thigh muscle fat replacement at baseline (PDFF 20-70%) already showed a significant increase in PDFF in 8/14 evaluated thigh muscles after one year. The standardized response mean (SRM) demonstrated a high responsiveness to change in PDFF for 6 individual muscles over 2 years in this group. We also found that tracking PDFF changes in individual muscles over time was more sensitive than PDFF measurements in muscle groups as a whole. In patients with early (<20%) or end stage (>70%) muscle fat replacement, or in the control group, PDFF did not increase significantly over two years of follow-up. Finally, we observed a moderately strong correlation between total thigh PDFF and the following clinical outcome measures at baseline: six-minute walk distance (6MWD), 10-meter walk test (10MWT), Medical Research Council (MRC) sum scores and Biodex® isometric dynamometry. We conclude that thigh muscle PDFF imaging is a sensitive outcome measure to track progressive muscle fat replacement in selected LGMDR12 patients even after one year of follow-up and should be included as an outcome measure in future clinical trials. [ABSTRACT FROM AUTHOR]

The free energy surface of zeolite ‐ catalyzed reactions at real operating conditions is typically complex. As such, techniques that allow sampling of larger portions of the potential and free energy landscape are required to mimic experimental conditions as closely as possible. Various points on the free energy surface can be connected by a multitude of reaction paths. Mapping the free energy surface by advanced molecular dynamics simulations of a zeolite ‐ catalyzed reaction can hence be compared with studying a map in an atlas to discover the possible means of transport to travel between two cities. For the complete story see the Full Paper on page 9385 by B. Ensing, V. Van Speybroeck et al. [ABSTRACT FROM AUTHOR]

Abstract: In Chlamydomonas reinhardtii, prolonged anaerobiosis leads to the expression of enzymes belonging to various fermentative pathways. Among them, oxygen-sensitive hydrogenases (HydA1/2) catalyze the synthesis of molecular hydrogen from protons and reduced ferredoxin in the stroma. In this work, by analyzing wild type and mutants affected in H2 production, we show that maximal PSII photosynthetic electron transfer during the first seconds of illumination after a prolonged dark-anaerobiosis period is linearly related to hydrogenase capacity. Based on the specific chlorophyll fluorescence induction kinetics typical of hydrogenase-deficient mutants, we set up an in vivo fluorescence imaging screening protocol allowing to isolate mutants impaired in hydrogenase expression or activity, as well as mutants altered in related metabolic pathways required for energy production in anaerobiosis. Compared to previously described screens for mutants impaired in H2 production, our screening method is remarkably fast, sensitive and non-invasive. Out of 3000 clones from a small-sized insertional mutant library, five mutants were isolated and the most affected one was analyzed and shown to be defective for the hydrogenase HydG assembly factor. [Copyright &y& Elsevier]

Images of the morphology of a polygonal network of ice-wedge casts are a valuable aid to paleoclimatological reconstructions. Usually such images are obtained by aerial photography showing polygonal crop marks reflecting textural differences between wedge filling and host material. Our objective was to investigate an alternative method by measuring the soil apparent electrical conductivity, (ECa) with an electromagnetic induction (EMI) sensor. Based on an aerial photograph showing polygonal crop marks in an agricultural field in Belgium. a test area of 0.63 ha was selected. A small part of the test area (6 by 6 m) was excavated revealing a clear pattern of ice-wedge casts. The wedges penetrated clay-rich Tertiary marine sediments, covered by a 0.6-m layer of eolian sandy sediments, and were associated with the permafrost during the last glacial period. We took 94 subsoil (0.6-0.8 m) samples distributed over the test area and analyzed their texture. The results showed a clear difference between the Eocene host material (on average 21% clay) and the Quaternary wedge filling (on average 6% clay). The test area was surveyed with an EMI sensor (we used an EM38DD) which resulted in an accurate image of the polygonal network. We concluded that an EMI survey is an appropriate technique to image the morphology of a polygonal network of subsoil ice-wedge casts. A final perspective comprises the strong heterogeneity of the subsoil, since nearly half of the subsoil consists of ice-wedge material. This might open perspectives for precision agriculture in such landscapes. [ABSTRACT FROM AUTHOR]

Methylations of ethene, propene, and butene by methanol over the acidic microporous H-ZSM-5 catalyst are studied by means of state of the art computational techniques, to derive Arrhenius plots and rate constants from first principles that can directly be compared with the experimental data. For these key elementary reactions in the methanol to hydrocarbons (MTH) process, direct kinetic data became available only recently [1. Catal. 2005, 224, 115-123; J. Catal. 2005, 234, 385-400]. At 350 °C, apparent activation energies of 103, 69, and 45 kJ/mol and rate constants of 2.6 x 10-2, 4.5 x 10, and 1.3 x 10 mol/(g h mbar) for ethene, propene, and butene were derived, giving following relative ratios for methylation kethene/kpropene/kbutene = 1:17:50. In this work, rate constants including pre- exponential factors are calculated which give very good agreement with the experimental data: apparent activation energies of 94, 62, and 37 kJ/mol for ethene, propene, and butene are found, and relative ratios of methylation ketl)ene/kpropene/kbutenc = 1:23:763. The entropies of gas phase alkenes are underestimated in the harmonic oscillator approximation due to the occurrence of internal rotations. These low vibrational modes were substituted by manually constructed partition functions. Overall, the absolute reaction rates can be calculated with near chemical accuracy, and qualitative trends are very well reproduced. In addition, the proposed scheme is computationally very efficient and constitutes significant progress in kinetic modeling of reactions in heterogeneous catalysis. [ABSTRACT FROM AUTHOR]

In photosynthetic eukaryotes, nonphotochemical plastoquinone (PQ) reduction is important for the regulation of photosynthetic electron flow. In green microalgae where this process has been demonstrated, the chloroplastic enzyme that catalyses nonphotochemical PQ reduction has not been identified yet. Here, we show by an RNA interference (RNAi) approach that the NDA2 gene, belonging to a type II NAD(P)H dehydrogenases family in the green microalga Chlamydomonas reinhardtii, encodes a chloroplastic dehydrogenase that functions to reduce PQ nonphotochemically in this alga. Using a specific antibody, we show that the Nda2 protein is localized in chloroplasts of wild-type cells and is absent in two Nda2-RNAi cell lines. In both mutant cell lines, nonphotochemical PQ reduction is severely affected, as indicated by altered chlorophyll fluorescence transients after saturating illumination. Compared with wild type, change in light excitation distribution between photosystems ('state transition') upon inhibition of mitochondrial electron transport is strongly impaired in transformed cells because of inefficient PQ reduction. Furthermore, the amount of hydrogen produced by Nda2-RNAi cells under sulfur deprivation is substantially decreased compared with wild type, which supports previous assumptions that endogenous substrates serve as source of electrons for hydrogen formation. These results demonstrate the importance of Nda2 for nonphotochemical PQ reduction and associated processes in C. reinhardtii. [ABSTRACT FROM AUTHOR]

Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature. [ABSTRACT FROM AUTHOR]

Summary Bacteria can have population structures ranging from the fully sexual to the highly clonal. Despite numerous studies, the population structure of Pseudomonas aeruginosa is still somewhat contentious. We used a polyphasic approach in order to shed new light on this issue. A data set consisting of three outer membrane (lipo)protein gene sequences (oprI , oprL and oprD ), a DNA-based fingerprint (amplified fragment length polymorphism), serotype and pyoverdine type of 73 P. aeruginosa clinical and environmental isolates, collected across the world, was analysed using biological data analysis software. We observed a clear mosaicism in the results, non-congruence between results of different typing methods and a microscale mosaic structure in the oprD gene. Hence, in this network, we also observed some clonal complexes characterized by an almost identical data set. The most recent clones exhibited serotypes O1, 6, 11 and 12. No obvious correlation was observed between these dominant clones and habitat or, with the exception of some recent clones, geographical origin. Our results are consistent with, and even clarify, some seemingly contradictory results in earlier epidemiological studies. Therefore, we suggest an epidemic population structure for P. aeruginosa , comparable with that of Neisseria meningitidis , a superficially clonal structure with frequent recombinations, in which occasionally highly successful epidemic clones arise. [ABSTRACT FROM AUTHOR]