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Motivation: Many enzymes are not absolutely specific, or even promiscuous: they can catalyze transformations of more compounds than the traditional ones as listed in e.g. KEGG. This information is currently only available in databases, such as the BRENDA enzyme activity database. In this paper, we propose to model enzyme aspecificity by predicting whether an input compound is likely to be transformed by a certain enzyme. Such a predictor has many applications, for example to complete reconstructed metabolic networks, to aid in metabolic engineering or to help identify unknown peaks in mass spectra. Results: We have developed a system for metabolite and reaction inference based on enzyme specificities (MaRIboES). It employs structural and stereochemistry similarity measures and molecular fingerprints to generalise enzymatic reactions based on data available in BRENDA. Leave-one-out cross-validation shows that 80% of known reactions are predicted well. Application to the yeast glycolytic and pentose phosphate pathways predicts a large number of known and new reactions, often leading to the formation of novel compounds, as well as a number of interesting bypasses and cross-links.

Main claims of the literature are that functional recovery of the paretic upper limb is mainly defined within the first month post stroke and that rehabilitation services should preferably be applied intensively and in a task-oriented way within this particular time window. EXplaining PLastICITy after stroke (acronym EXPLICIT-stroke) aims to explore the underlying mechanisms of post stroke upper limb recovery. Two randomized single blinded trials form the core of the programme, investigating the effects of early modified Constraint-Induced Movement Therapy (modified CIMT) and EMG-triggered Neuro-Muscular Stimulation (EMG-NMS) in patients with respectively a favourable or poor probability for recovery of dexterity.

Comparative analysis of metabolic networks in multiple species yields important information on their evolution, and has great practical value in metabolic engineering, human disease analysis, drug design etc. In this work, we aim to systematically search for conserved pathways in two species, quantify their similarities, and focus on the variations between them

This paper proposes a method for rainfall-runoff model calibration and performance analysis in the wavelet-domain by fitting the estimated wavelet-power spectrum (a representation of the time-varying frequency content of a time series) of a simulated discharge series to the one of the corresponding observed time series. As discussed in this paper, calibrating hydrological models so as to reproduce the time-varying frequency content of the observed signal can lead to different results than parameter estimation in the time-domain. Therefore, wavelet-domain parameter estimation has the potential to give new insights into model performance and to reveal model structural deficiencies. We apply the proposed method to synthetic case studies and a real-world discharge modeling case study and discuss how model diagnosis can benefit from an analysis in the wavelet-domain. The results show that for the real-world case study of precipitation – runoff modeling for a high alpine catchment, the calibrated discharge simulation captures the dynamics of the observed time series better than the results obtained through calibration in the time-domain. In addition, the wavelet-domain performance assessment of this case study highlights the frequencies that are not well reproduced by the model, which gives specific indications about how to improve the model structure.

Today, there is a growing interest in network water quality modelling. The water quality issues of interest relate to both dissolved and particulate substances. For dissolved substances the main interest is in residual chlorine and (microbiological) contaminant propagation; for particulate substances it is in sediment leading to discolouration. There is a strong influence of flows and velocities on transport, mixing, production and decay of these substances in the network. This imposes a different approach to demand modelling which is reviewed in this article. For the large diameter lines that comprise the transport portion of a typical municipal pipe system, a skeletonised network model with a top-down approach of demand pattern allocation, a hydraulic time step of 1 h, and a pure advection-reaction water quality model will usually suffice. For the smaller diameter lines that comprise the distribution portion of a municipal pipe system, an all-pipes network model with a bottom-up approach of demand pattern allocation, a hydraulic time step of 1 min or less, and a water quality model that considers dispersion and transients may be needed. Demand models that provide stochastic residential demands per individual home and on a one-second time scale are available. A stochastic demands based network water quality model needs to be developed and validated with field measurements. Such a model will be probabilistic in nature and will offer a new perspective for assessing water quality in the drinking water distribution system.

The flow through a unit of a drinking water treatment plant is one of the most important parameters in terms of a unit's effectiveness. In the present paper, a new EPAnet library is presented with the typical hydraulic elements for drinking water treatment processes well abstraction, rapid sand filtration and cascade and tower aeration. Using this treatment step library, a hydraulic model was set up, calibrated and validated for the drinking water treatment plant Harderbroek. With the actual valve position and pump speeds, the flows were calculated through the several treatment steps. A case shows the use of the model to calculate the new setpoints for the current frequency converters of the effluent pumps during a filter backwash.

A new treatment concept for drinking water production from surface water has been investigated on a pilot scale. The treatment concept consists of fluidized ion exchange (FIEX), ultrafiltration (UF), nanofiltration (NF), and granular activated carbon filtration (GAC). The FIEX process removed calcium and other divalent cations; the UF membrane removed particles and micro-organisms; and the NF membrane and GAC removed natural organic matter (NOM) and micro-pollutants. This study focused on the prevention of fouling of the UF and scaling of the NF and investigated the overall removal of micro-pollutants by the treatment concept. The results of the experiments showed that in 14 days of continuous operation at a flux of 65 l/hm2 the UF performance was stable with the FIEX pre-treated feed water without the aid of a coagulant. The scaling of the NF was also not observed even at 97% recovery. Different micro-pollutants were spiked in the NF feed water and their concentrations in the effluent of NF and GAC were measured. The combination of NF and GAC removed most of the micro pollutants successfully, except for the very polar substances with a molecular weight lower than 100 Daltons.

Based on a detailed experimental investigation in an aspect-ratio-4 rectangular cell in the range 3.7×107≤Ra≤3.7×109, we present evidence of possible scenarios of the long-term dynamics of large-scale circulations (LSC) in bounded large-aspect-ratio turbulent Rayleigh-Bénard convection. Karhunen-Loève analysis of instantaneous velocity fields from long-time particle image velocimetry measurements suggests two different states, but both appear to be produced by a single large-scale flow structure. The measurements provide a three-dimensional picture of LSC in the Γ=4 cell. A modified scaling relation between the LSC peak frequency ωp and Ra is proposed.

The hop plant, Humulus lupulus L., has an exceptionally high content of secondary metabolites, the hop -acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso--acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso--acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso--acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the S. cerevisiae haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso--acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso--acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso--acids and alteration of cell wall structure and, to a lesser extent, active export of iso--acids across the plasma membrane. Furthermore, iso--acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.

Bit interleaved coded modulation (BICM) schemes have been shown to increase the diversity order. This paper studies the extension of such schemes with iterative demodulation and decoding (ID) using error correcting codes coupled with rotated MPSK signal constellations with different symbol mappings and signal space diversity (SSD). Using extrinsic information transfer (EXIT) charts, an analysis of the impact of the rotation angle on the performance of the system is presented. It is shown that for a given signal constellation, labeling, error correcting code and Eb=N0-value, where conventional BICM-ID system’s decoding trajectory gets stuck in a Rayleigh fading channel, SSD with a well considered choice of the rotation angle allows for the convergence of iterative demodulation and decoding. Furthermore, it is shown that the proposed system can lead to a significant performance gain over BICM-ID. The optimal choice of the rotation angle for the coded system is shown to be dependent upon the signal labeling and the error correcting code being employed. Factors (degrees of freedom) that can effect the convergence behavior of the iterative demodulation and decoding of the proposed system are identified and their effect is analyzed.

In anaerobic cultures of wild-type Saccharomyces cerevisiae, glycerol production is essential to reoxidize NADH produced in biosynthetic processes. Consequently, glycerol is a major by-product during anaerobic production of ethanol by S. cerevisiae, the single largest fermentation process in industrial biotechnology. The present study investigates the possibility of completely eliminating glycerol production by engineering S. cerevisiae such that it can reoxidize NADH by the reduction of acetic acid to ethanol via NADH-dependent reactions. Acetic acid is available at significant amounts in lignocellulosic hydrolysates of agricultural residues. Consistent with earlier studies, deletion of the two genes encoding NAD-dependent glycerol-3-phosphate dehydrogenase (GPD1 and GPD2) led to elimination of glycerol production and an inability to grow anaerobically. However, when the E. coli mhpF gene, encoding the acetylating NAD-dependent acetaldehyde dehydrogenase (EC 1.2.1.10; acetaldehyde + NAD+ + coenzyme A acetyl coenzyme A + NADH + H+), was expressed in the gpd1 gpd2 strain, anaerobic growth was restored by supplementation with 2.0 g liter–1 acetic acid. The stoichiometry of acetate consumption and growth was consistent with the complete replacement of glycerol formation by acetate reduction to ethanol as the mechanism for NADH reoxidation. This study provides a proof of principle for the potential of this metabolic engineering strategy to improve ethanol yields, eliminate glycerol production, and partially convert acetate, which is a well-known inhibitor of yeast performance in lignocellulosic hydrolysates, to ethanol. Further research should address the kinetic aspects of acetate reduction and the effect of the elimination of glycerol production on cellular robustness (e.g., osmotolerance).

Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions.

We report on the first implementation of a single-photon avalanche diode (SPAD) in 90nm complementary metal oxide semiconductor (CMOS) technology. The detector features an octagonal multiplication region and a guard ring to prevent premature edge breakdown using a standard mask set exclusively. The proposed structure emerged from a systematic study aimed at miniaturization, while optimizing overall performance. The guard ring design is the result of an extensive modeling effort aimed at constraining the multiplication region within a well-defined area where the electric field exceeds the critical value for impact ionization. The device exhibits a dark count rate of 8.1 kHz, a maximum photon detection probability of 9% and the jitter of 398ps at a wavelength of 637nm, all of them measured at room temperature and 0.13V of excess bias voltage. An afterpulsing probability of 32% is achieved at the nominal dead time. Applications include time-of-flight 3D vision, fluorescence lifetime imaging microscopy, fluorescence correlation spectroscopy, and time-resolved gamma/X-ray imaging. Standard characterization of the SPAD was performed in different bias voltages and temperatures.

Seismic data enable imaging of the Earth, not only of velocity and density but also of attenuation contrasts. Unfortunately, the Born approximation of the constant-density visco-acoustic wave equation, which can serve as a forward modelling operator related to seismic migration, exhibits an ambiguity when attenuation is included. Different scattering models involving velocity and attenuation perturbations may provide nearly identical data. This result was obtained earlier for scatterers that did not contain a correction term for causality. Such a term leads to dispersion when considering a range of frequencies. We demonstrate that with this term, linearized inversion or iterative migration will almost, but not fully, remove the ambiguity. We also investigate if attenuation imaging suffers from the same ambiguity when using non-linear or full waveform inversion. A numerical experiment shows that non-linear inversion with causality convergences to the true model, whereas without causality, a substantial difference with the true model remains even after a very large number of iterations. For both linearized and non-linear inversion, the initial update in a gradient-based optimization scheme that minimizes the difference between modelled and observed data is still affected by the ambiguity and does not provide a good result. This first update corresponds to a classic migration operation. In our numerical experiments, the reconstructed model started to approximate the true model only after a large number of iterations.

The MnCoGe alloy can crystallize in either the hexagonal Ni2In- or the orthorhombic TiNiSi-type of structure. In both phases MnCoGe behaves like a typical ferromagnet with a second-order magnetic phase transition. For MnCoGeBx with B on interstitial positions, we discover a giant magnetocaloric effect associated with a single first-order magnetostructural phase transition, which can be achieved by tuning the magnetic and structural transitions to coincide. The results obtained on the MnCoGe-type alloys may be extensible to other types of magnetic materials undergoing a first-order structural transformation and can open up some possibilities for searching magnetic refrigerants for room-temperature applications

Fifteen essays in 'Architecture as a craft' present a vision of the architectural discipline in which the essence is sought in craft itself. The book is based on the eponymous symposium that the Delft University of Technology held at the Faculty of Architecture from May 13 to June 4, 2009. The texts can be divided into three main groups: 1. this group examines the architect's position; 2. the second group looks at architectural composition and the resources that architects use to produce a design, such as models and drawings; 3. the last group discusses the meaning of materialisation in architectural thinking.

This chapter discusses the theory of fracture mechanics based on the flat elliptical crack; the derivation of the mixed "mode I - II" - interaction equation, with the relations between the mode I and mode II stress intensities and energy release rates, based on an orthotropic-isotropic transformation of the Airy stress function; the derivation of the softening curve with the explanation of the measurements; the derivation of the power law; the energy method of notched beams and of joints loaded perpendicular to the grain; and the necessary rejection of the applied crack growth models and fictitious crack models

Background: Hip fracture patients often have an impaired nutritional status at the time of fracture, which can result in a higher complication rate, prolonged rehabilitation time and increased mortality. A study was designed to evaluate the effect of nutritional intervention on nutritional status, functional status, total length of stay, postoperative complications and cost-effectiveness. Methods: Open-labelled, multi-centre, randomized controlled trial in hip fracture patients aged 55 years and above. The intervention group receives dietetic counselling (by regular home visits and telephone calls) and oral nutritional supplementation for three months after surgery. The control group receives usual dietetic care as provided by the hospital. Outcome assessment is performed at three and six months after hip fracture. Discussion: Patient recruitment has started in July 2007 and has ended in December 2009. First results are expected in 2011. Trial registration: ClinicalTrials.gov NCT00523575