Showing papers by "Technical University of Denmark published in 2004"

Bioconductor: open software development for computational biology and bioinformatics

Abstract: The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.

Origin of the Overpotential for Oxygen Reduction at a Fuel-Cell Cathode

Abstract: We present a method for calculating the stability of reaction intermediates of electrochemical processes on the basis of electronic structure calculations. We used that method in combination with detailed density functional calculations to develop a detailed description of the free-energy landscape of the electrochemical oxygen reduction reaction over Pt(111) as a function of applied bias. This allowed us to identify the origin of the overpotential found for this reaction. Adsorbed oxygen and hydroxyl are found to be very stable intermediates at potentials close to equilibrium, and the calculated rate constant for the activated proton/electron transfer to adsorbed oxygen or hydroxyl can account quantitatively for the observed kinetics. On the basis of a database of calculated oxygen and hydroxyl adsorption energies, the trends in the oxygen reduction rate for a large number of different transition and noble metals can be accounted for. Alternative reaction mechanisms involving proton/electron transfer to ...

affy---analysis of Affymetrix GeneChip data at the probe level

Abstract: Motivation: The processing of the Affymetrix GeneChip data has been a recent focus for data analysts. Alternatives to the original procedure have been proposed and some of these new methods are widely used. Results: The affy package is an R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix. The package is currently in its second release, affy provides the user with extreme flexibility when carrying out an analysis and make it possible to access and manipulate probe intensity data. In this paper, we present the main classes and functions in the package and demonstrate how they can be used to process probe-level data. We also demonstrate the importance of probe-level analysis when using the Affymetrix GeneChip platform.

Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.

Abstract: Post-translational modifications (PTMs) occur on almost all proteins analyzed to date. The function of a modified protein is often strongly affected by these modifications and therefore increased knowledge about the potential PTMs of a target protein may increase our understanding of the molecular processes in which it takes part. High-throughput methods for the identification of PTMs are being developed, in particular within the fields of proteomics and mass spectrometry. However, these methods are still in their early stages, and it is indeed advantageous to cut down on the number of experimental steps by integrating computational approaches into the validation procedures. Many advanced methods for the prediction of PTMs exist and many are made publicly available. We describe our experiences with the development of prediction methods for phosphorylation and glycosylation sites and the development of PTM-specific databases. In addition, we discuss novel ideas for PTM visualization (exemplified by kinase landscapes) and improvements for prediction specificity (by using ESS--evolutionary stable sites). As an example, we present a new method for kinase-specific prediction of phosphorylation sites, NetPhosK, which extends our earlier and more general tool, NetPhos. The new server, NetPhosK, is made publicly available at the URL http://www.cbs.dtu.dk/services/NetPhosK/. The issues of underestimation, over-prediction and strategies for improving prediction specificity are also discussed.

Atomic-scale imaging of carbon nanofibre growth

Abstract: The synthesis of carbon nanotubes with predefined structure and functionality plays a central role in the field of nanotechnology1,2, whereas the inhibition of carbon growth is needed to prevent a breakdown of industrial catalysts for hydrogen and synthesis gas production3. The growth of carbon nanotubes and nanofibres has therefore been widely studied4,5,6,7,8,9,10. Recent advances in in situ techniques now open up the possibility of studying gas–solid interactions at the atomic level11,12. Here we present time-resolved, high-resolution in situ transmission electron microscope observations of the formation of carbon nanofibres from methane decomposition over supported nickel nanocrystals. Carbon nanofibres are observed to develop through a reaction-induced reshaping of the nickel nanocrystals. Specifically, the nucleation and growth of graphene layers are found to be assisted by a dynamic formation and restructuring of mono-atomic step edges at the nickel surface. Density-functional theory calculations indicate that the observations are consistent with a growth mechanism involving surface diffusion of carbon and nickel atoms. The finding that metallic step edges act as spatiotemporal dynamic growth sites may be important for understanding other types of catalytic reactions and nanomaterial syntheses.

Role of strain and ligand effects in the modification of the electronic and chemical properties of bimetallic surfaces

Abstract: Periodic density functional calculations are used to illustrate how the combination of strain and ligand effects modify the electronic and surface chemical properties of Ni, Pd, and Pt monolayers supported on other transition metals. Strain and the ligand effects are shown to change the width of the surface d band, which subsequently moves up or down in energy to maintain a constant band filling. Chemical properties such as the dissociative adsorption energy of hydrogen are controlled by changes induced in the average energy of the d band by modification of the d-band width.

Feature-based prediction of non-classical and leaderless protein secretion.

Abstract: We present a sequence-based method, SecretomeP, for the prediction of mammalian secretory proteins targeted to the non-classical secretory pathway, i.e. proteins without an N-terminal signal peptide. So far only a limited number of proteins have been shown experimentally to enter the non-classical secretory pathway. These are mainly fibroblast growth factors, interleukins and galectins found in the extracellular matrix. We have discovered that certain pathway-independent features are shared among secreted proteins. The method presented here is also capable of predicting (signal peptide-containing) secretory proteins where only the mature part of the protein has been annotated or cases where the signal peptide remains uncleaved. By scanning the entire human proteome we identified new proteins potentially undergoing non-classical secretion. Predictions can be made at http://www.cbs.dtu.dk/services/SecretomeP.

Space mapping: the state of the art

Abstract: We review the space-mapping (SM) technique and the SM-based surrogate (modeling) concept and their applications in engineering design optimization. For the first time, we present a mathematical motivation and place SM into the context of classical optimization. The aim of SM is to achieve a satisfactory solution with a minimal number of computationally expensive "fine" model evaluations. SM procedures iteratively update and optimize surrogates based on a fast physically based "coarse" model. Proposed approaches to SM-based optimization include the original algorithm, the Broyden-based aggressive SM algorithm, various trust-region approaches, neural SM, and implicit SM. Parameter extraction is an essential SM subproblem. It is used to align the surrogate (enhanced coarse model) with the fine model. Different approaches to enhance uniqueness are suggested, including the recent gradient parameter-extraction approach. Novel physical illustrations are presented, including the cheese-cutting and wedge-cutting problems. Significant practical applications are reviewed.

Analysis and prediction of leucine-rich nuclear export signals

Abstract: We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators of the subcellular location of proteins. This regulation has an impact on transcription and other nuclear processes, which are fundamental to the viability of the cell. NESs are studied in relation to cancer, the cell cycle, cell differentiation and other important aspects of molecular biology. Our conclusion from this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden Markov models in the prediction algorithm and verify the method on the most recently discovered NESs. The NES predictor (NetNES) is made available for general use at http://www.cbs.dtu.dk/.

Methane productivity of manure, straw and solid fractions of manure

Abstract: The methane productivity of manure in terms of volatile solids (VS), volume and livestock production was determined. The theoretical methane productivity is higher in pig (516 l kg −1 VS ) and sow (530 l kg −1 VS ) manure than in dairy cattle manure (469 l kg −1 VS ) , while the ultimate methane yield in terms of VS is considerably higher in pig (356 l kg −1 VS ) and sow manure (275 l kg −1 VS ) than in dairy cattle manure (148 l kg −1 VS ) . Methane productivity based on livestock units (LU) shows the lowest methane productivity for sows (165 m 3 CH 4 LU −1 ) , while the other animal categories are in the same range (282– 301 m 3 CH 4 LU −1 ). Pre-treatment of manure by separation is a way of making fractions of the manure that have a higher gas potential per volume. Theoretical methane potential and biodegradability of three types of fractions deriving from manure separation were tested. The volumetric methane yield of straw was found to be higher than the yield from total manure and the solid fractions of manure, due to the higher VS content, and hence the use of straw as bedding material will increase the volumetric as well as the livestock-based methane productivity.

An analytical model for the heat generation in friction stir welding

Abstract: The objective of this work is to establish an analytical model for heat generation by friction stir welding (FSW), based on different assumptions of the contact condition between the rotating tool surface and the weld piece. The material flow and heat generation are characterized by the contact conditions at the interface, and are described as sliding, sticking or partial sliding/sticking. Different mechanisms of heat generation are behind each contact condition, making this study important for further understanding of the real FSW process. The analytical expression for the heat generation is a modification of previous analytical models known from the literature and accounts for both conical surfaces and different contact conditions. Experimental results on plunge force and torque are used to determine the contact condition. The sliding condition yields a proportional relationship between the plunge force and heat generation. This is not demonstrated in the experiment, which suggests that the sticking contact condition is present at the tool/matrix interface.

PBI‐Based Polymer Membranes for High Temperature Fuel Cells – Preparation, Characterization and Fuel Cell Demonstration

Abstract: Proton exchange membrane fuel cell (PEMFC) technology based on perfluorosulfonic acid (PFSA) polymer membranes is briefly reviewed. The newest development in alternative polymer electrolytes for operation above 100 °C is summarized and discussed. As one of the successful approaches to high operational temperatures, the development and evaluation of acid doped polybenzimidazole (PBI) membranes are reviewed, covering polymer synthesis, membrane casting, acid doping, physicochemical characterization and fuel cell testing. A high temperature PEMFC system, operational at up to 200 °C based on phosphoric acid-doped PBI membranes, is demonstrated. It requires little or no gas humidification and has a CO tolerance of up to several percent. The direct use of reformed hydrogen from a simple methanol reformer, without the need for any further CO removal, has been demonstrated. A lifetime of continuous operation, for over 5000 h at 150 °C, and shutdown-restart thermal cycle testing for 47 cycles has been achieved. Other issues such as cooling, heat recovery, possible integration with fuel processing units, associated problems and further development are discussed.

Transformation and Release to the Gas Phase of Cl, K, and S during Combustion of Annual Biomass

Abstract: The transformation of inorganic constituents in annual biomass was experimentally investigated at grate-combustion conditions. A laboratory fixed-bed reactor was applied to obtain quantitative information of the release of Cl, K, and S to the gas phase from six distinctively different annual biomass fuels. Samples of 4.0 g of biomass were combusted at well-controlled conditions at temperatures from 500 to 1150 °C. The elemental release was quantified by analysis of the residual ash and a mass balance on the system. The experimental results revealed that potassium was released to the gas phase in significant amounts at combustion above 700 °C. The potassium release increased with the applied combustion temperature for all biomass fuels; however, the quantity released was largely determined by the ash composition. At 1150 °C, between 50 and 90% of the total potassium was released to the gas phase. The biomass fuels with an appreciable content of silicate showed the lower release of potassium. Between 25 and...

Prediction of proprotein convertase cleavage sites

Abstract: Many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides. Precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (PC) family. In mammals, seven members have been identified, with furin being the one first discovered and best characterized. Recently, the involvement of furin in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever has created additional focus on proprotein processing. We have developed a method for prediction of cleavage sites for PCs based on artificial neural networks. Two different types of neural networks have been constructed: a furin-specific network based on experimental results derived from the literature, and a general PC-specific network trained on data from the Swiss-Prot protein database. The method predicts cleavage sites in independent sequences with a sensitivity of 95% for the furin neural network and 62% for the general PC network. The ProP method is made publicly available at http://www.cbs.dtu.dk/services/ProP.

Activated sludge wastewater treatment plant modelling and simulation: state of the art

Abstract: This review paper focuses on modelling of wastewater treatment plants (WWTP). White-box modelling is widely applied in this field, with learning, design and process optimisation as the main applications. The introduction of the ASM model family by the IWA task group was of great importance, providing researchers and practitioners with a standardised set of basis models. This paper introduces the nowadays most frequently used white-box models for description of biological nitrogen and phosphorus removal activated sludge processes. These models are mainly applicable to municipal wastewater systems, but can be adapted easily to specific situations such as the presence of industrial wastewater. Some of the main model assumptions are highlighted, and their implications for practical model application are discussed. A step-wise procedure leads from the model purpose definition to a calibrated WWTP model. Important steps in the procedure are: model purpose definition, model selection, data collection, data reconciliation, calibration of the model parameters and model unfalsification. The model purpose, defined at the beginning of the procedure, influences the model selection, the data collection and the model calibration. In the model calibration a process engineering approach, i.e. based on understanding of the process and the model structure, is needed. A calibrated WWTP model, the result of an iterative procedure, can usually be obtained by only modifying few model parameters, using the default parameter sets as a starting point. Black-box, stochastic grey-box and hybrid models are useful in WWTP applications for prediction of the influent load, for estimation of biomass activities and effluent quality parameters. These modelling methodologies thus complement the process knowledge included in white-box models with predictions based on data in areas where the white-box model assumptions are not valid or where white-box models do not provide accurate predictions. Artificial intelligence (AI) covers a large spectrum of methods, and many of them have been applied in applications related to WWTPs. AI methodologies and white-box models can interact in many ways; supervisory control systems for WWTPs are one evident application. Modular agent-based systems combining several AI and modelling methods provide a great potential. In these systems, AI methods on one hand can maximise the knowledge extracted from data and operator experience, and subsequently apply this knowledge to improve WWTP control. White-box models on the other hand allow evaluating scenarios based on the available process knowledge about the WWTP. A white-box model calibration tool, an AI based WWTP design tool and a knowledge representation tool in the WWTP domain are other potential applications where fruitful interactions between AI methods and white-box models could be developed.

On the history of indoor air quality and health

Abstract: Man’s origin is in the tropical or near-tropical parts ofthe world. The spread into cold climates was possibleonly because of inventions such as clothing, housingand the use of fire (Sundell, 1994). However, in housesand shelters it is not only the thermal climate that haschanged. The climate shell also stops the free airmovement. The dilution of pollutants from close-to-man pollutant sources is diminished. The environmentwithin a shelter is always more polluted from indoorsources such as humans, open fires (still a major sourceof indoor air pollution in many developing regions)building materials, indoor activities, etc. than fromoutdoor air. This was and is the basis of the need forventilation and for discussions on indoor air quality(IAQ). Humans arrived in, e.g., southern Europe andChina a million years ago, but in America, northernEurope, Japan, etc. only some 10,000–40,000 yearsago, a period too short for major genetic changes. So ashumans we are still accustomed to a life outdoors in thewarm regions of Africa.As we spend most of our life indoors (in manyregions more than 90%), it is easy to understand thatthe most important environment in relation to ourhealth is the indoor environment (Sundell, 1999).During the breakthrough of modern hygiene, frommid 19th century, indoor environmental issues receivedmuch attention, as did the quality of drinking-waterand the treatment of sewage (e.g., linked to plaguessuch as cholera and tuberculosis).Ventilation comes from Latin ‘‘ventilare’’ meaning‘‘to expose to the wind’’. The main purpose ofbuildings is to create a climate more suitable forpersons and processes than the outdoor climate.Consequently, the main aim of ventilation in build-ings is to create an indoor air quality more suitablefor persons and processes than that naturally occur-ring in an unventilated building, and to reintroducethe positive effect of being ‘‘exposed to the wind’’,i.e. to dilute and remove the pollutants produced byman himself, his activities and the indoor surround-ings.Throughout history man has known that polluted airmay be detrimental to health. Greeks and Romanswere aware of the adverse effects of polluted air in,e.g., crowded cities and mines (Hippocrates, 460–377 BC).Abstract Indoor air is a dominant exposure for humans. More that half of thebody’s intake during a lifetime is air inhaled in the home. Thus, most illnessesrelated to environmental exposures stem from indoor air exposure. Indoor airwas believed to be a major environmental factor for more than a hundred years,from the start of the hygienic revolution, around 1850, until outdoor environ-mental issues entered the scene, and became dominant around 1960. Mainenvironmental issues today are outdoor air quality, energy use, and sustainablebuildings, but not indoor air quality (IAQ). But, there is mounting evidence thatexposure to IAQ is the cause of excessive morbidity and mortality. In developingregions indoor unvented burning of biomass for cooking is the cause of at least2,000,000 deaths a year (mainly women and children), and in the developedworld IAQ is a main cause of allergies, other hypersensitivity reactions, airwayinfections, and cancers. Cancer of the lungs is related to indoor radon and ETSexposure. Allergies, airway infections and sick building syndrome are associatedwith, e.g., ‘‘dampness’’, a low ventilation rate, and plasticizers. In the futuremore emphasis must be given to IAQ and health issues.

CO2 Multipliers in Multi-region Input-Output Models

Abstract: In order to achieve equitable reduction targets, international trade has to be taken into account when assessing nations' responsibility for abating climate change. Especially for open economies such as Denmark, greenhouse gases embodied in internationally traded commodities can have a considerable influence on the national 'greenhouse gas responsibility'. We set up a five-region input-output model including Denmark, Germany, Sweden and Norway in order to calculate CO2 multipliers and trade balances. We investigate multidirectional feedback between these countries, and hence the error inherent in a single-region input-output model. We also examine the effect of aggregation on the model results. In the case of Denmark, an 11 Mt CO2 trade surplus resulting from a single-region model turns into balance when multidirectional trade is considered. Moreover, aggregated models are likely to result in significant errors. Therefore, both the type and the degree of aggregation used for modelling CO2 responsibilities...

Gas sensing using air-guiding photonic bandgap fibers

Abstract: We report on experimental studies of gas sensing using air-guiding photonic bandgap fibers. The photonic bandgap fibers have at one end been spliced to standard single mode fibers for ease of use and improved stability

The effects of indoor air quality on performance and productivity

Abstract: UNLABELLED The main justification for ventilation has historically been to create a healthy indoor environment. Ventilation removes air pollutants originating inside the building, including bio-effluents. The outdoor air supply rate that has been found by experience to provide subjectively acceptable indoor air quality and to prevent the accumulation of moisture in the building is generally sufficient to maintain the concentration of pollutants at healthily low levels. Until 5 years ago this would have been the justification for current ventilation practices, but in 1999 the first of a series of experiments was published, revealing new mechanisms by which raised levels of indoor air pollution may reduce productivity, either in addition to or instead of having negative effects on comfort and health. It was shown in realistic experimental exposures lasting up to 5 h that the performance of simulated office work could be significantly increased by removing common indoor sources of air pollution, such as floor-coverings, used supply air filters and personal computers, or by keeping them in place and increasing the rate at which clean outdoor air was supplied from 3 to 10 to 30 l s(-1) per person. These short-term effects were demonstrated repeatedly even at pollutant levels that had no measurable effects on the perception of air quality by the occupants themselves, although there were effects on subclinical SBS symptoms such as headache. Temperature and noise distraction have since been studied in directly comparable exposures. The prediction arising from these experiments, that the performance of real office work over time would be significantly and substantially affected by the changes in indoor environmental quality that take place in the course of normal building operation, have recently been validated in 8-week field intervention experiments carried out in call-centers in northern Europe and the Tropics. These findings have far-reaching implications for the efficient use of energy in buildings. PRACTICAL IMPLICATIONS It has now been shown beyond reasonable doubt that poor indoor air quality in buildings can decrease productivity in addition to causing visitors to express dissatisfaction. The size of the effect on most aspects of office work performance appears to be as high as 6-9%, the higher value being obtained in field validation studies. It is usually more energy-efficient to eliminate sources of pollution than to increase outdoor air supply rates. The experiments summarized in this article have documented and quantified relationships that can be used in making cost-benefit analyses of either solution for a given building. The high cost of labor per unit floor area ensures that payback times will usually be as low as 2 years.

Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice.

Abstract: Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways to control certain bacterial infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra. Objectives: Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic lung infection by targeting bacterial quorum-sensing without directly killing bacteria or inhibiting their growth. Methods: Study I. Mice with Escherichia coli MT102 [luxR-Pluxl-gfp(ASV)] lung infection were injected intravenously with N-acyl homoserine lactones with or without furanones to test the interference of furanones with quorum-sensing. Study II. Mice with lung infection by Pseudomonas aeruginosa PAO1 [dsred, lasR-PlasB-gfp(ASV)] were injected intravenously with furanones to evaluate their inhibiting effects on quorum-sensing. Study III. Mice with P. aeruginosa PAO1 lung infection were treated with different doses of furanones to evaluate the therapeutic effects of furanones on the lung infection. Results: Furanones successfully interfered with N-acyl homoserine lactone and suppressed bacterial quorum-sensing in lungs, which resulted in decreases in expression of green fluorescent protein. Furanones accelerated lung bacterial clearance, and reduced the severity of lung pathology. In a lethal P. aeruginosa lung infection, treatment with furanone significantly prolonged the survival time of the mice. Conclusion: Synthetic furanone compounds inhibited bacterial quorum-sensing in P. aeruginosa and exhibited favourable therapeutic effects on P. aeruginosa lung infection.

Vapor-Phase Polymerization of 3,4-Ethylenedioxythiophene: A Route to Highly Conducting Polymer Surface Layers

Abstract: A new synthetic route to poly-3,4-ethylenedioxythiophene (PEDT) with a conductivity exceeding 1000 S/cm is described. The method is based on base-inhibited vapor-phase polymerization, where a surface covered with ferric p-toluenesulfonate as oxidant mixed with a volatile base (pyridine) is exposed to 3,4-ethylenedioxythiophene (EDT) vapors. The base is added to suppress an acid-initiated polymerization of EDT, leading to a product with little or no conjugation. The product of the base-inhibited vapor-phase polymerization is confirmed to be virtually identical to PEDT obtained by wet chemical oxidation by both spectroscopic and electrochemical methods. A possible reaction scheme for the acid-initiated polymerization is discussed.

Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin

Abstract: Summary Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli uri- nary tract infections (UTIs). These infections are initi- ated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we pro- vide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crys- tallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl man- nosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl a a a - D -mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (K d = 0.15 m m m M) than mannose (K d = 2.3 m M). Exploration of the binding affinities of a - D -mannosides with longer alkyl tails revealed affin- ities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affini- ties correlate exceptionally well with the relative con- centrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli . We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recur- rent UTIs.