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Sample records for regulatory odour model

  1. Regulatory odour model development: Survey of modelling tools and datasets with focus on building effects

    DEFF Research Database (Denmark)

    Olesen, H. R.; Løfstrøm, P.; Berkowicz, R.;

    dispersion models for estimating local concentration levels in general. However, the report focuses on some particular issues, which are relevant for subsequent work on odour due to animal production. An issue of primary concern is the effect that buildings (stables) have on flow and dispersion. The handling...... of building effects is a complicated problem, and a major part of the report is devoted to the treatment of building effects in dispersion models...

  2. Factors influencing separation distances against odour annoyance calculated by Gaussian and Lagrangian dispersion models

    Science.gov (United States)

    Piringer, Martin; Knauder, Werner; Petz, Erwin; Schauberger, Günther

    2016-09-01

    Direction-dependent separation distances to avoid odour annoyance, calculated with the Gaussian Austrian Odour Dispersion Model AODM and the Lagrangian particle diffusion model LASAT at two sites, are analysed and compared. The relevant short-term peak odour concentrations are calculated with a stability-dependent peak-to-mean algorithm. The same emission and meteorological data, but model-specific atmospheric stability classes are used. The estimate of atmospheric stability is obtained from three-axis ultrasonic anemometers using the standard deviations of the three wind components and the Obukhov stability parameter. The results are demonstrated for the Austrian villages Reidling and Weissbach with very different topographical surroundings and meteorological conditions. Both the differences in the wind and stability regimes as well as the decrease of the peak-to-mean factors with distance lead to deviations in the separation distances between the two sites. The Lagrangian model, due to its model physics, generally calculates larger separation distances. For worst-case calculations necessary with environmental impact assessment studies, the use of a Lagrangian model is therefore to be preferred over that of a Gaussian model. The study and findings relate to the Austrian odour impact criteria.

  3. Data-driven honeybee antennal lobe model suggests how stimulus-onset asynchrony can aid odour segregation.

    Science.gov (United States)

    Nowotny, Thomas; Stierle, Jacob S; Galizia, C Giovanni; Szyszka, Paul

    2013-11-01

    Insects have a remarkable ability to identify and track odour sources in multi-odour backgrounds. Recent behavioural experiments show that this ability relies on detecting millisecond stimulus asynchronies between odourants that originate from different sources. Honeybees, Apis mellifera, are able to distinguish mixtures where both odourants arrive at the same time (synchronous mixtures) from those where odourant onsets are staggered (asynchronous mixtures) down to an onset delay of only 6ms. In this paper we explore this surprising ability in a model of the insects' primary olfactory brain area, the antennal lobe. We hypothesize that a winner-take-all inhibitory network of local neurons in the antennal lobe has a symmetry-breaking effect, such that the response pattern in projection neurons to an asynchronous mixture is different from the response pattern to the corresponding synchronous mixture for an extended period of time beyond the initial odourant onset where the two mixture conditions actually differ. The prolonged difference between response patterns to synchronous and asynchronous mixtures could facilitate odoursegregation in downstream circuits of the olfactory pathway. We present a detailed data-driven model of the bee antennal lobe that reproduces a large data set of experimentally observed physiological odour responses, successfully implements the hypothesised symmetry-breaking mechanism and so demonstrates that this mechanism is consistent with our current knowledge of the olfactory circuits in the bee brain. This article is part of a Special Issue entitled Neural Coding 2012.

  4. Analysis and Modelling of Taste and Odour Events in a Shallow Subtropical Reservoir

    Directory of Open Access Journals (Sweden)

    Edoardo Bertone

    2016-08-01

    Full Text Available Understanding and predicting Taste and Odour events is as difficult as critical for drinking water treatment plants. Following a number of events in recent years, a comprehensive statistical analysis of data from Lake Tingalpa (Queensland, Australia was conducted. Historical manual sampling data, as well as data remotely collected by a vertical profiler, were collected; regression analysis and self-organising maps were the used to determine correlations between Taste and Odour compounds and potential input variables. Results showed that the predominant Taste and Odour compound was geosmin. Although one of the main predictors was the occurrence of cyanobacteria blooms, it was noticed that the cyanobacteria species was also critical. Additionally, water temperature, reservoir volume and oxidised nitrogen availability, were key inputs determining the occurrence and magnitude of the geosmin peak events. Based on the results of the statistical analysis, a predictive regression model was developed to provide indications on the potential occurrence, and magnitude, of peaks in geosmin concentration. Additionally, it was found that the blue green algae probe of the lake’s vertical profiler has the potential to be used as one of the inputs for an automated geosmin early warning system.

  5. Numerical modelling of odour dispersion around a cubical obstacle using large eddy simulation.

    Science.gov (United States)

    Dourado, Harerton Oliveira; Santos, Jane Meri; Reis, Neyval C; Mavroidis, Ilias

    2012-01-01

    In the present work two different large eddy simulation (LES) approaches, namely the Dynamic Smagorinsky model and the Wale model, are used to simulate the air flow and pollutant dispersion around a cubical obstacle. Results are compared with wind tunnel data (WT) and with results from the Smagorinsky LES model. Overall agreement was good between the different LES approaches and the WT results, both for the mean and fluctuating flow and concentration patterns. LES models can provide good estimates of concentration fluctuation intensity and enable the calculation of the intermittency factor. The model results indicate that LES is a viable tool for odour impact assessment.

  6. The Relationship between Odour Annoyance Scores and Modelled Ambient Air Pollution in Sarnia, “Chemical Valley”, Ontario

    Directory of Open Access Journals (Sweden)

    Dominic Odwa Atari

    2009-10-01

    Full Text Available This study aimed at establishing the relationship between annoyance scores and modelled air pollution in “Chemical Valley”, Sarnia, Ontario (Canada. Annoyance scores were taken from a community health survey (N = 774; and respondents’ exposure to nitrogen dioxide (NO2 and sulphur dioxide (SO2 were estimated using land use regression (LUR models. The associations were examined by univariate analysis while multivariate logistic regression was used to examine the determinants of odour annoyance. The results showed that odour annoyance was significantly correlated to modelled pollutants at the individual (NO2, r = 0.15; SO2, r = 0.13 and census tract (NO2, r = 0.56; SO2, r = 0.67 levels. The exposure-response relationships show that residents of Sarnia react to very low pollution concentrations levels even if they are within the Ontario ambient air quality criteria. The study found that exposure to high NO2 and SO2 concentrations, gender, and perception of health effects were significant determinants of individual odour annoyance reporting. The observed association between odour annoyance and modelled ambient pollution suggest that individual and census tract level annoyance scores may serve as proxies for air quality in exposed communities because they capture the within area spatial variability of pollution. However, questionnaire-based odour annoyance scores need to be validated longitudinally and across different scales if they are to be adopted for use at the national level.

  7. Improving odour assessment in LCA — the odour footprint

    DEFF Research Database (Denmark)

    Peters, Gregory M.; Murphy, Kathleen R.; Adamsen, Anders Peter S.

    2014-01-01

    in the life cycle assessment (LCA) community. This article aims to redress this. Results and discussion: We produced a list of 33 linear characterisation factors based on hydrogen sulphide equivalents, analogous to the linear carbon dioxide equivalency factors in use in carbon footprinting......, or the dichlorobenzene equivalency factors developed for assessment of toxic impacts in LCA. Like the latter, this odour footprint method does not take local populations and exposure pathway analysis into account—its intent is not to assess regulatory compliance or detailed design. The case study showed that despite...... assessment in LCA. Unlike it, the method presented here considers the persistence of odourants. Over time, we hope to increase the number of characterised odourants, enabling analysts to perform simple site-generic LCA on systems with odourant emissions. Methods: Firstly, a framework for the assessment...

  8. Odour concentration affects odour identity in honeybees

    National Research Council Canada - National Science Library

    Geraldine A Wright; Mitchell G.A Thomson; Brian H Smith

    2005-01-01

    ... such as the molecular identity of the odorant. The experiments with honeybees reported here show a departure from odour-concentration invariance and are consistent with a lower-concentration regime in which odour concentration contributes...

  9. Odour emissions from a waste treatment plant using an inverse dispersion technique

    Science.gov (United States)

    Schauberger, Günther; Piringer, Martin; Knauder, Werner; Petz, Erwin

    2011-03-01

    The determination of the in situ emission rate of pollution sources can often not be done directly. In the absence of emission measurements, the emission rate of the source can be assessed by an inverse dispersion technique using ambient concentration measurements and meteorological parameters as input. The dispersion model used is the Austrian regulatory Gaussian model. The method is applied to a thermal waste recycling plant. Seven chemical species (butyl acetate, benzene, ethyl acetate, toluene, m/p-xylene, o-xylene and α-pinene), are identified as odorants and measured over a period of 1½ years in the prevailing wind direction leeward of the plant. The overall odour emission rate is calculated by adding the odour emission rate of all single species, using the individual odour threshold concentration. The estimated odour emission rates range between 206 and 8950 OU s -1, caused by the wide variety of the odour thresholds of the seven species. The higher value is in the upper range of odour emission rates of modern thermal treatment plants for waste.

  10. Thrips responses to plant odours

    NARCIS (Netherlands)

    Kogel, de W.J.; Koschier, E.H.

    2002-01-01

    Thrips responses to plant odour compounds were assessed using a Y-tube olfactometer. Several compounds were attractive to adult Frankliniella occidentalis females, since the majority walked towards the odour source. Some odours that were attractive for western flower thrips appeared to be non-attrac

  11. The effects of odour and body posture on perceived duration

    Directory of Open Access Journals (Sweden)

    Eliane eSchreuder

    2014-02-01

    Full Text Available This study reports an examination of the internal clock model, according to which subjective time duration is influenced by attention and arousal state. In a time production task, we examine the hypothesis that an arousing odour and an upright body posture affect perceived duration.The experimental task was performed while participants were exposed to an odour and either sitting upright (arousing condition or lying down in a relaxing chair (relaxing condition. They were allocated to one of three experimental odour conditions: rosemary (arousing condition, peppermint (relaxing condition and no odour (control condition. The predicted effects of the odours were not borne out by the results. Self-reported arousal and pleasure states were measured before, during (after each body posture condition and post experimentally. Heart rate and skin conductance were measured before and during the experiment. As expected, odour had an effect on perceived duration. When participants were exposed to rosemary odour, they produced significantly shorter time intervals than in the no odour condition. This effect, however, could not be explained by increased arousal. There was no effect of body posture on perceived duration, even though body posture did induce arousal. The results do not support the proposed arousal mechanism of the internal clock model.

  12. Correlation between odour concentration and odour intensity from exposure to environmental odour

    Science.gov (United States)

    Yusoff, Syafinah; Qamaruz Zaman, Nastaein

    2017-08-01

    The encroachment of industries, agricultural activities and husbandries to the community area had been a major concern of late, especially in regards to the escalating reports of odour nuisances. A study was performed with the objective of establishing correlation between odour concentration and odour intensity, as an improved method to determine odour nuisances in the community. Universiti Sains Malaysia Engineering Campus was chosen as the study location, due to its vicinity to several odour sources including paper mill, palm oil mill and poultry farm. The odour survey was based on VDI 3940, to determine the level of odour intensity with the corresponding odour concentration measured using an infield olfactometer. The correlation between both methods shows a significant correlation by using Pearson Correlation with a level of confidence of 99.9 percent. The graph plotted between intensity and concentration shows the R2 value of 0.40 which indicated a good correlation between both methods, despite having a high variance and low in consistency. Therefore, this study concludes that the determination of odour concentration should be complemented with odour intensity in order to recognize the true impact of odour nuisance in a community.

  13. A review of odour impact criteria in selected countries around the world.

    Science.gov (United States)

    Brancher, Marlon; Griffiths, K David; Franco, Davide; de Melo Lisboa, Henrique

    2017-02-01

    Exposure to environmental odour can result in annoyance, health effects and depreciation of property values. Therefore, many jurisdictions classify odour as an atmospheric pollutant and regulate emissions and/or impacts from odour generating activities at a national, state or municipal level. In this work, a critical review of odour regulations in selected jurisdictions of 28 countries is presented. Individual approaches were identified as: comparing ambient air odour concentration and individual chemicals statistics against impact criteria (maximum impact standard); using fixed and variable separation distances (separation distance standard); maximum emission rate for mixtures of odorants and individual chemical species (maximum emission standard); number of complaints received or annoyance level determined via community surveys (maximum annoyance standard); and requiring use of best available technologies (BAT) to minimize odour emissions (technology standard). The comparison of model-predicted odour concentration statistics against odour impact criteria (OIC) is identified as one of the most common tools used by regulators to evaluate the risk of odour impacts in planning stage assessments and is also used to inform assessment of odour impacts of existing facilities. Special emphasis is given to summarizing OIC (concentration percentile and threshold) and the manner in which they are applied. The way short term odour peak to model time-step mean (peak-to-mean) effects is also captured. Furthermore, the fundamentals of odorant properties, dimensions of nuisance odour, odour sampling and analysis methods and dispersion modelling guidance are provided. Common elements of mature and effective odour regulation frameworks are identified and an integrated multi-tool strategy is recommended.

  14. Strategies to control odours in livestock facilities: a critical review

    Directory of Open Access Journals (Sweden)

    Y. Ubeda

    2013-11-01

    Full Text Available Odours generated in livestock buildings constitute one of the most relevant air quality issues of intensive livestock production. Reducing nuisance episodes related to odour exposure is therefore essential for a sustainable livestock production. In this study, the state-of-the-art on odour mitigation techniques in livestock housing is critically reviewed. Scientific advances in the last decade are revised and research needs are also identified. The complex nature of livestock odours is firstly reviewed and examined. Then, the most relevant odour control strategies are analyzed in terms of present knowledge and future needs. The strategies considered are: nutritional strategies, manure additives, building design, air filtration, manure covers, manure treatment systems and windbreaks. Finally, future research needs and priorities when establishing mitigation techniques are identified. Despite important recent advances, there are still some challenges for scientists, producers and regulators, particularly related to field evaluation of odours. Therefore, to control livestock odours effectively, using standardized field assessment techniques will be required. Also, investigating measurement and model errors may be useful to better understand the limitations of the current methods, as well as to identify research priorities.

  15. Synthesis and odour properties of floral smelling compounds.

    Science.gov (United States)

    Anselmi, C; Centini, M; Sega, A; Napolitano, E; Pelosi, P; Scesa, C

    1996-04-01

    Synopsis To provide further information on the relationships between chemical structure and floral odour, here we report the synthesis and the odour evaluation of some spirane derivatives, designed as conformational models of our previously described floral odorants. One of the new compounds (5-methyl-benzo[1,3]dioxole-2-spiro-1-cyclohexane), in particular, is endowed with a particularly pleasant odour of white flowers, can be easily prepared from commercial products and is more stable than other odorants of the same class; these characteristics make this odorant suitable for being used as an additive in perfumery and cosmetics.

  16. Modeling of hysteresis in gene regulatory networks.

    Science.gov (United States)

    Hu, J; Qin, K R; Xiang, C; Lee, T H

    2012-08-01

    Hysteresis, observed in many gene regulatory networks, has a pivotal impact on biological systems, which enhances the robustness of cell functions. In this paper, a general model is proposed to describe the hysteretic gene regulatory network by combining the hysteresis component and the transient dynamics. The Bouc-Wen hysteresis model is modified to describe the hysteresis component in the mammalian gene regulatory networks. Rigorous mathematical analysis on the dynamical properties of the model is presented to ensure the bounded-input-bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model can only generate a clockwise hysteresis loop while the modified model can describe both clockwise and counter clockwise hysteresis loops. Simulation studies have shown that the hysteresis loops from our model are consistent with the experimental observations in three mammalian gene regulatory networks and two E.coli gene regulatory networks, which demonstrate the ability and accuracy of the mathematical model to emulate natural gene expression behavior with hysteresis. A comparison study has also been conducted to show that this model fits the experiment data significantly better than previous ones in the literature. The successful modeling of the hysteresis in all the five hysteretic gene regulatory networks suggests that the new model has the potential to be a unified framework for modeling hysteresis in gene regulatory networks and provide better understanding of the general mechanism that drives the hysteretic function.

  17. ASSESSMENT OF ODOUR EMISSIONS FROM AN OPEN BIOFILTER

    Directory of Open Access Journals (Sweden)

    Marlon Brancher

    2014-12-01

    Full Text Available Odour annoyances are considered a major cause of public complaints to regulatory agencies regarding air quality and represent a growing social problem, especially in industrialized countries. In view of the need to diagnose odour sources for control and mitigation of possible impacts on communities, was assessed, through a case study, the odorous emissions from an open biofilter. The equipment was responsible for gas treatment generated in the wastewater plant treatment of a textile industry. Sampling was conducted in the inlet duct of the biofilter using direct sampling and on the emission surface (output using a hood (VDI 3477:2004. Samples were stored in plastic bags manufactured in polyvinyl fluoride (Tedlar® and transported to the laboratory, where the odour concentration (in UO m-3 was determined based on the dynamic olfactometry dilution procedure (EN 13725:2003. To calculate the odour emission rate (OER (in UO h-1, the volumetric flow rate (in m3 h-1 was measured in the inlet duct of the biofilter. The values obtained for the efficiency and the OER were 98.7 % and 0.34 x 106 UO h-1, respectively. Comparing the efficiency value with the criterion established by Article 12 of Resolution SEMA No 054:2006 (State of Paraná, Brazil, adopted as reference, the biofiltration system meets the minimum efficiency rating of 85 % required in removing odour.

  18. Attraction of Drosophila melanogaster males to food-related and fly odours.

    Science.gov (United States)

    Lebreton, Sébastien; Becher, Paul G; Hansson, Bill S; Witzgall, Peter

    2012-01-01

    The fruit fly Drosophila melanogaster has become a model for olfaction and odour-mediated behaviour. In the wild, Drosophila flies aggregate on decaying fruit where they mate and oviposit and a strategy to find mates would be to locate fruit which has already been colonized by other flies. We therefore developed a bioassay to investigate attraction of males to food and fly odours. We showed that upwind flights are initiated by food odours. At shorter distances, males are attracted by volatiles produced by conspecifics. However, only odours produced by copulating flies attract males. This suggests either a synergistic effect of both male and female odours or changes in pheromone release during mating, that indicate the presence of sexually receptive females. Our findings demonstrate the essential role of food odours and pheromones for mate location in D. melanogaster. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Current approaches to gene regulatory network modelling

    Directory of Open Access Journals (Sweden)

    Brazma Alvis

    2007-09-01

    Full Text Available Abstract Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more detail, comparing a direct network derived from transcription factor binding data and an indirect network derived from genome-wide expression data in mutants. Regarding the network dynamics we briefly describe discrete and continuous approaches to network modelling, then describe a hybrid model called Finite State Linear Model and demonstrate that some simple network dynamics can be simulated in this model.

  20. Modeling Emergence in Neuroprotective Regulatory Networks

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Haack, Jereme N.; McDermott, Jason E.; Stevens, S.L.; Stenzel-Poore, Mary

    2013-01-05

    The use of predictive modeling in the analysis of gene expression data can greatly accelerate the pace of scientific discovery in biomedical research by enabling in silico experimentation to test disease triggers and potential drug therapies. Techniques that focus on modeling emergence, such as agent-based modeling and multi-agent simulations, are of particular interest as they support the discovery of pathways that may have never been observed in the past. Thus far, these techniques have been primarily applied at the multi-cellular level, or have focused on signaling and metabolic networks. We present an approach where emergence modeling is extended to regulatory networks and demonstrate its application to the discovery of neuroprotective pathways. An initial evaluation of the approach indicates that emergence modeling provides novel insights for the analysis of regulatory networks that can advance the discovery of acute treatments for stroke and other diseases.

  1. Associative learning of complex odours in parasitoid host location

    NARCIS (Netherlands)

    Meiners, T.; Wäckers, F.L.; Lewis, W.J.

    2003-01-01

    In this paper we address the question how hymenopteran parasitoids deal with complex odour bouquets, using Microplitis croceipes (Cresson) (Hymenoptera: Braconidae) as a model. We examined the capacity of Microplitis croceipes to respond to individual compounds in flight chamber experiments after co

  2. Evolutionary algorithms in genetic regulatory networks model

    CERN Document Server

    Raza, Khalid

    2012-01-01

    Genetic Regulatory Networks (GRNs) plays a vital role in the understanding of complex biological processes. Modeling GRNs is significantly important in order to reveal fundamental cellular processes, examine gene functions and understanding their complex relationships. Understanding the interactions between genes gives rise to develop better method for drug discovery and diagnosis of the disease since many diseases are characterized by abnormal behaviour of the genes. In this paper we have reviewed various evolutionary algorithms-based approach for modeling GRNs and discussed various opportunities and challenges.

  3. Concept to assess the human perception of odour by estimating short-time peak concentrations from one-hour mean values. Reply to a comment by M\\"uller et al

    CERN Document Server

    Schauberger, Günther; Schmitzer, Rainer; Kamp, Martin; Sowa, Andreas; Koch, Roman; Eckhof, Wilfried; Grimm, Ewald; Kypke, Joachim; Hartung, Eberhard

    2012-01-01

    Biologically relevant exposure to environmental pollutants often shows a non-linear relationship. For their assessment, as a rule short term concentrations have to be determined instead of long term mean values. This is also the case for the perception of odour. Regulatory dispersion models like AUSTAL2000 calculate long term mean concentration values (one-hour), but provide no information on the fluctuation from this mean. The ratio between a short term mean value (relevant for odour perception) and the long term mean value (calculated by the dispersion model), called the peak-to-mean value, is usually used to describe these fluctuations. In general, this ratio can be defined in different ways. M\\"uller et al. (2012), in a comment to Schauberger et al. (2012) which includes a statement that AUSTAL2000 uses a constant factor of 4, argue that AUSTAL2000 does not apply a peak-to-mean factor and does not calculate odour exceedance probabilities. Instead it calculates the frequency of so-called odour-hours by app...

  4. Odour Detection Methods: Olfactometry and Chemical Sensors

    Directory of Open Access Journals (Sweden)

    Sara Lovascio

    2011-05-01

    Full Text Available The complexity of the odours issue arises from the sensory nature of smell. From the evolutionary point of view olfaction is one of the oldest senses, allowing for seeking food, recognizing danger or communication: human olfaction is a protective sense as it allows the detection of potential illnesses or infections by taking into account the odour pleasantness/unpleasantness. Odours are mixtures of light and small molecules that, coming in contact with various human sensory systems, also at very low concentrations in the inhaled air, are able to stimulate an anatomical response: the experienced perception is the odour. Odour assessment is a key point in some industrial production processes (i.e., food, beverages, etc. and it is acquiring steady importance in unusual technological fields (i.e., indoor air quality; this issue mainly concerns the environmental impact of various industrial activities (i.e., tanneries, refineries, slaughterhouses, distilleries, civil and industrial wastewater treatment plants, landfills and composting plants as sources of olfactory nuisances, the top air pollution complaint. Although the human olfactory system is still regarded as the most important and effective “analytical instrument” for odour evaluation, the demand for more objective analytical methods, along with the discovery of materials with chemo-electronic properties, has boosted the development of sensor-based machine olfaction potentially imitating the biological system. This review examines the state of the art of both human and instrumental sensing currently used for the detection of odours. The olfactometric techniques employing a panel of trained experts are discussed and the strong and weak points of odour assessment through human detection are highlighted. The main features and the working principles of modern electronic noses (E-Noses are then described, focusing on their better performances for environmental analysis. Odour emission monitoring

  5. Modeling genomic regulatory networks with big data.

    Science.gov (United States)

    Bolouri, Hamid

    2014-05-01

    High-throughput sequencing, large-scale data generation projects, and web-based cloud computing are changing how computational biology is performed, who performs it, and what biological insights it can deliver. I review here the latest developments in available data, methods, and software, focusing on the modeling and analysis of the gene regulatory interactions in cells. Three key findings are: (i) although sophisticated computational resources are increasingly available to bench biologists, tailored ongoing education is necessary to avoid the erroneous use of these resources. (ii) Current models of the regulation of gene expression are far too simplistic and need updating. (iii) Integrative computational analysis of large-scale datasets is becoming a fundamental component of molecular biology. I discuss current and near-term opportunities and challenges related to these three points.

  6. Regulatory Models and the Environment: Practice, Pitfalls, and Prospects

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, K. John; Graham, Judith A.; McKone, Thomas; Whipple, Chris

    2008-06-01

    Computational models support environmental regulatory activities by providing the regulator an ability to evaluate available knowledge, assess alternative regulations, and provide a framework to assess compliance. But all models face inherent uncertainties, because human and natural systems are always more complex and heterogeneous than can be captured in a model. Here we provide a summary discussion of the activities, findings, and recommendations of the National Research Council's Committee on Regulatory Environmental Models, a committee funded by the US Environmental Protection Agency to provide guidance on the use of computational models in the regulatory process. Modeling is a difficult enterprise even outside of the potentially adversarial regulatory environment. The demands grow when the regulatory requirements for accountability, transparency, public accessibility, and technical rigor are added to the challenges. Moreover, models cannot be validated (declared true) but instead should be evaluated with regard to their suitability as tools to address a specific question. The committee concluded that these characteristics make evaluation of a regulatory model more complex than simply comparing measurement data with model results. Evaluation also must balance the need for a model to be accurate with the need for a model to be reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs requires model evaluation to be applied over the"life cycle" of a regulatory model with an approach that includes different forms of peer review, uncertainty analysis, and extrapolation methods than for non-regulatory models.

  7. Evaluation of an Odour Emission Factor (OEF) to estimate odour emissions from landfill surfaces

    Science.gov (United States)

    Lucernoni, Federico; Tapparo, Federica; Capelli, Laura; Sironi, Selena

    2016-11-01

    Emission factors are fundamental tools for air quality management. Odour Emission Factors (OEFs) can be developed in analogy with the emission factors defined for other chemical compounds, which relate the quantity of a pollutant released to the atmosphere to a given associated activity. Landfills typically represent a common source of odour complaint; for this reason, the development of specific OEFs allowing the estimation of odour emissions from this kind of source would be of great interest both for the landfill design and management. This study proposes an up-to-date methodology for the development of an OEF for the estimation of odour emissions from landfills, thereby focusing on the odour emissions related to the emissions of landfill gas (LFG) from the exhausted landfill surface. The proposed approach is an "indirect" approach based on the quantification of the LFG emissions from methane concentration measurements carried out on an Italian landfill. The Odour Emission Rate (OER) is then obtained by multiplying the emitted gas flow rate by the LFG odour concentration. The odour concentration of the LFG emitted through the landfill surface was estimated by means of an ad hoc correlation investigated between methane concentration and odour concentration. The OEF for the estimation of odour emissions from landfill surfaces was computed, considering the landfill surface as the activity index, as the product between the mean specific LFG flux emitted through the surface resulting from the experimental campaigns, equal to 0.39 l/m2/h, and its odour concentration, which was estimated to be equal to 105‧000 eq. ouE/m3, thus giving an OEF of 0.011 ouE/m2/s. This value, which is considerably lower than those published in previous works, should be considered as an improved estimation based on the most recent developments of the research in the field of odour sampling on surface sources.

  8. Odour Pollution Measurement from Refuse Derive Fuel Operations Using Odour Concentration Meter (OCM XP-329

    Directory of Open Access Journals (Sweden)

    Zaini Sakawi

    2013-04-01

    Full Text Available Odour perception is subjective and difficult to be accurately measured between individuals. Hence many studies on odour issues are more commonly pertain to its intensity, concentration, types, standards, measurement methods, law and impacts on physical and human environments. Nevertheless, odour analysis can be conducted empirically or based on human sensorial. Among major sources of odour pollution are animal rearing, oil palm and rubber mills, dumpsites, industries and sewage treatments. This study attempted to measure odour pollution generated by Refuse Derived Fuel (RDF operation. The analysis was conducted at different times of day (morning, evening and night and weather conditions (normal days and after rains. 10 sampling stations were selected for observations using the Odour Concentration Meter Siri XP-329 III.The results indicated that there existed different level of odour concentrations on normal days and after rains due to the influence of meteorological environment. Distance factors also influenced the odour concentrations, whereby gradually, the stations further from RDF operation recorded higher odour concentrations

  9. Simple mathematical models of gene regulatory dynamics

    CERN Document Server

    Mackey, Michael C; Tyran-Kamińska, Marta; Zeron, Eduardo S

    2016-01-01

    This is a short and self-contained introduction to the field of mathematical modeling of gene-networks in bacteria. As an entry point to the field, we focus on the analysis of simple gene-network dynamics. The notes commence with an introduction to the deterministic modeling of gene-networks, with extensive reference to applicable results coming from dynamical systems theory. The second part of the notes treats extensively several approaches to the study of gene-network dynamics in the presence of noise—either arising from low numbers of molecules involved, or due to noise external to the regulatory process. The third and final part of the notes gives a detailed treatment of three well studied and concrete examples of gene-network dynamics by considering the lactose operon, the tryptophan operon, and the lysis-lysogeny switch. The notes contain an index for easy location of particular topics as well as an extensive bibliography of the current literature. The target audience of these notes are mainly graduat...

  10. Conversion of the chemical concentration of odorous mixtures into odour concentration and odour intensity: a comparison of methods

    CERN Document Server

    Wu, C; Zhao, P; Piringer, M; Schauberger, G

    2015-01-01

    Continuous odour measurements both of emissions as well as ambient concentrations are seldom realised, mainly because of their high costs. They are therefore often substituted by concentration measurements of odorous substances. Then a conversion of the chemical concentrations C (mg m-3) into odour concentrations COD (ouE m-3) and odour intensities OI is necessary. Four methods to convert the concentrations of single substances to the odour concentrations and odour intensities of an odorous mixture are investigated: (1) direct use of measured concentrations, (2) the sum of the odour activity value SOAV, (3) the sum of the odour intensities SOI, and (4) the equivalent odour concentration EOC, as a new method. The methods are evaluated with olfactometric measurements of seven substances as well as their mixtures. The results indicate that the SOI and EOC conversion methods deliver reliable values. These methods use not only the odour threshold concentration but also the slope of the Weber-Fechner law to include...

  11. Researches of odour emitted by household waste

    Directory of Open Access Journals (Sweden)

    Eglė Marčiulaitienė

    2015-10-01

    Full Text Available The article deals with odour emitted by household waste, the chemical composition of household waste. The experiment was made with food waste (1000 g placed in 5 litter containers. Food waste was containing products of animal origin (meat, fish, dairy products and plant origin (vegetables, fruit waste. Time of the experiment was 14 days 19±3 °C at environment temperature. Odour concentration is determined by dynamic olfactometry method. Studies have shown that the strongest odour of all household waste used in this experiment was emitted by meat and fish waste (76 444 OUE/m3. Meat and fish waste emits the strongest odour as waste contains proteins, their decomposition releases into the environment a strong unpleasant odour, hydrogen sulphide and ammonia. Protein degradation releases into the environment are, characterized by a strong unpleasant smell of hydrogen sulphide and ammonia gas. During the anaerobic decomposition of organic matter a variety of other fragrant compounds: alcohols (e.g., ethanol and methanol, vinegar, formic acid, etc. is found.

  12. [Self-perceived oral odour and social interaction

    NARCIS (Netherlands)

    Jongh, A. de; Baat, C. de; Horstman, M.; Wijk, A.J. van

    2013-01-01

    This study examined the influence of self-perceived oral odour on social interaction. A representative sample of 1,082 people from the Dutch population of 16 years and older, were surveyed. On average, the participants graded their oral odour as 66.8 on a scale 0-100; 4.2% judged their oral odour as

  13. Habitats as complex odour environments: how does plant diversity affect herbivore and parasitoid orientation?

    Directory of Open Access Journals (Sweden)

    Nicole Wäschke

    Full Text Available Plant diversity is known to affect success of host location by pest insects, but its effect on olfactory orientation of non-pest insect species has hardly been addressed. First, we tested in laboratory experiments the hypothesis that non-host plants, which increase odour complexity in habitats, affect the host location ability of herbivores and parasitoids. Furthermore, we recorded field data of plant diversity in addition to herbivore and parasitoid abundance at 77 grassland sites in three different regions in Germany in order to elucidate whether our laboratory results reflect the field situation. As a model system we used the herb Plantago lanceolata, the herbivorous weevil Mecinus pascuorum, and its larval parasitoid Mesopolobus incultus. The laboratory bioassays revealed that both the herbivorous weevil and its larval parasitoid can locate their host plant and host via olfactory cues even in the presence of non-host odour. In a newly established two-circle olfactometer, the weeviĺs capability to detect host plant odour was not affected by odours from non-host plants. However, addition of non-host plant odours to host plant odour enhanced the weeviĺs foraging activity. The parasitoid was attracted by a combination of host plant and host volatiles in both the absence and presence of non-host plant volatiles in a Y-tube olfactometer. In dual choice tests the parasitoid preferred the blend of host plant and host volatiles over its combination with non-host plant volatiles. In the field, no indication was found that high plant diversity disturbs host (plant location by the weevil and its parasitoid. In contrast, plant diversity was positively correlated with weevil abundance, whereas parasitoid abundance was independent of plant diversity. Therefore, we conclude that weevils and parasitoids showed the sensory capacity to successfully cope with complex vegetation odours when searching for hosts.

  14. Odour Prevention at Biodiesel Fuel Producing Enterprises

    Directory of Open Access Journals (Sweden)

    Kristina Montrimaite

    2012-03-01

    Full Text Available Gaseous, unpleasant, pungent and even harmful odour frequently leads to complaints and appeals to the authorities. For this reason an environmental review was carried out in a certain biodiesel fuel production enterprise, odour pollution sources were identified, their quantities estimated and their impact on the environment assessed. Following the initial environmental review, significant environmental aspects of biodiesel fuel production processes were evaluated. It was found that in technological processes of heating and pressing oil, triglycerides disintegrated in aromas causing discomfort. In order to reduce this impact, the appropriate economic management method and odour removal equipment are to be chosen. When solving this problem it is suggested to install biofilters - activated carbon adsorbers with a stationary adsorber layer and probiotics. In order to choose the adsorber, a calculation method of adsorber technical parameters has been developed in accordance with literature data. The proposed preventive odour reduction means and feasibility of their technical and economical application have been analysed.DOI: http://dx.doi.org/10.5755/j01.erem.59.1.676

  15. Measuring and Modeling the U.S. Regulatory Ecosystem

    Science.gov (United States)

    Bommarito, Michael J., II; Katz, Daniel Martin

    2017-07-01

    Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.

  16. Measuring and Modeling the U.S. Regulatory Ecosystem

    Science.gov (United States)

    Bommarito, Michael J., II; Katz, Daniel Martin

    2017-09-01

    Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.

  17. Odour emissions from poultry litter - A review litter properties, odour formation and odorant emissions from porous materials.

    Science.gov (United States)

    Dunlop, Mark W; Blackall, Patrick J; Stuetz, Richard M

    2016-07-15

    Odour emissions from meat chicken sheds can at times cause odour impacts on surrounding communities. Litter is seen as the primary source of this odour. Formation and emission of odour from meat chicken litter during the grow-out period are influenced by various factors such as litter conditions, the environment, microbial activity, properties of the odorous gases and management practices. Odour emissions vary spatially and temporally. This variability has made it challenging to understand how specific litter conditions contribute to odour emissions from the litter and production sheds. Existing knowledge on odorants, odour formation mechanisms and emission processes that contribute to odour emissions from litter are reviewed. Litter moisture content and water thermodynamics (i.e. water activity, Aw) are also examined as factors that contribute to microbial odour formation, physical litter conditions and the exchange of individual odorant gases at the air-water interface. Substantial opportunities exist for future research on litter conditions and litter formation mechanisms and how these contribute to odour emissions. Closing this knowledge gap will improve management strategies that intercept and interfere with odour formation and emission processes leading to an overall reduction in the potential to cause community impacts.

  18. (Q)SAR modeling and safety assessment in regulatory review.

    Science.gov (United States)

    Kruhlak, N L; Benz, R D; Zhou, H; Colatsky, T J

    2012-03-01

    The ability to predict clinical safety based on chemical structures is becoming an increasingly important part of regulatory decision making. (Quantitative) structure-activity relationship ((Q)SAR) models are currently used to evaluate late-arising safety concerns and possible nonclinical effects of a drug and its related compounds when adequate safety data are absent or equivocal. Regulatory use will likely increase with the standardization of analytical approaches, more complete and reliable data collection methods, and a better understanding of toxicity mechanisms.

  19. Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells

    Science.gov (United States)

    Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

    1996-01-01

    Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

  20. A stochastic differential equation model for transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Quirk Michelle D

    2007-05-01

    Full Text Available Abstract Background This work explores the quantitative characteristics of the local transcriptional regulatory network based on the availability of time dependent gene expression data sets. The dynamics of the gene expression level are fitted via a stochastic differential equation model, yielding a set of specific regulators and their contribution. Results We show that a beta sigmoid function that keeps track of temporal parameters is a novel prototype of a regulatory function, with the effect of improving the performance of the profile prediction. The stochastic differential equation model follows well the dynamic of the gene expression levels. Conclusion When adapted to biological hypotheses and combined with a promoter analysis, the method proposed here leads to improved models of the transcriptional regulatory networks.

  1. Calculation of odour emissions from aircraft engines at Copenhagen Airport.

    Science.gov (United States)

    Winther, Morten; Kousgaard, Uffe; Oxbøl, Arne

    2006-07-31

    In a new approach the odour emissions from aircraft engines at Copenhagen Airport are calculated using actual fuel flow and emission measurements (one main engine and one APU: Auxiliary Power Unit), odour panel results, engine specific data and aircraft operational data for seven busy days. The calculation principle assumes a linear relation between odour and HC emissions. Using a digitalisation of the aircraft movements in the airport area, the results are depicted on grid maps, clearly reflecting aircraft operational statistics as single flights or total activity during a whole day. The results clearly reflect the short-term temporal fluctuations of the emissions of odour (and exhaust gases). Aircraft operating at low engine thrust (taxiing, queuing and landing) have a total odour emission share of almost 98%, whereas the shares for the take off/climb out phases (2%) and APU usage (0.5%) are only marginal. In most hours of the day, the largest odour emissions occur, when the total amount of fuel burned during idle is high. However, significantly higher HC emissions for one specific engine cause considerable amounts of odour emissions during limited time periods. The experimentally derived odour emission factor of 57 OU/mg HC is within the range of 23 and 110 OU/mg HC used in other airport odour studies. The distribution of odour emission results between aircraft operational phases also correspond very well with the results for these other studies. The present study uses measurement data for a representative engine. However, the uncertainties become large when the experimental data is used to estimate the odour emissions for all aircraft engines. More experimental data is needed to increase inventory accuracy, and in terms of completeness it is recommended to make odour emission estimates also for engine start and the fuelling of aircraft at Copenhagen Airport in the future.

  2. Relative Contribution of Odour Intensity and Valence to Moral Decisions.

    Science.gov (United States)

    Cecchetto, Cinzia; Rumiati, Raffaella Ida; Parma, Valentina

    2017-01-01

    Meta-analytic evidence showed that the chemical senses affect moral decisions. However, how odours impact on morality is currently unclear. Through a set of three studies, we assess whether and how odour intensity biases moral choices (Study 1a), its psychophysiological responses (Study 1b), as well as the behavioural and psychophysiological effects of odour valence on moral choices (Study 2). Study 1a suggests that the presence of an odour plays a role in shaping moral choice. Study 1b reveals that of two iso-pleasant versions of the same neutral odour, only the one presented sub-threshold (vs. supra-threshold) favours deontological moral choices, those based on the principle of not harming others even when such harm provides benefits. As expected, this odour intensity effect is tracked by skin conductance responses, whereas no difference in cardiac activity - proxy for the valence dimension - is revealed. Study 2 suggests that the same neutral odour presented sub-threshold increases deontological choices even when compared to iso-intense ambiguous odour, perceived as pleasant or unpleasant by half of the participants, respectively. Skin conductance responses, as expected, track odour pleasantness, but cardiac activity fails to do so. Results are discussed in the context of mechanisms alternative to disgust induction underlying moral choices.

  3. Modeling regulatory networks with weight matrices

    DEFF Research Database (Denmark)

    Weaver, D.C.; Workman, Christopher; Stormo, Gary D.

    1999-01-01

    Systematic gene expression analyses provide comprehensive information about the transcriptional responseto different environmental and developmental conditions. With enough gene expression data points,computational biologists may eventually generate predictive computer models of transcription reg...

  4. Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour

    OpenAIRE

    Suarez, F.; Springfield, J; Levitt, M

    1998-01-01

    Background/Aims—While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour. 
Methods—Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus ...

  5. User's instructions for the erythropoiesis regulatory model

    Science.gov (United States)

    1978-01-01

    The purpose of the model provides a method to analyze some of the events that could account for the decrease in red cell mass observed in crewmen returning from space missions. The model is based on the premise that erythrocyte production is governed by the balance between oxygen supply and demand at a renal sensing site. Oxygen supply is taken to be a function of arterial oxygen tension, mean corpuscular hemoglobin concentration, oxy-hemoglobin carrying capacity, hematocrit, and blood flow. Erythrocyte destruction is based on the law of mass action. The instantaneous hematocrit value is derived by integrating changes in production and destruction rates and accounting for the degree of plasma dilution.

  6. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of ne

  7. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of

  8. Autonomous Boolean modelling of developmental gene regulatory networks

    Science.gov (United States)

    Cheng, Xianrui; Sun, Mengyang; Socolar, Joshua E. S.

    2013-01-01

    During early embryonic development, a network of regulatory interactions among genes dynamically determines a pattern of differentiated tissues. We show that important timing information associated with the interactions can be faithfully represented in autonomous Boolean models in which binary variables representing expression levels are updated in continuous time, and that such models can provide a direct insight into features that are difficult to extract from ordinary differential equation (ODE) models. As an application, we model the experimentally well-studied network controlling fly body segmentation. The Boolean model successfully generates the patterns formed in normal and genetically perturbed fly embryos, permits the derivation of constraints on the time delay parameters, clarifies the logic associated with different ODE parameter sets and provides a platform for studying connectivity and robustness in parameter space. By elucidating the role of regulatory time delays in pattern formation, the results suggest new types of experimental measurements in early embryonic development. PMID:23034351

  9. Canalization and symmetry in Boolean models for genetic regulatory networks

    Energy Technology Data Exchange (ETDEWEB)

    Reichhardt, C J Olson [Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Bassler, Kevin E [Department of Physics, University of Houston, Houston, TX 77204-5005 (United States)

    2007-04-20

    Canalization of genetic regulatory networks has been argued to be favoured by evolutionary processes due to the stability that it can confer to phenotype expression. We explore whether a significant amount of canalization and partial canalization can arise in purely random networks in the absence of evolutionary pressures. We use a mapping of the Boolean functions in the Kauffman N-K model for genetic regulatory networks onto a k-dimensional Ising hypercube (where k = K) to show that the functions can be divided into different classes strictly due to geometrical constraints. The classes can be counted and their properties determined using results from group theory and isomer chemistry. We demonstrate that partially canalizing functions completely dominate all possible Boolean functions, particularly for higher k. This indicates that partial canalization is extremely common, even in randomly chosen networks, and has implications for how much information can be obtained in experiments on native state genetic regulatory networks.

  10. Odourant dominance in olfactory mixture processing: what makes a strong odourant?

    Science.gov (United States)

    Schubert, Marco; Sandoz, Jean-Christophe; Galizia, Giovanni; Giurfa, Martin

    2015-03-07

    The question of how animals process stimulus mixtures remains controversial as opposing views propose that mixtures are processed analytically, as the sum of their elements, or holistically, as unique entities different from their elements. Overshadowing is a widespread phenomenon that can help decide between these alternatives. In overshadowing, an individual trained with a binary mixture learns one element better at the expense of the other. Although element salience (learning success) has been suggested as a main explanation for overshadowing, the mechanisms underlying this phenomenon remain unclear. We studied olfactory overshadowing in honeybees to uncover the mechanisms underlying olfactory-mixture processing. We provide, to our knowledge, the most comprehensive dataset on overshadowing to date based on 90 experimental groups involving more than 2700 bees trained either with six odourants or with their resulting 15 binary mixtures. We found that bees process olfactory mixtures analytically and that salience alone cannot predict overshadowing. After normalizing learning success, we found that an unexpected feature, the generalization profile of an odourant, was determinant for overshadowing. Odourants that induced less generalization enhanced their distinctiveness and became dominant in the mixture. Our study thus uncovers features that determine odourant dominance within olfactory mixtures and allows the referring of this phenomenon to differences in neural activity both at the receptor and the central level in the insect nervous system.

  11. Development of the Level 1 PSA Model for PGSFR Regulatory

    Energy Technology Data Exchange (ETDEWEB)

    Na, Hyun Ju; Lee, Yong Suk [FNC Tech., Yongin (Korea, Republic of); Shin, Andong; Suh, Nam Duk [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-10-15

    SFR (sodium-cooled fast reactor) is Gen-IV nuclear energy system, which is designed for stability, sustainability and proliferation resistance. KALIMER-600 and PGSFR (Prototype Gen-IV SFR) are under development in Korea with enhanced passive safety concepts, e.g. passive reactor shutdown, passive residual heat removal, and etc. Risk analysis from a regulatory perspective is necessary for regulatory body to support the safety and licensing review of SFR. Safety issues should be identified in the early design phase in order to prevent the unexpected cost increase and the delay of PGSFR licensing schedule. In this respect, the preliminary PSA Model of KALIMER-600 had been developed for regulatory. In this study, the development of PSA Level 1 Model is presented. The important impact factors in the risk analysis for the PGSFR, such as Core Damage Frequency (CDF), have been identified and the related safety insights have been derived. The PSA level 1 model for PGSFR regulatory is developed and the risk analysis is conducted. Regarding CDF, LOISF frequency, uncertainty parameter for passive system CCF, loss of 125V DC control center bus and damper CCF are identified as the important factors. Sensitivity analyses show that the CDF would be differentiated (lowered) according to their values.

  12. Regulatory ozone modeling: Status, directions, and research needs

    Energy Technology Data Exchange (ETDEWEB)

    Georgopoulos, P.G. [Environmental and Occupational Health Sciences Institute, Piscataway, NJ (United States)

    1995-03-01

    The Clean Air Act Amendments (CAAA) of 1990 have established selected comprehensive, three-dimensional, Photochemical Air Quality Simulation Models (PAQSMs) as the required regulatory tools for analyzing the urban and regional problem of high ambient ozone levels across the United States. These models are currently applied to study and establish strategies for meeting the National Ambient Air Quality Standard (NAAQS) for ozone in nonattainment areas; State Implementation Plans (SIPs) resulting from these efforts must be submitted to the U.S. Environmental Protection Agency (U.S. EPA) in November 1994. The following presentation provides an overview and discussion of the regulatory ozone modeling process and its implications. First, the PAQSM-based ozone attainment demonstration process is summarized in the framework of the 1994 SIPs. Then, following a brief overview of the representation of physical and chemical processes in PAOSMs, the essential attributes of standard modeling systems currently in regulatory use are presented in a nonmathematical, self-contained format, intended to provide a basic understanding of both model capabilities and limitations. The types of air quality, emission, and meteorological data needed for applying and evaluating PAOSMs are discussed, as well as the sources, availability, and limitations of existing databases. The issue of evaluating a model`s performance in order to accept it as a tool for policy making is discussed, and various methodologies for implementing this objective are summarized. 43 refs., 9 figs.

  13. Liking the odour, liking the food. Toddlers' liking of strongly flavoured foods correlates with liking of their odour.

    Science.gov (United States)

    Wagner, S; Issanchou, S; Chabanet, C; Lange, C; Schaal, B; Monnery-Patris, S

    2014-10-01

    Olfaction plays a significant role in the sensing of foods. However, little information is available at any age on the relationship between the hedonic responses to given food odours and the effective liking and disliking of foods bearing these same odours. The present study aimed to assess the relationships between food odour liking and liking of the corresponding foods. This study relied on a longitudinal design involving 235 toddlers who were assessed for both their observed liking of a set of food odours and their parent-reported liking of foods at 12 and 22 months. To assess odour liking, eight odorants representing pleasant and unpleasant foods were presented in bottles along with neutral stimuli. The participants' behaviour towards the odorized and control bottles was measured in terms of mouthing, a behaviour considered to reflect attraction. For each odorant, odour-liking scores were calculated relative to the control. The participants' food liking was rated by the parents at the periods 12-15 and 21-24 months. Positive correlations were found between the odour-liking scores for some of the odours and the liking of the associated foods. These correlations concerned foods with strong, unpleasant flavours at 12 months only, suggesting that the olfactory system acts as an 'alarm' system during this period of food transition. At 22 months, no significant correlations were found, except a marginal one for green vegetables. Whatever the age, no significant correlations were found for pleasant odours. Thus, some correlations were found between the observed odour liking for food-related odours and the liking for the corresponding foods. However, these relationships are subject to developmental fluctuations depending on the hedonic nature of the odorants and the age when infants are tested.

  14. Odour identification and discrimination in Dutch adults over 45 years

    NARCIS (Netherlands)

    Boesveldt, S.; Verbaan, D.; Knol, D.L.; Hilten, van J.J.; Berendse, H.W.

    2008-01-01

    OBJECTIVES: The aim of the study was to establish normative values for the two culture dependent components (odour identification and odour discrimination) of the "Sniffin' Sticks" test battery in the Dutch population over 45 years of age, and to assess the influence of age and sex on olfactory

  15. Odour identification and discrimination in Dutch adults over 45 years

    NARCIS (Netherlands)

    Boesveldt, S.; Verbaan, D.; Knol, D.L.; Hilten, van J.J.; Berendse, H.W.

    2008-01-01

    OBJECTIVES: The aim of the study was to establish normative values for the two culture dependent components (odour identification and odour discrimination) of the "Sniffin' Sticks" test battery in the Dutch population over 45 years of age, and to assess the influence of age and sex on olfactory func

  16. The scent of mixtures: rules of odour processing in ants.

    Science.gov (United States)

    Perez, Margot; Giurfa, Martin; d'Ettorre, Patrizia

    2015-03-02

    Natural odours are complex blends of numerous components. Understanding how animals perceive odour mixtures is central to multiple disciplines. Here we focused on carpenter ants, which rely on odours in various behavioural contexts. We studied overshadowing, a phenomenon that occurs when animals having learnt a binary mixture respond less to one component than to the other, and less than when this component was learnt alone. Ants were trained individually with alcohols and aldehydes varying in carbon-chain length, either as single odours or binary mixtures. They were then tested with the mixture and the components. Overshadowing resulted from the interaction between chain length and functional group: alcohols overshadowed aldehydes, and longer chain lengths overshadowed shorter ones; yet, combinations of these factors could cancel each other and suppress overshadowing. Our results show how ants treat binary olfactory mixtures and set the basis for predictive analyses of odour perception in insects.

  17. Antimicrobial textiles, skin-borne flora and odour.

    Science.gov (United States)

    Höfer, Dirk

    2006-01-01

    Along with climate and physical activity, textiles have an effect on sweating and the development of odours. Accordingly, textiles inadequately optimized in terms of clothing technology as a result of poorly cut structures or poor materials result in increased sweating and odour. However, the development of body odour itself cannot be avoided, even with optimally designed clothing. Therefore new textiles, 'treated with antimicrobial agents', have been developed, with the aim of reducing odour by decreasing the number of germs on the skin. From the scientific point of view, the interactions between textiles, sweat, skin and skin flora are extremely complex. For this reason, this article explains in more detail the basic principles of odour formation resulting from sweat and how this can be influenced by textiles treated with antimicrobial agents. With reference to the results of recent research, the article looks into questions of how textiles treated with antimicrobial agents have an effect on populations of skin bacteria.

  18. Smelly and Dirty: Valence, not semantics, of odours prompt cleaning behaviour

    DEFF Research Database (Denmark)

    Dijksterhuis, Garmt Bernard; Zandstra, Elizabeth; de Wijk, Rene;

    Odours typically associated with cleaning products, such as citrus, have been reported to activate cleaning behaviours. The aim of the present study was to test whether odours in general or pleasant odours specifically, would also do so. Furthermore, the concentration of the odour might be expect...

  19. Psychophysical properties of odour processing can be quantitatively described by relative AP latency patterns in mitral and tufted cells

    Directory of Open Access Journals (Sweden)

    Andreas T. Schaefer

    2012-05-01

    Full Text Available Electrophysiological and population imaging data in rodents show that olfactory bulb(OB activity is profoundly modulated by the odour sampling process while behavioralexperiments indicate that odour discrimination can occur within a single sniff. Thispaper addresses the question of whether action potential (AP latencies occurring acrossthe mitral and tufted cell (M/TC population within an individual sampling cycle couldaccount for the psychophysical properties of odour processing. To determine this wecreated an OB model (50 000 M/TCs exhibiting hallmarks of published in vivoproperties and used a template-matching algorithm to assess stimulus separation. Suchan AP latency-based scheme showed high reproducibility and sensitivity such that odourstimuli could be reliably separated independent of concentration. As in behavioralexperiments we found that very dissimilar odours (A vs B were accurately andrapidly discerned while very similar odours (binary mixtures, 0.4A/0.6B vs 0.6A/0.4Brequired up to 90 ms longer. As in lesion studies we find that AP latency-basedrepresentation is rather insensitive to disruption of large regions of the OB. The APlatency-based scheme described here therefore captures both temporal andpsychophysical properties of olfactory processing and suggests that the onset patterns ofM/TC activity in the OB represent stimulus specific features of olfactory stimuli.

  20. Dynamical modeling and analysis of large cellular regulatory networks

    Science.gov (United States)

    Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

    2013-06-01

    The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

  1. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    Science.gov (United States)

    Meng, Jia; Zhang, Jianqiu(Michelle); Qi, Yuan(Alan); Chen, Yidong; Huang, Yufei

    2010-12-01

    The problem of uncovering transcriptional regulation by transcription factors (TFs) based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM) is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ([InlineEquation not available: see fulltext.]) status and Estrogen Receptor negative ([InlineEquation not available: see fulltext.]) status, respectively.

  2. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    Directory of Open Access Journals (Sweden)

    Qi Yuan(Alan

    2010-01-01

    Full Text Available Abstract The problem of uncovering transcriptional regulation by transcription factors (TFs based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ( status and Estrogen Receptor negative ( status, respectively.

  3. STREAM: Static Thermodynamic REgulAtory Model of transcription.

    Science.gov (United States)

    Bauer, Denis C; Bailey, Timothy L

    2008-11-01

    Understanding the transcriptional regulation of a gene in detail is a crucial step towards uncovering and ultimately utilizing the regulatory grammar of the genome. Modeling transcriptional regulation using thermodynamic equations has become an increasingly important approach towards this goal. Here, we present stream, the first publicly available framework for modeling, visualizing and predicting the regulation of the transcription rate of a target gene. Given the concentrations of a set of transcription factors (TFs), the TF binding sites (TFBSs) in a regulatory DNA region, and the transcription rate of the target gene, stream will optimize its parameters to generate a model that best fits the input data. This trained model can then be used to (a) validate that the given set of TFs is able to regulate the target gene and (b) to predict the transcription rate under different conditions (e.g. different tissues, knockout/additional TFs or mutated/missing TFBSs). The platform independent executable of stream, as well as a tutorial and the full documentation, are available at http://bioinformatics.org.au/stream/. stream requires Java version 5 or higher.

  4. sanative measures against offensive odour that affect indigenous ...

    African Journals Online (AJOL)

    User

    ing of leather in a soapy water made with perfume toilet-soap after which drying is done under room temperature. ... sive odour in the indigenous tanned leathers and leather products. .... makers use both natural and artificial chemicals.

  5. Insights from Development of Regulatory PSA Model for SMART

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Ju; Cho, Nam Chul [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Kim, Inn Seock [ISSA Technology, Maryland (United States); Lee, Yong Suk [Seoul National University, Seoul (Korea, Republic of)

    2010-10-15

    SMART (System-Integrated Modular Advanced Reactor) is a first-of-the-kind integral reactor with 330 MW thermal power under active development by Korea Atomic Energy Research Institute (KAERI) for power generation and seawater desalination. SMART employs various design features that are not typically found in other nuclear power plants. Examples include a unique passive residual heat removal system (PRHRS), and enclosure of a pressurizer, eight helical steam generators, and eight canned reactor coolant pumps inside the reactor pressure vessel. This paper presents risk insights on the SMART reactor gained during the development of a regulatory PSA model by Korea Institute of Nuclear Safety (KINS)

  6. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  7. Analysis of deterministic cyclic gene regulatory network models with delays

    CERN Document Server

    Ahsen, Mehmet Eren; Niculescu, Silviu-Iulian

    2015-01-01

    This brief examines a deterministic, ODE-based model for gene regulatory networks (GRN) that incorporates nonlinearities and time-delayed feedback. An introductory chapter provides some insights into molecular biology and GRNs. The mathematical tools necessary for studying the GRN model are then reviewed, in particular Hill functions and Schwarzian derivatives. One chapter is devoted to the analysis of GRNs under negative feedback with time delays and a special case of a homogenous GRN is considered. Asymptotic stability analysis of GRNs under positive feedback is then considered in a separate chapter, in which conditions leading to bi-stability are derived. Graduate and advanced undergraduate students and researchers in control engineering, applied mathematics, systems biology and synthetic biology will find this brief to be a clear and concise introduction to the modeling and analysis of GRNs.

  8. Comparison of evolutionary algorithms in gene regulatory network model inference.

    LENUS (Irish Health Repository)

    2010-01-01

    ABSTRACT: BACKGROUND: The evolution of high throughput technologies that measure gene expression levels has created a data base for inferring GRNs (a process also known as reverse engineering of GRNs). However, the nature of these data has made this process very difficult. At the moment, several methods of discovering qualitative causal relationships between genes with high accuracy from microarray data exist, but large scale quantitative analysis on real biological datasets cannot be performed, to date, as existing approaches are not suitable for real microarray data which are noisy and insufficient. RESULTS: This paper performs an analysis of several existing evolutionary algorithms for quantitative gene regulatory network modelling. The aim is to present the techniques used and offer a comprehensive comparison of approaches, under a common framework. Algorithms are applied to both synthetic and real gene expression data from DNA microarrays, and ability to reproduce biological behaviour, scalability and robustness to noise are assessed and compared. CONCLUSIONS: Presented is a comparison framework for assessment of evolutionary algorithms, used to infer gene regulatory networks. Promising methods are identified and a platform for development of appropriate model formalisms is established.

  9. Food Preference and Appetite after Switching between Sweet and Savoury Odours in Women.

    Science.gov (United States)

    Ramaekers, Mariëlle G; Luning, Pieternel A; Lakemond, Catriona M M; van Boekel, Martinus A J S; Gort, Gerrit; Boesveldt, Sanne

    2016-01-01

    Exposure to food odours increases the appetite for congruent foods and decreases the appetite for incongruent foods. However, the effect of exposure to a variety of food odours, as often occurs in daily life, is unknown. Investigate how switching between sweet and savoury odours affects the appetite for sweet and savoury products. Thirty women (age: 18-45y; BMI: 18.5-25kg/m2) intensely smelled the contents of cups filled with banana, meat or water (no-odour) in a within-subject design with four combinations: no-odour/banana, no-odour/meat, meat/banana and banana/meat. Participants received one combination per test day. In each combination, two cups with different fillings were smelled for five minutes after each other. Treatment order was balanced as much as possible. The effects of previous exposure and current odour on the appetite for (in)congruent sweet and savoury products, and odour pleasantness were analysed. A change from meat to banana odour or banana to meat odour was referred to as switch, whereas a change from no-odour to meat odour or no-odour to banana odour was no-switch. The current odour (Pfood remained elevated during odour exposure, known as sensory-specific appetite, whereas the pleasantness of the odour decreased over time, previously termed olfactory sensory-specific satiety. This seeming contradiction may result from different mechanisms underlying the odour-induced anticipation of food intake versus the decrease in hedonic value during prolonged sensory stimulation.

  10. Modeling gene regulatory networks: A network simplification algorithm

    Science.gov (United States)

    Ferreira, Luiz Henrique O.; de Castro, Maria Clicia S.; da Silva, Fabricio A. B.

    2016-12-01

    Boolean networks have been used for some time to model Gene Regulatory Networks (GRNs), which describe cell functions. Those models can help biologists to make predictions, prognosis and even specialized treatment when some disturb on the GRN lead to a sick condition. However, the amount of information related to a GRN can be huge, making the task of inferring its boolean network representation quite a challenge. The method shown here takes into account information about the interactome to build a network, where each node represents a protein, and uses the entropy of each node as a key to reduce the size of the network, allowing the further inferring process to focus only on the main protein hubs, the ones with most potential to interfere in overall network behavior.

  11. Cumulative effects of noise and odour annoyances on environmental and health related quality of life.

    Science.gov (United States)

    Oiamo, Tor H; Luginaah, Isaac N; Baxter, Jamie

    2015-12-01

    Noise and odour annoyances are important considerations in research on health effects of air pollution and traffic noise. Cumulative exposures can occur via several chemical hazards or a combination of chemical and stressor-based hazards, and related health outcomes can be generalized as manifestations of physiological and/or psychological stress responses. A major research challenge in this field is to understand the combined health effects of physiological and psychological responses to exposure. The SF-12 Health Survey is a health related quality of life (HRQoL) instrument designed for the assessment of functional mental and physical health in clinical practice and therefore well suited to research on physiological health outcomes of exposure. However, previous research has not assessed its sensitivity to psychological stress as measured by noise annoyance and odour annoyance. The current study validated and tested this application of the SF-12 Health Survey in a cross-sectional study (n = 603) that included exposure assessment for traffic noise and air pollution in Windsor, Ontario, Canada. The results indicated that SF-12 scores in Windsor were lower than Canadian normative data. A structural equation model demonstrated that this was partially due to noise and odour annoyances, which were associated with covarying exposures to ambient nitrogen dioxide and traffic noise. More specifically, noise annoyance had a significant and negative effect on both mental and physical health factors of the SF-12 and there was a significant covariance between noise annoyance and odour annoyance. The study confirmed a significant effect of psychological responses to cumulative exposures on HRQoL. The SF-12 Health Survey shows promise with respect to assessing the cumulative health effects of outdoor air pollution and traffic noise.

  12. A Longitudinal Study of Decomposition Odour in Soil Using Sorbent Tubes and Solid Phase Microextraction

    Directory of Open Access Journals (Sweden)

    Katelynn A. Perrault

    2014-07-01

    Full Text Available Odour profiling of decomposed remains is important for understanding the mechanisms that cadaver dogs and forensically-relevant insects use to locate decomposed remains. The decomposition odour profile is complex and has been documented in outdoor terrestrial environments. The purpose of this study was to perform longitudinal analysis of the volatile organic compound (VOC profile in soils associated with decomposed remains across all stages of decomposition. Two VOC collection techniques (sorbent tubes and solid phase microextraction were used to collect a wider analyte range and to investigate differences in collection techniques. Pig carcasses were placed in an outdoor research facility in Australia to model the decomposition process and VOCs were collected intermittently over two months. VOCs of interest were identified over the duration of the trial, showing distinct trends in compound evolution and disappearance. The collection techniques were complementary, representing different subsets of VOCs from the overall profile. Sorbent tubes collected more decomposition-specific VOCs and these compounds were more effective at characterising the matrix over an extended period. Using both collection techniques improves the likelihood of identifying the complete VOC profile of decomposition odour. Such information is important for the search and recovery of victim remains in various stages of decomposition.

  13. Modelling non-stationary dynamic gene regulatory processes with the BGM model

    NARCIS (Netherlands)

    Grzegorczyk, Marco; Husmeier, Dirk; Rahnenfuehrer, Joerg

    2011-01-01

    Recently, a Bayesian network model for inferring non-stationary regulatory processes from gene expression time series has been proposed. The Bayesian Gaussian Mixture (BGM) Bayesian network model divides the data into disjunct compartments (data subsets) by a free allocation model, and infers networ

  14. An ensemble model of QSAR tools for regulatory risk assessment.

    Science.gov (United States)

    Pradeep, Prachi; Povinelli, Richard J; White, Shannon; Merrill, Stephen J

    2016-01-01

    Quantitative structure activity relationships (QSARs) are theoretical models that relate a quantitative measure of chemical structure to a physical property or a biological effect. QSAR predictions can be used for chemical risk assessment for protection of human and environmental health, which makes them interesting to regulators, especially in the absence of experimental data. For compatibility with regulatory use, QSAR models should be transparent, reproducible and optimized to minimize the number of false negatives. In silico QSAR tools are gaining wide acceptance as a faster alternative to otherwise time-consuming clinical and animal testing methods. However, different QSAR tools often make conflicting predictions for a given chemical and may also vary in their predictive performance across different chemical datasets. In a regulatory context, conflicting predictions raise interpretation, validation and adequacy concerns. To address these concerns, ensemble learning techniques in the machine learning paradigm can be used to integrate predictions from multiple tools. By leveraging various underlying QSAR algorithms and training datasets, the resulting consensus prediction should yield better overall predictive ability. We present a novel ensemble QSAR model using Bayesian classification. The model allows for varying a cut-off parameter that allows for a selection in the desirable trade-off between model sensitivity and specificity. The predictive performance of the ensemble model is compared with four in silico tools (Toxtree, Lazar, OECD Toolbox, and Danish QSAR) to predict carcinogenicity for a dataset of air toxins (332 chemicals) and a subset of the gold carcinogenic potency database (480 chemicals). Leave-one-out cross validation results show that the ensemble model achieves the best trade-off between sensitivity and specificity (accuracy: 83.8 % and 80.4 %, and balanced accuracy: 80.6 % and 80.8 %) and highest inter-rater agreement [kappa (κ): 0

  15. Fixed Points in Discrete Models for Regulatory Genetic Networks

    Directory of Open Access Journals (Sweden)

    Orozco Edusmildo

    2007-01-01

    Full Text Available It is desirable to have efficient mathematical methods to extract information about regulatory iterations between genes from repeated measurements of gene transcript concentrations. One piece of information is of interest when the dynamics reaches a steady state. In this paper we develop tools that enable the detection of steady states that are modeled by fixed points in discrete finite dynamical systems. We discuss two algebraic models, a univariate model and a multivariate model. We show that these two models are equivalent and that one can be converted to the other by means of a discrete Fourier transform. We give a new, more general definition of a linear finite dynamical system and we give a necessary and sufficient condition for such a system to be a fixed point system, that is, all cycles are of length one. We show how this result for generalized linear systems can be used to determine when certain nonlinear systems (monomial dynamical systems over finite fields are fixed point systems. We also show how it is possible to determine in polynomial time when an ordinary linear system (defined over a finite field is a fixed point system. We conclude with a necessary condition for a univariate finite dynamical system to be a fixed point system.

  16. Global QSAR models of skin sensitisers for regulatory purposes

    Directory of Open Access Journals (Sweden)

    Price Nick R

    2010-07-01

    Full Text Available Abstract Background The new European Regulation on chemical safety, REACH, (Registration, Evaluation, Authorisation and Restriction of CHemical substances, is in the process of being implemented. Many chemicals used in industry require additional testing to comply with the REACH regulations. At the same time EU member states are attempting to reduce the number of animals used in experiments under the 3 Rs policy, (refining, reducing, and replacing the use of animals in laboratory procedures. Computational techniques such as QSAR have the potential to offer an alternative for generating REACH data. The FP6 project CAESAR was aimed at developing QSAR models for 5 key toxicological endpoints of which skin sensitisation was one. Results This paper reports the development of two global QSAR models using two different computational approaches, which contribute to the hybrid model freely available online. Conclusions The QSAR models for assessing skin sensitisation have been developed and tested under stringent quality criteria to fulfil the principles laid down by the OECD. The final models, accessible from CAESAR website, offer a robust and reliable method of assessing skin sensitisation for regulatory use.

  17. Food Preference and Appetite after Switching between Sweet and Savoury Odours in Women.

    Directory of Open Access Journals (Sweden)

    Mariëlle G Ramaekers

    Full Text Available Exposure to food odours increases the appetite for congruent foods and decreases the appetite for incongruent foods. However, the effect of exposure to a variety of food odours, as often occurs in daily life, is unknown.Investigate how switching between sweet and savoury odours affects the appetite for sweet and savoury products.Thirty women (age: 18-45y; BMI: 18.5-25kg/m2 intensely smelled the contents of cups filled with banana, meat or water (no-odour in a within-subject design with four combinations: no-odour/banana, no-odour/meat, meat/banana and banana/meat. Participants received one combination per test day. In each combination, two cups with different fillings were smelled for five minutes after each other. Treatment order was balanced as much as possible. The effects of previous exposure and current odour on the appetite for (incongruent sweet and savoury products, and odour pleasantness were analysed. A change from meat to banana odour or banana to meat odour was referred to as switch, whereas a change from no-odour to meat odour or no-odour to banana odour was no-switch.The current odour (P<0.001, as opposed to the previous exposure (P = 0.71, determined the appetite for (incongruent sweet and savoury products, already one minute after a switch between sweet and savoury odours. The pleasantness of the odour decreased during odour exposure (P = 0.005.After a switch, the appetite for specific products quickly adjusted to the new odour and followed the typical pattern as found during odour exposure in previous studies. Interestingly, the appetite for the smelled food remained elevated during odour exposure, known as sensory-specific appetite, whereas the pleasantness of the odour decreased over time, previously termed olfactory sensory-specific satiety. This seeming contradiction may result from different mechanisms underlying the odour-induced anticipation of food intake versus the decrease in hedonic value during prolonged sensory

  18. Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

    Science.gov (United States)

    Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

    2016-05-01

    Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

  19. Ecological models for regulatory risk assessments of pesticides: Developing a strategy for the future.

    NARCIS (Netherlands)

    Thorbek, P.; Forbes, V.; Heimbach, F.; Hommen, U.; Thulke, H.H.; Brink, van den P.J.

    2010-01-01

    Ecological Models for Regulatory Risk Assessments of Pesticides: Developing a Strategy for the Future provides a coherent, science-based view on ecological modeling for regulatory risk assessments. It discusses the benefits of modeling in the context of registrations, identifies the obstacles that p

  20. Identifying gene regulatory network rewiring using latent differential graphical models.

    Science.gov (United States)

    Tian, Dechao; Gu, Quanquan; Ma, Jian

    2016-09-30

    Gene regulatory networks (GRNs) are highly dynamic among different tissue types. Identifying tissue-specific gene regulation is critically important to understand gene function in a particular cellular context. Graphical models have been used to estimate GRN from gene expression data to distinguish direct interactions from indirect associations. However, most existing methods estimate GRN for a specific cell/tissue type or in a tissue-naive way, or do not specifically focus on network rewiring between different tissues. Here, we describe a new method called Latent Differential Graphical Model (LDGM). The motivation of our method is to estimate the differential network between two tissue types directly without inferring the network for individual tissues, which has the advantage of utilizing much smaller sample size to achieve reliable differential network estimation. Our simulation results demonstrated that LDGM consistently outperforms other Gaussian graphical model based methods. We further evaluated LDGM by applying to the brain and blood gene expression data from the GTEx consortium. We also applied LDGM to identify network rewiring between cancer subtypes using the TCGA breast cancer samples. Our results suggest that LDGM is an effective method to infer differential network using high-throughput gene expression data to identify GRN dynamics among different cellular conditions.

  1. Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour.

    Science.gov (United States)

    Suarez, F L; Springfield, J; Levitt, M D

    1998-07-01

    While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour. Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus output. The concentrations of sulphur-containing gases in each passage were correlated with odour intensity assessed by two judges. Odour intensity was also determined after treatment of flatus samples with zinc acetate, which binds sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal. Utilising gastight Mylar pantaloons, the ability of a charcoal lined cushion to adsorb sulphur-containing gases instilled at the anus of eight subjects was assessed. The main sulphur-containing flatus component was hydrogen sulphide (1.06 (0.2) mumol/l), followed by methanethiol (0.21 (0.04) mumol/l) and dimethyl sulphide (0.08 (0.01) mumol/l) (means (SEM)). Malodour significantly correlated with hydrogen sulphide concentration (p flatus. The charcoal lined cushion effectively limits the escape of these sulphur-containing gases into the environment.

  2. Multivariate Hawkes process models of the occurrence of regulatory elements

    DEFF Research Database (Denmark)

    Carstensen, L; Sandelin, A; Winther, Ole

    2010-01-01

    BACKGROUND: A central question in molecular biology is how transcriptional regulatory elements (TREs) act in combination. Recent high-throughput data provide us with the location of multiple regulatory regions for multiple regulators, and thus with the possibility of analyzing the multivariate di...

  3. Fish odour triggers conspecific attraction behaviour in an aquatic invertebrate.

    Science.gov (United States)

    Kullmann, Harald; Thünken, Timo; Baldauf, Sebastian A; Bakker, Theo C M; Frommen, Joachim G

    2008-10-23

    Group living has evolved as an adaptation to predation in many animal species. In a multitude of vertebrates, the tendency to aggregate varies with the risk of predation, but experimental evidence for this is less well known in invertebrates. Here, we examine the tendency to aggregate in the freshwater amphipod Gammarus pulex in the absence and presence of predator fish odour. Without fish odour, the gammarids showed no significant tendency to aggregate. In contrast to this, in fish-conditioned water, they significantly preferred to stay close to conspecifics. Predation risk can, thus, influence gammarids social behaviour.

  4. Flatus, odour and the ostomist: coping strategies and interventions.

    Science.gov (United States)

    Williams, Julia

    Both new and established ostomists fear the loss of control over their bodily function that stoma surgery brings about. They often express feelings of embarrassment and isolation as they try and adjust to their new lifestyle. Quality-of-life studies often highlight flatus and odour to be two of the top five fears or worries among ostomists. This article reviews the current literature offering an insight into how flatus and odour impacts on an ostomist's life and considers interventions to assist the nurse in aiding the ostomist through this period of adaptation.

  5. Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies

    NARCIS (Netherlands)

    Kelling, F.J; Ialenti, F.; den Otter, C.J

    2002-01-01

    The presence of background odour was found to have a small but significant effect on the sensitivity of the antennal olfactory system of houseflies, Musca domestica Linnaeus (Diptera: Muscidae), to new pulses of odour. We show that cross-adaptation and cross-sensitization between a background odour

  6. Modeling for regulatory purposes (risk and safety assessment).

    Science.gov (United States)

    El-Masri, Hisham

    2013-01-01

    Chemicals provide many key building blocks that are converted into end-use products or used in industrial processes to make products that benefit society. Ensuring the safety of chemicals and their associated products is a key regulatory mission. Current processes and procedures for evaluating and assessing the impact of chemicals on human health, wildlife, and the environment were, in general, designed decades ago. These procedures depend on generation of relevant scientific knowledge in the laboratory and interpretation of this knowledge to refine our understanding of the related potential health risks. In practice, this often means that estimates of dose-response and time-course behaviors for apical toxic effects are needed as a function of relevant levels of exposure. In many situations, these experimentally determined functions are constructed using relatively high doses in experimental animals. In absence of experimental data, the application of computational modeling is necessary to extrapolate risk or safety guidance values for human exposures at low but environmentally relevant levels.

  7. Multivariate Hawkes process models of the occurrence of regulatory elements

    DEFF Research Database (Denmark)

    Carstensen, L; Sandelin, A; Winther, Ole;

    2010-01-01

    BACKGROUND: A central question in molecular biology is how transcriptional regulatory elements (TREs) act in combination. Recent high-throughput data provide us with the location of multiple regulatory regions for multiple regulators, and thus with the possibility of analyzing the multivariate di...... occurrences of multiple TREs along the genome that is capable of providing new insights into dependencies among elements involved in transcriptional regulation. The method is available as an R package from http://www.math.ku.dk/~richard/ppstat/.......BACKGROUND: A central question in molecular biology is how transcriptional regulatory elements (TREs) act in combination. Recent high-throughput data provide us with the location of multiple regulatory regions for multiple regulators, and thus with the possibility of analyzing the multivariate...

  8. Learning Transcriptional Regulatory Relationships Using Sparse Graphical Models

    OpenAIRE

    Xiang Zhang; Wei Cheng; Jennifer Listgarten; Carl Kadie; Shunping Huang; Wei Wang; David Heckerman

    2012-01-01

    Understanding the organization and function of transcriptional regulatory networks by analyzing high-throughput gene expression profiles is a key problem in computational biology. The challenges in this work are 1) the lack of complete knowledge of the regulatory relationship between the regulators and the associated genes, 2) the potential for spurious associations due to confounding factors, and 3) the number of parameters to learn is usually larger than the number of available microarray e...

  9. The future of genome-scale modeling of yeast through integration of a transcriptional regulatory network

    DEFF Research Database (Denmark)

    Liu, Guodong; Marras, Antonio; Nielsen, Jens

    2014-01-01

    regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network (TRN) for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model......Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional...... transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner....

  10. Olfactory Specific Satiety depends on degree of association between odour and food.

    Science.gov (United States)

    Stafford, Lorenzo D

    2016-03-01

    The pleasantness of a food odour decreases when that food is eaten to satiety or even smelled for a brief period (Olfactory Specific Satiety, OSS), which suggests that odours signal food variety and encourage approach behaviour toward novel foods. In the study here, we aimed to extend this theory to understand the consequence of manipulating the food consumed and its degree of association to the evaluated odour. We also wished to clarify if these effects related to individual sensitivity to the target odour. In the study here, participants (n = 94) rated the pleasantness of a food odour (isoamyl acetate) and then consumed confectionary that had either Low or High association to that odour or a No food control. This was followed by final pleasantness ratings for the odour and a threshold sensitivity test. Results revealed that in line with OSS, pleasantness decreased in the High association group only. This effect was not dependent on any differences in sensitivity to the target odour. These findings are consistent with OSS, and that this effect likely depends on activation of brain areas related to odour hedonics rather than the degree to which the odour is detected.

  11. Trapping mosquitoes using milk products as odour baits in western Kenya

    Directory of Open Access Journals (Sweden)

    Owino Eunice A

    2010-06-01

    Full Text Available Abstract Background Ample evidence has shown that blood seeking mosquitoes locate their hosts by following odours produced by the hosts. Odour baited traps would therefore, provide a solution in controlling diseases spread by mosquitoes. Comparative studies were undertaken to determine the relative efficacies of two odour baits i.e. Limburger cheese and African traditional milk cream in trapping mosquitoes in the field in western Kenya. Method Comparative efficacy studies were carried out in the field using Latin square experimental designs. In the first study, a counterflow geometry (CFG trap (MM-x model; American Biophysics Corp., USA. baited with Limburger cheese, man landing catches (MLC, Centres for Disease Control (CDC light trap and an entry trap were compared. In the second study, three CFG traps baited with either Limburger cheese, African traditional milk cream or with no bait were compared and in the third study four CDC traps baited with either Limburger cheese, African traditional milk cream, light or with no bait were compared. Parameters like species, catch size, abdominal status, parity status and size of the collected mosquitoes were compared. Results A total of 1,806 mosquitoes were collected (60% An. gambiae s.l and 25% An.funestus, culicines 15%. There was no significant difference in the number of An. funestus trapped by the CFG trap baited with Limburger cheese from those trapped by the MLC (P = 0.351. The Limburger cheese baited CFG trap collected significantly more gravid An. funestus than the MLC (P = 0.022. Furthermore, when the CFG trap baited with Limburger cheese and the CFG trap baited with milk cream were compared, there was no significant difference in the number of An. funestus collected (P = 0.573. The same trend was observed in the comparison of Limburger cheese baited CDC trap and milk cream baited CDC trap. Conclusions Limburger cheese and African traditional milk cream have a potential as effective odour

  12. Stable Gene Regulatory Network Modeling From Steady-State Data

    Directory of Open Access Journals (Sweden)

    Joy Edward Larvie

    2016-04-01

    Full Text Available Gene regulatory networks represent an abstract mapping of gene regulations in living cells. They aim to capture dependencies among molecular entities such as transcription factors, proteins and metabolites. In most applications, the regulatory network structure is unknown, and has to be reverse engineered from experimental data consisting of expression levels of the genes usually measured as messenger RNA concentrations in microarray experiments. Steady-state gene expression data are obtained from measurements of the variations in expression activity following the application of small perturbations to equilibrium states in genetic perturbation experiments. In this paper, the least absolute shrinkage and selection operator-vector autoregressive (LASSO-VAR originally proposed for the analysis of economic time series data is adapted to include a stability constraint for the recovery of a sparse and stable regulatory network that describes data obtained from noisy perturbation experiments. The approach is applied to real experimental data obtained for the SOS pathway in Escherichia coli and the cell cycle pathway for yeast Saccharomyces cerevisiae. Significant features of this method are the ability to recover networks without inputting prior knowledge of the network topology, and the ability to be efficiently applied to large scale networks due to the convex nature of the method.

  13. On Walter ’s Otherness in Odour of Chrysanthemums

    Institute of Scientific and Technical Information of China (English)

    李嵩皎

    2015-01-01

    Odour of Chrysanthemums is one of the British writer D. H. Lawrence’s short stories. In the story, character’s understanding of each other reflects the idea of otherness. This paper tries to analyze both Walter’s mother and Elizabeth’s understanding of Walter Bates. Then it points out that they did not really understand him, nor did they understand his otherness. Their failure to understand his otherness is a reason to the unhappy marriage to some extent.

  14. Odour avoidance learning in the larva of Drosophila melanogaster

    Indian Academy of Sciences (India)

    Sukant Khurana; Mohammed Bin AbuBaker; Obaid Siddiqi

    2009-10-01

    Drosophila larvae can be trained to avoid odours associated with electric shock. We describe here, an improved method of aversive conditioning and a procedure for decomposing learning retention curve that enables us to do a quantitative analysis of memory phases, short term (STM), middle term (MTM) and long term (LTM) as a function of training cycles. The same method of analysis when applied to learning mutants dunce, amnesiac, rutabaga and radish reveals memory deficits characteristic of the mutant strains.

  15. Characteristic odour in the blood reveals ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Horvath György

    2010-11-01

    Full Text Available Abstract Background Ovarian carcinoma represents about 4% of all cancers diagnosed in women worldwide. Mortality rate is high, over 50%, mainly due to late diagnosis. Currently there are no acceptable screening techniques available, although ovarian cancer belongs to the group of malignancies for which mortality could be dramatically reduced by early diagnosis. In a recently published study, we clearly demonstrated that human ovarian carcinoma tissues can be characterized by a specific odour, detectable by a trained dog. Another recent study confirmed these results using an electronic nose. Methods In the present work, we examined whether the cancer-specific odour can also be found in the blood. Two specially trained dogs were used. Both ovarian cancer tissues and blood from patients with ovarian carcinoma were tested. Results The tissue tests showed sensitivity of 100% and specificity of 95%, while the blood tests showed sensitivity of 100% and specificity of 98%. Conclusions The present study strongly suggests that the characteristic odour emitted by ovarian cancer samples is also present in blood (plasma taken from patients with the disease. This finding opens possibilities for future screening of healthy populations for early diagnosis of ovarian carcinoma. A future challenge is to develop a sensitive electronic nose for screening of ovarian carcinoma by testing the blood/plasma to detect the disease at a stage early enough for treatment to be effective.

  16. The Influence of Distance and Atmospheric Elements on the Concentration of Odour from Refuse Derived Fuel (RDF Operations

    Directory of Open Access Journals (Sweden)

    Zaini Sakawi

    2013-08-01

    Full Text Available Odour is an environmental element that occurs as varieties of aroma, either pleasant or otherwise to its immediate community. The various sources of odour pollution may come from either natural or of human activities. Odour concentration may change due to environmental factors such as atmosphere, topography, distance and mitigation efforts. This study describes a study on the influence of distance and athmospheric elements on concentration of odour generated by the Refuse Derived Fuel (RDF operations. The distribution of odour concentration was measured using Odour concentration meter XP-329 III series per its distance from the RDF operations. The results indicated that distance factors did influence the odour concentration. Results at test stations of distances farther from the RDF showed incrementally higher distribution of odour concentration compared to those nearer to the RDF. In addition, athmosperic elements like temperatures, humidity, wind speed and directions also evidenlty linked to the distribution of odour concentration.

  17. Characterisation of low-odour emissive polylactide/cellulose fibre biocomposites for car interior

    Directory of Open Access Journals (Sweden)

    D. Rusu

    2013-09-01

    Full Text Available Low odour-emissive polylactide/cellulose fibre biocomposites, intended for car interior, were prepared and characterised. The impact of the different stages of processing (drying cycles, compounding, injection moulding on the extent of polylactide degradation and on biocomposites properties was investigated by size exclusion chromatography, thermogravimetry, differential scanning calorimetry. In parallel, the odour emission of these materials was quantified via dynamic dilution olfactometry and Field of odours® method. The changes in molecular weight and global odour emission indicated that compounding had a strong impact on polylactide degradation and odour emission, while injection moulding had no significant impact. Adding 0.5 wt% of an absorbent agent based on poly(1-methylpyrrol-2-ylsquaraine could divide the global odour concentration by a factor 2. The morphology, mechanical and thermal properties of injection moulded PLAbiocomposites were not affected by the presence of the absorbent agent.

  18. A review of taste and odour events in Barcelona's drinking water area (1990-2004).

    Science.gov (United States)

    Boleda, M R; Díaz, A; Martí, I; Martín-Alonso, J; Matia, L; Romero, J; Ventura, F

    2007-01-01

    The main, relevant, solved problems associated with taste and odour incidents in Barcelona's drinking water area in the last 14 years are reviewed. Events produced by creosote, dioxanes and dioxolanes, dicylopentadiene, and diacetyl, among the anthropogenic compounds; geosmin, MIB and iodinated trihalomethanes and chlorobromoanisoles as examples of compounds of natural origin are exemplified. The determination of the odour threshold concentrations of selected odorous compounds is also shown as a tool to gain a better knowledge of future taste and odour events.

  19. Modeling regulatory cascades using Artificial Neural Networks: the case of transcriptional regulatory networks shaped during the yeast stress response.

    Science.gov (United States)

    Manioudaki, Maria E; Poirazi, Panayiota

    2013-01-01

    Over the last decade, numerous computational methods have been developed in order to infer and model biological networks. Transcriptional networks in particular have attracted significant attention due to their critical role in cell survival. The majority of network inference methods use genome-wide experimental data to search for modules of genes with coherent expression profiles and common regulators, often ignoring the multi-layer structure of transcriptional cascades. Modeling methodologies on the other hand assume a given network structure and vary significantly in their algorithmic approach, ranging from over-simplified representations (e.g., Boolean networks) to detailed -but computationally expensive-network simulations (e.g., with differential equations). In this work we use Artificial Neural Networks (ANNs) to model transcriptional regulatory cascades that emerge during the stress response in Saccharomyces cerevisiae and extend in three layers. We confine the structure of the ANNs to match the structure of the biological networks as determined by gene expression, DNA-protein interaction and experimental evidence provided in publicly available databases. Trained ANNs are able to predict the expression profile of 11 target genes across multiple experimental conditions with a correlation coefficient >0.7. When time-dependent interactions between upstream transcription factors (TFs) and their indirect targets are also included in the ANNs, accurate predictions are achieved for 30/34 target genes. Moreover, heterodimer formation is taken into account. We show that ANNs can be used to (1) accurately predict the expression of downstream genes in a 3-layer transcriptional cascade based on the expression of their indirect regulators and (2) infer the condition- and time-dependent activity of various TFs as well as during heterodimer formation. We show that a three-layer regulatory cascade whose structure is determined by co-expressed gene modules and their

  20. Food preference and appetite after switching between sweet and savoury odours in women

    OpenAIRE

    Ramaekers, Mariëlle G.; Luning, Pieternel A.; Lakemond, Catriona M. M.; van Boekel, Martinus A.J.S.; Gerrit Gort; Sanne Boesveldt

    2016-01-01

    Background Exposure to food odours increases the appetite for congruent foods and decreases the appetite for incongruent foods. However, the effect of exposure to a variety of food odours, as often occurs in daily life, is unknown. Objective Investigate how switching between sweet and savoury odours affects the appetite for sweet and savoury products. Design Thirty women (age: 18-45y; BMI: 18.5-25kg/m2) intensely smelled the contents of cups filled with banana, meat or water (no-odour) in a w...

  1. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Directory of Open Access Journals (Sweden)

    Haitao Guo

    2017-01-01

    Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

  2. Comparison of different measurement methods of odour and odorants used in the odour impact assessment of wastewater treatment plants in Poland.

    Science.gov (United States)

    Barczak, Radosław J; Kulig, Andrzej

    2017-02-01

    The aim of this study was to compare sensory and analytical methods used to measure odour and odorants concentrations for odour impact assessment on municipal wastewater treatment plants (WWTPs). A range of sources and odour or odorants concentrations were used to compare the methods. Four different odours and odorants measurement methods were compared: field olfactometry using Nasal Ranger(®) field olfactometer, dynamic olfactometry according to PN-EN 13725:2007 standard, colorimetric assays (hydrogen sulphide, ammonia) and gas chromatography-mass spectrometry (GC-MS) methods (methanethiol, ethanethiol, dimethyl sulphide). Mechanical-biological and mechanical-biological-chemical WWTPs were chosen. Receptor points were selected inside of 'closed' facilities of the technological line (screening rooms, mechanical thickening and dewatering building) and downwind at 'open' facilities (collection chambers, sand trap, mechanical thickeners) which were the most significant regarding the potential for odour nuisance. By the research, it is not possible to specify explicit dependencies between results obtained from different research methods used in the odour impact assessment of WWTPs. A strong correlation (Pearson's correlation coefficient was equal R = 0.79) was determined only once between odour concentrations measured by dynamic olfactometry and methanethiol concentrations in the screen room at the WWTP No. 3.

  3. Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells

    Directory of Open Access Journals (Sweden)

    Guthke Reinhard

    2010-11-01

    Full Text Available Abstract Background Reverse engineering of gene regulatory networks can be used to predict regulatory interactions of an organism faced with environmental changes, but can prove problematic, especially when focusing on complicated multi-factorial processes. Candida albicans is a major human fungal pathogen. During the infection process, this fungus is able to adapt to conditions of very low iron availability. Such adaptation is an important virulence attribute of virtually all pathogenic microbes. Understanding the regulation of iron acquisition genes will extend our knowledge of the complex regulatory changes during the infection process and might identify new potential drug targets. Thus, there is a need for efficient modelling approaches predicting key regulatory events of iron acquisition genes during the infection process. Results This study deals with the regulation of C. albicans iron uptake genes during adhesion to and invasion into human oral epithelial cells. A reverse engineering strategy is presented, which is able to infer regulatory networks on the basis of gene expression data, making use of relevant selection criteria such as sparseness and robustness. An exhaustive use of available knowledge from different data sources improved the network prediction. The predicted regulatory network proposes a number of new target genes for the transcriptional regulators Rim101, Hap3, Sef1 and Tup1. Furthermore, the molecular mode of action for Tup1 is clarified. Finally, regulatory interactions between the transcription factors themselves are proposed. This study presents a model describing how C. albicans may regulate iron acquisition during contact with and invasion of human oral epithelial cells. There is evidence that some of the proposed regulatory interactions might also occur during oral infection. Conclusions This study focuses on a typical problem in Systems Biology where an interesting biological phenomenon is studied using a small

  4. A boolean model of the cardiac gene regulatory network determining first and second heart field identity.

    Directory of Open Access Journals (Sweden)

    Franziska Herrmann

    Full Text Available Two types of distinct cardiac progenitor cell populations can be identified during early heart development: the first heart field (FHF and second heart field (SHF lineage that later form the mature heart. They can be characterized by differential expression of transcription and signaling factors. These regulatory factors influence each other forming a gene regulatory network. Here, we present a core gene regulatory network for early cardiac development based on published temporal and spatial expression data of genes and their interactions. This gene regulatory network was implemented in a Boolean computational model. Simulations reveal stable states within the network model, which correspond to the regulatory states of the FHF and the SHF lineages. Furthermore, we are able to reproduce the expected temporal expression patterns of early cardiac factors mimicking developmental progression. Additionally, simulations of knock-down experiments within our model resemble published phenotypes of mutant mice. Consequently, this gene regulatory network retraces the early steps and requirements of cardiogenic mesoderm determination in a way appropriate to enhance the understanding of heart development.

  5. A Boolean Model of the Cardiac Gene Regulatory Network Determining First and Second Heart Field Identity

    Science.gov (United States)

    Zhou, Dao; Kestler, Hans A.; Kühl, Michael

    2012-01-01

    Two types of distinct cardiac progenitor cell populations can be identified during early heart development: the first heart field (FHF) and second heart field (SHF) lineage that later form the mature heart. They can be characterized by differential expression of transcription and signaling factors. These regulatory factors influence each other forming a gene regulatory network. Here, we present a core gene regulatory network for early cardiac development based on published temporal and spatial expression data of genes and their interactions. This gene regulatory network was implemented in a Boolean computational model. Simulations reveal stable states within the network model, which correspond to the regulatory states of the FHF and the SHF lineages. Furthermore, we are able to reproduce the expected temporal expression patterns of early cardiac factors mimicking developmental progression. Additionally, simulations of knock-down experiments within our model resemble published phenotypes of mutant mice. Consequently, this gene regulatory network retraces the early steps and requirements of cardiogenic mesoderm determination in a way appropriate to enhance the understanding of heart development. PMID:23056457

  6. Combination of Neuro-Fuzzy Network Models with Biological Knowledge for Reconstructing Gene Regulatory Networks

    Institute of Scientific and Technical Information of China (English)

    Guixia Liu; Lei Liu; Chunyu Liu; Ming Zheng; Lanying Su; Chunguang Zhou

    2011-01-01

    Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly, in this paper, we propose a novel approach based on combining neuro-fuzzy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory networks, but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without factitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast. The results show that this approach can work effectively.

  7. Large-scale modeling of condition-specific gene regulatory networks by information integration and inference.

    Science.gov (United States)

    Ellwanger, Daniel Christian; Leonhardt, Jörn Florian; Mewes, Hans-Werner

    2014-12-01

    Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE (http://mips.helmholtz-muenchen.de/cogere), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient η(2) (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research.

  8. An information transmission model for transcription factor binding at regulatory DNA sites.

    Science.gov (United States)

    Tan, Mingfeng; Yu, Dong; Jin, Yuan; Dou, Lei; Li, Beiping; Wang, Yuelan; Yue, Junjie; Liang, Long

    2012-06-06

    Computational identification of transcription factor binding sites (TFBSs) is a rapid, cost-efficient way to locate unknown regulatory elements. With increased potential for high-throughput genome sequencing, the availability of accurate computational methods for TFBS prediction has never been as important as it currently is. To date, identifying TFBSs with high sensitivity and specificity is still an open challenge, necessitating the development of novel models for predicting transcription factor-binding regulatory DNA elements. Based on the information theory, we propose a model for transcription factor binding of regulatory DNA sites. Our model incorporates position interdependencies in effective ways. The model computes the information transferred (TI) between the transcription factor and the TFBS during the binding process and uses TI as the criterion to determine whether the sequence motif is a possible TFBS. Based on this model, we developed a computational method to identify TFBSs. By theoretically proving and testing our model using both real and artificial data, we found that our model provides highly accurate predictive results. In this study, we present a novel model for transcription factor binding regulatory DNA sites. The model can provide an increased ability to detect TFBSs.

  9. On the underlying assumptions of threshold Boolean networks as a model for genetic regulatory network behavior

    Science.gov (United States)

    Tran, Van; McCall, Matthew N.; McMurray, Helene R.; Almudevar, Anthony

    2013-01-01

    Boolean networks (BoN) are relatively simple and interpretable models of gene regulatory networks. Specifying these models with fewer parameters while retaining their ability to describe complex regulatory relationships is an ongoing methodological challenge. Additionally, extending these models to incorporate variable gene decay rates, asynchronous gene response, and synergistic regulation while maintaining their Markovian nature increases the applicability of these models to genetic regulatory networks (GRN). We explore a previously-proposed class of BoNs characterized by linear threshold functions, which we refer to as threshold Boolean networks (TBN). Compared to traditional BoNs with unconstrained transition functions, these models require far fewer parameters and offer a more direct interpretation. However, the functional form of a TBN does result in a reduction in the regulatory relationships which can be modeled. We show that TBNs can be readily extended to permit self-degradation, with explicitly modeled degradation rates. We note that the introduction of variable degradation compromises the Markovian property fundamental to BoN models but show that a simple state augmentation procedure restores their Markovian nature. Next, we study the effect of assumptions regarding self-degradation on the set of possible steady states. Our findings are captured in two theorems relating self-degradation and regulatory feedback to the steady state behavior of a TBN. Finally, we explore assumptions of synchronous gene response and asynergistic regulation and show that TBNs can be easily extended to relax these assumptions. Applying our methods to the budding yeast cell-cycle network revealed that although the network is complex, its steady state is simplified by the presence of self-degradation and lack of purely positive regulatory cycles. PMID:24376454

  10. Olfactory receptor cells on the cockroach antennae: responses to the direction and rate of change in food odour concentration.

    Science.gov (United States)

    Hinterwirth, Armin; Zeiner, Reinhard; Tichy, Harald

    2004-06-01

    In insects, information about food odour is encoded by olfactory receptor cells with characteristic response spectra, located in several types of cuticular sensilla. Within short, hair-like sensilla on the cockroach's antenna, antagonistic pairs of olfactory receptor cells shape information inflow to the CNS by providing excitatory responses for both increases and decreases in food odour concentration. The segregation of food odour information into parallel ON and OFF responses suggests that temporal concentration changes become enhanced in the sensory output. When food odour concentration changes slowly and continuously up and down with smooth transition from one direction to another, the ON and OFF olfactory cells not only signal a succession of odour concentrations but also the rate with which odour concentration happens to be changing. Access to the values of such cues is of great use to an insect orientating to an odour source. With them they may extract concentration gradients from odour plumes.

  11. Round robin test for odour testing of migration waters.

    Science.gov (United States)

    Rapp, Thomas; Günther, Herbert

    2015-04-15

    For a round robin test for EN 1420-1 (Odour assessment for organic materials in contact with drinking water) with 14 contributing laboratories from 10 European countries segments of a plastic pipe were sent to the laboratories which performed a migration test and an odour analysis of the migration waters (water that had contact with the organic material) according to the procedure described in the standard from 1999. In addition reference substances (Methyl tert-butyl ether, 1-butanol and hexanal) were investigated for their suitability to qualify the panels and the individual panellists. Methyl tert-butyl ether (MtBE) and 1-butanol proved to be suitable for this purpose, whereas hexanal showed a wide distribution of the individual odour threshold concentrations. Both possible testing options (unforced and forced choice) were performed and gave similar results. However, with respect to the qualification of the panellists and the data analysis the unforced choice procedure showed advantages. As human olfactory perception is used for the analysis, the reproducibility and the comparability between laboratories is of particular concern. For the pipe material the TON results of the different laboratories were in a range of ±1.5 dilutions based on a dilution factor of 2. This might be improved by taking the individual sensitivities of the panellists into account more strongly. Appropriate measures for the improvement of the test method appear to be the use of the proposed reference substances for the training of the panellists as well as the auditing and the selection of the panellists. The results of this round robin test are used in the revision process of the standard.

  12. Dietary composition affects odour emissions from meat chickens

    Directory of Open Access Journals (Sweden)

    Nishchal K. Sharma

    2015-03-01

    Full Text Available Abatement of odour emissions has become an important consideration to agricultural industries, including poultry production. The link between diet and odour emissions was studied in two experiments using Ross 308 male meat chickens reared in specially designed chambers in a climate controlled room. In the first experiment, two treatments were compared using three replicates of two birds per chamber. Two wheat-soy based treatment diets were formulated with or without canola seed, an ingredient rich in sulfur amino acids. Treatment 1 (T1 had 13.39 MJ/kg ME (as fed and used 60 g/kg canola seed without corn while Treatment 2 (T2 contained 12.90 MJ/kg ME (as fed and used 150 g/kg corn without canola seed. In the second experiment, birds were assigned to three dietary treatments of five replicates with five birds per replicate (chamber. The basal starter, grower and finisher diets in the control group (SBM group contained soybean meal in the range of 227–291 g/kg (as fed as the main protein source. The other treatments (CM and MBM groups contained either high levels of canola meal (174–190 g/kg or meat meal (74–110 g/kg at the expense of soybean meal. In both experiments, diets were isocaloric, isonitrogenous and contained similar digestible amino acid contents as per 2007 Aviagen Ross 308 guidelines. Emissions of odour were measured using Fourier transform infrared (FTIR spectroscopy. In both experiments, major odorous compounds detected included 2,3-butanedione (diacetyl, 2-butanone, dimethyl disulfide, methyl mercaptan, ethyl mercaptan, 2-butanol, 3-methyl-butanal, phenol and m-cresol. In the first experiment, T1 (with canola seed produced higher concentration of methyl mercaptan (P < 0.05 and lower diacetyl (P < 0.01 than T2. In the second experiment, methyl mercaptan emission was higher in SBM group (P = 0.01 and total elemental sulfur were higher in SBM and CM groups up to day 24 (P < 0.01. Results of these experiments

  13. Testing theOdour Quality of Non-Metallic Materials

    Directory of Open Access Journals (Sweden)

    AVIJIT SINGH GANGWAR

    2014-10-01

    Full Text Available This report has been compiled on the completion of 3 week summer training at ICAT. It discusses about a very necessary and least popular part of the Automotive Industry i.e. Testing and Certification. It discusses about one of the government notified Testing body ICAT which is one of just 6 such organisations in India.This report deals with the odour quality testing of non-metallic materials that are used for automobile compartment and parts associated with the compartment.

  14. Identification of the odour-active cyclic diketone cis-2,6-dimethyl-1,4-cyclohexanedione in roasted Arabica coffee brew.

    Science.gov (United States)

    Miyazato, Hironari; Nakamura, Michiaki; Hashimoto, Seiji; Hayashi, Shuichi

    2013-06-15

    We investigated odour-active trace compounds in roasted Brazilian Arabica coffee. Aroma dilution extract analysis (AEDA) applied to the volatile oil extracted from roasted coffee brew revealed 34 odour-active compounds. Among these, a pungent-smelling unknown odour-active compound was determined. The volatile oil was fractioned by silica gel column chromatography. Gas chromatography-olfactometry (GC-O) and multidimensional gas chromatography-mass spectrometry (MDGC-MS) of the fraction which contained a significant amount of the target unknown compound revealed the cyclic 1,4-diketone, cis-2,6-dimethyl-1,4-cyclohexanedione, which had a pungent odour, and was thus first identified in roasted coffee. Model experiments revealed that cis-2,6-dimethyl-1,4-cyclohexanedione was formed via thermal degradation of sugars, especially monosaccharides, under alkaline conditions. Further, we demonstrated that 2-hydroxy-3-pentanone and 1-hydroxy-2-propanone, thermal degradation products of monosaccharides, were closely related to the formation of cis-2,6-dimethyl-1,4-cyclohexanedione.

  15. Mutual information and the fidelity of response of gene regulatory models

    Science.gov (United States)

    Tabbaa, Omar P.; Jayaprakash, C.

    2014-08-01

    We investigate cellular response to extracellular signals by using information theory techniques motivated by recent experiments. We present results for the steady state of the following gene regulatory models found in both prokaryotic and eukaryotic cells: a linear transcription-translation model and a positive or negative auto-regulatory model. We calculate both the information capacity and the mutual information exactly for simple models and approximately for the full model. We find that (1) small changes in mutual information can lead to potentially important changes in cellular response and (2) there are diminishing returns in the fidelity of response as the mutual information increases. We calculate the information capacity using Gillespie simulations of a model for the TNF-α-NF-κ B network and find good agreement with the measured value for an experimental realization of this network. Our results provide a quantitative understanding of the differences in cellular response when comparing experimentally measured mutual information values of different gene regulatory models. Our calculations demonstrate that Gillespie simulations can be used to compute the mutual information of more complex gene regulatory models, providing a potentially useful tool in synthetic biology.

  16. Mutual information and the fidelity of response of gene regulatory models.

    Science.gov (United States)

    Tabbaa, Omar P; Jayaprakash, C

    2014-08-01

    We investigate cellular response to extracellular signals by using information theory techniques motivated by recent experiments. We present results for the steady state of the following gene regulatory models found in both prokaryotic and eukaryotic cells: a linear transcription-translation model and a positive or negative auto-regulatory model. We calculate both the information capacity and the mutual information exactly for simple models and approximately for the full model. We find that (1) small changes in mutual information can lead to potentially important changes in cellular response and (2) there are diminishing returns in the fidelity of response as the mutual information increases. We calculate the information capacity using Gillespie simulations of a model for the TNF-α-NF-κB network and find good agreement with the measured value for an experimental realization of this network. Our results provide a quantitative understanding of the differences in cellular response when comparing experimentally measured mutual information values of different gene regulatory models. Our calculations demonstrate that Gillespie simulations can be used to compute the mutual information of more complex gene regulatory models, providing a potentially useful tool in synthetic biology.

  17. Odours of Plasmodium falciparum-infected participants influence mosquito-host interactions

    NARCIS (Netherlands)

    Boer, De Jetske G.; Robinson, Ailie; Powers, Stephen J.; Burgers, Saskia L.G.E.; Caulfield, John C.; Birkett, Michael A.; Smallegange, Renate C.; Genderen, Van Perry J.J.; Bousema, Teun; Sauerwein, Robert W.; Pickett, John A.; Takken, Willem; Logan, James G.

    2017-01-01

    Malaria parasites are thought to influence mosquito attraction to human hosts, a phenomenon that may enhance parasite transmission. This is likely mediated by alterations in host odour because of its importance in mosquito host-searching behaviour. Here, we report that the human skin odour profile

  18. Consumption of garlic positively affects hedonic perception of axillary body odour.

    Science.gov (United States)

    Fialová, Jitka; Roberts, S Craig; Havlíček, Jan

    2016-02-01

    Beneficial health properties of garlic, as well as its most common adverse effect - distinctive breath odour - are well-known. In contrast, analogous research on the effect of garlic on axillary odour is currently missing. Here, in three studies varying in the amount and nature of garlic provided (raw garlic in study 1 and 2, garlic capsules in study 3), we tested the effect of garlic consumption on the quality of axillary odour. A balanced within-subject experimental design was used. In total, 42 male odour donors were allocated to either a "garlic" or "non-garlic" condition, after which they wore axillary pads for 12 h to collect body odour. One week later, the conditions were reversed. Odour samples were then judged for their pleasantness, attractiveness, masculinity and intensity by 82 women. We found no significant differences in ratings of any characteristics in study 1. However, the odour of donors after an increased garlic dosage was assessed as significantly more pleasant, attractive and less intense (study 2), and more attractive and less intense in study 3. Our results indicate that garlic consumption may have positive effects on perceived body odour hedonicity, perhaps due to its health effects (e.g., antioxidant properties, antimicrobial activity). Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Odour and ammonia removal from pig house exhaust air using a biotrickling filter

    NARCIS (Netherlands)

    Melse, R.W.; Mol, G.

    2004-01-01

    Odour from agricultural activities, such as the spreading of manure and the housing of animals, is increasingly being considered a nuisance in densely populated countries like the Netherlands. The objective of this research was to study the odour removal from pig house exhaust air by a biotrickling

  20. Characterisation of free and glycosidically bound odourant compounds of Aragonez clonal musts by GC-O.

    Science.gov (United States)

    Botelho, Goreti; Mendes-Faia, Arlete; Clímaco, Maria Cristina

    2010-01-11

    To evaluate the potential aroma of Aragonez clonal red musts, several free and glycosidically bound odourant compounds were extracted. Then, the gas chromatography-olfactometry (GC-O) posterior intensity method was used to evaluate their odour intensity and the compounds were identified by gas chromatography-mass spectrometry (GC-MS). A group of eight sniffers evaluated free and bound fractions of Aragonez musts and perceived forty-three and twenty-two odourant peaks respectively. Furaneol (burnt sugar, candy-cotton) and vanillin (vanilla, sweet) were identified in both free and bound fractions of Aragonez musts, indicating their grape-derived origin. Principal component analysis (PCA) was applied to the posterior intensity method data and a relationship between the different odourant compound variables and the free fractions was established. Two principal components (PCs) were found which together explained 100% of the total variance. A large number of potentially important but yet unknown odourants was detected by the GC-O analysis.

  1. Inferring gene regulatory networks via nonlinear state-space models and exploiting sparsity.

    Science.gov (United States)

    Noor, Amina; Serpedin, Erchin; Nounou, Mohamed; Nounou, Hazem N

    2012-01-01

    This paper considers the problem of learning the structure of gene regulatory networks from gene expression time series data. A more realistic scenario when the state space model representing a gene network evolves nonlinearly is considered while a linear model is assumed for the microarray data. To capture the nonlinearity, a particle filter-based state estimation algorithm is considered instead of the contemporary linear approximation-based approaches. The parameters characterizing the regulatory relations among various genes are estimated online using a Kalman filter. Since a particular gene interacts with a few other genes only, the parameter vector is expected to be sparse. The state estimates delivered by the particle filter and the observed microarray data are then subjected to a LASSO-based least squares regression operation which yields a parsimonious and efficient description of the regulatory network by setting the irrelevant coefficients to zero. The performance of the aforementioned algorithm is compared with the extended Kalman filter (EKF) and Unscented Kalman Filter (UKF) employing the Mean Square Error (MSE) as the fidelity criterion in recovering the parameters of gene regulatory networks from synthetic data and real biological data. Extensive computer simulations illustrate that the proposed particle filter-based network inference algorithm outperforms EKF and UKF, and therefore, it can serve as a natural framework for modeling gene regulatory networks with nonlinear and sparse structure.

  2. Evaluation of the chemical composition and correlation between the calculated and measured odour concentration of odorous gases from a landfill in Beijing, China

    Science.gov (United States)

    Wu, Chuandong; Liu, Jiemin; Zhao, Peng; Li, Wenhui; Yan, Luchun; Piringer, Martin; Schauberger, Günther

    2017-09-01

    Odorous gases emitted from landfills have always been a public concern, but studies evaluating the odour contribution and the correlation between the odour concentrations are limited. The objectives of this study were to assess the odour contribution and to correlate the measured odour concentration COD with the calculated odour concentration SOAV, which was calculated as sum of individual odour activity value (OAV). Odorous air samples from a landfill in Beijing were collected seasonally and measured by both gas chromatography and an olfactometer. Different from previous studies, we measured the odour threshold of 51 detected compounds using a uniform methodology to minimize the imprecision of citing odour threshold from disparate literature. The odour threshold is used to convert the individual chemical concentration into the OAV, which is used as a surrogate of the odour concentration. Evaluation of the OAV revealed that hydrogen sulfide (65.9%), dimethyl sulfide (14.4%) and trimethylamine (8.6%) contributed the most to the odour at the landfill. Moreover, the correlation between the calculated odour concentration SOAV and the measured odour concentration COD resulted in a linear regression equation of COD = 6.28 SOAV (r = 0.914, n = 24, p calculated odour concentration to measured odour concentration could be improved from less than 0.2 to 1.1. By the calibration of the calculated odour concentration SOAV, it is possible to use continuous measurements of chemical concentrations to derive odour concentration for this site for monitoring purposes.

  3. Models and Messengers of Resilience: A Theoretical Model of College Students' Resilience, Regulatory Strategy Use, and Academic Achievement

    Science.gov (United States)

    Johnson, Marcus L.; Taasoobshirazi, Gita; Kestler, Jessica L.; Cordova, Jackie R.

    2015-01-01

    We tested a theoretical model of college students' ratings of messengers of resilience and models of resilience, students' own perceived resilience, regulatory strategy use and achievement. A total of 116 undergraduates participated in this study. The results of a path analysis indicated that ratings of models of resilience had a direct effect on…

  4. Network modeling reveals prevalent negative regulatory relationships between signaling sectors in Arabidopsis immune signaling.

    Directory of Open Access Journals (Sweden)

    Masanao Sato

    Full Text Available Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2. This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i the components of the network are highly interconnected; and (ii negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector

  5. Bayesian Computation Methods for Inferring Regulatory Network Models Using Biomedical Data.

    Science.gov (United States)

    Tian, Tianhai

    2016-01-01

    The rapid advancement of high-throughput technologies provides huge amounts of information for gene expression and protein activity in the genome-wide scale. The availability of genomics, transcriptomics, proteomics, and metabolomics dataset gives an unprecedented opportunity to study detailed molecular regulations that is very important to precision medicine. However, it is still a significant challenge to design effective and efficient method to infer the network structure and dynamic property of regulatory networks. In recent years a number of computing methods have been designed to explore the regulatory mechanisms as well as estimate unknown model parameters. Among them, the Bayesian inference method can combine both prior knowledge and experimental data to generate updated information regarding the regulatory mechanisms. This chapter gives a brief review for Bayesian statistical methods that are used to infer the network structure and estimate model parameters based on experimental data.

  6. On the underlying assumptions of threshold Boolean networks as a model for genetic regulatory network behavior

    Directory of Open Access Journals (Sweden)

    Van eTran

    2013-12-01

    Full Text Available Boolean networks (BoN are relatively simple and interpretable models of gene regulatorynetworks. Specifying these models with fewer parameters while retaining their ability to describe complex regulatory relationships is an ongoing methodological challenge. Additionally, extending these models to incorporate variable gene decay rates, asynchronous gene response, and synergistic regulation while maintaining their Markovian nature increases the applicability of these models to genetic regulatory networks.We explore a previously-proposed class of BoNs characterized by linear threshold functions, which we refer to as threshold Boolean networks (TBN. Compared to traditional BoNs with unconstrained transition functions, these models require far fewer parameters and offer a more direct interpretation. However, the functional form of a TBN does result in a reduction in the regulatory relationships which can be modeled.We show that TBNs can be readily extended to permit self-degradation, with explicitly modeled degradation rates. We note that the introduction of variable degradation compromises the Markovian property fundamental to BoN models but show that a simple state augmentation procedure restores their Markovian nature. Next, we study the effect of assumptions regarding self-degradation on the set of possible steady states. Our findings are captured in two theorems relating self-degradation and regulatory feedback to the steady state behavior of a TBN. Finally, we explore assumptions of synchronous gene response and asynergistic regulation and show that TBNs can be easily extended to relax these assumptions.Applying our methods to the budding yeast cell-cycle network revealed that although the network is complex, its steady state is simplified by the presence of self-degradation and lack of purely positive regulatory cycles.

  7. Determination of odour threshold concentration ranges for some disinfectants and disinfection by-products for an Australian panel.

    Science.gov (United States)

    McDonald, S; Lethorn, A; Loi, C; Joll, C; Driessen, H; Heitz, A

    2009-01-01

    Taste-and-odour complaints are a leading cause of consumer dissatisfaction with drinking water. The aim of this study was to determine odour threshold concentration ranges and descriptors, using a Western Australian odour panel, for chlorine, bromine, chlorine added to bromide ions, the four major regulated trihalomethanes (THMs), and combined THMs. An odour panel was established and trained to determine odour threshold concentration ranges for odorous compounds typically found in drinking water at 25 degrees C, using modified flavour profile analysis (FPA) techniques. Bromine and chlorine had the same odour threshold concentration ranges and were both described as having a chlorinous odour by a majority of panellists, but the odour threshold concentration range of bromine expressed in free chlorine equivalents was lower that that of chlorine. It is likely that the free chlorine equivalent residuals measured in many parts of distribution systems in Western Australia are comprised of some portion of bromine and that bromine has the potential to cause chlorinous odours at a lower free chlorine equivalent concentration than chlorine itself. In fact, bromine is the likely cause of any chlorinous odours in Western Australian distributed waters when the free chlorine equivalent concentration is between 0.04 and 0.1 mg L(-1). Odour threshold concentrations for the four individual THMs ranged from 0.06-0.16 mg L(-1), and the odour threshold concentration range was 0.10 + or - 0.09 mg L(-1) when the four THMs were combined (in equal mass concentrations). These concentrations are below the maximum guideline value for total THM concentration in Australia so odours from these compounds may possibly be observed in distributed waters. However, while the presence of THMs may contribute to any sweet/fragrant/floral and chemical/hydrocarbon odours in local drinking waters, the THMs are unlikely to contribute to chlorinous odours.

  8. Detection and characterization of regulatory elements using probabilistic conditional random field and hidden Markov models

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Xiaobo Zhou

    2013-01-01

    By altering the electrostatic charge of histones or providing binding sites to protein recognition molecules,Chromatin marks have been proposed to regulate gene expression,a property that has motivated researchers to link these marks to cis-regulatory elements.With the help of next generation sequencing technologies,we can now correlate one specific chromatin mark with regulatory elements (e.g.enhancers or promoters) and also build tools,such as hidden Markov models,to gain insight into mark combinations.However,hidden Markov models have limitation for their character of generative models and assume that a current observation depends only on a current hidden state in the chain.Here,we employed two graphical probabilistic models,namely the linear conditional random field model and multivariate hidden Markov model,to mark gene regions with different states based on recurrent and spatially coherent character of these eight marks.Both models revealed chromatin states that may correspond to enhancers and promoters,transcribed regions,transcriptional elongation,and low-signal regions.We also found that the linear conditional random field model was more effective than the hidden Markov model in recognizing regulatory elements,such as promoter-,enhancer-,and transcriptional elongation-associated regions,which gives us a better choice.

  9. Finding cis-regulatory modules in Drosophila using phylogenetic hidden Markov models

    DEFF Research Database (Denmark)

    Wong, Wendy S W; Nielsen, Rasmus

    2007-01-01

    of the increasing availability of comparative genomic data. RESULTS: We develop a method for finding regulatory modules in Eukaryotic species using phylogenetic data. Using computer simulations and analysis of real data, we show that the use of phylogenetic hidden Markov model can lead to an increase in accuracy...

  10. Reconstruction of large-scale gene regulatory networks using Bayesian model averaging.

    Science.gov (United States)

    Kim, Haseong; Gelenbe, Erol

    2012-09-01

    Gene regulatory networks provide the systematic view of molecular interactions in a complex living system. However, constructing large-scale gene regulatory networks is one of the most challenging problems in systems biology. Also large burst sets of biological data require a proper integration technique for reliable gene regulatory network construction. Here we present a new reverse engineering approach based on Bayesian model averaging which attempts to combine all the appropriate models describing interactions among genes. This Bayesian approach with a prior based on the Gibbs distribution provides an efficient means to integrate multiple sources of biological data. In a simulation study with maximum of 2000 genes, our method shows better sensitivity than previous elastic-net and Gaussian graphical models, with a fixed specificity of 0.99. The study also shows that the proposed method outperforms the other standard methods for a DREAM dataset generated by nonlinear stochastic models. In brain tumor data analysis, three large-scale networks consisting of 4422 genes were built using the gene expression of non-tumor, low and high grade tumor mRNA expression samples, along with DNA-protein binding affinity information. We found that genes having a large variation of degree distribution among the three tumor networks are the ones that see most involved in regulatory and developmental processes, which possibly gives a novel insight concerning conventional differentially expressed gene analysis.

  11. Regulatory B cells and tolerance in transplantation: from animal models to human.

    Directory of Open Access Journals (Sweden)

    Melanie eChesneau

    2013-12-01

    Full Text Available Until recently, the role of B cells in transplantation was thought to be restricted to producing antibodies that have been clearly shown to be deleterious in the long term, but, in fact, B cells are also able to produce cytokine and to present antigen. Their role as regulatory cells in various pathological situations has also been highlighted, and their role in transplantation is beginning to emerge in animal, and also in human, models. This review summarizes the different studies in animals and humans that suggest a B-cell regulatory role in the transplant tolerance mechanisms.

  12. Odour perception following bilateral damage to the olfactory bulbs: a possible case of blind smell.

    Science.gov (United States)

    Zucco, Gesualdo M; Prior, Massimo; Sartori, Giuseppe; Stevenson, Richard J

    2013-02-01

    Unconsciously detected chemicals may affect human behaviour (Kirk-Smith et al., 1983; Stern and McClintock, 1998; Zucco et al., 2009), likeability judgements (Li et al., 2007) and brain activity (Lorig et al., 1990; Sobel et al., 1999). No studies, however, have investigated blind smell - the hypothetical olfactory counterpart of blindsight (Weiskrantz et al., 1974). In this report, free and cued olfactory identification of suprathreshold odorants varying in irritancy (i.e., low or no irritant odours versus irritant odours), and taste identification abilities, were examined in patient MB who had undergone surgery for a meningioma. Post-operative imaging revealed encephalomalacia in the left gyrus rectus, with ablation of the left olfactory bulb and damage to the right, subcortical abnormality on the left near the orbital cortex, and damage to a small section of the right gyrus rectus. On free identification MB, while denying a capacity to smell the odours, still correctly identified some and detected others significantly above chance. In contrast, awareness always accompanied correct detections of irritant odours. Cued odour identification was at chance and no taste impairments were observed. We suggest, tentatively, that MB's unusual pattern of awareness when detecting and identifying odours relative to irritant odours may represent an example of 'blind smell'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Preliminary observation on the effect of baking soda volume on controlling odour from discarded organic waste

    Energy Technology Data Exchange (ETDEWEB)

    Qamaruz-Zaman, N., E-mail: cenastaein@usm.my; Kun, Y.; Rosli, R.-N.

    2015-01-15

    Highlights: • Approximately 50 g baking soda reduced odour concentration by 70%. • Reducing volatile acid concentration reduces odour concentration. • Ammonia has less effect on odour concentration. - Abstract: Food wastes with high moisture and organic matter content are likely to emit odours as a result of the decomposition process. The management of odour from decomposing wastes is needed to sustain the interest of residents and local councils in the source separation of kitchen wastes. This study investigated the potential of baking soda (at 50 g, 75 g and 100 g per kg food waste) to control odour from seven days stored food waste. It was found that 50 g of baking soda, spread at the bottom of 8 l food wastes bin, can reduce the odour by about 70%. A higher amount (above 100 g) is not advised as a pH higher than 9.0 may be induced leading to the volatilization of odorous ammonia. This research finding is expected to benefit the waste management sector, food processing industries as well as the local authorities where malodour from waste storage is a pressing issue.

  14. An Updated GA Signaling 'Relief of Repression' Regulatory Model

    Institute of Scientific and Technical Information of China (English)

    Xiu-Hua Gao; Sen-Lin Xiao; Qin-Fang Yao; Yu-Juan Wang; Xiang-Dong Fu

    2011-01-01

    Gibberellic acid (GA)regulates many aspects of plant growth and development. The DELLA proteins act to restrain plant growth, and GA relieves this repression by promoting their degradation via the 26S proteasome pathway.The elucidation of the crystalline structure of the GA soluble receptor GID1 protein represents an important breakthrough for understanding the way in which GA is perceived and how it induces the destabilization of the DELLA proteins. Recent advances have revealed that the DELLA proteins are involved in protein-protein interactions within various environmental and hormone signaling pathways. In this review, we highlight our current understanding of the 'relief of repression" model that aims to explain the role of GA and the function of the DELLA proteins, incorporating the many aspects of cross-talk shown to exist in the control of plant development and the response to stress.

  15. Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours.

    Science.gov (United States)

    Dekker, Teun; Geier, Martin; Cardé, Ring T

    2005-08-01

    Female mosquitoes are noted for their ability to use odours to locate a host for a blood meal. Two sensory organs contribute to their sense of smell: the maxillary palps, which measure the level of CO2, and the antennae, which detect other host-released odours. To establish the relative importance and interactions of CO2 and other body emissions in freely flying mosquitoes, we presented female yellow fever mosquitoes Aedes aegypti L. with broad plumes of human skin odour and CO2 at natural concentrations and dilutions thereof in a wind tunnel. 3-D video-recorded flight tracks were reconstructed. Activation, flight velocity, upwind turning and source finding waned quickly as skin odours were diluted, whereas in the presence of CO2 these parameters remained unchanged over more than a 100-fold dilution from exhaled concentrations. Although mosquitoes were behaviourally less sensitive to skin odours than to CO2, their sensitivity to skin odours increased transiently by at least fivefold immediately following a brief encounter with a filament of CO2. This sensitization was reflected in flight velocity, track angle, turning rate upon entering and exiting the broad odour plume and, ultimately, in the source-finding rate. In Ae. aegypti, CO2 thus functions as a ;releaser' for a higher sensitivity and responsiveness to skin odours. The initially low responsiveness of mosquitoes to skin odours, their high sensitivity to CO2, and the sensitization of the olfactory circuitry by CO2 are ecologically relevant, because rapidly fluctuating CO2 levels reliably signal a potential host. Possible mechanisms of the instantaneous sensitization are considered.

  16. TIGER: Toolbox for integrating genome-scale metabolic models, expression data, and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Jensen Paul A

    2011-09-01

    Full Text Available Abstract Background Several methods have been developed for analyzing genome-scale models of metabolism and transcriptional regulation. Many of these methods, such as Flux Balance Analysis, use constrained optimization to predict relationships between metabolic flux and the genes that encode and regulate enzyme activity. Recently, mixed integer programming has been used to encode these gene-protein-reaction (GPR relationships into a single optimization problem, but these techniques are often of limited generality and lack a tool for automating the conversion of rules to a coupled regulatory/metabolic model. Results We present TIGER, a Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation. TIGER converts a series of generalized, Boolean or multilevel rules into a set of mixed integer inequalities. The package also includes implementations of existing algorithms to integrate high-throughput expression data with genome-scale models of metabolism and transcriptional regulation. We demonstrate how TIGER automates the coupling of a genome-scale metabolic model with GPR logic and models of transcriptional regulation, thereby serving as a platform for algorithm development and large-scale metabolic analysis. Additionally, we demonstrate how TIGER's algorithms can be used to identify inconsistencies and improve existing models of transcriptional regulation with examples from the reconstructed transcriptional regulatory network of Saccharomyces cerevisiae. Conclusion The TIGER package provides a consistent platform for algorithm development and extending existing genome-scale metabolic models with regulatory networks and high-throughput data.

  17. Sex determination strategies in 2012: towards a common regulatory model?

    Science.gov (United States)

    2012-01-01

    Sex determination is a complicated process involving large-scale modifications in gene expression affecting virtually every tissue in the body. Although the evolutionary origin of sex remains controversial, there is little doubt that it has developed as a process of optimizing metabolic control, as well as developmental and reproductive functions within a given setting of limited resources and environmental pressure. Evidence from various model organisms supports the view that sex determination may occur as a result of direct environmental induction or genetic regulation. The first process has been well documented in reptiles and fish, while the second is the classic case for avian species and mammals. Both of the latter have developed a variety of sex-specific/sex-related genes, which ultimately form a complete chromosome pair (sex chromosomes/gonosomes). Interestingly, combinations of environmental and genetic mechanisms have been described among different classes of animals, thus rendering the possibility of a unidirectional continuous evolutionary process from the one type of mechanism to the other unlikely. On the other hand, common elements appear throughout the animal kingdom, with regard to a) conserved key genes and b) a central role of sex steroid control as a prerequisite for ultimately normal sex differentiation. Studies in invertebrates also indicate a role of epigenetic chromatin modification, particularly with regard to alternative splicing options. This review summarizes current evidence from research in this hot field and signifies the need for further study of both normal hormonal regulators of sexual phenotype and patterns of environmental disruption. PMID:22357269

  18. Sex determination strategies in 2012: towards a common regulatory model?

    Directory of Open Access Journals (Sweden)

    Angelopoulou Roxani

    2012-02-01

    Full Text Available Abstract Sex determination is a complicated process involving large-scale modifications in gene expression affecting virtually every tissue in the body. Although the evolutionary origin of sex remains controversial, there is little doubt that it has developed as a process of optimizing metabolic control, as well as developmental and reproductive functions within a given setting of limited resources and environmental pressure. Evidence from various model organisms supports the view that sex determination may occur as a result of direct environmental induction or genetic regulation. The first process has been well documented in reptiles and fish, while the second is the classic case for avian species and mammals. Both of the latter have developed a variety of sex-specific/sex-related genes, which ultimately form a complete chromosome pair (sex chromosomes/gonosomes. Interestingly, combinations of environmental and genetic mechanisms have been described among different classes of animals, thus rendering the possibility of a unidirectional continuous evolutionary process from the one type of mechanism to the other unlikely. On the other hand, common elements appear throughout the animal kingdom, with regard to a conserved key genes and b a central role of sex steroid control as a prerequisite for ultimately normal sex differentiation. Studies in invertebrates also indicate a role of epigenetic chromatin modification, particularly with regard to alternative splicing options. This review summarizes current evidence from research in this hot field and signifies the need for further study of both normal hormonal regulators of sexual phenotype and patterns of environmental disruption.

  19. Odour Mapping Under Strong Backgrounds With a Metal Oxide Sensor Array

    Science.gov (United States)

    Ziyatdinov, Andrey; Calvo, José María Blanco; Lechón, Miguel; Bermúdez i Badia, Sergi; Verschure, Paul F. M. J.; Marco, Santiago; Perera, Alexandre

    2011-09-01

    This work describes the data from navigation experiments with the mobile robot, equipped with the sensor array of three MOX gas sensors. Performed four series of measurements aim to explore the capabilities of sensor array to build the odour map with one or two odour sources in the wind tunnel space. It was demonstrated that the method based on Independent Component Analysis (ICA) is able to discriminate two odour sources, that in future can be used in the surge-and-cast robot navigation algorithm.

  20. Taste and odour issues in South Korea's drinking water industry.

    Science.gov (United States)

    Bae, B U; Shin, H S; Choi, J J

    2007-01-01

    This paper reviews taste and odour (T&O) issues of South Korea's water industry. For this purpose, an overview of the water supply systems and drinking water standards is presented and some results from citizen surveys for customer satisfaction are included. A case study is presented in which the water intake was shifted from inside a main reservoir to a downstream location due to T&O problems. It is true that the South Korean water industry has long relied on the tolerance of consumers for periodic T&O events. Recently the South Korean water industry has become aware that the T&O problems are at the centre of consumers' concerns and has taken several positive approaches. These include monitoring T&O events using sensory and instrumental methods, installation of a baffled-channel PAC contactor and application of advanced water treatment processes.

  1. The analgesic effect of odour and music upon dressing change.

    Science.gov (United States)

    Kane, F M A; Brodie, E E; Coull, A; Coyne, L; Howd, A; Milne, A; Niven, C C; Robbins, R

    Vascular wounds may require frequent dressing changes over a long period of time, often involving pain, which may not be adequately controlled with conventional analgesia. Complementary analgesia may be beneficial as an adjunctive therapy. This pilot study presented eight patients with two odour therapies, lavender and lemon, two music therapies, relaxing and preferred music and a control condition, during vascular wound dressing changes. Although the therapies did not reduce the pain intensity during the dressing change there was a significant reduction in pain intensity for the lavender therapy and a reduction in pain intensity for the relaxing music therapy after the dressing change. This supports the use of these complementary therapies, which are inexpensive, easy to administer and have no known side effects, as adjunctive analgesia in this patient population. Earlier administration before dressing change may enhance these effects. Further research is required to ascertain why certain complementary therapies are more effective than others at relieving pain.

  2. Biofilter odour reduction level, measurements; Luktreduceringsgrad hos biofilter, faeltmaetningar

    Energy Technology Data Exchange (ETDEWEB)

    Arrhenius, Karine; Rosell, Lars; Tsetsilas, Sakis (SP, Boraas (Sweden)); Loevenklev, Maria; Blomqvist, Marie; Hall, Gunnar; Sverken, Anna; Widen, Helene (SIK, Goeteborg (Sweden)); Holmgren, Magnus Andreas (Vattenfall Power Consultants (Sweden))

    2010-07-01

    Biofilter is today the most common odour reduction method for biological treatment. A biofilter consists of a bed of organic material often made of compost together with another material which increases the porosity of the bed. Microorganisms in the compost use odorous compounds as nutrient by decomposing them. Resulting products are mainly carbon dioxide and water, mineral salts, other organic compounds and more microorganisms. In this project, seven biofilters implemented in Sweden have been tested in order to describe their status and function. A number of physical, chemical, microbiological and odour related parameters have be measured in the pipe which leads to the biofilter as well as on the surface of the biofilter in order to determine biofilters status and their effectiveness. Values from plants have been compared to published optimal values for each parameter. The goal of the project is to optimize biofilters function och prevent risks for performance disturbances. Results from the project can also be used as reference for plants which are planning process modifications as an increase of waste to be treated, substrate/material changes etc. Each plant has been visited during two days in August/September 2009. The following parameters have been measured: 1) physical parameters such as relative humidity, temperature, and pH, 2) chemical parameters such as incoming and out coming gas composition, gas composition variation with time, access to nutriments, 3) microbiological parameters such as the total number of microorganisms and the dominating microflora i respective biofilter and 4) odour related parameters through an evaluation of the contribution of individual compounds to the total out coming odour and in some cases, through a evaluation by olfactometry. All these parameters have been subsequently interpreted and treated in order to evaluate the status of the biofilter: description of the biofilter, its environment, the microbiological status, which flow

  3. Evaluating NOx emission inventories for regulatory air quality modeling using satellite and air quality model data

    Science.gov (United States)

    Kemball-Cook, Susan; Yarwood, Greg; Johnson, Jeremiah; Dornblaser, Bright; Estes, Mark

    2015-09-01

    The purpose of this study was to assess the accuracy of NOx emissions in the Texas Commission on Environmental Quality's (TCEQ) State Implementation Plan (SIP) modeling inventories of the southeastern U.S. We used retrieved satellite tropospheric NO2 columns from the Ozone Monitoring Instrument (OMI) together with NO2 columns from the Comprehensive Air Quality Model with Extensions (CAMx) to make top-down NOx emissions estimates using the mass balance method. Two different top-down NOx emissions estimates were developed using the KNMI DOMINO v2.0 and NASA SP2 retrievals of OMI NO2 columns. Differences in the top-down NOx emissions estimates made with these two operational products derived from the same OMI radiance data were sufficiently large that they could not be used to constrain the TCEQ NOx emissions in the southeast. The fact that the two available operational NO2 column retrievals give such different top-down NOx emissions results is important because these retrievals are increasingly being used to diagnose air quality problems and to inform efforts to solve them. These results reflect the fact that NO2 column retrievals are a blend of measurements and modeled data and should be used with caution in analyses that will inform policy development. This study illustrates both benefits and challenges of using satellite NO2 data for air quality management applications. Comparison with OMI NO2 columns pointed the way toward improvements in the CAMx simulation of the upper troposphere, but further refinement of both regional air quality models and the NO2 column retrievals is needed before the mass balance and other emission inversion methods can be used to successfully constrain NOx emission inventories used in U.S. regulatory modeling.

  4. Limitation of using synthetic human odours to test mosquito repellents

    Directory of Open Access Journals (Sweden)

    Mbeyela Edgar

    2009-07-01

    Full Text Available Abstract Background Gold-standard tests of mosquito repellents involve exposing human volunteers to host-seeking mosquitoes, to assess the protective efficacy of the repellents. These techniques are not exposure-free and cannot be performed prior to toxicological evaluation. It is postulated that synthetic lures could provide a useful assay that mimics in-vivo conditions for use in high-throughput screening for mosquito repellents. Methods This paper reports on a semi-field evaluation of repellents using a synthetic blend of human derived attractants for the malaria vector, Anopheles gambiae sensu stricto Different concentrations of known repellents, N, N diethyl-3-methylbenzamide (deet and Para-methane-3, 8, diol (PMD were added into traps baited with the synthetic blend, and resulting changes in mosquito catches were measured. Results All test concentrations of deet (0.001% to 100% reduced the attractiveness of the synthetic blend. However, PMD was repellent only at 0.25%. Above this concentration, it significantly increased the attractiveness of the blend. There was no relationship between the repellent concentrations and the change in mosquito catches when either deet (r2 = 0.033, P = 0.302 or PMD (r2 = 0.020, P = 0.578 was used. Conclusion It is concluded that while some repellents may reduce the attractiveness of synthetic human odours, others may instead increase their attractiveness. Such inconsistencies indicate that even though the synthetic attractants may provide exposure-free and consistent test media for repellents, careful selection and multiple-repellent tests are necessary to ascertain their suitability for use in repellent screening. The synthetic odour blend tested here is not yet sufficiently refined to serve as replacement for humans in repellent testing, but may be developed further and evaluated in different formats for exposure free repellent testing purposes.

  5. Revisited: The South Dakota Board of Nursing theory-based regulatory decisioning model.

    Science.gov (United States)

    Damgaard, Gloria; Bunkers, Sandra Schmidt

    2012-07-01

    The authors of this column describe the South Dakota Board of Nursing's 11 year journey utilizing a humanbecoming theory-based regulatory decisioning model. The column revisits the model with an emphasis on the cocreation of a strategic plan guiding the work of the South Dakota Board of Nursing through 2014. The strategic plan was influenced by the latest refinements of the humanbecoming postulates and the humanbecoming community change concepts. A graphic picture of the decisioning model is presented along with future plans for the theory-based model.

  6. Mosaic gene network modelling identified new regulatory mechanisms in HCV infection.

    Science.gov (United States)

    Popik, Olga V; Petrovskiy, Evgeny D; Mishchenko, Elena L; Lavrik, Inna N; Ivanisenko, Vladimir A

    2016-06-15

    Modelling of gene networks is widely used in systems biology to study the functioning of complex biological systems. Most of the existing mathematical modelling techniques are useful for analysis of well-studied biological processes, for which information on rates of reactions is available. However, complex biological processes such as those determining the phenotypic traits of organisms or pathological disease processes, including pathogen-host interactions, involve complicated cross-talk between interacting networks. Furthermore, the intrinsic details of the interactions between these networks are often missing. In this study, we developed an approach, which we call mosaic network modelling, that allows the combination of independent mathematical models of gene regulatory networks and, thereby, description of complex biological systems. The advantage of this approach is that it allows us to generate the integrated model despite the fact that information on molecular interactions between parts of the model (so-called mosaic fragments) might be missing. To generate a mosaic mathematical model, we used control theory and mathematical models, written in the form of a system of ordinary differential equations (ODEs). In the present study, we investigated the efficiency of this method in modelling the dynamics of more than 10,000 simulated mosaic regulatory networks consisting of two pieces. Analysis revealed that this approach was highly efficient, as the mean deviation of the dynamics of mosaic network elements from the behaviour of the initial parts of the model was less than 10%. It turned out that for construction of the control functional, data on perturbation of one or two vertices of the mosaic piece are sufficient. Further, we used the developed method to construct a mosaic gene regulatory network including hepatitis C virus (HCV) as the first piece and the tumour necrosis factor (TNF)-induced apoptosis and NF-κB induction pathways as the second piece. Thus

  7. Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

    Science.gov (United States)

    Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

    2014-01-01

    Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

  8. The moderating role of regulatory focus on the social modeling of food intake.

    Science.gov (United States)

    Florack, Arnd; Palcu, Johanna; Friese, Malte

    2013-10-01

    Regulatory focus theory proposes two distinct modi of self-regulation, a promotion focus and a prevention focus. According to this theory, individuals in a prevention focus apply behavioral strategies to successfully avoid unpleasant outcomes and maintain a safe and secure state. By contrast, individuals in a promotion focus apply behavioral strategies to realize pleasant outcomes and to advance the current state. Applied to the context of eating behavior, regulatory focus theory suggests that individuals in a prevention focus should be especially sensitive to avoid socially inappropriate eating behavior. A way to ensure socially appropriate eating behavior is to follow social models. In the present research, we therefore tested the assumption that a prevention focus leads to stronger modeling effects in eating behavior than a promotion focus. In two studies, we manipulated individual's self-regulation states by putting individuals in a state of reflection about their hopes and aspirations (promotion focus) vs. a state of reflection about their duties and responsibilities (prevention focus). Participants then observed the consumption behavior of a second participant who either consumed or did not consume offered food (Study 1) or received incidental information about the amount of food an ostensible previous participant had consumed (Study 2). Across both studies, participants in a prevention focus matched their food consumption more closely to that of a present (Study 1) and not-present social model (Study 2), compared to participants in a promotion focus. The results advance our understanding of modeling effects in food intake by showing the importance of regulatory orientations.

  9. Inference of gene regulatory networks from genetic perturbations with linear regression model.

    Directory of Open Access Journals (Sweden)

    Zijian Dong

    Full Text Available It is an effective strategy to use both genetic perturbation data and gene expression data to infer regulatory networks that aims to improve the detection accuracy of the regulatory relationships among genes. Based on both types of data, the genetic regulatory networks can be accurately modeled by Structural Equation Modeling (SEM. In this paper, a linear regression (LR model is formulated based on the SEM, and a novel iterative scheme using Bayesian inference is proposed to estimate the parameters of the LR model (LRBI. Comparative evaluations of LRBI with other two algorithms, the Adaptive Lasso (AL-Based and the Sparsity-aware Maximum Likelihood (SML, are also presented. Simulations show that LRBI has significantly better performance than AL-Based, and overperforms SML in terms of power of detection. Applying the LRBI algorithm to experimental data, we inferred the interactions in a network of 35 yeast genes. An open-source program of the LRBI algorithm is freely available upon request.

  10. Modeling regulatory policies associated with offshore structure removal requirements in the Gulf of Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, Mark J. [Center for Energy Studies, Louisiana State University, Energy Coast and Environment Building, Baton Rouge, LA (United States)

    2008-07-15

    Federal regulations require that a lease in the Outer Continental Shelf of the Gulf of Mexico be cleared of all structures within one year after production on the lease ceases, but in recent years, the Minerals Management Service has begun to encourage operators to remove idle (non-producing) structures on producing leases that are no longer ''economically viable''. At the end of 2003, there were 2175 producing structures, 898 idle (non-producing) structures, and 440 auxiliary (never-producing) structures on 1356 active leases; and 329 idle structures and 65 auxiliary structures on 273 inactive leases. The purpose of this paper is to model the impact of alternative regulatory policies on the removal trends of structures and the inventory of idle iron, and to provide first-order estimates of the cost of each regulatory option. A description of the modeling framework and implementation results is presented. (author)

  11. Neural model of gene regulatory network: a survey on supportive meta-heuristics.

    Science.gov (United States)

    Biswas, Surama; Acharyya, Sriyankar

    2016-06-01

    Gene regulatory network (GRN) is produced as a result of regulatory interactions between different genes through their coded proteins in cellular context. Having immense importance in disease detection and drug finding, GRN has been modelled through various mathematical and computational schemes and reported in survey articles. Neural and neuro-fuzzy models have been the focus of attraction in bioinformatics. Predominant use of meta-heuristic algorithms in training neural models has proved its excellence. Considering these facts, this paper is organized to survey neural modelling schemes of GRN and the efficacy of meta-heuristic algorithms towards parameter learning (i.e. weighting connections) within the model. This survey paper renders two different structure-related approaches to infer GRN which are global structure approach and substructure approach. It also describes two neural modelling schemes, such as artificial neural network/recurrent neural network based modelling and neuro-fuzzy modelling. The meta-heuristic algorithms applied so far to learn the structure and parameters of neutrally modelled GRN have been reviewed here.

  12. A biophysical model for identifying splicing regulatory elements and their interactions.

    Directory of Open Access Journals (Sweden)

    Ji Wen

    Full Text Available Alternative splicing (AS of precursor mRNA (pre-mRNA is a crucial step in the expression of most eukaryotic genes. Splicing factors (SFs play an important role in AS regulation by binding to the cis-regulatory elements on the pre-mRNA. Although many splicing factors (SFs and their binding sites have been identified, their combinatorial regulatory effects remain to be elucidated. In this paper, we derive a biophysical model for AS regulation that integrates combinatorial signals of cis-acting splicing regulatory elements (SREs and their interactions. We also develop a systematic framework for model inference. Applying the biophysical model to a human RNA-Seq data set, we demonstrate that our model can explain 49.1%-66.5% variance of the data, which is comparable to the best result achieved by biophysical models for transcription. In total, we identified 119 SRE pairs between different regions of cassette exons that may regulate exon or intron definition in splicing, and 77 SRE pairs from the same region that may arise from a long motif or two different SREs bound by different SFs. Particularly, putative binding sites of polypyrimidine tract-binding protein (PTB, heterogeneous nuclear ribonucleoprotein (hnRNP F/H and E/K are identified as interacting SRE pairs, and have been shown to be consistent with the interaction models proposed in previous experimental results. These results show that our biophysical model and inference method provide a means of quantitative modeling of splicing regulation and is a useful tool for identifying SREs and their interactions. The software package for model inference is available under an open source license.

  13. A Framework for Organizing Current and Future Electric Utility Regulatory and Business Models

    Energy Technology Data Exchange (ETDEWEB)

    Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fadrhonc, Emily Martin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-06-01

    In this report, we will present a descriptive and organizational framework for incremental and fundamental changes to regulatory and utility business models in the context of clean energy public policy goals. We will also discuss the regulated utility's role in providing value-added services that relate to distributed energy resources, identify the "openness" of customer information and utility networks necessary to facilitate change, and discuss the relative risks, and the shifting of risks, for utilities and customers.

  14. CD4+CD25+ regulatory T cells: II. Origin, disease models and clinical aspects

    DEFF Research Database (Denmark)

    Nielsen, Janne; Holm, Thomas Lindebo; Claesson, Mogens H

    2004-01-01

    Autoimmune diseases afflict approximately 5% of the population and reflect a failure in the immune system to discriminate between self and non-self resulting in the breakdown of self-tolerance. Regulatory CD4+CD25+ T cells (Treg cells) have been shown to play an important role in the maintenance ...... in disease models such as autoimmune gastritis and inflammatory bowel disease. Finally, we will consider some aspects of the therapeutic potential of Treg cells....

  15. Using Consensus Bayesian Network to Model the Reactive Oxygen Species Regulatory Pathway

    OpenAIRE

    Liangdong Hu; Limin Wang

    2013-01-01

    Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks...

  16. Maternal breast milk odour induces frontal lobe activation in neonates: a NIRS study.

    Science.gov (United States)

    Aoyama, Shiori; Toshima, Tamotsu; Saito, Yuri; Konishi, Nakao; Motoshige, Kyoko; Ishikawa, Nobutsune; Nakamura, Kazuhiro; Kobayashi, Masao

    2010-09-01

    We used near-infrared spectroscopy (NIRS) to examine differences in neonates' orbito-frontal cortical activation in response to the odours of maternal breast milk and formula milk in terms of changes in the oxygenation of cerebral blood flow. Twenty-six healthy neonates were tested in their cribs while they slept in a silent room. The neonates were exposed to each olfactory stimulus by an experimenter. NIRS monitoring was performed using optodes placed above the bilateral anterior orbito-frontal gyri. The differences in oxygenated haemoglobin (oxy-Hb) values between baseline and stimulation were defined as the change in oxy-Hb. The degrees of change were calculated by an analysis of variance (ANOVA). A 2 (stimulus: breast milk and formula milk) × 2 (probe location: right and left) ANOVA showed that the odour of maternal breast milk (right/left: M=0.28/0.48) induced a significantly (F=6.36, pmilk (right/left: M=-0.03/-0.07). Differences in the intensity of odour had no significant influence on the blood oxygenation of the orbito-frontal region. Maternal breast milk odour increased oxygenated blood flow in the orbito-frontal region to a greater extent than did formula milk odour. These results suggest that neonates can distinguish between the odours of maternal breast milk versus formula.

  17. Modeling Protected Species Habitat and Assigning Risk to Inform Regulatory Decisions

    Science.gov (United States)

    Montgomery, Robert A.; Rubeck-Schurtz, C. Nichole; Millenbah, Kelly F.; Roloff, Gary J.; Whalon, Mark E.; Olsen, Larry G.

    2009-07-01

    In the United States, environmental regulatory agencies are required to use “best available” scientific information when making decisions on a variety of issues. However, agencies are often hindered by coarse or incomplete data, particularly as it pertains to threatened and endangered species protection. Stakeholders often agree that more resolute and integrated processes for decision-making are desirable. We demonstrate a process that uses species occurrence data for a federally endangered insect (Karner blue butterfly), a readily available habitat modeling tool, and spatially explicit information about an important Michigan commodity (tart cherries). This case study has characteristics of many protected species regulatory decisions in that species occurrence data were sparse and unequally distributed; regulatory decisions (on pesticide use) were required with potentially significant impacts on a viable agricultural industry; and stakeholder relations were diverse, misinformed, and, in some situations, unjustly contentious. Results from our process include a large-scale, empirically derived habitat suitability map for the focal species and a risk ranking of tart cherry orchards with risk based on the likelihood that pesticide applications will influence the focal protected species. Although the majority (77%) of pesticide-influence zones overlapped Karner blue butterfly habitat, risk scores associated with each orchard were low. Through our process we demonstrated that spatially explicit models can help stakeholders visualize and quantify potential protected species effects. In addition, model outputs can serve to guide field activities (e.g., species surveys and implementation of pesticide buffer zones) that help minimize future effects.

  18. Time delay induced transition of gene switch and stochastic resonance in a genetic transcriptional regulatory model

    Science.gov (United States)

    2012-01-01

    Background Noise, nonlinear interactions, positive and negative feedbacks within signaling pathways, time delays, protein oligomerization, and crosstalk between different pathways are main characters in the regulatory of gene expression. However, only a single noise source or only delay time in the deterministic model is considered in the gene transcriptional regulatory system in previous researches. The combined effects of correlated noise and time delays on the gene regulatory model still remain not to be fully understood. Results The roles of time delay on gene switch and stochastic resonance are systematically explored based on a famous gene transcriptional regulatory model subject to correlated noise. Two cases, including linear time delay appearing in the degradation process (case I) and nonlinear time delay appearing in the synthesis process (case II) are considered, respectively. For case I: Our theoretical results show that time delay can induce gene switch, i.e., the TF-A monomer concentration shifts from the high concentration state to the low concentration state ("on"→"off"). With increasing the time delay, the transition from "on" to "off" state can be further accelerated. Moreover, it is found that the stochastic resonance can be enhanced by both the time delay and correlated noise intensity. However, the additive noise original from the synthesis rate restrains the stochastic resonance. It is also very interesting that a resonance bi-peaks structure appears under large additive noise intensity. The theoretical results by using small-delay time-approximation approach are consistent well with our numerical simulation. For case II: Our numerical simulation results show that time delay can also induce the gene switch, however different with case I, the TF-A monomer concentration shifts from the low concentration state to the high concentration state ("off"→"on"). With increasing time delay, the transition from "on" to "off" state can be further

  19. Development of thermal hydraulic models for the reliable regulatory auditing code

    Energy Technology Data Exchange (ETDEWEB)

    Chung, B. D.; Song, C. H.; Lee, Y. J.; Kwon, T. S. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2003-04-15

    The objective of this project is to develop thermal hydraulic models for use in improving the reliability of the regulatory auditing codes. The current year fall under the first step of the 3 year project, and the main researches were focused on identifying the candidate thermal hydraulic models for improvement and to develop prototypical model development. During the current year, the verification calculations submitted for the APR 1400 design certification have been reviewed, the experimental data from the MIDAS DVI experiment facility in KAERI have been analyzed and evaluated, candidate thermal hydraulic models for improvement have been identified, prototypical models for the improved thermal hydraulic models have been developed, items for experiment in connection with the model development have been identified, and preliminary design of the experiment has been carried out.

  20. Modeling of regulatory networks: theory and applications in the study of the Drosophila circadian clock.

    Science.gov (United States)

    Scribner, Elizabeth Y; Fathallah-Shaykh, Hassan M

    2011-01-01

    Biological networks can be very complex. Mathematical modeling and simulation of regulatory networks can assist in resolving unanswered questions about these complex systems, which are often impossible to explore experimentally. The network regulating the Drosophila circadian clock is particularly amenable to such modeling given its complexity and what we call the clockwork orange (CWO) anomaly. CWO is a protein whose function in the network as an indirect activator of genes per, tim, vri, and pdp1 is counterintuitive--in isolated experiments, CWO inhibits transcription of these genes. Although many different types of modeling frameworks have recently been applied to the Drosophila circadian network, this chapter focuses on the application of continuous deterministic dynamic modeling to this network. In particular, we present three unique systems of ordinary differential equations that have been used to successfully model different aspects of the circadian network. The last model incorporates the newly identified protein CWO, and we explain how this model's unique mathematical equations can be used to explore and resolve the CWO anomaly. Finally, analysis of these equations gives rise to a new network regulatory rule, which clarifies the unusual role of CWO in this dynamical system.

  1. A service-oriented architecture for integrating the modeling and formal verification of genetic regulatory networks

    Directory of Open Access Journals (Sweden)

    Page Michel

    2009-12-01

    Full Text Available Abstract Background The study of biological networks has led to the development of increasingly large and detailed models. Computer tools are essential for the simulation of the dynamical behavior of the networks from the model. However, as the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. Formal verification based on temporal logic and model checking provides promising methods to automate and scale the analysis of the models. However, a framework that tightly integrates modeling and simulation tools with model checkers is currently missing, on both the conceptual and the implementational level. Results We have developed a generic and modular web service, based on a service-oriented architecture, for integrating the modeling and formal verification of genetic regulatory networks. The architecture has been implemented in the context of the qualitative modeling and simulation tool GNA and the model checkers NUSMV and CADP. GNA has been extended with a verification module for the specification and checking of biological properties. The verification module also allows the display and visual inspection of the verification results. Conclusions The practical use of the proposed web service is illustrated by means of a scenario involving the analysis of a qualitative model of the carbon starvation response in E. coli. The service-oriented architecture allows modelers to define the model and proceed with the specification and formal verification of the biological properties by means of a unified graphical user interface. This guarantees a transparent access to formal verification technology for modelers of genetic regulatory networks.

  2. The European Model Company Act: How to choose an efficient regulatory approach?

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    European Company Law regulation is currently undergoing a reform. These reforms raise a number of regulatory questions, such as what the aims of companies legislation should be, and how these aims should best be met by regulation. Many of the reforms and discussions (both on EU and national level......) on the organization of company laws reflect an interesting paradigm shift. Whereas, previously company law was primarily focused on preventing abuse, there is now a trend towards legislation that promote commerce and satisfy the needs of business. This means that the goal of economic efficiency is having...... an increasing influence on the framing of company legislation, such as the choice between mandatory or default rules. This article introduces the project "European Company Law and the choice of Regulatory Method" which is carried out in collaboration with the European Model Company Act Group. The project aims...

  3. Adaptive modelling of gene regulatory network using Bayesian information criterion-guided sparse regression approach.

    Science.gov (United States)

    Shi, Ming; Shen, Weiming; Wang, Hong-Qiang; Chong, Yanwen

    2016-12-01

    Inferring gene regulatory networks (GRNs) from microarray expression data are an important but challenging issue in systems biology. In this study, the authors propose a Bayesian information criterion (BIC)-guided sparse regression approach for GRN reconstruction. This approach can adaptively model GRNs by optimising the l1-norm regularisation of sparse regression based on a modified version of BIC. The use of the regularisation strategy ensures the inferred GRNs to be as sparse as natural, while the modified BIC allows incorporating prior knowledge on expression regulation and thus avoids the overestimation of expression regulators as usual. Especially, the proposed method provides a clear interpretation of combinatorial regulations of gene expression by optimally extracting regulation coordination for a given target gene. Experimental results on both simulation data and real-world microarray data demonstrate the competent performance of discovering regulatory relationships in GRN reconstruction.

  4. Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations.

    Directory of Open Access Journals (Sweden)

    Xiaodong Cai

    Full Text Available Integrating genetic perturbations with gene expression data not only improves accuracy of regulatory network topology inference, but also enables learning of causal regulatory relations between genes. Although a number of methods have been developed to integrate both types of data, the desiderata of efficient and powerful algorithms still remains. In this paper, sparse structural equation models (SEMs are employed to integrate both gene expression data and cis-expression quantitative trait loci (cis-eQTL, for modeling gene regulatory networks in accordance with biological evidence about genes regulating or being regulated by a small number of genes. A systematic inference method named sparsity-aware maximum likelihood (SML is developed for SEM estimation. Using simulated directed acyclic or cyclic networks, the SML performance is compared with that of two state-of-the-art algorithms: the adaptive Lasso (AL based scheme, and the QTL-directed dependency graph (QDG method. Computer simulations demonstrate that the novel SML algorithm offers significantly better performance than the AL-based and QDG algorithms across all sample sizes from 100 to 1,000, in terms of detection power and false discovery rate, in all the cases tested that include acyclic or cyclic networks of 10, 30 and 300 genes. The SML method is further applied to infer a network of 39 human genes that are related to the immune function and are chosen to have a reliable eQTL per gene. The resulting network consists of 9 genes and 13 edges. Most of the edges represent interactions reasonably expected from experimental evidence, while the remaining may just indicate the emergence of new interactions. The sparse SEM and efficient SML algorithm provide an effective means of exploiting both gene expression and perturbation data to infer gene regulatory networks. An open-source computer program implementing the SML algorithm is freely available upon request.

  5. Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models.

    Directory of Open Access Journals (Sweden)

    Dmitry Svetlichnyy

    2015-11-01

    Full Text Available Cancer genomes contain vast amounts of somatic mutations, many of which are passenger mutations not involved in oncogenesis. Whereas driver mutations in protein-coding genes can be distinguished from passenger mutations based on their recurrence, non-coding mutations are usually not recurrent at the same position. Therefore, it is still unclear how to identify cis-regulatory driver mutations, particularly when chromatin data from the same patient is not available, thus relying only on sequence and expression information. Here we use machine-learning methods to predict functional regulatory regions using sequence information alone, and compare the predicted activity of the mutated region with the reference sequence. This way we define the Predicted Regulatory Impact of a Mutation in an Enhancer (PRIME. We find that the recently identified driver mutation in the TAL1 enhancer has a high PRIME score, representing a "gain-of-target" for MYB, whereas the highly recurrent TERT promoter mutation has a surprisingly low PRIME score. We trained Random Forest models for 45 cancer-related transcription factors, and used these to score variations in the HeLa genome and somatic mutations across more than five hundred cancer genomes. Each model predicts only a small fraction of non-coding mutations with a potential impact on the function of the encompassing regulatory region. Nevertheless, as these few candidate driver mutations are often linked to gains in chromatin activity and gene expression, they may contribute to the oncogenic program by altering the expression levels of specific oncogenes and tumor suppressor genes.

  6. A Hybrid Model of a Genetic Regulatory Network in Mammalian Sclera

    Directory of Open Access Journals (Sweden)

    Qin Shu

    2013-08-01

    Full Text Available Myopia in human and animals is caused by the axial elongation of the eye and is closely linked to the thinning of the sclera which supports the eye tissue. This thinning has been correlated with the overproduction of matrix metalloproteinase (MMP-2, an enzyme that degrades the collagen structure of the sclera. In this short paper, we propose a descriptive model of a regulatory network with hysteresis, which seems necessary for creating oscillatory behavior in the hybrid model between MMP-2, MT1-MMP and TIMP-2. Numerical results provide insight on the type of equilibria present in the system.

  7. A Dynamic Gene Regulatory Network Model That Recovers the Cyclic Behavior of Arabidopsis thaliana Cell Cycle

    Science.gov (United States)

    Ortiz-Gutiérrez, Elizabeth; García-Cruz, Karla; Azpeitia, Eugenio; Castillo, Aaron; Sánchez, María de la Paz; Álvarez-Buylla, Elena R.

    2015-01-01

    Cell cycle control is fundamental in eukaryotic development. Several modeling efforts have been used to integrate the complex network of interacting molecular components involved in cell cycle dynamics. In this paper, we aimed at recovering the regulatory logic upstream of previously known components of cell cycle control, with the aim of understanding the mechanisms underlying the emergence of the cyclic behavior of such components. We focus on Arabidopsis thaliana, but given that many components of cell cycle regulation are conserved among eukaryotes, when experimental data for this system was not available, we considered experimental results from yeast and animal systems. We are proposing a Boolean gene regulatory network (GRN) that converges into only one robust limit cycle attractor that closely resembles the cyclic behavior of the key cell-cycle molecular components and other regulators considered here. We validate the model by comparing our in silico configurations with data from loss- and gain-of-function mutants, where the endocyclic behavior also was recovered. Additionally, we approximate a continuous model and recovered the temporal periodic expression profiles of the cell-cycle molecular components involved, thus suggesting that the single limit cycle attractor recovered with the Boolean model is not an artifact of its discrete and synchronous nature, but rather an emergent consequence of the inherent characteristics of the regulatory logic proposed here. This dynamical model, hence provides a novel theoretical framework to address cell cycle regulation in plants, and it can also be used to propose novel predictions regarding cell cycle regulation in other eukaryotes. PMID:26340681

  8. Alignment and prediction of cis-regulatory modules based on a probabilistic model of evolution.

    Science.gov (United States)

    He, Xin; Ling, Xu; Sinha, Saurabh

    2009-03-01

    Cross-species comparison has emerged as a powerful paradigm for predicting cis-regulatory modules (CRMs) and understanding their evolution. The comparison requires reliable sequence alignment, which remains a challenging task for less conserved noncoding sequences. Furthermore, the existing models of DNA sequence evolution generally do not explicitly treat the special properties of CRM sequences. To address these limitations, we propose a model of CRM evolution that captures different modes of evolution of functional transcription factor binding sites (TFBSs) and the background sequences. A particularly novel aspect of our work is a probabilistic model of gains and losses of TFBSs, a process being recognized as an important part of regulatory sequence evolution. We present a computational framework that uses this model to solve the problems of CRM alignment and prediction. Our alignment method is similar to existing methods of statistical alignment but uses the conserved binding sites to improve alignment. Our CRM prediction method deals with the inherent uncertainties of binding site annotations and sequence alignment in a probabilistic framework. In simulated as well as real data, we demonstrate that our program is able to improve both alignment and prediction of CRM sequences over several state-of-the-art methods. Finally, we used alignments produced by our program to study binding site conservation in genome-wide binding data of key transcription factors in the Drosophila blastoderm, with two intriguing results: (i) the factor-bound sequences are under strong evolutionary constraints even if their neighboring genes are not expressed in the blastoderm and (ii) binding sites in distal bound sequences (relative to transcription start sites) tend to be more conserved than those in proximal regions. Our approach is implemented as software, EMMA (Evolutionary Model-based cis-regulatory Module Analysis), ready to be applied in a broad biological context.

  9. Alignment and prediction of cis-regulatory modules based on a probabilistic model of evolution.

    Directory of Open Access Journals (Sweden)

    Xin He

    2009-03-01

    Full Text Available Cross-species comparison has emerged as a powerful paradigm for predicting cis-regulatory modules (CRMs and understanding their evolution. The comparison requires reliable sequence alignment, which remains a challenging task for less conserved noncoding sequences. Furthermore, the existing models of DNA sequence evolution generally do not explicitly treat the special properties of CRM sequences. To address these limitations, we propose a model of CRM evolution that captures different modes of evolution of functional transcription factor binding sites (TFBSs and the background sequences. A particularly novel aspect of our work is a probabilistic model of gains and losses of TFBSs, a process being recognized as an important part of regulatory sequence evolution. We present a computational framework that uses this model to solve the problems of CRM alignment and prediction. Our alignment method is similar to existing methods of statistical alignment but uses the conserved binding sites to improve alignment. Our CRM prediction method deals with the inherent uncertainties of binding site annotations and sequence alignment in a probabilistic framework. In simulated as well as real data, we demonstrate that our program is able to improve both alignment and prediction of CRM sequences over several state-of-the-art methods. Finally, we used alignments produced by our program to study binding site conservation in genome-wide binding data of key transcription factors in the Drosophila blastoderm, with two intriguing results: (i the factor-bound sequences are under strong evolutionary constraints even if their neighboring genes are not expressed in the blastoderm and (ii binding sites in distal bound sequences (relative to transcription start sites tend to be more conserved than those in proximal regions. Our approach is implemented as software, EMMA (Evolutionary Model-based cis-regulatory Module Analysis, ready to be applied in a broad biological context.

  10. When the model fits the frame: the impact of regulatory fit on efficacy appraisal and persuasion in health communication.

    Science.gov (United States)

    Bosone, Lucia; Martinez, Frédéric; Kalampalikis, Nikos

    2015-04-01

    In health-promotional campaigns, positive and negative role models can be deployed to illustrate the benefits or costs of certain behaviors. The main purpose of this article is to investigate why, how, and when exposure to role models strengthens the persuasiveness of a message, according to regulatory fit theory. We argue that exposure to a positive versus a negative model activates individuals' goals toward promotion rather than prevention. By means of two experiments, we demonstrate that high levels of persuasion occur when a message advertising healthy dietary habits offers a regulatory fit between its framing and the described role model. Our data also establish that the effects of such internal regulatory fit by vicarious experience depend on individuals' perceptions of response-efficacy and self-efficacy. Our findings constitute a significant theoretical complement to previous research on regulatory fit and contain valuable practical implications for health-promotional campaigns. © 2015 by the Society for Personality and Social Psychology, Inc.

  11. Chemosensory processing in the fruit fly, Drosophila melanogaster: Generalization of a feeding response reveals overlapping odour representations

    Indian Academy of Sciences (India)

    Sathees B C Chandra; Sandeep Singh

    2005-12-01

    Insects are capable of detecting, and discriminating between, a very large number of odours. The biological relevance of many of those odours, particularly those related to food, must first be learned. Given that the number of sensory receptors and antennal lobe (AL) glomeruli is limited relative to the number of odours that must be detectable, this ability implies that the olfactory system makes use of a combinatorial coding scheme whereby each sensory cell or AL projection neuron can participate in coding for several different odours. An important step in understanding this coding scheme is to behaviourally quantify the degree to which sets of odours are discriminable. Here we evaluate odour discriminability in the fruit fly, Drosophila melanogaster, by first conditioning individual flies to not respond to any of several odourants using a nonassociative conditioning protocol (habituation). We show that flies habituate unconditioned leg movement responses to both mechanosensory and olfactory stimulation over 25 unreinforceed trials. Habituation is retained for at least 2 h and is subject to dishabituation. Finally, we test the degree to which the conditioned response generalizes to other odourants based on molecular features of the odourants (e.g. carbon chain length and the presence of a target functional group). These tests reveal predictable generalization gradients across these molecular features. These data substantiate the claim that these features are relevant coding dimensions in the fruit fly olfactory system, as has been shown for other insect and vertebrate species.

  12. Odour-evoked responses to queen pheromone components and to plant odours using optical imaging in the antennal lobe of the honey bee drone Apis mellifera L.

    Science.gov (United States)

    Sandoz, Jean-Christophe

    2006-09-01

    The primordial functional role of honey bee males (drones) is to mate with virgin queens, a behaviour relying heavily on the olfactory detection of queen pheromone. In the present work I studied olfactory processing in the drone antennal lobe (AL), the primary olfactory centre of the insect brain. In drones, the AL consists of about 103 ordinary glomeruli and four enlarged glomeruli, the macroglomeruli (MG). Two macroglomeruli (MG1 and MG2) and approximately 20 ordinary glomeruli occupy the anterior surface of the antennal lobe and are thus accessible to optical recordings. Calcium imaging was used to measure odour-evoked responses to queen pheromonal components and plant odours. MG2 responded specifically to the main component of the queen mandibular pheromone, 9-ODA. The secondary components HOB and HVA each triggered activity in one, but not the same, ordinary glomerulus. MG1 did not respond to any of the tested stimuli. Plant odours induced signals only in ordinary glomeruli in a combinatorial manner, as in workers. This study thus shows that the major queen pheromonal component is processed in the most voluminous macroglomerulus of the drone antennal lobe, and that plant odours, as well as some queen pheromonal components, are processed in ordinary glomeruli.

  13. NetDiff - Bayesian model selection for differential gene regulatory network inference.

    Science.gov (United States)

    Thorne, Thomas

    2016-12-16

    Differential networks allow us to better understand the changes in cellular processes that are exhibited in conditions of interest, identifying variations in gene regulation or protein interaction between, for example, cases and controls, or in response to external stimuli. Here we present a novel methodology for the inference of differential gene regulatory networks from gene expression microarray data. Specifically we apply a Bayesian model selection approach to compare models of conserved and varying network structure, and use Gaussian graphical models to represent the network structures. We apply a variational inference approach to the learning of Gaussian graphical models of gene regulatory networks, that enables us to perform Bayesian model selection that is significantly more computationally efficient than Markov Chain Monte Carlo approaches. Our method is demonstrated to be more robust than independent analysis of data from multiple conditions when applied to synthetic network data, generating fewer false positive predictions of differential edges. We demonstrate the utility of our approach on real world gene expression microarray data by applying it to existing data from amyotrophic lateral sclerosis cases with and without mutations in C9orf72, and controls, where we are able to identify differential network interactions for further investigation.

  14. Data-driven integration of genome-scale regulatory and metabolic network models

    Directory of Open Access Journals (Sweden)

    Saheed eImam

    2015-05-01

    Full Text Available Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription and signaling have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert – a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or more network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. In this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.

  15. Advances in the integration of transcriptional regulatory information into genome-scale metabolic models.

    Science.gov (United States)

    Vivek-Ananth, R P; Samal, Areejit

    2016-09-01

    A major goal of systems biology is to build predictive computational models of cellular metabolism. Availability of complete genome sequences and wealth of legacy biochemical information has led to the reconstruction of genome-scale metabolic networks in the last 15 years for several organisms across the three domains of life. Due to paucity of information on kinetic parameters associated with metabolic reactions, the constraint-based modelling approach, flux balance analysis (FBA), has proved to be a vital alternative to investigate the capabilities of reconstructed metabolic networks. In parallel, advent of high-throughput technologies has led to the generation of massive amounts of omics data on transcriptional regulation comprising mRNA transcript levels and genome-wide binding profile of transcriptional regulators. A frontier area in metabolic systems biology has been the development of methods to integrate the available transcriptional regulatory information into constraint-based models of reconstructed metabolic networks in order to increase the predictive capabilities of computational models and understand the regulation of cellular metabolism. Here, we review the existing methods to integrate transcriptional regulatory information into constraint-based models of metabolic networks.

  16. Development of thermal hydraulic models for the reliable regulatory auditing code

    Energy Technology Data Exchange (ETDEWEB)

    Chung, B. D.; Song, C. H.; Lee, Y. J.; Kwon, T. S.; Lee, S. W. [Korea Automic Energy Research Institute, Taejon (Korea, Republic of)

    2004-02-15

    The objective of this project is to develop thermal hydraulic models for use in improving the reliability of the regulatory auditing codes. The current year fall under the second step of the 3 year project, and the main researches were focused on the development of downcorner boiling model. During the current year, the bubble stream model of downcorner has been developed and installed in he auditing code. The model sensitivity analysis has been performed for APR1400 LBLOCA scenario using the modified code. The preliminary calculation has been performed for the experimental test facility using FLUENT and MARS code. The facility for air bubble experiment has been installed. The thermal hydraulic phenomena for VHTR and super critical reactor have been identified for the future application and model development.

  17. Robustness and state-space structure of Boolean gene regulatory models.

    Science.gov (United States)

    Willadsen, Kai; Wiles, Janet

    2007-12-21

    Robustness to perturbation is an important characteristic of genetic regulatory systems, but the relationship between robustness and model dynamics has not been clearly quantified. We propose a method for quantifying both robustness and dynamics in terms of state-space structures, for Boolean models of genetic regulatory systems. By investigating existing models of the Drosophila melanogaster segment polarity network and the Saccharomyces cerevisiae cell-cycle network, we show that the structure of attractor basins can yield insight into the underlying decision making required of the system, and also the way in which the system maximises its robustness. In particular, gene networks implementing decisions based on a few genes have simple state-space structures, and their attractors are robust by virtue of their simplicity. Gene networks with decisions that involve many interacting genes have correspondingly more complicated state-space structures, and robustness cannot be achieved through the structure of the attractor basins, but is achieved by larger attractor basins that dominate the state space. These different types of robustness are demonstrated by the two models: the D. melanogaster segment polarity network is robust due to simple attractor basins that implement decisions based on spatial signals; the S. cerevisiae cell-cycle network has a complicated state-space structure, and is robust only due to a giant attractor basin that dominates the state space.

  18. A Framework for Organizing Current and Future Electric Utility Regulatory and Business Models

    Energy Technology Data Exchange (ETDEWEB)

    Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fadrhonc, Emily Martin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-06-01

    Many regulators, utilities, customer groups, and other stakeholders are reevaluating existing regulatory models and the roles and financial implications for electric utilities in the context of today’s environment of increasing distributed energy resource (DER) penetrations, forecasts of significant T&D investment, and relatively flat or negative utility sales growth. When this is coupled with predictions about fewer grid-connected customers (i.e., customer defection), there is growing concern about the potential for serious negative impacts on the regulated utility business model. Among states engaged in these issues, the range of topics under consideration is broad. Most of these states are considering whether approaches that have been applied historically to mitigate the impacts of previous “disruptions” to the regulated utility business model (e.g., energy efficiency) as well as to align utility financial interests with increased adoption of such “disruptive technologies” (e.g., shareholder incentive mechanisms, lost revenue mechanisms) are appropriate and effective in the present context. A handful of states are presently considering more fundamental changes to regulatory models and the role of regulated utilities in the ownership, management, and operation of electric delivery systems (e.g., New York “Reforming the Energy Vision” proceeding).

  19. Evolution in performance assessment modeling as a result of regulatory review

    Energy Technology Data Exchange (ETDEWEB)

    Rowat, J.H.; Dolinar, G.M.; Stephens, M.E. [AECL Chalk River Labs., Ontario (Canada)] [and others

    1995-12-31

    AECL is planning to build the IRUS (Intrusion Resistant Underground Structure) facility for near-surface disposal of LLRW. The PSAR (preliminary safety assessment report) was subject to an initial regulatory review during mid-1992. The regulatory authority provided comments on many aspects of the safety assessment documentation including a number of questions on specific PA (Performance Assessment) modelling assumptions. As a result of these comments as well as a separate detailed review of the IRUS disposal concept, changes were made to the conceptual and mathematical models. The original disposal concept included a non-sorbing vault backfill, with a strong reliance on the wasteform as a barrier. This concept was altered to decrease reliance on the wasteform by replacing the original backfill with a sand/clinoptilolite mix, which is a better sorber of metal cations. This change lead to changes in the PA models which in turn altered the safety case for the facility. This, and other changes that impacted performance assessment modelling are the subject of this paper.

  20. Removal of garlic-like off-odours from crustacea by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, D.J.; Izzard, M.E. (Australian Atomic Energy Commission Research Establishment, Lucas Heights); Whitfield, F.B. (Commonwealth Scientific and Industrial Research Organization, North Ryde (Australia). Div. of Food Research)

    1985-04-01

    The strong garlic-like off-odours associated with the male shovel-nosed lobster (Ibacus peronii) and the royal red prawn (Hymenopenaeus sibogae) have been attributed principally to the presence of the sulphur-containing compound bis-(methylthio)-methane. In the male shovel-nosed lobster the concentration of this compound increases very rapidly following death, and a small number of contaminated crustacea may cause an entire consignment to be condemned. A method for removing this noxious odour was developed which involved gamma-irradiation of the affected crustacea using a cobalt-60 source. Eight lobsters were subjected to gamma-irradiation at a dose rate of 10 kGy an hour; one half of each was given a dose of 25 kGy and the other half a dose of 5 kGy. Results showed that a high dose completely removes the existing off-odour, and also prevents its further formation. With the lower dose the off-odour is not completely removed. A trial using fresh royal red prawns at doses of 0.5 and 1.0 kGy showed irradiation removed all traces of the off-odour, but in those irradiated at the higher dose a slight burnt flavour was noticeable.

  1. Odour removal with a trickling filter at a small WWTP strongly influenced by the tourism season.

    Science.gov (United States)

    Patria, L; Cathelain, M; Laurens, P; Barbere, J P

    2001-01-01

    Etaples-Le Touquet's wastewater treatment plant (WWTP) is based on a coastal area of the Artois-Picardie region. The pollution load can vary from 20,000 p.e. to 60,000 p.e. over a weekend or in summer. The Collectivity and the Water Agency decided to cover and ventilate the main odour source points of the plant. The foul air was directed to a 2,500 m3/h inorganic bed biofilter (Alizair) for odour control. An odour monitoring took place during the first year of operation taking into account cold and warm seasons, high and low tourism seasons. The Alizair biofilter appeared an appropriate odour control process for small sized wastewater treatment plants, easy to operate and efficient even in areas where tourism seasons have a great impact on the pollution load arriving at the plant. The neighbourhood did not complain about odours any more and the operator was very confident with such a simple and effective system. The local Authorities and the Water Agency agreed to recommend Alizair biofilters with an autotrophic biomass adapted in the case of an old WWTP that cannot be up graded any more or for large pumping stations and wastewater storage prior treatment.

  2. Odours of Plasmodium falciparum-infected participants influence mosquito-host interactions.

    Science.gov (United States)

    de Boer, Jetske G; Robinson, Ailie; Powers, Stephen J; Burgers, Saskia L G E; Caulfield, John C; Birkett, Michael A; Smallegange, Renate C; van Genderen, Perry J J; Bousema, Teun; Sauerwein, Robert W; Pickett, John A; Takken, Willem; Logan, James G

    2017-08-24

    Malaria parasites are thought to influence mosquito attraction to human hosts, a phenomenon that may enhance parasite transmission. This is likely mediated by alterations in host odour because of its importance in mosquito host-searching behaviour. Here, we report that the human skin odour profile is affected by malaria infection. We compared the chemical composition and attractiveness to Anopheles coluzzii mosquitoes of skin odours from participants that were infected by Controlled Human Malaria Infection with Plasmodium falciparum. Skin odour composition differed between parasitologically negative and positive samples, with positive samples collected on average two days after parasites emerged from the liver into the blood, being associated with low densities of asexual parasites and the absence of gametocytes. We found a significant reduction in mosquito attraction to skin odour during infection for one experiment, but not in a second experiment, possibly due to differences in parasite strain. However, it does raise the possibility that infection can affect mosquito behaviour. Indeed, several volatile compounds were identified that can influence mosquito behaviour, including 2- and 3-methylbutanal, 3-hydroxy-2-butanone, and 6-methyl-5-hepten-2-one. To better understand the impact of our findings on Plasmodium transmission, controlled studies are needed in participants with gametocytes and higher parasite densities.

  3. Simulating microinjection experiments in a novel model of the rat sleep-wake regulatory network.

    Science.gov (United States)

    Diniz Behn, Cecilia G; Booth, Victoria

    2010-04-01

    This study presents a novel mathematical modeling framework that is uniquely suited to investigating the structure and dynamics of the sleep-wake regulatory network in the brain stem and hypothalamus. It is based on a population firing rate model formalism that is modified to explicitly include concentration levels of neurotransmitters released to postsynaptic populations. Using this framework, interactions among primary brain stem and hypothalamic neuronal nuclei involved in rat sleep-wake regulation are modeled. The model network captures realistic rat polyphasic sleep-wake behavior consisting of wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep states. Network dynamics include a cyclic pattern of NREM sleep, REM sleep, and wake states that is disrupted by simulated variability of neurotransmitter release and external noise to the network. Explicit modeling of neurotransmitter concentrations allows for simulations of microinjections of neurotransmitter agonists and antagonists into a key wake-promoting population, the locus coeruleus (LC). Effects of these simulated microinjections on sleep-wake states are tracked and compared with experimental observations. Agonist/antagonist pairs, which are presumed to have opposing effects on LC activity, do not generally induce opposing effects on sleep-wake patterning because of multiple mechanisms for LC activation in the network. Also, different agents, which are presumed to have parallel effects on LC activity, do not induce parallel effects on sleep-wake patterning because of differences in the state dependence or independence of agonist and antagonist action. These simulation results highlight the utility of formal mathematical modeling for constraining conceptual models of the sleep-wake regulatory network.

  4. Prebiotics mitigate in vitro sulfur-containing odour generation in caecal content of pigs

    Directory of Open Access Journals (Sweden)

    Yuan Fan Deng

    2015-03-01

    Full Text Available The objective of this study was to examine the effects and role of prebiotics, such as inulin, fructo-oligosaccharides (FOS and galactooligosaccharides (GAS, to mitigate sulfur-containing odour gases, hydrogen sulfide (H2S and methyl mercaptan (CH3SH using pigs as in vitro study model. Inocula obtained from pigs were incubated at 39°C for 24 h using 550 mg sterilised substrate (caecal contents supplemented with or without 50 mg prebiotics. Production of total gas, H2S and CH3SH were determined. The results showed that total gas production for the caecal content of pigs was 57.3 mL, and that for H2S and CH3SH was 220.2 and 15.2 μL, respectively. The total gas production increased (P<0.05, whereas concentrations of H2S and CH3SH decreased (P<0.05 with supplementation of prebiotics. Among the prebiotics, inulin was the most effective in mitigating H2S and CH3SH productions, reducing the two malodorous gases by 14.7 and 19.8%, respectively. The reduction of the above two sulfur- containing gases was supported by lower sulfate-reducing bacteria population and higher sulfate radical concentrations in the prebiotics, particularly that of inulin supplementation group.

  5. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Directory of Open Access Journals (Sweden)

    Samra Khalid

    2016-10-01

    Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

  6. Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

    Science.gov (United States)

    Tareen, Samar H.K.; Siddiqa, Amnah; Bibi, Zurah; Ahmad, Jamil

    2016-01-01

    Background Breast cancer (BC) is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s). It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α) associated Biological Regulatory Network (BRN) for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN) to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs) such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR) for wet lab experiments as well as provided valuable insights in the treatment of cancers such as BC.

  7. Inferring cellular regulatory networks with Bayesian model averaging for linear regression (BMALR).

    Science.gov (United States)

    Huang, Xun; Zi, Zhike

    2014-08-01

    Bayesian network and linear regression methods have been widely applied to reconstruct cellular regulatory networks. In this work, we propose a Bayesian model averaging for linear regression (BMALR) method to infer molecular interactions in biological systems. This method uses a new closed form solution to compute the posterior probabilities of the edges from regulators to the target gene within a hybrid framework of Bayesian model averaging and linear regression methods. We have assessed the performance of BMALR by benchmarking on both in silico DREAM datasets and real experimental datasets. The results show that BMALR achieves both high prediction accuracy and high computational efficiency across different benchmarks. A pre-processing of the datasets with the log transformation can further improve the performance of BMALR, leading to a new top overall performance. In addition, BMALR can achieve robust high performance in community predictions when it is combined with other competing methods. The proposed method BMALR is competitive compared to the existing network inference methods. Therefore, BMALR will be useful to infer regulatory interactions in biological networks. A free open source software tool for the BMALR algorithm is available at https://sites.google.com/site/bmalr4netinfer/.

  8. Does warmth have a smell? The influence of ambient odour on perceived physical and social warmth

    DEFF Research Database (Denmark)

    Dijksterhuis, Garmt Bernard; Smeets, Monique; Brugman, Narelle

    are shown to exert effects on subsequent perceptions, as other studies have relied on present physically warm or cold primes. We surmise that associations of warmth acquired from exposure to advertisements in which pea soup is consumed during winter and in a socially warm setting can cue broad mental......Odour has a major influence on cognition and behaviour. We here examined its influence on temperature perception. Research on social warmth has shown that social behaviour can be influenced by physical warmth and vice versa. Most studies focussing on this subject used a physical prime to influence...... social warmth. In the current study odour primes previously associated with cues of warm temperature and social warmth are used instead. The aim of this study was to examine whether odour affects perceptions of physical and social warmth. Participants were primed with a warm (pea soup) or cold...

  9. Does warmth have a smell? The influence of ambient odour on perceived physical and social warmth

    DEFF Research Database (Denmark)

    Dijksterhuis, Garmt Bernard; Smeets, Monique; Brugman, Narelle

    Odour has a major influence on cognition and behaviour. We here examined its influence on temperature perception. Research on social warmth has shown that social behaviour can be influenced by physical warmth and vice versa. Most studies focussing on this subject used a physical prime to influence...... social warmth. In the current study odour primes previously associated with cues of warm temperature and social warmth are used instead. The aim of this study was to examine whether odour affects perceptions of physical and social warmth. Participants were primed with a warm (pea soup) or cold...... are shown to exert effects on subsequent perceptions, as other studies have relied on present physically warm or cold primes. We surmise that associations of warmth acquired from exposure to advertisements in which pea soup is consumed during winter and in a socially warm setting can cue broad mental...

  10. Towards biological plausibility of electronic noses: A spiking neural network based approach for tea odour classification.

    Science.gov (United States)

    Sarkar, Sankho Turjo; Bhondekar, Amol P; Macaš, Martin; Kumar, Ritesh; Kaur, Rishemjit; Sharma, Anupma; Gulati, Ashu; Kumar, Amod

    2015-11-01

    The paper presents a novel encoding scheme for neuronal code generation for odour recognition using an electronic nose (EN). This scheme is based on channel encoding using multiple Gaussian receptive fields superimposed over the temporal EN responses. The encoded data is further applied to a spiking neural network (SNN) for pattern classification. Two forms of SNN, a back-propagation based SpikeProp and a dynamic evolving SNN are used to learn the encoded responses. The effects of information encoding on the performance of SNNs have been investigated. Statistical tests have been performed to determine the contribution of the SNN and the encoding scheme to overall odour discrimination. The approach has been implemented in odour classification of orthodox black tea (Kangra-Himachal Pradesh Region) thereby demonstrating a biomimetic approach for EN data analysis.

  11. The origin of off-odours in packaged rucola (Eruca sativa).

    Science.gov (United States)

    Nielsen, Tim; Bergström, Birgitta; Borch, Elisabeth

    2008-09-01

    Rucola (Eruca sativa) was decontaminated and then reinoculated with selected microorganisms. The produce was then stored in three different atmospheres and at two temperatures. The accumulation of off-odours in the packaging headspace was analysed. A dozen compounds were detected by olfactometry but only dimethyl sulphide and dimethyl disulphide were considered to have a strong or moderate intensity. Thus, they were identified as the substances causing an unpleasant smell inside the bags. Inoculation with microorganisms resulted in higher production of off-odours. Samples inoculated with Pseudomonadaceae&Xanthamonadaceae were particularly potent in producing the two sulphides. The off-odour problem was much more prominent in samples that were kept in a packaging material that did not allow gas exchange resulting in oxygen levels below 1%. Higher levels of sulphides were detected at 8°C than at 4°C.

  12. Food neophobia and its relation with olfactory ability in common odour identification.

    Science.gov (United States)

    Demattè, M Luisa; Endrizzi, Isabella; Biasioli, Franco; Corollaro, Maria Laura; Pojer, Nicola; Zampini, Massimiliano; Aprea, Eugenio; Gasperi, Flavia

    2013-09-01

    Food neophobia is strictly connected with many different aspects of human feeding, ranging from food preferences to food choice, from active chemosensory exploration of the world (sniffing and tasting) to physiological responses associated with alertness. Therefore in this study, we tested the ability of 167 participants (54 women and 113 men, aged between 20 and 59 years old) to correctly identify 36 common odours, and we verified whether such ability could be related to their level of neophobia toward food and to demographic parameters (i.e., age, gender, and smoking habits). In the analyses, an advantage in odour identification abilities for non-neophobic people over more-neophobic participants was observed. As for participants' demographic information, a smaller reluctance to try new food in older than younger people was highlighted. The results of the present study suggest a connection between the attitude toward the exploration of the chemosensory environment and the ability to identify odours.

  13. Electroantennogram responses of tsetse flies (Glossina pallidipes) to host odours in an open field and riverine woodland

    NARCIS (Netherlands)

    Voskamp, K.E; den Otter, C.J; Noorman, N

    1998-01-01

    The present study was initiated to gain insight into the way in which tsetse flies (Glossina spp.) sense odours at different locations in odour plumes in both an open field and a wooded area. We recorded the antennal responses (EAGs) from stationary living female G. pallidipes 15 m upwind and at var

  14. A Sensitivity Study of the Validation of Three Regulatory Dispersion Models

    Directory of Open Access Journals (Sweden)

    Keith D.   Harsham

    2008-01-01

    Full Text Available Lidar measurements were made of the dispersion of the plume from a coastal industrial plant over three weeks between September 1996 and May 1998. 67 experimental runs were obtained, mostly of 30 min duration, and these were analysed to provide plume parameters (i.e. height, vertical and lateral spreads. These measurements were supplemented by local meteorological measurements at two portable meteorological stations and also by radiosonde measurements of wind, temperature and pressure profiles. The dispersion was modelled using three commercial regulatory models: ISC3 (EPA, Trinity Consultants and Lakes Environmental, UK-ADMS (CERC and AERMOD (EPA, Lakes Environmental. Where possible, each model was run applying all choices as between urban or rural surface characteristics; wind speed measured at 10 m or 100 m; and surface corrected for topography or topography plus buildings. We have compared the range of output from each model with the Lidar measurements. In the main, the models underestimated dispersion in the near field and overestimated it beyond a few hundred m. ISC tended to show the smallest dispersion, while AERMOD gave the largest values for the lateral spread and ADMS gave the largest values of the vertical spread. Buoyant plume rise was modelled well in neutral conditions but rather erratically in unstable conditions. The models are quite sensitive to the reasonable input choices listed above: the full range of sensitivity is comparable to the difference between the median modelled value and the measured value.

  15. Behavioral and olfactory responses of grasshopper hatchlings, Melanoplus sanguinipes, to plant odours and volatile compounds

    Institute of Scientific and Technical Information of China (English)

    KANG Le; T. L. Hopkins

    2004-01-01

    Behavior and olfactory responses of grasshopper hatchlings, Melanoplus sanguinipes (F.), to odours from plant foliage and volatile compounds were tested using a glass Y-tube olfactometer and electroantennogram (EAG) techniques respectively. In single choice trials, newly hatched hoppers were much more sensitive to the odour from intact leaves and chopped foliage of ryegrass and wheat than other plants. Chopped sorghum leaves, but not stem-cut sorghum, were also significantly attractive. The orientation responses of grasshopper hatchlings to these plants were highly consistent with those of last instar hoppers and adults. When ryegrass was employed as the control, the odour from stem-cut alfalfa was more attractive. There was no significant difference in hopper orientation responses to the odours from chopped seedlings of sorghum, alfalfa, wheat or ryegrass. However, significantly more hoppers preferred the chopped ryegrass control to chopped Louisanna sage. Measurement of the EAG response of first instar hoppers to these plant odours showed that the odour of Louisanna sage elicited the greatest response amplitudes. In olfactory tests using different volatile components, Z-3-hexenol, E-3-hexenol, Z-hex-3-enyl acetate, E-2-hexenal and hexenal gave greater EAG responses than geraniol and 1-octen-3-ol. These results are also consistent with comparable data from adults. Newly hatched grasshoppers had similar EAG response profiles to plant materials and chemicals to those of adults, although the absolute EAG values of young hoppers were much lower than those of adults. Therefore, newly hatched hoppers were able to distinguish plants from an air control, and even host plants from non-host plants, and the feeding experience of hoppers probably has little influence on their subsequent ability as adults to identify and locate food plants.

  16. Shades of yellow: interactive effects of visual and odour cues in a pest beetle

    Directory of Open Access Journals (Sweden)

    Sarah E.J. Arnold

    2016-07-01

    Full Text Available Background: The visual ecology of pest insects is poorly studied compared to the role of odour cues in determining their behaviour. Furthermore, the combined effects of both odour and vision on insect orientation are frequently ignored, but could impact behavioural responses. Methods: A locomotion compensator was used to evaluate use of different visual stimuli by a major coleopteran pest of stored grains (Sitophilus zeamais, with and without the presence of host odours (known to be attractive to this species, in an open-loop setup. Results: Some visual stimuli—in particular, one shade of yellow, solid black and high-contrast black-against-white stimuli—elicited positive orientation behaviour from the beetles in the absence of odour stimuli. When host odours were also present, at 90° to the source of the visual stimulus, the beetles presented with yellow and vertical black-on-white grating patterns changed their walking course and typically adopted a path intermediate between the two stimuli. The beetles presented with a solid black-on-white target continued to orient more strongly towards the visual than the odour stimulus. Discussion: Visual stimuli can strongly influence orientation behaviour, even in species where use of visual cues is sometimes assumed to be unimportant, while the outcomes from exposure to multimodal stimuli are unpredictable and need to be determined under differing conditions. The importance of the two modalities of stimulus (visual and olfactory in food location is likely to depend upon relative stimulus intensity and motivational state of the insect.

  17. An overview of the gene regulatory network controlling trichome development in the model plant, Arabidopsis

    Directory of Open Access Journals (Sweden)

    Sitakanta ePattanaik

    2014-06-01

    Full Text Available Trichomes are specialized epidermal cells located on aerial parts of plants and are associated with a wide array of biological processes. Trichomes protect plants from adverse conditions including UV light and herbivore attack and are also an important source of a number of phytochemicals. The simple unicellular trichomes of Arabidopsis serve as an excellent model to study molecular mechanism of cell differentiation and pattern formation in plants. The emerging picture suggests that the developmental process is controlled by a transcriptional network involving three major groups of transcription factors: the R2R3 MYB, basic helix-loop-helix (bHLH and WD40 repeat (WDR protein. These regulatory proteins form a trimeric activator complex that positively regulates trichome development. The single repeat R3 MYBs act as negative regulators of trichome development. They compete with the R2R3 MYBs to bind the bHLH factor and form a repressor complex. In addition to activator-repressor mechanism, a depletion mechanism may operate in parallel during trichome development. In this mechanism, the bHLH factor traps the WDR protein which results in depletion of WDR protein in neighboring cells. Consequently, the cells with high levels of bHLH and WDR proteins are developed into trichomes. A group of C2H2 zinc finger TFs has also been implicated in trichome development. Phytohormones, including gibberellins and jasmonic acid, play significant roles in this developmental process. Recently, microRNAs have been shown to be involved in trichome development. Furthermore, it has been demonstrated that the activities of the key regulatory proteins involved in trichome development are controlled by the 26S/ubiquitin proteasome system (UPS, highlighting the complexity of the regulatory network controlling this developmental process. To complement several excellent recent relevant reviews, this review focuses on the transcriptional network and hormonal interplay

  18. A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.

    Directory of Open Access Journals (Sweden)

    Jayson Gutiérrez

    Full Text Available The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks. Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/- feedback and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1 the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2 the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of

  19. Social insect colony as a biological regulatory system: modelling information flow in dominance networks.

    Science.gov (United States)

    Nandi, Anjan K; Sumana, Annagiri; Bhattacharya, Kunal

    2014-12-06

    Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the 'feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony.

  20. Using consensus bayesian network to model the reactive oxygen species regulatory pathway.

    Science.gov (United States)

    Hu, Liangdong; Wang, Limin

    2013-01-01

    Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway.

  1. Modeling disease risk through analysis of physical interactions between genetic variants within chromatin regulatory circuitry.

    Science.gov (United States)

    Corradin, Olivia; Cohen, Andrea J; Luppino, Jennifer M; Bayles, Ian M; Schumacher, Fredrick R; Scacheri, Peter C

    2016-11-01

    SNPs associated with disease susceptibility often reside in enhancer clusters, or super-enhancers. Constituents of these enhancer clusters cooperate to regulate target genes and often extend beyond the linkage disequilibrium (LD) blocks containing risk SNPs identified in genome-wide association studies (GWAS). We identified 'outside variants', defined as SNPs in weak LD with GWAS risk SNPs that physically interact with risk SNPs as part of a target gene's regulatory circuitry. These outside variants further explain variation in target gene expression beyond that explained by GWAS-associated SNPs. Additionally, the clinical risk associated with GWAS SNPs is considerably modified by the genotype of outside variants. Collectively, these findings suggest a potential model in which outside variants and GWAS SNPs that physically interact in 3D chromatin collude to influence target transcript levels as well as clinical risk. This model offers an additional hypothesis for the source of missing heritability for complex traits.

  2. Latent Tuberculosis: Models, Computational efforts and the Pathogen's regulatory mechanisms during dormancy

    Directory of Open Access Journals (Sweden)

    Gesham eMagombedze

    2013-08-01

    Full Text Available Latent tuberculosis is a clinical syndrome that occurs after an individual has been exposed to the Mycobacterium tuberculosis (Mtb bacillus, the infection has been established and an immune response has been generated to control the pathogen and force it into a quiescent state. Mtb can exit this quiescent state where it is unresponsive to treatment and elusive to the immune response, and enter a rapid replicating state, hence causing infection reactivation. It remains a grey area to understand how the pathogen causes a persistent infection and it is unclear whether the organism will be in a slow replicating state or a dormant non-replicating state. The ability of the pathogen to adapt to changing host immune response mechanisms, in which it is exposed to hypoxia, low pH, nitric oxide (NO, nutrient starvation and several other anti-microbial effectors, is associated with a high metabolic plasticity that enables it to metabolise under these different conditions. Adaptive gene regulatory mechanisms are thought to coordinate how the pathogen changes their metabolic pathways through mechanisms that sense changes in oxygen tension and other stress factors, hence stimulating the pathogen to make necessary adjustments to ensure survival. Here, we review studies that give insights into latency/dormancy regulatory mechanisms that enable infection persistence and pathogen adaptation to different stress conditions. We highlight what mathematical and computational models can do and what they should do to enhance our current understanding of TB latency.

  3. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

    Directory of Open Access Journals (Sweden)

    Georgios Liappas

    2015-01-01

    Full Text Available Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD.

  4. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

    Science.gov (United States)

    Liappas, Georgios; Gónzalez-Mateo, Guadalupe Tirma; Majano, Pedro; Sánchez- Tomero, José Antonio; Ruiz-Ortega, Marta; Martín, Pilar; Sanchez-Díaz, Raquel; Selgas, Rafael; López-Cabrera, Manuel; Aguilera Peralta, Abelardo

    2015-01-01

    Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD. PMID:26064907

  5. Development of an odorant emission model for sewage treatment works.

    Science.gov (United States)

    Gostelow, P; Parsons, S A; Cobb, J

    2001-01-01

    In the field of odour assessment, much attention has been paid to the measurement of odour concentration. Whilst the concentration of an odour at a receptor is a useful indicator of annoyance, the concentration at the source tells only half the story. The emission rate - the product of odour concentration and air flow rate - is required to appreciate the significance of odour sources. Knowledge of emission rates allows odour sources to be ranked in terms of significance and facilitates appropriate selection and design of odour control units. The emission rate is also a key input for atmospheric dispersion models. Given the increasing importance of odour to sewage treatment works operators, there is a clear need for predictive methods for odour emission rates. Theory suggests that the emission of odorants from sewage to air is controlled by mass transfer resistances in both the gas and liquid phase. These are in turn controlled by odorant and emission source characteristics. The required odorant characteristics are largely known, and mass transfer from many different types of emission sources have been studied. Sewage treatment processes can be described by one or more of six characteristic emission sources, these being quiescent surfaces, channels, weirs and drop structures, diffused aeration, surface aeration and flow over media. This paper describes the development of odorant mass transfer models for these characteristic emission types. The models have been applied in the form of spreadsheet models to the prediction of H2S emissions and the results compared with commercial VOC emission models.

  6. Multispecies QSAR modeling for predicting the aquatic toxicity of diverse organic chemicals for regulatory toxicology.

    Science.gov (United States)

    Singh, Kunwar P; Gupta, Shikha; Kumar, Anuj; Mohan, Dinesh

    2014-05-19

    The research aims to develop multispecies quantitative structure-activity relationships (QSARs) modeling tools capable of predicting the acute toxicity of diverse chemicals in various Organization for Economic Co-operation and Development (OECD) recommended test species of different trophic levels for regulatory toxicology. Accordingly, the ensemble learning (EL) approach based classification and regression QSAR models, such as decision treeboost (DTB) and decision tree forest (DTF) implementing stochastic gradient boosting and bagging algorithms were developed using the algae (P. subcapitata) experimental toxicity data for chemicals. The EL-QSAR models were successfully applied to predict toxicities of wide groups of chemicals in other test species including algae (S. obliguue), daphnia, fish, and bacteria. Structural diversity of the selected chemicals and those of the end-point toxicity data of five different test species were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W) statistics. Predictive and generalization abilities of the constructed QSAR models were compared using statistical parameters. The developed QSAR models (DTB and DTF) yielded a considerably high classification accuracy in complete data of model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26% and 92.14%-94.12% in four test species, respectively, whereas regression QSAR models (DTB and DTF) rendered high correlation (R(2)) between the measured and model predicted toxicity end-point values and low mean-squared error in model building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and 0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species. The developed QSAR models exhibited good predictive and generalization abilities in different test species of varied trophic levels and can be used for predicting the toxicities of new chemicals for screening and prioritization of chemicals for regulation.

  7. Modelling non-stationary gene regulatory processes with a non-homogeneous Bayesian network and the allocation sampler

    NARCIS (Netherlands)

    Grzegorczyk, Marco; Husmeier, Dirk; Edwards, Kieron D.; Ghazal, Peter; Millar, Andrew J.

    2008-01-01

    Method: The objective of the present article is to propose and evaluate a probabilistic approach based on Bayesian networks for modelling non-homogeneous and non-linear gene regulatory processes. The method is based on a mixture model, using latent variables to assign individual measurements to diff

  8. Modelling non-stationary gene regulatory processes with a non-homogeneous Bayesian network and the allocation sampler

    NARCIS (Netherlands)

    Grzegorczyk, Marco; Husmeier, Dirk; Edwards, Kieron D.; Ghazal, Peter; Millar, Andrew J.

    2008-01-01

    Method: The objective of the present article is to propose and evaluate a probabilistic approach based on Bayesian networks for modelling non-homogeneous and non-linear gene regulatory processes. The method is based on a mixture model, using latent variables to assign individual measurements to

  9. Formal modeling and analysis of the MAL-associated biological regulatory network: insight into cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Jamil Ahmad

    Full Text Available The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs. This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL--a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis.

  10. Modelling the bioaccumulation of persistent organic pollutants in agricultural food chains for regulatory exposure assessment.

    Science.gov (United States)

    Takaki, Koki; Wade, Andrew J; Collins, Chris D

    2017-02-01

    New models for estimating bioaccumulation of persistent organic pollutants in the agricultural food chain were developed using recent improvements to plant uptake and cattle transfer models. One model named AgriSim was based on K OW regressions of bioaccumulation in plants and cattle, while the other was a steady-state mechanistic model, AgriCom. The two developed models and European Union System for the Evaluation of Substances (EUSES), as a benchmark, were applied to four reported food chain (soil/air-grass-cow-milk) scenarios to evaluate the performance of each model simulation against the observed data. The four scenarios considered were as follows: (1) polluted soil and air, (2) polluted soil, (3) highly polluted soil surface and polluted subsurface and (4) polluted soil and air at different mountain elevations. AgriCom reproduced observed milk bioaccumulation well for all four scenarios, as did AgriSim for scenarios 1 and 2, but EUSES only did this for scenario 1. The main causes of the deviation for EUSES and AgriSim were the lack of the soil-air-plant pathway and the ambient air-plant pathway, respectively. Based on the results, it is recommended that soil-air-plant and ambient air-plant pathway should be calculated separately and the K OW regression of transfer factor to milk used in EUSES be avoided. AgriCom satisfied the recommendations that led to the low residual errors between the simulated and the observed bioaccumulation in agricultural food chain for the four scenarios considered. It is therefore recommended that this model should be incorporated into regulatory exposure assessment tools. The model uncertainty of the three models should be noted since the simulated concentration in milk from 5th to 95th percentile of the uncertainty analysis often varied over two orders of magnitude. Using a measured value of soil organic carbon content was effective to reduce this uncertainty by one order of magnitude.

  11. Regulatory effects on the population dynamics and wave propagation in a cell lineage model.

    Science.gov (United States)

    Wang, Mao-Xiang; Ma, Yu-Qiang; Lai, Pik-Yin

    2016-03-21

    We consider the interplay of cell proliferation, cell differentiation (and de-differentiation), cell movement, and the effect of feedback regulations on the population and propagation dynamics of different cell types in a cell lineage model. Cells are assumed to secrete and respond to negative feedback molecules which act as a control on the cell lineage. The cell densities are described by coupled reaction-diffusion partial differential equations, and the propagating wave front solutions in one dimension are investigated analytically and by numerical solutions. In particular, wavefront propagation speeds are obtained analytically and verified by numerical solutions of the equations. The emphasis is on the effects of the feedback regulations on different stages in the cell lineage. It is found that when the progenitor cell is negatively regulated, the populations of the cell lineage are strongly down-regulated with the steady growth rate of the progenitor cell being driven to zero beyond a critical regulatory strength. An analytic expression for the critical regulation strength in terms of the model parameters is derived and verified by numerical solutions. On the other hand, if the inhibition is acting on the differentiated cells, the change in the population dynamics and wave propagation speed is small. In addition, it is found that only the propagating speed of the progenitor cells is affected by the regulation when the diffusion of the differentiated cells is large. In the presence of de-differentiation, the effect on down-regulating the progenitor population is weakened and there is no effect on the propagation speed due to regulation, suggesting that the effect of regulatory control is diminished by de-differentiation pathways.

  12. Unconscious Odour Conditioning 25 Years Later: Revisiting and Extending "Kirk-Smith, Van Toller and Dodd"

    Science.gov (United States)

    Zucco, Gesualdo M.; Paolini, Michela; Schaal, Benoist

    2009-01-01

    The pioneering work by Kirk-Smith, Van Toller, and Dodd [Kirk-Smith, M. D., Van Toller, C., & Dodd, G. H. (1983). "Unconscious odour conditioning in human subjects." "Biological Psychology," 17, 221-231], established that an unnoticed odorant paired with an emotionally meaningful task can influence mood and attitudes when the odorant alone is…

  13. Identification of the odour and chemical composition of alumina refinery air emissions.

    Science.gov (United States)

    Coffey, P S; Ioppolo-Armanios, M

    2004-01-01

    Alcoa World Alumina Australia has undertaken comprehensive air emissions monitoring aimed at characterising and quantifying the complete range of emissions to the atmosphere from Bayer refining of alumina at its Western Australian refineries. To the best of our knowledge, this project represents the most complete air emissions inventory of a Bayer refinery conducted in the worldwide alumina industry. It adds considerably to knowledge of air emission factors available for use in emissions estimation required under national pollutant release and transfer registers (NPRTs), such as the Toxic Releases Inventory, USA, and the National Pollutant Inventory, Australia. It also allows the preliminary identification of the key chemical components responsible for characteristic alumina refinery odours and the contribution of these components to the quality, or hedonic tone, of the odours. The strength and acceptability of refinery odours to employees and neighbours appears to be dependent upon where and in what proportion the odorous gases have been emitted from the refineries. This paper presents the results of the programme and develops a basis for classifying the odour properties of the key emission sources in the alumina-refining process.

  14. Effectiveness of mechanical tongue cleaning on breath odour and tongue coating: a systematic review

    NARCIS (Netherlands)

    M.I. van der Sleen; D.E. Slot; E. van Trijffel; E.G. Winkel; G.A. van der Weijden

    2010-01-01

    Background:  The objective of this review was to summarize the available evidence regarding the effects of mechanical tongue cleaning compared with no mechanical tongue cleaning on breath odour and tongue coating (TC). Methods:  PubMed-MEDLINE, EMBASE and Cochrane-CENTRAL were searched to identify p

  15. Irradiation-induced off-odour in chicken and its possible control.

    Science.gov (United States)

    Patterson, R L; Stevenson, M H

    1995-07-01

    1. Volatiles isolated from irradiated raw chicken were analysed by gas chromatography (GC) in conjunction with olfactory assessment of the effluent carrier gas to locate compounds with strong smells. 2. Sixteen odours of differing intensities were registered, some, but not others, coinciding with recognisable GC peaks. Identifications were made on the basis of retention data, mass spectrometric information and odour quality agreement. 3. Dimethyltrisulphide was found to be the most potent and obnoxious compound (foul gas, sulphurous), followed by cis-3- and trans-6-nonenals (soapy), oct-1-en-3-one (mushroom) and bis(methylthio-)methane (foul). With the exception of oct-1-en-3-one, none of these compounds has been reported before in irradiated raw chicken. 4. alpha-Tocopherol and ascorbic acid induce stability in tissues in vivo and post mortem. Chickens were reared on diets supplemented with high concentrations (800 mg/kg food) of each of these vitamins. Yields of irradiation volatiles from the tissues of these birds were very much reduced, compared to yields from similar tissues from birds fed unsupplemented diets. 5. Concomitantly with the reduced yield of volatiles, less odour was associated with the samples when analysed by GC-olfactory analysis. 6. The use of enhanced concentrations of the two vitamins in combination in the diet of poultry may provide a means of controlling development of off-odour in irradiated raw chicken, thus improving acceptability to the consumer.

  16. Real time monitoring to the odour of excrement for health of infants and elderly completely bedridden

    Science.gov (United States)

    Ye, Jiancheng; Huang, Guoliang

    2017-01-01

    In the domain of biomedical signals measurements, monitoring human physiological parameters is an important issue. With the rapid development of wireless body area network, it makes monitor, transmit and record physiological parameters faster and more convenient. Infants and the elderly completely bedridden are two special groups of the society who need more medical care. According to researches investigating current frontier domains and the market products, the detection of physiological parameters from the excrement is rare. However, urine and faeces contain a large number of physiological information, which are high relative to health. The mainly distributed odour from urine is NH4 and the distributed odour from feces is mainly H2S, which are both could be detected by the sensors. In this paper, we introduce the design and implementation of a portable wireless device based on body area network for real time monitoring to the odour of excrement for health of infants and the elderly completely bedridden. The device not only could monitor in real time the emitted odour of faeces and urine for health analysis, but also measures the body temperature and environment humidity, and send data to the mobile phone of paramedics to alarm or the server for storage and process, which has prospect to monitoring infants and the paralysis elderly.

  17. Preliminary observation on the effect of baking soda volume on controlling odour from discarded organic waste.

    Science.gov (United States)

    Qamaruz-Zaman, N; Kun, Y; Rosli, R-N

    2015-01-01

    Food wastes with high moisture and organic matter content are likely to emit odours as a result of the decomposition process. The management of odour from decomposing wastes is needed to sustain the interest of residents and local councils in the source separation of kitchen wastes. This study investigated the potential of baking soda (at 50 g, 75 g and 100g per kg food waste) to control odour from seven days stored food waste. It was found that 50 g of baking soda, spread at the bottom of 8l food wastes bin, can reduce the odour by about 70%. A higher amount (above 100g) is not advised as a pH higher than 9.0 may be induced leading to the volatilization of odorous ammonia. This research finding is expected to benefit the waste management sector, food processing industries as well as the local authorities where malodour from waste storage is a pressing issue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Advances in the use of odour as forensic evidence through optimizing and standardizing instruments and canines.

    Science.gov (United States)

    Furton, Kenneth G; Caraballo, Norma Iris; Cerreta, Michelle M; Holness, Howard K

    2015-08-01

    This paper explores the advances made in identifying trace amounts of volatile organic compounds (VOCs) that originate from forensic specimens, such as drugs, explosives, live human scent and the scent of death, as well as the probative value for detecting such odours. The ability to locate and identify the VOCs liberated from or left by forensic substances is of increasing importance to criminal investigations as it can indicate the presence of contraband and/or associate an individual to a particular location or object. Although instruments have improved significantly in recent decades-with sensitivities now rivalling that of biological detectors-it is widely recognized that canines are generally still more superior for the detection of odourants due to their speed, versatility, ruggedness and discriminating power. Through advancements in the detection of VOCs, as well as increased standardization efforts for instruments and canines, the reliability of odour as evidence has continuously improved and is likely to continue to do so. Moreover, several legal cases in which this novel form of evidence has been accepted into US courts of law are discussed. As the development and implementation of best practice guidelines for canines and instruments increase, their reliability in detecting VOCs of interest should continue to improve, expanding the use of odour as an acceptable form of forensic evidence.

  19. The Analyses of the effects of Environmental Descriptions in Odour of Chrysanthemums

    Institute of Scientific and Technical Information of China (English)

    徐亚河

    2015-01-01

    Environment is an indispensable element of a story structure. In the short story Odour of Chrysanthemums, Laurence showed a se⁃ries of original environmental descriptions which play a important role to create specific atmosphere in an industrial society and express pro⁃tagonists’inner life.

  20. Food preference and intake in response to ambient odours in overweight and normal-weight females

    NARCIS (Netherlands)

    Zoon, H.F.A.; He, W.; Wijk, de R.A.; Graaf, de C.; Boesveldt, S.

    2014-01-01

    In our food abundant environment, food cues play an important role in the regulation of energy intake. Odours can be considered as external cues that can signal energy content in the anticipatory phase of eating. This study aims to determine whether exposure to olfactory cues associated with energy

  1. Industrial Dehumanization——Viewed from the husband and wife relationship in "Odour of Chrysanthemums"

    Institute of Scientific and Technical Information of China (English)

    何苗

    2007-01-01

    Lawrence is regarded as one of most accomplished short story writers in twentieth century, with "Odour of Chrysanthemums" one of his early works. Through the death of a miner, the text shows how humanity was ruined by industrial civilization. This essay is intended to unveil the destructive force by analyzing the relationship between the husband and wife.

  2. Effectiveness of mechanical tongue cleaning on breath odour and tongue coating : a systematic review

    NARCIS (Netherlands)

    Van der Sleen, M. I.; Slot, D. E.; Van Trijffel, E.; Winkel, E. G.; Van der Weijden, G. A.

    2010-01-01

    Background: The objective of this review was to summarize the available evidence regarding the effects of mechanical tongue cleaning compared with no mechanical tongue cleaning on breath odour and tongue coating (TC). Methods: PubMed-MEDLINE, EMBASE and Cochrane-CENTRAL were searched to identify pot

  3. Unconscious Odour Conditioning 25 Years Later: Revisiting and Extending "Kirk-Smith, Van Toller and Dodd"

    Science.gov (United States)

    Zucco, Gesualdo M.; Paolini, Michela; Schaal, Benoist

    2009-01-01

    The pioneering work by Kirk-Smith, Van Toller, and Dodd [Kirk-Smith, M. D., Van Toller, C., & Dodd, G. H. (1983). "Unconscious odour conditioning in human subjects." "Biological Psychology," 17, 221-231], established that an unnoticed odorant paired with an emotionally meaningful task can influence mood and attitudes when the odorant alone is…

  4. Ca(2+)-BK channel clusters in olfactory receptor neurons and their role in odour coding.

    Science.gov (United States)

    Bao, Guobin; de Jong, Daniëlle; Alevra, Mihai; Schild, Detlev

    2015-12-01

    Olfactory receptor neurons (ORNs) have high-voltage-gated Ca(2+) channels whose physiological impact has remained enigmatic since the voltage-gated conductances in this cell type were first described in the 1980s. Here we show that in ORN somata of Xenopus laevis tadpoles these channels are clustered and co-expressed with large-conductance potassium (BK) channels. We found approximately five clusters per ORN and twelve Ca(2+) channels per cluster. The action potential-triggered activation of BK channels accelerates the repolarization of action potentials and shortens interspike intervals during odour responses. This increases the sensitivity of individual ORNs to odorants. At the level of mitral cells of the olfactory bulb, odour qualities have been shown to be coded by first-spike-latency patterns. The system of Ca(2+) and BK channels in ORNs appears to be important for correct odour coding because the blockage of BK channels not only affects ORN spiking patterns but also changes the latency pattern representation of odours in the olfactory bulb.

  5. A method for independent modelling in support of regulatory review of dose assessments.

    Science.gov (United States)

    Dverstorp, Björn; Xu, Shulan

    2017-03-22

    Several countries consider geological disposal facilities as the preferred option for spent nuclear fuel due to their potential to provide isolation from the surface environment on very long timescales. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a license application for construction of a spent nuclear fuel repository. The disposal method involves disposing spent fuel in copper canisters with a cast iron insert at about 500 m depth in crystalline basement rock, and each canister is surrounded by a buffer of swelling bentonite clay. SKB's license application is supported by a post-closure safety assessment, SR-Site. SR-Site has been reviewed by the Swedish Radiation Safety Authority (SSM) for five years. The main method for review of SKB's license application is document review, which is carried out by SSM's staff and supported by SSM's external experts. The review has proven a challenging task due to its broad scope, complexity and multidisciplinary nature. SSM and its predecessors have, for several decades, been developing independent models to support regulatory reviews of post-closure safety assessments for geological repositories. For the review of SR-Site, SSM has developed a modelling approach with a structured application of independent modelling activities, including replication modelling, use of alternative conceptual models and bounding calculations, to complement the traditional document review. This paper describes this scheme and its application to biosphere and dose assessment modelling. SSM's independent modelling has provided important insights regarding quality and reasonableness of SKB's rather complex biosphere modelling and has helped quantifying conservatisms and highlighting conceptual uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Prioritizing predicted cis-regulatory elements for co-expressed gene sets based on Lasso regression models.

    Science.gov (United States)

    Hu, Hong; Roqueiro, Damian; Dai, Yang

    2011-01-01

    Computational prediction of cis-regulatory elements for a set of co-expressed genes based on sequence analysis provides an overwhelming volume of potential transcription factor binding sites. It presents a challenge to prioritize transcription factors for regulatory functional studies. A novel approach based on the use of Lasso regression models is proposed to address this problem. We examine the ability of the Lasso model using time-course microarray data obtained from a comprehensive study of gene expression profiles in skin and mucosal wounds in mouse over all stages of wound healing.

  7. Modelling the regulatory system for diabetes mellitus with a threshold window

    Science.gov (United States)

    Yang, Jin; Tang, Sanyi; Cheke, Robert A.

    2015-05-01

    Piecewise (or non-smooth) glucose-insulin models with threshold windows for type 1 and type 2 diabetes mellitus are proposed and analyzed with a view to improving understanding of the glucose-insulin regulatory system. For glucose-insulin models with a single threshold, the existence and stability of regular, virtual, pseudo-equilibria and tangent points are addressed. Then the relations between regular equilibria and a pseudo-equilibrium are studied. Furthermore, the sufficient and necessary conditions for the global stability of regular equilibria and the pseudo-equilibrium are provided by using qualitative analysis techniques of non-smooth Filippov dynamic systems. Sliding bifurcations related to boundary node bifurcations were investigated with theoretical and numerical techniques, and insulin clinical therapies are discussed. For glucose-insulin models with a threshold window, the effects of glucose thresholds or the widths of threshold windows on the durations of insulin therapy and glucose infusion were addressed. The duration of the effects of an insulin injection is sensitive to the variation of thresholds. Our results indicate that blood glucose level can be maintained within a normal range using piecewise glucose-insulin models with a single threshold or a threshold window. Moreover, our findings suggest that it is critical to individualise insulin therapy for each patient separately, based on initial blood glucose levels.

  8. Structural model of the Rev regulatory protein from equine infectious anemia virus.

    Directory of Open Access Journals (Sweden)

    Yungok Ihm

    Full Text Available Rev is an essential regulatory protein in the equine infectious anemia virus (EIAV and other lentiviruses, including HIV-1. It binds incompletely spliced viral mRNAs and shuttles them from the nucleus to the cytoplasm, a critical prerequisite for the production of viral structural proteins and genomic RNA. Despite its important role in production of infectious virus, the development of antiviral therapies directed against Rev has been hampered by the lack of an experimentally-determined structure of the full length protein. We have used a combined computational and biochemical approach to generate and evaluate a structural model of the Rev protein. The modeled EIAV Rev (ERev structure includes a total of 6 helices, four of which form an anti-parallel four-helix bundle. The first helix contains the leucine-rich nuclear export signal (NES. An arginine-rich RNA binding motif, RRDRW, is located in a solvent-exposed loop region. An ERLE motif required for Rev activity is predicted to be buried in the core of modeled structure where it plays an essential role in stabilization of the Rev fold. This structural model is supported by existing genetic and functional data as well as by targeted mutagenesis of residues predicted to be essential for overall structural integrity. Our predicted structure should increase understanding of structure-function relationships in Rev and may provide a basis for the design of new therapies for lentiviral diseases.

  9. Effects of dietary crude protein level on odour from pig manure.

    Science.gov (United States)

    Le, P D; Aarnink, A J A; Jongbloed, A W; Peet-Schwering, C M C Van der; Ogink, N W M; Verstegen, M W A

    2007-06-01

    The objective of this study was to determine the effects of dietary crude protein (CP) level on odour emission, odour intensity, hedonic tone, and ammonia emission from pig manure and on manure composition (pH, total nitrogen, ammonium, volatile fatty acids, indolic, phenolic and sulphur-containing compounds). An experiment was conducted with growing pigs (n = 18) in a randomised complete-block design with three treatments in six blocks. Treatment groups were 12%, 15% and 18% CP diets. Barley was exchanged for soya-bean meal. Crystalline amino acids (AA) were included in the 12% CP diet up to the level of pigs' requirement; the same amount of AA was added to the 15% and 18% CP diets. Pigs with an initial body weight (BW) of 36.5 ± 3.4 kg (mean ± s.d.) were individually penned in partly slatted floor pens and offered a daily feed allowance of 2.8 × maintenance requirement for net energy (NE: 293 kJ/kg BW0.75). Feed was mixed with water, 1/2.5 (w/w). Faeces and urine of each pig were accumulated together in a separate manure pit under the slatted floor. After an adaptation period of 2 weeks, the manure pits were cleaned and manure was collected. In the 5th week of the collection period, air samples for odour and ammonia analyses, and manure samples were collected directly from each manure pit. Air samples were analysed for odour concentration and for hedonic value and intensity above odour detection threshold. Manure samples were analysed for volatile fatty acids, and indolic, phenolic and sulphurous compounds, ammonium and total nitrogen concentrations. Reducing dietary CP from 18% to 12% lowered odour emission ( P acids and cresols concentrations in the manure of pigs fed different dietary CP levels were similar. A reduction of dietary CP and at the same time providing essential AA is an option to reduce odour emission as well as ammonia emission from pig manure.

  10. Calcium imaging in the ant Camponotus fellah reveals a conserved odour-similarity space in insects and mammals

    Directory of Open Access Journals (Sweden)

    Giurfa Martin

    2010-02-01

    Full Text Available Abstract Background Olfactory systems create representations of the chemical world in the animal brain. Recordings of odour-evoked activity in the primary olfactory centres of vertebrates and insects have suggested similar rules for odour processing, in particular through spatial organization of chemical information in their functional units, the glomeruli. Similarity between odour representations can be extracted from across-glomerulus patterns in a wide range of species, from insects to vertebrates, but comparison of odour similarity in such diverse taxa has not been addressed. In the present study, we asked how 11 aliphatic odorants previously tested in honeybees and rats are represented in the antennal lobe of the ant Camponotus fellah, a social insect that relies on olfaction for food search and social communication. Results Using calcium imaging of specifically-stained second-order neurons, we show that these odours induce specific activity patterns in the ant antennal lobe. Using multidimensional analysis, we show that clustering of odours is similar in ants, bees and rats. Moreover, odour similarity is highly correlated in all three species. Conclusion This suggests the existence of similar coding rules in the neural olfactory spaces of species among which evolutionary divergence happened hundreds of million years ago.

  11. Prior classical olfactory conditioning improves odour-cued flight orientation of honey bees in a wind tunnel.

    Science.gov (United States)

    Chaffiol, Antoine; Laloi, David; Pham-Delègue, Minh-Hà

    2005-10-01

    Odours are key cues used by the honey bee in various situations. They play an important role in sexual attraction, social behaviour and location of profitable food sources. Here, we were interested in the role of odours in orientation at short distance, for instance the approach flight to a floral patch or in close proximity to the hive entrance. Using a newly designed wind tunnel, we investigated the orientation behaviour of the bee towards two different odours: a social odour and a floral component, linalool. We then tested the effect of prior olfactory conditioning (conditioning of the proboscis extension reflex) on subsequent flight orientation. We showed that both stimuli induced orientated behaviour (orientated flights, circling around the odour source) in up to 70% of the worker bees, social odour being slightly more attractive than the linalool. We found thereafter that orientation performance towards the floral compound can be significantly enhanced by prior classical olfactory learning. This type of information transfer, from a Pavlovian associative context to an orientation task, might allow future foragers to acquire, within the hive, relevant information about the odours and food they will encounter during their later foraging bouts.

  12. Food preference and intake in response to ambient odours in overweight and normal-weight females.

    Science.gov (United States)

    Zoon, Harriët F A; He, Wei; de Wijk, René A; de Graaf, Cees; Boesveldt, Sanne

    2014-06-22

    In our food abundant environment, food cues play an important role in the regulation of energy intake. Odours can be considered as external cues that can signal energy content in the anticipatory phase of eating. This study aims to determine whether exposure to olfactory cues associated with energy dense foods leads to increased food intake and greater preference for energy-dense foods. In addition, we assessed whether BMI and hunger state modulated this effect. Twenty-five overweight (mean BMI: 31.3 kg/m(2), S.E.: 0.6) and 25 normal-weight (mean BMI: 21.9 kg/m(2), S.E.: 0.4) females, matched on age and restraint score, participated. In 6 separate sessions they were exposed to odours of three different categories (signalling non-food, high-energy food and low-energy food) in two motivational states (hungry and satiated). After 10 min of exposure food preference was assessed with a computerized two-item forced choice task and after 20 min a Bogus Taste Test was used to determine energy intake (kcal and g). In a hungry state, the participants ate more (ppreferred high-energy products significantly more often (pfood preference of overweight participants was less affected by their internal state (p=.068). Neither energy intake (kcal: p=.553; g: p=.683) nor food preference (p=.280) was influenced by ambient exposure to odours signalling different categories. Future studies need to explore whether food odours can indeed induce overeating. More insight is needed regarding the possible influence of context (e.g. short exposure duration, large variety of food) and personality traits (e.g. restraint, impulsive) on odour-induced overeating. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Technological and life cycle assessment of organics processing odour control technologies

    Energy Technology Data Exchange (ETDEWEB)

    Bindra, Navin [School of Engineering, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G2W1 (Canada); Dubey, Brajesh, E-mail: bkdubey@civil.iitkgp.ernet.in [School of Engineering, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G2W1 (Canada); Environmental Engineering Division, Department of Civil Engineering, Indian Institute of Technology, Kharagpur, West Bengal 721302 (India); Dutta, Animesh [School of Engineering, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G2W1 (Canada)

    2015-09-15

    As more municipalities and communities across developed world look towards implementing organic waste management programmes or upgrading existing ones, composting facilities are emerging as a popular choice. However, odour from these facilities continues to be one of the most important concerns in terms of cost & effective mitigation. This paper provides a technological and life cycle assessment of some of the different odour control technologies and treatment methods that can be implemented in organics processing facilities. The technological assessment compared biofilters, packed tower wet scrubbers, fine mist wet scrubbers, activated carbon adsorption, thermal oxidization, oxidization chemicals and masking agents. The technologies/treatment methods were evaluated and compared based on a variety of operational, usage and cost parameters. Based on the technological assessment it was found that, biofilters and packed bed wet scrubbers are the most applicable odour control technologies for use in organics processing faculties. A life cycle assessment was then done to compare the environmental impacts of the packed-bed wet scrubber system, organic (wood-chip media) bio-filter and inorganic (synthetic media) bio-filter systems. Twelve impact categories were assessed; cumulative energy demand (CED), climate change, human toxicity, photochemical oxidant formation, metal depletion, fossil depletion, terrestrial acidification, freshwater eutrophication, marine eutrophication, terrestrial eco-toxicity, freshwater eco-toxicity and marine eco-toxicity. The results showed that for all impact categories the synthetic media biofilter had the highest environmental impact, followed by the wood chip media bio-filter system. The packed-bed system had the lowest environmental impact for all categories. - Highlights: • Assessment of odour control technologies for organics processing facilities. • Comparative life cycle assessment of three odour control technologies was conducted

  14. Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour

    Directory of Open Access Journals (Sweden)

    McLean Lynn

    2010-06-01

    Full Text Available Abstract Background Among invertebrates, specific pheromones elicit inherent (fixed behavioural responses to coordinate social behaviours such as sexual recognition and attraction. By contrast, the much more complex social odours of mammals provide a broad range of information about the individual owner and stimulate individual-specific responses that are modulated by learning. How do mammals use such odours to coordinate important social interactions such as sexual attraction while allowing for individual-specific choice? We hypothesized that male mouse urine contains a specific pheromonal component that invokes inherent sexual attraction to the scent and which also stimulates female memory and conditions sexual attraction to the airborne odours of an individual scent owner associated with this pheromone. Results Using wild-stock house mice to ensure natural responses that generalize across individual genomes, we identify a single atypical male-specific major urinary protein (MUP of mass 18893Da that invokes a female's inherent sexual attraction to male compared to female urinary scent. Attraction to this protein pheromone, which we named darcin, was as strong as the attraction to intact male urine. Importantly, contact with darcin also stimulated a strong learned attraction to the associated airborne urinary odour of an individual male, such that, subsequently, females were attracted to the airborne scent of that specific individual but not to that of other males. Conclusions This involatile protein is a mammalian male sex pheromone that stimulates a flexible response to individual-specific odours through associative learning and memory, allowing female sexual attraction to be inherent but selective towards particular males. This 'darcin effect' offers a new system to investigate the neural basis of individual-specific memories in the brain and give new insights into the regulation of behaviour in complex social mammals. See associated

  15. Fatal attraction phenomenon in humans: cat odour attractiveness increased for toxoplasma-infected men while decreased for infected women.

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    Jaroslav Flegr

    2011-11-01

    Full Text Available BACKGROUND: Latent toxoplasmosis, a lifelong infection with the protozoan Toxoplasma gondii, has cumulative effects on the behaviour of hosts, including humans. The most impressive effect of toxoplasmosis is the "fatal attraction phenomenon," the conversion of innate fear of cat odour into attraction to cat odour in infected rodents. While most behavioural effects of toxoplasmosis were confirmed also in humans, neither the fatal attraction phenomenon nor any toxoplasmosis-associated changes in olfactory functions have been searched for in them. PRINCIPAL FINDINGS: Thirty-four Toxoplasma-infected and 134 noninfected students rated the odour of urine samples from cat, horse, tiger, brown hyena and dog for intensity and pleasantness. The raters were blind to their infection status and identity of the samples. No signs of changed sensitivity of olfaction were observed. However, we found a strong, gender dependent effect of toxoplasmosis on the pleasantness attributed to cat urine odour (p = 0.0025. Infected men rated this odour as more pleasant than did the noninfected men, while infected women rated the same odour as less pleasant than did noninfected women. Toxoplasmosis did not affect how subjects rated the pleasantness of any other animal species' urine odour; however, a non-significant trend in the same directions was observed for hyena urine. CONCLUSIONS: The absence of the effects of toxoplasmosis on the odour pleasantness score attributed to large cats would suggest that the amino acid felinine could be responsible for the fatal attraction phenomenon. Our results also raise the possibility that the odour-specific threshold deficits observed in schizophrenia patients could be caused by increased prevalence of Toxoplasma-infected subjects in this population rather than by schizophrenia itself. The trend observed with the hyena urine sample suggests that this carnivore, and other representatives of the Feliformia suborder, should be studied

  16. Public perception of odour and environmental pollution attributed to MSW treatment and disposal facilities: A case study

    Energy Technology Data Exchange (ETDEWEB)

    De Feo, Giovanni, E-mail: g.defeo@unisa.it [Department of Industrial Engineering, University of Salerno, via Ponte don Melillo 1, 84084 Fisciano (Italy); De Gisi, Sabino [Department of Industrial Engineering, University of Salerno, via Ponte don Melillo 1, 84084 Fisciano (Italy); Williams, Ian D. [Waste Management Research Group, Faculty of Engineering and the Environment, University of Southampton, Highfield, Southampton SO17 1BJ (United Kingdom)

    2013-04-15

    Highlights: ► Effects of closing MSW facilities on perception of odour and pollution studied. ► Residents’ perception of odour nuisance considerably diminished post closure. ► Odour perception showed an association with distance from MSW facilities. ► Media coverage increased knowledge about MSW facilities and how they operate. ► Economic compensation possibly affected residents’ views and concerns. - Abstract: If residents’ perceptions, concerns and attitudes towards waste management facilities are either not well understood or underestimated, people can produce strong opposition that may include protest demonstrations and violent conflicts such as those experienced in the Campania Region of Italy. The aim of this study was to verify the effects of the closure of solid waste treatment and disposal facilities (two landfills and one RDF production plant) on public perception of odour and environmental pollution. The study took place in four villages in Southern Italy. Identical questionnaires were administered to residents during 2003 and after the closure of the facilities occurred in 2008. The residents’ perception of odour nuisance considerably diminished between 2003 and 2009 for the nearest villages, with odour perception showing an association with distance from the facilities. Post closure, residents had difficulty in identifying the type of smell due to the decrease in odour level. During both surveys, older residents reported most concern about the potentially adverse health impacts of long-term exposure to odours from MSW facilities. However, although awareness of MSW facilities and concern about potentially adverse health impacts varied according to the characteristics of residents in 2003, substantial media coverage produced an equalisation effect and increased knowledge about the type of facilities and how they operated. It is possible that residents of the village nearest to the facilities reported lower awareness of and concern about

  17. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

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    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  18. The regulatory system for diabetes mellitus: Modeling rates of glucose infusions and insulin injections

    Science.gov (United States)

    Yang, Jin; Tang, Sanyi; Cheke, Robert A.

    2016-08-01

    Novel mathematical models with open and closed-loop control for type 1 or type 2 diabetes mellitus were developed to improve understanding of the glucose-insulin regulatory system. A hybrid impulsive glucose-insulin model with different frequencies of glucose infusions and insulin injections was analyzed, and the existence and uniqueness of the positive periodic solution for type 1 diabetes, which is globally asymptotically stable, was studied analytically. Moreover, permanence of the system for type 2 diabetes was demonstrated which showed that the glucose concentration level is uniformly bounded above and below. To investigate how to prevent hyperinsulinemia and hyperglycemia being caused by this system, we developed a model involving periodic intakes of glucose with insulin injections applied only when the blood glucose level reached a given critical glucose threshold. In addition, our numerical analysis revealed that the period, the frequency and the dose of glucose infusions and insulin injections are crucial for insulin therapies, and the results provide clinical strategies for insulin-administration practices.

  19. Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.

    Science.gov (United States)

    Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy

    2014-07-01

    International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment.

  20. Motivational cues predict the defensive system in team handball: A model based on regulatory focus theory.

    Science.gov (United States)

    Debanne, T; Laffaye, G

    2015-08-01

    This study was based on the naturalistic decision-making paradigm and regulatory focus theory. Its aim was to model coaches' decision-making processes for handball teams' defensive systems based on relevant cues of the reward structure, and to determine the weight of each of these cues. We collected raw data by video-recording 41 games that were selected using a simple random method. We considered the defensive strategy (DEF: aligned or staged) to be the dependent variable, and the three independent variables were (a) numerical difference between the teams; (b) score difference between the teams; and (c) game periods. We used a logistic regression design (logit model) and a multivariate logistic model to explain the link between DEF and the three category independent variables. Each factor was weighted differently during the decision-making process to select the defensive system, and combining these variables increased the impact on this process; for instance, a staged defense is 43 times more likely to be chosen during the final period in an unfavorable situation and in a man advantage. Finally, this shows that the coach's decision-making process could be based on a simple match or could require a diagnosis of the situation based on the relevant cues.

  1. Mean field analysis of a spatial stochastic model of a gene regulatory network.

    Science.gov (United States)

    Sturrock, M; Murray, P J; Matzavinos, A; Chaplain, M A J

    2015-10-01

    A gene regulatory network may be defined as a collection of DNA segments which interact with each other indirectly through their RNA and protein products. Such a network is said to contain a negative feedback loop if its products inhibit gene transcription, and a positive feedback loop if a gene product promotes its own production. Negative feedback loops can create oscillations in mRNA and protein levels while positive feedback loops are primarily responsible for signal amplification. It is often the case in real biological systems that both negative and positive feedback loops operate in parameter regimes that result in low copy numbers of gene products. In this paper we investigate the spatio-temporal dynamics of a single feedback loop in a eukaryotic cell. We first develop a simplified spatial stochastic model of a canonical feedback system (either positive or negative). Using a Gillespie's algorithm, we compute sample trajectories and analyse their corresponding statistics. We then derive a system of equations that describe the spatio-temporal evolution of the stochastic means. Subsequently, we examine the spatially homogeneous case and compare the results of numerical simulations with the spatially explicit case. Finally, using a combination of steady-state analysis and data clustering techniques, we explore model behaviour across a subregion of the parameter space that is difficult to access experimentally and compare the parameter landscape of our spatio-temporal and spatially-homogeneous models.

  2. Stochastic Boolean networks: An efficient approach to modeling gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Liang Jinghang

    2012-08-01

    Full Text Available Abstract Background Various computational models have been of interest due to their use in the modelling of gene regulatory networks (GRNs. As a logical model, probabilistic Boolean networks (PBNs consider molecular and genetic noise, so the study of PBNs provides significant insights into the understanding of the dynamics of GRNs. This will ultimately lead to advances in developing therapeutic methods that intervene in the process of disease development and progression. The applications of PBNs, however, are hindered by the complexities involved in the computation of the state transition matrix and the steady-state distribution of a PBN. For a PBN with n genes and N Boolean networks, the complexity to compute the state transition matrix is O(nN22n or O(nN2n for a sparse matrix. Results This paper presents a novel implementation of PBNs based on the notions of stochastic logic and stochastic computation. This stochastic implementation of a PBN is referred to as a stochastic Boolean network (SBN. An SBN provides an accurate and efficient simulation of a PBN without and with random gene perturbation. The state transition matrix is computed in an SBN with a complexity of O(nL2n, where L is a factor related to the stochastic sequence length. Since the minimum sequence length required for obtaining an evaluation accuracy approximately increases in a polynomial order with the number of genes, n, and the number of Boolean networks, N, usually increases exponentially with n, L is typically smaller than N, especially in a network with a large number of genes. Hence, the computational efficiency of an SBN is primarily limited by the number of genes, but not directly by the total possible number of Boolean networks. Furthermore, a time-frame expanded SBN enables an efficient analysis of the steady-state distribution of a PBN. These findings are supported by the simulation results of a simplified p53 network, several randomly generated networks and a

  3. High Dimensional ODEs Coupled with Mixed-Effects Modeling Techniques for Dynamic Gene Regulatory Network Identification.

    Science.gov (United States)

    Lu, Tao; Liang, Hua; Li, Hongzhe; Wu, Hulin

    2011-01-01

    Gene regulation is a complicated process. The interaction of many genes and their products forms an intricate biological network. Identification of this dynamic network will help us understand the biological process in a systematic way. However, the construction of such a dynamic network is very challenging for a high-dimensional system. In this article we propose to use a set of ordinary differential equations (ODE), coupled with dimensional reduction by clustering and mixed-effects modeling techniques, to model the dynamic gene regulatory network (GRN). The ODE models allow us to quantify both positive and negative gene regulations as well as feedback effects of one set of genes in a functional module on the dynamic expression changes of the genes in another functional module, which results in a directed graph network. A five-step procedure, Clustering, Smoothing, regulation Identification, parameter Estimates refining and Function enrichment analysis (CSIEF) is developed to identify the ODE-based dynamic GRN. In the proposed CSIEF procedure, a series of cutting-edge statistical methods and techniques are employed, that include non-parametric mixed-effects models with a mixture distribution for clustering, nonparametric mixed-effects smoothing-based methods for ODE models, the smoothly clipped absolute deviation (SCAD)-based variable selection, and stochastic approximation EM (SAEM) approach for mixed-effects ODE model parameter estimation. The key step, the SCAD-based variable selection of the proposed procedure is justified by investigating its asymptotic properties and validated by Monte Carlo simulations. We apply the proposed method to identify the dynamic GRN for yeast cell cycle progression data. We are able to annotate the identified modules through function enrichment analyses. Some interesting biological findings are discussed. The proposed procedure is a promising tool for constructing a general dynamic GRN and more complicated dynamic networks.

  4. Modeling Water Utility Investments and Improving Regulatory Policies using Economic Optimisation in England and Wales

    Science.gov (United States)

    Padula, S.; Harou, J. J.

    2012-12-01

    Water utilities in England and Wales are regulated natural monopolies called 'water companies'. Water companies must obtain periodic regulatory approval for all investments (new supply infrastructure or demand management measures). Both water companies and their regulators use results from least economic cost capacity expansion optimisation models to develop or assess water supply investment plans. This presentation first describes the formulation of a flexible supply-demand planning capacity expansion model for water system planning. The model uses a mixed integer linear programming (MILP) formulation to choose the least-cost schedule of future supply schemes (reservoirs, desalination plants, etc.) and demand management (DM) measures (leakage reduction, water efficiency and metering options) and bulk transfers. Decisions include what schemes to implement, when to do so, how to size schemes and how much to use each scheme during each year of an n-year long planning horizon (typically 30 years). In addition to capital and operating (fixed and variable) costs, the estimated social and environmental costs of schemes are considered. Each proposed scheme is costed discretely at one or more capacities following regulatory guidelines. The model uses a node-link network structure: water demand nodes are connected to supply and demand management (DM) options (represented as nodes) or to other demand nodes (transfers). Yields from existing and proposed are estimated separately using detailed water resource system simulation models evaluated over the historical period. The model simultaneously considers multiple demand scenarios to ensure demands are met at required reliability levels; use levels of each scheme are evaluated for each demand scenario and weighted by scenario likelihood so that operating costs are accurately evaluated. Multiple interdependency relationships between schemes (pre-requisites, mutual exclusivity, start dates, etc.) can be accounted for by

  5. Animal testing, 3R models and regulatory acceptance : Technology transition in a risk-averse context

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.|info:eu-repo/dai/nl/294583416

    2016-01-01

    Risk avoidance has resulted in a broad range of regulations to guarantee the safety of products such as pharmaceuticals and chemicals. Many of these regulations rely on animal tests. About 3 million laboratory animals are used annually in Europe to meet such regulatory requirements.Regulatory animal

  6. Animal testing, 3R models and regulatory acceptance : Technology transition in a risk-averse context

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.

    2016-01-01

    Risk avoidance has resulted in a broad range of regulations to guarantee the safety of products such as pharmaceuticals and chemicals. Many of these regulations rely on animal tests. About 3 million laboratory animals are used annually in Europe to meet such regulatory requirements.Regulatory animal

  7. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks

    Science.gov (United States)

    Laomettachit, Teeraphan; Chen, Katherine C.; Baumann, William T.

    2016-01-01

    To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a “standard component” modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild-type cells and the partial viability of the CLB2-dbΔ clb5Δ mutant strain. Our simulations show that mathematical modeling with “standard components” can capture in quantitative detail many essential properties of cell cycle control in budding yeast. PMID:27187804

  9. A model for the volume regulatory mechanism of the Airway Surface Layer

    Science.gov (United States)

    Lang, Michael; Rubinstein, Michael; Davis, C. William; Tarran, Robert; Boucher, Richard

    2006-03-01

    The airway surface layer (ASL) of a lung consists of two parts: a mucus layer with thickness of about 30 μm in contact with air and a periciliary layer (PCL) of about 7 μm below. Mucus collects dust and bacteria and is swept to throat by beating cilia, while riding on top of PCL. It is important that the thickness of PCL is matched with the length of cilia in order to optimize clearance of mucus. Decrease of PCL thickness would finally lead to an occlusion of the respiratory system. Experiments show that the height of PCL stays constant after removing mucus. When modifying height or composition of this open PCL by removing fluid or adding isotonic solution leads to the same final height of PCL. Thus, there must be a regulatory mechanism, that controls height, i.e. ASL volume. Additional experiments show that mechanical stimulus of the cells like shear leads to an increase of ASL volume, thus, the cell is able to actively adjust this volume. Based on these observations a class of models is introduced that describes the experiments and a specific minimum model for the given problem is proposed.

  10. Gene regulatory network modeling via global optimization of high-order dynamic Bayesian network

    Directory of Open Access Journals (Sweden)

    Xuan Nguyen

    2012-06-01

    Full Text Available Abstract Background Dynamic Bayesian network (DBN is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN. Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks. Results To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT. GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques. Conclusions Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.

  11. A regulatory network modeled from wild-type gene expression data guides functional predictions in Caenorhabditis elegans development

    Directory of Open Access Journals (Sweden)

    Stigler Brandilyn

    2012-06-01

    Full Text Available Abstract Background Complex gene regulatory networks underlie many cellular and developmental processes. While a variety of experimental approaches can be used to discover how genes interact, few biological systems have been systematically evaluated to the extent required for an experimental definition of the underlying network. Therefore, the development of computational methods that can use limited experimental data to define and model a gene regulatory network would provide a useful tool to evaluate many important but incompletely understood biological processes. Such methods can assist in extracting all relevant information from data that are available, identify unexpected regulatory relationships and prioritize future experiments. Results To facilitate the analysis of gene regulatory networks, we have developed a computational modeling pipeline method that complements traditional evaluation of experimental data. For a proof-of-concept example, we have focused on the gene regulatory network in the nematode C. elegans that mediates the developmental choice between mesodermal (muscle and ectodermal (skin cell fates in the embryonic C lineage. We have used gene expression data to build two models: a knowledge-driven model based on gene expression changes following gene perturbation experiments, and a data-driven mathematical model derived from time-course gene expression data recovered from wild-type animals. We show that both models can identify a rich set of network gene interactions. Importantly, the mathematical model built only from wild-type data can predict interactions demonstrated by the perturbation experiments better than chance, and better than an existing knowledge-driven model built from the same data set. The mathematical model also provides new biological insight, including a dissection of zygotic from maternal functions of a key transcriptional regulator, PAL-1, and identification of non-redundant activities of the T-box genes

  12. A regulatory network modeled from wild-type gene expression data guides functional predictions in Caenorhabditis elegans development.

    Science.gov (United States)

    Stigler, Brandilyn; Chamberlin, Helen M

    2012-06-26

    Complex gene regulatory networks underlie many cellular and developmental processes. While a variety of experimental approaches can be used to discover how genes interact, few biological systems have been systematically evaluated to the extent required for an experimental definition of the underlying network. Therefore, the development of computational methods that can use limited experimental data to define and model a gene regulatory network would provide a useful tool to evaluate many important but incompletely understood biological processes. Such methods can assist in extracting all relevant information from data that are available, identify unexpected regulatory relationships and prioritize future experiments. To facilitate the analysis of gene regulatory networks, we have developed a computational modeling pipeline method that complements traditional evaluation of experimental data. For a proof-of-concept example, we have focused on the gene regulatory network in the nematode C. elegans that mediates the developmental choice between mesodermal (muscle) and ectodermal (skin) cell fates in the embryonic C lineage. We have used gene expression data to build two models: a knowledge-driven model based on gene expression changes following gene perturbation experiments, and a data-driven mathematical model derived from time-course gene expression data recovered from wild-type animals. We show that both models can identify a rich set of network gene interactions. Importantly, the mathematical model built only from wild-type data can predict interactions demonstrated by the perturbation experiments better than chance, and better than an existing knowledge-driven model built from the same data set. The mathematical model also provides new biological insight, including a dissection of zygotic from maternal functions of a key transcriptional regulator, PAL-1, and identification of non-redundant activities of the T-box genes tbx-8 and tbx-9. This work provides a strong

  13. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Directory of Open Access Journals (Sweden)

    Deborah Chasman

    2016-07-01

    Full Text Available Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  14. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Science.gov (United States)

    Chasman, Deborah; Walters, Kevin B; Lopes, Tiago J S; Eisfeld, Amie J; Kawaoka, Yoshihiro; Roy, Sushmita

    2016-07-01

    Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  15. Design and application of a GC-SNIff/MS system for solving taste and odour episodes in drinking water.

    Science.gov (United States)

    Hochereau, C; Bruchet, A

    2004-01-01

    This paper describes the implementation of a GC-Sniff/MS system that allows the simultaneous determination of the odorous properties of compounds eluting from a GC column and their identification by MS. The technique was first tested with standard compounds then applied to real cases of taste and odour episodes. This approach allowed the identification of geosmin at low levels and suggested the possible implication of methylnaphthalene in the development of chemical odours. It provided the first clue of the presence of a halophenol with a very low odour threshold involved in a chlorophenolic odour episode. The chemical was finally identified as 2,6-dibromophenol. The method was also applied to the characterization of a complex mixture of additives leaching from a flexible rubber pipe. In the latter case, Time-of-Flight MS was also used to confirm the identity of the additives.

  16. Statistical approaches to use a model organism for regulatory sequences annotation of newly sequenced species.

    Directory of Open Access Journals (Sweden)

    Pietro Liò

    Full Text Available A major goal of bioinformatics is the characterization of transcription factors and the transcriptional programs they regulate. Given the speed of genome sequencing, we would like to quickly annotate regulatory sequences in newly-sequenced genomes. In such cases, it would be helpful to predict sequence motifs by using experimental data from closely related model organism. Here we present a general algorithm that allow to identify transcription factor binding sites in one newly sequenced species by performing Bayesian regression on the annotated species. First we set the rationale of our method by applying it within the same species, then we extend it to use data available in closely related species. Finally, we generalise the method to handle the case when a certain number of experiments, from several species close to the species on which to make inference, are available. In order to show the performance of the method, we analyse three functionally related networks in the Ascomycota. Two gene network case studies are related to the G2/M phase of the Ascomycota cell cycle; the third is related to morphogenesis. We also compared the method with MatrixReduce and discuss other types of validation and tests. The first network is well known and provides a biological validation test of the method. The two cell cycle case studies, where the gene network size is conserved, demonstrate an effective utility in annotating new species sequences using all the available replicas from model species. The third case, where the gene network size varies among species, shows that the combination of information is less powerful but is still informative. Our methodology is quite general and could be extended to integrate other high-throughput data from model organisms.

  17. Steady-State Analysis of Genetic Regulatory Networks Modelled by Probabilistic Boolean Networks

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2006-04-01

    Full Text Available Probabilistic Boolean networks (PBNs have recently been introduced as a promising class of models of genetic regulatory networks. The dynamic behaviour of PBNs can be analysed in the context of Markov chains. A key goal is the determination of the steady-state (long-run behaviour of a PBN by analysing the corresponding Markov chain. This allows one to compute the long-term influence of a gene on another gene or determine the long-term joint probabilistic behaviour of a few selected genes. Because matrix-based methods quickly become prohibitive for large sizes of networks, we propose the use of Monte Carlo methods. However, the rate of convergence to the stationary distribution becomes a central issue. We discuss several approaches for determining the number of iterations necessary to achieve convergence of the Markov chain corresponding to a PBN. Using a recently introduced method based on the theory of two-state Markov chains, we illustrate the approach on a sub-network designed from human glioma gene expression data and determine the joint steadystate probabilities for several groups of genes.

  18. Prioritization of chemicals in the aquatic environment based on risk assessment: analytical, modeling and regulatory perspective.

    Science.gov (United States)

    Guillén, D; Ginebreda, A; Farré, M; Darbra, R M; Petrovic, M; Gros, M; Barceló, D

    2012-12-01

    The extensive and intensive use of chemicals in our developed, highly technological society includes more than 100,000 chemical substances. Significant scientific evidence has lead to the recognition that their improper use and release may result in undesirable and harmful side-effects on both the human and ecosystem health. To cope with them, appropriate risk assessment processes and related prioritization schemes have been developed in order to provide the necessary scientific support for regulatory procedures. In the present paper, two of the elements that constitute the core of risk assessment, namely occurrence and hazard effects, have been discussed. Recent advances in analytical chemistry (sample pre-treatment and instrumental equipment, etc.) have allowed for more comprehensive monitoring of environmental pollution reaching limits of detection up to sub ng L(-1). Alternative to analytical measurements, occurrence models can provide risk managers with a very interesting approach for estimating environmental concentrations from real or hypothetical scenarios. The most representative prioritization schemes used for issuing lists of concerning chemicals have also been examined and put in the context of existing environmental policies for protection strategies and regulations. Finally, new challenges in the field of risk-assessment have been outlined, including those posed by new materials (i.e., nanomaterials), transformation products, multi-chemical exposure, or extension of the risk assessment process to the whole ecosystem.

  19. Fatal Attraction Phenomenon in Humans – Cat Odour Attractiveness Increased for Toxoplasma-Infected Men While Decreased for Infected Women

    OpenAIRE

    Jaroslav Flegr; Pavlína Lenochová; Zdeněk Hodný; Marta Vondrová

    2011-01-01

    BACKGROUND: Latent toxoplasmosis, a lifelong infection with the protozoan Toxoplasma gondii, has cumulative effects on the behaviour of hosts, including humans. The most impressive effect of toxoplasmosis is the "fatal attraction phenomenon," the conversion of innate fear of cat odour into attraction to cat odour in infected rodents. While most behavioural effects of toxoplasmosis were confirmed also in humans, neither the fatal attraction phenomenon nor any toxoplasmosis-associated changes i...

  20. Public perception of odour and environmental pollution attributed to MSW treatment and disposal facilities: a case study.

    Science.gov (United States)

    De Feo, Giovanni; De Gisi, Sabino; Williams, Ian D

    2013-04-01

    If residents' perceptions, concerns and attitudes towards waste management facilities are either not well understood or underestimated, people can produce strong opposition that may include protest demonstrations and violent conflicts such as those experienced in the Campania Region of Italy. The aim of this study was to verify the effects of the closure of solid waste treatment and disposal facilities (two landfills and one RDF production plant) on public perception of odour and environmental pollution. The study took place in four villages in Southern Italy. Identical questionnaires were administered to residents during 2003 and after the closure of the facilities occurred in 2008. The residents' perception of odour nuisance considerably diminished between 2003 and 2009 for the nearest villages, with odour perception showing an association with distance from the facilities. Post closure, residents had difficulty in identifying the type of smell due to the decrease in odour level. During both surveys, older residents reported most concern about the potentially adverse health impacts of long-term exposure to odours from MSW facilities. However, although awareness of MSW facilities and concern about potentially adverse health impacts varied according to the characteristics of residents in 2003, substantial media coverage produced an equalisation effect and increased knowledge about the type of facilities and how they operated. It is possible that residents of the village nearest to the facilities reported lower awareness of and concern about odour and environmental pollution because the municipality received economic compensation for their presence.

  1. Measurement of Odour in On-Site Sanitation Systems in Low-Income Settings

    DEFF Research Database (Denmark)

    Obeng, Peter Appiah; Oduro-Kwarteng, Sampson; Keraita, Bernard

    2016-01-01

    detector, and assess whether the concentrations of the compounds correlate with the perception of users of the facilities. The Aeroqual 500 portable gas detector with hydrogen sulphide and ammonia sensor heads was used to measure the concentrations of the compounds in 88 private and seven communal latrines...... sampled from a peri-urban community in Ghana. The odour perception of 189 and 165 users of private and communal latrines, respectively, was assessed on an ordinal scale. It was found that the concentrations of hydrogen sulphide and ammonia measured with the gas detector reflected the known variation...... of odour levels among different technology options and the perceptions of the latrine users. The concentrations of hydrogen sulphide measured in the water closet, ventilated improved pit (VIP) and the simple pit latrines were 0.01, 0.03 and 0.13 ppm, respectively; those of ammonia were undetected...

  2. Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Li, Jun-Lu; Chen, Ting-Sang; Yuan, Cong-Cong; Zhao, Guo-Qiang; Xu, Min; Li, Xiao-Yan; Cao, Jie; Xing, Li-Hua

    2017-08-01

    Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (P<0.05). The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points, which were significantly lower than those in groups B and D (P<0.05). FOXP3 mRNA levels were lowest at 4 h, and there was significant difference between groups B and D (P<0.05). The serum levels of IL-10 in groups A and C were almost normal at the three time points, but decreased significantly in groups B and D (P<0.05). The serum levels of IL-10 decreased to the lowest at 8 h, especially in group D (P<0.05). The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

  3. A model study of the morphogenesis of D. melanogaster mechanoreceptors: the central regulatory circuit.

    Science.gov (United States)

    Golubyatnikov, Vladimir P; Bukharina, Tatyana A; Furman, Dagmara P

    2015-02-01

    Macrochaetes (large bristles) are sensor organs of the Drosophila peripheral nervous system with a function of mechanoreceptors. An adult mechanoreceptor comprises four specialized cells: shaft (trichogen), socket (tormogen), neuron, and glial cell (thecogen). All these cells originate from a single cell, the so-called sensor organ precursor (SOP) cell. Separation of the SOP cell from the encompassing cells of the imaginal disc initiates a multistage process of sensory organ development. A characteristic feature of the SOP cell is the highest amount of the proneural proteins AS-C as compared with the encompassing ectodermal cells. The accumulation of proneural proteins and maintenance of their amount in the SOP cell at a necessary level is provided by the gene network with the achaete-scute gene complex (AS-C) as its key component. The activity of this complex is controlled by the central regulatory circuit (CRC). The CRC comprises the genes hairy, senseless (sens), charlatan (chn), scratch (scrt), daughterless (da), extramacrochaete (emc), and groucho (gro), coding for the transcription factors involved in the system of direct links and feedbacks and implementation of activation-repression relationships between the CRC components. The gene phyllopod (phyl), involved in degradation of the AS-C proteins, is also associated with the CRC functioning. In this paper, we propose a mathematical model for the CRC functioning as a regulator of the amount of proneural AS-C proteins in the SOP cell taking into account their degradation. The modeling has demonstrated that a change in the amount of proneural proteins in the SOP cell is stepwise rather than strictly monotonic. This prediction can be tested experimentally.

  4. Impact of a non-attentively perceived odour on subsequent food choices.

    Science.gov (United States)

    Gaillet-Torrent, M; Sulmont-Rossé, C; Issanchou, S; Chabanet, C; Chambaron, S

    2014-05-01

    Current research in psychology suggests that unconscious processes influence a significant proportion of choices and decisions. To study the impact of a non-attentively perceived odour on food choices, we used a priming paradigm. We had previously shown that non-attentively perceived fruity odours could impact food choice intentions (on a menu card), guiding participants toward items containing more fruit and/or vegetables. The present study was designed to extend these findings, in a real-life consumption setting. One hundred and fifteen participants took part in this study, and were assigned randomly to either a control or a scented condition. On arrival in the laboratory, they were seated in a waiting room. For the scented condition, they were unobtrusively exposed to a pear odour, while under the control condition the waiting room was non-odorised. Following this waiting period, all participants moved into a non-odorised test room where they were asked to choose, from dishes served buffet-style, the starter, main course and dessert that they would actually eat for lunch. The results showed that participants subjected to the scented condition chose to consume the 'fruity' dessert (compote) more frequently than those who had waited under the control condition, who chose more frequently the dessert without fruit (brownie). In line with the findings of our previous study, these results confirm the idea of priming effects 'specific to the food cue'. To conclude, a non-attentively perceived fruity odour was shown to influence actual food choices, guiding individuals towards more fruity desserts. The involvement of implicit processes in food choices should be taken into account in guidelines and strategies designed to promote healthy eating. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Practical discrimination of good and bad cooked food using metal oxide semiconductor odour sensor

    OpenAIRE

    2013-01-01

    An increasing concentration of ammonia in cooked food is in direct proportion to the extent of decay. This fact is used to design an electronic nose (e-nose) based on metal oxide semiconductor odour sensor circuit capable of discriminating good and bad cooked food. On the basis of the data produced by the e-nose circuit, a feedforward multilayer neural network is designed and trained to recognize varying concentrations of ammonia in the food. Test results o...

  6. Odour control in composting plants; Control de olores en plantas de compostaje

    Energy Technology Data Exchange (ETDEWEB)

    Santa Coloma, O.; Hoyo, M. del; Blanco, A.M.; Garcia, J. C.

    2000-07-01

    When planning a composting facility, it is important to predict potential sources of odors along with their emission rates, detectability, and intensity. This article explains the compounds thought to be responsible for odors at composting facilities and the existing technologies for composting odour control. It is described the bio filters whose use in the composting industry is expanding as engineering design criteria for this technology have become increasingly available. (Author)

  7. Odour-modulated collective network oscillations of olfactory interneurons in a terrestrial mollusc

    Science.gov (United States)

    Gelperin, Alan; Tank, David W.

    1990-05-01

    DETERMINATION of the dynamical structure of neural circuits—the general principles of how neural activity varies with time and manipulates information—is a prerequisite to understanding their computational function1. Rhythmically active or oscillating neural circuits are particularly interesting dynamical structures, as rhythms and oscillations are a prominent feature of mammalian central nervous system electrophysiology. Coherent oscillations by networks of interneurons are observed in the vertebrate olfactory system2,3 and have recently been described in mammalian visual cortex4-6. These interneuronal networks display oscillations in local field potential (LFP) and probability of producing action potentials that are highly correlated between subcircuits sharing the same stimulus features. Much less is known about the existence and importance of network oscillations in the higher centres of invertebrates7. Here we report that a network of olfactory inter-neurons in the cerebral ganglion of the terrestrial mollusc Limax maximus also displays coherent oscillations in LFP which are modified by odour input. This dynamical structure could be central to the odour recognition and odour learning ability of Limax8,9.

  8. A specific area of olfactory cortex involved in stress hormone responses to predator odours.

    Science.gov (United States)

    Kondoh, Kunio; Lu, Zhonghua; Ye, Xiaolan; Olson, David P; Lowell, Bradford B; Buck, Linda B

    2016-04-01

    Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.

  9. Regulatory framework and business models for charging plug-in electric vehicles: Infrastructure, agents, and commercial relationships

    Energy Technology Data Exchange (ETDEWEB)

    Gomez San Roman, Tomas [Instituto de Investigacion Tecnologica, Universidad Pontificia Comillas, Madrid (Spain); Momber, Ilan, E-mail: ilan.momber@iit.upcomillas.es [Instituto de Investigacion Tecnologica, Universidad Pontificia Comillas, Madrid (Spain); Rivier Abbad, Michel; Sanchez Miralles, Alvaro [Instituto de Investigacion Tecnologica, Universidad Pontificia Comillas, Madrid (Spain)

    2011-10-15

    Electric vehicles (EVs) present efficiency and environmental advantages over conventional transportation. It is expected that in the next decade this technology will progressively penetrate the market. The integration of plug-in electric vehicles in electric power systems poses new challenges in terms of regulation and business models. This paper proposes a conceptual regulatory framework for charging EVs. Two new electricity market agents, the EV charging manager and the EV aggregator, in charge of developing charging infrastructure and providing charging services are introduced. According to that, several charging modes such as EV home charging, public charging on streets, and dedicated charging stations are formulated. Involved market agents and their commercial relationships are analysed in detail. The paper elaborates the opportunities to formulate more sophisticated business models for vehicle-to-grid applications under which the storage capability of EV batteries is used for providing peak power or frequency regulation to support the power system operation. Finally penetration phase dependent policy and regulatory recommendations are given concerning time-of-use pricing, smart meter deployment, stable and simple regulation for reselling energy on private property, roll-out of public charging infrastructure as well as reviewing of grid codes and operational system procedures for interactions between network operators and vehicle aggregators. - Highlights: > A conceptual regulatory framework for charging EVs is proposed. > 2 new agents, EV charging point manager, EV aggregator and their functions are introduced. > Depending on private or public access of charging points, contractual relations change. > A classification of charging scenarios alludes implications on regulatory topics. > EV penetration phase dependent policy and regulatory recommendations are given.

  10. Boolean Modelling Reveals New Regulatory Connections between Transcription Factors Orchestrating the Development of the Ventral Spinal Cord

    Science.gov (United States)

    Lovrics, Anna; Gao, Yu; Juhász, Bianka; Bock, István; Byrne, Helen M.; Dinnyés, András; Kovács, Krisztián A.

    2014-01-01

    We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks. PMID:25398016

  11. Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

    KAUST Repository

    Lovrics, Anna

    2014-11-14

    We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.

  12. Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient.

    Science.gov (United States)

    Mohamed Salleh, Faridah Hani; Arif, Shereena Mohd; Zainudin, Suhaila; Firdaus-Raih, Mohd

    2015-12-01

    A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5.

  13. Impulsivity, perceived self-regulatory success in dieting, and body mass in children and adolescents: A moderated mediation model.

    Science.gov (United States)

    Meule, Adrian; Hofmann, Johannes; Weghuber, Daniel; Blechert, Jens

    2016-12-01

    Impulsivity has been suggested to contribute to overeating and obesity. However, findings are inconsistent and it appears that only specific facets of impulsivity are related to eating-related variables and to body mass. In the current study, relationships between self-reported impulsivity, perceived self-regulatory success in dieting, and objectively measured body mass were examined in N = 122 children and adolescents. Scores on attentional and motor impulsivity interactively predicted perceived self-regulatory success in dieting, but not body mass: Higher attentional impulsivity was associated with lower perceived self-regulatory success at high levels of motor impulsivity, but not at low levels of motor impulsivity. A moderated mediation model revealed an indirect effect of attentional and motor impulsivity on body mass, which was mediated by perceived self-regulatory success in dieting. Thus, results show that only specific facets of impulsivity are relevant in eating- and weight-regulation and interact with each other in the prediction of these variables. These facets of impulsivity, however, are not directly related to higher body mass, but indirectly via lower success in eating-related self-regulation in children and adolescents.

  14. Regulatory perspectives on model validation in high-level radioactive waste management programs: A joint NRC/SKI white paper

    Energy Technology Data Exchange (ETDEWEB)

    Wingefors, S.; Andersson, J.; Norrby, S. [Swedish Nuclear Power lnspectorate, Stockholm (Sweden). Office of Nuclear Waste Safety; Eisenberg, N.A.; Lee, M.P.; Federline, M.V. [U.S. Nuclear Regulatory Commission, Washington, DC (United States). Office of Nuclear Material Safety and Safeguards; Sagar, B.; Wittmeyer, G.W. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)

    1999-03-01

    Validation (or confidence building) should be an important aspect of the regulatory uses of mathematical models in the safety assessments of geologic repositories for the disposal of spent nuclear fuel and other high-level radioactive wastes (HLW). A substantial body of literature exists indicating the manner in which scientific validation of models is usually pursued. Because models for a geologic repository performance assessment cannot be tested over the spatial scales of interest and long time periods for which the models will make estimates of performance, the usual avenue for model validation- that is, comparison of model estimates with actual data at the space-time scales of interest- is precluded. Further complicating the model validation process in HLW programs are the uncertainties inherent in describing the geologic complexities of potential disposal sites, and their interactions with the engineered system, with a limited set of generally imprecise data, making it difficult to discriminate between model discrepancy and inadequacy of input data. A successful strategy for model validation, therefore, should attempt to recognize these difficulties, address their resolution, and document the resolution in a careful manner. The end result of validation efforts should be a documented enhancement of confidence in the model to an extent that the model's results can aid in regulatory decision-making. The level of validation needed should be determined by the intended uses of these models, rather than by the ideal of validation of a scientific theory. This white Paper presents a model validation strategy that can be implemented in a regulatory environment. It was prepared jointly by staff members of the U.S. Nuclear Regulatory Commission and the Swedish Nuclear Power Inspectorate-SKI. This document should not be viewed as, and is not intended to be formal guidance or as a staff position on this matter. Rather, based on a review of the literature and previous

  15. Building a self-regulatory model of sleep deprivation and deception: the role of caffeine and social influence.

    Science.gov (United States)

    Welsh, David T; Ellis, Aleksander P J; Christian, Michael S; Mai, Ke Michael

    2014-11-01

    Employees are getting less sleep, which has been shown to deplete self-regulatory resources and increase unethical behavior (Barnes, Schaubroeck, Huth, & Ghumman, 2011; Christian & Ellis, 2011). In this study, we extend the original mediated model by examining the role of 2 moderators in the relationship between sleep deprivation, depletion, and deceptive behavior. First, we derive psychological arguments from the psychopharmacology literature to hypothesize that caffeine moderates the relationship between sleep deprivation and depletion by replenishing self-regulatory resources. Second, we draw from recent research in social psychology to hypothesize that social influence moderates the relationship between depletion and deceptive behavior, such that depleted individuals are less able to resist the negative influence of others. Results of a laboratory study provide support for our expanded model combining mediation and moderation, adding to our understanding of the role of sleep deprivation in the incidence of workplace deception. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  16. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model

    OpenAIRE

    Pilat, Nina; Farkas, Andreas M.; Mahr, Benedikt; Schwarz, Christoph; Unger, Lukas; Hock, Karin; Oberhuber, Rupert; Aumayr, Klaus; Wrba, Fritz; Wekerle, Thomas

    2014-01-01

    Background The mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection. Metho...

  17. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  18. A Generic Integrated Physiologically based Whole-body Model of the Glucose-Insulin-Glucagon Regulatory System

    Science.gov (United States)

    Schaller, S; Willmann, S; Lippert, J; Schaupp, L; Pieber, T R; Schuppert, A; Eissing, T

    2013-01-01

    Models of glucose metabolism are a valuable tool for fundamental and applied medical research in diabetes. Use cases range from pharmaceutical target selection to automatic blood glucose control. Standard compartmental models represent little biological detail, which hampers the integration of multiscale data and confines predictive capabilities. We developed a detailed, generic physiologically based whole-body model of the glucose-insulin-glucagon regulatory system, reflecting detailed physiological properties of healthy populations and type 1 diabetes individuals expressed in the respective parameterizations. The model features a detailed representation of absorption models for oral glucose, subcutaneous insulin and glucagon, and an insulin receptor model relating pharmacokinetic properties to pharmacodynamic effects. Model development and validation is based on literature data. The quality of predictions is high and captures relevant observed inter- and intra-individual variability. In the generic form, the model can be applied to the development and validation of novel diabetes treatment strategies. PMID:23945606

  19. Activation, orientation and landing of female Culex quinquefasciatus in response to carbon dioxide and odour from human feet: 3-D flight analysis in a wind tunnel.

    Science.gov (United States)

    Lacey, E S; Cardé, R T

    2011-03-01

    This study investigated the interaction between carbon dioxide (CO(2) ) and human foot odour on activation, upwind orientation and landing of host-seeking female Culex quinquefasciatus (Say) (Diptera: Culicidae) in a wind tunnel. More mosquitoes landed on warmed glass beads coated with foot odour than on clean beads; adding a plume of 4% CO(2) did not influence the proportion of mosquitoes landing. A second experiment used 3-dimensional video tracking to assess flight performance. Activation was more rapid with CO(2) and with CO(2) + foot odour than with clean air or with foot odour alone. Upwind flights were fastest with CO(2) and with clean air, and slowest with foot odour; the CO(2) + foot odour treatment overlapped the previous three treatments in significance. Flight headings tended more towards due upwind with CO(2) and with clean air than with CO(2) + foot odour or with foot odour alone. In both experiments, many mosquitoes flew upwind in clean air. There was little evidence of females changing course upon entering or exiting the CO(2) plume or reacting to foot odour during flight.

  20. DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks.

    Science.gov (United States)

    Wang, Daifeng; He, Fei; Maslov, Sergei; Gerstein, Mark

    2016-10-01

    Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the "state" and "control" in the model refer to its own (internal) and another subsystem's (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model's parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with evolutionarily

  1. A discussion of regulatory requirements and air dispersion modeling approaches applicable to U.S. chemical demilitarization facilities.

    Science.gov (United States)

    Higgins, B W; Robbins, L B; Litynski, J

    1998-09-01

    Owners of hazardous waste treatment, storage, and disposal facilities, and certain major air pollution sources, must conduct several separate ambient air dispersion modeling analyses before beginning construction of new facilities or modifying existing facilities. These analyses are critical components of the environmental permitting and facility certification processes and must be completed to the satisfaction of federal, state, and local regulatory authorities. The U.S. Army has conducted air dispersion modeling for its proposed chemical agent disposal facilities to fulfill the following environmental regulatory and risk management requirements: (1) Resource Conservation and Recovery Act human health and ecological risk assessment analysis for the hazardous waste treatment and storage permit applications, (2) Quantitative Risk Assessment to support the site-specific risk management programs, and (3) Prevention of Significant Deterioration ambient air impact analysis for the air permit applications. The purpose of these air dispersion modeling studies is to show that the potential impacts on human health and the environment, due to operation of the chemical agent disposal facilities, are acceptable. This paper describes and compares the types of air dispersion models, modeling input data requirements, modeling algorithms, and approaches used to satisfy the three environmental regulatory and risk management requirements listed above. Although this paper discusses only one industry (i.e., chemical demilitarization), the information it contains could help those in other industries who need to communicate to the public the purpose and objectives of each modeling analysis. It may also be useful in integrating the results of each analysis into an overarching summary of compliance and potential risks.

  2. DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks

    Science.gov (United States)

    Gerstein, Mark

    2016-01-01

    Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem’s gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally–e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the “state” and “control” in the model refer to its own (internal) and another subsystem’s (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model’s parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with

  3. Dynamic RSA: Examining parasympathetic regulatory dynamics via vector-autoregressive modeling of time-varying RSA and heart period.

    Science.gov (United States)

    Fisher, Aaron J; Reeves, Jonathan W; Chi, Cyrus

    2016-07-01

    Expanding on recently published methods, the current study presents an approach to estimating the dynamic, regulatory effect of the parasympathetic nervous system on heart period on a moment-to-moment basis. We estimated second-to-second variation in respiratory sinus arrhythmia (RSA) in order to estimate the contemporaneous and time-lagged relationships among RSA, interbeat interval (IBI), and respiration rate via vector autoregression. Moreover, we modeled these relationships at lags of 1 s to 10 s, in order to evaluate the optimal latency for estimating dynamic RSA effects. The IBI (t) on RSA (t-n) regression parameter was extracted from individual models as an operationalization of the regulatory effect of RSA on IBI-referred to as dynamic RSA (dRSA). Dynamic RSA positively correlated with standard averages of heart rate and negatively correlated with standard averages of RSA. We propose that dRSA reflects the active downregulation of heart period by the parasympathetic nervous system and thus represents a novel metric that provides incremental validity in the measurement of autonomic cardiac control-specifically, a method by which parasympathetic regulatory effects can be measured in process.

  4. A dynamic genetic-hormonal regulatory network model explains multiple cellular behaviors of the root apical meristem of Arabidopsis thaliana.

    Science.gov (United States)

    García-Gómez, Mónica L; Azpeitia, Eugenio; Álvarez-Buylla, Elena R

    2017-04-01

    The study of the concerted action of hormones and transcription factors is fundamental to understand cell differentiation and pattern formation during organ development. The root apical meristem of Arabidopsis thaliana is a useful model to address this. It has a stem cell niche near its tip conformed of a quiescent organizer and stem or initial cells around it, then a proliferation domain followed by a transition domain, where cells diminish division rate before transiting to the elongation zone; here, cells grow anisotropically prior to their final differentiation towards the plant base. A minimal model of the gene regulatory network that underlies cell-fate specification and patterning at the root stem cell niche was proposed before. In this study, we update and couple such network with both the auxin and cytokinin hormone signaling pathways to address how they collectively give rise to attractors that correspond to the genetic and hormonal activity profiles that are characteristic of different cell types along A. thaliana root apical meristem. We used a Boolean model of the genetic-hormonal regulatory network to integrate known and predicted regulatory interactions into alternative models. Our analyses show that, after adding some putative missing interactions, the model includes the necessary and sufficient components and regulatory interactions to recover attractors characteristic of the root cell types, including the auxin and cytokinin activity profiles that correlate with different cellular behaviors along the root apical meristem. Furthermore, the model predicts the existence of activity configurations that could correspond to the transition domain. The model also provides a possible explanation for apparently paradoxical cellular behaviors in the root meristem. For example, how auxin may induce and at the same time inhibit WOX5 expression. According to the model proposed here the hormonal regulation of WOX5 might depend on the cell type. Our results

  5. Characterisation of aroma profiles of commercial sufus by odour activity value, gas chromatography-olfactometry, aroma recombination and omission studies.

    Science.gov (United States)

    Xiao, Zuobing; Shang, Yi; Chen, Feng; Niu, Yunwei; Gu, Yongbo; Liu, Shengjiang; Zhu, Jiancai

    2015-01-01

    Sufu is a solid-state fermented product made from soya beans. For the sake of quality control and regulation purposes, it is essential to be able to identify key odorants of various commercial sufus. To identify the aroma-active compounds in sufus, gas chromatography-olfactometry/aroma extract dilution analysis (GC-O/AEDA) was performed, and odour activity value (OAV) was estimated. The correlations between aroma profiles and identified aroma-active compounds were also investigated by principal component analysis. Results showed that 35 aroma-active compounds were detected through OAV calculation, while 28 compounds were identified by using GC-O/AEDA. Quantitative descriptive analysis revealed that aroma recombination model based on OAV calculation was more similar to original sufu in terms of aroma comparing to aroma recombination model based on GC-O/AEDA. Omission experiments further confirmed that the aroma compounds, such as ethyl butanoate, ethyl 2-methylbutanoate, ethyl hexanoate, (E,E)-2,4-decadienal and 2,6-dimethylpyrazine, contributed most significantly to the characteristic aroma of a commercial sufu.

  6. Transcriptional regulatory network refinement and quantification through kinetic modeling, gene expression microarray data and information theory

    Science.gov (United States)

    Sayyed-Ahmad, Abdallah; Tuncay, Kagan; Ortoleva, Peter J

    2007-01-01

    Background Gene expression microarray and other multiplex data hold promise for addressing the challenges of cellular complexity, refined diagnoses and the discovery of well-targeted treatments. A new approach to the construction and quantification of transcriptional regulatory networks (TRNs) is presented that integrates gene expression microarray data and cell modeling through information theory. Given a partial TRN and time series data, a probability density is constructed that is a functional of the time course of transcription factor (TF) thermodynamic activities at the site of gene control, and is a function of mRNA degradation and transcription rate coefficients, and equilibrium constants for TF/gene binding. Results Our approach yields more physicochemical information that compliments the results of network structure delineation methods, and thereby can serve as an element of a comprehensive TRN discovery/quantification system. The most probable TF time courses and values of the aforementioned parameters are obtained by maximizing the probability obtained through entropy maximization. Observed time delays between mRNA expression and activity are accounted for implicitly since the time course of the activity of a TF is coupled by probability functional maximization, and is not assumed to be proportional to expression level of the mRNA type that translates into the TF. This allows one to investigate post-translational and TF activation mechanisms of gene regulation. Accuracy and robustness of the method are evaluated. A kinetic formulation is used to facilitate the analysis of phenomena with a strongly dynamical character while a physically-motivated regularization of the TF time course is found to overcome difficulties due to omnipresent noise and data sparsity that plague other methods of gene expression data analysis. An application to Escherichia coli is presented. Conclusion Multiplex time series data can be used for the construction of the network of

  7. Transcriptional regulatory network refinement and quantification through kinetic modeling, gene expression microarray data and information theory

    Directory of Open Access Journals (Sweden)

    Tuncay Kagan

    2007-01-01

    Full Text Available Abstract Background Gene expression microarray and other multiplex data hold promise for addressing the challenges of cellular complexity, refined diagnoses and the discovery of well-targeted treatments. A new approach to the construction and quantification of transcriptional regulatory networks (TRNs is presented that integrates gene expression microarray data and cell modeling through information theory. Given a partial TRN and time series data, a probability density is constructed that is a functional of the time course of transcription factor (TF thermodynamic activities at the site of gene control, and is a function of mRNA degradation and transcription rate coefficients, and equilibrium constants for TF/gene binding. Results Our approach yields more physicochemical information that compliments the results of network structure delineation methods, and thereby can serve as an element of a comprehensive TRN discovery/quantification system. The most probable TF time courses and values of the aforementioned parameters are obtained by maximizing the probability obtained through entropy maximization. Observed time delays between mRNA expression and activity are accounted for implicitly since the time course of the activity of a TF is coupled by probability functional maximization, and is not assumed to be proportional to expression level of the mRNA type that translates into the TF. This allows one to investigate post-translational and TF activation mechanisms of gene regulation. Accuracy and robustness of the method are evaluated. A kinetic formulation is used to facilitate the analysis of phenomena with a strongly dynamical character while a physically-motivated regularization of the TF time course is found to overcome difficulties due to omnipresent noise and data sparsity that plague other methods of gene expression data analysis. An application to Escherichia coli is presented. Conclusion Multiplex time series data can be used for the

  8. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production

    Science.gov (United States)

    Walshaw, John; Peck, Michael W.; Barker, Gary C.

    2016-01-01

    Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. PMID:27855161

  9. Odour-tracking capability of a silkmoth driving a mobile robot with turning bias and time delay.

    Science.gov (United States)

    Ando, N; Emoto, S; Kanzaki, R

    2013-03-01

    The reconstruction of mechanisms behind odour-tracking behaviours of animals is expected to enable the development of biomimetic robots capable of adaptive behaviour and effectively locating odour sources. However, because the behavioural mechanisms of animals have not been extensively studied, their behavioural capabilities cannot be verified. In this study, we have employed a mobile robot driven by a genuine insect (insect-controlled robot) to evaluate the behavioural capabilities of a biological system implemented in an artificial system. We used a male silkmoth as the 'driver' and investigated its behavioural capabilities to imposed perturbations during odour tracking. When we manipulated the robot to induce the turning bias, it located the odour source by compensatory turning of the on-board moth. Shifting of the orientation paths to the odour plume boundaries and decreased orientation ability caused by covering the visual field suggested that the moth steered with bilateral olfaction and vision to overcome the bias. An evaluation of the time delays of the moth and robot movements suggested an acceptable range for sensory-motor processing when the insect system was directly applied to artificial systems. Further evaluations of the insect-controlled robot will provide a 'blueprint' for biomimetic robots and strongly promote the field of biomimetics.

  10. Volatile trace compounds released from municipal solid waste at the transfer stage: Evaluation of environmental impacts and odour pollution.

    Science.gov (United States)

    Zhao, Yan; Lu, Wenjing; Wang, Hongtao

    2015-12-30

    Odour pollution caused by municipal solid waste is a public concern. This study quantitatively evaluated the concentration, environmental impacts, and olfaction of volatile trace compounds released from a waste transfer station. Seventy-six compounds were detected, and ethanol presented the highest releasing rate and ratio of 14.76 kg/d and 12.30 g/t of waste, respectively. Life cycle assessment showed that trichlorofluoromethane and dichlorodifluoromethane accounted for more than 99% of impact potentials to global warming and approximately 70% to human toxicity (non-carcinogenic). The major contributor for both photochemical ozone formation and ecotoxicity was ethanol. A detection threshold method was also used to evaluate odour pollution. Five compounds including methane thiol, hydrogen sulphide, ethanol, dimethyl disulphide, and dimethyl sulphide, with dilution multiples above one, were considered the critical compounds. Methane thiol showed the highest contribution to odour pollution of more than 90%, as indicated by its low threshold. Comparison of the contributions of the compounds to different environmental aspects indicated that typical pollutants varied based on specific evaluation targets and therefore should be comprehensively considered. This study provides important information and scientific methodology to elucidate the impacts of odourant compounds to the environment and odour pollution.

  11. A model of gene expression based on random dynamical systems reveals modularity properties of gene regulatory networks.

    Science.gov (United States)

    Antoneli, Fernando; Ferreira, Renata C; Briones, Marcelo R S

    2016-06-01

    Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (ii) the assumptions about the stochastic processes used in the modeling are fairly general, in the sense that the only requirement is stationarity; (iii) there is a well developed mathematical theory, which is a blend of smooth dynamical systems theory, ergodic theory and stochastic analysis that allows one to extract relevant dynamical and statistical information without solving the system; (iv) one may obtain the classical rate equations form the corresponding stochastic version by averaging the dynamic random variables (small noise limit). It is important to emphasize that unlike the deterministic case, where coupling two equations is a trivial matter, coupling two RDS is non-trivial, specially in our case, where the coupling is performed between a state variable of one gene and the switching stochastic process of another gene and, hence, it is not a priori true that the resulting coupled system will satisfy the definition of a random dynamical system. We shall provide the necessary arguments that ensure that our coupling prescription does indeed furnish a coupled regulatory network of random dynamical systems. Finally, the fact that classical rate equations are the small noise limit of our stochastic model ensures that any validation or prediction made on the basis of the classical theory is also a validation or prediction of our model. We illustrate our framework with some simple examples of single-gene system and network motifs.

  12. Inference of gene regulatory networks with the strong-inhibition Boolean model

    Energy Technology Data Exchange (ETDEWEB)

    Xia Qinzhi; Liu Lulu; Ye Weiming; Hu Gang, E-mail: ganghu@bnu.edu.cn [Department of Physics, Beijing Normal University, Beijing 100875 (China)

    2011-08-15

    The inference of gene regulatory networks (GRNs) is an important topic in biology. In this paper, a logic-based algorithm that infers the strong-inhibition Boolean genetic regulatory networks (where regulation by any single repressor can definitely suppress the expression of the gene regulated) from time series is discussed. By properly ordering various computation steps, we derive for the first time explicit formulae for the probabilities at which different interactions can be inferred given a certain number of data. With the formulae, we can predict the precision of reconstructions of regulation networks when the data are insufficient. Numerical simulations coincide well with the analytical results. The method and results are expected to be applicable to a wide range of general dynamic networks, where logic algorithms play essential roles in the network dynamics and the probabilities of various logics can be estimated well.

  13. Changes of CD8+CD28- T regulatory cells in rat model of colitis induced by 2,4-dinitrofluorobenzene

    Institute of Scientific and Technical Information of China (English)

    Wen-Bin Xiao; Yu-Lan Liu

    2003-01-01

    AIM: To determine the changes of CD8+ T subsets especially CD8+CD28- T regulatory cells in rat model of experimental colitis induced by 2,4-dinitrofiuorobenzene (DNFB).METHODS: The rat model of experimental colitis was induced by enema with DNFB. Ten days later, colonic intraepithelial and splenic lymphocytes were isolated from colitis animals (n=16) and controls (n=8). The proportion of CD8+ T cells, CD8+CD28+ T cells and CD8+CD28- T regulatory cells were determined by flow cytometry.RESULTS: The model of experimental colitis was successfully established by DNFB that was demonstrated by bloody diarrhea, weight loss and colonic histopathology. The proportion of CD8+ T cells in either splenic or colonic intraepithelial lymphocytes was not significantly different between colitis animals and controls (spleen: 34.6±7.24 % vs33.5±9.41%,colon: 14.0±8.93 % vs 18.0±4.06 %, P>0.05). But CD8+CD28-T regulatory cells from colitis animals were significantly more than those from controls (spleen: 11.3±2.26 % vs5.64±1.01%,colon: 6.50±5.37 % vs 1.07±0.65 %, P<0.05). In contrast,CD8+CD28+ T cells from colitis animals were less than those from controls (spleen: 23.3±6.14 % vs27.8±9.70 %, P=0.06;colon: 7.52±4.18 % vs 16.9±4.07 %, P<0.05). The proportion of CD8+CD28- T regulatory cells in splenic and colonintraepithelial CD8+ T cells from colitis animals was higher than that from controls (spleen: 33.3±5.49 % vs 18.4±7.26 %,colon: 46.0±14.3 % vs6.10±3.72 %, P<0.005).CONCLUSION: Experimental colitis of rats can be induced by DNFB with simplicity and good reproducibility. The proportion of CD8+CD28- T regulatory cells in rats with experimental colitis is increased, which may be associated with the pathogenesis of colitis.

  14. Functional dissection of regulatory models using gene expression data of deletion mutants.

    Directory of Open Access Journals (Sweden)

    Jin'e Li

    Full Text Available Genome-wide gene expression profiles accumulate at an alarming rate, how to integrate these expression profiles generated by different laboratories to reverse engineer the cellular regulatory network has been a major challenge. To automatically infer gene regulatory pathways from genome-wide mRNA expression profiles before and after genetic perturbations, we introduced a new Bayesian network algorithm: Deletion Mutant Bayesian Network (DM_BN. We applied DM_BN to the expression profiles of 544 yeast single or double deletion mutants of transcription factors, chromatin remodeling machinery components, protein kinases and phosphatases in S. cerevisiae. The network inferred by this method identified causal regulatory and non-causal concurrent interactions among these regulators (genetically perturbed genes that are strongly supported by the experimental evidence, and generated many new testable hypotheses. Compared to networks reconstructed by routine similarity measures or by alternative Bayesian network algorithms, the network inferred by DM_BN excels in both precision and recall. To facilitate its application in other systems, we packaged the algorithm into a user-friendly analysis tool that can be downloaded at http://www.picb.ac.cn/hanlab/DM_BN.html.

  15. Prevention of volatile fatty acids production and limitation of odours from winery wastewaters by denitrification.

    Science.gov (United States)

    Bories, André; Guillot, Jean-Michel; Sire, Yannick; Couderc, Marie; Lemaire, Sophie-Andréa; Kreim, Virginie; Roux, Jean-Claude

    2007-07-01

    The effect of the addition of nitrate to winery wastewaters to control the formation of VFA in order to prevent odours during storage and treatment was studied in batch bioreactors at different NO(3)/chemical oxygen demand (COD) ratios and at full scale in natural evaporation ponds (2 x 7000 m(2)) by measuring olfactory intensity. In the absence of nitrate, butyric acid (2304 mgL(-1)), acetic acid (1633 mgL(-1)), propionic acid (1558 mgL(-1)), caproic acid (499 mgL(-1)) and valeric acid (298 mgL(-1)) were produced from reconstituted winery wastewater. For a ratio of NO(3)/COD=0.4 gg(-1), caproic and valeric acids were not formed. The production of butyric and propionic acids was reduced by 93.3% and 72.5%, respectively, at a ratio of NO(3)/COD=0.8, and by 97.4% and 100% at a ratio of NO(3)/COD=1.2 gg(-1). Nitrate delayed and decreased butyric acid formation in relation to the oxidoreduction potential. Studies in ponds showed that the addition of concentrated calcium nitrate (NITCAL) to winery wastewaters (3526 m(3)) in a ratio of NO(3)/COD=0.8 inhibited VFA production, with COD elimination (94%) and total nitrate degradation, and no final nitrite accumulation. On the contrary, in ponds not treated with nitrate, malodorous VFA (from propionic to heptanoïc acids) represented up to 60% of the COD. Olfactory intensity measurements in relation to the butanol scale of VFA solutions and the ponds revealed the pervasive role of VFA in the odour of the untreated pond as well as the clear decrease in the intensity and not unpleasant odour of the winery wastewater pond enriched in nitrates. The results obtained at full scale underscored the feasibility and safety of the calcium nitrate treatment as opposed to concentrated nitric acid.

  16. Technological and life cycle assessment of organics processing odour control technologies.

    Science.gov (United States)

    Bindra, Navin; Dubey, Brajesh; Dutta, Animesh

    2015-09-15

    As more municipalities and communities across developed world look towards implementing organic waste management programmes or upgrading existing ones, composting facilities are emerging as a popular choice. However, odour from these facilities continues to be one of the most important concerns in terms of cost & effective mitigation. This paper provides a technological and life cycle assessment of some of the different odour control technologies and treatment methods that can be implemented in organics processing facilities. The technological assessment compared biofilters, packed tower wet scrubbers, fine mist wet scrubbers, activated carbon adsorption, thermal oxidization, oxidization chemicals and masking agents. The technologies/treatment methods were evaluated and compared based on a variety of operational, usage and cost parameters. Based on the technological assessment it was found that, biofilters and packed bed wet scrubbers are the most applicable odour control technologies for use in organics processing faculties. A life cycle assessment was then done to compare the environmental impacts of the packed-bed wet scrubber system, organic (wood-chip media) bio-filter and inorganic (synthetic media) bio-filter systems. Twelve impact categories were assessed; cumulative energy demand (CED), climate change, human toxicity, photochemical oxidant formation, metal depletion, fossil depletion, terrestrial acidification, freshwater eutrophication, marine eutrophication, terrestrial eco-toxicity, freshwater eco-toxicity and marine eco-toxicity. The results showed that for all impact categories the synthetic media biofilter had the highest environmental impact, followed by the wood chip media bio-filter system. The packed-bed system had the lowest environmental impact for all categories.

  17. Differential interactions of sex pheromone and plant odour in the olfactory pathway of a male moth.

    Directory of Open Access Journals (Sweden)

    Nina Deisig

    Full Text Available Most animals rely on olfaction to find sexual partners, food or a habitat. The olfactory system faces the challenge of extracting meaningful information from a noisy odorous environment. In most moth species, males respond to sex pheromone emitted by females in an environment with abundant plant volatiles. Plant odours could either facilitate the localization of females (females calling on host plants, mask the female pheromone or they could be neutral without any effect on the pheromone. Here we studied how mixtures of a behaviourally-attractive floral odour, heptanal, and the sex pheromone are encoded at different levels of the olfactory pathway in males of the noctuid moth Agrotis ipsilon. In addition, we asked how interactions between the two odorants change as a function of the males' mating status. We investigated mixture detection in both the pheromone-specific and in the general odorant pathway. We used a recordings from individual sensilla to study responses of olfactory receptor neurons, b in vivo calcium imaging with a bath-applied dye to characterize the global input response in the primary olfactory centre, the antennal lobe and c intracellular recordings of antennal lobe output neurons, projection neurons, in virgin and newly-mated males. Our results show that heptanal reduces pheromone sensitivity at the peripheral and central olfactory level independently of the mating status. Contrarily, heptanal-responding olfactory receptor neurons are not influenced by pheromone in a mixture, although some post-mating modulation occurs at the input of the sexually isomorphic ordinary glomeruli, where general odours are processed within the antennal lobe. The results are discussed in the context of mate localization.

  18. Smelling your way to food: can bed bugs use our odour?

    Science.gov (United States)

    Harraca, V; Ryne, C; Birgersson, G; Ignell, R

    2012-02-15

    The resurgence in developed countries of the common bed bug, Cimex lectularius, has led to a search for new sustainable methods to monitor and control this human ectoparasite. Because of increased resistance to insecticides, traps baited with attractive cues are considered a promising method to be developed into efficient monitoring tools for bed bugs. Despite their potential as attractants, only a few studies have investigated the odorant cues implicated in the attraction of bed bugs to human hosts. In this study, we used aeration extracts from human volunteers to assess the role of olfaction in host searching by bed bugs. By coupled gas chromatography and single sensillum recordings on all the antennal sensilla, we measured the electrophysiological response elicited by the compounds present in our human odour extracts. Only five compounds were clearly detected by the olfactory receptor neurons housed in the smooth-peg sensilla of the bed bugs. We tested the behavioural effect of these extracts in a still-air arena and showed a gradient of repellence linked to the dose, as well as a higher propensity of local search behaviour associated with human odours containing a lower ratio of 6-methyl-5-hepten-2-one to C(7)-C(10) aldehydes. We conclude that human odour alone has a weak influence on the behaviour of C. lectularius and we propose that human kairomones may have a significant impact on bed bug behaviour in combination with heat and carbon dioxide, the only two currently known attractive vertebrate cues used by bed bugs for host seeking.

  19. Design, construction and operation of bio-filters for odour control sewage treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Eitner, D.; Gethke, H.G. (G+E Umwelttechnologie GmbH, Aachen (DE))

    1987-01-01

    It is known from waste water technology that the micro-organisms existing in a clarification plant under living conditions as optimal as possible, are capable of decomposing pollution in waste water. This knowledge has been used to search for low-cost waste air treatment technologies. Odour substances of a waste air are decomposed by microbial procedures. The possibility of biological waste air clarification by means of bio-filter plants or compost filter plants is discussed in this paper. There are indications of this technology as early as in the year 1928. Technical progress can be noted with this technology, as well.

  20. A case with fear of emitting body odour resulted in successful treatment with clomipramine.

    Science.gov (United States)

    Kizu, A; Miyoshi, N; Yoshida, Y; Miyagishi, T

    1994-11-01

    A patient with fear of emitting body odour of about 20 years' duration is reported. The patient was improved with clomipramine, a tricyclic antidepressant. Generally in Japan, he would be classified as having anthropophobia. However, according to the criteria advocated by Munro and Chmara (1982), he could be classified as having monosymptomatic hypochondriasis (MH). There are some reports that antidepressants have been effective in patients with either anthropophobia or MH. Therefore, a subgroup of patients which respond to antidepressants may exist in these disorders.

  1. Regulatory acceptance of animal models of disease to support clinical trials of medicines and advanced therapy medicinal products.

    Science.gov (United States)

    Cavagnaro, Joy; Silva Lima, Beatriz

    2015-07-15

    The utility of animal models of disease for assessing the safety of novel therapeutic modalities has become an increasingly important topic of discussion as research and development efforts focus on improving the predictive value of animal studies to support accelerated clinical development. Medicines are approved for marketing based upon a determination that their benefits outweigh foreseeable risks in specific indications, specific populations, and at specific dosages and regimens. No medicine is 100% safe. A medicine is less safe if the actual risks are greater than the predicted risks. The purpose of preclinical safety assessment is to understand the potential risks to aid clinical decision-making. Ideally preclinical studies should identify potential adverse effects and design clinical studies that will minimize their occurrence. Most regulatory documents delineate the utilization of conventional "normal" animal species to evaluate the safety risk of new medicines (i.e., new chemical entities and new biological entities). Animal models of human disease are commonly utilized to gain insight into the pathogenesis of disease and to evaluate efficacy but less frequently utilized in preclinical safety assessment. An understanding of the limitations of the animal disease models together with a better understanding of the disease and how toxicity may be impacted by the disease condition should allow for a better prediction of risk in the intended patient population. Importantly, regulatory authorities are becoming more willing to accept and even recommend data from experimental animal disease models that combine efficacy and safety to support clinical development.

  2. Structure of host-odour plumes influences catch of Anopheles gambiae s.s. and Aedes aegypti in a dual-choice olfactometer

    NARCIS (Netherlands)

    Dekker, T.; Takken, W.; Cardé, R.T.

    2001-01-01

    The effects of structure, concentration and composition of host-odour plumes on catch of female Anopheles gambiae Giles sensu stricto and Aedes aegypti (L.) (Diptera: Culicidae) were investigated in a dual-choice olfactometer. We demonstrate that the fine-scale structure of host-odour plumes

  3. Structure of host-odour plumes influences catch of Anopheles gambiae s.s. and Aedes aegypti in a dual-choice olfactometer

    NARCIS (Netherlands)

    Dekker, T.; Takken, W.; Cardé, R.T.

    2001-01-01

    The effects of structure, concentration and composition of host-odour plumes on catch of female Anopheles gambiae Giles sensu stricto and Aedes aegypti (L.) (Diptera: Culicidae) were investigated in a dual-choice olfactometer. We demonstrate that the fine-scale structure of host-odour plumes modulat

  4. Type-dependent irreversible stochastic spin models for genetic regulatory networks at the level of promotion-inhibition circuitry

    Science.gov (United States)

    Mendonça, J. Ricardo G.; de Oliveira, Mário J.

    2015-12-01

    We describe an approach to model genetic regulatory networks at the level of promotion-inhibition circuitry through a class of stochastic spin models that includes spatial and temporal density fluctuations in a natural way. The formalism can be viewed as an agent-based model formalism with agent behaviour ruled by a classical spin-like pseudo-Hamiltonian playing the role of a local, individual objective function. A particular but otherwise generally applicable choice for the microscopic transition rates of the models also makes them of independent interest. To illustrate the formalism, we investigate (by Monte Carlo simulations) some stationary state properties of the repressilator, a synthetic three-gene network of transcriptional regulators that possesses oscillatory behaviour.

  5. Financial constraints in capacity planning: a national utility regulatory model (NUREG). Volume I of III: methodology. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1981-10-29

    This report develops and demonstrates the methodology for the National Utility Regulatory (NUREG) Model developed under contract number DEAC-01-79EI-10579. It is accompanied by two supporting volumes. Volume II is a user's guide for operation of the NUREG software. This includes description of the flow of software and data, as well as the formats of all user data files. Finally, Volume III is a software description guide. It briefly describes, and gives a listing of, each program used in NUREG.

  6. Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment.

    Science.gov (United States)

    Djuris, Jelena; Djuric, Zorica

    2017-06-01

    Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbD-based submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Evaluating odour control technologies using reliability and sustainability criteria--a case study for water treatment plants.

    Science.gov (United States)

    Kraakman, N J R; Estrada, J M; Lebrero, R; Cesca, J; Muñoz, R

    2014-01-01

    Technologies for odour control have been widely reviewed and their optimal range of application and performance has been clearly established. Selection criteria, mainly driven by process economics, are usually based on the air flow volume, the inlet concentrations and the required removal efficiency. However, these criteria are shifting with social and environmental issues becoming as important as process economics. A methodology is illustrated to quantify sustainability and robustness of odour control technology in the context of odour control at wastewater treatment or water recycling plants. The most commonly used odour abatement techniques (biofiltration, biotrickling filtration, activated carbon adsorption, chemical scrubbing, activated sludge diffusion and biotrickling filtration coupled with activated carbon adsorption) are evaluated in terms of: (1) sustainability, with quantification of process economics, environmental performance and social impact using the sustainability metrics of the Institution of Chemical Engineers; (2) sensitivity towards design and operating parameters like utility prices (energy and labour), inlet odour concentration (H2S) and design safety (gas contact time); (3) robustness, quantifications of operating reliability, with recommendations to improve reliability during their lifespan of operations. The results show that the odour treatment technologies with the highest investments presented the lowest operating costs, which means that the net present value (NPV) should be used as a selection criterion rather than investment costs. Economies of scale are more important in biotechniques (biofiltration and biotrickling filtration) as, at increased airflows, their reduction in overall costs over 20 years (NPV20) is more extreme when compared to the physical/chemical technologies (chemical scrubbing and activated carbon filtration). Due to their low NPV and their low environmental impact, activated sludge diffusion and biotrickling

  8. Telecommunications Liberalisation in Africa: Proposed Regulatory Model for the SADC Region

    Directory of Open Access Journals (Sweden)

    Z. Ntozintle Jobodwana

    2009-12-01

    Full Text Available The liberalisation of the telecommunication industry in Africa, and the further development of the region’s physical infrastructure was accompanied by the further development of Africa’s information, communication and technology infrastructure. Competition within the industry stimulated heavy economic investment in other sectors of the economy. The outcome of liberalisation also included the establishment of community-based structures that continue to enable communities to manage their own development and gain access to information and communication technologies (ICTs in an unprecedented manner. The telecommunication infrastructure further stimulated the fast development of other related services, for example, e-commerce and mobile commerce (m-commerce, e-government, internet banking, mobile banking etcetera. Latest reports and statistics disclose that in Africa m-commerce is set to even overtake the development of e-commerce, through the popular use and penetration of mobile telephony whilst e-commerce development is constrained by difficulties in rolling out speedily fixed telephone lines. These new methods of communication have so intensified that there is hope that further penetration of mobile telephony would leap-frog economic growth and development in Africa, especially in rural communities. Therefore, innovations and investment in ICT’s are changing the world in a number of ways, resulting in a globally connected digital economy.  However, there are regulatory challenges that need to be addressed as a matter of urgency. Certain sections of the continent’s population, especially those in rural areas, have very limited access to ICT’s. This prevents them from exploiting opportunities offered by ICT’s. The main barriers to ICT access relate to inadequate regimes and their supporting legal frameworks, high cost of internet access, connectivity problems, the lack of technical skills to support

  9. IMMUNOBIOLOGICAL ACTIVITY OF REGULATORY PEPTIDE FRACTIONS SYNTHESIZED BY NEUTROPHILS, AS TESTED IN A MACROPHAGE MODEL

    Directory of Open Access Journals (Sweden)

    G. I. Vasilieva

    2010-01-01

    Full Text Available The article presents experimental data on regulatory effect of neutrophilokine helper fractions on the macrophage (Mph functional activity in the course of antiplague immunity formation. It has revealed that these fractions content biologically active, low-molecular weight peptides. They stimulate Mph killing activity by increasing phagosome-lysosome fusion, thus boosting transformation of monocytes to Mph, and causing redistribution of macrophage subpopulations in the total cellular pool. The helper effect of neutrophilokine fractions upon functional activity of MPh is more pronounced during secondary immune response.

  10. A model for the regulatory network controlling the dynamics of kinetochore microtubule plus-ends and poleward flux in metaphase.

    Science.gov (United States)

    Fernandez, Nicolas; Chang, Qiang; Buster, Daniel W; Sharp, David J; Ma, Ao

    2009-05-12

    Tight regulation of kinetochore microtubule dynamics is required to generate the appropriate position and movement of chromosomes on the mitotic spindle. A widely studied but mysterious aspect of this regulation occurs during metaphase when polymerization of kinetochore microtubule plus-ends is balanced by depolymerization at their minus-ends. Thus, kinetochore microtubules maintain a constant net length, allowing chromosomes to persist at the spindle equator, but consist of tubulin subunits that continually flux toward spindle poles. Here, we construct a feasible network of regulatory proteins for controlling kinetochore microtubule plus-end dynamics, which was combined with a Monte Carlo algorithm to simulate metaphase tubulin flux. We also test the network model by combining it with a force-balancing model explicitly taking force generators into account. Our data reveal how relatively simple interrelationships among proteins that stimulate microtubule plus-end polymerization, depolymerization, and dynamicity can induce robust flux while accurately predicting apparently contradictory results of knockdown experiments. The model also provides a simple and robust physical mechanism through which the regulatory networks at kinetochore microtubule plus- and minus-ends could communicate.

  11. Concierge, Wellness, and Block Fee Models of Primary Care: Ethical and Regulatory Concerns at the Public-Private Boundary.

    Science.gov (United States)

    Reid, Lynette

    2017-06-01

    In bioethics and health policy, we often discuss the appropriate boundaries of public funding; how the interface of public and private purchasers and providers should be organized and regulated receives less attention. In this paper, I discuss ethical and regulatory issues raised at this interface by three medical practice models (concierge care, executive wellness clinics, and block fee charges) in which physicians provide insured services (whether publicly insured, privately insured, or privately insured by public mandate) while requiring or requesting that patients pay for services or for the non-insured services of the physicians themselves or their associates. This choice for such practice models is different from the decision to design an insurance plan to include or exclude user fees, co-payments and deductibles. I analyze the issues raised with regards to familiar health care values of equity and efficiency, while highlighting additional concerns about fair terms of access, provider integrity, and fair competition. I then analyze the common Canadian regulatory response to block fee models, considering their extension to wellness clinics, with regards to fiduciary standards governing the physician-patient relationship and the role of informed consent. I close by highlighting briefly issues that are of common concern across different fundamental normative frameworks for health policy.

  12. Infection with an acanthocephalan manipulates an amphipod's reaction to a fish predator's odours.

    Science.gov (United States)

    Baldauf, Sebastian A; Thünken, Timo; Frommen, Joachim G; Bakker, Theo C M; Heupel, Oliver; Kullmann, Harald

    2007-01-01

    Many parasites with complex life cycles increase the chances of reaching a final host by adapting strategies to manipulate their intermediate host's appearance, condition or behaviour. The acanthocephalan parasite Pomphorhynchus laevis uses freshwater amphipods as intermediate hosts before reaching sexual maturity in predatory fish. We performed a series of choice experiments with infected and uninfected Gammarus pulex in order to distinguish between the effects of visual and olfactory predator cues on parasite-induced changes in host behaviour. When both visual and olfactory cues, as well as only olfactory cues were offered, infected and uninfected G. pulex showed significantly different preferences for the predator or the non-predator side. Uninfected individuals significantly avoided predator odours while infected individuals significantly preferred the side with predator odours. When only visual contact with a predator was allowed, infected and uninfected gammarids behaved similarly and had no significant preference. Thus, we believe we show for the first time that P. laevis increases its chance to reach a final host by olfactory-triggered manipulation of the anti-predator behaviour of its intermediate host.

  13. Elimination of sulphur odours at landfills by bioconversion and the corona discharge plasma technique.

    Science.gov (United States)

    Xia, Fangfang; Liu, Xin; Kang, Ying; He, Ruo; Wu, Zucheng

    2015-01-01

    Hydrogen sulphide (H2S) contributes a lot to odours at landfills, which is a threat to the environment and the health of the staff therein. To mitigate its emission, the bioconversion within landfill cover soils (LCSs) was introduced. H2S emission and concentration both in the field air above the landfill and in microcosm testing were surveyed. Results indicated that H2S emission and concentration in the landfill varied with landfill seasons and sites. There existed relationship between H2S concentration and fluxes spatially and temporally. To characterize and assess the spatial and temporal diversity of sulphur-oxidizing bacteria (SOB) and sulphate-reducing bacteria (SRB) in the LCSs, the terminal-restriction fragment length polymorphism technique was employed. Using the functional genes of dsrB and soxB, SOB, including Halothiobacillus, Rhodothalassium, Paracocccus, Allochromatium, and Thiobacillus, and SRB, including Desulfovibrio, Syntrophobacter, Desulfomonile and Desulfobacca, were identical and exhibited the dominant role in the LCSs. By employing an alternative available corona reactor, more than 90% removal efficiencies of sulphides were demonstrated, suggesting that the LCSs for eliminating odours in a lower concentration would be feasible.

  14. Developments in odour control and waste gas treatment biotechnology: a review.

    Science.gov (United States)

    Burgess, J E; Parsons, S A; Stuetz, R M

    2001-02-01

    Waste and wastewater treatment processes produce odours, which can cause a nuisance to adjacent populations and contribute significantly to atmospheric pollution. Sulphurous compounds are responsible for acid rain and mist; many organic compounds of industrial origin contribute to airborne public health concerns, as well as environmental problems. Waste gases from industry have traditionally been treated using physicochemical processes, such as scrubbing, adsorption, condensation, and oxidation, however, biological treatment of waste gases has gained support as an effective and economical option in the past few decades. One emergent technique for biological waste gas treatment is the use of existing activated sludge plants as bioscrubbers, thus treating the foul air generated by other process units of the wastewater treatment system on site, with no requirement for additional units or for interruption of wastewater treatment. Limited data are available regarding the performance of activated sludge diffusion of odorous air in spite of numerous positive reports from full-scale applications in North America. This review argues that the information available is insufficient for precise process design and optimization, and simultaneous activated sludge treatment of wastewater and airborne odours could be adopted worldwide.

  15. Niépce–Bell or Turing: how to test odour reproduction

    Science.gov (United States)

    2016-01-01

    Decades before the existence of anything resembling an artificial intelligence system, Alan Turing raised the question of how to test whether machines can think, or, in modern terminology, whether a computer claimed to exhibit intelligence indeed does so. This paper raises the analogous issue for olfaction: how to test the validity of a system claimed to reproduce arbitrary odours artificially, in a way recognizable to humans. Although odour reproduction systems are still far from being viable, the question of how to test candidates thereof is claimed to be interesting and non-trivial, and a novel method is proposed. Despite the similarity between the two questions and their surfacing long before the tested systems exist, the present question cannot be answered adequately by a Turing-like method. Instead, our test is very different: it is conditional, requiring from the artificial no more than is required from the original, and it employs a novel method of immersion that takes advantage of the availability of easily recognizable reproduction methods for sight and sound, a la Nicéphore Niépce and Alexander Graham Bell. PMID:28003527

  16. Odour maps in the brain of butterflies with divergent host-plant preferences.

    Directory of Open Access Journals (Sweden)

    Mikael A Carlsson

    Full Text Available Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca(2+ activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants.

  17. Performance study of biofilter developed to treat H2S from wastewater odour.

    Science.gov (United States)

    Omri, Ilhem; Aouidi, Fethia; Bouallagui, Hassib; Godon, Jean-Jacques; Hamdi, Moktar

    2013-04-01

    Biofiltration is an efficient biotechnological process used for waste gas abatement in various industrial processes. It offers low operating and capital costs and produces minimal secondary waste streams. The objective of this study was to evaluate the performance of a pilot scale biofilter in terms of pollutants' removal efficiencies and the bacterial dynamics under different inlet concentrations of H2S. The treatment of odourous pollutants by biofiltration was investigated at a municipal wastewater treatment plant (WWTP) (Charguia, Tunis, Tunisia). Sampling and analyses were conducted for 150 days. Inlet H2S concentration recorded was between 200 and 1300 mg H2S.m(-3). Removal efficiencies reached 99% for the majority of the running time at an empty bed retention time (EBRT) of 60 s. Heterotrophic bacteria were found to be the dominant microorganisms in the biofilter. The bacteria were identified as the members of the genus Bacillus, Pseudomonas and xanthomonadacea bacterium. The polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) method showed that bacterial community profiles changed with the H2S inlet concentration. Our results indicated that the biofilter system, containing peat as the packing material, was proved able to remove H2S from the WWTP odourous pollutants.

  18. Odour maps in the brain of butterflies with divergent host-plant preferences.

    Science.gov (United States)

    Carlsson, Mikael A; Bisch-Knaden, Sonja; Schäpers, Alexander; Mozuraitis, Raimondas; Hansson, Bill S; Janz, Niklas

    2011-01-01

    Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca(2+) activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants.

  19. Verification of key odorants in rose oil by gas chromatography-olfactometry/aroma extract dilution analysis, odour activity value and aroma recombination.

    Science.gov (United States)

    Xiao, Zuobing; Li, Jing; Niu, Yunwei; Liu, Qiang; Liu, Junhua

    2017-03-28

    Rose oil is much too expensive but very popular. It's well known that the flower oil's aroma profile hasn't been intensively investigated. In order to verify the aroma profile of rose oil, the synthetic blend of odorants was prepared and then compared with the original rose oil using electronic nose analysis (ENA) combined with quantitative descriptive analysis (QDA). The odorants from rose oils were screened out by Gas Chromatography-Olfactometry/aroma extract dilution analysis (GC-O/AEDA) combined with odour activity value (OAV). Both ENA and QDA indicated the recombination model derived from OAV and GC-O/AEDA closely resembled the original rose oil. The experiment results show that rose oxide, linalool, α-pinene, β-pinene, nonanal, heptanal citronellal, phenyl ethyl alcohol, benzyl alcohol, eugenol, methyl eugenol, β-citronellol, hexyl acetate, β-ionone, nerol, etc. are very important constituent to rose oil aroma profile.

  20. Exhaustion of the Brazilian electric sector regulatory model: theoretical versus practical aspects; Esgotamento do modelo regulatorio do setor eletrico brasileiro: aspectos teoricos versus aspectos praticos

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Marcio Giannini; Carpio, Lucio Guido Tapia [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Programa de Planejamento Energetico]. E-mails: marciogiannini@hotmail.com; guido@ppe.ufrj.br

    2002-07-01

    The recent Brazilian regulatory experience demonstrates that it is no easy the changing for a new performance and behaviour model in the electric sector, mainly when it is observed the distance among initial objectives of the reform and the obtained results. The reforms introduction in the sector, which in ultimate analysis aimed the efficiency increasing in the sector, supported by a fragile institutional structure and regulatory collapse, obtained as unfolding the crisis of the electric power in 2001. (author)

  1. Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle After Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades

    Directory of Open Access Journals (Sweden)

    Zhenling Yao

    2008-01-01

    Full Text Available Corticosteroids (CS effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX rats were given single doses of 50 mg/kg methylprednisolone (MPL intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1, uncoupling protein 3 (UCP3, pyruvate dehydrogenase kinase isoenzyme 4 (PDK4, fatty acid translocase (FAT and glycerol-3-phosphate acyltransferase (GPAT dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N and transcription factors. The oscillatory feature of endothelin-1 (ET-1 expression was depicted by a negative feedback loop. These integrated models provide test- able quantitative hypotheses for these regulatory cascades.

  2. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: expert opinions on the state of affairs and the way forward.

    Science.gov (United States)

    Schiffelers, Marie-Jeanne W A; Blaauboer, Bas J; Bakker, Wieger E; Beken, Sonja; Hendriksen, Coenraad F M; Koëter, Herman B W M; Krul, Cyrille

    2014-06-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers.

  3. Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing.

    Directory of Open Access Journals (Sweden)

    Jean-François Schmouth

    Full Text Available An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs, in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and β-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX. This method can be applied to most human genes for which a bacterial artificial chromosome (BAC construct can be derived and a mouse-null allele exists. This strategy comprises (1 the use of recombineering technology to create a human variant-harbouring BAC, (2 knock-in of this BAC into the mouse genome using Hprt docking technology, and (3 allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation.

  4. Odour evaluation in a WWTP. The case study of San Vicente de la Barquera (Cantabria); Evaluacion del olor generado en una EDAR. El caso de San Vicente de la Barquera (Cantabria)

    Energy Technology Data Exchange (ETDEWEB)

    Castillo Alonso, E.; Esteban Garcia, A. L.; Lobo Garcia de Cortazar, A.

    2005-07-01

    The aim of this study was to evaluate the odour problems in the WWTP located in San Vicente de la Barquera (Cantabria, Spain), before and after the set up of the odour treatment system. Odour was measured by determining the concentration of H{sub 2}S in air. A portable equipment with sensibility of 3 ppb was used. Odour maps, which reflect the concentration detected in each point corresponding to the different environmental and operational situations studied, were performed. The obtained results show the usefulness of the method used to detect the odour sources and nuisances in the WWTP area. (Author) 22 refs.

  5. Plant odours with potential for a push-pull strategy to control the onion thrips (Thrips tabaci)

    NARCIS (Netherlands)

    Tol, van R.W.H.M.; James, D.E.; Kogel, de W.J.; Teulon, D.A.J.

    2007-01-01

    We compared the efficacy of four plant essential oils to repel onion thrips, Thrips tabaci (Lindeman) (Thysanoptera: Thripidae), in the presence of an attractive odour, ethyl iso-nicotinate in a pasture field. Four horizontal white sticky plates were placed adjacent to (directions: N, S, E, W) a cen

  6. Identification of food spoilage in the smart home based on neural and fuzzy processing of odour sensor responses.

    Science.gov (United States)

    Green, Geoffrey C; Chan, Adrian D C; Goubran, Rafik A

    2009-01-01

    Adopting the use of real-time odour monitoring in the smart home has the potential to alert the occupant of unsafe or unsanitary conditions. In this paper, we measured (with a commercial metal-oxide sensor-based electronic nose) the odours of five household foods that had been left out at room temperature for a week to spoil. A multilayer perceptron (MLP) neural network was trained to recognize the age of the samples (a quantity related to the degree of spoilage). For four of these foods, median correlation coefficients (between target values and MLP outputs) of R > 0.97 were observed. Fuzzy C-means clustering (FCM) was applied to the evolving odour patterns of spoiling milk, which had been sampled more frequently (4h intervals for 7 days). The FCM results showed that both the freshest and oldest milk samples had a high degree of membership in "fresh" and "spoiled" clusters, respectively. In the future, as advancements in electronic nose development remove the present barriers to acceptance, signal processing methods like those explored in this paper can be incorporated into odour monitoring systems used in the smart home.

  7. Field background odour should be taken into account when formulating a pest attractant based on plant volatiles

    Science.gov (United States)

    Cai, Xiaoming; Bian, Lei; Xu, Xiuxiu; Luo, Zongxiu; Li, Zhaoqun; Chen, Zongmao

    2017-01-01

    Attractants for pest monitoring and controlling can be developed based on plant volatiles. Previously, we showed that tea leafhopper (Empoasca onukii) preferred grapevine, peach plant, and tea plant odours to clean air. In this research, we formulated three blends with similar attractiveness to leafhoppers as peach, grapevine, and tea plant volatiles; these blends were composed of (Z)-3-hexenyl acetate, (E)-ocimene, (E)-4,8-dimethyl-1,3,7-nonatriene, benzaldehyde, and ethyl benzoate. Based on these five compounds, we developed two attractants, formula-P and formula-G. The specific component relative to tea plant volatiles in formula-P was benzaldehyde, and that in formula-G was ethyl benzoate. These two compounds played a role in attracting leafhoppers. In laboratory assays, the two attractants were more attractive than tea plant volatiles to the leafhoppers, and had a similar level of attractiveness. However, the leafhoppers were not attracted to formula-P in the field. A high concentration of benzaldehyde was detected in the background odour of the tea plantations. In laboratory tests, benzaldehyde at the field concentration was attractive to leafhoppers. Our results indicate that the field background odour can interfere with a point-releasing attractant when their components overlap, and that a successful attractant must differ from the field background odour. PMID:28150728

  8. Behavioural and nociceptive response in male and female spiny mice (Acomys cahirinus) upon exposure to snake odour

    NARCIS (Netherlands)

    Carere, C; Casetti, R; de Acetis, L; Perretta, G; Cirulli, F; Alleva, E

    1999-01-01

    Predator cues (both mammalian odour or avian vocalizations) are known to elicit fear-associated responses in rodents, including analgesia. In previous studies it was reported that spiny mice fail to show fear responses when presented with the calls of an owl. In order to test the hypothesis that thi

  9. Pigeon navigation: exposure to environmental odours prior to release is sufficient for homeward orientation, but not for homing.

    Science.gov (United States)

    Gagliardo, Anna; Pollonara, Enrica; Wikelski, Martin

    2016-08-15

    The role of environmental olfactory information in pigeon navigation has been extensively studied by analysing vanishing bearing distributions and homing performances of homing pigeons subjected to manipulation of their olfactory perception and/or the olfactory information they were exposed to during transportation and at the release site. However, their behaviour during the homing flight remains undocumented. In this experiment we report the analysis of tracks of birds made anosmic at the release site by washing their olfactory mucosa with zinc sulfate. We thus can assess the role of local odours at the release site as well as the role of environmental odours perceived on the way, far from the release site. We observed that pigeons transported and kept at the release site in purified air and made anosmic at the release site were unable to orient towards home and were impaired at homing. By contrast, pigeons allowed to smell environmental odours during transportation and at the release site, although made anosmic prior to release, displayed unimpaired homeward orientation, but nevertheless showed impaired homing performance. These results are consistent with the view that local odours at the release site are critical for determining the direction of displacement (olfactory map) and suggest that pigeons consult the olfactory map also during their homing flight in order to be able to find their way home.

  10. Plant odours with potential for a push-pull strategy to control the onion thrips (Thrips tabaci)

    NARCIS (Netherlands)

    Tol, van R.W.H.M.; James, D.E.; Kogel, de W.J.; Teulon, D.A.J.

    2007-01-01

    We compared the efficacy of four plant essential oils to repel onion thrips, Thrips tabaci (Lindeman) (Thysanoptera: Thripidae), in the presence of an attractive odour, ethyl iso-nicotinate in a pasture field. Four horizontal white sticky plates were placed adjacent to (directions: N, S, E, W) a

  11. Behavioural and nociceptive response in male and female spiny mice (Acomys cahirinus) upon exposure to snake odour

    NARCIS (Netherlands)

    Carere, C; Casetti, R; de Acetis, L; Perretta, G; Cirulli, F; Alleva, E

    1999-01-01

    Predator cues (both mammalian odour or avian vocalizations) are known to elicit fear-associated responses in rodents, including analgesia. In previous studies it was reported that spiny mice fail to show fear responses when presented with the calls of an owl. In order to test the hypothesis that

  12. QSTR modeling for qualitative and quantitative toxicity predictions of diverse chemical pesticides in honey bee for regulatory purposes.

    Science.gov (United States)

    Singh, Kunwar P; Gupta, Shikha; Basant, Nikita; Mohan, Dinesh

    2014-09-15

    Pesticides are designed toxic chemicals for specific purposes and can harm nontarget species as well. The honey bee is considered a nontarget test species for toxicity evaluation of chemicals. Global QSTR (quantitative structure-toxicity relationship) models were established for qualitative and quantitative toxicity prediction of pesticides in honey bee (Apis mellifera) based on the experimental toxicity data of 237 structurally diverse pesticides. Structural diversity of the chemical pesticides and nonlinear dependence in the toxicity data were evaluated using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) QSTR models were constructed for classification (two and four categories) and function optimization problems using the toxicity end point in honey bees. The predictive power of the QSTR models was tested through rigorous validation performed using the internal and external procedures employing a wide series of statistical checks. In complete data, the PNN-QSTR model rendered a classification accuracy of 96.62% (two-category) and 95.57% (four-category), while the GRNN-QSTR model yielded a correlation (R(2)) of 0.841 between the measured and predicted toxicity values with a mean squared error (MSE) of 0.22. The results suggest the appropriateness of the developed QSTR models for reliably predicting qualitative and quantitative toxicities of pesticides in honey bee. Both the PNN and GRNN based QSTR models constructed here can be useful tools in predicting the qualitative and quantitative toxicities of the new chemical pesticides for regulatory purposes.

  13. An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

    Directory of Open Access Journals (Sweden)

    Chang-Min Lee

    Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

  14. hARACNe: improving the accuracy of regulatory model reverse engineering via higher-order data processing inequality tests.

    Science.gov (United States)

    Jang, In Sock; Margolin, Adam; Califano, Andrea

    2013-08-01

    A key goal of systems biology is to elucidate molecular mechanisms associated with physiologic and pathologic phenotypes based on the systematic and genome-wide understanding of cell context-specific molecular interaction models. To this end, reverse engineering approaches have been used to systematically dissect regulatory interactions in a specific tissue, based on the availability of large molecular profile datasets, thus improving our mechanistic understanding of complex diseases, such as cancer. In this paper, we introduce high-order Algorithm for the Reconstruction of Accurate Cellular Network (hARACNe), an extension of the ARACNe algorithm for the dissection of transcriptional regulatory networks. ARACNe uses the data processing inequality (DPI), from information theory, to detect and prune indirect interactions that are unlikely to be mediated by an actual physical interaction. Whereas ARACNe considers only first-order indirect interactions, i.e. those mediated by only one extra regulator, hARACNe considers a generalized form of indirect interactions via two, three or more other regulators. We show that use of higher-order DPI resulted in significantly improved performance, based on transcription factor (TF)-specific ChIP-chip data, as well as on gene expression profile following RNAi-mediated TF silencing.

  15. Characterization of volatile metabolites associated with confinement odour during the shelf-life of vacuum packed lamb meat under different storage conditions.

    Science.gov (United States)

    Reis, Marlon M; Reis, Mariza G; Mills, John; Ross, Colleen; Brightwell, Gale

    2016-03-01

    Confinement odour was investigated. Volatiles were extracted directly from the pack, using solid phase microextraction and analysed by gas chromatography-mass spectrometry. Sensory evaluation and microbiological analysis of the meat surface were also performed. Commercial samples of vacuum packed lamb legs (n=85), from two meat processing plants, were kept for 7weeks at -1.5°C then at different regimes of temperature (-1.5 to +4°C) until 11, 12 or 13weeks. Persistent odour was observed in 66% of samples, confinement odour in 24% and no odour in 11%. Volatiles associated with confinement odour (3-methyl-butanal, 3-hydroxy-2-butanone and sulphur dioxide) corresponded with end/sub products of glucose fermentation and catabolism of amino acids by bacteria (all bacteria naturally found in meat and do not represent a risk to health). Confinement odour could indicate a stage at which the environment for bacteria growth is becoming favourable for the production of volatiles with strong odours that are noticed by the consumer.

  16. Interactions of carbon dioxide and food odours in Drosophila: olfactory hedonics and sensory neuron properties.

    Science.gov (United States)

    Faucher, Cécile P; Hilker, Monika; de Bruyne, Marien

    2013-01-01

    Behavioural responses of animals to volatiles in their environment are generally dependent on context. Most natural odours are mixtures of components that can each induce different behaviours when presented on their own. We have investigated how a complex of two olfactory stimuli is evaluated by Drosophila flies in a free-flying two-trap choice assay and how these stimuli are encoded in olfactory receptor neurons. We first observed that volatiles from apple cider vinegar attracted flies while carbon dioxide (CO2) was avoided, confirming their inherent positive and negative values. In contradiction with previous results obtained from walking flies in a four-field olfactometer, in the present assay the addition of CO2 to vinegar increased rather than decreased the attractiveness of vinegar. This effect was female-specific even though males and females responded similarly to CO2 and vinegar on their own. To test whether the female-specific behavioural response to the mixture correlated with a sexual dimorphism at the peripheral level we recorded from olfactory receptor neurons stimulated with vinegar, CO2 and their combination. Responses to vinegar were obtained from three neuron classes, two of them housed with the CO2-responsive neuron in ab1 sensilla. Sensitivity of these neurons to both CO2 and vinegar per se did not differ between males and females and responses from female neurons did not change when CO2 and vinegar were presented simultaneously. We also found that CO2-sensitive neurons are particularly well adapted to respond rapidly to small concentration changes irrespective of background CO2 levels. The ability to encode temporal properties of stimulations differs considerably between CO2- and vinegar-sensitive neurons. These properties may have important implications for in-flight navigation when rapid responses to fragmented odour plumes are crucial to locate odour sources. However, the flies' sex-specific response to the CO2-vinegar combination and the

  17. Interactions of carbon dioxide and food odours in Drosophila: olfactory hedonics and sensory neuron properties.

    Directory of Open Access Journals (Sweden)

    Cécile P Faucher

    Full Text Available Behavioural responses of animals to volatiles in their environment are generally dependent on context. Most natural odours are mixtures of components that can each induce different behaviours when presented on their own. We have investigated how a complex of two olfactory stimuli is evaluated by Drosophila flies in a free-flying two-trap choice assay and how these stimuli are encoded in olfactory receptor neurons. We first observed that volatiles from apple cider vinegar attracted flies while carbon dioxide (CO2 was avoided, confirming their inherent positive and negative values. In contradiction with previous results obtained from walking flies in a four-field olfactometer, in the present assay the addition of CO2 to vinegar increased rather than decreased the attractiveness of vinegar. This effect was female-specific even though males and females responded similarly to CO2 and vinegar on their own. To test whether the female-specific behavioural response to the mixture correlated with a sexual dimorphism at the peripheral level we recorded from olfactory receptor neurons stimulated with vinegar, CO2 and their combination. Responses to vinegar were obtained from three neuron classes, two of them housed with the CO2-responsive neuron in ab1 sensilla. Sensitivity of these neurons to both CO2 and vinegar per se did not differ between males and females and responses from female neurons did not change when CO2 and vinegar were presented simultaneously. We also found that CO2-sensitive neurons are particularly well adapted to respond rapidly to small concentration changes irrespective of background CO2 levels. The ability to encode temporal properties of stimulations differs considerably between CO2- and vinegar-sensitive neurons. These properties may have important implications for in-flight navigation when rapid responses to fragmented odour plumes are crucial to locate odour sources. However, the flies' sex-specific response to the CO2-vinegar

  18. Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model

    Directory of Open Access Journals (Sweden)

    Romina D'Aurizio

    2016-07-01

    Full Text Available microRNAs (miRNAs are small non-coding RNAs that play an important role in the post- transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction. Tbx5 is a member of the T-box gene family which acts as transcription factor involved in the vertebrate heart development. Alteration of Tbx5 level affects the expression of hundreds of genes. Haploinsufficiency and gene duplication of Tbx5 are at the basis of the cardiac abnormalities associated with Holt-Oram syndrome (HOS. Recent data indicate that miRNAs might be an important part of the regulatory circuit through which Tbx5 controls heart development. Using high-throughput technology we characterized genome-widely the miRNA and mRNA expression profiles in WT and Tbx5 depleted zebrafish embryos at two developmental time points, 24 and 48 hours post fertilization (hpf. We found that several miRNAs which are potential effectors of Tbx5 are differentially expressed, some of them are already known to be involved in cardiac development and functions, such as miR-30, miR-34, miR-190, miR-21. We performed an integrated analysis of miRNA expression data with gene expression profiles to refine computational target prediction approaches by means of the inversely correlation of miRNA-mRNA expressions. Interestingly these targets have roles in cardiac contractility, cardiomyocyte proliferation/apoptosis and valve formation which are crucial functions regulated by Tbx5. This approach allowed to discover complex regulatory circuits involving novel miRNAs and protein coding genes not considered before in the HOS such as miR-34a and

  19. Discovering miRNA Regulatory Networks in Holt–Oram Syndrome Using a Zebrafish Model

    Science.gov (United States)

    D’Aurizio, Romina; Russo, Francesco; Chiavacci, Elena; Baumgart, Mario; Groth, Marco; D’Onofrio, Mara; Arisi, Ivan; Rainaldi, Giuseppe; Pitto, Letizia; Pellegrini, Marco

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the post-transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis, and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts, and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction. Tbx5 is a member of the T-box gene family, which acts as transcription factor involved in the vertebrate heart development. Alteration of Tbx5 level affects the expression of hundreds of genes. Haploinsufficiency and gene duplication of Tbx5 are at the basis of the cardiac abnormalities associated with Holt–Oram syndrome (HOS). Recent data indicate that miRNAs might be an important part of the regulatory circuit through which Tbx5 controls heart development. Using high-throughput technologies, we characterized genome-widely the miRNA and mRNA expression profiles in WT- and Tbx5-depleted zebrafish embryos at two crucial developmental time points, 24 and 48 h post fertilization (hpf). We found that several miRNAs, which are potential effectors of Tbx5, are differentially expressed; some of them are already known to be involved in cardiac development and functions, such as miR-30, miR-34, miR-190, and miR-21. We performed an integrated analysis of miRNA expression data with gene expression profiles to refine computational target prediction approaches by means of the inversely correlation of miRNA–mRNA expressions, and we highlighted targets, which have roles in cardiac contractility, cardiomyocyte proliferation/apoptosis, and morphogenesis, crucial functions regulated by Tbx5. This approach allowed to discover complex regulatory circuits involving novel miRNAs and protein coding genes not considered before in the HOS such as miR-34a and

  20. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J.; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M. E. (Bette); Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M.; Whelan, Maurice

    2016-12-19

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.

  1. Odours from pulp mill effluent treatment ponds: the origin of significant levels of geosmin and 2-methylisoborneol (MIB).

    Science.gov (United States)

    Watson, Susan B; Ridal, Jeff; Zaitlin, Beryl; Lo, Amy

    2003-06-01

    Pulp and paper mills are well known for their sharp, sulphurous stack emissions, but the secondary treatment units also can be significant contributors to local odour. This study investigated the source(s) of earthy/musty emissions from a mixed hardwood pulp mill in response to a high local odour. Samples from five sites in the mill over five months were analyzed for earthy/musty volatile organic compounds (VOCs), examined microscopically, and plated for bacteria and moulds. In all cases, activated sludge showed substantial geosmin levels and to a lesser extent 2-methylisoborneol (MIB) at 2000-9000 times their odour threshold concentrations (OTCs). These VOCs were lower or absent upstream and downstream, suggesting that they were produced within the bioreactor. Geosmin and MIB were highest in late summer and declined over winter, and correlated with different operating parameters. Geosmin was most closely coupled with temperature and MIB with nitrogen uptake. Cyanobacteria were present in all sludge samples, but actinomycetes were not found. Gram-negative bacteria and one fungal species isolated from the bioreactor and secondary outfall tested negative for geosmin or MIB. We conclude: (i) geosmin and MIB contribute significantly to airborne odours from this mill, but are diluted below OTC levels at the river; (ii) these VOCs are generated by biota in the activated sludge; and (iii) cyanobacteria are likely primary source(s). The growth of cyanobacteria in activated sludge represents a loss of energy to the heterotrophic population; thus earthy/musty odours may represent a diagnostic for less than optimal conditions.

  2. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.; Blaauboer, B.J.; Bakker, W.E.; Beken, S.; Hendriksen, C.F.M.; Koeter, H.; Krul, C.A.M.

    2014-01-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these

  3. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.; Blaauboer, B.J.; Bakker, W.E.; Beken, S.; Hendriksen, C.F.M.; Koeter, H.; Krul, C.A.M.

    2014-01-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these mo

  4. Floral odour chemistry defines species boundaries and underpins strong reproductive isolation in sexually deceptive orchids.

    Science.gov (United States)

    Peakall, Rod; Whitehead, Michael R

    2014-01-01

    The events leading to speciation are best investigated in systems where speciation is ongoing or incomplete, such as incipient species. By examining reproductive barriers among incipient sister taxa and their congeners we can gain valuable insights into the relative timing and importance of the various barriers involved in the speciation process. The aim of this study was to identify the reproductive barriers among sexually deceptive orchid taxa in the genus Chiloglottis. The study targeted four closely related taxa with varying degrees of geographic overlap. Chemical, morphological and genetic evidence was combined to explore the basis of reproductive isolation. Of primary interest was the degree of genetic differentiation among taxa at both nuclear and chloroplast DNA markers. To objectively test whether or not species boundaries are defined by the chemistry that controls pollinator specificity, genetic analysis was restricted to samples of known odour chemistry. Floral odour chemical analysis was performed for 600+ flowers. The three sympatric taxa were defined by their specific chiloglottones, the semiochemicals responsible for pollinator attraction, and were found to be fully cross-compatible. Multivariate morphometric analysis could not reliably distinguish among the four taxa. Although varying from very low to moderate, significant levels of genetic differentiation were detected among all pairwise combinations of taxa at both nuclear and chloroplast loci. However, the levels of genetic differentiation were lower than expected for mature species. Critically, a lack of chloroplast DNA haplotype sharing among the morphologically indistinguishable and most closely related taxon pair confirmed that chemistry alone can define taxon boundaries. The results confirmed that pollinator isolation, mediated by specific pollinator attraction, underpins strong reproductive isolation in these taxa. A combination of large effective population sizes, initial neutral mutations

  5. Changes in responsiveness to kit odours across pregnancy: relevance for the onset of maternal behaviour

    Directory of Open Access Journals (Sweden)

    Rosario Chirino

    2015-06-01

    Full Text Available Virgin does are indifferent to foster kits but lesions to the main or accessory olfactory systems allow them to behave “maternally” (i.e., they crouch over the litter and allow suckling. This suggests that kit-derived olfactory cues are aversive to virgins but not to lactating does. We hypothesised that the valence of such olfactory cues changes throughout gestation so that, at parturition, does are attracted to the newborn and can then show placentophagia, clean the kits and nurse them. To explore this hypothesis we exposed does to 2 nest boxes containing a variety of pup-derived vs. “neutral” odours, quantifying the number of sniffs and entrances to each box over 60 min. Virgins, confronted with 2 different types of contrasts, showed no significant differences in the number of sniffs or entrances directed at any of the 2 boxes. Pregnant rabbits sniffed the “kit-odour” box significantly more than the “neutral” one as early as gestation day 7, depending on the animals’ experience with the experimental setup and kit odours as virgins. The number of sniffs declined in late pregnancy in all groups. Entrances into the “kit-odour” box were few and significantly higher than those shown towards the “neutral” box only in 1 group. Our findings agree with a correlation between a shift in the valence of kit-derived olfactory cues and the hormonal changes known to occur throughout pregnancy. The relevance of this phenomenon for the onset of maternal responsiveness at parturition is discussed.

  6. Field testing of different chemical combinations as odour baits for trapping wild mosquitoes in The Gambia.

    Directory of Open Access Journals (Sweden)

    Musa Jawara

    Full Text Available Odour baited traps have potential use in population surveillance of insect vectors of disease, and in some cases for vector population reduction. Established attractants for human host-seeking mosquitoes include a combination of CO(2 with L-lactic acid and ammonia, on top of which additional candidate compounds are being tested. In this field study in rural Gambia, using Latin square experiments with thorough randomization and replication, we tested nine different leading candidate combinations of chemical odorants for attractiveness to wild mosquitoes including anthropophilic malaria vectors, using modified Mosquito Magnet-X (MM-X counterflow traps outside experimental huts containing male human sleepers. Highest catches of female mosquitoes, particularly of An. gambiae s.l. and Mansonia species, were obtained by incorporation of tetradecanoic acid. As additional carboxylic acids did not increase the trap catches further, this 'reference blend' (tetradecanoic acid with L-lactic acid, ammonia and CO(2 was used in subsequent experiments. MM-X traps with this blend caught similar numbers of An. gambiae s.l. and slightly more Mansonia and Culex mosquitoes than a standard CDC light trap, and these numbers were not significantly affected by the presence or absence of human sleepers in the huts. Experiments with CO(2 produced from overnight yeast cultures showed that this organic source was effective in enabling trap attractiveness for all mosquito species, although at a slightly lower efficiency than obtained with use of CO(2 gas cylinders. Although further studies are needed to discover additional chemicals that increase attractiveness, as well as to optimise trap design and CO(2 source for broader practical use, the odour-baited traps described here are safe and effective for sampling host-seeking mosquitoes outdoors and can be incorporated into studies of malaria vector ecology.

  7. GRNsight: a web application and service for visualizing models of small- to medium-scale gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Kam D. Dahlquist

    2016-09-01

    Full Text Available GRNsight is a web application and service for visualizing models of gene regulatory networks (GRNs. A gene regulatory network (GRN consists of genes, transcription factors, and the regulatory connections between them which govern the level of expression of mRNA and protein from genes. The original motivation came from our efforts to perform parameter estimation and forward simulation of the dynamics of a differential equations model of a small GRN with 21 nodes and 31 edges. We wanted a quick and easy way to visualize the weight parameters from the model which represent the direction and magnitude of the influence of a transcription factor on its target gene, so we created GRNsight. GRNsight automatically lays out either an unweighted or weighted network graph based on an Excel spreadsheet containing an adjacency matrix where regulators are named in the columns and target genes in the rows, a Simple Interaction Format (SIF text file, or a GraphML XML file. When a user uploads an input file specifying an unweighted network, GRNsight automatically lays out the graph using black lines and pointed arrowheads. For a weighted network, GRNsight uses pointed and blunt arrowheads, and colors the edges and adjusts their thicknesses based on the sign (positive for activation or negative for repression and magnitude of the weight parameter. GRNsight is written in JavaScript, with diagrams facilitated by D3.js, a data visualization library. Node.js and the Express framework handle server-side functions. GRNsight’s diagrams are based on D3.js’s force graph layout algorithm, which was then extensively customized to support the specific needs of GRNs. Nodes are rectangular and support gene labels of up to 12 characters. The edges are arcs, which become straight lines when the nodes are close together. Self-regulatory edges are indicated by a loop. When a user mouses over an edge, the numerical value of the weight parameter is displayed. Visualizations can

  8. TREXMO: A Translation Tool to Support the Use of Regulatory Occupational Exposure Models.

    Science.gov (United States)

    Savic, Nenad; Racordon, Dimitri; Buchs, Didier; Gasic, Bojan; Vernez, David

    2016-10-01

    Occupational exposure models vary significantly in their complexity, purpose, and the level of expertise required from the user. Different parameters in the same model may lead to different exposure estimates for the same exposure situation. This paper presents a tool developed to deal with this concern-TREXMO or TRanslation of EXposure MOdels. TREXMO integrates six commonly used occupational exposure models, namely, ART v.1.5, STOFFENMANAGER(®) v.5.1, ECETOC TRA v.3, MEASE v.1.02.01, EMKG-EXPO-TOOL, and EASE v.2.0. By enabling a semi-automatic translation between the parameters of these six models, TREXMO facilitates their simultaneous use. For a given exposure situation, defined by a set of parameters in one of the models, TREXMO provides the user with the most appropriate parameters to use in the other exposure models. Results showed that, once an exposure situation and parameters were set in ART, TREXMO reduced the number of possible outcomes in the other models by 1-4 orders of magnitude. The tool should manage to reduce the uncertain entry or selection of parameters in the six models, improve between-user reliability, and reduce the time required for running several models for a given exposure situation. In addition to these advantages, registrants of chemicals and authorities should benefit from more reliable exposure estimates for the risk characterization of dangerous chemicals under Regulation, Evaluation, Authorisation and restriction of CHemicals (REACH).

  9. Manufacturing models permitting roll out/scale out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability.

    Science.gov (United States)

    Hourd, Paul; Ginty, Patrick; Chandra, Amit; Williams, David J

    2014-08-01

    Manufacturing of more-than-minimally manipulated autologous cell therapies presents a number of unique challenges driven by complex supply logistics and the need to scale out production to multiple manufacturing sites or near the patient within hospital settings. The existing regulatory structure in Europe and the United States imposes a requirement to establish and maintain comparability between sites. Under a single market authorization, this is likely to become an unsurmountable burden beyond two or three sites. Unless alternative manufacturing approaches can be found to bridge the regulatory challenge of comparability, realizing a sustainable and investable business model for affordable autologous cell therapy supply is likely to be extremely demanding. Without a proactive approach by the regulators to close this "translational gap," these products may not progress down the development pipeline, threatening patient accessibility to an increasing number of clinician-led autologous cellular therapies that are already demonstrating patient benefits. We propose three prospective manufacturing models for the scale out/roll out of more-than-minimally manipulated clinically led autologous cell therapy products and test their prospects for addressing the challenge of product comparability with a selected expert reference panel of US and UK thought leaders. This paper presents the perspectives and insights of the panel and identifies where operational, technological and scientific improvements should be prioritized. The main purpose of this report is to solicit feedback and seek input from key stakeholders active in the field of autologous cell therapy in establishing a consensus-based manufacturing approach that may permit the roll out of clinically led autologous cell therapies.

  10. Regulatory T cell memory

    Science.gov (United States)

    Rosenblum, Michael D.; Way, Sing Sing; Abbas, Abul K.

    2016-01-01

    Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime challenge models of infection. However, recent work has also identified persistently expanded populations of antigen-specific regulatory T cells that protect against aberrant immune responses. In this Review, we consider the parallels between memory effector T cells and memory regulatory T cells, along with the functional implications of regulatory memory in autoimmunity, antimicrobial host defence and maternal fetal tolerance. In addition, we discuss emerging evidence for regulatory T cell memory in humans and key unanswered questions in this rapidly evolving field. PMID:26688349

  11. QSAR models for reproductive toxicity and endocrine disruption in regulatory use - a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemela, J.R.; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  12. Stochastic Noise in Auto-regulatory Genetic Network: Model-dependence and Statistical Complication

    Institute of Scientific and Technical Information of China (English)

    Ying-zi Shang

    2008-01-01

    For the single gene network model, there are two basic types. For convenience, we call them TypeⅠ and Type Ⅱ, respectively. The Type Ⅰ model describes both the dynamics of mRNA and protein. The Type Ⅱ model is a simplification of the Type Ⅰ model based on the assumption that the change rate of mRNA is much faster than protein because the half-life of mRNA is short compared with that of protein, the Type Ⅱ model describes only the dynamics of protein. The analysis of the Type Ⅰ model is based on the assumption that the ratio of the protein decay rate to the mRNA decay rate is small enough. The main results for Type Ⅰ model show that the Fano factor of the protein must be bigger than one if there is no negative feedback on the transcription. If there is negative feedback, the relative fluctuation strength in the number of proteins is determined by the size of the feedback regulation strength. For the Type Ⅱ model, the Fano factor of the protein depends on the effect of the feedback regulation on the translation, i.e., the Fano factor equals one if there is no feedback, and is less than one (or bigger than one) if there is negative feedback (or positive feedback). These results show clearly that the analysis of the steady-state statistical properties of single gene network is model-dependent.

  13. TREXMO: a translation tool to support the use of regulatory occupational exposure models

    OpenAIRE

    Savic, Nenad; Racordon, Dimitri; Buchs, Didier; Gasic, Bojan; Vernez, Dernez

    2016-01-01

    Occupational exposure models vary significantly in their complexity, purpose, and the level of expertise required from the user. Different parameters in the same model may lead to different exposure estimates for the same exposure situation. This paper presents a tool developed to deal with this concern-TREXMO or TRanslation of EXposure MOdels. TREXMO integrates six commonly used occupational exposure models, namely, ART v.1.5, STOFFENMANAGER(®) v.5.1, ECETOC TRA v.3, MEASE v.1.02.01, EMKG-EX...

  14. Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

    NARCIS (Netherlands)

    Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

    2003-01-01

    Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

  15. Integrated signaling pathway and gene expression regulatory model to dissect dynamics of Escherichia coli challenged mammary epithelial cells.

    Science.gov (United States)

    den Breems, Nicoline Y; Nguyen, Lan K; Kulasiri, Don

    2014-12-01

    Cells transform external stimuli, through the activation of signaling pathways, which in turn activate gene regulatory networks, in gene expression. As more omics data are generated from experiments, eliciting the integrated relationship between the external stimuli, the signaling process in the cell and the subsequent gene expression is a major challenge in systems biology. The complex system of non-linear dynamic protein interactions in signaling pathways and gene networks regulates gene expression. The complexity and non-linear aspects have resulted in the study of the signaling pathway or the gene network regulation in isolation. However, this limits the analysis of the interaction between the two components and the identification of the source of the mechanism differentiating the gene expression profiles. Here, we present a study of a model of the combined signaling pathway and gene network to highlight the importance of integrated modeling. Based on the experimental findings we developed a compartmental model and conducted several simulation experiments. The model simulates the mRNA expression of three different cytokines (RANTES, IL8 and TNFα) regulated by the transcription factor NFκB in mammary epithelial cells challenged with E. coli. The analysis of the gene network regulation identifies a lack of robustness and therefore sensitivity for the transcription factor regulation. However, analysis of the integrated signaling and gene network regulation model reveals distinctly different underlying mechanisms in the signaling pathway responsible for the variation between the three cytokine's mRNA expression levels. Our key findings reveal the importance of integrating the signaling pathway and gene expression dynamics in modeling. Modeling infers valid research questions which need to be verified experimentally and can assist in the design of future biological experiments.

  16. Intrinsic dynamics of heart regulatory systems on short time-scales: from experiment to modelling

    CERN Document Server

    Khovanov, I A; McClintock, P V E; Stefanovska, A

    2009-01-01

    We discuss open problems related to the stochastic modeling of cardiac function. The work is based on an experimental investigation of the dynamics of heart rate variability (HRV) in the absence of respiratory perturbations. We consider first the cardiac control system on short time scales via an analysis of HRV within the framework of a random walk approach. Our experiments show that HRV on timescales of less than a minute takes the form of free diffusion, close to Brownian motion, which can be described as a non-stationary process with stationary increments. Secondly, we consider the inverse problem of modeling the state of the control system so as to reproduce the experimentally observed HRV statistics of. We discuss some simple toy models and identify open problems for the modelling of heart dynamics.

  17. Trapping of the malaria vector Anopheles gambiae with odour-baited MM-X traps in semi-field conditions in western Kenya

    NARCIS (Netherlands)

    Njiru, B.N.; Mukabana, W.R.; Takken, W.; Knols, B.G.J.

    2006-01-01

    Background - The successful development of odour-baited trapping systems for mosquitoes depends on the identification of behaviourally active semiochemicals, besides the design and operating principles of such devices. A large variety of 'attractants' has been identified in laboratory investigations

  18. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models.

    Science.gov (United States)

    Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rachmilewitz, Eliezer; Breda, Laura; Rivella, Stefano; Rechavi, Gideon

    2006-07-01

    beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of beta-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.

  19. The regulatory logic of m-xylene biodegradation by Pseudomonas putida mt-2 exposed by dynamic modelling of the principal node Ps/Pr of the TOL plasmid.

    Science.gov (United States)

    Koutinas, Michalis; Lam, Ming-Chi; Kiparissides, Alexandros; Silva-Rocha, Rafael; Godinho, Miguel; Livingston, Andrew G; Pistikopoulos, Efstratios N; de Lorenzo, Victor; Dos Santos, Vitor A P Martins; Mantalaris, Athanasios

    2010-06-01

    The structure of the extant transcriptional control network of the TOL plasmid pWW0 born by Pseudomonas putida mt-2 for biodegradation of m-xylene is far more complex than one would consider necessary from a mere engineering point of view. In order to penetrate the underlying logic of such a network, which controls a major environmental cleanup bioprocess, we have developed a dynamic model of the key regulatory node formed by the Ps/Pr promoters of pWW0, where the clustering of control elements is maximal. The model layout was validated with batch cultures estimating parameter values and its predictive capability was confirmed with independent sets of experimental data. The model revealed how regulatory outputs originated in the divergent and overlapping Ps/Pr segment, which expresses the transcription factors XylS and XylR respectively, are computed into distinct instructions to the upper and lower catabolic xyl operons for either simultaneous or stepwise consumption of m-xylene and/or succinate. In this respect, the model reveals that the architecture of the Ps/Pr is poised to discriminate the abundance of alternative and competing C sources, in particular m-xylene versus succinate. The proposed framework provides a first systemic understanding of the causality and connectivity of the regulatory elements that shape this exemplary regulatory network, facilitating the use of model analysis towards genetic circuit optimization.

  20. Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use.

    Science.gov (United States)

    Behrsing, Holger; Raabe, Hans; Manuppello, Joseph; Bombick, Betsy; Curren, Rodger; Sullivan, Kristie; Sethi, Sanjay; Phipps, Richard; Tesfaigzi, Yohannes; Yan, Sherwin; D'Ruiz, Carl; Tarran, Robert; Constant, Samuel; Phillips, Gary; Gaça, Marianna; Hayden, Patrick; Cao, Xuefei; Mathis, Carole; Hoeng, Julia; Braun, Armin; Hill, Erin

    2016-05-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a

  1. Beyond the French Flag Model: Exploiting Spatial and Gene Regulatory Interactions for Positional Information

    Science.gov (United States)

    Hillenbrand, Patrick; Gerland, Ulrich; Tkačik, Gašper

    2016-01-01

    A crucial step in the early development of multicellular organisms involves the establishment of spatial patterns of gene expression which later direct proliferating cells to take on different cell fates. These patterns enable the cells to infer their global position within a tissue or an organism by reading out local gene expression levels. The patterning system is thus said to encode positional information, a concept that was formalized recently in the framework of information theory. Here we introduce a toy model of patterning in one spatial dimension, which can be seen as an extension of Wolpert’s paradigmatic “French Flag” model, to patterning by several interacting, spatially coupled genes subject to intrinsic and extrinsic noise. Our model, a variant of an Ising spin system, allows us to systematically explore expression patterns that optimally encode positional information. We find that optimal patterning systems use positional cues, as in the French Flag model, together with gene-gene interactions to generate combinatorial codes for position which we call “Counter” patterns. Counter patterns can also be stabilized against noise and variations in system size or morphogen dosage by longer-range spatial interactions of the type invoked in the Turing model. The simple setup proposed here qualitatively captures many of the experimentally observed properties of biological patterning systems and allows them to be studied in a single, theoretically consistent framework. PMID:27676252

  2. The attraction of virgin female hide beetles (Dermestes maculatus to cadavers by a combination of decomposition odour and male sex pheromones

    Directory of Open Access Journals (Sweden)

    von Hoermann Christian

    2012-08-01

    Full Text Available Abstract Introduction The hide beetle Dermestes maculatus (Coleoptera: Dermestidae feeds as an adult and larva on decomposing animal remains and can also be found on human corpses. Therefore, forensic entomological questions with regard to when and how the first receptive females appear on carcasses are important, as the developmental stages of their larvae can be used to calculate the post-mortem interval. To date, we know that freshly emerged males respond to the cadaver odour of post-bloated carcasses (approximately 9 days after death at Tmean = 27°C, being attracted by benzyl butyrate. This component occurs at its highest concentration at this stage of decay. The aim of our study was to determine the principle of attraction of virgin females to the feeding and breeding substrate. For this purpose, we tested the response of these females to headspace samples of piglet cadavers and male sex pheromones [(Z9-unsaturated fatty acid isopropyl esters] in a Y-olfactometer. Because we expected that such an odour combination is of importance for virgin female attraction, we tested the following two questions: 1 Are virgin female hide beetles attracted by a combination of cadaver odour and male sex pheromones? 2 During which decomposition stage do the first virgin females respond to cadaver odour when combined with male sex pheromones? Results We found that young virgin females were attracted to the cadaver by a combination of cadaver odour and male sex pheromones. Neither cadaver odour alone nor male sex pheromones alone was significantly more attractive than a solvent control. Our results also gave a weak indication that the first young virgin females respond as early as the post-bloating stage to its associated decomposition odour when combined with male sex pheromones. Conclusions Our results indicate that freshly emerged males possibly respond to cadaver odour and visit carcasses before virgin females. Being attracted to cadavers when male sex

  3. Measurement and modeling of transcriptional noise in the cell cycle regulatory network.

    Science.gov (United States)

    Ball, David A; Adames, Neil R; Reischmann, Nadine; Barik, Debashis; Franck, Christopher T; Tyson, John J; Peccoud, Jean

    2013-10-01

    Fifty years of genetic and molecular experiments have revealed a wealth of molecular interactions involved in the control of cell division. In light of the complexity of this control system, mathematical modeling has proved useful in analyzing biochemical hypotheses that can be tested experimentally. Stochastic modeling has been especially useful in understanding the intrinsic variability of cell cycle events, but stochastic modeling has been hampered by a lack of reliable data on the absolute numbers of mRNA molecules per cell for cell cycle control genes. To fill this void, we used fluorescence in situ hybridization (FISH) to collect single molecule mRNA data for 16 cell cycle regulators in budding yeast, Saccharomyces cerevisiae. From statistical distributions of single-cell mRNA counts, we are able to extract the periodicity, timing, and magnitude of transcript abundance during the cell cycle. We used these parameters to improve a stochastic model of the cell cycle to better reflect the variability of molecular and phenotypic data on cell cycle progression in budding yeast.

  4. Predictive modeling of migration from packaging materials into food products for regulatory purposes

    NARCIS (Netherlands)

    Helmroth, I.E.; Rijk, R.; Dekker, M.; Jongen, W.M.F.

    2002-01-01

    Migration of low-molecular weight compounds is one of the most important problems of packaging plastics and other plastics intended to come into contact with food products. Since migration experiments are time consuming and expensive, predictive modelling has been introduced as a promising alternati

  5. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  6. Visual stimuli induced by self-motion and object-motion modify odour-guided flight of male moths (Manduca sexta L.).

    Science.gov (United States)

    Verspui, Remko; Gray, John R

    2009-10-01

    Animals rely on multimodal sensory integration for proper orientation within their environment. For example, odour-guided behaviours often require appropriate integration of concurrent visual cues. To gain a further understanding of mechanisms underlying sensory integration in odour-guided behaviour, our study examined the effects of visual stimuli induced by self-motion and object-motion on odour-guided flight in male M. sexta. By placing stationary objects (pillars) on either side of a female pheromone plume, moths produced self-induced visual motion during odour-guided flight. These flights showed a reduction in both ground and flight speeds and inter-turn interval when compared with flight tracks without stationary objects. Presentation of an approaching 20 cm disc, to simulate object-motion, resulted in interrupted odour-guided flight and changes in flight direction away from the pheromone source. Modifications of odour-guided flight behaviour in the presence of stationary objects suggest that visual information, in conjunction with olfactory cues, can be used to control the rate of counter-turning. We suggest that the behavioural responses to visual stimuli induced by object-motion indicate the presence of a neural circuit that relays visual information to initiate escape responses. These behavioural responses also suggest the presence of a sensory conflict requiring a trade-off between olfactory and visually driven behaviours. The mechanisms underlying olfactory and visual integration are discussed in the context of these behavioural responses.

  7. Acquired liking for sweet-paired odours is related to the disinhibition but not restraint factor from the Three Factor Eating Questionnaire.

    Science.gov (United States)

    Yeomans, Martin R; Mobini, Sirous; Bertenshaw, Emma J; Gould, Natalie J

    2009-02-16

    Previous research suggests that women scoring high on dietary restraint may be insensitive to flavour-flavour learning, but no study has yet explored this using the olfactory conditioning paradigm. Accordingly, 56 women who were sweet likers were classified as either high or low on both the Three Factor Eating Questionnaire restraint and disinhibition scales. They evaluated two odours before and after disguised pairings of one odour with 10% sucrose and the other with 0.01% quinine. Liking for the quinine-paired odour decreased post-training, with no effects of restraint or disinhibition. In contrast, the increase in liking for the sucrose-paired odour was significantly greater in women classified as scoring high in disinhibition, but was unaffected by restraint. Sweetness of the sucrose paired odour increased, and bitterness of the quinine-paired odour decreased, similarly in all groups. These data suggest that sensitivity of restrained eaters to flavour-based learning may result from their attitude to the food used as reinforcer rather than some basic failure in the learning process, and also suggest that women scoring high on disinhibition may show heightened sensitivity to hedonic cues.

  8. 77 FR 50172 - Expert Forum on the Use of Performance-Based Regulatory Models in the U.S. Oil and Gas Industry...

    Science.gov (United States)

    2012-08-20

    ... Occupational Safety and Health Administration Expert Forum on the Use of Performance-Based Regulatory Models in... Engineering Safety, OSHA, Directorate of Standards and Guidance, Room N-3609, U.S. Department of Labor, 200..., business sizes, etc.? 3. Is there a way to advance the use of performance-based regulations and...

  9. Dissecting regulatory networks of filopodia formation in a Drosophila growth cone model.

    Directory of Open Access Journals (Sweden)

    Catarina Gonçalves-Pimentel

    Full Text Available F-actin networks are important structural determinants of cell shape and morphogenesis. They are regulated through a number of actin-binding proteins. The function of many of these proteins is well understood, but very little is known about how they cooperate and integrate their activities in cellular contexts. Here, we have focussed on the cellular roles of actin regulators in controlling filopodial dynamics. Filopodia are needle-shaped, actin-driven cell protrusions with characteristic features that are well conserved amongst vertebrates and invertebrates. However, existing models of filopodia formation are still incomplete and controversial, pieced together from a wide range of different organisms and cell types. Therefore, we used embryonic Drosophila primary neurons as one consistent cellular model to study filopodia regulation. Our data for loss-of-function of capping proteins, enabled, different Arp2/3 complex components, the formin DAAM and profilin reveal characteristic changes in filopodia number and length, providing a promising starting point to study their functional relationships in the cellular context. Furthermore, the results are consistent with effects reported for the respective vertebrate homologues, demonstrating the conserved nature of our Drosophila model system. Using combinatorial genetics, we demonstrate that different classes of nucleators cooperate in filopodia formation. In the absence of Arp2/3 or DAAM filopodia numbers are reduced, in their combined absence filopodia are eliminated, and in genetic assays they display strong functional interactions with regard to filopodia formation. The two nucleators also genetically interact with enabled, but not with profilin. In contrast, enabled shows strong genetic interaction with profilin, although loss of profilin alone does not affect filopodia numbers. Our genetic data support a model in which Arp2/3 and DAAM cooperate in a common mechanism of filopodia formation that

  10. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

    Science.gov (United States)

    Bae, Min-Jung; See, Hye-Jeong; Choi, Gyeyoung; Kang, Chang-Yuil; Shon, Dong-Hwa; Shin, Hee Soon

    2016-01-01

    The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  11. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Directory of Open Access Journals (Sweden)

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  12. Improved inference of gene regulatory networks through integrated Bayesian clustering and dynamic modeling of time-course expression data.

    Science.gov (United States)

    Godsey, Brian

    2013-01-01

    Inferring gene regulatory networks from expression data is difficult, but it is common and often useful. Most network problems are under-determined--there are more parameters than data points--and therefore data or parameter set reduction is often necessary. Correlation between variables in the model also contributes to confound network coefficient inference. In this paper, we present an algorithm that uses integrated, probabilistic clustering to ease the problems of under-determination and correlated variables within a fully Bayesian framework. Specifically, ours is a dynamic Bayesian network with integrated Gaussian mixture clustering, which we fit using variational Bayesian methods. We show, using public, simulated time-course data sets from the DREAM4 Challenge, that our algorithm outperforms non-clustering methods in many cases (7 out of 25) with fewer samples, rarely underperforming (1 out of 25), and often selects a non-clustering model if it better describes the data. Source code (GNU Octave) for BAyesian Clustering Over Networks (BACON) and sample data are available at: http://code.google.com/p/bacon-for-genetic-networks.

  13. Dispersion modeling in assessing air quality of industrial projects under Indian regulatory regime

    Directory of Open Access Journals (Sweden)

    Amitava Bandyopadhyay

    2010-01-01

    Full Text Available Environmental impact assessment (EIA studies conducted over the years as a part of obtaining environmental clearance in accordance with Indian regulation have been given significant attention towards carrying out Gaussian dispersion modeling for predicting the ground level concentration (GLC of pollutants, especially for SO2. Making any adhoc decision towards recommending flue gas desulfurization (FGD system in Indian fossil fuel combustion operations is not realistic considering the usage of fuel with low sulfur content. Thus a predictive modeling is imperative prior to making any conclusive decision. In the light of this finding, dispersion modeling has been accorded in Indian environmental regulations. This article aims at providing approaches to ascertain pollution potential for proposed power plant operation either alone or in presence of other industrial operations under different conditions. In order to assess the performance of the computational work four different cases were analyzed based on worst scenario. Results obtained through predictions were compared with National Ambient Air Quality Standards (NAAQS of India. One specific case found to overshoot the ambient air quality adversely in respect of SO2 and was therefore, suggested to install a FGD system with at least 80 % SO2 removal efficiency. With this recommendation, the cumulative prediction yielded a very conservative resultant value of 24 hourly maximum GLC of SO2 as against a value that exceeded well above the stipulated value without considering the FGD system. The computational algorithm developed can therefore, be gainfully utilized for the purpose of EIA analysis in Indian condition.

  14. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency

    Science.gov (United States)

    Artyomov, Maxim; Meissner, Alex; Chakraborty, Arup

    2010-03-01

    Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology.

  15. Integrative analysis of time course microarray data and DNA sequence data via log-linear models for identifying dynamic transcriptional regulatory networks.

    Science.gov (United States)

    Choi, Hyung-Seok; Kim, Youngchul; Cho, Kwang-Hyun; Park, Taesung

    2013-01-01

    Since eukaryotic transcription is regulated by sets of Transcription Factors (TFs) having various transcriptional time delays, identification of temporal combinations of activated TFs is important to reconstruct Transcriptional Regulatory Networks (TRNs). Our methods combine time course microarray data, information on physical binding between the TFs and their targets and the regulatory sequences of genes using a log-linear model to reconstruct dynamic functional TRNs of the yeast cell cycle and human apoptosis. In conclusion, our results suggest that the proposed dynamic motif search method is more effective in reconstructing TRNs than the static motif search method.

  16. Study of the art: canine olfaction used for cancer detection on the basis of breath odour. Perspectives and limitations.

    Science.gov (United States)

    Jezierski, Tadeusz; Walczak, Marta; Ligor, Tomasz; Rudnicka, Joanna; Buszewski, Bogusław

    2015-05-06

    Experimental studies using trained dogs to identify breath odour markers of human cancer, published in the recent decade, have been analyzed and compared with the authors' own results. Particular published studies differ as regards the experimental setup, kind of odour samples (breath, urine, tumor tissue, serum), sample collection methods, dogs' characteristics and dog training methods as well as in results presented in terms of detection sensitivity and specificity. Generally it can be stated that trained dogs are able to distinguish breath odour samples typical for patients with lung cancer and other cancers from samples typical for healthy humans at a 'better than by chance' rate. Dogs' indications were positively correlated with content of 2-pentanone and ethyl acetate (r = 0.97 and r = 0.85 respectively) and negatively correlated with 1-propanol and propanal in breath samples (r = -0.98 and -0.87 respectively). The canine method has some advantages as a potential cancer-screening method, due to its non-invasiveness, simplicity of odour sampling and storage, ease of testing and interpretation of results and relatively low costs. Disadvantages and limitations of this method are related to the fact that it is still not known exactly to which chemical compounds and/or their combinations the dogs react. So far it could not be confirmed that dogs are able to sniff out early preclinical cancer stages with approximately the same accuracy as already diagnosed cases. The detection accuracy may vary due to failure in conditioning of dogs, decreasing motivation or confounding factors. The dogs' performance should be systematically checked in rigorous double-blind procedures. Recommendations for methodological standardization have been proposed.

  17. Differential memory persistence of odour mixture and components in newborn rabbits: Competition between the whole and its parts.

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    Gérard eCoureaud

    2014-06-01

    Full Text Available Interacting with the mother during the daily nursing, newborn rabbits experience her body odour cues. In particular, the mammary pheromone (MP contained in rabbit milk triggers the typical behaviour which helps to localize and seize the nipples. It also promotes the very rapid appetitive learning of simple or complex stimuli (odorants or mixtures through associative conditioning. We previously showed that 24h after MP-induced conditioning to odorants A (ethyl isobutyrate or B (ethyl maltol, newborn rabbits perceive the AB mixture in a weak configural way, i.e. they perceive the odour of the AB configuration in addition to the odours of the elements. Moreover, after conditioning to the mixture, elimination of the memories of A and B does not affect the memory of AB, suggesting independent elemental and configural memories of the mixture. Here, we evaluated whether configural memory persistence differs from elemental one. First, whereas 1 or 3-day-old pups conditioned to A or B maintained their responsiveness to the conditioned odorant for 4 days, those conditioned to AB did not respond to the mixture after the same retention period. Second, the pups conditioned to AB still responded to A and B 4 days after conditioning, which indicates stronger retention of the elements than of the configuration when all information are learned together. Third, we determined whether the memory of the elements competes with the memory of the configuration: after conditioning to AB, when the memories of A and B were erased using pharmacological treatment, the memory of the mixture was extended to day 5. Thus, newborn rabbits have access to both elemental and configural information in certain odour mixtures, and competition between these distinct representations of the mixture influences the persistence of their memories. Such effects certainly occur in the natural context of mother-pup interactions and may contribute to early acquisition of knowledge about the

  18. The Nationwide Airport Noise Impact Model and Its Application to Regulatory Alternatives

    Science.gov (United States)

    1987-07-01

    1.032 2000 267,955 15,283 5.70 1.057 2010 283,238 Assumptions: Lifetime births per woman: 1.9 Life expectancy at birth , 2080: 81.0 Net immigration...Div., Civil Aeronautics Board, Feb. 1982. 11. Warren, D., "Area Equivalent Method on Lotus 1-2-3 T M ", Federal Aviation Administration, Report EE-84-12...both cases using the FAA Area Equivalent Model. ’Warren, D. "Area Equivalent Method on Lotus i-2-3 T M". Federal Aviation Administration, Report EE-84

  19. Improving Metabolic Pathway Efficiency by Statistical Model-Based Multivariate Regulatory Metabolic Engineering.

    Science.gov (United States)

    Xu, Peng; Rizzoni, Elizabeth Anne; Sul, Se-Yeong; Stephanopoulos, Gregory

    2017-01-20

    Metabolic engineering entails target modification of cell metabolism to maximize the production of a specific compound. For empowering combinatorial optimization in strain engineering, tools and algorithms are needed to efficiently sample the multidimensional gene expression space and locate the desirable overproduction phenotype. We addressed this challenge by employing design of experiment (DoE) models to quantitatively correlate gene expression with strain performance. By fractionally sampling the gene expression landscape, we statistically screened the dominant enzyme targets that determine metabolic pathway efficiency. An empirical quadratic regression model was subsequently used to identify the optimal gene expression patterns of the investigated pathway. As a proof of concept, our approach yielded the natural product violacein at 525.4 mg/L in shake flasks, a 3.2-fold increase from the baseline strain. Violacein production was further increased to 1.31 g/L in a controlled benchtop bioreactor. We found that formulating discretized gene expression levels into logarithmic variables (Linlog transformation) was essential for implementing this DoE-based optimization procedure. The reported methodology can aid multivariate combinatorial pathway engineering and may be generalized as a standard procedure for accelerating strain engineering and improving metabolic pathway efficiency.

  20. IT Management Model for Financial Report Issuance and Regulatory and Legal Compliance

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    José Rogério Poggio Moreira

    2013-10-01

    Full Text Available The development of information systems for financial report issuance must be adherent to the demands of the law and regulations that regulate the financial market. In order to perform this task, organizations need to implement control in the Information Technology (IT area to maintain their systems´ conformity to laws and regulations. In the development of this work, it was found, through a state-of-art study, that there are no proposals contemplating the solution of this problem in its totality. In order to achieve this goal, in this paper it is presented a model for Information Technology management constituted by COBIT, ITIL and BPM management good practices, together with SOA and XBRL Technologies. This model is composed by 03 layers that aim at structuring the organization IT and business processes, besides defining a process for implementing SOA and integrating its Web services with XBRL language. One can expect this work to contribute to companies to decrease the negative impact coming from the lack of conformity with laws and regulations, through the creation of a corporative and IT environment that is flexible and more adaptable to changes, which may occur in legal demands, as well as improving the quality and reliability of financial report issuance.

  1. Cell model for the study of receptor and regulatory functions of human proHB-EGF

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    N. V. Korotkevych

    2014-08-01

    Full Text Available Developing of new models and approaches, particularly with fluorescent techniques, for investigation of intracellular transport of proHB-EGF and its ligand-receptor complexes is strongly required. In order to create a model for studying proHB-EGF functions the genetic construction pEGFP-N1-proHB-EGF, encoding proHB-EGF-EGFP which is fluorescent-labeled form of proHB-EGF with enhanced green fluorescent protein EGFP in the cytoplasmic terminus of the molecule, was obtained. Eukaryotic cells expressing fusion protein proHB-EGF-EGFP on the cell surface were obtained by transfection with pEGFP-N1-proHB-EGF. Expressed in the Vero cells proHB-EGF-EGFP could bind fluorescent derivative of nontoxic receptor-binding subunit B of diphtheria toxin mCherry-SubB. After stimulation of transfected cells with TPA (12-O-Tetradecanoylphorbol-13-acetate, proHB-EGF-EGFP formed a fluorescentl-labeled C-terminal fragment of the molecule – CTF-EGFP. Thus, the obtained genetic construction pEGFP-N1-proHB-EGF could be helpful in visualization of molecules proHB-EGF and CTF in cells, may open new possibilities for the studying of their functions, such as receptor function of proHB-EGF for diphtheria toxin, intracellular translocation of CTF and provide possibilities for natural proHB-EGF ligands search.

  2. Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria.

    Science.gov (United States)

    Achtman, Ariel H; Pilat, Sandra; Law, Charity W; Lynn, David J; Janot, Laure; Mayer, Matt L; Ma, Shuhua; Kindrachuk, Jason; Finlay, B Brett; Brinkman, Fiona S L; Smyth, Gordon K; Hancock, Robert E W; Schofield, Louis

    2012-05-23

    Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defense regulator (IDR) peptides, based on host defense peptides. The Plasmodium berghei ANKA model of experimental cerebral malaria was adapted to use as a preclinical screen by combining late-stage intervention in established infections with advanced bioinformatic analysis of early transcriptional changes in co-regulated gene sets. Coadministration of IDR-1018 with standard first-line antimalarials increased survival of infected mice while down-regulating key inflammatory networks associated with fatality. Thus, IDR peptides provided host-directed adjunctive therapy for severe disease in combination with antimalarial treatment.

  3. Rule-based regulatory and metabolic model for Quorum sensing in P. aeruginosa.

    Science.gov (United States)

    Schaadt, Nadine S; Steinbach, Anke; Hartmann, Rolf W; Helms, Volkhard

    2013-08-21

    In the pathogen P. aeruginosa, the formation of virulence factors is regulated via Quorum sensing signaling pathways. Due to the increasing number of strains that are resistant to antibiotics, there is a high interest to develop novel antiinfectives. In the combat of resistant bacteria, selective blockade of the bacterial cell-to-cell communication (Quorum sensing) has gained special interest as anti-virulence strategy. Here, we modeled the las, rhl, and pqs Quorum sensing systems by a multi-level logical approach to analyze how enzyme inhibitors and receptor antagonists effect the formation of autoinducers and virulence factors. Our rule-based simulations fulfill the behavior expected from literature considering the external level of autoinducers. In the presence of PqsBCD inhibitors, the external HHQ and PQS levels are indeed clearly reduced. The magnitude of this effect strongly depends on the inhibition level. However, it seems that the pyocyanin pathway is incomplete. To match experimental observations we suggest a modified network topology in which PqsE and PqsR acts as receptors and an autoinducer as ligand that up-regulate pyocyanin in a concerted manner. While the PQS biosynthesis is more appropriate as target to inhibit the HHQ and PQS formation, blocking the receptor PqsR that regulates the biosynthesis reduces the pyocyanin level stronger.

  4. A modulated empirical Bayes model for identifying topological and temporal estrogen receptor α regulatory networks in breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Yuming

    2011-05-01

    Full Text Available Abstract Background Estrogens regulate diverse physiological processes in various tissues through genomic and non-genomic mechanisms that result in activation or repression of gene expression. Transcription regulation upon estrogen stimulation is a critical biological process underlying the onset and progress of the majority of breast cancer. Dynamic gene expression changes have been shown to characterize the breast cancer cell response to estrogens, the every molecular mechanism of which is still not well understood. Results We developed a modulated empirical Bayes model, and constructed a novel topological and temporal transcription factor (TF regulatory network in MCF7 breast cancer cell line upon stimulation by 17β-estradiol stimulation. In the network, significant TF genomic hubs were identified including ER-alpha and AP-1; significant non-genomic hubs include ZFP161, TFDP1, NRF1, TFAP2A, EGR1, E2F1, and PITX2. Although the early and late networks were distinct ( Conclusions We identified a number of estrogen regulated target genes and established estrogen-regulated network that distinguishes the genomic and non-genomic actions of estrogen receptor. Many gene targets of this network were not active anymore in anti-estrogen resistant cell lines, possibly because their DNA methylation and histone acetylation patterns have changed.

  5. Combination Effect of Regulatory T-Cell Depletion and Ionizing Radiation in Mouse Models of Lung and Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Son, Cheol-Hun [Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Bae, Jae-Ho [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Shin, Dong-Yeok; Lee, Hong-Rae; Jo, Wol-Soon; Yang, Kwangmo [Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Park, You-Soo, E-mail: biotek01@hanmail.net [Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

    2015-06-01

    Purpose: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during radiation therapy. Methods and Materials: We used LD-CTX and anti-CD25 monoclonal antibody as a means to inhibit Tregs and improve the therapeutic effect of radiation in a mouse model of lung and colon cancer. Mice were irradiated on the tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once per week for 3 weeks. Results: Combined treatment of LD-CTX or anti-CD25 antibody with radiation significantly decreased Tregs in the spleen and tumor compared with control and irradiation only in both lung and colon cancer. Combinatorial treatments resulted in a significant increase in the effector T cells, longer survival rate, and suppressed irradiated and distal nonirradiated tumor growth. Specifically, the combinatorial treatment of LD-CTX with radiation resulted in outstanding regression of local and distant tumors in colon cancer, and almost all mice in this group survived until the end of the study. Conclusions: Our results suggest that Treg depletion strategies may enhance radiation-mediated antitumor immunity and further improve outcomes after radiation therapy.

  6. Eucheuma cottonii Sulfated Oligosaccharides Decrease Food Allergic Responses in Animal Models by Up-regulating Regulatory T (Treg) Cells.

    Science.gov (United States)

    Xu, Sha-Sha; Liu, Qing-Mei; Xiao, An-Feng; Maleki, Soheila J; Alcocer, Marcos; Gao, Yuan-Yuan; Cao, Min-Jie; Liu, Guang-Ming

    2017-04-19

    In the present study, the anti-food allergy activity of Eucheuma cottonii sulfated oligosaccharide (ESO) was investigated. ESO was obtained by enzymatic degradation and purified by column chromatography. RBL-2H3 cells and BALB/c mouse model were used to test the anti-food allergy activity of ESO. The effects of ESO on the regulatory T (Treg) cells and bone marrow-derived mast cells (BMMCs) were investigated by flow cytometry. The results of in vivo assay showed that ESO decreased the levels of mast cell protease-1 and histamine and inhibited the levels of specific IgE by 77.7%. In addition, the production of interleukin (IL)-4 and IL-13 was diminished in the ESO groups compared to the non-ESO-treated group. Furthermore, ESO could up-regulate Treg cells by 22.2-97.1%. In conclusion, ESO decreased the allergy response in mice by reducing basophil degranulation, up-regulating Treg cells via Forkhead box protein 3 (Foxp3), and releasing IL-10. ESO may have preventive and therapeutic potential in allergic disease.

  7. Identification of the Rage-dependent gene regulatory network in a mouse model of skin inflammation

    Directory of Open Access Journals (Sweden)

    Gebhardt Christoffer

    2010-10-01

    Full Text Available Abstract Background In the past, molecular mechanisms that drive the initiation of an inflammatory response have been studied intensively. However, corresponding mechanisms that sustain the expression of inflammatory response genes and hence contribute to the establishment of chronic disorders remain poorly understood. Recently, we provided genetic evidence that signaling via the receptor for advanced glycation end products (Rage drives the strength and maintenance of an inflammatory reaction. In order to decipher the mode of Rage function on gene transcription levels during inflammation, we applied global gene expression profiling on time-resolved samples of mouse back skin, which had been treated with the phorbol ester TPA, a potent inducer of skin inflammation. Results Ranking of TPA-regulated genes according to their time average mean and peak expression and superimposition of data sets from wild-type (wt and Rage-deficient mice revealed that Rage signaling is not essential for initial changes in TPA-induced transcription, but absolutely required for sustained alterations in transcript levels. Next, we used a data set of differentially expressed genes between TPA-treated wt and Rage-deficient skin and performed computational analysis of their proximal promoter regions. We found a highly significant enrichment for several transcription factor binding sites (TFBS leading to the prediction that corresponding transcription factors, such as Sp1, Tcfap2, E2f, Myc and Egr, are regulated by Rage signaling. Accordingly, we could confirm aberrant expression and regulation of members of the E2f protein family in epidermal keratinocytes of Rage-deficient mice. Conclusions In summary, our data support the model that engagement of Rage converts a transient cellular stimulation into sustained cellular dysfunction and highlight a novel role of the Rb-E2f pathway in Rage-dependent inflammation during pathological conditions.

  8. Regulatory Foci and Organizational Commitment

    Science.gov (United States)

    Markovits, Yannis; Ullrich, Johannes; van Dick, Rolf; Davis, Ann J.

    2008-01-01

    We use regulatory focus theory to derive specific predictions regarding the differential relationships between regulatory focus and commitment. We estimated a structural equation model using a sample of 520 private and public sector employees and found in line with our hypotheses that (a) promotion focus related more strongly to affective…

  9. Investigation of the efficacy of immunocastration aimed at the prevention of sex odour in boar meat

    Directory of Open Access Journals (Sweden)

    Aleksić Jelena

    2012-01-01

    Full Text Available Disadvantage of meat known as boar taint is caused by steroids, androstenone being of particular importance, as well as indole and its derivatives, among which the best known is skatole. The common practice in Europe, in order to control these changes in meat, is castration without anesthesia. This intervention causes pain and stress to animals, thus undermining animal welfare. Many countries considering animal welfare try to find the alternative solutions in order to avoid castration. The alternative to surgical castration and possible solution to the problem of sex odour in the meat, as well as androstenone and skatole contents decrease in the boar's fat is immunological castration of boars (immunocastration. Average skatole content in fat tissue of boars was significantly higher (0.21±0.03 μg/g compared to skatole content in fat tissue of the castrates, or immunocastrates (0.12±0.02 μg/g. In adipose tissue of the castrates and immunocastrates there was no significant difference in the average content of skatole. The content of androstenone in the adipose tissue of immunocastrates was below detection limits, and the average androstenone level in adipose tissue of boars was 0.66±0.13 μg/g. The obtained results show that immunocastration is justified in consideration of the meat quality and can completely replace castration in male animals, which is in compliance with the preservation of animal welfare in rearing fattening young boars.

  10. Integration of advanced oxidation processes at mild conditions in wet scrubbers for odourous sulphur compounds treatment.

    Science.gov (United States)

    Vega, Esther; Martin, Maria J; Gonzalez-Olmos, Rafael

    2014-08-01

    The effectiveness of different advanced oxidation processes on the treatment of a multicomponent aqueous solution containing ethyl mercaptan, dimethyl sulphide and dimethyl disulphide (0.5 mg L(-1) of each sulphur compound) was investigated with the objective to assess which one is the most suitable treatment to be coupled in wet scrubbers used in odour treatment facilities. UV/H2O2, Fenton, photo-Fenton and ozone treatments were tested at mild conditions and the oxidation efficiency obtained was compared. The oxidation tests were carried out in magnetically stirred cylindrical quartz reactors using the same molar concentration of oxidants (hydrogen peroxide or ozone). The results show that ozone and photo-Fenton are the most efficient treatments, achieving up to 95% of sulphur compounds oxidation and a mineralisation degree around 70% in 10 min. Furthermore, the total costs of the treatments taking into account the capital and operational costs were also estimated for a comparative purpose. The economic analysis revealed that the Fenton treatment is the most economical option to be integrated in a wet scrubber to remove volatile organic sulphur compounds, as long as there are no space constraints to install the required reactor volume. In the case of reactor volume limitation or retrofitting complexities, the ozone and photo-Fenton treatments should be considered as viable alternatives.

  11. Study on the Control of Polluted Odour Gas by Biological Treatment Technology

    Directory of Open Access Journals (Sweden)

    Wen Dong

    2017-07-01

    Full Text Available In order to improve the quality of the environment as well as its purification capacity, to reduce environmental costs and achieve clean and efficient management of malodorous gas pollution, on the basis of fully understanding the theory of biotechnology, this paper presents the research of biotechnology to control the pollution of malodorous pollutants. In this research, the biofiltration method was used to control the odour gas ammonia produced in waste composting, which can effectively purify gases, with a high ammonia removal rate. One week after the ammonia removal experiment, the removal rate was detected to be around 79.3 %. Twenty-four days after the experiment, the removal rate stabilized at around 98 %. Through the test of pH value of nutrient solution, it was found that the change in pH value corresponded to the increase in removal rate. There are many advantages of applying biotechnology to filter malodorous polluted gases, such as low energy consumption, high degree of purification, good environmental compatibility, simple operation and maintenance, and no secondary pollution. Therefore, it has good application prospects.

  12. Biofiltration of odours - industrial pilot to treat methyl ethyl ketone and toluene

    Energy Technology Data Exchange (ETDEWEB)

    Otten, L.; Elsie, K. [Univ. of Guelph, School of Engineering, Guelph, Ontario (Canada)

    2002-06-15

    Methyl ethyl ketone and toluene in the off-gases of a plant producing polyvinyl chloride sheeting for the automotive industry and swimming pools caused frequent odour complaints from the neighbourhood. A pilot project was developed to investigate the removal of the compounds under actual operating conditions by passing part of the exhaust through a compost-based, three-stage biofilter. It was determined over the 156 days of operation that the removal efficiencies of methyl ethyl ketone and toluene averaged 73% and 49%, respectively. It was also shown that shutdowns and disruptions of the laminating process for short and extended periods did not affect the biofilter performance. Addition of 100g/L solution of KNO{sub 3} as a nitrogen source did not improve the performance. Carbon dioxide concentration data and the presence of an average microbial population of 52 million colony forming units per gram provided evidence that biological degradation played a significant role in the reduction of methyl ethyl ketone and toluene in the off-gases of the laminator. (author)

  13. Class I histone deacetylase inhibitor entinostat suppresses regulatory T cells and enhances immunotherapies in renal and prostate cancer models.

    Directory of Open Access Journals (Sweden)

    Li Shen

    Full Text Available BACKGROUND: Immunosuppressive factors such as regulatory T cells (Tregs limit the efficacy of immunotherapies. Histone deacetylase (HDAC inhibitors have been reported to have antitumor activity in different malignancies and immunomodulatory effects. Herein, we report the Tregs-targeting and immune-promoting effect of a class I specific HDAC inhibitor, entinostat, in combination with either IL-2 in a murine renal cell carcinoma (RENCA model or a survivin-based vaccine therapy (SurVaxM in a castration resistant prostate cancer (CR Myc-CaP model. METHODS AND RESULTS: RENCA or CR Myc-CaP tumors were implanted orthotopically or subcutaneously, respectively. Inoculated mice were randomized into four treatment groups: vehicle, entinostat, cytokine or vaccine, and combination. Tregs in the blood were assessed by FACS analysis. Real time quantitative PCR and Western blot analysis of isolated T cell subpopulations from spleen were performed to determine Foxp3 gene and protein expression. The suppressive function of Tregs was tested by T cell proliferation assay. Low dose (5 mg/kg entinostat reduced Foxp3 levels in Tregs and this was associated with enhanced tumor growth inhibition in combination with either IL-2 or a SurVaxM vaccine. Entinostat down-regulated Foxp3 expression transcriptionally and blocked Tregs suppressive function without affecting T effector cells (Teffs. In vitro low dose entinostat (0.5 µM induced STAT3 acetylation and a specific inhibitor of STAT3 partially rescued entinostat-induced down-regulation of Foxp3, suggesting that STAT3 signaling is involved in Foxp3 down-regulation by entinostat. CONCLUSIONS: These results demonstrate a novel immunomodulatory effect of class I HDAC inhibition and provide a rationale for the clinical testing of entinostat to enhance cancer immunotherapy.

  14. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Cirera Salicio, Susanna; Zhernakova, Daria V.

    2014-01-01

    interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model...... in a porcine model. Methods We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes...... in humans and rodents, e.g. CSF1R and MARC2. Conclusions To our knowledge, this is the first study to apply systems biology approaches using porcine adipose tissue RNA-Sequencing data in a genetically characterized porcine model for obesity. We revealed complex networks, pathways, candidate and regulatory...

  15. A software tool to model genetic regulatory networks. Applications to the modeling of threshold phenomena and of spatial patterning in Drosophila.

    Directory of Open Access Journals (Sweden)

    Rui Dilão

    Full Text Available We present a general methodology in order to build mathematical models of genetic regulatory networks. This approach is based on the mass action law and on the Jacob and Monod operon model. The mathematical models are built symbolically by the Mathematica software package GeneticNetworks. This package accepts as input the interaction graphs of the transcriptional activators and repressors of a biological process and, as output, gives the mathematical model in the form of a system of ordinary differential equations. All the relevant biological parameters are chosen automatically by the software. Within this framework, we show that concentration dependent threshold effects in biology emerge from the catalytic properties of genes and its associated conservation laws. We apply this methodology to the segment patterning in Drosophila early development and we calibrate the genetic transcriptional network responsible for the patterning of the gap gene proteins Hunchback and Knirps, along the antero-posterior axis of the Drosophila embryo. In this approach, the zygotically produced proteins Hunchback and Knirps do not diffuse along the antero-posterior axis of the embryo of Drosophila, developing a spatial pattern due to concentration dependent thresholds. This shows that patterning at the gap genes stage can be explained by the concentration gradients along the embryo of the transcriptional regulators.

  16. Effect of whey protein concentrate and sodium chloride concentrations on the odour profile of sous vide cooked whole-muscle beef from Argentina.

    Science.gov (United States)

    Grigioni, G; Langman, L; Szerman, N; Irurueta, M; Vaudagna, S R

    2008-07-01

    Semitendinosus muscles added with whey protein concentrate (WPC) and sodium chloride (NaCl) were submitted to sous vide cooking. Four enhancement treatments and a control were tested: 0.875% WPC (w/w)+0.625% NaCl, 2.625% WPC+0.625% NaCl, 0.875% WPC+1.875% NaCl, 2.625% WPC+1.875% NaCl, and control (non-injected muscles). Odour analyses were carried out with an electronic nose (EN) system. EN data were evaluated applying Principal Component Analysis, Linear Discriminant Analysis and Partial Least Squares algorithm. EN was able to discriminate the odour profiles of cooked enhanced beef as a function of the amount of WPC added. No significant differences in odour profiles were observed regarding NaCl concentration. These results agreed with those obtained when odour profiles were analysed in WPC dispersions. The reported results support the applicability of EN methodology for analysing the impact of processing parameters on beef odour profiles.

  17. A combined perceptual, physico-chemical, and imaging approach to 'odour-distances' suggests a categorizing function of the Drosophila antennal lobe.

    Directory of Open Access Journals (Sweden)

    Thomas Niewalda

    Full Text Available How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3-octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours.

  18. Guatemalan potato moth Tecia solanivora distinguish odour profiles from qualitatively different potatoes Solanum tuberosum L.

    Science.gov (United States)

    Karlsson, Miriam Frida; Birgersson, Göran; Witzgall, Peter; Lekfeldt, Jonas Duus Stevens; Nimal Punyasiri, P A; Bengtsson, Marie

    2013-01-01

    Guatemalan potato moth, Tecia solanivora, lay eggs in the soil nearby potato Solanum spp. and larvae feed on the tubers. We investigated the oviposition behaviour of T. solanivora females and the survival of larval offspring on healthy vs. stressed, i.e. light exposed and/or damaged potato tubers. In choice tests, females laid significantly more eggs in response to potato odour of healthy tubers and female oviposition preference correlated with higher larval survival. Survival of larvae was negatively correlated with the tuber content of the steroid glycoalkaloids α-solanine and α-chaconine: healthy potatoes contained lower amounts than stressed tubers, ranging from 25 to 500 μg g⁻¹ and from 30 to 600 μg g⁻¹, respectively. Analysis of volatile compounds emitted by potato tubers revealed that stressed tubers could clearly be distinguished from healthy tubers by the composition of their volatile profiles. Compounds that contributed to this difference were e.g. decanal, nonanal, isopropyl myristate, phenylacetaldehyde, benzothiazole, heptadecane, octadecane, myristicin, E,E-α-farnesene and verbenone. Oviposition assays, when female moths were not in contact with the tubers, clearly demonstrated that volatiles guide the females to lay fewer eggs on stressed tubers that are of inferior quality for the larvae. We propose that volatiles, such as sesquiterpenes and aldehydes, mediate oviposition behaviour and are correlated with biosynthetically related, non-volatile compounds, such as steroidal glycoalkaloids, which influence larval survival. We conclude that the oviposition response and larval survival of T. solanivora on healthy vs. stressed tubers supports the preference performance hypothesis for insect herbivores.

  19. THREATS/RISKS IN POULTRY FARMS: MICROBIOLOGICAL CONTAMINANTS, DUST, ODOURS AND BIOLOGICAL METHOD FOR ELIMINATION

    Directory of Open Access Journals (Sweden)

    Katarzyna Matusiak

    2017-06-01

    Full Text Available The aim of the study was to evaluate the microbiological contamination, odour and dust concentration in poultry farms. In addition, the effectiveness of biopreparation and Yucca schidigera plant extract in manure hygienisation and selected odorous compounds removal was determined. The airborne total dust concentration at poultry production premises averaged 1.44 mg/m3 with a high percentage of the PM10 fraction. High number of bacteria and fungi at 106-1010 CFU / g. was determined in both poultry manure and settled dust. Poultry farm’s air limits of the bacteria and fungi number have not been exceeded. Reported concentrations of PM2.5 and PM10 fractions were 18-20 times higher than acceptable for a 24-hour exposure determined by the World Health Organization. Volatile odorous compounds dominant in poultry farms were: ammonia, acrolein, methyl amine, acetic acid, acetaldehyde and formaldehyde. The concentrations are variable depending on the farm type and stage of the cycle production. The permissible concentration/ exposure limits of ammonia in the air has been exceeded in the laying hens farms I and II, while the concentration of carbon dioxide exceeded the limit value in the third stage of the cycle production on broiler farm III and was close to the limit for laying hens farm I. The maximum cytotoxicity of odorous compounds mixture tested on chick liver hepatocellular carcinoma cell line LMH was 45.7%. It was confirmed by cells morphologic changes after the odorous compounds treatment (ammonia, di-, and trimethylamine. Mineral-microbial biopreparation with Yucca schidigera extract reduced the total number of microorganisms by 1 logarythmic unit in poultry manure and decreased concentration of odorous compounds by 37% - 70% depending on the compound. The use in sequence Y. schidigera extract, and then after 2 days biopreparation can be an effective way to reduce microbiological and odorous hazards on poultry farms.

  20. Responses of tadpoles to hybrid predator odours: strong maternal signatures and the potential risk/response mismatch.

    Science.gov (United States)

    Chivers, Douglas P; Mathiron, Anthony; Sloychuk, Janelle R; Ferrari, Maud C O

    2015-06-22

    Previous studies have established that when a prey animal knows the identity of a particular predator, it can use this knowledge to make an 'educated guess' about similar novel predators. Such generalization of predator recognition may be particularly beneficial when prey are exposed to introduced and invasive species of predators or hybrids. Here, we examined generalization of predator recognition for woodfrog tadpoles exposed to novel trout predators. Tadpoles conditioned to recognize tiger trout, a hybrid derived from brown trout and brook trout, showed generalization of recognition of several unknown trout odours. Interestingly, the tadpoles showed stronger responses to odours of brown trout than brook trout. In a second experiment, we found that tadpoles trained to recognize brown trout showed stronger responses to tiger trout than those tadpoles trained to recognize brook trout. Given that tiger trout always have a brown trout mother and a brook trout father, these results suggest a strong maternal signature in trout odours. Tadpoles that were trained to recognize both brown trout and brook trout showed stronger response to novel tiger trout than those trained to recognize only brown trout or only brook trout. This is consistent with a peak shift in recognition, whereby cues that are intermediate between two known cues evoke stronger responses than either known cue. Given that our woodfrog tadpoles have no evolutionary or individual experience with trout, they have no way of knowing whether or not brook trout, brown trout or tiger trout are more dangerous. The differential intensity of responses that we observed to hybrid trout cues and each of the parental species indicates that there is a likely mismatch between risk and anti-predator response intensity. Future work needs to address the critical role of prey naivety on responses to invasive and introduced hybrid predators.

  1. Blue tits (Cyanistes caeruleus) respond to an experimental change in the aromatic plant odour composition of their nest.

    Science.gov (United States)

    Mennerat, A

    2008-11-01

    Although the use of olfaction by birds is now widely recognised, the olfactory abilities of passerine birds remain poorly explored, for historical reasons. Several studies however suggest that passerines can perceive volatile compounds in several biologically relevant contexts. In Corsica, recent findings suggest that cavity-nesting blue tits may use volatile compounds in the context of nest building and maintenance. Although they build their nests mainly from moss, female blue tits also frequently incorporate fragments of several species of aromatic plants in the nest cup. In field experiments, breeding female blue tits altered their nest maintenance behaviour in response to experimental addition of aromatic plants in their nest. In aviary experiments, captive male blue tits could be trained to detect lavender odour from a distance. Here I report results from a field study aimed to test whether adult blue tits altered their chick-feeding behaviour after an experimental change in nest odour composition. I experimentally added fragments of aromatic plant species that differed from those brought in the nests before the start of the experiment in a set of experimental nests and added moss, the basic nest material, in a set of control nests. Both male and female blue tits hesitated significantly longer entering the nest cavity after addition of new aromatic plant fragments, as compared to moss addition. This response was especially observed during the first visit following the experimental change in nest plant composition. Nest composition treatment had no effect on the time spent in the nest. This study demonstrates that free-ranging blue tits detect changes in nest odour from outside the nest cavity.

  2. Modelling the effects of odours and spying parasitoids on fruit fly population dynamics

    NARCIS (Netherlands)

    Lof, M.E.

    2012-01-01

    The study of the role of chemical information in species interactions has been mostly restricted to studies at the level of individual organisms. The central question in this thesis is how intraspecific chemical information conveyance and exploitation thereof by a natural enemy affects the spatial p

  3. Attraction of the cutaneous leishmaniasis vector Nyssomyia neivai (Diptera: Psychodidae) to host odour components in a wind tunnel

    Science.gov (United States)

    2012-01-01

    Background Laboratory studies of host-seeking olfactory behaviour in sandflies have largely been restricted to the American visceral leishmaniasis vector Lutzomyia longipalpis. In comparison, almost nothing is known about the chemical ecology of related species, which transmit American cutaneous leishmaniasis (ACL), due in part to difficulties in raising these insects in the laboratory. Understanding how ACL vectors locate their hosts will be essential to developing new vector control strategies to combat this debilitating disease. Methods This study examined host-odour seeking behaviour of the ACL vector Nyssomyia neivai (Pinto) (=Lutzomyia neivai) using a wind tunnel olfactometer. The primary aim was to determine whether field-collected female N. neivai would respond to host odours in the laboratory, thereby eliminating the need to maintain colonies of these insects for behavioural experiments. Responses to two key host odour components, 1-octen-3-ol and lactic acid, and a commercially-available mosquito lure (BG-Lure™) were assessed and compared relative to an air control. We also tested whether trials could be conducted outside of the normal evening activity period of N. neivai without impacting on fly behaviour, and whether the same flies could be used to assess baseline responses to air without affecting responses to octenol, thereby reducing the number of flies required for experiments. Results Octenol was found to both activate host-seeking behaviour and attract female N. neivai in the wind tunnel, while lactic acid elicited weaker responses of activation and attractiveness under identical conditions. The BG-Lure did not activate or attract N. neivai under test conditions. Further experiments showed that sandfly behaviour in the wind tunnel was not affected by time of day, such that experiments need not be restricted to nocturnal hours. Moreover, using the same flies to measure both baseline responses to air and attraction to test compounds did not affect

  4. UV-based advanced oxidation processes for the treatment of odour compounds: efficiency and by-product formation.

    Science.gov (United States)

    Zoschke, Kristin; Dietrich, Norman; Börnick, Hilmar; Worch, Eckhard

    2012-10-15

    The occurrence of the taste and odour compounds geosmin and 2-methyl isoborneol (2-MIB) affects the organoleptic quality of raw waters from drinking water reservoirs worldwide. UV-based oxidation processes for the removal of these substances are an alternative to adsorption and biological processes, since they additionally provide disinfection of the raw water. We could show that the concentration of geosmin and 2-MIB could be reduced by VUV irradiation and the combination of UV irradiation with ozone and hydrogen peroxide in pure water and water from a drinking water reservoir. The figure of merit EE/O is an appropriate tool to compare the AOPs and showed that VUV and UV/O(3) yielded the lowest treatment costs for the odour compounds in pure and raw water, respectively. Additionally, VUV irradiation with addition of ozone, generated by the VUV lamp, was evaluated. The generation of ozone and the irradiation were performed in a single reactor system using the same low-pressure mercury lamp, thereby reducing the energy consumption of the treatment process. The formation of the undesired by-products nitrite and bromate was investigated. The combination of VUV irradiation with ozone produced by a VUV lamp avoided the formation of relevant concentrations of the by-products. The internal generation of ozone is capable to produce ozone concentrations sufficient to reduce EE/O below 1 kWh m(-3) and without the risk of the formation of nitrite or bromate above the maximum contaminant level.

  5. Plant odour processing in the antennal lobe of male and female grapevine moths, Lobesia botrana (Lepidoptera: Tortricidae).

    Science.gov (United States)

    Masante-Roca, I; Gadenne, C; Anton, S

    2002-12-01

    Moths of Lobesia botrana (Lepidoptera: Tortricidae) are confronted with different volatiles emitted from the host plant during the different seasons. To test the hypothesis of plasticity of central plant odour processing in moths of different generations in the future, we first investigated the responses of antennal lobe (AL) interneurons of laboratory-reared virgin and mated males and females. We used intracellular recording and staining techniques while stimulating the antenna with a range of host and non-host plant odours. The AL structure of L. botrana is similar to that found in other Lepidoptera species studied. The most frequent physiological responses for all types of moths were obtained with (E)-2-hexenal, and with thujyl alcohol and beta-thujone, components of tansy, a behaviourally attractive non-host plant. Some broadly responding neurons were capable of distinguishing between different compounds through different response patterns (excitation/inhibition) and/or different dose-response characteristics. Response characteristics (response spectra, threshold and specificity) of neurons were similar, independent of sex or mating status of the moths. Significant differences between the groups were, however, found in the proportion of responding neurons for a few tested components.

  6. Trust, regulatory processes and NICE decision-making: Appraising cost-effectiveness models through appraising people and systems.

    Science.gov (United States)

    Brown, Patrick; Hashem, Ferhana; Calnan, Michael

    2016-02-01

    This article presents an ethnographic study of regulatory decision-making regarding the cost-effectiveness of expensive medicines at the National Institute for Health and Care Excellence (NICE) in England. We explored trust as one important mechanism by which problems of complexity and uncertainty were resolved. Existing studies note the salience of trust for regulatory decisions, by which the appraisal of people becomes a proxy for appraising technologies themselves. Although such (dis)trust in manufacturers was one important influence, we describe a more intricate web of (dis)trust relations also involving various expert advisors, fellow committee members and committee Chairs. Within these complex chains of relations, we found examples of both more blind-acquiescent and more critical-Investigative forms of trust as well as, at times, pronounced distrust. Difficulties in overcoming uncertainty through other means obliged trust in some contexts, although not in others. (Dis)trust was constructed through inferences involving abstract systems alongside actors' oral and written presentations-of-self. Systemic features and 'forced options' to trust indicate potential insidious processes of regulatory capture.

  7. In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.

    Science.gov (United States)

    Lennernäs, H; Lindahl, A; Van Peer, A; Ollier, C; Flanagan, T; Lionberger, R; Nordmark, A; Yamashita, S; Yu, L; Amidon, G L; Fischer, V; Sjögren, E; Zane, P; McAllister, M; Abrahamsson, B

    2017-04-03

    The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.

  8. Inferring polymorphism-induced regulatory gene networks active in human lymphocyte cell lines by weighted linear mixed model analysis of multiple RNA-Seq datasets.

    Directory of Open Access Journals (Sweden)

    Wensheng Zhang

    Full Text Available Single-nucleotide polymorphisms (SNPs contribute to the between-individual expression variation of many genes. A regulatory (trait-associated SNP is usually located near or within a (host gene, possibly influencing the gene's transcription or/and post-transcriptional modification. But its targets may also include genes that are physically farther away from it. A heuristic explanation of such multiple-target interferences is that the host gene transfers the SNP genotypic effects to the distant gene(s by a transcriptional or signaling cascade. These connections between the host genes (regulators and the distant genes (targets make the genetic analysis of gene expression traits a promising approach for identifying unknown regulatory relationships. In this study, through a mixed model analysis of multi-source digital expression profiling for 140 human lymphocyte cell lines (LCLs and the genotypes distributed by the international HapMap project, we identified 45 thousands of potential SNP-induced regulatory relationships among genes (the significance level for the underlying associations between expression traits and SNP genotypes was set at FDR < 0.01. We grouped the identified relationships into four classes (paradigms according to the two different mechanisms by which the regulatory SNPs affect their cis- and trans- regulated genes, modifying mRNA level or altering transcript splicing patterns. We further organized the relationships in each class into a set of network modules with the cis- regulated genes as hubs. We found that the target genes in a network module were often characterized by significant functional similarity, and the distributions of the target genes in three out of the four networks roughly resemble a power-law, a typical pattern of gene networks obtained from mutation experiments. By two case studies, we also demonstrated that significant biological insights can be inferred from the identified network modules.

  9. Mathematical model of the glucose–insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kyungreem [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kang, Hyuk [National Institute for Mathematical Sciences, Daejeon 305-340 (Korea, Republic of); Choi, M.Y., E-mail: mychoi@snu.ac.kr [Department of Physics and Astronomy and Center for Theoretical Physics, Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Jinwoong, E-mail: jwkim@snu.ac.kr [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Myung-Shik [Department of Medicine, Samsung Medical Center, and School of Medicine, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of)

    2012-10-01

    A theoretical approach to the glucose–insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca{sup 2+} concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose–insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination. -- Highlights: ► We present a mathematical model for the glucose–insulin regulatory system. ► This model combines the microscopic insulin secretion mechanism in a pancreatic β-cell and macroscopic glucose dynamics at the whole-body level. ► This work is expected to provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  10. A multiscale modelling methodology applicable for regulatory purposes taking into account effects of complex terrain and buildings on pollutant dispersion: a case study for an inner Alpine basin.

    Science.gov (United States)

    Oettl, D

    2015-11-01

    Dispersion modelling in complex terrain always has been challenging for modellers. Although a large number of publications are dedicated to that field, candidate methods and models for usage in regulatory applications are scarce. This is all the more true when the combined effect of topography and obstacles on pollutant dispersion has to be taken into account. In Austria, largely situated in Alpine regions, such complex situations are quite frequent. This work deals with an approach, which is in principle capable of considering both buildings and topography in simulations by combining state-of-the-art wind field models at the micro- (methodology is not suited for computing detailed time and space variations of pollutant concentrations.

  11. Guatemalan potato moth Tecia solanivora distinguish odour profiles from qualitatively different potatoes Solanum tuberosum L.

    DEFF Research Database (Denmark)

    Karlsson, Miriam Frida; Birgersson, Göran; Witzgall, Peter

    2013-01-01

    . In choice tests, females laid significantly more eggs in response to potato odour of healthy tubers and female oviposition preference correlated with higher larval survival. Survival of larvae was negatively correlated with the tuber content of the steroid glycoalkaloids α-solanine and α-chaconine: healthy...

  12. Relationship between Mood Change, Odour and Its Physiological Effects in Humans While Inhaling the Fragrances of Essential Oils as well as Linalool and Its Enantiomers

    Directory of Open Access Journals (Sweden)

    Tomomi Matumura

    2013-03-01

    Full Text Available Humans can detect and discriminate a vast number of odours. The number perceived as distinguishable is estimated to be more than ten thousand. Humans are capable of distinguishing even slight alterations in the structure of an odorous molecule. A pair of enantiomers of an odorant, which possess the same molecular structures except for the chiral position, can trigger profoundly different odour perceptions. How precisely can humans and their olfactory system detect and discriminate such a great variety of odours and such subtle differences in the molecular structures? In a series of studies, we have attempted to examine the relationship between mood change, odour and its physiological effects, by focusing on the possible verbal and non-verbal changes in humans induced by smelling the fragrances of essential oils as well as linalool and its enantiometric isomers. In this article, we provide an overview of our recent verbal and non-verbal studies. We then discuss how our findings may contribute to the assessment of psychophysiological responses of essential oils as well as how our research can contribute to the study of human chemoreception science, by shedding light on the sophistication of the olfactory system in its ability to detect and discriminate odors.

  13. Odours Discrimination between Familiar and Unfamiliar Individuals by Crocodile Lizard (Shinisaurus crocodilurus)%鳄蜥对熟悉和陌生个体气味的辨别

    Institute of Scientific and Technical Information of China (English)

    蒋洁; 武正军; 于海; 黄乘明; 蔡凤金; 王振兴; 何南

    2012-01-01

    个体辨别对于减少同种争斗以及配偶选择具有重要意义.我们用棉棒粘取鳄蜥(Shinisaurus crocodilurus)尿液作为气味源,以香水作为对照,测定鳄蜥对熟悉个体气味、陌生个体气味以及香水的舔舌次数和舔舌潜伏期,来探讨鳄蜥通过化学信息辨别熟悉和陌生个体的能力.结果显示,不论是雌性还是雄性,对不同个体尿液的舔舌次数均显著高于对香水的,舔舌潜伏期显著短于香水的;尽管雄性对陌生同性个体气味与熟悉同性个体气味的舔舌次数无显著差异,但对前者的舔舌潜伏期显著短于后者;雄性对陌生雌性气味的舔舌次数显著多于熟悉雌性气味的,对前者的舔舌潜伏期显著短于后者;雌性对陌生雄性气味的舔舌潜伏期显著短于对熟悉雄性气味的;雄鳄蜥对陌生雌性气味的舔舌次数显著多于雌鳄蜥对陌生雄性的.结果表明,鳄蜥能辨别同种个体的化学信息,并能通过化学信息来辨别熟悉和陌生个体,推测鳄蜥的这种辨别能力对其领域分配以及繁殖交配有重要作用.%Chemical discrimination is important for reptiles in reducing population competition and mating choice. In order to understand the discriminating ability of Crocodile Lizard ( Shinisaurus crocodilurus) on familiar and unfamiliar individual through chemical cues, we used cotton swabs containing perfume ( cologne) , chemical stimuli from urine of familiar and unfamiliar individuals as chemical odours, to test the discrimination ability of lizard by counting the times of tongue flicking and latency duration. Both of male and female Crocodile Lizards flicked their tongue much higher frequency when they were served cotton swabs with familiar and unfamiliar odours than they did with cologne; the latency time toward familiar and unfamiliar odours were significantly shorter than that toward cologne. However, the tongue-flick frequency of males toward unfamiliar and

  14. Effect of reuterin-producing Lactobacillus reuteri coupled with glycerol on the volatile fraction, odour and aroma of semi-hard ewe milk cheese.

    Science.gov (United States)

    Gómez-Torres, Natalia; Ávila, Marta; Delgado, David; Garde, Sonia

    2016-09-02

    The effect of the biopreservation system formed by Lactobacillus reuteri INIA P572, a reuterin-producing strain, and glycerol (required for reuterin production), on the volatile fraction, aroma and odour of industrial sized semi-hard ewe milk cheese (Castellano type) was investigated over a 3-month ripening period. The volatile compounds were extracted and analyzed by SPME-GC-MS and cheese odour and aroma profiles were studied by descriptive sensory analysis. Control cheese was made only with a mesophilic starter and experimental cheeses with L. reuteri were made with and without glycerol. The addition of L. reuteri INIA P572 to milk enhanced the formation of six volatile compounds. Despite the changes in the volatile compounds profile, the use of L. reuteri INIA P572 did not noticeably affect the sensory characteristics of cheese. On the other hand, the addition of L. reuteri INIA P572 coupled with 30mM glycerol enhanced the formation of twelve volatile compounds, but decreased the formation of five ones. The use of the biopreservation system did not affect overall odour and aroma quality of cheese although it resulted in a significant decrease of the odour intensity scores. In addition, this cheese received significant higher scores for "cheesy" aroma and significant lower scores for the aroma attributes "milky", "caramel" and "yogurt-like". The first two axes of a principal component analysis (PCA) performed for selected volatile compounds and sensory characteristics, accounting for 75% of the variability between cheeses, separated cheeses made with L. reuteri INIA P572 and glycerol from the rest of cheeses, and also differentiated control cheese from cheeses made with L. reuteri INIA P572 from day 60 onward. Our results showed that the reuterin-producing L. reuteri INIA P572 strain, when coupled with glycerol, may be a suitable biopreservation system to use in cheese without affecting odour and aroma quality.

  15. The role of Personal Self-Regulation and Regulatory Teaching to predict motivational-affective variables, achievement and satisfaction: A structural model

    Directory of Open Access Journals (Sweden)

    Jesus ede la Fuente

    2015-04-01

    Full Text Available The present investigation examines how personal self-regulation (presage variable and regulatory teaching (process variable of teaching relate to learning approaches, strategies for coping with stress, and self-regulated learning (process variables of learning and, finally, how they relate to performance and satisfaction with the learning process (product variables. The objective was to clarify the associative and predictive relations between these variables, as contextualized in two different models that use the presage-process-product paradigm (the Biggs and DEDEPRO models. A total of 1101 university students participated in the study. The design was cross-sectional and retrospective with attributional (or selection variables, using correlations and structural analysis. The results provide consistent and significant empirical evidence for the relationships hypothesized, incorporating variables that are part of and influence the teaching-learning process in Higher Education. Findings confirm the importance of interactive relationships within the teaching-learning process, where personal self-regulation is assumed to take place in connection with regulatory teaching. Variables that are involved in the relationships validated here reinforce the idea that both personal factors and teaching and learning factors should be taken into consideration when dealing with a formal teaching-learning context at university.

  16. Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

    Directory of Open Access Journals (Sweden)

    Peng Chien

    2010-06-01

    datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.

  17. Modification of the FoxP3 transcription factor principally affects inducible T regulatory cells in a model of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johan Verhagen

    Full Text Available T regulatory (Treg cells expressing the transcription factor FoxP3 play a key role in protection against autoimmune disease. GFP-FoxP3 reporter mice have been used widely to study the induction, function and stability of both thymically- and peripherally-induced Treg cells. The N-terminal modification of FoxP3, however, affects its interaction with transcriptional co-factors; this can alter Treg cell development and function in certain self-antigen specific animal models. Interestingly, Treg cell function can be negatively or positively affected, depending on the nature of the model. In this study, we focused on the effect of the GFP-FoxP3 reporter on Treg cell development and function in the Tg4 mouse model. In this model, T cells express a transgenic T cell receptor (TCR specific for the Myelin Basic Protein (MBP peptide Ac1-9, making the animals susceptible to experimental autoimmune encephalomyelitis (EAE, a disease akin to multiple sclerosis in humans. Unlike diabetes-susceptible mice, Tg4 FoxP3(gfp mice did not develop spontaneous autoimmune disease and did not demonstrate augmented susceptibility to induced disease. Concurrently, thymic generation of natural Treg cells was not negatively affected. The induction of FoxP3 expression in naive peripheral T cells was, however, significantly impaired as a result of the transgene. This study shows that the requirements for the interaction of FoxP3 with co-factors, which governs its regulatory ability, differ not only between natural and inducible Treg cells but also between animal models of diseases such as diabetes and EAE.

  18. Temporal pattern of ICAM-I mediated regulatory T cell recruitment to sites of inflammation in adoptive transfer model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sebastian Doerck

    Full Text Available Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS. However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3 only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development.

  19. 基因表达调控机制--操纵子模型的确立%The establishment of genetic regulatory mechanisms-operon model

    Institute of Scientific and Technical Information of China (English)

    向义和

    2013-01-01

    笔者介绍了基因表达调控机制--操纵子模型建立的过程:诱导物和阻遏物的发现及对其性质的研究;调节基因和操纵基因的发现及对其性能的分析;操纵子模型建立和实验验证。%The establishment of genetic regulatory mechanisms-operon model is introduced. The key events include the discovery of inducer, repressor, regulator gene and operator, the study of their properties, the establishment of operon model and the evidence of experiment.

  20. Resistance to re-challenge in the Brown Norway rat model of vasculitis is not always complete and may reveal separate effector and regulatory populations

    Science.gov (United States)

    Vinen, C S; Turner, D R; Oliveira, D B G

    2004-01-01

    Administration of mercuric chloride to Brown Norway rats results in T helper type 2 (Th2)- dominated autoimmunity characterized by high immunoglobulin E (IgE) concentrations, the production of multiple IgG autoantibodies, including those to glomerular basement membrane (GBM), arthritis and caecal vasculitis. After 14 days animals immunoregulate and auto-immunity resolves even if mercuric chloride injections are continued. In a third phase, if animals are re-challenged with mercuric chloride 6 weeks later, they show only attenuated autoimmunity with lower anti-GBM antibody concentrations and arthritis scores. Resistance to the induction of anti-GBM antibodies can also be achieved following an initial challenge with low-dose (one-tenth standard dose) mercuric chloride. We have now studied this resistant phase in more detail. We have shown, first, that following an initial full-dose mercuric chloride challenge, resistance also affects susceptibility to caecal vasculitis. Second, following an initial full-dose mercuric chloride challenge, the IgE response upon re-challenge is initially accelerated but subsequently enters a resistant phase and third, following an initial challenge with low-dose mercuric chloride, resistance is also seen to the induction of caecal vasculitis but is not seen in IgE serology (where results suggest competing effector and regulatory cell populations). Studying such regulatory phases in animal models of autoimmunity may be of benefit in the future in designing new therapies for human vasculitis. PMID:15379988

  1. Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease.

    Science.gov (United States)

    Mack, Douglas G; Falta, Michael T; McKee, Amy S; Martin, Allison K; Simonian, Philip L; Crawford, Frances; Gordon, Terry; Mercer, Robert R; Hoover, Mark D; Marrack, Philippa; Kappler, John W; Tuder, Rubin M; Fontenot, Andrew P

    2014-06-10

    Susceptibility to chronic beryllium disease (CBD) is linked to certain HLA-DP molecules, including HLA-DP2. To elucidate the molecular basis of this association, we exposed mice transgenic (Tg) for HLA-DP2 to beryllium oxide (BeO) via oropharyngeal aspiration. As opposed to WT mice, BeO-exposed HLA-DP2 Tg mice developed mononuclear infiltrates in a peribronchovascular distribution that were composed of CD4(+) T cells and included regulatory T (Treg) cells. Beryllium-responsive, HLA-DP2-restricted CD4(+) T cells expressing IFN-γ and IL-2 were present in BeO-exposed HLA-DP2 Tg mice and not in WT mice. Using Be-loaded HLA-DP2-peptide tetramers, we identified Be-specific CD4(+) T cells in the mouse lung that recognize identical ligands as CD4(+) T cells derived from the human lung. Importantly, a subset of HLA-DP2 tetramer-binding CD4(+) T cells expressed forkhead box P3, consistent with the expansion of antigen-specific Treg cells. Depletion of Treg cells in BeO-exposed HLA-DP2 Tg mice exacerbated lung inflammation and enhanced granuloma formation. These findings document, for the first time to our knowledge, the development of a Be-specific adaptive immune response in mice expressing HLA-DP2 and the ability of Treg cells to modulate the beryllium-induced granulomatous immune response.

  2. Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms.

    Directory of Open Access Journals (Sweden)

    Alan E Bilsland

    2014-02-01

    Full Text Available Cancer cells depend on transcription of telomerase reverse transcriptase (TERT. Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3'-oxime (BIO predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several

  3. Finding Groups Using Model-Based Cluster Analysis: Heterogeneous Emotional Self-Regulatory Processes and Heavy Alcohol Use Risk

    Science.gov (United States)

    Mun, Eun Young; von Eye, Alexander; Bates, Marsha E.; Vaschillo, Evgeny G.

    2008-01-01

    Model-based cluster analysis is a new clustering procedure to investigate population heterogeneity utilizing finite mixture multivariate normal densities. It is an inferentially based, statistically principled procedure that allows comparison of nonnested models using the Bayesian information criterion to compare multiple models and identify the…

  4. Finding Groups Using Model-Based Cluster Analysis: Heterogeneous Emotional Self-Regulatory Processes and Heavy Alcohol Use Risk

    Science.gov (United States)

    Mun, Eun Young; von Eye, Alexander; Bates, Marsha E.; Vaschillo, Evgeny G.

    2008-01-01

    Model-based cluster analysis is a new clustering procedure to investigate population heterogeneity utilizing finite mixture multivariate normal densities. It is an inferentially based, statistically principled procedure that allows comparison of nonnested models using the Bayesian information criterion to compare multiple models and identify the…

  5. A regulatory model for conformity evaluation in natural gas building installations; Um modelo regulatorio para avaliacao da conformidade das instalacoes prediais de gas natural

    Energy Technology Data Exchange (ETDEWEB)

    Fossa, Alberto Jose; Santos, Edmilson Moutinho dos [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Eletrotecnica e Energia

    2008-07-01

    The challenge of the Brazilian growth needs to consider necessarily the energy arrangements, and natural gas has relevant participation in this matter. The possibility of its end use that make possible an effective adequacy of our energy matrix must be supported by modern concepts of quality and conformity. In this particular, the program of 'Tecnologia Industrial Basica' (TIB), including concepts and application of conformity evaluation processes, is considered basic for the construction of a consistent gas market. This paper present the Brazilian reality related to TIB aspects and elements, from which it constructs a technician and regulatory building gas installations model proposal for a conformity evaluation program in the country. (author)

  6. Self-regulatory strength depletion and muscle-endurance performance: a test of the limited-strength model in older adults.

    Science.gov (United States)

    Bray, Steven R; Martin Ginis, Kathleen A; Woodgate, Jennifer

    2011-07-01

    Self-regulation consumes a form of strength or energy. The authors investigated aftereffects of self-regulation depletion on muscle-endurance performance in older adults. Participants (N = 61, mean age = 71) were randomized to a self-regulation-depletion or control group and completed 2 muscle-endurance performance tasks involving isometric handgrip squeezing that were separated by a cognitive-depletion task. The depletion group showed greater deterioration of muscle-endurance performance than controls, F(1, 59) = 7.31, p = .009. Results are comparable to those of younger adults in a similar study and support Baumeister et al.'s limited-strength model. Self-regulation may contribute to central-nervous-system fatigue; however, biological processes may allow aging muscle to offset depletion of self-regulatory resources affecting muscle-endurance performance.

  7. Adoptive transfer of T regulatory cells inhibits lipopolysaccharide-induced inflammation in fetal brain tissue in a late-pregnancy preterm birth mouse model.

    Science.gov (United States)

    Wang, Fan; Xiao, Mi; Chen, Ru-Juan; Lin, Xiao-Jie; Siddiq, Muhammad; Liu, Li

    2017-02-01

    To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6), CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in the fetal brain tissue. Foxp3, IL-6, and TLR-4 expression were detected by polymerase chain reaction and Western blot; CD68 expression level was detected using immunochemical analysis. Foxp3, IL-6, TLR-4, and CD68 expressions in fetal brain were significantly induced by maternal LPS administration, and the increased expression levels were markedly reduced by adoptive transfer of Tregs. Maternal LPS exposure significantly induced inflammation in perinatal brain tissue, and Tregs negatively regulated this LPS-induced inflammation. © 2016 International Federation for Cell Biology.

  8. Identification of SNP-containing regulatory motifs in the myelodysplastic syndromes model using SNP arrays and gene expression arrays

    Institute of Scientific and Technical Information of China (English)

    Jing Fan; Jennifer G.Dy; Chung-Che Chang; Xiaobo Zhou

    2013-01-01

    Myelodysplastic syndromes have increased in frequency and incidence in the American population,but patient prognosis has not significantly improved over the last decade.Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified.In this study,we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor-binding sites (TFBS).We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS.The potential regulation of SNP-containing motifs affects only when certain mutations occur.These motifs can be identified from a group of co-expressed genes with copy number variation.Then,we used a sliding window to identify motif candidates near SNPs on gene sequences.The candidates were filtered by coarse thresholding and fine statistical testing.Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure,we identified 28 SNP-containing motifs as candidate TFBS.We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database.Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes.The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes.Thus,our proposed method,a novel strategy for associating two data categories,is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.

  9. Expression of Smad7 and Smad ubiquitin regulatory factor 2 in a rat model of chronic pancreatitis.

    Science.gov (United States)

    Hou, Xiao Jia; Jin, Zhen Dong; Jiang, Fei; Zhu, Jian Wei; Li, Zhao Shen

    2015-07-01

    To quantify the expressions of Smad7 and Smad ubiquitin regulatory factor 2 (Smurf2) in the pancreas in rats with chronic pancreatitis (CP). A total of 16 male Wistar rats were randomly divided into the control group and the CP group, with 8 rats in each group. CP was induced in vivo with dibutyltin dichloride (DBTC). Four weeks after DBTC administration, histological assessment and the measurement of hydroxyproline content in the pancreatic tissues were performed to assess the inflammation and fibrosis of the pancreas. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) for transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) were applied to assess activated pancreatic stellate cells (PSC) and TGF-β1 expression. Smad7 and Smurf2 expressions in the pancreas were measured using Western blot and RT-PCR. Typical histopathological characteristics of DBTC-induced CP in the rats with extensively activated PSC. Compared with the control group, the expressions of TGF-β1, α-SMA and hydroxyproline content in the pancreatic tissues in the CP group were significantly increased. Meanwhile, the mRNA and protein expressions of Smad7 and Smurf2 were significant increased in the fibrotic pancreas, in which the expressions of Smad7 proteins showed an obvious reduction compared with controls. The dysregulation of Smad7 and Smurf2 may be associated with the pathogenesis of pancreatic fibrosis through the TGF-β signaling pathway. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  10. Global Summit on Regulatory Science 2013.

    Science.gov (United States)

    Howard, Paul C; Tong, Weida; Weichold, Frank; Healy, Marion; Slikker, William

    2014-12-01

    Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed.

  11. Boolean modeling: a logic-based dynamic approach for understanding signaling and regulatory networks and for making useful predictions.

    Science.gov (United States)

    Albert, Réka; Thakar, Juilee

    2014-01-01

    The biomolecules inside or near cells form a complex interacting system. Cellular phenotypes and behaviors arise from the totality of interactions among the components of this system. A fruitful way of modeling interacting biomolecular systems is by network-based dynamic models that characterize each component by a state variable, and describe the change in the state variables due to the interactions in the system. Dynamic models can capture the stable state patterns of this interacting system and can connect them to different cell fates or behaviors. A Boolean or logic model characterizes each biomolecule by a binary state variable that relates the abundance of that molecule to a threshold abundance necessary for downstream processes. The regulation of this state variable is described in a parameter free manner, making Boolean modeling a practical choice for systems whose kinetic parameters have not been determined. Boolean models integrate the body of knowledge regarding the components and interactions of biomolecular systems, and capture the system's dynamic repertoire, for example the existence of multiple cell fates. These models were used for a variety of systems and led to important insights and predictions. Boolean models serve as an efficient exploratory model, a guide for follow-up experiments, and as a foundation for more quantitative models.

  12. Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model

    Science.gov (United States)

    Nagata, Yuka; Yamamoto, Takeshi; Hayashi, Michie; Hayashi, Shusaku; Kadowaki, Makoto

    2017-01-01

    Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT. The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount. Allergic symptoms decreased in the OIT-treated FA mice. OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased the level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma. Moreover, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, and the combination therapy further suppressed the Th2 immune responses and the mast cell degranulation. In addition, OIT significantly increased the population of Foxp3+ CD4+ regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto. Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon. These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment. PMID:28107533

  13. Statement on the suitability of the BEEHAVE model for its potential use in a regulatory context and for the risk assessment of multiple stressors in honeybees at the landscape level

    DEFF Research Database (Denmark)

    EFSA PPR Panel (EFSA Panel on Plant Protection Products and their Residues); Topping, Christopher John

    2015-01-01

    The Panel has interpreted the Terms of Reference by carrying out a stepwise evaluation of the BEEHAVE simulation model with a view to assessing its suitability for use in a regulatory context and for risk assessment of multiple stressors at the landscape level. The EFSA opinion on good modelling...... usable in a regulatory context primarily because it needs a pesticide module. BEEHAVE has a Varroa/virus module, although this seems to underestimate the impact of Varroa/virus on colony survival, and additional stressors (chemical and biological) would need to be added to allow investigation...

  14. VEN-120, a Recombinant Human Lactoferrin, Promotes a Regulatory T Cell [Treg] Phenotype and Drives Resolution of Inflammation in Distinct Murine Models of Inflammatory Bowel Disease.

    Science.gov (United States)

    MacManus, Christopher F; Collins, Colm B; Nguyen, Tom T; Alfano, Randall W; Jedlicka, Paul; de Zoeten, Edwin F

    2017-09-01

    Inflammatory bowel disease [IBD] is characterised by a disruption of immune homeostasis, which is tightly regulated to protect against harmful pathogens yet not react to commensal antigens. Animal studies indicate that regulatory T cells [Treg] modulate the immune response to prevent IBD development. Lactoferrin [LF] is an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and at mucosal sites. However, the effect of LF on specific T lymphocyte populations has not been studied. Here, we identify a novel mechanism by which a recombinant human LF, VEN-120, regulates T cell populations in health and disease. Two murine models of intestinal inflammation, the dextran sodium sulphate colitis model and the TNFΔARE/+ model of ileitis, were used to study the anti-inflammatory and T cell modulating ability of VEN-120. Flow cytometry was used to evaluate T cell populations within the lamina propria and mesenteric lymph nodes, and to evaluate the effect of VEN-120 on CD4+ T cells in vitro. VEN-120 reduced inflammation in both models of IBD, accompanied by increased Tregs in the intestinal lamina propria. Treatment of CD4+ T cells in vitro resulted in an upregulation of Treg genes and skewing towards a Treg population. This in vitro T cell skewing translated to an increase of Treg homing to the intestinal lamina propria and associated lymph tissue in healthy mice. These data provide a novel immunological mechanism by which VEN-120 modulates T cells to restrict inflammatory T cell-driven disease.

  15. Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.

    NARCIS (Netherlands)

    Gordon, S.; Daneshian, M.; Bouwstra, J.A.; Caloni, F.; Constant, S.; Davies, D.E.; Dandekar, G.; Guzman, C.A.; Fabian, E.; Haltner, E.; Hartung, T.; Hasiwa, N.; Hayden, P.; Kandarova, H.; Khare, S.; Krug, H.F.; Kneuer, C.; Leist, M.; Lian, G.; Marx, U.; Metzger, M.; Ott, K.; Prieto, P.; Roberts, M.S.; Roggen, E.L.; Tralau, T.; Braak, van den C.; Walles, H.; Lehr, C.M.

    2015-01-01

    Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields,

  16. Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.

    NARCIS (Netherlands)

    Gordon, S.; Daneshian, M.; Bouwstra, J.A.; Caloni, F.; Constant, S.; Davies, D.E.; Dandekar, G.; Guzman, C.A.; Fabian, E.; Haltner, E.; Hartung, T.; Hasiwa, N.; Hayden, P.; Kandarova, H.; Khare, S.; Krug, H.F.; Kneuer, C.; Leist, M.; Lian, G.; Marx, U.; Metzger, M.; Ott, K.; Prieto, P.; Roberts, M.S.; Roggen, E.L.; Tralau, T.; Braak, van den C.; Walles, H.; Lehr, C.M.

    2015-01-01

    Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields,

  17. Key considerations for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection

    OpenAIRE

    Elliker, Kevin R; Sommerville, Barbara A; Donald M. Broom; Neal, David E.; Armstrong, Sarah; Williams, Hywel C

    2014-01-01

    Background Cancer detection using sniffer dogs is a potential technology for clinical use and research. Our study sought to determine whether dogs could be trained to discriminate the odour of urine from men with prostate cancer from controls, using rigorous testing procedures and well-defined samples from a major research hospital. Methods We attempted to train ten dogs by initially rewarding them for finding and indicating individual prostate cancer urine samples (Stage 1). If dogs were suc...

  18. Petri nets in Snoopy: a unifying framework for the graphical display, computational modelling, and simulation of bacterial regulatory networks.

    Science.gov (United States)

    Marwan, Wolfgang; Rohr, Christian; Heiner, Monika

    2012-01-01

    Using the example of phosphate regulation in enteric bacteria, we demonstrate the particular suitability of stochastic Petri nets to model biochemical phenomena and their simulative exploration by various features of the software tool Snoopy.

  19. On the Path to SunShot. Utility Regulatory and Business Model Reforms for Addressing the Financial Impacts of Distributed Solar on Utilities

    Energy Technology Data Exchange (ETDEWEB)

    Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Miller, John [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sigrin, Ben [National Renewable Energy Lab. (NREL), Golden, CO (United States); Reiter, Emerson [National Renewable Energy Lab. (NREL), Golden, CO (United States); Cory, Karlynn [National Renewable Energy Lab. (NREL), Golden, CO (United States); McLaren, Joyce [National Renewable Energy Lab. (NREL), Golden, CO (United States); Seel, Joachim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Darghouth, Naim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-01

    Net-energy metering (NEM) has helped drive the rapid growth of distributed PV (DPV) but has raised concerns about electricity cost shifts, utility financial losses, and inefficient resource allocation. These concerns have motivated real and proposed reforms to utility regulatory and business models. This report explores the challenges and opportunities associated with such reforms in the context of the U.S. Department of Energy's SunShot Initiative. Most of the reforms to date address NEM concerns by reducing the benefits provided to DPV customers and thus constraining DPV deployment. Eliminating NEM nationwide, by compensating exports of PV electricity at wholesale rather than retail rates, could cut cumulative DPV deployment by 20% in 2050 compared with a continuation of current policies. This would slow the PV cost reductions that arise from larger scale and market certainty. It could also thwart achievement of the SunShot deployment goals even if the initiative's cost targets are achieved. This undesirable prospect is stimulating the development of alternative reform strategies that address concerns about distributed PV compensation without inordinately harming PV economics and growth. These alternatives fall into the categories of facilitating higher-value DPV deployment, broadening customer access to solar, and aligning utility profits and earnings with DPV. Specific strategies include utility ownership and financing of DPV, community solar, distribution network operators, services-driven utilities, performance-based incentives, enhanced utility system planning, pricing structures that incentivize high-value DPV configurations, and decoupling and other ratemaking reforms that reduce regulatory lag. These approaches represent near- and long-term solutions for preserving the legacy of the SunShot Initiative.

  20. Response to Nuclear Regulatory Commission`s ten questions pertaining to site-specific models for use in the license termination rule: Multimedia Environmental Pollutant Assessment System (MEPAS)

    Energy Technology Data Exchange (ETDEWEB)

    Buck, J.W.; Whelan, G.; Strenge, D.L.; Hoopes, B.L.; McDonald, J.P.; Castleton, K.J.; Pelton, M.A.; Gelston, G.M.; Taira, R.Y. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-05-01

    This paper is in response to the US Nuclear Regulatory Commission (NRC) ten questions posed at the Modeling Workshop held November 13 and 14, 1997. The ten questions were developed in advance of the workshop to allow model developers to prepare a presentation at the Workshop. This paper is an expanded version of the Multimedia Environmental Pollutant Assessment System (MEPAS) presentation given at the Modeling Workshop by Pacific Northwest National Laboratory (PNNL) staff. This paper is organized by the ten questions asked by the NRC, each section devoted to a single question. The current version of methodology is MEPAS 3.2 (NRC 1997) and the discussion in this paper will pertain to that version. In some cases, MEPAS 4.0, which is currently being developed under the Framework for Risk Analysis in Multimedia Environmental Systems (FRAMES) (Whelan et al. 1997), will be referenced to inform the reader of potential capabilities in the near future. A separate paper is included in the document that discusses the FRAMES concept.

  1. Chemical compositions and muddy flavour/odour of protein hydrolysate from Nile tilapia and broadhead catfish mince and protein isolate.

    Science.gov (United States)

    Yarnpakdee, Suthasinee; Benjakul, Soottawat; Penjamras, Pimpimol; Kristinsson, Hordur G

    2014-01-01

    Chemical compositions and muddy compounds in dorsal and ventral muscles of Nile tilapia and broadhead catfish were comparatively studied. On a dry weight basis, Nile tilapia was rich in protein (93.1-93.8%), whilst broadhead catfish contained protein (55.2-59.5%) and lipid (36.6-42.4%) as the major constituents. Ventral portion had higher lipid or phospholipid contents with coincidentally higher geosmin and/or 2-methylisoborneol (2-MIB) contents. Geosmin was found in mince of Nile tilapia and broadhead catfish at levels of 1.5 and 3.2μg/kg, respectively. Broadhead catfish mince had 2-MIB at level of 0.8μg/kg, but no 2-MIB was detected in Nile tilapia counterpart. When pre-washing and alkaline solubilisation were applied for preparing protein isolate (PI), lipid and phospholipid contents were lowered with concomitant decrease in geosmin and 2-MIB contents. Protein hydrolysate produced from PI had a lighter colour and a lower amount of muddy compounds, compared with that prepared from mince. Therefore, PI from both Nile tilapia and broadhead catfish could serve as the promising proteinaceous material, yielding protein hydrolysate with the negligible muddy odour and flavour.

  2. Unraveling the Light-Specific Metabolic and Regulatory Signatures of Rice through Combined in Silico Modeling and Multiomics Analysis.

    Science.gov (United States)

    Lakshmanan, Meiyappan; Lim, Sun-Hyung; Mohanty, Bijayalaxmi; Kim, Jae Kwang; Ha, Sun-Hwa; Lee, Dong-Yup

    2015-12-01

    Light quality is an important signaling component upon which plants orchestrate various morphological processes, including seed germination and seedling photomorphogenesis. However, it is still unclear how plants, especially food crops, sense various light qualities and modulate their cellular growth and other developmental processes. Therefore, in this work, we initially profiled the transcripts of a model crop, rice (Oryza sativa), under four different light treatments (blue, green, red, and white) as well as in the dark. Concurrently, we reconstructed a fully compartmentalized genome-scale metabolic model of rice cells, iOS2164, containing 2,164 unique genes, 2,283 reactions, and 1,999 metabolites. We then combined the model with transcriptome profiles to elucidate the light-specific transcriptional signatures of rice metabolism. Clearly, light signals mediated rice gene expressions, differentially regulating numerous metabolic pathways: photosynthesis and secondary metabolism were up-regulated in blue light, whereas reserve carbohydrates degradation was pronounced in the dark. The topological analysis of gene expression data with the rice genome-scale metabolic model further uncovered that phytohormones, such as abscisate, ethylene, gibberellin, and jasmonate, are the key biomarkers of light-mediated regulation, and subsequent analysis of the associated genes' promoter regions identified several light-specific transcription factors. Finally, the transcriptional control of rice metabolism by red and blue light signals was assessed by integrating the transcriptome and metabolome data with constraint-based modeling. The biological insights gained from this integrative systems biology approach offer several potential applications, such as improving the agronomic traits of food crops and designing light-specific synthetic gene circuits in microbial and mammalian systems.

  3. A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Sara N Gentry

    Full Text Available Hierarchical organized tissue structures, with stem cell driven cell differentiation, are critical to the homeostatic maintenance of most tissues, and this underlying cellular architecture is potentially a critical player in the development of a many cancers. Here, we develop a mathematical model of mutation acquisition to investigate how deregulation of the mechanisms preserving stem cell homeostasis contributes to tumor initiation. A novel feature of the model is the inclusion of both extrinsic and intrinsic chemical signaling and interaction with the niche to control stem cell self-renewal. We use the model to simulate the effects of a variety of types and sequences of mutations and then compare and contrast all mutation pathways in order to determine which ones generate cancer cells fastest. The model predicts that the sequence in which mutations occur significantly affects the pace of tumorigenesis. In addition, tumor composition varies for different mutation pathways, so that some sequences generate tumors that are dominated by cancerous cells with all possible mutations, while others are primarily comprised of cells that more closely resemble normal cells with only one or two mutations. We are also able to show that, under certain circumstances, healthy stem cells diminish due to the displacement by mutated cells that have a competitive advantage in the niche. Finally, in the event that all homeostatic regulation is lost, exponential growth of the cancer population occurs in addition to the depletion of normal cells. This model helps to advance our understanding of how mutation acquisition affects mechanisms that influence cell-fate decisions and leads to the initiation of cancers.

  4. Using probabilistic terrorism risk modeling for regulatory benefit-cost analysis: application to the Western hemisphere travel initiative in the land environment.

    Science.gov (United States)

    Willis, Henry H; LaTourrette, Tom

    2008-04-01

    This article presents a framework for using probabilistic terrorism risk modeling in regulatory analysis. We demonstrate the framework with an example application involving a regulation under consideration, the Western Hemisphere Travel Initiative for the Land Environment, (WHTI-L). First, we estimate annualized loss from terrorist attacks with the Risk Management Solutions (RMS) Probabilistic Terrorism Model. We then estimate the critical risk reduction, which is the risk-reducing effectiveness of WHTI-L needed for its benefit, in terms of reduced terrorism loss in the United States, to exceed its cost. Our analysis indicates that the critical risk reduction depends strongly not only on uncertainties in the terrorism risk level, but also on uncertainty in the cost of regulation and how casualties are monetized. For a terrorism risk level based on the RMS standard risk estimate, the baseline regulatory cost estimate for WHTI-L, and a range of casualty cost estimates based on the willingness-to-pay approach, our estimate for the expected annualized loss from terrorism ranges from $2.7 billion to $5.2 billion. For this range in annualized loss, the critical risk reduction for WHTI-L ranges from 7% to 13%. Basing results on a lower risk level that results in halving the annualized terrorism loss would double the critical risk reduction (14-26%), and basing the results on a higher risk level that results in a doubling of the annualized terrorism loss would cut the critical risk reduction in half (3.5-6.6%). Ideally, decisions about terrorism security regulations and policies would be informed by true benefit-cost analyses in which the estimated benefits are compared to costs. Such analyses for terrorism security efforts face substantial impediments stemming from the great uncertainty in the terrorist threat and the very low recurrence interval for large attacks. Several approaches can be used to estimate how a terrorism security program or regulation reduces the

  5. Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications.

    Directory of Open Access Journals (Sweden)

    Simon Schafferer

    Full Text Available Multiple system atrophy (MSA is a fatal rapidly progressive α-synucleinopathy, characterized by α-synuclein accumulation in oligodendrocytes. It is accepted that the pathological α-synuclein accumulation in the brain of MSA patients plays a leading role in the disease process, but little is known about the events in the early stages of the disease. In this study we aimed to define potential roles of the miRNA-mRNA regulatory network in the early pre-motor stages of the disease, i.e., downstream of α-synuclein accumulation in oligodendroglia, as assessed in a transgenic mouse model of MSA. We investigated the expression patterns of miRNAs and their mRNA targets in substantia nigra (SN and striatum, two brain regions that undergo neurodegeneration at a later stage in the MSA model, by microarray and RNA-seq analysis, respectively. Analysis was performed at a time point when α-synuclein accumulation was already present in oligodendrocytes at neuropathological examination, but no neuronal loss nor deficits of motor function had yet occurred. Our data provide a first evidence for the leading role of gene dysregulation associated with deficits in immune and inflammatory responses in the very early, non-symptomatic disease stages of MSA. While dysfunctional homeostasis and oxidative stress were prominent in SN in the early stages of MSA, in striatum differential gene expression in the non-symptomatic phase was linked to oligodendroglial dysfunction, disturbed protein handling, lipid metabolism, transmembrane transport and altered cell death control, respectively. A large number of putative miRNA-mRNAs interaction partners were identified in relation to the control of these processes in the MSA model. Our results support the role of early changes in the miRNA-mRNA regulatory network in the pathogenesis of MSA preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way

  6. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    Science.gov (United States)

    2014-01-01

    Background Obesity is a complex metabolic condition in strong association with various diseases, like type 2 diabetes, resulting in major public health and economic implications. Obesity is the result of environmental and genetic factors and their interactions, including genome-wide genetic interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model for human obesity, offering the possibility to study in-depth organ-level transcriptomic regulations of obesity, unfeasible in humans. Our aim was to reveal adipose tissue co-expression networks, pathways and transcriptional regulations of obesity using RNA Sequencing based systems biology approaches in a porcine model. Methods We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P < 0.001). Functional annotation identified pathways enlightening the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E-7), and immune-related complications (e.g. Natural killer cell mediated cytotoxity, P = 3.8E-5; B cell receptor signaling pathway, P = 7.2E-5). Lemon-Tree identified three potential regulator genes, using confident scores, for the WGCNA module which was associated with osteoclast differentiation: CCR1, MSR1 and SI1 (probability scores respectively 95.30, 62.28, and

  7. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model.

    Science.gov (United States)

    Kogelman, Lisette J A; Cirera, Susanna; Zhernakova, Daria V; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N

    2014-09-30

    Obesity is a complex metabolic condition in strong association with various diseases, like type 2 diabetes, resulting in major public health and economic implications. Obesity is the result of environmental and genetic factors and their interactions, including genome-wide genetic interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model for human obesity, offering the possibility to study in-depth organ-level transcriptomic regulations of obesity, unfeasible in humans. Our aim was to reveal adipose tissue co-expression networks, pathways and transcriptional regulations of obesity using RNA Sequencing based systems biology approaches in a porcine model. We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E-7), and immune-related complications (e.g. Natural killer cell mediated cytotoxity, P = 3.8E-5; B cell receptor signaling pathway, P = 7.2E-5). Lemon-Tree identified three potential regulator genes, using confident scores, for the WGCNA module which was associated with osteoclast differentiation: CCR1, MSR1 and SI1 (probability scores respectively 95.30, 62.28, and 34.58). Moreover, detection of differentially connected genes identified various genes previously identified to be

  8. Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging.

    Directory of Open Access Journals (Sweden)

    Christine Duval

    Full Text Available To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3 was compared to that of tissues containing natural photo-aged fibroblasts (n = 3 which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the

  9. The regulation of regulation: IL-10 increases CD4(+) CD25(+) regulatory T cells but impairs their immunosuppressive activity in murine models with schistosomiasis japonica or asthma.

    Science.gov (United States)

    He, Lei; Zhou, Sha; Qi, Qianqian; Chi, Ying; Zhu, Jifeng; Xu, Zhipeng; Wang, Xuefeng; Hoellwarth, Jason; Liu, Feng; Chen, Xiaojun; Su, Chuan

    2017-08-11

    CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) play an important role in maintaining immune homeostasis. Interleukin 10 (IL-10), a cytokine with anti-inflammatory capacities, also has a critical role in controlling immune responses. In addition, it is well known that production of IL-10 is one of suppression mechanisms by Tregs. However, the action of IL-10 on Tregs themselves remains insufficiently understood. In this study, by using a Schistosoma japonicum (S. japonicum)-infected murine model, we show that the elevated IL-10 contributed to Treg induction but impaired their immunosuppressive function. Our investigations further suggest that this may relate to up-regulating serum TGF-β level but decreasing membrane-bound TGF-β (mTGF-β) of Tregs by IL-10 during S. japonicum infection. In addition, similar IL-10-mediated regulation on Tregs was also confirmed in the murine model of asthma. In general, our findings identify a previously unrecognized opposite regulation of IL-10 on Tregs and provide a deep insight into the precise regulation in immune responses. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Synthetic biology between challenges and risks: suggestions for a model of governance and a regulatory framework, based on fundamental rights.

    Science.gov (United States)

    Colussi, Ilaria Anna

    2013-01-01

    This paper deals with the emerging synthetic biology, its challenges and risks, and tries to design a model for the governance and regulation of the field. The model is called of "prudent vigilance" (inspired by the report about synthetic biology, drafted by the U.S. Presidential Commission on Bioethics, 2010), and it entails (a) an ongoing and periodically revised process of assessment and management of all the risks and concerns, and (b) the adoption of policies - taken through "hard law" and "soft law" sources - that are based on the principle of proportionality (among benefits and risks), on a reasonable balancing between different interests and rights at stake, and are oriented by a constitutional frame, which is represented by the protection of fundamental human rights emerging in the field of synthetic biology (right to life, right to health, dignity, freedom of scientific research, right to environment). After the theoretical explanation of the model, its operability is "checked", by considering its application with reference to only one specific risk brought up by synthetic biology - biosecurity risk, i.e. the risk of bioterrorism.

  11. Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a murine model of cerebral infarction by arterial embolization.

    Science.gov (United States)

    Lapuente Chala, Catalina; Rengifo Valbuena, Carlos Augusto; Avila Rodríguez, Marco Fidel; Céspedes Rubio, Angel

    2013-01-01

    The pathophysiology of cerebral ischemia is essential for early diagnosis, neurologic recovery, the early onset of drug treatment and the prognosis of ischemic events. Experimental models of cerebral ischemia can be used to evaluate the cellular response phenomena and possible neurological protection by drugs. To characterize the cellular changes in the neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide (DMSO) on a model of ischemia caused by cerebral embolism. Twenty Wistar rats were divided into four groups (n= 5). The infarct was induced with α-bovine thrombin (40 NIH/Unit.). The treated group received 90 mg (100 μL) of DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune-reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J-Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software (Prism 5). Cerebral embolism induced reproducible and reliable lesions in the cortex and hippocampus (CA1)., similar to those of focal models. DMSO did not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented the morphological damage of neurons, and significantly reduced astrocytic hyperactivity in the somato-sensory cortex and CA1 (p DMSO on astrocyte hyperreactivity and neuronal-astroglial cytoarchitecture , gives it potential neuroprotective properties for the treatment of thromboembolic cerebral ischemia in the acute phase.

  12. Development of a modelling framework in response to new European energy-efficiency regulatory obligations. The Irish experience

    Energy Technology Data Exchange (ETDEWEB)

    Hull, David [Arup Consulting Engineers, 15 Oliver Plunkett Street, Cork (Ireland); O Gallachoir, Brian P. [Department of Civil and Environmental Engineering, University College Cork, College Road, Cork (Ireland); Environmental Research Institute, University College Cork, Lee Road, Cork (Ireland); Walker, Neil [School of Geography, Planning and Environmental Policy, University College Dublin, Belfield, Dublin 4 (Ireland)

    2009-12-15

    Momentum has been building for an EU-wide approach to energy policy in which energy end-use efficiency is regarded as one of the main planks. Member States are already obliged to plan for the achievement of energy savings targets in respect of the period 2008-2016 and they now face additional economy-wide targets for 2020. Efficiency investments are widely regarded as capable of improving industrial competitiveness, security of energy supply and the abatement of greenhouse gas emissions. Nevertheless, the design of policy packages may involve trade-offs between these objectives. The challenge for energy modellers is to quantify future energy savings associated with combinations of efficiency measures. This paper draws on the international experience in energy modelling and tracks recent progress that has been made towards a harmonised European framework for verification of savings. It points to the significant development work that remains to be done, particularly to enable an increased reliance on bottom-up evaluation methods. One significant gap in our knowledge relates to the required adjustment of technical savings due to behavioural factors such as rebound effects. The paper uses one country (Ireland) as a case study to demonstrate how a framework is being developed to respond to these new requirements. (author)

  13. Development of a modelling framework in response to new European energy-efficiency regulatory obligations: The Irish experience

    Energy Technology Data Exchange (ETDEWEB)

    Hull, David [Arup Consulting Engineers, 15 Oliver Plunkett Street, Cork (Ireland); O Gallachoir, Brian P. [Department of Civil and Environmental Engineering, University College Cork, College Road, Cork (Ireland); Environmental Research Institute, University College Cork, Lee Road, Cork (Ireland); Walker, Neil, E-mail: neil.walker@ucd.i [School of Geography, Planning and Environmental Policy, University College Dublin, Belfield, Dublin 4 (Ireland)

    2009-12-15

    Momentum has been building for an EU-wide approach to energy policy in which energy end-use efficiency is regarded as one of the main planks. Member States are already obliged to plan for the achievement of energy savings targets in respect of the period 2008-2016 and they now face additional economy-wide targets for 2020. Efficiency investments are widely regarded as capable of improving industrial competitiveness, security of energy supply and the abatement of greenhouse gas emissions. Nevertheless, the design of policy packages may involve trade-offs between these objectives. The challenge for energy modellers is to quantify future energy savings associated with combinations of efficiency measures. This paper draws on the international experience in energy modelling and tracks recent progress that has been made towards a harmonised European framework for verification of savings. It points to the significant development work that remains to be done, particularly to enable an increased reliance on bottom-up evaluation methods. One significant gap in our knowledge relates to the required adjustment of technical savings due to behavioural factors such as rebound effects. The paper uses one country (Ireland) as a case study to demonstrate how a framework is being developed to respond to these new requirements.

  14. Integrated genome-scale analysis of the transcriptional regulatory landscape in a blood stem/progenitor cell model.

    Science.gov (United States)

    Wilson, Nicola K; Schoenfelder, Stefan; Hannah, Rebecca; Sánchez Castillo, Manuel; Schütte, Judith; Ladopoulos, Vasileios; Mitchelmore, Joanna; Goode, Debbie K; Calero-Nieto, Fernando J; Moignard, Victoria; Wilkinson, Adam C; Jimenez-Madrid, Isabel; Kinston, Sarah; Spivakov, Mikhail; Fraser, Peter; Göttgens, Berthold

    2016-03-31

    Comprehensive study of transcriptional control processes will be required to enhance our understanding of both normal and malignant hematopoiesis. Modern sequencing technologies have revolutionized our ability to generate genome-scale expression and histone modification profiles, transcription factor (TF)-binding maps, and also comprehensive chromatin-looping information. Many of these technologies, however, require large numbers of cells, and therefore cannot be applied to rare hematopoietic stem/progenitor cell (HSPC) populations. The stem cell factor-dependent multipotent progenitor cell line HPC-7 represents a well-recognized cell line model for HSPCs. Here we report genome-wide maps for 17 TFs, 3 histone modifications, DNase I hypersensitive sites, and high-resolution promoter-enhancer interactomes in HPC-7 cells. Integrated analysis of these complementary data sets revealed TF occupancy patterns of genomic regions involved in promoter-anchored loops. Moreover, preferential associations between pairs of TFs bound at either ends of chromatin loops led to the identification of 4 previously unrecognized protein-protein interactions between key blood stem cell regulators. All HPC-7 data sets are freely available both through standard repositories and a user-friendly Web interface. Together with previously generated genome-wide data sets, this study integrates HPC-7 data into a genomic resource on par with ENCODE tier 1 cell lines and, importantly, is the only current model with comprehensive genome-scale data that is relevant to HSPC biology. © 2016 by The American Society of Hematology.

  15. Large-Scale Recurrent Neural Network Based Modelling of Gene Regulatory Network Using Cuckoo Search-Flower Pollination Algorithm.

    Science.gov (United States)

    Mandal, Sudip; Khan, Abhinandan; Saha, Goutam; Pal, Rajat K

    2016-01-01

    The accurate prediction of genetic networks using computational tools is one of the greatest challenges in the postgenomic era. Recurrent Neural Network is one of the most popular but simple approaches to model the network dynamics from time-series microarray data. To date, it has been successfully applied to computationally derive small-scale artificial and real-world genetic networks with high accuracy. However, they underperformed for large-scale genetic networks. Here, a new methodology has been proposed where a hybrid Cuckoo Search-Flower Pollination Algorithm has been implemented with Recurrent Neural Network. Cuckoo Search is used to search the best combination of regulators. Moreover, Flower Pollination Algorithm is applied to optimize the model parameters of the Recurrent Neural Network formalism. Initially, the proposed method is tested on a benchmark large-scale artificial network for both noiseless and noisy data. The results obtained show that the proposed methodology is capable of increasing the inference of correct regulations and decreasing false regulations to a high degree. Secondly, the proposed methodology has been validated against the real-world dataset of the DNA SOS repair network of Escherichia coli. However, the proposed method sacrifices computational time complexity in both cases due to the hybrid optimization process.

  16. Using Boolean Logic Modeling of Gene Regulatory Networks to Exploit the Links Between Cancer and Metabolism for Therapeutic Purposes.

    Science.gov (United States)

    Arshad, Osama A; Venkatasubramani, Priyadharshini S; Datta, Aniruddha; Venkatraj, Jijayanagaram

    2016-01-01

    The uncontrolled cell proliferation that is characteristically associated with cancer is usually accompanied by alterations in the genome and cell metabolism. Indeed, the phenomenon of cancer cells metabolizing glucose using a less efficient anaerobic process even in the presence of normal oxygen levels, termed the Warburg effect, is currently considered to be one of the hallmarks of cancer. Diabetes, much like cancer, is defined by significant metabolic changes. Recent epidemiological studies have shown that diabetes patients treated with the antidiabetic drug Metformin have significantly lowered risk of cancer as compared to patients treated with other antidiabetic drugs. We utilize a Boolean logic model of the pathways commonly mutated in cancer to not only investigate the efficacy of Metformin for cancer therapeutic purposes but also demonstrate how Metformin in concert with other cancer drugs could provide better and less toxic clinical outcomes as compared to using cancer drugs alone.

  17. Mammals of Australia's tropical savannas: a conceptual model of assemblage structure and regulatory factors in the Kimberley region.

    Directory of Open Access Journals (Sweden)

    Ian J Radford

    Full Text Available We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011 were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:--low numbers of mammals, State II:--dominated by omnivorous rodents and State III:--dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but-unlike arid regions-were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the

  18. Mammals of Australia's Tropical Savannas: A Conceptual Model of Assemblage Structure and Regulatory Factors in the Kimberley Region

    Science.gov (United States)

    Radford, Ian J.; Dickman, Christopher R.; Start, Antony N.; Palmer, Carol; Carnes, Karin; Everitt, Corrin; Fairman, Richard; Graham, Gordon; Partridge, Thalie; Thomson, Allan

    2014-01-01

    We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:- low numbers of mammals, State II:- dominated by omnivorous rodents and State III:- dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but—unlike arid regions—were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the already

  19. Mammals of Australia's tropical savannas: a conceptual model of assemblage structure and regulatory factors in the Kimberley region.

    Science.gov (United States)

    Radford, Ian J; Dickman, Christopher R; Start, Antony N; Palmer, Carol; Carnes, Karin; Everitt, Corrin; Fairman, Richard; Graham, Gordon; Partridge, Thalie; Thomson, Allan

    2014-01-01

    We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:--low numbers of mammals, State II:--dominated by omnivorous rodents and State III:--dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but-unlike arid regions-were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the already-articulated cat

  20. Identifying regulational alterations in gene regulatory networks by state space representation of vector autoregressive models and variational annealing.

    Science.gov (United States)

    Kojima, Kaname; Imoto, Seiya; Yamaguchi, Rui; Fujita, André; Yamauchi, Mai; Gotoh, Noriko; Miyano, Satoru

    2012-01-01

    In the analysis of effects by cell treatment such as drug dosing, identifying changes on gene network structures between normal and treated cells is a key task. A possible way for identifying the changes is to compare structures of networks estimated from data on normal and treated cells separately. However, this approach usually fails to estimate accurate gene networks due to the limited length of time series data and measurement noise. Thus, approaches that identify changes on regulations by using time series data on both conditions in an efficient manner are demanded. We propose a new statistical approach that is based on the state space representation of the vector autoregressive model and estimates gene networks on two different conditions in order to identify changes on regulations between the conditions. In the mathematical model of our approach, hidden binary variables are newly introduced to indicate the presence of regulations on each condition. The use of the hidden binary variables enables an efficient data usage; data on both conditions are used for commonly existing regulations, while for condition specific regulations corresponding data are only applied. Also, the similarity of networks on two conditions is automatically considered from the design of the potential function for the hidden binary variables. For the estimation of the hidden binary variables, we derive a new variational annealing method that searches the configuration of the binary variables maximizing the marginal likelihood. For the performance evaluation, we use time series data from two topologically similar synthetic networks, and confirm that our proposed approach estimates commonly existing regulations as well as changes on regulations with higher coverage and precision than other existing approaches in almost all the experimental settings. For a real data application, our proposed approach is applied to time series data from normal Human lung cells and Human lung cells treated by

  1. Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

    Science.gov (United States)

    Wang, Di; Wang, Wei; Zhou, Yulin; Wang, Juan; Jia, Dongxu; Wong, Hei Kiu; Zhang, Zhang-Jin

    2015-10-08

    Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.

  2. Regulatory Impact Analysis Practice in New Zealand in the Light of Models of Evaluation Use – Inspiration for the Polish Government

    Directory of Open Access Journals (Sweden)

    Tomasz Kupiec

    2015-06-01

    Full Text Available Purpose: The paper describes the functioning of the RIA system in New Zealand using the analogy of RIA and the evaluation of public interventions. Presented solutions can provide nspiration for the Polish government in the process of improving the quality and extent of the use of RIA. Methodology: The analysis is based on a review of government documents and literature, as well as individual interviews and correspondence with representatives of the government of NZ. Conclusions: The RIA system in NZ is not error-free and its shortcomings include inter alia the lack of solutions with respect to ex-post analysis and insufficiently rigorous methodological approach. At the same time, a number of solutions can be regarded as good practice, e.g.: regular external quality reviews of RIS, obligation to supplement each RIS with ‘quality assessment’ and a ‘disclosure statement’ outlining their credibility and utility. Practical implications: The presented strengths of the RIA system in NZ may serve as an inspiration for modifying the RIA system in Poland. Originality: The RIA system is presented through the prism of the model of evaluation use, which is a related tool of collecting information about non-regulatory interventions.

  3. Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+ T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

    Directory of Open Access Journals (Sweden)

    Takaya Yamada

    2012-01-01

    Full Text Available Sublingual immunotherapy (SLIT has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs, but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN, which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

  4. On the Path to SunShot - Utility Regulatory Business Model Reforms forAddressing the Financial Impacts of Distributed Solar on Utilities

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2016-05-01

    Net-energy metering (NEM) with volumetric retail electricity pricing has enabled rapid proliferation of distributed photovoltaics (DPV) in the United States. However, this transformation is raising concerns about the potential for higher electricity rates and cost-shifting to non-solar customers, reduced utility shareholder profitability, reduced utility earnings opportunities, and inefficient resource allocation. Although DPV deployment in most utility territories remains too low to produce significant impacts, these concerns have motivated real and proposed reforms to utility regulatory and business models, with profound implications for future DPV deployment. This report explores the challenges and opportunities associated with such reforms in the context of the U.S. Department of Energy’s SunShot Initiative. As such, the report focuses on a subset of a broader range of reforms underway in the electric utility sector. Drawing on original analysis and existing literature, we analyze the significance of DPV’s financial impacts on utilities and non-solar ratepayers under current NEM rules and rate designs, the projected effects of proposed NEM and rate reforms on DPV deployment, and alternative reforms that could address utility and ratepayer concerns while supporting continued DPV growth. We categorize reforms into one or more of four conceptual strategies. Understanding how specific reforms map onto these general strategies can help decision makers identify and prioritize options for addressing specific DPV concerns that balance stakeholder interests.

  5. Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis.

    Science.gov (United States)

    Borbély, Éva; Botz, Bálint; Bölcskei, Kata; Kenyér, Tibor; Kereskai, László; Kiss, Tamás; Szolcsányi, János; Pintér, Erika; Csepregi, Janka Zsófia; Mócsai, Attila; Helyes, Zsuzsanna

    2015-03-01

    The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro-immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology. Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed. In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice. Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important

  6. Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells

    Directory of Open Access Journals (Sweden)

    Cheng M

    2013-10-01

    Full Text Available Mingrong Cheng,1,2,* Hongzhi Xu,3,* Yong Wang,4,* Houxiang Chen,5 Bing He,3 Xiaoyan Gao,6 Yingchun Li,2 Jiang Han,1 Zhiping Zhang1 1Department of General Surgery, 2Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People’s Republic of China; 6Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU, gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS. The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T

  7. Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

    Directory of Open Access Journals (Sweden)

    Christopher D Brown

    Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

  8. Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma

    National Research Council Canada - National Science Library

    Heier, I; Hofgaard, P. O; Brandtzæg, P; Jahnsen, F. L; Karlsson, M

    2008-01-01

    Regulatory T cells (T regs ) may inhibit immunity against cancer. Induction and expansion of T regs in the immunosuppressive microenvironment created by a growing tumour appear to be one of the mechanisms by which it can evade host defence...

  9. Analysis of odour compounds from scented consumer products using gas chromatography-mass spectrometry and gas chromatography-olfactometry.

    Science.gov (United States)

    Bartsch, Jennifer; Uhde, Erik; Salthammer, Tunga

    2016-01-21

    Scented consumer products are being bought in increasing amounts and gaining more popularity. There is, however, relatively little information available about their ingredients, emissions and allergenic potential. Frequently, a mixture of different fragrance substances and not solely an individual substance contributes to the overall desired smell. The aim of this study was to investigate the odorous volatile organic compounds (OVOCs) in consumer products containing fragrances. Over 44 products were selected: various scented candles, printing products with different scent types and other products types particularly meant to be used indoors. Measurements were carried out in a desiccator. Air samples were collected on thermal desorption tubes to determine the released fragrance substances by means of gas chromatography-mass spectrometry (GC-MS). Moreover, gas chromatography-olfactometry (GC-O) was used to obtain sensory data and to ensure no important odorant was overlooked. Using both methods it was possible to distinguish between odour active and inactive compounds and subsequently to identify almost 300 different odorants across all scented products. Besides the advantage of differentiation, as the human nose is a very sensitive detector, GC-O was found to be a useful tool for detecting traces and chosen target compounds. One focus in this study lay on the 26 EU-regulated fragrance allergens to prove their relevance in scented consumer goods. In total, 18 of them were identified, with at least one substance being present in almost every product. Benzyl alcohol, cinnamaldehyde, citronellol, eugenol, linalool and limonene were the prevalently detected allergens. Particularly linalool and limonene were observed in over 50% of the products. In addition, eugenol appeared to be one of the most frequently detected compounds in trace-level concentrations in the candle emissions.

  10. Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Warren C Plaisted

    Full Text Available We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs derived from human embryonic stem cells (hESCs in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs. Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.

  11. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  12. Short-term experiments in using digestate products as substitutes for mineral (N) fertilizer: Agronomic performance, odours, and ammonia emission impacts.

    Science.gov (United States)

    Riva, C; Orzi, V; Carozzi, M; Acutis, M; Boccasile, G; Lonati, S; Tambone, F; D'Imporzano, G; Adani, F

    2016-03-15

    Anaerobic digestion produces a biologically stable and high-value fertilizer product, the digestate, which can be used as an alternative to mineral fertilizers on crops. However, misuse of digestate can lead to annoyance for the public (odours) and to environmental problems such as nitrate leaching and ammonia emissions into the air. Full field experimental data are needed to support the use of digestate in agriculture, promoting its correct management. In this work, short-term experiments were performed to substitute mineral N fertilizers (urea) with digestate and products derived from it to the crop silage maize. Digestate and the liquid fraction of digestate were applied to soil at pre-sowing and as topdressing fertilizers in comparison with urea, both by surface application and subsurface injection during the cropping seasons 2012 and 2013. After each fertilizer application, both odours and ammonia emissions were measured, giving data about digestate and derived products' impacts. The AD products could substitute for urea without reducing crop yields, apart from the surface application of AD-derived fertilizers. Digestate and derived products, because of high biological stability acquired during the AD, had greatly reduced olfactometry impact, above all when they were injected into soils (82-88% less odours than the untreated biomass, i.e. cattle slurry). Ammonia emission data indicated, as expected, that the correct use of digestate and derived products required their injection into the soil avoiding, ammonia volatilization into the air and preserving fertilizer value. Sub-surface injection allowed ammonia emissions to be reduced by 69% and 77% compared with surface application during the 2012 and 2013 campaigns. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Regulating regulatory T cells.

    Science.gov (United States)

    Le, N T; Chao, N

    2007-01-01

    Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.